TY - JOUR T1 - Cochlear outer hair cell bending in an external electric field. AN - 85256834; pmid-9284333 AB - We have used a high-resolution motion analysis system to reinvestigate shape changes in isolated guinea pig cochlear outer hair cells (OHCs) evoked by low-frequency (2-3 Hz) external electric stimulation. This phenomenon of electromotility is presumed to result from voltage-dependent structural changes in the lateral plasma membrane of the OHC. In addition to well-known longitudinal movements, OHCs were found to display bending movements when the alternating external electric field gradients were oriented perpendicular to the cylindrical cell body. The peak-to-peak amplitude of the bending movement was found to be as large as 0.7 microm. The specific sulfhydryl reagents, p-chloromercuriphenylsulfonic acid and p-hydroxymercuriphenylsulfonic acid, that suppress electrically evoked longitudinal OHCs movements, also inhibit the bending movements, indicating that these two movements share the same underlying mechanism. The OHC bending is likely to result from an electrical charge separation that produces depolarization of the lateral plasma membrane on one side of the cell and hyperpolarization on the other side. In the cochlea, OHC bending could produce radial distortions in the sensory epithelium and influence the micromechanics of the organ of Corti. JF - Biophysical Journal AU - Frolenkov, G I AU - Kalinec, F AU - Tavartkiladze, G A AU - Kachar, B AD - Section on Structural Cell Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1997 SP - 1665 EP - 1672 VL - 73 IS - 3 SN - 0006-3495, 0006-3495 KW - Cell Movement KW - Cochlea KW - In Vitro KW - Guinea Pigs KW - Hair Cells, Outer KW - Animal KW - Electric Stimulation KW - Time Factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85256834?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biophysical+Journal&rft.atitle=Cochlear+outer+hair+cell+bending+in+an+external+electric+field.&rft.au=Frolenkov%2C+G+I%3BKalinec%2C+F%3BTavartkiladze%2C+G+A%3BKachar%2C+B&rft.aulast=Frolenkov&rft.aufirst=G&rft.date=1997-09-01&rft.volume=73&rft.issue=3&rft.spage=1665&rft.isbn=&rft.btitle=&rft.title=Biophysical+Journal&rft.issn=00063495&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Apoptosis and hair cell degeneration in the vestibular sensory epithelia of the guinea pig following a gentamicin insult. AN - 85236359; pmid-9307323 AB - Apoptosis plays a key role in the steady state of continuously renewing tissues. The goal of this study was to determine whether apoptosis was a mode of hair cell loss in mammalian inner ear sensory epithelia. Hair cell loss was induced by systemic treatment with the ototoxic aminoglycoside antibiotic gentamicin in guinea pig. The vestibular sensory epithelia were examined at different times after administration via semi-thin and thin sections in situ labeling by the terminal deoxynucleotidyl transferase catalysis of digoxigenin tagged nucleotides to the free 3'-OH ends of fragmented DNA. Apoptotic labeling was detected 3-7 days after treatment. The majority of the apoptotic nuclei was found adjacent to the luminal surface. Analysis of semi-thin and thin sections revealed two modes of hair cell degeneration: (1) Apoptosis within the epithelium, showing typical morphological changes of condensation and fragmentation of the nucleus and modifications of cytoplasmic organelles. (2) Swelling of the cell, vacuolation and distortion of cell shape, and extrusion into the lumen. The results indicated that vestibular hair cells undergo apoptosis after ototoxic traumas. JF - Hearing Research AU - Lang, H AU - Liu, C AD - Beijing Institute of Otolaryngology, Chong Nei, People's Republic of China. PY - 1997 SP - 177 EP - 184 VL - 111 IS - 1-2 SN - 0378-5955, 0378-5955 KW - Comparative Study KW - Hair Cells KW - Cell Size KW - Apoptosis KW - Epithelial Cells KW - Genetic Techniques KW - Guinea Pigs KW - Digoxigenin KW - Animal KW - Vestibule KW - DNA Fragmentation KW - Ear Diseases KW - Gentamicins KW - Antibiotics, Aminoglycoside UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85236359?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hearing+Research&rft.atitle=Apoptosis+and+hair+cell+degeneration+in+the+vestibular+sensory+epithelia+of+the+guinea+pig+following+a+gentamicin+insult.&rft.au=Lang%2C+H%3BLiu%2C+C&rft.aulast=Lang&rft.aufirst=H&rft.date=1997-09-01&rft.volume=111&rft.issue=1-2&rft.spage=177&rft.isbn=&rft.btitle=&rft.title=Hearing+Research&rft.issn=03785955&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Effect of recombinant alpha-interferon on pharmacokinetics, biodistribution, toxicity, and efficacy of 131I-labeled monoclonal antibody CC49 in breast cancer: a phase II trial. AN - 79641162; 9815842 AB - Preclinical studies have demonstrated that recombinant IFN-alpha (rIFN-alpha) can enhance the tumor associated glycoprotein 72 (TAG-72) on tumors. To determine whether rIFN-alpha could enhance TAG-72 expression in vivo in patients, 15 women with breast cancer were randomized to receive daily injections of rIFN-alpha (3 x 10(6) units/m2 for 14 days) beginning on day 1 (group 1 = 7 patients) or on day 6 (group 2 = 8 patients). On day 3, all patients received a 10-20-mCi tracer dose of 131I-CC49, a high-affinity murine monoclonal antibody reactive against TAG-72, followed by a therapy dose of 60-75 mCi/m2 of 131I-CC49 on day 6. Whole body and single-photon emission computed tomography scans along with whole blood pharmacokinetics were performed following tracer and treatment phases. Hematological toxicity was considerable; reversible grade 3-4 neutropenia and thrombocytopenia was observed in 12 of 15 patients. Twelve of 14 patients tested developed human antimouse antibodies 3-6 weeks after treatment. For group 1 patients, whole blood residence time increased significantly between that predicted from the tracer doses and therapy doses (42.6 +/- 4.7 versus 51.5 +/- 4.8 h, respectively; P < 0.01). The calculated radiation absorbed dose to red marrow from therapy compared to tracer activity was also significantly higher for this group (1.25 +/- 0.35 versus 1. 07 +/- 0.26 cGy/mCi; P < 0.05). Treatment with rIFN-alpha was found to enhance TAG-72 expression in tumors from patients receiving rIFN-alpha (group 1) by 46 +/- 19% (P < 0.05) compared to only 1.3 +/- 0.95% in patients not initially receiving IFN (group 2). The uptake of CC49 in tumors was also significantly increased in rIFN-alpha-treated patients. One partial and two minor tumor responses were seen. In summary, rIFN-alpha treatment altered the pharmacokinetics and tumor uptake of 131I-CC49 in patients at the expense of increased toxicity. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Macey, D J AU - Grant, E J AU - Kasi, L AU - Rosenblum, M G AU - Zhang, H Z AU - Katz, R L AU - Rieger, P T AU - LeBherz, D AU - South, M AU - Greiner, J W AU - Schlom, J AU - Podoloff, D A AU - Murray, J L AD - National Cancer Institute, Bethesda, Maryland 20815, and the University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 1547 EP - 1555 VL - 3 IS - 9 SN - 1078-0432, 1078-0432 KW - Antibodies, Anti-Idiotypic KW - 0 KW - Antibodies, Monoclonal KW - Antigens, Neoplasm KW - Antineoplastic Agents KW - Glycoproteins KW - Immunoconjugates KW - Interferon-alpha KW - Iodine Radioisotopes KW - Recombinant Proteins KW - tumor-associated antigen 72 KW - interferon alfa-2a KW - 47RRR83SK7 KW - Index Medicus KW - Animals KW - Drug Administration Schedule KW - Tomography, Emission-Computed, Single-Photon KW - Combined Modality Therapy KW - Humans KW - Neutropenia -- chemically induced KW - Mice KW - Tissue Distribution KW - Antibodies, Anti-Idiotypic -- biosynthesis KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Antibody Specificity KW - Adult KW - Treatment Outcome KW - Neoplasm Metastasis KW - Thrombocytopenia -- chemically induced KW - Middle Aged KW - Bone Marrow -- radiation effects KW - Lymphatic Metastasis -- radiotherapy KW - Female KW - Interferon-alpha -- pharmacology KW - Glycoproteins -- biosynthesis KW - Interferon-alpha -- administration & dosage KW - Antigens, Neoplasm -- biosynthesis KW - Breast Neoplasms -- radiotherapy KW - Immunoconjugates -- therapeutic use KW - Antibodies, Monoclonal -- therapeutic use KW - Breast Neoplasms -- immunology KW - Glycoproteins -- immunology KW - Immunoconjugates -- pharmacokinetics KW - Antigens, Neoplasm -- immunology KW - Iodine Radioisotopes -- pharmacokinetics KW - Breast Neoplasms -- diagnostic imaging KW - Interferon-alpha -- therapeutic use KW - Antineoplastic Agents -- administration & dosage KW - Breast Neoplasms -- metabolism KW - Glycoproteins -- genetics KW - Iodine Radioisotopes -- therapeutic use KW - Radioimmunotherapy KW - Antibodies, Monoclonal -- pharmacokinetics KW - Iodine Radioisotopes -- adverse effects KW - Immunoconjugates -- adverse effects KW - Antibodies, Monoclonal -- adverse effects KW - Antigens, Neoplasm -- genetics KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79641162?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Effect+of+recombinant+alpha-interferon+on+pharmacokinetics%2C+biodistribution%2C+toxicity%2C+and+efficacy+of+131I-labeled+monoclonal+antibody+CC49+in+breast+cancer%3A+a+phase+II+trial.&rft.au=Macey%2C+D+J%3BGrant%2C+E+J%3BKasi%2C+L%3BRosenblum%2C+M+G%3BZhang%2C+H+Z%3BKatz%2C+R+L%3BRieger%2C+P+T%3BLeBherz%2C+D%3BSouth%2C+M%3BGreiner%2C+J+W%3BSchlom%2C+J%3BPodoloff%2C+D+A%3BMurray%2C+J+L&rft.aulast=Macey&rft.aufirst=D&rft.date=1997-09-01&rft.volume=3&rft.issue=9&rft.spage=1547&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-22 N1 - Date created - 1999-03-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alcohol problems in a general hospital--a prevalence study. AN - 79585794; 9529584 AB - The prevalence of problem drinking among medical and surgical in-patients in a general hospital was studied using the CAGE questionnaire. Almost a quarter (23.3%) of the in-patients had associated drinking problems which were more among medical than surgical in-patients. In a large majority of these patients, the associated problem drinking was not recognised by the treating medical professionals. Routine administration of instruments like CAGE which are brief and easy to use would contribute to the early detection and management of alcohol problems in the general hospital setting. JF - Journal of the Indian Medical Association AU - Sri, E V AU - Raguram, R AU - Srivastava, M AD - Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bangalore. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 505 EP - 506 VL - 95 IS - 9 SN - 0019-5847, 0019-5847 KW - Index Medicus KW - Mass Screening KW - India -- epidemiology KW - Humans KW - Surveys and Questionnaires KW - Hospitals, General KW - Male KW - Female KW - Prevalence KW - Alcoholism -- epidemiology KW - Alcoholism -- diagnosis KW - Inpatients UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79585794?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+Indian+Medical+Association&rft.atitle=Alcohol+problems+in+a+general+hospital--a+prevalence+study.&rft.au=Sri%2C+E+V%3BRaguram%2C+R%3BSrivastava%2C+M&rft.aulast=Sri&rft.aufirst=E&rft.date=1997-09-01&rft.volume=95&rft.issue=9&rft.spage=505&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+Indian+Medical+Association&rft.issn=00195847&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-13 N1 - Date created - 1998-05-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Smokeless tobacco: an addicting drug. AN - 79582501; 9524433 AB - In 1986, the Surgeon General concluded that smokeless tobacco is an addictive drug sharing many qualities with other drugs of abuse such as morphine and cocaine. Smokeless tobacco can be used to deliver psycho-active and dependence-producing levels of nicotine. Tolerance develops with repeated use, causing the user to increase nicotine dosing through increased use and/or switching to products with higher nicotine yields. Clinical signs of nicotine withdrawal develop upon cessation of use. Recent data show that smokeless tobacco products vary widely in their nicotine dosing capabilities. Low-dose products tend to be those commonly marketed toward, and used by, young people without previous smokeless tobacco experience. Many of these people develop dependence and switch to high-dose products. The present article discusses each of these qualities of smokeless tobacco in greater detail. The article also discusses qualities of smokeless tobacco that make it an effective nicotine delivery device that leads to addiction. JF - Advances in dental research AU - Henningfield, J E AU - Fant, R V AU - Tomar, S L AD - Clinical Pharmacology Research Branch, National Institute on Drug Abuse Addiction Research Center, Baltimore, Maryland 21224, USA. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 330 EP - 335 VL - 11 IS - 3 SN - 0895-9374, 0895-9374 KW - Nicotine KW - 6M3C89ZY6R KW - Dentistry KW - Substance Withdrawal Syndrome -- etiology KW - Humans KW - Plants, Toxic KW - Tobacco Use Disorder -- physiopathology KW - Nicotine -- pharmacokinetics KW - Behavior, Addictive -- etiology KW - Nicotine -- adverse effects KW - Tobacco, Smokeless -- adverse effects KW - Nicotine -- administration & dosage KW - Tobacco Use Disorder -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79582501?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+dental+research&rft.atitle=Smokeless+tobacco%3A+an+addicting+drug.&rft.au=Henningfield%2C+J+E%3BFant%2C+R+V%3BTomar%2C+S+L&rft.aulast=Henningfield&rft.aufirst=J&rft.date=1997-09-01&rft.volume=11&rft.issue=3&rft.spage=330&rft.isbn=&rft.btitle=&rft.title=Advances+in+dental+research&rft.issn=08959374&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-02 N1 - Date created - 1998-04-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Epidemiology of cancer and other systemic effects associated with the use of smokeless tobacco. AN - 79582021; 9524431 AB - Persons who use chewing tobacco and snuff experience an increased risk of oral cancer. Because of the pharmacologic properties of nicotine and other constituents of smokeless tobacco, there is also concern that smokeless tobacco products may lead to cardiovascular diseases as well. The relatively few human population studies to date conflict with respect to whether smokeless tobacco use elevates cardiovascular risk factors or leads to cardiovascular disease or death from cardiovascular causes. Hemoglobin adducts to carcinogens present in smokeless tobacco products are measurable in the blood of smokeless tobacco users, indicating that smokeless-tobacco-related carcinogens circulate throughout the body. This prompts a concern that smokeless tobacco may increase risks of other cancers as well. The evidence to date from epidemiologic studies indicates no relationship between smokeless tobacco and bladder cancer, but there is suggestive evidence linking smokeless tobacco use to prostate cancer risk. Only single studies have been conducted of some cancers, and inconsistencies among studies of the same cancer site have been reported. Molecular epidemiologic studies may help identify markers of malignant transformation in smokeless tobacco users that may help in early intervention to prevent or ameliorate the consequences of oral cancer. Further studies are needed to determine more clearly the cardiovascular and non-oral cancer risks potentially associated with smokeless tobacco use. JF - Advances in dental research AU - Winn, D M AD - Division of Intramural Research, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892-6401, USA. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 313 EP - 321 VL - 11 IS - 3 SN - 0895-9374, 0895-9374 KW - Nicotine KW - 6M3C89ZY6R KW - Dentistry KW - Risk Factors KW - Humans KW - Nicotine -- adverse effects KW - Mouth Neoplasms -- etiology KW - Adult KW - Sweden -- epidemiology KW - Aged KW - Middle Aged KW - Europe -- epidemiology KW - Adolescent KW - United States -- epidemiology KW - Mouth Neoplasms -- epidemiology KW - Plants, Toxic KW - Cardiovascular Diseases -- etiology KW - Cardiovascular Diseases -- epidemiology KW - Tobacco, Smokeless -- adverse effects KW - Neoplasms -- epidemiology KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79582021?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+dental+research&rft.atitle=Epidemiology+of+cancer+and+other+systemic+effects+associated+with+the+use+of+smokeless+tobacco.&rft.au=Winn%2C+D+M&rft.aulast=Winn&rft.aufirst=D&rft.date=1997-09-01&rft.volume=11&rft.issue=3&rft.spage=313&rft.isbn=&rft.btitle=&rft.title=Advances+in+dental+research&rft.issn=08959374&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-02 N1 - Date created - 1998-04-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pt-ATP as an antineoplastic agent in an experimental mice model system. AN - 79440980; 9387898 AB - The antineoplastic activity of a platinum complex K4 (Pt Cl2 ATP) (Pt-ATP) has been investigated in transplantable tumors, both in an ascitic and solid (Ehrlich ascites carcinoma) tumor model. It has been observed that the drug at the total dose of 10 mg/kg body weight successfully inhibited the tumor burden both in ascitic and solid tumor system and subsequently increased the host's life span. An assessment of the in vitro (3H) thymidine incorporation into TCA precipitable material of EAC tumor cells done in the presence of Pt-ATP indicates that the drug inhibits (3H) thymidine incorporation in tumor cells. The drug has no appreciable toxic effect on the peripheral blood cells as well as bone marrow and spleenic cellularity. JF - Journal of experimental & clinical cancer research : CR AU - Pal, S AU - Mukherjea, K AU - Bhattacharya, R AU - Maity, P AD - Department of Cell Biology, Chittaranjan National Cancer Institute, Calcutta, India. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 255 EP - 260 VL - 16 IS - 3 SN - 0392-9078, 0392-9078 KW - Antineoplastic Agents KW - 0 KW - Organoplatinum Compounds KW - platinum dichloride-adenosine triphosphate complex KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Lethal Dose 50 KW - Disease Models, Animal KW - Mice KW - Male KW - Organoplatinum Compounds -- pharmacology KW - Cisplatin -- toxicity KW - Adenosine Triphosphate -- analogs & derivatives KW - Carcinoma, Ehrlich Tumor -- drug therapy KW - Cisplatin -- pharmacology KW - Adenosine Triphosphate -- toxicity KW - Organoplatinum Compounds -- toxicity KW - Antineoplastic Agents -- pharmacology KW - Adenosine Triphosphate -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79440980?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.atitle=Pt-ATP+as+an+antineoplastic+agent+in+an+experimental+mice+model+system.&rft.au=Pal%2C+S%3BMukherjea%2C+K%3BBhattacharya%2C+R%3BMaity%2C+P&rft.aulast=Pal&rft.aufirst=S&rft.date=1997-09-01&rft.volume=16&rft.issue=3&rft.spage=255&rft.isbn=&rft.btitle=&rft.title=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.issn=03929078&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-01-27 N1 - Date created - 1998-01-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Elevated mutant frequencies in gene lacI in splenic lipopolysaccharide blasts after exposure to activated phagocytes in vitro. AN - 79358937; 9341754 AB - The interaction of B lymphocytes with phagocytes is critical for shaping the humoral immune response, as well as various aspects of normal and malignant B cell development, and has therefore been studied by immunologists in great detail. However, one potential outcome of this confrontation is often neglected, namely the mutagenicity of phagocytes to B lymphocytes. We are interested in phagocyte-induced B cell mutagenesis and have conducted a feasibility study on the utility of a transgenic reporter assay to evaluate mutant frequencies in B cells that have encountered phagocytes. An in vitro co-incubation system was designed in which splenic lipopolysaccharide (LPS) blasts carrying a phage lambda-derived lacI transgene were exposed to pristane-elicited peritoneal exudate cells (PEC). Mutant frequencies in LPS blasts were significantly increased (up to 6-fold) when the cells were co-incubated with PEC that had been stimulated by phorbol myristate acetate to undergo an oxidative burst. The lacI-based transgenic mutation assay proved also useful for assessing mutagenicity in vivo, as demonstrated by the detection of elevated mutant frequencies in the spleen (3-fold) and the inflammatory granuloma (4.7-fold) obtained from pristane-treated mice. We propose to utilize the lacI-based transgenic mutagenesis assay as a tool to evaluate mutational levels during normal and aberrant B cell differentiation. JF - European journal of immunology AU - Felix, K AU - Lin, S AU - Janz, S AD - Institut für Klinische Molekularbiologie and Tumorgenetik, GSF, München, Germany. felixk@dc37a.nci.nih.gov Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 2160 EP - 2164 VL - 27 IS - 9 SN - 0014-2980, 0014-2980 KW - Bacterial Proteins KW - 0 KW - Escherichia coli Proteins KW - Lac Repressors KW - Repressor Proteins KW - Terpenes KW - pristane KW - 26HZV48DT1 KW - Index Medicus KW - Animals KW - Bacterial Proteins -- genetics KW - Spleen -- cytology KW - Mice KW - Mice, Inbred BALB C KW - Mice, Transgenic KW - Repressor Proteins -- genetics KW - Mutagenesis KW - Lymphocyte Activation KW - Mutagenicity Tests KW - Peritoneal Cavity -- cytology KW - Mice, Inbred C57BL KW - Lac Operon KW - B-Lymphocytes -- physiology KW - Phagocytes -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79358937?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+immunology&rft.atitle=Elevated+mutant+frequencies+in+gene+lacI+in+splenic+lipopolysaccharide+blasts+after+exposure+to+activated+phagocytes+in+vitro.&rft.au=Felix%2C+K%3BLin%2C+S%3BJanz%2C+S&rft.aulast=Felix&rft.aufirst=K&rft.date=1997-09-01&rft.volume=27&rft.issue=9&rft.spage=2160&rft.isbn=&rft.btitle=&rft.title=European+journal+of+immunology&rft.issn=00142980&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-14 N1 - Date created - 1997-11-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Influence of diet on mammary cancer in transgenic mice bearing an oncogene expressed in mammary tissue. AN - 79355035; 9342440 AB - Breast cancer is one of the most common cancers in women. The laboratory rat treated with strong carcinogen is the most commonly used animal model for study of breast cancer. Transgenic mouse lines with homologues of human breast cancer oncogenes have been developed. The transgenic mouse line TG.NK with c-neu, the human breast cancer oncogene homologue of erbB2, was evaluated to determine its suitability for study of intervention strategies to delay/prevent the development of breast cancer. There were no palpable mammary tumor masses up to 22-weeks of age, and almost all mice fed a purified diet developed palpable mammary tumors by 28-weeks of age. Nonpurified diets decreased the incidence and multiplicity, and delayed the development of mammary tumors as compared to a purified diet. Increasing the fiber content of nonpurified diet decreased the tumor incidence further. There is approximately a 19-week interval between weaning and development of palpable mammary masses to evaluate intervention strategies to delay or prevent the development of mammary cancer in the TG.NK mouse model. Fiber from nonpurified cereal ingredients appears to be highly beneficial in delaying the development of mammary cancer in TG.NK mice, and this observation is in agreement with human epidemiological findings. Therefore, the TG.NK transgenic mouse with oncogene c-neu (erbB2), appears to be a useful animal model for evaluation of dietary intervention strategies. JF - Breast cancer research and treatment AU - Rao, G N AU - Ney, E AU - Herbert, R A AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 149 EP - 158 VL - 45 IS - 2 SN - 0167-6806, 0167-6806 KW - Index Medicus KW - Animals KW - Mice KW - Mice, Transgenic KW - Female KW - Mammary Neoplasms, Animal -- etiology KW - Oncogenes -- genetics KW - Mammary Neoplasms, Animal -- pathology KW - Mammary Neoplasms, Animal -- genetics KW - Dietary Fiber -- adverse effects KW - Diet -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79355035?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Breast+cancer+research+and+treatment&rft.atitle=Influence+of+diet+on+mammary+cancer+in+transgenic+mice+bearing+an+oncogene+expressed+in+mammary+tissue.&rft.au=Rao%2C+G+N%3BNey%2C+E%3BHerbert%2C+R+A&rft.aulast=Rao&rft.aufirst=G&rft.date=1997-09-01&rft.volume=45&rft.issue=2&rft.spage=149&rft.isbn=&rft.btitle=&rft.title=Breast+cancer+research+and+treatment&rft.issn=01676806&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-18 N1 - Date created - 1997-11-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - L-methionine induces stage-dependent changes of differentiation and oxidative activity in sea urchin embryogenesis. AN - 79348703; 9335071 AB - This study was to investigate developmental toxicity of some selected low molecular weight antioxidants, by utilising sea urchin embryos and gametes as model system. Sea urchin embryos or sperm were exposed at different developmental stages to L-methionine or some selected low molecular weight antioxidants: a) N-acetylcysteine; b) L-carnosine; c) L-homocarnosine, and d) L-anserine. L-methionine displayed developmental toxicity at levels > or = 10(-5) M, whereas the other agents tested were mostly active at levels > or = 10(-4) M. When embryos were exposed to 10(-4) M L-methionine or N-acetylcysteine at different developmental stages, the most severe effects were exerted by early exposures (0 to 2 hr after fertilisation), whereas later exposures turned to lesser or no effects. Cytogenetic analysis of L-methionine-exposed embryos showed a significant mitogenic effect and increase of mitotic aberrations. Fertilisation success was decreased by L-methionine (10(-6) M to 10(-3) M) added at the moment of fertilisation, with increasing developmental and cytogenetic abnormalities in the offspring. The formation of reactive oxygen species in embryos and gametes was determined by: a) analysing the DNA oxidative product, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and b) luminol-dependent chemiluminescence. The results showed that: 1) 8-OHdG levels were increased during embryogenesis; 2) fertilisation was associated with a double-wave luminol-dependent chemiluminescence emission; 3) luminol-dependent chemiluminescence was maximal in cleavage, declining down to zero in plutei, and 4) an embryotoxic L-methionine or N-acetylcysteine level (10(-4) M) turned to a decrease in reactive oxygen species formation. The data suggest that L-methionine- or N-acetylcysteine-induced developmental toxicity is confined to early stages. A role for oxidative activity is suggested in modulating cell differentiation and embryogenesis, consistent with antioxidant-induced damage to early life stages. JF - Pharmacology & toxicology AU - Pagano, G AU - Bonassi, S AU - De Biase, A AU - Degan, P AU - Deeva, I B AU - Doronin, Y K AU - Iaccarino, M AU - Oral, R AU - Warnau, M AU - Korkina, L G AD - National Cancer Institute, G. Pascale Foundation, Napoli, Italy. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 134 EP - 143 VL - 81 IS - 3 SN - 0901-9928, 0901-9928 KW - Antioxidants KW - 0 KW - Free Radical Scavengers KW - Reactive Oxygen Species KW - homocarnosine KW - 3650-73-5 KW - 8-oxo-7-hydrodeoxyguanosine KW - 88847-89-6 KW - Carnosine KW - 8HO6PVN24W KW - Methionine KW - AE28F7PNPL KW - Deoxyguanosine KW - G9481N71RO KW - Anserine KW - HDQ4N37UGV KW - Acetylcysteine KW - WYQ7N0BPYC KW - Index Medicus KW - Animals KW - Chromosome Aberrations -- genetics KW - Stereoisomerism KW - Carnosine -- analogs & derivatives KW - Acetylcysteine -- toxicity KW - Luminescent Measurements KW - Mitosis -- genetics KW - Carnosine -- toxicity KW - Anserine -- toxicity KW - Mitosis -- drug effects KW - Deoxyguanosine -- analysis KW - Embryo, Nonmammalian -- drug effects KW - Deoxyguanosine -- analogs & derivatives KW - Free Radical Scavengers -- toxicity KW - Antioxidants -- toxicity KW - Germ Cells -- drug effects KW - Sea Urchins -- embryology KW - Methionine -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79348703?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacology+%26+toxicology&rft.atitle=L-methionine+induces+stage-dependent+changes+of+differentiation+and+oxidative+activity+in+sea+urchin+embryogenesis.&rft.au=Pagano%2C+G%3BBonassi%2C+S%3BDe+Biase%2C+A%3BDegan%2C+P%3BDeeva%2C+I+B%3BDoronin%2C+Y+K%3BIaccarino%2C+M%3BOral%2C+R%3BWarnau%2C+M%3BKorkina%2C+L+G&rft.aulast=Pagano&rft.aufirst=G&rft.date=1997-09-01&rft.volume=81&rft.issue=3&rft.spage=134&rft.isbn=&rft.btitle=&rft.title=Pharmacology+%26+toxicology&rft.issn=09019928&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-22 N1 - Date created - 1997-12-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transforming growth factor-beta protects human hNT cells from degeneration induced by beta-amyloid peptide: involvement of the TGF-beta type II receptor. AN - 79342908; 9332729 AB - Post-mitotic, human neurons (hNT cells) which have a phenotype similar to that of terminally differentiated neurons of the central nervous system were generated by treating the NT2/D1 human teratocarcinoma cell line with retinoic acid. Treatment of both hNT and NT2/D1 cells with 10(-5) M beta-amyloid peptide fragment 25-35 (A beta P) for 24 h resulted in a decrease in cell viability as determined by MTT incorporation and Trypan blue exclusion, and also induced an apoptotic morphology in hNT cells. Pre-treatment of cells for 24 h with 10 ng/ml TGF-beta 1 or 2 before addition of A beta P reduced the apoptotic morphology of hNT cells and increased cell viability in hNT cells, but not in NT2/D1 cells. Results of RT-PCR, immunohistochemistry and analysis of receptor cross-linking of [125I]TGF-beta 1 to the cell membrane, all showed that the TGF-beta type II receptor is expressed by hNT cells, but not NT2/D1 cells. These results suggest that TGF-beta can protect human, terminally differentiated, TGF-beta type II receptor-positive neurons from A beta P toxicity. We propose that the increased expression of TGF-beta in brains of patients with Alzheimer's disease may offer some degree of neuroprotection if neurons also express a functional TGF-beta type II receptor. JF - Brain research. Molecular brain research AU - Ren, R F AU - Hawver, D B AU - Kim, R S AU - Flanders, K C AD - Laboratory of Chemoprevention, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 315 EP - 322 VL - 48 IS - 2 SN - 0169-328X, 0169-328X KW - Amyloid beta-Peptides KW - 0 KW - Neuroprotective Agents KW - Peptide Fragments KW - Receptors, Transforming Growth Factor beta KW - Transforming Growth Factor beta KW - amyloid beta-protein (25-35) KW - Tretinoin KW - 5688UTC01R KW - Index Medicus KW - Phenotype KW - Tumor Cells, Cultured KW - Cell Differentiation -- physiology KW - Humans KW - Peptide Fragments -- pharmacology KW - Cell Line KW - Neuroprotective Agents -- pharmacology KW - Tretinoin -- pharmacology KW - Transforming Growth Factor beta -- pharmacology KW - Nerve Degeneration KW - Receptors, Transforming Growth Factor beta -- physiology KW - Neurons -- drug effects KW - Neurons -- cytology KW - Amyloid beta-Peptides -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79342908?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Gut+epithelial+cells+as+targets+for+gene+therapy+of+hemophilia&rft.au=Lozier%2C+J+N%3BYankaskas%2C+J+R%3BRamsey%2C+W+J%3BChen%2C+Lin%3BBerschneider%2C+H%3BMorgan%2C+R+A&rft.aulast=Lozier&rft.aufirst=J&rft.date=1997-08-01&rft.volume=8&rft.issue=12&rft.spage=1481&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 completed - 1998-02-17 N1 - Date created - 1998-02-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Promotion of dimethylbenz[a]anthracene-initiated mammary carcinogenesis by iron in female Sprague-Dawley rats. AN - 79327741; 9328172 AB - Iron body-stores and iron dietary intake have been sporadically reported to increase the risk of cancer in humans. To investigate the effect of iron on the development of mammary tumors, female Sprague-Dawley rats were given dimethylbenz[a]anthracene (DMBA) (5 mg/kg, i.g., 1x) at 55 days of age. Eight days later, rats received iron(II) sulfate s.c. (50 micromol/kg, 2x/week) for 53 weeks. Mammary tumors started to appear 6-8 weeks after DMBA initiation. At 20 weeks after DMBA treatment, iron(II) increased mammary tumor frequency twofold (11/30 versus 5/30 with DMBA alone). Tumor frequency increased with time and was significantly higher in iron-promoted rats after 40 weeks of treatment (24/30 versus 11/30, P = 0.001). Also, mammary tumors in iron-promoted rats were significantly larger than in DMBA-only rats at 20 weeks after initiation (P = 0.04) and this difference remained significant through the observation time point at 40 weeks. Iron could be detected histochemically in the stromal connective tissue, but not in the epithelial cells of mammary carcinomas. Mammary tumors in the DMBA-only group were mostly adenomas and adenocarcinomas, while those promoted by iron sulfate included fibroadenomas, adenomas and adenocarcinomas. Thus, iron(II) administered s.c. subsequent to DMBA initiation, greatly accelerated mammary carcinogenesis, implying its promoting activity for mammary tissue of female rats. JF - Carcinogenesis AU - Diwan, B A AU - Kasprzak, K S AU - Anderson, L M AD - Intramural Research Support Program, SAIC Frederick, NCI-Frederick Cancer Research and Development Center, MD 21702, USA. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 1757 EP - 1762 VL - 18 IS - 9 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Iron KW - E1UOL152H7 KW - Index Medicus KW - Rats KW - Animals KW - Adenocarcinoma -- metabolism KW - Rats, Sprague-Dawley KW - Fibroadenoma -- metabolism KW - Adenoma -- metabolism KW - Cocarcinogenesis KW - Adenocarcinoma -- chemically induced KW - Fibroadenoma -- chemically induced KW - Adenoma -- chemically induced KW - Weight Gain KW - Female KW - Mammary Neoplasms, Experimental -- chemically induced KW - 9,10-Dimethyl-1,2-benzanthracene -- toxicity KW - Carcinogens -- toxicity KW - Mammary Neoplasms, Experimental -- metabolism KW - Iron -- toxicity KW - Iron -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79327741?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Promotion+of+dimethylbenz%5Ba%5Danthracene-initiated+mammary+carcinogenesis+by+iron+in+female+Sprague-Dawley+rats.&rft.au=Diwan%2C+B+A%3BKasprzak%2C+K+S%3BAnderson%2C+L+M&rft.aulast=Diwan&rft.aufirst=B&rft.date=1997-09-01&rft.volume=18&rft.issue=9&rft.spage=1757&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-13 N1 - Date created - 1997-11-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sensitivity of Escherichia coli (MutT) and human (MTH1) 8-oxo-dGTPases to in vitro inhibition by the carcinogenic metals, nickel(II), copper(II), cobalt(II) and cadmium(II). AN - 79327163; 9328176 AB - The toxicity of Ni(II), Co(II) and Cu(II) in animals, and that of Cd(II) in cultured cells, has been associated with generation of the promutagenic lesion 8-oxo-7,8-dihydroguanine (8-oxoguanine) in DNA, among other effects. One possible source of this base may be 8-oxo-7,8-dihydro-2'-deoxyguanosine-5'-triphosphate (8-oxo-dGTP), a product of oxidative damage to the nucleotide pool, from which it is incorporated into DNA. To promote such incorporation, the metals would have to inhibit specific cellular 8-oxo-dGTPases that eliminate 8-oxo-dGTP from the nucleotide pool. The present study was designed to test such inhibition in vitro on 8-oxo-dGTPases from two different species, the human MTH1 protein and Escherichia coli MutT protein. In the presence of Mg(II), the natural activator of 8-oxo-dGTPases, all four metals were found to inhibit both enzymes. For MTH1, the IC50 values (+/- SE; n = 3-4) were 17 +/- 2 microM for Cu(II), 30 +/- 8 microM for Cd(II), 376 +/- 71 microM for Co(II) and 801 +/- 97 microM for Ni(II). For MutT, they were 60 +/- 6 microM for Cd(II), 102 +/- 8 microM for Cu(II), 1461 +/- 96 microM for Ni(II) and 8788 +/- 1003 microM for Co(II). Thus, Cu(II) and Cd(II) emerged as much stronger inhibitors than Ni(II) and Co(II), and MTH1 appeared to be generally more sensitive to metal inhibition than MutT. Interestingly, in the absence of Mg(II), the activity of the enzymes could be restored by Co(II) to 73% of that with Mg(II) alone for MutT, and 34% for MTH1, the other metals being much less or non-effective. The difference in sensitivity to metal inhibition between the two enzymes may reflect the differences in the amino acid ligands, especially the cysteine ligand, outside their evolutionarily conserved Mg(II)-binding active sites, which might indicate predominantly non-competitive or uncompetitive mechanism of the inhibition. The overall results suggest that inhibition of 8-oxo-dGTPases may be involved in the mechanisms of induction of the 8-oxoguanine lesion in DNA by the metal ions studied, especially the non-redox-active Cd(II) cation. JF - Carcinogenesis AU - Porter, D W AU - Yakushiji, H AU - Nakabeppu, Y AU - Sekiguchi, M AU - Fivash, M J AU - Kasprzak, K S AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute-FCRDC, Frederick, MD 21702, USA. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 1785 EP - 1791 VL - 18 IS - 9 SN - 0143-3334, 0143-3334 KW - Bacterial Proteins KW - 0 KW - Carcinogens KW - Enzyme Inhibitors KW - Escherichia coli Proteins KW - Metals KW - Cadmium KW - 00BH33GNGH KW - Cobalt KW - 3G0H8C9362 KW - Copper KW - 789U1901C5 KW - Nickel KW - 7OV03QG267 KW - Phosphoric Monoester Hydrolases KW - EC 3.1.3.2 KW - Pyrophosphatases KW - EC 3.6.1.- KW - mutT protein, E coli KW - 8-oxodGTPase KW - EC 3.6.1.55 KW - DNA Repair Enzymes KW - EC 6.5.1.- KW - Index Medicus KW - Cadmium -- pharmacology KW - Nickel -- pharmacology KW - Humans KW - Escherichia coli -- enzymology KW - Cobalt -- pharmacology KW - Copper -- pharmacology KW - Carcinogens -- pharmacology KW - Metals -- pharmacology KW - Bacterial Proteins -- antagonists & inhibitors KW - Enzyme Inhibitors -- pharmacology KW - Phosphoric Monoester Hydrolases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79327163?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Sensitivity+of+Escherichia+coli+%28MutT%29+and+human+%28MTH1%29+8-oxo-dGTPases+to+in+vitro+inhibition+by+the+carcinogenic+metals%2C+nickel%28II%29%2C+copper%28II%29%2C+cobalt%28II%29+and+cadmium%28II%29.&rft.au=Porter%2C+D+W%3BYakushiji%2C+H%3BNakabeppu%2C+Y%3BSekiguchi%2C+M%3BFivash%2C+M+J%3BKasprzak%2C+K+S&rft.aulast=Porter&rft.aufirst=D&rft.date=1997-09-01&rft.volume=18&rft.issue=9&rft.spage=1785&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-13 N1 - Date created - 1997-11-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Smad4 (homolog of human DPC4) and Smad2 (homolog of human JV18-1): candidates for murine lung tumor resistance and suppressor genes. AN - 79327124; 9328171 AB - In this study we investigated the mouse mad-related genes, Smad4/Dpc4 and Smad2 (homolog of JV18-1), as candidates for involvement in lung tumor resistance and suppression. These genes are located in a region of mouse chromosome 18 that is syntenic with human 18q21.1, where several genes that are mutated in various cancers have been mapped. A newly identified murine lung tumor resistance locus, Par2 has also been mapped to this region of chromosome 18. We found no mutations in the coding regions of either gene in 11 lung tumors from B6CF1 (C57BL/6 x BALB/c) mice by RT-PCR and SSCP/RFLP, suggesting that these genes are not mutated in lung carcinogenesis in this strain. Moreover, loss of heterozygosity in this region of chromosome 18 was not detected in 28 lung adenocarcinomas from B6CF1 mice, 17 lung adenocarcinomas from B6C3F1 mice or 18 lung adenocarcinomas from AB6F1 mice. These data provide evidence that a 'classical' tumor suppressor gene for mouse lung carcinogenesis in these strains does not reside in this region. In order to investigate Smad4/Dpc4 and Smad2 as candidates for the Par2 resistance locus mapped to this region, we also sequenced the coding regions of both genes in cDNA from normal lungs of A/J, BALB/c and C57BL/6 inbred strains of mice. No polymorphisms were detected in the coding region of Smad4. In Smad2, two sequence polymorphisms were identified that are not in the conserved regions of the gene. Northern blot analysis revealed no differential expression in normal lung tissue among the three strains for either gene. Thus, in this study we found no evidence that either Smad4 or Smad2 represents the Par2 lung tumor resistance locus or is a lung tumor suppressor gene in the B6CF1 mice. JF - Carcinogenesis AU - Devereux, T R AU - Anna, C H AU - Patel, A C AU - White, C M AU - Festing, M F AU - You, M AD - Laboratory of Molecular Carcinogenesis, NIEHS, Research Triangle Park, NC 27709, USA. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 1751 EP - 1755 VL - 18 IS - 9 SN - 0143-3334, 0143-3334 KW - DNA-Binding Proteins KW - 0 KW - SMAD4 protein, human KW - Smad4 Protein KW - Smad4 protein, mouse KW - Trans-Activators KW - Index Medicus KW - Animals KW - Polymorphism, Genetic KW - Humans KW - Mice, Inbred C57BL KW - Mice KW - Genetic Predisposition to Disease KW - Mice, Inbred BALB C KW - Species Specificity KW - Male KW - Female KW - Gene Deletion KW - Trans-Activators -- genetics KW - Genes, Tumor Suppressor KW - Lung Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79327124?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Smad4+%28homolog+of+human+DPC4%29+and+Smad2+%28homolog+of+human+JV18-1%29%3A+candidates+for+murine+lung+tumor+resistance+and+suppressor+genes.&rft.au=Devereux%2C+T+R%3BAnna%2C+C+H%3BPatel%2C+A+C%3BWhite%2C+C+M%3BFesting%2C+M+F%3BYou%2C+M&rft.aulast=Devereux&rft.aufirst=T&rft.date=1997-09-01&rft.volume=18&rft.issue=9&rft.spage=1751&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-13 N1 - Date created - 1997-11-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic construction and characterization of an anti-monkey CD3 single-chain immunotoxin with a truncated diphtheria toxin. AN - 79324638; 9327133 AB - We have previously developed a chemically conjugated anti-rhesus monkey CD3 immunotoxin FN18-CRM9 that can deplete in vivo T cells and induce long term tolerance of mismatched renal allograft in rhesus monkeys. This immunotoxin is a monkey analogue of anti-human CD3 immunotoxin UCHT1-CRM9. In this study, we cloned the light and heavy chain variable regions of anti-monkey CD3 monoclonal antibody FN18 and constructed a single-chain Fv (sFv) by linking variable light and variable heavy regions with a (Gly4Ser)3 linker. The single-chain immunotoxin DT390-FN18sFv was constructed by ligating the sFv to the carboxyl terminus of DT390, a truncated form of diphtheria toxin. The DT390-FN18sFv fusion protein was expressed in Escherichia coli and purified with Ni-RTA affinity and anion exchange columns. Similar to the chemically conjugated immunotoxin FN18-CRM9, DT390-FN18sFv can also specifically inhibit protein synthesis in primary monkey T cells in a dose-dependent manner. DT390-FN18sFv at 10(-7) mol/L or FN18-CRM9 at 10(-8) mol/L is sufficient to reduce protein synthesis of monkey primary T cells to less than 5% of the control. The 50% inhibition dosage (IC50) of FN18-CRM9 is 1 x 10(-10) mol/L, while the IC50 of DT390-FN18sFv is 1 x 10(-8) mol/ L, reflecting the lowered affinity of monovalent Fab' FN18 to its parental divalent antibody. The availability of functional FN18sFv will provide the basis for the construction of divalent anti-CD3 immunotoxins for preclinical studies on the induction of tolerance in organ transplantation and experimental autoimmune diseases. JF - Bioconjugate chemistry AU - Ma, S AU - Hu, H AU - Thompson, J AU - Stavrou, S AU - Scharff, J AU - Neville, D M AD - Section on Biophysical Chemistry, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-4034, USA. PY - 1997 SP - 695 EP - 701 VL - 8 IS - 5 SN - 1043-1802, 1043-1802 KW - Antigens, CD3 KW - 0 KW - Diphtheria Toxin KW - Immunotoxins KW - Adenosine Diphosphate Ribose KW - 20762-30-5 KW - Index Medicus KW - Animals KW - Escherichia coli -- metabolism KW - Fluorescence KW - Amino Acid Sequence KW - Macaca mulatta -- immunology KW - Cell Separation KW - Adenosine Diphosphate Ribose -- metabolism KW - Cloning, Molecular KW - Cytotoxicity, Immunologic KW - Hybridomas -- metabolism KW - Base Sequence KW - Blotting, Western KW - Molecular Sequence Data KW - Mutation KW - T-Lymphocytes -- immunology KW - Antigens, CD3 -- genetics KW - Immunotoxins -- isolation & purification KW - Immunotoxins -- genetics KW - Diphtheria Toxin -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79324638?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioconjugate+chemistry&rft.atitle=Genetic+construction+and+characterization+of+an+anti-monkey+CD3+single-chain+immunotoxin+with+a+truncated+diphtheria+toxin.&rft.au=Ma%2C+S%3BHu%2C+H%3BThompson%2C+J%3BStavrou%2C+S%3BScharff%2C+J%3BNeville%2C+D+M&rft.aulast=Ma&rft.aufirst=S&rft.date=1997-09-01&rft.volume=8&rft.issue=5&rft.spage=695&rft.isbn=&rft.btitle=&rft.title=Bioconjugate+chemistry&rft.issn=10431802&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-28 N1 - Date created - 1997-11-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Kinetics of wound-induced v-Ha-ras transgene expression and papilloma development in transgenic Tg.AC mice. AN - 79323513; 9328441 AB - The Tg.AC transgenic mouse, which harbors an activated v-Ha-ras coding region that is fused to an embryonic zeta globin transcriptional control region and a 3' simian virus 40 polyadenylation sequence, rapidly develops epidermal papillomas in response to topical application of chemical carcinogens or tumor promoters or to full-thickness wounding of the dorsal skin. In this report, we investigated the localization and temporal induction of v-Ha-ras transgene expression after full-thickness wounding of Tg.AC mouse skin. Surgically inflicted full-thickness incisions 3 cm long yielded four to six papillomas per Tg.AC mouse by 5 wk after wounding. Similar wounding of the FVB/N isogenic host strain did not produce tumors, which implicates a causal role for the v-Ha-ras transgene. Reverse transcription-polymerase chain reaction assays detected the v-Ha-ras transgene transcript in total RNA samples isolated from wound-associated tissue 3 and 4 wk after wounding. Tissues 1-2 wk after wounding and all non-wound-associated tissues were negative for transgene expression. In situ hybridization experiments using transgene-specific 35S-labeled antisense RNA probes localized transgene expression to the basal epidermal cells in wound-induced papillomas. Adjacent normal and hyperplastic skin tissues were negative for transgene expression by this assay. This work supports the hypothesis that the wound repair response leads to the transcriptional activation and continued expression of the v-Ha-ras transgene in specific cells in the skin, which alters normal epithelial differentiation and ultimately results in neoplastic growth. JF - Molecular carcinogenesis AU - Cannon, R E AU - Spalding, J W AU - Trempus, C S AU - Szczesniak, C J AU - Virgil, K M AU - Humble, M C AU - Tennant, R W AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 108 EP - 114 VL - 20 IS - 1 SN - 0899-1987, 0899-1987 KW - RNA, Messenger KW - 0 KW - Index Medicus KW - Polymerase Chain Reaction KW - Mice, Inbred Strains KW - Animals KW - In Situ Hybridization KW - RNA, Messenger -- metabolism KW - Gene Expression KW - Mice KW - RNA, Messenger -- genetics KW - Mice, Transgenic KW - Female KW - Skin Neoplasms -- genetics KW - Genes, ras KW - Gene Expression Regulation, Neoplastic KW - Papilloma -- etiology KW - Skin Neoplasms -- etiology KW - Transgenes KW - Wounds and Injuries -- metabolism KW - Papilloma -- genetics KW - Wounds and Injuries -- complications KW - Skin Neoplasms -- metabolism KW - Papilloma -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79323513?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Kinetics+of+wound-induced+v-Ha-ras+transgene+expression+and+papilloma+development+in+transgenic+Tg.AC+mice.&rft.au=Cannon%2C+R+E%3BSpalding%2C+J+W%3BTrempus%2C+C+S%3BSzczesniak%2C+C+J%3BVirgil%2C+K+M%3BHumble%2C+M+C%3BTennant%2C+R+W&rft.aulast=Cannon&rft.aufirst=R&rft.date=1997-09-01&rft.volume=20&rft.issue=1&rft.spage=108&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 - 1997-10-23 N1 - Date created - 1997-10-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - New strains of inbred SENCAR mice with increased susceptibility to induction of papillomas and squamous cell carcinomas in skin. AN - 79321406; 9328445 AB - To develop mouse strains useful for studies of susceptibility and resistance to the induction of skin tumors, three new inbred SENCAR strains were independently derived by random inbreeding of outbred SENCAR mice. Characterization of these mice for sensitivity to skin tumor development indicated that mice of all three strains displayed increased sensitivity to initiation by 7,12-dimethylbenz[a]anthracene (DMBA), urethane, or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA). Promotion by mezerein as well as carcinogenesis by repeated treatment with DMBA or MNNG produced papillomas with a high frequency of conversion to squamous cell carcinomas (SCCs). Compared with outbred SENCAR mice, development of both squamous papillomas and carcinomas was increased at least two-fold by all protocols tested. The F1 hybrid between SENCARA/Pt males and resistant BALB/cAnPt females was resistant to the induction of both papillomas and SCCs after initiation by 2 microg of DMBA and promotion by 20 weekly applications of 2 microg of TPA. Papillomas developed in all of the SENCARA/Pt mice, none of the BALB/cAnPt mice, and 12% of the F1 progeny. Thus, at these doses of initiator and promoter, resistance was incompletely dominant in the F1 hybrid. However, the responsiveness of the F1 mice could be increased substantially by increasing the dose of the promoter. JF - Molecular carcinogenesis AU - Hennings, H AU - Lowry, D T AU - Yuspa, S H AU - Mock, B AU - Potter, M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 143 EP - 150 VL - 20 IS - 1 SN - 0899-1987, 0899-1987 KW - Carcinogens KW - 0 KW - Diterpenes KW - Terpenes KW - Methylnitronitrosoguanidine KW - 12H3O2UGSF KW - mezerein KW - 34807-41-5 KW - Urethane KW - 3IN71E75Z5 KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Index Medicus KW - Sensitivity and Specificity KW - Animals KW - Disease Susceptibility KW - Mice KW - Mice, Inbred BALB C KW - Phenotype KW - Mice, Inbred SENCAR KW - Female KW - Male KW - Skin Neoplasms -- genetics KW - Cocarcinogenesis KW - Skin Neoplasms -- chemically induced KW - Carcinoma, Squamous Cell -- genetics KW - Carcinoma, Squamous Cell -- chemically induced KW - Papilloma -- genetics KW - Papilloma -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79321406?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=New+strains+of+inbred+SENCAR+mice+with+increased+susceptibility+to+induction+of+papillomas+and+squamous+cell+carcinomas+in+skin.&rft.au=Hennings%2C+H%3BLowry%2C+D+T%3BYuspa%2C+S+H%3BMock%2C+B%3BPotter%2C+M&rft.aulast=Hennings&rft.aufirst=H&rft.date=1997-09-01&rft.volume=20&rft.issue=1&rft.spage=143&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 - 1997-10-23 N1 - Date created - 1997-10-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Decreases in phorbol ester-induced papilloma development in v-Ha-ras transgenic TG.AC mice during reduced gene dosage of bcl-2. AN - 79320103; 9328437 AB - We have demonstrated that induction of transgene expression in the v-Ha-ras-transgenic TG.AC mouse is a critical event in skin tumorigenesis and that cutaneous papillomas arise from follicular epidermis after treatment with chemical carcinogens. The sensitivity of TG.AC mice to skin tumorigenesis, coupled with their low incidence of spontaneous skin tumors, makes this strain a good model for identifying carcinogens and for investigating the roles that other genes may play in the development of skin neoplasia. To investigate the possible involvement of the bcl-2 gene in skin tumorigenesis in the TG.AC mouse, we crossed heterozygous bcl-2-knockout mice (C57BI/6, 129 background) with TG.AC mice (FVB/N background). Female mice were genotyped by using a neo cassette to identify bcl-2-deficient mice. In addition, homozygous TG.AC mice were bred with FVB/N mice to generate hemizygous TG.AC mice on an FVB/N background to serve as a gene-dosage control. The F1 progeny consisted of FVB/N(v-Ha-ras+/-):C57BI/6,129(bcl-2+/+),FVB/N(v-Ha-ra s+/-):C57BI/6,129(bcl-2+/-), and FVB/N(v-Ha-ras+/-,bcl-2+/+). Ten-week-old mice were dosed twice weekly for 10 wk with acetone, 1.25 microg of 7,12-tetradecanoylphorbol-13-acetate (TPA), or 2.5 microg of TPA, and papillomas were counted weekly. Papillomas were analyzed for ras transgene and bcl-2 expression by reverse transcription-polymerase chain reaction, v-Ha-ras expression by in situ hybridization, and proliferating cell nuclear antigen expression by immunohistochemical analysis. Fewer papillomas (P < 0.05) were observed at the low dose of TPA (1.25 microg) in mice carrying the bcl-2 knockout allele than in the wild-type mice, suggesting that reduction of the bcl-2 gene product affects the susceptibility of TG.AC mice to TPA-induced papillomas. However, at the high dose of TPA (2.5 microg), there was no difference in papilloma response between knockout and wild-type mice, regardless of strain background. This suggests that at the higher dose of TPA, the effect of reduction in bcl-2 gene product was obscured. These results support the hypothesis that bcl-2 plays a limited role in skin tumorigenesis in the TG.AC mouse. JF - Molecular carcinogenesis AU - Trempus, C S AU - Haseman, J K AU - Tennant, R W AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 68 EP - 77 VL - 20 IS - 1 SN - 0899-1987, 0899-1987 KW - Carcinogens KW - 0 KW - Proto-Oncogene Proteins c-bcl-2 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Proto-Oncogene Proteins c-bcl-2 -- biosynthesis KW - Genotype KW - Animals KW - Gene Transfer Techniques KW - Gene Expression KW - Mice KW - Mice, Transgenic KW - Male KW - Female KW - Skin Neoplasms -- genetics KW - Genes, ras KW - Genes, bcl-2 KW - Cocarcinogenesis KW - Skin Neoplasms -- chemically induced KW - Papilloma -- genetics KW - Papilloma -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79320103?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Decreases+in+phorbol+ester-induced+papilloma+development+in+v-Ha-ras+transgenic+TG.AC+mice+during+reduced+gene+dosage+of+bcl-2.&rft.au=Trempus%2C+C+S%3BHaseman%2C+J+K%3BTennant%2C+R+W&rft.aulast=Trempus&rft.aufirst=C&rft.date=1997-09-01&rft.volume=20&rft.issue=1&rft.spage=68&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 - 1997-10-23 N1 - Date created - 1997-10-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selenocysteine tRNAs as central components of selenoprotein biosynthesis in eukaryotes. AN - 79319691; 9315302 AB - Selenocysteine (Sec) tRNAs serve as carrier molecules for the biosynthesis of Sec from serine and to donate Sec to protein in response to specific UGA codons. In this study, we describe the current status of Sec tRNAs in higher animals and further we examine: (i) the Sec tRNA population in Drosophila; (ii) transcription of the Sec tRNA in vivo (in Xenopus oocytes) and in vitro (in Xenopus oocyte extracts); (iii) the effect of selenium on the Sec tRNA population in various rat tissues following replenishment of extremely selenium deficient rats with this element; and (iv) the biosynthesis of the modified bases on Sec tRNA in Xenopus oocytes. JF - Biomedical and environmental sciences : BES AU - Park, S I AU - Park, J M AU - Chittum, H S AU - Yang, E S AU - Carlson, B A AU - Lee, B J AU - Hatfield, D L AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 116 EP - 124 VL - 10 IS - 2-3 SN - 0895-3988, 0895-3988 KW - Proteins KW - 0 KW - RNA, Transfer, Amino Acid-Specific KW - Selenoproteins KW - tRNA, selenocysteine- KW - Serine-tRNA Ligase KW - EC 6.1.1.11 KW - Index Medicus KW - Animals KW - Serine-tRNA Ligase -- genetics KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Xenopus KW - Mice KW - Drosophila -- genetics KW - Nucleic Acid Conformation KW - Chromosome Mapping KW - RNA, Transfer, Amino Acid-Specific -- chemistry KW - Protein Biosynthesis KW - RNA, Transfer, Amino Acid-Specific -- genetics KW - RNA, Transfer, Amino Acid-Specific -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79319691?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biomedical+and+environmental+sciences+%3A+BES&rft.atitle=Selenocysteine+tRNAs+as+central+components+of+selenoprotein+biosynthesis+in+eukaryotes.&rft.au=Park%2C+S+I%3BPark%2C+J+M%3BChittum%2C+H+S%3BYang%2C+E+S%3BCarlson%2C+B+A%3BLee%2C+B+J%3BHatfield%2C+D+L&rft.aulast=Park&rft.aufirst=S&rft.date=1997-09-01&rft.volume=10&rft.issue=2-3&rft.spage=116&rft.isbn=&rft.btitle=&rft.title=Biomedical+and+environmental+sciences+%3A+BES&rft.issn=08953988&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-05 N1 - Date created - 1997-11-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of differentially expressed genes in chemically induced skin tumors. AN - 79318826; 9328439 AB - Previous studies have demonstrated a role for the fos gene in promoting malignant conversion of mouse skin tumors. In the study reported here, differential display was performed to identify fos- and jun-regulated genes that are differentially expressed during premalignant progression. Total RNA isolated from variants of the papilloma cell line SP-1 transduced with retroviral vectors expressing v-jun and v-fos alone or in tandem was analyzed for the presence of differentially expressed transcripts by using 35 different primer combinations. Differentially expressed clones were rescreened by dot-blot analysis by using cDNA from chemically induced tumors with a high or low risk of malignant conversion. Three differentially displayed fragments were isolated in this analysis. Homology searches indicated that these fragments shared significant homology with the apoptosis inhibitor bcl-2, human alternative splicing factor/splicing factor 2 (ASF/SF2), and a novel gene not present in the GenBank or EMBL databases. In situ hybridization indicated that the expression levels of the bcl-2 homolog increased with malignant potential in chemically derived mouse skin tumors. A similar analysis indicated that expression of the ASF/SF2 homolog was greater in papillomas than in normal skin or in squamous cell carcinomas. Transcripts for this gene were most abundant in the granular layer. The expression pattern of the third differential display fragment was consistent with that of a tumor suppressor gene. This gene was expressed at very high levels in normal skin and benign papillomas but was essentially undetectable in squamous cell carcinomas. Through this approach, we identified known and novel genes that may contribute to malignant progression in epidermal tumors. JF - Molecular carcinogenesis AU - Rutberg, S E AU - Lee, E J AU - Hansen, L H AU - Glick, A B AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 88 EP - 98 VL - 20 IS - 1 SN - 0899-1987, 0899-1987 KW - DNA, Neoplasm KW - 0 KW - DNA, Viral KW - Transcription Factor AP-1 KW - Index Medicus KW - Animals KW - Transcription Factor AP-1 -- metabolism KW - Humans KW - Mice KW - Papilloma -- genetics KW - Risk Factors KW - Keratinocytes -- metabolism KW - Mice, Inbred SENCAR KW - Carcinoma -- metabolism KW - Papilloma -- chemically induced KW - DNA, Neoplasm -- metabolism KW - Papilloma -- metabolism KW - Cell Line KW - Female KW - Carcinoma -- chemically induced KW - Carcinoma -- genetics KW - DNA, Viral -- metabolism KW - Skin Neoplasms -- genetics KW - Gene Expression Regulation, Neoplastic KW - Skin Neoplasms -- chemically induced KW - Genes, fos KW - Skin Neoplasms -- metabolism KW - Genes, jun UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79318826?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Identification+of+differentially+expressed+genes+in+chemically+induced+skin+tumors.&rft.au=Rutberg%2C+S+E%3BLee%2C+E+J%3BHansen%2C+L+H%3BGlick%2C+A+B%3BYuspa%2C+S+H&rft.aulast=Rutberg&rft.aufirst=S&rft.date=1997-09-01&rft.volume=20&rft.issue=1&rft.spage=88&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 - 1997-10-23 N1 - Date created - 1997-10-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A gene for Parkinson disease. AN - 79317711; 9311360 AB - Until recently, the possibility that genetic factors contributed significantly to the pathogenesis of Parkinson disease (PD) was accorded relatively short shift. Few patients with obviously familial PD are seen in common practice, and families with parkinsonism often present with rather atypical features. The discovery that the neurotoxin N-methyltetrahydropyridine (MPTP) rapidly induces an illness similar to sporadic PD added fuel to those arguing that environmental factors must be largely responsible. But more recently, this view has begun to shift because no generally plausible environmental factors emerged and data favoring a genetic component began to mount. Now it is clear that the cause of PD may on occasion be purely genetic and involve autosomal dominant as well as various other inheritance patterns. Moreover, it has become increasingly apparent that even in sporadic cases, the disease most likely reflects some combination of genetic susceptibility and environmental insult. In such instances, the genetic component presumably acts by increasing the vulnerability of dopamine-containing neurons in the nigrostriatal system to injury by 1 or more common, possibly by themselves relatively innocuous, environmental factors. This view has now been substantially reinforced and our ability to understand the pathogenesis of PD dramatically advanced by the recent identification of a gene responsible for PD in 4 unrelated families. JF - Archives of neurology AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological, Disorders and Stroke, National Institues of Health, Bethesda, Md., USA. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 1156 EP - 1157 VL - 54 IS - 9 SN - 0003-9942, 0003-9942 KW - Nerve Tissue Proteins KW - 0 KW - Synucleins KW - Abridged Index Medicus KW - Index Medicus KW - Environment KW - Genes, Dominant KW - Humans KW - Genetic Predisposition to Disease KW - Parkinson Disease -- etiology KW - Nerve Tissue Proteins -- genetics KW - Parkinson Disease -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79317711?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neurology&rft.atitle=A+gene+for+Parkinson+disease.&rft.au=Chase%2C+T+N&rft.aulast=Chase&rft.aufirst=T&rft.date=1997-09-01&rft.volume=54&rft.issue=9&rft.spage=1156&rft.isbn=&rft.btitle=&rft.title=Archives+of+neurology&rft.issn=00039942&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-23 N1 - Date created - 1997-10-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sex-dependent differences in the disposition of 2,4-dichlorophenoxyacetic acid in Sprague-Dawley rats, B6C3F1 mice, and Syrian hamsters. AN - 79314397; 9311622 AB - 2,4-Dichlorophenoxyacetic acid (2,4-D), a widely used broadleaf herbicide, is under investigation in a study of peroxisome proliferators. To supplement that study, male and female rats, mice, and hamsters were dosed with 14C-2,4-D orally at 5 and 200 mg/kg and tissue distributions were determined. Blood, liver, kidney, muscle, skin, fat, brain, testes, and ovaries were examined. At early time points tissues from female rats consistently contained higher amounts of radioactivity than did corresponding tissues from males (up to 9 times). By 72 hr, tissue levels were equivalent and males and females had excreted equal amounts of radioactivity. This sex difference was absent in mice. In hamsters, males had higher tissue levels than females. Taurine, glycine, and glucuronide conjugates of 2,4-D were excreted along with parent. Metabolite profiles differed between species qualitatively and quantitatively; however, differences between sexes were minimal. Plasma elimination curves were generated in male and female rats after iv and oral administration. Kinetic analysis revealed significant differences in elimination and exposure parameters consistent with a greater ability to clear 2,4-D by male rats relative to females. This suggests that at equivalent doses, female rats are exposed to higher concentrations of 2,4-D for a longer time than males and may be more susceptible to 2,4-D-induced toxicity. These sex-dependent variations in the clearance of 2,4-D in rats and hamsters may indicate a need for sex-specific models to accurately assess human health risks. JF - Drug metabolism and disposition: the biological fate of chemicals AU - Griffin, R J AU - Godfrey, V B AU - Kim, Y C AU - Burka, L T AD - National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 1065 EP - 1071 VL - 25 IS - 9 SN - 0090-9556, 0090-9556 KW - Herbicides KW - 0 KW - 2,4-Dichlorophenoxyacetic Acid KW - 2577AQ9262 KW - Index Medicus KW - Animals KW - Sex Factors KW - Area Under Curve KW - Mice KW - Biological Availability KW - Rats KW - Mice, Inbred Strains KW - Rats, Sprague-Dawley KW - Half-Life KW - Mesocricetus KW - Female KW - Male KW - Cricetinae KW - Herbicides -- pharmacokinetics KW - 2,4-Dichlorophenoxyacetic Acid -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79314397?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Sex-dependent+differences+in+the+disposition+of+2%2C4-dichlorophenoxyacetic+acid+in+Sprague-Dawley+rats%2C+B6C3F1+mice%2C+and+Syrian+hamsters.&rft.au=Griffin%2C+R+J%3BGodfrey%2C+V+B%3BKim%2C+Y+C%3BBurka%2C+L+T&rft.aulast=Griffin&rft.aufirst=R&rft.date=1997-09-01&rft.volume=25&rft.issue=9&rft.spage=1065&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 - 1997-11-05 N1 - Date created - 1997-11-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Opposing activities of c-Fos and Fra-2 on AP-1 regulated transcriptional activity in mouse keratinocytes induced to differentiate by calcium and phorbol esters. AN - 79312434; 9315102 AB - The major differentiation products of maturing keratinocytes contain AP-1 regulatory motifs, and AP-1 DNA binding activity increases in cultured keratinocytes induced to differentiate by calcium. Here, we have analysed AP-1 transcriptional activity in mouse keratinocytes treated with calcium and 12-O-tetradecanoyl phorbol-13-acetate (TPA), two agents that induce terminal differentiation of keratinocytes with different phenotypic consequences. Reporter constructs representing multimers of AP-1 sequences found in keratinocyte marker genes demonstrated that the calcium-induced AP-1 DNA binding activity does not correlate with transcriptional activation. Moreover, expression from active subunits of the profilaggrin and spr 1 promoters increased in calcium-treated keratinocytes when the AP-1 sites were disrupted, indicating that AP-1 may negatively regulate certain promoters in these cells. In contrast, AP-1 reporter activity was increased in keratinocytes treated with TPA. This induction was dependent upon the expression of c-Fos since AP-1 transcriptional activity was not increased in TPA-treated keratinocytes derived from c-fos null mice. Analysis of AP-1 protein expression in calcium- and TPA-treated keratinocytes demonstrated that only TPA increased the expression of c-Jun, while Jun B and Jun D were induced by both of these agents. c-Fos was expressed only in TPA treated keratinocytes, Fra-2 was expressed only in calcium-treated cells, and Fra-1 was expressed in both. Exogenous expression of Fra-2 repressed AP-1 transcriptional activity in TPA-treated keratinocytes, while c-Fos expression activated the AP-1 sequence in calcium-treated keratinocytes. These data indicate that Fra-2 and c-Fos play opposing roles in regulating AP-1 activity in keratinocytes and that multiple inducer-dependent regulatory pathways may exist for the expression of keratinocyte differentiation markers. JF - Oncogene AU - Rutberg, S E AU - Saez, E AU - Lo, S AU - Jang, S I AU - Markova, N AU - Spiegelman, B M AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 1337 EP - 1346 VL - 15 IS - 11 SN - 0950-9232, 0950-9232 KW - DNA-Binding Proteins KW - 0 KW - Fos-Related Antigen-2 KW - Fosl2 protein, mouse KW - Intermediate Filament Proteins KW - Protein Precursors KW - Transcription Factor AP-1 KW - Transcription Factors KW - filaggrin KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Protein Precursors -- metabolism KW - Protein Precursors -- genetics KW - Calcium -- pharmacology KW - Mice KW - Intermediate Filament Proteins -- metabolism KW - Transcriptional Activation KW - Binding Sites KW - Intermediate Filament Proteins -- genetics KW - Base Sequence KW - Promoter Regions, Genetic KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Gene Expression Regulation KW - Transcription Factors -- drug effects KW - Transcription Factor AP-1 -- metabolism KW - Keratinocytes -- drug effects KW - DNA-Binding Proteins -- genetics KW - DNA-Binding Proteins -- drug effects KW - Cell Differentiation -- genetics KW - Keratinocytes -- metabolism KW - Genes, fos KW - Cell Differentiation -- drug effects KW - Transcription Factors -- genetics KW - Transcription Factor AP-1 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79312434?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Opposing+activities+of+c-Fos+and+Fra-2+on+AP-1+regulated+transcriptional+activity+in+mouse+keratinocytes+induced+to+differentiate+by+calcium+and+phorbol+esters.&rft.au=Rutberg%2C+S+E%3BSaez%2C+E%3BLo%2C+S%3BJang%2C+S+I%3BMarkova%2C+N%3BSpiegelman%2C+B+M%3BYuspa%2C+S+H&rft.aulast=Rutberg&rft.aufirst=S&rft.date=1997-09-01&rft.volume=15&rft.issue=11&rft.spage=1337&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-30 N1 - Date created - 1997-10-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA damage, DNA repair, and alcohol toxicity--a review. AN - 79305694; 9309320 AB - Alcohol (ethanol) is clearly a toxic substance when consumed in excess. Chronic alcohol abuse results in a variety of pathological effects, including damage to the liver and brain, as well as other organs, and is associated with an increased risk of certain types of cancers. Alcohol consumption by pregnant women can result in fetal alcohol effects and fetal alcohol syndrome. All of these toxic effects are well documented. What is needed at present is a complete understanding of the molecular mechanisms by which alcohol causes these toxic effects. Such an understanding may lead to better treatments of some of these toxic effects. This review, focuses on the possibility that toxic effects of ethanol are mediated, at least in part, by damage to DNA. In particular, I emphasize data on the production of endogenous DNA-damaging molecules as a result of alcohol consumption and metabolism. Specific examples of DNA-damaging molecules to be considered are reactive oxygen species, including oxygen radicals, lipid peroxidation products, and acetaldehyde. The relevant DNA repair pathways that protect cells against DNA damage produced by these molecules will also be reviewed. The goal of this review is to integrate recent results from the fields of mutagenesis and DNA repair with the alcohol toxicity literature, with the aim of stimulating research into the role of DNA damage in different types of alcohol toxicity and the role of DNA repair in protecting cells from alcohol-related damage. JF - Alcoholism, clinical and experimental research AU - Brooks, P J AD - Section on Molecular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland 20852, USA. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 1073 EP - 1082 VL - 21 IS - 6 SN - 0145-6008, 0145-6008 KW - DNA Adducts KW - 0 KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Animals KW - Humans KW - Lipid Peroxidation -- drug effects KW - Infant, Newborn KW - Carcinogenicity Tests KW - DNA Adducts -- drug effects KW - Female KW - Pregnancy KW - Ethanol -- toxicity KW - DNA Repair -- drug effects KW - DNA Damage -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79305694?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Both+thyroid+hormone+and+9-cis+retinoic+acid+receptors+are+required+to+efficiently+mediate+the+effects+of+thyroid+hormone+on+embryonic+development+and+specific+gene+regulation+in+Xenopus+laevis.&rft.au=Puzianowska-Kuznicka%2C+M%3BDamjanovski%2C+S%3BShi%2C+Y+B&rft.aulast=Puzianowska-Kuznicka&rft.aufirst=M&rft.date=1997-08-01&rft.volume=17&rft.issue=8&rft.spage=4738&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-04 N1 - Date created - 1997-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Control of cell-type specific gene expression in Dictyostelium by the general transcription factor GBF. AN - 79305026; 9310334 AB - To understand how positional information within an organism specifies patterning during development, we are analyzing spatially regulated gene expression in Dictyostelium. CAR3 is a member of the cAMP, 7-span receptor family which directs the transition from unicellular to multicellular organism and regulates cellular differentiation and pattern formation. CAR3 mRNA is expressed maximally at 8-10 hours of development, as individual cells aggregate and differentiate, and is accumulated to equivalent levels in all cells. CAR3 is also induced in shaking cultures by response to extracellular cAMP. We now show, by extensive mutagenesis, that the maximum length of contiguous sequences required for accurate spatiotemporal regulation of CAR3 is approx. 350 bp. These sequences include three significant elements located in upstream and transcribed regions. Arrays of G-boxes (GBF regulatory sites) are centered near positions -165 and +50 and, although either is sufficient for induction by cAMP and expression in prespore cells, both are required for expression in prestalk cells. Another GC-rich element near position -80 is required for maximal expression of prespore-specific constructs, although full-length promoters carrying clustered mutations through the -80 region are still expressed in all cells, but with slightly reduced expression. Spatiotemporal expression of CAR3 during development, thus, requires cell-specific combinatorial interactions of multiple but redundant regulatory components. These essential elements are located in upstream and transcribed regions. However, most surprisingly, a primary control for spatial patterning of CAR3 expression appears to be mediated by GBF, a general transcription factor expressed ubiquitously during Dictyostelium development following early aggregation. JF - Development (Cambridge, England) AU - Gollop, R AU - Kimmel, A R AD - Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 3395 EP - 3405 VL - 124 IS - 17 SN - 0950-1991, 0950-1991 KW - CAR3 protein, Dictyostelium discoideum KW - 0 KW - DNA, Fungal KW - DNA, Protozoan KW - DNA-Binding Proteins KW - G-Box Binding Factors KW - RNA, Fungal KW - RNA, Messenger KW - RNA, Protozoan KW - Receptors, Cyclic AMP KW - Transcription Factors KW - Cyclic AMP KW - E0399OZS9N KW - Index Medicus KW - RNA, Fungal -- genetics KW - Animals KW - Genes, Fungal KW - Spores, Fungal -- genetics KW - RNA, Fungal -- metabolism KW - DNA, Protozoan -- genetics KW - Spores, Fungal -- growth & development KW - RNA, Messenger -- genetics KW - Promoter Regions, Genetic KW - Base Sequence KW - RNA, Messenger -- metabolism KW - RNA, Protozoan -- metabolism KW - Cyclic AMP -- metabolism KW - Genes, Protozoan KW - Molecular Sequence Data KW - Spores, Fungal -- metabolism KW - DNA, Fungal -- genetics KW - RNA, Protozoan -- genetics KW - Binding Sites -- genetics KW - Mutation KW - Signal Transduction KW - Gene Expression Regulation, Developmental KW - Dictyostelium -- genetics KW - Receptors, Cyclic AMP -- genetics KW - Transcription Factors -- metabolism KW - Dictyostelium -- metabolism KW - Dictyostelium -- growth & development KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79305026?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Control+of+cell-type+specific+gene+expression+in+Dictyostelium+by+the+general+transcription+factor+GBF.&rft.au=Gollop%2C+R%3BKimmel%2C+A+R&rft.aulast=Gollop&rft.aufirst=R&rft.date=1997-09-01&rft.volume=124&rft.issue=17&rft.spage=3395&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 - 1997-10-28 N1 - Date created - 1997-10-28 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U87514; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Eosinophils inhibit retroviral transduction of human target cells by a ribonuclease-dependent mechanism. AN - 79301684; 9307075 AB - Human eosinophils contain a number of granule proteins for which specific physiological roles remain unclear. The combined ribonucleolytic and membrane disruptive properties of the eosinophil-derived neurotoxin and eosinophil cationic protein, respectively, suggest the possibility that eosinophils might participate in host defense against enveloped single-stranded RNA viruses. To test this hypothesis, stocks of a replication-defective retrovirus encoding the reporter gene beta-galactosidase were pretreated with isolated human eosinophils, then used to transduce human erythroleukemia (K-562) target cells. Histochemical staining for beta-galactosidase activity was used to detect and quantitate the transduced cells. Co-incubation of retrovirus with eosinophils (0.4 x 10[6]/mL) before target cell transduction resulted in a marked decrease in transduction efficiency corresponding to an approximately 20-fold dilution of viral stock (P < 0.01), an effect that was directly proportional to the concentration of eosinophils, and that was reversed in the presence of ribonuclease inhibitor. Reverse transcriptase-polymerase chain reaction analysis demonstrated loss of the retroviral RNA genome as a result of eosinophil pretreatment, indicating that eosinophils are capable of mediating direct ribonucleolytic destruction of the isolated retroviral particles. Our results demonstrate that eosinophils function as effective anti-retroviral agents in vitro via the actions of their secreted ribonucleases, and suggest that eosinophils may represent an unrecognized arm of host defense against enveloped single-stranded RNA viral pathogens. JF - Journal of leukocyte biology AU - Domachowske, J B AU - Rosenberg, H F AD - Laboratory of Host Defenses, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 363 EP - 368 VL - 62 IS - 3 SN - 0741-5400, 0741-5400 KW - Ribonucleases KW - EC 3.1.- KW - Index Medicus KW - Immunity, Cellular KW - Humans KW - Retroviridae Infections -- immunology KW - Eosinophils -- physiology KW - Eosinophils -- enzymology KW - Transduction, Genetic KW - Ribonucleases -- metabolism KW - Retroviridae -- growth & development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79301684?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+leukocyte+biology&rft.atitle=Eosinophils+inhibit+retroviral+transduction+of+human+target+cells+by+a+ribonuclease-dependent+mechanism.&rft.au=Domachowske%2C+J+B%3BRosenberg%2C+H+F&rft.aulast=Domachowske&rft.aufirst=J&rft.date=1997-09-01&rft.volume=62&rft.issue=3&rft.spage=363&rft.isbn=&rft.btitle=&rft.title=Journal+of+leukocyte+biology&rft.issn=07415400&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-10 N1 - Date created - 1997-10-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cisplatin-DNA adduct determination in the hepatic albumin gene as compared to whole genomic DNA. AN - 79301299; 9305578 AB - A quantitative time-resolved fluorometriC PCR-stop assay has been used to determine cisplatin-DNA adducts in a 1.612 kb region and a polymorphic 1.85 kb region of the rat liver albumin gene containing parts of exons B and C and all of the BC intron. The values were compared to adducts in the whole rat liver genome determined by atomic absorbance spectrometry (AAS). Initial validation of the PCR-stop assay involved modification of purified rat liver DNA in vitro to desired levels by incubation with different concentrations of cisplatin. In these DNA samples, cisplatin-DNA adduct levels determined in the 1612 base pair fragment by PCR-stop assay were shown to be similar to those determined in the whole genomic DNA by AAS. In freshly isolated primary rat hepatocytes cultured for 2 h with 50, 75, 100, and 150 microM cisplatin, adduct levels determined by the PCR-stop assay were similar to those measured by AAS. Cultured MH1C1 rat hepatoma cells, which express albumin, had a polymorphism in the rat albumin gene such that the fragment amplified with the same primers was about 1.85 kb (13% larger). When MH1C1 cells were exposed to 5, 15, 25, 50, and 75 microM cisplatin for 24 h, 50% cell kill was at 21.0 +/- 5.5 microM cisplatin. For doses of 15-75 microM cisplatin, the cisplatin-DNA adduct levels in this fragment, measured by PCR-stop assay, were about one-half of those in the whole genomic DNA measured by AAS. In addition, MH1C1 cells exposed to 150 microM cisplatin for 4 h and subsequently incubated with fresh medium for 24 h showed no change in adduct level in whole genomic DNA during this time but showed a 29% adduct removal in the 1.85 kb fragment. The data demonstrate that this 1.85 kb region containing expressed regions of the albumin gene has undergone both less adduction and more rapid adduct removal, as compared to the MH1C1 genome as a whole. JF - Chemical research in toxicology AU - Zhang, Z AU - Poirier, M C AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Zhangz@DC37A.NCI.NIH.GOV Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 971 EP - 977 VL - 10 IS - 9 SN - 0893-228X, 0893-228X KW - Albumins KW - 0 KW - DNA Adducts KW - DNA KW - 9007-49-2 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Rats KW - Polymerase Chain Reaction KW - Animals KW - Rats, Sprague-Dawley KW - Tumor Cells, Cultured KW - Liver Neoplasms, Experimental -- metabolism KW - Genome KW - Female KW - Cell Line KW - DNA Adducts -- analysis KW - Albumins -- genetics KW - DNA -- analysis KW - Cisplatin -- analysis KW - Liver -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79301299?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cisplatin-DNA+adduct+determination+in+the+hepatic+albumin+gene+as+compared+to+whole+genomic+DNA.&rft.au=Zhang%2C+Z%3BPoirier%2C+M+C&rft.aulast=Zhang&rft.aufirst=Z&rft.date=1997-09-01&rft.volume=10&rft.issue=9&rft.spage=971&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 - 1998-01-13 N1 - Date created - 1998-01-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Partial cloning of rat CD34 cDNA and expression during stem cell-dependent liver regeneration in the adult rat. AN - 79295229; 9303503 AB - The sialomucin CD34 is expressed on human and mouse hematopoietic stem cells and is used as an important marker for isolating the hematopoietic stem/progenitor cells. The involvement of hepatic stem cells in liver regeneration under certain conditions in adult rats is now well supported. The objective of the present research was to explore the idea that CD34 might also be expressed on hepatic stem cell progeny. Polymerase chain reaction (PCR)-based cloning of rat CD34 was partially accomplished. During the hepatic stem cell activation (2-acetylaminofluorene/partial hepatectomy [AAF/PH] model), the CD34 transcripts were increased and reached the peak level between 9 and 12 days after partial hepatectomy when the progenitor cells (e.g., oval cells, early hepatocytes in basophilic foci, and intestinal type of cells) are most abundant. Both in situ hybridization and immunohistochemistry, using anti-mouse CD34 antibody, which recognizes the cytoplasmic domain, clearly showed the expression of CD34 on oval cells as well as on endothelial cells of large hepatic vessels. In addition, bile ductular epithelial (BDE) cells both in the AAF/PH model and in normal liver expressed CD34, suggesting a close relationship between BDE cells and the hepatic stem-cell compartment. Taken together, the data indicate that CD34 would, similar to its role in the hematopoietic system, be an important probe for characterizing the cellular biology of the hepatic stem-cell compartment. JF - Hepatology (Baltimore, Md.) AU - Omori, N AU - Omori, M AU - Evarts, R P AU - Teramoto, T AU - Miller, M J AU - Hoang, T N AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, DBS, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 720 EP - 727 VL - 26 IS - 3 SN - 0270-9139, 0270-9139 KW - Antigens, CD34 KW - 0 KW - DNA, Complementary KW - 2-Acetylaminofluorene KW - 9M98QLJ2DL KW - Index Medicus KW - Animals KW - 2-Acetylaminofluorene -- toxicity KW - Sequence Homology, Nucleic Acid KW - Humans KW - Gene Expression KW - Organ Specificity KW - Mice KW - Cloning, Molecular KW - Rats KW - Polymerase Chain Reaction KW - Rats, Inbred F344 KW - Base Sequence KW - In Situ Hybridization KW - Sequence Alignment KW - Alternative Splicing KW - Hepatectomy KW - Molecular Sequence Data KW - Mice, Inbred C57BL KW - Male KW - Liver -- pathology KW - Liver -- immunology KW - Antigens, CD34 -- biosynthesis KW - Hematopoietic Stem Cells -- physiology KW - Liver Regeneration -- physiology KW - Liver -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79295229?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Partial+cloning+of+rat+CD34+cDNA+and+expression+during+stem+cell-dependent+liver+regeneration+in+the+adult+rat.&rft.au=Omori%2C+N%3BOmori%2C+M%3BEvarts%2C+R+P%3BTeramoto%2C+T%3BMiller%2C+M+J%3BHoang%2C+T+N%3BThorgeirsson%2C+S+S&rft.aulast=Omori&rft.aufirst=N&rft.date=1997-09-01&rft.volume=26&rft.issue=3&rft.spage=720&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 - 1997-10-08 N1 - Date created - 1997-10-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Safety, tolerance, and pharmacokinetics of amphotericin B lipid complex in children with hepatosplenic candidiasis. AN - 79290694; 9303390 AB - The safety, tolerance, and pharmacokinetics of amphotericin B lipid complex (ABLC) were studied in a cohort of pediatric cancer patients. Six children with hepatosplenic candidiasis (HSC) received 2.5 mg of ABLC/kg of body weight/day for 6 weeks for a total dosage of 105 mg/kg. Mean serum creatinine (0.85 +/- 0.12 mg/dl at baseline) was stable at the end of therapy at 0.85 +/- 0.18 mg/dl and at 1-month follow-up at 0.72 +/- 0.12 mg/dl. There was no increase in hepatic transaminases. Mean plasma concentrations over the dosing interval (C(ave)) and area under the curve from 0 to 24 h (AUC(0-24h)) increased between the first and seventh doses but were similar between doses 7 and 42, suggesting that steady state was achieved by day 7 of therapy. Following the final (42nd) dose of ABLC, mean AUC(0-24h) was 11.9 +/- 2.6 microg h/ml, C(ave) was 0.50 +/- 0.11 microg/ml, maximum concentration of the drug in whole blood was 1.69 +/- 0.75 microg/ml, and clearance was 3.64 +/- 0.78 ml/min/kg. Response of hepatic and splenic lesions was monitored by serial computerized tomographic and magnetic resonance imaging scans. The five evaluable patients responded to ABLC with complete or partial resolution of physical findings and of lesions of HSC. During the course of ABLC infusions and follow-up, there was no progression of HSC, breakthrough fungemia, or posttherapy recurrence. Hepatic lesions continued to resolve after the completion of administration of ABLC. Thus, ABLC administered in multiple doses to children was safe, was characterized by a steady state attainable within 1 week of therapy, and was effective in treatment of HSC. JF - Antimicrobial agents and chemotherapy AU - Walsh, T J AU - Whitcomb, P AU - Piscitelli, S AU - Figg, W D AU - Hill, S AU - Chanock, S J AU - Jarosinski, P AU - Gupta, R AU - Pizzo, P A AD - Infectious Diseases Section, Pediatric Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 1944 EP - 1948 VL - 41 IS - 9 SN - 0066-4804, 0066-4804 KW - Antifungal Agents KW - 0 KW - Drug Combinations KW - Phosphatidylcholines KW - Phosphatidylglycerols KW - liposomal amphotericin B KW - Amphotericin B KW - 7XU7A7DROE KW - Index Medicus KW - Humans KW - Child KW - Adolescent KW - Male KW - Female KW - Child, Preschool KW - Splenic Diseases -- metabolism KW - Splenic Diseases -- drug therapy KW - Phosphatidylcholines -- pharmacokinetics KW - Antifungal Agents -- adverse effects KW - Antifungal Agents -- pharmacokinetics KW - Candidiasis -- metabolism KW - Amphotericin B -- pharmacokinetics KW - Phosphatidylglycerols -- adverse effects KW - Phosphatidylglycerols -- pharmacokinetics KW - Antifungal Agents -- therapeutic use KW - Liver Diseases -- metabolism KW - Liver Diseases -- microbiology KW - Candidiasis -- drug therapy KW - Phosphatidylcholines -- adverse effects KW - Phosphatidylcholines -- therapeutic use KW - Splenic Diseases -- microbiology KW - Amphotericin B -- adverse effects KW - Phosphatidylglycerols -- therapeutic use KW - Amphotericin B -- therapeutic use KW - Liver Diseases -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79290694?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+agents+and+chemotherapy&rft.atitle=Safety%2C+tolerance%2C+and+pharmacokinetics+of+amphotericin+B+lipid+complex+in+children+with+hepatosplenic+candidiasis.&rft.au=Walsh%2C+T+J%3BWhitcomb%2C+P%3BPiscitelli%2C+S%3BFigg%2C+W+D%3BHill%2C+S%3BChanock%2C+S+J%3BJarosinski%2C+P%3BGupta%2C+R%3BPizzo%2C+P+A&rft.aulast=Walsh&rft.aufirst=T&rft.date=1997-09-01&rft.volume=41&rft.issue=9&rft.spage=1944&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+agents+and+chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-31 N1 - Date created - 1997-10-31 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Med. 1991 Aug;91(2):142-50 [1867240] Am J Med. 1991 Aug;91(2):137-41 [1867239] Biochim Biophys Acta. 1992 Jun 30;1107(2):271-82 [1504072] Leuk Lymphoma. 1993 Jul;10(4-5):369-76 [8220136] Mycoses. 1993 May-Jun;36(5-6):187-92 [8264715] Antimicrob Agents Chemother. 1995 May;39(5):1065-9 [7625790] Cancer. 1995 Dec 1;76(11):2357-62 [8635043] Clin Infect Dis. 1996 May;22 Suppl 2:S133-44 [8722841] Adv Pediatr Infect Dis. 1996;11:187-290 [8718464] Radiology. 1982 Feb;142(2):375-80 [6948317] Rev Infect Dis. 1984 Sep-Oct;6(5):689-703 [6390640] J Clin Oncol. 1987 Feb;5(2):310-7 [3806172] J Infect Dis. 1987 Apr;155(4):766-74 [3819480] Ann Intern Med. 1988 Jan;108(1):88-100 [3276268] J Pediatr. 1988 Sep;113(3):559-63 [3411404] Proc Natl Acad Sci U S A. 1988 Aug;85(16):6122-6 [3413081] Antimicrob Agents Chemother. 1989 Nov;33(11):1989-93 [2610508] J Clin Oncol. 1990 Feb;8(2):280-6 [2299371] Mycoses. 1990 Jun;33(6):283-90 [2259369] Ann Intern Med. 1991 Apr 15;114(8):664-6 [2003714] J Infect Dis. 1991 Aug;164(2):418-21 [1856491] J Infect Dis. 1991 Dec;164(6):1232-5 [1955725] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunoglobulin/Myc recombinations in murine Peyer's patch follicles. AN - 79269359; 9290947 AB - Immunoglobulin heavy chain (Igh)/Myc recombinations are a hallmark of pristane-induced mouse plasmacytomas but are also frequently found in non-tumorous tissues. Here we describe for the first time a PCR-based technique for detecting fusions between Igh mu or Igh alpha and Myc in situ. Igh/Myc recombinations were found in transplanted and primary plasmacytomas. In addition, the gut-associated lymphoid tissues of plasmacytoma-free BALB/c mice were investigated for the presence of Igh/Myc fusions. Igh/Myc rearrangements were detected in Peyer's patch follicles and in the intestinal lamina propria both in normal mice and in mice shortly after pristane treatment. The sequence analysis showed that i) three to five different Igh/Myc hybrid sequences were present in individual follicles, ii) Igh/Myc recombinations can be subjected to additional switch recombinations as shown by related sequences in neighboring cells, and iii) cells harboring these rearrangements migrate into the adjacent lamina propria. The results indicate that Peyer's patches are a hyper-recombinogenic tissue. Myc recombination-positive cells are present in at least 100-fold more frequently than expected if recombinations were random, which suggests that this kind of trans-chromosomal rearrangement may be targeted. JF - Genes, chromosomes & cancer AU - Müller, J R AU - Mushinski, E B AU - Williams, J A AU - Hausner, P F AD - Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 1 EP - 8 VL - 20 IS - 1 SN - 1045-2257, 1045-2257 KW - DNA Primers KW - 0 KW - DNA, Neoplasm KW - Immunoglobulin Heavy Chains KW - Index Medicus KW - Animals KW - Polymerase Chain Reaction -- methods KW - Mice KW - DNA, Neoplasm -- analysis KW - Sequence Analysis, DNA KW - Mice, Inbred BALB C KW - Peyer's Patches -- immunology KW - Plasmacytoma -- genetics KW - Peyer's Patches -- ultrastructure KW - Plasmacytoma -- chemically induced KW - Genes, myc KW - Recombination, Genetic KW - Plasmacytoma -- immunology KW - Intestinal Neoplasms -- chemically induced KW - Intestinal Neoplasms -- immunology KW - Intestinal Neoplasms -- genetics KW - Immunoglobulin Heavy Chains -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79269359?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes%2C+chromosomes+%26+cancer&rft.atitle=Immunoglobulin%2FMyc+recombinations+in+murine+Peyer%27s+patch+follicles.&rft.au=M%C3%BCller%2C+J+R%3BMushinski%2C+E+B%3BWilliams%2C+J+A%3BHausner%2C+P+F&rft.aulast=M%C3%BCller&rft.aufirst=J&rft.date=1997-09-01&rft.volume=20&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Genes%2C+chromosomes+%26+cancer&rft.issn=10452257&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-16 N1 - Date created - 1997-10-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant RFB4 immunotoxins exhibit potent cytotoxic activity for CD22-bearing cells and tumors. AN - 79268610; 9292538 AB - Many B-cell malignancies express the CD22 antigen on their cell surface. To kill cells expressing this antigen, the RFB4 monoclonal antibody (MoAb) has been linked chemically with either deglycosylated ricin A chain or truncated versions of Pseudomonas exotoxin. These immunotoxins exhibited selective cytotoxic activity for CD22+ cells and antitumor activity in nude mouse models bearing human B-cell lymphomas. To construct a recombinant immunotoxin targeted to CD22, we first cloned the variable portions of the heavy and light chains of RFB4. The cloned Fv fragments were joined by a newly created disulfide bond to form a disulfide stabilized (ds) construct. The RFB4 construct was combined by gene fusion with PE38, a truncated version of PE. The recombinant immunotoxin was then expressed in Escherichia coli, purified by column chromatography and tested for cytotoxicity activity. RFB4(dsFv)PE38 retained its binding activity for CD22, was very stable at 37 degrees C and exhibited selective cytotoxic activity for CD22+-cultured cell lines. Because of its favorable binding characteristics and potency for CD22-positive cell lines, RFB4(dsFv)PE38 was tested for antitumor activity in a nude mouse model of human lymphoma. CA46 cells were injected subcutaneously and then treated with the RFB4(dsFv)PE38 immunotoxin. Antitumor activity was dose responsive and was not evident when an irrelevant immunotoxin was administered on the same schedule. JF - Blood AU - Mansfield, E AU - Amlot, P AU - Pastan, I AU - FitzGerald, D J AD - Laboratory of Molecular Biology, DCBDC, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/09/01/ PY - 1997 DA - 1997 Sep 01 SP - 2020 EP - 2026 VL - 90 IS - 5 SN - 0006-4971, 0006-4971 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD KW - Antigens, Differentiation, B-Lymphocyte KW - CD22 protein, human KW - Cd22 protein, mouse KW - Cell Adhesion Molecules KW - Immunotoxins KW - Lectins KW - Recombinant Proteins KW - Sialic Acid Binding Ig-like Lectin 2 KW - Ricin KW - 9009-86-3 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Base Sequence KW - Tumor Cells, Cultured KW - Humans KW - Recombinant Proteins -- immunology KW - Molecular Sequence Data KW - Mice KW - Amino Acid Sequence KW - Recombinant Proteins -- therapeutic use KW - Antibodies, Monoclonal -- therapeutic use KW - Antibodies, Monoclonal -- immunology KW - Neoplasms -- drug therapy KW - Immunotoxins -- immunology KW - Antigens, Differentiation, B-Lymphocyte -- immunology KW - Immunotoxins -- therapeutic use KW - Antigens, CD -- immunology KW - Neoplasms -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79268610?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Recombinant+RFB4+immunotoxins+exhibit+potent+cytotoxic+activity+for+CD22-bearing+cells+and+tumors.&rft.au=Mansfield%2C+E%3BAmlot%2C+P%3BPastan%2C+I%3BFitzGerald%2C+D+J&rft.aulast=Mansfield&rft.aufirst=E&rft.date=1997-09-01&rft.volume=90&rft.issue=5&rft.spage=2020&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-30 N1 - Date created - 1997-09-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Novel signal transduction and peptide specificity of glucagon-like peptide receptor in 3T3-L1 adipocytes. AN - 79259997; 9284947 AB - Glucagon-like peptide-1 (7-36) amide (GLP-1), in addition to its well known effect of enhancing glucose-mediated insulin release, has been shown to have insulinomimetic effects and to enhance insulin-mediated glucose uptake and lipid synthesis in 3T3-L1 adipocytes. To elucidate the mechanisms of GLP-1 action in these cells, we studied the signal transduction and peptide specificity of the GLP-1 response. In 3T3-L1 adipocytes, GLP-1 caused a decrease in intracellular cAMP levels which is the opposite to the response observed in pancreatic beta cells in response to the same peptide. In 3T3-L1 adipocytes, free intracellular calcium was not modified by GLP-1. Peptide specificity was examined to help determine if a different GLP receptor isoform was expressed in 3T3-L1 adipocytes vs. beta cells. Peptides with partial homology to GLP-1 such as GLP-2, GLP-1 (1-36), and glucagon all lowered cAMP levels in 3T3-L1 adipocytes. In addition, an antagonist of pancreatic GLP-1 receptor, exendin-4 (9-39), acted as an agonist to decrease cAMP levels in 3T3-L1 adipocytes as did exendin-4 (1-39), a known agonist for the pancreatic GLP-1 receptor. Binding studies using 125I-GLP-1 also suggest that pancreatic GLP-1 receptor isoform is not responsible for the effect of GLP-1 and related peptides in 3T3-L1 adipocytes. Based on these results, we propose that the major form of the GLP receptor in 3T3-L1 adipocytes is functionally different from the pancreatic GLP-1 receptor. JF - Journal of cellular physiology AU - Montrose-Rafizadeh, C AU - Yang, H AU - Wang, Y AU - Roth, J AU - Montrose, M H AU - Adams, L G AD - Gerontology Research Center, National Institute on Aging, NIH, Baltimore, Maryland 21224-2780, USA. chahrzad@vax.grc.nia.nih.gov Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 275 EP - 283 VL - 172 IS - 3 SN - 0021-9541, 0021-9541 KW - Glp1r protein, mouse KW - 0 KW - Glucagon-Like Peptide-1 Receptor KW - Peptide Fragments KW - Peptides KW - Receptors, Gastrointestinal Hormone KW - Receptors, Glucagon KW - Venoms KW - gastric inhibitory polypeptide receptor KW - glucagon-like peptide 1 (7-36)amide KW - 119637-73-9 KW - Gastric Inhibitory Polypeptide KW - 59392-49-3 KW - Glucagon-Like Peptides KW - 62340-29-8 KW - Glucagon-Like Peptide 1 KW - 89750-14-1 KW - Glucagon KW - 9007-92-5 KW - exenatide KW - 9P1872D4OL KW - Cyclic AMP KW - E0399OZS9N KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Glucagon -- pharmacology KW - Mice KW - Calcium -- metabolism KW - Binding, Competitive KW - Receptors, Gastrointestinal Hormone -- metabolism KW - Cyclic AMP -- metabolism KW - CHO Cells KW - Lipolysis -- drug effects KW - Gastric Inhibitory Polypeptide -- pharmacology KW - Cricetinae KW - Peptides -- metabolism KW - Adipocytes -- metabolism KW - Peptides -- pharmacology KW - Signal Transduction KW - Receptors, Glucagon -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79259997?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Novel+signal+transduction+and+peptide+specificity+of+glucagon-like+peptide+receptor+in+3T3-L1+adipocytes.&rft.au=Montrose-Rafizadeh%2C+C%3BYang%2C+H%3BWang%2C+Y%3BRoth%2C+J%3BMontrose%2C+M+H%3BAdams%2C+L+G&rft.aulast=Montrose-Rafizadeh&rft.aufirst=C&rft.date=1997-09-01&rft.volume=172&rft.issue=3&rft.spage=275&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+physiology&rft.issn=00219541&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-16 N1 - Date created - 1997-09-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A mutational analysis of residues essential for ligand recognition at the human P2Y1 receptor. AN - 79257158; 9281613 AB - We conducted a mutational analysis of residues potentially involved in the adenine nucleotide binding pocket of the human P2Y1 receptor. Mutated receptors were expressed in COS-7 cells with an epitope tag that permitted confirmation of expression in the plasma membrane, and agonist-promoted inositol phosphate accumulation was assessed as a measure of receptor activity. Residues in transmembrane helical domains (TMs) 3, 5, 6, and 7 predicted by molecular modeling to be involved in ligand recognition were replaced with alanine and, in some cases, by other amino acids. The potent P2Y1 receptor agonist 2-methylthio-ATP (2-MeSATP) had no activity in cells expressing the R128A, R310A, and S314A mutant receptors, and a markedly reduced potency of 2-MeSATP was observed with the K280A and Q307A mutants. These results suggest that residues on the exofacial side of TM3 and TM7 are critical determinants of the ATP binding pocket. In contrast, there was no change in the potency or maximal effect of 2-MeSATP with the S317A mutant receptor. Alanine replacement of F131, H132, Y136, F226, or H277 resulted in mutant receptors that exhibited a 7-18-fold reduction in potency compared with that observed with the wild-type receptor. These residues thus seem to subserve a less important modulatory role in ligand binding to the P2Y1 receptor. Because changes in the potency of 2-methylthio-ADP and 2-(hexylthio)-AMP paralleled the changes in potency of 2-MeSATP at these mutant receptors, the beta- and gamma-phosphates of the adenine nucleotides seem to be less important than the alpha-phosphate in ligand/P2Y1 receptor interactions. However, T221A and T222A mutant receptors exhibited much larger reductions in triphosphate (89- and 33-fold versus wild-type receptors, respectively) than in diphosphate or monophosphate potency. This result may be indicative of a greater role of these TM5 residues in gamma-phosphate recognition. Taken together, the results suggest that the adenosine and alpha-phosphate moieties of ATP bind to critical residues in TM3 and TM7 on the exofacial side of the human P2Y1 receptor. JF - Molecular pharmacology AU - Jiang, Q AU - Guo, D AU - Lee, B X AU - Van Rhee, A M AU - Kim, Y C AU - Nicholas, R A AU - Schachter, J B AU - Harden, T K AU - Jacobson, K A AD - Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 499 EP - 507 VL - 52 IS - 3 SN - 0026-895X, 0026-895X KW - Inositol Phosphates KW - 0 KW - Ligands KW - P2RY1 protein, human KW - Receptors, Purinergic P2 KW - Receptors, Purinergic P2Y1 KW - Adenosine Monophosphate KW - 415SHH325A KW - Type C Phospholipases KW - EC 3.1.4.- KW - Index Medicus KW - Animals KW - Inositol Phosphates -- biosynthesis KW - Enzyme Activation KW - DNA Mutational Analysis KW - Humans KW - Amino Acid Sequence KW - Adenosine Monophosphate -- pharmacology KW - Type C Phospholipases -- metabolism KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Adenosine Monophosphate -- analogs & derivatives KW - Adenosine Monophosphate -- metabolism KW - COS Cells -- metabolism KW - Molecular Sequence Data KW - COS Cells -- physiology KW - Enzyme-Linked Immunosorbent Assay KW - Sequence Homology, Amino Acid KW - Protein Conformation KW - Receptors, Purinergic P2 -- genetics KW - Receptors, Purinergic P2 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79257158?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+mutational+analysis+of+residues+essential+for+ligand+recognition+at+the+human+P2Y1+receptor.&rft.au=Jiang%2C+Q%3BGuo%2C+D%3BLee%2C+B+X%3BVan+Rhee%2C+A+M%3BKim%2C+Y+C%3BNicholas%2C+R+A%3BSchachter%2C+J+B%3BHarden%2C+T+K%3BJacobson%2C+K+A&rft.aulast=Jiang&rft.aufirst=Q&rft.date=1997-09-01&rft.volume=52&rft.issue=3&rft.spage=499&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 - 1997-10-02 N1 - Date created - 1997-10-02 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1DDD; PDB N1 - SuppNotes - Cited By: J Biol Chem. 1989 Aug 15;264(23):13572-8 [2547766] Biochem J. 1988 Jun 1;252(2):583-93 [2843174] J Biol Chem. 1992 May 25;267(15):10764-70 [1587851] EMBO J. 1993 Apr;12(4):1693-703 [8385611] Nature. 1993 Apr 22;362(6422):770-2 [8469290] J Med Chem. 1993 Nov 26;36(24):3937-46 [8254622] J Biol Chem. 1994 Jan 28;269(4):2373-6 [8300561] Pharmacol Rev. 1994 Jun;46(2):143-56 [7938164] J Biol Chem. 1994 Nov 11;269(45):27900-6 [7961722] Br J Pharmacol. 1994 Oct;113(2):614-20 [7834215] J Biol Chem. 1995 Mar 3;270(9):4185-8 [7876172] Neuron. 1995 Apr;14(4):825-31 [7718244] Pharmacol Ther. 1994;64(3):445-75 [7724657] J Biol Chem. 1995 Jun 9;270(23):13987-97 [7775460] J Biol Chem. 1995 Sep 1;270(35):20485-90 [7657625] Biochem Pharmacol. 1996 Feb 23;51(4):545-55 [8619901] Br J Pharmacol. 1996 May;118(1):167-73 [8733591] Eur J Pharmacol. 1995 Nov 30;291(3):281-9 [8719412] Mol Pharmacol. 1996 Sep;50(3):512-21 [8794889] Br J Pharmacol. 1996 Aug;118(8):1959-64 [8864529] Drug Des Discov. 1995 Nov;13(2):133-54 [8872457] Br J Pharmacol. 1997 May;121(2):338-44 [9154346] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] Mol Cell Biol. 1983 Feb;3(2):280-9 [6300662] Biochem J. 1983 May 15;212(2):473-82 [6309146] Methods Enzymol. 1987;152:684-704 [3657593] Mol Pharmacol. 1991 Jul;40(1):8-15 [1649965] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Distinct loci mediate the direct and indirect actions of the anesthetic etomidate at GABA(A) receptors. AN - 79247082; 9282957 AB - Most general anesthetics produce two distinct actions at GABA(A) receptors. Thus, these drugs augment GABA-gated chloride currents (referred to as an indirect action) and, at higher concentrations, elicit chloride currents in the absence of GABA (referred to as a direct action). Because a beta subunit appears to be required for the direct action of intravenous anesthetics in recombinant GABA(A) receptors, site-directed mutagenesis of the beta3 subunit was performed to identify amino acid residues that are critical for this action. In HEK293 cells expressing a prototypical GABA(A) receptor composed of alpha1beta3gamma2 subunits, mutation of amino acid 290 from Asn to Ser dramatically reduced both etomidate-induced chloride currents and its ability to stimulate [3H]flunitrazepam binding. By contrast, the ability of etomidate to augment GABA-gated chloride currents and GABA-enhanced [3H]flunitrazepam binding was retained. The demonstration that the direct, but not the indirect, actions of etomidate are dependent on beta3(Asn290) indicates that the dual actions of this intravenous anesthetic at GABA(A) receptors are mediated via distinct loci. JF - Journal of neurochemistry AU - Moody, E J AU - Knauer, C AU - Granja, R AU - Strakhova, M AU - Skolnick, P AD - Laboratory of Neuroscience, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-0008, U.S.A. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 1310 EP - 1313 VL - 69 IS - 3 SN - 0022-3042, 0022-3042 KW - Anesthetics, Intravenous KW - 0 KW - Chloride Channels KW - Macromolecular Substances KW - Receptors, GABA-A KW - Recombinant Proteins KW - Flunitrazepam KW - 620X0222FQ KW - Etomidate KW - Z22628B598 KW - Index Medicus KW - Animals KW - Recombinant Proteins -- drug effects KW - Humans KW - Chloride Channels -- physiology KW - Mutagenesis, Site-Directed KW - Rats KW - Patch-Clamp Techniques KW - Transfection KW - Recombinant Proteins -- metabolism KW - Point Mutation KW - Chloride Channels -- drug effects KW - Flunitrazepam -- metabolism KW - Cell Line KW - Receptors, GABA-A -- physiology KW - Anesthetics, Intravenous -- pharmacology KW - Receptors, GABA-A -- biosynthesis KW - Receptors, GABA-A -- drug effects KW - Etomidate -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79247082?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=Distinct+loci+mediate+the+direct+and+indirect+actions+of+the+anesthetic+etomidate+at+GABA%28A%29+receptors.&rft.au=Moody%2C+E+J%3BKnauer%2C+C%3BGranja%2C+R%3BStrakhova%2C+M%3BSkolnick%2C+P&rft.aulast=Moody&rft.aufirst=E&rft.date=1997-09-01&rft.volume=69&rft.issue=3&rft.spage=1310&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-25 N1 - Date created - 1997-09-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Magnetic field exposure assessment in a case-control study of childhood leukemia. AN - 79239636; 9270962 AB - Epidemiologic evaluation of the relation between magnetic field exposures and cancer depends critically on study design, particularly the methods used for exposure assessment. We incorporated a complex magnetic field exposure assessment protocol into a large incident case-control study of childhood leukemia. We measured residential magnetic fields using a standard protocol in current and former homes of 638 cases and 620 controls and determined wire codes for 414 case-control pairs. We chose a time-weighted average of magnetic field measurements in each eligible home, weighted by the time the subject lived in each home as the main exposure metric for each subject. We found that 24-hour bedroom magnetic field measurements adequately characterize children's residential exposure and that measuring other rooms contributes only slightly to the estimate of average residential exposure to magnetic fields. Front door measured fields provide useful exposure information when interior measurements are missing. If feasible, measuring multiple homes in which the subject has resided is preferable to measuring a single home. A similar distribution of wire codes for controls agreeing or refusing to participate in our study implies that risk estimates derived from wire code data will not be influenced by response bias. JF - Epidemiology (Cambridge, Mass.) AU - Kleinerman, R A AU - Linet, M S AU - Hatch, E E AU - Wacholder, S AU - Tarone, R E AU - Severson, R K AU - Kaune, W T AU - Friedman, D R AU - Haines, C M AU - Muirhead, C R AU - Boice, J D AU - Robison, L L AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20892-7362, USA. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 575 EP - 583 VL - 8 IS - 5 SN - 1044-3983, 1044-3983 KW - Index Medicus KW - Infant KW - Reproducibility of Results KW - Humans KW - Electric Wiring -- standards KW - Surveys and Questionnaires KW - Infant, Newborn KW - Case-Control Studies KW - Child KW - Patient Selection KW - Adolescent KW - United States -- epidemiology KW - Child, Preschool KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- epidemiology KW - Radiation Monitoring -- standards KW - Radiation Monitoring -- methods KW - Housing KW - Electromagnetic Fields -- adverse effects KW - Environmental Exposure -- adverse effects KW - Research Design KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79239636?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epidemiology+%28Cambridge%2C+Mass.%29&rft.atitle=Magnetic+field+exposure+assessment+in+a+case-control+study+of+childhood+leukemia.&rft.au=Kleinerman%2C+R+A%3BLinet%2C+M+S%3BHatch%2C+E+E%3BWacholder%2C+S%3BTarone%2C+R+E%3BSeverson%2C+R+K%3BKaune%2C+W+T%3BFriedman%2C+D+R%3BHaines%2C+C+M%3BMuirhead%2C+C+R%3BBoice%2C+J+D%3BRobison%2C+L+L&rft.aulast=Kleinerman&rft.aufirst=R&rft.date=1997-09-01&rft.volume=8&rft.issue=5&rft.spage=575&rft.isbn=&rft.btitle=&rft.title=Epidemiology+%28Cambridge%2C+Mass.%29&rft.issn=10443983&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-03 N1 - Date created - 1997-10-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevalence and correlates of alcohol use and DSM-IV alcohol dependence in the United States: results of the National Longitudinal Alcohol Epidemiologic Survey. AN - 79236957; 9273910 AB - The purpose of this study was to present updated estimates of the prevalence of, and to examine the correlates of, alcohol use and DSM-IV alcohol dependence in a representative sample of the U.S. population. This study was based on the National Institute on Alcohol Abuse and Alcoholism's National Longitudinal Alcohol Epidemiologic Survey (NLAES), a representative sample (N = 42,862) of the United States population aged 18 years and older. The prevalence of lifetime alcohol use was 66.0%, with 44.4% of the respondents reporting alcohol use during the past 12 months. Lifetime and 12-month prevalences of alcohol dependence were estimated at 13.3% and 4.4%, respectively. Men were significantly more likely than women to use alcohol, and alcohol use and dependence were much more common among cohorts born after Prohibition and after World War II. Members of the youngest cohorts, between the ages of 18 and 24 years at the time of the interview, were more likely to use drugs, to become dependent and to persist in dependence compared to the older cohorts. In addition, the conditional probability of dependence among users was greatest in Cohort 1 (born between 1968 and 1974) after early adolescence compared to Cohort 2 (born between 1958 and 1967), despite the finding that the probability of lifetime use was lower in Cohort 1 compared to Cohort 2. The sociodemographic correlates of first use, onset of dependence and persistence of dependence varied as a function of the stage of progression. Implications of these findings are discussed in terms of changes over time in drinking patterns, dependence liability and vulnerability among recent alcohol users. JF - Journal of studies on alcohol AU - Grant, B F AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892-7003, USA. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 464 EP - 473 VL - 58 IS - 5 SN - 0096-882X, 0096-882X KW - Index Medicus KW - Age Factors KW - Sex Factors KW - Humans KW - Aged KW - Longitudinal Studies KW - Socioeconomic Factors KW - Adult KW - Cohort Studies KW - Middle Aged KW - Adolescent KW - United States -- epidemiology KW - Female KW - Male KW - Prevalence KW - Psychiatric Status Rating Scales KW - Alcoholism -- epidemiology KW - Alcoholism -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79236957?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Prostaglandins%2C+leukotrienes%2C+and+essential+fatty+acids&rft.atitle=Protein+kinase+C+mediates+angiotensin+II-induced+contractions+and+the+release+of+endothelin+and+prostacyclin+in+rat+aortic+rings.&rft.au=Oriji%2C+G+K%3BKeiser%2C+H+R&rft.aulast=Oriji&rft.aufirst=G&rft.date=1997-08-01&rft.volume=57&rft.issue=2&rft.spage=135&rft.isbn=&rft.btitle=&rft.title=Prostaglandins%2C+leukotrienes%2C+and+essential+fatty+acids&rft.issn=09523278&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-24 N1 - Date created - 1997-11-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutational analysis of the adeno-associated virus type 2 Rep68 protein helicase motifs. AN - 79214278; 9261429 AB - The adeno-associated virus type 2 (AAV) Rep78 and Rep68 proteins are required for viral replication. These proteins are encoded by unspliced and spliced transcripts, respectively, from the p5 promoter of AAV and therefore have overlapping amino acid sequences. The Rep78 and Rep68 proteins share a variety of activities including endonuclease, helicase, and ATPase activities and the ability to bind AAV hairpin DNA. The part of the amino acid sequence which is identical in Rep78 and Rep68 contains consensus helicase motifs that are conserved among the parvovirus replication proteins. In the present study, we mutated highly conserved amino acids within these helicase motifs. The mutant proteins were synthesized as maltose binding protein-Rep68 fusions in Escherichia coli cells and affinity purified on amylose resin. The fusion proteins were assayed in vitro, and their activities were directly compared to those of the fusion protein MBP-Rep68 delta, which contains most of the amino acid sequences common to Rep78 and Rep68 and was demonstrated previously to have all of the in vitro activities of wild-type Rep78 and Rep68. Our analysis showed that almost all mutations in the putative helicase motifs severely reduced or abolished helicase activity in vitro. Most mutants also had ATPase activity less than one-eighth of the wild-type levels and lacked endonuclease activity. JF - Journal of virology AU - Walker, S L AU - Wonderling, R S AU - Owens, R A AD - Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA. Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 6996 EP - 7004 VL - 71 IS - 9 SN - 0022-538X, 0022-538X KW - Carrier Proteins KW - 0 KW - DNA, Viral KW - DNA-Binding Proteins KW - Escherichia coli Proteins KW - Maltose-Binding Proteins KW - Monosaccharide Transport Proteins KW - Nucleotides KW - Recombinant Fusion Proteins KW - Viral Proteins KW - maltose transport system, E coli KW - rep proteins, Adeno-associated virus 2 KW - 137750-19-7 KW - Endonucleases KW - EC 3.1.- KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - DNA Helicases KW - EC 3.6.4.- KW - Index Medicus KW - Carrier Proteins -- genetics KW - DNA Mutational Analysis KW - Adenosine Triphosphatases -- metabolism KW - Gene Expression KW - Amino Acid Sequence KW - Recombinant Fusion Proteins -- metabolism KW - Endonucleases -- metabolism KW - Mutagenesis, Site-Directed KW - Molecular Sequence Data KW - Recombinant Fusion Proteins -- genetics KW - Sequence Homology, Amino Acid KW - Nucleotides -- pharmacology KW - DNA, Viral -- metabolism KW - Viral Proteins -- genetics KW - Dependovirus -- metabolism KW - Dependovirus -- enzymology KW - DNA Helicases -- metabolism KW - Dependovirus -- genetics KW - DNA-Binding Proteins -- genetics KW - DNA Helicases -- genetics KW - Viral Proteins -- metabolism KW - ATP-Binding Cassette Transporters KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79214278?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Mutational+analysis+of+the+adeno-associated+virus+type+2+Rep68+protein+helicase+motifs.&rft.au=Walker%2C+S+L%3BWonderling%2C+R+S%3BOwens%2C+R+A&rft.aulast=Walker&rft.aufirst=S&rft.date=1997-09-01&rft.volume=71&rft.issue=9&rft.spage=6996&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-17 N1 - Date created - 1997-09-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7966-72 [8755586] Proc Natl Acad Sci U S A. 1990 Mar;87(6):2211-5 [2156265] J Virol. 1997 Apr;71(4):2722-30 [9060625] J Biol Chem. 1993 Feb 5;268(4):2269-72 [8381400] Proc Natl Acad Sci U S A. 1976 Mar;73(3):742-6 [1062784] Virology. 1977 May 15;78(2):488-99 [867815] J Virol. 1983 Feb;45(2):555-64 [6300419] J Virol. 1984 Aug;51(2):329-39 [6086948] Cell. 1983 May;33(1):135-43 [6088052] J Virol. 1984 Sep;51(3):611-9 [6088786] Nucleic Acids Res. 1993 Jun 11;21(11):2541-7 [8332451] J Virol. 1994 Feb;68(2):797-804 [8289383] J Biol Chem. 1994 Feb 4;269(5):3283-9 [8106366] J Virol. 1994 May;68(5):2947-57 [8151765] Cancer Lett. 1994 Jun 30;81(2):129-36 [8012930] Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):5808-12 [8016070] J Virol. 1994 Aug;68(8):4998-5006 [8035499] Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):10039-43 [7937833] J Virol. 1995 Apr;69(4):2038-46 [7884849] J Virol. 1995 Jun;69(6):3542-8 [7538173] Virology. 1995 Oct 1;212(2):562-73 [7571426] J Virol. 1995 Nov;69(11):6787-96 [7474090] Biochem Biophys Res Commun. 1996 Mar 18;220(2):294-9 [8645299] J Virol. 1996 Jul;70(7):4783-6 [8676507] J Mol Biol. 1984 Oct 15;179(1):1-20 [6094825] J Virol. 1986 Feb;57(2):656-69 [3502703] J Virol. 1986 Jun;58(3):921-36 [3701931] J Virol. 1986 Oct;60(1):251-8 [3018288] J Virol. 1986 Dec;60(3):1085-97 [3783814] J Virol. 1986 Dec;60(3):823-32 [3023672] J Gen Virol. 1987 Mar;68 ( Pt 3):885-93 [3819702] Virology. 1987 Nov;161(1):18-28 [2823460] J Virol. 1988 Aug;62(8):2903-15 [2839709] J Virol. 1989 Feb;63(2):873-82 [2536109] J Virol. 1989 Jul;63(7):3034-9 [2542611] J Virol. 1989 Jul;63(7):3095-104 [2542617] FEBS Lett. 1990 Mar 12;262(1):145-8 [2156730] Cell. 1990 May 4;61(3):447-57 [2159383] J Virol. 1990 Dec;64(12):6204-13 [2173787] Trends Biochem Sci. 1990 Nov;15(11):430-4 [2126155] Nature. 1991 May 2;351(6321):78-80 [1851252] Virology. 1991 Sep;184(1):14-22 [1651588] Genomics. 1991 Jul;10(3):831-4 [1653762] Virology. 1991 Nov;185(1):323-36 [1833875] J Virol. 1992 Feb;66(2):1119-28 [1309894] J Mol Biol. 1992 May 5;225(1):193-216 [1583690] J Virol. 1992 Jul;66(7):4050-7 [1318396] EMBO J. 1992 Dec;11(13):5071-8 [1334463] J Virol. 1993 Feb;67(2):989-96 [8380474] J Virol. 1993 Feb;67(2):997-1005 [8380475] Virology. 1989 Jul;171(1):239-47 [2545030] Gene. 1989 Apr 15;77(1):51-9 [2744487] Virology. 1989 Nov;173(1):120-8 [2554565] Cell. 1990 Jan 12;60(1):105-13 [2153052] J Virol. 1997 Mar;71(3):2528-34 [9032395] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Diversity among the primate eosinophil-derived neurotoxin genes: a specific C-terminal sequence is necessary for enhanced ribonuclease activity. AN - 79205913; 9254715 AB - The human eosinophil-derived neurotoxin (hEDN) is a secretory effector protein from eosinophilic leukocytes that is a member of the ribonuclease A (RNase A) family of ribonucleases. EDN is a rapidly evolving protein, accumulating non-silent mutations at a rate exceeding those of most other functional coding sequences studied in primates. Although all primate EDNs retain the structural and functional residues known to be prerequisites for ribonuclease activity, we have shown previously that recombinant EDN derived from a New World monkey sequence ( Saguinus oedipus ) had significantly less catalytic activity than the human (hEDN) ortholog.In this work, we have prepared recombinant proteins from EDN from sequences derived from orangutan (Pongo pygmaeus, oEDN) and Old World monkey (Macaca fascicularis, mcEDN) genomic DNAs, and from a second New World monkey sequence (Aotus trivirgatus, omEDN) as well. The catalytic efficiencies [ k cat/ K m (M-1s-1)] determined for both oEDN and mcEDN were similar to that determined previously for hEDN, while omEDN displayed approximately 100-fold less catalytic activity. The relative ribonuclease activities of hEDN/omEDN chimeras pointed to a C-terminal segment as crucial to the enhanced catalytic activity hEDN, and substitution of Arg 132-Ile 133 of hEDN with the Thr-Thr pair at the analogous position in omEDN resulted in an approximately 10-fold reduction in hEDN's catalytic efficiency. However, the reverse substitution, Arg-Ile for Thr-Thr in omEDN, did not enhance the catalytic efficiency of this relatively inactive protein. These results indicate that the Arg and/or Ile residues adjacent to the C-terminus are necessary (but not sufficient) for enhanced ribonuclease activity among the primate EDNs, and will permit prediction of the relative ribonuclease activities based on differences in primary structure. JF - Nucleic acids research AU - Rosenberg, H F AU - Dyer, K D AD - Laboratory of Host Defenses, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. hr2k@nih.gov Y1 - 1997/09/01/ PY - 1997 DA - 1997 Sep 01 SP - 3532 EP - 3536 VL - 25 IS - 17 SN - 0305-1048, 0305-1048 KW - Neurotoxins KW - 0 KW - Peptide Fragments KW - Recombinant Fusion Proteins KW - Recombinant Proteins KW - Eosinophil-Derived Neurotoxin KW - EC 3.1.- KW - Ribonucleases KW - Index Medicus KW - Animals KW - Macaca fascicularis KW - Humans KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Mutagenesis KW - Polymerase Chain Reaction KW - Molecular Sequence Data KW - Aotus trivirgatus KW - Pongo pygmaeus KW - Peptide Fragments -- chemistry KW - Neurotoxins -- metabolism KW - Peptide Fragments -- genetics KW - Neurotoxins -- genetics KW - Ribonucleases -- metabolism KW - Neurotoxins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79205913?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Diversity+among+the+primate+eosinophil-derived+neurotoxin+genes%3A+a+specific+C-terminal+sequence+is+necessary+for+enhanced+ribonuclease+activity.&rft.au=Rosenberg%2C+H+F%3BDyer%2C+K+D&rft.aulast=Rosenberg&rft.aufirst=H&rft.date=1997-09-01&rft.volume=25&rft.issue=17&rft.spage=3532&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-02 N1 - Date created - 1997-10-02 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U88827; GENBANK N1 - SuppNotes - Cited By: J Immunol. 1986 Nov 1;137(9):2913-7 [3760576] Biochemistry. 1986 Jun 17;25(12):3527-32 [2424496] Proc Natl Acad Sci U S A. 1987 Dec;84(23):8330-4 [3479795] Proc Natl Acad Sci U S A. 1989 Jun;86(12):4460-4 [2734298] J Immunol. 1989 Aug 1;143(3):952-5 [2745977] FEBS Lett. 1989 Aug 28;254(1-2):1-4 [2673839] Essays Biochem. 1991;26:89-103 [1778187] J Biol Chem. 1992 Jul 25;267(21):14859-65 [1634526] J Neurosci. 1994 Feb;14(2):538-44 [8301353] J Biol Chem. 1995 Apr 7;270(14):7876-81 [7713881] Nat Genet. 1995 Jun;10(2):219-23 [7663519] J Biol Chem. 1995 Sep 15;270(37):21539-44 [7665566] J Mol Biol. 1996 Jul 26;260(4):540-52 [8759319] Nucleic Acids Res. 1996 Sep 15;24(18):3507-13 [8836175] Proc Natl Acad Sci U S A. 1979 Mar;76(3):1443-7 [286329] J Biochem. 1981 Apr;89(4):1005-16 [6788751] Proc Natl Acad Sci U S A. 1981 Aug;78(8):5165-9 [6946462] J Mol Evol. 1984;20(1):2-15 [6429338] Biochem Biophys Res Commun. 1986 Sep 30;139(3):1239-42 [3768000] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer feasibility studies among migrant farmworkers. The Farmworker Epidemiology Research Group. AN - 79128166; 9219661 JF - American journal of industrial medicine AU - Zahm, S H AU - Blair, A AD - Occupational Epidemiology Branch, National Cancer Institute, Rockville, MD 20892-7364, USA. zahms@epndce.nci.nih.gov Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 301 EP - 302 VL - 32 IS - 3 SN - 0271-3586, 0271-3586 KW - Index Medicus KW - Feasibility Studies KW - Humans KW - Adult KW - Program Development KW - United States -- epidemiology KW - Occupational Exposure KW - Agricultural Workers' Diseases -- etiology KW - Agricultural Workers' Diseases -- epidemiology KW - Neoplasms -- epidemiology KW - Transients and Migrants KW - Research Design KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79128166?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=Cancer+feasibility+studies+among+migrant+farmworkers.+The+Farmworker+Epidemiology+Research+Group.&rft.au=Zahm%2C+S+H%3BBlair%2C+A&rft.aulast=Zahm&rft.aufirst=S&rft.date=1997-09-01&rft.volume=32&rft.issue=3&rft.spage=301&rft.isbn=&rft.btitle=&rft.title=American+journal+of+industrial+medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-18 N1 - Date created - 1997-09-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Particle size distribution of PAHs in the ambient air of southern Taiwan AN - 16507325; 4399496 AB - Polycyclic aromatic hydrocarbon (PAH) and their derivatives produced by incomplete combustion of organic material are ubiquitous in the atmospheric environment. Information of the characteristics of PAHs in Taiwan's urban air is especially important because Taiwan is a traffic congestion and densely populated area. The main objective of this study is to characterize the atmospheric particle size distributions of PAHs in the ambient air of a traffic intersection, a petrochemical-industry (PCI) site, and a rural site, respectively. During the sampling periods, atmospheric particle and PAH mass distributions were measured with two MOUDIs (Micro-orifice Uniform Deposit Impactors) and one NRI (Noll Rotary Impactor) from August 1994 to January 1995 in southern Taiwan. The particle-size was divided into 12 stages and the size ranges covered were from 0.056 to 100 mu m. In this study, the particle size distribution of PAHs associated with dC/dlogDp and cumulative percent in the ambient air of traffic intersection, PCI and rural sites were compared and discussed. JF - J. AEROSOL SCI. AU - Chen, Shui-Jen AU - Hwang, Ping-Shium AU - Hsieh, Lien-Te AU - Jian, Wei-Jain AU - Liao, Shi-Hu AU - Chiu, Shui-Chi Y1 - 1997/09// PY - 1997 DA - Sep 1997 SP - S129 EP - S130 VL - 28 IS - suppl. 1 KW - Pollution Abstracts KW - P 0000:AIR POLLUTION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16507325?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Apollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=J.+AEROSOL+SCI.&rft.atitle=Particle+size+distribution+of+PAHs+in+the+ambient+air+of+southern+Taiwan&rft.au=Chen%2C+Shui-Jen%3BHwang%2C+Ping-Shium%3BHsieh%2C+Lien-Te%3BJian%2C+Wei-Jain%3BLiao%2C+Shi-Hu%3BChiu%2C+Shui-Chi&rft.aulast=Chen&rft.aufirst=Shui-Jen&rft.date=1997-09-01&rft.volume=28&rft.issue=suppl.+1&rft.spage=S129&rft.isbn=&rft.btitle=&rft.title=J.+AEROSOL+SCI.&rft.issn=00218502&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - CONF T1 - Emission factors of air pollutants from the stationary sources of petrochemical plant AN - 16505777; 4399505 AB - The environmental regulation becomes stricter than before in recent years because of the environmental awareness in Taiwan. In the petrochemical processes, air pollutants emitted from stacks such as SO sub(2), NOx, CO, particulate matter and plume opacity are regulated by the Environmental Protection Administration (EPA) of Taiwan Government. Stacks reached a certain scale are required to be installed with a continuous emission monitoring system (CEMS). The CEMS is applied extensive to monitor air pollutants emission from the stationary sources such as petrochemical industries, power plants, steel refinery factories, and waste incinerators. The wide usage of CEMS is able to continuous detect the concentrations of air pollutants and to promote the accuracy of conventional method such as visible determination for the opacity of stack plume emitted from the stationary sources. JF - J. AEROSOL SCI. AU - Chen, Shui-Jen AU - Hsu, Ju-Kai AU - Lee, Wen-Jhy AU - Lee, Ja-To AU - Su, Chun-Jen Y1 - 1997/09// PY - 1997 DA - Sep 1997 SP - S261 EP - S262 VL - 28 IS - suppl. 1 KW - Pollution Abstracts KW - P 0000:AIR POLLUTION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16505777?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Apollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=J.+AEROSOL+SCI.&rft.atitle=Emission+factors+of+air+pollutants+from+the+stationary+sources+of+petrochemical+plant&rft.au=Chen%2C+Shui-Jen%3BHsu%2C+Ju-Kai%3BLee%2C+Wen-Jhy%3BLee%2C+Ja-To%3BSu%2C+Chun-Jen&rft.aulast=Chen&rft.aufirst=Shui-Jen&rft.date=1997-09-01&rft.volume=28&rft.issue=suppl.+1&rft.spage=S261&rft.isbn=&rft.btitle=&rft.title=J.+AEROSOL+SCI.&rft.issn=00218502&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Functional and biophysical characterization of recombinant human hepatocyte growth factor isoforms produced in Escherichia coli AN - 16448170; 4343866 AB - Hepatocyte growth factor (HGF) is a pluripotent secreted protein that stimulates a wide array of cellular targets, including hepatocytes and other epithelial cells, melanocytes, endothelial and haematopoietic cells. Multiple mRNA species transcribed from a single HGF gene encode at least three distinct proteins: the full-length HGF protein and two truncated HGF isoforms that encompass the N-terminal (N) domain through kringle 1 (NK1) or through kringle 2 (NK2). We report the high-level expression in Escherichia coli of NK1 and NK2, as well as the individual kringle 1 (K1) and N domains of HGF. All proteins accumulated as insoluble aggregates that were solubilized, folded and purified in high yield using a simple procedure that included two gel-filtration steps. Characterization of the purified proteins indicated chemical and physical homogeneity, and analysis by CD suggested native conformations. Although the K1 and N-terminal domains of HGF have limited biological activity, spectroscopic evidence indicated that the conformation of each matched that observed when the domains were components of biologically active NK1. Both NK1 and NK2 produced in bacteria were functionally equivalent to proteins generated by eukaryotic systems, as indicated by mitogenicity, cell scatter, and receptor binding and activation assays. These data indicate that all four bacterially produced HGF derivatives are well suited for detailed structural analysis. JF - Biochemical Journal AU - Stahl, S J AU - Wingfield, P T AU - Kaufman, J D AU - Pannell, L K AU - Cioce, V AU - Sakata, H AU - Taylor, W G AU - Rubin, J S AU - Bottaro, D P AD - Protein Expression Laboratory, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bldg 6B, Rm. 1B130, 6 Center Dr., MSC 2775, National Institutes of Health, Bethesda, MD 20892-2775, USA Y1 - 1997/09// PY - 1997 DA - Sep 1997 SP - 763 EP - 772 VL - 326 IS - 3 SN - 0264-6021, 0264-6021 KW - Escherichia coli KW - hepatocyte growth factor KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33340:Other proteins, peptides, amino acids KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16448170?accountid=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=The+American+journal+of+clinical+nutrition&rft.atitle=Effects+of+supplemental+beta-carotene%2C+cigarette+smoking%2C+and+alcohol+consumption+on+serum+carotenoids+in+the+Alpha-Tocopherol%2C+Beta-Carotene+Cancer+Prevention+Study.&rft.au=Albanes%2C+D%3BVirtamo%2C+J%3BTaylor%2C+P+R%3BRautalahti%2C+M%3BPietinen%2C+P%3BHeinonen%2C+O+P&rft.aulast=Albanes&rft.aufirst=D&rft.date=1997-08-01&rft.volume=66&rft.issue=2&rft.spage=366&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+clinical+nutrition&rft.issn=00029165&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - The risk of bovine spongiform encephalopathy (`mad cow disease') to human health AN - 16441954; 4338177 AB - Some human cases of the transmissible neurodegenerative disorder Creutzfeldt-Jakob disease recently seen in Great Britain are thought to have resulted from eating beef infected with the agent of bovine spongiform encephalopathy. Reasons for and against this presumption are explained, and the question of a similar situation occurring in countries other than Britain--in particular, the United States--is discussed in terms of the existence of scrapie (in sheep) or unrecognized bovine spongiform encephalopathy (in cattle), the practice of recycling nonedible sheep and cattle tissue for animal nutrition, and precautionary measures already taken or under consideration by government agencies. JF - Journal of the American Medical Association AU - Brown, P AD - Bldg 36, Room 5B21, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 1997/09// PY - 1997 DA - Sep 1997 SP - 1008 EP - 1011 VL - 278 IS - 12 SN - 0098-7484, 0098-7484 KW - Creutzfeldt-Jakob disease KW - animals KW - bovine spongiform encephalopathy KW - cattle KW - central nervous system KW - food chains KW - humans KW - neuropathy KW - CSA Neurosciences Abstracts; Virology & AIDS Abstracts; Risk Abstracts KW - V 22130:Diseases associated with slow viruses KW - R2 23060:Medical and environmental health KW - N3 11115:Neurogenetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16441954?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Medical+Association&rft.atitle=The+risk+of+bovine+spongiform+encephalopathy+%28%60mad+cow+disease%27%29+to+human+health&rft.au=Brown%2C+P&rft.aulast=Brown&rft.aufirst=P&rft.date=1997-09-01&rft.volume=278&rft.issue=12&rft.spage=1008&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Medical+Association&rft.issn=00987484&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 - Potency of wild-type or sabin trivalent inactivated poliovirus vaccine, by enzyme-linked immunosorbent assay using monoclonal antibodies specific for each antigenic site AN - 16279302; 4289817 AB - Potency testing of inactivated poliovirus vaccine (IPV) is hampered by the absence of a standardized in vitro test, as well as the lack of a generally accepted quantitative animal test. In vitro tests must be able to measure selectively the content of the "D" antigen in the vaccine which induces virus neutralizing antibodies. We tested 12 poliovirus type 1, 12 type 2 and six type 3, D antigen-specific monoclonal mouse antibodies (mAb) for use in the enzyme-linked immunosorbent assay (ELISA). We characterized the site-specific reactivities of three mAbs, one for each poliovirus type. The reactivity of the complete mAb panel encompassed the important antigenic sites on the virus surface of each of the poliovirus serotypes. Some of the mAbs were cross-reactive between wild-type and Sabin strain IPV. At least one mAb of each poliovirus type that was D antigen-specific and reacted with both wild-type and Sabin IPV was directed against an antigenic site thought to be immunogenic in humans. These reagents may be useful for improved standardization of the ELISA for IPV. JF - Biologicals AU - Sawyer, LA AU - Wood, D AU - Ferguson, M AU - Crainic, R AU - Beuvery, E C AU - McInnis, J AU - Albrecht, P AD - Virology Branch, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 6003 Executive Boulevard, 3A15, MSC-7630, Bethesda, MD 20892-7630, USA Y1 - 1997/09// PY - 1997 DA - Sep 1997 SP - 299 EP - 306 VL - 25 IS - 3 SN - 1045-1056, 1045-1056 KW - enzyme-linked immunosorbent assay KW - monoclonal antibodies KW - poliovirus KW - vaccines KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - W3 33365:Vaccines (other) KW - V 22097:Immunization: Vaccines & vaccination: Human KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16279302?accountid=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=Biologicals&rft.atitle=Potency+of+wild-type+or+sabin+trivalent+inactivated+poliovirus+vaccine%2C+by+enzyme-linked+immunosorbent+assay+using+monoclonal+antibodies+specific+for+each+antigenic+site&rft.au=Sawyer%2C+LA%3BWood%2C+D%3BFerguson%2C+M%3BCrainic%2C+R%3BBeuvery%2C+E+C%3BMcInnis%2C+J%3BAlbrecht%2C+P&rft.aulast=Sawyer&rft.aufirst=LA&rft.date=1997-09-01&rft.volume=25&rft.issue=3&rft.spage=299&rft.isbn=&rft.btitle=&rft.title=Biologicals&rft.issn=10451056&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Effect of different types and amounts of fat on the development of mammary tumors in rodents: A review AN - 16238441; 4225442 AB - We performed a meta-analysis on data extracted from 97 reports of experiments, involving a total of 12,803 mice or rats, studying the effect on mammary tumor incidence of different types of dietary fatty acids. Fatty acids were categorized into saturated, monounsaturated, n-6 polyunsaturated, and n-3 polyunsaturated. We modeled the relation between tumor incidence and percentage of total calories from these fatty acids using conditional logistic regression and allowing for varying effects between experiments, and for each fatty acid we estimated the effect of substituting the fatty acid calories for nonfat calories. Our results show that n-6 polyunsaturated fatty acids (PUFAs) have a strong tumor-enhancing effect and that saturated fats have a weaker tumor-enhancing effect. The n-3 PUFAs have a small protective effect that is not statistically significant. There is no significant effect of monounsaturated fats. n-6 PUFAs have a stronger tumor-enhancing effect at levels under 4% of total calories, but an effect is still present at intake levels greater than 4% of calories. In addition, when the intake of n-6 PUFAs is at least 4% of calories, the n-6 PUFA effect remains stronger than the saturated fat effect. JF - Cancer Research AU - Fay, M P AU - Freedman, L S AU - Clifford, C K AU - Midthune, D N AD - Biometry Branch, Division of Cancer Prevention and Control, National Cancer Institute, Executive Plaza North, Suite 344, 6130 Executive Blvd. MSC 7354, Bethesda, MD 20892-7354, USA Y1 - 1997/09// PY - 1997 DA - Sep 1997 SP - 3979 EP - 3988 VL - 57 IS - 18 SN - 0008-5472, 0008-5472 KW - Dietary intake KW - Fatty acids KW - Mammary gland KW - Reviews KW - Tumorigenesis KW - rodents KW - Toxicology Abstracts KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16238441?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Research&rft.atitle=Effect+of+different+types+and+amounts+of+fat+on+the+development+of+mammary+tumors+in+rodents%3A+A+review&rft.au=Fay%2C+M+P%3BFreedman%2C+L+S%3BClifford%2C+C+K%3BMidthune%2C+D+N&rft.aulast=Fay&rft.aufirst=M&rft.date=1997-09-01&rft.volume=57&rft.issue=18&rft.spage=3979&rft.isbn=&rft.btitle=&rft.title=Cancer+Research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Early bactericidal activity of isoniazid in pulmonary tuberculosis. Optimization of methodology AN - 16230197; 4226850 AB - Early bactericidal activity (EBA) of antituberculosis drugs is the rate of decrease in the concentration of tubercle bacilli sputum during the initial days of therapy. The study reported here was designed to optimize the methodology for obtaining precise EBA measurements. The study compared the results with two versus five treatment days; overnight sputum collections with early morning collections; and quantitative smears for acid-fast bacilli (AFB) with quantitative cultures. Isoniazid (INH) was used as a model drug. Among 28 smear-positive patients enrolled in the study in five cities in the United States, 16 were evaluable (INH-susceptible tuberculosis [TB] and adequate sputum collections). The mean baseline bacterial load was 6.69 log sub(10) cfu/ml (SE = 0.24). Quantitative culture of 10- or 12-h sputum collections obtained on two baseline days and treatment Day 5 was the optimal method for EBA measurement. The mean 5-d EBA was 0.21 log sub(10) cfu/ml/d (SE = 0.03; p < 0.001), and the EBA appeared to be constant during the first five treatment days. On the basis of these data, multiarm studies of investigational drugs will require 25 evaluable subjects per arm to detect (80% power and two-tailed alpha of 0.05) an EBA at least 50% as large as the EBA of INH. In countries with a low incidence of TB, the usefulness of this methodology for rapidly assessing new antituberculosis agents may be limited by the relatively large number of subjects required to compare EBA values across treatment arms. JF - American Journal of Respiratory and Critical Care Medicine AU - Hafner, R AU - Cohn, JA AU - Wright, D J AU - Dunlap, N E AU - Egorin, MJ AU - Enama, ME AU - Muth, K AU - Peloquin, CA AU - Mor, N AU - Heifets, L B AD - DAIDS, NIAID, NIH, Solar 2C25, 6003 Executive Blvd., Rockville, MD 20852, USA Y1 - 1997/09// PY - 1997 DA - Sep 1997 SP - 918 EP - 923 VL - 156 IS - 3, pt. 1 SN - 1073-449X, 1073-449X KW - bactericidal activity KW - culture KW - isoniazid KW - smears KW - sputum KW - tuberculosis KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts B: Bacteriology KW - A 01116:Bacteria KW - J 02845:Ear, nose and respiratory tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16230197?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Respiratory+and+Critical+Care+Medicine&rft.atitle=Early+bactericidal+activity+of+isoniazid+in+pulmonary+tuberculosis.+Optimization+of+methodology&rft.au=Hafner%2C+R%3BCohn%2C+JA%3BWright%2C+D+J%3BDunlap%2C+N+E%3BEgorin%2C+MJ%3BEnama%2C+ME%3BMuth%2C+K%3BPeloquin%2C+CA%3BMor%2C+N%3BHeifets%2C+L+B&rft.aulast=Hafner&rft.aufirst=R&rft.date=1997-09-01&rft.volume=156&rft.issue=3%2C+pt.+1&rft.spage=918&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Retroviral transfer of acid alpha -glucosidase cDNA to enzyme-deficient myoblasts results in phenotypic spread of the genotypic correction by both secretion and fusion AN - 16096746; 4203054 AB - Myoblasts have properties that make them suitable vehicles for gene replacement therapy, and lysosomal storage diseases are attractive targets for such therapy. Type II Glycogen Storage Disease, a deficiency of acid alpha -glucosidase (GAA), results in the abnormal accumulation of glycogen in skeletal and cardiac muscle lysosomes. The varied manifestations of the enzyme deficiency in affected patients are ultimately lethal. We used a retroviral vector carrying the cDNA encoding for GAA to replace the enzyme in deficient myoblasts and fibroblasts and analyzed the properties of the transduced cells. The transferred gene was efficiently expressed, and the de novo-synthesized enzyme reached lysosomes where it digested glycogen. In enzyme-deficient myoblasts after transduction, enzyme activity rose to more than 30-fold higher than in normal myoblasts and increased about five-fold more when the cells were allowed to differentiate into myotubes. The transduced cells secreted GAA that was endocytosed via the mannose-6-phosphate receptor into lysosomes of deficient cells and digested glycogen. Moreover, the transduced myoblasts were able to fuse with and provide enzyme for GAA-deficient fusion partners. Thus, the gene-corrected cells, which appear otherwise normal, may ultimately provide phenotypic correction to neighboring GAA-deficient cells by fusion and to distant cells by secretion and uptake mechanisms. JF - Human Gene Therapy AU - Zaretsky, J Z AU - Candotti, F AU - Boerkoel, C AU - Adams, E M AU - Yewdell, J W AU - Blaese, R M AU - Plotz, PH AD - Arthritis and Rheumatism Branch, NIAMS, NIH, Bldg. 10/9N228, Bethesda, MD 20892, USA Y1 - 1997/09// PY - 1997 DA - Sep 1997 SP - 1555 EP - 1563 VL - 8 IS - 13 SN - 1043-0342, 1043-0342 KW - acid alpha -glucosidase KW - acid maltase deficiency KW - glycogen KW - man KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - gene transfer KW - retrovirus KW - myoblasts KW - lysosomes 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/16096746?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Retroviral+transfer+of+acid+alpha+-glucosidase+cDNA+to+enzyme-deficient+myoblasts+results+in+phenotypic+spread+of+the+genotypic+correction+by+both+secretion+and+fusion&rft.au=Zaretsky%2C+J+Z%3BCandotti%2C+F%3BBoerkoel%2C+C%3BAdams%2C+E+M%3BYewdell%2C+J+W%3BBlaese%2C+R+M%3BPlotz%2C+PH&rft.aulast=Zaretsky&rft.aufirst=J&rft.date=1997-09-01&rft.volume=8&rft.issue=13&rft.spage=1555&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 - 2011-12-14 N1 - SubjectsTermNotLitGenreText - gene transfer; retrovirus; myoblasts; lysosomes ER - TY - JOUR T1 - Altered ParA partition proteins of plasmid P1 act via the partition site to block plasmid propagation AN - 16078841; 4113857 AB - The partition system of the P1 plasmid, P1par, consists of the ParA and ParB proteins and a cis-acting site, parS. It is responsible for the orderly segregation of plasmid copies to daughter cells. Plasmids with null mutations in parA or parB replicate normally, but missegregate. ParB binds specifically to the parS site, but the role of ParA and its ATPase activity in partition is unclear. We describe a novel class of parA mutants that cannot be established or maintained as plasmids unless complemented by the wild-type gene. One, parAM3141, is conditional: it can be maintained in cells in minimal medium but cannot be established in cells growing in L broth. The lack of plasmid propagation in L broth-grown cells was shown to be caused by a ParB-dependent activity of the mutant ParA protein that blocks plasmid propagation by an interaction at the parS site. Thus, ParA acts to modify the ParB-parS complex, probably by binding to it. Partition is thought to involve selection of pairs of plasmids before segregation, either by physical pairing of copies or by binding of copies to paired host sites. We suggest that ParA is involved in this reaction and that the mutant ParA protein forms paired complexes that cannot unpair. JF - Molecular Microbiology AU - Youngren, B AU - Austin, S AD - ABL-Basic Res. Prog., NCI-Frederick Cancer Res. and Dev. Cent., Frederick, MD 21702-1201, USA Y1 - 1997/09// PY - 1997 DA - Sep 1997 SP - 1023 EP - 1030 VL - 25 IS - 6 SN - 0950-382X, 0950-382X KW - plasmid P1 KW - ParA protein KW - ParB protein KW - parA gene KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - bacteria KW - mutants KW - J 02760:Plasmids KW - G 07203:Plasmids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16078841?accountid=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=Altered+ParA+partition+proteins+of+plasmid+P1+act+via+the+partition+site+to+block+plasmid+propagation&rft.au=Youngren%2C+B%3BAustin%2C+S&rft.aulast=Youngren&rft.aufirst=B&rft.date=1997-09-01&rft.volume=25&rft.issue=6&rft.spage=1023&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 N1 - SubjectsTermNotLitGenreText - mutants; bacteria ER - TY - JOUR T1 - Cloning of adeno-associated virus type 4 (AAV4) and generation of recombinant AAV4 particles AN - 16025556; 4096951 AB - We have cloned and characterized the full-length genome of adeno-associated virus type 4 (AAV4). The genome of AAV4 is 4,767 nucleotides in length and contains an expanded p5 promoter region compared to AAV2 and AAV3. Within the inverted terminal repeat (ITR), several base changes were identified with respect to AAV2. However, these changes did not affect the ability of this region to fold into a hairpin structure. Within the ITR, the terminal resolution site and Rep binding sites were conserved; however, the Rep binding site was expanded from three GAGC repeats to four. The Rep gene product of AAV4 shows greater than 90% homology to the Rep products of serotypes 2 and 3, with none of the changes occurring in regions which had previously been shown to affect the known functions of Rep68 or Rep78. Most of the differences in the capsid proteins lie in regions which are thought to be on the exterior surface of the viral capsid. It is these unique regions which are most likely to be responsible for the lack of cross-reacting antibodies and the altered tissue tropism compared to AAV2. The results of our studies, performed with a recombinant version of AAV4 carrying a lacZ reporter gene, suggest that AAV4 can transduce human, monkey, and rat cells. Furthermore, comparison of transduction efficiencies in a number of cell lines, competition cotransduction experiments, and the effect of trypsin on transduction efficiency all suggest that the cellular receptor for AAV4 is distinct from that of AAV2. JF - Journal of Virology AU - Chiorini, JA AU - Yang, L AU - Liu, Yuejiang AU - Safer, B AU - Kotin, R M AD - NIH/NHLBI/MHB, Bldg. 10/7D18, 10 Center Dr. MSC 1654, Bethesda, MD 20892-1654, USA Y1 - 1997/09// PY - 1997 DA - Sep 1997 SP - 6823 EP - 6833 VL - 71 IS - 9 SN - 0022-538X, 0022-538X KW - Rep protein KW - cloning KW - nucleotide sequence KW - recombinants KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - adeno-associated virus 4 KW - capsids KW - genomes KW - transduction KW - V 22050:Viral genetics including virus reactivation KW - W3 33058:Cloning vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16025556?accountid=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+Virology&rft.atitle=Cloning+of+adeno-associated+virus+type+4+%28AAV4%29+and+generation+of+recombinant+AAV4+particles&rft.au=Chiorini%2C+JA%3BYang%2C+L%3BLiu%2C+Yuejiang%3BSafer%2C+B%3BKotin%2C+R+M&rft.aulast=Chiorini&rft.aufirst=JA&rft.date=1997-09-01&rft.volume=71&rft.issue=9&rft.spage=6823&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - recombinants; capsids; transduction; genomes; adeno-associated virus 4 ER - TY - JOUR T1 - Bubonic plague: a molecular genetic case history of the emergence of an infectious disease AN - 1492620643; 18525952 AB - Yersinia pestis, the bacterial agent of bubonic plague, is transmitted primarily by fleas and has been responsible for devastating epidemics throughout history. Y. pseudotuberculosis is a food- and water-borne pathogen that causes a much more benign enteric disease in humans. Despite these profoundly different pathogenesis strategies, the two bacteria are very closely related phylogenetically. Thus, identifying the specific genetic differences between them should provide an instructive case study in the evolution of microbial pathogenicity. Some key pathogenesis-related genes of Y. pestis and Y. pseudotuberculosis that have been described to date are compared in this review. Factors that potentiate plague transmission as well as disease are discussed, since dependence on the blood-sucking flea for transmission likely fueled the selection of virulent Y. pestis strains able to produce a high-density bacteremia. Retracing the evolutionary steps between these two Yersinia species may ultimately furnish a historical model for the sudden emergence of new human disease agents. JF - Journal of Molecular Medicine (Berlin, Germany) AU - Hinnebusch, BJoseph AD - Laboratory of Microbial Structure and Function, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 S. 4th Street, Hamilton, MT 59840 USA, US Y1 - 1997/09// PY - 1997 DA - September 1997 SP - 645 EP - 652 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 75 IS - 9 SN - 0946-2716, 0946-2716 KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - Phylogeny KW - Epidemics KW - Food KW - Yersinia pestis KW - Bacteremia KW - Pathogens KW - Models KW - Infectious diseases KW - Pathogenicity KW - Plague KW - Pseudotuberculosis KW - Evolution KW - Benign KW - J 02400:Human Diseases KW - G 07770:Bacteria UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1492620643?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Medicine+%28Berlin%2C+Germany%29&rft.atitle=Bubonic+plague%3A+a+molecular+genetic+case+history+of+the+emergence+of+an+infectious+disease&rft.au=Hinnebusch%2C+BJoseph&rft.aulast=Hinnebusch&rft.aufirst=BJoseph&rft.date=1997-09-01&rft.volume=75&rft.issue=9&rft.spage=645&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Medicine+%28Berlin%2C+Germany%29&rft.issn=09462716&rft_id=info:doi/10.1007%2Fs001090050148 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2014-01-01 N1 - Last updated - 2016-04-13 N1 - SubjectsTermNotLitGenreText - Phylogeny; Epidemics; Pathogenicity; Infectious diseases; Food; Bacteremia; Pathogens; Plague; Pseudotuberculosis; Evolution; Benign; Models; Yersinia pestis DO - http://dx.doi.org/10.1007/s001090050148 ER - TY - JOUR T1 - The catalytic domain of protein kinase C chimeras modulates the affinity and targeting of phorbol ester-induced translocation. AN - 79228234; 9268359 AB - Emerging evidence suggests important differences among protein kinase C (PKC) isozymes in terms of their regulation and biological functions. PKC is regulated by multiple interdependent mechanisms, including enzymatic activation, translocation of the enzyme in response to activation, phosphorylation, and proteolysis. As part of our ongoing studies to define the factors contributing to the specificity of PKC isozymes, we prepared chimeras between the catalytic and regulatory domains of PKCalpha, -delta, and -epsilon. These chimeras, which preserve the overall structure of the native PKC enzymes, were stably expressed in NIH 3T3 fibroblasts. Their intracellular distribution was similar to that of the endogenous enzymes, and they responded with translocation upon treatment with phorbol 12-myristate 13-acetate (PMA). We found that the potency of PMA for translocation of the PKCalpha/x chimeras from the soluble fraction was influenced by the catalytic domain. The ED50 for translocation of PKCalpha/alpha was 26 nM, in marked contrast to the ED50 of 0.9 nM in the case of the PKCalpha/epsilon chimera. In addition to this increase in potency, the site of translocation was also changed; the PKCalpha/epsilon chimera translocated mainly into the cytoskeletal fraction. PKCx/epsilon chimeras displayed twin isoforms with different mobilities on Western blots. PMA treatment increased the proportion of the higher mobility isoform. The two PKCx/epsilon isoforms differed in their localization; moreover, their localization pattern depended on the regulatory domain. Our results emphasize the complex contributions of the regulatory and catalytic domains to the overall behavior of PKC. JF - The Journal of biological chemistry AU - Acs, P AU - Bögi, K AU - Lorenzo, P S AU - Marquez, A M AU - Bíró, T AU - Szállási, Z AU - Blumberg, P M AD - Molecular Mechanisms of Tumor Promotion Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/08/29/ PY - 1997 DA - 1997 Aug 29 SP - 22148 EP - 22153 VL - 272 IS - 35 SN - 0021-9258, 0021-9258 KW - Isoenzymes KW - 0 KW - Phorbol Esters KW - Recombinant Fusion Proteins KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Animals KW - 3T3 Cells KW - Phorbol 12,13-Dibutyrate -- metabolism KW - Mice KW - Catalysis KW - Biological Transport -- drug effects KW - Binding Sites KW - Recombinant Fusion Proteins -- metabolism KW - Phorbol Esters -- pharmacology KW - Protein Kinase C -- genetics KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79228234?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=The+catalytic+domain+of+protein+kinase+C+chimeras+modulates+the+affinity+and+targeting+of+phorbol+ester-induced+translocation.&rft.au=Acs%2C+P%3BB%C3%B6gi%2C+K%3BLorenzo%2C+P+S%3BMarquez%2C+A+M%3BB%C3%ADr%C3%B3%2C+T%3BSz%C3%A1ll%C3%A1si%2C+Z%3BBlumberg%2C+P+M&rft.aulast=Acs&rft.aufirst=P&rft.date=1997-08-29&rft.volume=272&rft.issue=35&rft.spage=22148&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-02 N1 - Date created - 1997-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Brain serotonin neurotoxicity and primary pulmonary hypertension from fenfluramine and dexfenfluramine. A systematic review of the evidence. AN - 79244635; 9272900 AB - Obesity is an important clinical problem, and the use of dexfenfluramine hydrochloride for weight reduction has been widely publicized since its approval by the Food and Drug Administration. However, animal and human studies have demonstrated toxic effects of fenfluramines that clinicians should be aware of when considering prescribing the drugs. Our purpose was to systematically review data on brain serotonin neurotoxicity in animals treated with fenfluramines and the evidence linking fenfluramines to primary pulmonary hypertension (PPH). Archival articles and reviews identified through a computerized search of MEDLINE from 1966 to April 1997 using "fenfluramine(s)," "serotonin," "neurotoxicity," "behavior," "anorexigens," "weight loss," and "primary pulmonary hypertension" as index terms. Reports dealing with long-term effects of fenfluramines on brain serotonin neurons, body weight, and pulmonary function in animals and humans. Reports were reviewed by individuals with expertise in serotonin neurobiology, neurotoxicity, neuropsychiatry, and pulmonary medicine and evaluated for appropriateness for inclusion in this review. Fenfluramines cause dose-related, long-lasting reductions in serotonin axonal markers in all the animal species tested and with all the routes of drug administration used. Doses of fenfluramines that produce signs of brain serotonin neurotoxicity in animals are on the same order as those used to treat humans for weight loss when one takes into account known relations between body mass and drug clearance. However, no human studies have been conducted, and the pathological and clinical potential for neurotoxicity in humans is unknown. Appetite suppressants-most commonly fenfluramines-increase the risk of developing PPH (odds ratio, 6.3), particularly when used for more than 3 months (odds ratio, >20). Fenfluramine and dexfenfluramine have been demonstrated to damage brain serotonin neurons in animal studies. It is not known if such damage occurs in humans or if there are clinical consequences. Use of fenfluramines is associated with an increased risk of PPH. Future studies should address the long-term consequences of prolonged use of fenfluramines. JF - JAMA AU - McCann, U D AU - Seiden, L S AU - Rubin, L J AU - Ricaurte, G A AD - Unit on Anxiety Disorders, Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, Md 20892-1272, USA. umccann@helix.nih.gov Y1 - 1997/08/27/ PY - 1997 DA - 1997 Aug 27 SP - 666 EP - 672 VL - 278 IS - 8 SN - 0098-7484, 0098-7484 KW - Appetite Depressants KW - 0 KW - Serotonin Uptake Inhibitors KW - Fenfluramine KW - 2DS058H2CF KW - Serotonin KW - 333DO1RDJY KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Axons -- drug effects KW - Humans KW - Body Weight -- drug effects KW - Fenfluramine -- adverse effects KW - Hypertension, Pulmonary -- chemically induced KW - Appetite Depressants -- adverse effects KW - Brain Chemistry -- drug effects KW - Brain -- drug effects KW - Serotonin -- metabolism KW - Serotonin Uptake Inhibitors -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79244635?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Brain+serotonin+neurotoxicity+and+primary+pulmonary+hypertension+from+fenfluramine+and+dexfenfluramine.+A+systematic+review+of+the+evidence.&rft.au=McCann%2C+U+D%3BSeiden%2C+L+S%3BRubin%2C+L+J%3BRicaurte%2C+G+A&rft.aulast=McCann&rft.aufirst=U&rft.date=1997-08-27&rft.volume=278&rft.issue=8&rft.spage=666&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-10 N1 - Date created - 1997-09-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: JAMA. 1997 Dec 24-31;278(24):2142 [9417003] JAMA. 1997 Dec 24-31;278(24):2141-2; author reply 2142 [9417002] JAMA. 1997 Dec 24-31;278(24):2141; author reply 2142 [9417001] JAMA. 1997 Dec 24-31;278(24):2141; author reply 2142 [9417000] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genomic instability and telomerase activity in human bronchial epithelial cells during immortalization by human papillomavirus-16 E6 and E7 genes. AN - 79257076; 9281374 AB - Human papilloma virus types 16 and 18 contribute to the development of cervical carcinomas in which the E6 and E7 genes are frequently retained and expressed in the tumors. Our study explored the ability of the E6 and/or E7 genes to immortalize normal human bronchial epithelial (NHBE) cells and to reactivate telomerase expression in these cells. We have introduced the human papillomavirus type 16 E6 or E7 genes alone or in combination (E6/E7) into NHBE cells using the retroviral construct pLXSN. Cells expressing either the E6 or the E7 oncoproteins alone displayed an increased colony-forming efficiency and a slightly extended in vitro life span before entering a crisis, from which immortalized cell lines were not obtained. Telomerase activity was not detected in cells expressing either E6 or E7 individually. Cells expressing the E6/E7 oncoproteins in combination had a substantially increased life span before entering crisis. A subpopulation of these cells escaped from crisis and achieved 130 population doublings, suggesting immortalization. Telomerase activity was detected in these postcrisis cells, but was not detected prior to crisis. In addition, karyotypic analysis showed evidence of genomic instability in mass cultures as well as clones expressing E6, E7, or E6/E7. Abnormalities included numerous monosomies and trisomies, chromatid gaps and breaks, double minutes, and aberrant chromosomes. These results demonstrate that expression of E6 and/or E7 is sufficient to induce genomic instability and an extended life span to NHBE cells, but the presence of both E6 and E7, along with at least one additional genetic or epigenetic event achieved during crisis, was required for reactivation of telomerase and the immortalization in this human cell type. JF - Experimental cell research AU - Coursen, J D AU - Bennett, W P AU - Gollahon, L AU - Shay, J W AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1997/08/25/ PY - 1997 DA - 1997 Aug 25 SP - 245 EP - 253 VL - 235 IS - 1 SN - 0014-4827, 0014-4827 KW - E6 protein, Human papillomavirus type 16 KW - 0 KW - Oncogene Proteins, Viral KW - Papillomavirus E7 Proteins KW - Recombinant Proteins KW - Repressor Proteins KW - oncogene protein E7, Human papillomavirus type 16 KW - Telomerase KW - EC 2.7.7.49 KW - Index Medicus KW - Recombinant Proteins -- biosynthesis KW - Humans KW - Chromosome Mapping KW - Cell Survival KW - Polymerase Chain Reaction KW - Bronchi KW - Transfection KW - Cell Aging KW - Cells, Cultured KW - Kinetics KW - Epithelium KW - Genes, Viral KW - Colony-Forming Units Assay KW - Cell Division KW - Chromosome Aberrations KW - Oncogene Proteins, Viral -- genetics KW - Transcription, Genetic KW - Papillomaviridae -- genetics KW - Oncogene Proteins, Viral -- biosynthesis KW - Telomerase -- metabolism KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79257076?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+cell+research&rft.atitle=Genomic+instability+and+telomerase+activity+in+human+bronchial+epithelial+cells+during+immortalization+by+human+papillomavirus-16+E6+and+E7+genes.&rft.au=Coursen%2C+J+D%3BBennett%2C+W+P%3BGollahon%2C+L%3BShay%2C+J+W%3BHarris%2C+C+C&rft.aulast=Coursen&rft.aufirst=J&rft.date=1997-08-25&rft.volume=235&rft.issue=1&rft.spage=245&rft.isbn=&rft.btitle=&rft.title=Experimental+cell+research&rft.issn=00144827&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-30 N1 - Date created - 1997-09-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High potency antagonists of the pancreatic glucagon-like peptide-1 receptor. AN - 79216050; 9261127 AB - GLP-1-(7-36)-amide and exendin-4-(1-39) are glucagon-like peptide-1 (GLP-1) receptor agonists, whereas exendin-(9-39) is the only known antagonist. To analyze the transition from agonist to antagonist and to identify the amino acid residues involved in ligand activation of the GLP-1 receptor, we used exendin analogs with successive N-terminal truncations. Chinese hamster ovary cells stably transfected with the rat GLP-1 receptor were assayed for changes in intracellular cAMP caused by the test peptides in the absence or presence of half-maximal stimulatory doses of GLP-1. N-terminal truncation of a single amino acid reduced the agonist activity of the exendin peptide, whereas N-terminal truncation of 3-7 amino acids produced antagonists that were 4-10-fold more potent than exendin-(9-39). N-terminal truncation of GLP-1 by 2 amino acids resulted in weak agonist activity, but an 8-amino acid N-terminal truncation inactivated the peptide. Binding studies performed using 125I-labeled GLP-1 confirmed that all bioactive peptides specifically displaced tracer with high potency. In a set of exendin/GLP-1 chimeric peptides, substitution of GLP-1 sequences into exendin-(3-39) produced loss of antagonist activity with conversion to a weak agonist. The results show that receptor binding and activation occur in separate domains of exendin, but they are more closely coupled in GLP-1. JF - The Journal of biological chemistry AU - Montrose-Rafizadeh, C AU - Yang, H AU - Rodgers, B D AU - Beday, A AU - Pritchette, L A AU - Eng, J AD - Laboratory of Clinical Physiology, NIA, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1997/08/22/ PY - 1997 DA - 1997 Aug 22 SP - 21201 EP - 21206 VL - 272 IS - 34 SN - 0021-9258, 0021-9258 KW - Gastrointestinal Hormones KW - 0 KW - Glp1r protein, rat KW - Glucagon-Like Peptide-1 Receptor KW - Peptide Fragments KW - Peptides KW - Receptors, Glucagon KW - Recombinant Fusion Proteins KW - Venoms KW - glucagon-like peptide 1 (7-36)amide KW - 119637-73-9 KW - exendin (9-39) KW - 5313W10MYT KW - Glucagon-Like Peptides KW - 62340-29-8 KW - Glucagon-Like Peptide 1 KW - 89750-14-1 KW - Glucagon KW - 9007-92-5 KW - exenatide KW - 9P1872D4OL KW - Cyclic AMP KW - E0399OZS9N KW - Index Medicus KW - Animals KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Recombinant Fusion Proteins -- chemistry KW - Rats KW - Transfection KW - Binding, Competitive KW - Cyclic AMP -- metabolism KW - Molecular Sequence Data KW - CHO Cells KW - Sequence Deletion KW - Cricetinae KW - Gastrointestinal Hormones -- chemistry KW - Receptors, Glucagon -- agonists KW - Peptide Fragments -- chemistry KW - Receptors, Glucagon -- antagonists & inhibitors KW - Peptides -- chemistry KW - Venoms -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79216050?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=High+potency+antagonists+of+the+pancreatic+glucagon-like+peptide-1+receptor.&rft.au=Montrose-Rafizadeh%2C+C%3BYang%2C+H%3BRodgers%2C+B+D%3BBeday%2C+A%3BPritchette%2C+L+A%3BEng%2C+J&rft.aulast=Montrose-Rafizadeh&rft.aufirst=C&rft.date=1997-08-22&rft.volume=272&rft.issue=34&rft.spage=21201&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-15 N1 - Date created - 1997-09-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - CYP2E1 genetic polymorphisms and risk of nasopharyngeal carcinoma in Taiwan. AN - 79234328; 9274915 AB - Nasopharyngeal carcinoma occurs disproportionately among individuals of Chinese descent. The cytochrome P450 2E1 enzyme (CYP2E1) is known to activate nitrosamines and other carcinogens that are possibly involved in the development of this disease. Certain alleles of the CYP2E1 gene are thought to be more highly expressed than others, and their distribution varies between Asian and Caucasian populations. We conducted a case-control study to investigate whether such variations affect the risk of developing nasopharyngeal cancer. Three hundred sixty-four patients with nasopharyngeal carcinoma (96% of 378 eligible patients) and 320 control subjects (86% of 374 eligible subjects) were studied. A risk factor questionnaire was administered to participants to assess factors postulated to be linked to nasopharyngeal carcinoma. Peripheral blood was obtained from all subjects and DNA was purified from nucleated cells. A polymerase chain reaction-based restriction fragment length polymorphism assay that used the restriction enzymes Rsa I and Dra I was used to detect wild-type and variant forms of the CYP2E1 gene. Individuals homozygous for an allele of the CYP2E1 gene that is detected by Rsa I digestion (c2 allele) were found to have an increased risk of nasopharyngeal carcinoma (relative risk [RR] = 2.6; 95% confidence interval [CI] = 1.2-5.7); this effect was limited to nonsmokers (RR = 9.3; 95% CI = 2.7-32) and was not affected by alcohol consumption. Our findings suggest that the CYP2E1 genotype is a determinant of nasopharyngeal carcinoma risk. JF - Journal of the National Cancer Institute AU - Hildesheim, A AU - Anderson, L M AU - Chen, C J AU - Cheng, Y J AU - Brinton, L A AU - Daly, A K AU - Reed, C D AU - Chen, I H AU - Caporaso, N E AU - Hsu, M M AU - Chen, J Y AU - Idle, J R AU - Hoover, R N AU - Yang, C S AU - Chhabra, S K AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. Hildesha@epndce.nci.nih.gov Y1 - 1997/08/20/ PY - 1997 DA - 1997 Aug 20 SP - 1207 EP - 1212 VL - 89 IS - 16 SN - 0027-8874, 0027-8874 KW - Carcinogens KW - 0 KW - Nitrosamines KW - Ethanol KW - 3K9958V90M KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Index Medicus KW - Taiwan KW - Humans KW - Nitrosamines -- adverse effects KW - Aged KW - Ethanol -- adverse effects KW - Risk KW - Alleles KW - Risk Factors KW - Adult KW - Surveys and Questionnaires KW - Case-Control Studies KW - Middle Aged KW - Female KW - Male KW - Carcinogens -- adverse effects KW - Polymorphism, Genetic KW - Nasopharyngeal Neoplasms -- genetics KW - Cytochrome P-450 CYP2E1 -- genetics KW - Asian Continental Ancestry Group -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79234328?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=CYP2E1+genetic+polymorphisms+and+risk+of+nasopharyngeal+carcinoma+in+Taiwan.&rft.au=Hildesheim%2C+A%3BAnderson%2C+L+M%3BChen%2C+C+J%3BCheng%2C+Y+J%3BBrinton%2C+L+A%3BDaly%2C+A+K%3BReed%2C+C+D%3BChen%2C+I+H%3BCaporaso%2C+N+E%3BHsu%2C+M+M%3BChen%2C+J+Y%3BIdle%2C+J+R%3BHoover%2C+R+N%3BYang%2C+C+S%3BChhabra%2C+S+K&rft.aulast=Hildesheim&rft.aufirst=A&rft.date=1997-08-20&rft.volume=89&rft.issue=16&rft.spage=1207&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-08 N1 - Date created - 1997-09-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Design of sensitive fluorogenic substrates for human cathepsin D. AN - 79252572; 9280316 AB - Cathepsin D is a lysosomal aspartic proteinase that has been implicated in several pathological processes such as breast cancer and Alzheimer's disease. We designed and synthesized a number of quenched fluorogenic substrates with P2 variations in the series AcEE(EDANS)KPIXFFRLGK(DABCYL)E-NH2, where X=cysteine, methylcysteine, ethylcysteine, tert-butylcysteine, carboxymethylcysteine, methionine, valine or isoleucine. Most of the fluorogenic substrates exhibited greater k(cat)/Km ratios than the best cathepsin D substrates described so far. Differences in kinetic constants, which were rationalized using structure-based modeling, might make certain substrates useful for particular applications, such as active site titrations or initial velocity determination using a fluorescent plate reader. JF - FEBS letters AU - Gulnik, S V AU - Suvorov, L I AU - Majer, P AU - Collins, J AU - Kane, B P AU - Johnson, D G AU - Erickson, J W AD - Structural Biochemistry Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201, USA. gulnik@ncifcrf.gov Y1 - 1997/08/18/ PY - 1997 DA - 1997 Aug 18 SP - 379 EP - 384 VL - 413 IS - 2 SN - 0014-5793, 0014-5793 KW - Fluorescent Dyes KW - 0 KW - Naphthalenesulfonates KW - Oligopeptides KW - 5-((2-aminoethyl)amino)naphthalene-1-sulfonic acid KW - 50402-56-7 KW - 4-(4-dimethylaminophenylazo)benzoic acid KW - 6268-49-1 KW - p-Dimethylaminoazobenzene KW - A49L8E13FD KW - Cathepsin D KW - EC 3.4.23.5 KW - Index Medicus KW - Liver -- enzymology KW - p-Dimethylaminoazobenzene -- analogs & derivatives KW - Spectrometry, Fluorescence -- methods KW - Models, Molecular KW - Humans KW - Substrate Specificity KW - Hydrogen Bonding KW - Protein Conformation KW - Cathepsin D -- metabolism KW - Fluorescent Dyes -- metabolism KW - Oligopeptides -- metabolism KW - Fluorescent Dyes -- chemical synthesis KW - Cathepsin D -- chemistry KW - Oligopeptides -- chemical synthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79252572?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEBS+letters&rft.atitle=Design+of+sensitive+fluorogenic+substrates+for+human+cathepsin+D.&rft.au=Gulnik%2C+S+V%3BSuvorov%2C+L+I%3BMajer%2C+P%3BCollins%2C+J%3BKane%2C+B+P%3BJohnson%2C+D+G%3BErickson%2C+J+W&rft.aulast=Gulnik&rft.aufirst=S&rft.date=1997-08-18&rft.volume=413&rft.issue=2&rft.spage=379&rft.isbn=&rft.btitle=&rft.title=FEBS+letters&rft.issn=00145793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-23 N1 - Date created - 1997-09-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Semiautomated resolution of overlapping stutter patterns in genomic microsatellite analysis. AN - 79292379; 9300082 AB - Microsatellites are polymorphic, short nucleotide repeating units scattered more or less randomly throughout the genome. They are readily detectable by polymerase chain reaction (PCR) and often used as genomic markers. One problem in the analysis of microsatellite data is the appearance of secondary bands during PCR that result in extended banding patterns. These "stutter" patterns may overlap in heterozygous alleles and obscure the overall pattern, severely interfering with analysis. This paper develops a model that successfully predicts the general shape of stutter patterns. It then presents techniques for measuring the intensity of the individual contributing alleles. The model is based on the assumption that there is a certain probability of losing or gaining a microsatellite repeat unit during each PCR cycle. The effect is cumulative, with the chance of losing a repeat unit being much greater than that of gaining one, which leads to a gradual reduction in the mean length of the pattern with increased PCR cycles. This can be modeled quantitatively to predict the shape of the stutter pattern, a prediction borne out by experiment. Next, a least-squares technique is presented that is used to analyze the overlapping stutter patterns and determine the relative concentration of each microsatellite in heterozygous alleles. The technique is based on the observation that, at least for microsatellites of approximately the same length, the relative intensity of each band in the stutter pattern is approximately the same for each allele. The stutter shape is most easily determined from homozygous alleles. It can also be approximated from heterozygous samples if the difference between the lengths of the primary microsatellite bands can be determined. JF - Analytical biochemistry AU - Miller, M J AU - Yuan, B Z AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. mark@helix.nih.gov Y1 - 1997/08/15/ PY - 1997 DA - 1997 Aug 15 SP - 50 EP - 56 VL - 251 IS - 1 SN - 0003-2697, 0003-2697 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Alleles KW - Loss of Heterozygosity KW - Humans KW - Algorithms KW - Cell Line KW - Models, Theoretical KW - Microsatellite Repeats KW - DNA -- isolation & purification KW - Polymerase Chain Reaction -- methods KW - DNA -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79292379?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Analytical+biochemistry&rft.atitle=Semiautomated+resolution+of+overlapping+stutter+patterns+in+genomic+microsatellite+analysis.&rft.au=Miller%2C+M+J%3BYuan%2C+B+Z&rft.aulast=Miller&rft.aufirst=M&rft.date=1997-08-15&rft.volume=251&rft.issue=1&rft.spage=50&rft.isbn=&rft.btitle=&rft.title=Analytical+biochemistry&rft.issn=00032697&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-24 N1 - Date created - 1997-11-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Designing and analysing case-control studies to exploit independence of genotype and exposure. AN - 79234666; 9265696 AB - Genetic susceptibility and environmental exposures play a synergistic role in the aetiology of many diseases. We consider a case-control study of a rare disease in relation to a categorical exposure and a genetic factor under the assumption that the genotype and the exposure occur independently in the population under study. Using a logistic model for risk, we describe maximum likelihood methods based on log-linear models that explicitly impose the independence assumption, something the usual logistic regression analyses cannot do. The estimator of the genotype-exposure interaction effect depends only on data from cases. Estimators for genotype and for exposure effects depend also no data from controls, but only through their respective marginal totals. All three estimators have smaller variance than they would were independence not enforced. These results have important implications for design: (i) Case-only studies can efficiently estimate gene-by-environment interactions. (ii) Studies where controls are genotyped anonymously can estimate genotype, exposure, and interaction effects as efficiently as designs where genotype and exposure data are linked. This feature addresses a growing concern of human subjects review boards. (iii) Exposure and interaction effects, but not genotype effects, can be estimated from studies where genetic information is only collected from cases (although one can recover the genotype effect if external gene prevalence data exist). Such designs have the compensatory benefit that the response rate (hence, validity) is higher when controls are not subjected to intrusive tissue sampling. However, the independence assumption can be checked only with linked genotype and exposure data for some controls. We illustrate the methods by applying them to recent study of cleft palate in relation to maternal cigarette smoking and to a variant of the transforming growth factor alpha gene in the child. JF - Statistics in medicine AU - Umbach, D M AU - Weinberg, C R AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1997/08/15/ PY - 1997 DA - 1997 Aug 15 SP - 1731 EP - 1743 VL - 16 IS - 15 SN - 0277-6715, 0277-6715 KW - Index Medicus KW - Cleft Palate -- etiology KW - Pregnancy Complications KW - Cleft Palate -- epidemiology KW - Epidemiologic Methods KW - Humans KW - Linear Models KW - Smoking -- adverse effects KW - Likelihood Functions KW - Research Design KW - Pregnancy KW - Cleft Palate -- genetics KW - Risk Factors KW - Mathematical Computing KW - Female KW - Genotype KW - Risk KW - Logistic Models KW - Case-Control Studies KW - Environmental Exposure -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79234666?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Statistics+in+medicine&rft.atitle=Designing+and+analysing+case-control+studies+to+exploit+independence+of+genotype+and+exposure.&rft.au=Umbach%2C+D+M%3BWeinberg%2C+C+R&rft.aulast=Umbach&rft.aufirst=D&rft.date=1997-08-15&rft.volume=16&rft.issue=15&rft.spage=1731&rft.isbn=&rft.btitle=&rft.title=Statistics+in+medicine&rft.issn=02776715&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-25 N1 - Date created - 1997-09-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synergy between transforming growth factor alpha and hepatitis B virus surface antigen in hepatocellular proliferation and carcinogenesis. AN - 79233130; 9270035 AB - Chronic infection with hepatitis B virus (HBV) can cause liver cancer in humans. Transgenic mice expressing the major envelope protein of HBV, HBV surface antigen (HBsAg), represent an experimental model for some of the histopathological effects of infection in humans, including prolonged hepatocellular injury, necrosis, hyperplasia, and an elevated incidence of liver tumors. The regenerative hyperplastic response to the chronic liver damage is thought to be a critical factor in the increased risk of cancer. However, little is known about the cellular factors that mediate regenerative proliferation. One candidate is the hepatocyte mitogen transforming growth factor alpha (TGF-alpha); in HBV-infected patients with liver cancer, TGF-alpha and HBsAg accumulate in the same hepatocytes. Transgenic mice overexpressing TGF-alpha demonstrate enhanced hepatocyte proliferation rates and develop hepatocellular carcinomas. In this study, we have analyzed the effect of TGF-alpha and HBsAg coexpression in the liver using a bitransgenic mouse model. We show that hepatocytes harboring both the TGF-alpha and HBsAg transgenes exhibited an increase in growth relative to hepatocytes with either transgene alone. Furthermore, bitransgenic males but not females had a dramatically accelerated appearance of hepatocellular carcinomas, compared to single transgenic TGF-alpha or HBsAg littermates. These results demonstrate synergistic activity between HBsAg and TGF-alpha in the liver, probably by first stimulating quiescent hepatocytes to enter G1 and by subsequently promoting their transit through the cell cycle, respectively. Moreover, our data support the contention that TGF-alpha participates in HBV-induced hepatocarcinogenesis in infected patients. JF - Cancer research AU - Jakubczak, J L AU - Chisari, F V AU - Merlino, G AD - Molecular Genetics Section, Laboratory of Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892-4255 USA. Y1 - 1997/08/15/ PY - 1997 DA - 1997 Aug 15 SP - 3606 EP - 3611 VL - 57 IS - 16 SN - 0008-5472, 0008-5472 KW - Hepatitis B Surface Antigens KW - 0 KW - Neoplasm Proteins KW - Proliferating Cell Nuclear Antigen KW - RNA, Messenger KW - Transforming Growth Factor alpha KW - Index Medicus KW - Animals KW - Necrosis KW - Sex Factors KW - RNA, Messenger -- metabolism KW - Humans KW - Proliferating Cell Nuclear Antigen -- analysis KW - Mice KW - Mice, Transgenic KW - Male KW - Female KW - Cell Division KW - Liver Neoplasms -- pathology KW - Transforming Growth Factor alpha -- genetics KW - Carcinoma, Hepatocellular -- etiology KW - Hepatitis B Surface Antigens -- genetics KW - Neoplasm Proteins -- genetics KW - Carcinoma, Hepatocellular -- pathology KW - Hepatitis B Surface Antigens -- metabolism KW - Transforming Growth Factor alpha -- metabolism KW - Liver Neoplasms -- etiology KW - Neoplasm Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79233130?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Synergy+between+transforming+growth+factor+alpha+and+hepatitis+B+virus+surface+antigen+in+hepatocellular+proliferation+and+carcinogenesis.&rft.au=Jakubczak%2C+J+L%3BChisari%2C+F+V%3BMerlino%2C+G&rft.aulast=Jakubczak&rft.aufirst=J&rft.date=1997-08-15&rft.volume=57&rft.issue=16&rft.spage=3606&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-09 N1 - Date created - 1997-09-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibitors of both nuclear factor-kappaB and activator protein-1 activation block the neoplastic transformation response. AN - 79232256; 9270030 AB - Cross-coupling of active protein-1 (AP-1) and nuclear factor (NF)-kappaB has been reported. In the present study, we investigated the possibility that both of these two transcription factors might contribute to the process of tumor promoter-induced transformation. To establish a stable reporter cell system, two reporter genes were stably transfected into a JB6 mouse tumor promotion-sensitive (P+) cell line: a luciferase reporter controlled by a collagenase AP-1 sequence and a chloramphenicol acetyltransferase reporter controlled by an interleukin 6 NF-kappaB sequence. This double-reporter cell line maintained the phenotype of tumor promotion sensitivity and was able to report basal or induced AP-1 and NF-kappaB transactivation. The cytokine tumor promoter tumor necrosis factor (TNF)-alpha transactivated NF-kappaB and AP-1 for both DNA binding and transcriptional activity. Pyrrolidine dithiocarbamate, an antioxidant that acts as an NF-kappaB inhibitor, efficiently inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA) or TNF-alpha induced NF-kappaB as well as AP-1 transactivation and cell transformation, suggesting dependency of transformation on both transcription factors. The AP-1 transrepressing-retinoid SR11302 transrepressed AP-1 and cell transformation when these were TPA induced but not when TNF-alpha induced, indicating different signaling pathways for TNF-alpha and TPA. Supershift electrophoresis mobility shift assay revealed that Jun B and c-Jun were absent from the AP-1/DNA complex following TNF-alpha but present following TPA treatment. Together, these results suggest that both AP-1 and NF-kappaB activation may be required for transformation whether induced by TPA or by TNF, and the differential sensitivity of TPA and TNF-alpha-induced transformation to inhibition by a retinoid might be explained by differences in the composition of the DNA-bound AP-1 complexes. JF - Cancer research AU - Li, J J AU - Westergaard, C AU - Ghosh, P AU - Colburn, N H AD - Laboratory of Biochemical Physiology, National Cancer Institute, Frederick Cancer Research and Development Center, NIH, Maryland 21702, USA. lij@ncifcrf.gov Y1 - 1997/08/15/ PY - 1997 DA - 1997 Aug 15 SP - 3569 EP - 3576 VL - 57 IS - 16 SN - 0008-5472, 0008-5472 KW - Anticarcinogenic Agents KW - 0 KW - Carcinogens KW - NF-kappa B KW - Pyrrolidines KW - Retinoids KW - SR 11302 KW - Thiocarbamates KW - Transcription Factor AP-1 KW - Tumor Necrosis Factor-alpha KW - pyrrolidine dithiocarbamic acid KW - 25769-03-3 KW - DNA KW - 9007-49-2 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Carcinogens -- pharmacology KW - DNA -- metabolism KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Cells, Cultured -- drug effects KW - Mice KW - Retinoids -- pharmacology KW - Tetradecanoylphorbol Acetate -- antagonists & inhibitors KW - Carcinogens -- antagonists & inhibitors KW - Transfection KW - Anticarcinogenic Agents -- pharmacology KW - Genes, Reporter KW - Pyrrolidines -- pharmacology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Tumor Necrosis Factor-alpha -- antagonists & inhibitors KW - Thiocarbamates -- pharmacology KW - Time Factors KW - NF-kappa B -- drug effects KW - Transcription Factor AP-1 -- antagonists & inhibitors KW - Transcription Factor AP-1 -- metabolism KW - Transcriptional Activation -- drug effects KW - Transcription Factor AP-1 -- drug effects KW - Transcription Factor AP-1 -- genetics KW - NF-kappa B -- genetics KW - Cell Transformation, Neoplastic -- genetics KW - NF-kappa B -- metabolism KW - NF-kappa B -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79232256?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inhibitors+of+both+nuclear+factor-kappaB+and+activator+protein-1+activation+block+the+neoplastic+transformation+response.&rft.au=Li%2C+J+J%3BWestergaard%2C+C%3BGhosh%2C+P%3BColburn%2C+N+H&rft.aulast=Li&rft.aufirst=J&rft.date=1997-08-15&rft.volume=57&rft.issue=16&rft.spage=3569&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-09 N1 - Date created - 1997-09-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Specific chromosomal changes in albumin simian virus 40 T antigen transgenic rat liver neoplasms. AN - 79232219; 9270012 AB - Hepatocytes isolated from 3-month-old female rats bearing the albumin promoter/enhancer SV40 T antigen construct as a transgene demonstrated a 20% aneuploidy rate and a significant duplication of chromosome 1. Other chromosome changes were observed but were not statistically significant. At this time in the development of hepatic lesions, only a relatively small number of microscopic altered hepatic foci could be noted. By contrast, hepatocytes isolated from the age-matched nontransgenic controls demonstrated only 1% aneuploidy. One hundred % of the metaphase spreads isolated from hepatocellular neoplasms in transgenic rats were aneuploid. Although there were many random changes, 70% of the neoplastic cells demonstrated an amplification of all or portions of chromosome 1q. Only 2% of the neoplastic cells had both a trisomy and a duplication. The smallest region of chromosome 1 that was duplicated was that between bands q3.7 and q4.3. A loss of chromosome 3 was detected in 50% of the neoplasms, as well as a loss of chromosome 6 in 72% of the neoplastic cells. The carcinomas with the highest proliferation rate had also lost at least one copy of chromosome 15 in 70% of the cells. The loss of chromosomes 3, 6, and 15 indicates that these regions may harbor one or more tumor suppressor genes. The amplification of a specific region of chromosome 1 is thus the first karyotypic alteration that can be identified in hepatocytes from livers from which hepatic neoplasms will arise. This indicates that expression or repression of one or more genes in this region may confer a growth advantage to preneoplastic hepatocytes, facilitating their transit to the neoplastic state in the stage of progression. Changes in chromosomes 3, 6, and 15 that occur subsequent to duplication of the q3.7-q4.3 region of chromosome 1 are changes possibly reflecting alteration of tumor suppressor genes with further enhancement of neoplastic growth. JF - Cancer research AU - Sargent, L M AU - Dragan, Y P AU - Sattler, G AU - Xu, Y H AU - Wiley, J AU - Pitot, H C AD - Laboratory of Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20284, USA. Y1 - 1997/08/15/ PY - 1997 DA - 1997 Aug 15 SP - 3451 EP - 3456 VL - 57 IS - 16 SN - 0008-5472, 0008-5472 KW - Antigens, Polyomavirus Transforming KW - 0 KW - Index Medicus KW - Rats KW - Karyotyping KW - Animals KW - Rats, Sprague-Dawley KW - Chromosome Aberrations KW - Animals, Genetically Modified KW - Antigens, Polyomavirus Transforming -- genetics KW - Male KW - Female KW - Liver Neoplasms, Experimental -- genetics KW - Precancerous Conditions -- genetics KW - Chromosome Deletion KW - Precancerous Conditions -- chemically induced KW - Liver Neoplasms, Experimental -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79232219?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Specific+chromosomal+changes+in+albumin+simian+virus+40+T+antigen+transgenic+rat+liver+neoplasms.&rft.au=Sargent%2C+L+M%3BDragan%2C+Y+P%3BSattler%2C+G%3BXu%2C+Y+H%3BWiley%2C+J%3BPitot%2C+H+C&rft.aulast=Sargent&rft.aufirst=L&rft.date=1997-08-15&rft.volume=57&rft.issue=16&rft.spage=3451&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-09 N1 - Date created - 1997-09-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of A2a extracellular adenosine receptor-mediated signaling in adenosine-mediated inhibition of T-cell activation and expansion. AN - 79225514; 9269779 AB - Accumulation of adenosine and of deoxyadenosine in the absence of adenosine deaminase activity (ADA) activity results in lymphocyte depletion and in severe combined immunodeficiency (ADA SCID), which is currently explained by direct cell death-causing effects of intracellular products of adenosine metabolism. We explored the alternative mechanisms of peripheral T-cell depletion as due to inhibition of T-cell expansion by extracellular adenosine-mediated signaling through purinergic receptors. The strong inhibition of the T-cell receptor (TCR)-triggered proliferation and of upregulation of interleukin-2 receptor alpha chain (CD25) molecules, but not the direct lymphotoxicity, were observed at low concentrations of extracellular adenosine. These effects of extracellular adenosine (Ado) are likely to be mediated by A2a receptor-mediated signaling rather than by intracellular toxicity of adenosine catabolites, because (1) poorly metabolized adenosine analogs cause the accumulation of cAMP and strong inhibition of TCR-triggered CD25 upregulation; (2) the A2a, but not the A1 or A3, receptors are the major expressed and functionally coupled adenosine receptors in mouse peripheral T and B lymphocytes, and the adenosine-induced cAMP accumulation in lymphocytes correlates with the expression of A2a receptors; (3) the specific agonist of A2a receptor, CGS21680, induces increases in [cAMP]i in lymphocytes, whereas the specific antagonist of A2a receptor, CSC, inhibits the effects of Ado and CGS21680; and (4) the increases in [cAMP]i mimic the adenosine-induced inhibition of TCR-triggered CD25 upregulation and splenocyte proliferation. These studies suggest the possible role of adenosine receptors in the regulation of lymphocyte expansion and point to the downregulation of A2a purinergic receptors on T cells as a potentially attractive pharmacologic target. JF - Blood AU - Huang, S AU - Apasov, S AU - Koshiba, M AU - Sitkovsky, M AD - Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1892, USA. Y1 - 1997/08/15/ PY - 1997 DA - 1997 Aug 15 SP - 1600 EP - 1610 VL - 90 IS - 4 SN - 0006-4971, 0006-4971 KW - Antigens, Surface KW - 0 KW - Antihypertensive Agents KW - Phenethylamines KW - Purinergic P1 Receptor Agonists KW - Receptor, Adenosine A2A KW - Receptors, Antigen, T-Cell KW - Receptors, Interleukin-2 KW - Receptors, Purinergic P1 KW - 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine KW - 120225-54-9 KW - Cyclic AMP KW - E0399OZS9N KW - Adenosine KW - K72T3FS567 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Blotting, Northern KW - B-Lymphocytes -- cytology KW - Receptors, Interleukin-2 -- biosynthesis KW - Receptors, Antigen, T-Cell -- metabolism KW - Cell Division -- drug effects KW - Mice KW - Antihypertensive Agents -- pharmacology KW - Mice, Inbred DBA KW - B-Lymphocytes -- drug effects KW - Cyclic AMP -- metabolism KW - Antigens, Surface -- metabolism KW - Phenethylamines -- pharmacology KW - Lymphocyte Activation -- drug effects KW - Adenosine -- physiology KW - Adenosine -- pharmacology KW - Receptors, Purinergic P1 -- physiology KW - Adenosine -- analogs & derivatives KW - T-Lymphocytes -- drug effects KW - T-Lymphocytes -- immunology KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79225514?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Role+of+A2a+extracellular+adenosine+receptor-mediated+signaling+in+adenosine-mediated+inhibition+of+T-cell+activation+and+expansion.&rft.au=Huang%2C+S%3BApasov%2C+S%3BKoshiba%2C+M%3BSitkovsky%2C+M&rft.aulast=Huang&rft.aufirst=S&rft.date=1997-08-15&rft.volume=90&rft.issue=4&rft.spage=1600&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-24 N1 - Date created - 1997-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ribonuclease and high salt sensitivity of the ribonucleoprotein complex formed by the human LINE-1 retrotransposon. AN - 79292216; 9300051 AB - P40 is encoded by the first open reading frame of the human LINE-1 retrotransposon and is found in a large cytoplasmic ribonucleoprotein (RNP) complex, the p40 RNP-complex, in association with LINE-1 RNA(s) in human teratocarcinoma cell lines. We report here investigations on the stability of the p40 RNP-complex against various nucleases and high salt (0.5 M NaCl) treatment. The results indicate that (1) the p40 RNP-complex is dissociated after ribonuclease or high salt treatment, (2) DNase I does not disrupt the complex, (3) after dissociation of the complex, p40 maintain protein-protein interactions but in smaller complexes, and (4) p40 is not associated with the LINE-1 RNA(s) after high salt treatment. These observations suggest that the RNA molecule(s) is(are) essential for the stability of the large p40 complex and that the complex has a structure which allows various nucleases to reach the RNA. These features are distinct from those of typical virus and virus-like particles of retroviruses and other retrotransposons, respectively. Together with the fact that no significant sequence homology exists between p40 and the gag and gag-like proteins, it is likely that the p40 RNP-complex is structurally different from the typical virus and virus-like particles. JF - Journal of molecular biology AU - Hohjoh, H AU - Singer, M F AD - Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/08/08/ PY - 1997 DA - 1997 Aug 08 SP - 7 EP - 12 VL - 271 IS - 1 SN - 0022-2836, 0022-2836 KW - Cross-Linking Reagents KW - 0 KW - Retroelements KW - Ribonucleoproteins KW - Saline Solution, Hypertonic KW - Ribonucleases KW - EC 3.1.- KW - Deoxyribonuclease I KW - EC 3.1.21.1 KW - Ribonuclease, Pancreatic KW - EC 3.1.27.5 KW - Index Medicus KW - Blotting, Western KW - Tumor Cells, Cultured KW - Humans KW - Repetitive Sequences, Nucleic Acid KW - Teratoma KW - Ribonuclease, Pancreatic -- metabolism KW - Saline Solution, Hypertonic -- pharmacology KW - Ribonucleoproteins -- chemistry KW - Retroelements -- drug effects KW - Ribonucleases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79292216?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+biology&rft.atitle=Ribonuclease+and+high+salt+sensitivity+of+the+ribonucleoprotein+complex+formed+by+the+human+LINE-1+retrotransposon.&rft.au=Hohjoh%2C+H%3BSinger%2C+M+F&rft.aulast=Hohjoh&rft.aufirst=H&rft.date=1997-08-08&rft.volume=271&rft.issue=1&rft.spage=7&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-08 N1 - Date created - 1997-10-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The rat TSHbeta gene contains distinct response elements for regulation by retinoids and thyroid hormone. AN - 79283898; 9296372 AB - We have previously shown that thyroid stimulating hormone-beta (TSHbeta) mRNA levels are modulated by vitamin A status in vivo and using transient transfection, that suppression of rat TSHbeta gene promoter activity by all-trans retinoic acid (RA) requires RA receptor (RAR) and retinoid X receptor (RXR). In this paper we have used deletion analysis to delineate the sequences of the rTSHbeta gene involved in RA regulation, their relationship to the rTSHbeta gene negative thyroid hormone response elements and the retinoid receptor species that interact with these sequences. Using transient transfection in CV-1 cells, we found that the -204/+9 region of the rat TSHbeta gene, when fused to a luciferase reporter, was sufficient for suppression by all-trans-RA in the presence of RAR/RXR. Thus, regulation by RA did not involve the major rTSHbeta negative TRE located between +15 and +43. Mutational analysis also showed that the minor rTSHbeta negative TRE between -11 and +5 was not required by suppression by RA. However, in a heterologous promoter this sequence element acted as a strong positive RARE. The combination of RA and T3 treatment caused synergistic inhibition of rat TSHbeta gene expression in the presence of RAR/RXR and TR. EMSA analysis demonstrated that the -204/-79 sequence binds RAR/RXR heterodimer. Therefore, we conclude that there are separate response elements for RA and T3 on the rat TSHbeta gene, that the RARE binds RAR/RXR heterodimer and that RA and T3 interact functionally via these elements in the negative regulation of rat TSHbeta gene expression. JF - Molecular and cellular endocrinology AU - Breen, J J AU - Hickok, N J AU - Gurr, J A AD - Department of Biochemistry, Temple University School of Medicine, Philadelphia, PA 19140, USA. jb253x@nih.gov Y1 - 1997/08/08/ PY - 1997 DA - 1997 Aug 08 SP - 137 EP - 146 VL - 131 IS - 2 SN - 0303-7207, 0303-7207 KW - RNA, Messenger KW - 0 KW - Receptors, Retinoic Acid KW - Recombinant Fusion Proteins KW - Retinoid X Receptors KW - Retinoids KW - Thyroid Hormones KW - Transcription Factors KW - Triiodothyronine KW - 06LU7C9H1V KW - Tretinoin KW - 5688UTC01R KW - Thyrotropin KW - 9002-71-5 KW - Luciferases KW - EC 1.13.12.- KW - Index Medicus KW - Receptors, Retinoic Acid -- genetics KW - Tretinoin -- pharmacology KW - Transcription Factors -- physiology KW - Animals KW - Drug Interactions KW - Triiodothyronine -- pharmacology KW - Dimerization KW - Transcription Factors -- genetics KW - Rats KW - Receptors, Retinoic Acid -- physiology KW - Base Sequence KW - Transfection KW - Luciferases -- genetics KW - Cell Line KW - Thyrotropin -- genetics KW - Thyroid Hormones -- pharmacology KW - RNA, Messenger -- metabolism KW - Gene Expression Regulation -- drug effects KW - Retinoids -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79283898?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+endocrinology&rft.atitle=The+rat+TSHbeta+gene+contains+distinct+response+elements+for+regulation+by+retinoids+and+thyroid+hormone.&rft.au=Breen%2C+J+J%3BHickok%2C+N+J%3BGurr%2C+J+A&rft.aulast=Breen&rft.aufirst=J&rft.date=1997-08-08&rft.volume=131&rft.issue=2&rft.spage=137&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+endocrinology&rft.issn=03037207&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-02 N1 - Date created - 1997-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metabolism and disposition of dimethyl hydrogen phosphite in rats and mice. AN - 79152463; 9233382 AB - A study of dimethyl hydrogen phosphite (DMHP) by the National Toxicology Program (NTP) indicated that chronic administration by oral gavage resulted in an increased incidence of neoplastic lesions in the lungs and forestomachs of Fischer 344 rats but not in B6C3F1 mice. The current study was designed to evaluate the metabolic basis, if any, of this species selectivity by studying the metabolism and disposition of [14C]DMHP in the respective strains of rats and mice. Results of this study indicate that DMHP administered at a range of dose of 10-200 mg/kg was readily and near completely absorbed from the gastrointestinal tracts of rats and mice. DMHP-derived radioactivity was eliminated primarily as CO2 in the expired air, 44-57%, and urine, 28-49%, and very little was collected in feces, 1-2%, or as volatile organics, 2-3%. DMHP-derived radioactivity was widely distributed in tissues of rats and mice, with the highest concentrations observed in the liver, kidneys, spleen, lungs, and forestomach, and the lowest in brain, skeletal muscle, and adipose tissue. The disappearance of radioactivity from mouse tissues was approximately twice as rapid as from rat tissues. In vitro, DMHP was metabolized to formaldehyde by the microsomal fractions of liver, lungs, kidneys, forestomach, and glandular stomach. In vivo, DMHP was metabolized to the product of demethylation, monomethyl hydrogen phosphite (MMHP), which was excreted in urine. Results of this study indicate that the NTP carcinogenicity study with DMHP was carried out within the dose range in which the absorption, metabolism, and disposition of DMHP are linear in both species. Apparent species-dependent differences in the metabolism and disposition of DMHP are limited to the more rapid metabolism and elimination by the mouse. Therefore, the species-dependent variations in the carcinogenicity of DMHP are most likely attributable to factors other than metabolism and disposition. JF - Journal of toxicology and environmental health AU - Nomeir, A A AU - Matthews, H B AD - Toxicology Research and Testing Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. Amin.Nomeir@spcorp.com Y1 - 1997/08/08/ PY - 1997 DA - 1997 Aug 08 SP - 489 EP - 501 VL - 51 IS - 5 SN - 0098-4108, 0098-4108 KW - Carbon Radioisotopes KW - 0 KW - Fixatives KW - Organophosphonates KW - Phosphites KW - Formaldehyde KW - 1HG84L3525 KW - dimethyl hydrogen phosphite KW - ST4TBO000H KW - Index Medicus KW - Administration, Oral KW - Animals KW - Intestinal Absorption KW - Mice KW - Tissue Distribution KW - Rats KW - Rats, Inbred F344 KW - Formaldehyde -- metabolism KW - Microsomes -- metabolism KW - Species Specificity KW - Urine -- chemistry KW - Breath Tests KW - Male KW - Phosphites -- metabolism KW - Fixatives -- pharmacokinetics KW - Phosphites -- pharmacokinetics KW - Fixatives -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79152463?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+toxicology+and+environmental+health&rft.atitle=Metabolism+and+disposition+of+dimethyl+hydrogen+phosphite+in+rats+and+mice.&rft.au=Nomeir%2C+A+A%3BMatthews%2C+H+B&rft.aulast=Nomeir&rft.aufirst=A&rft.date=1997-08-08&rft.volume=51&rft.issue=5&rft.spage=489&rft.isbn=&rft.btitle=&rft.title=Journal+of+toxicology+and+environmental+health&rft.issn=00984108&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-13 N1 - Date created - 1997-08-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Loss of p21CIP1/WAF1 does not recapitulate accelerated malignant conversion caused by p53 loss in experimental skin carcinogenesis. AN - 79219075; 9264409 AB - The p21(CIP1/WAF1) protein is considered a downstream effector of tumor suppression by p53. We have previously demonstrated that p53 null keratinocytes have lower basal p21(CIP1/WAF1) mRNA levels and that tumors derived from these cells following transduction with the v-ras(Ha) oncogene grow faster than wildtype keratinocytes and rapidly progress to undifferentiated carcinomas (Cancer Res 54: 5584-5592, 1994). In this study, primary keratinocytes differing in p21(CIP1/WAF1) gene dose were transduced with v-ras(Ha) encoding retrovirus and grafted to nude mouse hosts to test whether the p53 null phenotype is mediated through p21(CIP1/WAF1). Resulting tumors from all genotypes were well differentiated papillomas; focal carcinomas were observed in 43, 30 and 44% of papillomas derived from +/+, +/- and -/- keratinocytes, respectively. p21(CIP1/WAF1) deficient keratinocytes expressing v-ras(Ha) do not display the degree of increased growth observed in p53 deficient tumors in vivo or the decreased responsiveness to negative growth regulation by Ca2+ in vitro. These results suggest that p21(CIP1/WAF1) does not regulate the differentiated phenotype or malignant progression of v-ras(Ha) initiated keratinocytes and that additional functions of the p53 protein other than transcriptional regulation of the p21(CIP1/WAF1) gene are required for p53 mediated tumor suppression. JF - Oncogene AU - Weinberg, W C AU - Montano, N E AU - Deng, C AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/08/07/ PY - 1997 DA - 1997 Aug 07 SP - 685 EP - 690 VL - 15 IS - 6 SN - 0950-9232, 0950-9232 KW - Cdkn1a protein, mouse KW - 0 KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - Transforming Growth Factor beta KW - Tumor Suppressor Protein p53 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Keratinocytes -- transplantation KW - Transforming Growth Factor beta -- pharmacology KW - Animals KW - Transcription, Genetic KW - Mice, Nude KW - Mice KW - Papilloma -- genetics KW - Mice, Inbred BALB C KW - Fibroblasts KW - Neoplasm Transplantation KW - Calcium -- metabolism KW - Genes, ras KW - Cells, Cultured KW - Keratinocytes -- virology KW - Retroviridae -- genetics KW - Carcinoma -- metabolism KW - Gene Dosage KW - Immunohistochemistry KW - Papilloma -- metabolism KW - Carcinoma -- genetics KW - Skin Neoplasms -- genetics KW - Tumor Suppressor Protein p53 -- metabolism KW - Skin Neoplasms -- metabolism KW - Cyclins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79219075?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Loss+of+p21CIP1%2FWAF1+does+not+recapitulate+accelerated+malignant+conversion+caused+by+p53+loss+in+experimental+skin+carcinogenesis.&rft.au=Weinberg%2C+W+C%3BMontano%2C+N+E%3BDeng%2C+C&rft.aulast=Weinberg&rft.aufirst=W&rft.date=1997-08-07&rft.volume=15&rft.issue=6&rft.spage=685&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-05 N1 - Date created - 1997-09-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Accelerated titration designs for phase I clinical trials in oncology. AN - 79207529; 9262252 AB - Many cancer patients in phase I clinical trials are treated at doses of chemotherapeutic agents that are below the biologically active level, thus reducing their chances for therapeutic benefit. Current phase I trials often take a long time to complete and provide little information about interpatient variability or cumulative toxicity. Our objective was to develop alternative designs for phase I trials so that fewer patients are treated at subtherapeutic dose levels, trials are of reduced duration, and important information (i.e., cumulative toxicity and maximum tolerated dose) needed to plan phase II trials is obtained. We fit a stochastic model to data from 20 phase I trials involving the study of nine different drugs. We then simulated new data from the model with the parameters estimated from the actual trials and evaluated the performance of alternative phase I designs on this simulated data. Four designs were evaluated. Design 1 was a conventional design (similar to the commonly used modified Fibonacci method) using cohorts of three to six patients, with 40% dose-step increments and no intrapatient dose escalation. Designs 2 through 4 included only one patient per cohort until one patient experienced dose-limiting toxic effects or two patients experienced grade 2 toxic effects (during their first course of treatment for designs 2 and 3 or during any course of treatment for design 4). Designs 3 and 4 used 100% dose steps during this initial accelerated phase. After the initial accelerated phase, designs 2 through 4 resorted to standard cohorts of three to six patients, with 40% dose-step increments. Designs 2 through 4 used intrapatient dose escalation if the worst toxicity is grade 0-1 in the previous course for that patient. Only three of the actual trials demonstrated cumulative toxic effects of the chemotherapeutic agents in patients. The average number of patients required for a phase I trial was reduced from 39.9 for design 1 to 24.4, 20.7, and 21.2 for designs 2, 3, and 4, respectively. The average number of patients who would be expected to have grade 0-1 toxicity as their worst toxicity over three cycles of treatment is 23.3 for design 1, but only 7.9, 3.9, and 4.8 for designs 2, 3, and 4, respectively. The average number of patients with grade 3 toxicity as their worst toxicity increases from 5.5 for design 1 to 6.2, 6.8, and 6.2 for designs 2, 3, and 4, respectively. The average number of patients with grade 4 toxicity as their worst toxicity increases from 1.9 for design 1 to 3.0, 4.3, and 3.2 for designs 2, 3, and 4, respectively. Accelerated titration (i.e., rapid intrapatient drug dose escalation) designs appear to effectively reduce the number of patients who are under-treated, speed the completion of phase I trials, and provide a substantial increase in the information obtained. JF - Journal of the National Cancer Institute AU - Simon, R AU - Freidlin, B AU - Rubinstein, L AU - Arbuck, S G AU - Collins, J AU - Christian, M C AD - Division of Cancer Treatment, Diagnosis, and Centers, National Cancer Institute, Bethesda, MD, USA. Y1 - 1997/08/06/ PY - 1997 DA - 1997 Aug 06 SP - 1138 EP - 1147 VL - 89 IS - 15 SN - 0027-8874, 0027-8874 KW - Antineoplastic Agents KW - 0 KW - Quinoxalines KW - Sulfanilamides KW - 5-chloroquinoxaline-2-sulfanilamide KW - O0408QB48D KW - Index Medicus KW - Sulfanilamides -- administration & dosage KW - Quinoxalines -- adverse effects KW - Drug Administration Schedule KW - Humans KW - Sulfanilamides -- adverse effects KW - Models, Statistical KW - Quinoxalines -- administration & dosage KW - Neoplasms -- drug therapy KW - Antineoplastic Agents -- administration & dosage KW - Clinical Trials, Phase I as Topic -- standards KW - Research Design KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79207529?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Accelerated+titration+designs+for+phase+I+clinical+trials+in+oncology.&rft.au=Simon%2C+R%3BFreidlin%2C+B%3BRubinstein%2C+L%3BArbuck%2C+S+G%3BCollins%2C+J%3BChristian%2C+M+C&rft.aulast=Simon&rft.aufirst=R&rft.date=1997-08-06&rft.volume=89&rft.issue=15&rft.spage=1138&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-28 N1 - Date created - 1997-08-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HIV-1 coreceptor activity of CCR5 and its inhibition by chemokines: independence from G protein signaling and importance of coreceptor downmodulation. AN - 79217655; 9268166 AB - HIV-1 infection requires the presence of specific chemokine receptors on CD4+ target cells to enable the fusion reactions involved in virus entry. CCR5 is a major fusion coreceptor for macrophage-tropic HIV-1 isolates. HIV-1 entry and fusion are mediated by the viral envelope glycoprotein (Env) and are inhibited by CCR5 ligands, but the mechanisms are unknown. Here, we test the role of G protein signaling and CCR5 surface downmodulation by two separate approaches: direct inactivation of CCR5 signaling by mutagenesis and inactivation of G(i)-type G proteins with pertussis toxin. A CCR5 mutant lacking the last 45 amino acids of the cytoplasmic C-terminus (CCR5306) was created that was expressed on transfected cells at levels comparable to cells expressing CCR5 and displayed normal chemokine binding affinity. CCR5 ligands induced calcium flux and receptor downmodulation in cells expressing CCR5, but not in cells expressing CCR5306. Nevertheless, CCR5 or CCR5306, when coexpressed with CD4, supported comparable HIV-1 Env-mediated cell fusion. Consistent with this, treatment of CCR5-expressing cells with pertussis toxin completely blocked ligand-induced transient calcium flux, but did not affect Env-mediated cell fusion or HIV-1 infection. Also, pertussis toxin did not block chemokine inhibition of Env-mediated cell fusion or HIV-1 infection. However, chemokines inhibited Env-mediated cell fusion less efficiently for CCR5306 than for CCR5. We conclude that the C-terminal domain of CCR5 is critical for G protein signaling and receptor downmodulation from the surface, but that neither function is required for CCR5 fusion coreceptor activity. The contrasting phenotypes of CCR5 and CCR5306 suggest that coreceptor downmodulation and direct blockage of Env interaction sites both contribute to chemokine inhibition of HIV-1 infection. JF - Virology AU - Alkhatib, G AU - Locati, M AU - Kennedy, P E AU - Murphy, P M AU - Berger, E A AD - The Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/08/04/ PY - 1997 DA - 1997 Aug 04 SP - 340 EP - 348 VL - 234 IS - 2 SN - 0042-6822, 0042-6822 KW - Chemokines KW - 0 KW - Receptors, CCR5 KW - Receptors, Cytokine KW - Receptors, HIV KW - Viral Envelope Proteins KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - AIDS/HIV KW - Virus Replication KW - Animals KW - 3T3 Cells KW - Down-Regulation KW - HeLa Cells KW - Humans KW - Mice KW - Chemokines -- metabolism KW - HIV Infections -- virology KW - GTP-Binding Proteins -- metabolism KW - Receptors, HIV -- metabolism KW - Viral Envelope Proteins -- metabolism KW - HIV-1 -- physiology KW - Receptors, Cytokine -- metabolism KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79217655?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=HIV-1+coreceptor+activity+of+CCR5+and+its+inhibition+by+chemokines%3A+independence+from+G+protein+signaling+and+importance+of+coreceptor+downmodulation.&rft.au=Alkhatib%2C+G%3BLocati%2C+M%3BKennedy%2C+P+E%3BMurphy%2C+P+M%3BBerger%2C+E+A&rft.aulast=Alkhatib&rft.aufirst=G&rft.date=1997-08-04&rft.volume=234&rft.issue=2&rft.spage=340&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-09 N1 - Date created - 1997-09-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Validity and reliability of Structured Interview for Competency Incompetency Assessment Testing and Ranking Inventory. AN - 85256273; pmid-9257221 AB - The Structured Interview for Competency and Incompetency Assessment Testing and Ranking Inventory (SICIATRI) is a structured interview guide to assess the competency for giving informed consent to treatment among psychiatric and medical patients. The competency levels of 48 psychiatric and medical inpatients were assessed by SICIATRI. A relatively high- inter-rater reliability of the SICIATRI items (over half of the items had kappa > or = .60) and concurrent validity (sensitivity = .83, specificity = .67 as measured against the global judgement of competency rating by the attending physician) were obtained. In addition to its brevity (it takes about 20 minutes to complete), these findings may warrant application of this instrument in a clinical setting. JF - Journal of Clinical Psychology AU - Tomoda, A AU - Yasumiya, R AU - Sumiyama, T AU - Tsukada, K AU - Hayakawa, T AU - Matsubara, K AU - Kitamura, F AU - Kitamura, T AD - National Institute of Mental Health, NCNP, Chiba, Japan. PY - 1997 SP - 443 EP - 450 VL - 53 IS - 5 SN - 0021-9762, 0021-9762 KW - Sensitivity and Specificity KW - Reproducibility of Results KW - Human KW - Aged KW - Personality Inventory KW - Psychometrics KW - Psychiatric Status Rating Scales KW - Hospitalization KW - Mental Disorders KW - Patient Acceptance of Health Care KW - Adult KW - Middle Age KW - Support, Non-U.S. Gov't KW - Informed Consent KW - Male KW - Female KW - Mental Competency UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85256273?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Clinical+Psychology&rft.atitle=Validity+and+reliability+of+Structured+Interview+for+Competency+Incompetency+Assessment+Testing+and+Ranking+Inventory.&rft.au=Tomoda%2C+A%3BYasumiya%2C+R%3BSumiyama%2C+T%3BTsukada%2C+K%3BHayakawa%2C+T%3BMatsubara%2C+K%3BKitamura%2C+F%3BKitamura%2C+T&rft.aulast=Tomoda&rft.aufirst=A&rft.date=1997-08-01&rft.volume=53&rft.issue=5&rft.spage=443&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Psychology&rft.issn=00219762&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Immunolocalization of anion exchanger 2alpha in auditory sensory hair cells. AN - 85240094; pmid-9282896 AB - We have previously reported the isolation from a guinea pig organ of Corti cDNA library of a cDNA clone that encodes a novel isoform of the anion exchanger 2 (AE2) protein (Negrini, Rivolta, Kalinec and Kachar, 1995. Cloning of an organ of Corti anion exchanger 2 isoform with a truncated C-terminal domain. Biophys. Acta, 1236, 207-211). The deduced protein, named AE2alpha, has a conserved cytoplasmic domain and a short membrane domain with only two membrane spanning regions, as opposed to the fourteen present in the conventional AE2. Now, we are showing the immunolocalization and preliminary characterization of this protein using an antipeptide antibody specific for this novel AE2 isoform. In Western blots, this antibody binds to an approximately 89 kDa polypeptide that corresponds to a phosphorylated protein with serines as main phosphate acceptor residues. In immunofluorescence experiments, the antibody labels the stereocilia and the lateral wall of the outer hair cells and the stereocilia of the inner hair cells. Our results suggest that AE2alpha is a membrane-cytoskeletal linker in regions of the hair cell, where sensory transduction mechanisms take place. JF - Hearing Research AU - Kalinec, F AU - Kalinec, G AU - Negrini, C AU - Kachar, B AD - Section on Structural Cell Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20850, USA. PY - 1997 SP - 141 EP - 146 VL - 110 IS - 1-2 SN - 0378-5955, 0378-5955 KW - Animals KW - Microscopy, Phase-Contrast KW - Guinea Pigs KW - Amino Acid Sequence KW - Neurons, Afferent KW - Precipitin Tests KW - Membrane Proteins KW - Nerve Tissue Proteins KW - Antibody Specificity KW - Blotting, Western KW - Phosphorylation KW - Hair Cells, Outer KW - Hair Cells, Inner KW - Molecular Sequence Data KW - Fluorescent Antibody Technique KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85240094?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hearing+Research&rft.atitle=Immunolocalization+of+anion+exchanger+2alpha+in+auditory+sensory+hair+cells.&rft.au=Kalinec%2C+F%3BKalinec%2C+G%3BNegrini%2C+C%3BKachar%2C+B&rft.aulast=Kalinec&rft.aufirst=F&rft.date=1997-08-01&rft.volume=110&rft.issue=1-2&rft.spage=141&rft.isbn=&rft.btitle=&rft.title=Hearing+Research&rft.issn=03785955&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Low glucose metabolism during brain stimulation in older Down's syndrome subjects at risk for Alzheimer's disease prior to dementia. AN - 85239582; pmid-9247390 AB - OBJECTIVE: Down's syndrome is characterized by the genetically programmed accumulation of substantial Alzheimer's disease neuropathology after age 40 and the development of early dementia years later, providing a unique human model to investigate the preclinical phases of Alzheimer's disease. Older nondemented adults with Down's syndrome show normal rates of regional cerebral glucose metabolism at rest before the onset of dementia, indicating that their neurons maintain function at rest. The authors hypothesized that an audiovisual stimulation paradigm, acting as a stress test, would reveal abnormalities in cerebral glucose metabolism before dementia in the neocortical parietal and temporal areas most vulnerable to Alzheimer's disease. METHOD: Regional cerebral glucose metabolism was assessed by means of positron emission tomography (PET) with [18F]fluorodeoxyglucose in eight younger (mean age = 35 years, SD = 2) and eight older (mean age = 50, SD = 7) healthy, nondemented adults with trisomy 21 Down's syndrome. PET scans were performed at rest and during audiovisual stimulation in the same scanning session. Levels of general intellectual functioning and compliance were similar in the two groups. RESULTS: At rest the two groups showed no difference in glucose metabolism in any cerebral region. In contrast, during audiovisual stimulation the older subjects with Down's syndrome had significantly lower glucose metabolic rates in the parietal and temporal cortical areas. CONCLUSIONS: Abnormalities in cerebral metabolism during stimulation appeared in the first cortical regions typically affected in Alzheimer's disease. These results indicate that a stress test paradigm can detect metabolic abnormalities in the preclinical stages of Alzheimer's disease despite normal cerebral metabolism at rest. JF - The American Journal of Psychiatry AU - Pietrini, P AU - Dani, A AU - Furey, M L AU - Alexander, G E AU - Freo, U AU - Grady, C L AU - Mentis, M J AU - Mangot, D AU - Simon, E W AU - Horwitz, B AU - Haxby, J V AU - Schapiro, M B AD - Laboratory of Neurosciences, National Institute on Aging, NIH, Bethesda, MD 20892, USA. PY - 1997 SP - 1063 EP - 1069 VL - 154 IS - 8 SN - 0002-953X, 0002-953X KW - Age Factors KW - Motion Pictures KW - Human KW - Alzheimer Disease KW - Brain KW - Glucose KW - Parietal Lobe KW - Auditory Perception KW - Risk Factors KW - Fludeoxyglucose F 18 KW - Temporal Lobe KW - Adult KW - Middle Age KW - Deoxyglucose KW - Support, Non-U.S. Gov't KW - Tomography, Emission-Computed KW - Down Syndrome KW - Visual Perception KW - Photic Stimulation KW - Acoustic Stimulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85239582?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+Journal+of+Psychiatry&rft.atitle=Low+glucose+metabolism+during+brain+stimulation+in+older+Down%27s+syndrome+subjects+at+risk+for+Alzheimer%27s+disease+prior+to+dementia.&rft.au=Pietrini%2C+P%3BDani%2C+A%3BFurey%2C+M+L%3BAlexander%2C+G+E%3BFreo%2C+U%3BGrady%2C+C+L%3BMentis%2C+M+J%3BMangot%2C+D%3BSimon%2C+E+W%3BHorwitz%2C+B%3BHaxby%2C+J+V%3BSchapiro%2C+M+B&rft.aulast=Pietrini&rft.aufirst=P&rft.date=1997-08-01&rft.volume=154&rft.issue=8&rft.spage=1063&rft.isbn=&rft.btitle=&rft.title=The+American+Journal+of+Psychiatry&rft.issn=0002953X&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Modifications in aerodynamic variables by persons who stutter under fluency-evoking conditions. AN - 85232317; pmid-9263947 AB - The purposes of this study were to (a) compare the effects of fluency-evoking conditions on aerodynamic variables in 10 persons who stutter with those previously reported for 12 individuals who do not stutter; (b) determine if any changes demonstrated in the amplitude and/or timing of aerodynamic variables were accounted for by changes in speech intensity; and (c) determine if any amplitude or timing changes in flow and intraoral pressure were related to improved fluency. The fluency-evoking conditions were choral reading (CR), metronome-pacing (MET), delayed auditory feedback (DAF), and noise (NOISE). From 8 words beginning with plosive consonants in CVC contexts read aloud in sentences, measures were made of 8 variables, including closure duration, amplitude and time to maximum airflow and intraoral pressure for initial plosives, and the duration and intensity of the following vowel. Speech rate was also computed. Only fluently produced target words from persons who stutter were analyzed. All persons who stutter showed improved fluency under all conditions. Both groups demonstrated significant (p < or = 0.006) condition effects for peak flow, vowel intensity, and pressure rise time. Thus, fluency-evoking conditions affected these variables regardless of speaker type. Both groups changed peak pressure in similar directions from baseline depending on condition, but not significantly for each group in the same conditions. Persons who stutter significantly increased speech rate for CR, DAF, and NOISE; and persons who do not stutter significantly decreased rate under DAF. The reported changes in peak pressure and peak flow could not be accounted for by changes in vowel intensity. Larger improvements in fluency occurred under conditions when peak flow and peak pressure values were decreased from baseline. Thus, variables that were modified by both groups when speaking under conditions were also the variables related to changes in fluency for the persons who stutter. JF - Journal of Speech, Language, and Hearing Research AU - Stager, S V AU - Denman, D W AU - Ludlow, C L AD - Voice and Speech Section, NIDCD, NIH, Bethesda, MD, USA. PY - 1997 SP - 832 EP - 847 VL - 40 IS - 4 SN - 1092-4388, 1092-4388 KW - Severity of Illness Index KW - Speech Production Measurement KW - Comparative Study KW - Pulmonary Ventilation KW - Human KW - Adult KW - Middle Age KW - Stuttering KW - Female KW - Male UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85232317?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Speech%2C+Language%2C+and+Hearing+Research&rft.atitle=Modifications+in+aerodynamic+variables+by+persons+who+stutter+under+fluency-evoking+conditions.&rft.au=Stager%2C+S+V%3BDenman%2C+D+W%3BLudlow%2C+C+L&rft.aulast=Stager&rft.aufirst=S&rft.date=1997-08-01&rft.volume=40&rft.issue=4&rft.spage=832&rft.isbn=&rft.btitle=&rft.title=Journal+of+Speech%2C+Language%2C+and+Hearing+Research&rft.issn=10924388&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Planned early neck dissection before radiation for persistent neck nodes after induction chemotherapy. AN - 85193856; pmid-9261021 AB - Optimal management of advanced neck metastases as part of an organ preservation treatment approach for head and neck squamous carcinoma (HNSC) is unclear. Since 1989, our management paradigm for patients on organ preservation was modified to incorporate planned early neck dissection before radiation therapy for patients who did not achieve a complete response (CR) of neck nodes after induction chemotherapy (IC). The purpose of this study was to determine if planned early neck dissection is a safe and effective approach in the management of advanced nodal disease as part of organ preservation. Fifty-eight consecutive patients with advanced HNSC who were entered in organ preservation trials using induction chemotherapy and radiation with surgical salvage were studied. Median follow-up was 26 months. Of the 58 patients, 71% were stage IV. Patients were grouped by nodal response to chemotherapy and N class, and were analyzed with respect to patterns of recurrence, complications, and survival. Overall, the rate of CR of neck nodes was 49%. Fifty-one percent had less than a complete response of neck nodes after IC and required planned early neck dissection. There were no significant differences in patterns of recurrence, complications, interval time to start of radiation, recurrence, or survival rates between the CR and less than CR groups. These data suggest that planned early neck dissection for patients with less than CR in the neck after IC is not detrimental with respect to neck relapse or overall survival. We believe that planned early neck dissection can be safely incorporated into future organ preservation treatment protocols for patients with advanced head and neck carcinoma. JF - The Laryngoscope AU - Thomas, G R AU - Greenberg, J AU - Wu, K T AU - Moe, K AU - Esclamado, R AU - Bradford, C AU - Carroll, W AU - Eisbruch, A AU - Urba, S AU - Wolf, G T AD - Head and Neck Tumor Biology Section, NIDCD/NIH, Bethesda, Maryland, USA. PY - 1997 SP - 1129 EP - 1137 VL - 107 IS - 8 SN - 0023-852X, 0023-852X KW - Disease-Free Survival KW - Combined Modality Therapy KW - Lymphatic Metastasis KW - Human KW - Salvage Therapy KW - Retrospective Studies KW - Aged KW - Aged, 80 and over KW - Head and Neck Neoplasms KW - Adult KW - Antineoplastic Combined Chemotherapy Protocols KW - Middle Age KW - Neoplasm Recurrence, Local KW - Carcinoma, Squamous Cell KW - Male KW - Female KW - Survival Analysis KW - Neck Dissection UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85193856?accountid=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+Laryngoscope&rft.atitle=Planned+early+neck+dissection+before+radiation+for+persistent+neck+nodes+after+induction+chemotherapy.&rft.au=Thomas%2C+G+R%3BGreenberg%2C+J%3BWu%2C+K+T%3BMoe%2C+K%3BEsclamado%2C+R%3BBradford%2C+C%3BCarroll%2C+W%3BEisbruch%2C+A%3BUrba%2C+S%3BWolf%2C+G+T&rft.aulast=Thomas&rft.aufirst=G&rft.date=1997-08-01&rft.volume=107&rft.issue=8&rft.spage=1129&rft.isbn=&rft.btitle=&rft.title=The+Laryngoscope&rft.issn=0023852X&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Recent advances in understanding of vanilloid receptors: a therapeutic target for treatment of pain and inflammation in skin. AN - 79553476; 9487017 AB - C-fiber sensory afferent neurons, which contain neuropeptides such as calcitonin-gene related peptide and substance P, mediate a wide variety of physiologic responses, including chemogenic pain, thermoregulation, and neurogenic inflammation. Capsaicin, the pungent constituent in red pepper, functions to activate and then, at higher doses and longer times, desensitize this class of neurons. This latter response provides the basis for the therapeutic application of capsaicin. A major advance in the field has been the identification of resiniferatoxin, a phorbol-related diterpene, as an analog of capsaicin that is ultrapotent but with differential selectivity. In particular, resiniferatoxin is only similar in potency for induction of pain but is much more effective for desensitization. Structure-activity analysis in whole animal experiments provides further evidence for dissociation of biologic endpoints, strongly arguing for the existence of vanilloid receptor subclasses. Using resiniferatoxin, we have been able to define specific, high-affinity receptors for capsaicin both in animal models such as rats and in man. Of great importance, the pharmacologic characterization in cultured dorsal root ganglion cells of the high-affinity resiniferatoxin-binding site and of the physiologic response believed to be directly coupled to the receptor, viz. calcium uptake, differed in structure-activity and in cooperativity. We conclude that multiple high-affinity vanilloid receptor subclasses mediate vanilloid response; moreover, the resiniferatoxin-selective subclass of vanilloid receptors is not the voltage-independent, cation-nonselective ion channel as previously believed. Optimization of ligands for the individual vanilloid receptor subclasses should revolutionize this therapeutic area. JF - The journal of investigative dermatology. Symposium proceedings AU - Biro, T AU - Acs, G AU - Acs, P AU - Modarres, S AU - Blumberg, P M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 1997/08// PY - 1997 DA - August 1997 SP - 56 EP - 60 VL - 2 IS - 1 SN - 1087-0024, 1087-0024 KW - Diterpenes KW - 0 KW - Neurotoxins KW - Receptors, Drug KW - resiniferatoxin KW - A5O6P1UL4I KW - Capsaicin KW - S07O44R1ZM KW - Index Medicus KW - Ganglia, Spinal -- cytology KW - Diterpenes -- pharmacology KW - Animals KW - Humans KW - Ganglia, Spinal -- metabolism KW - Neurotoxins -- pharmacology KW - Radioligand Assay KW - Ganglia, Spinal -- drug effects KW - Receptors, Drug -- classification KW - Pain -- drug therapy KW - Receptors, Drug -- drug effects KW - Capsaicin -- analogs & derivatives KW - Dermatitis -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79553476?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+journal+of+investigative+dermatology.+Symposium+proceedings&rft.atitle=Recent+advances+in+understanding+of+vanilloid+receptors%3A+a+therapeutic+target+for+treatment+of+pain+and+inflammation+in+skin.&rft.au=Biro%2C+T%3BAcs%2C+G%3BAcs%2C+P%3BModarres%2C+S%3BBlumberg%2C+P+M&rft.aulast=Biro&rft.aufirst=T&rft.date=1997-08-01&rft.volume=2&rft.issue=1&rft.spage=56&rft.isbn=&rft.btitle=&rft.title=The+journal+of+investigative+dermatology.+Symposium+proceedings&rft.issn=10870024&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-10 N1 - Date created - 1998-03-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dose-response relationships for endocrine disruptors: what we know and what we don't know. AN - 79341368; 9339476 JF - Regulatory toxicology and pharmacology : RTP AU - Lucier, G W AD - National Institute of Environmental Health Sciences/National Toxicology Program, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/08// PY - 1997 DA - August 1997 SP - 34 EP - 35 VL - 26 IS - 1 Pt 1 SN - 0273-2300, 0273-2300 KW - Gonadal Steroid Hormones KW - 0 KW - Xenobiotics KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Humans KW - Endocrine System Diseases -- chemically induced KW - Male KW - Female KW - Risk Assessment KW - Xenobiotics -- administration & dosage KW - Gonadal Steroid Hormones -- antagonists & inhibitors KW - Gonadal Steroid Hormones -- agonists KW - Endocrine System -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79341368?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Regulatory+toxicology+and+pharmacology+%3A+RTP&rft.atitle=Dose-response+relationships+for+endocrine+disruptors%3A+what+we+know+and+what+we+don%27t+know.&rft.au=Lucier%2C+G+W&rft.aulast=Lucier&rft.aufirst=G&rft.date=1997-08-01&rft.volume=26&rft.issue=1+Pt+1&rft.spage=34&rft.isbn=&rft.btitle=&rft.title=Regulatory+toxicology+and+pharmacology+%3A+RTP&rft.issn=02732300&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-14 N1 - Date created - 1997-11-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Potentiation of NMDA receptor-mediated responses by dynorphin at low extracellular glycine concentrations. AN - 79304814; 9307096 AB - The effect of dynorphin A(1-13) on N-methyl-D-aspartate (NMDA)-activated currents was investigated in the presence of low extracellular glycine concentrations in Xenopus oocytes expressing recombinant heteromeric NMDA receptors and in cultured hippocampal neurons with the use of voltage-clamp techniques. At an extracellular added glycine concentration of 100 nM, dynorphin A(1-13) (10 microM) greatly increased the amplitude of NMDA-activated currents for all heteromeric subunit combinations tested; on average, the potentiation was: epsilon1/zeta1, 3,377 +/- 1,416% (mean +/- SE); epsilon2/zeta1, 1,897 +/- 893%; epsilon3/zeta1, 4,356 +/- 846%; and epsilon4/zeta1, 1,783 +/- 503%. Potentiation of NMDA-activated current by dynorphin A(1-13) was concentration dependent between 0.1 and 10 microM dynorphin A(1-13), with a half-maximal concentration value of 2.77 microM and an apparent Hill coefficient of 2.53, for epsilon2/zeta1 subunits at 100 nM added extracellular glycine. Percentage potentiation by dynorphin A(1-13) was maximal at the lowest glycine concentrations tested (0.01 and 0.1 microM), and decreased with increasing glycine concentration. No significant potentiation was observed at glycine concentrations > 0.1 microM for epsilon1/zeta1, epsilon2/zeta1, and epsilon4/zeta1 subunits, or at > 1 microM for epsilon3/zeta1 subunits. Potentiation of NMDA-activated currents by dynorphin A(1-13) was not inhibited by 1 microM of the kappa-opioid receptor antagonist nor-binaltorphimine, and potentiation was not observed with 10 microM of the kappa-opioid receptor agonist trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl] benzene-acetamide. Potentiation of NMDA-activated current by dynorphin A(1-13) was inhibited by the glycine antagonist kynurenic acid (50 microM). NMDA-activated current was also potentiated at low glycine concentrations by 10 microM dynorphin A(2-13) or (3-13), both of which have a glycine as the first amino acid, but not by 10 microM dynorphin A(4-13), which does not have glycine as an amino acid. In hippocampal neurons, 10 microM dynorphin A(1-13) or (2-13) potentiated steady-state NMDA-activated current in the absence of added extracellular glycine. The extracellular free glycine concentration, determined by high-performance liquid chromatography, was between 26 and 36 nM for the bathing solution in presence or absence of 10 microM dynorphin A(1-13), (2-13), (3-13), or (4-13), and did not differ significantly among these solutions. The observations are consistent with the potentiation of NMDA-activated current at low extracellular glycine concentrations resulting from an interaction of the glycine amino acids in dynorphin A(1-13) with the glycine coagonist site on the NMDA receptor. Because dynorphin A is an endogenous peptide that can be coreleased with glutamate at glutamatergic synapses, the potentiation of NMDA receptor-mediated responses could be an important physiological regulator of NMDA receptor function at these synapses. JF - Journal of neurophysiology AU - Zhang, L AU - Peoples, R W AU - Oz, M AU - Harvey-White, J AU - Weight, F F AU - Brauneis, U AD - Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/08// PY - 1997 DA - August 1997 SP - 582 EP - 590 VL - 78 IS - 2 SN - 0022-3077, 0022-3077 KW - Analgesics, Opioid KW - 0 KW - Excitatory Amino Acid Agonists KW - Peptide Fragments KW - Receptors, N-Methyl-D-Aspartate KW - Receptors, Opioid, kappa KW - dynorphin (1-13) KW - 72957-38-1 KW - Dynorphins KW - 74913-18-1 KW - Glycine KW - TE7660XO1C KW - Index Medicus KW - Xenopus laevis KW - Animals KW - Cells, Cultured KW - Neurons -- drug effects KW - Hippocampus -- cytology KW - Oocytes -- drug effects KW - Receptors, Opioid, kappa -- drug effects KW - Mice KW - Drug Synergism KW - Hippocampus -- drug effects KW - Receptors, N-Methyl-D-Aspartate -- physiology KW - Receptors, N-Methyl-D-Aspartate -- agonists KW - Glycine -- pharmacology KW - Analgesics, Opioid -- pharmacology KW - Peptide Fragments -- pharmacology KW - Excitatory Amino Acid Agonists -- pharmacology KW - Dynorphins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79304814?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurophysiology&rft.atitle=Potentiation+of+NMDA+receptor-mediated+responses+by+dynorphin+at+low+extracellular+glycine+concentrations.&rft.au=Zhang%2C+L%3BPeoples%2C+R+W%3BOz%2C+M%3BHarvey-White%2C+J%3BWeight%2C+F+F%3BBrauneis%2C+U&rft.aulast=Zhang&rft.aufirst=L&rft.date=1997-08-01&rft.volume=78&rft.issue=2&rft.spage=582&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurophysiology&rft.issn=00223077&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-23 N1 - Date created - 1997-10-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicity of methoxyacetic acid in cultured human luteal cells. AN - 79289276; 9299193 AB - Ethylene glycol monomethyl ether (EGME) and its proximate metabolite, 2-methoxyacetic acid (MAA), increase ovarian luteal cell progesterone production in the female rat in vivo and in cultured rat luteal cells in vitro, respectively. In order to better assess the potential hazard of EGME and MAA to women, these studies were conducted to determine whether the same concentrations of MAA increase progesterone in human luteinized granulosa cells as in rat luteal cells. Human cells were collected from healthy anonymous oocyte donors, washed, plated 25,000 viable cells per well, and treated with 10 IU hCG and 0-5 mM MAA for 6-48 hr. Progesterone in media was significantly elevated after 24 hr incubation at >/=1 mM MAA. MAA had no effect on ATP levels at 6 or 24 hr. Thus, MAA increased progesterone production in cultured human luteal cells at the same concentration as MAA increased progesterone in rat luteal cells. The implication is that EGME has the potential to alter ovarian luteal function in women. These data should be useful for determining the real health hazards and potential risks of EGME exposure. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Almekinder, J L AU - Lennard, D E AU - Walmer, D K AU - Davis, B J AD - Laboratory of Experimental Pathology, NIEHS, Research Triangle Park, North Carolina, 27709, USA. Y1 - 1997/08// PY - 1997 DA - August 1997 SP - 191 EP - 194 VL - 38 IS - 2 SN - 0272-0590, 0272-0590 KW - Acetates KW - 0 KW - Ethylene Glycols KW - Solvents KW - Progesterone KW - 4G7DS2Q64Y KW - Cyclic AMP KW - E0399OZS9N KW - methyl cellosolve KW - EK1L6XWI56 KW - methoxyacetic acid KW - F11T1H7Q7W KW - Index Medicus KW - Animals KW - Solvents -- toxicity KW - Granulosa Cells -- drug effects KW - Humans KW - Hydrogen-Ion Concentration KW - Radioimmunoassay KW - Granulosa Cells -- metabolism KW - Progesterone -- biosynthesis KW - Rats KW - Ethylene Glycols -- toxicity KW - Cells, Cultured KW - Cyclic AMP -- metabolism KW - Female KW - Ovary -- metabolism KW - Ovary -- cytology KW - Ovary -- drug effects KW - Acetates -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79289276?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Toxicity+of+methoxyacetic+acid+in+cultured+human+luteal+cells.&rft.au=Almekinder%2C+J+L%3BLennard%2C+D+E%3BWalmer%2C+D+K%3BDavis%2C+B+J&rft.aulast=Almekinder&rft.aufirst=J&rft.date=1997-08-01&rft.volume=38&rft.issue=2&rft.spage=191&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-23 N1 - Date created - 1997-10-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A recombinant single-chain human class II MHC molecule (HLA-DR1) as a covalently linked heterotrimer of alpha chain, beta chain, and antigenic peptide, with immunogenicity in vitro and reduced affinity for bacterial superantigens. AN - 79280762; 9295029 AB - Major histocompatibility complex (MHC) class II molecules bind to numerous peptides and display these on the cell surface for T cell recognition. In a given immune response, receptors on T cells recognize antigenic peptides that are a minor population of MHC class II-bound peptides. To control which peptides are presented to T cells, it may be desirable to use recombinant MHC molecules with covalently bound antigenic peptides. To study T cell responses to such homogeneous peptide-MHC complexes, we engineered an HLA-DR1 cDNA coding for influenza hemagglutinin, influenza matrix, or HIV p24 gag peptides covalently attached via a peptide spacer to the N terminus of the DR1 beta chain. Co-transfection with DR alpha cDNA into mouse L cells resulted in surface expression of HLA-DR1 molecules that reacted with monoclonal antibodies (mAb) specific for correctly folded HLA-DR epitopes. This suggested that the spacer and peptide did not alter expression or folding of the molecule. We then engineered an additional peptide spacer between the C terminus of a truncated beta chain (without transmembrane or cytoplasmic domains) and the N terminus of full-length DR alpha chain. Transfection of this cDNA into mouse L cells resulted in surface expression of the entire covalently linked heterotrimer of peptide, beta chain, and alpha chain with the expected molecular mass of approximately 66 kDa. These single-chain HLA-DR1 molecules reacted with mAb specific for correctly folded HLA-DR epitopes, and identified one mAb with [MHC + peptide] specificity. Affinity-purified soluble secreted single-chain molecules with truncated alpha chain moved in electrophoresis as compact class II MHC dimers. Cell surface two-chain or single-chain HLA-DR1 molecules with a covalent HA peptide stimulated HLA-DR1-restricted HA-specific T cells. They were immunogenic in vitro for peripheral blood mononuclear cells. The two-chain and single-chain HLA-DR1 molecules with covalent HA peptide had reduced binding for the bacterial superantigens staphylococcal enterotoxin A and B and almost no binding for toxic shock syndrome toxin-1. The unique properties of these engineered HLA-DR1 molecules may facilitate our understanding of the complex nature of antigen recognition and aid in the development of novel vaccines with reduced superantigen binding. JF - European journal of immunology AU - Zhu, X AU - Bavari, S AU - Ulrich, R AU - Sadegh-Nasseri, S AU - Ferrone, S AU - McHugh, L AU - Mage, M AD - Laboratory of Biochemistry, DCBDC, NCI, NIH, Bethesda, MD 20892, USA. Y1 - 1997/08// PY - 1997 DA - August 1997 SP - 1933 EP - 1941 VL - 27 IS - 8 SN - 0014-2980, 0014-2980 KW - Antigens, Bacterial KW - 0 KW - DNA Primers KW - DNA, Complementary KW - Epitopes KW - HLA-DR1 Antigen KW - Recombinant Proteins KW - Superantigens KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Solubility KW - DNA, Complementary -- genetics KW - Epitopes -- genetics KW - DNA Primers -- genetics KW - Humans KW - Mice KW - Recombinant Proteins -- genetics KW - Precipitin Tests KW - Protein Binding KW - Molecular Weight KW - Polymerase Chain Reaction KW - Base Sequence KW - Protein Engineering KW - Transfection KW - Recombinant Proteins -- metabolism KW - In Vitro Techniques KW - Epitopes -- chemistry KW - Recombinant Proteins -- chemistry KW - T-Lymphocytes -- immunology KW - Cell Line KW - Epitopes -- metabolism KW - Protein Conformation KW - Superantigens -- metabolism KW - Antigens, Bacterial -- metabolism KW - HLA-DR1 Antigen -- metabolism KW - HLA-DR1 Antigen -- genetics KW - HLA-DR1 Antigen -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79280762?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+immunology&rft.atitle=A+recombinant+single-chain+human+class+II+MHC+molecule+%28HLA-DR1%29+as+a+covalently+linked+heterotrimer+of+alpha+chain%2C+beta+chain%2C+and+antigenic+peptide%2C+with+immunogenicity+in+vitro+and+reduced+affinity+for+bacterial+superantigens.&rft.au=Zhu%2C+X%3BBavari%2C+S%3BUlrich%2C+R%3BSadegh-Nasseri%2C+S%3BFerrone%2C+S%3BMcHugh%2C+L%3BMage%2C+M&rft.aulast=Zhu&rft.aufirst=X&rft.date=1997-08-01&rft.volume=27&rft.issue=8&rft.spage=1933&rft.isbn=&rft.btitle=&rft.title=European+journal+of+immunology&rft.issn=00142980&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-30 N1 - Date created - 1997-09-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of a dominant negative ras on myocardial hypertrophy by using adenoviral-mediated gene transfer. AN - 79269917; 9288147 AB - The small guanosine triphosphate-binding protein ras regulates a signal transduction cascade linking cell surface receptors to mitogen-activated protein kinase (MAPK). Because the molecular signaling mechanisms underlying cardiac hypertrophy remain unclear, the current study examined the regulatory role of ras in both the biochemical and morphologic aspects of hypertrophy. Adenoviral-mediated gene transfer was used to express a dominant negative mutant of ras (rasN17) at high efficiency in primary neonatal ventricular myocytes. Beta-galactosidase staining and Western blot analysis confirmed successful transfection and expression of the rasN17 gene product. MAPK activity was measured by an in vitro kinase assay resulting in radioactive phosphorus labeled product. Morphologic hypertrophy was assessed by fluorescein-conjugated phalloidin. Compared with uninfected or control adenoviral-infected cells, myocytes infected with rasN17 demonstrated attenuated basal MAPK activity. In contrast, rasN17 expression did not affect endothelin 1-induced MAPK activation. Morphologic studies showed that although rasN17 produced a phenotypic difference in the basal state, the ability of cardiac myocytes to morphologically respond to endothelin 1 stimulation, as manifested by sarcomeric reorganization, remained unaltered by the expression of the rasN17 gene product. Endothelin 1-stimulated MAPK activation and endothelin 1-induced morphologic hypertrophy are ras-independent processes. JF - Surgery AU - Pracyk, J B AU - Hegland, D D AU - Tanaka, K AD - Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md., USA. Y1 - 1997/08// PY - 1997 DA - August 1997 SP - 404 EP - 10; discussion 410-1 VL - 122 IS - 2 SN - 0039-6060, 0039-6060 KW - Endothelin-1 KW - 0 KW - Recombinant Fusion Proteins KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Abridged Index Medicus KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - Adenoviridae KW - Animals KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Enzyme Activation KW - Gene Expression KW - Sarcomeres -- pathology KW - Mutagenesis, Site-Directed KW - Rats KW - Animals, Newborn KW - Sarcomeres -- physiology KW - Rats, Sprague-Dawley KW - Transfection KW - Cells, Cultured KW - Genetic Vectors KW - Point Mutation KW - beta-Galactosidase -- biosynthesis KW - Endothelin-1 -- pharmacology KW - Genes, ras KW - Myocardium -- cytology KW - Myocardium -- pathology KW - Myocardium -- enzymology KW - Cardiomegaly -- physiopathology KW - Cardiomegaly -- pathology KW - Cardiomegaly -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79269917?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Surgery&rft.atitle=Effect+of+a+dominant+negative+ras+on+myocardial+hypertrophy+by+using+adenoviral-mediated+gene+transfer.&rft.au=Pracyk%2C+J+B%3BHegland%2C+D+D%3BTanaka%2C+K&rft.aulast=Pracyk&rft.aufirst=J&rft.date=1997-08-01&rft.volume=122&rft.issue=2&rft.spage=404&rft.isbn=&rft.btitle=&rft.title=Surgery&rft.issn=00396060&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-02 N1 - Date created - 1997-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Accelerated onset of uterine tumors in transgenic mice with aberrant expression of the estrogen receptor after neonatal exposure to diethylstilbestrol. AN - 79269496; 9290700 AB - The role of estrogen and the estrogen receptor (ER) in the induction and promotion of tumors was investigated by using transgenic MT-mER mice, which overexpress the ER. It was hypothesized that because of this abnormal expression of the ER, the reproductive-tract tissues of the MT-mER mice may be more susceptible to tumors after neonatal exposure to the potent synthetic estrogen diethylstilbestrol (DES). Normally non-estrogen responsive tissues that may have expressed ER as a result of the transgene were also studied for DES-induced tumors. Wild-type and MT-mER littermates were treated with 2 micrograms/pup/d DES 1-5 d after birth and then killed at 4, 8, 12, and 18 mo of age. The DES-treated MT-mER mice demonstrated a significantly higher incidence of uterine adenocarcinoma at 8 mo (73%) than the DES-treated wild-type mice (46%). The tumors of the MT-mER mice were often more aggressive than those in the wild-type animals. These tumors were also preceeded at 4 mo by a significantly higher incidence of the preneoplastic lesion atypical hyperplasia in the MT-mER mice (26% compared with 0% in the wild-type mice). Other DES-induced abnormalities were observed at equal rates in the wild-type and MT-mER mice. Although no tumors were observed in untreated wild-type females, a single untreated MT-mER female had uterine adenocarcinoma at 18 mo. These data indicate that the level of ER present in a tissue may also be a determining factor in development of estrogen-responsive tumors. JF - Molecular carcinogenesis AU - Couse, J F AU - Davis, V L AU - Hanson, R B AU - Jefferson, W N AU - McLachlan, J A AU - Bullock, B C AU - Newbold, R R AU - Korach, K S AD - Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/08// PY - 1997 DA - August 1997 SP - 236 EP - 242 VL - 19 IS - 4 SN - 0899-1987, 0899-1987 KW - Carcinogens KW - 0 KW - Receptors, Estrogen KW - Diethylstilbestrol KW - 731DCA35BT KW - Index Medicus KW - Uterus -- metabolism KW - Mice, Inbred Strains KW - Animals KW - Hyperplasia -- chemically induced KW - Body Weight -- drug effects KW - Mice KW - Metaplasia -- chemically induced KW - Uterus -- pathology KW - Mice, Transgenic KW - Uterus -- drug effects KW - Female KW - Uterine Neoplasms -- ultrastructure KW - Cocarcinogenesis KW - Receptors, Estrogen -- biosynthesis KW - Adenocarcinoma -- chemically induced KW - Uterine Neoplasms -- chemically induced KW - Diethylstilbestrol -- toxicity KW - Adenocarcinoma -- ultrastructure KW - Carcinogens -- toxicity KW - Receptors, Estrogen -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79269496?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Accelerated+onset+of+uterine+tumors+in+transgenic+mice+with+aberrant+expression+of+the+estrogen+receptor+after+neonatal+exposure+to+diethylstilbestrol.&rft.au=Couse%2C+J+F%3BDavis%2C+V+L%3BHanson%2C+R+B%3BJefferson%2C+W+N%3BMcLachlan%2C+J+A%3BBullock%2C+B+C%3BNewbold%2C+R+R%3BKorach%2C+K+S&rft.aulast=Couse&rft.aufirst=J&rft.date=1997-08-01&rft.volume=19&rft.issue=4&rft.spage=236&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 - 1997-09-30 N1 - Date created - 1997-09-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retinoic acid as a therapy for emphysema? AN - 79268760; 9287482 AB - In concert with its action as a morphogen during embryonal development, retinoic acid appears to be able to regenerate lung alveoli in an experimental model of elastase-induced emphysema in rats, thereby inhibiting manifestation of the disease. The application to humans is now an interesting possibility. JF - Nutrition reviews AU - DeLuca, L M AU - Ross, S A AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 1997/08// PY - 1997 DA - August 1997 SP - 307 EP - 308 VL - 55 IS - 8 SN - 0029-6643, 0029-6643 KW - Tretinoin KW - 5688UTC01R KW - Pancreatic Elastase KW - EC 3.4.21.36 KW - Index Medicus KW - Rats KW - Animals KW - Humans KW - Emphysema -- chemically induced KW - Tretinoin -- therapeutic use KW - Emphysema -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79268760?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nutrition+reviews&rft.atitle=Retinoic+acid+as+a+therapy+for+emphysema%3F&rft.au=DeLuca%2C+L+M%3BRoss%2C+S+A&rft.aulast=DeLuca&rft.aufirst=L&rft.date=1997-08-01&rft.volume=55&rft.issue=8&rft.spage=307&rft.isbn=&rft.btitle=&rft.title=Nutrition+reviews&rft.issn=00296643&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-02 N1 - Date created - 1997-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of genetic alterations in uterine leiomyomas and leiomyosarcomas by comparative genomic hybridization. AN - 79265807; 9290705 AB - Uterine leiomyomas are the most prevalent tumor type in women of reproductive age and are the most common reason for hysterectomies. Although uterine leiomyomas are considered to be benign, they are a major public health concern for women. In contrast, leiomyosarcomas are rare but highly malignant uterine tumors. They may arise in uteri with preexisting leiomyomas and histologically sometimes resemble leiomyomas, thus causing controversy about whether leiomyosarcomas arise within leiomyomas. In this study, we used comparative genomic hybridization (CGH) to identify genetic alterations unique to each tumor type and alterations that are common between the two tumors. We analyzed 14 cases of uterine leiomyomas and eight cases of uterine leiomyosarcomas. Only two of the 14 leiomyomas exhibited genetic alterations, and those were restricted to gains on chromosomes 14 and 19 and losses on chromosomes 1 and 4. In addition, 68 leiomyomas were examined for loss of heterozygosity on chromosomes 1 and 4, and only three tumors exhibited any losses. In contrast, all eight leiomyosarcomas showed gains and losses of DNA by CGH, and in many cases multiple changes were observed. The most commonly observed genetic aberration, occurring in five tumors, was gains on both arms of chromosome 1, suggesting that this chromosome contains loci involved in the development of leiomyosarcoma. Our results do not provide evidence for the progression from benign leiomyoma to malignant leiomyosarcoma. Moreover, the large number of random chromosomal alterations in the leiomyosarcomas suggests that increased genetic instability plays a role in the formation of these tumors. JF - Molecular carcinogenesis AU - Packenham, J P AU - du Manoir, S AU - Schrock, E AU - Risinger, J I AU - Dixon, D AU - Denz, D N AU - Evans, J A AU - Berchuck, A AU - Barrett, J C AU - Devereux, T R AU - Ried, T AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/08// PY - 1997 DA - August 1997 SP - 273 EP - 279 VL - 19 IS - 4 SN - 0899-1987, 0899-1987 KW - DNA, Neoplasm KW - 0 KW - Index Medicus KW - Chromosomes, Human, Pair 1 KW - Humans KW - DNA, Neoplasm -- genetics KW - DNA, Neoplasm -- analysis KW - Nucleic Acid Hybridization KW - Female KW - Chromosomes, Human, Pair 4 KW - Gene Deletion KW - Leiomyoma -- genetics KW - Uterine Neoplasms -- genetics KW - Leiomyoma -- pathology KW - Chromosome Aberrations KW - Leiomyosarcoma -- pathology KW - Leiomyosarcoma -- genetics KW - Uterine Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79265807?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Analysis+of+genetic+alterations+in+uterine+leiomyomas+and+leiomyosarcomas+by+comparative+genomic+hybridization.&rft.au=Packenham%2C+J+P%3Bdu+Manoir%2C+S%3BSchrock%2C+E%3BRisinger%2C+J+I%3BDixon%2C+D%3BDenz%2C+D+N%3BEvans%2C+J+A%3BBerchuck%2C+A%3BBarrett%2C+J+C%3BDevereux%2C+T+R%3BRied%2C+T&rft.aulast=Packenham&rft.aufirst=J&rft.date=1997-08-01&rft.volume=19&rft.issue=4&rft.spage=273&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 - 1997-09-30 N1 - Date created - 1997-09-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Polymerase chain reaction-single-strand conformation polymorphism analysis for the VHL gene in chemically induced kidney tumors of rats using intron-derived primers. AN - 79264747; 9290699 AB - von Hippel-Lindau (VHL) gene mutations occur throughout three exons including the exon-intron boundaries in human VHL disease-associated and sporadic renal cell carcinomas. To explore the possible role of the VHL gene in chemically induced rat kidney tumors originating from various cell types, more than 150 bp of Fischer 344 and Noble rat VHL intron sequences flanking the three exons was determined by dideoxy sequencing. Five primer sets were selected for polymerase chain reaction amplification of the coding regions of rat VHL exons 1-3 and the exon-intron boundaries. Tissues from 10 renal eosinophilic epithelial tumors induced by N-nitrosoethyl(2-hydroxyethyl)amine, 10 nephroblastomas induced by N-nitroso-N-ethylurea, and seven renal mesenchymal tumors induced by N-nitrosomethyl(methoxymethyl)amine were examined for VHL mutations by polymerase chain reaction-single-strand conformation polymorphism analysis. No mutation was detected in any tumor type, indicating that VHL mutations are not involved in the pathogenesis of rat kidney tumors arising from the distal region of the renal tubules, the metanephric blastema, or stromal tissues of the cortex. JF - Molecular carcinogenesis AU - Shiao, Y H AU - Diwan, B A AU - Perantoni, A O AU - Calvert, R J AU - Zbar, B AU - Lerman, M I AU - Rice, J M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201, USA. Y1 - 1997/08// PY - 1997 DA - August 1997 SP - 230 EP - 235 VL - 19 IS - 4 SN - 0899-1987, 0899-1987 KW - DNA Primers KW - 0 KW - DNA, Neoplasm KW - Index Medicus KW - Animals KW - Exons KW - DNA, Neoplasm -- analysis KW - Wilms Tumor -- chemically induced KW - Wilms Tumor -- genetics KW - Polymorphism, Single-Stranded Conformational KW - Rats KW - Genetic Testing KW - Base Sequence KW - Rats, Inbred F344 KW - Molecular Sequence Data KW - DNA, Neoplasm -- genetics KW - Epithelium KW - Kidney Neoplasms -- genetics KW - Kidney Neoplasms -- chemically induced KW - Polymerase Chain Reaction -- methods KW - von Hippel-Lindau Disease -- genetics KW - Introns KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79264747?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Polymerase+chain+reaction-single-strand+conformation+polymorphism+analysis+for+the+VHL+gene+in+chemically+induced+kidney+tumors+of+rats+using+intron-derived+primers.&rft.au=Shiao%2C+Y+H%3BDiwan%2C+B+A%3BPerantoni%2C+A+O%3BCalvert%2C+R+J%3BZbar%2C+B%3BLerman%2C+M+I%3BRice%2C+J+M&rft.aulast=Shiao&rft.aufirst=Y&rft.date=1997-08-01&rft.volume=19&rft.issue=4&rft.spage=230&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 - 1997-09-30 N1 - Date created - 1997-09-30 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U78352; GENBANK; U78353; U78351; U78354 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drug abuse and addiction treatment research. The next generation. AN - 79259181; 9283502 JF - Archives of general psychiatry AU - Leshner, A I AD - National Institute on Drug Abuse, Rockville, MD 20857, USA. Y1 - 1997/08// PY - 1997 DA - August 1997 SP - 691 EP - 694 VL - 54 IS - 8 SN - 0003-990X, 0003-990X KW - Antipsychotic Agents KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Drug Therapy, Combination KW - Mental Disorders -- therapy KW - Combined Modality Therapy KW - Behavior Therapy KW - Mental Disorders -- epidemiology KW - Humans KW - Antipsychotic Agents -- therapeutic use KW - Diagnosis, Dual (Psychiatry) KW - Schizophrenia -- drug therapy KW - Schizophrenia -- epidemiology KW - Research -- trends KW - Comorbidity KW - Substance-Related Disorders -- therapy KW - Substance-Related Disorders -- diagnosis KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79259181?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+general+psychiatry&rft.atitle=Drug+abuse+and+addiction+treatment+research.+The+next+generation.&rft.au=Leshner%2C+A+I&rft.aulast=Leshner&rft.aufirst=A&rft.date=1997-08-01&rft.volume=54&rft.issue=8&rft.spage=691&rft.isbn=&rft.btitle=&rft.title=Archives+of+general+psychiatry&rft.issn=0003990X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-16 N1 - Date created - 1997-09-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Arch Gen Psychiatry. 1997 Aug;54(8):713-20 [9283506] Arch Gen Psychiatry. 1997 Aug;54(8):700-5 [9283504] Arch Gen Psychiatry. 1997 Aug;54(8):696-9 [9283503] Arch Gen Psychiatry. 1997 Aug;54(8):737-42 [9283509] Arch Gen Psychiatry. 1997 Aug;54(8):730-5 [9283508] Arch Gen Psychiatry. 1997 Aug;54(8):706-12 [9283505] Arch Gen Psychiatry. 1997 Aug;54(8):721-6 [9283507] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevalence, characteristics, and impact of childhood sexual abuse in a Southwestern American Indian tribe. AN - 79252760; 9280382 AB - There were two objectives; first, to investigate the prevalence and characteristics of child sexual abuse in an American Indian community, and second, to determine whether persons with histories of child sexual abuse are at greater risk to develop psychiatric disorders and behavioral problems than persons who report no such history. A sample of 582 Southwestern American Indian tribal members was collected for a genetic and linkage study on alcoholism and psychiatric disorders in three large and interrelated pedigrees. Subjects were recruited from the community without knowledge of their clinical histories or those of their relatives. Child sexual abuse and psychiatric disorders were assessed using a semi-structured psychiatric interview. Females were more likely to be sexually abused as children (49%) than were males (14%). Intrafamilial members accounted for 78% of the reported child sexual abuse. Sexually abused males and females were more likely to report childhood and adult behavioral problems than were nonabused subjects. There was a strong relationship between multiple psychiatric disorders and child sexual abuse, with sexually abused males and females more likely to be diagnosed with > or = 3 psychiatric disorders, both including and excluding alcohol dependence or abuse, than were nonabused subjects. Child sexual abuse in this population is both an index of family dysfunction and community disorganization as well as a predictor of later behavioral patterns and psychopathology. JF - Child abuse & neglect AU - Robin, R W AU - Chester, B AU - Rasmussen, J K AU - Jaranson, J M AU - Goldman, D AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, USA. Y1 - 1997/08// PY - 1997 DA - August 1997 SP - 769 EP - 787 VL - 21 IS - 8 SN - 0145-2134, 0145-2134 KW - Index Medicus KW - Southwestern United States -- epidemiology KW - Age Factors KW - Odds Ratio KW - Chi-Square Distribution KW - Humans KW - Retrospective Studies KW - Aged KW - Child KW - Neurotic Disorders -- epidemiology KW - Cohort Effect KW - Aged, 80 and over KW - Juvenile Delinquency -- statistics & numerical data KW - Adult KW - Sampling Studies KW - Adolescent KW - Male KW - Social Behavior Disorders -- epidemiology KW - Age of Onset KW - Child, Preschool KW - Cross-Sectional Studies KW - Logistic Models KW - Confidence Intervals KW - Middle Aged KW - Sex Distribution KW - Female KW - Substance-Related Disorders -- epidemiology KW - Prevalence KW - Child Abuse, Sexual -- ethnology KW - Child Abuse, Sexual -- psychology KW - Family Health -- ethnology KW - Child Abuse, Sexual -- statistics & numerical data KW - Indians, North American -- psychology KW - Indians, North American -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79252760?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Child+abuse+%26+neglect&rft.atitle=Prevalence%2C+characteristics%2C+and+impact+of+childhood+sexual+abuse+in+a+Southwestern+American+Indian+tribe.&rft.au=Robin%2C+R+W%3BChester%2C+B%3BRasmussen%2C+J+K%3BJaranson%2C+J+M%3BGoldman%2C+D&rft.aulast=Robin&rft.aufirst=R&rft.date=1997-08-01&rft.volume=21&rft.issue=8&rft.spage=769&rft.isbn=&rft.btitle=&rft.title=Child+abuse+%26+neglect&rft.issn=01452134&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-31 N1 - Date created - 1997-10-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oral tolerance in a murine model of relapsing experimental autoimmune uveoretinitis (EAU): induction of protective tolerance in primed animals. AN - 79248232; 9276535 AB - Oral administration of uveitogenic retinal antigens suppresses the expression of EAU induced by a subsequent immunization with these antigens. Effectiveness and mechanisms of oral tolerance in EAU have mainly been studied in the acute, monophasic model in Lewis rats by feeding antigen prior to induction of disease. In this study we investigated the effect of oral tolerance induction in the acute as well as the chronic-relapsing models in the B10.A mouse. In acute murine EAU we could effectively suppress disease by induction of oral tolerance prior to immunization. In the chronic-relapsing EAU, antigen feeding was started only after the animals had recovered from their first attack of uveitis. Under these experimental conditions the subsequent relapse was largely prevented. These experiments demonstrate that oral tolerance may have practical clinical implications in uveitis, which is predominantly a chronic-relapsing condition in humans. JF - Clinical and experimental immunology AU - Thurau, S R AU - Chan, C C AU - Nussenblatt, R B AU - Caspi, R R AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 1997/08// PY - 1997 DA - August 1997 SP - 370 EP - 376 VL - 109 IS - 2 SN - 0009-9104, 0009-9104 KW - Eye Proteins KW - 0 KW - Retinol-Binding Proteins KW - interstitial retinol-binding protein KW - Index Medicus KW - Acute Disease KW - Administration, Oral KW - Animals KW - Disease Models, Animal KW - Mice KW - Immunization KW - Recurrence KW - Lymphocyte Activation KW - Retinol-Binding Proteins -- immunology KW - Eye Proteins -- immunology KW - Chronic Disease KW - Female KW - Male KW - Uveitis -- prevention & control KW - Autoimmune Diseases -- prevention & control KW - Uveitis -- pathology KW - Retinitis -- pathology KW - Retinitis -- prevention & control KW - Autoimmune Diseases -- pathology KW - Autoimmune Diseases -- chemically induced KW - Retinitis -- chemically induced KW - Immune Tolerance KW - Uveitis -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79248232?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+and+experimental+immunology&rft.atitle=Oral+tolerance+in+a+murine+model+of+relapsing+experimental+autoimmune+uveoretinitis+%28EAU%29%3A+induction+of+protective+tolerance+in+primed+animals.&rft.au=Thurau%2C+S+R%3BChan%2C+C+C%3BNussenblatt%2C+R+B%3BCaspi%2C+R+R&rft.aulast=Thurau&rft.aufirst=S&rft.date=1997-08-01&rft.volume=109&rft.issue=2&rft.spage=370&rft.isbn=&rft.btitle=&rft.title=Clinical+and+experimental+immunology&rft.issn=00099104&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-09 N1 - Date created - 1997-09-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of abused drugs on psychomotor performance. AN - 79220565; 9260070 AB - Some abused drugs have been reported to alter performance on naturalistic tasks such as driving and also on laboratory tasks. The performance effects of several drug classes were examined using a repeated measures design. Eight volunteers were administered 2 doses of ethanol, marijuana, amphetamine, hydromorphone, pentobarbital, or placebo on separate days. The larger dose of each increased subjective drug strength; however, only ethanol and pentobarbital impaired performance on circular lights, digit symbol substitution, and serial math tasks. Both ethanol and pentobarbital impaired performance on card-sorting tasks; impairment was evident at lower doses as the cognitive load increased. Results illustrate differences among drugs in producing performance impairment at doses that cause subjective effects. Increasing cognitive requirements uncovered performance impairment at lower doses. JF - Experimental and clinical psychopharmacology AU - Pickworth, W B AU - Rohrer, M S AU - Fant, R V AD - Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. wpickwo@irp.nida.nih.gov Y1 - 1997/08// PY - 1997 DA - August 1997 SP - 235 EP - 241 VL - 5 IS - 3 SN - 1064-1297, 1064-1297 KW - Central Nervous System Depressants KW - 0 KW - Central Nervous System Stimulants KW - Hypnotics and Sedatives KW - Narcotics KW - Ethanol KW - 3K9958V90M KW - Amphetamine KW - CK833KGX7E KW - Pentobarbital KW - I4744080IR KW - Hydromorphone KW - Q812464R06 KW - Index Medicus KW - Central Nervous System Stimulants -- pharmacology KW - Double-Blind Method KW - Ethanol -- pharmacology KW - Hydromorphone -- pharmacology KW - Humans KW - Narcotics -- pharmacology KW - Hypnotics and Sedatives -- pharmacology KW - Pentobarbital -- pharmacology KW - Central Nervous System Depressants -- pharmacology KW - Marijuana Smoking -- psychology KW - Cognition -- drug effects KW - Adult KW - Cross-Over Studies KW - Amphetamine -- pharmacology KW - Male KW - Psychomotor Performance -- drug effects KW - Substance-Related Disorders -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79220565?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effects+of+abused+drugs+on+psychomotor+performance.&rft.au=Pickworth%2C+W+B%3BRohrer%2C+M+S%3BFant%2C+R+V&rft.aulast=Pickworth&rft.aufirst=W&rft.date=1997-08-01&rft.volume=5&rft.issue=3&rft.spage=235&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 - 1997-09-22 N1 - Date created - 1997-09-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Anticonvulsant and behavioral effects of neuroactive steroids alone and in conjunction with diazepam. AN - 79216338; 9262314 AB - Epilepsy continues to be a significant clinical problem as current medications neither adequately control seizures nor are free of untoward side-effects. Modulation of the neuroactive steroid site on the gamma-aminobutyric acid (GABA)A receptor complex may be an important new direction for pharmaceutical interventions in epilepsy. In this study we evaluated the protective actions of four neuroactive steroids, 3alpha-hydroxy-5alpha-pregnan-20-one, the 3beta-methylated analog, ganaxolone (3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one), 3alpha-hydroxy-5beta-pregnan-20-one and Co 2-1068 (3beta-(4acetylphenyl)ethynyl-3alpha,21-dihydroxy-5beta++ +-20-one-21-hemisuccinate), against several standard convulsive tests in male, Swiss-Webster mice. Consistent with their GABAergic actions, the neuroactive steroids as well as diazepam and phenobarbital dose-dependently protected against clonic convulsions induced by pentylenetetrazol; the N-methyl-D-aspartate receptor antagonist, dizocilpine, was ineffective. In contrast to diazepam and phenobarbital, however, all of the neuroactive steroids and dizocilpine produced full protection against cocaine-induced convulsions. Some of the neuroactive steroids, as well as dizocilpine, were efficacious against the seizures and lethality induced by N-methyl-D-aspartate. Pregnenolone, a steroid devoid of GABAergic activity, was not effective in any of the convulsant models. Although all of the compounds produced motor toxicity in high doses as measured by the inverted-screen test, the neuroactive steroids demonstrated an equivalent or improved separation between anticonvulsant potency and motoric impairment. Inactive doses of the neuroactive steroids markedly enhanced the anticonvulsant effects of diazepam against pentylenetetrazol without significantly increasing motor toxicity. This adjunct treatment resulted in protective indices ranging from 60 to 360 compared to 12 for diazepam alone. The distinct profile of anticonvulsant activity of the neuroactive steroids may be related to their combined actions on gamma-aminobutyric acid, N-methyl-D-aspartate receptors, or voltage-operated Ca++ channels. These results help to define the neuroactive steroids as a novel class of antiepileptic agents and suggest their potential in clinical practice. JF - The Journal of pharmacology and experimental therapeutics AU - Gasior, M AU - Carter, R B AU - Goldberg, S R AU - Witkin, J M AD - Preclinical Pharmacology Laboratory, Addiction Research Center, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA. mgasior@irp.nida.nih.gov Y1 - 1997/08// PY - 1997 DA - August 1997 SP - 543 EP - 553 VL - 282 IS - 2 SN - 0022-3565, 0022-3565 KW - Anticonvulsants KW - 0 KW - Excitatory Amino Acid Antagonists KW - Neuroprotective Agents KW - Steroids KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - Cocaine KW - I5Y540LHVR KW - Diazepam KW - Q3JTX2Q7TU KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Animals KW - Phenobarbital -- pharmacology KW - Mice KW - Cocaine -- pharmacology KW - Male KW - Neuroprotective Agents -- pharmacology KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Dizocilpine Maleate -- pharmacology KW - Diazepam -- administration & dosage KW - Anticonvulsants -- pharmacology KW - Diazepam -- pharmacology KW - Steroids -- pharmacology KW - Steroids -- administration & dosage KW - Motor Activity -- drug effects KW - Anticonvulsants -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79216338?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neurology&rft.atitle=A+gene+for+Parkinson+disease.&rft.au=Chase%2C+T+N&rft.aulast=Chase&rft.aufirst=T&rft.date=1997-09-01&rft.volume=54&rft.issue=9&rft.spage=1156&rft.isbn=&rft.btitle=&rft.title=Archives+of+neurology&rft.issn=00039942&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-11 N1 - Date created - 1997-09-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retinoic acid inhibition of cell cycle progression in MCF-7 human breast cancer cells. AN - 79215095; 9260897 AB - Cell cycle analysis indicates that retinoic acid (RA) inhibition of MCF-7 cell growth occurs through induction of G1 arrest with a concomitant reduction in the proportion of cells in S and G2 + M phases. RA did not affect cyclins D1, A, and E and cyclin-dependent kinase 2 (CDK2) expression, but significantly reduced cyclin D3 and CDK4 expression after 24 h. RA also inhibited cyclin B1 and CDC2 expression, possibly responsible for the reduction of the proportion of cells in G2 + M and S phases. RA did not induce p16 and p27 expression, but obviously reduced p21 level in MCF-7 cells. The retinoid markedly reduced pRB protein level and abrogated pRB phosphorylation after 48 h; it also reduced transcription factor E2F1 expression at both the mRNA and protein levels. E2F1 promoter activity was reduced by 60%, which is probably responsible, at least in part, for the reduction of E2F1 expression in RA-treated MCF-7 cells. These observations demonstrate a marked effect of RA on some of the key cell cycle regulatory proteins in MCF-7 cells. Cyclin D3 and CDK4 are likely the early targets of RA, followed by reduced pRB expression and phosphorylation, as well as by the inhibition of the E2F1 transcription factor which controls progression from G1 to S phase. Most of these events precede the observed reduction in MCF-7 cell growth, which begins at Day 3 of RA treatment. JF - Experimental cell research AU - Zhu, W Y AU - Jones, C S AU - Kiss, A AU - Matsukuma, K AU - Amin, S AU - De Luca, L M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1997/08/01/ PY - 1997 DA - 1997 Aug 01 SP - 293 EP - 299 VL - 234 IS - 2 SN - 0014-4827, 0014-4827 KW - CDKN1A protein, human KW - 0 KW - Carrier Proteins KW - Cell Cycle Proteins KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - DNA-Binding Proteins KW - E2F Transcription Factors KW - E2F1 Transcription Factor KW - E2F1 protein, human KW - Enzyme Inhibitors KW - RNA, Messenger KW - Retinoblastoma Protein KW - Retinoblastoma-Binding Protein 1 KW - Transcription Factor DP1 KW - Transcription Factors KW - Tretinoin KW - 5688UTC01R KW - Cyclin-Dependent Kinases KW - EC 2.7.11.22 KW - Index Medicus KW - Cyclin-Dependent Kinases -- metabolism KW - Cyclins -- biosynthesis KW - Transcription Factors -- metabolism KW - Humans KW - Transcription Factors -- genetics KW - RNA, Messenger -- biosynthesis KW - Phosphorylation KW - Retinoblastoma Protein -- metabolism KW - Cyclin-Dependent Kinases -- antagonists & inhibitors KW - Cyclins -- metabolism KW - Promoter Regions, Genetic -- genetics KW - Gene Expression Regulation -- drug effects KW - Cell Division KW - Tretinoin -- pharmacology KW - Carcinoma -- pathology KW - Breast Neoplasms -- pathology KW - Carcinoma -- enzymology KW - Breast Neoplasms -- metabolism KW - Carcinoma -- metabolism KW - Breast Neoplasms -- enzymology KW - Cell Cycle -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79215095?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+cell+research&rft.atitle=Retinoic+acid+inhibition+of+cell+cycle+progression+in+MCF-7+human+breast+cancer+cells.&rft.au=Zhu%2C+W+Y%3BJones%2C+C+S%3BKiss%2C+A%3BMatsukuma%2C+K%3BAmin%2C+S%3BDe+Luca%2C+L+M&rft.aulast=Zhu&rft.aufirst=W&rft.date=1997-08-01&rft.volume=234&rft.issue=2&rft.spage=293&rft.isbn=&rft.btitle=&rft.title=Experimental+cell+research&rft.issn=00144827&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-11 N1 - Date created - 1997-09-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Illegal drug use among rural adults: mental health consequences and treatment utilization. AN - 79214801; 9261493 AB - This study uses the National Household Survey on Drug Abuse to examine mental health consequences and treatment utilization among nonmetropolitan and rural adults. The study employs an ecological system perspective, dividing the study population into three groups: nonmetropolitan-rural, nonmetropolitan-urban, and metropolitan-rural. Logistic regression analysis is used to examine four sets of factors related to self-report of mental health problems among drug-using adults, including community level features, family characteristics, personal characteristics, and stress factors. Perceived ease of purchasing cocaine, number of moves in last five years, employment in blue-collar occupations, number of jobs in last five years, and residence in neighborhoods with a low rate (< 10%) of minority households were significantly related to self-report problems. Results of the analysis are discussed in terms of barriers to utilization of treatment and rehabilitation services among nonmetropolitan and rural adults, such as availability and access to facilities and professional services, social stigma, ability to afford services, and the difficulty for rural communities to support inhospital and outpatient services. JF - The American journal of drug and alcohol abuse AU - Robertson, E B AU - Donnermeyer, J F AD - National Institute on Drug Abuse, Rockville, Maryland, USA. Y1 - 1997/08// PY - 1997 DA - August 1997 SP - 467 EP - 484 VL - 23 IS - 3 SN - 0095-2990, 0095-2990 KW - Psychotropic Drugs KW - 0 KW - Street Drugs KW - Index Medicus KW - Urban Population -- statistics & numerical data KW - Humans KW - Minority Groups -- statistics & numerical data KW - Aged KW - Unemployment -- statistics & numerical data KW - Comorbidity KW - Cross-Sectional Studies KW - Population Density KW - Risk Factors KW - Adult KW - Incidence KW - Middle Aged KW - United States -- epidemiology KW - Female KW - Male KW - Rural Population -- statistics & numerical data KW - Mental Disorders -- epidemiology KW - Community Mental Health Services -- utilization KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79214801?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+drug+and+alcohol+abuse&rft.atitle=Illegal+drug+use+among+rural+adults%3A+mental+health+consequences+and+treatment+utilization.&rft.au=Robertson%2C+E+B%3BDonnermeyer%2C+J+F&rft.aulast=Robertson&rft.aufirst=E&rft.date=1997-08-01&rft.volume=23&rft.issue=3&rft.spage=467&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+drug+and+alcohol+abuse&rft.issn=00952990&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-30 N1 - Date created - 1997-09-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Advanced-stage cervical carcinomas are defined by a recurrent pattern of chromosomal aberrations revealing high genetic instability and a consistent gain of chromosome arm 3q. AN - 79211467; 9258658 AB - We have analyzed 30 cases of advanced-stage cervical squamous cell carcinoma (stages IIb-IV) by comparative genomic hybridization (CGH). The most consistent chromosomal gain in the aneuploid tumors was mapped to chromosome arm 3q in 77% of the cases. Acquisition of genetic material also occurred frequently on Iq (47%), 5p (30%), 6p (27%), and 20 (23%). Recurrent losses were mapped on 2q (33%), 3p (50%), 4 (33%), 8p (23%), and 13q (27%). High-level copy number increases were mapped to chromosome 8, chromosome arms 3q, 5p, 8q, 12p, 14q, 17q, 19q, 20p, and 20q, and chromosomal bands 3q26-27, 9p23-24, 11q22-23, and 12p13. In the majority of the cases, the presence of high-risk human papilloma virus genomes was detected. High proliferative activity was accompanied by crude aneuploidy. Increased p21/WAF-I activity, but low or undetectable expression of TP53 were representative for the immunophenotype. This study confirms the importance of a gain of chromosome arm 3q in cervical carcinogenesis and identifies additional, recurrent chromosomal aberrations that are required for progression from stage I tumors to advanced-stage carcinomas. JF - Genes, chromosomes & cancer AU - Heselmeyer, K AU - Macville, M AU - Schröck, E AU - Blegen, H AU - Hellström, A C AU - Shah, K AU - Auer, G AU - Ried, T AD - Diagnostic Development Branch, National Center for Human Genome Research, National Institutes of Health, Bethesda, MD 20892-4470, USA. Y1 - 1997/08// PY - 1997 DA - August 1997 SP - 233 EP - 240 VL - 19 IS - 4 SN - 1045-2257, 1045-2257 KW - DNA, Neoplasm KW - 0 KW - Index Medicus KW - Karyotyping KW - Neoplasm Staging KW - Humans KW - Tumor Virus Infections KW - Aged KW - DNA, Neoplasm -- analysis KW - Nucleic Acid Hybridization KW - Papillomaviridae -- isolation & purification KW - Adult KW - Papillomavirus Infections KW - Flow Cytometry KW - Middle Aged KW - Ploidies KW - Cell Cycle KW - Immunohistochemistry KW - Female KW - Carcinoma, Squamous Cell -- pathology KW - Chromosomes, Human, Pair 3 -- genetics KW - Chromosome Aberrations KW - Carcinoma, Squamous Cell -- genetics KW - Uterine Cervical Neoplasms -- genetics KW - Uterine Cervical Neoplasms -- pathology KW - Carcinoma, Squamous Cell -- virology KW - Uterine Cervical Neoplasms -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79211467?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes%2C+chromosomes+%26+cancer&rft.atitle=Advanced-stage+cervical+carcinomas+are+defined+by+a+recurrent+pattern+of+chromosomal+aberrations+revealing+high+genetic+instability+and+a+consistent+gain+of+chromosome+arm+3q.&rft.au=Heselmeyer%2C+K%3BMacville%2C+M%3BSchr%C3%B6ck%2C+E%3BBlegen%2C+H%3BHellstr%C3%B6m%2C+A+C%3BShah%2C+K%3BAuer%2C+G%3BRied%2C+T&rft.aulast=Heselmeyer&rft.aufirst=K&rft.date=1997-08-01&rft.volume=19&rft.issue=4&rft.spage=233&rft.isbn=&rft.btitle=&rft.title=Genes%2C+chromosomes+%26+cancer&rft.issn=10452257&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-24 N1 - Date created - 1997-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutations of the conserved DRS motif in the second intracellular loop of the gonadotropin-releasing hormone receptor affect expression, activation, and internalization. AN - 79209767; 9259312 AB - The GnRH receptor is an unusual member of the G protein-coupled receptor (GPCR) superfamily with several unique features. One of these is a variant of the conserved DRY motif that is located at the junction of the third transmembrane domain and the second intracellular (2i) loop of most GPCRs. In the GnRH receptor, the Tyr residue of the conserved triplet is replaced by Ser, giving a DRS sequence. The aspartate and arginine residues of the triplet are highly conserved in almost all GPCRs. The functional importance of these residues was evaluated in wild type and mutant GnRH receptors expressed in COS-7 cells. Mutants in which Asp138 was replaced by Asn or Glu were poorly expressed, but showed significantly increased internalization and exhibited augmented inositol phosphate generation to maximal agonist stimulation compared with the wild type receptor. In contrast, receptors in which Arg139 was substituted with Gln, Ala, or Ser showed reduced internalization, and the GnRH-induced inositol phosphate response for the Arg139Gln mutant was significantly impaired in proportion to its low expression level. Replacing Ser140 with Ala affected neither internalization nor signal transduction. The role of the polar amino acids at the C terminus of the 2i loop was evaluated in two additional mutants (Ser151Ala, Ser153Ala, and Ser151Ala, Ser153Ala, Lys154Gln, Glu156Gln). Both of these mutants exhibited agonist-induced inositol phosphate responses similar to that of the wild type receptor, but showed increased receptor internalization. This mutational analysis indicates that the conserved Asp and Arg residues in the DRY/S triplet make important contributions to the structural integrity of the receptor and influence receptor expression, agonist-induced activation, and internalization. JF - Molecular endocrinology (Baltimore, Md.) AU - Arora, K K AU - Cheng, Z AU - Catt, K J AD - Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/08// PY - 1997 DA - August 1997 SP - 1203 EP - 1212 VL - 11 IS - 9 SN - 0888-8809, 0888-8809 KW - Inositol Phosphates KW - 0 KW - Iodine Radioisotopes KW - Receptors, LHRH KW - Recombinant Proteins KW - Gonadotropin-Releasing Hormone KW - 33515-09-2 KW - Guanosine 5'-O-(3-Thiotriphosphate) KW - 37589-80-3 KW - Index Medicus KW - Recombinant Proteins -- drug effects KW - Animals KW - COS Cells KW - Inositol Phosphates -- metabolism KW - Amino Acid Sequence KW - Recombinant Proteins -- genetics KW - Guanosine 5'-O-(3-Thiotriphosphate) -- pharmacology KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Gonadotropin-Releasing Hormone -- metabolism KW - Conserved Sequence KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Signal Transduction KW - Protein Conformation KW - Receptors, LHRH -- drug effects KW - Receptors, LHRH -- genetics KW - Mutation KW - Receptors, LHRH -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79209767?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.atitle=Mutations+of+the+conserved+DRS+motif+in+the+second+intracellular+loop+of+the+gonadotropin-releasing+hormone+receptor+affect+expression%2C+activation%2C+and+internalization.&rft.au=Arora%2C+K+K%3BCheng%2C+Z%3BCatt%2C+K+J&rft.aulast=Arora&rft.aufirst=K&rft.date=1997-08-01&rft.volume=11&rft.issue=9&rft.spage=1203&rft.isbn=&rft.btitle=&rft.title=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.issn=08888809&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-06 N1 - Date created - 1997-10-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutagenesis reveals structure-activity parallels between human A2A adenosine receptors and biogenic amine G protein-coupled receptors. AN - 79205629; 9258366 AB - Structure-affinity relationships for ligand binding at the human A2A adenosine receptor have been probed using site-directed mutagenesis in the transmembrane helical domains (TMs). The mutant receptors were expressed in COS-7 cells and characterized by binding of the radioligands [3H]CGS21680, [3H]NECA, and [3H]XAC. Three residues, at positions essential for ligand binding in other G protein-coupled receptors, were individually mutated. The residue V(3.32) in the A2A receptor that is homologous to the essential aspartate residue of TM3 in the biogenic amine receptors, i.e., V84(3.32), may be substituted with L (present in the A3 receptor) but not with D (in biogenic amine receptors) or A. H250(6.52), homologous to the critical N507 of rat m3 muscarinic acetylcholine receptors, may be substituted with other aromatic residues or with N but not with A (Kim et al. J. Biol. Chem. 1995, 270, 13987-13997). H278(7.43), homologous to the covalent ligand anchor site in rhodopsin, may not be substituted with either A, K, or N. Both V84L(3.32) and H250N(6.52) mutant receptors were highly variable in their effect on ligand competition depending on the structural class of the ligand. Adenosine-5'-uronamide derivatives were more potent at the H250N(6.52) mutant receptor than at wild type receptors. Xanthines tended to be close in potency (H250N(6.52)) or less potent (V84L(3.32)) than at wild type receptors. The affinity of CGS21680 increased as the pH was lowered to 5.5 in both the wild type and H250N(6.52) mutant receptors. Thus, protonation of H250(6.52) is not involved in this pH dependence. These data are consistent with a molecular model predicting the proximity of bound agonist ligands to TM3, TM5, TM6, and TM7. JF - Journal of medicinal chemistry AU - Jiang, Q AU - Lee, B X AU - Glashofer, M AU - van Rhee, A M AU - Jacobson, K A AD - Molecular Recognition Section, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/08/01/ PY - 1997 DA - 1997 Aug 01 SP - 2588 EP - 2595 VL - 40 IS - 16 SN - 0022-2623, 0022-2623 KW - Affinity Labels KW - 0 KW - Iodobenzenes KW - Ligands KW - Phenethylamines KW - Purinergic P1 Receptor Agonists KW - Receptor, Adenosine A2A KW - Receptors, Biogenic Amine KW - Receptors, Purinergic P1 KW - Xanthines KW - 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine KW - 120225-54-9 KW - 2-(4-(2-(2-((4-aminophenyl)methylcarbonylamino)ethylaminocarbonyl)ethyl)phenyl)ethylamino-5'-N-ethylcarboxamidoadenosine KW - 124190-27-8 KW - Adenosine-5'-(N-ethylcarboxamide) KW - 35920-39-9 KW - 8-(4-((2-aminoethyl)aminocarbonylmethyloxy)phenyl)-1,3-dipropylxanthine KW - 96865-92-8 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Adenosine KW - K72T3FS567 KW - Index Medicus KW - Animals KW - COS Cells KW - Models, Molecular KW - Adenosine -- analogs & derivatives KW - Humans KW - Hydrogen-Ion Concentration KW - Xanthines -- metabolism KW - Structure-Activity Relationship KW - Rats KW - Phenethylamines -- metabolism KW - Mutagenesis, Site-Directed KW - GTP-Binding Proteins -- metabolism KW - Affinity Labels -- metabolism KW - Enzyme-Linked Immunosorbent Assay KW - Models, Chemical KW - Iodobenzenes -- metabolism KW - Adenosine -- metabolism KW - Receptors, Purinergic P1 -- genetics KW - Receptors, Biogenic Amine -- genetics KW - Receptors, Biogenic Amine -- metabolism KW - Receptors, Purinergic P1 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79205629?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Mutagenesis+reveals+structure-activity+parallels+between+human+A2A+adenosine+receptors+and+biogenic+amine+G+protein-coupled+receptors.&rft.au=Jiang%2C+Q%3BLee%2C+B+X%3BGlashofer%2C+M%3Bvan+Rhee%2C+A+M%3BJacobson%2C+K+A&rft.aulast=Jiang&rft.aufirst=Q&rft.date=1997-08-01&rft.volume=40&rft.issue=16&rft.spage=2588&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 - 1997-09-10 N1 - Date created - 1997-09-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Methods Enzymol. 1987;152:684-704 [3657593] J Med Chem. 1993 Apr 16;36(8):967-76 [8478909] J Biol Chem. 1989 Aug 15;264(23):13572-8 [2547766] Proc Natl Acad Sci U S A. 1989 Sep;86(17):6572-6 [2771944] J Biol Chem. 1989 Oct 5;264(28):16470-7 [2570781] J Pharmacol Exp Ther. 1989 Dec;251(3):888-93 [2600819] J Mol Recognit. 1989 Dec;2(4):170-8 [2561548] Biochem Pharmacol. 1990 Aug 15;40(4):827-34 [2143655] J Biol Chem. 1991 Jan 5;266(1):5-8 [1670767] Mol Pharmacol. 1991 Jul;40(1):8-15 [1649965] EMBO J. 1991 Dec;10(12):3729-34 [1657592] J Med Chem. 1992 Feb 7;35(3):407-22 [1738138] J Biol Chem. 1992 Apr 5;267(10):6770-5 [1532391] J Recept Res. 1992;12(2):149-69 [1583620] J Biol Chem. 1992 May 25;267(15):10764-70 [1587851] Drug Des Discov. 1995 Nov;13(2):133-54 [8872457] Mol Pharmacol. 1993 Jun;43(6):931-40 [8316224] J Biol Chem. 1994 Jan 28;269(4):2373-6 [8300561] J Biol Chem. 1994 Jan 28;269(4):2728-32 [8300604] Mol Pharmacol. 1994 May;45(5):871-7 [8190104] J Biol Chem. 1994 Jul 8;269(27):18016-20 [8027060] J Biol Chem. 1994 Jul 22;269(29):18870-6 [8034642] J Biol Chem. 1994 Sep 23;269(38):23383-6 [8089099] Biochem Biophys Res Commun. 1994 Sep 15;203(2):1096-101 [8093027] Eur J Pharmacol. 1994 Jun 15;268(1):95-104 [7925617] J Neurochem. 1994 Oct;63(4):1477-84 [7931300] Pharmacol Rev. 1994 Jun;46(2):143-56 [7938164] J Biol Chem. 1994 Nov 11;269(45):27900-6 [7961722] Neuron. 1995 Apr;14(4):825-31 [7718244] J Comput Aided Mol Des. 1995 Feb;9(1):44-54 [7751869] J Biol Chem. 1995 Jun 9;270(23):13987-97 [7775460] J Biol Chem. 1995 Sep 1;270(35):20485-90 [7657625] J Neurochem. 1995 Nov;65(5):2105-15 [7595496] J Med Chem. 1996 Jan 19;39(2):398-406 [8558508] J Med Chem. 1996 Feb 2;39(3):781-8 [8576921] J Med Chem. 1996 Jul 19;39(15):2980-9 [8709132] Mol Pharmacol. 1996 Sep;50(3):512-21 [8794889] Mol Pharmacol. 1996 Oct;50(4):789-98 [8863823] Eur J Pharmacol. 1996 Aug 29;310(2-3):269-72 [8884226] Mol Pharmacol. 1986 Apr;29(4):331-46 [3010074] Mol Cell Biol. 1983 Feb;3(2):280-9 [6300662] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] Biochem Pharmacol. 1973 Dec 1;22(23):3099-108 [4202581] Science. 1989 May 5;244(4904):569-72 [2541503] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clarithromycin lowers plasma zidovudine levels in persons with human immunodeficiency virus infection. AN - 79191435; 9257746 AB - The use of antiretroviral agents and drugs for the treatment and prophylaxis of opportunistic infections has lengthened the survival of persons with AIDS. In the era of multidrug therapy, drug interactions are important considerations in designing effective and tolerable regimens. Clarithromycin has had a significant impact on the treatment of disseminated Mycobacterium avium complex infection, and zidovudine is the best-studied and one of the most widely used antiretroviral agents in this population. We conducted a study to determine the maximally tolerated dose of clarithromycin and the pharmacokinetics of clarithromycin and zidovudine individually and in combination. Mixing studies were conducted to simulate potential interaction in the gastric environment. The simultaneous administration of zidovudine and clarithromycin had little impact on the pharmacokinetics of clarithromycin or of its major metabolite. However, coadministration of zidovudine and clarithromycin at three doses (500 mg orally [p.o.] twice daily [b.i.d.], 1,000 mg p.o. b.i.d., and 2,000 mg p.o. b.i.d.) reduced the maximum concentration of zidovudine by 41% (P < 0.005) and the area under the concentration-time curve from 0 to 4 h for zidovudine by 25% (P < 0.05) and increased the time to maximum concentration of zidovudine by 84% (P < 0.05), compared with zidovudine administered alone. Mixing studies did not detect the formation of insoluble complexes due to chelation, suggesting that the decrease in zidovudine concentrations results from some other mechanism. Simultaneous administration of zidovudine and clarithromycin appears to decrease the levels of zidovudine in serum, and it may be advisable that these drugs not be given at the same time. Drug interactions should be carefully evaluated in persons with advanced human immunodeficiency virus infection who are receiving multiple pharmacologic agents. JF - Antimicrobial agents and chemotherapy AU - Polis, M A AU - Piscitelli, S C AU - Vogel, S AU - Witebsky, F G AU - Conville, P S AU - Petty, B AU - Kovacs, J A AU - Davey, R T AU - Walker, R E AU - Falloon, J AU - Metcalf, J A AU - Craft, C AU - Lane, H C AU - Masur, H AD - National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, Maryland 20982-1880, USA. mpolis@nih.gov Y1 - 1997/08// PY - 1997 DA - August 1997 SP - 1709 EP - 1714 VL - 41 IS - 8 SN - 0066-4804, 0066-4804 KW - Anti-Bacterial Agents KW - 0 KW - Anti-HIV Agents KW - Zidovudine KW - 4B9XT59T7S KW - Clarithromycin KW - H1250JIK0A KW - Index Medicus KW - AIDS/HIV KW - Drug Interactions KW - Humans KW - Adult KW - Middle Aged KW - Time Factors KW - Male KW - Zidovudine -- pharmacokinetics KW - Anti-HIV Agents -- pharmacokinetics KW - HIV Infections -- blood KW - Clarithromycin -- pharmacology KW - Zidovudine -- blood KW - HIV Infections -- drug therapy KW - Anti-Bacterial Agents -- adverse effects KW - Anti-Bacterial Agents -- pharmacology KW - Clarithromycin -- pharmacokinetics KW - Anti-HIV Agents -- blood KW - Anti-Bacterial Agents -- pharmacokinetics KW - Clarithromycin -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79191435?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+agents+and+chemotherapy&rft.atitle=Clarithromycin+lowers+plasma+zidovudine+levels+in+persons+with+human+immunodeficiency+virus+infection.&rft.au=Polis%2C+M+A%3BPiscitelli%2C+S+C%3BVogel%2C+S%3BWitebsky%2C+F+G%3BConville%2C+P+S%3BPetty%2C+B%3BKovacs%2C+J+A%3BDavey%2C+R+T%3BWalker%2C+R+E%3BFalloon%2C+J%3BMetcalf%2C+J+A%3BCraft%2C+C%3BLane%2C+H+C%3BMasur%2C+H&rft.aulast=Polis&rft.aufirst=M&rft.date=1997-08-01&rft.volume=41&rft.issue=8&rft.spage=1709&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+agents+and+chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-25 N1 - Date created - 1997-09-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Antimicrob Agents Chemother. 1993 Nov;37(11):2364-70 [8031351] Ann Intern Med. 1994 Dec 15;121(12):905-11 [7978715] Ann Intern Med. 1994 Dec 15;121(12):974-6 [7978725] J Infect Dis. 1995 Mar;171(3):747-50 [7876634] Antimicrob Agents Chemother. 1995 Jun;39(6):1355-60 [7574530] N Engl J Med. 1996 Aug 8;335(6):377-83 [8676931] J Clin Pharmacol. 1993 Aug;33(8):719-26 [8408732] J Pharmacokinet Biopharm. 1978 Apr;6(2):165-75 [671222] J Antimicrob Chemother. 1989 Nov;24(5):719-29 [2599996] Am Rev Respir Dis. 1991 Sep;144(3 Pt 1):564-9 [1832527] J Chromatogr. 1991 Nov 15;571(1-2):199-208 [1839793] Arch Intern Med. 1993 Feb 8;153(3):368-72 [8427539] N Engl J Med. 1996 Aug 8;335(6):384-91 [8663871] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phe576 plays an important role in the secondary structure and intracellular signaling of the human luteinizing hormone/chorionic gonadotropin receptor. AN - 79185100; 9253338 AB - Recent studies have identified multiple activating mutations in the sixth transmembrane domain of LH/chorionic gonadotropin receptor (LH/CGR) in patients with male-limited precocious puberty. Computer analysis suggested that these mutations had an effect on the secondary structure of the third cytoplasmic loop and sixth transmembrane domain, and that Phe576 was a critical conformational bridging residue between these regions that might be important for receptor activity. We made four amino acid substitutions of the Phe576 (F576I, F576G, F576Y, F576E) in the LH/CG receptor to analyze its functional role. Computer analysis of secondary structure predicted that the F576E mutant changed the secondary structure to a totally helical conformation in the region of the third intracellular and sixth transmembrane domain. In contrast, the F576G, F576I, and F576Y mutants were predicted to change the helical conformation in the region to an extended conformation. In expression studies, mutations of Phe576 produced functional changes in cAMP and inositol phosphate (IP) signaling, and human CG (hCG) binding. Mutations predicted to cause an extended conformation exhibited two functional patterns: first, constitutively activating in cAMP signaling without changes in IP signaling or hCG binding (F576I and F576G), and second, constitutively activating in cAMP signaling with decreased hCG-induced cAMP and IP signaling and with both higher affinity and lower capacity of hCG binding (F576Y). The mutation predicted to cause a totally helical conformation resulted in no cAMP response and a minimal IP response to hCG stimulation, with negligible hCG binding (F576E). These data suggest that the common change induced by the F576I, F576G, and F576Y mutations to an extended conformation on the third cytoplasmic loop and sixth transmembrane domain of the LH/CGR results in increased Gs coupling and activation of adenylyl cyclase. The F576Y mutation appears to have an additional effect, beyond a modification in receptor conformation, that leads to higher affinity and lower capacity of hCG binding, as well as altered Gq coupling and phospholipase C activation. The F576E mutation has a distinct and different impact on receptor conformation, which leads to negligible hCG binding and minimal function; however, the F576E mutation may provide a clue to understanding the receptor mutations that result in loss of function and pseudohermaphroditism. We conclude that Phe576 plays an important role in the human LH/CGR with respect to receptor conformation, Gs coupling, and cAMP signaling consistent with predictions from mutations associated with male-limited precocious puberty. JF - The Journal of clinical endocrinology and metabolism AU - Yano, K AU - Kohn, L D AU - Saji, M AU - Okuno, A AU - Cutler, G B AD - Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA. Y1 - 1997/08// PY - 1997 DA - August 1997 SP - 2586 EP - 2591 VL - 82 IS - 8 SN - 0021-972X, 0021-972X KW - Chorionic Gonadotropin KW - 0 KW - Inositol Phosphates KW - Receptors, LH KW - Phenylalanine KW - 47E5O17Y3R KW - Cyclic AMP KW - E0399OZS9N KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - COS Cells KW - Inositol Phosphates -- metabolism KW - Humans KW - Amino Acid Sequence KW - Mutagenesis KW - Structure-Activity Relationship KW - Chorionic Gonadotropin -- pharmacology KW - Transfection KW - Chorionic Gonadotropin -- metabolism KW - Cyclic AMP -- metabolism KW - Molecular Sequence Data KW - Protein Conformation KW - Protein Structure, Secondary KW - Receptors, LH -- chemistry KW - Receptors, LH -- genetics KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79185100?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+endocrinology+and+metabolism&rft.atitle=Phe576+plays+an+important+role+in+the+secondary+structure+and+intracellular+signaling+of+the+human+luteinizing+hormone%2Fchorionic+gonadotropin+receptor.&rft.au=Yano%2C+K%3BKohn%2C+L+D%3BSaji%2C+M%3BOkuno%2C+A%3BCutler%2C+G+B&rft.aulast=Yano&rft.aufirst=K&rft.date=1997-08-01&rft.volume=82&rft.issue=8&rft.spage=2586&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+endocrinology+and+metabolism&rft.issn=0021972X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-28 N1 - Date created - 1997-08-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of supplemental beta-carotene, cigarette smoking, and alcohol consumption on serum carotenoids in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. AN - 79179388; 9250116 AB - We determined whether serum carotenoid or retinol concentrations were altered by beta-carotene supplementation in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study and whether such effects were modified by alcohol consumption or cigarette use. Participants in this substudy were 491 randomly selected men aged 58-76 y from the metropolitan Helsinki study center [237 receiving supplemental beta-carotene (20 mg/d) and 254 not receiving such supplementation]. Dietary carotenoids, retinol, and alcohol, and serum beta-carotene, alpha-tocopherol, retinol, and cholesterol were assessed at baseline. After an average of 6.7 y of supplementation, serum was collected and carotenoid, retinol, and alpha-tocopherol concentrations were determined by HPLC. Serum carotenoid fractions were highly correlated with each other (P 12.9 g/d, median) was related to lower (10-38%) concentrations of carotenoids, particularly beta-carotene, alpha-carotene, and beta-cryptoxanthin, in both the supplemented and unsupplemented groups. Smoking status did not significantly influence the supplementation-related differences in serum carotenoid and retinol values but concentrations of carotenoids were generally highest in participants who quit smoking while in the study and lowest in current smokers of > or = 20 cigarettes/d. This study showed that serum concentrations of non-beta-carotene carotenoids are altered by long-term beta-carotene supplementation and confirms the adverse effects of alcohol and cigarette smoking on serum carotenoids. JF - The American journal of clinical nutrition AU - Albanes, D AU - Virtamo, J AU - Taylor, P R AU - Rautalahti, M AU - Pietinen, P AU - Heinonen, O P AD - National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1997/08// PY - 1997 DA - August 1997 SP - 366 EP - 372 VL - 66 IS - 2 SN - 0002-9165, 0002-9165 KW - Placebos KW - 0 KW - beta Carotene KW - 01YAE03M7J KW - Carotenoids KW - 36-88-4 KW - Abridged Index Medicus KW - Index Medicus KW - Plants, Toxic KW - Double-Blind Method KW - Humans KW - Tobacco KW - Aged KW - Middle Aged KW - Male KW - beta Carotene -- administration & dosage KW - Smoking -- blood KW - Carotenoids -- blood KW - Alcohol Drinking -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79179388?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+clinical+nutrition&rft.atitle=Effects+of+supplemental+beta-carotene%2C+cigarette+smoking%2C+and+alcohol+consumption+on+serum+carotenoids+in+the+Alpha-Tocopherol%2C+Beta-Carotene+Cancer+Prevention+Study.&rft.au=Albanes%2C+D%3BVirtamo%2C+J%3BTaylor%2C+P+R%3BRautalahti%2C+M%3BPietinen%2C+P%3BHeinonen%2C+O+P&rft.aulast=Albanes&rft.aufirst=D&rft.date=1997-08-01&rft.volume=66&rft.issue=2&rft.spage=366&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+clinical+nutrition&rft.issn=00029165&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-08 N1 - Date created - 1997-09-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Am J Clin Nutr 1997 Dec;66(6):1491 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protein kinase C mediates angiotensin II-induced contractions and the release of endothelin and prostacyclin in rat aortic rings. AN - 79178036; 9250696 AB - Angiotensin II (Ang II) stimulation of vascular smooth muscle results in a myriad of intracellular signals that interact to produce the final physiologic response of the cell. We used rat aortic rings to investigate the role of protein kinase C (PKC) in Ang II-induced contractions and in the concomitant release of endothelin (ET) and prostacyclin (PGI2). Ang II (10(-9) M) produced a rapid contraction which was sustained for 10 min. When aortic rings were pretreated with graded concentrations of each of the four different inhibitors of PKC, that is, (i) 1-(5-isoquinolinesulfonylmethyl) piperazine (H7); (ii) 1-(5-isoquinolinesulfonyl) piperazine(CL); (iii) staurosporine; or (iv) calphostin C, inhibition of Ang II-induced contractions began at 10(-9) M, and was nearly complete at 10(-6) M. Ang II-induced contractions were associated with a 10-fold increase in the release of both ET and PGI2. Pretreatment with 10(-6) M of any one of the same four PKC inhibitors blocked Ang II-induced release of both ET and PGI2. Pretreatment with a blocker of the endothelin-A receptor, BQ123 (10(-6) M), inhibited, by approximately 50%, Ang II-induced contractions, and the release of both ET and PGI2. In aortic rings denuded of endothelium, Ang II-induced contractions, and the release of both ET and PGI2 were significantly reduced, compared to intact rings. We conclude that PKC mediates Ang II-induced contractions in rat aortic rings and that the secondary release of both ET and PGI2 during Ang II-induced contractions is mediated, at least in part, by PKC. In addition, approximately half of Ang II-induced contractile force and of PGI2 release is dependent upon the ET released from endothelial cells. JF - Prostaglandins, leukotrienes, and essential fatty acids AU - Oriji, G K AU - Keiser, H R AD - Hypertension-Endocrine Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/08// PY - 1997 DA - August 1997 SP - 135 EP - 141 VL - 57 IS - 2 SN - 0952-3278, 0952-3278 KW - Endothelin Receptor Antagonists KW - 0 KW - Endothelins KW - Enzyme Inhibitors KW - Naphthalenes KW - Peptides, Cyclic KW - Vasoconstrictor Agents KW - Angiotensin II KW - 11128-99-7 KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine KW - 84477-87-2 KW - Epoprostenol KW - DCR9Z582X0 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Staurosporine KW - H88EPA0A3N KW - calphostin C KW - I271P23G24 KW - cyclo(Trp-Asp-Pro-Val-Leu) KW - S2A8YZM151 KW - Index Medicus KW - Naphthalenes -- pharmacology KW - Osmolar Concentration KW - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine -- pharmacology KW - Animals KW - Dose-Response Relationship, Drug KW - Aorta, Thoracic -- physiology KW - Phorbol 12,13-Dibutyrate -- pharmacology KW - Rats KW - Staurosporine -- pharmacology KW - Aorta, Thoracic -- drug effects KW - Enzyme Inhibitors -- pharmacology KW - Peptides, Cyclic -- pharmacology KW - Male KW - Protein Kinase C -- metabolism KW - Protein Kinase C -- drug effects KW - Muscle, Smooth, Vascular -- physiology KW - Vasoconstrictor Agents -- pharmacology KW - Protein Kinase C -- antagonists & inhibitors KW - Muscle Contraction -- drug effects KW - Muscle, Smooth, Vascular -- drug effects KW - Endothelins -- secretion KW - Muscle Contraction -- physiology KW - Endothelins -- drug effects KW - Epoprostenol -- secretion KW - Angiotensin II -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79178036?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Prostaglandins%2C+leukotrienes%2C+and+essential+fatty+acids&rft.atitle=Protein+kinase+C+mediates+angiotensin+II-induced+contractions+and+the+release+of+endothelin+and+prostacyclin+in+rat+aortic+rings.&rft.au=Oriji%2C+G+K%3BKeiser%2C+H+R&rft.aulast=Oriji&rft.aufirst=G&rft.date=1997-08-01&rft.volume=57&rft.issue=2&rft.spage=135&rft.isbn=&rft.btitle=&rft.title=Prostaglandins%2C+leukotrienes%2C+and+essential+fatty+acids&rft.issn=09523278&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-21 N1 - Date created - 1997-10-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The linoleic acid metabolite, (13S)-hydroperoxyoctadecadienoic acid, augments the epidermal growth factor receptor signaling pathway by attenuation of receptor dephosphorylation. Differential response in Syrian hamster embryo tumor suppressor phenotypes. AN - 79166994; 9235921 AB - In Syrian hamster embryo (SHE) fibroblasts, epidermal growth factor receptor (EGFR) tyrosine kinase activity regulates the metabolism of endogenous linoleic acid to (13S)-hydroperoxyoctadecadienoic acid (13S)-HPODE). (13S)-HPODE stimulates EGF-dependent mitogenesis in a SHE cell phenotype, which expresses tumor suppressor genes (supB+), but was not effective in a variant that does not express these suppressor genes (supB-). In the present study, we have investigated the potential effects of this lipid metabolite on the EGFR signaling pathways in these two SHE cell lines. Treatment of quiescent SHE cells with EGF produced a rapid, transient increase in the tyrosine phosphorylation of EGFR. Dependence on EGF concentration for EGFR tyrosine phosphorylation was similar in both SHE cell lines, but a more prolonged phosphorylation was detected in the supB- variant. Incubation of supB+ cells with (13S)-HPODE and EGF increased EGFR autophosphorylation and tyrosine phosphorylation on several signaling proteins with Src homology-2 domains including GTPase-activating protein. The lipid metabolite did not significantly alter EGF-dependent tyrosine phosphorylation in the supB- variant. Tyrosine phosphorylation of mitogen-activated protein (MAP) kinase was also measured. The addition of (13S)-HPODE increased the extent and duration of MAP kinase tyrosine phosphorylation in supB+ cells but not in the supB- variant. MAP kinase activity in supB+ cells, as measured in immunoprecipitates from cells after the addition of EGF, was increased by the presence of (13S)-HPODE. The addition of (13S)-HPODE did not directly alter EGFR kinase activity or the internalization of the EGFR. However, the addition of (13S)-HPODE to supB+ cells extended the tyrosine phosphorylation of the EGFR in response to EGF. The dephosphorylation of the EGFR was measured directly, and a slower rate was observed in the supB- compared with the supB+ cells. Incubation of the supB+ cells with (13S)-HPODE attenuated the dephosphorylation of the EGFR. Thus, (13S)-HPODE stimulates EGF-dependent mitogenesis and up-regulation of EGF-dependent tyrosine phosphorylation by inhibiting the dephosphorylation of the EGFR. This study shows that a metabolite of an essential dietary fatty acid, linoleic acid, can modulate tyrosine phosphorylation and activity of key signal transduction proteins in a growth factor mitogenic pathway. JF - The Journal of biological chemistry AU - Glasgow, W C AU - Hui, R AU - Everhart, A L AU - Jayawickreme, S P AU - Angerman-Stewart, J AU - Han, B B AU - Eling, T E AD - Eicosanoid Biochemistry Section, Laboratory of Molecular Carcinogenesis, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/08/01/ PY - 1997 DA - 1997 Aug 01 SP - 19269 EP - 19276 VL - 272 IS - 31 SN - 0021-9258, 0021-9258 KW - Linoleic Acids KW - 0 KW - Lipid Peroxides KW - 13-hydroperoxy-9,11-octadecadienoic acid KW - 23017-93-8 KW - Arachidonic Acid KW - 27YG812J1I KW - Tyrosine KW - 42HK56048U KW - Epidermal Growth Factor KW - 62229-50-9 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Index Medicus KW - Phenotype KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Animals KW - Phosphorylation KW - Signal Transduction -- drug effects KW - Mesocricetus KW - Tyrosine -- metabolism KW - Epidermal Growth Factor -- pharmacology KW - Arachidonic Acid -- metabolism KW - Cricetinae KW - Receptor, Epidermal Growth Factor -- drug effects KW - Receptor, Epidermal Growth Factor -- metabolism KW - Genes, Tumor Suppressor KW - Linoleic Acids -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79166994?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+linoleic+acid+metabolite%2C+%2813S%29-hydroperoxyoctadecadienoic+acid%2C+augments+the+epidermal+growth+factor+receptor+signaling+pathway+by+attenuation+of+receptor+dephosphorylation.+Differential+response+in+Syrian+hamster+embryo+tumor+suppressor+phenotypes.&rft.au=Glasgow%2C+W+C%3BHui%2C+R%3BEverhart%2C+A+L%3BJayawickreme%2C+S+P%3BAngerman-Stewart%2C+J%3BHan%2C+B+B%3BEling%2C+T+E&rft.aulast=Glasgow&rft.aufirst=W&rft.date=1997-08-01&rft.volume=272&rft.issue=31&rft.spage=19269&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-21 N1 - Date created - 1997-08-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Targeted disruption of the epidermal growth factor receptor impairs growth of squamous papillomas expressing the v-ras(Ha) oncogene but does not block in vitro keratinocyte responses to oncogenic ras. AN - 79164259; 9242447 AB - We have assessed the role of epidermal growth factor receptor (EGFR) signaling in biological responses to the v-ras(Ha) oncogene using primary keratinocytes from Egfr -/- mice and wild-type littermates. On the basis of several criteria, Egfr -/- keratinocytes were unresponsive to either acute or chronic exposure to several EGFR ligands but were stimulated to proliferate in response to several other mitogens. Although conditioned medium from primary keratinocytes transduced with v-ras(Ha) retrovirus (v-ras(Ha) keratinocytes) was a potent mitogen for wild-type but not Egfr -/- keratinocytes, v-ras(Ha) transduction of primary keratinocytes of either genotype resulted in a strong mitogenic response, arguing against an obligatory role for EGFR activation in v-ras(Ha)-mediated stimulation of keratinocyte proliferation. Infection with high-titer v-ras(Ha) retrovirus altered the keratin expression pattern in keratinocytes of both genotypes, suppressing differentiation-specific keratins K1 and K10 while activating aberrant expression of K8 and K18. In wild-type but not Egfr -/- cultures, K1 and K10 were also suppressed following infection at lower retroviral titers, presumably as a result of paracrine EGFR activation on uninfected cells present in these cultures. Squamous papillomas produced by grafting Egfr -/- v-ras(Ha) keratinocytes onto nude mice were only 21% of the size of wild-type v-ras(Ha) tumors, and a striking redistribution of S-phase cells was detected by immunostaining for bromodeoxyuridine. In Egfr -/- v-ras(Ha) papillomas, the fraction of total labeled nuclei detected in suprabasal layers was increased from 19 to 39%. In contrast, the basal layer labeling index of Egfr -/- papillomas was reduced to 34%, compared to 43% in wild-type tumors. Our results indicate that, although autocrine EGFR signaling is not required for keratinocyte responses to oncogenic ras in culture or benign tumor formation in nude mouse grafts, disruption of this pathway impairs growth of v-ras(Ha) papillomas by a mechanism that may involve alterations in keratinocyte cell cycle progression and/or migration in vivo. JF - Cancer research AU - Dlugosz, A A AU - Hansen, L AU - Cheng, C AU - Alexander, N AU - Denning, M F AU - Threadgill, D W AU - Magnuson, T AU - Coffey, R J AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1997/08/01/ PY - 1997 DA - 1997 Aug 01 SP - 3180 EP - 3188 VL - 57 IS - 15 SN - 0008-5472, 0008-5472 KW - Culture Media, Conditioned KW - 0 KW - Keratins KW - 68238-35-7 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Bromodeoxyuridine KW - G34N38R2N1 KW - Index Medicus KW - Neoplasm Transplantation KW - Keratins -- metabolism KW - Culture Media, Conditioned -- pharmacology KW - Animals KW - Apoptosis KW - Fluorescent Antibody Technique, Indirect KW - Cells, Cultured KW - Cell Division -- physiology KW - Mice KW - Papilloma -- genetics KW - Time Factors KW - Papilloma -- metabolism KW - Mice, Knockout KW - Keratinocytes -- physiology KW - Keratinocytes -- drug effects KW - Genes, ras -- physiology KW - Receptor, Epidermal Growth Factor -- physiology KW - Receptor, Epidermal Growth Factor -- deficiency UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79164259?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Targeted+disruption+of+the+epidermal+growth+factor+receptor+impairs+growth+of+squamous+papillomas+expressing+the+v-ras%28Ha%29+oncogene+but+does+not+block+in+vitro+keratinocyte+responses+to+oncogenic+ras.&rft.au=Dlugosz%2C+A+A%3BHansen%2C+L%3BCheng%2C+C%3BAlexander%2C+N%3BDenning%2C+M+F%3BThreadgill%2C+D+W%3BMagnuson%2C+T%3BCoffey%2C+R+J%3BYuspa%2C+S+H&rft.aulast=Dlugosz&rft.aufirst=A&rft.date=1997-08-01&rft.volume=57&rft.issue=15&rft.spage=3180&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-11 N1 - Date created - 1997-09-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Both thyroid hormone and 9-cis retinoic acid receptors are required to efficiently mediate the effects of thyroid hormone on embryonic development and specific gene regulation in Xenopus laevis. AN - 79155763; 9234730 AB - Tissue culture transfection and in vitro biochemical studies have suggested that heterodimers of thyroid hormone receptors (TRs) and 9-cis retinoic acid receptors (RXRs) are the likely in vivo complexes that mediate the biological effects of thyroid hormone, 3,5,3'-triiodothyronine (T3). However, direct in vivo evidence for such a hypothesis has been lacking. We have previously reported a close correlation between the coordinated expression of TR and RXR genes and tissue-dependent temporal regulation of organ transformations during Xenopus laevis metamorphosis. By introducing TRs and RXRs either individually or together into developing Xenopus embryos, we demonstrate here that RXRs are critical for the developmental function of TRs. Precocious expression of TRs and RXRs together but not individually leads to drastic, distinct embryonic abnormalities, depending upon the presence or absence of T3, and these developmental effects require the same receptor domains as those required for transcriptional regulation by TR-RXR heterodimers. More importantly, the overexpressed TR-RXR heterodimers faithfully regulate endogenous T3 response genes that are normally regulated by T3 only during metamorphosis. That is, they repress the genes in the absence of T3 and activate them in the presence of the hormone. On the other hand, the receptors have no effect on a retinoic acid (RA) response gene. Thus, RA- and T3 receptor-mediated teratogenic effects in Xenopus embryos occur through distinct molecular pathways, even though the resulting phenotypes have similarities. JF - Molecular and cellular biology AU - Puzianowska-Kuznicka, M AU - Damjanovski, S AU - Shi, Y B AD - Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-5431, USA. Y1 - 1997/08// PY - 1997 DA - August 1997 SP - 4738 EP - 4749 VL - 17 IS - 8 SN - 0270-7306, 0270-7306 KW - Hedgehog Proteins KW - 0 KW - Proteins KW - RNA, Messenger KW - Receptors, Retinoic Acid KW - Receptors, Thyroid Hormone KW - Retinoid X Receptors KW - Trans-Activators KW - Transcription Factors KW - Triiodothyronine KW - 06LU7C9H1V KW - DNA KW - 9007-49-2 KW - Iodide Peroxidase KW - EC 1.11.1.8 KW - Matrix Metalloproteinase 11 KW - EC 3.4.24.- KW - Metalloendopeptidases KW - Index Medicus KW - Animals KW - Dimerization KW - DNA -- metabolism KW - Transcriptional Activation -- physiology KW - Microinjections KW - Iodide Peroxidase -- genetics KW - Proteins -- genetics KW - Metamorphosis, Biological KW - Metalloendopeptidases -- genetics KW - Receptors, Retinoic Acid -- genetics KW - Receptors, Retinoic Acid -- metabolism KW - Transcription Factors -- physiology KW - Triiodothyronine -- pharmacology KW - Transcription Factors -- metabolism KW - Receptors, Thyroid Hormone -- genetics KW - Receptors, Thyroid Hormone -- metabolism KW - Receptors, Thyroid Hormone -- physiology KW - Xenopus laevis -- embryology KW - Transcription Factors -- genetics KW - Xenopus laevis -- genetics KW - Receptors, Retinoic Acid -- physiology KW - Gene Expression Regulation, Developmental UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79155763?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Both+thyroid+hormone+and+9-cis+retinoic+acid+receptors+are+required+to+efficiently+mediate+the+effects+of+thyroid+hormone+on+embryonic+development+and+specific+gene+regulation+in+Xenopus+laevis.&rft.au=Puzianowska-Kuznicka%2C+M%3BDamjanovski%2C+S%3BShi%2C+Y+B&rft.aulast=Puzianowska-Kuznicka&rft.aufirst=G&rft.date=1997-09-01&rft.volume=45&rft.issue=2&rft.spage=149&rft.isbn=&rft.btitle=&rft.title=Breast+cancer+research+and+treatment&rft.issn=01676806&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-25 N1 - Date created - 1997-08-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Development. 1991 Dec;113(4):1145-58 [1811933] Dev Genet. 1992;13(4):289-301 [1291156] EMBO J. 1995 May 1;14(9):2020-33 [7744009] Mol Endocrinol. 1995 Jan;9(1):34-43 [7760849] Nature. 1995 Oct 5;377(6548):397-404 [7566114] Nature. 1995 Oct 5;377(6548):454-7 [7566127] Curr Biol. 1995 Jun 1;5(6):612-4 [7552169] Genes Dev. 1995 Nov 1;9(21):2696-711 [7590246] Science. 1995 Nov 24;270(5240):1354-7 [7481822] Cell. 1995 Dec 15;83(6):835-9 [8521507] Cell Tissue Res. 1996 Feb;283(2):325-9 [8593661] Bioessays. 1993 Apr;15(4):239-48 [8517853] Mol Endocrinol. 1995 Jan;9(1):96-107 [7760854] Mol Endocrinol. 1995 Feb;9(2):243-54 [7776974] J Biol Chem. 1995 Aug 4;270(31):18479-83 [7629175] Genes Dev. 1993 Jul;7(7B):1411-22 [8392478] Genes Dev. 1993 Jul;7(7B):1423-35 [8392479] J Biol Chem. 1993 Aug 5;268(22):16270-8 [8344914] Mol Cell Biol. 1993 Dec;13(12):7540-52 [7504177] Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3067-71 [8159708] Science. 1994 Jun 3;264(5164):1455-8 [8197458] J Biol Chem. 1994 Sep 30;269(39):24459-65 [7929109] J Biol Chem. 1994 Oct 7;269(40):24699-705 [7929143] FEBS Lett. 1994 Nov 21;355(1):61-4 [7957964] Annu Rev Biochem. 1994;63:451-86 [7979245] Dev Biol. 1995 Jan;167(1):252-62 [7851646] Cell. 1995 Feb 24;80(4):517-20 [7867057] Nature. 1995 Mar 2;374(6517):91-4 [7870181] Proc Natl Acad Sci U S A. 1996 Feb 6;93(3):1205-9 [8577741] J Biol Chem. 1996 Mar 15;271(11):6273-82 [8626421] Bioessays. 1996 May;18(5):391-9 [8639162] Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):1803-7 [8700839] Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):1924-9 [8700860] Mol Cell Biol. 1996 Aug;16(8):4465-77 [8754847] Nature. 1996 Sep 5;383(6595):99-103 [8779723] Curr Top Dev Biol. 1996;32:205-35 [8929670] Nucleic Acids Res. 1995 Jul 11;23(13):2555-62 [7630736] J Biol Chem. 1982 Jan 25;257(2):930-8 [6274872] Nature. 1986 Dec 18-31;324(6098):635-40 [2879242] Nature. 1986 Dec 18-31;324(6098):641-6 [2879243] Science. 1988 May 13;240(4854):889-95 [3283939] Nature. 1989 Jul 13;340(6229):140-4 [2739735] Nature. 1989 Jul 20;340(6230):242-4 [2569164] Nature. 1989 Aug 24;340(6235):653-6 [2549424] Cell. 1989 Nov 17;59(4):697-708 [2555064] Int Rev Cytol. 1989;119:97-149 [2695486] Biotechniques. 1988 Mar;6(3):196-7, 199-200 [2483319] Genes Dev. 1990 Jun;4(6):932-42 [2384214] Proc Natl Acad Sci U S A. 1990 Sep;87(18):7090-4 [2402492] Mol Endocrinol. 1990 Sep;4(9):1293-301 [2172797] Nature. 1990 Dec 20-27;348(6303):699-704 [1701851] Genes Dev. 1990 Nov;4(11):1917-24 [2276625] New Biol. 1989 Dec;1(3):329-36 [2562125] Genes Dev. 1991 Feb;5(2):175-87 [1671660] Proc Natl Acad Sci U S A. 1991 May 1;88(9):3666-70 [1850835] Mol Endocrinol. 1991 Feb;5(2):201-8 [1645454] Mol Cell Biol. 1991 Oct;11(10):5079-89 [1656222] Development. 1991 Aug;112(4):933-43 [1935702] Development. 1991 Aug;112(4):945-58 [1682132] Cell. 1991 Dec 20;67(6):1251-66 [1662118] Cell. 1992 Jan 24;68(2):377-95 [1310259] Cell. 1992 Jan 24;68(2):397-406 [1310260] Nature. 1992 Jan 30;355(6359):441-6 [1310350] EMBO J. 1992 Mar;11(3):1015-23 [1347744] Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2321-5 [1312717] EMBO J. 1992 Apr;11(4):1419-35 [1314168] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Endogenously produced nitric oxide increases tumor necrosis factor-alpha production in transfected human U937 cells. AN - 79155600; 9242548 AB - Various functions of human phagocytes are modulated by nitric oxide (NO). We transfected the human U937 monoblastoid cell line with an expression vector containing human endothelial NO synthase (eNOS) or murine inducible NOS (iNOS) cDNA to study the regulatory role of NO without the nonspecific effects associated with exogenous NO sources. Western blot confirmed expression of eNOS or iNOS in respectively transfected cells, but not in naive or empty-vector transfected cells. Transfectants expressing iNOS, a calcium-independent enzyme, but not eNOS, a calcium-dependent enzyme, spontaneously produced NO (P < .001). The NO release from iNOS-transfected cells, as measured by nitrite and nitrate accumulation and by cyclic guanosine monophosphate (cGMP) increases in rat reporter cells, was inhibitable (P < .01 for both) with N(omega)-methyl-L-arginine (L-NMA), a NOS inhibitor. The eNOS transfectants were shown to contain functional enzyme by the conversion of L-arginine to L-citrulline in fractionated cells (P = .0001) and by exposing intact cells to calcium ionophore using the cGMP reporter cell assay (P = .0001). After differentiation with phorbol-12-myristate-13-acetate (PMA), iNOS transfectants produced more tumor necrosis factor-alpha (TNF-alpha) (124.9 +/- 25.4 pg/5 x 10(5) cells per 24 hours) than did empty-vector transfected cells (21.9 +/- 1.9 pg/5 x 10(5) cells per 24 hours; P = .02). This effect was inhibited by 500 micromol/L L-NMA (54.4 +/- 3.1 pg/5 x 10(5) cells per 24 hours; P = .05). However, in the presence of high concentrations of lipopolysaccharide (1 microg/mL), which further increased NO production in iNOS transfected cells (P = .044), TNF-alpha production was similar comparing PMA-differentiated iNOS and empty-vector transfectants (12.2 +/- 0.8 and 13.1 +/- 1.7 ng/5 x 10(5) cells per 24 hours, respectively; P = .5). The results show that under certain conditions endogenously produced NO can upregulate TNF-alpha production in human phagocytes. JF - Blood AU - Yan, L AU - Wang, S AU - Rafferty, S P AU - Wesley, R A AU - Danner, R L AD - Critical Care Medicine Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/08/01/ PY - 1997 DA - 1997 Aug 01 SP - 1160 EP - 1167 VL - 90 IS - 3 SN - 0006-4971, 0006-4971 KW - DNA, Complementary KW - 0 KW - Neoplasm Proteins KW - Recombinant Fusion Proteins KW - Tumor Necrosis Factor-alpha KW - omega-N-Methylarginine KW - 27JT06E6GR KW - Citrulline KW - 29VT07BGDA KW - Nitric Oxide KW - 31C4KY9ESH KW - Arginine KW - 94ZLA3W45F KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Cyclic GMP KW - H2D2X058MU KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - DNA, Complementary -- genetics KW - Arginine -- metabolism KW - Humans KW - Cyclic GMP -- physiology KW - Mice KW - Recombinant Fusion Proteins -- metabolism KW - Rats KW - Tumor Cells, Cultured KW - Second Messenger Systems -- physiology KW - Enzyme Induction -- drug effects KW - Transfection KW - Genetic Vectors KW - Nitric Oxide Synthase -- genetics KW - Tetradecanoylphorbol Acetate -- pharmacology KW - omega-N-Methylarginine -- pharmacology KW - Cell Differentiation -- drug effects KW - Nitric Oxide Synthase -- metabolism KW - Citrulline -- metabolism KW - Gene Expression Regulation, Neoplastic KW - Neoplasm Proteins -- biosynthesis KW - Lymphoma, Large B-Cell, Diffuse -- pathology KW - Neoplasm Proteins -- genetics KW - Tumor Necrosis Factor-alpha -- biosynthesis KW - Nitric Oxide -- physiology KW - Tumor Necrosis Factor-alpha -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79155600?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Endogenously+produced+nitric+oxide+increases+tumor+necrosis+factor-alpha+production+in+transfected+human+U937+cells.&rft.au=Yan%2C+L%3BWang%2C+S%3BRafferty%2C+S+P%3BWesley%2C+R+A%3BDanner%2C+R+L&rft.aulast=Yan&rft.aufirst=L&rft.date=1997-08-01&rft.volume=90&rft.issue=3&rft.spage=1160&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-25 N1 - Date created - 1997-08-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of drm, a novel gene whose expression is suppressed in transformed cells and which can inhibit growth of normal but not transformed cells in culture. AN - 79154128; 9234736 AB - Using differential display analysis, we compared the expression of RNA in v-mos-transformed cells and their flat revertant and isolated a novel gene, drm (down-regulated in mos-transformed cells), whose expression is down-regulated in parental v-mos-transformed cells but which is expressed at a high level in the revertant and normal rat fibroblasts (REF-1 cells). Analysis of different oncogene-transformed cells revealed that drm gene expression was also suppressed in REF-1 cells transformed by v-ras, v-src, v-raf, and v-fos. The drm cDNA contains a 184-amino-acid-protein-encoding open reading frame which shows no significant homologies to known genes in DNA databases. Polyclonal antibodies raised against drm peptide detect a protein with the predicted size of 20.7 kDa in normal cells and under nonpermissive conditions in cells conditionally transformed by v-mos but not in parental v-mos-transformed cells. Northern analysis of normal adult tissues shows that drm is expressed as a 4.4-kb message in a tissue-specific manner, with high expression in the brain, spleen, kidney, and testis and little or no expression in the heart, liver, and skeletal muscle. In situ hybridization analysis in adult rat tissue reveals good correlation with this pattern and indicates that drm mRNA is most highly expressed in nondividing and terminally differentiated cells, such as neurons, type 1 lung cells, and goblet cells. Transfection of a drug-selectable drm expression vector dramatically reduced the efficiency of colony formation in REF-1 and CHO cells, and the drm-transfected REF-1 survivors expressed low or nondetectable levels of exogenous drm mRNA. The toxic effects of drm can be overcome by cotransfection with constructs expressing oncogenic ras; furthermore, cells expressing high levels of drm and conditionally transformed with mos-expressing Moloney murine sarcoma virus rapidly undergo apoptosis when shifted to the nonpermissive temperature. Taken together, our data suggest that cells expressing high levels of drm undergo apoptotic death in the absence of oncogene-induced transformation and that drm represents a novel gene with potential roles in cell growth control or viability and tissue-specific differentiation. JF - Molecular and cellular biology AU - Topol, L Z AU - Marx, M AU - Laugier, D AU - Bogdanova, N N AU - Boubnov, N V AU - Clausen, P A AU - Calothy, G AU - Blair, D G AD - Intramural Research Support Program, SAIC Frederick, NCI-FCRDC, Maryland 21702-1201, USA. Y1 - 1997/08// PY - 1997 DA - August 1997 SP - 4801 EP - 4810 VL - 17 IS - 8 SN - 0270-7306, 0270-7306 KW - Bone Morphogenetic Proteins KW - 0 KW - Cktsf1b1 protein, rat KW - DNA, Complementary KW - Proteins KW - RNA, Messenger KW - Index Medicus KW - Animals KW - Genes, mos -- physiology KW - Apoptosis KW - DNA, Complementary -- genetics KW - RNA, Messenger -- analysis KW - Organ Specificity KW - Amino Acid Sequence KW - Sequence Analysis, DNA KW - Molecular Weight KW - Rats KW - Rats, Sprague-Dawley KW - Base Sequence KW - Oncogenes KW - Molecular Sequence Data KW - Cell Line, Transformed KW - Sequence Homology, Amino Acid KW - Cell Line KW - Cell Division KW - Gene Expression Regulation, Neoplastic -- genetics KW - Proteins -- chemistry KW - Proteins -- analysis KW - Fibroblasts -- cytology KW - Proteins -- genetics KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79154128?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Identification+of+drm%2C+a+novel+gene+whose+expression+is+suppressed+in+transformed+cells+and+which+can+inhibit+growth+of+normal+but+not+transformed+cells+in+culture.&rft.au=Topol%2C+L+Z%3BMarx%2C+M%3BLaugier%2C+D%3BBogdanova%2C+N+N%3BBoubnov%2C+N+V%3BClausen%2C+P+A%3BCalothy%2C+G%3BBlair%2C+D+G&rft.aulast=Topol&rft.aufirst=L&rft.date=1997-08-01&rft.volume=17&rft.issue=8&rft.spage=4801&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-25 N1 - Date created - 1997-08-25 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - Y10019; GENBANK N1 - SuppNotes - Cited By: Annu Rev Physiol. 1992;54:351-71 [1562179] Mol Biol (Mosk). 1991 Mar-Apr;25(2):541-51 [1715510] Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7742-6 [1457005] Science. 1992 Aug 14;257(5072):967-71 [1354393] J Biol Chem. 1992 Oct 25;267(30):21375-83 [1400449] Annu Rev Cell Biol. 1992;8:197-225 [1335743] Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):383-7 [8380636] Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):985-9 [8381540] Science. 1993 Feb 12;259(5097):971-4 [8438157] Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2593-7 [8385338] Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7039-43 [8346214] Annu Rev Biochem. 1993;62:623-51 [8394683] Science. 1994 Jan 28;263(5146):526-9 [8290962] Cancer Res. 1994 Feb 1;54(3):646-8 [8306325] J Biol Chem. 1994 Jun 17;269(24):16521-4 [8206964] Oncogene. 1994 Oct;9(10):2785-91 [8084583] Cell. 1994 Oct 21;79(2):341-51 [7954800] Cancer Res. 1995 Feb 15;55(4):895-900 [7850806] Curr Opin Cell Biol. 1994 Dec;6(6):795-803 [7880525] J Cell Sci. 1994 Dec;107 ( Pt 12):3569-77 [7706406] Cell Growth Differ. 1995 Jan;6(1):27-38 [7718484] EMBO J. 1995 Apr 3;14(7):1372-81 [7729415] Mol Cell Biol. 1995 May;15(5):2754-62 [7739556] Semin Nephrol. 1995 Jan;15(1):9-28 [7754257] Semin Nephrol. 1995 Jul;15(4):327-40 [7569412] Cell Growth Differ. 1995 Sep;6(9):1119-27 [8519689] Oncogene. 1996 Jan 18;12(2):337-44 [8570210] Nature. 1996 Aug 15;382(6592):595-601 [8757128] Biochem Biophys Res Commun. 1966 Jun 13;23(5):641-6 [5963888] Eur J Biochem. 1973 Jul 2;36(1):32-8 [4200179] Virology. 1979 Jun;95(2):303-16 [462797] Science. 1981 Dec 11;214(4526):1205-10 [7302589] Cell. 1982 May;29(1):161-9 [6286138] J Virol. 1983 Feb;45(2):773-81 [6300434] Anal Biochem. 1987 Apr;162(1):156-9 [2440339] Nucleic Acids Res. 1987 Oct 26;15(20):8125-48 [3313277] EMBO J. 1989 Aug;8(8):2283-90 [2477241] Science. 1989 Dec 15;246(4936):1406-12 [2574499] Science. 1990 Aug 17;249(4970):796-8 [1697103] Mol Cell Biol. 1992 Jun;12(6):2570-80 [1317006] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Automatic Semantic Priming of Nouns and Verbs in Patients with Alzheimer's Disease AN - 58349533; 9810536 AB - Effects of Alzheimer's disease on semantic representations of nouns & verbs in subjects (Ss) with Alzheimer's disease (N = 16, mean age 73) were examined & compared to representations in normal control Ss (N = 16, mean age 74). A semantic priming experiment used a short & a long stimulus onset asynchrony to control for the effects of attention on priming. Stimuli consisted of semantically unrelated word pairs (target & prime) selected from four sets of semantically related word pairs; motion verbs, non-motion verbs, concrete nouns, & abstract nouns. Neither S group demonstrated priming for abstract nouns or non-motion verb pairs. Control Ss showed priming for concrete nouns & motion verbs but Alzheimer's Ss demonstrated priming only for concrete nouns. A dissociation was indicated between concrete nouns & motion verbs for Ss with Alzheimer's disease. It was suggested that concrete nouns have a widely distributed neuroanatomic representation, while motion verbs have a more focal representation, & motion verbs, as a result, are more vulnerable to the effects of Alzheimer's disease. 3 Tables, 2 Figures, 1 Appendix, 67 References. D. Taylor JF - Neuropsychologia AU - Bushell, Camille M AU - Martin, Alex AD - Laboratory Brain & Cognition National Instit Mental Health, Bldg 10 Room 4C-104 10 Center Dr MSC-1366 Bethesda MD 20896-1366 alex@codon.nih.gov Y1 - 1997/08// PY - 1997 DA - August 1997 SP - 1059 EP - 1067 VL - 35 IS - 8 SN - 0028-3932, 0028-3932 KW - Nouns (59650) KW - Priming (67670) KW - Alzheimers Disease (01900) KW - Neurolinguistics (57250) KW - Verbs (93900) KW - Attention (05350) KW - Semantic Processing (76760) KW - article KW - 6410: language-pathological and normal; language-pathological and normal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/58349533?accountid=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=Neuropsychologia&rft.atitle=Automatic+Semantic+Priming+of+Nouns+and+Verbs+in+Patients+with+Alzheimer%27s+Disease&rft.au=Bushell%2C+Camille+M%3BMartin%2C+Alex&rft.aulast=Bushell&rft.aufirst=Camille&rft.date=1997-08-01&rft.volume=35&rft.issue=8&rft.spage=1059&rft.isbn=&rft.btitle=&rft.title=Neuropsychologia&rft.issn=00283932&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 - NUPSA6 N1 - SubjectsTermNotLitGenreText - Alzheimers Disease (01900); Semantic Processing (76760); Nouns (59650); Verbs (93900); Priming (67670); Attention (05350); Neurolinguistics (57250) ER - TY - JOUR T1 - Mediation of oxidative DNA damage by nickel(II) and copper(II) complexes with the N-terminal sequence of human protamine HP2 AN - 16271822; 4285633 AB - The potential of Ni(II) and Cu(II) complexes with Arg-Thr-His-Gly-Gln-Ser-His-Tyr-Arg-Arg-Arg-His-Cys-Ser-Arg-amide (HP2 sub(1-15)), a peptide modeling the N-terminal amino acid sequence of human protamine HP2, to mediate oxidative DNA damage was studied by measurements of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) generation from 2'-deoxyguanosine (dG) and calf thymus DNA and by formation of double-strand breaks in calf thymus DNA. The concentrations of reagents were 0.1 mM dG and the metal-HP2 sub(1-15) complex, 1 mM H sub(2)O sub(2), 1.5 mM DNA (per phosphate group), 100 mM phosphate buffer, pH 7.4, ambient O sub(2). Samples were incubated at 37 degree C for 16-24 h. The Cu(II)-HP2 sub(1-15) complex was found to be an effective promoter of the formation of 8-oxo-dG from both dG and DNA with ambient O sub(2) (approximately 13- and 3-fold increase versus the oxidant alone, respectively) and H sub(2)O sub(2) (approximately 25-fold increase in either case). The Ni(II)-HP2 sub(1-15) complex was ineffective with O sub(2) versus 8-oxo-dG production from both substrates but markedly enhanced the attack of H sub(2)O sub(2) on dG and DNA (approximately 5-fold increase of 8-oxo-dG production in either case). Both Cu(II)- and Ni(II)-HP2 sub(1-15) equally promoted double-strand scission by H sub(2)O sub(2) in calf thymus DNA. The promotion by the complexes of dG and DNA oxidation with H sub(2)O sub(2) was accompanied by oxidative damage to the complexes themselves, consisting of decreasing contents of their His (to approximately 50% of control in either complex) and especially Tyr (down to 48% of control in Cu(II)- and 19% in Ni(II)-HP2 sub(1-15)) residues, as well as appearance of aspartic acid, the known oxidation product of His residues in peptides (up to 22% vs Gly for Cu(II)- and 10% for Ni(II)-HP2 sub(1-15)). The above results provide a novel chemical mechanism of Cu(II) and Ni(II) toxicity and may have wide implications for reproductive and transgenerational effects of metal exposure. JF - Chemical Research in Toxicology AU - Bal, W AU - Lukszo, J AU - Kasprzak, K S AD - NCI-FCRDC, Bldg 538, Rm 205, Frederick, MD 21702-1201, USA Y1 - 1997/08// PY - 1997 DA - Aug 1997 SP - 915 EP - 921 VL - 10 IS - 8 SN - 0893-228X, 0893-228X KW - DNA damage KW - N-terminus KW - copper KW - man KW - nickel KW - oxidative stress KW - protamine HP2 KW - Toxicology Abstracts KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16271822?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+Research+in+Toxicology&rft.atitle=Mediation+of+oxidative+DNA+damage+by+nickel%28II%29+and+copper%28II%29+complexes+with+the+N-terminal+sequence+of+human+protamine+HP2&rft.au=Bal%2C+W%3BLukszo%2C+J%3BKasprzak%2C+K+S&rft.aulast=Bal&rft.aufirst=W&rft.date=1997-08-01&rft.volume=10&rft.issue=8&rft.spage=915&rft.isbn=&rft.btitle=&rft.title=Chemical+Research+in+Toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Binding of nickel(II) and copper(II) to the N-terminal sequence of human protamine HP2 AN - 16269741; 4285634 AB - A potentiometric and spectroscopic (UV/vis and CD) study of Cu(II) and Ni(II) binding to the N-terminal pentadecapeptide of human protamine HP2 (HP2 sub(1-15)) was performed. The results indicate that the N-terminal tripeptide motif Arg-Thr-His is the exclusive binding site for both metal ions at a metal to HP2 sub(1-15) molar ratio not higher than 1. The very high value of protonation-corrected stability constant (log *K) for Ni(II)-HP2 sub(1-15) complex, -19.29, indicates that HP2 has the potential to sequester Ni(II) from other peptide and protein carriers, including albumin. The same is likely for Cu(II) (log *K = -13.13). The CD spectra of Cu(II) and Ni(II) complexes of HP2 sub(1-15) indicate that the N-terminal metal binding affects the overall conformation of the peptide that, in turn, may alter interaction of HP2 with DNA. These results imply HP2 as a likely target for the toxic metals Ni(II) and Cu(II). JF - Chemical Research in Toxicology AU - Bal, W AU - Jezowska-Bojczuk, M AU - Kasprzak, K S AD - NCI-FCRDC, Bldg 538, Rm 205, Frederick, MD 21702-1201, USA Y1 - 1997/08// PY - 1997 DA - Aug 1997 SP - 906 EP - 914 VL - 10 IS - 8 SN - 0893-228X, 0893-228X KW - DNA KW - N-terminus KW - copper KW - man KW - nickel KW - protamine HP2 KW - spectroscopy KW - Toxicology Abstracts KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16269741?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+Research+in+Toxicology&rft.atitle=Binding+of+nickel%28II%29+and+copper%28II%29+to+the+N-terminal+sequence+of+human+protamine+HP2&rft.au=Bal%2C+W%3BJezowska-Bojczuk%2C+M%3BKasprzak%2C+K+S&rft.aulast=Bal&rft.aufirst=W&rft.date=1997-08-01&rft.volume=10&rft.issue=8&rft.spage=906&rft.isbn=&rft.btitle=&rft.title=Chemical+Research+in+Toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Stabilization of protein structures AN - 16261673; 4229933 AB - The technique of protein stabilization has been improving steadily in recent years, but it is only in the past year or two that the stability of some protein molecules has been improved to the level of those from extreme thermophilic organisms. This was achieved by multiple mutations and often by utilizing the knowledge gained from the homologous protein structures from extreme thermophiles. JF - Current Opinion in Biotechnology AU - Lee, Byungkook AU - Vasmatzis, G AD - Laboratory of Molecular Biology, Division of Cancer Biology, Diagnosis, and Centers National Cancer Institute, National Institutes of Health Building 37, Room 4B15, 37 Convent DR MSC 4255, Bethesda, MD 20892-4255, USA Y1 - 1997/08// PY - 1997 DA - Aug 1997 SP - 423 EP - 428 VL - 8 IS - 4 SN - 0958-1669, 0958-1669 KW - protein engineering KW - reviews KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33340:Other proteins, peptides, amino acids KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16261673?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Opinion+in+Biotechnology&rft.atitle=Stabilization+of+protein+structures&rft.au=Lee%2C+Byungkook%3BVasmatzis%2C+G&rft.aulast=Lee&rft.aufirst=Byungkook&rft.date=1997-08-01&rft.volume=8&rft.issue=4&rft.spage=423&rft.isbn=&rft.btitle=&rft.title=Current+Opinion+in+Biotechnology&rft.issn=09581669&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Reliable determination of binding affinity and kinetics using surface plasmon resonance biosensors AN - 16256972; 4229940 AB - Progress has been made in the identification of experimental and analytical procedures that allow for a more reliable determination of equilibrium and kinetic constants. Possible origins of the frequently observed deviations of the measured binding progress from that expected for chemical binding of pseudo-first order, and appropriate experimental controls have been proposed. Improved analytical approaches include the application of global analysis and analytical corrections for the influence of mass transport. JF - Current Opinion in Biotechnology AU - Schuck, P AD - Molecular Interactions Resource, Biomedical Engineering and Instrumentation Program, National Center for Research Resources, National Institutes of Health, Bld13, Room 3N17, 13 South Drive MSC 5766, Bethesda, MD 20892-5766, USA Y1 - 1997/08// PY - 1997 DA - Aug 1997 SP - 498 EP - 502 VL - 8 IS - 4 SN - 0958-1669, 0958-1669 KW - biosensors KW - reviews KW - surface plasmon resonance KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W 30965:Miscellaneous, Reviews KW - W3 33250:Methods: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16256972?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Opinion+in+Biotechnology&rft.atitle=Reliable+determination+of+binding+affinity+and+kinetics+using+surface+plasmon+resonance+biosensors&rft.au=Schuck%2C+P&rft.aulast=Schuck&rft.aufirst=P&rft.date=1997-08-01&rft.volume=8&rft.issue=4&rft.spage=498&rft.isbn=&rft.btitle=&rft.title=Current+Opinion+in+Biotechnology&rft.issn=09581669&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - In vitro cytotoxicity of diverse preparations used in dental practice to human gingival keratinocytes AN - 16224908; 4218614 AB - The cytotoxicities of diverse preparations used for dental practice were examined with normal human keratinocytes from gingival tissues by the uptake of neutral red (NR assay). Cultures from different individuals were established, and secondary cultures in serum-free medium were used. The cytotoxicities to cells treated for 2 days with gargles, mouthwashes, gingival massages, fluoride preparations, dentifrices and local anaesthetics were determined from the dose-response curves of inhibition of NR uptake. As a quantitative measure of cytotoxicity, NR sub(50) (the concentration of the preparations that resulted in a 50% decrease in NR uptake relative to untreated controls) was interpolated from dose-response curves. Dentifrices examined showed cytotoxicity similar to gingival massages but were more cytotoxic than any fluoride preparations, local anaesthetics, and most gargles and mouthwashes. The cytotoxicities of dentifrices were at least 6.5-fold those of fluoride preparations and 7.9-fold those of local anaesthetics. The results provide useful estimates of relative toxicities of dental preparations to human oral mucosa and are useful as a standard for cytotoxic assessment of newly developed preparations for dental use. JF - Toxicology In Vitro AU - Tsutsui, T AU - Tanaka, Y AU - Ushimura, A AU - Ide, T AU - Matsumura, M AU - Barrett, J C AD - Lab. of Molecular Carcinogenesis, Environmental Carcinogenesis Program, National Institute of Environmental Health Sciences, National Institutes of Health, PO Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1997/08// PY - 1997 DA - Aug 1997 SP - 393 EP - 398 VL - 11 IS - 4 SN - 0887-2333, 0887-2333 KW - dental restorative materials KW - dental sealants KW - gingiva KW - keratinocytes KW - man KW - Toxicology Abstracts KW - X 24111:Acute exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16224908?accountid=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+In+Vitro&rft.atitle=In+vitro+cytotoxicity+of+diverse+preparations+used+in+dental+practice+to+human+gingival+keratinocytes&rft.au=Tsutsui%2C+T%3BTanaka%2C+Y%3BUshimura%2C+A%3BIde%2C+T%3BMatsumura%2C+M%3BBarrett%2C+J+C&rft.aulast=Tsutsui&rft.aufirst=T&rft.date=1997-08-01&rft.volume=11&rft.issue=4&rft.spage=393&rft.isbn=&rft.btitle=&rft.title=Toxicology+In+Vitro&rft.issn=08872333&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 - Microbial factors in disease emergence illustrated by streptococcal toxic shock syndrome AN - 16214461; 4209326 JF - FEMS Immunology and Medical Microbiology AU - Krause, R AD - Fogarty International Center, National Institutes of Health, Building 16, Room 202B, Bethesda, MD 20892, USA Y1 - 1997/08// PY - 1997 DA - Aug 1997 SP - 227 EP - 232 PB - ELSEVIER SCIENCE B.V. VL - 18 IS - 4 SN - 0928-8244, 0928-8244 KW - Microbiology Abstracts B: Bacteriology KW - J 02823:In vitro and in vivo effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16214461?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEMS+Immunology+and+Medical+Microbiology&rft.atitle=Microbial+factors+in+disease+emergence+illustrated+by+streptococcal+toxic+shock+syndrome&rft.au=Krause%2C+R&rft.aulast=Krause&rft.aufirst=R&rft.date=1997-08-01&rft.volume=18&rft.issue=4&rft.spage=227&rft.isbn=&rft.btitle=&rft.title=FEMS+Immunology+and+Medical+Microbiology&rft.issn=09288244&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 - Kinetic and stoichiometric analysis for the binding of Escherichia coli ribonuclease HI to RNA-DNA hybrids using surface plasmon resonance AN - 16094877; 4202058 AB - To understand how ribonucleases H recognize RNA-DNA hybrid substrates, we analyzed kinetic parameters of binding of Escherichia coli RNase HI to RNA-DNA hybrids ranging in length from 18 to 36 base pairs (bp) using surface plasmon resonance (BIAcore super(TM)). The k sub(on) and k sub(off) values for the binding of the enzyme to the 36-bp substrate were 1.5 x 10 super(6) M super(-1) s super(-1) and 3.2 x 10 super(-2) s super(-1), respectively. Similar values were obtained with the shorter substrates. Using uncleavable 2'-O-methylated RNA-DNA substrates, values for k sub(on) and k sub(off) were 2.1 x 10 super(5) M super(-1) s super(-1) and 1.3 x 10 super(-1) s super(-1) in the absence of Mg super(2+) that were further reduced in the presence of Mg super(2+) to 7.4 x 10 super(3) M super(-1) s super(-1) and 2.6 x 10 super(-2) s super(-1). Kinetic parameters similar to the wild-type enzyme were obtained using an active-site mutant enzyme, Asp super(134) replaced by Ala, whereas a greatly reduced on-rate was observed for another inactive mutant enzyme, in which the basic protrusion is eliminated, thereby distinguishing between poor catalysis and inability to bind to the substrate. Stoichiometric analyses of RNase HI binding to substrates of 18, 24, 30, and 36 bp are consistent with previous reports suggesting that RNase HI binds to 9-10 bp of RNA-DNA hybrid. JF - Journal of Biological Chemistry AU - Haruki, M AU - Noguchi, E AU - Kanaya, S AU - Crouch, R J AD - Lab. Mol. Genet., NICHD, Natl. Institutes Health, Bethesda, MD 20892-2790, USA Y1 - 1997/08// PY - 1997 DA - Aug 1997 SP - 22015 EP - 22022 VL - 272 IS - 35 SN - 0021-9258, 0021-9258 KW - DNA KW - ribonuclease HI KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - RNA KW - Escherichia coli KW - J 02726:RNA and ribosomes KW - N 14711:RNases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16094877?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Kinetic+and+stoichiometric+analysis+for+the+binding+of+Escherichia+coli+ribonuclease+HI+to+RNA-DNA+hybrids+using+surface+plasmon+resonance&rft.au=Haruki%2C+M%3BNoguchi%2C+E%3BKanaya%2C+S%3BCrouch%2C+R+J&rft.aulast=Haruki&rft.aufirst=M&rft.date=1997-08-01&rft.volume=18&rft.issue=9&rft.spage=1785&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; RNA; DNA ER - TY - JOUR T1 - The trp RNA-binding attenuation protein (TRAP) from Bacillus subtilis binds to unstacked trp leader RNA AN - 16075850; 4111107 AB - TRAP (trp RNA-binding attenuation protein) is a tryptophan-activated RNA-binding protein that regulates expression of the trp biosynthetic genes by binding to a series of GAG and UAG trinucleotide repeats generally separated by two or three spacer nucleotides. Previously, we showed that TRAP contains 11 identical subunits arranged in a symmetrical ring. Based on this structure, we proposed a model for the TRAP-3RNA interaction where the RNA wraps around the protein with each repeat of the RNA contacting one or a combination of two adjacent subunits of the TRAP oligomer. Here, we have shown that RNAs selected in vitro based on their ability to bind tryptophan-activated TRAP contain multiple G/UAG repeats and show a strong bias for pyrimidines as the spacer nucleotides between these repeats. The affinity of the TRAP-RNA interaction displays a nonlinear temperature dependence, increasing between 5 degree C and 47 degree C and then decreasing from 47 degree C to 67 degree C. Differential scanning calorimetry and circular dichroism spectroscopy demonstrate that TRAP is highly thermostable with few detectable changes in the structure between 25 degree C and 70 degree C, suggesting that the temperature dependence of this interaction reflects changes in the RNA. Results from circular dichroism and UV absorbance spectroscopy support this hypothesis, demonstrating that trp leader RNA becomes unstacked upon binding TRAP. We propose that the bias toward pyrimidines in the spacer nucleotides of the in vitro selected RNAs represents the inability of Us and Cs to form stable base stacking interactions, which allows the flexibility needed for the RNA to wrap around the TRAP oligomer. JF - Journal of Biological Chemistry AU - Baumann, C AU - Xirasagar, S AU - Gollnick, P AD - National Cancer Institute, National Institutes of Health, Laboratory of Receptor Biology and Gene Expression, Bethesda, MD, 20892, USA Y1 - 1997/08// PY - 1997 DA - Aug 1997 SP - 19863 EP - 19869 VL - 272 IS - 32 SN - 0021-9258, 0021-9258 KW - TRAP protein KW - trp gene KW - RNA-binding protein KW - tryptophan KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Bacillus subtilis KW - RNA KW - J 02726:RNA and ribosomes KW - N 14930:Transcription factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16075850?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=The+trp+RNA-binding+attenuation+protein+%28TRAP%29+from+Bacillus+subtilis+binds+to+unstacked+trp+leader+RNA&rft.au=Baumann%2C+C%3BXirasagar%2C+S%3BGollnick%2C+P&rft.aulast=Baumann&rft.aufirst=C&rft.date=1997-08-01&rft.volume=272&rft.issue=32&rft.spage=19863&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bacillus subtilis; RNA ER - TY - JOUR T1 - Gut epithelial cells as targets for gene therapy of hemophilia AN - 16059912; 4106640 AB - Gut epithelium is an attractive target for gene therapy of hemophilia due to the large number of rapidly dividing cells that should be readily accessible to a wide range of vectors by a noninvasive route of administration. We have performed in vitro tests to determine the suitability of gut epithelial cells for gene transfer, protein synthesis, and secretion of coagulation factors VIII and IX. The results with retroviral vectors indicate that transduced epithelial cells from human, rat, or porcine small or large intestine can synthesize significant amounts of factor VIII or factor IX and that two-thirds or more of the recombinant protein is secreted in a basolateral direction (i.e., away from the lumen and toward underlying capillaries and lymphatics). Furthermore, we have demonstrated that intestinal epithelial cells are susceptible to efficient gene transfer by lipofection and adenovirus vectors. In the case of factor IX, we have produced a high-titer adenovirus vector capable of transducing gut epithelial cells resulting in synthesis of factor IX. The results of our in vitro studies indicate that gene transfer targeting gut epithelium as a new approach to hemophilia gene therapy is rational and merits in vivo studies in hemophilia animal models. JF - Human Gene Therapy AU - Lozier, J N AU - Yankaskas, J R AU - Ramsey, W J AU - Chen, Lin AU - Berschneider, H AU - Morgan, R A AD - Gene Transfer Technology Section, Clinical Gene Therapy Branch, National Human Genome Research Institute, National Institutes of Health, Building 10, Room 10C103 MSC-1851, Bethesda, MD 20892-1851, USA Y1 - 1997/08// PY - 1997 DA - Aug 1997 SP - 1481 EP - 1490 VL - 8 IS - 12 SN - 1043-0342, 1043-0342 KW - coagulation factor IX KW - coagulation factor VIII KW - epithelial cells KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - gene therapy KW - gut KW - hemophilia 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/16059912?accountid=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=Gut+epithelial+cells+as+targets+for+gene+therapy+of+hemophilia&rft.au=Lozier%2C+J+N%3BYankaskas%2C+J+R%3BRamsey%2C+W+J%3BChen%2C+Lin%3BBerschneider%2C+H%3BMorgan%2C+R+A&rft.aulast=Lozier&rft.aufirst=J&rft.date=1997-08-01&rft.volume=8&rft.issue=12&rft.spage=1481&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 - 2011-12-14 N1 - SubjectsTermNotLitGenreText - gene therapy; gut; hemophilia ER - TY - JOUR T1 - Cancer coverage and tobacco advertising in African-American women's popular magazines AN - 16038869; 4092534 AB - Mass circulating magazines offer an opportunity to inform large segments of the population about preventive health behaviors relevant for cancer control. We collected information about the number and type of cancer articles from January 1987 through December 1994 in Jet, Ebony and Essence magazines. These magazines each have a principal readership of African-American women and a paid circulation of 1,000,000 or more annually. Cancer articles were counted if the content was gender neutral or specifically targeted for women. There were 84 articles on cancer including 6 on lung cancer and 3 on other tobacco-related cancers. Nine additional references to lung cancer were mentioned under the general cancer category, but lung cancer was not the primary focus of the articles. There were 24 articles on breast cancer and 9 on cervical cancer over the 8 year period. Most of the articles (>70%) were short fillers of less than one page in length. A prevention focus was included in 42.2%, 75.0%, and 71.0% of the cancer articles in Jet, Ebony, and Essence respectively. Of the 649 health articles, 116 were on cardiovascular disease. In contrast, there were 1,477 tobacco advertisements over the 8 years. The number of cancer articles was not significantly associated with the number of tobacco advertisements. Because tobacco-related cancers are entirely preventable and contribute to the significant cancer burden, the lack of coverage of tobacco-related cancers is a missed opportunity for health promotion among African-American females. JF - Journal of Community Health AU - Hoffman-Goetz, L AU - Gerlach, K K AU - Marino, C AU - Mills, S L AD - NCI, Executive Plaza North Rm. 232, 6130 Executive Blvd., Bethesda, MD 20892-7332, USA Y1 - 1997/08// PY - 1997 DA - Aug 1997 SP - 261 EP - 270 VL - 22 IS - 4 SN - 0094-5145, 0094-5145 KW - African Americans KW - advertising KW - Health & Safety Science Abstracts KW - ethnic groups KW - communications KW - education KW - females KW - tobacco KW - cancer KW - H SM10.21:CANCER UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16038869?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Community+Health&rft.atitle=Cancer+coverage+and+tobacco+advertising+in+African-American+women%27s+popular+magazines&rft.au=Hoffman-Goetz%2C+L%3BGerlach%2C+K+K%3BMarino%2C+C%3BMills%2C+S+L&rft.aulast=Hoffman-Goetz&rft.aufirst=L&rft.date=1997-08-01&rft.volume=22&rft.issue=4&rft.spage=261&rft.isbn=&rft.btitle=&rft.title=Journal+of+Community+Health&rft.issn=00945145&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 - cancer; tobacco; ethnic groups; females; education; communications ER - TY - JOUR T1 - The temperature-sensitive (ts) phenotype of cold-passaged (cp) live attenuated respiratory syncytial virus vaccine candidate, designated cpts530, results from a single amino acid substitution in the L protein AN - 16026655; 4092288 AB - cpts530, a candidate live-virus vaccine, is an attenuated strain of human respiratory syncytial virus (RSV). It was derived by subjecting a cold-passaged (cp) strain of RSV to a single round of chemical mutagenesis. cpts530 is a temperature-sensitive (ts) mutant that is attenuated in mice and chimpanzees, and its ts phenotype exhibits a high level of stability during replication in both species. In the present study, the complete nucleotide sequence of cpts530 RSV was determined. The five mutations known to be present in the parent cpRSV were retained in its cpts530 derivative, and one additional nucleotide change was identified at nucleotide (nt) 10060, which resulted in a phenylalanine-to-leucine change at amino acid 521 in the large polymerase (L) protein. To determine if this single amino acid substitution was indeed responsible for the ts phenotype of cpts530, it was introduced alone or in combination with the cp mutations into the full-length cDNA clone of the wild-type A2 RSV. Analysis of infectious viruses recovered from mutant cDNAs indicated that this single mutation specified complete restriction of plaque formation of recombinant cp530 in HEp-2 cell monolayer cultures at 40 degree C, and the level of temperature sensitivity was not influenced by the presence of the five cpRSV mutations. These findings identify the phenylalanine-to-leucine change at amino acid 521 in the L protein as the mutation that specifies the ts phenotype of cpts530. Furthermore, these findings illustrate the feasibility of using the cDNA-based recovery system to analyze and construct defined attenuated vaccine viruses. JF - Journal of Virology AU - Juhasz, K AU - Whitehead, S S AU - Bui, P T AU - Biggs, J M AU - Boulanger, CA AU - Collins, P L AU - Murphy, B R AD - NIH, LID, NIAID, 7 Center Dr., MSC-0720, Bethesda, MD 20892-0720, USA Y1 - 1997/08// PY - 1997 DA - Aug 1997 SP - 5814 EP - 5819 VL - 71 IS - 8 SN - 0022-538X, 0022-538X KW - L protein KW - phenylalanine KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - vaccines KW - respiratory syncytial virus KW - temperature-sensitive mutant KW - mutation KW - A 01100:Viruses KW - V 22098:Immunization: Vaccines & vaccination: Animal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16026655?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Virology&rft.atitle=The+temperature-sensitive+%28ts%29+phenotype+of+cold-passaged+%28cp%29+live+attenuated+respiratory+syncytial+virus+vaccine+candidate%2C+designated+cpts530%2C+results+from+a+single+amino+acid+substitution+in+the+L+protein&rft.au=Juhasz%2C+K%3BWhitehead%2C+S+S%3BBui%2C+P+T%3BBiggs%2C+J+M%3BBoulanger%2C+CA%3BCollins%2C+P+L%3BMurphy%2C+B+R&rft.aulast=Juhasz&rft.aufirst=K&rft.date=1997-08-01&rft.volume=71&rft.issue=8&rft.spage=5814&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - respiratory syncytial virus; vaccines; temperature-sensitive mutant; mutation ER - TY - JOUR T1 - Molecular characterization of the promoter region of a neuroendocrine tumor marker, IA-1. AN - 79178144; 9245732 AB - IA-1 is an intronless gene, which encodes a 510 amino acid protein with a zinc-finger DNA-binding motif that is expressed in tumors of neuroendocrine origin. The 5'-upstream region of the IA-1 gene was recently sequenced. In this paper, the regulatory elements and the promoter region of the 5'-upstream region were analyzed by use of a series of deletion mutants (ranging from +26 bp to -2090 bp upstream of the IA-1 gene), which were tested in a pituitary tumor cell line, AtT-20, and Hela cells by transient transfection assays. These experiments showed that a 506 base pair upstream sequence was sufficient for maximal expression of a reporter gene. Multiple known regulatory elements were found within this region including three E boxes and a clustered Sp-1 site. In addition, Southwestern blot analysis, using a radiolabeled promoter sequence (extending from -108 bp to -66 bp) and nuclear extracts from both neuroendocrine and non-neuroendocrine cell lines, revealed four promoter binding proteins designated PBP1, PBP2, PBP3 and PBP4 with molecular weights of 55 kD, 32 kD, 29 kD, and 27/28 kD, respectively. These studies suggest that several different regulatory elements in the 5'-upstream region of the IA-1 gene and at least four different nuclear proteins may be involved in the cell-specific expression of IA-1. JF - Biochemical and biophysical research communications AU - Li, Q AU - Notkins, A L AU - Lan, M S AD - Oral Infection and Immunity Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/07/30/ PY - 1997 DA - 1997 Jul 30 SP - 776 EP - 781 VL - 236 IS - 3 SN - 0006-291X, 0006-291X KW - Biomarkers, Tumor KW - 0 KW - DNA-Binding Proteins KW - Neoplasm Proteins KW - Nuclear Proteins KW - Repressor Proteins KW - Sp1 Transcription Factor KW - INSM1 protein, human KW - 147955-03-1 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Nuclear Proteins -- analysis KW - Regulatory Sequences, Nucleic Acid KW - Tumor Cells, Cultured KW - Transfection KW - Humans KW - DNA -- metabolism KW - Sp1 Transcription Factor -- metabolism KW - Nuclear Proteins -- metabolism KW - Mutagenesis KW - Gene Deletion KW - Binding Sites KW - Neuroendocrine Tumors -- chemistry KW - Promoter Regions, Genetic KW - Neoplasm Proteins -- genetics KW - DNA-Binding Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79178144?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=Molecular+characterization+of+the+promoter+region+of+a+neuroendocrine+tumor+marker%2C+IA-1.&rft.au=Li%2C+Q%3BNotkins%2C+A+L%3BLan%2C+M+S&rft.aulast=Li&rft.aufirst=Q&rft.date=1997-07-30&rft.volume=236&rft.issue=3&rft.spage=776&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-15 N1 - Date created - 1997-09-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A nested case-control study of non-Hodgkin lymphoma and serum organochlorine residues. AN - 79166351; 9242800 AB - The steady worldwide increase in the incidence of non-Hodgkin lymphoma during the past few decades remains mostly unexplained. Several studies suggest that there may be an association between the agricultural use of the organochlorine 1,1,1-trichloro-2,2'bis(p-chlorophenyl)ethane (DDT) and increased risk of non-Hodgkin lymphoma. We have investigated the association between risk of non-Hodgkin lymphoma and body burden of selected organochlorines in the general population in a nested case-control study. We measured prediagnostic serum concentrations of DDT, its metabolites, and other organochlorines, including polychlorinated biphenyls (PCBs), in 74 cases of non-Hodgkin lymphoma and 147 matched controls identified from a prospective cohort of 25,802 adults, established in 1974 in Washington County, Maryland, USA. We report results for total lipid-corrected serum concentrations of DDT and total PCBs. There was a strong dose-response relation between quartiles of total lipid-corrected serum PCB concentrations and risk of non-Hodgkin lymphoma overall (odds ratios by quartile: 1.0; 1.3 [95% CI 0.5-3.3]; 2.8 [1.1-7.6]); and 4.5 [1.7-12.0]; p for trend = 0.0008) and separately in men and in women. There was also evidence suggesting that seropositivity for the Epstein-Barr virus early antigen potentiated the effects of serum PCBs. By contrast, total lipid-corrected serum concentrations of DDT were not associated with risk of non-Hodgkin lymphoma. These results should be regarded as hypothesis-generating. Before causal inferences can be made about exposure to PCBs and increased risk of non-Hodgkin lymphoma, our findings require replication and the biological plausibility of the association needs further investigation. JF - Lancet (London, England) AU - Rothman, N AU - Cantor, K P AU - Blair, A AU - Bush, D AU - Brock, J W AU - Helzlsouer, K AU - Zahm, S H AU - Needham, L L AU - Pearson, G R AU - Hoover, R N AU - Comstock, G W AU - Strickland, P T AD - Division of Cancer Edidemiology and Genetics (EPN 418), National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1997/07/26/ PY - 1997 DA - 1997 Jul 26 SP - 240 EP - 244 VL - 350 IS - 9073 SN - 0140-6736, 0140-6736 KW - Insecticides KW - 0 KW - DDT KW - CIW5S16655 KW - Abridged Index Medicus KW - Index Medicus KW - Body Burden KW - Humans KW - DDT -- adverse effects KW - Herpesviridae Infections -- complications KW - Herpesvirus 4, Human -- isolation & purification KW - Registries KW - DDT -- blood KW - Adult KW - Case-Control Studies KW - Incidence KW - Middle Aged KW - Maryland -- epidemiology KW - Female KW - Male KW - Tumor Virus Infections -- complications KW - Lymphoma, Non-Hodgkin -- epidemiology KW - Insecticides -- adverse effects KW - Lymphoma, Non-Hodgkin -- blood KW - Lymphoma, Non-Hodgkin -- etiology KW - Insecticides -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79166351?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Effect+of+recombinant+alpha-interferon+on+pharmacokinetics%2C+biodistribution%2C+toxicity%2C+and+efficacy+of+131I-labeled+monoclonal+antibody+CC49+in+breast+cancer%3A+a+phase+II+trial.&rft.au=Macey%2C+D+J%3BGrant%2C+E+J%3BKasi%2C+L%3BRosenblum%2C+M+G%3BZhang%2C+H+Z%3BKatz%2C+R+L%3BRieger%2C+P+T%3BLeBherz%2C+D%3BSouth%2C+M%3BGreiner%2C+J+W%3BSchlom%2C+J%3BPodoloff%2C+D+A%3BMurray%2C+J+L&rft.aulast=Macey&rft.aufirst=D&rft.date=1997-09-01&rft.volume=3&rft.issue=9&rft.spage=1547&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-21 N1 - Date created - 1997-08-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of aging on vulnerability of striatal D1 and D2 dopamine receptor-containing neurons to kainic acid. AN - 79284649; 9296569 AB - Kainic acid lesions elicit reductions in ligand binding to both D1 and D2 striata dopamine receptors in young and old rats. Relative reductions are greatest for both receptors in young animals than old. In addition, D1 receptor binding is reduced more than D2 at both ages. These findings support the idea that those dopamine receptor neurons lost during aging may reside in a kainic acid sensitive population. JF - Brain research AU - Zhang, L AU - Joseph, J A AU - Roth, G S AD - Laboratory of Cellular and Molecular Biology, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Johns Hopkins Bayview Medical Center, Baltimore, MD 21224, USA. Y1 - 1997/07/25/ PY - 1997 DA - 1997 Jul 25 SP - 264 EP - 266 VL - 763 IS - 2 SN - 0006-8993, 0006-8993 KW - Excitatory Amino Acid Agonists KW - 0 KW - Neurotoxins KW - Receptors, Dopamine D1 KW - Receptors, Dopamine D2 KW - Kainic Acid KW - SIV03811UC KW - Index Medicus KW - Rats KW - Corpus Striatum -- cytology KW - Animals KW - Corpus Striatum -- chemistry KW - Protein Binding -- drug effects KW - Rats, Wistar KW - Neurotoxins -- pharmacology KW - Aging -- physiology KW - Receptors, Dopamine D1 -- analysis KW - Kainic Acid -- pharmacology KW - Neurons -- chemistry KW - Neurons -- drug effects KW - Excitatory Amino Acid Agonists -- pharmacology KW - Receptors, Dopamine D2 -- analysis KW - Receptors, Dopamine D1 -- metabolism KW - Receptors, Dopamine D2 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79284649?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+aging+on+vulnerability+of+striatal+D1+and+D2+dopamine+receptor-containing+neurons+to+kainic+acid.&rft.au=Zhang%2C+L%3BJoseph%2C+J+A%3BRoth%2C+G+S&rft.aulast=Zhang&rft.aufirst=L&rft.date=1997-07-25&rft.volume=763&rft.issue=2&rft.spage=264&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 - 1997-10-23 N1 - Date created - 1997-10-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High-activity catechol-O-methyltransferase allele is more prevalent in polysubstance abusers. AN - 79204969; 9259381 AB - Allelic variants at the catechol-O-methyltransferase (COMT) locus are candidates to contribute to genetic components of interindividual differences in vulnerability to substance abuse. COMT plays a prominent role in dopaminergic circuits important for drug reward, and COMT alleles encode enzymes whose activities vary from three- to four-fold. We compared COMT allele frequencies in control research volunteers reporting insignificant lifetime use of addictive substances with those in volunteers reporting substantial polysubstance use. Homozygosity for the high-activity COMT allele was found in 18% of controls, 31% of volunteers with high lifetime substance use, and 39% meeting DSMIII-R substance abuse criteria [odds ratio (relative risks) 2.0 (control vs. use; 95% confidence interval 1.2-3.5; P < 0.013) and 2.8 (control vs. DSM; 1.3-6.1; P < 0.008)]. Individuals with the high-activity COMT variant may have greater genetic vulnerability to drug abuse. JF - American journal of medical genetics AU - Vandenbergh, D J AU - Rodriguez, L A AU - Miller, I T AU - Uhl, G R AU - Lachman, H M AD - Molecular Neurobiology Branch, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, Maryland, USA. Y1 - 1997/07/25/ PY - 1997 DA - 1997 Jul 25 SP - 439 EP - 442 VL - 74 IS - 4 SN - 0148-7299, 0148-7299 KW - Codon KW - 0 KW - Catechol O-Methyltransferase KW - EC 2.1.1.6 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Genotype KW - Odds Ratio KW - Alleles KW - Codon -- genetics KW - Reward KW - Gene Frequency KW - Disease Susceptibility KW - Polymorphism, Restriction Fragment Length KW - Humans KW - Dopamine -- metabolism KW - Catechol O-Methyltransferase -- genetics KW - Substance-Related Disorders -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79204969?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=High-activity+catechol-O-methyltransferase+allele+is+more+prevalent+in+polysubstance+abusers.&rft.au=Vandenbergh%2C+D+J%3BRodriguez%2C+L+A%3BMiller%2C+I+T%3BUhl%2C+G+R%3BLachman%2C+H+M&rft.aulast=Vandenbergh&rft.aufirst=D&rft.date=1997-07-25&rft.volume=74&rft.issue=4&rft.spage=439&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 - 1997-11-06 N1 - Date created - 1997-11-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glucose transporter isoforms GLUT1 and GLUT3 transport dehydroascorbic acid. AN - 79151220; 9228080 AB - Dehydroascorbic acid (DHA) is rapidly taken up by cells and reduced to ascorbic acid (AA). Using the Xenopus laevis oocyte expression system we examined transport of DHA and AA via glucose transporter isoforms GLUT1-5 and SGLT1. The apparent Km of DHA transport via GLUT1 and GLUT3 was 1.1 +/- 0.2 and 1.7 +/- 0.3 mM, respectively. High performance liquid chromatography analysis confirmed 100% reduction of DHA to AA within oocytes. GLUT4 transport of DHA was only 2-4-fold above control and transport kinetics could not be calculated. GLUT2, GLUT5, and SGLT1 did not transport DHA and none of the isoforms transported AA. Radiolabeled sugar transport confirmed transporter function and identity of all cDNA clones was confirmed by restriction fragment mapping. GLUT1 and GLUT3 cDNA were further verified by polymerase chain reaction. DHA transport activity in both GLUT1 and GLUT3 was inhibited by 2-deoxyglucose, D-glucose, and 3-O-methylglucose among other hexoses while fructose and L-glucose showed no inhibition. Inhibition by the endofacial inhibitor, cytochalasin B, was non-competitive and inhibition by the exofacial inhibitor, 4,6-O-ethylidene-alpha-glucose, was competitive. Expressed mutant constructs of GLUT1 and GLUT3 did not transport DHA. DHA and 2-deoxyglucose uptake by Chinese hamster ovary cells overexpressing either GLUT1 or GLUT3 was increased 2-8-fold over control cells. These studies suggest GLUT1 and GLUT3 isoforms are the specific glucose transporter isoforms which mediate DHA transport and subsequent accumulation of AA. JF - The Journal of biological chemistry AU - Rumsey, S C AU - Kwon, O AU - Xu, G W AU - Burant, C F AU - Simpson, I AU - Levine, M AD - NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/07/25/ PY - 1997 DA - 1997 Jul 25 SP - 18982 EP - 18989 VL - 272 IS - 30 SN - 0021-9258, 0021-9258 KW - Glucose Transporter Type 1 KW - 0 KW - Glucose Transporter Type 2 KW - Glucose Transporter Type 3 KW - Glucose Transporter Type 4 KW - Glucose Transporter Type 5 KW - Membrane Glycoproteins KW - Monosaccharide Transport Proteins KW - Muscle Proteins KW - Nerve Tissue Proteins KW - SLC2A1 protein, human KW - SLC2A3 protein, human KW - SLC2A4 protein, human KW - SLC5A1 protein, human KW - Slc2a1 protein, rat KW - Slc2a3 protein, rat KW - Slc2a4 protein, rat KW - Slc5a1 protein, rat KW - Sodium-Glucose Transporter 1 KW - Deoxyglucose KW - 9G2MP84A8W KW - Dehydroascorbic Acid KW - Y2Z3ZTP9UM KW - Index Medicus KW - Animals KW - Humans KW - Biological Transport KW - Rats KW - Mutagenesis, Site-Directed KW - Xenopus laevis KW - Oocytes -- metabolism KW - Kinetics KW - Restriction Mapping KW - CHO Cells KW - Membrane Glycoproteins -- metabolism KW - Cricetinae KW - Deoxyglucose -- metabolism KW - Monosaccharide Transport Proteins -- metabolism KW - Dehydroascorbic Acid -- metabolism KW - Monosaccharide Transport Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79151220?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Sex-dependent+differences+in+the+disposition+of+2%2C4-dichlorophenoxyacetic+acid+in+Sprague-Dawley+rats%2C+B6C3F1+mice%2C+and+Syrian+hamsters.&rft.au=Griffin%2C+R+J%3BGodfrey%2C+V+B%3BKim%2C+Y+C%3BBurka%2C+L+T&rft.aulast=Griffin&rft.aufirst=R&rft.date=1997-09-01&rft.volume=25&rft.issue=9&rft.spage=1065&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 - 1997-09-09 N1 - Date created - 1997-09-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Determination of tamoxifen and metabolites in serum by capillary electrophoresis using a nonaqueous buffer system. AN - 79231688; 9271143 AB - Tamoxifen (TAM), an antiestrogen, is widely used to treat hormone-dependent breast cancer in post-menopausal women. TAM may be used as a chemopreventive agent in women of child-bearing age; however, few data exist describing potential TAM-induced fetal toxicity. In support of the National Toxicology Program's characterization of reproductive and developmental effects of TAM, this work describes an analytical technique utilizing capillary electrophoresis (CE) for the detection of circulating levels of TAM, N-desmethyltamoxifen (DMT), and 4-hydroxytamoxifen (4-HT) in maternal rodent serum. Greater than 90% of 3H-labeled TAM was extractable from serum using 98:2 hexane-isoamyl alcohol. Optimum separation of TAM, DMT, and 4-HT was obtained on a 57 cmx50 microm capillary using a nonaqueous buffer system of 1:1 methanol-acetonitrile containing 50 mM ammonium acetate and 1% acetic acid. 4-Dimethylaminopyridine was used as internal standard. Temperature and voltage were optimized at 40 degrees C and 15 kV, respectively. The limit of detection of TAM by UV detection at 214 nm was approximately 800 amol. TAM and DMT were confirmed in serum of female rats 4 h following a single oral dose of 120 mg/kg. Transplacental exposure of TAM to fetal tissue will be evaluated using this technique. JF - Journal of chromatography. B, Biomedical sciences and applications AU - Sanders, J M AU - Burka, L T AU - Shelby, M D AU - Newbold, R R AU - Cunningham, M L AD - National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1997/07/18/ PY - 1997 DA - 1997 Jul 18 SP - 181 EP - 185 VL - 695 IS - 1 SN - 1387-2273, 1387-2273 KW - Anticarcinogenic Agents KW - 0 KW - Buffers KW - Tamoxifen KW - 094ZI81Y45 KW - afimoxifene KW - 17197F0KYM KW - N-desmethyltamoxifen KW - OOJ759O35C KW - Index Medicus KW - Sensitivity and Specificity KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Spectrophotometry, Ultraviolet KW - Female KW - Electrophoresis, Capillary KW - Tamoxifen -- blood KW - Anticarcinogenic Agents -- blood KW - Tamoxifen -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79231688?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+chromatography.+B%2C+Biomedical+sciences+and+applications&rft.atitle=Determination+of+tamoxifen+and+metabolites+in+serum+by+capillary+electrophoresis+using+a+nonaqueous+buffer+system.&rft.au=Sanders%2C+J+M%3BBurka%2C+L+T%3BShelby%2C+M+D%3BNewbold%2C+R+R%3BCunningham%2C+M+L&rft.aulast=Sanders&rft.aufirst=J&rft.date=1997-07-18&rft.volume=695&rft.issue=1&rft.spage=181&rft.isbn=&rft.btitle=&rft.title=Journal+of+chromatography.+B%2C+Biomedical+sciences+and+applications&rft.issn=13872273&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-25 N1 - Date created - 1997-09-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Growth inhibition and induction of apoptosis by HGF in transformed rat liver epithelial cells. AN - 79164953; 9240448 AB - Recently we demonstrated in a transgenic mouse model that hepatocyte growth factor (HGF) inhibits c-myc dependent hepatocarcinogenesis. The inhibitory effects of HGF in carcinogenesis were further characterized using a series of rat liver epithelial (RLE) cell lines which were transformed in vitro with either aflatoxin or oncogenes, or spontaneously. HGF caused a cytostatic effect and enhanced cell motility in spontaneously and aflatoxin-transformed cells. In normal RLE cells HGF was slightly stimulatory and did not induce scattering. The HGF receptor was tyrosine phosphorylated in all cell lines, indicating that it is functionally active and capable of signaling events. In the aflatoxin transformed cells HGF also induced apoptosis, associated with constitutive c-myc expression and 1 Kb bax-alpha transcripts. These findings indicate that transformed RLE cell lines may provide a useful model to further examine the mechanism(s) by which HGF and its receptor modulate neoplastic development. JF - Biochemical and biophysical research communications AU - Conner, E A AU - Wirth, P J AU - Kiss, A AU - Santoni-Rugiu, E AU - Thorgeirsson, S S AD - Division of Basic Sciences, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1997/07/18/ PY - 1997 DA - 1997 Jul 18 SP - 396 EP - 401 VL - 236 IS - 2 SN - 0006-291X, 0006-291X KW - Bax protein, rat KW - 0 KW - Growth Inhibitors KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - bcl-2-Associated X Protein KW - Phosphotyrosine KW - 21820-51-9 KW - Hepatocyte Growth Factor KW - 67256-21-7 KW - Proto-Oncogene Proteins c-met KW - EC 2.7.10.1 KW - Receptor Protein-Tyrosine Kinases KW - Index Medicus KW - Rats KW - Animals KW - Tumor Cells, Cultured KW - Phosphorylation KW - Genes, p53 KW - Epithelial Cells KW - Genes, myc KW - Phosphotyrosine -- metabolism KW - Gene Expression KW - Receptor Protein-Tyrosine Kinases -- metabolism KW - Proto-Oncogene Proteins -- genetics KW - Liver -- cytology KW - Hepatocyte Growth Factor -- pharmacology KW - Growth Inhibitors -- pharmacology KW - Apoptosis -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79164953?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Growth+inhibition+and+induction+of+apoptosis+by+HGF+in+transformed+rat+liver+epithelial+cells.&rft.au=Conner%2C+E+A%3BWirth%2C+P+J%3BKiss%2C+A%3BSantoni-Rugiu%2C+E%3BThorgeirsson%2C+S+S&rft.aulast=Conner&rft.aufirst=E&rft.date=1997-07-18&rft.volume=236&rft.issue=2&rft.spage=396&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-28 N1 - Date created - 1997-08-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ligand-induced internalization of cholecystokinin receptors. Demonstration of the importance of the carboxyl terminus for ligand-induced internalization of the rat cholecystokinin type B receptor but not the type A receptor. AN - 79122043; 9218453 AB - Internalization of a variety of different heptahelical G protein-coupled receptors has been shown to be influenced by a number of different structural determinants of the receptors, including the carboxyl terminus. To investigate the role of the carboxyl terminus of cholecystokinin (CCK) receptors in receptor internalization, the rat wild type (WT) CCK-A receptor (WT CCKAR) and the rat WT CCK-B receptor (WT CCKBR) were truncated after amino acid residue 399 (CCKAR Tr399) and 408 (CCKBR Tr408), thereby deleting the carboxyl-terminal 45 and 44 residues, respectively. All WT and mutant CCK receptors were stably expressed in NIH/3T3 cells. Internalization of the CCKAR Tr399 was not significantly different from the WT CCKAR. In contrast, internalization of the CCKBR Tr408 was decreased to 26% compared with the WT CCKBR internalization of 92%. The mutation of all 10 serine and threonine residues (as potential phosphorylation sites) in the carboxyl terminus of the CCKBR to alanines (mutant CCKBR DeltaS/T) could account for the majority of this effect (39% internalization). All mutant receptors displayed similar ligand binding characteristics, G protein coupling, and signal transduction as their respective WT receptors, indicating that the carboxyl termini are not necessary for these processes. Thus, internalization of the CCKBR, unlike that of the CCKAR, depends on the carboxyl terminus of the receptor. These results suggest that, despite the high degree of homology between CCKAR and CCKBR, the structural determinants that mediate the interaction with the endocytic pathway reside in different regions of the receptors. JF - The Journal of biological chemistry AU - Pohl, M AU - Silvente-Poirot, S AU - Pisegna, J R AU - Tarasova, N I AU - Wank, S A AD - Digestive Diseases Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/07/18/ PY - 1997 DA - 1997 Jul 18 SP - 18179 EP - 18184 VL - 272 IS - 29 SN - 0021-9258, 0021-9258 KW - Fluorescent Dyes KW - 0 KW - Iodine Radioisotopes KW - Ligands KW - Receptor, Cholecystokinin A KW - Receptor, Cholecystokinin B KW - Receptors, Cholecystokinin KW - Recombinant Proteins KW - Rhodamines KW - Sincalide KW - M03GIQ7Z6P KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Protein Structure, Secondary KW - Amino Acid Sequence KW - Mice KW - Radioligand Assay KW - Rats KW - Calcium -- metabolism KW - Mutagenesis, Site-Directed KW - Transfection KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Molecular Sequence Data KW - Substrate Specificity KW - Recombinant Proteins -- chemistry KW - Sequence Deletion KW - Sincalide -- metabolism KW - Receptors, Cholecystokinin -- metabolism KW - Receptors, Cholecystokinin -- chemistry KW - Sincalide -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79122043?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Ligand-induced+internalization+of+cholecystokinin+receptors.+Demonstration+of+the+importance+of+the+carboxyl+terminus+for+ligand-induced+internalization+of+the+rat+cholecystokinin+type+B+receptor+but+not+the+type+A+receptor.&rft.au=Pohl%2C+M%3BSilvente-Poirot%2C+S%3BPisegna%2C+J+R%3BTarasova%2C+N+I%3BWank%2C+S+A&rft.aulast=Pohl&rft.aufirst=M&rft.date=1997-07-18&rft.volume=272&rft.issue=29&rft.spage=18179&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-18 N1 - Date created - 1997-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - P. falciparum rosetting mediated by a parasite-variant erythrocyte membrane protein and complement-receptor 1 AN - 1520377291; 13691608 AB - The factors determining disease severity in malaria are complex and include host polymorphisms, acquired immunity and parasite virulence. Studies in Africa have shown that severe malaria is associated with the ability of erythrocytes infected with the parasite Plasmodium falciparum to bind uninfected erythrocytes and form rosettes. The molecular basis of rosetting is not well understood, although a group of low-molecular-mass proteins called rosettins have been described as potential parasite ligands. Infected erythrocytes also bind to endothelial cells, and this interaction is mediated by the parasite-derived variant erythrocyte membrane protein PfEMP1 (refs 7, 8), which is encoded by the var gene family. Here we report that the parasite ligand for rosetting in a P. falciparum clone is PfEMP1, encoded by a specific var gene. We also report that complement-receptor 1 (CR1) on erythrocytes plays a role in the formation of rosettes and that erythrocytes with a common African CR1 polymorphism (Sl(a super(-))) have reduced adhesion to the domain of PfEMP1 that binds normal erythrocytes. Thus we describe a new adhesive function for PfEMP1 and raise the possibility that CR1 polymorphisms in Africans that influence the interaction between erythrocytes and PfEMP1 may protect against severe malaria. JF - Nature AU - Rowe, JAlexandra AU - Moulds, Joann M AU - Newbold, Christopher I AU - Miller, Louis H AD - [1] Laboratory of Parasitic Diseases, NIAID, NIH, 9000 Rockville Pike, Bethesda, Maryland, 20892, USA [2] Molecular Parasitology Group, Institute of Molecular Medicine, John Radcliffe Hospital, OxfordOX3 9DU, UK Y1 - 1997/07/17/ PY - 1997 DA - 1997 Jul 17 SP - 292 EP - 295 PB - Nature Publishing Group, The Macmillan Building London N1 9XW UK VL - 388 IS - 6639 SN - 0028-0836, 0028-0836 KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; ASFA 1: Biological Sciences & Living Resources; ASFA 3: Aquatic Pollution & Environmental Quality KW - Parasites KW - Human diseases KW - var gene KW - Erythrocytes KW - Malaria KW - Plasmodium falciparum KW - Membrane proteins KW - Immunity KW - Hosts KW - Adhesion KW - Public health KW - Endothelial cells KW - Virulence KW - Africa KW - Adhesives KW - Complement receptors KW - Ligands KW - Q1 08423:Behaviour KW - Q5 08524:Public health, medicines, dangerous organisms KW - K 03320:Cell Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1520377291?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=P.+falciparum+rosetting+mediated+by+a+parasite-variant+erythrocyte+membrane+protein+and+complement-receptor+1&rft.au=Rowe%2C+JAlexandra%3BMoulds%2C+Joann+M%3BNewbold%2C+Christopher+I%3BMiller%2C+Louis+H&rft.aulast=Rowe&rft.aufirst=JAlexandra&rft.date=1997-07-17&rft.volume=388&rft.issue=6639&rft.spage=292&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/10.1038%2F40888 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2014-04-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Virulence; Parasites; Human diseases; Erythrocytes; Malaria; Hosts; Adhesion; Ligands; Public health; Endothelial cells; var gene; Immunity; Membrane proteins; Adhesives; Complement receptors; Plasmodium falciparum; Africa DO - http://dx.doi.org/10.1038/40888 ER - TY - JOUR T1 - Benzene and the dose-related incidence of hematologic neoplasms in China. Chinese Academy of Preventive Medicine--National Cancer Institute Benzene Study Group. AN - 79143982; 9230889 AB - Benzene is a widely distributed environmental contaminant known to cause leukemia, particularly acute nonlymphocytic leukemia, and perhaps other hematologic neoplasms and disorders. Few epidemiologic studies, however, have been able to address relationships between the extent of benzene exposure and the level of risk. A large cohort study was carried out in China to evaluate the risks of developing specific hematologic neoplasms and selected related disorders in relationship to quantitative estimates of occupational benzene exposure. A cohort of 74828 benzene-exposed and 35805 unexposed workers employed from 1972 through 1987 in 12 cities in China was identified and followed to determine the incidence of hematologic neoplasms and related disorders. Estimates of benzene exposure were derived from work histories and available historic benzene measurements. Existing pathologic material and supporting medical records were reviewed to establish diagnoses of disease. Relative risks (RRs) (i.e., ratios of incidence rates for specific hematologic neoplasms and related disorders in the benzene-exposed group to incidence rates in the unexposed group) were determined by use of Poisson regression analysis, with stratification by age and sex. For workers historically exposed to benzene at average levels of less than 10 parts per million (ppm), the RR for all hematologic neoplasm combined was 2.2 (95% confidence interval [CI] = 1.1-4.2), and, for the combination of acute nonlymphocytic leukemia and related myelodysplastic syndromes, the RR was 3.2 (95% CI = 1.0-10.1). For individuals who were occupationally exposed to benzene at constant levels of 25 ppm or more, the RR for the combination of acute nonlymphocytic leukemia and related myelodysplastic syndromes was 7.1 (95% CI = 2.1-23.7). Workers with 10 or more years of benzene exposure had an RR of developing non-Hodgkin's lymphoma of 4.2 (95% CI = 1.1-15.9), and the development of this neoplasm was linked most strongly to exposure that had occurred at least 10 years before diagnosis (i.e., distant exposure) (P for trend = .005, two-sided). In contrast, the risk for the combination of acute nonlymphocytic leukemia and related myelodysplastic syndromes was significantly increased among those with more recent benzene exposure (P for trend = .003, two-sided), but it was not linked to distant exposure (P for trend = .51, two-sided). The results of this study suggest that benzene exposure is associated with a spectrum of hematologic neoplasms and related disorders in humans. Risks for these conditions are elevated at average benzene-exposure levels of less than 10 ppm and show a tendency, although not a strong one, to rise with increasing levels of exposure. The temporal pattern of benzene exposure appears to be important in determining the risk of developing specific diseases. JF - Journal of the National Cancer Institute AU - Hayes, R B AU - Yin, S N AU - Dosemeci, M AU - Li, G L AU - Wacholder, S AU - Travis, L B AU - Li, C Y AU - Rothman, N AU - Hoover, R N AU - Linet, M S AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/07/16/ PY - 1997 DA - 1997 Jul 16 SP - 1065 EP - 1071 VL - 89 IS - 14 SN - 0027-8874, 0027-8874 KW - Benzene KW - J64922108F KW - Index Medicus KW - Risk KW - Dose-Response Relationship, Drug KW - Humans KW - China -- epidemiology KW - Cohort Studies KW - Incidence KW - Poisson Distribution KW - Time Factors KW - Sex Distribution KW - Age Distribution KW - Hematologic Neoplasms -- chemically induced KW - Occupational Exposure -- adverse effects KW - Hematologic Neoplasms -- epidemiology KW - Benzene -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79143982?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Benzene+and+the+dose-related+incidence+of+hematologic+neoplasms+in+China.+Chinese+Academy+of+Preventive+Medicine--National+Cancer+Institute+Benzene+Study+Group.&rft.au=Hayes%2C+R+B%3BYin%2C+S+N%3BDosemeci%2C+M%3BLi%2C+G+L%3BWacholder%2C+S%3BTravis%2C+L+B%3BLi%2C+C+Y%3BRothman%2C+N%3BHoover%2C+R+N%3BLinet%2C+M+S&rft.aulast=Hayes&rft.aufirst=R&rft.date=1997-07-16&rft.volume=89&rft.issue=14&rft.spage=1065&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-05 N1 - Date created - 1997-08-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Natl Cancer Inst. 1998 Mar 18;90(6):469-71 [9521175] J Natl Cancer Inst. 1997 Nov 19;89(22):1728-9 [9390548] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - National Institutes of Health Consensus Development conference statement: Breast cancer screening for women ages 40-49, January 21-23, 1997 AN - 221008729; 97374434; 9230883; 03334982 AB - OBJECTIVE: To provide health care providers, patients, and the general public with a responsible assessment of currently available data regarding the effectiveness of mammography screening for women ages 40-49. PARTICIPANTS: A non-Federal, nonadvocate, 12-member panel representing the fields of oncology, radiology, obstetrics and gynecology, geriatrics, public health, and epidemiology and including patient representatives. In addition, 32 experts in oncology, surgical oncology, radiology, public health, and epidemiology, presented data to the panel and to a conference audience of 1,100. EVIDENCE: The literature was searched through Medline and an extensive bibliography of references was provided to the panel and the conference audience. Experts prepared abstracts with relevant citations from the literature. Scientific evidence was given precedence over clinical anecdotal experience. CONSENSUS PROCESS: The panel, answering predefined questions, developed its conclusions based on the scientific evidence presented in open forum and the scientific literature. The panel composed a draft statement that was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised draft statement at the end of the conference. The final statement with a minority report was completed within several weeks after the conference. CONCLUSIONS: The Panel concludes that the data currently available do not warrant a universal recommendation for mammography for all women in their forties. Each woman should decide for herself whether to undergo mammography. Her decision may be based not only on an objective analysis of the scientific evidence and consideration of her individual medical history, but also on how she perceives and weighs each potential risk and benefit, the values she places on each, and how she deals with uncertainty. However, it is not sufficient just to advise a woman to make her own decision about mammograms. Given both the importance and the complexity of the issues involved in assessing the evidence, a woman should have access to the best possible relevant information regarding both benefits and risks, presented in an understandable and usable form. Information should be developed for women in their forties regarding potential benefits and risks to be provided to enable each woman to make the most appropriate decision. In addition, educational material to accompany this information should be prepared that will lead women step by step through the process of using such information in the best possible way for reaching a decision. For women in their forties who choose to have mammography performed, the costs of the mammograms should be reimbursed by third-party payors or covered by health maintenance organizations so that financial impediments will not influence a woman's decision. Additionally, a woman's health care provider must be equipped with sufficient information to facilitate her decisionmaking process. Therefore, educational material for physicians should be developed to assist them in providing the guidance and support needed by the women in their care who are making difficult decisions regarding mammography. The two panel members writing a minority report believed the risks of mammography to be overemphasized by the majority and concluded that the data did support a recommendation for mammography screening for all women in this age group and that the survival benefit and diagnosis at an earlier stage outweigh the potential risks. JF - Journal of the National Cancer Institute AU - National Institutes of Health Consensus Development Panel AD - National Institutes of Health Consensus Development Panel Y1 - 1997/07/16/ PY - 1997 DA - 1997 Jul 16 SP - 1015 EP - 26 CY - Oxford PB - Oxford Publishing Limited(England) VL - 89 IS - 14 SN - 00278874 KW - Medical Sciences--Oncology KW - Mammography KW - Breast cancer KW - Palpation KW - Anxiety KW - Breast Neoplasms -- psychology KW - Humans KW - Decision Making KW - False Positive Reactions KW - False Negative Reactions KW - Breast Neoplasms -- mortality KW - Survival Rate KW - Risk Factors KW - Adult KW - Middle Aged KW - Female KW - Age Factors KW - Breast Neoplasms -- diagnosis KW - Mammography -- adverse effects KW - Breast Neoplasms -- prevention & control KW - Mass Screening -- standards UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/221008729?accountid=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=Journal+of+the+National+Cancer+Institute&rft.atitle=National+Institutes+of+Health+Consensus+Development+conference+statement%3A+Breast+cancer+screening+for+women+ages+40-49%2C+January+21-23%2C+1997&rft.au=National+Institutes+of+Health+Consensus+Development+Panel&rft.aulast=National+Institutes+of+Health+Consensus+Development+Panel&rft.aufirst=&rft.date=1997-07-16&rft.volume=89&rft.issue=14&rft.spage=1015&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Name - National Institutes of Health N1 - Copyright - Copyright Superintendent of Documents Jul 16, 1997 N1 - Last updated - 2014-05-23 N1 - CODEN - JNCIEQ ER - TY - JOUR T1 - Handling of gene-transfer products by the National Institutes of Health Clinical Center pharmacy department. AN - 79181791; 9248603 AB - Policies and procedures for handling gene-transfer products at the National Institutes of Health (NIH) Clinical Center pharmacy department are described. The pharmacy at the Clinical Center is responsible for handling in vivo gene-transfer delivery systems, which are gene-transfer products that are prepared for direct administration to patients. The gene-transfer products currently handled by the pharmacy are investigational and are composed of viruses containing the gene encoding either of the melanoma antigens MART-1 and gp100. The pharmacy has prepared guidelines, based on the principles of aseptic technique and FDA guidelines for manufacturing facilities, intended to help pharmacy personnel safely dilute a concentrated gene-transfer product into a dose suitable for administration. Before a product is handled, the biological safety level is determined and a biohazard sign is posted. Worksheets detailing all supplies, calculations for dilutions, and procedures that will be required are prepared in advance; the worksheets are part of a drug fact sheet prepared for all investigational drugs dispensed. Personnel must be properly trained and dressed in protective clothing. Aseptic technique and decontamination procedures are used as specified in the guidelines, and all materials used are disposed of as biohazardous waste. All work is documented. If a worker is accidentally exposed, standard procedures are followed. The handling of gene-transfer products at the NIH Clinical Center pharmacy is based on the principles of aseptic technique, FDA guidelines, and experience. JF - American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists AU - DeCederfelt, H J AU - Grimes, G J AU - Green, L AU - DeCederfelt, R O AU - Daniels, C E AD - Pharmacy Department, Warren Grant Magnuson Clinical Center (WGMCC), National Institutes of Health, Bethesda, MD 20892-1196, USA. hdecederfe@pop.cc.nih.gov Y1 - 1997/07/15/ PY - 1997 DA - 1997 Jul 15 SP - 1604 EP - 1610 VL - 54 IS - 14 SN - 1079-2082, 1079-2082 KW - Index Medicus KW - United States KW - Decontamination -- methods KW - Occupational Exposure -- prevention & control KW - Protective Clothing KW - Humans KW - Safety KW - National Institutes of Health (U.S.) KW - Education, Pharmacy, Continuing KW - Guidelines as Topic KW - Pharmacy Service, Hospital -- organization & administration KW - Gene Transfer Techniques KW - Genetic Vectors KW - Pharmacy Service, Hospital -- standards KW - Containment of Biohazards -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79181791?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+health-system+pharmacy+%3A+AJHP+%3A+official+journal+of+the+American+Society+of+Health-System+Pharmacists&rft.atitle=Handling+of+gene-transfer+products+by+the+National+Institutes+of+Health+Clinical+Center+pharmacy+department.&rft.au=DeCederfelt%2C+H+J%3BGrimes%2C+G+J%3BGreen%2C+L%3BDeCederfelt%2C+R+O%3BDaniels%2C+C+E&rft.aulast=DeCederfelt&rft.aufirst=H&rft.date=1997-07-15&rft.volume=54&rft.issue=14&rft.spage=1604&rft.isbn=&rft.btitle=&rft.title=American+journal+of+health-system+pharmacy+%3A+AJHP+%3A+official+journal+of+the+American+Society+of+Health-System+Pharmacists&rft.issn=10792082&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-08 N1 - Date created - 1997-10-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxidative DNA damage in tissues of pregnant female mice and fetuses caused by the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). AN - 79156688; 9233836 AB - The tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), induces the promutagenic oxidative-damage DNA lesion, 8-oxo-2'-deoxyguanosine (8-oxo-dG), in adult animals. To investigate whether this alteration occurs in DNA after transplacental exposure, pregnant Swiss mice were administered single or multiple doses of NNK. The 8-oxo-dG was quantified in placenta, and maternal and fetal tissues. In maternal lungs, single and multiple doses of NNK significantly increased levels of 8-oxo-dG by 23% and 32%, respectively. In maternal liver, a significant 38% increase was observed after multiple dose treatment. In the fetuses, a significant 45% increase in 8-oxo-dG levels was observed in liver after multiple doses of NNK. This is the first demonstration of oxidative DNA damage after transplacental exposure to NNK, and supports the concept of maternal smoking as a contributor to the development of childhood cancer. JF - Cancer letters AU - Sipowicz, M A AU - Amin, S AU - Desai, D AU - Kasprzak, K S AU - Anderson, L M AD - Division of Basic Science, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702, USA. sipowicz@ncifcrf.gov Y1 - 1997/07/15/ PY - 1997 DA - 1997 Jul 15 SP - 87 EP - 91 VL - 117 IS - 1 SN - 0304-3835, 0304-3835 KW - Nitrosamines KW - 0 KW - 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone KW - 7S395EDO61 KW - Index Medicus KW - Plants, Toxic KW - Oxidation-Reduction KW - Maternal-Fetal Exchange KW - Animals KW - Tobacco KW - Mice KW - Female KW - Pregnancy KW - Nitrosamines -- toxicity KW - DNA Damage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79156688?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=Oxidative+DNA+damage+in+tissues+of+pregnant+female+mice+and+fetuses+caused+by+the+tobacco-specific+nitrosamine%2C+4-%28methylnitrosamino%29-1-%283-pyridyl%29-1-butanone+%28NNK%29.&rft.au=Sipowicz%2C+M+A%3BAmin%2C+S%3BDesai%2C+D%3BKasprzak%2C+K+S%3BAnderson%2C+L+M&rft.aulast=Sipowicz&rft.aufirst=M&rft.date=1997-07-15&rft.volume=117&rft.issue=1&rft.spage=87&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-14 N1 - Date created - 1997-08-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Breast cancer cells have lower activating protein 1 transcription factor activity than normal mammary epithelial cells. AN - 79151019; 9230221 AB - To determine whether normal breast cells have different levels of activating protein 1 (AP-1) expression and activation relative to breast cancer cells, we have compared the level of c-Jun and c-Fos expression and AP-1 activity in human mammary epithelial cells (HMECs) at different stages of transformation (normal proliferating HMECs, immortal HMECs, oncogene-transformed HMECs, and breast cancer cell lines). These studies demonstrated that normal and immortal HMECs have a high basal level of expression of cJun and cFos and higher AP-1 DNA-binding and transcriptional activating activities than do oncogene-transformed HMECs or human breast cancer cells, with a gradual decrease in AP-1 transactivating activity as cells progress through the carcinogenesis pathway (normal > immortal > oncogene-transformed > cancer cell lines). The AP-1 activity in normal or immortal cells was not modulated by growth factor supplementation or oncogene overexpression, as it is in breast cancer cells. However, the addition of suramin, a nonspecific growth factor antagonist, did inhibit AP-1 in these HMECs, suggesting that this high level of AP-1 present in normal HMECs may be due to autocrine stimulation of growth factor pathways. The differences in AP-1 activity in normal and malignant breast cells may indicate that normal cells are more dependent on AP-1-mediated signals for their growth than are breast cancer cells. JF - Cancer research AU - Smith, L M AU - Birrer, M J AU - Stampfer, M R AU - Brown, P H AD - Division of Cancer Prevention and Control, National Cancer Institute, Rockville, Maryland 20850, USA. Y1 - 1997/07/15/ PY - 1997 DA - 1997 Jul 15 SP - 3046 EP - 3054 VL - 57 IS - 14 SN - 0008-5472, 0008-5472 KW - Transcription Factor AP-1 KW - 0 KW - Epidermal Growth Factor KW - 62229-50-9 KW - Index Medicus KW - Transfection KW - Humans KW - Genes, fos KW - Epidermal Growth Factor -- pharmacology KW - Female KW - Epithelium -- chemistry KW - Cell Line KW - Genes, jun KW - Breast Neoplasms -- genetics KW - Transcription Factor AP-1 -- analysis KW - Breast Neoplasms -- chemistry KW - Breast -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79151019?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Breast+cancer+cells+have+lower+activating+protein+1+transcription+factor+activity+than+normal+mammary+epithelial+cells.&rft.au=Smith%2C+L+M%3BBirrer%2C+M+J%3BStampfer%2C+M+R%3BBrown%2C+P+H&rft.aulast=Smith&rft.aufirst=L&rft.date=1997-07-15&rft.volume=57&rft.issue=14&rft.spage=3046&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-07 N1 - Date created - 1997-08-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Benzene poisoning, a risk factor for hematological malignancy, is associated with the NQO1 609C-->T mutation and rapid fractional excretion of chlorzoxazone. AN - 79149389; 9230185 AB - Benzene is a ubiquitous occupational hematotoxin and leukemogen, but people vary in their response to this toxic agent. To evaluate the impact of interindividual variation in enzymes that activate (i.e., CYP2E1) and detoxify (i.e., NQO1) benzene and its metabolites, we carried out a case-control study in Shanghai, China, of occupational benzene poisoning (BP; i.e., hematotoxicity), which we show is itself strongly associated with subsequent development of acute nonlymphocytic leukemia and the related myelodysplastic syndromes (relative risk, 70.6; 95% confidence interval, 11.4-439.3). CYP2E1 and NQO1 genotypes were determined by PCR-RFLP, and CYP2E1 enzymatic activity was estimated by the fractional excretion of chlorzoxazone (fe(6-OH)) for 50 cases of BP and 50 controls. Subjects with both a rapid fe(6-OH). and two copies of the NQO1 609C-->T mutation had a 7.6-fold (95% confidence interval, 1.8-31.2) increased risk of BP compared to subjects with a slow fe(6-OH) who carried one or two wild-type NQO1 alleles. In contrast, the CYP2E1 PstI/RsaI polymorphism did not influence BP risk. This is the first report that provides evidence of human susceptibility to benzene-related disease. Further evaluation of susceptibility for hematotoxicity and hematological malignancy among workers with a history of occupational exposure to benzene is warranted. JF - Cancer research AU - Rothman, N AU - Smith, M T AU - Hayes, R B AU - Traver, R D AU - Hoener, B AU - Campleman, S AU - Li, G L AU - Dosemeci, M AU - Linet, M AU - Zhang, L AU - Xi, L AU - Wacholder, S AU - Lu, W AU - Meyer, K B AU - Titenko-Holland, N AU - Stewart, J T AU - Yin, S AU - Ross, D AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1997/07/15/ PY - 1997 DA - 1997 Jul 15 SP - 2839 EP - 2842 VL - 57 IS - 14 SN - 0008-5472, 0008-5472 KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - NAD(P)H Dehydrogenase (Quinone) KW - EC 1.6.5.2 KW - Chlorzoxazone KW - H0DE420U8G KW - Benzene KW - J64922108F KW - Index Medicus KW - NAD(P)H Dehydrogenase (Quinone) -- genetics KW - Risk Factors KW - Humans KW - Cohort Studies KW - Retrospective Studies KW - Cytochrome P-450 CYP2E1 -- genetics KW - Hematologic Neoplasms -- chemically induced KW - Occupational Exposure -- adverse effects KW - Chlorzoxazone -- metabolism KW - Mutation KW - Benzene -- poisoning UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79149389?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Benzene+poisoning%2C+a+risk+factor+for+hematological+malignancy%2C+is+associated+with+the+NQO1+609C--%26gt%3BT+mutation+and+rapid+fractional+excretion+of+chlorzoxazone.&rft.au=Rothman%2C+N%3BSmith%2C+M+T%3BHayes%2C+R+B%3BTraver%2C+R+D%3BHoener%2C+B%3BCampleman%2C+S%3BLi%2C+G+L%3BDosemeci%2C+M%3BLinet%2C+M%3BZhang%2C+L%3BXi%2C+L%3BWacholder%2C+S%3BLu%2C+W%3BMeyer%2C+K+B%3BTitenko-Holland%2C+N%3BStewart%2C+J+T%3BYin%2C+S%3BRoss%2C+D&rft.aulast=Rothman&rft.aufirst=N&rft.date=1997-07-15&rft.volume=57&rft.issue=14&rft.spage=2839&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-07 N1 - Date created - 1997-08-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Aryl hydrocarbon receptor knockout mice (AHR-/-) exhibit liver retinoid accumulation and reduced retinoic acid metabolism. AN - 79149351; 9230184 AB - Livers from aryl hydrocarbon receptor-null mice showed a 3-fold increase in retinoids and a 65% decrease in retinoic acid metabolism. Levels of expression of the retinoic acid 4-hydroxylase, P450RAI, did not change, whereas cytochrome P4501A2 levels were lower in the null mouse, as shown earlier; however, this enzyme was found not to be active toward retinoic acid. These data suggest that aryl hydrocarbon receptor controls retinoic acid catabolism, through modulation of an unidentified target gene. Aldehyde dehydrogenases 1 and 2 were down-regulated markedly in the aryl hydrocarbon receptor-deficient mouse liver. 2,3,7,8-Tetrachlorodibenzo-p-dioxin induced cytochrome P4501A2 but not the aldehyde dehydrogenases in wild-type mice, suggesting that aryl hydrocarbon receptor is not involved directly in the down-regulation of this gene. Transglutaminase II, a retinoic acid-responsive gene product, was increased 2-fold, consistent with the liver fibrosis phenotype observed in the null mice. These findings suggest a molecular connection between xenobiotic-activated receptor signaling and retinoid homeostasis. JF - Cancer research AU - Andreola, F AU - Fernandez-Salguero, P M AU - Chiantore, M V AU - Petkovich, M P AU - Gonzalez, F J AU - De Luca, L M AD - Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 1997/07/15/ PY - 1997 DA - 1997 Jul 15 SP - 2835 EP - 2838 VL - 57 IS - 14 SN - 0008-5472, 0008-5472 KW - Polychlorinated Dibenzodioxins KW - 0 KW - Receptors, Aryl Hydrocarbon KW - Retinoids KW - Tretinoin KW - 5688UTC01R KW - Index Medicus KW - Animals KW - Polychlorinated Dibenzodioxins -- toxicity KW - Mice KW - Male KW - Mice, Knockout KW - Retinoids -- metabolism KW - Receptors, Aryl Hydrocarbon -- physiology KW - Tretinoin -- metabolism KW - Liver -- metabolism KW - Receptors, Aryl Hydrocarbon -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79149351?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Aryl+hydrocarbon+receptor+knockout+mice+%28AHR-%2F-%29+exhibit+liver+retinoid+accumulation+and+reduced+retinoic+acid+metabolism.&rft.au=Andreola%2C+F%3BFernandez-Salguero%2C+P+M%3BChiantore%2C+M+V%3BPetkovich%2C+M+P%3BGonzalez%2C+F+J%3BDe+Luca%2C+L+M&rft.aulast=Andreola&rft.aufirst=F&rft.date=1997-07-15&rft.volume=57&rft.issue=14&rft.spage=2835&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-07 N1 - Date created - 1997-08-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Calorie restriction induces a p53-independent delay of spontaneous carcinogenesis in p53-deficient and wild-type mice. AN - 79147863; 9230186 AB - We reported previously that calorie restriction (CR) delays spontaneous carcinogenesis in p53-deficient (p53-/-) mice, suggesting that CR modulates carcinogenesis by p53-independent mechanisms. To further evaluate the role of p53, we monitored tumor development in p53-/- and wild-type (p53+/+) mice fed ad libitum (AL) or a CR regimen (60% of AL calorie intake). CR delayed tumor mortality in p53-/- and p53+/+ mice (mean time to death, 169 and 648 days, respectively) relative to AL feeding (104 and 470 days). The estimated age-specific cancer death rate AL:CR ratios were 4.3 for p53-/- mice and 4.4 for p53+/+ mice. Thus, despite the accelerated onset of carcinogenesis in p53-/- mice, the tumor-delaying effect of CR was similar in the two genotypes. JF - Cancer research AU - Hursting, S D AU - Perkins, S N AU - Brown, C C AU - Haines, D C AU - Phang, J M AD - Division of Basic Sciences, National Cancer Institute, NIH, Frederick Cancer Research and Development Center, Maryland 21702-1201, USA. Y1 - 1997/07/15/ PY - 1997 DA - 1997 Jul 15 SP - 2843 EP - 2846 VL - 57 IS - 14 SN - 0008-5472, 0008-5472 KW - Tumor Suppressor Protein p53 KW - 0 KW - Index Medicus KW - Animals KW - Diet, Reducing KW - Mice KW - Tumor Suppressor Protein p53 -- physiology KW - Energy Intake KW - Neoplasms, Experimental -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79147863?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Calorie+restriction+induces+a+p53-independent+delay+of+spontaneous+carcinogenesis+in+p53-deficient+and+wild-type+mice.&rft.au=Hursting%2C+S+D%3BPerkins%2C+S+N%3BBrown%2C+C+C%3BHaines%2C+D+C%3BPhang%2C+J+M&rft.aulast=Hursting&rft.aufirst=S&rft.date=1997-07-15&rft.volume=57&rft.issue=14&rft.spage=2843&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-07 N1 - Date created - 1997-08-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunodominance of a low-affinity major histocompatibility complex-binding myelin basic protein epitope (residues 111-129) in HLA-DR4 (B1*0401) subjects is associated with a restricted T cell receptor repertoire. AN - 79121493; 9218510 AB - The pathogenesis of multiple sclerosis (MS) is currently ascribed in part to a T cell-mediated process targeting myelin components. The T cell response to one candidate autoantigen, myelin basic protein (MBP), in the context of HLA-DR15Dw2, has been previously studied in detail. However, the characteristics of cellular immunity in the context of other MS-associated HLA-DR haplotypes are scarcely known. MBP-specific T cell lines (TCL) were generated from HLA-DR4 (B1*0401)-positive MS subjects. Out of 275 MBP-specific TCL, 178 (64. 7%) specifically recognized region MBP(111-129), predominantly in the context of DRB1*0401. The major T cell epitope for MBP recognition corresponded to residues MBP(116-123). These TCL expressed disparate profiles of cytokine secretion and cytotoxicity. T cell receptor analysis, on the other hand, revealed a strikingly limited heterogeneity of rearrangements. In contrast to MBP(81-99), which binds with high affinity to HLA-DR15 and is recognized by a diverse T cell repertoire, MBP(111-129) binds weakly to DRB1*0401, suggesting that only high affinity T cell receptors might be able to efficiently engage such unstable MHC/peptide complexes, thus accounting for the T cell receptor restriction we observed. This study provides new insight about MBP recognition and proposes an alternative mechanism for immunodominance of self-antigen T cell epitopes in humans. JF - The Journal of clinical investigation AU - Muraro, P A AU - Vergelli, M AU - Kalbus, M AU - Banks, D E AU - Nagle, J W AU - Tranquill, L R AU - Nepom, G T AU - Biddison, W E AU - McFarland, H F AU - Martin, R AD - Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1400, USA. pmuraro@box-p.nih.gov Y1 - 1997/07/15/ PY - 1997 DA - 1997 Jul 15 SP - 339 EP - 349 VL - 100 IS - 2 SN - 0021-9738, 0021-9738 KW - Coumarins KW - 0 KW - Cytokines KW - DNA, Complementary KW - HLA-DR Antigens KW - HLA-DR4 Antigen KW - HLA-DRB1 Chains KW - HLA-DRB1*04:01 antigen KW - Immunodominant Epitopes KW - Myelin Basic Protein KW - Peptide Fragments KW - Receptors, Antigen, T-Cell KW - 7-amino-4-methylcoumarin-3-acetic acid KW - M8OUC6R993 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Cytokines -- secretion KW - CD4-Positive T-Lymphocytes -- immunology KW - Amino Acid Sequence KW - Protein Binding KW - Peptide Fragments -- immunology KW - Coumarins -- metabolism KW - Adult KW - Binding, Competitive KW - Molecular Sequence Data KW - Cytotoxicity Tests, Immunologic KW - Middle Aged KW - Male KW - Female KW - Autoimmune Diseases -- immunology KW - Cell Division KW - HLA-DR Antigens -- immunology KW - Myelin Basic Protein -- metabolism KW - Receptors, Antigen, T-Cell -- immunology KW - Myelin Basic Protein -- chemistry KW - Multiple Sclerosis -- immunology KW - HLA-DR4 Antigen -- genetics KW - Receptors, Antigen, T-Cell -- genetics KW - HLA-DR4 Antigen -- immunology KW - Myelin Basic Protein -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79121493?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+investigation&rft.atitle=Immunodominance+of+a+low-affinity+major+histocompatibility+complex-binding+myelin+basic+protein+epitope+%28residues+111-129%29+in+HLA-DR4+%28B1*0401%29+subjects+is+associated+with+a+restricted+T+cell+receptor+repertoire.&rft.au=Muraro%2C+P+A%3BVergelli%2C+M%3BKalbus%2C+M%3BBanks%2C+D+E%3BNagle%2C+J+W%3BTranquill%2C+L+R%3BNepom%2C+G+T%3BBiddison%2C+W+E%3BMcFarland%2C+H+F%3BMartin%2C+R&rft.aulast=Muraro&rft.aufirst=P&rft.date=1997-07-15&rft.volume=100&rft.issue=2&rft.spage=339&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+investigation&rft.issn=00219738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-15 N1 - Date created - 1997-08-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1996 Feb;70(2):843-51 [8551623] Nature. 1996 Jan 25;379(6563):343-6 [8552189] Tissue Antigens. 1996 Apr;47(4):275-83 [8773316] Immunol Today. 1996 Apr;17(4):152-9 [8871344] J Immunol. 1992 Mar 1;148(5):1359-66 [1371525] Eur J Immunol. 1992 Mar;22(3):753-8 [1372258] Eur J Immunol. 1992 Apr;22(4):1083-7 [1372558] Annu Rev Immunol. 1992;10:153-87 [1375472] Neuroepidemiology. 1992;11(2):85-9 [1495578] Ann Neurol. 1992 Sep;32(3):330-8 [1384421] Springer Semin Immunopathol. 1992;14(1):79-93 [1440199] J Neuroimmunol. 1993 Feb;42(2):199-207 [7679119] Tissue Antigens. 1993 Jan;41(1):20-5 [8456439] Eur J Immunol. 1993 May;23(5):1153-9 [8477809] Eur J Immunol. 1993 Jun;23(6):1232-9 [7684682] J Neurol Neurosurg Psychiatry. 1993 Jun;56(6):722-3 [8099604] Nature. 1993 Jul 15;364(6434):243-7 [7686632] J Immunol. 1993 Nov 1;151(9):4732-42 [8409432] Ann Neurol. 1993 Oct;34(4):524-35 [7692808] Int Immunol. 1993 Sep;5(9):1151-8 [7694643] J Clin Invest. 1993 Dec;92(6):2633-43 [7504690] J Exp Med. 1994 Jan 1;179(1):279-90 [7505801] J Exp Med. 1994 Jan 1;179(1):323-8 [8270877] Genomics. 1994 Feb;19(3):478-93 [8188290] J Exp Med. 1994 Jun 1;179(6):2017-22 [8195723] Int Immunol. 1994 May;6(5):751-9 [7521668] Immunol Today. 1994 Aug;15(8):362-6 [7916949] Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12463-6 [7528922] J Immunol. 1995 Jan 15;154(2):555-66 [7529279] J Exp Med. 1995 May 1;181(5):1847-55 [7722459] J Immunol. 1995 May 15;154(10):5216-27 [7537302] Eur J Immunol. 1995 Apr;25(4):958-68 [7537675] Crit Rev Clin Lab Sci. 1995;32(2):121-82 [7598789] Eur J Immunol. 1995 Jul;25(7):2119-22 [7621887] Immunity. 1995 Oct;3(4):407-15 [7584132] Eur J Immunogenet. 1995 Aug;22(4):289-97 [7495781] Nature. 1971 Jan 1;229(5279):22-4 [4098981] Prep Biochem. 1972;2(2):139-65 [4623901] Science. 1973 Aug 31;181(4102):872-3 [4125048] J Immunogenet. 1976 Aug;3(4):263-74 [1109134] Cell Immunol. 1977 Mar 15;29(2):265-71 [67899] Eur J Immunol. 1981 Apr;11(4):311-6 [6166480] Proc Natl Acad Sci U S A. 1984 Jul;81(14):4302-6 [6431406] Proc Natl Acad Sci U S A. 1985 Aug;82(15):5131-5 [2410914] Proc Natl Acad Sci U S A. 1985 Dec;82(24):8624-8 [3866244] Anal Biochem. 1987 Apr;162(1):156-9 [2440339] Neurology. 1988 May;38(5):739-42 [2452382] Neurology. 1988 Nov;38(11):1749-53 [2903464] Neurology. 1989 Feb;39(2 Pt 1):275-7 [2783768] J Neuroimmunol. 1989 Jun;23(1):55-66 [2470781] Immunol Today. 1989 May;10(5):164-9 [2663017] J Neurosci Res. 1989 Jun;23(2):207-16 [2474079] Proc Natl Acad Sci U S A. 1989 Sep;86(18):7113-7 [2571150] J Immunol. 1989 Dec 15;143(12):3881-6 [2480377] J Immunol. 1990 Jul 15;145(2):540-8 [1694881] Nature. 1990 Jul 12;346(6280):183-7 [1694970] J Clin Invest. 1990 Sep;86(3):981-5 [1697609] Neurology. 1990 Nov;40(11):1770-6 [1700336] J Exp Med. 1991 Jan 1;173(1):19-24 [1702137] J Immunol. 1991 Jan 15;146(2):515-20 [1702803] Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2466-70 [1706524] J Neuroimmunol. 1991 Jun;32(3):279-83 [2033119] J Neurosci Res. 1991 Feb;28(2):280-90 [1709690] Biochemistry. 1991 Sep 24;30(38):9177-87 [1892827] Annu Rev Immunol. 1991;9:493-525 [1910687] Eur J Immunogenet. 1995 Aug;22(4):335-60 [7495785] Hum Immunol. 1995 Jul;43(3):207-18 [7558938] Immunogenetics. 1995;42(6):455-500 [8550092] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Crystalluria and urinary tract abnormalities associated with indinavir. AN - 79109620; 9230000 AB - Indinavir, a protease inhibitor widely used to treat patients with HIV infection, has been associated with nephrolithiasis. Distinctive urinary crystals and a spectrum of urologic disorders were noted in patients receiving indinavir. To determine the composition of urinary crystals and the frequency of asymptomatic crystalluria and urinary tract symptoms in patients receiving indinavir. Patients with HIV infection who were enrolled in studies conducted at the National Institutes of Health. Microscopic urinalysis, high-performance liquid chromatography (HPLC) and mass spectrometry of urinary crystals and stones, and clinical evaluation of patients with urologic symptoms. Of 240 patients receiving indinavir, 142 provided urine specimens for analysis. Twenty-nine (20%) had crystals consisting of plate-like rectangles and fan-shaped or starburst forms. Mass spectrometry and HPLC confirmed that these crystals were composed of indinavir. Of 40 patients who were not receiving indinavir, none had similar crystals (P < 0.001). Nineteen of the 240 patients receiving indinavir (8%) developed urologic symptoms. Of these, 7 (3%) had nephrolithiasis and the other 12 (5%) had previously undescribed syndromes: crystalluria associated with dysuria and crystalluria associated with back or flank pain. Four of the patients with the latter syndrome had radiographic evidence of intrarenal sludging. Indinavir forms characteristic crystals in the urine. This crystalluria may be associated with dysuria and urinary frequency, with flank or back pain associated with intrarenal sludging, and with the classic syndrome of renal colic. JF - Annals of internal medicine AU - Kopp, J B AU - Miller, K D AU - Mican, J A AU - Feuerstein, I M AU - Vaughan, E AU - Baker, C AU - Pannell, L K AU - Falloon, J AD - National Institute of Diabetes and Digestive and Kidney Diseases, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1997/07/15/ PY - 1997 DA - 1997 Jul 15 SP - 119 EP - 125 VL - 127 IS - 2 SN - 0003-4819, 0003-4819 KW - Anti-HIV Agents KW - 0 KW - HIV Protease Inhibitors KW - Indinavir KW - 5W6YA9PKKH KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Mass Spectrometry KW - Kidney Calculi -- chemically induced KW - Pain -- chemically induced KW - Risk Factors KW - Humans KW - Adult KW - Middle Aged KW - Urine -- chemistry KW - Male KW - Female KW - Chromatography, High Pressure Liquid KW - Urination Disorders -- chemically induced KW - Urologic Diseases -- chemically induced KW - Urologic Diseases -- urine KW - Anti-HIV Agents -- adverse effects KW - HIV Protease Inhibitors -- adverse effects KW - Indinavir -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79109620?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+internal+medicine&rft.atitle=Crystalluria+and+urinary+tract+abnormalities+associated+with+indinavir.&rft.au=Kopp%2C+J+B%3BMiller%2C+K+D%3BMican%2C+J+A%3BFeuerstein%2C+I+M%3BVaughan%2C+E%3BBaker%2C+C%3BPannell%2C+L+K%3BFalloon%2C+J&rft.aulast=Kopp&rft.aufirst=J&rft.date=1997-07-15&rft.volume=127&rft.issue=2&rft.spage=119&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 - 1997-07-22 N1 - Date created - 1997-07-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Ann Intern Med. 1998 Feb 15;128(4):321 [9471941] Ann Intern Med. 1998 Feb 15;128(4):320-1 [9471940] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of cranial electrostimulation therapy on short-term smoking cessation. AN - 79103093; 9209728 AB - The effects of cranial electrical stimulation (CES) on short-term smoking cessation were evaluated in a double-blind study of cigarette smokers who wished to stop smoking. Subjects were randomly assigned to a CES- (n = 51) or a sham-treated group (n = 50). On 5 consecutive days subjects received CES treatments (30-microA, 2-msec, 10-Hz pulsed signal) or no electrical current (sham). There were no significant differences between groups on daily cigarettes smoked, exhaled carbon monoxide, urinary cotinine levels, treatment retention, smoking urges, or total tobacco withdrawal scores, although subjects in the CES group had less cigarette craving and anxiety during the first 2 experimental days. The ineffectiveness of CES to reduce withdrawal symptoms and facilitate smoking cessation are similar to results of other clinical studies of CES in drug dependence, although positive effects of CES in animal studies have been reported. JF - Biological psychiatry AU - Pickworth, W B AU - Fant, R V AU - Butschky, M F AU - Goffman, A L AU - Henningfield, J E AD - National Institute on Drug Abuse, Addiction Research Center, Baltimore, Maryland 21224, USA. Y1 - 1997/07/15/ PY - 1997 DA - 1997 Jul 15 SP - 116 EP - 121 VL - 42 IS - 2 SN - 0006-3223, 0006-3223 KW - Nicotine KW - 6M3C89ZY6R KW - Carbon Monoxide KW - 7U1EE4V452 KW - Index Medicus KW - Substance Withdrawal Syndrome -- physiopathology KW - Double-Blind Method KW - Substance Withdrawal Syndrome -- diagnosis KW - Humans KW - Nicotine -- adverse effects KW - Neurologic Examination KW - Carbon Monoxide -- pharmacokinetics KW - Brain -- physiopathology KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Substance Withdrawal Syndrome -- therapy KW - Female KW - Male KW - Smoking Cessation -- methods KW - Electric Stimulation Therapy -- instrumentation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79103093?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Novel+signal+transduction+and+peptide+specificity+of+glucagon-like+peptide+receptor+in+3T3-L1+adipocytes.&rft.au=Montrose-Rafizadeh%2C+C%3BYang%2C+H%3BWang%2C+Y%3BRoth%2C+J%3BMontrose%2C+M+H%3BAdams%2C+L+G&rft.aulast=Montrose-Rafizadeh&rft.aufirst=C&rft.date=1997-09-01&rft.volume=172&rft.issue=3&rft.spage=275&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+physiology&rft.issn=00219541&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-19 N1 - Date created - 1997-08-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Biol Psychiatry. 1998 Mar 15;43(6):468-9 [9532355] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Segmental genomic replacement by Cre-mediated recombination: genotoxic stress activation of the p53 promoter in single-copy transformants. AN - 79098326; 9207031 AB - Genotoxic stress results in transcriptional activation of the p53 promoter. To gain more detailed information on genotoxic induction of the p53 promoter at a uniform genomic locus, we have developed an efficient strategy for replacing a defined genomic segment in mouse NIH 3T3 cells with exogenous transfected DNA using a 'double lox' targeting strategy mediated by Cre DNA recombinase. The strategy utilizes a pair of heterospecific lox sites engineered both into the genome and onto the targeting DNA. This allows direct replacement of genomic DNA by a Cre-catalyzed double crossover event. p53-CAT reporter constructs were site-specifically placed into the genomic target 20-fold more efficiently by double lox recombination than by Cre-mediated single crossover insertional recombination, and the absolute frequency of site-specific double lox targeting exceeded the frequency of transformation due to random illegitimate recombination of transfected DNA into the genome. Resulting targeted single-copy integrants of the p53-CAT reporter show strong genotoxic induction by mitomycin C, and a dynamic range of induction that exceeds that seen in transient transfection assays. The double lox strategy is generally applicable to Cre-mediated genomic targeting in any cell and should be of particular utility in the site-specific targeting of DNA into embryonic stem (ES) cells for the production of gene-modified mice. JF - Nucleic acids research AU - Bethke, B AU - Sauer, B AD - National Institutes of Health, National Institute of Diabetes, Digestive and Kidney Disease, Bethesda, MD 2089-1800, USA. Y1 - 1997/07/15/ PY - 1997 DA - 1997 Jul 15 SP - 2828 EP - 2834 VL - 25 IS - 14 SN - 0305-1048, 0305-1048 KW - Mutagens KW - 0 KW - Tumor Suppressor Protein p53 KW - Viral Proteins KW - Mitomycin KW - 50SG953SK6 KW - DNA KW - 9007-49-2 KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Cre recombinase KW - EC 2.7.7.- KW - Integrases KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Mitomycin -- pharmacology KW - Mice KW - Mutagens -- pharmacology KW - Mutagenesis, Site-Directed KW - Chloramphenicol O-Acetyltransferase -- genetics KW - Base Sequence KW - Transfection KW - Blotting, Southern KW - Genetic Vectors KW - Recombination, Genetic KW - Molecular Sequence Data KW - Gene Expression Regulation -- drug effects KW - Promoter Regions, Genetic KW - Integrases -- metabolism KW - Cloning, Molecular -- methods KW - Tumor Suppressor Protein p53 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79098326?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Segmental+genomic+replacement+by+Cre-mediated+recombination%3A+genotoxic+stress+activation+of+the+p53+promoter+in+single-copy+transformants.&rft.au=Bethke%2C+B%3BSauer%2C+B&rft.aulast=Bethke&rft.aufirst=B&rft.date=1997-07-15&rft.volume=25&rft.issue=14&rft.spage=2828&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-04 N1 - Date created - 1997-09-04 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - J04238; GENBANK N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1982 Jun;79(11):3398-402 [6954485] Nucleic Acids Res. 1996 Dec 1;24(23):4608-13 [8972844] Cell. 1983 Sep;34(2):343-58 [6616614] Mol Cell Biol. 1984 Sep;4(9):1689-94 [6092932] Nucleic Acids Res. 1986 Mar 11;14(5):2287-300 [3457367] EMBO J. 1986 Dec 1;5(12):3133-42 [3102226] Mol Cell Biol. 1987 Jul;7(7):2425-34 [3475566] Mol Cell Biol. 1987 Aug;7(8):2745-52 [3670292] Proc Natl Acad Sci U S A. 1987 Dec;84(24):9108-12 [2827167] Mol Cell Biol. 1989 May;9(5):2163-72 [2664471] Mol Cell Biol. 1991 Mar;11(3):1402-8 [1996101] New Biol. 1990 May;2(5):441-9 [2288914] Nature. 1991 Mar 21;350(6315):243-6 [1672446] Cell. 1991 Jun 28;65(7):1153-63 [2065352] Cytogenet Cell Genet. 1991;57(1):18-22 [1713140] Cancer Res. 1991 Dec 1;51(23 Pt 1):6304-11 [1933891] Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6232-6 [1631115] Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):7905-9 [1518811] Oncogene. 1993 Feb;8(2):307-18 [8426740] Cancer Res. 1993 May 15;53(10 Suppl):2212-6 [8485705] Nucleic Acids Res. 1993 May 11;21(9):2025-9 [8502542] Mol Cell Biol. 1993 Jul;13(7):4242-50 [8321226] Methods Enzymol. 1993;225:890-900 [8231893] J Biol Chem. 1994 Aug 5;269(31):20067-74 [8051093] Bioessays. 1994 Aug;16(8):541-7 [8086003] Mol Cell Biol. 1995 Aug;15(8):4489-96 [7623839] Cell. 1996 Jul 12;86(1):13-9 [8689680] Mol Cell Biol. 1982 Sep;2(9):1044-51 [6960240] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential activation and desensitization of sensory neurons by resiniferatoxin. AN - 79089387; 9204943 AB - Recently, with use of rat dorsal root ganglion (DRG) neurons we have been able to dissociate the binding affinities of vanilloids from their potencies to induce 45Ca uptake, which suggests the existence of distinct classes of the vanilloid receptor (). In the present study, we have demonstrated that the ultrapotent capsaicin analog resiniferatoxin (RTX) desensitized rat DRG neurons to the subsequent induction of 45Ca uptake by capsaicin and RTX with affinity and cooperativity similar to that found for [3H]RTX binding, contrasting with a approximately 10-fold weaker potency and lack of cooperativity to induce 45Ca uptake. Likewise, the competitive antagonist capsazepine inhibited RTX-induced desensitization with potency similar to that for inhibition of specific [3H]RTX binding, whereas the potency of capsazepine was approximately 10-fold higher for inhibiting RTX-induced 45Ca uptake. Finally, the noncompetitive antagonist ruthenium red inhibited both the RTX-induced desensitization and 45Ca uptake but showed approximately 60-fold selectivity for inhibiting RTX-induced desensitization. The RTX-induced desensitization was not associated with loss of specific [3H]RTX binding, suggesting lack of gross cell toxicity. In contrast to RTX, capsaicin caused desensitization with a potency corresponding to that for 45Ca uptake and did so in a noncooperative manner. Unlike the RTX-induced desensitization, the desensitization by capsaicin was blocked by ruthenium red only at doses that blocked 45Ca uptake and depended on external calcium. Our findings provide further support for the existence of vanilloid receptor subtypes on DRG neurons with distinct pharmacology and distinct patterns of desensitization. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Acs, G AU - Biro, T AU - Acs, P AU - Modarres, S 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, Maryland 20892, USA. Y1 - 1997/07/15/ PY - 1997 DA - 1997 Jul 15 SP - 5622 EP - 5628 VL - 17 IS - 14 SN - 0270-6474, 0270-6474 KW - Diterpenes KW - 0 KW - resiniferatoxin KW - A5O6P1UL4I KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Dose-Response Relationship, Drug KW - Cells, Cultured -- drug effects KW - Female KW - Diterpenes -- pharmacology KW - Calcium -- metabolism KW - Ion Transport -- drug effects KW - Neurons, Afferent -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79089387?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.atitle=Pt-ATP+as+an+antineoplastic+agent+in+an+experimental+mice+model+system.&rft.au=Pal%2C+S%3BMukherjea%2C+K%3BBhattacharya%2C+R%3BMaity%2C+P&rft.aulast=Pal&rft.aufirst=S&rft.date=1997-09-01&rft.volume=16&rft.issue=3&rft.spage=255&rft.isbn=&rft.btitle=&rft.title=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.issn=03929078&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-21 N1 - Date created - 1997-07-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A small, stable RNA induced by oxidative stress: role as a pleiotropic regulator and antimutator. AN - 79147855; 9230301 AB - Exposure of E. coli to hydrogen peroxide induces the transcription of a small RNA denoted oxyS. The oxyS RNA is stable, abundant, and does not encode a protein. oxyS activates and represses the expression of numerous genes in E. coli, and eight targets, including genes encoding the transcriptional regulators FhlA and sigma(S), were identified. oxyS expression also leads to a reduction in spontaneous and chemically-induced mutagenesis. Our results suggest that the oxyS RNA acts as a regulator that integrates adaptation to hydrogen peroxide with other cellular stress responses and helps to protect cells against oxidative damage. JF - Cell AU - Altuvia, S AU - Weinstein-Fischer, D AU - Zhang, A AU - Postow, L AU - Storz, G AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/07/11/ PY - 1997 DA - 1997 Jul 11 SP - 43 EP - 53 VL - 90 IS - 1 SN - 0092-8674, 0092-8674 KW - Bacterial Proteins KW - 0 KW - RNA, Bacterial KW - Recombinant Proteins KW - Methylnitronitrosoguanidine KW - 12H3O2UGSF KW - Hydrogen Peroxide KW - BBX060AN9V KW - Index Medicus KW - Gene Expression Regulation, Bacterial KW - Polymerase Chain Reaction KW - Genes, Bacterial KW - Base Sequence KW - Bacterial Proteins -- biosynthesis KW - Recombinant Proteins -- biosynthesis KW - Acclimatization KW - Molecular Sequence Data KW - Nucleic Acid Conformation KW - Mutagenesis KW - Cloning, Molecular KW - Oxidative Stress -- physiology KW - RNA, Bacterial -- biosynthesis KW - RNA, Bacterial -- chemistry KW - Hydrogen Peroxide -- pharmacology KW - Escherichia coli -- drug effects KW - Transcription, Genetic KW - Escherichia coli -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79147855?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell&rft.atitle=A+small%2C+stable+RNA+induced+by+oxidative+stress%3A+role+as+a+pleiotropic+regulator+and+antimutator.&rft.au=Altuvia%2C+S%3BWeinstein-Fischer%2C+D%3BZhang%2C+A%3BPostow%2C+L%3BStorz%2C+G&rft.aulast=Altuvia&rft.aufirst=S&rft.date=1997-07-11&rft.volume=90&rft.issue=1&rft.spage=43&rft.isbn=&rft.btitle=&rft.title=Cell&rft.issn=00928674&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-26 N1 - Date created - 1997-08-26 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U87390; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of four amino acids in the gastrin-releasing peptide receptor that are required for high affinity agonist binding. AN - 79132496; 9211882 AB - The bombesin family of G-protein-coupled receptors includes the gastrin-releasing peptide receptor (GRP-R), the neuromedin B receptor (NMB-R), bombesin receptor subtype 3 (BRS-3), and bombesin receptor subtype 4 (bb4). All species homologues of GRP-R, NMB-R, and bb4 bind bombesin with dissociation constants in the nanomolar range; by comparison, human BRS-3 binds bombesin at much lower affinity (Kd >> 1 microM). We used this difference to help identify candidate residues that were potentially critical for forming the bombesin binding pocket. We reasoned that amino acids essential for bombesin binding would be conserved among all homologues of bb4, NMB-R, and GRP-R; conversely, at least one of these amino acids would not be conserved among homologues of BRS-3. Amino acid sequence alignment revealed nine residues that fit this model. We replaced each of these amino acids in mouse GRP-R with the homologous amino acid in human BRS-3. Four substitutions resulted in a significant decrease in bombesin affinity (R288H, Q121R, P199S, and A308S). The analogous mutations in BRS-3 (R127Q, H294R, S205P, and S315A) together resulted in a receptor with a 100-fold increase in bombesin and GRP affinities relative to wild-type BRS-3. From this, we propose a preliminary map of some of the amino acids comprising the agonist binding pocket. JF - The Journal of biological chemistry AU - Akeson, M AU - Sainz, E AU - Mantey, S A AU - Jensen, R T AU - Battey, J F AD - Laboratory of Molecular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Maryland 20850, USA. Y1 - 1997/07/11/ PY - 1997 DA - 1997 Jul 11 SP - 17405 EP - 17409 VL - 272 IS - 28 SN - 0021-9258, 0021-9258 KW - Peptides KW - 0 KW - Receptors, Bombesin KW - bombesin receptor subtype 3 KW - bombesin receptor subtype 4 KW - Glutamine KW - 0RH81L854J KW - Gastrin-Releasing Peptide KW - 80043-53-4 KW - Arginine KW - 94ZLA3W45F KW - Proline KW - 9DLQ4CIU6V KW - Alanine KW - OF5P57N2ZX KW - Bombesin KW - PX9AZU7QPK KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Bombesin -- metabolism KW - Guinea Pigs KW - Models, Molecular KW - Humans KW - Peptides -- metabolism KW - Amino Acid Sequence KW - Mice KW - Mice, Inbred BALB C KW - Protein Binding KW - Structure-Activity Relationship KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Point Mutation KW - Molecular Sequence Data KW - Receptors, Bombesin -- genetics KW - Proline -- chemistry KW - Proline -- metabolism KW - Arginine -- metabolism KW - Glutamine -- metabolism KW - Arginine -- chemistry KW - Alanine -- metabolism KW - Glutamine -- chemistry KW - Alanine -- chemistry KW - Receptors, Bombesin -- metabolism KW - Receptors, Bombesin -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79132496?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Identification+of+four+amino+acids+in+the+gastrin-releasing+peptide+receptor+that+are+required+for+high+affinity+agonist+binding.&rft.au=Akeson%2C+M%3BSainz%2C+E%3BMantey%2C+S+A%3BJensen%2C+R+T%3BBattey%2C+J+F&rft.aulast=Akeson&rft.aufirst=M&rft.date=1997-07-11&rft.volume=272&rft.issue=28&rft.spage=17405&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-14 N1 - Date created - 1997-08-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Trial of calcium to prevent preeclampsia. AN - 79075692; 9211675 AB - Previous trials have suggested that calcium supplementation during pregnancy may reduce the risk of preeclampsia. However, differences in study design and a low dietary calcium intake in the populations studied limit acceptance of the data. We randomly assigned 4589 healthy nulliparous women who were 13 to 21 weeks pregnant to receive daily treatment with either 2 g of elemental calcium or placebo for the remainder of their pregnancies. Surveillance for preeclampsia was conducted by personnel unaware of treatment-group assignments, using standardized measurements of blood pressure and urinary protein excretion at uniformly scheduled prenatal visits, protocols for monitoring these measurements during the hospitalization for delivery, and reviews of medical records of unscheduled outpatient visits and all hospitalizations. Calcium supplementation did not significantly reduce the incidence or severity of preeclampsia or delay its onset. Preeclampsia occurred in 158 of the 2295 women in the calcium group (6.9 percent) and 168 of the 2294 women in the placebo group (7.3 percent) (relative risk, 0.94; 95 percent confidence interval, 0.76 to 1.16). There were no significant differences between the two groups in the prevalence of pregnancy-associated hypertension without preeclampsia (15.3 percent vs. 17.3 percent) or of all hypertensive disorders (22.2 percent vs. 24.6 percent). The mean systolic and diastolic blood pressures during pregnancy were similar in both groups. Calcium did not reduce the numbers of preterm deliveries, small-for-gestational-age births, or fetal and neonatal deaths; nor did it increase urolithiasis during pregnancy. Calcium supplementation during pregnancy did not prevent preeclampsia, pregnancy-associated hypertension, or adverse perinatal outcomes in healthy nulliparous women. JF - The New England journal of medicine AU - Levine, R J AU - Hauth, J C AU - Curet, L B AU - Sibai, B M AU - Catalano, P M AU - Morris, C D AU - DerSimonian, R AU - Esterlitz, J R AU - Raymond, E G AU - Bild, D E AU - Clemens, J D AU - Cutler, J A AD - Division of Epidemiology, Statistics, and Prevention Research, National Institute of Child Health and Human Development, Bethesda, Md 20892-7510, USA. Y1 - 1997/07/10/ PY - 1997 DA - 1997 Jul 10 SP - 69 EP - 76 VL - 337 IS - 2 SN - 0028-4793, 0028-4793 KW - Calcium KW - SY7Q814VUP KW - Abridged Index Medicus KW - Index Medicus KW - United States KW - Parity KW - Pregnancy -- urine KW - Pregnancy Complications, Cardiovascular -- epidemiology KW - Proteinuria -- epidemiology KW - Humans KW - Urinary Calculi -- chemically induced KW - Pregnancy Complications, Cardiovascular -- prevention & control KW - Hypertension -- epidemiology KW - Hypertension -- prevention & control KW - Adult KW - Urinary Calculi -- epidemiology KW - Case-Control Studies KW - Incidence KW - Female KW - Pregnancy Outcome KW - Pre-Eclampsia -- prevention & control KW - Pre-Eclampsia -- epidemiology KW - Calcium -- urine KW - Calcium -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79075692?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+journal+of+medicine&rft.atitle=Trial+of+calcium+to+prevent+preeclampsia.&rft.au=Levine%2C+R+J%3BHauth%2C+J+C%3BCuret%2C+L+B%3BSibai%2C+B+M%3BCatalano%2C+P+M%3BMorris%2C+C+D%3BDerSimonian%2C+R%3BEsterlitz%2C+J+R%3BRaymond%2C+E+G%3BBild%2C+D+E%3BClemens%2C+J+D%3BCutler%2C+J+A&rft.aulast=Levine&rft.aufirst=R&rft.date=1997-07-10&rft.volume=337&rft.issue=2&rft.spage=69&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=00284793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-15 N1 - Date created - 1997-07-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: N Engl J Med. 1997 Jul 10;337(2):124-5 [9211683] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nitric oxide trapping of the tyrosyl radical of prostaglandin H synthase-2 leads to tyrosine iminoxyl radical and nitrotyrosine formation. AN - 79100392; 9202025 AB - The determination of protein nitrotyrosine content has become a frequently used technique for the detection of oxidative tissue damage. Protein nitration has been suggested to be a final product of the production of highly reactive nitrogen oxide intermediates (e. g. peroxynitrite) formed in reactions between nitric oxide (NO.) and oxygen-derived species such as superoxide. The enzyme prostaglandin H synthase-2 (PHS-2) forms one or more tyrosyl radicals during its enzymatic catalysis of prostaglandin formation. In the presence of the NO.-generator diethylamine nonoate, the electron spin resonance spectrum of the PHS-2-derived tyrosyl radical is replaced by the spectrum of another free radical containing a nitrogen atom. The magnitude of the nitrogen hyperfine coupling constant in the latter species unambiguously identifies it as an iminoxyl radical, which is likely formed by the oxidation of nitrosotyrosine, a stable product of the addition of NO. to tyrosyl radical. Addition of superoxide dismutase did not alter the spectra, indicating that peroxynitrite was not involved. Western blot analysis of PHS-2 after exposure to the NO.-generator revealed nitrotyrosine formation. The results provide a mechanism for nitric oxide-dependent tyrosine nitration that does not require formation of more highly reactive nitrogen oxide intermediates such as peroxynitrite or nitrogen dioxide. JF - The Journal of biological chemistry AU - Gunther, M R AU - Hsi, L C AU - Curtis, J F AU - Gierse, J K AU - Marnett, L J AU - Eling, T E AU - Mason, R P AD - Laboratory of Pharmacology and Chemistry, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. gunther@niehs.nih.gov Y1 - 1997/07/04/ PY - 1997 DA - 1997 Jul 04 SP - 17086 EP - 17090 VL - 272 IS - 27 SN - 0021-9258, 0021-9258 KW - Free Radicals KW - 0 KW - Hydrazines KW - Mutagens KW - Nitrates KW - Nitrogen Oxides KW - peroxynitric acid KW - 26404-66-0 KW - Arachidonic Acid KW - 27YG812J1I KW - Nitric Oxide KW - 31C4KY9ESH KW - Tyrosine KW - 42HK56048U KW - 1,1-diethyl-2-hydroxy-2-nitrosohydrazine KW - 86831-65-4 KW - Prostaglandin-Endoperoxide Synthases KW - EC 1.14.99.1 KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Index Medicus KW - Blotting, Western KW - Mutagens -- metabolism KW - Humans KW - Electron Spin Resonance Spectroscopy KW - Nitrates -- metabolism KW - Superoxide Dismutase -- metabolism KW - Hydrazines -- metabolism KW - Arachidonic Acid -- metabolism KW - Prostaglandin-Endoperoxide Synthases -- metabolism KW - Nitric Oxide -- metabolism KW - Tyrosine -- metabolism KW - Tyrosine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79100392?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Nitric+oxide+trapping+of+the+tyrosyl+radical+of+prostaglandin+H+synthase-2+leads+to+tyrosine+iminoxyl+radical+and+nitrotyrosine+formation.&rft.au=Gunther%2C+M+R%3BHsi%2C+L+C%3BCurtis%2C+J+F%3BGierse%2C+J+K%3BMarnett%2C+L+J%3BEling%2C+T+E%3BMason%2C+R+P&rft.aulast=Gunther&rft.aufirst=M&rft.date=1997-07-04&rft.volume=272&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 - 1997-07-31 N1 - Date created - 1997-07-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutation analysis of the transforming growth factor-beta type II receptor in human cell lines resistant to growth inhibition by transforming growth factor-beta. AN - 79149608; 9233784 AB - The transforming growth factor-beta (TGF-beta) binds the type II TGF-beta growth factor receptor (RII) to inhibit the growth of most epithelial tissues. Most human colon and gastric cancers with microsatellite instability (MI) have frameshift mutations in polynucleotide repeats within the RII coding region; these mutations truncate the receptor protein and disable the serine/threonine kinase to produce TGF-beta resistance. To further investigate the type, frequency and tissue distribution of RII mutations, we selected 24 human cancer cell lines from various tissues which were previously reported to be resistant to the inhibitory effects of TGF-beta. We developed protocols for non-isotopic SSCP analysis of PCR products from genomic DNA samples, and we tested them for microsatellite instability. PCR-SSCP analysis followed by DNA sequencing identified deletion mutations in the exon 3 poly-adenine tract in three colon tumor cell lines: LS174T and SW48 had a single base deletion and LS411 had a two base deletion. Among the 24 previously unreported cell lines, only these three demonstrated microsatellite instability. These and other recent data indicate that RII mutations are essentially confined to colon and gastric cancers with microsatellite instability. The narrow spectrum of tissues containing RII mutations illustrates the complexity of genetic checkpoints in human carcinogenesis. JF - Oncogene AU - Vincent, F AU - Nagashima, M AU - Takenoshita, S AU - Khan, M A AU - Gemma, A AU - Hagiwara, K AU - Bennett, W P AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/07/03/ PY - 1997 DA - 1997 Jul 03 SP - 117 EP - 122 VL - 15 IS - 1 SN - 0950-9232, 0950-9232 KW - Receptors, Transforming Growth Factor beta KW - 0 KW - Transforming Growth Factor beta KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - transforming growth factor-beta type II receptor KW - EC 2.7.11.30 KW - Index Medicus KW - Polymerase Chain Reaction KW - Microsatellite Repeats KW - Colonic Neoplasms -- genetics KW - Tumor Cells, Cultured KW - Stomach Neoplasms -- genetics KW - Humans KW - DNA Mutational Analysis KW - Cell Division -- drug effects KW - Polymorphism, Single-Stranded Conformational KW - Transforming Growth Factor beta -- pharmacology KW - Receptors, Transforming Growth Factor beta -- genetics KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79149608?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Mutation+analysis+of+the+transforming+growth+factor-beta+type+II+receptor+in+human+cell+lines+resistant+to+growth+inhibition+by+transforming+growth+factor-beta.&rft.au=Vincent%2C+F%3BNagashima%2C+M%3BTakenoshita%2C+S%3BKhan%2C+M+A%3BGemma%2C+A%3BHagiwara%2C+K%3BBennett%2C+W+P&rft.aulast=Vincent&rft.aufirst=F&rft.date=1997-07-03&rft.volume=15&rft.issue=1&rft.spage=117&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-19 N1 - Date created - 1997-08-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemopreventive efficacy of anethole trithione, N-acetyl-L-cysteine, miconazole and phenethylisothiocyanate in the DMBA-induced rat mammary cancer model. AN - 79113074; 9212229 AB - The chemopreventive efficacy of N-acetyl-L-cysteine (NAC), anethole trithione, miconazole and phenethylisothiocyanate (PEITC), each of which would be expected to alter carcinogen metabolism, was examined in the dimethylbenzanthracene (DMBA) mammary carcinogenesis model. In this protocol, animals were exposed to non-toxic doses of the chemopreventives in the diet beginning 7 days prior to DMBA administration and then continuously throughout the duration of the assay (100 days post carcinogen). Miconazole, an antifungal agent with relatively broad inhibitory activity toward a variety of cytochromes P450, increased mammary tumor latency, decreased tumor incidence at the highest dose and decreased tumor multiplicity up to 60%. Anethole trithione, a substituted dithiolthione and an analog of the relatively broad-spectrum chemopreventive oltipraz, was administered in the diet and significantly inhibited mammary cancer multiplicity but not cancer incidence. NAC, an antimucolytic agent, failed to inhibit DMBA-induced mammary tumorigenesis. Surprisingly, treatment with DMBA plus PEITC, a potent inhibitor of cytochrome P450 2E1, actually increased the multiplicity of tumors relative to that observed with DMBA alone. JF - International journal of cancer AU - Lubet, R A AU - Steele, V E AU - Eto, I AU - Juliana, M M AU - Kelloff, G J AU - Grubbs, C J AD - National Cancer Institute, Division of Cancer Prevention and Control, Bethesda, MD, USA. Y1 - 1997/07/03/ PY - 1997 DA - 1997 Jul 03 SP - 95 EP - 101 VL - 72 IS - 1 SN - 0020-7136, 0020-7136 KW - Anticarcinogenic Agents KW - 0 KW - Isothiocyanates KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - phenethyl isothiocyanate KW - 6U7TFK75KV KW - Miconazole KW - 7NNO0D7S5M KW - Anethole Trithione KW - QUY32964DJ KW - Acetylcysteine KW - WYQ7N0BPYC KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Body Weight -- drug effects KW - Time Factors KW - Female KW - Mammary Neoplasms, Experimental -- chemically induced KW - Isothiocyanates -- pharmacology KW - Anticarcinogenic Agents -- pharmacology KW - Acetylcysteine -- pharmacology KW - Miconazole -- pharmacology KW - Mammary Neoplasms, Experimental -- prevention & control KW - Anethole Trithione -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79113074?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Chemopreventive+efficacy+of+anethole+trithione%2C+N-acetyl-L-cysteine%2C+miconazole+and+phenethylisothiocyanate+in+the+DMBA-induced+rat+mammary+cancer+model.&rft.au=Lubet%2C+R+A%3BSteele%2C+V+E%3BEto%2C+I%3BJuliana%2C+M+M%3BKelloff%2C+G+J%3BGrubbs%2C+C+J&rft.aulast=Lubet&rft.aufirst=R&rft.date=1997-07-03&rft.volume=72&rft.issue=1&rft.spage=95&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Medical+Association&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-23 N1 - Date created - 1997-07-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Residential exposure to magnetic fields and acute lymphoblastic leukemia in children. AN - 79054550; 9203424 AB - Previous studies found associations between childhood leukemia and surrogate indicators of exposure to magnetic fields (the power-line classification since known as "wire coding"), but not between childhood leukemia and measurements of 60-Hz residential magnetic fields. We enrolled 638 children with acute lymphoblastic leukemia (ALL) who were under 15 years of age and were registered with the Children's Cancer Group and 620 controls in a study of residential exposure to magnetic fields generated by nearby power lines. In the subjects' current and former homes, data collectors measured magnetic fields for 24 hours in the child's bedroom and for 30 seconds in three or four other rooms and outside the front door. A computer algorithm assigned wire-code categories; based on the distance and configuration of nearby power lines, to the subjects' main residences (for 416 case patients and 416 controls) and to those where the family had lived during the mother's pregnancy with the subject (for 230 case patients and 230 controls). The risk of childhood ALL was not linked to summary time-weighted average residential magnetic-field levels, categorized according to a priori criteria. The odds ratio for ALL was 1.24 (95 percent confidence interval, 0.86 to 1.79) at exposures of 0.200 mu T or greater as compared with less than 0.065 mu T. The risk of ALL was not increased among children whose main residences were in the highest wire-code category (odds ratio as compared with the lowest category, 0.88; 95 percent confidence interval, 0.48 to 1.63). Furthermore, the risk was not significantly associated with either residential magnetic-field levels or the wire codes of the homes mothers resided in when pregnant with the subjects. Our results provide little evidence that living in homes characterized by high measured time-weighted average magnetic-field levels or by the highest wire-code category increases the risk of ALL in children. JF - The New England journal of medicine AU - Linet, M S AU - Hatch, E E AU - Kleinerman, R A AU - Robison, L L AU - Kaune, W T AU - Friedman, D R AU - Severson, R K AU - Haines, C M AU - Hartsock, C T AU - Niwa, S AU - Wacholder, S AU - Tarone, R E AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Md 20892-7362, USA. Y1 - 1997/07/03/ PY - 1997 DA - 1997 Jul 03 SP - 1 EP - 7 VL - 337 IS - 1 SN - 0028-4793, 0028-4793 KW - Abridged Index Medicus KW - Index Medicus KW - Infant KW - Risk KW - Odds Ratio KW - Housing KW - Humans KW - Case-Control Studies KW - Child KW - Dose-Response Relationship, Radiation KW - Male KW - Female KW - Child, Preschool KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- epidemiology KW - Electromagnetic Fields -- adverse effects KW - Environmental Exposure -- adverse effects KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79054550?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+journal+of+medicine&rft.atitle=Residential+exposure+to+magnetic+fields+and+acute+lymphoblastic+leukemia+in+children.&rft.au=Linet%2C+M+S%3BHatch%2C+E+E%3BKleinerman%2C+R+A%3BRobison%2C+L+L%3BKaune%2C+W+T%3BFriedman%2C+D+R%3BSeverson%2C+R+K%3BHaines%2C+C+M%3BHartsock%2C+C+T%3BNiwa%2C+S%3BWacholder%2C+S%3BTarone%2C+R+E&rft.aulast=Linet&rft.aufirst=M&rft.date=1997-07-03&rft.volume=337&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=00284793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-08 N1 - Date created - 1997-07-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: N Engl J Med. 1997 Nov 13;337(20):1471; author reply 1473-4 [9380106] N Engl J Med. 1997 Nov 13;337(20):1473; author reply 1473-4 [9380112] N Engl J Med. 1997 Jul 3;337(1):44-6 [9203432] N Engl J Med. 1997 Nov 13;337(20):1473; author reply 1473-4 [9380111] N Engl J Med. 1997 Nov 13;337(20):1472; author reply 1473-4 [9380110] N Engl J Med. 1997 Nov 13;337(20):1472; author reply 1473-4 [9380109] N Engl J Med. 1997 Nov 13;337(20):1471-2; author reply 1473-4 [9380107] N Engl J Med. 1997 Nov 13;337(20):1472; author reply 1473-4 [9380108] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The solid-phase synthesis of 2-5-linked oligoriboadenylates containing 8-bromoadenine AN - 954582808; 13858680 AB - To increase the accessibility of 8-bromo-2',5'-oligoadenylates, we developed a synthesis of 2'-5'-linked oligoriboadenylates containing varying numbers of 8-bromoadenosine residues based on the use of a CPG-LCA solid support and the phosphoramidite approach. Although N super(6)benzoyl protection was satisfactory for incorporation of nonmodified adenine residues into 2',5'-oligonucleotides, the effective incorporation of 8-bromoadenine into such 2',5'-linked oligomers required use of a non acyl protecting group. Amidine protection of the purine exocyclic amino function proved compatible with all aspects of the phophoramidite approach and with the hydroxyl protection groups employed. JF - Applied Biochemistry and Biotechnology AU - Lesiak, Krystyna B AU - Uznanski, Bogdan AU - Torrence, Paul F AD - Section on Biomedical Chemistry,Laboratory of Medicinal Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 20892, Bethesda, MD Y1 - 1997/07// PY - 1997 DA - July 1997 SP - 33 EP - 44 PB - Humana Press Inc., 999 Riverview Dr., Ste. 208 Totowa NJ 07512 USA VL - 67 IS - 1-2 SN - 0273-2289, 0273-2289 KW - Biotechnology and Bioengineering Abstracts KW - Adenine KW - Solid phase methods KW - Protecting groups KW - purines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/954582808?accountid=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=Applied+Biochemistry+and+Biotechnology&rft.atitle=The+solid-phase+synthesis+of+2-5-linked+oligoriboadenylates+containing+8-bromoadenine&rft.au=Lesiak%2C+Krystyna+B%3BUznanski%2C+Bogdan%3BTorrence%2C+Paul+F&rft.aulast=Lesiak&rft.aufirst=Krystyna&rft.date=1997-07-01&rft.volume=67&rft.issue=1-2&rft.spage=33&rft.isbn=&rft.btitle=&rft.title=Applied+Biochemistry+and+Biotechnology&rft.issn=02732289&rft_id=info:doi/10.1007%2FBF02787839 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-03-01 N1 - Last updated - 2016-03-17 N1 - SubjectsTermNotLitGenreText - Adenine; Solid phase methods; Protecting groups; purines DO - http://dx.doi.org/10.1007/BF02787839 ER - TY - JOUR T1 - Attention-related modulation of activity in primary and secondary auditory cortex. AN - 85278760; pmid-9261818 AB - We investigated the effects of auditory attention on brain activity using functional magnetic resonance imaging. Subjects listened to three word lists, three times each, and were instructed to count the number of times they heard a target word during two of these presentations. For the third, they listened to the words without counting. All subjects showed significant areas of activation in auditory cortex during the listening conditions compared to rest. There was significantly more activation and a larger area of activation, particularly in association cortex, in the left temporal lobe during counting of targets compared to the no-target conditions, with a similar trend in the right hemisphere. These results provide evidence of an attention-related enhancement of both activation magnitude and extent in auditory cortex. JF - Neuroreport AU - Grady, C L AU - Van Meter J W AU - Maisog, J M AU - Pietrini, P AU - Krasuski, J AU - Rauschecker, J P AD - Laboratory of Neurosciences, National Institute on Aging, Bethesda, MD, USA. PY - 1997 SP - 2511 EP - 2516 VL - 8 IS - 11 SN - 0959-4965, 0959-4965 KW - Auditory Cortex KW - Magnetic Resonance Imaging KW - Human KW - Adult KW - Brain KW - Attention KW - Speech KW - Female KW - Male KW - Brain Mapping KW - Auditory Perception UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85278760?accountid=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=Attention-related+modulation+of+activity+in+primary+and+secondary+auditory+cortex.&rft.au=Grady%2C+C+L%3BVan+Meter+J+W%3BMaisog%2C+J+M%3BPietrini%2C+P%3BKrasuski%2C+J%3BRauschecker%2C+J+P&rft.aulast=Grady&rft.aufirst=C&rft.date=1997-07-01&rft.volume=8&rft.issue=11&rft.spage=2511&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 - Optimization of noninvasive activation studies with 15O-water and three-dimensional positron emission tomography. AN - 85273068; pmid-9270489 AB - We investigated the effects of varying the injected dose, speed of injection, and scan duration to maximize the sensitivity of noninvasive activation studies with 15O-water and three-dimensional positron emission tomography. A covert word generation task was used in four subjects with bolus injections of 2.5 to 3D mCi of 15O-water. The noise equivalent counts (NEC) for the whole brain peaked at an injected dose of 12 to 15 mCi. This was lower than expected from phantom studies, presumably because of the effect of radioactivity outside of the brain. A 10 mCi injection gave an NEC of 92.4 +/- 2.2% of the peak value. As the scan duration increased from 60 to 90 to 120 seconds, the areas of activation decreased in size or were no longer detected. Therefore, we selected a 1 minute scan using 10 mCi for bolus injections. We then performed simulation studies to evaluate, for a given CBF change, the effect on signal-to-noise ratio (S/N) of longer scan duration with slow tracer infusions. Using a measured arterial input function from a bolus injection, new input functions for longer duration injections and the corresponding tissue data were simulated. Combining information about image noise derived from Hoffman brain phantom studies with the simulated tissue data allowed calculation of the S/N for a given CBF change. The simulation shows that a slow infusion permits longer scan acquisitions with only a small loss in S/N. This allows the investigator to choose the injection duration, and thus the time period during which scan values are sensitive to regional CBF. JF - Journal of Cerebral Blood Flow and Metabolism AU - Sadato, N AU - Carson, R E AU - Daube-Witherspoon, M E AU - Campbell, G AU - Hallett, M AU - Herscovitch, P AD - Human Motor Control Section, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA. PY - 1997 SP - 732 EP - 739 VL - 17 IS - 7 SN - 0271-678X, 0271-678X KW - Models, Cardiovascular KW - Artifacts KW - Computer Simulation KW - Human KW - Oxygen Radioisotopes KW - Adult KW - Aged KW - Middle Age KW - Female KW - Male KW - Tomography, Emission-Computed KW - Cerebrovascular Circulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85273068?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Cerebral+Blood+Flow+and+Metabolism&rft.atitle=Optimization+of+noninvasive+activation+studies+with+15O-water+and+three-dimensional+positron+emission+tomography.&rft.au=Sadato%2C+N%3BCarson%2C+R+E%3BDaube-Witherspoon%2C+M+E%3BCampbell%2C+G%3BHallett%2C+M%3BHerscovitch%2C+P&rft.aulast=Sadato&rft.aufirst=N&rft.date=1997-07-01&rft.volume=17&rft.issue=7&rft.spage=732&rft.isbn=&rft.btitle=&rft.title=Journal+of+Cerebral+Blood+Flow+and+Metabolism&rft.issn=0271678X&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Force generation in the outer hair cell of the cochlea. AN - 85258140; pmid-9199816 AB - The outer hair cell of the mammalian cochlea has a unique motility directly dependent on the membrane potential. Examination of the force generated by the cell is an important step in clarifying the detailed mechanism as well as the biological importance of this motility. We performed a series of experiments to measure force in which an elastic probe was attached to the cell near the cuticular plate and the cell was driven with voltage pulses delivered from a patch pipette under whole-cell voltage clamp. The axial stiffness was also determined with the same cell by stretching it with the patch pipette. The isometric force generated by the cell is around 0.1 nN/mV, somewhat smaller than 0.15 nN/mV, predicted by an area motor model based on mechanical isotropy, but larger than in earlier reports in which the membrane potential was not controlled. The axial stiffness obtained, however, was, on average, 510 nN per unit strain, about half of the value expected from the mechanical isotropy of the membrane. We extended the area motor theory incorporating mechanical orthotropy to accommodate the axial stiffness determined. The force expected from the orthotropic model was within experimental uncertainties. JF - Biophysical Journal AU - Iwasa, Kuni H AU - Adachi, M AD - National Institute on Deafness and Other Communication Disorders PY - 1997 SP - 546 EP - 555 VL - 73 IS - 1 SN - 0006-3495, 0006-3495 KW - Cochlea KW - Cell Movement KW - Patch-Clamp Techniques KW - Models, Structural KW - Guinea Pigs KW - Kinetics KW - Hair Cells, Outer KW - Cell Membrane KW - Animal KW - Membrane Potentials KW - Time Factors KW - Elasticity KW - Mathematics KW - Models, Biological UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85258140?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biophysical+Journal&rft.atitle=Force+generation+in+the+outer+hair+cell+of+the+cochlea.&rft.au=Iwasa%2C+Kuni+H%3BAdachi%2C+M&rft.aulast=Iwasa&rft.aufirst=Kuni&rft.date=1997-07-01&rft.volume=73&rft.issue=1&rft.spage=546&rft.isbn=&rft.btitle=&rft.title=Biophysical+Journal&rft.issn=00063495&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Inbred strain differences in prepulse inhibition of the mouse startle response. AN - 85257949; pmid-9266614 AB - Prepulse inhibition is the phenomenon in which a weak prepulse stimulus suppresses the response to a startling stimulus. Patients with schizophrenia have impaired prepulse inhibition which is thought to reflect dysfunctional sensorimotor gating mechanisms. To investigate the potential genetic basis for differences in sensorimotor gating, the responses of 13 inbred strains of mice were evaluated using the prepulse inhibition paradigm. Ten male mice from A/J, AKR/J, BALB/cByJ, BUB/BnJ, C3H/HeJ, C57BL/6J, C57BL/10J, DBA/2J, FVB/NJ, ST/bJ, 129/J, 129/SvJ, 129/SvEvTac inbred strains were tested for acoustic prepulse inhibition of acoustic and tactile startle responses. There was a wide range of responses among the inbred strains of mice. Exact strain distributions were determined for each combination of prepulse sound level and startle stimulus. In general, mice from the 129/SvEvTac, AKR/J, 129/J, and 129/SvJ strains displayed high levels of prepulse inhibition of both the acoustic and tactile startle responses. C57BL/6J, C57BL/10J and BUB/BnJ mice showed low levels of prepulse inhibition. There was also a wide range in the amplitude of the acoustic and tactile startle responses. C57BL/10J and FVB/NJ mice displayed the greatest startle responses and DBA/2J, 129/J and 129/SvJ had the poorest startle responses. There was no correlation between the level of prepulse inhibition and the amplitude of the startle response. These findings indicate that inbred strains of mice may be a useful tool to study the genetic basis of sensorimotor gating. JF - Psychopharmacology AU - Paylor, R AU - Crawley, J N AD - Section on Behavioral Neuropharmacology, National Institute of Mental Health, Bethesda, MD 20892-1375, USA. PY - 1997 SP - 169 EP - 180 VL - 132 IS - 2 SN - 0033-3158, 0033-3158 KW - Genetics, Behavioral KW - Mice, Inbred Strains KW - Comparative Study KW - Startle Reaction KW - Animal KW - Acoustic Stimulation KW - Mice KW - Physical Stimulation KW - Male UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85257949?accountid=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=Psychopharmacology&rft.atitle=Inbred+strain+differences+in+prepulse+inhibition+of+the+mouse+startle+response.&rft.au=Paylor%2C+R%3BCrawley%2C+J+N&rft.aulast=Paylor&rft.aufirst=R&rft.date=1997-07-01&rft.volume=132&rft.issue=2&rft.spage=169&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Analysis of transforming growth factor (TGF)-alpha/epidermal growth factor receptor, hepatocyte growth Factor/c-met,TGF-beta receptor type II, and p53 expression in human hepatocellular carcinomas. AN - 79638531; 9815784 AB - Experimental data suggest that dysregulation of growth factors and the cognate receptors may play an important role in hepatocarcinogenesis. The objective of the present study was to characterize the expression of two hepatotrophic growth factor/receptor systems [transforming growth factor-alpha/epidermal growth factor receptor (TGF-alpha/EGFR) and hepatocyte growth factor/c-met receptor (HGF/c-met)], both of which are implicated in the development of human liver tumors. In addition, we have analyzed the expression of transforming growth factor-beta receptor type II (TGF-beta-RII) and p53, genes associated with growth inhibition and tumor suppression, respectively. Surgical biopsy specimens from 86 human hepatocellular carcinomas were analyzed. TGF-alpha was overexpressed in 17%, equally expressed in 21%, and down-regulated in 62% of the hepatocellular carcinomas when compared to the surrounding hepatic tissue. No major changes were found with EGFR expression. HGF was over-expressed in 33% and down-regulated in 21% of the tumors. The c-met receptor was overexpressed in 20%, equally expressed in 48%, and down-regulated in 32% of the neoplasms. In contrast, TGF-beta-RII was overexpressed in only 8%, equal in 42%, and down-regulated in 50% of tumors. Nuclear staining of p53, indicative of a mutation(s), was observed in the great majority of the tumors (80%), whereas no nuclear p53 was detected in peritumoral tissues. Interestingly, simultaneous down-regulation of c-met and TGF-beta-RII was observed in 23% of the hepatocellular carcinomas, 85% of which also showed nuclear p53 staining. Taken together, our data suggest that down-regulation of c-met and TGF-beta-RII may, together with p53 mutations, play a significant role in human liver carcinogenesis. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Kiss, A AU - Wang, N J AU - Xie, J P AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1997/07// PY - 1997 DA - July 1997 SP - 1059 EP - 1066 VL - 3 IS - 7 SN - 1078-0432, 1078-0432 KW - Receptors, Transforming Growth Factor beta KW - 0 KW - Tumor Suppressor Protein p53 KW - Proto-Oncogene Proteins c-met KW - EC 2.7.10.1 KW - Receptor, Epidermal Growth Factor KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - transforming growth factor-beta type II receptor KW - EC 2.7.11.30 KW - Index Medicus KW - Liver -- pathology KW - Skin -- metabolism KW - Humans KW - Hepatitis B -- metabolism KW - Aged KW - Liver -- metabolism KW - Gene Expression Regulation, Neoplastic KW - Tumor Suppressor Protein p53 -- analysis KW - Hepatitis B -- pathology KW - Adult KW - Middle Aged KW - Immunohistochemistry KW - China KW - Female KW - Male KW - Receptors, Transforming Growth Factor beta -- analysis KW - Receptors, Transforming Growth Factor beta -- genetics KW - Carcinoma, Hepatocellular -- surgery KW - Proto-Oncogene Proteins c-met -- analysis KW - Receptor, Epidermal Growth Factor -- analysis KW - Proto-Oncogene Proteins c-met -- genetics KW - Liver Neoplasms -- pathology KW - Genes, p53 KW - Receptor, Epidermal Growth Factor -- genetics KW - Carcinoma, Hepatocellular -- genetics KW - Carcinoma, Hepatocellular -- pathology KW - Liver Neoplasms -- surgery KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79638531?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Analysis+of+transforming+growth+factor+%28TGF%29-alpha%2Fepidermal+growth+factor+receptor%2C+hepatocyte+growth+Factor%2Fc-met%2CTGF-beta+receptor+type+II%2C+and+p53+expression+in+human+hepatocellular+carcinomas.&rft.au=Kiss%2C+A%3BWang%2C+N+J%3BXie%2C+J+P%3BThorgeirsson%2C+S+S&rft.aulast=Kiss&rft.aufirst=A&rft.date=1997-07-01&rft.volume=3&rft.issue=7&rft.spage=1059&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-25 N1 - Date created - 1999-02-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A pilot study of gamma-1b-interferon in combination with fluorouracil, leucovorin, and alpha-2a-interferon. AN - 79638411; 9815792 AB - The combination of IFN-alpha-2a (IFN-alpha) and IFN-gamma-1b (IFN-gamma) has been found to produce more than additive cytotoxicity with fluorouracil (5-FU) in HT 29 colon cancer cells due to enhanced DNA-directed effects. We therefore studied the combination of IFN-gamma with IFN-alpha, 5-FU, and leucovorin (LV) in a clinical trial. Fifty-three patients received an initial cycle of 5 million units (MU)/m2 IFN-alpha s.c. on days 1-7 with 500 mg/m2 LV and 370 mg/m2 5-FU i.v. on days 2-6. IFN-gamma was then added once tolerable doses of 5-FU and IFN-alpha were established for each patient. IFN-gamma was administered at one of six dose levels between 0.3-4.8 MU/m2 s.c. on days 1-7. This design permitted comparison of the clinical toxicity and pharmacokinetics of 5-FU in two consecutive cycles in an individual treated with the same doses of 5-FU/LV/IFN-alpha in the absence and presence of IFN-gamma. In 43 matched patient cycles, the addition of IFN-gamma did not seem to worsen gastrointestinal toxicity, and skin toxicity tended to be milder. 5-FU clearance was higher in 14 cycles with IFN-gamma compared to the patient's prior cycle with the same doses of 5-FU/LV/IFN-alpha: 798 +/- 309 versus 601 +/- 250 ml/min/m2 (mean +/- SD; P = 0.04). In these 28 cycles, the median 5-FU clearance was significantly lower in 11 cycles that were complicated by more severe diarrhea: 524 versus 798 ml/min/m2 (grade 2 versus 0-1; P = 0. 0032). Overall, 38% and 26% of patients had grade 3-4 diarrhea and mucositis. Dose reductions of IFN-gamma for chronic fatigue, malaise, or anorexia were ultimately required more frequently with >/=2.4 MU/m2 (P = 0.018), and the maximum tolerated dose of IFN-gamma was considered to be 1.2 MU/m2/ day. Objective responses were seen in 41% of 29 measurable colorectal cancer patients. Compared to our previous experience with 5-FU/LV/IFN-alpha, IFN-gamma and IFN-alpha appeared to have opposite effects on 5-FU clearance. These results suggest that any potential benefit of adding IFN-alpha to 5-FU/LV on this schedule may not depend solely on alterations in 5-FU clearance. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Grem, J L AU - McAtee, N AU - Murphy, R F AU - Balis, F M AU - Cullen, E AU - Chen, A P AU - Hamilton, J M AU - Steinberg, S M AU - Quinn, M AU - Sorensen, J M AU - Arbuck, S G AU - Lawrence, D AU - Pang, J AU - Allegra, C J AD - Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Naval Medical Center, Bethesda, Maryland 20889, USA. jgremj@helix.nih.gov Y1 - 1997/07// PY - 1997 DA - July 1997 SP - 1125 EP - 1134 VL - 3 IS - 7 SN - 1078-0432, 1078-0432 KW - Antineoplastic Agents KW - 0 KW - Interferon-alpha KW - Recombinant Proteins KW - interferon alfa-2a KW - 47RRR83SK7 KW - Interferon-gamma KW - 82115-62-6 KW - Leucovorin KW - Q573I9DVLP KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Drug Administration Schedule KW - Combined Modality Therapy KW - Humans KW - Adult KW - Metabolic Clearance Rate KW - Aged KW - Pilot Projects KW - Middle Aged KW - Male KW - Female KW - Clinical Protocols KW - Fluorouracil -- therapeutic use KW - Fluorouracil -- adverse effects KW - Interferon-alpha -- therapeutic use KW - Interferon-alpha -- adverse effects KW - Interferon-gamma -- therapeutic use KW - Antineoplastic Agents -- pharmacokinetics KW - Neoplasms -- therapy KW - Fluorouracil -- pharmacokinetics KW - Antineoplastic Agents -- therapeutic use KW - Interferon-gamma -- adverse effects KW - Leucovorin -- therapeutic use KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79638411?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=A+pilot+study+of+gamma-1b-interferon+in+combination+with+fluorouracil%2C+leucovorin%2C+and+alpha-2a-interferon.&rft.au=Grem%2C+J+L%3BMcAtee%2C+N%3BMurphy%2C+R+F%3BBalis%2C+F+M%3BCullen%2C+E%3BChen%2C+A+P%3BHamilton%2C+J+M%3BSteinberg%2C+S+M%3BQuinn%2C+M%3BSorensen%2C+J+M%3BArbuck%2C+S+G%3BLawrence%2C+D%3BPang%2C+J%3BAllegra%2C+C+J&rft.aulast=Grem&rft.aufirst=J&rft.date=1997-07-01&rft.volume=3&rft.issue=7&rft.spage=1125&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-25 N1 - Date created - 1999-02-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - What studies of fusion peptides tell us about viral envelope glycoprotein-mediated membrane fusion (review). AN - 79440421; 9394290 AB - This review describes the numerous and innovative methods used to study the structure and function of viral fusion peptides. The systems studied include both intact fusion proteins and synthetic peptides interacting with model membranes. The strategies and methods include dissecting the fusion process into intermediate stages, comparing the effects of sequence mutations, electrophysiological patch clamp methods, hydrophobic photolabelling, video microscopy of the redistribution of both aqueous and lipophilic fluorescent probes between cells, standard optical spectroscopy of peptides in solution (circular dichroism and fluorescence) and attenuated total reflection-Fourier transform infrared spectroscopy of peptides bound to planar bilayers. Although the goal of a detailed picture of the fusion pore has not been achieved for any of the intermediate stages, important properties useful for constraining the development of models are emerging. For example, the presence of alpha-helical structure in at least part of the fusion peptide is strongly correlated with activity; whereas, beta-structure tends to be less prevalent, associated with non-native experimental conditions, and more related to vesicle aggregation than fusion. The specific angle of insertion of the peptides into the membrane plane is also found to be an important characteristic for the fusion process. A shallow penetration, extending only to the central aliphatic core region, is likely responsible for the destabilization of the lipids required for coalescence of the apposing membranes and fusion. The functional role of the fusion peptides (which tend to be either nonpolar or aliphatic) is then to bind to and dehydrate the outer bilayers at a localized site; and thus reduce the energy barrier for the formation of highly curved, lipidic 'stalk' intermediates. In addition, the importance of the formation of specific, 'higher-order' fusion peptide complexes has also been shown. Recent crystallographic structures of core domains of two more fusion proteins (in addition to influenza haemagglutinin) has greatly facilitated the development of prototypic models of the fusion site. This latter effort will undoubtedly benefit from the insights and constraints gained from the studies of fusion peptides. JF - Molecular membrane biology AU - Durell, S R AU - Martin, I AU - Ruysschaert, J M AU - Shai, Y AU - Blumenthal, R AD - National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1997 SP - 97 EP - 112 VL - 14 IS - 3 SN - 0968-7688, 0968-7688 KW - Hemagglutinin Glycoproteins, Influenza Virus KW - 0 KW - Membrane Lipids KW - Membrane Proteins KW - Viral Fusion Proteins KW - Index Medicus KW - Animals KW - Orthomyxoviridae -- physiology KW - Hemagglutinin Glycoproteins, Influenza Virus -- physiology KW - Models, Molecular KW - Membrane Lipids -- metabolism KW - Amino Acid Sequence KW - Sequence Homology KW - Protein Binding KW - Hemagglutinin Glycoproteins, Influenza Virus -- genetics KW - Structure-Activity Relationship KW - Mutagenesis KW - Sequence Alignment KW - Molecular Sequence Data KW - Virus Physiological Phenomena KW - Consensus Sequence KW - Hemagglutinin Glycoproteins, Influenza Virus -- chemistry KW - Orthomyxoviridae -- genetics KW - Membrane Proteins -- physiology KW - Membrane Fusion -- physiology KW - Viral Fusion Proteins -- chemistry KW - Viral Fusion Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79440421?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+membrane+biology&rft.atitle=What+studies+of+fusion+peptides+tell+us+about+viral+envelope+glycoprotein-mediated+membrane+fusion+%28review%29.&rft.au=Durell%2C+S+R%3BMartin%2C+I%3BRuysschaert%2C+J+M%3BShai%2C+Y%3BBlumenthal%2C+R&rft.aulast=Durell&rft.aufirst=S&rft.date=1997-07-01&rft.volume=14&rft.issue=3&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=Molecular+membrane+biology&rft.issn=09687688&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-04 N1 - Date created - 1998-02-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Overview of pathophysiology and rationale for treatment of sickle cell anemia. AN - 79314524; 9317195 AB - Sickle cell anemia occurs in individuals who are homozygous for a single nucleotide substitution in codon 6 of the beta-globin gene. This single mutation leads to the formation of abnormal hemoglobin, HbS (alpha2betas[s]2), which is much less soluble when deoxygenated than hemoglobin A (HbA) (alpha2beta2). This insolubility causes aggregates of HbS to form inside sickle erythrocytes as they traverse the circulation. With full deoxygenation, polymer becomes so extensive that the cells become sickled in shape. Yet, even with high oxygen saturation values, quantities of HbS polymer may be sufficient to alter the rheologic properties of sickle erythrocytes in the absence of morphologic changes, and cells can occlude end arterioles, leading to chronic hemolysis and microinfarction of diverse tissues. Ultimately, this process leads to vaso-occlusive crises and irreversible tissue damage. Nonetheless, the spectrum of disease severity even among patients with grossly equivalent hematologic indices suggests that many other factors-including genetic, cellular, physiologic, and psychosocial-play a substantial role in determining the course of this disorder. Of the genetic factors, the level of fetal hemoglobin in particular has been established to favorably modify the clinical manifestations of patients with sickle cell disease and related conditions. Recent advances in the understanding of the molecular and cellular pathophysiology of sickle cell disease, coupled with new insights into the developmental regulation of human globin gene expression, have provided the scientific impetus and clinical rationale to attempt to augment the postnatal production of fetal hemoglobin. Furthermore, contemporary understanding of the quantitative relationship between the extent of HbS polymerization within the red cells and the degree of red blood cell and/or organ pathology has now enabled investigators to predict to what extent this intracellular pathogenic process must be inhibited to achieve clinically significant amelioration of disease manifestation. These areas will be covered in this overview. This is a US government work. There are no restrictions on its use. JF - Seminars in hematology AU - Rodgers, G P AD - Hematology Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1822, USA. Y1 - 1997/07// PY - 1997 DA - July 1997 SP - 2 EP - 7 VL - 34 IS - 3 Suppl 3 SN - 0037-1963, 0037-1963 KW - Antineoplastic Agents KW - 0 KW - Antisickling Agents KW - Hemoglobin, Sickle KW - Globins KW - 9004-22-2 KW - Fetal Hemoglobin KW - 9034-63-3 KW - Hydroxyurea KW - X6Q56QN5QC KW - Index Medicus KW - Hemoglobin, Sickle -- metabolism KW - Antisickling Agents -- adverse effects KW - Antisickling Agents -- therapeutic use KW - Humans KW - Globins -- genetics KW - Point Mutation KW - Hydroxyurea -- therapeutic use KW - Fetal Hemoglobin -- metabolism KW - Hydroxyurea -- adverse effects KW - Antineoplastic Agents -- therapeutic use KW - Anemia, Sickle Cell -- physiopathology KW - Anemia, Sickle Cell -- drug therapy KW - Anemia, Sickle Cell -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79314524?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Overview+of+pathophysiology+and+rationale+for+treatment+of+sickle+cell+anemia.&rft.au=Rodgers%2C+G+P&rft.aulast=Rodgers&rft.aufirst=G&rft.date=1997-07-01&rft.volume=34&rft.issue=3+Suppl+3&rft.spage=2&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 - 1997-10-31 N1 - Date created - 1997-10-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibitory monoclonal antibodies to human cytochrome P450 2D6. AN - 79281646; 9296346 AB - Two monoclonal antibodies (MAbs) have been isolated that bind to human P450 2D6 and inhibit 2D6 catalyzed bufuralol 1-hydroxylation by 90%. One but not both of the MAbs immunoblotted 2D6. The MAbs were highly specific to 2D6 and did not cross-react with other P450s. Inhibitory monoclonal antibodies will be useful for determining the contribution of 2D6 to the metabolism of a wide variety of 2D6 and other P450 substrates in human tissues containing multiple P450s. JF - Biochemical pharmacology AU - Krausz, K W AU - Yang, T J AU - Gonzalez, F J AU - Shou, M AU - Gelboin, H V AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, U.S.A. Y1 - 1997/07/01/ PY - 1997 DA - 1997 Jul 01 SP - 15 EP - 17 VL - 54 IS - 1 SN - 0006-2952, 0006-2952 KW - Antibodies, Monoclonal KW - 0 KW - Cytochrome P-450 CYP2D6 Inhibitors KW - Ethanolamines KW - Phenanthrenes KW - phenanthrene KW - 448J8E5BST KW - bufuralol KW - 891H89GFT4 KW - Cytochrome P-450 CYP2D6 KW - EC 1.14.14.1 KW - Index Medicus KW - Phenanthrenes -- metabolism KW - Ethanolamines -- metabolism KW - Humans KW - Cytochrome P-450 CYP2D6 -- immunology KW - Cytochrome P-450 CYP2D6 -- biosynthesis KW - Cross Reactions KW - Hydroxylation KW - Antibodies, Monoclonal -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79281646?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+antibodies+to+human+cytochrome+P450+2D6.&rft.au=Krausz%2C+K+W%3BYang%2C+T+J%3BGonzalez%2C+F+J%3BShou%2C+M%3BGelboin%2C+H+V&rft.aulast=Krausz&rft.aufirst=K&rft.date=1997-07-01&rft.volume=54&rft.issue=1&rft.spage=15&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 - 1997-10-09 N1 - Date created - 1997-10-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Abnormal cerebral perfusion in chronic methamphetamine abusers: a study using 99MTc-HMPAO and SPECT. AN - 79250730; 9278950 AB - 1. Cerebral blood flow of nine methamphetamine abusers with technetium-99m-hexamethylpropyleneamine oxime (HMPAO) and single photon emission computed tomography (SPECT) as well as morphological examination with magnetic resonance imaging (MRI) were investigated. 2. Six of these subjects exhibited multiple focal perfusion deficits in cerebral cortices without abnormalities in MRI including cerebral atrophy and/or infarctions. 3. Cerebral perfusion deficits were detected in methamphetamine abusers even after a long abstinence period, suggesting that vascular changes were irreversible to some degree. 4. HMPAO SPECT study appeared to be sensitive to the detection of cerebral perfusion abnormalities in drug abusers. JF - Progress in neuro-psychopharmacology & biological psychiatry AU - Iyo, M AU - Namba, H AU - Yanagisawa, M AU - Hirai, S AU - Yui, N AU - Fukui, S AD - Division of Drug Dependence and Psychotropic Drug Clinical Research, National Institute of Mental Health, National Center of Neurology and Psychiatry, Chiba, Japan. Y1 - 1997/07// PY - 1997 DA - July 1997 SP - 789 EP - 796 VL - 21 IS - 5 SN - 0278-5846, 0278-5846 KW - Technetium Tc 99m Exametazime KW - 3B744AG22N KW - Methamphetamine KW - 44RAL3456C KW - Index Medicus KW - Magnetic Resonance Imaging KW - Tomography, Emission-Computed, Single-Photon KW - Humans KW - Adult KW - Adolescent KW - Male KW - Female KW - Substance-Related Disorders -- physiopathology KW - Cerebrovascular Circulation -- physiology KW - Substance-Related Disorders -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79250730?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Progress+in+neuro-psychopharmacology+%26+biological+psychiatry&rft.atitle=Abnormal+cerebral+perfusion+in+chronic+methamphetamine+abusers%3A+a+study+using+99MTc-HMPAO+and+SPECT.&rft.au=Iyo%2C+M%3BNamba%2C+H%3BYanagisawa%2C+M%3BHirai%2C+S%3BYui%2C+N%3BFukui%2C+S&rft.aulast=Iyo&rft.aufirst=M&rft.date=1997-07-01&rft.volume=21&rft.issue=5&rft.spage=789&rft.isbn=&rft.btitle=&rft.title=Progress+in+neuro-psychopharmacology+%26+biological+psychiatry&rft.issn=02785846&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-29 N1 - Date created - 1997-10-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of the INT6 mammary tumor gene product. AN - 79215531; 9260927 AB - INT6 is a unique gene, highly conserved throughout evolution and associated with mammary tumorigenesis in the mouse. Although it is expressed in all adult tissues of the mouse and early in embryonic development, its function is unknown. To study the normal distribution and the potential function of the Int6 gene products, we produced antibodies against synthetic peptides specific for the Int6 protein. Western blot and immunoprecipitation analysis demonstrated a 43-kD major gene product that is localized in the cytosolic fraction of mammary cell homogenates. This latter observation is supported by immunoperoxidase analysis, which shows a strong staining anti-Int6 peptide in the perinuclear region of the HC11 mammary epithelial cell line, suggesting a possible localization in the Golgi apparatus. Further immunocytochemical studies in the mouse embryo show that Int6 expression is prevalent in migrating neural crest cells, in the notochord, and in condensing cartilage between 9.5 and 14.5 days of development. In these embryonic tissues, Int6 staining co-localizes with the staining of ricinus lectin, and giantin, proteins that are specifically associated with the Golgi apparatus. The restricted expression of the protein within the Golgi apparatus and its strong conservation throughout evolution suggest that Int6 may perform an essential cellular function. JF - DNA and cell biology AU - Diella, F AU - Levi, G AU - Callahan, R AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/07// PY - 1997 DA - July 1997 SP - 839 EP - 847 VL - 16 IS - 7 SN - 1044-5498, 1044-5498 KW - Antibodies KW - 0 KW - Eukaryotic Initiation Factor-3 KW - Membrane Proteins KW - Peptides KW - Proto-Oncogene Proteins KW - RNA, Messenger KW - Recombinant Fusion Proteins KW - macrogolgin KW - Ricin KW - 9009-86-3 KW - Index Medicus KW - Peptides -- chemical synthesis KW - Animals KW - Neural Crest KW - Protein Processing, Post-Translational KW - RNA, Messenger -- analysis KW - Organ Specificity KW - Mice KW - Amino Acid Sequence KW - Membrane Proteins -- analysis KW - Molecular Weight KW - Cartilage -- embryology KW - Base Sequence KW - Ricin -- analysis KW - Molecular Sequence Data KW - Cartilage -- chemistry KW - Notochord KW - Cytosol -- chemistry KW - Cell Line KW - Epithelium -- chemistry KW - Female KW - Gene Expression Regulation, Developmental KW - Proto-Oncogene Proteins -- analysis KW - Mammary Glands, Animal -- chemistry KW - Proto-Oncogene Proteins -- chemistry KW - Proto-Oncogene Proteins -- metabolism KW - Golgi Apparatus -- chemistry KW - Proto-Oncogene Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79215531?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=DNA+and+cell+biology&rft.atitle=Characterization+of+the+INT6+mammary+tumor+gene+product.&rft.au=Diella%2C+F%3BLevi%2C+G%3BCallahan%2C+R&rft.aulast=Diella&rft.aufirst=F&rft.date=1997-07-01&rft.volume=16&rft.issue=7&rft.spage=839&rft.isbn=&rft.btitle=&rft.title=DNA+and+cell+biology&rft.issn=10445498&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-05 N1 - Date created - 1997-09-05 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - L35556; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dideoxy fingerprinting assay for BRCA1 mutation analysis. AN - 79190318; 9254884 AB - Since the isolation of BRCA1, the familial breast/ovarian cancer predisposition gene, much effort has been invested in characterizing the mutation spectrum. The large size of the gene and the wide distribution of its more than 100 mutations has increased the challenge of this endeavor such that traditional mutation detection techniques are inadequate. We examined the sensitivity of dideoxy fingerprinting (DDF), which combine a Sanger sequencing reaction with multiple-fragment single-strand conformation analysis (SSCA), as a mutation detection technique to screen BRCA1. Here we describe the technique and compare its sensitivity with that of SSCA in detecting 21 previously described BRCA1 sequence variants. All the variants were detected by DDF, but only 17 of 21 (81%) were observed by SSCA under standard conditions. Three of four alterations missed by SSCA were base substitutions. As a BRCA1 mutation detection technique, DDF was more sensitive than SSCA and may prove to be a useful research tool in defining the mutation spectrum within this and other genes. JF - Molecular carcinogenesis AU - Lancaster, J M AU - Berchuck, A AU - Futreal, P A AU - Wiseman, R W AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA. Y1 - 1997/07// PY - 1997 DA - July 1997 SP - 176 EP - 179 VL - 19 IS - 3 SN - 0899-1987, 0899-1987 KW - DNA, Neoplasm KW - 0 KW - Index Medicus KW - Sensitivity and Specificity KW - Breast Neoplasms -- genetics KW - Polymerase Chain Reaction KW - Humans KW - Polymorphism, Single-Stranded Conformational KW - DNA Mutational Analysis -- methods KW - DNA, Neoplasm -- genetics KW - DNA, Neoplasm -- analysis KW - Genes, BRCA1 KW - DNA Fingerprinting -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79190318?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dideoxy+fingerprinting+assay+for+BRCA1+mutation+analysis.&rft.au=Lancaster%2C+J+M%3BBerchuck%2C+A%3BFutreal%2C+P+A%3BWiseman%2C+R+W&rft.aulast=Lancaster&rft.aufirst=J&rft.date=1997-07-01&rft.volume=19&rft.issue=3&rft.spage=176&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 - 1997-08-29 N1 - Date created - 1997-08-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential effects of p53 mutants on the growth of human bronchial epithelial cells. AN - 79190083; 9254886 AB - We investigated the effects of five different p53 mutants on the growth of primary cultures of normal human bronchial epithelial (NHBE) cells. The five defective viral pZIP-Neo constructs contained the following mutations at mutational hot-spots found in human cancers: codons 143ala, 175his, 248trp, 249ser, and 273his. NHBE cells were infected with the p53 mutants, wild-type p53, or the pZIP-Neo vector control. The 143ala, 248trp, and 273his mutants, as well as wild-type p53, decreased the colony-forming efficiency and inhibited the growth of NHBE cells. The 175his mutant did not significantly change the growth rates. In NHBE cells from three donors, the 249ser mutant conferred a substantial growth advantage to the NHBE cells in a colony-forming-efficiency assay. In NHBE cells isolated from one donor, the 249ser mutant also produced a significant life span extension. These cells grew rapidly through 80 population doublings and entered an apparent "crisis" in passage 14. Karyotypic analyses of one culture at multiple passages revealed aneuploid populations with alterations of chromosomes 5, 11, and 13; quantitative DNA analysis detected aneuploidy in late passages from that culture and two other primary cultures. These data demonstrated that the codon 249ser mutation could provide a growth advantage to bronchial epithelial cells and suggest that this mutant protein can induce genomic instability. JF - Molecular carcinogenesis AU - Coursen, J D AU - Bennett, W P AU - Khan, M A AU - Forrester, K AU - Pietenpol, J A AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1997/07// PY - 1997 DA - July 1997 SP - 191 EP - 203 VL - 19 IS - 3 SN - 0899-1987, 0899-1987 KW - DNA, Complementary KW - 0 KW - RNA, Messenger KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Polymerase Chain Reaction KW - DNA, Complementary -- genetics KW - RNA, Messenger -- metabolism KW - Epithelial Cells KW - Transfection KW - Humans KW - DNA, Complementary -- metabolism KW - Epithelium -- physiology KW - Cell Division -- physiology KW - Epithelium -- metabolism KW - DNA, Complementary -- analysis KW - Cell Survival -- physiology KW - Cell Line KW - Tumor Suppressor Protein p53 -- biosynthesis KW - Tumor Suppressor Protein p53 -- physiology KW - Genes, p53 KW - Bronchi -- cytology KW - Bronchi -- metabolism KW - Tumor Suppressor Protein p53 -- genetics KW - Bronchi -- physiology KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79190083?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Differential+effects+of+p53+mutants+on+the+growth+of+human+bronchial+epithelial+cells.&rft.au=Coursen%2C+J+D%3BBennett%2C+W+P%3BKhan%2C+M+A%3BForrester%2C+K%3BPietenpol%2C+J+A%3BHarris%2C+C+C&rft.aulast=Coursen&rft.aufirst=J&rft.date=1997-07-01&rft.volume=19&rft.issue=3&rft.spage=191&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 - 1997-08-29 N1 - Date created - 1997-08-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A dominant negative mutant of jun blocking 12-O-tetradecanoylphorbol-13-acetate-induced invasion in mouse keratinocytes. AN - 79187780; 9254887 AB - We previously reported that induced activator protein-1 (AP-1) transcriptional activity appears to be required for tumor promoter-induced transformation in mouse epidermal JB6 cells. To extend this investigation to a keratinocyte culture model and a transgenic mouse model, we constructed K14TAM67, a keratin 14 promoter-controlled version of the dominant negative jun mutant to directly block AP-1 activity and possibly indirectly block NF kappa B activity in basal squamous epithelia. This study was directed at characterizing TAM67 expression and biological activity in the mouse cell line 308, a keratinocyte model for studying carcinogenesis. Cotransfection of K14TAM67 with luciferase plasmid reporter DNAs produced inhibition of basal and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced AP-1 and NF kappa B activity but had no effect on p53-dependent transcriptional activity. In an in vitro invasion assay, stable expression of TAM67 in 308 cells blocked TPA-induced Matrigel invasion. This suggests that blocking TPA-induced AP-1- or NF kappa B-regulated gene expression by TAM67 inhibits TPA-induced progression. Recombinant tissue inhibitor of metalloproteinase 1 reduced TPA-induced in vitro invasion, thus implicating metalloproteinases at least in part in the transcription factor-dependent process. Analysis of mRNA levels for members of the matrix metalloproteinase (MMP) family, however, revealed that the expression of any single MMP family member did not correlate with regulation of AP-1 or NF kappa B activity. However, the combination of substantial levels of mRNA for stromelysin-1, stromelysin-2, collagenase, membrane type 1 MMP, and gelatinase A occurred only in TPA-treated cells in the absence of TAM67. These results suggest that the action of the dominant negative jun mutant on AP-1 and NF kappa B gene regulation results in complex alterations in the levels of downstream effector genes, such as the metalloproteinases, that effect TPA-induced cellular invasion. JF - Molecular carcinogenesis AU - Dong, Z AU - Crawford, H C AU - Lavrovsky, V AU - Taub, D AU - Watts, R AU - Matrisian, L M AU - Colburn, N H AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland, USA. Y1 - 1997/07// PY - 1997 DA - July 1997 SP - 204 EP - 212 VL - 19 IS - 3 SN - 0899-1987, 0899-1987 KW - Anticarcinogenic Agents KW - 0 KW - Carcinogens KW - Glycoproteins KW - NF-kappa B KW - Proto-Oncogene Proteins c-jun KW - RNA, Messenger KW - Tissue Inhibitor of Metalloproteinases KW - Transcription Factor AP-1 KW - Tumor Suppressor Protein p53 KW - Matrix Metalloproteinases, Membrane-Associated KW - EC 3.4.24.- KW - Metalloendopeptidases KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Tumor Suppressor Protein p53 -- physiology KW - Transcription Factor AP-1 -- antagonists & inhibitors KW - Transcriptional Activation -- drug effects KW - Mice KW - NF-kappa B -- physiology KW - Transcription Factor AP-1 -- physiology KW - Glycoproteins -- pharmacology KW - RNA, Messenger -- metabolism KW - Transfection KW - Metalloendopeptidases -- biosynthesis KW - Metalloendopeptidases -- metabolism KW - Cell Line KW - NF-kappa B -- antagonists & inhibitors KW - Carcinogens -- pharmacology KW - Proto-Oncogene Proteins c-jun -- physiology KW - Keratinocytes -- drug effects KW - Anticarcinogenic Agents -- pharmacology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Proto-Oncogene Proteins c-jun -- genetics KW - Keratinocytes -- cytology KW - Cell Transformation, Neoplastic -- drug effects KW - Keratinocytes -- metabolism KW - Mutation KW - Tetradecanoylphorbol Acetate -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79187780?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+dominant+negative+mutant+of+jun+blocking+12-O-tetradecanoylphorbol-13-acetate-induced+invasion+in+mouse+keratinocytes.&rft.au=Dong%2C+Z%3BCrawford%2C+H+C%3BLavrovsky%2C+V%3BTaub%2C+D%3BWatts%2C+R%3BMatrisian%2C+L+M%3BColburn%2C+N+H&rft.aulast=Dong&rft.aufirst=Z&rft.date=1997-07-01&rft.volume=19&rft.issue=3&rft.spage=204&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 - 1997-08-29 N1 - Date created - 1997-08-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Heterocyclic amines, cytochrome P4501A2, and N-acetyltransferase: issues involved in incorporating putative genetic susceptibility markers into epidemiological studies. AN - 79174960; 9250630 AB - Heterocyclic amines (HCAs), which are found mainly in well-cooked meat, require metabolic activation to function as mutagens and animal carcinogens. Enzymes such as cytochrome P4501A2 (CYP1A2) and N-acetyltransferase (NAT2) perform this task and are subject to interindividual variation. The source of this variation may be genetic, as in the case of NAT2, or both genetic and environmental as with CYP1A2. The present study examined the effect of HCAs on the NAT2 and CYP1A2 phenotypes in 33 males and 33 females. The subjects consumed a low HCA-containing diet for 1 week followed by a high HCA diet for the subsequent week. The subjects were phenotyped for CYP1A2 and NAT2 at the time of entry into the study (free-living), 1 week later (end of low-HCA or low-induction diet) and 2 weeks later (end of high-HCA or high-induction diet). Consistent with genetic sources of variability, NAT2 showed little effect of a high-HCA diet and exhibited high intraindividual correlation. CYP1A2, in contrast, was induced by a high-HCA diet and exhibited a more modest intraindividual correlation. Incorporating putative genetic susceptibility makers in population studies requires consideration of issues of induction and inhibition of metabolizing enzymes, and effects of covariates. JF - Annals of epidemiology AU - Sinha, R AU - Caporaso, N AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20892, USA. Y1 - 1997/07// PY - 1997 DA - July 1997 SP - 350 EP - 356 VL - 7 IS - 5 SN - 1047-2797, 1047-2797 KW - Amines KW - 0 KW - Heterocyclic Compounds KW - Mutagens KW - Cytochrome P-450 CYP1A2 KW - EC 1.14.14.1 KW - Arylamine N-Acetyltransferase KW - EC 2.3.1.5 KW - Index Medicus KW - Phenotype KW - Genotype KW - Genetic Variation KW - Polymorphism, Genetic KW - Humans KW - Normal Distribution KW - Enzyme Induction KW - Male KW - Female KW - Heterocyclic Compounds -- metabolism KW - Disease Susceptibility KW - Cytochrome P-450 CYP1A2 -- genetics KW - Epidemiologic Methods KW - Mutagens -- metabolism KW - Amines -- metabolism KW - Diet KW - Arylamine N-Acetyltransferase -- biosynthesis KW - Cytochrome P-450 CYP1A2 -- biosynthesis KW - Arylamine N-Acetyltransferase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79174960?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+epidemiology&rft.atitle=Heterocyclic+amines%2C+cytochrome+P4501A2%2C+and+N-acetyltransferase%3A+issues+involved+in+incorporating+putative+genetic+susceptibility+markers+into+epidemiological+studies.&rft.au=Sinha%2C+R%3BCaporaso%2C+N&rft.aulast=Sinha&rft.aufirst=R&rft.date=1997-07-01&rft.volume=7&rft.issue=5&rft.spage=350&rft.isbn=&rft.btitle=&rft.title=Annals+of+epidemiology&rft.issn=10472797&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-09 N1 - Date created - 1997-10-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A case-control study of cytochrome P450 1A1, glutathione S-transferase M1, cigarette smoking and lung cancer susceptibility (Massachusetts, United States) AN - 79156028; 9242469 AB - Cytochrome P450 1A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) genetic polymorphisms are involved in the activation and detoxification of chemical carcinogens found in tobacco smoke; thus they may influence host susceptibility to lung cancer. In this study at Massachusetts General Hospital (Boston, MA, USA) of 416 cases and 446 controls (mostly White) we evaluated the association between the CYP1A1 MspI and GSTM1 polymorphisms and lung cancer risk, and their interaction with cigarette smoke. The CYP1A1 MspI heterozygous genotype was present in 18 percent of cases and 16 percent of controls, and one percent of cases and controls were CYP1A1 MspI homozygous variant. The GSTM1 null genotype was detected in 54 percent of cases and 52 percent of controls. After adjusting for age, gender, pack-years of smoking, and years since quitting smoking, while neither the CYP1A1 MspI heterozygous genotype alone nor the GSTM1 null genotype alone were associated with a significant increase in lung cancer risk, having both genetic traits was associated with a twofold increase in risk (95 percent confidence interval [CI] = 1.0-3.4). Our data did not provide enough evidence for a substantial modification of the effect of pack-years on lung cancer risk by the CYP1A1 MspI and GSTM1 genotypes. However, limitations of our study preclude a conclusion about this potential interaction. JF - Cancer causes & control : CCC AU - Garcia-Closas, M AU - Kelsey, K T AU - Wiencke, J K AU - Xu, X AU - Wain, J C AU - Christiani, D C AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. Y1 - 1997/07// PY - 1997 DA - July 1997 SP - 544 EP - 553 VL - 8 IS - 4 SN - 0957-5243, 0957-5243 KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Homozygote KW - Humans KW - Aged KW - Genotype KW - Heterozygote Detection KW - Aged, 80 and over KW - Risk Factors KW - Adult KW - Case-Control Studies KW - Middle Aged KW - Genetic Predisposition to Disease KW - Female KW - Male KW - Lung Neoplasms -- enzymology KW - Lung Neoplasms -- etiology KW - Cytochrome P-450 CYP1A1 -- genetics KW - Polymorphism, Genetic -- genetics KW - Smoking -- adverse effects KW - Glutathione Transferase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79156028?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+mutational+analysis+of+residues+essential+for+ligand+recognition+at+the+human+P2Y1+receptor.&rft.au=Jiang%2C+Q%3BGuo%2C+D%3BLee%2C+B+X%3BVan+Rhee%2C+A+M%3BKim%2C+Y+C%3BNicholas%2C+R+A%3BSchachter%2C+J+B%3BHarden%2C+T+K%3BJacobson%2C+K+A&rft.aulast=Jiang&rft.aufirst=Q&rft.date=1997-09-01&rft.volume=52&rft.issue=3&rft.spage=499&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 - 1997-09-18 N1 - Date created - 1997-09-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Cancer Causes Control 1998 Jan;9(1):126 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vitamin A and birth defects. AN - 79150495; 9240579 AB - Our objective was to determine whether moderate doses of vitamin A are teratogenic. This was a geographically based case-control study. Women whose pregnancies produced offspring with neural tube defects (n = 548) or major malformations other than neural tube defects (n = 387) and normal control subjects (n = 573) were interviewed to determine periconceptional vitamin A supplement exposure levels. The proportion of women consuming doses of vitamin A between 8000 and 25,000 IU was no greater in the major malformations group or the group with neural tube defects than in the normal control group. For exposure from supplements and fortified cereals combined, women consuming >8000 and >10,000 IU daily had odds ratios for major malformations of 0.79 (95% confidence interval 0.40 to 1.53) and 0.73 (95% confidence interval 0.27 to 1.96), respectively, compared with women consuming 8000 and >10,000 IU, respectively, versus exposure to <5000 IU. This study found no association between periconceptional vitamin A exposure at doses >8000 IU or >10,000 IU per day and malformations in general, cranial neural crest defects, or neural tube defects. If vitamin A is a teratogen, the minimum teratogenic dose appears to be well above the level consumed by most women during organogenesis. JF - American journal of obstetrics and gynecology AU - Mills, J L AU - Simpson, J L AU - Cunningham, G C AU - Conley, M R AU - Rhoads, G G AD - National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/07// PY - 1997 DA - July 1997 SP - 31 EP - 36 VL - 177 IS - 1 SN - 0002-9378, 0002-9378 KW - Vitamin A KW - 11103-57-4 KW - Abridged Index Medicus KW - Index Medicus KW - Dose-Response Relationship, Drug KW - Humans KW - Food, Fortified KW - Adult KW - Infant, Newborn KW - Case-Control Studies KW - Incidence KW - Female KW - Pregnancy Outcome KW - Pregnancy KW - Vitamin A -- adverse effects KW - Vitamin A -- administration & dosage KW - Neural Crest -- abnormalities KW - Congenital Abnormalities -- epidemiology KW - Neural Tube Defects -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79150495?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+obstetrics+and+gynecology&rft.atitle=Vitamin+A+and+birth+defects.&rft.au=Mills%2C+J+L%3BSimpson%2C+J+L%3BCunningham%2C+G+C%3BConley%2C+M+R%3BRhoads%2C+G+G&rft.aulast=Mills&rft.aufirst=J&rft.date=1997-07-01&rft.volume=177&rft.issue=1&rft.spage=31&rft.isbn=&rft.btitle=&rft.title=American+journal+of+obstetrics+and+gynecology&rft.issn=00029378&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-19 N1 - Date created - 1997-08-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antitumor activity of a monoclonal antibody directed against gastrin-releasing peptide in patients with small cell lung cancer. AN - 79144556; 9228385 AB - Small cell lung cancer (SCLC) cells express and secrete gastrin-releasing peptide (GRP) which binds to receptors and stimulates growth of these cells. A murine monoclonal antibody, 2A11, which binds GRP with high affinity, decreased growth of SCLC cells in vitro and in athymic nude mice. A phase 1 trial and pharmacokinetic modeling in patients with lung cancer has defined the phase 2 dose of 2A11 but the antitumor activity in patients is unknown. Thirteen patients with previously treated SCLC received 2A11 at 250 mg/m2 over 1 h three times per week for 4 weeks. Serum GRP, urine GRP, serum levels of 2A11, and human antimouse antibodies (HAMA) were determined. One of 12 (8%; 95% confidence interval, 0 to 38%) evaluable patients had complete resolution of radiographically detectable tumor lasting 4 months. Four patients (33%) had stable disease. No toxic reactions were observed. The pretreatment serum GRP level of the responding patient was 3.1 fmol/mL and the median of nine nonresponding patients was 7.3 fmol/mL (range, <1.0 to 29.0). The mean trough serum 2A11 level was 49+/-18 microg/mL in the responding patient and 32 to 487 mg/mL (median, 117) in 10 nonresponding patients. HAMA did not increase during 2A11 administration in any patient. Interruption of the GRP autocrine growth factor loop with 2A11 results in clinical antitumor activity in a minority of patients with previously treated SCLC. Further evaluation of the antitumor effects of 2A11 is warranted to define characteristics associated with response to 2A11. JF - Chest AU - Kelley, M J AU - Linnoila, R I AU - Avis, I L AU - Georgiadis, M S AU - Cuttitta, F AU - Mulshine, J L AU - Johnson, B E AD - Navy Medical Oncology Branch, National Cancer Institute, Bethesda, Md 20889-5105, USA. mk4m@nih.gov Y1 - 1997/07// PY - 1997 DA - July 1997 SP - 256 EP - 261 VL - 112 IS - 1 SN - 0012-3692, 0012-3692 KW - Antibodies, Monoclonal KW - 0 KW - Peptides KW - Gastrin-Releasing Peptide KW - 80043-53-4 KW - Bombesin KW - PX9AZU7QPK KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Humans KW - Middle Aged KW - Mice, Nude KW - Mice KW - Male KW - Female KW - Carcinoma, Small Cell -- therapy KW - Bombesin -- immunology KW - Antibodies, Monoclonal -- pharmacokinetics KW - Peptides -- immunology KW - Lung Neoplasms -- therapy KW - Antibodies, Monoclonal -- administration & dosage KW - Antibodies, Monoclonal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79144556?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chest&rft.atitle=Antitumor+activity+of+a+monoclonal+antibody+directed+against+gastrin-releasing+peptide+in+patients+with+small+cell+lung+cancer.&rft.au=Kelley%2C+M+J%3BLinnoila%2C+R+I%3BAvis%2C+I+L%3BGeorgiadis%2C+M+S%3BCuttitta%2C+F%3BMulshine%2C+J+L%3BJohnson%2C+B+E&rft.aulast=Kelley&rft.aufirst=M&rft.date=1997-07-01&rft.volume=112&rft.issue=1&rft.spage=256&rft.isbn=&rft.btitle=&rft.title=Chest&rft.issn=00123692&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-12 N1 - Date created - 1997-08-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Calretinin-immunoreactive dopaminergic neurons from embryonic rat mesencephalon are resistant to levodopa-induced neurotoxicity. AN - 79142296; 9225735 AB - Levodopa, which is used in the treatment of Parkinson's disease, has known cytotoxic effects on dopaminergic neurons grown in culture. Calretinin (CR) is a cytosolic calcium-binding protein found in specific subpopulations of neurons as well as in some nonneuronal tissue. CR is expressed in 10% of rat embryo dopaminergic neurons grown in vitro. Since it has been postulated that CR provides neuroprotection due to its calcium-binding properties, we investigated whether CR-containing dopaminergic neurons were spared from levodopa toxicity. Incubation of mesencephalic cells with 10(-5) to 10(-7) M levodopa on Days 1-6 in vitro produced no significant effects on the number of dopaminergic neurons containing CR, but resulted in the loss of approximately 65% of the dopaminergic cells which did not contain CR. The remaining CR-negative dopaminergic neurons exhibited dose-dependent reductions in neurite length. The neuronal processes in CR-containing dopaminergic cells retained a smooth bipolar appearance. CR-immunoreactive cells which did not contain dopamine showed slight neurite length decreases at the highest drug concentrations but no changes in neuron number. These results indicate that CR may protect dopaminergic neurons from levodopa-induced toxicity. JF - Experimental neurology AU - Isaacs, K R AU - Wolpoe, M E AU - Jacobowitz, D M AD - NIMH, Laboratory of Clinical Science, NIH, Bethesda, Maryland 20892, USA. Y1 - 1997/07// PY - 1997 DA - July 1997 SP - 25 EP - 32 VL - 146 IS - 1 SN - 0014-4886, 0014-4886 KW - Calb2 protein, rat KW - 0 KW - Calbindin 2 KW - Nerve Tissue Proteins KW - Neurotoxins KW - S100 Calcium Binding Protein G KW - Levodopa KW - 46627O600J KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Stem Cells -- drug effects KW - Animals KW - Drug Resistance KW - Stem Cells -- physiology KW - Neurites -- physiology KW - Rats KW - Tyrosine 3-Monooxygenase -- analysis KW - Rats, Sprague-Dawley KW - Neurites -- ultrastructure KW - Stem Cells -- cytology KW - Cell Survival -- drug effects KW - Cells, Cultured KW - Neurites -- drug effects KW - Embryo, Mammalian KW - S100 Calcium Binding Protein G -- physiology KW - S100 Calcium Binding Protein G -- analysis KW - Nerve Tissue Proteins -- physiology KW - Levodopa -- toxicity KW - Neurons -- metabolism KW - Neurons -- drug effects KW - Neurons -- cytology KW - S100 Calcium Binding Protein G -- biosynthesis KW - Dopamine -- physiology KW - Mesencephalon -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79142296?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+neurology&rft.atitle=Calretinin-immunoreactive+dopaminergic+neurons+from+embryonic+rat+mesencephalon+are+resistant+to+levodopa-induced+neurotoxicity.&rft.au=Isaacs%2C+K+R%3BWolpoe%2C+M+E%3BJacobowitz%2C+D+M&rft.aulast=Isaacs&rft.aufirst=K&rft.date=1997-07-01&rft.volume=146&rft.issue=1&rft.spage=25&rft.isbn=&rft.btitle=&rft.title=Experimental+neurology&rft.issn=00144886&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-07 N1 - Date created - 1997-08-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A prospective randomized evaluation of the prophylactic use of low-dose dopamine in cancer patients receiving interleukin-2. AN - 79120875; 9220319 AB - The administration of high-dose interleukin-2 (IL-2) causes tumor regression in 17-25% of patients with metastatic melanoma or renal cell carcinoma. Renal dysfunction is a common dose-limiting toxicity of IL-2 administration, limiting 26% of treatment cycles. We have conducted a prospective randomized trial to evaluate whether the prophylactic administration of low-dose dopamine (2 mg/kg/min) can minimize renal toxicity and thus affect the amount of IL-2 administered. Forty-two patients were randomly assigned to receive systemic high-dose IL-2 with standard supportive measures (group A = 21 patients) or with the addition of prophylactic dopamine (group B = 21 patients) at 2 mg/kg/min. For patients in group B, dopamine was instituted 1 h before the initiation of IL-2 administration and was discontinued 6-12 h after the maximum number of doses of IL-2 were given. There was no difference in the amount of IL-2 administered for each course of therapy for groups A and B. Despite differences in urine flow (milliliters per kilogram per day), fluid balance (liters per day), and overall weight gain, prophylactic low-dose dopamine did not significantly alter maximum plasma urea or creatinine levels in group B when compared with the control group (group A). The overall toxicity profile considering all grade 3 and 4 toxicities for patients in groups A and B was comparable. Thus, there is no evidence to support the routine use of prophylactic low-dose dopamine in patients receiving high-dose IL-2. JF - Journal of immunotherapy (Hagerstown, Md. : 1997) AU - Cormier, J N AU - Hurst, R AU - Vasselli, J AU - Lee, D AU - Kim, C J AU - McKee, M AU - Venzon, D AU - White, D AU - Marincola, F M AU - Rosenberg, S A AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/07// PY - 1997 DA - July 1997 SP - 292 EP - 300 VL - 20 IS - 4 SN - 1524-9557, 1524-9557 KW - Interleukin-2 KW - 0 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Prospective Studies KW - Humans KW - Adult KW - Oliguria -- prevention & control KW - Aged KW - Middle Aged KW - Male KW - Female KW - Kidney Neoplasms -- therapy KW - Interleukin-2 -- adverse effects KW - Carcinoma, Renal Cell -- therapy KW - Kidney -- drug effects KW - Melanoma -- therapy KW - Dopamine -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79120875?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunotherapy+%28Hagerstown%2C+Md.+%3A+1997%29&rft.atitle=A+prospective+randomized+evaluation+of+the+prophylactic+use+of+low-dose+dopamine+in+cancer+patients+receiving+interleukin-2.&rft.au=Cormier%2C+J+N%3BHurst%2C+R%3BVasselli%2C+J%3BLee%2C+D%3BKim%2C+C+J%3BMcKee%2C+M%3BVenzon%2C+D%3BWhite%2C+D%3BMarincola%2C+F+M%3BRosenberg%2C+S+A&rft.aulast=Cormier&rft.aufirst=J&rft.date=1997-07-01&rft.volume=20&rft.issue=4&rft.spage=292&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunotherapy+%28Hagerstown%2C+Md.+%3A+1997%29&rft.issn=15249557&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-18 N1 - Date created - 1997-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulatory sequences for the transcription of the laminin B2 gene in astrocytes. AN - 79120405; 9221905 AB - Astrocytes synthesize only the B2 chain of laminin and that this chain is sufficient to stimulate neurite outgrowth. In this study, we have examined laminin B1 and B2 promoter constructs in various cell types in order to understand the transcriptional regulation of laminin B2 gene in astrocytes. Comparison of nuclear factor binding by Southwestern analysis with the highly active B2 promoter fragment revealed different patterns of nuclear factor binding. In HepG2 cells, two proteins of 105 and 98 kDa were identified while, in primary astrocytes, human U251 and rat C6 glioma cells, a greater number of nuclear proteins ranging from 43 to 212 kDa were detected. The laminin B1 promoter construct was inactive in transient transfection experiments in astrocytes yet active in the HepG2 hepatoma cells which synthesize both the B1 and B2 chains. In contrast, the laminin B2 promoter construct was active in both astrocytes and HepG2 cells. These results are consistent with the lack of laminin B1 mRNA expression in astrocytes and suggest that the differential regulation of the laminin B1 and B2 gene is controlled at the transcriptional level. Delineation of the 5'-flanking regions responsible for basal levels of B2 laminin promoter activity revealed a silencer-like segment between -830 and -224 which reduced promoter activity. Deletion analysis further revealed that B2 laminin promoter possesses a highly active short promoter (-94 to +106) and basal transcriptional activity resides within -61 to +106. DNase 1 footprinting, gel-shift competition assays and site-directed mutagenesis of a highly active short promoter revealed that this region contained binding sites for cell-type nuclear factors. The shortest construct containing only residues -21 to +106 was inactive in HepG2 and U251 glioma cells. In primary astrocytes, however, this construct showed a high level of transcriptional activity. Deletion of 47 bp (+59 to +106) in 5'-UTR completely blocked promoter activity in astrocytes confirming that this downstream region is important for transcriptional activity in primary astrocytes. Together, these results suggest that astrocytes may utilize mutually exclusive transcription factors and regulatory sequences, in addition to common factors in the control of the laminin B2 promoter. JF - Brain research. Molecular brain research AU - Kedar, V AU - Freese, E AU - Hempel, F G AD - Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. vishramk@qimr.edu.au Y1 - 1997/07// PY - 1997 DA - July 1997 SP - 87 EP - 98 VL - 47 IS - 1-2 SN - 0169-328X, 0169-328X KW - Laminin KW - 0 KW - Transcription Factors KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Base Sequence KW - Cells, Cultured KW - Molecular Sequence Data KW - Promoter Regions, Genetic -- genetics KW - Laminin -- genetics KW - Transcription Factors -- genetics KW - Astrocytes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79120405?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Regulatory+sequences+for+the+transcription+of+the+laminin+B2+gene+in+astrocytes.&rft.au=Kedar%2C+V%3BFreese%2C+E%3BHempel%2C+F+G&rft.aulast=Kedar&rft.aufirst=V&rft.date=1997-07-01&rft.volume=47&rft.issue=1-2&rft.spage=87&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 - 1997-09-17 N1 - Date created - 1997-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Barriers to alcoholism treatment: reasons for not seeking treatment in a general population sample. AN - 79112545; 9203117 AB - The present study reports responses to numerous direct questions related to reasons for not seeking alcoholism treatment given the perceived need for treatment among respondents classified with an alcohol use disorder (N = 964, 69.8% male, 93.5% nonblack) in a larger representative sample of the United States population. Data were derived from the 1992 National Longitudinal Alcohol Epidemiologic Survey, a national probability sample of 42,862 respondents, aged 18 years and older, from the noninstitutionalized population of the contiguous states. Lack of confidence in the alcoholism treatment system and its effectiveness, stigmatization and denial were identified as significant barriers to alcoholism treatment at the aggregate level. In general, enabling factors such as lack of financial resources or facilities for child care were much less important barriers to care than were individual predisposing factors including attitudes towards alcoholism treatment. Important sociodemographic differences in identified barriers to care are discussed in terms of their minimization through proposed changes in education, screening, outreach, detection, and referral patterns in alcoholism treatment delivery systems. JF - Journal of studies on alcohol AU - Grant, B F AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892-7003, USA. Y1 - 1997/07// PY - 1997 DA - July 1997 SP - 365 EP - 371 VL - 58 IS - 4 SN - 0096-882X, 0096-882X KW - Index Medicus KW - Attitude to Health KW - Denial (Psychology) KW - Humans KW - Adult KW - Treatment Outcome KW - Aged KW - Middle Aged KW - Longitudinal Studies KW - Adolescent KW - United States -- epidemiology KW - Male KW - Female KW - Alcoholism -- rehabilitation KW - Motivation KW - Alcoholism -- epidemiology KW - Patient Acceptance of Health Care KW - Alcoholism -- psychology KW - Health Services Accessibility -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79112545?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+studies+on+alcohol&rft.atitle=Barriers+to+alcoholism+treatment%3A+reasons+for+not+seeking+treatment+in+a+general+population+sample.&rft.au=Grant%2C+B+F&rft.aulast=Grant&rft.aufirst=B&rft.date=1997-07-01&rft.volume=58&rft.issue=4&rft.spage=365&rft.isbn=&rft.btitle=&rft.title=Journal+of+studies+on+alcohol&rft.issn=0096882X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-12 N1 - Date created - 1997-08-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sonodynamic toxicity of gallium-porphyrin analogue ATX-70 in human leukemia cells. AN - 79107946; 9216617 AB - Low concentrations (> or = 1 microM) of the gallium-porphyrin analogue ATX-70 significantly enhanced cellular toxicity in human leukemia HL-525 cells exposed to 50 kHz ultrasound. The mechanism of this ATX-70-dependent sonosensitization is unknown, but we have established the requirement of extracellular localization of ATX-70 molecules for sonosensitization. Short-lived toxic intermediates produced from ATX-70 by ultrasound are implicated in the mechanism, since no cytotoxicity was found when medium containing ATX-70 was sonicated and subsequently added to the cells. However, we were unable to demonstrate the existence of radical intermediates by EPR spin trapping with the nitroso spin trap, DBNBS, and ATX-70-dependent sonotoxicity could not be ameliorated by the addition of up to 70 mM POBN and DMPO spin traps during ultrasound exposure. JF - Radiation research AU - Miyoshi, N AU - Misík, V AU - Riesz, P AD - Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/07// PY - 1997 DA - July 1997 SP - 43 EP - 47 VL - 148 IS - 1 SN - 0033-7587, 0033-7587 KW - Free Radicals KW - 0 KW - Porphyrins KW - ATX 70 KW - 135099-39-7 KW - Nitrogen KW - N762921K75 KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Space life sciences KW - Leukemia -- therapy KW - Tumor Cells, Cultured KW - Combined Modality Therapy KW - Oxygen -- pharmacology KW - Humans KW - Electron Spin Resonance Spectroscopy KW - Cell Death KW - Temperature KW - Nitrogen -- pharmacology KW - Porphyrins -- toxicity KW - Porphyrins -- chemistry KW - Ultrasonic Therapy -- methods KW - Porphyrins -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79107946?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Sonodynamic+toxicity+of+gallium-porphyrin+analogue+ATX-70+in+human+leukemia+cells.&rft.au=Miyoshi%2C+N%3BMis%C3%ADk%2C+V%3BRiesz%2C+P&rft.aulast=Miyoshi&rft.aufirst=N&rft.date=1997-07-01&rft.volume=148&rft.issue=1&rft.spage=43&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 - 1997-08-01 N1 - Date created - 1997-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A novel calcium-activated apamin-insensitive potassium current in pituitary gonadotrophs. AN - 79104227; 9202201 AB - In cultured rat pituitary gonadotrophs, GnRH-induced oscillations in cytosolic calcium concentration ([Ca2+]i) are associated with periodic membrane hyperpolarization. The hyperpolarizing waves are secondary to the activation of apamin-sensitive Ca2+-activated K+ channels that account for a single class of 125I-apamin binding sites present in these cells. In a substantial fraction of gonadotrophs, however, we observed a Ca2+-controlled oscillatory current that was resistant to apamin, even at concentrations five orders of magnitude higher than the dissociation constant (Kd) observed in the binding experiments. With the K+ in the pipette, the apamin-resistant current showed a reversal potential of -42 mV, nearly 40 mV more positive than that of the apamin-sensitive current. With Cs+ in place of K+ in the pipette solution, both the size of the apamin-insensitive current and its reversal potential remained unchanged. Ion substitution studies further revealed that the reversal potential was independent of Cl-. In contrast, an 11 mV hyperpolarizing shift in the reversal potential occurred when extracellular Na+ was reduced to 80 mM. In cells expressing apamin-resistant conductances, addition of apamin evoked a marked increase in the duration of the action potentials and reduction in the frequency of spontaneous spiking. In the presence of GnRH, gonadotrophs exhibit the typical burst pattern of electrical activity. Further exposure of the cells to apamin depolarized the membrane from a silent phase bursting level of about -80 mV to a new level of about -40 mV. These observations indicate that, in addition to apamin-sensitive current, a subpopulation of pituitary gonadotrophs also expresses a cationic component of the Ca2+-activated membrane conductance that has the potential to remodulate spontaneous and agonist-induced electrical activity. JF - Endocrinology AU - Vergara, L AU - Rojas, E AU - Stojilkovic, S S AD - Laboratory of Cell Biology and Biochemistry, National Institute of Diabetes and Digestive and Kidney Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/07// PY - 1997 DA - July 1997 SP - 2658 EP - 2664 VL - 138 IS - 7 SN - 0013-7227, 0013-7227 KW - Neurotoxins KW - 0 KW - Potassium Channels KW - Apamin KW - 24345-16-2 KW - Gonadotropin-Releasing Hormone KW - 33515-09-2 KW - Calcium KW - SY7Q814VUP KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Binding, Competitive KW - Ovariectomy KW - Membrane Potentials -- drug effects KW - Gonadotropin-Releasing Hormone -- pharmacology KW - Female KW - Calcium -- metabolism KW - Potassium Channels -- metabolism KW - Pituitary Gland, Anterior -- physiology KW - Neurotoxins -- pharmacology KW - Apamin -- pharmacology KW - Potassium Channels -- drug effects KW - Pituitary Gland, Anterior -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79104227?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+novel+calcium-activated+apamin-insensitive+potassium+current+in+pituitary+gonadotrophs.&rft.au=Vergara%2C+L%3BRojas%2C+E%3BStojilkovic%2C+S+S&rft.aulast=Vergara&rft.aufirst=L&rft.date=1997-07-01&rft.volume=138&rft.issue=7&rft.spage=2658&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-24 N1 - Date created - 1997-07-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant toxins containing human granulocyte-macrophage colony-stimulating factor and either pseudomonas exotoxin or diphtheria toxin kill gastrointestinal cancer and leukemia cells. AN - 79100393; 9207460 AB - The granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR) is a potential target for toxin-directed therapy, because it is overexpressed on many leukemias and solid tumors and apparently not on stem cells. To investigate the potential therapeutic use of GM-CSF toxins, we fused human GM-CSF to truncated forms of either Pseudomonas exotoxin (PE) or diphtheria toxin (DT) and tested the cytotoxicity of the resulting GM-CSF-PE38KDEL and DT388-GM-CSF on human gastrointestinal (GI) carcinomas and leukemias. Toward gastric and colon cancer cell lines, GM-CSF-PE38KDEL was much more cytotoxic than DT388-GM-CSF, with IC50s (concentration resulting in 50% inhibition of protein synthesis) of 0.5 to 10 ng/mL compared with 4 to 400 ng/mL, respectively. In contrast, toward leukemia lines and fresh bone marrow cells DT388-GM-CSF was more cytotoxic than GM-CSF-PE38KDEL. The cytotoxicity of both GM-CSF-PE38KDEL and DT388-GM-CSF toward the human cells was specific, because it could be competed by an excess of GM-CSF. Binding studies indicated that human GM-CSF receptors were present on all of the human GI and leukemic cell lines tested, at levels of 540 to 3,700 sites per cell (kd = 0.2 to 2 nmol/L), and the number of sites per cell did not correlate with the cell type. A similar pattern of cytotoxicity was found with recombinant immunotoxins binding to the transferrin receptor, in that anti-TFR(Fv)-PE38KDEL was much more cytotoxic than DT388-anti-TFR(Fv) toward GI cells, but both were similar in their cytotoxic activity toward leukemia cells. The fact that PE is more effective than DT in killing GI but not leukemic tumor cells targeted by GM-CSF indicates a fundamental difference in the way PE or DT gains access to the cytosol in these cells. GM-CSF-PE38KDEL and DT388-GM-CSF deserve further evaluation as possible treatments for selected tumors. JF - Blood AU - Kreitman, R J AU - Pastan, I AD - Division of Cancer Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/07/01/ PY - 1997 DA - 1997 Jul 01 SP - 252 EP - 259 VL - 90 IS - 1 SN - 0006-4971, 0006-4971 KW - Diphtheria Toxin KW - 0 KW - Exotoxins KW - Recombinant Fusion Proteins KW - Recombinant Proteins KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Abridged Index Medicus KW - Index Medicus KW - Recombinant Proteins -- toxicity KW - Tumor Cells, Cultured KW - Humans KW - Pseudomonas KW - Cell Death -- drug effects KW - Leukemia -- pathology KW - Leukemia -- drug therapy KW - Granulocyte-Macrophage Colony-Stimulating Factor -- toxicity KW - Diphtheria Toxin -- toxicity KW - Exotoxins -- toxicity KW - Gastrointestinal Neoplasms -- drug therapy KW - Recombinant Fusion Proteins -- toxicity KW - Gastrointestinal Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79100393?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Recombinant+toxins+containing+human+granulocyte-macrophage+colony-stimulating+factor+and+either+pseudomonas+exotoxin+or+diphtheria+toxin+kill+gastrointestinal+cancer+and+leukemia+cells.&rft.au=Kreitman%2C+R+J%3BPastan%2C+I&rft.aulast=Kreitman&rft.aufirst=R&rft.date=1997-07-01&rft.volume=90&rft.issue=1&rft.spage=252&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-22 N1 - Date created - 1997-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gender differences in DSM-IV alcohol use disorders and major depression as distributed in the general population: clinical implications. AN - 79099001; 9202877 AB - This study examined gender differences within and between five groups of subjects drawn from a large representative sample of the United States population and classified as having either major depression (MDD) only, alcohol use disorder (AUD) only, or primary, secondary, or concurrent depression to determine if these diagnostic profiles (1) were consistent with those drawn on clinical samples and (2) might suggest potential clinical implications. Respondents (N = 9,985) from a nationally representative survey of the United States population met DSM-IV criteria for classification into these five mutually exclusive groups that were compared within and between groups by gender on the characteristics of each disorder. The results were consistent with those of other studies: (1) gender distributions of AUD and depressive disorder remain almost mirror opposites, and (2) comorbid disorders are more severe than either of the conditions appearing singly. Findings of particular interest were that the synergistic effects of an alcohol and a depressive condition operate equally for both men and women with concurrent depression. This points to the necessity of attending carefully to gender biases when dealing with comorbid conditions, last we fail to take alcoholism in the presence of depression seriously enough in women and vice versa in men. Additionally, women with primary depression are at high risk for suicide and thus may require special attention in the evaluative phase of treatment. JF - Comprehensive psychiatry AU - Hanna, E Z AU - Grant, B F AD - National Institute on Alcohol Abuse and Alcoholism, Division of Biometry and Epidemiology, Bethesda, MD 20892-7003, USA. PY - 1997 SP - 202 EP - 212 VL - 38 IS - 4 SN - 0010-440X, 0010-440X KW - Index Medicus KW - Causality KW - Age Factors KW - Analysis of Variance KW - Sex Factors KW - Chi-Square Distribution KW - Humans KW - Diagnosis, Dual (Psychiatry) -- classification KW - Longitudinal Studies KW - Comorbidity KW - Socioeconomic Factors KW - Cross-Sectional Studies KW - Adult KW - Health Surveys KW - Sampling Studies KW - Adolescent KW - United States -- epidemiology KW - Male KW - Female KW - Substance-Related Disorders -- epidemiology KW - Depressive Disorder -- epidemiology KW - Alcoholism -- epidemiology KW - Alcoholism -- classification KW - Depressive Disorder -- physiopathology KW - Alcoholism -- physiopathology KW - Depressive Disorder -- classification KW - Alcoholism -- complications KW - Depressive Disorder -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79099001?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Comprehensive+psychiatry&rft.atitle=Gender+differences+in+DSM-IV+alcohol+use+disorders+and+major+depression+as+distributed+in+the+general+population%3A+clinical+implications.&rft.au=Hanna%2C+E+Z%3BGrant%2C+B+F&rft.aulast=Hanna&rft.aufirst=E&rft.date=1997-07-01&rft.volume=38&rft.issue=4&rft.spage=202&rft.isbn=&rft.btitle=&rft.title=Comprehensive+psychiatry&rft.issn=0010440X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-20 N1 - Date created - 1997-08-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Indomethacin is a potent inhibitor of pristane and plastic disc induced plasmacytomagenesis in a hypersusceptible BALB/c congenic strain. AN - 79098264; 9207461 AB - Continuous indomethacin (INDO) administration in the drinking water (10 to 20 microg/mL) profoundly inhibited plasmacytoma (PCT) development initiated by three 0.2- or 0.5-mL intraperitoneal (i.p.) injections of pristane in hypersusceptible BALB/c.DBA/2-Idh1-Pep3 congenic mice. The most effective inhibitions were obtained with continuous INDO treatment. When treatment was delayed until 50 to 60 days after the first pristane injection, there was approximately a 50% reduction in PCT incidence. The primary action of pristane is the induction of a chronic inflammation in the peritoneal connective tissues and the formation of a microenvironment where PCTs develop. INDO, a powerful inhibitor of prostaglandin synthases (cyclooxygenases 1 and 2), did not inhibit the formation of mesenteric oil granuloma nor the appearance of cells in this chronic inflammatory tissue carrying c-myc illegitimately joined to an Ig heavy chain switch region, ie, the t(12;15) chromosomal translocation. INDO inhibited PCT induction by the i.p. implantation of 21 x 2 mm polycarbonate discs. These solid objects predominantly induce the formation of a patchy fibroplastic tissue on contacting peritoneal surfaces. These and previous data indicate that indomethacin inhibits an intermediate stage in PCT development after the arrival of cells bearing the T(12;15) translocation in the oil granuloma and before these cells acquire transplantability to a pristane-conditioned host. The biological mechanism that explains how INDO inhibits PCT development is not yet established but appears to result from decreased production of prostaglandins in chronic inflammatory tissues (oil granuloma, fibroplasia), suggesting that prostaglandins play an active role in oil and solid plastic induced PCT formation. JF - Blood AU - Potter, M AU - Wax, J AU - Jones, G M AD - Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1997/07/01/ PY - 1997 DA - 1997 Jul 01 SP - 260 EP - 269 VL - 90 IS - 1 SN - 0006-4971, 0006-4971 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Carcinogens KW - Terpenes KW - pristane KW - 26HZV48DT1 KW - Indomethacin KW - XXE1CET956 KW - Abridged Index Medicus KW - Index Medicus KW - Administration, Oral KW - Animals KW - Mice KW - Genetic Predisposition to Disease KW - Foreign Bodies KW - Mice, Inbred BALB C KW - Drug Antagonism KW - Plasmacytoma -- prevention & control KW - Plasmacytoma -- genetics KW - Plasmacytoma -- chemically induced KW - Terpenes -- antagonists & inhibitors KW - Anti-Inflammatory Agents, Non-Steroidal -- administration & dosage KW - Indomethacin -- administration & dosage KW - Carcinogens -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79098264?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Indomethacin+is+a+potent+inhibitor+of+pristane+and+plastic+disc+induced+plasmacytomagenesis+in+a+hypersusceptible+BALB%2Fc+congenic+strain.&rft.au=Potter%2C+M%3BWax%2C+J%3BJones%2C+G+M&rft.aulast=Potter&rft.aufirst=M&rft.date=1997-07-01&rft.volume=90&rft.issue=1&rft.spage=260&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-22 N1 - Date created - 1997-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Endothelial apoptosis in Braf-deficient mice. AN - 79096147; 9207797 AB - Tyrosine kinase growth factor receptors and Ras/Raf/MEK/MAPK signalling have been implicated in the suppression as well as augmentation of programmed cell death. In addition, a Ras-independent role for Raf as a suppressor of programmed cell death has been suggested by the recent finding that Craf1 interacts with members of the Bcl-2 family at mitochondrial membranes. However, genetic studies of C. elegans and Drosophila, as well as the targeted mutagenesis of the murine Araf gene, have failed to support such a role. Here we show that mice with a targeted disruption in the Braf gene die of vascular defects during mid-gestation. Braf -/- embryos, unlike Araf -/- or Craf1 -/- embryos (L.W. et al., unpublished), show an increased number of endothelial precursor cells, dramatically enlarged blood vessels and apoptotic death of differentiated endothelial cells. These results establish Braf as a critical signalling factor in the formation of the vascular system and provide the first genetic evidence for an essential role of Raf gene in the regulation of programmed cell death. JF - Nature genetics AU - Wojnowski, L AU - Zimmer, A M AU - Beck, T W AU - Hahn, H AU - Bernal, R AU - Rapp, U R AU - Zimmer, A AD - Section on Genetics, National Institute of Mental Health/National Human Genome Research Institute, Bethesda, Maryland 20892, USA. Y1 - 1997/07// PY - 1997 DA - July 1997 SP - 293 EP - 297 VL - 16 IS - 3 SN - 1061-4036, 1061-4036 KW - Proto-Oncogene Proteins KW - 0 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Proto-Oncogene Proteins c-raf KW - Index Medicus KW - Animals KW - Blotting, Northern KW - Homozygote KW - Cell Differentiation KW - Mice KW - Histocytochemistry KW - Mice, Transgenic KW - Genotype KW - In Situ Hybridization KW - Stem Cells -- cytology KW - Blotting, Southern KW - Heterozygote KW - Embryo, Mammalian -- cytology KW - Gene Targeting KW - Signal Transduction KW - Gene Expression Regulation, Developmental KW - Apoptosis KW - Endothelium, Vascular -- cytology KW - Protein-Serine-Threonine Kinases -- deficiency KW - Endothelium, Vascular -- embryology KW - Proto-Oncogene Proteins -- deficiency KW - Protein-Serine-Threonine Kinases -- genetics KW - Proto-Oncogene Proteins -- genetics KW - Proto-Oncogene Proteins -- physiology KW - Protein-Serine-Threonine Kinases -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79096147?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Endothelial+apoptosis+in+Braf-deficient+mice.&rft.au=Wojnowski%2C+L%3BZimmer%2C+A+M%3BBeck%2C+T+W%3BHahn%2C+H%3BBernal%2C+R%3BRapp%2C+U+R%3BZimmer%2C+A&rft.aulast=Wojnowski&rft.aufirst=L&rft.date=1997-07-01&rft.volume=16&rft.issue=3&rft.spage=293&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 - 1997-07-29 N1 - Date created - 1997-07-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Nat Genet. 1997 Jul;16(3):214-5 [9207779] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Insulin-like growth factor 1 (IGF-1) alters drug sensitivity of HBL100 human breast cancer cells by inhibition of apoptosis induced by diverse anticancer drugs. AN - 79093466; 9205078 AB - In this study, we tested the hypothesis that insulin-like growth factor-1 (IGF-1) modulates apoptosis in human breast cancer cells, HBL100, induced by diverse chemotherapeutic drugs. IGF-1 increased cell survival of HBL100 cells treated with 5-fluorouracil (antimetabolite), methotrexate (antimetabolite), tamoxifen (antiestrogen/antiproliferative), or camptothecin (topoisomerase 1 inhibitor) and after serum withdrawal. Elevated cell survival was not due to an increase in cell proliferation by IGF-1, but rather to an inhibition of apoptosis. Evidence for death by apoptosis was supported by cellular morphology and DNA fragmentation. There were no changes observed in Bcl-2 protein or bax mRNA levels. Extracellular matrix (ECM) is known to influence the apoptotic response of cells; therefore, the antiapoptotic effect of IGF-1 on breast cancer cells was examined using different ECMs: laminin, collagen IV, or Matrigel. IGF-1 protected cells from apoptosis induced by methotrexate on all ECMs tested, providing the first evidence that IGF-1 protects against apoptosis in three-dimensional culture systems. These data provide the rationale to search for drugs that lower serum IGF-1 in an effort to improve the efficacy of chemotherapeutic drugs for the treatment of breast cancer. JF - Cancer research AU - Dunn, S E AU - Hardman, R A AU - Kari, F W AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/07/01/ PY - 1997 DA - 1997 Jul 01 SP - 2687 EP - 2693 VL - 57 IS - 13 SN - 0008-5472, 0008-5472 KW - Antineoplastic Agents KW - 0 KW - BAX protein, human KW - Drug Combinations KW - Laminin KW - Proteoglycans KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - bcl-2-Associated X Protein KW - Tamoxifen KW - 094ZI81Y45 KW - matrigel KW - 119978-18-6 KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Collagen KW - 9007-34-5 KW - Fluorouracil KW - U3P01618RT KW - Camptothecin KW - XT3Z54Z28A KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Tamoxifen -- pharmacology KW - Methotrexate -- pharmacology KW - Blotting, Northern KW - Extracellular Matrix -- physiology KW - Camptothecin -- pharmacology KW - Humans KW - Proto-Oncogene Proteins -- metabolism KW - Proteoglycans -- physiology KW - Blotting, Western KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Laminin -- physiology KW - Proto-Oncogene Proteins c-bcl-2 -- metabolism KW - Fluorouracil -- pharmacology KW - Microscopy, Electron KW - Time Factors KW - Collagen -- physiology KW - Female KW - Breast Neoplasms -- drug therapy KW - Apoptosis -- drug effects KW - Insulin-Like Growth Factor I -- pharmacology KW - Breast Neoplasms -- ultrastructure KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79093466?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Insulin-like+growth+factor+1+%28IGF-1%29+alters+drug+sensitivity+of+HBL100+human+breast+cancer+cells+by+inhibition+of+apoptosis+induced+by+diverse+anticancer+drugs.&rft.au=Dunn%2C+S+E%3BHardman%2C+R+A%3BKari%2C+F+W%3BBarrett%2C+J+C&rft.aulast=Dunn&rft.aufirst=S&rft.date=1997-07-01&rft.volume=57&rft.issue=13&rft.spage=2687&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-25 N1 - Date created - 1997-07-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of human immunodeficiency virus and colony-stimulating factors on the production of interleukin 6 and tumor necrosis factor alpha by monocyte/macrophages. AN - 79090622; 9197377 AB - Patients infected with human immunodeficiency virus (HIV) frequently have increased production of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), and these cytokines may in turn contribute to the disease pathogenesis. It has been hypothesized that secretion of these cytokines by HIV-exposed mononuclear cells or HIV-infected monocyte/macrophages (M/Ms) is the principal source of their overproduction in HIV-infected patients, and the present study was undertaken to explore this issue. We observed that in the absence of endotoxin or cytokines, M/Ms productively infected by HIV do not produce detectable IL-6 or TNF-alpha. However, granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine that enhances HIV replication in M/Ms and is frequently used to propagate monocytotropic strains of HIV, can induce the relatively long-term production of IL-6 (up to 47 U/ml) and TNF-alpha (up to 47 pg/ml) by M/Ms, even in the absence of HIV. Also, HIV induced production of a relatively small (< or = 9 U/ml) quantity of IL-6 in M/Ms stimulated with macrophage-colony stimulating factor (M-CSF). Finally, while highly concentrated HIV induced production of both cytokines by either M/Ms or peripheral blood mononuclear cells (PBMCs), this production was almost completely eliminated when care was taken to avoid contamination of HIV by endotoxin. These data suggest that the excess IL-6 and TNF-alpha in HIV-infected patients does not simply result from their production by HIV-infected M/Ms and that alternative mechanisms are involved in this process. JF - AIDS research and human retroviruses AU - Foli, A AU - Saville, M W AU - May, L T AU - Webb, D S AU - Yarchoan, R AD - HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1997/07/01/ PY - 1997 DA - 1997 Jul 01 SP - 829 EP - 839 VL - 13 IS - 10 SN - 0889-2229, 0889-2229 KW - Colony-Stimulating Factors KW - 0 KW - Cytokines KW - Endotoxins KW - Interleukin-6 KW - Tumor Necrosis Factor-alpha KW - Macrophage Colony-Stimulating Factor KW - 81627-83-0 KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Index Medicus KW - AIDS/HIV KW - Macrophages -- immunology KW - Endotoxins -- isolation & purification KW - Cytokines -- biosynthesis KW - Humans KW - Macrophage Colony-Stimulating Factor -- pharmacology KW - HIV Infections -- etiology KW - Granulocyte-Macrophage Colony-Stimulating Factor -- pharmacology KW - Macrophages -- drug effects KW - Cells, Cultured KW - Monocytes -- immunology KW - HIV Infections -- immunology KW - Monocytes -- drug effects KW - Endotoxins -- toxicity KW - HIV-1 -- pathogenicity KW - HIV-1 -- isolation & purification KW - Tumor Necrosis Factor-alpha -- biosynthesis KW - Interleukin-6 -- biosynthesis KW - Colony-Stimulating Factors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79090622?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+research+and+human+retroviruses&rft.atitle=Effects+of+human+immunodeficiency+virus+and+colony-stimulating+factors+on+the+production+of+interleukin+6+and+tumor+necrosis+factor+alpha+by+monocyte%2Fmacrophages.&rft.au=Foli%2C+A%3BSaville%2C+M+W%3BMay%2C+L+T%3BWebb%2C+D+S%3BYarchoan%2C+R&rft.aulast=Foli&rft.aufirst=A&rft.date=1997-07-01&rft.volume=13&rft.issue=10&rft.spage=829&rft.isbn=&rft.btitle=&rft.title=AIDS+research+and+human+retroviruses&rft.issn=08892229&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-22 N1 - Date created - 1997-08-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic mapping of the Brca2 breast cancer susceptibility gene on mouse chromosome 5. AN - 79090095; 9196008 JF - Mammalian genome : official journal of the International Mammalian Genome Society AU - McAllister, K A AU - Ramachandran, S AU - Haugen-Strano, A AU - Fiedorek, F T AU - Wiseman, R W AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/07// PY - 1997 DA - July 1997 SP - 540 EP - 541 VL - 8 IS - 7 SN - 0938-8990, 0938-8990 KW - BRCA2 Protein KW - 0 KW - Neoplasm Proteins KW - Transcription Factors KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Alleles KW - Molecular Sequence Data KW - Mice, Inbred C57BL KW - Mice KW - Sequence Homology, Amino Acid KW - Neoplasm Proteins -- genetics KW - Transcription Factors -- genetics KW - Chromosome Mapping UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79090095?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mammalian+genome+%3A+official+journal+of+the+International+Mammalian+Genome+Society&rft.atitle=Genetic+mapping+of+the+Brca2+breast+cancer+susceptibility+gene+on+mouse+chromosome+5.&rft.au=McAllister%2C+K+A%3BRamachandran%2C+S%3BHaugen-Strano%2C+A%3BFiedorek%2C+F+T%3BWiseman%2C+R+W&rft.aulast=McAllister&rft.aufirst=K&rft.date=1997-07-01&rft.volume=8&rft.issue=7&rft.spage=540&rft.isbn=&rft.btitle=&rft.title=Mammalian+genome+%3A+official+journal+of+the+International+Mammalian+Genome+Society&rft.issn=09388990&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-31 N1 - Date created - 1997-07-31 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U89503; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulation of levodopa-induced motor response complications by NMDA antagonists in Parkinson's disease. AN - 79080428; 9195602 AB - The complex dopamine-glutamate interactions within the basal ganglia are disrupted by chronic nigrostriatal denervation and standard replacement therapy with levodopa. Acute N-methyl-D-aspartate (NMDA) receptor blockade is able to overcome the changes in dopamine D1- and D2-dependent responses and the progressive shortening in the duration of response induced by long-term exposure to levodopa in 6-hydroxydopamine-lesioned rats. Preliminary results further suggest that NMDA receptor blockade can counteract levodopa-induced dyskinesias in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned non-human primates and parkinsonian patients without substantially altering the motor benefit derived from levodopa. These results appear to be in accordance with our 2-deoxyglucose studies in 6-hydroxydopamine-lesioned rats showing that NMDA receptor blockade can attenuate many of the changes in synaptic activity induced by levodopa, particularly in the striatopallidal complex. Taken together, our observations suggest that abnormal glutamate transmission or dysregulation of NMDA receptor-mediated mechanisms contribute to levodopa-induced motor response complications. Additional preclinical and clinical experiments need to be completed with well tolerated glutamate antagonists to determine the full potential of glutamate receptor blockade as a long-term strategy against levodopa-related motor response complications in Parkinson's disease. JF - Neuroscience and biobehavioral reviews AU - Blanchet, P J AU - Papa, S M AU - Metman, L V AU - Mouradian, M M AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892-1406, USA. Y1 - 1997/07// PY - 1997 DA - July 1997 SP - 447 EP - 453 VL - 21 IS - 4 SN - 0149-7634, 0149-7634 KW - Antiparkinson Agents KW - 0 KW - Excitatory Amino Acid Antagonists KW - Receptors, N-Methyl-D-Aspartate KW - Levodopa KW - 46627O600J KW - Index Medicus KW - Rats KW - Animals KW - Parkinson Disease, Secondary -- physiopathology KW - Antiparkinson Agents -- adverse effects KW - Parkinson Disease, Secondary -- chemically induced KW - Excitatory Amino Acid Antagonists -- therapeutic use KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Levodopa -- therapeutic use KW - Antiparkinson Agents -- therapeutic use KW - Levodopa -- adverse effects KW - Parkinson Disease, Secondary -- drug therapy KW - Movement -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79080428?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience+and+biobehavioral+reviews&rft.atitle=Modulation+of+levodopa-induced+motor+response+complications+by+NMDA+antagonists+in+Parkinson%27s+disease.&rft.au=Blanchet%2C+P+J%3BPapa%2C+S+M%3BMetman%2C+L+V%3BMouradian%2C+M+M%3BChase%2C+T+N&rft.aulast=Blanchet&rft.aufirst=P&rft.date=1997-07-01&rft.volume=21&rft.issue=4&rft.spage=447&rft.isbn=&rft.btitle=&rft.title=Neuroscience+and+biobehavioral+reviews&rft.issn=01497634&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-05 N1 - Date created - 1997-08-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The immediate-early gene product Egr-1 regulates the human interleukin-2 receptor beta-chain promoter through noncanonical Egr and Sp1 binding sites. AN - 79080385; 9199305 AB - The interleukin-2 IL-2 receptor beta-chain (IL-2Rbeta) is an essential component of the receptors for IL-2 and IL-15. Although IL-2Rbeta is constitutively expressed by lymphocytes, its expression can be further induced by a number of stimuli, including phorbol 12-myristate 13-acetate (PMA). We have now characterized factors that bind to an enhancer region located between nucleotides -170 and -139 of the human IL-2Rbeta promoter. Both Sp1 and Sp3 bound to the 5' portion of this region, whereas a PMA-inducible factor (PIF) mainly bound to its 3' portion and bound to the Sp binding motifs as well. In Jurkat T cells, induction of PIF DNA binding activity was rapidly induced, required de novo protein synthesis, and was sustained at a high level for at least 23 h. Interestingly, PIF was constitutively activated in human T-cell leukemia virus type 1-transformed MT-2 cells. In this paper, we demonstrate that PIF is Egr-1 based on its recognition by anti-Egr-1 antisera in gel mobility shift assays, even though the IL-2Rbeta DNA binding motif differed substantially from the canonical Egr-1 binding site. In addition, Egr-1 bound to the Sp binding site. In Jurkat cells, both sites were required for maximal IL-2Rbeta promoter activity, and in HeLaS3 cells, transfection of Egr-1 could drive activity of a reporter construct containing both sites. Moreover, Sp1 and Egr-1 could form a complex with kinetics that correlated with the production of Egr-1 in Jurkat cells upon PMA stimulation. Thus, Sp1 and Egr-1 physically and functionally cooperate to mediate maximal IL-2Rbeta promoter activity. JF - Molecular and cellular biology AU - Lin, J X AU - Leonard, W J AD - Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1674, USA. Y1 - 1997/07// PY - 1997 DA - July 1997 SP - 3714 EP - 3722 VL - 17 IS - 7 SN - 0270-7306, 0270-7306 KW - DNA-Binding Proteins KW - 0 KW - EGR1 protein, human KW - Early Growth Response Protein 1 KW - IL15RA protein, human KW - Immediate-Early Proteins KW - Receptors, Interleukin-15 KW - Receptors, Interleukin-2 KW - SP3 protein, human KW - Sp1 Transcription Factor KW - Transcription Factors KW - Sp3 Transcription Factor KW - 148710-94-5 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - HeLa Cells KW - Humans KW - Sp1 Transcription Factor -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Gene Expression Regulation KW - T-Lymphocytes KW - Binding Sites KW - Transcription Factors -- physiology KW - Promoter Regions, Genetic KW - Transcription Factors -- metabolism KW - Enhancer Elements, Genetic KW - DNA-Binding Proteins -- physiology KW - Receptors, Interleukin-2 -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79080385?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=The+immediate-early+gene+product+Egr-1+regulates+the+human+interleukin-2+receptor+beta-chain+promoter+through+noncanonical+Egr+and+Sp1+binding+sites.&rft.au=Lin%2C+J+X%3BLeonard%2C+W+J&rft.aulast=Lin&rft.aufirst=J&rft.date=1997-07-01&rft.volume=17&rft.issue=7&rft.spage=3714&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-24 N1 - Date created - 1997-07-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6958-62 [1495986] J Exp Med. 1990 May 1;171(5):1821-6 [2110244] Nucleic Acids Res. 1992 Nov 11;20(21):5519-25 [1454515] J Immunol. 1993 Feb 1;150(3):960-70 [8380826] Cell Growth Differ. 1993 Jan;4(1):17-23 [8381016] Cell. 1993 Jan 29;72(2):197-209 [7678779] J Immunol. 1993 Mar 1;150(5):1979-87 [8436829] Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3265-9 [8475068] Mol Cell Biol. 1993 Aug;13(8):4556-71 [8336701] Immunol Today. 1994 Jun;15(6):274-81 [8068174] Mol Cell Biol. 1994 Oct;14(10):6570-83 [7935378] Curr Opin Immunol. 1994 Aug;6(4):631-5 [7946053] Annu Rev Biochem. 1994;63:1045-83 [7979236] J Immunol. 1995 Feb 1;154(3):1007-13 [7822778] Science. 1995 Apr 14;268(5208):251-5 [7716517] Prog Nucleic Acid Res Mol Biol. 1995;50:191-224 [7754034] Science. 1995 Jun 9;268(5216):1472-6 [7770771] Curr Top Microbiol Immunol. 1995;193:79-89 [7648879] J Biol Chem. 1995 Sep 22;270(38):22500-6 [7673240] Immunobiology. 1995 Jul;193(2-4):128-36 [8530135] Annu Rev Immunol. 1996;14:179-205 [8717512] Proc Natl Acad Sci U S A. 1990 Jun;87(12):4869-73 [2352954] Immunology. 1991 Feb;72(2):167-73 [2016116] Biochim Biophys Acta. 1991 Apr 16;1072(1):63-80 [2018779] Cell. 1991 May 3;65(3):493-505 [1850324] Genes Dev. 1991 May;5(5):820-6 [1851121] Immunology. 1991 May;73(1):64-70 [2045128] J Clin Invest. 1991 Aug;88(2):571-7 [1864967] J Immunol. 1992 Jun 1;148(11):3418-26 [1588041] Int Immunol. 1992 Apr;4(4):487-91 [1350462] J Virol. 1993 Oct;67(10):6224-33 [7690421] J Virol. 1993 Dec;67(12):6937-44 [8230415] Cell. 1994 Apr 8;77(1):5-8 [8156597] Proc Natl Acad Sci U S A. 1994 May 24;91(11):4940-4 [8197161] EMBO J. 1994 Jun 15;13(12):2822-30 [8026467] Mol Cell Biol. 1982 Sep;2(9):1044-51 [6960240] Cell. 1983 Mar;32(3):669-80 [6187469] Proc Natl Acad Sci U S A. 1987 Mar;84(5):1182-6 [3469660] Nature. 1987 Jun 11-17;327(6122):518-22 [3108674] Science. 1987 Jun 5;236(4806):1237-45 [3296191] Science. 1987 Oct 2;238(4823):75-8 [3116668] Cell. 1988 Apr 8;53(1):37-43 [3127059] Oncogene Res. 1987 Sep-Oct;1(4):343-55 [3130602] Proc Natl Acad Sci U S A. 1988 Nov;85(21):7857-61 [3141919] Science. 1989 May 5;244(4904):551-6 [2785715] Mol Cell Biol. 1989 May;9(5):2083-8 [2501658] Mol Cell Biol. 1989 Nov;9(11):4889-95 [2513479] Leuk Res. 1990;14(3):263-71 [2319807] Mol Cell Biol. 1990 May;10(5):1931-9 [2109185] Mol Cell Biol. 1992 Oct;12(10):4251-61 [1341900] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Refocusing neutralizing antibody response by targeted dampening of an immunodominant epitope. AN - 79076202; 9200464 AB - Immunodominant epitopes are known to suppress a primary immune response to other antigenic determinants by a number of mechanisms. Many pathogens have used this strategy to subvert the immune response and may be a mechanism responsible for limited vaccine efficacies. HIV-1 vaccine efficacy appears to be complicated similarly by a limited, immunodominant, isolate-restricted immune response generally directed toward determinants in the third variable domain (V3) of the major envelope glycoprotein, gp120. To overcome this problem, we have investigated an approach based on masking the V3 domain through addition of N-linked carbohydrate and reduction in net positive charge. N-linked modified gp120s were expressed by recombinant vaccinia virus and used to immunize guinea pigs by infection and protein boosting. This modification resulted in variable site-specific glycosylation and antigenic dampening, without loss of gp120/CD4 binding or virus neutralization. Most importantly, V3 epitope dampening shifted the dominant type-specific neutralizing Ab response away from V3 to an epitope in the first variable domain (V1) of gp120. Interestingly, in the presence of V3 dampening V1 changes from an immunodominant non-neutralizing epitope to a primary neutralizing epitope with broader neutralizing properties. In addition, Ab responses were also observed to conserved domains in C1 and C5. These results suggest that selective epitope dampening can lead to qualitative shifts in the immune response resulting in second order neutralizing responses that may prove useful in the fine manipulation of the immune response and in the development of more broadly protective vaccines and therapeutic strategies. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Garrity, R R AU - Rimmelzwaan, G AU - Minassian, A AU - Tsai, W P AU - Lin, G AU - de Jong, J J AU - Goudsmit, J AU - Nara, P L AD - Division of Basic Sciences, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC), MD 21702, USA. garrity@sri.org Y1 - 1997/07/01/ PY - 1997 DA - 1997 Jul 01 SP - 279 EP - 289 VL - 159 IS - 1 SN - 0022-1767, 0022-1767 KW - AIDS Vaccines KW - 0 KW - Antibodies, Viral KW - HIV Envelope Protein gp120 KW - Immunodominant Epitopes KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Mutagenesis, Site-Directed KW - Transfection KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Cell Line KW - Immunodominant Epitopes -- immunology KW - HIV-1 -- immunology KW - HIV Envelope Protein gp120 -- immunology KW - Immunodominant Epitopes -- genetics KW - AIDS Vaccines -- immunology KW - HIV Envelope Protein gp120 -- genetics KW - Immunodominant Epitopes -- analysis KW - Antibodies, Viral -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79076202?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Refocusing+neutralizing+antibody+response+by+targeted+dampening+of+an+immunodominant+epitope.&rft.au=Garrity%2C+R+R%3BRimmelzwaan%2C+G%3BMinassian%2C+A%3BTsai%2C+W+P%3BLin%2C+G%3Bde+Jong%2C+J+J%3BGoudsmit%2C+J%3BNara%2C+P+L&rft.aulast=Garrity&rft.aufirst=R&rft.date=1997-07-01&rft.volume=159&rft.issue=1&rft.spage=279&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-14 N1 - Date created - 1997-07-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inactivation of the human immunodeficiency virus type 1 inhibitory elements allows Rev-independent expression of Gag and Gag/protease and particle formation. AN - 79069180; 9188551 AB - The expression of gag, pol, and env of human immunodeficiency virus type 1 (HIV-1) depends on the presence of the viral Rev protein. This dependence is, at least in part, due to the presence of negatively acting sequences (inhibitory or instability elements [INS]) located within unspliced and partially spliced mRNAs. The positive interaction of Rev with the Rev-responsive element in these mRNAs counteracts the negative effects of the inhibitory sequences. Here, we demonstrate that in addition to the previously identified INS1 within p17gag, several other INS elements exist within the gag/pol region of HIV-1. These elements act independently of each other and were eliminated by mutagenesis after the introduction of multiple point mutations not affecting the coding region, leading to constitutive high levels of Gag expression. Expression vectors containing an intact or nearly intact p55gag region allowed the production of immature viral particles in mammalian cells in the absence of any other HIV proteins. The introduction of additional mutations in the protease region allowed efficient production of Gag/protease, which resulted in processing of the Pr55gag precursor and production of mature Gag particles with a lentivirus-like conical-core structure. The elimination of a newly identified INS element within pol and the previously identified CRS located within int was accomplished by the same methodology. Sequence comparisons of the identified inhibitory elements revealed no apparent homologies and demonstrated that these sequences are not splice sites. These results demonstrate that the elimination of INS elements leads to efficient expression of HIV-1 mRNAs in the absence of Rev or any posttranscriptional activating mechanisms. JF - Journal of virology AU - Schneider, R AU - Campbell, M AU - Nasioulas, G AU - Felber, B K AU - Pavlakis, G N AD - Human Retrovirus Section, National Cancer Institute-Frederick Cancer Research and Development Center, ABL-Basic Research Program, Maryland 21702-1201, USA. Y1 - 1997/07// PY - 1997 DA - July 1997 SP - 4892 EP - 4903 VL - 71 IS - 7 SN - 0022-538X, 0022-538X KW - DNA, Viral KW - 0 KW - Gene Products, gag KW - Gene Products, rev KW - HIV Core Protein p24 KW - Protein Precursors KW - RNA, Messenger KW - RNA, Viral KW - p55 gag precursor protein, Human immunodeficiency virus 1 KW - rev Gene Products, Human Immunodeficiency Virus KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - HIV Protease KW - EC 3.4.23.- KW - Index Medicus KW - AIDS/HIV KW - Virus Assembly KW - HIV Core Protein p24 -- genetics KW - Gene Products, gag -- genetics KW - HeLa Cells KW - Humans KW - Jurkat Cells KW - Protein Precursors -- genetics KW - Amino Acid Sequence KW - HIV Reverse Transcriptase -- genetics KW - Base Sequence KW - Tumor Cells, Cultured KW - Molecular Sequence Data KW - HIV-1 -- genetics KW - HIV Protease -- genetics KW - Gene Products, rev -- metabolism KW - Gene Expression Regulation, Viral KW - Gene Products, rev -- genetics KW - HIV-1 -- physiology KW - Genes, gag UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79069180?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Inactivation+of+the+human+immunodeficiency+virus+type+1+inhibitory+elements+allows+Rev-independent+expression+of+Gag+and+Gag%2Fprotease+and+particle+formation.&rft.au=Schneider%2C+R%3BCampbell%2C+M%3BNasioulas%2C+G%3BFelber%2C+B+K%3BPavlakis%2C+G+N&rft.aulast=Schneider&rft.aufirst=R&rft.date=1997-07-01&rft.volume=71&rft.issue=7&rft.spage=4892&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-10 N1 - Date created - 1997-07-10 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - M38432; GENBANK; K03455 N1 - SuppNotes - Cited By: Virology. 1973 Apr;52(2):456-67 [4705382] J Virol. 1992 Dec;66(12):7176-82 [1433510] EMBO J. 1985 Dec 30;4(13B):3727-33 [4092694] J Virol. 1986 Aug;59(2):284-91 [3016298] Cell. 1986 Aug 29;46(5):659-67 [3488815] Virology. 1993 Apr;193(2):661-71 [7681610] Virology. 1993 Apr;193(2):981-5 [8460500] Mol Cell Biol. 1994 Jan;14(1):416-26 [7903419] J Virol. 1994 May;68(5):2986-93 [8151769] J Virol. 1994 Aug;68(8):4927-36 [8035491] Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8314-8 [8078879] AIDS Res Hum Retroviruses. 1996 Jul 20;12(11):993-9 [8827215] J Biol Chem. 1997 Jan 24;272(4):2307-11 [8999938] Mol Cell Biol. 1987 Feb;7(2):725-37 [3821727] J Virol. 1989 Mar;63(3):1265-74 [2783738] Proc Natl Acad Sci U S A. 1989 Mar;86(5):1495-9 [2784208] Genes Dev. 1989 Jan;3(1):60-72 [2496006] Proc Natl Acad Sci U S A. 1989 Nov;86(22):8964-7 [2479031] J Virol. 1990 Jun;64(6):2519-29 [2335812] J Virol. 1990 Dec;64(12):6010-7 [2243384] Genes Dev. 1991 Feb;5(2):221-31 [1899842] Genes Dev. 1991 Feb;5(2):232-43 [1995415] Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3195-9 [2014240] Mol Cell Biol. 1991 May;11(5):2760-8 [1850103] New Biol. 1990 Dec;2(12):1111-22 [2088501] Annu Rev Biochem. 1991;60:577-630 [1883204] J Virol. 1991 Oct;65(10):5305-13 [1895385] J Virol. 1991 Nov;65(11):5732-43 [1656066] Biochim Biophys Acta. 1991 Nov 11;1090(3):281-92 [1954250] J Virol. 1992 Jan;66(1):150-9 [1727477] Mol Cell Biol. 1992 Mar;12(3):1375-86 [1545819] Microbiol Rev. 1992 Sep;56(3):375-94 [1406488] Nature. 1985 Jul 18-24;316(6025):262-5 [2410792] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of the gene start and gene end signals of human respiratory syncytial virus: quasi-templated initiation at position 1 of the encoded mRNA. AN - 79066971; 9188557 AB - The gene start (GS) and gene end (GE) transcription signals of human respiratory syncytial virus (RSV) strain A2 were analyzed in helper-dependent monocistronic and dicistronic minireplicons which were complemented by a standard RSV strain. The GS signal, which is the start site for mRNA synthesis, is highly conserved for the first nine genes: 3'-CCCCGUUUA(U/C) (negative sense). This conserved version of the signal was analyzed by "saturation" mutagenesis, in which all 10 positions, as well as one downstream and one upstream position, were changed one at a time into each of the other three nucleotides. Most of the positions appear to contribute to the signal: positions 1, 3, 6, 7, and, in particular, 9 were the most sensitive, whereas position 5 was relatively insensitive. The effect of nucleotide substitution in the first position of the signal was examined further by cDNA cloning and sequence analysis of the residual mRNA which was produced. For the two mutants examined (1C to U, and 1C to A), the site of initiation was unchanged. However, the mRNAs were dimorphic with regard to the assignment of the 5'-terminal nucleotide: two-thirds contained the predicted mutant substitution, and one-third contained the parental assignment. Intracellular minigenome contained only the mutant assignment, indicating that the heterogeneity was at the level of transcription by the RSV polymerase. This suggests that the templated mutant assignment at position 1 can sometimes be overridden by an innate preference for the parental assignment, a phenomenon which we dubbed quasi-templated initiation. The GS signal of the L gene, encoding the 10th RSV mRNA, contains three differences (3'-CCCUGUUUUA) compared to the conserved version. It was shown to be equal in efficiency to the conserved version. This was unexpected, since the saturation mutagenesis described above indicated that U in place of A at position 9 should be highly inhibitory. Instead, the A at position 10 of the L GS signal was found to be critical for activity, indicating that an essential A residue indeed was present in both versions of the GS signal but that its spacing differed. The GE signal, which directs termination and polyadenylation, has more sequence diversity in nature than does the GS signal. The naturally occurring GE signals of strain A2 were compared by their individual incorporation into a dicistronic minigenome. They were similar in the ability to produce translatable mRNA except in the cases of NS1 and NS2, which were approximately 60% as efficient. JF - Journal of virology AU - Kuo, L AU - Fearns, R AU - Collins, P L AD - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-0720, USA. Y1 - 1997/07// PY - 1997 DA - July 1997 SP - 4944 EP - 4953 VL - 71 IS - 7 SN - 0022-538X, 0022-538X KW - RNA, Messenger KW - 0 KW - RNA, Viral KW - Index Medicus KW - Blotting, Northern KW - Tumor Cells, Cultured KW - Humans KW - Sequence Analysis, RNA KW - Genome, Viral KW - Mutation KW - Respiratory Syncytial Virus, Human -- genetics KW - Gene Expression Regulation, Viral UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79066971?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Analysis+of+the+gene+start+and+gene+end+signals+of+human+respiratory+syncytial+virus%3A+quasi-templated+initiation+at+position+1+of+the+encoded+mRNA.&rft.au=Kuo%2C+L%3BFearns%2C+R%3BCollins%2C+P+L&rft.aulast=Kuo&rft.aufirst=L&rft.date=1997-07-01&rft.volume=71&rft.issue=7&rft.spage=4944&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-10 N1 - Date created - 1997-07-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1984 Nov;52(2):364-9 [6492254] Proc Natl Acad Sci U S A. 1983 Jun;80(11):3208-12 [6190173] Proc Natl Acad Sci U S A. 1986 Jul;83(13):4594-8 [3460060] Proc Natl Acad Sci U S A. 1987 Aug;84(15):5134-8 [2440043] Methods Enzymol. 1987;154:367-82 [3323813] J Gen Virol. 1988 Nov;69 ( Pt 11):2901-6 [3183631] Virus Res. 1991 Mar;18(2-3):263-70 [2042399] Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9663-7 [1946383] J Virol. 1992 Mar;66(3):1370-6 [1738196] Virus Res. 1992 Jun;24(1):115-21 [1626423] J Gen Virol. 1993 Mar;74 ( Pt 3):485-90 [8445369] J Virol. 1995 Apr;69(4):2412-9 [7884888] J Virol. 1995 Sep;69(9):5677-86 [7637014] Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11563-7 [8524804] Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):81-5 [8552680] J Virol. 1996 Sep;70(9):6143-50 [8709239] J Virol. 1996 Aug;70(8):5075-82 [8764015] J Virol. 1996 Oct;70(10):6634-41 [8794298] J Virol. 1996 Oct;70(10):6892-901 [8794332] Cell. 1981 Feb;23(2):477-84 [6258804] Proc Natl Acad Sci U S A. 1984 Dec;81(24):7683-7 [6096849] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - AIDS, Policy and Bioethics: Ethical Dilemmas Facing China in HIV Prevention AN - 61508557; 199803508 AB - Assesses the current situation of the acquired immune deficiency syndrome/human immunodeficiency virus (AIDS/HIV) epidemic in the People's Republic of China, & proposes a new ethical framework for HIV prevention. Factors that promote widespread infection are not addressed by China's inadequate prevention policy, which has taken a conventional public health approach & ignored HIV's special nature as an epidemic & ethical issues in its prevention. This is seen in beliefs (eg, HIV as a punishment) & practices (eg, detaining of homosexuals without charge, laws against prostitution & drug use) that have led to discrimination & stigmatization of AIDS patients, HIV+ people, their family members, & high-risk groups. The ethical dilemma between keeping a restrictive policy for ideological purity or turning to a more supportive policy is discussed. A new ethical framework, based on the principles of tolerance, autonomy, beneficence & care, is called for to evaluate & improve HIV prevention efforts. Adapted from the source document. JF - Bioethics AU - Wang, Yan-Guang AD - Instit Philosophy Chinese Academy Social Sciences, 5 Jianguomen Nei Da Jie 5 Hao Beijing People's Republic China Y1 - 1997/07// PY - 1997 DA - July 1997 SP - 323 EP - 327 VL - 11 IS - 3-4 SN - 0269-9702, 0269-9702 KW - Peoples Republic of China KW - Prevention KW - Acquired Immune Deficiency Syndrome KW - Bioethics KW - Health Policy KW - article KW - 7211: social planning/policy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61508557?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocialservices&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioethics&rft.atitle=AIDS%2C+Policy+and+Bioethics%3A+Ethical+Dilemmas+Facing+China+in+HIV+Prevention&rft.au=Wang%2C+Yan-Guang&rft.aulast=Wang&rft.aufirst=Yan-Guang&rft.date=1997-07-01&rft.volume=11&rft.issue=3-4&rft.spage=323&rft.isbn=&rft.btitle=&rft.title=Bioethics&rft.issn=02699702&rft_id=info:doi/ LA - English DB - Social Services Abstracts N1 - Date revised - 2007-05-01 N1 - Last updated - 2016-09-28 N1 - SubjectsTermNotLitGenreText - Acquired Immune Deficiency Syndrome; Bioethics; Health Policy; Peoples Republic of China; Prevention ER - TY - JOUR T1 - Linkage and association of a functional DRD2 variant [Ser311Cys] and DRD2 markers to alcoholism, substance abuse and schizophrenia in southwestern American Indians AN - 16451979; 4363785 AB - Alcoholism is one of a group of common psychiatric diseases which are well-defined clinically and strongly influenced genetically, but which are likely to be highly heterogeneous in causation, genetically and otherwise. Dopamine is a key neurotransmitter in drug-mediated reinforcement. Based on association studies with the Taq1A downstream marker, the D2 dopamine receptor has been proposed to be the "Reward Deficiency Syndrome Gene." Ser311Cys, a naturally occurring variant which largely inactivates transduction after D2 receptor activation, was abundant (0.16) in a Southwestern American Indian population we studied. Therefore, we were able to provide a critical test of the D2 hypothesis of vulnerability to alcoholism by evaluating Ser311Cys and also the intron-2 STR and Taq1A markers at this locus in a total of 459 subjects, including 373 sib pairs, from large families. The result is that neither alcoholism, substance use disorders nor schizophrenia show a relationship to Ser311Cys genotype, even when the 15 Cys311/Cys311 homozygous individuals are compared to others. Furthermore, sib pair analysis incorporating information across all three sib pair categories: concordant affected, discordant and concordant unaffected revealed no effect of DRD2 genotype or haplotype on alcoholism or substance use disorder. JF - American Journal of Medical Genetics 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 20852, USA Y1 - 1997/07// PY - 1997 DA - Jul 1997 SP - 386 EP - 394 PB - JOHN WILEY & SONS, INC. VL - 74 IS - 4 SN - 0148-7299, 0148-7299 KW - DRD2 gene KW - Native Americans KW - alcoholism KW - drug abuse KW - ethnic groups KW - linkage analysis KW - man KW - schizophrenia KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - X 24180:Social poisons & drug abuse KW - N3 11115:Neurogenetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16451979?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Medical+Genetics&rft.atitle=Linkage+and+association+of+a+functional+DRD2+variant+%5BSer311Cys%5D+and+DRD2+markers+to+alcoholism%2C+substance+abuse+and+schizophrenia+in+southwestern+American+Indians&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=1997-07-01&rft.volume=74&rft.issue=4&rft.spage=386&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Novel 7-alkyl methylenedioxy-camptothecin derivatives exhibit increased cytotoxicity and induce persistent cleavable complexes both with purified mammalian topoisomerase I and in human colon carcinoma SW620 cells AN - 16308666; 4252297 AB - An alkylating camptothecin (CPT) derivative, 7-chloromethyl-10,11-methylenedioxy-camptothecin (7-CM-MDO-CPT) was recently shown to produce irreversible topoisomerase I (top1) cleavage complexes by binding to the +1 base of the scissile strand of a top1 cleavage site. We demonstrate that 7-CM-EDO-CPT (7-chloromethyl-10,11-ethylenedioxy-camptothecin) also induces irreversible top1-DNA complexes. 7-CM-MDO-CPT, 7-CM-EDO-CPT, and the nonalkylating derivative 7-ethyl-10,11-methylenedioxy-camptothecin (7-E-MDO-CPT) also induced reversible top1 cleavable complexes, which were markedly more stable to salt-induced reversal than those induced by 7-ethyl-10-hyroxy-CPT, the active metabolite of CPT-11. This greater stability of the top1 cleavable complexes was contributed by the 7-alkyl and the 10,11-methylene- (or ethylene-) dioxy substitutions. Studies in SW620 cells showed that 7-E-MDO-CPT, 7-CM-MDO-CPT, and 7-CM-EDO-CPT are more potent inducers of cleavable complexes and more cytotoxic than CPT. The reversal of the cleavable complexes induced by 7-E-MDO-CPT, 7-CM-MDO-CPT, and 7-CM-EDO-CPT was markedly slower after drug removal than that for CPT, which is consistent with the data with purified top1. By contrast to CPT, 7-E-MDO-CPT, 7-CM-MDO-CPT, and 7-CM-EDO-CPT were cytotoxic irrespective of the presence of 10 mu M aphidicolin. These results suggest that 7-E-MDO-CPT, 7-CM-MDO-CPT, and 7-CM-EDO-CPT are more potent top1 poisons than CPT and produce long lasting top1 cleavable complexes and greater cytotoxicity than CPT in cells. JF - Molecular Pharmacology AU - Valenti, M AU - Nieves-Neira, W AU - Kohlhagen, G AU - Kohn, K W AU - Wall, ME AU - Wani, M C AU - Pommier, Y AD - Bldg. 37, Room 5C25, NIH/NCI, Bethesda, MD 20892-4255, USA Y1 - 1997/07// PY - 1997 DA - Jul 1997 SP - 82 EP - 87 VL - 52 IS - 1 SN - 0026-895X, 0026-895X KW - 7-chloromethyl-10,11-ethylenedioxy-camptothecin KW - 7-chloromethyl-10,11-ethylenedioxycamptothecin KW - 7-chloromethyl-10,11-methylenedioxy-camptothecin KW - 7-chloromethyl-10,11-methylenedioxycamptothecin KW - 7-ethyl-10,11-methylenedioxy-camptothecin KW - 7-ethyl-10,11-methylenedioxycamptothecin KW - 7-ethyl-10-hydroxy-camptothecin KW - DNA topoisomerase KW - SW620 cells KW - camptothecin KW - colon carcinoma KW - cytotoxicity KW - man KW - Toxicology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - X 24117:Biochemistry KW - N 14731:DNA-unwinding enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16308666?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Pharmacology&rft.atitle=Novel+7-alkyl+methylenedioxy-camptothecin+derivatives+exhibit+increased+cytotoxicity+and+induce+persistent+cleavable+complexes+both+with+purified+mammalian+topoisomerase+I+and+in+human+colon+carcinoma+SW620+cells&rft.au=Valenti%2C+M%3BNieves-Neira%2C+W%3BKohlhagen%2C+G%3BKohn%2C+K+W%3BWall%2C+ME%3BWani%2C+M+C%3BPommier%2C+Y&rft.aulast=Valenti&rft.aufirst=M&rft.date=1997-07-01&rft.volume=52&rft.issue=1&rft.spage=82&rft.isbn=&rft.btitle=&rft.title=Molecular+Pharmacology&rft.issn=0026895X&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 - Cancer risk and mortality patterns among silicotic men in Sweden and Denmark AN - 16271121; 4254939 AB - Data from nationwide registry-based cohorts of patients hospitalized for silicosis in Sweden from 1965 to 1983 and Denmark from 1977 to 1989 were linked to national cancer registries in both countries and to mortality data in Sweden to evaluate the risk of cancer and other disorders among hospitalized silicotic patients. The overall cancer standardized incidence ratio (SIR) was 1.5 (95% confidence interval [CI], 1.3 to 1.7) in Sweden and 1.7 (95% CI, 1.2 to 2.3) in Denmark, primarily because of elevations in primary lung cancer in both Sweden (SIR, 3.1; CI, 2.1 to 4.2) and Denmark (SIR, 2.9; CI, 1.5 to 5.2). For Sweden, the all-causes standardized mortality ratio (SMR) was 2.0 (1.9 to 2.2). The SMR for all malignancies was 1.5 (1.2 to 1.7), primarily because of excesses of lung cancer (SMR, 2.9; CI, 2.1 to 3.9). The significant increase in mortality for all infectious and parasitic conditions (SMR, 11.2) was primarily due to tuberculosis (SMR, 21.8). Significant excesses in mortality from silicosis (SMR, 523), bronchitis (SMR, 2.6) and emphysema (SMR, 6.7) contributed to the elevation in nonmalignant respiratory deaths (SMR, 8.8), whereas excess mortality from musculoskeletal disorders (SMR, 5.9) was due to six deaths from autoimmune diseases. Despite limitations of the available data, our findings are consistent with previous reports indicating that silicotic patients are at elevated risk of lung cancer, nonmalignant respiratory diseases, tuberculosis, and certain autoimmune disorders. JF - Journal of Occupational and Environmental Medicine AU - Brown, L M AU - Gridley, G AU - Olsen, J H AU - Mellemkjaer, L AU - Linet AU - Fraumeni, JF Jr AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Executive Plaza North, Room 415, 6130 Executive Blvd MSC 7368, Bethesda, MD 20892-7368, USA Y1 - 1997/07// PY - 1997 DA - Jul 1997 SP - 633 EP - 638 VL - 39 IS - 7 SN - 1076-2752, 1076-2752 KW - Denmark KW - Sweden KW - cancer KW - lung cancer KW - mortality KW - respiratory tract diseases KW - risk assessment KW - silicosis KW - statistical analysis KW - tuberculosis KW - Toxicology Abstracts; Risk Abstracts; Health & Safety Science Abstracts KW - R2 23080:Industrial and labor KW - H 11000:Diseases/Injuries/Trauma KW - R2 23060:Medical and environmental health KW - H 1000:Occupational Safety and Health KW - X 24152:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16271121?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Occupational+and+Environmental+Medicine&rft.atitle=Cancer+risk+and+mortality+patterns+among+silicotic+men+in+Sweden+and+Denmark&rft.au=Brown%2C+L+M%3BGridley%2C+G%3BOlsen%2C+J+H%3BMellemkjaer%2C+L%3BLinet%3BFraumeni%2C+JF+Jr&rft.aulast=Brown&rft.aufirst=L&rft.date=1997-07-01&rft.volume=39&rft.issue=7&rft.spage=633&rft.isbn=&rft.btitle=&rft.title=Journal+of+Occupational+and+Environmental+Medicine&rft.issn=10762752&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Cigarette smoking and solvent use among Japanese adolescents AN - 16240401; 4230081 AB - To examine the relationship between cigarette smoking and solvent use among Japanese adolescents, epidemiologic data from a survey of 4433 junior high school students were analyzed. For both males and females, the frequency of cigarette smoking was positively associated with curiosity about solvent use, familiarity with solvent use, the perception of closeness to solvent users and the lifetime and past-year prevalence rates of solvent use. On the other hand, the frequency of smoking was negatively associated with the endorsement of the current Japanese law which maintains the illegality of solvent use. These results are reported for the first time from epidemiologic-based data among early adolescents in Japan. Although correlational, they suggest the role of cigarette smoking for Japanese adolescents in the initiation of other illicit drug use in these age groups. JF - Drug and Alcohol Dependence AU - Wada, K AU - Price, RKato AU - Fukui, S AD - Division of Drug Dependence and Psychotropic Drug Clinical Research, National Institute of Mental Health, National Center of Neurology and Psychiatry, 1-7-3, Kohnodai, Ichikawa-shi, Chiba-ken 272, Japan Y1 - 1997/07// PY - 1997 DA - Jul 1997 SP - 137 EP - 145 VL - 46 IS - 3 SN - 0376-8716, 0376-8716 KW - Japan KW - adolescence KW - cigarette smoking KW - drug abuse KW - man KW - solvents KW - Toxicology Abstracts KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16240401?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+and+Alcohol+Dependence&rft.atitle=Cigarette+smoking+and+solvent+use+among+Japanese+adolescents&rft.au=Wada%2C+K%3BPrice%2C+RKato%3BFukui%2C+S&rft.aulast=Wada&rft.aufirst=K&rft.date=1997-07-01&rft.volume=46&rft.issue=3&rft.spage=137&rft.isbn=&rft.btitle=&rft.title=Drug+and+Alcohol+Dependence&rft.issn=03768716&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Michellamines D-F, new HIV-inhibitory dimeric naphthylisoquinoline alkaloids, and korupensamine E, a new antimalarial monomer, from Ancistrocladus korupensis AN - 16231972; 4218543 AB - New monomeric (korupensamine E, 6) and dimeric (michellamines D-F, 7-9) naphthylisoquinoline alkaloids have been isolated from exracts of the tropical liana Ancistrocladus korupensis. Structures were determined by spectroanalytical methods, and stereochemistry was defined through NOE correlations, chemical degradation, and CD spectroscopy. Michellamines D-F exhibited in vitro HIV-inhibitory activity comparable to michellamine B, and korupensamine E exhibited in vitro antimalarial activity comparable to korupensamines A-D. JF - Journal of Natural Products AU - Hallock, Y F AU - Manfredi, K P AU - Dai, Jin-Rui AU - Cardellina, JH II AU - Gulakowski, R J AU - McMahon, J B AU - Schaeffer, M AU - Stahl, M AU - Gulden, K-P AU - Bringmann, G AU - Francois, G AU - Boyd, M R AD - Laboratory of Drug Discovery Research and Development, Developmental Therapeutics Program, Division of Cancer Treatment, Diagnosis and Centers, National Cancer Institute, Frederick, Maryland 21702-1201, USA Y1 - 1997/07// PY - 1997 DA - Jul 1997 SP - 677 EP - 683 VL - 60 IS - 7 SN - 0163-3864, 0163-3864 KW - Ancistrocladus korupensis KW - antimalarial agents KW - antiviral agents KW - human immunodeficiency virus KW - korupensamine E KW - naphthylisoquinoline alkaloids KW - Biotechnology and Bioengineering Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts C: Algology, Mycology & Protozoology; Virology & AIDS Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - V 22002:AIDS: Molecular and in vitro aspects KW - W3 33370:Antibiotics KW - A 01068:Antiviral & viricidal KW - W 30965:Miscellaneous, Reviews KW - K 03063:Effects of physical & chemical factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16231972?accountid=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+Natural+Products&rft.atitle=Michellamines+D-F%2C+new+HIV-inhibitory+dimeric+naphthylisoquinoline+alkaloids%2C+and+korupensamine+E%2C+a+new+antimalarial+monomer%2C+from+Ancistrocladus+korupensis&rft.au=Hallock%2C+Y+F%3BManfredi%2C+K+P%3BDai%2C+Jin-Rui%3BCardellina%2C+JH+II%3BGulakowski%2C+R+J%3BMcMahon%2C+J+B%3BSchaeffer%2C+M%3BStahl%2C+M%3BGulden%2C+K-P%3BBringmann%2C+G%3BFrancois%2C+G%3BBoyd%2C+M+R&rft.aulast=Hallock&rft.aufirst=Y&rft.date=1997-07-01&rft.volume=60&rft.issue=7&rft.spage=677&rft.isbn=&rft.btitle=&rft.title=Journal+of+Natural+Products&rft.issn=01633864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Minimal variation in the Pfs28 ookinete antigen from Philippine field isolates of Plasmodium falciparum AN - 16108165; 4207568 AB - Disrupting the sexual stage of the malaria parasite life cycle is the main goal of transmission-blocking vaccine development. A 28-kilodalton surface antigen, Pfs28, is expressed on the ookinete stage of the human malaria parasite, Plasmodium falciparum, antibodies to which inhibit ookinete development in the mosquito midgut. Homologues of Pfs28 in the avian malaria parasite, P. gallinaceum, and the rodent malarial parasite, P. berghei, confer transmission-blocking immunity experimental malaria parasite infections in their respective hosts. Polymorphism of malaria parasite antigens makes the determination of their amino acid sequence diversity in field isolates prior to vaccine trials a prudent exercise. JF - Molecular and Biochemical Parasitology AU - Hafalla, JCR AU - Santiago, MLO AU - Pasay, MCJ AU - Ramirez, B L AU - Gozar, MMG AU - Saul, A AU - Kaslow, D C AD - Malaria Vaccines Sect., Lab. Parasitic Dis., NIAID, Natl. Institutes Health, Malaria Vaccine Sect., Rm. B1-31, Bldg. 4, Bethesda, MD 20892, USA Y1 - 1997/07// PY - 1997 DA - Jul 1997 SP - 97 EP - 99 VL - 87 IS - 1 SN - 0166-6851, 0166-6851 KW - Pfs28 antigen KW - endoparasites KW - ookinetes KW - ASFA 3: Aquatic Pollution & Environmental Quality; Microbiology Abstracts C: Algology, Mycology & Protozoology; Immunology Abstracts KW - Philippines KW - vaccines KW - malaria KW - Plasmodium falciparum KW - Freshwater KW - antigens KW - K 03086:Immunology & vaccination KW - F 06013:Protozoa KW - Q5 08524:Public health, medicines, dangerous organisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16108165?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+Biochemical+Parasitology&rft.atitle=Minimal+variation+in+the+Pfs28+ookinete+antigen+from+Philippine+field+isolates+of+Plasmodium+falciparum&rft.au=Hafalla%2C+JCR%3BSantiago%2C+MLO%3BPasay%2C+MCJ%3BRamirez%2C+B+L%3BGozar%2C+MMG%3BSaul%2C+A%3BKaslow%2C+D+C&rft.aulast=Hafalla&rft.aufirst=JCR&rft.date=1997-07-01&rft.volume=87&rft.issue=1&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=Molecular+and+Biochemical+Parasitology&rft.issn=01666851&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2014-05-06 N1 - SubjectsTermNotLitGenreText - vaccines; malaria; endoparasites; antigens; ookinetes; Plasmodium falciparum; Philippines; Freshwater ER - TY - JOUR T1 - The Borrelia burgdorferi circular plasmid cp26: Conservation of plasmid structure and targeted inactivation of the ospC gene AN - 16089552; 4200775 AB - The 26 to 28 kb circular plasmid of B. burgdorferi sensu lato (cp26) is ubiquitous among bacteria of this group and contains loci implicated in the mouse-tick transmission cycle. Restriction mapping and Southern hybridization indicated that the structure of cp26 is conserved among isolates from different origins and culture passage histories. The cp26 ospC gene encodes an outer surface protein whose synthesis within infected ticks increases when the ticks feed, and whose synthesis in culture increases after a temperature upshift. Previous studies of ospC coding sequences showed them to have stretches of sequence apparently derived from the ospC genes of distantly related isolates by homologous recombination after DNA transfer. We found conservation of the promoter regions of the ospC and guaA genes, which are divergently transcribed. We also demonstrated that the increase in OspC protein after a temperature upshift parallels increases in mRNA levels, as expected if regulatory regions adjoin the conserved sequences in the promoter regions. Finally, we used directed insertion to inactivate the ospC gene of a non-infectious isolate. This first example of directed gene inactivation in B. burgdorferi shows that the OspC protein is not required for stable maintenance of cp26 or growth in culture. JF - Molecular Microbiology AU - Tilly, K AU - Casjens, S AU - Stevenson, B AU - Bono, J L AU - Samuels, D S AU - Hogan, D AU - Rosa, P AD - Laboratory of Microbial Structure and Function, National Institute of Allergy and Infectious Diseases, Rocky Mountain Laboratories, 903 South 4th Street, Hamilton, MT 59840, USA Y1 - 1997/07// PY - 1997 DA - Jul 1997 SP - 361 EP - 373 VL - 25 IS - 2 SN - 0950-382X, 0950-382X KW - ospC gene KW - plasmid pcp26 KW - plasmid cp26 KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - restriction endonuclease mapping KW - hybridization analysis KW - Borrelia burgdorferi KW - mutation KW - Lyme disease KW - J 02760:Plasmids KW - G 07203:Plasmids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16089552?accountid=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=The+Borrelia+burgdorferi+circular+plasmid+cp26%3A+Conservation+of+plasmid+structure+and+targeted+inactivation+of+the+ospC+gene&rft.au=Tilly%2C+K%3BCasjens%2C+S%3BStevenson%2C+B%3BBono%2C+J+L%3BSamuels%2C+D+S%3BHogan%2C+D%3BRosa%2C+P&rft.aulast=Tilly&rft.aufirst=K&rft.date=1997-07-01&rft.volume=25&rft.issue=2&rft.spage=361&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 N1 - SubjectsTermNotLitGenreText - Borrelia burgdorferi; restriction endonuclease mapping; hybridization analysis; mutation; Lyme disease ER - TY - JOUR T1 - Green fluorescent protein retroviral vectors: Low titer and high recombination frequency suggest a selective disadvantage AN - 16081907; 4111372 AB - Green fluorescent protein (GFP) has been used as a reporter molecule for gene expression because it fluoresces green after blue-light excitation. Inclusion of this gene in a vector could allow rapid, nontoxic selection of successfully transduced cells. However, many attempts by our laboratory to isolate stable retroviral producer cell clones secreting biologically active vectors containing either the highly fluorescent S65T-GFP mutant or humanized GFP have failed. Vector plasmids containing various forms of GFP and the neomycin resistance gene were transfected into three different packaging cell lines and fluorescence was observed for several days, but stable clones selected with G418 no longer fluoresced. Using confocal microscopy, the brightest cells were observed to contract and die within a matter of days. RNA slot-blot analysis of retroviral producer supernatants showed no viral production from the GFP plasmid-transfected clones, although all clones derived after transfection with an identical retroviral construct not containing GFP produced virus. Genomic Southern analysis of the GFP-transduced clones showed a much higher probability of rearrangement of the priviral sequences than in the control non-GFP clones. Overall, 18/34 S65T-GFP clones and 17/33 humanized-GFP clones had rearrangements, whereas 2/15 control non-GFP clones had rearrangements. Hence, producer cells expressing high levels of these GFP genes seem to be selected against, with stable clones undergoing major rearrangements or other mutations that both abrogate GFP expression and prevent vector production. These observations indicate that GFP may not be an appropriate reporter gene for gene transfer applications in our vector/packaging system. JF - Human Gene Therapy AU - Hanazono, Y AU - Yu, Jian-Mei AU - Dunbar, CE AU - Emmons, RVB AD - Building 10, Room 7C103, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 1997/07// PY - 1997 DA - Jul 1997 SP - 1313 EP - 1319 VL - 8 IS - 11 SN - 1043-0342, 1043-0342 KW - green fluorescent protein KW - packaging cells KW - producer cells KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - retrovirus KW - expression vectors KW - reporter gene KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16081907?accountid=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=Green+fluorescent+protein+retroviral+vectors%3A+Low+titer+and+high+recombination+frequency+suggest+a+selective+disadvantage&rft.au=Hanazono%2C+Y%3BYu%2C+Jian-Mei%3BDunbar%2C+CE%3BEmmons%2C+RVB&rft.aulast=Hanazono&rft.aufirst=Y&rft.date=1997-07-01&rft.volume=8&rft.issue=11&rft.spage=1313&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 - 2011-12-14 N1 - SubjectsTermNotLitGenreText - retrovirus; expression vectors; reporter gene ER - TY - JOUR T1 - Efficient gene targeting in mouse embryonic stem cells AN - 16056621; 4102864 AB - We developed methods to improve the efficiency of gene correction in mouse embryonic stem cells using homologous recombination of a replacement vector. The absolute frequency of homologous recombination in mouse embryonic stem (ES) cells, defined as the frequency of homologous recombination per electroporated cell, is approximately 10 super(-5) to 10 super(-6) by current procedures. Our method for gene targeting in mouse ES cells produces an absolute frequency of 10 super(-1). The protocol uses micro-electroporation chambers and a modified electroporation procedure that does not cause significant cell death. Plating and growth of the electroporated cells at an optimum density to maintain viability significantly increased the recovery of targeted cells. Due to the high frequency of targeting, corrected cells could be isolated by screening colonies obtained after growth without selection. Alternatively, colony formation and the absolute frequency could be increased by co-plating the electroporated cells with nonelectroporated ES cells before the addition of selective medium. These parental cells were nonirradiated but were killed in the selective medium. Plating density and efficiency of colony formation are therefore critical factors for obtaining a high absolute frequency of homologous recombination. Because this frequency is extremely high, these methods can be used to perform gene targeting without the use of selectable markers. JF - Gene Therapy AU - Templeton, N S AU - Roberts, D D AU - Safer, B AD - NCI-FCRDC, ABL-Basic Res. Prog., PO Box B, Boyles St., Bldg. 535, Rm. 226A, Frederick, MD 21702-1201, USA Y1 - 1997/07// PY - 1997 DA - Jul 1997 SP - 700 EP - 709 VL - 4 IS - 7 SN - 0969-7128, 0969-7128 KW - Lesch-Nyhan syndrome KW - embryonic stem cells KW - knockout mice KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Genetics Abstracts KW - gene therapy KW - gene targeting KW - Electroporation KW - G 07398:GENERAL 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/16056621?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gene+Therapy&rft.atitle=Efficient+gene+targeting+in+mouse+embryonic+stem+cells&rft.au=Templeton%2C+N+S%3BRoberts%2C+D+D%3BSafer%2C+B&rft.aulast=Templeton&rft.aufirst=N&rft.date=1997-07-01&rft.volume=4&rft.issue=7&rft.spage=700&rft.isbn=&rft.btitle=&rft.title=Gene+Therapy&rft.issn=09697128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - gene therapy; Electroporation; gene targeting ER - TY - JOUR T1 - Improved DNA: Liposome complexes for increased systemic delivery and gene expression AN - 16046439; 4087792 AB - To increase cationic liposome-mediated intravenous DNA delivery extruded DOTAP:cholesterol liposomes were used to form complexes with DNA, resulting in enhanced expression of the chloramphenicol acetyltransferase gene in most tissues examined. The DNA:liposome ratio, and mild sonication, heating, and extrusion steps used for liposome preparation were crucial for improved systemic delivery. Size fractionation studies showed that maximal gene expression was produced by a homogeneous population of DNA:liposome complexes between 200 to 450 nm in size. Cryo-electron microscopy examination demonstrates that the DNA:liposome complexes have a novel morphology, and that the DNA is condensed on the interior of invaginated liposomes between two lipid bilayers. This structure could account for the high efficiency of gene delivery in vivo and for the broad tissue distribution of the DNA:liposome complexes. Ligands can be placed on the outside of this structure to provide for targeted gene delivery. JF - Nature Biotechnology AU - Templeton, N S AU - Lasic, D D AU - Frederik, P M AU - Strey, H H AU - Roberts, D D AU - Pavlakis, G N AD - NCI-FCRDC, ABL-Basic Research Program, P.O. Box B, Boyles Street, Bldg. 535, Rm. 226A, Frederick, MD 21702-1201, USA Y1 - 1997/07// PY - 1997 DA - Jul 1997 SP - 647 EP - 652 VL - 15 IS - 7 SN - 1087-0156, 1087-0156 KW - 1,2-bis(oleoyloxy)-3-(trimethyl ammonio)propane KW - cholesterol KW - dimethyldioctadecylammonium KW - gene delivery KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - liposomes KW - lipids KW - DNA KW - W 30965:Miscellaneous, Reviews KW - W3 33390:Products: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16046439?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Biotechnology&rft.atitle=Improved+DNA%3A+Liposome+complexes+for+increased+systemic+delivery+and+gene+expression&rft.au=Templeton%2C+N+S%3BLasic%2C+D+D%3BFrederik%2C+P+M%3BStrey%2C+H+H%3BRoberts%2C+D+D%3BPavlakis%2C+G+N&rft.aulast=Templeton&rft.aufirst=N&rft.date=1997-07-01&rft.volume=15&rft.issue=7&rft.spage=647&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - liposomes; lipids; DNA ER - TY - JOUR T1 - Characterization of cp18, a naturally truncated member of the cp32 family of Borrelia burgdorferi plasmids AN - 16023458; 4096928 AB - We have mapped the genes encoding the antigenic lipoproteins OspE and OspF to an approximately 18-kb circular plasmid in Borrelia burgdorferi N40. Sequencing and restriction mapping have revealed that this plasmid, cp18, is homologous to an 18-kb region of the cp32 circular plasmids found in the Lyme disease spirochetes. Our data show that cp18 may have arisen from an ancestral cp32 plasmid by deletion of a 14-kb region of DNA, indicating that a significant portion of the cp32 plasmid is not essential in cis for plasmid maintenance. These findings suggest that a relatively small recombinant plasmid capable of being stably maintained in B. burgdorferi could be constructed from a cp32 plasmid. JF - Journal of Bacteriology AU - Stevenson, B AU - Casjens, S AU - Van-Vugt, R AU - Porcella, S F AU - Tilly, K AU - Bono, J L AU - Rosa, P AD - Lab. Microbial Struct. and Function, Rocky Mountain Labs., NIAID, NIH, 903 South Fourth St., Hamilton, MT 59840, USA Y1 - 1997/07// PY - 1997 DA - Jul 1997 SP - 4285 EP - 4291 VL - 179 IS - 13 SN - 0021-9193, 0021-9193 KW - ospE gene KW - ospF gene KW - plasmid pcp18 KW - Microbiology Abstracts B: Bacteriology KW - Borrelia burgdorferi KW - gene mapping KW - J 02760:Plasmids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16023458?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=Characterization+of+cp18%2C+a+naturally+truncated+member+of+the+cp32+family+of+Borrelia+burgdorferi+plasmids&rft.au=Stevenson%2C+B%3BCasjens%2C+S%3BVan-Vugt%2C+R%3BPorcella%2C+S+F%3BTilly%2C+K%3BBono%2C+J+L%3BRosa%2C+P&rft.aulast=Stevenson&rft.aufirst=B&rft.date=1997-07-01&rft.volume=179&rft.issue=13&rft.spage=4285&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Borrelia burgdorferi; gene mapping ER - TY - JOUR T1 - Interlaboratory agreement among results of human papillomavirus type 16 enzyme-linked immunosorbent assays AN - 16019294; 4091067 AB - Serological assays for measuring antibodies to human papillomavirus type 16 (HPV-16) virus-like particles (VLPs) have become important epidemiologic tools in recent years. However, the interlaboratory replicability of these assays has not been assessed. In this investigation, three laboratories tested a panel of specimens obtained from two different groups: 265 subjects in a vulvar cancer case-control study and 107 healthy volunteer blood donors. Each laboratory used an enzyme-linked immunosorbent assay (ELISA), but no attempt was made to standardize assay procedures among the three laboratories. The data showed good day-to-day intralaboratory replicability in laboratory 1 (correlation coefficient, greater than or equal to 0.88) and good intra-assay variability in laboratory 3 (correlation coefficient, greater than or equal to 0.93). Interlaboratory correlations, likewise, ranged between 0.61 and 0.80 in both case-control study subjects and healthy blood donors, indicating that ELISA optical density (OD) values between laboratories were linearly related regardless of the population. Kappa coefficients ( Kappa ), based on each laboratory's categorical interpretation of its results (as positive or negative), showed good agreement ( Kappa , >0.6) in case-control study subjects and moderate agreement ( Kappa , greater than or equal to 0.4) in blood donors, a population that had few strongly positive sera. When OD values near seropositive cutoffs were treated as indeterminates, there was little discordance between laboratories in either population. The data suggest that each laboratory measured the same humoral immune response and that their HPV-16 VLP ELISAs performed similarly (Pearson correlations). Interlaboratory differences, however, probably due to reagents and procedures, were considerably greater than intralaboratory day-to-day variability. Interlaboratory agreement in determining seropositivity ( Kappa ) could be improved by sharing positive and negative serum controls and by treating marginal results as indeterminate. As part of continuing cooperation to improve interlaboratory agreement, we are preparing bulk serum control specimens to be shared and made available to interested researchers. JF - Journal of Clinical Microbiology AU - Strickler, H D AU - Hildesheim, A AU - Viscidi, R P AU - Shah, K V AU - Goebel, B AU - Drummond, J AU - Waters, D AU - Sun, Y AU - Hubbert, N L AU - Wacholder, S AU - Brinton, LA AU - Han, C AU - Nasca, P C AU - McClimens, R AD - Viral Epidemiol. Branch, NCI, NIH, EPN Rm. 434, Bethesda, MD 20892, USA Y1 - 1997/07// PY - 1997 DA - Jul 1997 SP - 1751 EP - 1756 VL - 35 IS - 7 SN - 0095-1137, 0095-1137 KW - standards KW - human papilloma virus 16 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - laboratories KW - diagnostic agents KW - enzyme-linked immunosorbent assay KW - A 01114:Viruses KW - V 22091:Immunological techniques & reagents UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16019294?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Clinical+Microbiology&rft.atitle=Interlaboratory+agreement+among+results+of+human+papillomavirus+type+16+enzyme-linked+immunosorbent+assays&rft.au=Strickler%2C+H+D%3BHildesheim%2C+A%3BViscidi%2C+R+P%3BShah%2C+K+V%3BGoebel%2C+B%3BDrummond%2C+J%3BWaters%2C+D%3BSun%2C+Y%3BHubbert%2C+N+L%3BWacholder%2C+S%3BBrinton%2C+LA%3BHan%2C+C%3BNasca%2C+P+C%3BMcClimens%2C+R&rft.aulast=Strickler&rft.aufirst=H&rft.date=1997-07-01&rft.volume=35&rft.issue=7&rft.spage=1751&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Microbiology&rft.issn=00951137&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - diagnostic agents; enzyme-linked immunosorbent assay; laboratories ER - TY - JOUR T1 - Cloning and expression of the Borrelia burgdorferi lon gene AN - 16015599; 4089889 AB - The ATP-dependent protease Lon (La) of Escherichia coli degrades abnormal proteins and is involved in the regulation of capsular polysaccharide synthesis. In addition, mutations in the E. coli lon gene suppress temperature-sensitive mutations in other genes. The lon gene of Borrelia burgdorferi, encoding a homolog of the Lon protease, has been cloned and sequenced. The gene encodes a protein of 806 amino acids. The deduced amino acid sequence of the B. burgdorferi Lon protease shares substantial sequence identity with those of other known Lon proteases. The transcription start point of the B. burgdorferi lon gene was identified by primer extension analysis and the potential promoter did not show similarities to the consensus heat-shock promoter in E. coli. The 5'-end of the B. burgdorferi lon gene appears to suppress the temperature-sensitive phenotype of an E. coli lpxA mutant. JF - Gene AU - Cloud, J L AU - Marconi, R T AU - Eggers, CH AU - Garon, C F AU - Tilly, K AU - Samuels, D S AD - Microscopy Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, MT 59840, USA Y1 - 1997/07// PY - 1997 DA - Jul 1997 SP - 137 EP - 141 PB - ELSEVIER SCIENCE B.V. VL - 194 IS - 1 SN - 0378-1119, 0378-1119 KW - nucleotide sequence KW - amino acid sequence prediction KW - lon gene KW - Lon proteinase KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - heat shock KW - Borrelia burgdorferi KW - transcription initiation KW - G 07321:GENERAL KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16015599?accountid=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=Gene&rft.atitle=Cloning+and+expression+of+the+Borrelia+burgdorferi+lon+gene&rft.au=Cloud%2C+J+L%3BMarconi%2C+R+T%3BEggers%2C+CH%3BGaron%2C+C+F%3BTilly%2C+K%3BSamuels%2C+D+S&rft.aulast=Cloud&rft.aufirst=J&rft.date=1997-07-01&rft.volume=194&rft.issue=1&rft.spage=137&rft.isbn=&rft.btitle=&rft.title=Gene&rft.issn=03781119&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; transcription initiation; heat shock ER - TY - JOUR T1 - Discovery of cyanovirin-N, a novel human immunodeficiency virus-inactivating protein that binds viral surface envelope glycoprotein gp120: Potential applications to microbicide development AN - 16000438; 4081317 AB - We have isolated and sequenced a novel 11-kDa virucidal protein, named cyanovirin-N (CV-N), from cultures of the cyanobacterium (blue-green alga) Nostoc ellipsosporum. We also have produced CV-N recombinantly by expression of a corresponding DNA sequence in Escherichia coli. Low nanomolar concentrations of either natural or recombinant CV-N irreversibly inactivate diverse laboratory strains and primary isolates of human immunodeficiency virus (HIV) type 1 as well as strains of HIV type 2 and simian immunodeficiency virus. In addition, CV-N aborts cell-to-cell fusion and transmission of HIV-1 infection. Continuous, 2-day exposures of uninfected CEM-SS cells or peripheral blood lymphocytes to high concentrations (e.g., 9,000 nM) of CV-N were not lethal to these representative host cell types. The antiviral activity of CV-N is due, at least in part, to unique, high-affinity interactions of CV-N with the viral surface envelope glycoprotein gp120. The biological activity of CV-N is highly resistant to physicochemical denaturation, further enhancing its potential as an anti-HIV microbicide. JF - Antimicrobial Agents & Chemotherapy AU - Boyd, M R AU - Gustafson, K R AU - McMahon, J B AU - Shoemaker, R H AU - O'Keefe, B R AU - Mori, T AU - Gulakowski, R J AU - Wu, L AU - Rivera, MI AU - Laurencot, C M AU - Currens, MJ AU - Cardellina, JH II AU - Buckheit, RW Jr AU - Nara, P L AD - Lab. Drug Discovery Res. & Dev., DTP, DCTDC, NCI-FCRDC, Bldg. 1052, Rm. 121, Frederick, MD 21702-1201, USA Y1 - 1997/07// PY - 1997 DA - Jul 1997 SP - 1521 EP - 1530 VL - 41 IS - 7 SN - 0066-4804, 0066-4804 KW - cyanovirin-N KW - glycoprotein gp120 KW - inhibition KW - Biotechnology and Bioengineering Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - adherence KW - cell fusion KW - antiviral agents KW - Human immunodeficiency virus KW - V 22002:AIDS: Molecular and in vitro aspects KW - W3 33370:Antibiotics KW - A 01069:Antimicrobial & microbiocidal KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16000438?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+Agents+%26+Chemotherapy&rft.atitle=Discovery+of+cyanovirin-N%2C+a+novel+human+immunodeficiency+virus-inactivating+protein+that+binds+viral+surface+envelope+glycoprotein+gp120%3A+Potential+applications+to+microbicide+development&rft.au=Boyd%2C+M+R%3BGustafson%2C+K+R%3BMcMahon%2C+J+B%3BShoemaker%2C+R+H%3BO%27Keefe%2C+B+R%3BMori%2C+T%3BGulakowski%2C+R+J%3BWu%2C+L%3BRivera%2C+MI%3BLaurencot%2C+C+M%3BCurrens%2C+MJ%3BCardellina%2C+JH+II%3BBuckheit%2C+RW+Jr%3BNara%2C+P+L&rft.aulast=Boyd&rft.aufirst=M&rft.date=1997-07-01&rft.volume=41&rft.issue=7&rft.spage=1521&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+Agents+%26+Chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - adherence; antiviral agents; cell fusion; Human immunodeficiency virus ER - TY - JOUR T1 - Flavone acetic acid stimulates nitric oxide and peroxynitrite production in subcutaneous mouse tumors. AN - 79109873; 9207186 AB - Flavone acetic acid (FAA) has powerful anti-tumor activity against many types of solid murine tumors, but its biochemical mechanism of action is not understood. The present study examined the role of tumor vasculature and nitric oxide in mediating the anti-tumor effects of FAA. Athymic nude mice bearing subcutaneous RJ2-14 tumors were treated with a single dose of FAA, 200 mg/kg i.p., and euthanized at various times. Apoptosis within tumors was apparent during the first six hours of FAA treatment. We found that Type III, endothelial nitric oxide synthase (NOS) activity was significantly increased in tumors, but not in other tissues, as early as two hours after FAA dosing. FAA also stimulated the formation of the toxic peroxynitrite radical in tumors within two hours of treatment as assessed by immunostaining for nitrotyrosine. Staining was observed in dilated tumor vessels and surrounding tumor cells and correlated with the presence of apoptosis. Tumor endothelium may therefore be a critical target for FAA activity via stimulation of the nitric oxide pathway. JF - Biochemical and biophysical research communications AU - Harris, S R AU - Thorgeirsson, U P AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/06/27/ PY - 1997 DA - 1997 Jun 27 SP - 509 EP - 514 VL - 235 IS - 3 SN - 0006-291X, 0006-291X KW - Antineoplastic Agents KW - 0 KW - Flavonoids KW - Free Radicals KW - Nitrates KW - peroxynitric acid KW - 26404-66-0 KW - Nitric Oxide KW - 31C4KY9ESH KW - flavone acetic acid KW - 87626-55-9 KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Calcium -- metabolism KW - Animals KW - Kinetics KW - Apoptosis -- drug effects KW - Cell Division -- drug effects KW - Mice, Nude KW - Mice KW - Cell Line, Transformed KW - Time Factors KW - Free Radicals -- metabolism KW - Adenocarcinoma -- metabolism KW - Nitrates -- metabolism KW - Nitric Oxide -- biosynthesis KW - Flavonoids -- pharmacology KW - Nitric Oxide Synthase -- metabolism KW - Adenocarcinoma -- drug therapy KW - Antineoplastic Agents -- pharmacology KW - Adenocarcinoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79109873?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Flavone+acetic+acid+stimulates+nitric+oxide+and+peroxynitrite+production+in+subcutaneous+mouse+tumors.&rft.au=Harris%2C+S+R%3BThorgeirsson%2C+U+P&rft.aulast=Harris&rft.aufirst=S&rft.date=1997-06-27&rft.volume=235&rft.issue=3&rft.spage=509&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-24 N1 - Date created - 1997-07-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recruitment of p300/CBP in p53-dependent signal pathways. AN - 79109198; 9215639 AB - The products of the p53 and CBP/p300 genes have been individually implicated in control of cell growth and regulation of transcription. p53 is known to act as a positive and negative regulator of gene expression. Here we show that p53, in both wild-type and mutant conformation, forms a specific protein complex with p300. However, in its wild-type but not mutant conformation, p53 inhibits a promoter containing the DNA-binding sequences for the transcription factor AP1, in a p300-dependent manner. p300 stimulates the transcriptional activity of p53 on p53-regulated promoters, and it enhances the responsiveness to a physiological upstream modulator of p53 function, ionizing radiation. A dominant negative form of p300 prevents transcriptional activation by p53, and it counteracts p53-mediated G1 arrest and apoptosis. The data implicate p300 as an important component of p53-signaling, thus providing new insight into the mechanisms of cellular proliferation. JF - Cell AU - Avantaggiati, M L AU - Ogryzko, V AU - Gardner, K AU - Giordano, A AU - Levine, A S AU - Kelly, K AD - Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/06/27/ PY - 1997 DA - 1997 Jun 27 SP - 1175 EP - 1184 VL - 89 IS - 7 SN - 0092-8674, 0092-8674 KW - Nuclear Proteins KW - 0 KW - Trans-Activators KW - Transcription Factor AP-1 KW - Transcription Factors KW - Tumor Suppressor Protein p53 KW - CREB-Binding Protein KW - EC 2.3.1.48 KW - CREBBP protein, human KW - Index Medicus KW - Animals KW - Transcription Factor AP-1 -- metabolism KW - Apoptosis -- physiology KW - Humans KW - Cell Division -- physiology KW - Breast Neoplasms KW - Mutagenesis -- physiology KW - Tumor Cells, Cultured KW - Transfection KW - Cercopithecus aethiops KW - Kidney -- cytology KW - Cell Line KW - Transcription, Genetic -- physiology KW - G1 Phase -- physiology KW - Signal Transduction -- physiology KW - Nuclear Proteins -- genetics KW - Transcription Factors -- metabolism KW - Tumor Suppressor Protein p53 -- genetics KW - Nuclear Proteins -- metabolism KW - Tumor Suppressor Protein p53 -- metabolism KW - Transcription Factors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79109198?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell&rft.atitle=Recruitment+of+p300%2FCBP+in+p53-dependent+signal+pathways.&rft.au=Avantaggiati%2C+M+L%3BOgryzko%2C+V%3BGardner%2C+K%3BGiordano%2C+A%3BLevine%2C+A+S%3BKelly%2C+K&rft.aulast=Avantaggiati&rft.aufirst=M&rft.date=1997-06-27&rft.volume=89&rft.issue=7&rft.spage=1175&rft.isbn=&rft.btitle=&rft.title=Cell&rft.issn=00928674&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-07 N1 - Date created - 1997-08-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chromosomal translocations deregulating c-myc are associated with normal immune responses. AN - 79134199; 9223664 AB - Plasmacytomas induced in BALB/c mice by pristane consistently evidence chromosomal translocations involving the c-myc gene and one of the Ig loci. This observation has lead to the suggestion that c-myc deregulation is a critical event in the generation of such tumors. However, it is not clear whether c-myc translocation is related to pristane treatment or occurs in normal lymphocyte populations nor whether such translocations occur normally, and at similar frequencies, in strains genetically resistant to plasmacytoma development, such as DBA/2. In order to address these questions, a Long Distance PCR assay with single copy sensitivity was employed to assess the frequency of c-myc/IgA translocations in normal and immunized mice of both plasmacytoma resistant and susceptible lineages in the absence of pristane treatment. Our data demonstrate that spontaneous translocations occur in normal DBA/2 and BALB/c mice with no significant differences in frequency. A 3-5-fold increase in translocation frequency was observed in mice immunized with cholera toxin, a strong stimulator of IgA responses. We conclude that c-myc deregulation by chromosomal translocation is associated with normal physiological processes of B-cell differentiation and, as such, can not be the determining factor leading to malignancy. JF - Oncogene AU - Roschke, V AU - Kopantzev, E AU - Dertzbaugh, M AU - Rudikoff, S AD - Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/06/26/ PY - 1997 DA - 1997 Jun 26 SP - 3011 EP - 3016 VL - 14 IS - 25 SN - 0950-9232, 0950-9232 KW - Immunoglobulin A KW - 0 KW - Cholera Toxin KW - 9012-63-9 KW - Index Medicus KW - Animals KW - Base Sequence KW - Cholera Toxin -- immunology KW - Molecular Sequence Data KW - Immunoglobulin A -- genetics KW - Mice KW - Genetic Predisposition to Disease KW - Mice, Inbred BALB C KW - Immunization KW - Female KW - Mice, Inbred DBA KW - Plasmacytoma -- genetics KW - Genes, myc KW - Plasmacytoma -- immunology KW - Translocation, Genetic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79134199?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chromosomal+translocations+deregulating+c-myc+are+associated+with+normal+immune+responses.&rft.au=Roschke%2C+V%3BKopantzev%2C+E%3BDertzbaugh%2C+M%3BRudikoff%2C+S&rft.aulast=Roschke&rft.aufirst=V&rft.date=1997-06-26&rft.volume=14&rft.issue=25&rft.spage=3011&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-07 N1 - Date created - 1997-08-07 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U67983; GENBANK; U67968 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Targeting nitric oxide (NO) delivery in vivo. Design of a liver-selective NO donor prodrug that blocks tumor necrosis factor-alpha-induced apoptosis and toxicity in the liver. AN - 79095558; 9207935 AB - We have designed a drug that protects the liver from apoptotic cell death by organ-selective pharmacological generation of the bioregulatory agent, nitric oxide (NO). The discovery strategy involved three steps: identifying a diazeniumdiolate ion (R2N[N(O)NO]-, where R2N = pyrrolidinyl) that spontaneously decomposes to NO with a very short half-life (3 s) at physiological pH; converting this ion to a series of potential prodrug derivatives by covalent attachment of protecting groups that we postulated might be rapidly removed by enzymes prevalent in the liver; and screening the prodrug candidates in vitro and in vivo to select a lead and to confirm the desired activity. Of five cell types examined, only cultured hepatocytes metabolized O2-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO/NO) to NO, triggering cyclic guanosine 3',5'-monophosphate (cGMP) synthesis and protecting the hepatocytes from apoptotic cell death induced by treatment with tumor necrosis factor-alpha (TNF alpha) plus actinomycin D. In vivo, V-PYRRO/NO increased liver cGMP levels while minimally affecting systemic hemodynamics, protecting rats dosed with TNF alpha plus galactosamine from apoptosis and hepatotoxicity. The results illustrate the potential utility of diazeniumdiolates for targeting NO delivery in vivo and suggest a possible therapeutic strategy for hepatic disorders such as fulminant liver failure. JF - Journal of medicinal chemistry AU - Saavedra, J E AU - Billiar, T R AU - Williams, D L AU - Kim, Y M AU - Watkins, S C AU - Keefer, L K AD - Intramural Research Support Program, SAIC Frederick, NCI-FCRDC, Maryland 21702, USA. Y1 - 1997/06/20/ PY - 1997 DA - 1997 Jun 20 SP - 1947 EP - 1954 VL - 40 IS - 13 SN - 0022-2623, 0022-2623 KW - O(2)-vinyl-1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate KW - 0 KW - Prodrugs KW - Pyrrolidines KW - Tumor Necrosis Factor-alpha KW - Nitric Oxide KW - 31C4KY9ESH KW - Galactosamine KW - 7535-00-4 KW - Cyclic GMP KW - H2D2X058MU KW - Index Medicus KW - Rats KW - Hemodynamics -- drug effects KW - Galactosamine -- pharmacology KW - Animals KW - Rats, Sprague-Dawley KW - DNA Fragmentation -- drug effects KW - Mice KW - Cyclic GMP -- biosynthesis KW - Drug Design KW - Male KW - Cell Line KW - Drug Delivery Systems KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Liver -- metabolism KW - Nitric Oxide -- metabolism KW - Pyrrolidines -- metabolism KW - Nitric Oxide -- administration & dosage KW - Prodrugs -- administration & dosage KW - Prodrugs -- chemical synthesis KW - Tumor Necrosis Factor-alpha -- toxicity KW - Liver -- drug effects KW - Prodrugs -- pharmacology KW - Apoptosis -- drug effects KW - Tumor Necrosis Factor-alpha -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79095558?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Targeting+nitric+oxide+%28NO%29+delivery+in+vivo.+Design+of+a+liver-selective+NO+donor+prodrug+that+blocks+tumor+necrosis+factor-alpha-induced+apoptosis+and+toxicity+in+the+liver.&rft.au=Saavedra%2C+J+E%3BBilliar%2C+T+R%3BWilliams%2C+D+L%3BKim%2C+Y+M%3BWatkins%2C+S+C%3BKeefer%2C+L+K&rft.aulast=Saavedra&rft.aufirst=J&rft.date=1997-06-20&rft.volume=40&rft.issue=13&rft.spage=1947&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 - 1997-08-07 N1 - Date created - 1997-08-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of murine embryonic growth by human immunodeficiency virus envelope protein and its prevention by vasoactive intestinal peptide and activity-dependent neurotrophic factor. AN - 79077458; 9185505 AB - Intrauterine growth retardation and neurodevelopmental handicaps are common among infants born to HIV-positive mothers and may be due to the actions of virions and/or maternally derived viral products. The viral envelope protein, gp120, is toxic to neurons, induces neuronal dystrophy, and retards behavioral development in neonatal rats. Vasoactive intestinal peptide, a neuropeptide regulator of early postimplantation embryonic growth, and the neuroprotective protein, activity-dependent neurotrophic factor, prevent gp120-induced neurotoxicity. Whole embryo culture of gestational day 9.5 mouse embryos was used to assess the effect of gp120 on growth. Embryos treated with gp120 exhibited a dose-dependent inhibition of growth. gp120-treated embryos (10(-8) M) grew 1.2 somites in the 6-h incubation period, compared with 3.9 somites by control embryos. Embryos treated with gp120 were significantly smaller in cross-sectional area and had significantly less DNA and protein than controls. Growth inhibition induced by gp120 was prevented by cotreatment with vasoactive intestinal peptide or activity-dependent neurotrophic factor. gp120 may play a role in the growth retardation and developmental delays experienced by infants born to HIV-positive mothers. Vasoactive intestinal peptide and related factors may provide a therapeutic strategy in preventing developmental deficits. JF - The Journal of clinical investigation AU - Dibbern, D A AU - Glazner, G W AU - Gozes, I AU - Brenneman, D E AU - Hill, J M AD - Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/06/15/ PY - 1997 DA - 1997 Jun 15 SP - 2837 EP - 2841 VL - 99 IS - 12 SN - 0021-9738, 0021-9738 KW - Adcyap1 protein, mouse KW - 0 KW - Adcyap1 protein, rat KW - Culture Media KW - HIV Envelope Protein gp120 KW - Nerve Growth Factors KW - Nerve Tissue Proteins KW - Neuropeptides KW - Neuroprotective Agents KW - Oligopeptides KW - Pituitary Adenylate Cyclase-Activating Polypeptide KW - Proteins KW - activity-dependent neurotrophic factor KW - Vasoactive Intestinal Peptide KW - 37221-79-7 KW - DNA KW - 9007-49-2 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Neuropeptides -- pharmacology KW - Nerve Growth Factors -- pharmacology KW - DNA -- metabolism KW - Mice KW - Embryo, Mammalian -- metabolism KW - Proteins -- metabolism KW - Rats KW - Rats, Sprague-Dawley KW - Culture Techniques KW - Fetal Growth Retardation -- etiology KW - Fetal Growth Retardation -- prevention & control KW - Male KW - Vasoactive Intestinal Peptide -- pharmacology KW - HIV Envelope Protein gp120 -- pharmacology KW - Embryonic and Fetal Development KW - Nerve Tissue Proteins -- pharmacology KW - Neuroprotective Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79077458?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+investigation&rft.atitle=Inhibition+of+murine+embryonic+growth+by+human+immunodeficiency+virus+envelope+protein+and+its+prevention+by+vasoactive+intestinal+peptide+and+activity-dependent+neurotrophic+factor.&rft.au=Dibbern%2C+D+A%3BGlazner%2C+G+W%3BGozes%2C+I%3BBrenneman%2C+D+E%3BHill%2C+J+M&rft.aulast=Dibbern&rft.aufirst=D&rft.date=1997-06-15&rft.volume=99&rft.issue=12&rft.spage=2837&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+investigation&rft.issn=00219738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - 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Last updated - 2017-01-18 ER - TY - JOUR T1 - Contribution of oncogenes and tumor suppressor genes to myeloid leukemia. AN - 79087158; 9196020 JF - Biochimica et biophysica acta AU - Wolff, L AD - Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, MD, USA. lwolff@helix.nih.gov Y1 - 1997/06/07/ PY - 1997 DA - 1997 Jun 07 SP - F67 EP - 104 VL - 1332 IS - 3 SN - 0006-3002, 0006-3002 KW - Index Medicus KW - Animals KW - Transformation, Genetic KW - Humans KW - Disease Models, Animal KW - Gene Expression Regulation KW - Retroviridae -- genetics KW - Myelodysplastic Syndromes -- genetics KW - Translocation, Genetic KW - Signal Transduction KW - Mutagenesis, Insertional KW - Oncogenes KW - Genes, Tumor Suppressor KW - Leukemia, Myeloid -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79087158?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochimica+et+biophysica+acta&rft.atitle=Contribution+of+oncogenes+and+tumor+suppressor+genes+to+myeloid+leukemia.&rft.au=Wolff%2C+L&rft.aulast=Wolff&rft.aufirst=L&rft.date=1997-06-07&rft.volume=1332&rft.issue=3&rft.spage=F67&rft.isbn=&rft.btitle=&rft.title=Biochimica+et+biophysica+acta&rft.issn=00063002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-07 N1 - Date created - 1997-07-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of a phenobarbital-responsive enhancer module in mouse P450 Cyp2b10 gene. AN - 79044907; 9169466 AB - Induction of drug- and carcinogen-metabolizing cytochrome P450s by xenobiotic chemicals is a common cellular defense mechanism, usually leading to increased detoxification of xenobiotics but sometimes, paradoxically, to formation of more toxic and carcinogenic metabolites. Phenobarbital (PB) is an archetypal representative for chemicals including industrial solvents, pesticides, plant products, and clinically used drugs that induce several genes within CYP subfamilies 2B, 2A, 2C, and 3A in rodents and humans. Although the transcription of these CYP genes is activated by PB, the associated molecular mechanisms have not yet been elucidated. Here we have analyzed, in detail, enhancer activity of a far upstream region of mouse Cyp2b10 gene and report a 132-base pair PB-responsive enhancer module (PBREM) with a 33-base pair core element containing binding sites for nuclear factor I- and nuclear receptor-like factors. Mutations of these binding sites abolish the ability of PBREM to respond to inducers in mouse primary hepatocytes. JF - The Journal of biological chemistry AU - Honkakoski, P AU - Negishi, M AD - Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/06/06/ PY - 1997 DA - 1997 Jun 06 SP - 14943 EP - 14949 VL - 272 IS - 23 SN - 0021-9258, 0021-9258 KW - CCAAT-Enhancer-Binding Proteins KW - 0 KW - DNA-Binding Proteins KW - NFI Transcription Factors KW - Nuclear Proteins KW - Receptors, Cytoplasmic and Nuclear KW - Recombinant Proteins KW - Transcription Factors KW - Y-Box-Binding Protein 1 KW - YBX1 protein, human KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Steroid Hydroxylases KW - EC 1.14.- KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - Cyp2b10 protein, mouse KW - Cytochrome P450 Family 2 KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Animals KW - Base Composition KW - Recombinant Proteins -- biosynthesis KW - Transcription Factors -- metabolism KW - Cell Nucleus -- metabolism KW - Humans KW - Mice KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Transfection KW - Cells, Cultured KW - Receptors, Cytoplasmic and Nuclear -- metabolism KW - DNA Footprinting KW - Molecular Sequence Data KW - Mice, Inbred C57BL KW - Enzyme Induction KW - Male KW - DNA-Binding Proteins -- metabolism KW - Phenobarbital -- pharmacology KW - Liver -- enzymology KW - Cytochrome P-450 Enzyme System -- genetics KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Enhancer Elements, Genetic -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79044907?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Characterization+of+a+phenobarbital-responsive+enhancer+module+in+mouse+P450+Cyp2b10+gene.&rft.au=Honkakoski%2C+P%3BNegishi%2C+M&rft.aulast=Honkakoski&rft.aufirst=P&rft.date=1997-06-06&rft.volume=272&rft.issue=23&rft.spage=14943&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-26 N1 - Date created - 1997-06-26 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U67059; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Determinants of chromatin disruption and transcriptional regulation instigated by the thyroid hormone receptor: hormone-regulated chromatin disruption is not sufficient for transcriptional activation. AN - 79116382; 9214633 AB - Chromatin disruption and transcriptional activation are both thyroid hormone-dependent processes regulated by the heterodimer of thyroid hormone receptor and 9-cis retinoic acid receptor (TR-RXR). In the absence of hormone, TR-RXR binds to nucleosomal DNA, locally disrupts histone-DNA contacts and generates a DNase I-hypersensitive site. Chromatin-bound unliganded TR-RXR silences transcription of the Xenopus TRbetaA gene within a canonical nucleosomal array. On addition of hormone, the receptor directs the extensive further disruption of chromatin structure over several hundred base pairs of DNA and activates transcription. We define a domain of the TR protein necessary for directing this extensive hormone-dependent chromatin disruption. Particular TR-RXR heterodimers containing mutations in this domain are able to bind both hormone and their thyroid hormone receptor recognition element (TRE) within chromatin, yet are unable to direct the extensive hormone-dependent disruption of chromatin or to activate transcription. We distinguish the hormone-dependent disruption of chromatin and transcriptional activation as independently regulated events through the mutagenesis of basal promoter elements and by altering the position and number of TREs within the TRbetaA promoter. Chromatin disruption alone on a minichromosome is shown to be insufficient for transcriptional activation of the TRbetaA gene. JF - The EMBO journal AU - Wong, J AU - Shi, Y B AU - Wolffe, A P AD - Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892-5431, USA. Y1 - 1997/06/02/ PY - 1997 DA - 1997 Jun 02 SP - 3158 EP - 3171 VL - 16 IS - 11 SN - 0261-4189, 0261-4189 KW - Chromatin KW - 0 KW - Ligands KW - Nucleosomes KW - Receptors, Retinoic Acid KW - Receptors, Thyroid Hormone KW - Triiodothyronine KW - 06LU7C9H1V KW - Index Medicus KW - Animals KW - Nucleosomes -- metabolism KW - Molecular Sequence Data KW - Xenopus KW - Transcription, Genetic KW - Amino Acid Sequence KW - Protein Binding KW - Mutagenesis KW - Binding Sites KW - Receptors, Retinoic Acid -- metabolism KW - Chromatin -- metabolism KW - Triiodothyronine -- metabolism KW - Receptors, Thyroid Hormone -- metabolism KW - Receptors, Thyroid Hormone -- genetics KW - Transcriptional Activation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79116382?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+EMBO+journal&rft.atitle=Determinants+of+chromatin+disruption+and+transcriptional+regulation+instigated+by+the+thyroid+hormone+receptor%3A+hormone-regulated+chromatin+disruption+is+not+sufficient+for+transcriptional+activation.&rft.au=Wong%2C+J%3BShi%2C+Y+B%3BWolffe%2C+A+P&rft.aulast=Wong&rft.aufirst=J&rft.date=1997-06-02&rft.volume=16&rft.issue=11&rft.spage=3158&rft.isbn=&rft.btitle=&rft.title=The+EMBO+journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-31 N1 - Date created - 1997-07-31 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1975 May;72(5):1843-7 [168578] Mol Cell Biol. 1995 Mar;15(3):1499-512 [7862143] Cell. 1984 Aug;38(1):29-38 [6088072] Cell. 1985 Oct;42(3):799-808 [2996776] EMBO J. 1986 Oct;5(10):2681-7 [3023055] EMBO J. 1986 Oct;5(10):2689-96 [3536481] EMBO J. 1987 Aug;6(8):2321-8 [2822386] Science. 1988 May 13;240(4854):889-95 [3283939] Cell. 1989 May 5;57(3):449-57 [2541913] Nature. 1989 Jul 20;340(6230):242-4 [2569164] Nature. 1989 Aug 24;340(6235):653-6 [2549424] Cell. 1989 Nov 17;59(4):697-708 [2555064] Cell. 1990 Mar 9;60(5):719-31 [2155706] Mol Cell Biol. 1990 May;10(5):2247-60 [2183026] Proc Natl Acad Sci U S A. 1990 Sep;87(18):7090-4 [2402492] EMBO J. 1991 Feb;10(2):361-8 [1899374] EMBO J. 1991 Nov;10(11):3419-28 [1717265] J Biol Chem. 1992 Jan 15;267(2):733-8 [1730664] Nucleic Acids Res. 1992 Jan 25;20(2):273-8 [1311071] EMBO J. 1992 Mar;11(3):1015-23 [1347744] Genes Dev. 1992 Mar;6(3):411-25 [1547940] Science. 1992 Dec 4;258(5088):1598-604 [1360703] J Biol Chem. 1993 Jan 25;268(3):2021-8 [8420976] J Mol Biol. 1993 Jun 5;231(3):658-67 [8515443] Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10668-72 [7902566] Mol Cell Biol. 1994 Jan;14(1):32-41 [8264599] J Mol Biol. 1994 Feb 25;236(3):685-90 [8114086] Science. 1994 Jun 3;264(5164):1455-8 [8197458] Science. 1994 Jul 1;265(5168):53-60 [8016655] EMBO J. 1994 Jul 1;13(13):3039-49 [8039499] Nature. 1995 Mar 2;374(6517):91-4 [7870181] EMBO J. 1995 Apr 18;14(8):1737-51 [7737125] EMBO J. 1995 May 1;14(9):2020-33 [7744009] Mol Endocrinol. 1995 Jan;9(1):34-43 [7760849] EMBO J. 1995 May 15;14(10):2209-16 [7774579] Mol Endocrinol. 1995 Feb;9(2):243-54 [7776974] J Biol Chem. 1995 Aug 4;270(31):18479-83 [7629175] Nature. 1995 Oct 5;377(6548):454-7 [7566127] Genes Dev. 1995 Nov 1;9(21):2696-711 [7590246] Genes Dev. 1995 Nov 15;9(22):2770-9 [7590252] Nature. 1995 Dec 14;378(6558):690-7 [7501015] Cell. 1996 Jan 26;84(2):235-44 [8565069] Cell. 1996 Mar 22;84(6):843-51 [8601308] Science. 1996 Apr 19;272(5260):408-11 [8602529] Nature. 1996 Sep 5;383(6595):99-103 [8779723] Cell. 1996 Nov 29;87(5):953-9 [8945521] EMBO J. 1988 Jul;7(7):2221-8 [3046934] Science. 1992 Mar 20;255(5051):1573-6 [1347958] Methods Cell Biol. 1991;36:657-62 [1811156] Mol Cell Biol. 1994 Sep;14(9):5756-65 [8065310] Genes Dev. 1994 Jun 15;8(12):1400-10 [7926740] J Biol Chem. 1994 Oct 7;269(40):24699-705 [7929143] EMBO J. 1994 Oct 17;13(20):4856-62 [7957055] Mol Cell Biol. 1995 Jan;15(1):76-86 [7799971] Cell. 1983 May;33(1):65-76 [6088056] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Impaired host defense, hematopoiesis, granulomatous inflammation and type 1-type 2 cytokine balance in mice lacking CC chemokine receptor 1. AN - 79035860; 9166425 AB - CC chemokine receptor 1 (CCR1) is expressed in neutrophils, monocytes, lymphocytes, and eosinophils, and binds the leukocyte chemoattractant and hematopoiesis regulator macrophage inflammatory protein (MIP)-1alpha, as well as several related CC chemokines. Four other CCR subtypes are known; their leukocyte and chemokine specificities overlap with, but are not identical to, CCR1, suggesting that CCR1 has both redundant and specific biologic roles. To test this, we have developed CCR1-deficient mice (-/-) by targeted gene disruption. Although the distribution of mature leukocytes was normal, steady state and induced trafficking and proliferation of myeloid progenitor cells were disordered in -/- mice. Moreover, mature neutrophils from -/- mice failed to chemotax in vitro and failed to mobilize into peripheral blood in vivo in response to MIP-1alpha. Consistent with this, -/- mice had accelerated mortality when challenged with Aspergillus fumigatus, a fungus controlled principally by neutrophils. To test the role of CCR1 in granuloma formation, we injected Schistosoma mansoni eggs intravenously, and observed a 40% reduction in the size of lung granulomas in -/- mice compared to +/+ littermates. This was associated with increased interferon-gamma and decreased interleukin-4 production in -/- versus +/+ lung lymph node cells stimulated with egg-specific antigen, suggesting that CCR1 influences the inflammatory response not only through direct effects on leukocyte chemotaxis, but also through effects on the type 1-type 2 cytokine balance. Thus CCR1 has nonredundant functions in hematopoiesis, host defense, and inflammation. JF - The Journal of experimental medicine AU - Gao, J L AU - Wynn, T A AU - Chang, Y AU - Lee, E J AU - Broxmeyer, H E AU - Cooper, S AU - Tiffany, H L AU - Westphal, H AU - Kwon-Chung, J AU - Murphy, P M AD - Laboratory of Host Defenses,National Institute of Allergy and Infectio us Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/06/02/ PY - 1997 DA - 1997 Jun 02 SP - 1959 EP - 1968 VL - 185 IS - 11 SN - 0022-1007, 0022-1007 KW - Ccr1 protein, mouse KW - 0 KW - Chemokine CCL3 KW - Chemokine CCL4 KW - Cytokines KW - Macrophage Inflammatory Proteins KW - Receptors, CCR1 KW - Receptors, Chemokine KW - Receptors, Cytokine KW - Interleukin-4 KW - 207137-56-2 KW - Interferon-gamma KW - 82115-62-6 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Macrophage Inflammatory Proteins -- pharmacology KW - Mice KW - Hematopoietic Stem Cells -- physiology KW - Mutagenesis -- genetics KW - Mice, Transgenic KW - Chemotaxis, Leukocyte KW - Calcium -- metabolism KW - Interleukin-4 -- metabolism KW - Aspergillus fumigatus KW - Mice, Inbred C57BL KW - Interferon-gamma -- metabolism KW - Gene Targeting KW - Schistosomiasis mansoni -- immunology KW - Macrophages -- metabolism KW - Cell Division KW - Receptors, Cytokine -- physiology KW - Receptors, Cytokine -- deficiency KW - Neutrophils -- immunology KW - Receptors, Cytokine -- genetics KW - Granuloma -- immunology KW - Cytokines -- metabolism KW - Hematopoiesis KW - Aspergillosis -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79035860?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Impaired+host+defense%2C+hematopoiesis%2C+granulomatous+inflammation+and+type+1-type+2+cytokine+balance+in+mice+lacking+CC+chemokine+receptor+1.&rft.au=Gao%2C+J+L%3BWynn%2C+T+A%3BChang%2C+Y%3BLee%2C+E+J%3BBroxmeyer%2C+H+E%3BCooper%2C+S%3BTiffany%2C+H+L%3BWestphal%2C+H%3BKwon-Chung%2C+J%3BMurphy%2C+P+M&rft.aulast=Gao&rft.aufirst=J&rft.date=1997-06-02&rft.volume=185&rft.issue=11&rft.spage=1959&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 - 1997-06-30 N1 - Date created - 1997-06-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: N Engl J Med. 1976 Aug 5;295(6):302-4 [778616] Science. 1995 Sep 15;269(5230):1583-5 [7667639] Crit Rev Oncol Hematol. 1988;8(3):173-226 [3048745] J Exp Med. 1989 Nov 1;170(5):1583-94 [2478652] Nature. 1990 Mar 29;344(6265):442-4 [2320111] Blood. 1990 Sep 15;76(6):1110-6 [2205307] Cell. 1991 Jun 28;65(7):1153-63 [2065352] Cell. 1992 Jun 12;69(6):915-26 [1606615] J Immunol. 1992 Aug 1;149(3):1004-9 [1634758] Cell. 1993 Feb 12;72(3):415-25 [7679328] J Immunol. 1993 Apr 15;150(8 Pt 1):3448-58 [7682242] J Exp Med. 1993 May 1;177(5):1421-7 [7683036] J Immunol. 1993 May 15;150(10):4550-60 [8482847] J Exp Med. 1993 Jun 1;177(6):1551-9 [8496676] J Immunol. 1993 Aug 1;151(3):1430-40 [8335939] J Biol Chem. 1993 Jul 25;268(21):15419-24 [8340371] Science. 1993 Aug 27;261(5125):1182-4 [7689250] Exp Hematol. 1994 Feb;22(2):186-93 [8299739] Adv Immunol. 1994;55:97-179 [8304236] Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2752-6 [8146186] J Exp Med. 1994 May 1;179(5):1551-61 [7909326] Science. 1994 Jul 29;265(5172):682-4 [8036519] J Biol Chem. 1994 Oct 21;269(42):26381-9 [7929358] J Biol Chem. 1994 Nov 18;269(46):28539-42 [7961796] J Immunol. 1995 May 15;154(10):5376-83 [7730638] J Leukoc Biol. 1995 May;57(5):752-62 [7539029] Blood. 1995 Jun 15;85(12):3412-5 [7540061] J Immunol. 1995 Nov 15;155(10):5003-10 [7594507] J Immunol. 1995 Dec 1;155(11):5299-305 [7594543] J Biol Chem. 1995 Dec 15;270(50):29671-5 [8530354] Biochem Biophys Res Commun. 1996 Jun 25;223(3):679-84 [8687456] Science. 1996 Jun 28;272(5270):1955-8 [8658171] J Exp Med. 1996 Jun 1;183(6):2437-48 [8676064] J Leukoc Biol. 1996 Jul;60(1):147-52 [8699119] Nature. 1996 Aug 15;382(6592):635-8 [8757135] Cell. 1996 Aug 9;86(3):367-77 [8756719] Nature. 1996 Aug 22;382(6593):722-5 [8751444] Science. 1996 Sep 27;273(5283):1856-62 [8791590] Cytokine Growth Factor Rev. 1996 Jun;7(1):47-64 [8864354] J Exp Med. 1996 Nov 1;184(5):1825-32 [8920870] J Leukoc Biol. 1996 Nov;60(5):658-66 [8929558] Mol Med. 1997 Jan;3(1):23-36 [9132277] Blood Cells Mol Dis. 1998 Mar;24(1):14-30 [9516378] J Biol Chem. 1995 Jul 21;270(29):17494-501 [7542241] J Immunol. 1995 Aug 15;155(4):2158-64 [7636264] J Biol Chem. 1995 Aug 18;270(33):19495-500 [7642634] DNA Cell Biol. 1995 Aug;14(8):673-80 [7646814] Nat Genet. 1995 Jun;10(2):224-8 [7663520] J Exp Med. 1988 Feb 1;167(2):570-81 [3279154] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Frequency-dependent changes of regional cerebral blood flow during finger movements: functional MRI compared to PET. AN - 85274456; pmid-9236723 AB - To evaluate the effect of the repetition rate of a simple movement on the magnitude of neuronal recruitment in the primary sensorimotor cortex, we used a blood flow-sensitive, echo planar functional magnetic resonance imaging (fMRI) sequence in six normal volunteers. Three of the volunteers also had [15O]water positron emission tomography (PET) studies using the same paradigm. Previous PET studies had shown an increase in regional CBF (rCBF) with movement frequencies up to 2 Hz and then a plateau of regional cerebral blood flow (rCBF) at faster frequencies. To evaluate the extent of the activation, the correlation coefficient (cc) of the Fourier-transformed time-signal intensity change with the Fourier-transformed reference function was calculated pixel by pixel. The degree of activation was measured as the signal percent change of each region of interest with a cc > 0.5. The left primary sensorimotor cortex was constantly activated at 1, 1.5, 2, and 4 Hz, while there was only inconsistent activation at 0.25 and 0.5 Hz. Percent change in signal intensity linearly increased from 1 to 4 Hz. Area of activation increased up to 2 Hz and showed a tendency to decrease at higher frequencies. Individual analysis of PET data showed activation in the same location as that revealed by fMRI. The combination of progressively increasing signal intensity with an area that increases to 2 Hz and declines at faster frequencies explains the PET finding of plateau of rCBF at the faster frequencies. Functional magnetic resonance imaging shows similar results to PET, but is better able to dissociate area and magnitude of change. JF - Journal of Cerebral Blood Flow and Metabolism AU - Sadato, N AU - Ibañez V AU - Campbell, G AU - Deiber, M P AU - Le Bihan D AU - Hallett, M AD - Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1428, USA. PY - 1997 SP - 670 EP - 679 VL - 17 IS - 6 SN - 0271-678X, 0271-678X KW - Reference Values KW - Chi-Square Distribution KW - Human KW - Brain KW - Cerebrovascular Circulation KW - Fourier Analysis KW - Movement KW - Cerebral Cortex KW - Fingers KW - Comparative Study KW - Adult KW - Recruitment (Neurology) KW - Male KW - Female KW - Magnetic Resonance Imaging KW - Tomography, Emission-Computed UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85274456?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Cerebral+Blood+Flow+and+Metabolism&rft.atitle=Frequency-dependent+changes+of+regional+cerebral+blood+flow+during+finger+movements%3A+functional+MRI+compared+to+PET.&rft.au=Sadato%2C+N%3BIba%C3%B1ez+V%3BCampbell%2C+G%3BDeiber%2C+M+P%3BLe+Bihan+D%3BHallett%2C+M&rft.aulast=Sadato&rft.aufirst=N&rft.date=1997-06-01&rft.volume=17&rft.issue=6&rft.spage=670&rft.isbn=&rft.btitle=&rft.title=Journal+of+Cerebral+Blood+Flow+and+Metabolism&rft.issn=0271678X&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Assessment of whole-brain vasodilatory capacity with acetazolamide challenge at 1.5 T using dynamic contrast imaging with frequency-shifted burst. AN - 85264934; pmid-9194443 AB - PURPOSE: To determine whether whole-brain acetazolamide-induced changes in regional cerebral blood volume (rCBV) can be assessed on a conventional gradient 1.5-T MR system using 3-D dynamic susceptibility contrast-enhanced MR imaging. METHODS: A 3-D frequency-shifted (FS) burst technique was used to assess the intravascular first pass of contrast agent. Changes in rCBV were calculated in 40 volunteers before and after acetazolamide (n = 30) or saline (n = 10) injection using customized analysis software on an independent workstation. A single-section gradient-echo technique with better spatial resolution was used in one additional volunteer to examine the effect of partial volume averaging on calculation of absolute rCBV. RESULTS: A statistically significant increase in rCBV (gray matter = 23%, white master = 32.5%) was noted after acetazolamide compared with saline. Baseline fractional CBVs were 22% +/- 3% for gray matter and 12% +/- 2% for white matter. Partial volume averaging was probably responsible for a systematic but linear overestimation of absolute rCBV. CONCLUSION: Acetazolamide-induced changes in rCBV can be assessed using 3-D dynamic susceptibility contrast-enhanced MR imaging with FS-burst on a conventional gradient 1.5-T MR system. Values obtained with this technique overestimate absolute rCBV but are systematically biased and can be used for intersubject and intrasubject ratio comparisons. JF - AJNR. American Journal of Neuroradiology AU - Petrella, J R AU - DeCarli, C AU - Dagli, M AU - Duyn, J H AU - Grandin, C B AU - Frank, J A AU - Hoffman, E A AU - Theodore, W H AD - Laboratory of Diagnostic Radiology Research, National Institutes of Health, Bethesda, Md 20892, USA. PY - 1997 SP - 1153 EP - 1161 VL - 18 IS - 6 SN - 0195-6108, 0195-6108 KW - Magnetic Resonance Imaging KW - Vasodilator Agents KW - Organometallic Compounds KW - Human KW - Acetazolamide KW - Brain KW - Aged KW - Contrast Media KW - Regional Blood Flow KW - Drug Combinations KW - Pentetic Acid KW - Gadolinium DTPA KW - Aged, 80 and over KW - Vasodilation KW - Meglumine KW - Adult KW - Middle Age KW - Support, Non-U.S. Gov't KW - Image Processing, Computer-Assisted KW - Male KW - Female UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85264934?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AJNR.+American+Journal+of+Neuroradiology&rft.atitle=Assessment+of+whole-brain+vasodilatory+capacity+with+acetazolamide+challenge+at+1.5+T+using+dynamic+contrast+imaging+with+frequency-shifted+burst.&rft.au=Petrella%2C+J+R%3BDeCarli%2C+C%3BDagli%2C+M%3BDuyn%2C+J+H%3BGrandin%2C+C+B%3BFrank%2C+J+A%3BHoffman%2C+E+A%3BTheodore%2C+W+H&rft.aulast=Petrella&rft.aufirst=J&rft.date=1997-06-01&rft.volume=18&rft.issue=6&rft.spage=1153&rft.isbn=&rft.btitle=&rft.title=AJNR.+American+Journal+of+Neuroradiology&rft.issn=01956108&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Unnatural practices, unspeakable actions: a study of delayed auditory feedback in schizophrenia. AN - 85239541; pmid-9167517 AB - OBJECTIVE: It has been suggested that auditory hallucinations and delusions of control in persons with schizophrenia could involve a disconnection between an "intention center" and a "monitoring center." METHOD: To test this model directly, the authors used a delayed auditory feedback paradigm in which the subject hears his or her own speech delayed electronically by a fraction of a second. In normal, subjects this produces dysfluency, which is thought to occur because an expectancy about the perceptual arrival of speech, formed in a monitoring center on the basis of corollary discharge from an intention center, is violated. If, however, a disconnection were present in schizophrenia, such an expectancy would not be formed; hence, less dysfluency should occur. Fifteen patients with chronic schizophrenia (10 of whom experienced auditory hallucinations and/or delusions of control) and 19 normal subjects were studied. RESULTS: Rather than exhibiting less dysfluency than the normal subjects, patients with delusions and/or hallucinations exhibited significantly more dysfluency. CONCLUSIONS: These results do not support a cognitive model of disconnection. JF - The American Journal of Psychiatry AU - Goldberg, T E AU - Gold, J M AU - Coppola, R AU - Weinberger, D R AD - Clinical Brain Disorders Branch, NIMH, Washington, DC, USA. PY - 1997 SP - 858 EP - 860 VL - 154 IS - 6 SN - 0002-953X, 0002-953X KW - Schizophrenia KW - Models, Psychological KW - Delusions KW - Human KW - Adult KW - Hallucinations KW - Female KW - Male KW - Schizophrenic Psychology KW - Feedback KW - Speech KW - Auditory Perception UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85239541?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+Journal+of+Psychiatry&rft.atitle=Unnatural+practices%2C+unspeakable+actions%3A+a+study+of+delayed+auditory+feedback+in+schizophrenia.&rft.au=Goldberg%2C+T+E%3BGold%2C+J+M%3BCoppola%2C+R%3BWeinberger%2C+D+R&rft.aulast=Goldberg&rft.aufirst=T&rft.date=1997-06-01&rft.volume=154&rft.issue=6&rft.spage=858&rft.isbn=&rft.btitle=&rft.title=The+American+Journal+of+Psychiatry&rft.issn=0002953X&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Glutamate receptors are selectively targeted to postsynaptic sites in neurons. AN - 85161062; pmid-9208861 AB - The objective of the present study was to determine if a neuron that expresses multiple glutamate receptors targets the same receptors to all glutamatergic postsynaptic populations, or if the receptors are differentially targeted to specific postsynaptic populations. As a model for this study, we chose the fusiform cell of the dorsal cochlear nucleus. This neuron expresses multiple glutamate receptors and receives two distinct glutamatergic inputs: parallel fibers synapse on apical dendrites, and auditory nerve fibers synapse on basal dendrites. Pre- and postembedding immunocytochemistry were combined with retrograde tracing to identify the receptors expressed on postsynaptic membranes of parallel fiber and auditory nerve synapses. Most receptors were found at both populations of synapses, but the AMPA receptor subunit, GluR4, and the metabotropic receptor, mGluR1 alpha, were found only at the auditory nerve synapse. These results demonstrate that glutamate receptors are targeted to specific postsynaptic populations of glutamatergic synapses. JF - Neuron AU - Rubio, M E AU - Wenthold, R J AD - Laboratory of Neurochemistry, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1997 SP - 939 EP - 950 VL - 18 IS - 6 SN - 0896-6273, 0896-6273 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85161062?accountid=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=Neuron&rft.atitle=Glutamate+receptors+are+selectively+targeted+to+postsynaptic+sites+in+neurons.&rft.au=Rubio%2C+M+E%3BWenthold%2C+R+J&rft.aulast=Rubio&rft.aufirst=M&rft.date=1997-06-01&rft.volume=18&rft.issue=6&rft.spage=939&rft.isbn=&rft.btitle=&rft.title=Neuron&rft.issn=08966273&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Characterizing swallowing abnormalities in progressive supranuclear palsy. AN - 85160192; pmid-9191782 AB - The dysphagia that occurs as an early sign of progressive supranuclear palsy (PSP), and which may predispose patients to aspiration pneumonia, has never been fully characterized. We evaluated 27 patients (mean +/- SEM: age, 64.9 +/- 1 years; symptom duration, 52 +/- 5 months) who met the clinical National Institute of Neurological Disorders and Stroke and Society for PSP (NINDS-SPSP) criteria for possible or probable PSP, with a swallowing questionnaire, an oral motor and speech examination, and either a modified barium swallow or ultrasound studies. Twenty-eight age- and sex-matched healthy controls (age, 65.6 +/- 1.5 years) were also evaluated with the questionnaire, oral examination, and the ultrasound study. We used ANOVA statistics to evaluate differences between groups; nonparametric correlations to assess associations between swallowing and motor and cognitive abnormalities; and logistic regression analysis to determine if the items of the questionnaire or oral examination predicted ultrasound or modified barium swallow abnormalities. While PSP patients had at least one complaint on the swallowing questionnaire (mean, 6.6), healthy controls had fewer and less relevant complaints (0.3). Patients with moderate-to-severe cognitive disabilities had significantly more complaints of dysphagia than those with mild or no impairment. PSP patients' oral motor skills and speech were mildly impaired but significantly different from those of controls. In the ultrasound studies, PSP patients had significantly fewer continuous swallows and required a longer duration to complete their swallows than did healthy controls. They also had mild-to-moderate abnormalities in the modified barium swallow study. The swallowing questionnaire, oral motor examination, and speech production examination accurately predicted the abnormalities detected with the swallowing studies. While 75% of patients had abnormal speech, all but one had abnormal swallowing studies. Thus, although dysphagia is associated with dysarthria, the two conditions are not always paired in the same patient. Our results suggest that the swallowing questionnaire and oral motor examination are an easy and cost-effective method to predict the swallowing disturbances in PSP. JF - Neurology AU - Litvan, I AU - Sastry, N AU - Sonies, B C AD - Neuroepidemiology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-9130, USA. PY - 1997 SP - 1654 EP - 1662 VL - 48 IS - 6 SN - 0028-3878, 0028-3878 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85160192?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=Characterizing+swallowing+abnormalities+in+progressive+supranuclear+palsy.&rft.au=Litvan%2C+I%3BSastry%2C+N%3BSonies%2C+B+C&rft.aulast=Litvan&rft.aufirst=I&rft.date=1997-06-01&rft.volume=48&rft.issue=6&rft.spage=1654&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Synthesis of the dodecasaccharide fragment representing the O-polysaccharide of Vibrio cholerae O:1, serotype Ogawa, bearing an aglycon offering flexibility for chemical linking to proteins AN - 815538254; 13879701 AB - Two azidohexasaccharide building blocks, of which the glycosyl acceptor was the 5-(methoxycarbonyl)pentyl glycoside, were coupled using the trichloroacetimidate technology. The 12 azido functions present in the dodecasaccharide thus formed were then converted to amino groups using hydrogen sulfide as a reducing reagent. Subsequent N-acylation with 4-O-benzyl-L-glycero-tetronic acid, followed by catalytic debenzylation yielded the desired spacer-equipped, title dodecasaccharide. JF - Glycoconjugate Journal AU - Ogawa, Yuji AU - Kovac, Pavol AD - NIDDK, National Institutes of Health, 8 Center Drive, Bethesda, Maryland, 20892-0815, USA Y1 - 1997/06// PY - 1997 DA - June 1997 SP - 433 EP - 438 PB - Springer-Verlag, P.O. Box 2485 Secaucus NJ 07096-2485 USA VL - 14 IS - 4 SN - 0282-0080, 0282-0080 KW - ASFA 3: Aquatic Pollution & Environmental Quality; ASFA 1: Biological Sciences & Living Resources; Microbiology Abstracts B: Bacteriology KW - Vibrio cholerae KW - Glycosides KW - glycoconjugates KW - Amino groups KW - Serotypes KW - glycosides KW - Flexibility KW - Hydrogen sulphide KW - Proteins KW - Hydrogen sulfide KW - Dodecasaccharides KW - Q1 08201:General KW - J 02490:Miscellaneous KW - Q5 08524:Public health, medicines, dangerous organisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/815538254?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Glycoconjugate+Journal&rft.atitle=Synthesis+of+the+dodecasaccharide+fragment+representing+the+O-polysaccharide+of+Vibrio+cholerae+O%3A1%2C+serotype+Ogawa%2C+bearing+an+aglycon+offering+flexibility+for+chemical+linking+to+proteins&rft.au=Ogawa%2C+Yuji%3BKovac%2C+Pavol&rft.aulast=Ogawa&rft.aufirst=Yuji&rft.date=1997-06-01&rft.volume=14&rft.issue=4&rft.spage=433&rft.isbn=&rft.btitle=&rft.title=Glycoconjugate+Journal&rft.issn=02820080&rft_id=info:doi/10.1023%2FA%3A1018591132723 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-11-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Glycosides; Hydrogen sulphide; Flexibility; Proteins; Amino groups; glycoconjugates; Serotypes; glycosides; Hydrogen sulfide; Dodecasaccharides; Vibrio cholerae DO - http://dx.doi.org/10.1023/A:1018591132723 ER - TY - JOUR T1 - Assessment of motor and process skills as a measure of IADL functioning in pharmacologic studies of people with Alzheimer's disease: a pilot study. AN - 79304843; 9309491 AB - The purpose of this pilot study was to evaluate the usefulness of the Assessment of Motor and Process Skills (AMPS) as an outcome measure of instrumental activities of daily living (IADL) in pharmacologic studies of people with Alzheimer's disease. The AMPS simultaneously measures motor and process skills and their effect on the ability of the person to perform familiar IADL tasks. We administered the AMPS to 11 Alzheimer inpatients in a 3 1/2-month, double-blind, placebo-controlled, crossover study of fluoxetine and selegiline administered as single agents and in combination with physostigmine. Results indicated that there was a significant difference in IADL ability among study conditions for process skills, but not for motor skills, thereby suggesting that the AMPS is useful as a sensitive outcome measure of IADL ability in drug trials with this population. JF - International psychogeriatrics AU - Oakley, F AU - Sunderland, T AD - Occupational Therapy Section, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892-1604, USA. Y1 - 1997/06// PY - 1997 DA - June 1997 SP - 197 EP - 206 VL - 9 IS - 2 SN - 1041-6102, 1041-6102 KW - Nootropic Agents KW - 0 KW - Fluoxetine KW - 01K63SUP8D KW - Selegiline KW - 2K1V7GP655 KW - Physostigmine KW - 9U1VM840SP KW - Index Medicus KW - Drug Therapy, Combination KW - Reproducibility of Results KW - Double-Blind Method KW - Humans KW - Treatment Outcome KW - Cross-Over Studies KW - Aged KW - Pilot Projects KW - Psychometrics KW - Male KW - Female KW - Neuropsychological Tests -- statistics & numerical data KW - Fluoxetine -- adverse effects KW - Selegiline -- administration & dosage KW - Alzheimer Disease -- drug therapy KW - Nootropic Agents -- administration & dosage KW - Physostigmine -- administration & dosage KW - Activities of Daily Living -- psychology KW - Nootropic Agents -- adverse effects KW - Alzheimer Disease -- classification KW - Alzheimer Disease -- diagnosis KW - Selegiline -- adverse effects KW - Fluoxetine -- administration & dosage KW - Motor Skills -- drug effects KW - Activities of Daily Living -- classification KW - Problem Solving -- drug effects KW - Physostigmine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79304843?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+psychogeriatrics&rft.atitle=Assessment+of+motor+and+process+skills+as+a+measure+of+IADL+functioning+in+pharmacologic+studies+of+people+with+Alzheimer%27s+disease%3A+a+pilot+study.&rft.au=Oakley%2C+F%3BSunderland%2C+T&rft.aulast=Oakley&rft.aufirst=F&rft.date=1997-06-01&rft.volume=9&rft.issue=2&rft.spage=197&rft.isbn=&rft.btitle=&rft.title=International+psychogeriatrics&rft.issn=10416102&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-04 N1 - Date created - 1997-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Model-based approaches to studying fertility and contraceptive efficacy. AN - 79265826; 9288326 AB - Statistical methods recently developed to aid in identifying environmental exposures with reproductive toxicity can also be applied to trials of interventions undertaken specifically to impair fertility, i.e. methods of contraception. Although only applicable in a trial that includes a reliable benchmark for identifying the day of ovulation, the proposed measures of contraceptive efficacy derived from such a trial offer certain interpretive advantages over the more traditional approaches of evaluating contraceptives. Extensions of the same models also allow one to evaluate efficacy under any assumed pattern of imperfect use. One can also evaluate methods based on biomarkers for the fertile phase of the cycle, such as hydration of the cervical mucus, that may prove to be enormously helpful to couples who wish to use periodic abstinence as their method. In prospective studies of fertility, couples who occasionally use a barrier method should not be excluded from the study, but can be retained, without biasing the estimates for fertility parameters. JF - Advances in contraception : the official journal of the Society for the Advancement of Contraception AU - Weinberg, C R AU - Zhou, H AD - Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. PY - 1997 SP - 97 EP - 103 VL - 13 IS - 2-3 SN - 0267-4874, 0267-4874 KW - Index Medicus KW - Humans KW - Models, Biological KW - Female KW - Fertility KW - Contraception -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79265826?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+contraception+%3A+the+official+journal+of+the+Society+for+the+Advancement+of+Contraception&rft.atitle=Model-based+approaches+to+studying+fertility+and+contraceptive+efficacy.&rft.au=Weinberg%2C+C+R%3BZhou%2C+H&rft.aulast=Weinberg&rft.aufirst=C&rft.date=1997-06-01&rft.volume=13&rft.issue=2-3&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=Advances+in+contraception+%3A+the+official+journal+of+the+Society+for+the+Advancement+of+Contraception&rft.issn=02674874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-15 N1 - Date created - 1997-10-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 12th meeting of the Scientific Group on Methodologies for the Safety Evaluation of Chemicals: susceptibility to environmental hazards. AN - 79189459; 9255554 AB - The 12th meeting of the Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SGOMSEC) considered the topic of methodologies for determining human and ecosystem susceptibility to environmental hazards. The report prepared at the meeting describes measurement of susceptibility through the use of biological markers of exposure, biological markers of effect, and biomarkers directly indicative of susceptibility of humans or of ecosystems. The utility and validity of these biological markers for the study of susceptibility are evaluated, as are opportunities for developing newer approaches for the study of humans or of ecosystems. For the first time a SGOMSEC workshop also formally considered the issue of ethics in relation to methodology, an issue of particular concern for studies of susceptibility. JF - Environmental health perspectives AU - Barrett, J C AU - Vainio, H AU - Peakall, D AU - Goldstein, B D AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. Y1 - 1997/06// PY - 1997 DA - June 1997 SP - 699 EP - 737 VL - 105 Suppl 4 SN - 0091-6765, 0091-6765 KW - Biomarkers KW - 0 KW - DNA Adducts KW - Hazardous Substances KW - Index Medicus KW - Gene Expression -- drug effects KW - Ecosystem KW - Animals KW - DNA Adducts -- analysis KW - Humans KW - Ethics KW - Mutation KW - Environmental Monitoring -- methods KW - Hazardous Substances -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79189459?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=Environmental+health+perspectives&rft.atitle=12th+meeting+of+the+Scientific+Group+on+Methodologies+for+the+Safety+Evaluation+of+Chemicals%3A+susceptibility+to+environmental+hazards.&rft.au=Barrett%2C+J+C%3BVainio%2C+H%3BPeakall%2C+D%3BGoldstein%2C+B+D&rft.aulast=Barrett&rft.aufirst=J&rft.date=1997-06-01&rft.volume=105+Suppl+4&rft.issue=&rft.spage=699&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 - 1997-09-11 N1 - Date created - 1997-09-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer Res. 1993 Feb 1;53(3):460-3 [8425177] Arch Toxicol. 1993;67(3):173-8 [8494496] Cancer Epidemiol Biomarkers Prev. 1991 Nov-Dec;1(1):13-9 [1845163] 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Carcinogenesis. 1995 Aug;16(8):1913-7 [7543377] J Toxicol Environ Health. 1995 Aug;45(4):369-96 [7643427] Rapid Commun Mass Spectrom. 1995;9(9):735-43 [7655068] Chromosoma. 1995 Jul;103(10):725-31 [7664620] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA adducts as exposure biomarkers and indicators of cancer risk. AN - 79186950; 9255579 AB - Quantitation of DNA adducts in human tissues has been achieved with highly sensitive techniques based on adduct radiolabeling, antisera specific for DNA adducts or modified DNA, and/or adduct structural characterization using chemical instrumentation. Combinations of these approaches now promise to elucidate specific adduct structures and provide detection limits in the range of 1 adduct/10(9) nucleotides. Documentation of human exposure and biologically effective dose (i.e., chemical bound to DNA) has been achieved for a wide variety of chemical carcinogens, including polycyclic aromatic hydrocarbons (PAHs), aromatic amines, heterocyclic amines, aflatoxins, nitrosamines, cancer chemotherapeutic agents, styrene, and malondialdehyde. Due to difficulties in exposure documentation, dosimetry has not been precise with most environmental and occupational exposures, even though increases in human blood cell DNA adduct levels may correlate approximately with dose. Perhaps more significant are observations that lowering exposure results in decreasing DNA adduct levels. DNA adduct dosimetry for environmental agents has been achieved with dietary contaminants. For example, blood cell polycyclic aromatic hydrocarbon-DNA adduct levels were shown to correlate with frequency of charbroiled meat consumption in California firefighters. In addition, in China urinary excretion of the aflatoxin B1-N7-guanine (AFB1-N7-G) adduct was shown to increase linearly with the aflatoxin content of ingested food. Assessment of DNA adduct formation as an indicator of human cancer risk requires a prospective nested case-control study design. This has been achieved in one investigation of hepatocellular carcinoma and urinary aflatoxin adducts using subjects followed by a Shanghai liver cancer registry. Individuals who excreted the AFB1-N7-G adduct had a 9.1-fold adjusted increased relative risk of hepatocellular carcinoma compared to individuals with no adducts. Future advances in this field will be dependent on chemical characterization of specific DNA adducts formed in human tissues, more-precise molecular dosimetry, efforts to correlate DNA adducts with cancer risk, and elucidation of opportunities to reduce human DNA adduct levels. JF - Environmental health perspectives AU - Poirier, M C AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. poirierm@dc37a.nci.nih.gov Y1 - 1997/06// PY - 1997 DA - June 1997 SP - 907 EP - 912 VL - 105 Suppl 4 SN - 0091-6765, 0091-6765 KW - Biomarkers KW - 0 KW - DNA Adducts KW - Index Medicus KW - Humans KW - Risk Assessment KW - DNA Adducts -- analysis KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79186950?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=DNA+adducts+as+exposure+biomarkers+and+indicators+of+cancer+risk.&rft.au=Poirier%2C+M+C&rft.aulast=Poirier&rft.aufirst=M&rft.date=1997-06-01&rft.volume=105+Suppl+4&rft.issue=&rft.spage=907&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 - 1997-09-11 N1 - Date created - 1997-09-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Lancet. 1992 Apr 18;339(8799):943-6 [1348796] Carcinogenesis. 1992 Jul;13(7):1053-74 [1638670] Carcinogenesis. 1992 Jul;13(7):1257-9 [1638694] Cancer Res. 1992 Oct 1;52(19):5307-12 [1394135] Chem Res Toxicol. 1992 Nov-Dec;5(6):749-55 [1489923] Carcinogenesis. 1993 Feb;14(2):199-204 [8435861] Cancer Res. 1993 Apr 1;53(7):1522-8 [8453617] Carcinogenesis. 1993 Apr;14(4):545-50 [8386066] Mutat Res. 1993 Jul;288(1):19-29 [7686262] Mutat Res. 1993 Jul;288(1):5-18 [7686266] Cancer Epidemiol Biomarkers Prev. 1992 Mar-Apr;1(3):221-7 [1339082] Environ Health Perspect. 1993 Mar;99:143-7 [8319612] Prog Nucleic Acid Res Mol Biol. 1984;31:1-58 [6085171] Proc Natl Acad Sci U S A. 1985 Oct;82(19):6492-6 [3931076] Proc Natl Acad Sci U S A. 1985 Oct;82(19):6672-6 [2413443] Int J Cancer. 1985 Dec 15;36(6):661-5 [4066072] Environ Health Perspect. 1985 Oct;62:95-9 [4085452] J Clin Invest. 1986 Feb;77(2):545-50 [3944268] Cancer Res. 1986 Jul;46(7):3249-53 [3085918] Carcinogenesis. 1986 Sep;7(9):1543-51 [3017601] Carcinogenesis. 1986 Dec;7(12):2071-5 [3779901] Cancer Res. 1987 Jun 1;47(11):3000-4 [3552211] Cancer Res. 1988 Apr 15;48(8):2156-61 [3349485] Cancer Res. 1988 Nov 15;48(22):6328-31 [3141043] Cancer Res. 1988 Nov 15;48(22):6336-42 [3180051] Mutat Res. 1988 Nov;202(1):85-91 [2847037] Cancer Res. 1989 Jan 1;49(1):93-7 [2908856] J Invest Dermatol. 1989 Sep;93(3):341-4 [2768834] Arch Toxicol Suppl. 1989;13:55-65 [2673151] Gastroenterology. 1989 Nov;97(5):1281-7 [2551766] Proc Natl Acad Sci U S A. 1989 Dec;86(24):9697-701 [2602371] J Invest Dermatol. 1990 Feb;94(2):241-6 [2299199] Carcinogenesis. 1990 Feb;11(2):205-11 [2105856] Carcinogenesis. 1990 Mar;11(3):431-6 [2311187] Cancer Res. 1990 May 1;50(9):2759-64 [2328502] J Natl Cancer Inst. 1990 Jun 6;82(11):927-33 [2111410] Carcinogenesis. 1990 Jul;11(7):1229-31 [2372881] Int Arch Occup Environ Health. 1990;62(4):299-303 [2379960] Prog Clin Biol Res. 1990;340C:247-57 [2199982] Prog Clin Biol Res. 1990;340C:271-82 [2381929] Scand J Work Environ Health. 1990 Jun;16(3):158-62 [2382118] Carcinogenesis. 1990 Sep;11(9):1677-81 [2119262] Environ Health Perspect. 1993 Mar;99:307-9 [8319650] Environ Health Perspect. 1993 Mar;99:33-7 [8319651] Environ Health Perspect. 1993 Mar;99:89-97 [8319665] Cancer Res. 1993 Aug 15;53(16):3694-9 [8339278] Cancer Epidemiol Biomarkers Prev. 1993 Jul-Aug;2(4):341-7 [8348057] Free Radic Res Commun. 1986;1(3):163-72 [2577733] Carcinogenesis. 1993 Dec;14(12):2523-6 [8269622] Cancer Epidemiol Biomarkers Prev. 1994 Jan-Feb;3(1):3-10 [8118382] Environ Health Perspect. 1994 Oct;102 Suppl 6:11-6 [7889831] Cancer Res. 1988 Apr 15;48(8):2288-91 [3127049] Cancer Res. 1988 Oct 1;48(19):5597-603 [3046743] Carcinogenesis. 1988 Oct;9(10):1909-11 [2458857] Nature. 1977 Nov 10;270(5633):186-8 [927533] FEBS Lett. 1978 Aug 15;92(2):207-10 [81140] Z Naturforsch C. 1978 Nov-Dec;33(11-12):897-901 [154226] J Natl Cancer Inst. 1981 Sep;67(3):515-9 [6944523] Environ Mutagen. 1984;6(6):879-87 [6389112] Proc Natl Acad Sci U S A. 1984 Dec;81(24):7728-31 [6440143] Cancer Res. 1990 Oct 15;50(20):6580-4 [2208119] Cancer Res. 1991 Jan 1;51(1):190-4 [1988083] Basic Life Sci. 1990;53:63-81 [2126432] Free Radic Res Commun. 1990;11(1-3):23-7 [2074046] Carcinogenesis. 1991 Mar;12(3):503-8 [2009595] Carcinogenesis. 1991 May;12(5):865-71 [2029751] Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5350-4 [2052611] Carcinogenesis. 1991 Aug;12(8):1445-9 [1860165] Cancer Res. 1991 Sep 15;51(18 Suppl):5023s-5044s [1884379] Carcinogenesis. 1991 Sep;12(9):1727-32 [1654227] Chem Res Toxicol. 1991 May-Jun;4(3):364-8 [1912321] Prog Clin Biol Res. 1991;372:205-18 [1956919] Cancer Res. 1992 Jan 1;52(1):149-53 [1727376] Cancer Res. 1992 Jan 1;52(1):45-52 [1727385] Mutat Res. 1992 Jan;281(1):11-6 [1371585] Cancer Res. 1992 Mar 15;52(6):1510-4 [1540959] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Assessment of cocaine use with quantitative urinalysis and estimation of new uses. AN - 79172691; 9246799 AB - Qualitative urinalysis methods of monitoring cocaine use may over-detect frequency of use, possibly decreasing the ability of clinical trials to detect effective treatments. Quantitative urinalysis and newly developed criteria for identifying new cocaine use were evaluated as alternative measures of cocaine use. Urine specimens collected in a cocaine dosing study in non-treatment-seeking subjects (n = 5) and a cocaine treatment trial (n = 37) were analyzed for the cocaine metabolite, benzoylecgonine, with qualitative and quantitative methods. Pharmacokinetic criteria ('New Use' rules) were applied to quantitative data to identify occasions of new cocaine use. Results were compared to known cocaine administrations in the laboratory study and to self-reported drug use and qualitative urinalysis for subjects in the clinical trial. New Use criteria correctly identified cocaine administrations in the cocaine dosing study in all but a small number of specimens. In the clinical trial, quantitative urinalysis and estimated New Uses provided more information about patterns and frequency of use than qualitative urinalysis in the different treatment conditions in the clinical trial. Interpretation of quantitative urinalysis with New Use rules appears to be a useful method for monitoring treatment outcome and may be more accurate than traditional qualitative urinalysis in estimating frequency of cocaine use. JF - Addiction (Abingdon, England) AU - Preston, K L AU - Silverman, K AU - Schuster, C R AU - Cone, E J AD - National Institute on Drug Abuse, Intramural Research Program, NIH, Baltimore, MD 21224, USA. Y1 - 1997/06// PY - 1997 DA - June 1997 SP - 717 EP - 727 VL - 92 IS - 6 SN - 0965-2140, 0965-2140 KW - Narcotics KW - 0 KW - benzoylecgonine KW - 5353I8I6YS KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Drug Administration Schedule KW - Single-Blind Method KW - Humans KW - Adult KW - Cross-Over Studies KW - Aged KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Cocaine -- analogs & derivatives KW - Cocaine -- urine KW - Narcotics -- metabolism KW - Opioid-Related Disorders -- rehabilitation KW - Narcotics -- administration & dosage KW - Opioid-Related Disorders -- urine KW - Cocaine -- metabolism KW - Cocaine -- administration & dosage KW - Substance Abuse Detection -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79172691?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Addiction+%28Abingdon%2C+England%29&rft.atitle=Assessment+of+cocaine+use+with+quantitative+urinalysis+and+estimation+of+new+uses.&rft.au=Preston%2C+K+L%3BSilverman%2C+K%3BSchuster%2C+C+R%3BCone%2C+E+J&rft.aulast=Preston&rft.aufirst=K&rft.date=1997-06-01&rft.volume=92&rft.issue=6&rft.spage=717&rft.isbn=&rft.btitle=&rft.title=Addiction+%28Abingdon%2C+England%29&rft.issn=09652140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-26 N1 - Date created - 1997-08-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pica behavior associated with buprenorphine administration in the rat. AN - 79166957; 9241634 AB - Marked gastric distention was-observed in rats 20 h after they underwent partial hepatectomy under isoflurane anesthesia and received buprenorphine (0.3 mg/kg of body weight) after surgery. Hardwood bedding comprised the bulk of the gastric contents. A study was undertaken to determine the cause of the pica behavior (consumption of non-nutritive substances) and resultant gastric distention. Ten-week-old male Sprague Dawley rats were randomly assigned to one of six groups. Group-1 rats (n = 11) underwent laparotomy under isoflurane anesthesia, with buprenorphine (0.3 mg/kg) administered after surgery. Group-2 rats (n = 12) underwent laparotomy under isoflurane anesthesia with buprenorphine (0.05 mg/kg) administered after surgery. Group-3 rats (n = 24) underwent laparotomy under isoflurane anesthesia, with saline administered after surgery. Isoflurane was administered at the same rate, concentration, and duration for all groups that underwent laparotomy (groups 1 to 3). Buprenorphine or saline was administered subcutaneously as a single injection when anesthesia was discontinued (groups 1 to 3). Group-4 rats (n = 6) received buprenorphine (0.3 mg/kg) only. Group-5 rats (n = 6) received buprenorphine (0.05 mg/kg) only. Group-6 rats (n = 12) received saline only. Rats not undergoing laparotomy (groups 4 to 6) received buprenorphine or saline 18 to 20 h before euthanasia. Rats were housed individually in filter-topped polycarbonate cages containing hardwood bedding. A purified, pelleted diet and water were offered ad libitum. Food and water consumption were measured over the posttreatment period. Eighteen to 20 h after treatment, rats were euthanized, each stomach and its contents were weighed, contents were examined grossly, and wet and dry gastric content weights were recorded. All weights were significantly (P < 0.05) increased in rats receiving buprenorphine administered after surgery (groups 1 and 2), compared with rats of the control group (group 3). Weights of the stomach and contents, wet gastric contents, and dry gastric contents were significantly (P < 0.05) increased in rats receiving 0.3 mg of buprenorphine/kg only (group 4), compared with values for their controls (group 6). Hardwood bedding comprised the bulk of the gastric contents in all groups receiving buprenorphine. Stomachs of rats not receiving buprenorphine contained the purified diet with little or no hardwood bedding. These results indicate that a single injection of buprenorphine at a dosage of 0.05 or 0.3 mg/kg resulted in rats ingesting hardwood bedding, leading to gastric distention. It was concluded that pica behavior associated with administration of buprenorphine should be considered when evaluating experimental data from rats housed on contact bedding. JF - Laboratory animal science AU - Clark, J A AU - Myers, P H AU - Goelz, M F AU - Thigpen, J E AU - Forsythe, D B AD - Comparative Medicine Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. Y1 - 1997/06// PY - 1997 DA - June 1997 SP - 300 EP - 303 VL - 47 IS - 3 SN - 0023-6764, 0023-6764 KW - Analgesics, Opioid KW - 0 KW - Buprenorphine KW - 40D3SCR4GZ KW - Index Medicus KW - Rats KW - Gastric Dilatation -- veterinary KW - Animals KW - Rats, Sprague-Dawley KW - Gastric Dilatation -- etiology KW - Laparotomy -- veterinary KW - Gastrointestinal Contents KW - Random Allocation KW - Injections, Subcutaneous KW - Male KW - Behavior, Animal -- drug effects KW - Pica -- chemically induced KW - Buprenorphine -- administration & dosage KW - Buprenorphine -- adverse effects KW - Analgesics, Opioid -- adverse effects KW - Pica -- veterinary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79166957?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Laboratory+animal+science&rft.atitle=Pica+behavior+associated+with+buprenorphine+administration+in+the+rat.&rft.au=Clark%2C+J+A%3BMyers%2C+P+H%3BGoelz%2C+M+F%3BThigpen%2C+J+E%3BForsythe%2C+D+B&rft.aulast=Clark&rft.aufirst=J&rft.date=1997-06-01&rft.volume=47&rft.issue=3&rft.spage=300&rft.isbn=&rft.btitle=&rft.title=Laboratory+animal+science&rft.issn=00236764&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-28 N1 - Date created - 1997-08-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The two-stage model of carcinogenesis: overcoming the nonidentifiability dilemma. AN - 79151991; 9232019 AB - The two-stage mathematical model of carcinogenesis has been shown to be nonidentifiable whenever tumor incidence data alone is used to fit the model (Hanin and Yakovlev, 1996). This lack of identifiability implies that more than one parameter vector satisfies the optimization criteria for parameter estimation, e.g., maximum likelihood estimation. A question of greater concern to persons using the two-stage model of carcinogenesis is under what conditions can identifiable parameters be obtained from the observed experimental data. We outline how to obtain identifiable parameters for the two-stage model. JF - Risk analysis : an official publication of the Society for Risk Analysis AU - Sherman, C D AU - Portier, C J AD - National Institute of Environmental Health Sciences, Laboratory of Computational Biology and Risk Assessment, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/06// PY - 1997 DA - June 1997 SP - 367 EP - 374 VL - 17 IS - 3 SN - 0272-4332, 0272-4332 KW - Methylene Chloride KW - 588X2YUY0A KW - Index Medicus KW - Risk KW - Animals KW - Methylene Chloride -- toxicity KW - Humans KW - Liver Neoplasms, Experimental -- chemically induced KW - Mice KW - Likelihood Functions KW - Female KW - Cell Transformation, Neoplastic KW - Mathematics KW - Cocarcinogenesis KW - Models, Biological UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79151991?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Risk+analysis+%3A+an+official+publication+of+the+Society+for+Risk+Analysis&rft.atitle=The+two-stage+model+of+carcinogenesis%3A+overcoming+the+nonidentifiability+dilemma.&rft.au=Sherman%2C+C+D%3BPortier%2C+C+J&rft.aulast=Sherman&rft.aufirst=C&rft.date=1997-06-01&rft.volume=17&rft.issue=3&rft.spage=367&rft.isbn=&rft.btitle=&rft.title=Risk+analysis+%3A+an+official+publication+of+the+Society+for+Risk+Analysis&rft.issn=02724332&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-09 N1 - Date created - 1997-09-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Arsenic can mediate skin neoplasia by chronic stimulation of keratinocyte-derived growth factors. AN - 79119942; 9219559 AB - Although numerous epidemiological studies have shown that inorganic arsenicals are human skin carcinogens, there is currently no accepted mechanism for its action or an established animal model for its study. We observed increased mRNA transcripts and secretion of keratinocyte growth factors, including granulocyte macrophage-colony stimulating factor (GM-CSF) and transforming growth factor-alpha (TGF-alpha) and the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) in primary human epidermal keratinocytes cultured in the presence of low micromolar concentrations of sodium arsenite. Total cell numbers, as well as c-myc expression and incorporation of [3H]thymidine, both indicators of cell proliferation, were also elevated in keratinocyte cultures treated with sodium arsenite. As an in vivo model, the influence of arsenic on mouse skin tumor development was studied in transgenic TG.AC mice which carry the v-Ha-ras oncogene, and can serve as a genetically initiated model for skin carcinogenesis. Following low-dose application of 12-O-tetradecanoyl phorbol-13-acetate (TPA), a marked increase in the number of skin papillomas occurred in transgenic mice receiving arsenic in the drinking water as compared to control drinking water. Papillomas did not develop in arsenic-treated transgenic mice that had not received TPA or arsenic-treated wild-type FVB/N mice, suggesting that arsenic is neither a tumor initiator or promoter but rather an enhancer. Injection of anti-GM-CSF antibodies following application of TPA in transgenic mice reduced the number of papillomas. Consistent with that observed in human keratinocyte cultures, increases in GM-CSF and TGF-alpha mRNA transcripts were found within the epidermis of arsenic-treated mice when compared to controls within 6 weeks of treatment. These results suggest that arsenic enhances papilloma development via the chronic stimulation of keratinocyte-derived growth factors and represents the first example of a chemical carcinogen that acts in this manner. These studies suggest that in vitro studies with human keratinocyte cultures examined in conjunction with TG.AC transgenic mice can provide a useful model for examining the tumor enhancing properties of environmental chemicals. JF - Mutation research AU - Germolec, D R AU - Spalding, J AU - Boorman, G A AU - Wilmer, J L AU - Yoshida, T AU - Simeonova, P P AU - Bruccoleri, A AU - Kayama, F AU - Gaido, K AU - Tennant, R AU - Burleson, F AU - Dong, W AU - Lang, R W AU - Luster, M I AD - Environmental Immunology and Neurobiology Section, NIH, Research Triangle Park, NC 27709, USA. germolec@niehs.nih.gov Y1 - 1997/06// PY - 1997 DA - June 1997 SP - 209 EP - 218 VL - 386 IS - 3 SN - 0027-5107, 0027-5107 KW - Environmental Pollutants KW - 0 KW - Transforming Growth Factor alpha KW - Tumor Necrosis Factor-alpha KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Arsenic KW - N712M78A8G KW - Index Medicus KW - Animals KW - Environmental Pollutants -- toxicity KW - Humans KW - Mice KW - Female KW - Granulocyte-Macrophage Colony-Stimulating Factor -- biosynthesis KW - Arsenic -- toxicity KW - Skin Neoplasms -- etiology KW - Keratinocytes -- drug effects KW - Transforming Growth Factor alpha -- biosynthesis KW - Skin Neoplasms -- pathology KW - Tumor Necrosis Factor-alpha -- biosynthesis KW - Keratinocytes -- pathology KW - Keratinocytes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79119942?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Arsenic+can+mediate+skin+neoplasia+by+chronic+stimulation+of+keratinocyte-derived+growth+factors.&rft.au=Germolec%2C+D+R%3BSpalding%2C+J%3BBoorman%2C+G+A%3BWilmer%2C+J+L%3BYoshida%2C+T%3BSimeonova%2C+P+P%3BBruccoleri%2C+A%3BKayama%2C+F%3BGaido%2C+K%3BTennant%2C+R%3BBurleson%2C+F%3BDong%2C+W%3BLang%2C+R+W%3BLuster%2C+M+I&rft.aulast=Germolec&rft.aufirst=D&rft.date=1997-06-01&rft.volume=386&rft.issue=3&rft.spage=209&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-05 N1 - Date created - 1997-08-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Serum, plasma and paraffin-embedded tissues as sources of DNA for studying cancer susceptibility genes. AN - 79114869; 9214613 AB - The ability to isolate DNA from archived human serum, plasma and paraffin-embedded human tissues enhances opportunities to study breast, lung and other cancer risk factors. We report herein a simple and fast protocol for the extraction of genomic DNA from these sources. Using a phenol-based extraction method, the recovery for DNA is quantitative and reproducible. DNA yields in serum (250 microl) were between 162 and 1060 ng (n = 18 subjects), in plasma (250 microl) were between 165 and 375 ng (n = 5 subjects) and in embedded tissues (5-microm thick sections for ethanol fixed, and between 5- and 20-microm sections for formaldehyde fixation) were between 1 microg and 11.7 microg (n = 32 subjects). The extraction method was combined with newly designed PCR-based assays for cancer susceptibility marker genes such as CYP1A1 (exon 7), CYP2E1 (Dra1, Rsa1), GSTM1 and NAT2 [NAT2*5A (C481T), NAT2*6A (G590A), NAT2*7A (G857A)]. Genotyping results from the serum and paraffin-embedded tissues compared favorably to results from archived freshly frozen tissues, where concordance was 98% for serum, 100% for ethanol-fixed embedded tissues, and 97% for formaldehyde-fixed and paraffin-embedded tissues. This facile method will allow for the use of archived tissue samples of prospective cohort and other studies where intact DNA was not previously available. JF - Carcinogenesis AU - Blömeke, B AU - Bennett, W P AU - Harris, C C AU - Shields, P G AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH Bethesda, MD 20892, USA. Y1 - 1997/06// PY - 1997 DA - June 1997 SP - 1271 EP - 1275 VL - 18 IS - 6 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - DNA, Neoplasm KW - Isoenzymes KW - DNA KW - 9007-49-2 KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - Arylamine N-Acetyltransferase KW - EC 2.3.1.5 KW - NAT2 protein, human KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Lung Neoplasms -- enzymology KW - DNA, Neoplasm -- blood KW - Humans KW - Lung -- chemistry KW - Cytochrome P-450 CYP2E1 -- metabolism KW - DNA, Neoplasm -- isolation & purification KW - Arylamine N-Acetyltransferase -- metabolism KW - Isoenzymes -- metabolism KW - Biotransformation KW - Lung -- enzymology KW - Genetic Predisposition to Disease KW - Arylamine N-Acetyltransferase -- genetics KW - Paraffin Embedding KW - Cytochrome P-450 CYP1A1 -- genetics KW - Reproducibility of Results KW - Lung Neoplasms -- chemistry KW - Polymorphism, Genetic KW - Exons KW - Carcinogens -- pharmacokinetics KW - Glutathione Transferase -- metabolism KW - Cytochrome P-450 CYP1A1 -- metabolism KW - Glutathione Transferase -- genetics KW - Cytochrome P-450 CYP2E1 -- genetics KW - Isoenzymes -- genetics KW - Lung -- physiology KW - Inactivation, Metabolic KW - Polymerase Chain Reaction -- methods KW - Lung Neoplasms -- genetics KW - DNA -- isolation & purification KW - Oncogenes KW - DNA -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79114869?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Serum%2C+plasma+and+paraffin-embedded+tissues+as+sources+of+DNA+for+studying+cancer+susceptibility+genes.&rft.au=Bl%C3%B6meke%2C+B%3BBennett%2C+W+P%3BHarris%2C+C+C%3BShields%2C+P+G&rft.aulast=Bl%C3%B6meke&rft.aufirst=B&rft.date=1997-06-01&rft.volume=18&rft.issue=6&rft.spage=1271&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-25 N1 - Date created - 1997-07-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Grafting assay distinguishes promotion sensitive from promotion resistant JB6 cells. AN - 79114832; 9214594 AB - The JB6 mouse epidermal cell system has been used extensively as an in vitro transformation model for the study of tumor promotion. The standard JB6 cell assay for promotion of transformation is carried out in soft agar or other anchorage independent conditions. The present study was directed to the development of an in vivo model to distinguish the promotion resistant (P-) and promotion sensitive (P+) progression phenotypes. Results indicate that the grafting assay distinguishes P- and P+ cells in vivo with P+ but not P- cells forming tumors within 7-9 weeks. Expression of dominant negative mutant jun TAM67 blocks both anchorage independent transformation response and graft bed tumor formation by P+ cells, suggesting that the requirement for AP-1 activation in transformation now applies in vivo. Expression of mutated p53 produced a gain of P+ phenotype in P- cells in vitro, but not in vivo. Histochemical and Northern blot analysis for expression of various keratinocyte markers revealed no evidence for expression, suggesting a loss of keratinocyte markers following establishment in culture. In summary, the skin-grafting assay described in this study appears to be a valid in vivo assay for distinguishing the preneoplastic progression phenotypes represented by JB6 P- and P+ cells. JF - Carcinogenesis AU - Strickland, J AU - Sun, Y AU - Dong, Z AU - Colburn, N H AD - National Cancer Institute, Laboratory of Cellular Carcinogenesis and Tumor Promotion, Bethesda, MD 20892, USA. Y1 - 1997/06// PY - 1997 DA - June 1997 SP - 1135 EP - 1138 VL - 18 IS - 6 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - Transcription Factor AP-1 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Sensitivity and Specificity KW - Tetradecanoylphorbol Acetate -- toxicity KW - Animals KW - Skin Physiological Phenomena KW - Carcinogens -- toxicity KW - Disease Models, Animal KW - Mice KW - Mice, Nude KW - Mice, Inbred BALB C KW - Transcription Factor AP-1 -- physiology KW - Neoplasm Transplantation KW - Phenotype KW - Cell Line, Transformed KW - Mice, Inbred SENCAR KW - Mutation KW - Male KW - Fibroblasts -- drug effects KW - Skin -- drug effects KW - Skin Neoplasms -- etiology KW - Cell Transformation, Neoplastic -- chemically induced KW - Skin Neoplasms -- pathology KW - Skin -- cytology KW - Fibroblasts -- cytology KW - Fibroblasts -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79114832?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Grafting+assay+distinguishes+promotion+sensitive+from+promotion+resistant+JB6+cells.&rft.au=Strickland%2C+J%3BSun%2C+Y%3BDong%2C+Z%3BColburn%2C+N+H&rft.aulast=Strickland&rft.aufirst=J&rft.date=1997-06-01&rft.volume=18&rft.issue=6&rft.spage=1135&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-25 N1 - Date created - 1997-07-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ex vivo bone marrow purging with oligonucleotides. AN - 79106157; 9212920 JF - Antisense & nucleic acid drug development AU - Bergan, R C AD - Department of Cell and Cancer Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/06// PY - 1997 DA - June 1997 SP - 251 EP - 255 VL - 7 IS - 3 SN - 1087-2906, 1087-2906 KW - Oligonucleotides, Antisense KW - 0 KW - RNA, Messenger KW - RNA, Neoplasm KW - Fusion Proteins, bcr-abl KW - EC 2.7.10.2 KW - Index Medicus KW - Animals KW - RNA, Neoplasm -- antagonists & inhibitors KW - Genes, myc KW - Lymphoma, Large B-Cell, Diffuse -- pathology KW - Humans KW - Lysosomes -- metabolism KW - Neoplasms -- therapy KW - Neoplasms -- genetics KW - Fusion Proteins, bcr-abl -- biosynthesis KW - RNA, Messenger -- antagonists & inhibitors KW - Neoplasms -- pathology KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - Cell Compartmentation KW - Fusion Proteins, bcr-abl -- genetics KW - RNA, Neoplasm -- metabolism KW - Oligonucleotides, Antisense -- toxicity KW - Bone Marrow Purging KW - Oligonucleotides, Antisense -- pharmacokinetics KW - Neoplastic Stem Cells -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79106157?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antisense+%26+nucleic+acid+drug+development&rft.atitle=Ex+vivo+bone+marrow+purging+with+oligonucleotides.&rft.au=Bergan%2C+R+C&rft.aulast=Bergan&rft.aufirst=R&rft.date=1997-06-01&rft.volume=7&rft.issue=3&rft.spage=251&rft.isbn=&rft.btitle=&rft.title=Antisense+%26+nucleic+acid+drug+development&rft.issn=10872906&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-15 N1 - Date created - 1997-09-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cystic fibrosis gene mutation (deltaF508) is associated with an intrinsic abnormality in Ca2+-induced arachidonic acid release by epithelial cells. AN - 79105029; 9212168 AB - The mechanism(s) of chronic airway inflammation in cystic fibrosis (CF) remains poorly understood. We studied Ca2+-induced release of arachidonic acid (AA), a precursor of proinflammatory lipid mediators, in epithelial cell lines with the deltaF508 mutation in CF transmembrane conductance regulator (CFTR) gene and in those lacking this mutation or cells in which this mutation was corrected by a functional CFTR gene transfer. We found that: (i) the mutant cells manifested an abnormally high Ca2+-induced AA release as compared to controls, (ii) AA release appeared to be catalyzed by a phospholipase A2 (PLA2) but not by phospholipase C followed by diacylglycerol lipase, and (iii) either correction of the CFTR-mutation or inhibition of PLA2 activity rectified this AA release abnormality. Taken together, our results suggest that CFTR mutation is associated with an intrinsic abnormality in AA release by epithelial cells carrying the deltaF508 mutation and suggest that the mechanism of chronic airway inflammation in CF, at least in part, involves this abnormality. These results also partly explain the effectiveness of high-dose ibuprofen therapy in arresting the progression of destructive lung disease in CF. Furthermore, they raise the possibility that correction of abnormal AA release by inhibiting PLA2 activity may improve the therapeutic benefits of ibuprofen. JF - DNA and cell biology AU - Miele, L AU - Cordella-Miele, E AU - Xing, M AU - Frizzell, R AU - Mukherjee, A B AD - Section on Developmental Genetics, Heritable Disorders Branch, NICHD, Bethesda, MD 20892, USA. Y1 - 1997/06// PY - 1997 DA - June 1997 SP - 749 EP - 759 VL - 16 IS - 6 SN - 1044-5498, 1044-5498 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - CFTR protein, human KW - Chlorides KW - Cystic Fibrosis Transmembrane Conductance Regulator KW - 126880-72-6 KW - Arachidonic Acid KW - 27YG812J1I KW - Calcimycin KW - 37H9VM9WZL KW - Phospholipases A KW - EC 3.1.1.32 KW - Lipoprotein Lipase KW - EC 3.1.1.34 KW - Phospholipases A2 KW - EC 3.1.1.4 KW - Staurosporine KW - H88EPA0A3N KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Ibuprofen KW - WK2XYI10QM KW - Index Medicus KW - Phospholipases A -- antagonists & inhibitors KW - Anti-Inflammatory Agents, Non-Steroidal -- therapeutic use KW - Dose-Response Relationship, Drug KW - Cystic Fibrosis -- drug therapy KW - Humans KW - Ibuprofen -- administration & dosage KW - Chlorides -- metabolism KW - Cystic Fibrosis -- physiopathology KW - Ibuprofen -- pharmacology KW - Anti-Inflammatory Agents, Non-Steroidal -- administration & dosage KW - Calcimycin -- pharmacology KW - Precipitin Tests KW - Lipoprotein Lipase -- antagonists & inhibitors KW - Staurosporine -- pharmacology KW - Epithelial Cells KW - Ibuprofen -- therapeutic use KW - Cells, Cultured KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Epithelium -- metabolism KW - Phospholipases A -- metabolism KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology KW - Calcium -- metabolism KW - Arachidonic Acid -- antagonists & inhibitors KW - Mutation KW - Cystic Fibrosis Transmembrane Conductance Regulator -- genetics KW - Arachidonic Acid -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79105029?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=DNA+and+cell+biology&rft.atitle=Cystic+fibrosis+gene+mutation+%28deltaF508%29+is+associated+with+an+intrinsic+abnormality+in+Ca2%2B-induced+arachidonic+acid+release+by+epithelial+cells.&rft.au=Miele%2C+L%3BCordella-Miele%2C+E%3BXing%2C+M%3BFrizzell%2C+R%3BMukherjee%2C+A+B&rft.aulast=Miele&rft.aufirst=L&rft.date=1997-06-01&rft.volume=16&rft.issue=6&rft.spage=749&rft.isbn=&rft.btitle=&rft.title=DNA+and+cell+biology&rft.issn=10445498&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-25 N1 - Date created - 1997-07-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alteration of dopamine D2 receptors in human malignant stomach tissue. AN - 79102990; 9201092 AB - Dopamine is an important enteric neurotransmitter with a wide spectrum of physiological actions on the gastrointestinal tract. In addition, it showed inhibition of malignant cell proliferation as well as a protective influence on experimental carcinogenesis in the gastrointestinal tract of murine hosts. It is well established that dopamine acts on target cells through specific receptors. Therefore the status of dopamine receptors in malignant tumors of the stomach has been evaluated. Normal, benign, and malignant stomach tissue showed the presence of high-affinity D2 dopamine receptors. The concentration (Bmax) and affinity (Kd) of dopamine binding sites in normal and benign tumor tissues were similar. In malignant stomach tissue Bmax showed a significant decrease compared to normal and benign controls; however, Kd was similar. This alteration of dopamine receptors may be of significance in understanding the etiopathogenesis of gastric cancer at the level of peripheral neurotransmitters. Rational use of dopamine receptor antagonists for various stomach diseases may be suggested. JF - Digestive diseases and sciences AU - Basu, S AU - Dasgupta, P S AD - Department of Medical Oncology, Chittaranjan National Cancer Institute, Calcutta, India. Y1 - 1997/06// PY - 1997 DA - June 1997 SP - 1260 EP - 1264 VL - 42 IS - 6 SN - 0163-2116, 0163-2116 KW - Receptors, Dopamine D2 KW - 0 KW - Tritium KW - 10028-17-8 KW - Dopamine KW - VTD58H1Z2X KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Middle Aged KW - Male KW - Binding Sites KW - Adenocarcinoma -- metabolism KW - Stomach -- pathology KW - Stomach Neoplasms -- metabolism KW - Stomach -- metabolism KW - Dopamine -- metabolism KW - Receptors, Dopamine D2 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79102990?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Digestive+diseases+and+sciences&rft.atitle=Alteration+of+dopamine+D2+receptors+in+human+malignant+stomach+tissue.&rft.au=Basu%2C+S%3BDasgupta%2C+P+S&rft.aulast=Basu&rft.aufirst=S&rft.date=1997-06-01&rft.volume=42&rft.issue=6&rft.spage=1260&rft.isbn=&rft.btitle=&rft.title=Digestive+diseases+and+sciences&rft.issn=01632116&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-16 N1 - Date created - 1997-07-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of epitopes on a mutant form of Pseudomonas exotoxin using serum from humans treated with Pseudomonas exotoxin containing immunotoxins. AN - 79101979; 9209499 AB - PE38 is a 38-kDa derivative of the 66-kDa Pseudomonas exotoxin (PE) in which the cell binding domain of PE (domain Ia, amino acids 1-252) and a portion of domain Ib (amino acids 365-380) are deleted. The immunotoxins LMB-1 and LMB-7 contain PE38 and kill cancer cells by exploiting the cytotoxic action of PE38. The major human B cell epitopes of PE38 were mapped by measuring the reactivity of 45 serum samples from patients treated with the PE38-containing immunotoxins LMB-1 or LMB-7 to two panels of overlapping synthetic peptides representing the sequence of PE38. One panel of peptides is ten amino acids long and overlap by seven amino acids, and the second panel of peptides is twenty amino acids long and overlap by ten. Five major epitopes were identified: amino acids 274-283, 470-492, 531-540, 555-564, and the C-terminal amino acids 596-609. Two minor epitopes were identified as well: amino acids 501-510 and 582-589. These epitopes are predominantly located on the surface of the protein. The amino acids believed to be critical for binding are highly solvent-accessible residues. The results of the human antibody response to peptides are compared to the pattern of reactivity previously identified with serum samples obtained from monkeys administered LMB-1 and LMB-7. The epitopes between monkey and human are almost identical, demonstrating similarity in the response of antibody repertoires between the two species and providing further support that these are the immunodominant epitopes. This information is critical for genetically engineering less immunogenic immunotoxins and provides a foundation for the development of a vaccine against pseudomonal infections which plague immunocompromised individuals and individuals with cystic fibrosis. JF - European journal of immunology AU - Roscoe, D M AU - Pai, L H AU - Pastan, I AD - Laboratory of Molecular Biology, DCBDC, NCI, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1997/06// PY - 1997 DA - June 1997 SP - 1459 EP - 1468 VL - 27 IS - 6 SN - 0014-2980, 0014-2980 KW - Antibodies, Monoclonal KW - 0 KW - Bacterial Toxins KW - Epitopes, B-Lymphocyte KW - Exotoxins KW - Immunodominant Epitopes KW - Immunotoxins KW - Oligopeptides KW - Recombinant Fusion Proteins KW - Virulence Factors KW - immunotoxin LMB-7 KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Animals KW - Antigen-Antibody Reactions KW - Epitopes, B-Lymphocyte -- blood KW - Macaca fascicularis KW - Humans KW - Oligopeptides -- immunology KW - Oligopeptides -- genetics KW - Amino Acid Sequence KW - Epitopes, B-Lymphocyte -- genetics KW - Mutagenesis KW - Base Sequence KW - Oligopeptides -- blood KW - Adult KW - Molecular Sequence Data KW - Immunotherapy, Active KW - Epitopes, B-Lymphocyte -- immunology KW - Exotoxins -- genetics KW - Exotoxins -- blood KW - Recombinant Fusion Proteins -- immunology KW - Neoplasms -- blood KW - Exotoxins -- immunology KW - Neoplasms -- therapy KW - Immunotoxins -- blood KW - Immunodominant Epitopes -- blood KW - Recombinant Fusion Proteins -- blood KW - Immunodominant Epitopes -- immunology KW - Pseudomonas aeruginosa -- immunology KW - Immunodominant Epitopes -- genetics KW - Immunotoxins -- immunology KW - Neoplasms -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79101979?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+immunology&rft.atitle=Identification+of+epitopes+on+a+mutant+form+of+Pseudomonas+exotoxin+using+serum+from+humans+treated+with+Pseudomonas+exotoxin+containing+immunotoxins.&rft.au=Roscoe%2C+D+M%3BPai%2C+L+H%3BPastan%2C+I&rft.aulast=Roscoe&rft.aufirst=D&rft.date=1997-06-01&rft.volume=27&rft.issue=6&rft.spage=1459&rft.isbn=&rft.btitle=&rft.title=European+journal+of+immunology&rft.issn=00142980&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-22 N1 - Date created - 1997-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Behavioural and neurochemical characteristics of phentermine and fenfluramine administered separately and as a mixture in rats. AN - 79098243; 9203241 AB - Clinical case studies suggest that combined administration of the serotonergic agent fenfluramine (FEN) and the weak amphetamine-like anorexic agent phentermine (PHEN) may be useful in the treatment of alcohol and cocaine addictions. The present experiment examined the nature of the interaction between the two agonists using the drug discrimination paradigm. In vivo microdialysis served to examine the neurochemical profile of dopamine and serotonin release in the nucleus accumbens. In conscious rats, acute injections of FEN (1.0-2.0 mg/kg i.p.) or PHEN (1.0-2.0 mg/kg i.p.) selectively elevated levels of serotonin and dopamine in the nucleus accumbens, respectively. A mixture (1 mg/kg of each) increased levels of both amines by similar magnitudes to those observed with each individually. Three groups of Sprague-Dawley rats were trained to discriminate (1) FEN (1.0 mg/kg i.p.) alone, (2) PHEN (1.0 mg/kg i.p.) alone or a mixture (3) PHEN+FEN (1 mg/kg of each, i.p.) from saline under a fixed ratio (FR-10) schedule of food reinforcement. Rats acquired the mixture discrimination rapidly, while for the other groups the training dose had to be increased to 2.0 mg/kg to attain stimulus control. The individual components of the mixture at the training dose generalized partially to the mixture, and complete generalisation was observed following 3.0 mg/kg FEN or PHEN. Rats trained to discriminate the individual components showed respective cross-generalisation profiles. Generalisation to cocaine (0.3-10.0 mg/kg i.p.), amphetamine (0.1-3.0 mg/kg i.p.) and nicotine (0.1-0.8 mg/kg s.c.) was greatest in the MIX-trained rats, while partial or no generalisation was observed in rats trained to discriminate the individual compounds. From the present results, it may be concluded that the two drugs given as a mixture do not produce a novel cue. Rather, these aminergics appear to interact additively. Furthermore, the dual stimulation of the amines by the mixture may be the basis for the cueing effects of the FEN+PHEN drug mixture, and its effectiveness in treating drug addictions. JF - Psychopharmacology AU - Shoaib, M AU - Baumann, M H AU - Rothman, R B AU - Goldberg, S R AU - Schindler, C W AD - Preclinical Pharmacology Laboratory, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 1997/06// PY - 1997 DA - June 1997 SP - 296 EP - 306 VL - 131 IS - 3 SN - 0033-3158, 0033-3158 KW - Dopamine Uptake Inhibitors KW - 0 KW - Serotonin Agents KW - Street Drugs KW - Fenfluramine KW - 2DS058H2CF KW - Serotonin KW - 333DO1RDJY KW - Nicotine KW - 6M3C89ZY6R KW - Phentermine KW - C045TQL4WP KW - Amphetamine KW - CK833KGX7E KW - Cocaine KW - I5Y540LHVR KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Discrimination Learning -- drug effects KW - Animals KW - Drug Interactions KW - Dopamine -- metabolism KW - Nicotine -- administration & dosage KW - Cocaine -- administration & dosage KW - Microdialysis KW - Rats KW - Rats, Sprague-Dawley KW - Amphetamine -- administration & dosage KW - Nucleus Accumbens -- metabolism KW - Serotonin -- metabolism KW - Male KW - Phentermine -- pharmacology KW - Serotonin Agents -- pharmacology KW - Fenfluramine -- pharmacology KW - Dopamine Uptake Inhibitors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79098243?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology&rft.atitle=Behavioural+and+neurochemical+characteristics+of+phentermine+and+fenfluramine+administered+separately+and+as+a+mixture+in+rats.&rft.au=Shoaib%2C+M%3BBaumann%2C+M+H%3BRothman%2C+R+B%3BGoldberg%2C+S+R%3BSchindler%2C+C+W&rft.aulast=Shoaib&rft.aufirst=M&rft.date=1997-06-01&rft.volume=131&rft.issue=3&rft.spage=296&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-14 N1 - Date created - 1997-08-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo induction and in vitro inhibition of hepatic cytochrome P450 activity by the benzodiazepine anticonvulsants clonazepam and diazepam. AN - 79087329; 9193878 AB - The ability of the benzodiazepines, as a chemical class, to cause the induction and/or inhibition of cytochromes P450 has not been well characterized. In the present study, the induction of the cytochrome P450 2B subfamily (CYP2B) in vivo and the inhibition of CYP2B activity in vitro by selected benzodiazepines was examined in hepatic tissues derived from male F344/NCr rats. Initial studies of the in vivo induction or in vitro inhibition of benzyloxyresorufin O-dealkylation activity revealed that both clonazepam and diazepam were relatively effective in vivo inducers of CYP2B when administered in the diet at 500 ppm for 5 days and also were fairly potent inhibitors of the activity of these hemoproteins in vitro. Oxazepam, in contrast, was ineffective as an inducer or an inhibitor of this activity. Further studies were performed to characterize the subfamily selectivity of the P450 induction and inhibition displayed by clonazepam. Specifically, microsomes from rats treated with clonazepam (1000 or 1800 ppm in the diet for 5 days) were found to be highly induced with respect to catalytic activities mediated by CYP2B, including benzyloxyresorufin and pentoxyresorufin O-dealkylation or testosterone 16 beta-hydroxylation, but other CYP proteins were minimally induced. In addition to inducing the CYP2B subfamily, clonazepam also induced the RNA encoding other drug metabolizing enzymes (e.g., epoxide hydrolase and the glutathione S-transferase alpha-subfamily) that are typically induced by phenobarbital-type inducers. Finally, clonazepam proved to be a potent noncompetitive or "mixed-type" competitive inhibitor of catalytic activities mediated by CYP2B, but not by other CYP proteins (e.g. CYP2A, CYP3A) in microsomes derived from phenobarbital-pretreated rats. JF - Drug metabolism and disposition: the biological fate of chemicals AU - Nims, R W AU - Prough, R A AU - Jones, C R AU - Stockus, D L AU - Dragnev, K H AU - Thomas, P E AU - Lubet, R A AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1997/06// PY - 1997 DA - June 1997 SP - 750 EP - 756 VL - 25 IS - 6 SN - 0090-9556, 0090-9556 KW - Anticonvulsants KW - 0 KW - Clonazepam KW - 5PE9FDE8GB KW - Cytochrome P-450 CYP2B1 KW - EC 1.14.14.1 KW - Diazepam KW - Q3JTX2Q7TU KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Enzyme Induction KW - Male KW - Cytochrome P-450 CYP2B1 -- biosynthesis KW - Anticonvulsants -- pharmacology KW - Liver -- enzymology KW - Liver -- drug effects KW - Cytochrome P-450 CYP2B1 -- antagonists & inhibitors KW - Diazepam -- pharmacology KW - Clonazepam -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79087329?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=In+vivo+induction+and+in+vitro+inhibition+of+hepatic+cytochrome+P450+activity+by+the+benzodiazepine+anticonvulsants+clonazepam+and+diazepam.&rft.au=Nims%2C+R+W%3BPrough%2C+R+A%3BJones%2C+C+R%3BStockus%2C+D+L%3BDragnev%2C+K+H%3BThomas%2C+P+E%3BLubet%2C+R+A&rft.aulast=Nims&rft.aufirst=R&rft.date=1997-06-01&rft.volume=25&rft.issue=6&rft.spage=750&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 - 1997-08-15 N1 - Date created - 1997-08-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A review of research on the Alcohol Use Disorders Identification Test (AUDIT). AN - 79087290; 9194913 AB - Research on the core version of the Alcohol Use Disorders Identification Test (AUDIT) is reviewed. Sensitivities and specificities of the AUDIT or criteria of current hazardous use and, to a slightly lesser extent, lifetime alcohol dependence are high. In general, AUDIT scores are at least moderately related to other self-report alcohol screening tests. Several studies also show them as correlated with biochemical measures of drinking. Results of the AUDIT have also been associated with more distal indicators of problematic drinking. Indices of internal consistency, including Cronbach's alpha and item-total correlations, are generally in the 0.80's. Future directions for research on the AUDIT are suggested. JF - Alcoholism, clinical and experimental research AU - Allen, J P AU - Litten, R Z AU - Fertig, J B AU - Babor, T AD - Treatment Research Branch, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20852-7003, USA. Y1 - 1997/06// PY - 1997 DA - June 1997 SP - 613 EP - 619 VL - 21 IS - 4 SN - 0145-6008, 0145-6008 KW - Index Medicus KW - Mass Screening -- statistics & numerical data KW - Reproducibility of Results KW - Humans KW - Research KW - Psychometrics KW - Alcoholism -- epidemiology KW - Personality Inventory -- statistics & numerical data KW - Alcoholism -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79087290?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+review+of+research+on+the+Alcohol+Use+Disorders+Identification+Test+%28AUDIT%29.&rft.au=Allen%2C+J+P%3BLitten%2C+R+Z%3BFertig%2C+J+B%3BBabor%2C+T&rft.aulast=Allen&rft.aufirst=J&rft.date=1997-06-01&rft.volume=21&rft.issue=4&rft.spage=613&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 - 1997-08-20 N1 - Date created - 1997-08-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selective serotonin reuptake inhibitors dissociate fenfluramine's anorectic and neurotoxic effects: importance of dose, species and drug. AN - 79084503; 9190887 AB - Fenfluramine, a clinically prescribed appetite suppressant, has been found to damage brain serotonin (5-HT) neurons in every animal species tested to date. Recent findings indicate that fluoxetine, a selective 5-HT reuptake inhibitor (SSRI), can prevent fenfluramine-induced 5-HT neurotoxicity without blocking fenfluramine-induced appetite suppression. The purpose of our studies was several-fold: 1) To determine whether the ability for fluoxetine to dissociate fenfluramine-induced anorexia and neurotoxicity is dose-related; 2) to ascertain whether other SSRIs also prevent fenfluramine-induced neurotoxicity without altering its anorectic effect; 3) to determine whether similar fluoxetine/fenfluramine interactions are seen in another animal species (i.e., mice) and 4) to determine whether decreases in food intake seen after the fluoxetine/fenfluramine combination can be attributed to nonspecific behavioral suppression. Results from our studies indicate that fluoxetine's effects are, indeed, dose-related, because higher doses of fluoxetine are required to protect against the 5-HT neurotoxic effects of higher doses of fenfluramine. Further, our results indicate that fluoxetine's effects generalize to all other SSRIs tested (citalopram, paroxetine and sertraline), as well as to other species (mice). Finally, our results demonstrate that anorexia in animals receiving the fenfluramine/fluoxetine combination is not secondary to nonspecific behavioral suppression, because water intake is increased although food intake is decreased in the same animals. Together, these data suggest that the anorectic and 5-HT neurotoxic effects of fenfluramine may involve different mechanisms, and that by combining fenfluramine with SSRIs, it may be possible to exploit fenfluramine's clinically useful properties (e.g., anorexia) without risking brain 5-HT neural injury. JF - The Journal of pharmacology and experimental therapeutics AU - McCann, U D AU - Yuan, J AU - Hatzidimitriou, G AU - Ricaurte, G A AD - Biological Psychiatry Branch, National Institute of Mental Health, NIH, Bethesda, MD 20892-1272, USA. Y1 - 1997/06// PY - 1997 DA - June 1997 SP - 1487 EP - 1498 VL - 281 IS - 3 SN - 0022-3565, 0022-3565 KW - Neurotoxins KW - 0 KW - Serotonin Uptake Inhibitors KW - Fenfluramine KW - 2DS058H2CF KW - Serotonin KW - 333DO1RDJY KW - Index Medicus KW - Rats KW - Serotonin -- pharmacology KW - Animals KW - Rats, Sprague-Dawley KW - Mice KW - Male KW - Fenfluramine -- adverse effects KW - Fenfluramine -- administration & dosage KW - Brain -- drug effects KW - Serotonin Uptake Inhibitors -- pharmacology KW - Neurotoxins -- adverse effects KW - Anorexia -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79084503?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Selective+serotonin+reuptake+inhibitors+dissociate+fenfluramine%27s+anorectic+and+neurotoxic+effects%3A+importance+of+dose%2C+species+and+drug.&rft.au=McCann%2C+U+D%3BYuan%2C+J%3BHatzidimitriou%2C+G%3BRicaurte%2C+G+A&rft.aulast=McCann&rft.aufirst=U&rft.date=1997-06-01&rft.volume=281&rft.issue=3&rft.spage=1487&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-21 N1 - Date created - 1997-07-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hormone replacement therapy and risk for breast cancer. AN - 79082777; 9193889 AB - Because breast cancer will develop in one of every nine American women, even a small increase in risk associated with a widespread exposure is of substantial public health concern. Although most studies have not found ever use of estrogens to be a risk factor for breast cancer, it is not yet resolved whether current or long-term users experience some increase in risk. Given the fact that the indications for menopausal estrogen use have changed substantially over time, from short-term use for the relief of menopausal symptoms to long-term use for lifetime reduction of conditions such as cardiovascular disease and osteoporosis, it is imperative that the effects of long-term estrogen replacement on the risk for breast cancer be resolved. These studies are not without associated methodologic difficulties, with the ultimate interpretation of the association possibly dependent on the results of controlled clinical trials. Although such investigations are currently underway, the results will not be available for many years. To address more immediate concerns, continued emphasis should be placed on well-designed case-control and cohort studies. For the results to be reliable, attention must be directed to the effects of selection, recall and surveillance biases, confounding factors, detailed exposure relationships, subgroup variations, and disease associations. In addition, given the increasing trend for estrogens to be prescribed in combination with progestogens, the effects on breast tissue of this combined therapy merit immediate attention. JF - Endocrinology and metabolism clinics of North America AU - Brinton, L A AD - Environmental Epidemiology Branch, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 1997/06// PY - 1997 DA - June 1997 SP - 361 EP - 378 VL - 26 IS - 2 SN - 0889-8529, 0889-8529 KW - Progestins KW - 0 KW - Index Medicus KW - Drug Therapy, Combination KW - Progestins -- therapeutic use KW - Dose-Response Relationship, Drug KW - Risk Factors KW - Humans KW - Clinical Trials as Topic KW - Meta-Analysis as Topic KW - Female KW - Estrogen Replacement Therapy KW - Breast Neoplasms -- epidemiology KW - Breast Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79082777?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+and+metabolism+clinics+of+North+America&rft.atitle=Hormone+replacement+therapy+and+risk+for+breast+cancer.&rft.au=Brinton%2C+L+A&rft.aulast=Brinton&rft.aufirst=L&rft.date=1997-06-01&rft.volume=26&rft.issue=2&rft.spage=361&rft.isbn=&rft.btitle=&rft.title=Endocrinology+and+metabolism+clinics+of+North+America&rft.issn=08898529&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-07 N1 - Date created - 1997-08-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Design of a leucine zipper coiled coil stabilized 1.4 kcal mol-1 by phosphorylation of a serine in the e position. AN - 79072423; 9194187 AB - Using a dimeric bZIP protein, we have designed a leucine zipper that becomes more stable after a serine in the e position is phosphorylated by protein kinase A (delta delta GP = -1.4 kcal mol-1 dimer-1 or -0.7 kcal mol-1 residue-1). Mutagenesis studies indicate that three arginines form a network of inter-helical (i,i' + 5; i, i' + 2) and intra-helical (i, i + 4) attractive interactions with the phosphorylated serine. When the arginines are replaced with lysines, the stabilizing effect of serine phosphorylation is reduced (delta delta GP = -0.5 kcal mol-1 dimer-1). The hydrophobic interface of the leucine zipper needs a glycine in the d position to obtain an increase in stability after phosphorylation. The phosphorylated protein binds DNA with a 15-fold higher affinity. Using a transient transfection assay, we document a PKA dependent four-fold activation of a reporter gene. Phosphorylation of a threonine in the same e position decreases the stability by delta delta GP = +1.2 kcal mol-1 dimer-1. We present circular dichroism (CD) thermal denaturations of 15 bZIP proteins before and after phosphorylation. These data provide insights into the structural determinants that result in stabilization of a coiled coil by phosphorylation. JF - Protein science : a publication of the Protein Society AU - Szilák, L AU - Moitra, J AU - Vinson, C AD - Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/06// PY - 1997 DA - June 1997 SP - 1273 EP - 1283 VL - 6 IS - 6 SN - 0961-8368, 0961-8368 KW - Avian Proteins KW - 0 KW - Basic-Leucine Zipper Transcription Factors KW - Carrier Proteins KW - DNA Probes KW - DNA-Binding Proteins KW - G-Box Binding Factors KW - Phosphoproteins KW - Recombinant Proteins KW - Transcription Factors KW - Threonine KW - 2ZD004190S KW - Glutamic Acid KW - 3KX376GY7L KW - Serine KW - 452VLY9402 KW - Arginine KW - 94ZLA3W45F KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Glycine KW - TE7660XO1C KW - Index Medicus KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Centrifugation, Isopycnic KW - Glycine -- chemistry KW - Threonine -- metabolism KW - Threonine -- genetics KW - Mutagenesis, Site-Directed KW - Protein Engineering KW - Phosphorylation KW - Recombinant Proteins -- metabolism KW - Genes, Reporter KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - DNA Probes -- metabolism KW - Phosphoproteins -- metabolism KW - Arginine -- chemistry KW - Glycine -- metabolism KW - Protein Denaturation KW - Circular Dichroism KW - Amino Acid Sequence KW - Protein Binding KW - Transcriptional Activation KW - Hot Temperature KW - Glycine -- genetics KW - Threonine -- chemistry KW - Transfection KW - Protein Structure, Secondary KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- chemistry KW - DNA-Binding Proteins -- chemistry KW - Transcription Factors -- metabolism KW - Carrier Proteins -- genetics KW - DNA-Binding Proteins -- genetics KW - Transcription Factors -- genetics KW - Serine -- chemistry KW - Serine -- metabolism KW - Serine -- genetics KW - Leucine Zippers -- genetics KW - Transcription Factors -- chemistry KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79072423?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+science+%3A+a+publication+of+the+Protein+Society&rft.atitle=Design+of+a+leucine+zipper+coiled+coil+stabilized+1.4+kcal+mol-1+by+phosphorylation+of+a+serine+in+the+e+position.&rft.au=Szil%C3%A1k%2C+L%3BMoitra%2C+J%3BVinson%2C+C&rft.aulast=Szil%C3%A1k&rft.aufirst=L&rft.date=1997-06-01&rft.volume=6&rft.issue=6&rft.spage=1273&rft.isbn=&rft.btitle=&rft.title=Protein+science+%3A+a+publication+of+the+Protein+Society&rft.issn=09618368&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-13 N1 - Date created - 1997-08-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Mol Biol. 1975 Oct 25;98(2):293-304 [1195389] Nat Struct Biol. 1997 Feb;4(2):112-4 [9033589] Annu Rev Biophys Bioeng. 1984;13:145-65 [6378067] J Mol Biol. 1986 May 5;189(1):113-30 [3537305] Proc Natl Acad Sci U S A. 1987 Dec;84(24):8898-902 [3122208] J Biol Chem. 1989 Apr 25;264(12):6870-3 [2540166] Science. 1989 Nov 17;246(4932):911-6 [2683088] J Mol Biol. 1990 Dec 20;216(4):1031-44 [2266554] Oncogene. 1991 Jan;6(1):173-9 [1899479] J Biol Chem. 1991 Aug 15;266(23):15325-33 [1651325] J Biol Chem. 1991 Aug 25;266(24):15555-8 [1651913] Genes Dev. 1991 Sep;5(9):1553-67 [1884998] Mol Cell Biol. 1991 Oct;11(10):4863-75 [1922023] Science. 1991 Oct 25;254(5031):539-44 [1948029] Cell. 1992 Feb 21;68(4):699-708 [1739975] Cell. 1992 Sep 4;70(5):777-89 [1516134] Curr Opin Genet Dev. 1993 Apr;3(2):278-85 [8504253] Genes Dev. 1993 Jun;7(6):1047-58 [8504929] Science. 1993 Nov 26;262(5138):1401-7 [8248779] EMBO J. 1994 Jun 15;13(12):2849-61 [8026470] Protein Eng. 1994 Nov;7(11):1365-72 [7700868] Protein Sci. 1995 Mar;4(3):405-15 [7795524] FEBS Lett. 1995 Jul 24;368(3):452-4 [7635197] EMBO J. 1995 Nov 1;14(21):5329-37 [7489722] J Biol Chem. 1996 Jan 26;271(4):2040-7 [8567657] Nat Struct Biol. 1996 Jun;3(6):510-5 [8646536] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ethanol-exposed central neurons fail to migrate and undergo apoptosis. AN - 79071112; 9185667 AB - Prenatal exposure of human brain to ethanol impairs neuronal migration and differentiation and causes mental retardation. The present results indicate that the adverse effects of ethanol on brain development may be partly due to the ethanol-induced disturbance of neuronal interaction with laminin, a protein involved in neuronal migration and axon guidance. This report shows that physiological concentrations (IC50 = 28 mM) of ethanol inhibit neurite outgrowth and neuronal migration of the rat cerebellar granule neurons on a laminin substratum. The ethanol-treated granule neurons undergo apoptosis, degrade their laminin substratum, and appear to release and bind increased amounts of the B2-chain-derived peptides along their surfaces. A protease inhibitor aprotinin, and the NMDA receptor channel, and voltage-gated calcium channel antagonist MK801 partially protect cerebellar granule neurons from ethanol-induced neurotoxicity. These results imply that ethanol-treated granule neurons resemble the granule neurons of the homozygous weaver mouse cerebellum with respect to their apoptosis, laminin expression, and partial rescue by approtinin and MK-801. Thus, ethanol may influence neuronal survival and neurite outgrowth via molecular pathways similar to those involved in neuronal death in other neurodegenerative processes of the central nervous system. JF - Journal of neuroscience research AU - Liesi, P AD - Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland 20852, USA. liesi@helix.nih.gov Y1 - 1997/06/01/ PY - 1997 DA - 1997 Jun 01 SP - 439 EP - 448 VL - 48 IS - 5 SN - 0360-4012, 0360-4012 KW - Central Nervous System Depressants KW - 0 KW - Laminin KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Rats KW - Immunoblotting KW - Animals KW - Rats, Sprague-Dawley KW - Cerebellum -- cytology KW - Neurites -- drug effects KW - Dose-Response Relationship, Drug KW - Neurites -- physiology KW - Laminin -- pharmacology KW - Central Nervous System Depressants -- toxicity KW - Neurons -- drug effects KW - Neurons -- cytology KW - Apoptosis -- drug effects KW - Cell Movement -- drug effects KW - Ethanol -- toxicity KW - Neurons -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79071112?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Ethanol-exposed+central+neurons+fail+to+migrate+and+undergo+apoptosis.&rft.au=Liesi%2C+P&rft.aulast=Liesi&rft.aufirst=P&rft.date=1997-06-01&rft.volume=48&rft.issue=5&rft.spage=439&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 - 1997-07-28 N1 - Date created - 1997-07-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of galanin and the galanin antagonist M40 on delayed non-matching-to-position performance in rats lesioned with the cholinergic immunotoxin 192 IgG-saporin. AN - 79066799; 9189270 AB - Galanin is a 29-amino-acid neuropeptide that is overexpressed in Alzheimer's disease (AD) and impairs performance on rodent learning and memory tasks. M40, a peptidergic galanin receptor ligand, blocks galanin-induced impairments on delayed non-matching-to-position (DNMTP). The present experiments used the 192IgG-saporin lesion model of AD to evaluate the actions of galanin and M40 on DNMTP when cholinergic transmission was reduced. Hippocampal choline acetyltransferase levels were correlated with DNMTP choice accuracy in lesioned rats. Intracerebroventricular (icv) galanin reduced choice accuracy in both the lesioned and sham groups. M40 alone, either icv or intrahippocampal, did not affect choice accuracy in either group. These results suggest that excess galanin can produce further deficits in DNMTP performance in a lesion model of AD, but blocking endogenous galanin is not sufficient alone to improve performance in lesioned rats. JF - Behavioral neuroscience AU - McDonald, M P AU - Wenk, G L AU - Crawley, J N AD - Section on Behavioral Neuropharmacology, National Institute of Mental Health, Bethesda, Maryland 20892, USA. mikemc@codon.nih.gov Y1 - 1997/06// PY - 1997 DA - June 1997 SP - 552 EP - 563 VL - 111 IS - 3 SN - 0735-7044, 0735-7044 KW - 192 IgG-saporin KW - 0 KW - Antibodies, Monoclonal KW - Immunotoxins KW - M40 KW - Peptide Fragments KW - Receptors, Cholinergic KW - Receptors, Galanin KW - Receptors, Gastrointestinal Hormone KW - Ribosome Inactivating Proteins, Type 1 KW - Galanin KW - 88813-36-9 KW - N-Glycosyl Hydrolases KW - EC 3.2.2.- KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Disease Models, Animal KW - Hippocampus -- drug effects KW - Rats KW - Receptors, Gastrointestinal Hormone -- physiology KW - Brain Mapping KW - Rats, Sprague-Dawley KW - Receptors, Gastrointestinal Hormone -- drug effects KW - Hippocampus -- physiopathology KW - Male KW - Discrimination Learning -- drug effects KW - Orientation -- physiology KW - Discrimination Learning -- physiology KW - Alzheimer Disease -- physiopathology KW - Antibodies, Monoclonal -- pharmacology KW - Galanin -- pharmacology KW - Receptors, Cholinergic -- drug effects KW - Mental Recall -- physiology KW - Galanin -- antagonists & inhibitors KW - Receptors, Cholinergic -- physiology KW - Peptide Fragments -- pharmacology KW - Orientation -- drug effects KW - Immunotoxins -- pharmacology KW - Mental Recall -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79066799?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Behavioral+neuroscience&rft.atitle=Analysis+of+galanin+and+the+galanin+antagonist+M40+on+delayed+non-matching-to-position+performance+in+rats+lesioned+with+the+cholinergic+immunotoxin+192+IgG-saporin.&rft.au=McDonald%2C+M+P%3BWenk%2C+G+L%3BCrawley%2C+J+N&rft.aulast=McDonald&rft.aufirst=M&rft.date=1997-06-01&rft.volume=111&rft.issue=3&rft.spage=552&rft.isbn=&rft.btitle=&rft.title=Behavioral+neuroscience&rft.issn=07357044&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-12 N1 - Date created - 1997-08-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Promoter and species specific differential estrogen-mediated gene transcription in the uterus and cultured cells using structurally altered agonists. AN - 79066003; 9195474 AB - Certain types of estrogenic compounds have been shown to have tissue-specific actions. In addition, some tissues may exhibit differential gene regulation by agonists and antagonists. Our previous studies using structurally modified estrogenic molecules had indicated differential effects on specific estrogen responses, indicating that the activity of the estrogen receptor protein can be altered depending not only upon the structure of the bound ligand but also the regulated gene itself. The mechanism of differential induction, however, was not determined, and might involve altered binding to the estrogen response element (ERE), altered transcription, or post-transcriptional modification of gene products. Our previous studies indicated that differential induction by modified diethylstilbestrol (DES) agonists could not be accounted for by differences in ligand affinity for the estrogen receptor (ER) or differential binding of the ER to a consensus vitellogenin A2 (vit A2) ERE. To determine if this differential hormonal responsiveness was reflected at the level of transcription, we analyzed mouse uterine mRNA of several estrogen-responsive genes, including glucose-6-phosphate dehydrogenase (G6PD), ornithine decarboxylase (ODC) and lactoferrin, by Northern blot following injection with the modified agonists DES, indenestrol A (IA), indenestrol B (IB) and Z-pseudo DES (ZPD). All compounds induced the G6PD message, although IB and ZPD induced expression only transiently, while DES and IA maintained the message for 24 h. No difference in induction was seen for ODC message, which was induced equally by all the compounds. In contrast, lactoferrin, a highly estrogen-responsive gene, was induced only by DES and IA and not by the other agonists IB or ZPD, showing that the lactoferrin gene was differentially regulated by these compounds. To determine whether this difference was due to altered transcriptional activity, the mouse lactoferrin estrogen-responsive module (mERM) linked to a chloramphenicol acetyl transferase (CAT) reporter gene was tested in transfected cells. Using the mouse estrogen receptor in RL95 cells, DES and IA induced expression of CAT, but IB did not, confirming the differential response seen in vivo. To show whether this difference in transcription occurred because of altered binding to the lactoferrin ERE, which is not a perfect consensus ERE a gel shift assay was used to examine DNA binding of ER bound to the agonists. All ligands produced equivalent binding to the lactoferrin ERE suggesting that differential regulation was not a result of altered DNA binding. Taken together, these observations indicate that the differential induction of lactoferrin by these compounds occurs via altered activation of the transcriptional components unique to lactoferrin and is likely to involve altered interaction with co-activators. Surprisingly, unlike the mouse ER, the human estrogen receptor activated and induced expression of lactoferrin estrogen-responsive module-CAT with all the compounds. Mouse ER is also known to vary from the human ER in its activity with the triphenylethylene estrogen tamoxifen, which has agonist activity with the mouse ER but mixed antagonist/agonist activity with the human ER. The data show that human and mouse estrogen receptors are activated differently by this group of stilbestrol estrogen ligands when assayed on the lactoferrin response element, which is the first description of this type of gene and species specific difference. Lactoferrin gene regulation by estrogen receptor can be used as a model to study the mechanism of differential gene activation by different estrogen agonists and antagonists using a more physiological situation than commonly used with in vitro gene reporter systems. JF - Journal of molecular endocrinology AU - Curtis, S W AU - Shi, H AU - Teng, C AU - Korach, K S AD - Receptor Biology Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/06// PY - 1997 DA - June 1997 SP - 203 EP - 211 VL - 18 IS - 3 SN - 0952-5041, 0952-5041 KW - Estrogens KW - 0 KW - Oligonucleotide Probes KW - RNA, Messenger KW - Receptors, Estrogen KW - Diethylstilbestrol KW - 731DCA35BT KW - Glucosephosphate Dehydrogenase KW - EC 1.1.1.49 KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Lactoferrin KW - EC 3.4.21.- KW - Ornithine Decarboxylase KW - EC 4.1.1.17 KW - Index Medicus KW - Animals KW - Receptors, Estrogen -- drug effects KW - Ornithine Decarboxylase -- genetics KW - Oligonucleotide Probes -- genetics KW - Humans KW - Transcription, Genetic KW - Mice KW - Receptors, Estrogen -- metabolism KW - RNA, Messenger -- genetics KW - Models, Biological KW - Glucosephosphate Dehydrogenase -- genetics KW - Chloramphenicol O-Acetyltransferase -- genetics KW - Base Sequence KW - Receptors, Estrogen -- genetics KW - Lactoferrin -- genetics KW - RNA, Messenger -- metabolism KW - Cells, Cultured KW - Molecular Sequence Data KW - Diethylstilbestrol -- pharmacology KW - Diethylstilbestrol -- analogs & derivatives KW - Female KW - Uterus -- metabolism KW - Estrogens -- agonists KW - Promoter Regions, Genetic KW - Estrogens -- metabolism KW - Uterus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79066003?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+endocrinology&rft.atitle=Promoter+and+species+specific+differential+estrogen-mediated+gene+transcription+in+the+uterus+and+cultured+cells+using+structurally+altered+agonists.&rft.au=Curtis%2C+S+W%3BShi%2C+H%3BTeng%2C+C%3BKorach%2C+K+S&rft.aulast=Curtis&rft.aufirst=S&rft.date=1997-06-01&rft.volume=18&rft.issue=3&rft.spage=203&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+endocrinology&rft.issn=09525041&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-22 N1 - Date created - 1997-08-22 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - X53617; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of polymerization on the hypertensive action of diaspirin cross-linked hemoglobin in rats. AN - 79060270; 9178726 AB - It is believed that the hypertensive effect of diaspirin crosslinked hemoglobin, a viable blood substitute, can be resolved by polymerization, which reduces the diffusion of this derivative into the interstitial space between nitric oxide-producing endothelium and the target vascular smooth muscle. We studied the systemic and renal responses to infusion of three cell-free human hemoglobins in anesthetized isovolemic rats: unmodified (HbA0), crosslinked (alpha-DBBF), and polymerized crosslinked (poly alpha-DBBF). HbA0 produced a significant increase in mean arterial blood pressure (MAP) throughout the 60-minute infusion. alpha-DBBF, on the other hand, produced a more marked and prolonged increase in MAP over 120 minutes. Only a moderate increase in MAP was observed in rats after a 30-minute infusion with poly alpha-DBBF. The extent of renal insufficiency produced by these proteins, as determined by the glomerular filtration rate, was in the following order: HbA0 > poly alpha-DBBF > alpha-DBBF. Infusion of poly alpha-DBBF, under hypovolemic but not isovolemic conditions in rats, produced an increase in heart rate, cardiac output, and stroke volume and a decrease in total peripheral resistance after 60 minutes. Chemical polymerization to increase the size of alpha-DBBF does not appear to improve its hemodynamic properties in rats, especially under partial exchange transfusion, a more clinically relevant indication for a hemoglobin-based blood substitute. JF - The Journal of laboratory and clinical medicine AU - Abassi, Z AU - Kotob, S AU - Pieruzzi, F AU - Abouassali, M AU - Keiser, H R AU - Fratantoni, J C AU - Alayash, A I AD - National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1997/06// PY - 1997 DA - June 1997 SP - 603 EP - 610 VL - 129 IS - 6 SN - 0022-2143, 0022-2143 KW - Blood Substitutes KW - 0 KW - Cross-Linking Reagents KW - Hemoglobins KW - bis(3,5-dibromosalicyl)fumarate KW - 0E07K30TXY KW - Polyethylene Glycols KW - 30IQX730WE KW - succinyldisalicylic acid KW - 578-19-8 KW - Sodium KW - 9NEZ333N27 KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Aspirin KW - R16CO5Y76E KW - Potassium KW - RWP5GA015D KW - NG-Nitroarginine Methyl Ester KW - V55S2QJN2X KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Muscle, Smooth, Vascular -- physiology KW - Analysis of Variance KW - Muscle, Smooth, Vascular -- physiopathology KW - NG-Nitroarginine Methyl Ester -- pharmacology KW - Glomerular Filtration Rate -- drug effects KW - Aorta -- physiopathology KW - Humans KW - Cardiac Output -- drug effects KW - Endothelium, Vascular -- physiology KW - Nitric Oxide Synthase -- biosynthesis KW - Rats KW - Heart Rate -- drug effects KW - Endothelium, Vascular -- drug effects KW - Aorta -- drug effects KW - Potassium -- urine KW - Sodium -- urine KW - Male KW - Endothelium, Vascular -- enzymology KW - Aorta -- physiology KW - Muscle, Smooth, Vascular -- drug effects KW - Vascular Resistance -- drug effects KW - Rats, Sprague-Dawley KW - Enzyme Induction KW - Stroke Volume -- drug effects KW - Hemodynamics -- drug effects KW - Hypertension -- chemically induced KW - Hypertension -- physiopathology KW - Hemoglobins -- toxicity KW - Hemoglobins -- isolation & purification KW - Aspirin -- analogs & derivatives KW - Blood Pressure -- drug effects KW - Blood Substitutes -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79060270?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+laboratory+and+clinical+medicine&rft.atitle=Effects+of+polymerization+on+the+hypertensive+action+of+diaspirin+cross-linked+hemoglobin+in+rats.&rft.au=Abassi%2C+Z%3BKotob%2C+S%3BPieruzzi%2C+F%3BAbouassali%2C+M%3BKeiser%2C+H+R%3BFratantoni%2C+J+C%3BAlayash%2C+A+I&rft.aulast=Abassi&rft.aufirst=Z&rft.date=1997-06-01&rft.volume=129&rft.issue=6&rft.spage=603&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+laboratory+and+clinical+medicine&rft.issn=00222143&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-26 N1 - Date created - 1997-06-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Lab Clin Med. 1997 Jun;129(6):580-3 [9178723] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - P-glycoprotein substrates and antagonists cluster into two distinct groups. AN - 79057634; 9187269 AB - To gather further insight into the interaction between P-glycoprotein (Pgp) and its substrates, 167 compounds were analyzed in multidrug resistant human colon carcinoma cells. These compounds were selected from the National Cancer Institute Drug Screen repository using computer-generated correlations with known Pgp substrates and antagonists. The compounds were prospectively defined as Pgp substrates if cytotoxicity was increased > or =4-fold by the addition of cyclosporin A (CsA) and as Pgp antagonists if inhibition of efflux increased rhodamine accumulation by 4-fold. Among the 84 agents that met either criterion, 35 met only the criterion for substrates, 42 met only the criterion for antagonists, and only seven met both criteria. Thus, compounds interacting with Pgp form two distinct groups: one comprising cytotoxic compounds that are transported and have poor or no antagonistic activity and a second comprising compounds with antagonistic activity and no evidence of significant transport. Vinblastine accumulation and kinetic studies performed on a subset of 18 compounds similarly differentiated substrates and antagonists, but inhibition of 3H-azidopine labeling and induction of ATPase activity did not. These data support an emerging concept of Pgp in which multiple regions instead of specific sites are involved in drug transport. JF - Molecular pharmacology AU - Scala, S AU - Akhmed, N AU - Rao, U S AU - Paull, K AU - Lan, L B AU - Dickstein, B AU - Lee, J S AU - Elgemeie, G H AU - Stein, W D AU - Bates, S E AD - Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/06// PY - 1997 DA - June 1997 SP - 1024 EP - 1033 VL - 51 IS - 6 SN - 0026-895X, 0026-895X KW - Affinity Labels KW - 0 KW - Antineoplastic Agents KW - Antineoplastic Agents, Phytogenic KW - Azides KW - Dihydropyridines KW - Fluorescent Dyes KW - Immunosuppressive Agents KW - P-Glycoprotein KW - Rhodamines KW - Tritium KW - 10028-17-8 KW - Vinblastine KW - 5V9KLZ54CY KW - azidopine KW - 63XR70204A KW - Cyclosporine KW - 83HN0GTJ6D KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - Index Medicus KW - Drug Screening Assays, Antitumor KW - Drug Interactions KW - Humans KW - Antineoplastic Agents -- pharmacokinetics KW - Vinblastine -- pharmacokinetics KW - Adenosine Triphosphatases -- metabolism KW - Dihydropyridines -- metabolism KW - Immunosuppressive Agents -- pharmacology KW - Drug Resistance, Multiple KW - Stimulation, Chemical KW - Antineoplastic Agents, Phytogenic -- pharmacokinetics KW - Azides -- metabolism KW - Biological Transport, Active -- drug effects KW - Adenosine Triphosphatases -- drug effects KW - Tumor Cells, Cultured KW - Cyclosporine -- pharmacology KW - Colonic Neoplasms -- drug therapy KW - Affinity Labels -- metabolism KW - Fluorescent Dyes -- pharmacokinetics KW - Colonic Neoplasms -- metabolism KW - Substrate Specificity KW - Antineoplastic Agents -- pharmacology KW - Rhodamines -- pharmacokinetics KW - P-Glycoprotein -- metabolism KW - P-Glycoprotein -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79057634?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=P-glycoprotein+substrates+and+antagonists+cluster+into+two+distinct+groups.&rft.au=Scala%2C+S%3BAkhmed%2C+N%3BRao%2C+U+S%3BPaull%2C+K%3BLan%2C+L+B%3BDickstein%2C+B%3BLee%2C+J+S%3BElgemeie%2C+G+H%3BStein%2C+W+D%3BBates%2C+S+E&rft.aulast=Scala&rft.aufirst=S&rft.date=1997-06-01&rft.volume=51&rft.issue=6&rft.spage=1024&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 - 1997-07-14 N1 - Date created - 1997-07-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Constitutive expression of mature transforming growth factor beta1 in the liver accelerates hepatocarcinogenesis in transgenic mice. AN - 79056564; 9187100 AB - Transforming growth factor beta-1 (TGF-beta1) is a potent inhibitor of hepatocyte growth both in vivo and in vitro. In this study, we analyzed the effects of TGF-beta1 on both naturally occurring and diethylnitrosamine-induced hepatocarcinogenesis using single transgenic TGF-beta1 and double transgenic c-myc/TGF-beta1 mice in which the expression of both transgenes was targeted to the liver. Hepatocellular tumors developed spontaneously in 59% (10 of 17) of the TGF-beta1 mice by 16-18 months of age. Coexpression of TGF-beta1 and c-myc transgenes in the liver accelerated hepatic tumor growth in both the presence and absence of carcinogenic treatment. Moreover, diethylnitrosamine-initiated tumors in the c-myc/TGF-beta1 mice showed a high rate of malignant conversion associated with a reduced expression or lack of TGF-beta receptor type II. The results suggest that overexpression of TGF-beta1 may contribute to liver carcinogenesis and that loss of TGF-beta receptor type II transduced inhibitory growth signals and up-regulation of c-myc are critical steps in liver tumor progression. JF - Cancer research AU - Factor, V M AU - Kao, C Y AU - Santoni-Rugiu, E AU - Woitach, J T AU - Jensen, M R AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1997/06/01/ PY - 1997 DA - 1997 Jun 01 SP - 2089 EP - 2095 VL - 57 IS - 11 SN - 0008-5472, 0008-5472 KW - RNA, Messenger KW - 0 KW - Receptors, Transforming Growth Factor beta KW - Transforming Growth Factor beta KW - Diethylnitrosamine KW - 3IQ78TTX1A KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - Animals KW - Blotting, Northern KW - RNA, Messenger -- metabolism KW - Receptors, Transforming Growth Factor beta -- metabolism KW - RNA, Messenger -- analysis KW - Mice KW - Up-Regulation KW - Mice, Transgenic KW - Immunohistochemistry KW - Signal Transduction KW - Liver Neoplasms, Experimental -- metabolism KW - Genes, myc KW - Liver Neoplasms, Experimental -- chemically induced 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/79056564?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Constitutive+expression+of+mature+transforming+growth+factor+beta1+in+the+liver+accelerates+hepatocarcinogenesis+in+transgenic+mice.&rft.au=Factor%2C+V+M%3BKao%2C+C+Y%3BSantoni-Rugiu%2C+E%3BWoitach%2C+J+T%3BJensen%2C+M+R%3BThorgeirsson%2C+S+S&rft.aulast=Factor&rft.aufirst=V&rft.date=1997-06-01&rft.volume=57&rft.issue=11&rft.spage=2089&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-10 N1 - Date created - 1997-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sequence and chromosomal mapping of the mouse homolog (Madh4) of the human DPC4/MADH4 gene. AN - 79043110; 9166592 JF - Mammalian genome : official journal of the International Mammalian Genome Society AU - Anna, C H AU - Devereux, T R AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/06// PY - 1997 DA - June 1997 SP - 443 EP - 444 VL - 8 IS - 6 SN - 0938-8990, 0938-8990 KW - DNA-Binding Proteins KW - 0 KW - SMAD4 protein, human KW - Smad4 Protein KW - Smad4 protein, mouse KW - Trans-Activators KW - Index Medicus KW - Dinucleotide Repeats KW - Animals KW - Microsatellite Repeats -- genetics KW - Blotting, Northern KW - Humans KW - Amino Acid Sequence KW - Mice KW - Tissue Distribution KW - Sequence Analysis, DNA KW - Mice, Inbred BALB C KW - Lung -- physiology KW - Mice, Inbred DBA KW - Cloning, Molecular KW - Polymerase Chain Reaction KW - Mice, Inbred Strains KW - Molecular Sequence Data KW - Mice, Inbred C57BL KW - Mice, Inbred C3H KW - Crosses, Genetic KW - Female KW - Male KW - Trans-Activators -- metabolism KW - Trans-Activators -- genetics KW - Sequence Homology, Amino Acid KW - Chromosome Mapping UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79043110?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mammalian+genome+%3A+official+journal+of+the+International+Mammalian+Genome+Society&rft.atitle=Sequence+and+chromosomal+mapping+of+the+mouse+homolog+%28Madh4%29+of+the+human+DPC4%2FMADH4+gene.&rft.au=Anna%2C+C+H%3BDevereux%2C+T+R&rft.aulast=Anna&rft.aufirst=C&rft.date=1997-06-01&rft.volume=8&rft.issue=6&rft.spage=443&rft.isbn=&rft.btitle=&rft.title=Mammalian+genome+%3A+official+journal+of+the+International+Mammalian+Genome+Society&rft.issn=09388990&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-30 N1 - Date created - 1997-06-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetically null mice reveal a central role for epidermal growth factor receptor in the differentiation of the hair follicle and normal hair development. AN - 79038815; 9176390 AB - Mice harboring a targeted disruption of the epidermal growth factor receptor (EGFR) allele exhibit a severely disorganized hair follicle phenotype, fuzzy coat, and systemic disease resulting in death before 3 weeks. This skin phenotype was reproduced in whole skin grafts and in grafts of EGFR null hair follicle buds onto nude mice, providing a model to evaluate the natural evolution of skin lacking the EGFR. Hair follicles in grafts of null skin did not progress from anagen to telogen and scanning electron micrografts revealed wavy, flattened hair fibers with cuticular abnormalities. Many of the EGFR null hair follicles in the grafted skin were consumed by an inflammatory reaction resulting in complete hair loss in 67% of the grafts by 10 weeks. Localization of follicular differentiation markers including keratin 6, transglutaminase, and the hair keratins mHa2 and hacl-1 revealed a pattern of premature differentiation within the null hair follicles. In intact EGFR null mice, proliferation in the interfollicular epidermis, but not hair follicles, was greatly decreased in the absence of EGFR. In contrast, grafting of EGFR null skin resulted in a hyperplastic response in the epidermis that did not resolve even after 10 weeks, although the wound-induced hyperplasia in EGFR wild-type grafts had resolved within 3 to 4 weeks. Thus, epithelial expression of the EGFR has complex functions in the skin. It is important in delaying follicular differentiation, may serve to protect the hair follicle from immunological reactions, and modifies both normal and wound-induced epidermal proliferation but seems dispensable for follicular proliferation. JF - The American journal of pathology AU - Hansen, L A AU - Alexander, N AU - Hogan, M E AU - Sundberg, J P AU - Dlugosz, A AU - Threadgill, D W AU - Magnuson, T AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institute of Health, Bethesda, Maryland 20892-0001, USA. Y1 - 1997/06// PY - 1997 DA - June 1997 SP - 1959 EP - 1975 VL - 150 IS - 6 SN - 0002-9440, 0002-9440 KW - Antigens, Differentiation KW - 0 KW - Intermediate Filament Proteins KW - Membrane Proteins KW - filaggrin KW - loricrin KW - Keratins KW - 68238-35-7 KW - Transglutaminases KW - EC 2.3.2.13 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Age Factors KW - Antigens, Differentiation -- metabolism KW - Skin Transplantation KW - Cell Differentiation KW - Intermediate Filament Proteins -- analysis KW - Mice, Nude KW - Mice KW - Keratins -- analysis KW - Membrane Proteins -- analysis KW - Mice, Knockout KW - Animals, Newborn KW - In Situ Hybridization KW - Transglutaminases -- metabolism KW - Epithelium -- physiology KW - Immunohistochemistry KW - Microscopy, Electron, Scanning KW - Cell Division KW - Hair Follicle -- ultrastructure KW - Hair Follicle -- physiology KW - Receptor, Epidermal Growth Factor -- metabolism KW - Skin Physiological Phenomena KW - Receptor, Epidermal Growth Factor -- genetics KW - Hair Follicle -- metabolism KW - Hair -- ultrastructure KW - Hair -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79038815?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Genetically+null+mice+reveal+a+central+role+for+epidermal+growth+factor+receptor+in+the+differentiation+of+the+hair+follicle+and+normal+hair+development.&rft.au=Hansen%2C+L+A%3BAlexander%2C+N%3BHogan%2C+M+E%3BSundberg%2C+J+P%3BDlugosz%2C+A%3BThreadgill%2C+D+W%3BMagnuson%2C+T%3BYuspa%2C+S+H&rft.aulast=Hansen&rft.aufirst=L&rft.date=1997-06-01&rft.volume=150&rft.issue=6&rft.spage=1959&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+pathology&rft.issn=00029440&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-03 N1 - Date created - 1997-07-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Invest Dermatol. 1996 Feb;106(2):294-304 [8601731] J Biol Chem. 1984 Jul 10;259(13):8037-40 [6203901] J Invest Dermatol. 1984 Aug;83(2):118-23 [6088642] J Invest Dermatol. 1984 Nov;83(5):385-93 [6092481] J Invest Dermatol. 1985 Mar;84(3):172-5 [3871824] Br J Dermatol. 1986 Mar;114(3):279-83 [2869777] Cell. 1987 Sep 25;50(7):1131-7 [3497724] Mol Cell Biol. 1988 May;8(5):2195-203 [3133554] Arch Dermatol Res. 1990;281(8):530-5 [2322011] J Invest Dermatol. 1990 Jun;94(6):742-8 [1693937] Nucleic Acids Res. 1990 Aug 11;18(15):4401-7 [2388825] J Cell Physiol. 1991 Feb;146(2):277-89 [1999476] Genes Dev. 1991 May;5(5):714-27 [1709129] J Invest Dermatol. 1991 Sep;97(3):417-20 [1714928] J Invest Dermatol. 1992 Jan;98(1):109-15 [1370228] Am J Pathol. 1992 Apr;140(4):915-25 [1532884] Ann N Y Acad Sci. 1991 Dec 26;642:243-51; discussion 251-2 [1809084] Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6896-900 [1379725] J Biol Chem. 1992 Oct 25;267(30):21277-80 [1383221] Biol Reprod. 1992 Nov;47(5):903-15 [1477216] J Invest Dermatol. 1993 Mar;100(3):229-36 [8440892] Cell. 1993 Apr 23;73(2):249-61 [8477444] Cell. 1993 Apr 23;73(2):263-78 [8477445] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6076-80 [7687059] Exp Cell Res. 1993 Dec;209(2):216-23 [8262138] Cell Growth Differ. 1993 Dec;4(12):1071-82 [8117621] J Invest Dermatol. 1994 May;102(5):716-20 [7513738] Exp Cell Res. 1994 Jun;212(2):190-200 [7514534] Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7822-6 [8052666] Br J Dermatol. 1994 Aug;131(2):177-83 [7917980] Cell Growth Differ. 1994 Dec;5(12):1283-92 [7535082] J Invest Dermatol. 1995 May;104(5 Suppl):42S-43S [7537786] Science. 1995 Jul 14;269(5221):230-4 [7618084] Science. 1995 Jul 14;269(5221):234-8 [7618085] J Dermatol. 1995 Jun;22(6):385-95 [7650236] EMBO J. 1995 Nov 1;14(21):5216-23 [7489711] Cell. 1995 Dec 15;83(6):957-68 [8521519] Cancer Lett. 1979 Apr;6(4-5):301-10 [373879] J Endocrinol. 1981 Feb;88(2):293-9 [6970792] Anat Rec. 1983 Jan;205(1):47-55 [6601466] Dev Biol. 1983 Dec;100(2):506-12 [6317490] Dev Biol. 1965 Dec;12(3):394-407 [5884352] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Factors influencing utilization of mental health and substance abuse services by American Indian men and women. AN - 79034326; 9175194 AB - This study investigated the effects of gender, number of lifetime psychiatric diagnoses, and childhood victimization on utilization of mental health and substance abuse treatment services in a Southwestern American Indian tribe. A total of 582 individuals were recruited based on tribal enrollment and membership in large multigenerational pedigrees. Subjects were interviewed using a modified version of the Schedule for Affective Disorders and Schizophrenia-Lifetime Version, a semistructured psychiatric interview. For this study the definition of childhood victimization was limited to childhood sexual abuse. Fifty-six percent of the subjects had received mental health treatment, substance abuse treatment, or both. Patterns of service utilization differed by gender with the odds of inpatient and substance abuse treatment higher for men than for women. Women were more likely than men to receive mental health treatment. Subjects who had been sexually abused as children were more likely to have three or more psychiatric diagnoses and to have received extensive treatment, compared with subjects who reported no childhood sexual abuse history. Logistic regression demonstrated strong relationships between number of psychiatric diagnoses and the likelihood of treatment among both men and women. Gender, number of psychiatric diagnoses, and childhood sexual abuse are strong predictors of utilization of mental health and substance abuse treatment services. These factors should be considered in designing treatment interventions. JF - Psychiatric services (Washington, D.C.) AU - Robin, R W AU - Chester, B AU - Rasmussen, J K AU - Jaranson, J M AU - Goldman, D AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD, USA. Y1 - 1997/06// PY - 1997 DA - June 1997 SP - 826 EP - 832 VL - 48 IS - 6 SN - 1075-2730, 1075-2730 KW - Index Medicus KW - Southwestern United States -- epidemiology KW - Regression Analysis KW - Humans KW - Aged KW - Child KW - Likelihood Functions KW - Child Abuse, Sexual -- psychology KW - Aged, 80 and over KW - Risk Factors KW - Adult KW - Child Abuse, Sexual -- statistics & numerical data KW - Middle Aged KW - Female KW - Male KW - Mental Disorders -- rehabilitation KW - Mental Disorders -- epidemiology KW - Patient Acceptance of Health Care -- statistics & numerical data KW - Mental Health Services -- utilization KW - Indians, North American -- psychology KW - Substance-Related Disorders -- rehabilitation KW - Indians, North American -- statistics & numerical data KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79034326?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychiatric+services+%28Washington%2C+D.C.%29&rft.atitle=Factors+influencing+utilization+of+mental+health+and+substance+abuse+services+by+American+Indian+men+and+women.&rft.au=Robin%2C+R+W%3BChester%2C+B%3BRasmussen%2C+J+K%3BJaranson%2C+J+M%3BGoldman%2C+D&rft.aulast=Robin&rft.aufirst=R&rft.date=1997-06-01&rft.volume=48&rft.issue=6&rft.spage=826&rft.isbn=&rft.btitle=&rft.title=Psychiatric+services+%28Washington%2C+D.C.%29&rft.issn=10752730&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-12 N1 - Date created - 1997-08-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential functional significance of AP-1 binding sites in the promoter of the gene encoding mouse tissue inhibitor of metalloproteinases-3. AN - 79032902; 9182717 AB - Tissue inhibitor of metalloproteinases-3 (TIMP-3) is an extracellular-matrix-associated protein that suppresses tumorigenicity or invasion in several model systems. We have identified, by in vitro footprinting, six AP-1 (activator protein-1) or AP-1-like binding sites in the mouse TIMP-3 promoter that bind purified c-Jun homodimers. Electrophoretic mobility shift assays revealed that the non-consensus fifth AP-1 binding site (AP-720; nt -720 to -714) had the strongest binding activity for recombinant c-Jun protein, and that the fourth binding site (AP-763; nt -763 to -754) and AP-720 showed strong binding activity for cellular nuclear proteins. Antibody supershift and blocking experiments suggest that AP-720, but not AP-763, binds authentic AP-1 components. Transient transfection reporter assays of deletion constructs showed that the region spanning AP-720 has the highest transcriptional activity, and that sequences 5' to this region (nt -2846 to -747) may contain negative regulatory elements. The deletion construct containing about 500 nt 5' to the transcriptional start, but no AP-1 sites, showed lower but significant activity, suggesting both AP-1-dependent and -independent regulation of the mouse TIMP-3 promoter. Mutational inactivation of AP-720 abolished the activity increment that distinguished the reporter construct containing both AP-720 and sixth AP-1 binding site (AP-617; nt -617 to -611) from that containing only AP-617. In summary, we report here that both AP-1 and non-AP-1 elements contribute to activity, with the non-consensus AP-1 site at -720 showing the greatest functional significance among the AP-1 sites. JF - The Biochemical journal AU - Kim, H AU - Pennie, W D AU - Sun, Y AU - Colburn, N H AD - Gene Regulation Section, Laboratory of Biochemical Physiology, National Cancer Institute, Frederick Cancer Research & Development Center, Frederick, MD 21702, USA. Y1 - 1997/06/01/ PY - 1997 DA - 1997 Jun 01 SP - 547 EP - 553 VL - 324 ( Pt 2) SN - 0264-6021, 0264-6021 KW - Proteins KW - 0 KW - Proto-Oncogene Proteins c-jun KW - Recombinant Fusion Proteins KW - Tissue Inhibitor of Metalloproteinase-3 KW - Transcription Factor AP-1 KW - Luciferases KW - EC 1.13.12.- KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Dimerization KW - Transcription, Genetic KW - Mice KW - Proto-Oncogene Proteins c-jun -- metabolism KW - Protein Binding KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Recombinant Fusion Proteins -- metabolism KW - Transfection KW - DNA Footprinting KW - Genes, Reporter KW - Luciferases -- genetics KW - Sequence Deletion KW - Promoter Regions, Genetic KW - Transcription Factor AP-1 -- metabolism KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79032902?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Differential+functional+significance+of+AP-1+binding+sites+in+the+promoter+of+the+gene+encoding+mouse+tissue+inhibitor+of+metalloproteinases-3.&rft.au=Kim%2C+H%3BPennie%2C+W+D%3BSun%2C+Y%3BColburn%2C+N+H&rft.aulast=Kim&rft.aufirst=H&rft.date=1997-06-01&rft.volume=324+%28+Pt+2%29&rft.issue=&rft.spage=547&rft.isbn=&rft.btitle=&rft.title=The+Biochemical+journal&rft.issn=02646021&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-08 N1 - Date created - 1997-07-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1979 Oct 18;281(5732):589-91 [492322] Int J Cancer. 1995 Nov 27;63(5):680-7 [7591285] Cell. 1987 Jun 19;49(6):729-39 [3034432] Mol Cell Biol. 1988 Aug;8(8):3227-34 [2850484] J Biol Chem. 1991 Apr 15;266(11):7199-206 [1849903] Environ Health Perspect. 1991 Jun;93:111-9 [1773784] Science. 1992 Aug 14;257(5072):967-71 [1354393] Biochim Biophys Acta. 1992 Nov 15;1171(1):41-55 [1420363] Crit Rev Oral Biol Med. 1993;4(2):197-250 [8435466] Mol Carcinog. 1993;8(1):49-57 [8352891] Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):609-13 [8290571] Gene. 1994 Feb 25;139(2):185-91 [8112602] Cancer Res. 1994 Mar 1;54(5):1139-44 [8118794] J Biol Chem. 1994 Mar 25;269(12):9352-60 [8132674] Gene. 1994 Apr 20;141(2):293-7 [8163205] Cancer Res. 1994 Apr 15;54(8):2091-4 [8174111] Genomics. 1994 Jan 1;19(1):86-90 [8188246] J Biol Chem. 1994 Jul 22;269(29):18953-60 [8034652] FEBS Lett. 1994 Sep 26;352(2):171-4 [7925969] Dev Dyn. 1994 Jul;200(3):177-97 [7949367] Nucleic Acids Res. 1994 Dec 25;22(25):5672-8 [7838721] DNA Cell Biol. 1994 Jul;13(7):711-8 [7772252] J Biol Chem. 1995 Jun 16;270(24):14313-8 [7782289] Dev Dyn. 1995 Apr;202(4):388-96 [7626795] J Biol Chem. 1995 Aug 18;270(33):19312-9 [7642607] Biochem J. 1995 Oct 15;311 ( Pt 2):549-54 [7487894] Carcinog Compr Surv. 1985;8:341-67 [3157452] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Association of ketamine-induced psychosis with focal activation of the prefrontal cortex in healthy volunteers. AN - 79032529; 9167508 AB - Agents that antagonize the N-methyl-D-aspartic acid (NMDA) receptor, such as phencyclidine and ketamine, produce an acute psychotic state in normal individuals that resembles some symptoms of schizophrenia. The aim of this study was to determine which brain regions are involved in NMDA receptor-mediated psychosis. Positron emission tomography with [18F]fluorodeoxyglucose was used to determine cerebral metabolic activity in 17 healthy volunteers while an acute psychotic state was induced simultaneously by the administration of subanesthetic doses of ketamine. Ketamine produced focal increases in metabolic activity in the prefrontal cortex and an acute psychotic state. A change in one psychotic symptom, conceptual disorganization, was significantly related to prefrontal activation. These data suggest that the prefrontal cortex may be involved in mediating NMDA receptor-induced psychosis. JF - The American journal of psychiatry AU - Breier, A AU - Malhotra, A K AU - Pinals, D A AU - Weisenfeld, N I AU - Pickar, D AD - Experimental Therapeutics Branch, NIMH, Bethesda, MD 20892, USA. Y1 - 1997/06// PY - 1997 DA - June 1997 SP - 805 EP - 811 VL - 154 IS - 6 SN - 0002-953X, 0002-953X KW - Fluorine Radioisotopes KW - 0 KW - Receptors, N-Methyl-D-Aspartate KW - Fluorodeoxyglucose F18 KW - 0Z5B2CJX4D KW - Ketamine KW - 690G0D6V8H KW - Deoxyglucose KW - 9G2MP84A8W KW - Glucose KW - IY9XDZ35W2 KW - Abridged Index Medicus KW - Index Medicus KW - Dose-Response Relationship, Drug KW - Glucose -- metabolism KW - Humans KW - Psychiatric Status Rating Scales KW - Receptors, N-Methyl-D-Aspartate -- drug effects KW - Adult KW - Deoxyglucose -- analogs & derivatives KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Tomography, Emission-Computed KW - Female KW - Functional Laterality KW - Male KW - Prefrontal Cortex -- diagnostic imaging KW - Prefrontal Cortex -- metabolism KW - Psychoses, Substance-Induced -- psychology KW - Psychoses, Substance-Induced -- metabolism KW - Psychoses, Substance-Induced -- etiology KW - Prefrontal Cortex -- drug effects KW - Ketamine -- administration & dosage KW - Ketamine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79032529?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+psychiatry&rft.atitle=Association+of+ketamine-induced+psychosis+with+focal+activation+of+the+prefrontal+cortex+in+healthy+volunteers.&rft.au=Breier%2C+A%3BMalhotra%2C+A+K%3BPinals%2C+D+A%3BWeisenfeld%2C+N+I%3BPickar%2C+D&rft.aulast=Breier&rft.aufirst=A&rft.date=1997-06-01&rft.volume=154&rft.issue=6&rft.spage=805&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+psychiatry&rft.issn=0002953X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-18 N1 - Date created - 1997-06-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Complete sustained response of a refractory, post-transplantation, large B-cell lymphoma to an anti-CD22 immunotoxin. AN - 79019337; 9163289 JF - Annals of internal medicine AU - Senderowicz, A M AU - Vitetta, E AU - Headlee, D AU - Ghetie, V AU - Uhr, J W AU - Figg, W D AU - Lush, R M AU - Stetler-Stevenson, M AU - Kershaw, G AU - Kingma, D W AU - Jaffe, E S AU - Sausville, E A AD - National Cancer Institute, National institutes of Health, Bethesda, Maryland, USA. Y1 - 1997/06/01/ PY - 1997 DA - 1997 Jun 01 SP - 882 EP - 885 VL - 126 IS - 11 SN - 0003-4819, 0003-4819 KW - Antigens, CD KW - 0 KW - Antigens, Differentiation, B-Lymphocyte KW - CD22 protein, human KW - Cell Adhesion Molecules KW - Immunotoxins KW - Lectins KW - Sialic Acid Binding Ig-like Lectin 2 KW - Ricin KW - 9009-86-3 KW - Abridged Index Medicus KW - Index Medicus KW - Risk Factors KW - Humans KW - Adult KW - Glomerulonephritis, IGA -- surgery KW - Herpesvirus 4, Human KW - Female KW - Lymphoma, B-Cell -- therapy KW - Postoperative Complications -- immunology KW - Ricin -- therapeutic use KW - Lymphoma, B-Cell -- virology KW - Antigens, Differentiation, B-Lymphocyte -- immunology KW - Kidney Transplantation -- immunology KW - Immunotoxins -- therapeutic use KW - Antigens, CD -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79019337?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+internal+medicine&rft.atitle=Complete+sustained+response+of+a+refractory%2C+post-transplantation%2C+large+B-cell+lymphoma+to+an+anti-CD22+immunotoxin.&rft.au=Senderowicz%2C+A+M%3BVitetta%2C+E%3BHeadlee%2C+D%3BGhetie%2C+V%3BUhr%2C+J+W%3BFigg%2C+W+D%3BLush%2C+R+M%3BStetler-Stevenson%2C+M%3BKershaw%2C+G%3BKingma%2C+D+W%3BJaffe%2C+E+S%3BSausville%2C+E+A&rft.aulast=Senderowicz&rft.aufirst=A&rft.date=1997-06-01&rft.volume=126&rft.issue=11&rft.spage=882&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 - 1997-05-29 N1 - Date created - 1997-05-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Rep78 gene product of adeno-associated virus (AAV) self-associates to form a hexameric complex in the presence of AAV ori sequences. AN - 79004985; 9151837 AB - The Rep78 and Rep68 proteins of adeno-associated virus (AAV) are replication initiator proteins that bind the viral replicative-form origin of replication, nick the origin in a site- and strand-specific fashion, and mediate vectorial unwinding of the DNA duplex via an ATP-dependent helicase activity, thus initiating a strand displacement mechanism of viral DNA replication. Genetic and biochemical studies have identified Rep mutants that demonstrate a trans-dominant negative phenotype in vitro and in vivo, suggesting the possibility that multimerization of Rep is essential for certain replicative functions. In this study, we have investigated the ability of the largest of the Rep proteins, Rep78, to self-associate in vitro and in vivo. Self-association of Rep78 in vivo was demonstrated through the use of a mammalian two-hybrid system. Rep-Rep protein interaction was confirmed in vitro through coimmunoprecipitation experiments with a bacterially expressed maltose-binding protein-Rep78 fusion protein in combination with [35S]methionine-labeled Rep78 synthesized in a coupled in vitro transcription-translation system. Mapping studies with N- and C-terminal truncation mutant forms of Rep indicate that amino acid sequences required for maximal self-association occur between residues 164 and 484. Site-directed mutagenesis identified two essential motifs within this 321-amino-acid region: (i) a putative alpha-helix bearing a 3,4-hydrophobic heptad repeat reminiscent of those found in coiled-coil domains and (ii) a previously recognized nucleoside triphosphate-binding motif. Deletion of either of these regions from the full-length polypeptide resulted in severe impairment of Rep-Rep interaction. In addition, gel filtration chromatography and protein cross-linking experiments indicated that Rep78 forms a hexameric complex in the presence of AAV ori sequences. JF - Journal of virology AU - Smith, R H AU - Spano, A J AU - Kotin, R M AD - Molecular Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892, USA. Y1 - 1997/06// PY - 1997 DA - June 1997 SP - 4461 EP - 4471 VL - 71 IS - 6 SN - 0022-538X, 0022-538X KW - DNA, Viral KW - 0 KW - DNA-Binding Proteins KW - Deoxyribonucleoproteins KW - Macromolecular Substances KW - Recombinant Proteins KW - Viral Proteins KW - origin-binding proteins, viral KW - rep proteins, Adeno-associated virus 2 KW - 137750-19-7 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Deoxyribonucleoproteins -- chemistry KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Recombinant Proteins -- chemistry KW - Protein Binding KW - DNA Replication KW - DNA, Viral -- chemistry KW - DNA-Binding Proteins -- chemistry KW - Viral Proteins -- chemistry KW - Dependovirus -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79004985?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=The+Rep78+gene+product+of+adeno-associated+virus+%28AAV%29+self-associates+to+form+a+hexameric+complex+in+the+presence+of+AAV+ori+sequences.&rft.au=Smith%2C+R+H%3BSpano%2C+A+J%3BKotin%2C+R+M&rft.aulast=Smith&rft.aufirst=R&rft.date=1997-06-01&rft.volume=71&rft.issue=6&rft.spage=4461&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-09 N1 - Date created - 1997-06-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1979 Nov;76(11):5567-71 [230481] J Virol. 1982 Feb;41(2):518-26 [6281463] J Mol Biol. 1982 Mar 25;156(1):203-19 [7047751] J Virol. 1983 Feb;45(2):555-64 [6300419] Gene. 1983 Jul;23(1):65-73 [6352411] J Virol. 1992 Feb;66(2):1119-28 [1309894] Proc Natl Acad Sci U S A. 1992 May 15;89(10):4673-7 [1316616] Nucleic Acids Res. 1992 Jul 11;20(13):3279-85 [1630899] J Virol. 1992 Oct;66(10):6058-69 [1326656] EMBO J. 1992 Dec;11(13):5071-8 [1334463] J Virol. 1993 Feb;67(2):997-1005 [8380475] J Biol Chem. 1993 Feb 5;268(4):2269-72 [8381400] J Biol Chem. 1993 Feb 15;268(5):3781-90 [7679117] J Biol Chem. 1993 May 15;268(14):10668-75 [8486715] Genes Dev. 1993 Jun;7(6):1047-58 [8504929] J Biol Chem. 1993 Nov 15;268(32):23830-6 [8226920] J Biol Chem. 1993 Nov 25;268(33):24647-54 [8227024] J Virol. 1994 Feb;68(2):1128-38 [8289342] J Virol. 1994 Feb;68(2):797-804 [8289383] J Biol Chem. 1994 Feb 4;269(5):3283-9 [8106366] J Virol. 1994 May;68(5):2947-57 [8151765] Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):5808-12 [8016070] J Virol. 1990 Apr;64(4):1764-70 [2157057] Cell. 1990 May 4;61(3):447-57 [2159383] Microbiol Rev. 1990 Sep;54(3):316-29 [2215424] J Virol. 1990 Dec;64(12):6204-13 [2173787] Virology. 1991 Sep;184(1):14-22 [1651588] EMBO J. 1991 Dec;10(12):3941-50 [1657596] J Virol. 1995 Sep;69(9):5422-30 [7636987] J Virol. 1995 Sep;69(9):5485-96 [7636994] J Virol. 1995 Nov;69(11):6787-96 [7474090] Virology. 1994 Aug 1;202(2):760-70 [8030239] J Virol. 1994 Aug;68(8):4988-97 [8035498] J Virol. 1994 Aug;68(8):4998-5006 [8035499] J Virol. 1994 Sep;68(9):5656-66 [8057446] J Virol. 1994 Sep;68(9):6029-37 [8057478] Blood. 1994 Sep 1;84(5):1492-500 [8068942] J Clin Invest. 1994 Oct;94(4):1440-8 [7929819] J Virol. 1994 Nov;68(11):7448-57 [7933128] Nucleic Acids Res. 1994 Oct 11;22(20):4031-8 [7937127] Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):10039-43 [7937833] Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):10183-7 [7524085] Prog Nucleic Acid Res Mol Biol. 1994;48:29-52 [7938552] Hum Gene Ther. 1994 Jul;5(7):793-801 [7981305] J Gen Virol. 1994 Dec;75 ( Pt 12):3385-92 [7996133] Virology. 1995 Jan 10;206(1):254-62 [7831779] Nat Genet. 1994 Oct;8(2):148-54 [7842013] J Virol. 1995 Apr;69(4):2038-46 [7884849] J Biol Chem. 1995 Mar 31;270(13):7462-73 [7706292] J Virol. 1995 Jun;69(6):3542-8 [7538173] Virology. 1995 May 10;209(1):122-35 [7747462] Bioessays. 1995 Mar;17(3):237-45 [7748178] Virology. 1995 Jun 1;209(2):692-5 [7778304] Curr Top Microbiol Immunol. 1984;109:147-65 [6321111] EMBO J. 1982;1(8):945-51 [6329717] J Virol. 1986 Jun;58(3):921-36 [3701931] Cell. 1986 Jun 6;45(5):721-32 [3518947] Nucleic Acids Res. 1986 May 27;14(10):4229-38 [2940511] J Gen Virol. 1987 Mar;68 ( Pt 3):885-93 [3819702] Adv Virus Res. 1987;33:91-174 [3296697] Adv Virus Res. 1987;32:243-306 [3039813] Science. 1988 Jun 24;240(4860):1759-64 [3289117] J Virol. 1988 Aug;62(8):2745-54 [2839699] Biochim Biophys Acta. 1988 Dec 20;951(2-3):425-9 [2850017] J Virol. 1989 Feb;63(2):873-82 [2536109] Nature. 1989 Apr 20;338(6217):658-62 [2539565] J Virol. 1989 Jul;63(7):3095-104 [2542617] Virology. 1989 Nov;173(1):120-8 [2554565] Nucleic Acids Res. 1989 Nov 11;17(21):8413-40 [2555771] Cell. 1990 Jan 12;60(1):105-13 [2153052] Proc Natl Acad Sci U S A. 1990 Mar;87(6):2211-5 [2156265] FEBS Lett. 1990 Mar 12;262(1):145-8 [2156730] J Virol. 1995 Nov;69(11):6880-5 [7474103] J Virol. 1995 Nov;69(11):7334-8 [7474165] Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11824-8 [8524857] J Virol. 1996 Apr;70(4):2440-8 [8642672] Hum Gene Ther. 1995 Dec;6(12):1531-41 [8664378] Virology. 1996 Jul 1;221(1):208-17 [8661429] Curr Top Microbiol Immunol. 1996;218:25-33 [8794243] J Biol Chem. 1996 Oct 11;271(41):25360-8 [8810301] Hum Gene Ther. 1996 Aug 20;7(13):1615-9 [8864762] Trends Biochem Sci. 1996 Oct;21(10):375-82 [8918191] J Biol Chem. 1969 Aug 25;244(16):4406-12 [5806584] Nature. 1970 Aug 15;227(5259):680-5 [5432063] Prog Med Virol. 1970;12:211-39 [4991627] Nucleic Acids Res. 1979 Nov 24;7(6):1513-23 [388356] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of human immunodeficiency virus type 1 matrix revertants: effects on virus assembly, Gag processing, and Env incorporation into virions. AN - 79004225; 9151831 AB - The matrix protein of human immunodeficiency virus type 1 (HIV-1) has been postulated to serve a variety of functions in the virus life cycle. Previously, we introduced a large number of mutations into the HIV-1 matrix and determined the effects on virus replication. These studies identified domains involved in virus assembly and release and envelope glycoprotein incorporation into virions. Here we describe the identification and characterization of viral revertants containing second-site changes in the matrix which compensate for the effects of four of the original mutations on matrix function. Specifically, mutations at matrix residues 4 and 6 severely impaired virus assembly and release; substitutions at residues 4 and 6 reversed the phenotype of the amino acid 4 change while second-site mutations at matrix positions 10, 69, and 97 partially or fully reversed the phenotype of the amino acid 6 substitution. A mutation at matrix residue 62 reversed the effect of a position 34 change which blocks envelope glycoprotein incorporation into virions, and substitutions at residues 27 and 51 reversed the phenotype of a position 86 mutation which redirects virus assembly to the cytoplasm. In addition to determining the effects of the compensatory changes in the context of the original mutations, we also introduced and analyzed the second-site changes alone in the context of the wild-type molecular clone. The data presented here define potential intermolecular and intramolecular interactions which occur in the matrix during the virus life cycle and have implications for our understanding of the relationship between matrix structure and function. JF - Journal of virology AU - Ono, A AU - Huang, M AU - Freed, E O AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0460, USA. Y1 - 1997/06// PY - 1997 DA - June 1997 SP - 4409 EP - 4418 VL - 71 IS - 6 SN - 0022-538X, 0022-538X KW - Gene Products, env KW - 0 KW - Gene Products, gag KW - Myristates KW - Viral Matrix Proteins KW - Index Medicus KW - AIDS/HIV KW - Mutagenesis, Site-Directed KW - Myristates -- metabolism KW - HeLa Cells KW - Humans KW - Protein Processing, Post-Translational KW - Morphogenesis KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Protein Structure, Tertiary KW - Gene Products, env -- metabolism KW - Virion -- ultrastructure KW - HIV-1 -- genetics KW - Gene Products, gag -- metabolism KW - Viral Matrix Proteins -- metabolism KW - HIV-1 -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79004225?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Characterization+of+human+immunodeficiency+virus+type+1+matrix+revertants%3A+effects+on+virus+assembly%2C+Gag+processing%2C+and+Env+incorporation+into+virions.&rft.au=Ono%2C+A%3BHuang%2C+M%3BFreed%2C+E+O&rft.aulast=Ono&rft.aufirst=A&rft.date=1997-06-01&rft.volume=71&rft.issue=6&rft.spage=4409&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-09 N1 - Date created - 1997-06-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1994 Mar;68(3):1689-96 [8107229] Cell. 1997 Jan 24;88(2):171-3; discussion 173-4 [9008157] J Virol. 1994 Apr;68(4):2556-69 [8139035] J Virol. 1994 May;68(5):3232-42 [8151785] Nature. 1994 May 12;369(6476):107-8 [8192816] J Virol. 1994 Aug;68(8):5311-20 [8035531] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):6992-6 [8041734] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7311-5 [8041786] Nature. 1994 Aug 25;370(6491):666-8 [8065455] J Mol Biol. 1967 Jun 14;26(2):365-9 [4291934] J Virol. 1986 Aug;59(2):284-91 [3016298] Virology. 1987 Jan;156(1):171-6 [3643678] J Virol. 1989 Jan;63(1):267-72 [2462060] Proc Natl Acad Sci U S A. 1988 Dec;85(24):9580-4 [2849111] Proc Natl Acad Sci U S A. 1990 Jan;87(2):523-7 [2405382] AIDS. 1991 Jun;5(6):617-37 [1652977] AIDS. 1991 Jun;5(6):639-54 [1883539] J Virol. 1992 Aug;66(8):4966-71 [1629961] J Virol. 1992 Sep;66(9):5667-70 [1501299] J Virol. 1993 Jul;67(7):4264-73 [7685414] J Virol. 1993 Nov;67(11):6387-94 [8411340] Nature. 1993 Oct 14;365(6447):666-9 [8105392] J Virol. 1994 Oct;68(10):6782-6 [8084015] J Mol Biol. 1994 Nov 25;244(2):198-223 [7966331] J Virol. 1995 Jan;69(1):365-75 [7983731] J Virol. 1995 Mar;69(3):1984-9 [7853546] Cell. 1995 Feb 10;80(3):379-88 [7859280] J Virol. 1995 Jun;69(6):3949-54 [7745752] J Virol. 1996 Jan;70(1):341-51 [8523546] Nature. 1995 Dec 14;378(6558):743-7 [7501025] J Virol. 1996 Feb;70(2):1016-26 [8551559] Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):3099-104 [8610175] J Virol. 1996 Sep;70(9):6384-9 [8709267] J Virol. 1996 Dec;70(12):8540-8 [8970978] J Virol. 1996 Dec;70(12):8645-52 [8970990] J Virol. 1994 Apr;68(4):2503-12 [8139032] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evidence that complex formation by Bas1p and Bas2p (Pho2p) unmasks the activation function of Bas1p in an adenine-repressible step of ADE gene transcription. AN - 78998029; 9154826 AB - Bas1p and Bas2p (Pho2p) are Myb-related and homeodomain DNA binding proteins, respectively, required for transcription of adenine biosynthetic genes in Saccharomyces cerevisiae. The repression of ADE genes in adenine-replete cells involves down-regulation of the functions of one or both of these activator proteins. A LexA-Bas2p fusion protein was found to activate transcription from a lexAop-lacZ reporter independently of both BAS1 function and the adenine levels in the medium. In contrast, a LexA-Bas1p fusion activated the lexAop reporter in a BAS2-dependent and adenine-regulated fashion. The DNA binding activity of Bas2p was not needed for its ability to support activation of the lexAop reporter by LexA-Bas1p, indicating that LexA-Bas1p recruits Bas2p to this promoter. The activation functions of both authentic Bas1p and LexA-Bas1p were stimulated under adenine-repressing conditions by overexpression of Bas2p, suggesting that complex formation by these proteins is inhibited in adenine-replete cells. Replacement of Asp-617 with Asn in Bas1p or LexA-Bas1p allowed either protein to activate transcription under repressing conditions in a manner fully dependent on Bas2p, suggesting that this mutation reduces the negative effect of adenine on complex formation by Bas1p and Bas2p. Deletions of N-terminal and C-terminal segments from the Bas1p moiety of LexA-Bas1p allowed high-level activation by the truncated proteins independently of Bas2p and adenine levels in the medium. From these results we propose that complex formation between Bas1p and Bas2p unmasks a latent activation function in Bas1p as a critical adenine-regulated step in transcription of the ADE genes. JF - Molecular and cellular biology AU - Zhang, F AU - Kirouac, M AU - Zhu, N AU - Hinnebusch, A G AU - Rolfes, R J AD - Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA. Y1 - 1997/06// PY - 1997 DA - June 1997 SP - 3272 EP - 3283 VL - 17 IS - 6 SN - 0270-7306, 0270-7306 KW - BAS1 protein, S cerevisiae KW - 0 KW - Bacterial Proteins KW - DNA, Fungal KW - Fungal Proteins KW - Homeodomain Proteins KW - LexA protein, Bacteria KW - Macromolecular Substances KW - PHO2 protein, S cerevisiae KW - Repressor Proteins KW - Saccharomyces cerevisiae Proteins KW - Trans-Activators KW - Aspartic Acid KW - 30KYC7MIAI KW - Serine Endopeptidases KW - EC 3.4.21.- KW - Adenine KW - JAC85A2161 KW - Index Medicus KW - Bacterial Proteins -- genetics KW - Models, Molecular KW - Bacterial Proteins -- metabolism KW - Repressor Proteins -- metabolism KW - Repressor Proteins -- genetics KW - Transcriptional Activation KW - Binding Sites KW - Saccharomyces cerevisiae KW - Mutagenesis, Site-Directed KW - Serine Endopeptidases -- metabolism KW - Serine Endopeptidases -- genetics KW - Down-Regulation -- drug effects KW - DNA, Fungal -- metabolism KW - Fungal Proteins -- chemistry KW - Trans-Activators -- metabolism KW - Fungal Proteins -- metabolism KW - Trans-Activators -- genetics KW - Trans-Activators -- chemistry KW - Adenine -- biosynthesis KW - Transcription, Genetic KW - Adenine -- physiology KW - Fungal Proteins -- genetics KW - Adenine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78998029?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Evidence+that+complex+formation+by+Bas1p+and+Bas2p+%28Pho2p%29+unmasks+the+activation+function+of+Bas1p+in+an+adenine-repressible+step+of+ADE+gene+transcription.&rft.au=Zhang%2C+F%3BKirouac%2C+M%3BZhu%2C+N%3BHinnebusch%2C+A+G%3BRolfes%2C+R+J&rft.aulast=Zhang&rft.aufirst=F&rft.date=1997-06-01&rft.volume=17&rft.issue=6&rft.spage=3272&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-19 N1 - Date created - 1997-06-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell Biol. 1995 Aug;15(8):4309-18 [7623825] Mol Gen Genet. 1996 Jun 12;251(3):358-64 [8676879] Gene. 1988 Dec 30;74(2):527-34 [3073106] Genetics. 1989 May;122(1):19-27 [2659436] Cell. 1989 Jun 30;57(7):1275-83 [2500253] Mol Cell Biol. 1989 May;9(5):2050-7 [2664469] Science. 1989 Nov 17;246(4932):931-5 [2683089] Nucleic Acids Res. 1990 May 11;18(9):2769-76 [2187179] Mol Cell Biol. 1993 Aug;13(8):5099-111 [8336737] Mol Cell Biol. 1993 Sep;13(9):5524-37 [8355698] Mol Cell Biol. 1993 Oct;13(10):6102-13 [8413212] Cell. 1993 Nov 19;75(4):791-803 [8242750] EMBO J. 1990 Aug;9(8):2523-8 [2196175] Cell. 1990 Aug 24;62(4):631-47 [2167175] Mol Cell Biol. 1991 May;11(5):2723-35 [2017175] Gene. 1992 Jan 2;110(1):119-22 [1544568] Mol Cell Biol. 1992 Jul;12(7):3006-14 [1620111] Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6746-50 [1495962] J Biol Chem. 1973 Jun 10;248(11):3860-75 [4575197] Gene. 1983 Nov;25(1):71-82 [6319233] Mol Gen Genet. 1984;197(2):345-6 [6394957] Mol Cell Biol. 1985 Sep;5(9):2349-60 [3915540] J Mol Biol. 1986 Aug 20;190(4):519-28 [3097325] Proc Natl Acad Sci U S A. 1987 Mar;84(5):1340-4 [2881299] Science. 1987 Aug 21;237(4817):874-80 [3303332] Genetics. 1987 Aug;116(4):541-5 [3305158] Mol Cell Biol. 1988 Jan;8(1):210-25 [3275867] Proc Natl Acad Sci U S A. 1988 Apr;85(7):2120-4 [3281162] Cell. 1988 May 6;53(3):339-40 [2896548] Mol Cell Biol. 1988 Sep;8(9):3827-36 [3065626] Curr Genet. 1993 Dec;24(6):472-80 [8299166] Science. 1994 Feb 25;263(5150):1153-6 [8108735] EMBO J. 1994 May 1;13(9):2192-9 [8187772] J Biol Chem. 1994 Jul 1;269(26):17663-9 [8021277] Science. 1994 Oct 7;266(5182):122-6 [7939631] EMBO J. 1994 Oct 17;13(20):4848-55 [7957054] EMBO J. 1994 Nov 15;13(22):5410-20 [7957107] Genes Dev. 1994 Nov 15;8(22):2781-91 [7958933] Mol Cell Biol. 1995 Mar;15(3):1220-33 [7862116] Mol Cell Biol. 1995 Jun;15(6):3354-62 [7760831] EMBO J. 1995 Jul 3;14(13):3170-83 [7621830] Mol Cell Biol. 1995 Aug;15(8):4319-30 [7623826] Genetics. 1995 May;140(1):103-14 [7635278] J Biol Chem. 1995 Dec 8;270(49):29151-61 [7493941] Science. 1996 Jan 12;271(5246):209-12 [8539622] Cell. 1996 Mar 8;84(5):699-709 [8625408] Cell. 1996 Mar 8;84(5):711-22 [8625409] Yeast. 1985 Dec;1(2):83-138 [3916863] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neurophysiological signs of cocaine dependence: increased electroencephalogram beta during withdrawal. AN - 78984779; 9146819 AB - To determine whether a central nervous system marker of cocaine dependence might exist, the resting electroencephalogram (EEG) of 33 drug-free, cocaine-dependent men (DSM-III-R criteria) was compared with two control groups [nondrug group (n = 10) and drug group who abused drugs, but were not cocaine dependent (n = 20)]. The EEG was recorded from eight sites after about 10 days of monitored abstinence (range 4-15 days) on a closed research ward for the drug-using individuals. The EEG was recorded for the nondrug control group as outpatients. The drug history was determined by the drug history questionnaire and a medical screening interview. The percent of EEG beta activity for the cocaine-dependent subjects was greater than that of both control groups (p < .05) as well as a normative database (HZI: Tarrytown, NY). The percent of EEG beta in frontal and central areas of the cocaine-dependent individuals was correlated with the frequency of cocaine use during the last 30 days. High levels of EEG beta may be a neurophysiological withdrawal sign in cocaine-dependent men. JF - Biological psychiatry AU - Herning, R I AU - Guo, X AU - Better, W E AU - Weinhold, L L AU - Lange, W R AU - Cadet, J L AU - Gorelick, D A AD - Division of Intramural Research, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1997/06/01/ PY - 1997 DA - 1997 Jun 01 SP - 1087 EP - 1094 VL - 41 IS - 11 SN - 0006-3223, 0006-3223 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Humans KW - Adult KW - Male KW - Substance Withdrawal Syndrome KW - Electroencephalography KW - Substance-Related Disorders KW - Beta Rhythm UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78984779?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biological+psychiatry&rft.atitle=Neurophysiological+signs+of+cocaine+dependence%3A+increased+electroencephalogram+beta+during+withdrawal.&rft.au=Herning%2C+R+I%3BGuo%2C+X%3BBetter%2C+W+E%3BWeinhold%2C+L+L%3BLange%2C+W+R%3BCadet%2C+J+L%3BGorelick%2C+D+A&rft.aulast=Herning&rft.aufirst=R&rft.date=1997-06-01&rft.volume=41&rft.issue=11&rft.spage=1087&rft.isbn=&rft.btitle=&rft.title=Biological+psychiatry&rft.issn=00063223&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-22 N1 - Date created - 1997-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risk factors, aetiology, therapy and outcome in 123 episodes of breakthrough bacteraemia and fungaemia during antimicrobial prophylaxis and therapy in cancer patients AN - 17117270; 4425285 AB - One hundred and twenty-three breakthrough bacteraemias (BB) were defined during a 5-year period in a National Cancer Centre, among 9986 admissions and a total of 979 bacteraemic episodes analysed. Of 123 bacteraemias in 103 patients, 77 were polymicrobial and 116 of the 323 organisms isolated were resistant to currently administered antimicrobial agents. Sixty-seven of the bacteraemic episodes were catheter-associated, as confirmed by the isolation of the same organisms from both blood and catheter tip. The strains isolated most frequently were coagulase-negative staphylococci (30.5%), corynebacteria (10%), Pseudomonas aeruginosa (10%), Enterococcus faecalis (9%) and viridans streptococci (8.5%). Gram-positive aerobes accounted for two-thirds of all micro-organisms isolated during breakthrough bacteraemic and fungaemic episodes. Polymicrobial episodes were associated more frequently with vascular catheters and neutropenia, and had a less favourable outcome than monomicrobial infections. Relapse was associated more frequently with catheter-related episodes, but the overall mortality rate was similar and independent of catheter insertion. Breakthrough bacteraemic and fungaemic episodes were associated more frequently with acute leukaemia. Catheter removal, as an independent variable, and modification of antimicrobial therapy were essential for better outcome. JF - Journal of Medical Microbiology AU - Spanik, S AU - Trupl, J AU - Kunova, A AU - Drgona, L AU - Salek, T AU - Mardiak, J AU - Kukuckova, E AU - Studena, M AU - Pichna, P AU - Oravcova, E AU - Grey, E AU - Koren, P AU - Svec, J AU - Lacka, J AU - Sufliarsky, J AU - Krcmery, V AD - St. Elizabeth National Cancer Institute, Bratislava, Slovak Republic Y1 - 1997/06// PY - 1997 DA - Jun 1997 SP - 517 EP - 523 VL - 46 IS - 6 SN - 0022-2615, 0022-2615 KW - antibiotics KW - bacteremia KW - cancer patients KW - fungemia KW - man KW - risk factors KW - Microbiology Abstracts B: Bacteriology KW - Streptococcus KW - Staphylococcus KW - Enterococcus faecalis KW - Pseudomonas aeruginosa KW - Corynebacterium KW - J 02855:Human Bacteriology: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17117270?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Medical+Microbiology&rft.atitle=Risk+factors%2C+aetiology%2C+therapy+and+outcome+in+123+episodes+of+breakthrough+bacteraemia+and+fungaemia+during+antimicrobial+prophylaxis+and+therapy+in+cancer+patients&rft.au=Spanik%2C+S%3BTrupl%2C+J%3BKunova%2C+A%3BDrgona%2C+L%3BSalek%2C+T%3BMardiak%2C+J%3BKukuckova%2C+E%3BStudena%2C+M%3BPichna%2C+P%3BOravcova%2C+E%3BGrey%2C+E%3BKoren%2C+P%3BSvec%2C+J%3BLacka%2C+J%3BSufliarsky%2C+J%3BKrcmery%2C+V&rft.aulast=Spanik&rft.aufirst=S&rft.date=1997-06-01&rft.volume=46&rft.issue=6&rft.spage=517&rft.isbn=&rft.btitle=&rft.title=Journal+of+Medical+Microbiology&rft.issn=00222615&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Corynebacterium; Enterococcus faecalis; Pseudomonas aeruginosa; Staphylococcus; Streptococcus ER - TY - JOUR T1 - Phosphotyrosyl-based motifs in the structure-based design of protein-tyrosine kinase-dependent signal transduction inhibitors AN - 16239916; 4229894 AB - Transmission of extracellular signals from the cell membrane to the nucleus depends on modification of phosphorylation states of intracellular proteins. Tyrosine, serine and threonine residues are the principal amino acid targets of these phosphorylation events, with tyrosyl residues being particularly important for pathways mediated by growth factors and cytokines. Aberrations in phosphotyrosyl (pTyr)-dependent signalling can contribute to a variety of diseases, including cancers, and for this reason selective modulation of pTyr-dependent signalling may afford new therapeutic approaches. The design of such therapeutics is facilitated by the functional compartmentalization of pTyr dependent signalling into three broad categories: (1) the generation of pTyr residues by protein-tyrosine kinases (PTK); (2) pTyr-dependent protein-protein associations mediated by binding modules such as Src homology 2 (SH2) and phosphotyrosine binding (PTB) domains and (3) the dephosphorylation of pTyr residues by protein-tyrosine phosphatases (PTPs). The pTyr residue itself, which is a unifying component of this signalling triad, potentially affords a starting point for the design of antagonists. In the PTK, SH2/PTB and PTP domain signalling environments, the pTyr residue plays unique roles by participating in interactions characteristic to each. Therefore, depending on which aspects of the L-4'-phosphotyrosyl structure are emphasized, and the manner in which they are utilized, inhibitors can be potentially directed against distinct legs of the signalling triad. This review will provide examples of this, by examining several series of compounds that have been prepared as inhibitors of either PTKs, SH2/PTB domains or PTPs. Also described will be how the pTyr structure can serve as a thematic Rosetta stone for the development of signal transduction inhibitors. JF - Current Pharmaceutical Design AU - Burke, TR Jr AU - Yao, Zhu-Jun AU - Smyth AU - Ye, Bin AD - Laboratory of Medicinal Chemistry, Building 37, Room 5C06, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 1997/06// PY - 1997 DA - Jun 1997 SP - 291 EP - 304 VL - 3 IS - 3 SN - 1381-6128, 1381-6128 KW - phosphotyrosine KW - protein-tyrosine kinase KW - reviews KW - signal transduction inhibitors KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33340:Other proteins, peptides, amino acids KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16239916?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Pharmaceutical+Design&rft.atitle=Phosphotyrosyl-based+motifs+in+the+structure-based+design+of+protein-tyrosine+kinase-dependent+signal+transduction+inhibitors&rft.au=Burke%2C+TR+Jr%3BYao%2C+Zhu-Jun%3BSmyth%3BYe%2C+Bin&rft.aulast=Burke&rft.aufirst=TR&rft.date=1997-06-01&rft.volume=3&rft.issue=3&rft.spage=291&rft.isbn=&rft.btitle=&rft.title=Current+Pharmaceutical+Design&rft.issn=13816128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - An investigation of the effect of paternal occupation group at conception on birth weight and gestational age AN - 16232793; 4227621 AB - The occupational histories of fathers were collected prospectively as part of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC), and were used to investigate the association of paternal job title with a baby's birth weight and gestational age. The analysis cohort consisted of 4,795 singleton live-born babies whose fathers responded fully to questionnaire items regarding occupational history. Jobs were coded using the British Standard Occupational Codes and classified into nine major occupational groups. A 73-gram difference (95% CI: 0.16, 145.17) was found between the mean birth weight of full-term babies born of professional fathers (3,543 gm) and of fathers working in craft and related occupations (3,470 gm). This difference decreased and lost significance after controlling for sociodemographic variables. No difference was found in the mean birth weight of preterm babies, or in the rate of preterm delivery, when analyzed by paternal occupation at conception. Our results suggest that when important sociodemographic variables are known, the father's job title alone may not be a useful predictor of birth weight or preterm delivery. JF - American Journal of Industrial Medicine AU - Shea, K M AU - Farrow, A AU - Little, R AD - Epidemiol. Branch, MD A3-05, NIEHS, P.O. Box 12233, 111 TW Alexander Dr., Research Triangle Park, NC 27709, USA Y1 - 1997/06// PY - 1997 DA - Jun 1997 SP - 738 EP - 743 VL - 31 IS - 6 SN - 0271-3586, 0271-3586 KW - birth weight KW - children KW - gestation KW - occupational exposure KW - paternal effects KW - reproduction KW - xenobiotics KW - Toxicology Abstracts KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16232793?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Industrial+Medicine&rft.atitle=An+investigation+of+the+effect+of+paternal+occupation+group+at+conception+on+birth+weight+and+gestational+age&rft.au=Shea%2C+K+M%3BFarrow%2C+A%3BLittle%2C+R&rft.aulast=Shea&rft.aufirst=K&rft.date=1997-06-01&rft.volume=31&rft.issue=6&rft.spage=738&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Industrial+Medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Defective HIV-1 provirus encoding a multitarget-ribozyme inhibits accumulation of spliced and unspliced HIV-1 mRNAs, reduces infectivity of viral progeny, and protects the cells from pathogenesis AN - 16098575; 4203527 AB - A HeLa T4 cell line containing a defective human immunodeficiency virus type 1 (HIV-1) DNA (HD4) was isolated. After transactivation with Tat, the HD4 DNA was transcribed into a single 3.7-kb mRNA that encodes a chimeric CD4/Env protein and a multitarget-ribozyme directed against multiple sites within the gp120 coding region of HIV-1 RNA. Early steps in HIV infection such as entry, reverse transcription, and proviral DNA formation were not affected in HD4 cells, and HD4 was efficiently transactivated after either HIV-1 or HIV-2 infections. HIV-2, which lacks all of the HIV-1-specific ribozyme target sites, replicated to high levels in HD4 cells whereas HIV-1 replication was selectively inhibited. Despite a reduced accumulation of all HIV-1 transcripts, transactivation of HD4 was efficient. Surprisingly, the most abundant, multiply spliced mRNAs were reduced even though they lack all of the ribozyme target sites. These results strongly suggest that the ribozyme co-localizes with unspliced HIV-1 pre-mRNA and/or genomic HIV-1 RNA in the nucleus. Cleavage of these precursor RNAs explains the reduction of all spliced and unspliced HIV-1 RNAs. Cleavage of genomic RNA probably contributed to the three-fold reduction in the infectivity of viral progeny. Thus, the HD4 ribozyme RNA functioned as a ribozyme in the nucleus and as a mRNA for a chimeric CD4/Env protein in the cytoplasm. Its unusual large size for a ribozyme (3.7 kb) indicates that, in the future, other antiviral proteins, like negative transdominant mutant HIV-1 proteins, may also be encoded to increase its antiviral potential in a gene therapy approach. JF - Human Gene Therapy AU - Paik, Soon-Young AU - Banerjea, A AU - Chen, Chang-Jie AU - Ye, Zhiping AU - Harmison, G G AU - Schubert, M AD - National Institute of Neurological Disorders and Stroke, National Institutes of Health, 36 Convent Drive MSC4164, Building 36, Room 5W21, Bethesda, MD 20892-4164 USA Y1 - 1997/06// PY - 1997 DA - Jun 1997 SP - 1115 EP - 1124 VL - 8 IS - 9 SN - 1043-0342, 1043-0342 KW - CD4 antigen KW - DNA KW - Env protein KW - envelope protein KW - ribozyme KW - ribozymes KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Genetics Abstracts KW - RNA KW - human immunodeficiency virus 1 KW - human immunodeficiency virus 2 KW - V 22002:AIDS: Molecular and in vitro aspects KW - G 07313:Viruses KW - W3 33243:Molecular methods KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16098575?accountid=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=Brain%2C+Behavior%2C+and+Immunity&rft.atitle=The+effects+of+daily+distress+and+personality+on+genital+HSV+shedding+and+lesions+in+a+randomized%2C+double-blind%2C+placebo-controlled%2C+crossover+trial+of+acyclovir+in+HSV-2+seropositive+women&rft.au=Strachan%2C+Eric%3BSaracino%2C+Misty%3BSelke%2C+Stacy%3BMagaret%2C+Amalia%3BBuchwald%2C+Dedra%3BWald%2C+Anna&rft.aulast=Strachan&rft.aufirst=Eric&rft.date=2011-10-01&rft.volume=25&rft.issue=7&rft.spage=1475&rft.isbn=&rft.btitle=&rft.title=Brain%2C+Behavior%2C+and+Immunity&rft.issn=08891591&rft_id=info:doi/10.1016%2Fj.bbi.2011.06.003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - RNA; DNA; human immunodeficiency virus 1; human immunodeficiency virus 2 ER - TY - JOUR T1 - The binding-site sizes of Escherichia coli single-stranded-DNA-binding protein and mammalian replication protein A are 65 and greater than or equal to 54 nucleotides respectively AN - 16091207; 4200591 AB - The electrophoretic mobilities of complexes formed with single-stranded (ss) DNA and tetrameric Escherichia coli ssDNA-binding protein (EcoSSB) or mammalian replication protein A (RPA) were analysed. The electrophoretic mobilities of the complexes in a native polyacrylamide gel increased as the lengths of the DNA increased from 28 to 70 nt, thus revealing paradoxical `descending-staircase' patterns. Increases in the electrophoretic mobilities of EcoSSB/ssDNA complexes were observed when the lengths of the bound DNA were increased by 1 nt. Quantitative analyses of the complexes suggested that the binding-sites sizes of EcoSSB and RPA were 65 and greater than or equal to 54 nt respectively. The binding-site size for RPA is at least 24 nt larger than previously reported. JF - Biochemical Journal AU - Mitas, M AU - Chock, J Y AU - Christy, M AD - Laboratory of Biochemical Genetics, Bldg. 36, Rm. 1C06, National Institutes of Health, Bethesda, MD 20982, USA Y1 - 1997/06// PY - 1997 DA - Jun 1997 SP - 957 EP - 961 VL - 324 IS - 3 SN - 0264-6021, 0264-6021 KW - mammals KW - replication protein A KW - single-stranded DNA-binding protein KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - DNA-binding protein KW - Escherichia coli KW - J 02727:Amino acids, peptides and proteins KW - N 14940:Nucleic acid-binding proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16091207?accountid=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=Biochemical+Journal&rft.atitle=The+binding-site+sizes+of+Escherichia+coli+single-stranded-DNA-binding+protein+and+mammalian+replication+protein+A+are+65+and+greater+than+or+equal+to+54+nucleotides+respectively&rft.au=Mitas%2C+M%3BChock%2C+J+Y%3BChristy%2C+M&rft.aulast=Mitas&rft.aufirst=M&rft.date=1997-06-01&rft.volume=324&rft.issue=3&rft.spage=957&rft.isbn=&rft.btitle=&rft.title=Biochemical+Journal&rft.issn=02646021&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; DNA-binding protein ER - TY - JOUR T1 - Synthesis and immunological properties of Vi and di-O-acetyl pectin protein conjugates with adipic acid dihydrazide as the linker AN - 16060369; 4099185 AB - The Vi capsular polysaccharide of Salmonella typhi, a licensed vaccine for typhoid fever in individuals greater than or equal to 5 years old, induces low and short-lived antibodies in children, and reinjection does not elicit booster responses at any age. Its immunogenicity was improved by binding Vi to proteins by using N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP) as a linker. Similar findings were observed with the structurally related, di-O-acetyl derivative of pectin [poly- alpha (1 arrow right 4)-D-GalpA] designated OAcP. Protein conjugates of Vi and OAcP were synthesized by carbodiimide-mediated synthesis with adipic acid dihydrazide (ADH) as the linker. Hydrazide groups were introduced into proteins (bovine serum albumin or recombinant Pseudomonas aeruginosa exoprotein A) by treatment with ADH and 1-ethyl-3(3-dimethylaminopropyl carbodiimide (EDC). The resultant adipic acid hydrazide derivatives (AH-proteins), containing 2.3 to 3.4% AH, had antigenic and physicochemical properties similar to those of the native proteins. The AH-proteins were bound to Vi and OAcP by treatment with EDC. The immunogenicity of Vi or OAcP, alone or as protein conjugates, was evaluated in young outbred mice and guinea pigs by subcutaneous injection of 2.5 and 5.0 mu g, respectively, of polysaccharide, and antibodies were measured by enzyme-linked immunosorbent assay. All conjugates were significantly more immunogenic than Vi or OAcP alone and induced booster responses with 5- to 25-fold increases of antibodies. Vi conjugates were significantly more immunogenic than their OAcP analogs. A carboxymethyl derivative of yeast beta -glucan enhanced the anti-Vi response elicited by an OAcP conjugate but had no effect on the immunogenicity of Vi or of OAcP alone. Vi and OAcP conjugates synthesized by this scheme will be evaluated clinically. JF - Infection and Immunity AU - Kossaczka, Z AU - Bystricky, S AU - Bryla, DA AU - Shiloach, J AU - Robbins, J B AU - Szu, S C AD - Laboratory of Developmental and Molecular Immunity, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA Y1 - 1997/06// PY - 1997 DA - Jun 1997 SP - 2088 EP - 2093 VL - 65 IS - 6 SN - 0019-9567, 0019-9567 KW - Vi antigen KW - animal models KW - double prime Vi antigen KW - mice KW - pectin KW - polysaccharides KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Microbiology Abstracts B: Bacteriology KW - typhoid fever KW - vaccines KW - Salmonella typhi KW - immunogenicity KW - capsules KW - W3 33365:Vaccines (other) KW - F 06807:Active immunization KW - J 02833:Immune response and immune mechanisms KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16060369?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Synthesis+and+immunological+properties+of+Vi+and+di-O-acetyl+pectin+protein+conjugates+with+adipic+acid+dihydrazide+as+the+linker&rft.au=Kossaczka%2C+Z%3BBystricky%2C+S%3BBryla%2C+DA%3BShiloach%2C+J%3BRobbins%2C+J+B%3BSzu%2C+S+C&rft.aulast=Kossaczka&rft.aufirst=Z&rft.date=1997-06-01&rft.volume=76&rft.issue=3&rft.spage=267&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+Clinical+Psychiatry&rft.issn=01606689&rft_id=info:doi/10.4088%2FJCP.13m08922 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - typhoid fever; vaccines; immunogenicity; capsules; Salmonella typhi ER - TY - JOUR T1 - Using structural information to create physiologically based pharmacokinetic models for all polychlorinated biphenyls I. Tissue:Blood partition coefficients AN - 16059225; 4106956 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 tissue-to-blood partition coefficients. Tissue:blood partition coefficients relate the compound's concentration in a target tissue to its concentration in blood under equilibrium conditions. Data on the adipose:plasma partition coefficients of 24 PCBs were used in a regression analysis to find an expression for the adipose:plasma partition coefficient as a function of molecular structure. Using stepwise regression, it was found that three simple structural descriptors were sufficient to predict adipose:plasma partition coefficients for all 209 PCB congeners. Data on the distribution of PCBs among blood components were used to derive the adipose:blood partition coefficient from the adipose:plasma partition coefficient. The lipid contents of liver, muscle, and skin were used to derive the tissue:blood partition coefficient for those tissues from the adipose:blood partition coefficient. These results allow for the calculation of tissue:blood partition coefficients for liver, skin, muscles, and fat for all 209 PCB congeners. JF - Toxicology and Applied Pharmacology AU - Parham, F M AU - Kohn, M C AU - Matthews, H B AU - DeRosa, C AU - Portier, C J AD - OAO/National Institute of Environmental Health Sciences, Research Tringle Park, NC 27709, USA Y1 - 1997/06// PY - 1997 DA - Jun 1997 SP - 340 EP - 347 VL - 144 IS - 2 SN - 0041-008X, 0041-008X KW - pharmacokinetics KW - tissue:blood partition coefficients KW - polychlorinated biphenyls KW - PCB KW - Toxicology Abstracts KW - models KW - lipids KW - muscles KW - liver KW - skin KW - X 24222:Analytical procedures KW - X 24153:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16059225?accountid=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+I.+Tissue%3ABlood+partition+coefficients&rft.au=Parham%2C+F+M%3BKohn%2C+M+C%3BMatthews%2C+H+B%3BDeRosa%2C+C%3BPortier%2C+C+J&rft.aulast=Parham&rft.aufirst=F&rft.date=1997-06-01&rft.volume=144&rft.issue=2&rft.spage=340&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; lipids; liver; skin; muscles ER - TY - JOUR T1 - Differential recognition of members of the carcinoembryonic antigen family by Opa variants of Neisseria gonorrhoeae AN - 16058002; 4098904 AB - Opacity (Opa) protein variation in Neisseria gonorrhoeae is implicated in the pathogenesis of gonorrhea, possibly by mediating adherence and entry of the bacteria into human tissues. One particular Opa protein mediates adherence to epithelial cells through cell surface proteoglycans. Recently, two other eukaryotic cell receptors for Opa proteins have been reported. These receptors are members of a subgroup of the carcinoembryonic (CEA) gene family that express CD66 antigens. CEA family members vary in their distribution in human tissues. In order to understand whether interactions between Opa and CEA-like molecules play any role in pathogenesis, we must investigate which CEA family members are able to serve as Opa receptors and which Opa proteins recognize CEA-like molecules. We therefore studied HeLa cells that were stably transfected with five different members of the CEA family, i.e., CEA, CEA gene family member 1a (CGM1a), CGM6, nonspecific cross-reacting antigen (NCA), and biliary glycoprotein a (BGPa). We infected these transfectants with all possible 11 Opa variants of gonococcal strain MS11 and determined the numbers of bacteria that were bound and internalized. To account for proteoglycan-mediated adherence, infection assays were also performed in the presence of heparin. Our results show that of the 11 Opa variants of MS11, the same 4 recognized CGM1a and NCA. CGM6, however, was not recognized by any Opa variant of MS11. CEA was recognized by at least 9 of 11 Opa variants, and the BGP transfectants specifically bound and internalized 10 of 11 Opa variants and also bound Opa-negative gonococci. Immunofluorescence experiments showed that clustering of CEA-like molecules occurred upon infection of HeLa transfectants with those Opa variants that interacted specifically with the CEA family member. Together these data show that CEA family members are differentially recognized by gonococcal Opa variants, suggesting that this phenomenon may contribute to cell tropism displayed by gonococci. JF - Infection and Immunity AU - Bos, M P AU - Grunert, F AU - Belland, R J AD - Rocky Mountain Laboratories, NIH, NIAID, 903 South 4th St., Hamilton, MT 59840, USA Y1 - 1997/06// PY - 1997 DA - Jun 1997 SP - 2353 EP - 2361 VL - 65 IS - 6 SN - 0019-9567, 0019-9567 KW - Opa protein KW - Microbiology Abstracts B: Bacteriology KW - HeLa cells KW - gonorrhea KW - receptors KW - cell adhesion KW - Neisseria gonorrhoeae KW - J 02832:Antigenic properties and virulence UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16058002?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Differential+recognition+of+members+of+the+carcinoembryonic+antigen+family+by+Opa+variants+of+Neisseria+gonorrhoeae&rft.au=Bos%2C+M+P%3BGrunert%2C+F%3BBelland%2C+R+J&rft.aulast=Bos&rft.aufirst=M&rft.date=1997-06-01&rft.volume=65&rft.issue=6&rft.spage=2353&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 - Neisseria gonorrhoeae; cell adhesion; receptors; HeLa cells; gonorrhea ER - TY - JOUR T1 - Antisense--protein kinase A: A single-gene-based therapeutic approach AN - 16030659; 4097868 AB - The ability to block expression of individual genes that are casually related to cancer provides a powerful tool to explore the molecular basis of normal growth regulation as well as the opportunity for therapeutic intervention. One technique for turning off a single activated gene is the use of antisense oligodeoxynucleotides and their analogs. Changing the ratio of the two isoforms of the cyclic AMP (cAMP)-dependent protein kinase, type I (PKA-I) and type II (PKA-II), which are distinguished by different regulatory subunits, RI and RII, has been linked to cell growth and differentiation. An enhanced expression of RI/PKA-I correlates with active cell growth and cell transformation, whereas a decrease in RI/PKA-I and an increase of RII/PKA-II are related to growth inhibition and differentiation-maturation. RI is the major R subunit of PKA detected in a variety of human cancer cell lines and primary tumors. It was discovered that 8-C1-cAMP, a site-selective cAMP analog, exhibits potent growth inhibition in vitro and in vivo in a broad spectrum of human carcinomas, fibrosarcomas, and leukemias without causing cytotoxicity. The molecular mechanism for such potency in the growth-inhibitory effect of 8-C1-cAMP and other site-selective cAMP analogs takes advantage of the ability of these analogs to modulate selectively two isoforms of cAMP receptor proteins, the positive and negative intracellular signal transducers of cAMP. The differentiating and antiproliferative activity of 8-C1-cAMP has been attributed primarily to downregulation of PKA-I. This mechanism involves initial activation of the holoenzyme and subsequent proteolysis of the dissociated RI and C subunits. The evidence presented shows that the sequence-specific inhibition of RI sub( alpha ) gene expression by antisense oligonucleotides results in the differentiation of leukemia cells and growth arrest of cancer cells of epithelial origin and tumors in nude mice. The antisense restrains tumor growth by turning on the signals for blockade of tumor cell survival. RI sub( alpha ) antisense thus provides a single-gene-based therapeutic approach to cancer. JF - Antisense and Nucleic Acid Drug Development AU - Cho-Chung, Y S AU - Nesterova, M AU - Kondrashin, A AU - Noguchi, K AU - Srivastava, R AU - Pepe, S AD - National Cancer Institute Building 10, Room 5B05, Bethesda, MD 20892-1750, USA Y1 - 1997/06// PY - 1997 DA - Jun 1997 SP - 217 EP - 223 VL - 7 IS - 3 SN - 1087-2906, 1087-2906 KW - cyclic AMP KW - man KW - oligodeoxyribonucleotides KW - protein kinase A KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Genetics Abstracts KW - antisense KW - gene therapy KW - carcinoma KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews KW - W3 33380:Antisense UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16030659?accountid=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=Antisense--protein+kinase+A%3A+A+single-gene-based+therapeutic+approach&rft.au=Cho-Chung%2C+Y+S%3BNesterova%2C+M%3BKondrashin%2C+A%3BNoguchi%2C+K%3BSrivastava%2C+R%3BPepe%2C+S&rft.aulast=Cho-Chung&rft.aufirst=Y&rft.date=1997-06-01&rft.volume=7&rft.issue=3&rft.spage=217&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 - 2011-12-14 N1 - SubjectsTermNotLitGenreText - gene therapy; antisense; carcinoma ER - TY - JOUR T1 - Recruiting the 2-5A system for antisense therapeutics AN - 16030648; 4097870 AB - Full realization of the enormous potential of antisense oligonucleotides as therapeutic agents will require a continuing marriage of the fields of organic chemistry and biochemistry to explore the biologic consequences of novel chemical structures and to discover and integrate heretofore unknown biologic processes into the design of antisense therapeutics Figure 1 is a view of the process and barriers that must be overcome to develop an antisense oligonucleotide with satisfactory activity in an intact cell. The candidate antisense reagent must associate with a specific region in the targeted RNA to form a 1:1 complex. If this complex formation can be viewed as an equilibrium process, it would be subject to the principle of Le Chatelier. For instance, the concentration of the antisense agent would be limited by its ability to enter the cell, its ability to access the RNA once in the cell, and the efflux rate for the antisense oligomer. The concentration of antisense oligomer would also be decreased by degradation, possibly to catabolites that may in themselves exhibit activities of a nonspecific or even toxic nature. In addition, the antisense reagent may form nonproductive and nonspecific interactions with other cellular components, and this may also lead to unwanted side effects. Available sites in the mRNA for annealing of the antisense nucleic acid may be limited by insufficient affinity for a particular nucleotide sequence, by RNA secondary structure, or by proteins bound to the RNA. All of the foregoing factors will act to lower the effective concentrations of both antisense reagent and target RNA, thereby lowering the extent of hybrid formation of antisense agent with RNA. JF - Antisense and Nucleic Acid Drug Development AU - Torrence, P F AU - Xiao, Wei AU - Li, Guiying AU - Cramer, H AU - Player, M R AU - Silverman, R H AD - Section on Biomedical Chemistry, Laboratory of Medicinal Chemistry, National Institute of Diabetes and, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0805, USA Y1 - 1997/06// PY - 1997 DA - Jun 1997 SP - 203 EP - 206 VL - 7 IS - 3 SN - 1087-2906, 1087-2906 KW - oligoribonucleotides KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Genetics Abstracts KW - antisense KW - gene therapy KW - RNA KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews KW - W3 33380:Antisense UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16030648?accountid=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=Recruiting+the+2-5A+system+for+antisense+therapeutics&rft.au=Torrence%2C+P+F%3BXiao%2C+Wei%3BLi%2C+Guiying%3BCramer%2C+H%3BPlayer%2C+M+R%3BSilverman%2C+R+H&rft.aulast=Torrence&rft.aufirst=P&rft.date=1997-06-01&rft.volume=7&rft.issue=3&rft.spage=203&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 - 2011-12-14 N1 - SubjectsTermNotLitGenreText - gene therapy; antisense; RNA ER - TY - JOUR T1 - Identification and characterization of thymidylate synthase from Neisseria gonorrhoeae AN - 16018442; 4089817 AB - Thymidylate synthase converts deoxyuridylate to deoxythymidylate. The thyA gene has been cloned and sequenced from Neisseria gonorrhoeae MS11. This gene has an open reading frame of 795-801 bp and encodes a product which shares 71% identity with its Escherichia coli homolog. Unlike its E. coli counterpart, gonococcal thyA has a large, upstream transcribed region (300+ bp) that lacks a translatable reading frame. Gonococcal thyA is capable of complementing an E. coli thyA null mutant and shares similar levels of sensitivity with trimethoprim. JF - FEMS Microbiology Letters AU - Carlson, J H AU - Hill, SA AD - Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Laboratory of Microbial Structure and Function, Rocky Mountain Laboratories, Hamilton, MT 59840, USA Y1 - 1997/06// PY - 1997 DA - Jun 1997 SP - 225 EP - 230 PB - ELSEVIER SCIENCE B.V. VL - 151 IS - 2 SN - 0378-1097, 0378-1097 KW - cloning KW - nucleotide sequence KW - trimethoprim KW - thyA gene KW - deoxyuridylate KW - deoxythymidylate KW - thymidylate synthase KW - Genetics Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts B: Bacteriology KW - antibiotic resistance KW - Escherichia coli KW - Neisseria gonorrhoeae KW - A 01006:Enzymes & cofactors KW - J 02728:Enzymes KW - G 07321:GENERAL UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16018442?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEMS+Microbiology+Letters&rft.atitle=Identification+and+characterization+of+thymidylate+synthase+from+Neisseria+gonorrhoeae&rft.au=Carlson%2C+J+H%3BHill%2C+SA&rft.aulast=Carlson&rft.aufirst=J&rft.date=1997-06-01&rft.volume=151&rft.issue=2&rft.spage=225&rft.isbn=&rft.btitle=&rft.title=FEMS+Microbiology+Letters&rft.issn=03781097&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Neisseria gonorrhoeae; Escherichia coli; antibiotic resistance ER - TY - JOUR T1 - Wip1, a novel human protein phosphatase that is induced in response to ionizing radiation in a p53-dependent manner AN - 15995142; 4079872 AB - Exposure of mammalian cells to ionizing radiation (IR) induces a complex array of cellular responses including cell cycle arrest and /or apoptosis. IR-induced G super(1) arrest has been shown to depend on the presence of the tumor suppressor p53, which acts as a transcriptional activator of several genes. p53 also plays a role in the induction of apoptosis in response to DNA damage, and this pathway can be activated by both transcription-dependent and -independent mechanisms. Here we report the identification of a novel transcript whose expression is induced in response to IR in a p53-dependent manner, and that shows homology to the type 2C protein phosphatases. We have named this novel gene, wip1. In vitro, recombinant Wip1 displayed characteristics of a type 2C phosphatase, including Mg super(2+) dependence and relative insensitivity to okadaic acid. Studies performed in several cell lines revealed that wip1 accumulation following IR correlates with the presence of wild-type p53. The accumulation of wip1 mRNA following IR was rapid and transient, and the protein was localized to the nucleus. Similar to waf1, ectopic expression of wip1 in human cells suppressed colony formation. These results suggest that Wip1 might contribute to growth inhibitory pathways activated in response to DNA damage in a p53-dependent manner. JF - Proceedings of the National Academy of Sciences, USA AU - Fiscella, M AU - Zhang, HongLiang AU - Fan, S AU - Sakaguchi, K AU - Shen, Songfa AU - Mercer, W E AU - Vande Woude, GF AU - O'Connor, P M AU - Appella, E AD - Advanced BioScience Laboratories-Basic, Laboratory of Cell Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, 37 Convent Drive, MSC 4255, Bethesda, MD 20892-4255, USA Y1 - 1997/06// PY - 1997 DA - Jun 1997 SP - 6048 EP - 6053 VL - 94 IS - 12 SN - 0027-8424, 0027-8424 KW - Saos-2 cells KW - man KW - cDNA KW - nucleotide sequence KW - Wip1 protein KW - protein-tyrosine-phosphatase KW - okadaic acid KW - Toxicology Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Genetics Abstracts; Oncogenes & Growth Factors Abstracts KW - ionizing radiation KW - DNA damage KW - U.V. radiation KW - N 14630:Chemical reactions & interactions, including effects of radiation KW - X 24210:Radiation & radioactive materials KW - G 07431:Enzymes KW - B 26405:p53 gene, anti-suppressor genes (K-rev/rap/rab/RSU-1) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15995142?accountid=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=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Wip1%2C+a+novel+human+protein+phosphatase+that+is+induced+in+response+to+ionizing+radiation+in+a+p53-dependent+manner&rft.au=Fiscella%2C+M%3BZhang%2C+HongLiang%3BFan%2C+S%3BSakaguchi%2C+K%3BShen%2C+Songfa%3BMercer%2C+W+E%3BVande+Woude%2C+GF%3BO%27Connor%2C+P+M%3BAppella%2C+E&rft.aulast=Fiscella&rft.aufirst=M&rft.date=1997-06-01&rft.volume=94&rft.issue=12&rft.spage=6048&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 N1 - SubjectsTermNotLitGenreText - ionizing radiation; DNA damage; U.V. radiation ER - TY - JOUR T1 - Preferential formation and decreased removal of cisplatin-DNA adducts in Chinese hamster ovary cell mitochondrial DNA as compared to nuclear DNA AN - 15972921; 4070948 AB - Levels of DNA adducts in Chinese hamster ovary (CHO) cells exposed to cis-diamminedichloroplatinum(II) (cisplatin) for 24 h, have been shown to be 4- to 6-fold higher in mitochondrial (mt) DNA as compared to nuclear (n) DNA (Olivero et al., Mutation Res., 346 (1995) 221). The aim of the present study was to understand if the preferential cisplatin binding in mtDNA is partially caused by lack of adduct removal in the mitochondria. Chinese hamster ovary cells were exposed for 6 h to 50 mu M cisplatin, followed by incubation for 24 and 48 h in cisplatin-free medium. At the 30-h time point (6 h with cisplatin, 24 h without cisplatin), half of the cells from each plate were harvested and the remainder were cultured and harvested at 54 h (6 h with cisplatin, 48 h without cisplatin). The 30- and 54-h time points are called `T30' and `T54', respectively. Cisplatin-DNA adducts were measured in DNA from nuclear and mitochondrial fractions by dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA), a sensitive competitive microtiter-based immunoassay utilizing antiserum elicited against cisplatin-modified DNA. An initial higher level of cisplatin-DNA adducts was observed in mtDNA when compared to nDNA, at T30. In addition, a lack of removal of adducts in mtDNA was demonstrated in cells at T54. Dilution of DNA adducts by DNA replication was documented in pulse-chase experiments that employed [3H]thymidine incorporation. Adduct removal by repair-related mechanisms was considered to comprise the difference between total DNA adduct removal and adduct removal related to DNA replication. The final results demonstrated that both, higher initial binding and lack of removal of cisplatin-DNA adducts appear to contribute to the preferential cisplatin-mtDNA binding observed in CHO cells. JF - Mutation Research-Genetic Toxicology and Environmental Mutagenesis AU - Olivero, O A AU - Chang, P K AU - Lopez-Larraza, D M AU - Semino-Mora, M C AU - Poirier, M C AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD 20892, USA Y1 - 1997/06// PY - 1997 DA - Jun 1997 SP - 79 EP - 86 PB - ELSEVIER SCIENCE B.V. VL - 391 IS - 1-2 SN - 1383-5718, 1383-5718 KW - CHO cells KW - cisplatin KW - Biochemistry Abstracts 2: Nucleic Acids; Toxicology Abstracts KW - DNA adducts KW - nuclei KW - mitochondrial DNA KW - N 14630:Chemical reactions & interactions, including effects of radiation KW - X 24117:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15972921?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+Research-Genetic+Toxicology+and+Environmental+Mutagenesis&rft.atitle=Preferential+formation+and+decreased+removal+of+cisplatin-DNA+adducts+in+Chinese+hamster+ovary+cell+mitochondrial+DNA+as+compared+to+nuclear+DNA&rft.au=Olivero%2C+O+A%3BChang%2C+P+K%3BLopez-Larraza%2C+D+M%3BSemino-Mora%2C+M+C%3BPoirier%2C+M+C&rft.aulast=Olivero&rft.aufirst=O&rft.date=1997-06-01&rft.volume=391&rft.issue=1-2&rft.spage=79&rft.isbn=&rft.btitle=&rft.title=Mutation+Research-Genetic+Toxicology+and+Environmental+Mutagenesis&rft.issn=13835718&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - DNA adducts; mitochondrial DNA; nuclei ER - TY - JOUR T1 - Visualization of G protein-coupled receptor trafficking with the aid of the green fluorescent protein. Endocytosis and recycling of cholecystokinin receptor type A AN - 15964217; 4067016 AB - A chimeric protein consisting of the cholecystokinin receptor type A (CCKAR) and the green fluorescent protein (GFP) was used for studying receptor localization, internalization, and recycling in live cells in real time in four different cell lines. Fusion of the C terminus of the CCKAR to the N terminus of the GFP did not alter receptor ligand binding affinity, signal transduction, or the pattern of receptor surface expression and receptor-mediated cholecystokinin (CCK) internalization. The use of a new GFP mutant with increased fluorescence allowed the continuous observation of CCKAR-GFP in stably expressing cell lines. Newly obtained biologically active fluorescent derivatives of CCK were used for simultaneous observation of receptor and ligand trafficking in CHO, NIH/3T3, and HeLa cells stably expressing the fluorescent CCKAR and in transiently transfected COS-1 cells. Receptor internalization was predominantly ligand dependent in HeLa, COS-1, and CHO cells, but was mostly constitutive in NIH/3T3 cells, suggesting the existence of cell-specific regulation of receptor internalization. The CCKAR antagonists, L-364,718 and CCK 27-32 amide potently inhibited spontaneous internalization of the receptor. The average sorting time of CCK and the receptor in the endosomes was about 25 min. The receptor recycled back to the cell membrane with an average time of 60 min. While the ligands sorted to lysosomes, no receptor molecules could be detected there, and no receptor degradation was observed during recycling. These results demonstrate the usefulness of GFP tagging for real time imaging of G protein-coupled receptor trafficking in living cells and suggest that this technique may be successfully applied to the study of the regulation and trafficking mechanisms of other recruiters. JF - Journal of Biological Chemistry AU - Tarasova, NI AU - Stauber, R H AU - Choi, Joon Ki AU - Hudson, E A AU - Czerwinski, G AU - Miller, J L AU - Pavlakis, G N AU - Michejda, C J AU - Wank, SA AD - Digestive Dis. Branch, NIDDK, Natl. Inst. Health, Bethesda, MD 20892, USA Y1 - 1997/06// PY - 1997 DA - Jun 1997 SP - 14817 EP - 14824 VL - 272 IS - 23 SN - 0021-9258, 0021-9258 KW - cholecystokinin receptors KW - green fluorescent protein KW - guanine nucleotide-binding protein KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - endocytosis KW - W 30965:Miscellaneous, Reviews KW - W3 33230:Cell structure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15964217?accountid=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=Visualization+of+G+protein-coupled+receptor+trafficking+with+the+aid+of+the+green+fluorescent+protein.+Endocytosis+and+recycling+of+cholecystokinin+receptor+type+A&rft.au=Tarasova%2C+NI%3BStauber%2C+R+H%3BChoi%2C+Joon+Ki%3BHudson%2C+E+A%3BCzerwinski%2C+G%3BMiller%2C+J+L%3BPavlakis%2C+G+N%3BMichejda%2C+C+J%3BWank%2C+SA&rft.aulast=Tarasova&rft.aufirst=NI&rft.date=1997-06-01&rft.volume=272&rft.issue=23&rft.spage=14817&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 - 2011-12-14 N1 - SubjectsTermNotLitGenreText - endocytosis ER - TY - JOUR T1 - Plasmid maintenance functions of the large virulence plasmid of Shigella flexneri AN - 15963467; 4066795 AB - The large virulence plasmid pMYSH6000 of Shigella flexneri contains a replicon and a plasmid maintenance stability determinant (Stb) on adjacent SalI fragments. The presence of a RepFIIA replicon on the SalI C fragment was confirmed, and the complete sequence of the adjacent SalI O fragment was determined. It shows homology to part of the transfer (tra) operon of the F plasmid. Stb stabilizes a partition-defective P1 miniplasmid in Escherichia coli. A 1.1-kb region containing a homolog of the F trbH gene was sufficient to confer stability. However, the trbH open reading frame could be interrupted without impairing stability. Deletion analysis implicated the involvement of two small open reading frames, STBORF1 and STBORF2, that fully overlap trbH in the opposite direction. These open reading frames are closely related to the vagC and vagD genes of the Salmonella dublin virulence plasmid and to open reading frame pairs in the F trbH region and in the chromosomes of Dichelobacter nodosus and Haemophilus influenzae. Stb appears to promote better-than-random distribution of plasmid copies and is a plasmid incompatibility determinant. The F homolog does not itself confer stability but exerts incompatibility against the activity of the Stb system. Stb is likely to encode either an active partition system or a postsegregational killing system. It shows little similarity to previously studied plasmid stability loci, but the genetic organization of STBORF1 and STBORF2 resembles that of postsegregational killing mechanisms. JF - Journal of Bacteriology AU - Radnedge, L AU - Davis, MA AU - Youngren, B AU - Austin, S J AD - Gene Regulation and Chromosome Biol. Lab., ABL-Basic Res. Prog., NCI-Frederick Cancer Res. and Dev. Cent., Frederick, MD 21702-1201, USA Y1 - 1997/06// PY - 1997 DA - Jun 1997 SP - 3670 EP - 3675 VL - 179 IS - 11 SN - 0021-9193, 0021-9193 KW - maintenance KW - plasmid pMYSH6000 KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - Shigella flexneri KW - virulence KW - J 02760:Plasmids KW - G 07203:Plasmids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15963467?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=Plasmid+maintenance+functions+of+the+large+virulence+plasmid+of+Shigella+flexneri&rft.au=Radnedge%2C+L%3BDavis%2C+MA%3BYoungren%2C+B%3BAustin%2C+S+J&rft.aulast=Radnedge&rft.aufirst=L&rft.date=1997-06-01&rft.volume=179&rft.issue=11&rft.spage=3670&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Shigella flexneri; virulence ER - TY - JOUR T1 - Assessment of neurotoxicity from potential medications for drug abuse: ibogaine testing and brain imaging. AN - 79164973; 9237447 AB - New technologies utilized for monitoring brain function can be more sensitive in the assessment of desired or undesired pharmacological effects than can clinical examination. Nonetheless, careful case-by-case analysis is required to determine to what extent a change detected with a sensitive imaging modality will have clinical significance. Whereas in some instances the technology may suggest a subclinical condition years before clinical signs develop, in other instances changes seen may be compensated for through system reserves, redundancy, or plasticity. Furthermore, simultaneous application of several assay instruments, including behavioral, electrophysiological, and nuclear medicine approaches, may be appropriate and useful for establishing correlations between changes in specific aspects of brain function and amelioration of a disease (drug abuse disorder) or its sequelae. In the example of ibogaine, a testing strategy was developed to assess human subjects for possible changes in cerebellar function (that were suggested by preclinical findings indicating subtle damage). Thus, subjects may be tested for subclinical alterations during and immediately following a clinical trial. This "harbinger of toxicity" approach would provide clinicians the critical data necessary for appropriate follow-up of subjects as well as the propriety of continuance of the clinical trials within the ibogaine project. JF - Annals of the New York Academy of Sciences AU - Vocci, F J AU - London, E D AD - Medications Development Division, National Institute on Drug Abuse, Rockville, Maryland 20857, USA. fv6k@nih.gov Y1 - 1997/05/30/ PY - 1997 DA - 1997 May 30 SP - 29 EP - 39; discussion 39-40 VL - 820 SN - 0077-8923, 0077-8923 KW - Hallucinogens KW - 0 KW - Ibogaine KW - 3S814I130U KW - Index Medicus KW - Magnetic Resonance Imaging KW - Animals KW - Tomography, Emission-Computed, Single-Photon KW - Humans KW - Tomography, Emission-Computed KW - Radiography KW - Substance-Related Disorders -- pathology KW - Brain -- pathology KW - Brain -- drug effects KW - Substance-Related Disorders -- drug therapy KW - Substance-Related Disorders -- diagnostic imaging KW - Brain -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79164973?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Assessment+of+neurotoxicity+from+potential+medications+for+drug+abuse%3A+ibogaine+testing+and+brain+imaging.&rft.au=Vocci%2C+F+J%3BLondon%2C+E+D&rft.aulast=Vocci&rft.aufirst=F&rft.date=1997-05-30&rft.volume=820&rft.issue=&rft.spage=29&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-21 N1 - Date created - 1997-08-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo imaging of fatty acid incorporation into brain to examine signal transduction and neuroplasticity involving phospholipids. AN - 79164242; 9237449 AB - An in vivo method is presented that allows quantification and imaging of fatty acid incorporation into different brain phospholipids in relation to membrane synthesis, neuroplasticity, and signal transduction. The method can be used with positron emission tomography, and may help to evaluate brain phospholipid metabolism in humans with brain tumors, neurodegenerative disease, cerebral ischemia or trauma, or neurotoxic effects of drugs or other agents. JF - Annals of the New York Academy of Sciences AU - Rapoport, S I AU - Purdon, D AU - Shetty, H U AU - Grange, E AU - Smith, Q AU - Jones, C AU - Chang, M C AD - Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA. SIR@HELIX.NIH.GOV Y1 - 1997/05/30/ PY - 1997 DA - 1997 May 30 SP - 56 EP - 73; discussion 73-4 VL - 820 SN - 0077-8923, 0077-8923 KW - Fatty Acids KW - 0 KW - Phospholipids KW - Index Medicus KW - Animals KW - Injections, Intravenous KW - Humans KW - Radionuclide Imaging KW - Animals, Domestic KW - Fatty Acids -- administration & dosage KW - Brain -- pathology KW - Phospholipids -- metabolism KW - Brain -- metabolism KW - Neuronal Plasticity KW - Brain -- diagnostic imaging KW - Signal Transduction KW - Fatty Acids -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79164242?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+imaging+of+fatty+acid+incorporation+into+brain+to+examine+signal+transduction+and+neuroplasticity+involving+phospholipids.&rft.au=Rapoport%2C+S+I%3BPurdon%2C+D%3BShetty%2C+H+U%3BGrange%2C+E%3BSmith%2C+Q%3BJones%2C+C%3BChang%2C+M+C&rft.aulast=Rapoport&rft.aufirst=S&rft.date=1997-05-30&rft.volume=820&rft.issue=&rft.spage=56&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-21 N1 - Date created - 1997-08-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Applications of fourier transform infrared imaging microscopy in neurotoxicity. AN - 79162032; 9237459 JF - Annals of the New York Academy of Sciences AU - Lewis, E N AU - Kidder, L H AU - Levin, I W AU - Kalasinsky, V F AU - Hanig, J P AU - Lester, D S AD - Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. neil@spy.niddk.nih.gov Y1 - 1997/05/30/ PY - 1997 DA - 1997 May 30 SP - 234 EP - 46; discussion 246-7 VL - 820 SN - 0077-8923, 0077-8923 KW - Index Medicus KW - Radiography KW - Spectroscopy, Fourier Transform Infrared -- methods KW - Nervous System -- metabolism KW - Nervous System -- diagnostic imaging KW - Nervous System -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79162032?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Applications+of+fourier+transform+infrared+imaging+microscopy+in+neurotoxicity.&rft.au=Lewis%2C+E+N%3BKidder%2C+L+H%3BLevin%2C+I+W%3BKalasinsky%2C+V+F%3BHanig%2C+J+P%3BLester%2C+D+S&rft.aulast=Lewis&rft.aufirst=E&rft.date=1997-05-30&rft.volume=820&rft.issue=&rft.spage=234&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-21 N1 - Date created - 1997-08-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Anterograde transport of endogenous brain-derived neurotrophic factor in hippocampal mossy fibers. AN - 79135814; 9223060 AB - Neurotrophic factors such as brain-derived neurotrophic factor (BDNF) are assumed to provide trophic support via a target-derived, retrograde mechanism of action. However, recent studies suggest that neurotrophic factors can act in an autocrine fashion and perhaps even in an anterograde direction similar to neurotransmitters. To further explore this hypothesis, we compared the neuroanatomical pattern of BDNF mRNA and protein in response to electroconvulsive seizures (ECS) or kainic acid-induced seizure activity. Using in situ hybridization, we found that chronic ECS induced BDNF mRNA predominantly in the granule neurons of the dentate gyrus. However, immunohistochemistry with an anti-BDNF antibody revealed that ECS increased endogenous BDNF protein in the mossy fibers, which are composed of axons projecting from the granule neurons of the dentate gyrus to the CA3 pyramidal layer of the hippocampus. Kainic acid administration (10 mg/kg, i.p., once) was used to lesion CA3 neurons selectively, as these are a possible retrograde source of BDNF protein in mossy fibers. Three weeks later, a prolonged elevation of BDNF mRNA in granule neurons, but not elsewhere in hippocampus, was accompanied by an increase in BDNF protein in the mossy fibers. These results suggest that BDNF was transcribed and translated in granule neuron cell bodies but transported in an anterograde direction to provide trophic support of CA3 pyramidal neurons. JF - Neuroreport AU - Smith, M A AU - Zhang, L X AU - Lyons, W E AU - Mamounas, L A AD - Molecular Neurobiology Unit, National Institute on Aging, NIH, Baltimore, MD 21224, USA. Y1 - 1997/05/27/ PY - 1997 DA - 1997 May 27 SP - 1829 EP - 1834 VL - 8 IS - 8 SN - 0959-4965, 0959-4965 KW - Brain-Derived Neurotrophic Factor KW - 0 KW - Excitatory Amino Acid Agonists KW - Kainic Acid KW - SIV03811UC KW - Index Medicus KW - Seizures -- chemically induced KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Blotting, Western KW - Seizures -- metabolism KW - Electroshock KW - Biological Transport, Active KW - Immunohistochemistry KW - Male KW - Brain-Derived Neurotrophic Factor -- metabolism KW - Nerve Fibers -- metabolism KW - Hippocampus -- metabolism KW - Hippocampus -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79135814?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Anterograde+transport+of+endogenous+brain-derived+neurotrophic+factor+in+hippocampal+mossy+fibers.&rft.au=Smith%2C+M+A%3BZhang%2C+L+X%3BLyons%2C+W+E%3BMamounas%2C+L+A&rft.aulast=Smith&rft.aufirst=M&rft.date=1997-05-27&rft.volume=8&rft.issue=8&rft.spage=1829&rft.isbn=&rft.btitle=&rft.title=Neuroreport&rft.issn=09594965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-29 N1 - Date created - 1997-08-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 8-cyclopentyl-1,3-dipropylxanthine and other xanthines differentially bind to the wild-type and delta F508 first nucleotide binding fold (NBF-1) domains of the cystic fibrosis transmembrane conductance regulator. AN - 79050521; 9174362 AB - Cystic fibrosis is an autosomal recessive disorder affecting chloride transport in pancreas, lung, and other tissues, which is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). Certain alkyl xanthines such as CPX (8-cyclopentyl-1,3-dipropylxanthine) stimulate Cl- efflux from cells bearing the delta F508 genotype common to most cases of cystic fibrosis. We have hypothesized that the CFTR molecule itself might be the site for CPX action, perhaps in the region of the first nucleotide binding fold (NBF-1) domain. Therefore, to test this hypothesis directly we have used a rapid membrane filtration assay to measure the kinetics of association and dissociation of [3H]CPX to both recombinant NBF-1 and recombinant NBF-1 bearing the delta F508 mutation. We report that [3H]CPX binds with higher affinity to the delta F508-NBF-1 of CFTR (Kd = 1.0 nM) than to the wild-type NBF-1 of CFTR (Kd = 17.0 nM). These Kd values were calculated from direct measurements of the association and dissociation rate constants. The rate constants for the dissociation reaction of the wild-type NBF-1 and delta F508-NBF-1 of CFTR were not different from each other. However, the corresponding rate constants for the association reaction were k(+1) (NBF-1) = 4.7 +/- 0.9 x 10(4) M(-1) s(-1) and k(+1) (delta F508-NBF-1) = 1.6 +/- 0.3 x 10(5) M(-1) s(-1), respectively. These Kd values were corroborated by equilibrium-binding experiments, which gave very similar values. We have also measured the relative displacement of various xanthines from both wild-type NBF-1 and delta F508-NBF-1, in anticipation that the order of potencies for binding might parallel the action of the different xanthines on CF cells. For wild-type NBF-1, the rank order was DA-CPX > DAX > CPX > caffeine > adenosine >> IBMX > 2-thioCPX. For delta F508-NBF-1, the rank order was DAX > CPX > caffeine > DA-CPX > adenosine >> IBMX > 2-thioCPX. These relative potencies show close parallels with previously observed relative potencies of these drugs on CF cells, and thus lend strong support to the hypothesis that the mechanism of action on CF cells may involve direct interaction with the CFTR molecule itself. JF - Biochemistry AU - Cohen, B E AU - Lee, G AU - Jacobson, K A AU - Kim, Y C AU - Huang, Z AU - Sorscher, E J AU - Pollard, H B AD - Laboratory of Cell Biology and Genetics, NIDDK, NIH, Bethesda, Maryland 20892, USA. Y1 - 1997/05/27/ PY - 1997 DA - 1997 May 27 SP - 6455 EP - 6461 VL - 36 IS - 21 SN - 0006-2960, 0006-2960 KW - Carrier Proteins KW - 0 KW - DNA-Binding Proteins KW - NUBP1 protein, human KW - Xanthines KW - Cystic Fibrosis Transmembrane Conductance Regulator KW - 126880-72-6 KW - Xanthine KW - 1AVZ07U9S7 KW - 1,3-dipropyl-8-cyclopentylxanthine KW - 9PTP4FOI9E KW - Adenosine KW - K72T3FS567 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Binding, Competitive -- genetics KW - Adenosine -- pharmacology KW - Kinetics KW - Protein Structure, Tertiary KW - Cystic Fibrosis Transmembrane Conductance Regulator -- metabolism KW - Carrier Proteins -- metabolism KW - Cystic Fibrosis Transmembrane Conductance Regulator -- drug effects KW - Carrier Proteins -- genetics KW - DNA-Binding Proteins -- genetics KW - DNA-Binding Proteins -- drug effects KW - Xanthines -- metabolism KW - Xanthines -- pharmacology KW - Cystic Fibrosis Transmembrane Conductance Regulator -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79050521?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=8-cyclopentyl-1%2C3-dipropylxanthine+and+other+xanthines+differentially+bind+to+the+wild-type+and+delta+F508+first+nucleotide+binding+fold+%28NBF-1%29+domains+of+the+cystic+fibrosis+transmembrane+conductance+regulator.&rft.au=Cohen%2C+B+E%3BLee%2C+G%3BJacobson%2C+K+A%3BKim%2C+Y+C%3BHuang%2C+Z%3BSorscher%2C+E+J%3BPollard%2C+H+B&rft.aulast=Cohen&rft.aufirst=B&rft.date=1997-05-27&rft.volume=36&rft.issue=21&rft.spage=6455&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-24 N1 - Date created - 1997-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Microinjected cDNA encoding JAK2 protein-tyrosine kinase induces DNA synthesis in NIH 3T3 cells. AN - 79078653; 9188787 AB - Microinjection of expression plasmids encoding either JAK2 or hyperactive (Ndelta661)rJAK2 into serum-starved NIH 3T3 cells resulted in 20-30-fold induction of DNA synthesis. Control microinjections of buffer or parental pcDNA3 vector resulted in only 3-5-fold induction of DNA synthesis. Induction of DNA synthesis was blocked when plasmid encoding JAK2 was microinjected in the presence of the JAK2-selective inhibitor AG-490, whereas AG-490 did not block DNA synthesis induced by microinjected plasmid encoding (Ndelta661)rJAK2. The ability of JAK2 to initiate the G(o)/S cell cycle transition is comparable to that of other proto-oncogenes, and supports a mechanistic role for overexpressed Janus kinases in carcinogenesis. JF - FEBS letters AU - Smith, M R AU - Duhe, R J AU - Liu, Y AU - Farrar, W L AD - Intramural Research Support Program, Science Applications International Corporation Frederick, National Cancer Institute - Frederick Cancer Research and Development Center, MD 21702-1201, USA. Y1 - 1997/05/26/ PY - 1997 DA - 1997 May 26 SP - 327 EP - 330 VL - 408 IS - 3 SN - 0014-5793, 0014-5793 KW - Enzyme Inhibitors KW - 0 KW - Nitriles KW - Proto-Oncogene Proteins KW - Recombinant Proteins KW - Tyrphostins KW - alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide KW - DNA KW - 9007-49-2 KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Jak2 protein, mouse KW - EC 2.7.10.2 KW - Janus Kinase 2 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Microinjections -- methods KW - Nitriles -- pharmacology KW - Recombinant Proteins -- biosynthesis KW - Mice KW - Plasmids KW - DNA Replication -- drug effects KW - Transfection -- methods KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Enzyme Inhibitors -- pharmacology KW - Recombinant Proteins -- antagonists & inhibitors KW - Protein-Tyrosine Kinases -- antagonists & inhibitors KW - Protein-Tyrosine Kinases -- biosynthesis KW - Protein-Tyrosine Kinases -- metabolism KW - DNA -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79078653?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEBS+letters&rft.atitle=Microinjected+cDNA+encoding+JAK2+protein-tyrosine+kinase+induces+DNA+synthesis+in+NIH+3T3+cells.&rft.au=Smith%2C+M+R%3BDuhe%2C+R+J%3BLiu%2C+Y%3BFarrar%2C+W+L&rft.aulast=Smith&rft.aufirst=M&rft.date=1997-05-26&rft.volume=408&rft.issue=3&rft.spage=327&rft.isbn=&rft.btitle=&rft.title=FEBS+letters&rft.issn=00145793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-10 N1 - Date created - 1997-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mammalian GADD34, an apoptosis- and DNA damage-inducible gene. AN - 79015773; 9153226 AB - The mammalian cellular response to genotoxic stress is a complex process involving many known and probably many as yet unknown genes. Induction of the human DNA damage- and growth arrest-inducible gene, GADD34, by ionizing radiation was only seen in certain cell lines and correlated with apoptosis following ionizing radiation. In addition, the kinetics and dose response of GADD34 to ionizing radiation closely paralleled that of the apoptosis inhibitor, BAX. However, unlike BAX, the GADD34 response was independent of cellular p53 status. The carboxyl terminus of GADD34 has homology with the carboxyl termini of two viral proteins, one of which is known to prevent apoptosis of virus infected cells. The association of GADD34 expression with certain types of apoptosis and its homology with a known apoptosis regulator suggests that GADD34 may play a role in apoptosis as well. JF - The Journal of biological chemistry AU - Hollander, M C AU - Zhan, Q AU - Bae, I AU - Fornace, A J AD - Laboratory of Molecular Pharmacology, Division of Basic Science, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/05/23/ PY - 1997 DA - 1997 May 23 SP - 13731 EP - 13737 VL - 272 IS - 21 SN - 0021-9258, 0021-9258 KW - Antigens, Differentiation KW - 0 KW - Antineoplastic Agents, Alkylating KW - Cell Cycle Proteins KW - DNA, Complementary KW - Proteins KW - Methyl Methanesulfonate KW - AT5C31J09G KW - PPP1R15A protein, human KW - EC 3.1.3.16 KW - Ppp1r15a protein, mouse KW - Protein Phosphatase 1 KW - Index Medicus KW - Animals KW - Antineoplastic Agents, Alkylating -- pharmacology KW - Sequence Homology, Nucleic Acid KW - Humans KW - In Situ Hybridization, Fluorescence KW - Mice KW - Amino Acid Sequence KW - Chromosome Mapping KW - Molecular Weight KW - Methyl Methanesulfonate -- pharmacology KW - Promoter Regions, Genetic KW - Base Sequence KW - Tumor Cells, Cultured KW - Molecular Sequence Data KW - DNA, Complementary -- chemistry KW - Sequence Homology, Amino Acid KW - Cricetinae KW - Gene Library KW - Apoptosis KW - DNA Damage KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79015773?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Mammalian+GADD34%2C+an+apoptosis-+and+DNA+damage-inducible+gene.&rft.au=Hollander%2C+M+C%3BZhan%2C+Q%3BBae%2C+I%3BFornace%2C+A+J&rft.aulast=Hollander&rft.aufirst=M&rft.date=1997-05-23&rft.volume=272&rft.issue=21&rft.spage=13731&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-02 N1 - Date created - 1997-07-02 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U83984; GENBANK; U83983; U83982; U83981 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The negative signaling molecule SH2 domain-containing inositol-polyphosphate 5-phosphatase (SHIP) binds to the tyrosine-phosphorylated beta subunit of the high affinity IgE receptor. AN - 79002086; 9153264 AB - The SH2 domain-containing inositol-polyphosphate 5-phosphatase, SHIP, associates with FcgammaRIIB and negatively regulates both B-cell and mast cell function. We report here that SHIP was tyrosine-phosphorylated after high affinity IgE receptor (FcepsilonRI) aggregation in rat basophilic leukemia RBL-2H3 cells. The tyrosine phosphorylation of SHIP was an early event after receptor aggregation and was present in cells deficient in the protein-tyrosine kinase Syk. Furthermore it was not secondary to the increase of intracellular calcium or the activation of protein kinase C. SHIP was precipitated by immobilized phosphorylated synthetic peptides based on the immunoreceptor tyrosine-based activation motif (ITAM) of the beta but not the gamma subunit of the high affinity IgE receptor. Tyrosine phosphorylation of SHIP and its association with the tyrosine-phosphorylated beta subunit of FcepsilonRI could play an important role in down-regulating receptor-mediated signal transduction in mast cells. Thus, whereas the activation molecule Syk associates with the gamma subunit ITAM, the beta subunit ITAM binds the negative signaling molecule SHIP. Therefore, unlike B cells where the antigen receptor and coreceptors such as FcgammaRIIB or CD22 each recruits molecules with opposite effects, the FcepsilonRI contains subunits which recruit molecules that activate and inhibit signal transduction. JF - The Journal of biological chemistry AU - Kimura, T AU - Sakamoto, H AU - Appella, E AU - Siraganian, R P AD - Laboratory of Immunology, NIDR, NCI, National Institutes of Health, Bethesda, Maryland 20892-1188, USA. tk51w@nih.gov Y1 - 1997/05/23/ PY - 1997 DA - 1997 May 23 SP - 13991 EP - 13996 VL - 272 IS - 21 SN - 0021-9258, 0021-9258 KW - Carcinogens KW - 0 KW - Enzyme Precursors KW - Intracellular Signaling Peptides and Proteins KW - Ionophores KW - Receptors, IgE KW - Calcimycin KW - 37H9VM9WZL KW - Tyrosine KW - 42HK56048U KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - SYK protein, human KW - EC 2.7.10.2 KW - Syk Kinase KW - Syk protein, rat KW - Phosphoric Monoester Hydrolases KW - EC 3.1.3.2 KW - INPPL1 protein, human KW - EC 3.1.3.86 KW - Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Carcinogens -- pharmacology KW - Enzyme Precursors -- metabolism KW - Amino Acid Sequence KW - Protein-Tyrosine Kinases -- metabolism KW - Calcimycin -- pharmacology KW - Rats KW - Calcium -- metabolism KW - Down-Regulation KW - Ionophores -- pharmacology KW - Phosphorylation KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Protein Conformation KW - Receptors, IgE -- metabolism KW - Tyrosine -- metabolism KW - Phosphoric Monoester Hydrolases -- metabolism KW - src Homology Domains UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79002086?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+negative+signaling+molecule+SH2+domain-containing+inositol-polyphosphate+5-phosphatase+%28SHIP%29+binds+to+the+tyrosine-phosphorylated+beta+subunit+of+the+high+affinity+IgE+receptor.&rft.au=Kimura%2C+T%3BSakamoto%2C+H%3BAppella%2C+E%3BSiraganian%2C+R+P&rft.aulast=Kimura&rft.aufirst=T&rft.date=1997-05-23&rft.volume=272&rft.issue=21&rft.spage=13991&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-02 N1 - Date created - 1997-07-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Osmium Hydrazido and Dinitrogen Complexes. AN - 1859359399; 11669870 AB - [Os(tpy)(bpy)(NH(3))](PF(6))(2) (1) was oxidized electrochemically in the presence of a series of amines in aqueous solutions buffered to pH 7. With secondary aliphatic amines, electrolysis gave [Os(tpy)(bpy)(NNR(2))](PF(6))(3) (3); number of electrons n = 4.6-5.0. 3 was reduced to [Os(tpy)(bpy)(NNR(2))](PF(6))(2) (2) in aqueous and nonaqueous solutions with n = 1.0. The structures of 2 were determined by X-ray crystallography for NR(2) = diethylamide (2a) and morpholide (2c) and were found to exhibit bent hydrazido(2-) coordination (Os-N-N = 137 degrees ). The salts crystallized in the triclinic system, space group P&onemacr;. For 2a, a = 9.004(1) Å, b = 9.796(1) Å, c = 20.710(2) Å, alpha = 88.78(2) degrees, beta = 85.43(2) degrees, gamma = 86.22(2) degrees, and Z = 2. For 2c, a = 9.632(8) Å, b = 21.229(9) Å, c = 9.039(5) Å, alpha = 97.41(4) degrees, beta = 94.28(5) degrees, gamma = 85.07(5) degrees, and Z = 2. Solutions of 2 were protonated in strongly acidic media to give hydrazido(1-) complexes. The pK(a) of the protonated form of 2a is 0.90 +/- 0.01. Reduction of 2 in aqueous solutions of pH <1 gave 1 and NH(2)R(2)(+) with n = 4.0. At higher pH, there is evidence for an Os(II) hydrazine intermediate. Oxidation of 3 by one electron afforded transiently stable species which decomposed to give [Os(tpy)(bpy)(NCCH(3))](3+) in acetonitrile solution. Pseudo-first-order rate constants of 8.1 +/- 0.9 s(-)(1) and 0.200 +/-.005 s(-)(1) were estimated by cyclic voltammetry on solutions of 2a and 2b(NR(2) = piperidide), respectively. Oxidation of 1 at pH 7, in the presence of primary aliphatic amines or ammonia, occurred with n = 5.9-6.2, and generated [Os(II)(tpy)(bpy)(N(2))](PF(6))(2) (4). JF - Inorganic chemistry AU - Coia, George M. AU - Devenney, Martin AU - White, Peter S. AU - Meyer, Thomas J. AU - Wink, David A. AD - Chemistry Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland 21702. Y1 - 1997/05/21/ PY - 1997 DA - 1997 May 21 SP - 2341 EP - 2351 VL - 36 IS - 11 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859359399?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Inorganic+chemistry&rft.atitle=Osmium+Hydrazido+and+Dinitrogen+Complexes.&rft.au=Coia%2C+George+M.%3BDevenney%2C+Martin%3BWhite%2C+Peter+S.%3BMeyer%2C+Thomas+J.%3BWink%2C+David+A.&rft.aulast=Coia&rft.aufirst=George&rft.date=1997-05-21&rft.volume=36&rft.issue=11&rft.spage=2341&rft.isbn=&rft.btitle=&rft.title=Inorganic+chemistry&rft.issn=1520-510X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2001-10-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Zidovudine safety and tolerance among uninfected healthcare workers: a brief update. AN - 79641884; 9845499 JF - The American journal of medicine AU - Beekmann, S E AU - Fahrner, R AU - Henderson, D K AU - Gerberding, J L AD - National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1997/05/19/ PY - 1997 DA - 1997 May 19 SP - 63 EP - 64 VL - 102 IS - 5B SN - 0002-9343, 0002-9343 KW - Anti-HIV Agents KW - 0 KW - Zidovudine KW - 4B9XT59T7S KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Prospective Studies KW - Humans KW - Confounding Factors (Epidemiology) KW - Research Design KW - Zidovudine -- adverse effects KW - HIV Infections -- prevention & control KW - Health Personnel KW - Anti-HIV Agents -- adverse effects KW - Occupational Exposure -- adverse effects KW - HIV Infections -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79641884?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Zidovudine+safety+and+tolerance+among+uninfected+healthcare+workers%3A+a+brief+update.&rft.au=Beekmann%2C+S+E%3BFahrner%2C+R%3BHenderson%2C+D+K%3BGerberding%2C+J+L&rft.aulast=Beekmann&rft.aufirst=S&rft.date=1997-05-19&rft.volume=102&rft.issue=5B&rft.spage=63&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 - 1998-12-14 N1 - Date created - 1998-12-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of skin dendritic cells in the initiation of human immunodeficiency virus infection. AN - 79640599; 9845491 AB - Human immunodeficiency virus (HIV) can be transmitted by accidental puncture with needles containing HIV-contaminated blood. However, the molecular and cellular interactions that occur between HIV and cells of the skin following percutaneous needlestick injury are unknown. Direct inoculation of exogenous virus into recipient blood vessels of the dermis is possible. In addition, skin dendritic cells (DC; e.g., epidermal Langerhans cells, dermal DC, lymphatic veiled cells) may also play a role in the initiation of HIV infection. Evidence to suggest that DC are important in primary HIV infection is derived largely from in vitro experiments and animal models. For example, cutaneous DC can be infected with HIV in vitro, can capture HIV on their cell surface (independent from DC infection), and can efficiently transmit HIV to CD4+ T cells. In recent in vivo experiments using rhesus macaques, submucosal DC were the first cells infected following intravaginal exposure to simian immunodeficiency virus (SIV). In this review, I discuss the possible immunologic events that occur within skin and draining lymph nodes following needlestick exposure to HIV-contaminated blood, with a particular emphasis on DC-HIV interactions. JF - The American journal of medicine AU - Blauvelt, A AD - Dermatology Branch, National Cancer Institute, Bethesda, Maryland 20892-1908, USA. Y1 - 1997/05/19/ PY - 1997 DA - 1997 May 19 SP - 16 EP - 20 VL - 102 IS - 5B SN - 0002-9343, 0002-9343 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Humans KW - In Vitro Techniques KW - Dendritic Cells KW - Needlestick Injuries -- complications KW - Skin -- immunology KW - HIV Infections -- immunology KW - Health Personnel KW - Occupational Exposure -- adverse effects KW - HIV Infections -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79640599?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=The+role+of+skin+dendritic+cells+in+the+initiation+of+human+immunodeficiency+virus+infection.&rft.au=Blauvelt%2C+A&rft.aulast=Blauvelt&rft.aufirst=A&rft.date=1997-05-19&rft.volume=102&rft.issue=5B&rft.spage=16&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 - 1998-12-14 N1 - Date created - 1998-12-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immune response to human immunodeficiency virus (HIV) in healthcare workers occupationally exposed to HIV-contaminated blood. AN - 79638771; 9845492 AB - Exposure to human immunodeficiency virus (HIV) does not necessarily induce infection or seroconversion defined by standard criteria based on enzyme-linked immunosorbent assay (ELISA), Western Blot, or polymerase chain reaction (PCR) techniques, but it can induce HIV-specific cell-mediated immune responses. Healthcare workers (HCWs) occupationally exposed to HIV represent a unique population with low-level exposure to HIV for whom time and type of exposure are specifically recorded. Although the frequency of seroconversion in HCWs occupationally exposed to HIV contaminated body fluids is relatively low, a higher proportion of HIV-exposed HCWs seem to exhibit in vitro cellular responses to HIV envelope peptides. Our findings indicate that parenteral exposure to HIV can induce cell-mediated immune responses in the absence of seroconversion. The significance of these responses is not known, but it is possible that the low incidence of HIV infection after exposure might be due, in part, to a protective cellular immune response to low HIV inocula. JF - The American journal of medicine AU - Pinto, L A AU - Landay, A L AU - Berzofsky, J A AU - Kessler, H A AU - Shearer, G M AD - Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/05/19/ PY - 1997 DA - 1997 May 19 SP - 21 EP - 24 VL - 102 IS - 5B SN - 0002-9343, 0002-9343 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Humans KW - T-Lymphocytes, Cytotoxic KW - T-Lymphocytes, Helper-Inducer KW - HIV Infections -- immunology KW - Health Personnel KW - Occupational Exposure -- adverse effects KW - HIV Infections -- etiology KW - T-Lymphocytes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79638771?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Immune+response+to+human+immunodeficiency+virus+%28HIV%29+in+healthcare+workers+occupationally+exposed+to+HIV-contaminated+blood.&rft.au=Pinto%2C+L+A%3BLanday%2C+A+L%3BBerzofsky%2C+J+A%3BKessler%2C+H+A%3BShearer%2C+G+M&rft.aulast=Pinto&rft.aufirst=L&rft.date=1997-05-19&rft.volume=102&rft.issue=5B&rft.spage=21&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 - 1998-12-14 N1 - Date created - 1998-12-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Residential and occupational exposure to sunlight and mortality from non-Hodgkin's lymphoma: composite (threefold) case-control study. AN - 79034785; 9167561 AB - To determine whether non-Hodgkin's lymphoma mortality is associated with sunlight exposure. Three case-control studies based on death certificates of non-Hodgkin's lymphoma, melanoma, and skin cancer mortality examining associations with potential sunlight exposure from residence and occupation. 24 states in the United States. All cases were deaths from non-Hodgkin's lymphoma, melanoma, and non-melanotic skin cancer between 1984 and 1991. Two age, sex, and race frequency matched controls per case were selected from non-cancer deaths. Odds ratios for non-Hodgkin's lymphoma, melanoma, and skin cancer from residential and occupational sunlight exposure adjusted for age, sex, race, socioeconomic status, and farming occupation. Non-Hodgkin's lymphoma mortality was not positively associated with sunlight exposure based on residence. Both melanoma and skin cancer were positively associated with residential sunlight exposure. Adjusted odds ratios for residing in states with the highest sunlight exposure were 0.83 (95% confidence interval 0.81 to 0.86) for non-Hodgkin's lymphoma, 1.12 (1.06 to 1.19) for melanoma, and 1.30 (1.18 to 1.43) for skin cancer. In addition, non-Hodgkin's lymphoma mortality was not positively associated with occupational sunlight exposure (odds ratio 0.88; 0.81 to 0.96). Skin cancer was slightly positively associated with occupational sunlight exposure (1.14; 0.96 to 1.36). Unlike skin cancer and to some extent melanoma, non-Hodgkin's lymphoma mortality was not positively associated with exposure to sunlight. The findings do not therefore support the hypothesis that sunlight exposure contributes to the rising rates of non-Hodgkin's lymphoma. JF - BMJ (Clinical research ed.) AU - Freedman, D M AU - Zahm, S H AU - Dosemeci, M AD - Division of Cancer Prevention and Control, National Cancer Institute, Rockville, MD 20892-7335, USA. Y1 - 1997/05/17/ PY - 1997 DA - 1997 May 17 SP - 1451 EP - 1455 VL - 314 IS - 7092 SN - 0959-8138, 0959-8138 KW - Abridged Index Medicus KW - Index Medicus KW - Occupational Exposure KW - Melanoma -- mortality KW - Humans KW - Aged KW - Multivariate Analysis KW - Socioeconomic Factors KW - Risk Factors KW - Adult KW - Case-Control Studies KW - Middle Aged KW - Residence Characteristics KW - United States -- epidemiology KW - Female KW - Male KW - Skin Neoplasms -- mortality KW - Lymphoma, Non-Hodgkin -- mortality KW - Sunlight -- adverse effects KW - Environmental Exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79034785?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BMJ+%28Clinical+research+ed.%29&rft.atitle=Residential+and+occupational+exposure+to+sunlight+and+mortality+from+non-Hodgkin%27s+lymphoma%3A+composite+%28threefold%29+case-control+study.&rft.au=Freedman%2C+D+M%3BZahm%2C+S+H%3BDosemeci%2C+M&rft.aulast=Freedman&rft.aufirst=D&rft.date=1997-05-17&rft.volume=314&rft.issue=7092&rft.spage=1451&rft.isbn=&rft.btitle=&rft.title=BMJ+%28Clinical+research+ed.%29&rft.issn=09598138&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-11 N1 - Date created - 1997-06-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: BMJ. 1997 May 17;314(7092):1483 [9167588] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A recombinant adenovirus expressing p27Kip1 induces cell cycle arrest and loss of cyclin-Cdk activity in human breast cancer cells. AN - 79055662; 9178904 AB - In order to elucidate the biochemical mechanisms by which the universal cyclin kinase inhibitor p27Kip1 regulates cell cycle progression in human breast cancer cells, a recombinant adenovirus expressing human p27 was constructed (Adp27). Upon infection of human breast cancer cells MDA-MB-231 and MCF-7 with Adp27, a high level of p27 expression was observed, and this resulted in a marked decrease in the proportion of cells in S-phase. In multiple cell lines, comparison of the cytotoxicity of Adp27 with another adenovirus vector expressing the related universal cyclin kinase inhibitor WAF1/Cip1 (AdWAF1), showed Adp27 to be markedly more (up to 56-fold) toxic than AdWAF1. DNA histograms showed Adp27 to cause a G1/S arrest at lower viral doses than AdWAF1. Analysis of cyclin dependent kinase activity following Adp27 infections showed decreased Cdk2 and cyclin B1-Cdc2 activity at lower viral doses when compared with AdWAF1. Adp27 is therefore potentially useful for studies of growth regulation and for gene therapy when growth inhibition is desired. JF - Oncogene AU - Craig, C AU - Wersto, R AU - Kim, M AU - Ohri, E AU - Li, Z AU - Katayose, D AU - Lee, S J AU - Trepel, J AU - Cowan, K AU - Seth, P AD - Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/05/15/ PY - 1997 DA - 1997 May 15 SP - 2283 EP - 2289 VL - 14 IS - 19 SN - 0950-9232, 0950-9232 KW - Cell Cycle Proteins KW - 0 KW - Microtubule-Associated Proteins KW - Tumor Suppressor Proteins KW - Cyclin-Dependent Kinase Inhibitor p27 KW - 147604-94-2 KW - Cyclin-Dependent Kinases KW - EC 2.7.11.22 KW - Index Medicus KW - Tumor Cells, Cultured KW - Humans KW - Cyclin-Dependent Kinases -- metabolism KW - Breast Neoplasms -- genetics KW - Microtubule-Associated Proteins -- genetics KW - Breast Neoplasms -- pathology KW - Cell Cycle -- genetics KW - Breast Neoplasms -- enzymology KW - Adenoviridae -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79055662?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+recombinant+adenovirus+expressing+p27Kip1+induces+cell+cycle+arrest+and+loss+of+cyclin-Cdk+activity+in+human+breast+cancer+cells.&rft.au=Craig%2C+C%3BWersto%2C+R%3BKim%2C+M%3BOhri%2C+E%3BLi%2C+Z%3BKatayose%2C+D%3BLee%2C+S+J%3BTrepel%2C+J%3BCowan%2C+K%3BSeth%2C+P&rft.aulast=Craig&rft.aufirst=C&rft.date=1997-05-15&rft.volume=14&rft.issue=19&rft.spage=2283&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-25 N1 - Date created - 1997-06-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of a dominant-negative mutant TGF-beta type II receptor in transgenic mice reveals essential roles for TGF-beta in regulation of growth and differentiation in the exocrine pancreas. AN - 79054377; 9184209 AB - Using a dominant-negative mutant receptor (DNR) approach in transgenic mice, we have functionally inactivated transforming growth factor-beta (TGF-beta) signaling in select epithelial cells. The dominant-negative mutant type II TGF-beta receptor blocked signaling by all three TGF-beta isoforms in primary hepatocyte and pancreatic acinar cell cultures generated from transgenic mice, as demonstrated by the loss of growth inhibitory and gene induction responses. However, it had no effect on signaling by activin, the closest TGF-beta family member. DNR transgenic mice showed increased proliferation of pancreatic acinar cells and severely perturbed acinar differentiation. These results indicate that TGF-beta negatively controls growth of acinar cells and is essential for the maintenance of a differentiated acinar phenotype in the exocrine pancreas in vivo. In contrast, such abnormalities were not observed in the liver. Additional abnormalities in the pancreas included fibrosis, neoangiogenesis and mild macrophage infiltration, and these were associated with a marked up-regulation of TGF-beta expression in transgenic acinar cells. This transgenic model of targeted functional inactivation of TGF-beta signaling provides insights into mechanisms whereby loss of TGF-beta responsiveness might promote the carcinogenic process, both through direct effects on cell proliferation, and indirectly through up-regulation of TGF-betas with associated paracrine effects on stromal compartments. JF - The EMBO journal AU - Böttinger, E P AU - Jakubczak, J L AU - Roberts, I S AU - Mumy, M AU - Hemmati, P AU - Bagnall, K AU - Merlino, G AU - Wakefield, L M AD - Laboratory of Chemoprevention, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/05/15/ PY - 1997 DA - 1997 May 15 SP - 2621 EP - 2633 VL - 16 IS - 10 SN - 0261-4189, 0261-4189 KW - Fibronectins KW - 0 KW - Proliferating Cell Nuclear Antigen KW - Receptors, Transforming Growth Factor beta KW - Transforming Growth Factor beta KW - Metallothionein KW - 9038-94-2 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - transforming growth factor-beta type II receptor KW - EC 2.7.11.30 KW - Index Medicus KW - Animals KW - Apoptosis KW - Gene Expression KW - Cell Differentiation KW - Liver -- metabolism KW - Metallothionein -- genetics KW - Mice KW - Proliferating Cell Nuclear Antigen -- isolation & purification KW - Fibronectins -- secretion KW - Homeostasis KW - Mice, Transgenic KW - Pancreatic Neoplasms -- etiology KW - Phenotype KW - Promoter Regions, Genetic KW - Mutation KW - Immunohistochemistry KW - Signal Transduction KW - Cell Division KW - Receptors, Transforming Growth Factor beta -- genetics KW - Pancreas -- abnormalities KW - Pancreas -- growth & development KW - Transforming Growth Factor beta -- metabolism KW - Receptors, Transforming Growth Factor beta -- deficiency UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79054377?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+EMBO+journal&rft.atitle=Expression+of+a+dominant-negative+mutant+TGF-beta+type+II+receptor+in+transgenic+mice+reveals+essential+roles+for+TGF-beta+in+regulation+of+growth+and+differentiation+in+the+exocrine+pancreas.&rft.au=B%C3%B6ttinger%2C+E+P%3BJakubczak%2C+J+L%3BRoberts%2C+I+S%3BMumy%2C+M%3BHemmati%2C+P%3BBagnall%2C+K%3BMerlino%2C+G%3BWakefield%2C+L+M&rft.aulast=B%C3%B6ttinger&rft.aufirst=E&rft.date=1997-05-15&rft.volume=16&rft.issue=10&rft.spage=2621&rft.isbn=&rft.btitle=&rft.title=The+EMBO+journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-07 N1 - Date created - 1997-07-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer. 1981 Mar 15;47(6 Suppl):1528-34 [6268274] Cancer Res. 1996 Nov 15;56(22):5146-9 [8912849] Environ Health Perspect. 1984 Jun;56:219-27 [6383798] Proc Natl Acad Sci U S A. 1986 Jun;83(12):4167-71 [2424019] Science. 1987 Oct 9;238(4824):188-93 [2821617] J Cell Biol. 1989 Feb;108(2):653-60 [2465297] J Cell Biol. 1989 Jul;109(1):429-40 [2745556] Mol Cell Biol. 1989 Dec;9(12):5508-15 [2586525] Eur J Cell Biol. 1990 Feb;51(1):64-75 [2184038] Cell. 1990 Jun 15;61(6):1121-35 [1693546] Growth Factors. 1990;3(1):45-52 [2383401] Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):93-7 [1986386] Development. 1991 Jan;111(1):131-43 [1707784] Am J Physiol. 1992 Feb;262(2 Pt 1):G364-8 [1539670] Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5408-12 [1608949] Nature. 1992 Sep 24;359(6393):295-300 [1406933] Gastroenterology. 1992 Dec;103(6):1883-92 [1451981] Cell. 1992 Dec 11;71(6):1003-14 [1333888] Science. 1993 May 28;260(5112):1335-8 [8388126] J Biol Chem. 1993 Jun 5;268(16):11500-3 [8389353] Mol Cell Biol. 1993 Sep;13(9):5266-75 [8355681] Nature. 1994 Aug 4;370(6488):341-7 [8047140] Genes Dev. 1995 Apr 15;9(8):945-55 [7774812] Gastroenterology. 1995 Sep;109(3):1005-9 [7657086] Genes Dev. 1996 Jan 1;10(1):1-15 [8557188] Science. 1996 Jan 19;271(5247):350-3 [8553070] Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):5877-82 [8650186] Int J Cancer. 1996 Jul 17;67(2):283-8 [8760600] Nature. 1996 Sep 12;383(6596):168-72 [8774881] Biotechniques. 1996 Jul;21(1):57-60 [8816236] Nature. 1996 Oct 31;383(6603):832-6 [8893010] Environ Health Perspect. 1984 Jun;56:187-203 [6383797] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of the multidrug resistance-associated protein gene in refractory lymphoma: quantitation by a validated polymerase chain reaction assay. AN - 79034019; 9160686 AB - Previous work investigating the role of MDR-1 overexpression in relapsed and refractory lymphoma led us to investigate a possible role for multidrug resistance-associated protein (MRP) as a cause of resistance in patients who did not overexpress MDR-1. A quantitative polymerase chain reaction (PCR) method for measuring MRP expression was validated. Immunoblot analysis suggested that no major discrepancy was present between mRNA expression and protein levels. MRP levels were found to be independent of sample tumor content by immunophenotyping, suggesting that the presence of normal cells had no significant impact on measurements of MRP expression. We evaluated MRP in 55 biopsy samples from 40 patients with refractory lymphoma enrolled on a trial of infusional chemotherapy (EPOCH). Pre- and post-EPOCH samples were available from 15 patients. MRP levels were also evaluated in 16 newly diagnosed, untreated lymphoma patient samples. No significant difference in MRP mRNA expression was noted between pre- and post-EPOCH groups. Also, MRP levels in the newly diagnosed patient samples were not significantly different from either pre- or post-EPOCH groups. Two of 15 paired pre- and post-EPOCH patient samples exhibited overexpression of MRP after EPOCH chemotherapy, with measured increases of 10-fold and 18-fold. We conclude that MRP overexpression is not responsible for non-P-glycoprotein (Pgp)-mediated drug resistance in the majority of these patients, although it may be important in a subset of patients. Defining this subset prospectively could aid in the development of clinical trials of MRP modulation in drug-resistant lymphoma. JF - Blood AU - Zhan, Z AU - Sandor, V A AU - Gamelin, E AU - Regis, J AU - Dickstein, B AU - Wilson, W AU - Fojo, A T AU - Bates, S E AD - National Institutes of Health, National Cancer Institute, Medicine Branch, Bethesda, MD 20892, USA. Y1 - 1997/05/15/ PY - 1997 DA - 1997 May 15 SP - 3795 EP - 3800 VL - 89 IS - 10 SN - 0006-4971, 0006-4971 KW - DNA, Neoplasm KW - 0 KW - Neoplasm Proteins KW - P-Glycoprotein KW - RNA, Messenger KW - RNA, Neoplasm KW - Vincristine KW - 5J49Q6B70F KW - Etoposide KW - 6PLQ3CP4P3 KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Verapamil KW - CJ0O37KU29 KW - Prednisone KW - VB0R961HZT KW - Abridged Index Medicus KW - Index Medicus KW - RNA, Neoplasm -- biosynthesis KW - Prednisone -- pharmacology KW - Carcinoma, Small Cell -- pathology KW - Cyclophosphamide -- administration & dosage KW - Etoposide -- pharmacology KW - Tumor Cells, Cultured -- metabolism KW - Humans KW - Vincristine -- pharmacology KW - Vincristine -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacology KW - Biopsy KW - Doxorubicin -- administration & dosage KW - RNA, Neoplasm -- genetics KW - Verapamil -- pharmacology KW - RNA, Messenger -- genetics KW - RNA, Messenger -- biosynthesis KW - Polymerase Chain Reaction KW - HL-60 Cells -- metabolism KW - Breast Neoplasms -- pathology KW - Doxorubicin -- pharmacology KW - Etoposide -- administration & dosage KW - DNA, Neoplasm -- genetics KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Prednisone -- administration & dosage KW - Lung Neoplasms -- pathology KW - Cyclophosphamide -- pharmacology KW - Neoplasm Proteins -- biosynthesis KW - P-Glycoprotein -- physiology KW - Neoplasm Proteins -- antagonists & inhibitors KW - P-Glycoprotein -- biosynthesis KW - P-Glycoprotein -- antagonists & inhibitors KW - Gene Expression Regulation, Neoplastic KW - P-Glycoprotein -- genetics KW - Neoplasm Proteins -- physiology KW - Lymphoma -- genetics KW - Drug Resistance, Neoplasm -- genetics KW - Neoplasm Proteins -- genetics KW - Lymphoma -- drug therapy KW - Lymphoma -- metabolism KW - Lymphoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79034019?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Expression+of+the+multidrug+resistance-associated+protein+gene+in+refractory+lymphoma%3A+quantitation+by+a+validated+polymerase+chain+reaction+assay.&rft.au=Zhan%2C+Z%3BSandor%2C+V+A%3BGamelin%2C+E%3BRegis%2C+J%3BDickstein%2C+B%3BWilson%2C+W%3BFojo%2C+A+T%3BBates%2C+S+E&rft.aulast=Zhan&rft.aufirst=Z&rft.date=1997-05-15&rft.volume=89&rft.issue=10&rft.spage=3795&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-19 N1 - Date created - 1997-06-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Improved biodistribution of 125I-labeled anti-Tac disulfide-stabilized Fv fragment by blocking its binding to the alpha subunit of the interleukin 2 receptor in the circulation with preinjected humanized anti-Tac IgG. AN - 79028238; 9157991 AB - Animal studies using radiolabeled anti-Tac disulfide-stabilized Fv (dsFv) monoclonal antibody have shown formation of complexes in serum with the soluble alpha subunit of the interleukin 2 receptor alpha (sIL-2R alpha). In this study, we improved the targeting of 125I-labeled anti-Tac dsFv to receptor-positive tumors in the presence of circulating receptor by preinjecting unlabeled humanized anti-Tac IgG antibody (HuTac IgG). We used mice bearing SP2/Tac tumor xenografts that express the IL-2R alpha. A positive correlation was seen between tumor size and the concentration of circulating receptor. Tumor-bearing mice were injected with 125I-labeled anti-Tac dsFv (400 ng), either alone or 15 min after injection of HuTac IgG. The 125I-labeled anti-Tac dsFv formed high molecular weight complexes with the sIL-2R alpha. The fraction of the dsFv present in the complexes increased as tumor size increased (greater sIL-2R alpha levels). The fractions of dsFv in the complexes were 9.9- to 11.6-fold higher when sIL-2R alpha was not blocked with preinjected HuTac IgG. The administration of a 12-fold molar excess of HuTac IgG over sIL-2R alpha resulted in >80% of the 125I activity present as the dsFv rather than in the complexes. Furthermore, the biodistribution of 125I-labeled anti-Tac dsFv was improved by blocking its binding to sIL-2R alpha by preinjecting HuTac IgG. Specifically, in the preinjected group, at 15 min postinjection, the 125I-labeled anti-Tac dsFv levels in tumor increased to 10.8% compared to 5.6% injected dose per gram in the non-preinjected group. In summary, our studies showed that preinjection of HuTac IgG can block the formation of complexes of circulating sIL-2R alpha and 125I-labeled anti-Tac dsFv. This blockade is associated with faster blood clearance, higher tumor uptake, and greater tumor:nontumor ratios of the radiolabeled antibody fragment. JF - Cancer research AU - Kobayashi, H AU - Yoo, T M AU - Drumm, D AU - Kim, M K AU - Sun, B F AU - Le, N AU - Webber, K O AU - Pastan, I AU - Waldmann, T A AU - Paik, C H AU - Carrasquillo, J A AD - Department of Nuclear Medicine, National Cancer Institute, NIH, Bethesda, Maryland 20892-1180, USA. Y1 - 1997/05/15/ PY - 1997 DA - 1997 May 15 SP - 1955 EP - 1961 VL - 57 IS - 10 SN - 0008-5472, 0008-5472 KW - Antibodies, Monoclonal KW - 0 KW - Disulfides KW - Immunoglobulin Fragments KW - Immunoglobulin G KW - Immunotoxins KW - Iodine Radioisotopes KW - Macromolecular Substances KW - Receptors, Interleukin-2 KW - Index Medicus KW - Neoplasms, Experimental -- ultrastructure KW - Neoplasm Transplantation KW - Disulfides -- pharmacokinetics KW - Animals KW - Antibodies, Monoclonal -- pharmacokinetics KW - Humans KW - Transplantation, Heterologous KW - Neoplasms, Experimental -- metabolism KW - Mice, Nude KW - Mice KW - Tissue Distribution KW - Female KW - Receptors, Interleukin-2 -- blood KW - Immunotoxins -- pharmacokinetics KW - Receptors, Interleukin-2 -- metabolism KW - Immunoglobulin G -- pharmacology KW - Immunoglobulin Fragments -- metabolism KW - Receptors, Interleukin-2 -- immunology KW - Iodine Radioisotopes -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79028238?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Improved+biodistribution+of+125I-labeled+anti-Tac+disulfide-stabilized+Fv+fragment+by+blocking+its+binding+to+the+alpha+subunit+of+the+interleukin+2+receptor+in+the+circulation+with+preinjected+humanized+anti-Tac+IgG.&rft.au=Kobayashi%2C+H%3BYoo%2C+T+M%3BDrumm%2C+D%3BKim%2C+M+K%3BSun%2C+B+F%3BLe%2C+N%3BWebber%2C+K+O%3BPastan%2C+I%3BWaldmann%2C+T+A%3BPaik%2C+C+H%3BCarrasquillo%2C+J+A&rft.aulast=Kobayashi&rft.aufirst=H&rft.date=1997-05-15&rft.volume=57&rft.issue=10&rft.spage=1955&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-10 N1 - Date created - 1997-06-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Distinctions between CD8+ and CD4+ T-cell regenerative pathways result in prolonged T-cell subset imbalance after intensive chemotherapy. AN - 79026466; 9160675 AB - Rapid recovery of CD4+ T cells after intensive chemotherapy is limited by an age-dependent decline in thymopoiesis. Here we sought to determine whether similar limitations exist for CD8+ T-cell regeneration. After intensive chemotherapy, CD8+ T cells had a faster effective doubling time than CD4+ T cells (median, 12.6 v 28.2 days, P < .05). Accordingly, at 3 months posttherapy, mean CD8+ T-cell number had returned to baseline, whereas mean CD4+ T-cell number was only 35% of pretherapy values (P < .05). These differences were primarily due to very rapid expansion of CD8+CD57+ and CD8+CD28- subsets. At 3 months posttherapy, there was no relationship between age and CD8+ T-cell number (R = -.02), whereas CD4+ T-cell number was inversely related to age (R = -.66) and there were no discernible differences in CD8+ recovery among patients with or without thymic enlargement, whereas CD4+ recovery was enhanced in patients with thymic enlargement after chemotherapy (P < .01). Therefore thymic-independent pathways of T-cell regeneration appear to rapidly regenerate substantial numbers of CD8+, but not CD4+ T cells, resulting in prolonged T-cell subset imbalance after T-cell depletion. These inherent distinctions between CD4+ v CD8+ T-cell regeneration may have significant implications for immunotherapeutic strategies undertaken to eradicate minimal residual neoplastic disease after cytoreductive chemotherapy. JF - Blood AU - Mackall, C L AU - Fleisher, T A AU - Brown, M R AU - Andrich, M P AU - Chen, C C AU - Feuerstein, I M AU - Magrath, I T AU - Wexler, L H AU - Dimitrov, D S AU - Gress, R E AD - Laboratory of Mathematical Biology, National Cancer Institute, and the Clinical Pathology Department, National Institutes of Health, Bethesda, MD 20892-1928, USA. Y1 - 1997/05/15/ PY - 1997 DA - 1997 May 15 SP - 3700 EP - 3707 VL - 89 IS - 10 SN - 0006-4971, 0006-4971 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Neoplasm, Residual KW - Neoplasms -- drug therapy KW - Age Factors KW - Humans KW - Thymus Gland -- pathology KW - Child KW - Child, Preschool KW - Infant KW - Neoplasms -- pathology KW - Neoplasm Recurrence, Local -- immunology KW - Adult KW - Follow-Up Studies KW - Adolescent KW - Female KW - Male KW - Neoplasms -- immunology KW - Lymphocyte Count -- drug effects KW - CD8-Positive T-Lymphocytes -- pathology KW - Lymphopenia -- chemically induced KW - Hematopoiesis -- drug effects KW - Lymphopenia -- pathology KW - CD4-Positive T-Lymphocytes -- pathology KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79026466?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Distinctions+between+CD8%2B+and+CD4%2B+T-cell+regenerative+pathways+result+in+prolonged+T-cell+subset+imbalance+after+intensive+chemotherapy.&rft.au=Mackall%2C+C+L%3BFleisher%2C+T+A%3BBrown%2C+M+R%3BAndrich%2C+M+P%3BChen%2C+C+C%3BFeuerstein%2C+I+M%3BMagrath%2C+I+T%3BWexler%2C+L+H%3BDimitrov%2C+D+S%3BGress%2C+R+E&rft.aulast=Mackall&rft.aufirst=C&rft.date=1997-05-15&rft.volume=89&rft.issue=10&rft.spage=3700&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-19 N1 - Date created - 1997-06-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selenophosphate synthetase: enzyme labeling studies with [gamma-32P]ATP, [beta-32P]ATP, [8-14C]ATP, and [75Se]selenide. AN - 79026394; 9169026 AB - Selenophosphate synthetase catalyzes a reaction in which ATP and selenide are converted to H3SeP03, H3P04, and AMP in a 1:1:1 ratio. Selenophosphate is derived from the gamma phosphoryl group and orthophosphate from the beta phosphoryl group of ATP. In the absence of selenide, a slow reaction in which ATP is converted quantitatively to 2 H3P04 and AMP occurs. Labeling experiments carried out to detect a putative enzyme-bound pyrophosphate intermediate in the overall reaction showed that up to 0.6 equivalent of the 32P label from [gamma-32P]ATP was bound to protein under enzyme turnover conditions, but only a negligible amount of 32P from [beta-32P]ATP was present. Thus, no Enz-PP intermediate was present in a detectable amount under the experimental conditions used. Isolated enzyme samples contained 75Se from 75Se-labeled selenide and [14C]AMP from [8-14C]ATP in amounts similar to the bound 32P from [gamma-32P]ATP, suggesting that two of the final products, selenophosphate and AMP, were the radioactive compounds detected in these experiments. JF - Archives of biochemistry and biophysics AU - Liu, S Y AU - Stadtman, T C AD - Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/05/15/ PY - 1997 DA - 1997 May 15 SP - 353 EP - 359 VL - 341 IS - 2 SN - 0003-9861, 0003-9861 KW - Bacterial Proteins KW - 0 KW - Carbon Radioisotopes KW - Drosophila Proteins KW - Enzymes KW - Isotopes KW - Phosphorus Radioisotopes KW - Sulfides KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Phosphotransferases KW - EC 2.7.- KW - selenophosphate synthetase KW - EC 2.7.9.3 KW - Selenium KW - H6241UJ22B KW - Cysteine KW - K848JZ4886 KW - Tellurium KW - NQA0O090ZJ KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Molecular Structure KW - Cysteine -- chemistry KW - Sulfides -- metabolism KW - Carbon Radioisotopes -- metabolism KW - Escherichia coli -- genetics KW - Phosphorus Radioisotopes -- metabolism KW - Escherichia coli -- enzymology KW - Tellurium -- metabolism KW - Binding Sites KW - Selenium -- metabolism KW - Bacterial Proteins -- genetics KW - Enzymes -- chemistry KW - Isotope Labeling -- methods KW - Bacterial Proteins -- metabolism KW - Adenosine Triphosphate -- metabolism KW - Enzymes -- metabolism KW - Adenosine Triphosphate -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79026394?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+biochemistry+and+biophysics&rft.atitle=Selenophosphate+synthetase%3A+enzyme+labeling+studies+with+%5Bgamma-32P%5DATP%2C+%5Bbeta-32P%5DATP%2C+%5B8-14C%5DATP%2C+and+%5B75Se%5Dselenide.&rft.au=Liu%2C+S+Y%3BStadtman%2C+T+C&rft.aulast=Liu&rft.aufirst=S&rft.date=1997-05-15&rft.volume=341&rft.issue=2&rft.spage=353&rft.isbn=&rft.btitle=&rft.title=Archives+of+biochemistry+and+biophysics&rft.issn=00039861&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-30 N1 - Date created - 1997-06-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of vascular endothelial growth factor-induced endothelial cell migration by ETS1 antisense oligonucleotides. AN - 79021987; 9157999 AB - Vascular endothelial growth factor (VEGF) increased the level of ETS1 mRNA in human umbilical vein endothelial cells (HUVEC) and human lung microvascular endothelial cells (HMVEC-L) over 5-fold. Protein levels were shown to increase concordantly. VEGF was also found to stimulate the invasiveness of endothelial cells as measured by migration through Matrigel- or gelatin-coated membranes. The VEGF-induced invasiveness was inhibited by ETS1 antisense oligonucleotides but not by a sense control. In addition, the ETS1 antisense oligonucleotides reduced the levels of ETS1 and urokinase-type plasminogen activator mRNAs. The antisense oligonucleotides directed against the ETS1 gene thus altered a cellular property of endothelial cells that is correlated with the ability of the cells to migrate through basement membranes. Together, these observations demonstrate a direct role for the ETS1 gene in angiogenesis. JF - Cancer research AU - Chen, Z AU - Fisher, R J AU - Riggs, C W AU - Rhim, J S AU - Lautenberger, J A AD - Scientific Applications International Corporation, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA. Y1 - 1997/05/15/ PY - 1997 DA - 1997 May 15 SP - 2013 EP - 2019 VL - 57 IS - 10 SN - 0008-5472, 0008-5472 KW - Drug Combinations KW - 0 KW - ETS1 protein, human KW - Endothelial Growth Factors KW - Laminin KW - Lymphokines KW - Oligonucleotides, Antisense KW - Proteoglycans KW - Proto-Oncogene Protein c-ets-1 KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-ets KW - RNA, Messenger KW - Transcription Factors KW - Vascular Endothelial Growth Factor A KW - Vascular Endothelial Growth Factors KW - matrigel KW - 119978-18-6 KW - Gelatin KW - 9000-70-8 KW - Collagen KW - 9007-34-5 KW - Urokinase-Type Plasminogen Activator KW - EC 3.4.21.73 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Gene Expression -- drug effects KW - Membranes KW - Humans KW - Cell Division -- drug effects KW - RNA, Messenger -- genetics KW - RNA, Messenger -- biosynthesis KW - Stimulation, Chemical KW - RNA, Messenger -- metabolism KW - Urokinase-Type Plasminogen Activator -- drug effects KW - Cells, Cultured KW - Cell Movement -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Gene Expression Regulation -- drug effects KW - Endothelial Growth Factors -- pharmacology KW - Proto-Oncogene Proteins -- biosynthesis KW - Endothelium, Vascular -- drug effects KW - Endothelium, Vascular -- cytology KW - Lymphokines -- pharmacology KW - Lymphokines -- antagonists & inhibitors KW - Oligonucleotides, Antisense -- pharmacology KW - Proto-Oncogene Proteins -- genetics KW - Transcription Factors -- genetics KW - Transcription Factors -- biosynthesis KW - Endothelial Growth Factors -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79021987?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inhibition+of+vascular+endothelial+growth+factor-induced+endothelial+cell+migration+by+ETS1+antisense+oligonucleotides.&rft.au=Chen%2C+Z%3BFisher%2C+R+J%3BRiggs%2C+C+W%3BRhim%2C+J+S%3BLautenberger%2C+J+A&rft.aulast=Chen&rft.aufirst=Z&rft.date=1997-05-15&rft.volume=57&rft.issue=10&rft.spage=2013&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-10 N1 - Date created - 1997-06-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antigen activation of mitogen-activated protein kinase in mast cells through protein kinase C-dependent and independent pathways. AN - 78998327; 9144516 AB - We demonstrate discrete pathways for activation of mitogen-activated protein (MAP) kinase in cultured RBL-2H3 mast cells through protein kinase C (PKC), cytosolic calcium, and a third pathway that provides sustained signals for activation in Ag-stimulated cells. Thus, p42 MAP kinase was activated by increasing intracellular free Ca2+ with thapsigargin or by stimulating PKC with PMA. The latter stimulation was selectively blocked by the protein kinase C inhibitor, Ro31-7549. Stimulation of p42 MAP kinase by Ag resulted in relatively sustained activation of MAP kinase which was only partially suppressed by Ro31-7549. Kinetic studies revealed two components of the MAP kinase response to Ag: a rapid but transient component that was Ro31-7549 sensitive and presumably PKC dependent; and a more sustained component that was Ro31-7549 resistant and presumably PKC independent. Similarly, Ro31-7549 inhibited the early but not late release of arachidonic acid, a finding that was consistent with the known regulation of phospholipase A2 by MAP kinase. Early tyrosine phosphorylation events which were thought to be essential for Ag-induced activation of p42 MAP kinase and release of arachidonic acid were unaffected by Ro31-7549. The findings suggested that release of arachidonic acid was regulated primarily through MAP kinase but that PKC may transiently influence this release, either directly or indirectly through MAP kinase. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Zhang, C AU - Hirasawa, N AU - Beaven, M A AD - Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/05/15/ PY - 1997 DA - 1997 May 15 SP - 4968 EP - 4975 VL - 158 IS - 10 SN - 0022-1767, 0022-1767 KW - Antigens KW - 0 KW - Cell Cycle Proteins KW - Enzyme Precursors KW - Indoles KW - Intracellular Signaling Peptides and Proteins KW - Maleimides KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-vav KW - Vav1 protein, rat KW - Ro 31-7549 KW - 125313-65-7 KW - Phosphotyrosine KW - 21820-51-9 KW - Arachidonic Acid KW - 27YG812J1I KW - Thapsigargin KW - 67526-95-8 KW - Carbachol KW - 8Y164V895Y KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Syk Kinase KW - EC 2.7.10.2 KW - Syk protein, rat KW - Protein Kinase C KW - EC 2.7.11.13 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Mitogen-Activated Protein Kinase 3 KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinases KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Enzyme Precursors -- metabolism KW - Proto-Oncogene Proteins -- metabolism KW - Phosphotyrosine -- metabolism KW - GTP-Binding Proteins -- physiology KW - Protein-Tyrosine Kinases -- metabolism KW - Arachidonic Acid -- metabolism KW - Thapsigargin -- pharmacology KW - Rats KW - Calcium -- metabolism KW - Cells, Cultured KW - Enzyme Activation -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Indoles -- pharmacology KW - Antigens -- immunology KW - Carbachol -- pharmacology KW - Maleimides -- pharmacology KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Protein Kinase C -- antagonists & inhibitors KW - Mast Cells -- enzymology KW - Protein Kinase C -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78998327?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Clinical+Neuropsychology&rft.atitle=Stress+management+and+multiple+sclerosis%3A+A+randomized+controlled+trial&rft.au=Artemiadis%2C+Artemios+K.%3BVervainioti%2C+Angeliki+A.%3BAlexopoulos%2C+Evangelos+C.%3BRombos%2C+Antonis%3BAnagnostouli%2C+Maria+C.%3BDarviri%2C+Christina&rft.aulast=Artemiadis&rft.aufirst=Artemios&rft.date=2012-06-01&rft.volume=27&rft.issue=4&rft.spage=406&rft.isbn=&rft.btitle=&rft.title=Archives+of+Clinical+Neuropsychology&rft.issn=08876177&rft_id=info:doi/10.1093%2Farclin%2Facs039 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-02 N1 - Date created - 1997-06-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hypoglycemic effect of insulin-like growth factor-1 in mice lacking insulin receptors. AN - 78997363; 9153298 AB - We have investigated the metabolic actions of recombinant human IGF-1 in mice genetically deficient of insulin receptors (IR-/-). After intraperitoneal administration, IGF-1 caused a prompt and sustained decrease of plasma glucose levels in IR-/- mice. Plasma free fatty acid concentrations were unaffected. Interestingly, the effects of IGF-1 were identical in normal mice (IR+/+) and in IR-/- mice. Despite decreased glucose levels, IR-/- mice treated with IGF-1 died within 2-3 d of birth, like sham-treated IR-/- controls. In skeletal muscle, IGF-1 treatment caused phosphorylation of IGF-1 receptors and increased the levels of the phosphatidylinositol-3-kinase p85 subunit detected in antiphosphotyrosine immunoprecipitates, consistent with the possibility that IGF-1 stimulates glucose uptake in a phosphatidylinositol-3-kinase-dependent manner. IGF-1 receptor phosphorylation and coimmunoprecipitation of phosphatidylinositol3-kinase by antiphosphotyrosine antibodies was also observed in liver, and was associated with a decrease in mRNA levels of the key gluconeogenetic enzyme phosphoenolpyruvate carboxykinase. Thus, the effect of IGF-1 on plasma glucose levels may be accounted for by increased peripheral glucose use and by inhibition of hepatic gluconeogenesis. These data indicate that IGF-1 can mimic insulin's effects on glucose metabolism by acting through its own receptor. The failure of IGF-1 to rescue the lethal phenotype due to lack of insulin receptors suggests that IGF-1 receptors cannot effectively mediate all the metabolic actions of insulin receptors. JF - The Journal of clinical investigation AU - Di Cola, G AU - Cool, M H AU - Accili, D AD - Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/05/15/ PY - 1997 DA - 1997 May 15 SP - 2538 EP - 2544 VL - 99 IS - 10 SN - 0021-9738, 0021-9738 KW - Blood Glucose KW - 0 KW - Fatty Acids, Nonesterified KW - Recombinant Proteins KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Receptor, IGF Type 1 KW - EC 2.7.10.1 KW - Receptor, Insulin KW - Abridged Index Medicus KW - Index Medicus KW - Injections, Intraperitoneal KW - Animals KW - Recombinant Proteins -- pharmacology KW - Exons KW - Humans KW - Liver -- metabolism KW - Mice KW - Mice, Knockout KW - Polymerase Chain Reaction KW - Animals, Newborn KW - Phosphorylation KW - Cells, Cultured KW - Heterozygote KW - Simian virus 40 KW - Fatty Acids, Nonesterified -- blood KW - Muscle, Skeletal -- metabolism KW - Recombinant Proteins -- administration & dosage KW - Cell Transformation, Viral KW - Receptor, Insulin -- genetics KW - Receptor, Insulin -- deficiency KW - Blood Glucose -- metabolism KW - Receptor, IGF Type 1 -- metabolism KW - Blood Glucose -- drug effects KW - Receptor, Insulin -- biosynthesis KW - Receptor, IGF Type 1 -- biosynthesis KW - Insulin-Like Growth Factor I -- administration & dosage KW - Hypoglycemia -- chemically induced KW - Insulin-Like Growth Factor I -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78997363?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+investigation&rft.atitle=Hypoglycemic+effect+of+insulin-like+growth+factor-1+in+mice+lacking+insulin+receptors.&rft.au=Di+Cola%2C+G%3BCool%2C+M+H%3BAccili%2C+D&rft.aulast=Di+Cola&rft.aufirst=G&rft.date=1997-05-15&rft.volume=99&rft.issue=10&rft.spage=2538&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+investigation&rft.issn=00219738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-17 N1 - Date created - 1997-06-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1994 Nov 18;269(46):28783-9 [7961833] Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10350-4 [1332046] Endocr Rev. 1995 Apr;16(2):117-42 [7781591] Endocr Rev. 1995 Apr;16(2):143-63 [7540132] Diabetes Metab Rev. 1995 Apr;11(1):47-62 [7600907] Biochem Soc Trans. 1995 Aug;23(3):500-6 [8566401] Diabetes. 1996 Jan;45(1):91-100 [8522066] Nat Genet. 1996 Jan;12(1):106-9 [8528241] J Clin Invest. 1996 Jan 1;97(1):81-91 [8550854] EMBO J. 1996 Apr 1;15(7):1542-7 [8612577] Diabetes Metab. 1996 Jul;22(4):261-7 [8767173] Diabetologia. 1997 Apr;40(4):412-20 [9112018] Endocrinology. 1979 Sep;105(3):723-30 [111916] J Biol Chem. 1984 Mar 10;259(5):3090-5 [6321495] Methods Enzymol. 1985;109:385-96 [2581111] J Biol Chem. 1985 Sep 5;260(19):10748-60 [2993287] Biochemistry. 1986 Sep 23;25(19):5560-4 [2946318] N Engl J Med. 1987 Jul 16;317(3):137-40 [3299085] J Clin Invest. 1988 Apr;81(4):976-81 [2832449] Mol Endocrinol. 1990 Feb;4(2):329-36 [1691820] J Clin Invest. 1992 Dec;90(6):2234-41 [1469083] Mol Endocrinol. 1992 Dec;6(12):2219-28 [1283442] Biochem J. 1993 Mar 1;290 ( Pt 2):419-26 [8452530] Endocrinology. 1993 Apr;132(4):1421-30 [8384986] J Biol Chem. 1993 Apr 15;268(11):8204-12 [8385139] Diabetes. 1993 May;42(5):696-705 [8482426] Lancet. 1993 Jun 12;341(8859):1536-7 [8099407] J Clin Invest. 1993 Jun;91(6):2453-62 [8514857] Cell. 1993 Oct 8;75(1):73-82 [8402902] J Clin Invest. 1993 Nov;92(5):2249-56 [8227340] Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10360-4 [8234298] Diabetes. 1994 Mar;43(3):369-74 [8314009] J Biol Chem. 1994 Feb 4;269(5):3568-73 [8106400] Ann Intern Med. 1994 Apr 1;120(7):593-601 [8116999] J Clin Invest. 1994 Mar;93(3):1131-9 [8132753] Adv Exp Med Biol. 1993;343:133-44 [8184735] Curr Opin Genet Dev. 1994 Feb;4(1):47-54 [8193539] J Clin Endocrinol Metab. 1994 Jul;79(1):205-10 [8027228] Eur J Endocrinol. 1994 Sep;131(3):251-7 [7921209] Am J Physiol. 1994 Sep;267(3 Pt 1):E461-6 [7943226] Diabetes. 1990 Sep;39(9):1028-32 [2166697] N Engl J Med. 1990 Nov 15;323(20):1425-6 [2233914] Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):214-8 [1846039] Nature. 1991 Jul 4;352(6330):73-7 [1648180] Adv Exp Med Biol. 1991;293:273-88 [1685051] Physiol Rev. 1992 Apr;72(2):507-62 [1557431] Diabete Metab. 1992;18(1 Pt 2):156-60 [1563551] J Cell Biochem. 1992 Jan;48(1):43-50 [1316361] Diabetes. 1992 Jun;41(6):691-7 [1587396] EMBO J. 1992 Sep;11(9):3469-79 [1380456] Diabetes. 1992 Nov;41(11):1473-90 [1327927] Endocrinology. 1992 Nov;131(5):2357-64 [1385101] Pediatr Res. 1994 Dec;36(6):749-54 [7534902] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genome scan for teratogen-induced clefting susceptibility loci in the mouse: evidence of both allelic and locus heterogeneity distinguishing cleft lip and cleft palate. AN - 78980679; 9144220 AB - Nonsyndromic clefting of the lip and palate in humans has a highly complex etiology, with both multiple genetic loci and exposure to teratogens influencing susceptibility. Previous studies using mouse models have examined only very small portions of the genome. Here we report the findings of a genome-wide search for susceptibility genes for teratogen-induced clefting in the AXB and BXA set of recombinant inbred mouse strains. We compare results obtained using phenytoin (which induces cleft lip) and 6-aminonicotinamide (which induces cleft palate). We use a new statistical approach based on logistic regression suitable for these categorical data to identify several chromosomal regions as possible locations of clefting susceptibility loci, and we review candidate genes located within each region. Because cleft lip and cleft palate do not frequently co-aggregate in human families and because these structures arise semi-independently during development, these disorders are usually considered to be distinct in etiology. Our data, however, implicate several of the same chromosomal regions for both forms of clefting when teratogen-induced. Furthermore, different parental strain alleles are usually associated with clefting of the lip versus that of the palate (i.e., allelic heterogeneity). Because several other chromosomal regions are associated with only one form of clefting, locus heterogeneity also appears to be involved. Our findings in this mouse model suggest several priority areas for evaluation in human epidemiological studies. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Diehl, S R AU - Erickson, R P AD - Oral Health Promotion, Risk Factors, and Molecular Epidemiology Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892-6401, USA. Y1 - 1997/05/13/ PY - 1997 DA - 1997 May 13 SP - 5231 EP - 5236 VL - 94 IS - 10 SN - 0027-8424, 0027-8424 KW - Teratogens KW - 0 KW - 6-Aminonicotinamide KW - 329-89-5 KW - Phenytoin KW - 6158TKW0C5 KW - Index Medicus KW - Regression Analysis KW - Mice, Inbred A KW - Animals KW - Alleles KW - Disease Susceptibility KW - Humans KW - Mice, Inbred C57BL KW - Crosses, Genetic KW - Mice KW - Abnormalities, Drug-Induced -- genetics KW - Cleft Palate -- chemically induced KW - Cleft Palate -- genetics KW - Chromosome Mapping KW - Cleft Lip -- genetics KW - Cleft Lip -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78980679?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genome+scan+for+teratogen-induced+clefting+susceptibility+loci+in+the+mouse%3A+evidence+of+both+allelic+and+locus+heterogeneity+distinguishing+cleft+lip+and+cleft+palate.&rft.au=Diehl%2C+S+R%3BErickson%2C+R+P&rft.aulast=Diehl&rft.aufirst=S&rft.date=1997-05-13&rft.volume=94&rft.issue=10&rft.spage=5231&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-05 N1 - Date created - 1997-06-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Immunogenetics. 1981;13(5):443-50 [7197664] J Embryol Exp Morphol. 1958 Mar;6(1):105-16 [13539273] J Leukoc Biol. 1984 Sep;36(3):357-64 [6592283] Am J Med Genet. 1984 Sep;19(1):9-18 [6496575] Genetics. 1986 Jul;113(3):735-44 [3732790] Genetics. 1986 Jul;113(3):745-54 [3525322] Genetics. 1986 Jul;113(3):755-64 [3732791] Am J Hum Genet. 1986 Nov;39(5):603-11 [3788974] Genet Res. 1987 Feb;49(1):43-9 [3569906] Genomics. 1987 Dec;1(4):293-6 [2896625] Teratology. 1988 Mar;37(3):283-7 [2966993] Am J Hum Genet. 1989 Sep;45(3):348-53 [2570526] Science. 1994 Jun 17;264(5166):1715-23 [8209252] Nature. 1994 Jul 28;370(6487):304-7 [7913519] Genetics. 1990 Sep;126(1):201-5 [2227380] Nature. 1991 Apr 11;350(6318):473-9 [1673020] Am J Hum Genet. 1991 Sep;49(3):674-81 [1882845] Am J Hum Genet. 1992 Feb;50(2):270-7 [1346481] Am J Hum Genet. 1992 May;50(5):1129-36 [1570839] Am J Hum Genet. 1992 Aug;51(2):323-32 [1642234] Am J Hum Genet. 1992 Sep;51(3):648-53 [1307687] Am J Med Genet. 1992 Sep 15;44(2):261-8 [1360769] Am J Hum Genet. 1992 Dec;51(6):1377-85 [1361101] Mamm Genome. 1992;3(12):669-80 [1477475] Am J Hum Genet. 1993 Feb;52(2):434-7 [8094269] Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2989-93 [8096643] J Craniofac Genet Dev Biol. 1993 Jan-Mar;13(1):1-5 [8478414] Am J Hum Genet. 1993 May;52(5):1006-11 [8488830] Am J Med Genet. 1992 Jan 1;42(1):5-9 [1308365] J Embryol Exp Morphol. 1966 Dec;16(3):543-58 [5297683] Teratology. 1969 Nov;2(4):371-6 [5362427] Am J Hum Genet. 1974 Mar;26(2):162-76 [4823025] J Immunogenet. 1979 Aug;6(4):253-62 [230263] Proc Natl Acad Sci U S A. 1980 May;77(5):2782-5 [6248866] Proc Natl Acad Sci U S A. 1981 May;78(5):3147-50 [6942422] Nat Genet. 1994 Apr;6(4):348-56 [7914451] Nat Genet. 1994 Jun;7(2):154-7 [7920633] Clin Genet. 1994 Sep;46(3):255-6 [7820940] Am J Hum Genet. 1995 Jan;56(1):310-8 [7825592] Am J Hum Genet. 1995 Jan;56(1):339-41 [7825598] Cell. 1995 Feb 10;80(3):431-7 [7859284] Nature. 1995 Mar 23;374(6520):354-6 [7885473] Am J Epidemiol. 1995 Apr 1;141(7):629-36 [7702037] Hum Mol Genet. 1995 Jan;4(1):121-8 [7711723] Mamm Genome. 1995 Feb;6(2):63-9 [7767007] J Craniofac Genet Dev Biol. 1995 Jan-Mar;15(1):1-12 [7601909] J Craniofac Genet Dev Biol. 1995 Apr-Jun;15(2):66-71 [7635931] Am J Hum Genet. 1995 Aug;57(2):227-32 [7668246] Am J Hum Genet. 1995 Aug;57(2):257-72 [7668251] Am J Hum Genet. 1995 Nov;57(5):1130-6 [7485164] Nat Genet. 1995 Nov;11(3):344-6 [7581464] Nat Genet. 1995 Dec;11(4):409-14 [7493021] Nat Genet. 1995 Dec;11(4):415-21 [7493022] Hum Mol Genet. 1995 Aug;4(8):1387-90 [7581378] Am J Hum Genet. 1996 Mar;58(3):551-61 [8644715] Behav Genet. 1996 Mar;26(2):149-60 [8639150] Genomics. 1996 May 1;33(3):337-51 [8660993] J Craniofac Genet Dev Biol. 1996 Oct-Dec;16(4):242-8 [8897214] J Med Genet. 1982 Feb;19(1):8-15 [7200146] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interaction of c-myc with transforming growth factor alpha and hepatocyte growth factor in hepatocarcinogenesis. AN - 79084408; 9202759 AB - Double transgenic mice bearing fusion genes consisting of mouse albumin enhancer/promoter-mouse c-myc cDNA and mouse metallothionein 1 promoter-human TGF-alpha cDNA were generated to investigate the interaction of these genes in hepatic oncogenesis and to provide a general paradigm for characterizing the interaction of nuclear oncogenes and growth factors in tumorigenesis. Coexpression of c-myc and TGF-alpha as transgenes in the mouse liver resulted in a tremendous acceleration of neoplastic development in this organ as compared to expression of either of these transgenes alone. The two distinct cellular reactions that occurred in the liver of the double transgenic mice prior to the appearance of liver tumors were dysplastic and apoptotic changes in the existing hepatocytes followed by emergence of multiple focal lesions composed of both hyperplastic and dysplastic cell populations. These observations suggest that the interaction of c-myc and TGF-alpha, during development of hepatic neoplasia contributes to the selection and expansion of the preneoplastic cell populations which consequently increases the probability of malignant conversion. These studies have now been extended to examine the interaction of hepatocyte growth factor (HGF) with c-myc during hepatocarcinogenesis in the transgenic mouse model. While sustained overexpression of c-myc in the liver leads to cancer, coexpression of HGF and c-myc in the liver delayed the appearance of preneoplastic lesions and prevented malignant conversion. Similarly, tumor promotion by phenobarbital was completely inhibited in the c-myc/HGF double transgenic mice whereas phenobarbital was an effective tumor promoter in the c-myc single transgenic mice. The results indicate that HGF may function as a tumor suppressor during early stages of liver carcinogenesis, and suggest the possibility of therapeutic application for this cytokine. Furthermore, we show for the first time that interaction of c-myc with HGF or TGF-alpha results in profoundly different outcomes of the neoplastic process in the liver. JF - Mutation research AU - Thorgeirsson, S S AU - Santoni-Rugiu, E AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. snorri_thorgeirsson@nih.gov Y1 - 1997/05/12/ PY - 1997 DA - 1997 May 12 SP - 221 EP - 234 VL - 376 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Anticarcinogenic Agents KW - 0 KW - Carcinogens KW - Proto-Oncogene Proteins c-myc KW - Transforming Growth Factor alpha KW - Hepatocyte Growth Factor KW - 67256-21-7 KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - Animals KW - Gene Expression KW - Mice KW - Phenobarbital -- antagonists & inhibitors KW - Mice, Transgenic KW - Neoplasms, Experimental KW - Carcinogens -- antagonists & inhibitors KW - Liver Neoplasms, Experimental -- genetics KW - Hepatocyte Growth Factor -- physiology KW - Liver Neoplasms, Experimental -- etiology KW - Transforming Growth Factor alpha -- physiology KW - Proto-Oncogene Proteins c-myc -- physiology KW - Liver Neoplasms -- etiology KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79084408?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Interaction+of+c-myc+with+transforming+growth+factor+alpha+and+hepatocyte+growth+factor+in+hepatocarcinogenesis.&rft.au=Thorgeirsson%2C+S+S%3BSantoni-Rugiu%2C+E&rft.aulast=Thorgeirsson&rft.aufirst=S&rft.date=1997-05-12&rft.volume=376&rft.issue=1-2&rft.spage=221&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-17 N1 - Date created - 1997-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cells lacking CIP1/WAF1 genes exhibit preferential sensitivity to cisplatin and nitrogen mustard. AN - 79050011; 9174048 AB - We have previously shown that p53 disruption sensitizes certain cancer cell types to cisplatin (CDDP) (Fan et al., 1995). In the present study we investigated the role of the p53 downstream effector, p21CIP1/WAF1 (p21), in this sensitization. Studies were performed in human colon cancer HCT-116 cells and murine embryonic fibroblasts (MEF) with intact versus disrupted p21 genes. For comparison, HCT-116 cells lacking p53 function were also prepared through stable transfection with the human papillomavirus type-16 E6 gene. HCT-116/E6 cells were found to be more sensitive than control transfectants to CDDP and another DNA crosslinking agent, nitrogen mustard (HN2). HCT-116 cells with disrupted p21 genes also exhibited greater CDDP and HN2-sensitivity than parental HCT-116 cells. In contrast, the clonogenic survival of HCT-116 cells exposed to ionizing radiation, adriamycin, taxol or vincristine was not affected by p53 or p21 disruption. Sensitization of HCT-116/p21-/- cells to CDDP and HN2 was not limited to the HCT-116 cell background since MEF from p21 knockout mice were also more sensitive to these DNA crosslinking agents. Investigations into a possible cause of this enhanced sensitivity revealed that HCT-116 cells lacking p53 or p21 function exhibited a reduced ability to repair cisplatin-damaged CAT-reporter plasmids transfected into the cells. In addition, we found that HCT-116/p21-/- cells were much more susceptible to HN2-induced cell cycle delay than parental cells. Our results suggest that p21 disruption preferentially sensitizes at least some cell types to DNA crosslinking agents. JF - Oncogene AU - Fan, S AU - Chang, J K AU - Smith, M L AU - Duba, D AU - Fornace, A J AU - O'Connor, P M AD - Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/05/08/ PY - 1997 DA - 1997 May 08 SP - 2127 EP - 2136 VL - 14 IS - 18 SN - 0950-9232, 0950-9232 KW - Antineoplastic Agents KW - 0 KW - Antineoplastic Agents, Alkylating KW - CDKN1A protein, human KW - Cdkn1a protein, mouse KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - E6 protein, Human papillomavirus type 16 KW - Oncogene Proteins, Viral KW - Radiation-Sensitizing Agents KW - Repressor Proteins KW - Mechlorethamine KW - 50D9XSG0VR KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Animals KW - Antineoplastic Agents, Alkylating -- pharmacology KW - Radiation-Sensitizing Agents -- pharmacology KW - Humans KW - S Phase -- genetics KW - Mice, Transgenic KW - Gene Expression Regulation, Neoplastic KW - G2 Phase -- genetics KW - Chloramphenicol O-Acetyltransferase -- drug effects KW - Genes, Reporter KW - Oncogene Proteins, Viral -- genetics KW - Colonic Neoplasms -- pathology KW - Cell Cycle -- genetics KW - Fibroblasts -- drug effects KW - S Phase -- drug effects KW - Colonic Neoplasms -- genetics KW - Plasmids -- genetics KW - Mice KW - Chloramphenicol O-Acetyltransferase -- metabolism KW - Fibroblasts -- metabolism KW - DNA Repair -- drug effects KW - DNA Repair -- genetics KW - Chloramphenicol O-Acetyltransferase -- genetics KW - G2 Phase -- drug effects KW - Transfection KW - Colonic Neoplasms -- drug therapy KW - Antineoplastic Agents -- pharmacology KW - Cell Cycle -- drug effects KW - Genes, p53 KW - Cyclins -- drug effects KW - Cisplatin -- pharmacology KW - Cyclins -- metabolism KW - Mechlorethamine -- pharmacology KW - Cyclins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79050011?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cells+lacking+CIP1%2FWAF1+genes+exhibit+preferential+sensitivity+to+cisplatin+and+nitrogen+mustard.&rft.au=Fan%2C+S%3BChang%2C+J+K%3BSmith%2C+M+L%3BDuba%2C+D%3BFornace%2C+A+J%3BO%27Connor%2C+P+M&rft.aulast=Fan&rft.aufirst=S&rft.date=1997-05-08&rft.volume=14&rft.issue=18&rft.spage=2127&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-23 N1 - Date created - 1997-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Altered expression of Erg and Ets-2 transcription factors is associated with genetic changes at 21q22.2-22.3 in immortal and cervical carcinoma cell lines. AN - 79039365; 9174050 AB - Human Papillomavirus (HPV) type 16 is the most frequently detected HPV in cervical cancer. Although epidemiologic and experimental evidence indicates a prominent role for HPV infection in the development of this disease, other factors are also involved. Altered expression of the ets family transcription factors erg and ets-2 was found associated with the development of cervical carcinoma. Overexpression also occurred in a HPV-16-immortalized cervical cell line, CX16-2, which has HPV integrated at a translocation breakpoint t(19;21) involving 21q22.2-22.3, where these genes have been mapped. Six of 10 cervical carcinoma cell lines overexpressed ets-2 RNA suggesting an association of overexpression with cervical cell neoplasia. A clonally related pair of cervical carcinoma cell lines, C-4I and C-4II, showed differential expression of erg and ets-2. C-4I overexpressed ets-2 RNA compared to normal cervical cells and C-4II. C-4II expressed a 5.3 kb erg transcript not seen in C-4I, ectocervical cells or other cervical carcinoma cell lines examined. Pulsed field gel electrophoresis was used to analyse changes in DNA fragments related to structural changes and to construct a physical map encompassing erg and ets-2. Alterations in erg and ets-2 RNA expression in each of three different cell lines examined were associated with translocations. Association between altered expression of erg and ets-2 and altered regional structural suggests that these genes are important targets in cervical carcinogenesis. JF - Oncogene AU - Simpson, S AU - Woodworth, C D AU - DiPaolo, J A AD - Laboratory of Biology, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1997/05/08/ PY - 1997 DA - 1997 May 08 SP - 2149 EP - 2157 VL - 14 IS - 18 SN - 0950-9232, 0950-9232 KW - DNA-Binding Proteins KW - 0 KW - E6 protein, Human papillomavirus type 16 KW - EGR1 protein, human KW - ERF protein, human KW - ERG protein, human KW - ETS2 protein, human KW - Early Growth Response Protein 1 KW - Immediate-Early Proteins KW - Oncogene Proteins, Viral KW - Papillomavirus E7 Proteins KW - Proto-Oncogene Protein c-ets-2 KW - Proto-Oncogene Proteins KW - Repressor Proteins KW - Retroviridae Proteins, Oncogenic KW - Trans-Activators KW - Transcription Factors KW - Transcriptional Regulator ERG KW - oncogene protein E7, Human papillomavirus type 16 KW - Index Medicus KW - Blotting, Northern KW - Humans KW - DNA-Binding Proteins -- genetics KW - Translocation, Genetic KW - Gene Expression Regulation, Neoplastic KW - Cervix Uteri -- physiology KW - Retroviridae Proteins, Oncogenic -- genetics KW - Epithelium -- virology KW - Tumor Cells, Cultured KW - DNA Methylation KW - Restriction Mapping KW - Oncogene Proteins, Viral -- genetics KW - Cervix Uteri -- cytology KW - Cervix Uteri -- virology KW - Epithelium -- pathology KW - Cell Transformation, Neoplastic KW - Female KW - Carcinoma -- pathology KW - Trans-Activators -- genetics KW - Chromosomes, Human, Pair 21 KW - Uterine Cervical Neoplasms -- genetics KW - Proto-Oncogene Proteins -- genetics KW - Transcription Factors -- genetics KW - Uterine Cervical Neoplasms -- pathology KW - Carcinoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79039365?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Altered+expression+of+Erg+and+Ets-2+transcription+factors+is+associated+with+genetic+changes+at+21q22.2-22.3+in+immortal+and+cervical+carcinoma+cell+lines.&rft.au=Simpson%2C+S%3BWoodworth%2C+C+D%3BDiPaolo%2C+J+A&rft.aulast=Simpson&rft.aufirst=S&rft.date=1997-05-08&rft.volume=14&rft.issue=18&rft.spage=2149&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-23 N1 - Date created - 1997-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Relation of age and apolipoprotein E to cognitive function in Down syndrome adults. AN - 85277295; pmid-9223061 AB - To test the cognitive effects of aging and apolipoprotein E (APOE) in individuals at high risk for Alzheimer's disease (AD), we assessed APOE genotypes and performance on a battery of neuropsychological tests in 41 non-demented, Down syndrome (DS) adults. Old DS subjects (ages 41-61 years) showed poorer memory and orientation scores than young DS adults (ages 22-38 years), but the groups did not differ in other measures after we controlled for intellectual function. Language ability was inversely related to APOE genotype, even after age was controlled for, with the presence of the epsilon 2 allele corresponding to better language skills than epsilon 4. Age-related cognitive changes in non-demented DS adults are consistent with the early effects of AD. The relationship between basic linguistic skills and APOE genotype supports this genetic factor in influencing the development of dementia and AD neuropathology in DS. JF - Neuroreport AU - Alexander, G E AU - Saunders, A M AU - Szczepanik, J AU - Strassburger, T L AU - Pietrini, P AU - Dani, A AU - Furey, M L AU - Mentis, M J AU - Roses, A D AU - Rapoport, S I AU - Schapiro, M B AD - Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1997 SP - 1835 EP - 1840 VL - 8 IS - 8 SN - 0959-4965, 0959-4965 KW - Support, U.S. Gov't, P.H.S. KW - Human KW - Aging KW - Genetic Markers KW - Apolipoproteins E KW - Cognition KW - Genotype KW - Alleles KW - Risk Factors KW - Adult KW - Support, Non-U.S. Gov't KW - Middle Age KW - Down Syndrome KW - Neuropsychological Tests KW - Male KW - Female UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85277295?accountid=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=Relation+of+age+and+apolipoprotein+E+to+cognitive+function+in+Down+syndrome+adults.&rft.au=Alexander%2C+G+E%3BSaunders%2C+A+M%3BSzczepanik%2C+J%3BStrassburger%2C+T+L%3BPietrini%2C+P%3BDani%2C+A%3BFurey%2C+M+L%3BMentis%2C+M+J%3BRoses%2C+A+D%3BRapoport%2C+S+I%3BSchapiro%2C+M+B&rft.aulast=Alexander&rft.aufirst=G&rft.date=1997-05-01&rft.volume=8&rft.issue=8&rft.spage=1835&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 - Detection, classification, and superposition resolution of action potentials in multiunit single-channel recordings by an on-line real-time neural network. AN - 85254041; pmid-9125825 AB - Determination of single-unit spike trains from multiunit recordings obtained during extracellular recording has been the focus of many studies over the last two decades. In multiunit recordings, superpositions can occur with high frequency if the firing rates of the neurons are high or correlated, making superposition resolution imperative for accurate spike train determination. In this work, a connectionist neural network (NN) was applied to the spike sorting challenge. A novel training scheme was developed which enabled the NN to resolve some superpositions using single-channel recordings. Simulated multiunit spike trains were constructed from templates and noise segments that were extracted from real extracellular recordings. The simulations were used to determine the performances of the NN and a simple matched template filter (MTF), which was used as a basis for comparison. The network performed as well as the MTF in identifying nonoverlapping spikes, and was significantly better in resolving superpositions and rejecting noise. An on-line, real-time implementation of the NN discriminator, using a high-speed digital signal processor mounted inside an IBM-PC, is now in use in six laboratories. JF - IEEE Transactions on Bio-Medical Engineering AU - Chandra, R AU - Optican, L M AD - Laboratory of Sensorimotor Research, National Eye Institute, NIH, Bethesda, MD 20892, USA. PY - 1997 SP - 403 EP - 412 VL - 44 IS - 5 SN - 0018-9294, 0018-9294 KW - Sensitivity and Specificity KW - Human KW - Analog-Digital Conversion KW - Temporal Lobe KW - Infant, Newborn KW - Animal KW - Algorithms KW - Models, Neurological KW - Haplorhini KW - False Positive Reactions KW - Signal Processing, Computer-Assisted KW - Neural Networks (Computer) KW - Action Potentials KW - Online Systems UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85254041?accountid=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=IEEE+Transactions+on+Bio-Medical+Engineering&rft.atitle=Detection%2C+classification%2C+and+superposition+resolution+of+action+potentials+in+multiunit+single-channel+recordings+by+an+on-line+real-time+neural+network.&rft.au=Chandra%2C+R%3BOptican%2C+L+M&rft.aulast=Chandra&rft.aufirst=R&rft.date=1997-05-01&rft.volume=44&rft.issue=5&rft.spage=403&rft.isbn=&rft.btitle=&rft.title=IEEE+Transactions+on+Bio-Medical+Engineering&rft.issn=00189294&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Three-dimensional cortical morphometry of the planum temporale in childhood-onset schizophrenia. AN - 85242605; pmid-9137128 AB - OBJECTIVE: Anomalous planum temporale asymmetry has been linked to both schizophrenia and dyslexia. The authors examined the planum temporale of adolescents with childhood-onset schizophrenia who had a high rate of prepsychotic language disorders. METHOD: Planum temporale area and asymmetry were measured in 16 right-handed adolescent patients with schizophrenia who had experienced onset of psychosis by age 12. The same measures were made in 16 healthy adolescents matched for age, sex, and handedness. RESULTS: No differences between the healthy adolescents and those with schizophrenia in planum temporale area or asymmetry were observed. Prepsychotic language disorder predicted abnormal planum temporale asymmetry in the adolescents with schizophrenia. CONCLUSIONS: These findings do not support anomalous planum temporale asymmetry as a basis for psychopathology in childhood-onset schizophrenia. JF - The American Journal of Psychiatry AU - Jacobsen, L K AU - Giedd, J N AU - Tanrikut, C AU - Brady, D R AU - Donohue, B C AU - Hamburger, S D AU - Kumra, S AU - Alaghband-Rad, J AU - Rumsey, J M AU - Rapoport, J L AD - Child Psychiatry Branch, NIMH, Bethesda, MD 20892, USA. PY - 1997 SP - 685 EP - 687 VL - 154 IS - 5 SN - 0002-953X, 0002-953X KW - Schizophrenia KW - Age Factors KW - Age of Onset KW - Human KW - Adult KW - Temporal Lobe KW - Brain KW - Language Disorders KW - Child KW - Adolescent KW - Laterality KW - Schizophrenia, Childhood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85242605?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+Journal+of+Psychiatry&rft.atitle=Three-dimensional+cortical+morphometry+of+the+planum+temporale+in+childhood-onset+schizophrenia.&rft.au=Jacobsen%2C+L+K%3BGiedd%2C+J+N%3BTanrikut%2C+C%3BBrady%2C+D+R%3BDonohue%2C+B+C%3BHamburger%2C+S+D%3BKumra%2C+S%3BAlaghband-Rad%2C+J%3BRumsey%2C+J+M%3BRapoport%2C+J+L&rft.aulast=Jacobsen&rft.aufirst=L&rft.date=1997-05-01&rft.volume=154&rft.issue=5&rft.spage=685&rft.isbn=&rft.btitle=&rft.title=The+American+Journal+of+Psychiatry&rft.issn=0002953X&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Compartmentalized vesicular traffic around the hair cell cuticular plate. AN - 85237608; pmid-9165351 AB - Through thin-section and freeze-fracture electron microscopy, we identify structural correlates of an intense vesicular traffic in a narrow band of cytoplasm around the cuticular plate of the bullfrog vestibular hair cells. Myriads of coated and uncoated vesicles associated with longitudinally oriented microtubules populate the narrow cytoplasmic region between the cuticular plate and the actin network of the apical junctional belt. If microtubules in the sensory hair cells, like those in axons, are pathways for organelle transport, then the characteristic distribution of microtubules around the cuticular plate represents transport pathways across the apical region of the hair cells. This compartmentalized membrane traffic system appears to support an intense vesicular release and uptake along a band of apical plasma membrane near the cell border. Functions of this transport system may include membrane recycling as well as exocytotic and endocytotic exchange between the hair cell cytoplasm and the endolymphatic compartment. JF - Hearing Research AU - Kachar Bechara AU - Battaglia, A AU - Fex, J AD - National Institute on Deafness and Other Communication Disorders PY - 1997 SP - 102 EP - 112 VL - 107 IS - 1-2 SN - 0378-5955, 0378-5955 KW - Endocytosis KW - Freeze Fracturing KW - Hair Cells KW - Rana catesbeiana KW - Acoustic Maculae KW - Cytoplasm KW - Cell Compartmentation KW - Cell Membrane KW - Exocytosis KW - Animal KW - Microscopy, Electron KW - Epithelium KW - Microscopy, Electron, Scanning UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85237608?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hearing+Research&rft.atitle=Compartmentalized+vesicular+traffic+around+the+hair+cell+cuticular+plate.&rft.au=Kachar+Bechara%3BBattaglia%2C+A%3BFex%2C+J&rft.aulast=Kachar+Bechara&rft.aufirst=&rft.date=1997-05-01&rft.volume=107&rft.issue=1-2&rft.spage=102&rft.isbn=&rft.btitle=&rft.title=Hearing+Research&rft.issn=03785955&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Hypoxia-induced ABR change and heat shock protein expression in the pontine auditory pathway of young rabbits. AN - 85232873; pmid-9200505 AB - The auditory brainstem response (ABR) was compared with the immunohistochemical expression of heat shock protein (HSP-72) and microtubule-associated protein 2 (MAP-2) of the brainstem auditory pathway in young rabbits subjected to hypoxic stress. Severe hypoxia for 2 h produced significant prolongation and decreased amplitude of the later component of ABR. HSP-72 expression was distinctly increased in the cochlear nucleus, but there was less induction in the inferior colliculus under severe hypoxia. MAP-2 immunostaining of neuropiles in the inferior collicular nucleus was decreased slightly after severe-long hypoxia, but cytoplasmic staining did not change. The present ABR change, which was produced by brainstem hypoxia-ischemia and acidosis, may be due to the neural cytoarchitectural derangement and less induction of stress proteins in the upper brainstem. JF - Brain Research AU - Inagaki, M AU - Kaga, M AU - Isumi, H AU - Hirano, S AU - Takashima, S AU - Nanba, E AD - National Institute of Mental Health, National Center of Neurology and Psychiatry (NCNP), Ichikawa, Japan. PY - 1997 SP - 111 EP - 118 VL - 757 IS - 1 SN - 0006-8993, 0006-8993 KW - Bicarbonates KW - Blood Pressure KW - Auditory Pathways KW - Microtubule-Associated Proteins KW - Animal KW - Rabbits KW - Organ Specificity KW - Oxygen KW - Heart Rate KW - Evoked Potentials, Auditory KW - Support, Non-U.S. Gov't KW - Immunohistochemistry KW - Female KW - Partial Pressure KW - Pons KW - Heat-Shock Proteins KW - Carbon Dioxide KW - Anoxia UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85232873?accountid=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+Research&rft.atitle=Hypoxia-induced+ABR+change+and+heat+shock+protein+expression+in+the+pontine+auditory+pathway+of+young+rabbits.&rft.au=Inagaki%2C+M%3BKaga%2C+M%3BIsumi%2C+H%3BHirano%2C+S%3BTakashima%2C+S%3BNanba%2C+E&rft.aulast=Inagaki&rft.aufirst=M&rft.date=1997-05-01&rft.volume=757&rft.issue=1&rft.spage=111&rft.isbn=&rft.btitle=&rft.title=Brain+Research&rft.issn=00068993&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Neonatal ablations of the amygdala and inferior temporal cortex alter the vocal response to social separation in rhesus macaques. AN - 85230513; pmid-9203547 AB - Rhesus macaques that had received bilateral ablations to either the amygdala or area TE in inferior temporal cortex in the 1st week of life were briefly separated from familiar conspecifics at 10-14.5 months of age in order to assess the vocal response to this mild challenge. Sound spectrograms were subjected to quantitative analysis and compared with calls from normal, age-matched controls subjected to the same testing conditions. Animals with TE damage called at a higher rate than animals in the other two groups. TE subjects also produced more coos than controls. Males with TE lesions produced noisy calls at a higher rate than males of the other two groups. Females did not differ between groups in this measure. Analysis of the detailed acoustic structure of the 'coo' indicated significant differences in a measure of slope of the fundamental frequency (rate of frequency change over time) between amygdalectomized animals and those of the other 2 groups. The amygdalectomized monkeys produced calls with lower slope values, giving the calls a less inflected quality both in sonagrams and to the listener. These findings suggest an important role for the amygdala and inferior temporal cortex in regulating the vocal response to social separation during development. JF - Brain Research AU - Newman, J D AU - Bachevalier, J AD - Laboratory of Comparative Ethology, NICHD, Poolesville, MD 20837, USA. PY - 1997 SP - 180 EP - 186 VL - 758 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Vocalization, Animal KW - Temporal Lobe KW - Animal KW - Amygdala KW - Macaca mulatta KW - Behavior, Animal KW - Female KW - Male KW - Social Isolation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85230513?accountid=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+Research&rft.atitle=Neonatal+ablations+of+the+amygdala+and+inferior+temporal+cortex+alter+the+vocal+response+to+social+separation+in+rhesus+macaques.&rft.au=Newman%2C+J+D%3BBachevalier%2C+J&rft.aulast=Newman&rft.aufirst=J&rft.date=1997-05-01&rft.volume=758&rft.issue=1-2&rft.spage=180&rft.isbn=&rft.btitle=&rft.title=Brain+Research&rft.issn=00068993&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Altered patterns of cerebral activity during speech and language production in developmental stuttering. An H2(15)O positron emission tomography study. AN - 85225904; pmid-9183248 AB - To assess dynamic brain function in adults who had stuttered since childhood, regional cerebral blood flow (rCBF) was measured with H2O and PET during a series of speech and language tasks designed to evoke or attenuate stuttering. Speech samples were acquired simultaneously and quantitatively compared with the PET images. Both hierarchical task contrasts and correlational analyses (rCBF versus weighted measures of dysfluency) were performed. rCBF patterns in stuttering subjects differed markedly during the formulation and expression of language, failing to demonstrate left hemispheric lateralization typically observed in controls; instead, regional responses were either absent, bilateral or lateralized to the right hemisphere. Significant differences were detected between groups when all subjects were fluent-during both language formulation and non-linguistic oral motor tasks-demonstrating that cerebral function may be fundamentally different in persons who stutter, even in the absence of stuttering. Comparison of scans acquired during fluency versus dysfluency-evoking tasks suggested that during the production of stuttered speech, anterior forebrain regions-which play an a role in the regulation of motor function-are disproportionately active in stuttering subjects, while post-rolandic regions-which play a role in perception and decoding of sensory information-are relatively silent. Comparison of scans acquired during these conditions in control subjects, which provide information about the sensorimotor or cognitive features of the language tasks themselves, suggest a mechanism by which fluency-evoking maneuvers might differentially affect activity in these anterior and posterior brain regions and may thus facilitate fluent speech production in individuals who stutter. Both correlational and contrast analyses suggest that right and left hemispheres play distinct and opposing roles in the generation of stuttering symptoms: activation of left hemispheric regions appears to be related to the production of stuttered speech, while activation of right hemispheric regions may represent compensatory processes associated with attenuation of stuttering symptoms. JF - Brain AU - Braun, Allen R AU - Varga, M AU - Stager, S AU - Schulz, G AU - Selbie, S AU - Maisog, J M AU - Carson, R E AU - Ludlow, C L AD - National Institute on Deafness and Other Communication Disorders Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 761 EP - 784 VL - 120 ( Pt 5) SN - 0006-8950, 0006-8950 KW - Developmental Disabilities KW - Laryngeal Muscles KW - Human KW - Brain KW - Muscles KW - Water KW - Infant KW - Oxygen Radioisotopes KW - Adult KW - Middle Age KW - Stuttering KW - Mouth KW - Speech KW - Male KW - Female KW - Phonetics KW - Tomography, Emission-Computed UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85225904?accountid=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=Altered+patterns+of+cerebral+activity+during+speech+and+language+production+in+developmental+stuttering.+An+H2%2815%29O+positron+emission+tomography+study.&rft.au=Braun%2C+Allen+R%3BVarga%2C+M%3BStager%2C+S%3BSchulz%2C+G%3BSelbie%2C+S%3BMaisog%2C+J+M%3BCarson%2C+R+E%3BLudlow%2C+C+L&rft.aulast=Braun&rft.aufirst=Allen&rft.date=1997-05-01&rft.volume=120+%28+Pt+5%29&rft.issue=&rft.spage=761&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 - Endolymphatic sac tumors. A source of morbid hearing loss in von Hippel-Lindau disease. AN - 85223667; pmid-9145719 AB - OBJECTIVES: Isolated reports suggest a possible association of endolymphatic sac tumors (ELSTs), which are extremely rare in the general population, with von Hippel-Lindau disease (VHL). To determine if hearing loss and ELSTs are a component of VHL, we examined prevalence, clinical presentation, and natural history of hearing loss and ELSTs in VHL. DESIGN: Brain magnetic resonance images (MRIs) from 374 patients screened for VHL were reviewed for evidence of ELSTs. The VHL patients with MRI evidence suggestive of ELSTs or a history of hearing loss, tinnitus, or vertigo underwent additional radiologic and audiologic evaluations. To further assess prevalence of hearing loss and ELST in VHL, the next 66 patients screened in the VHL clinic (49 with proven VHL, 17 at risk for VHL) received MRI and audiologic assessment. SETTING: Referral center. PARTICIPANTS: Study subjects comprised 374 persons screened for VHL, 66 consecutive patients with VHL or at risk for VHL, 4 patients with 6 ELSTs, and 13 previously reported patients with VHL and invasive tumors of the temporal bone. INTERVENTION: Magnetic resonance image and computed tomographic (CT) scan of the posterior fossa and audiologic assessment. MAIN OUTCOME MEASURES: Any ELST visible on MRI or CT and hearing loss compatible with ELST. RESULTS: Magnetic resonance imaging revealed evidence of 15 ELSTs in 13 (11%) of 121 patients with VHL, but in none of the 253 patients without evidence of VHL (P<.001). Clinical findings in these 13 patients included hearing loss (13), tinnitus (12), vertigo (8), and facial paresis (1). Mean age at onset of hearing loss was 22 years (range, 12-50 years). Hearing for pure tones was abnormal in all affected ears and in 6 of the 11 additional, allegedly unaffected ears. In 8 patients (62%), hearing loss was the first manifestation of VHL. Presence or absence of hearing loss was associated with duration of symptoms (P<.002) and with tumor size (P<.01). Further, 43 (65%) of the 66 patients from the VHL clinic had pure tone threshold abnormalities, abnormalities that occurred bilaterally in 23 (54%) of the 43 affected subjects; however, evidence is lacking for a definitive association with ELST (3 [6%] of 49 patients with proven VHL had ELST evident on MRI). CONCLUSIONS: Hearing loss and ELSTs are frequently associated with VHL syndrome and should be considered when screening individuals at risk for VHL and when monitoring patients with an established diagnosis of VHL. Many patients with VHL have hearing loss without radiographic evidence of an ELST. Whether it is caused by an ELST that is too small to be detected by MRI or is produced by some other etiology is still unknown. Audiologic evaluation and MRI should allow early detection and enhance management of hearing loss in these patients. JF - JAMA AU - Manski, T J AU - Heffner, D K AU - Glenn, G M AU - Patronas, N J AU - Pikus, A T AU - Katz, D AU - Lebovics, R AU - Sledjeski, K AU - Choyke, P L AU - Zbar, B AU - Linehan, W M AU - Oldfield, E H AD - Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1414, USA. PY - 1997 SP - 1461 EP - 1466 VL - 277 IS - 18 SN - 0098-7484, 0098-7484 KW - Magnetic Resonance Imaging KW - Hippel-Lindau Disease KW - Hearing Disorders KW - Ear Neoplasms KW - Audiometry KW - Age of Onset KW - Genes, Tumor Suppressor KW - Humans KW - Cranial Fossa, Posterior KW - Petrous Bone KW - Brain KW - Retrospective Studies KW - Tomography, X-Ray Computed KW - Proteins KW - Hearing Loss KW - Mutation KW - Ubiquitin-Protein Ligases KW - Endolymphatic Sac KW - Ligases KW - Tumor Suppressor Proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85223667?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=JAMA&rft.atitle=Endolymphatic+sac+tumors.+A+source+of+morbid+hearing+loss+in+von+Hippel-Lindau+disease.&rft.au=Manski%2C+T+J%3BHeffner%2C+D+K%3BGlenn%2C+G+M%3BPatronas%2C+N+J%3BPikus%2C+A+T%3BKatz%2C+D%3BLebovics%2C+R%3BSledjeski%2C+K%3BChoyke%2C+P+L%3BZbar%2C+B%3BLinehan%2C+W+M%3BOldfield%2C+E+H&rft.aulast=Manski&rft.aufirst=T&rft.date=1997-05-01&rft.volume=277&rft.issue=18&rft.spage=1461&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Familial factors associated with the characteristics of nonmaternal care for infants AN - 839069575; 1653317 JF - Journal of marriage and the family Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 389 EP - 408 VL - 59 IS - 2 SN - 0022-2445, 0022-2445 KW - Sociology KW - Infancy KW - Family KW - Child care UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/839069575?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aibss&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+marriage+and+the+family&rft.atitle=Familial+factors+associated+with+the+characteristics+of+nonmaternal+care+for+infants&rft.au=&rft.aulast=&rft.aufirst=&rft.date=1997-05-01&rft.volume=59&rft.issue=2&rft.spage=389&rft.isbn=&rft.btitle=&rft.title=Journal+of+marriage+and+the+family&rft.issn=00222445&rft_id=info:doi/ LA - English DB - International Bibliography of the Social Sciences (IBSS) N1 - Date revised - 2013-06-12 N1 - Last updated - 2013-09-16 N1 - SubjectsTermNotLitGenreText - 4748; 2192; 6490 2211 652 5676 646 6091 2212 ER - TY - JOUR T1 - Survival of patients with limited-stage small cell lung cancer treated with individualized chemotherapy selected by in vitro drug sensitivity testing. AN - 79645706; 9815744 AB - Our purpose was to study the feasibility of determining individualized chemotherapy regimens by in vitro drug sensitivity testing (DST) for patients with limited-stage small cell lung cancer (SCLC) and to evaluate patient response and survival. Fifty-four previously untreated patients with limited-stage small cell cancer were studied. Fresh tumor specimens for DST were collected, when possible, from patients' biopsies before the start of treatment. The differential staining cytotoxicity assay was used to determine the in vitro sensitivity of the tumor cells to different drugs. From these results, an in vitro best regimen (IVBR), a three-drug combination of previously proven efficacy of seven active drugs in SCLC, was selected. Patients were initially treated with four cycles of etoposide/cisplatin and concurrent radiotherapy. This was followed by four cycles of either individualized chemotherapy regimens based on the results of DST or, when DST results were not available, four cycles of vincristine, doxorubicin, and cyclophosphamide. Eighteen patients (33%) underwent biopsy procedures that provided tissue specimens for DST. The biopsy specimens contained tumor cells in 16 of 18 patients. The median duration from diagnosis to start of treatment was 22 days (range, 4-58 days) for the 18 patients who underwent elective thoracic biopsies compared to 21 days (range, 2-74 days) for members of the group that did not (P2 = 0.58). Time from thoracic biopsy to initiation of chemotherapy was a median of 4 days (range, 2-22 days). DST was done in 10 patients, and IVBR was administered to 8 patients. The median actuarial survival of 8 patients treated with their IVBR was 38.5 months compared to 19 months for the 46 patients treated with empiric chemotherapy. Selection of individualized chemotherapy regimens is labor intensive but feasible in limited-stage SCLC. Treatment with an individualized IVBR in our patients was associated with prolonged patient survival; however, because of the nature of our study design, other factors could have affected the results. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Cortazar, P AU - Gazdar, A F AU - Woods, E AU - Russell, E AU - Steinberg, S M AU - Williams, J AU - Ihde, D C AU - Johnson, B E AD - National Cancer Institute-Navy Medical Oncology Branch, Biostatistics and Data Management Section, National Naval Medical Center, Bethesda, Maryland 20889-5105, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 741 EP - 747 VL - 3 IS - 5 SN - 1078-0432, 1078-0432 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Tumor Cells, Cultured KW - Survival Rate KW - Neoplasm Staging KW - Cell Survival -- drug effects KW - Combined Modality Therapy KW - Humans KW - Middle Aged KW - Follow-Up Studies KW - Biopsy KW - Drug Screening Assays, Antitumor -- methods KW - Time Factors KW - Carcinoma, Small Cell -- pathology KW - Lung Neoplasms -- radiotherapy KW - Carcinoma, Small Cell -- mortality KW - Lung Neoplasms -- drug therapy KW - Carcinoma, Small Cell -- radiotherapy KW - Antineoplastic Agents -- toxicity KW - Lung Neoplasms -- mortality KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Antineoplastic Agents -- therapeutic use KW - Carcinoma, Small Cell -- drug therapy KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79645706?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Survival+of+patients+with+limited-stage+small+cell+lung+cancer+treated+with+individualized+chemotherapy+selected+by+in+vitro+drug+sensitivity+testing.&rft.au=Cortazar%2C+P%3BGazdar%2C+A+F%3BWoods%2C+E%3BRussell%2C+E%3BSteinberg%2C+S+M%3BWilliams%2C+J%3BIhde%2C+D+C%3BJohnson%2C+B+E&rft.aulast=Cortazar&rft.aufirst=P&rft.date=1997-05-01&rft.volume=3&rft.issue=5&rft.spage=741&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-12 N1 - Date created - 1999-02-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A pediatric phase I trial and pharmacokinetic study of thioguanine administered by continuous i.v. infusion. AN - 79643234; 9815740 AB - Although mercaptopurine is the thiopurine antimetabolite predominantly used in the treatment of childhood acute lymphoblastic leukemia (ALL), thioguanine (TG) is more potent than mercaptopurine in in vitro cytotoxicity studies in human leukemic cell lines and leukemic cells from patients with ALL. We conducted a pediatric Phase I trial of TG administered as a continuous i.v. infusion (CIV). A pharmacokinetically guided dose escalation was performed to define the dose rate of TG required to achieve a steady-state plasma concentration (Css) exceeding the target concentration of 1 microM, and then the maximum tolerated duration of infusion of TG at this dose rate was defined. Eighteen patients (median age, 18 years; range, 4-25 years) with refractory malignancies (16 solid tumors and 2 ALL) were enrolled in this study. The starting dose rate of 10 mg/m2/h administered for 24 h achieved an average Css of 0.9 microM (range, 0.7-1.2 microM). Therefore, the dose rate was escalated to 20 mg/m2/h, which achieved an average Css of 4.1 microM (range, 1. 0-8.3 microM). This disproportionate increase in the Css of TG suggested a capacity-limited (saturable) elimination process, and a pharmacokinetic model incorporating two compartments with capacity-limited elimination from the central compartment was developed to describe the disposition of TG. The TG clearances (derived from model parameters) at the 10- and 20-mg/m2/h dose rates were 987 and 608 ml/min/m2, respectively. Dose-limiting myelosuppression (absolute granulocyte count < 500/mm3 and platelet count < 25,000/mm3) was observed in two of three patients treated with a dose rate of 20 mg/m2/h administered for 36 h. Administration of CIV of TG at 20 mg/m2/h for 24 h was well tolerated in nine patients. Nonhematological toxicities included nonneutropenic infections and mild, reversible changes in hepatic function tests. The recommended dose rate and duration for CIV of TG is 20 mg/m2/h for 24 h. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Kitchen, B J AU - Balis, F M AU - Poplack, D G AU - O'Brien, M AU - Craig, C E AU - Adamson, P C AD - Pediatric Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 713 EP - 717 VL - 3 IS - 5 SN - 1078-0432, 1078-0432 KW - Antimetabolites, Antineoplastic KW - 0 KW - Thioguanine KW - FTK8U1GZNX KW - Index Medicus KW - Infusions, Intravenous KW - Humans KW - Adult KW - Metabolic Clearance Rate KW - Child KW - Adolescent KW - Models, Biological KW - Male KW - Female KW - Child, Preschool KW - Thioguanine -- pharmacokinetics KW - Antimetabolites, Antineoplastic -- administration & dosage KW - Thioguanine -- administration & dosage KW - Antimetabolites, Antineoplastic -- adverse effects KW - Thioguanine -- adverse effects KW - Antimetabolites, Antineoplastic -- pharmacokinetics KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79643234?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=A+pediatric+phase+I+trial+and+pharmacokinetic+study+of+thioguanine+administered+by+continuous+i.v.+infusion.&rft.au=Kitchen%2C+B+J%3BBalis%2C+F+M%3BPoplack%2C+D+G%3BO%27Brien%2C+M%3BCraig%2C+C+E%3BAdamson%2C+P+C&rft.aulast=Kitchen&rft.aufirst=B&rft.date=1997-05-01&rft.volume=3&rft.issue=5&rft.spage=713&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-12 N1 - Date created - 1999-02-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I study of topotecan followed sequentially by doxorubicin in patients with advanced malignancies. AN - 79639620; 9815746 AB - Inhibitors of topoisomerase I and topoisomerase II have demonstrated synergy when administered sequentially in several tumor models while having a diminished antitumor effect when given concurrently. To explore the potential for clinical sequence-dependent synergy, we instituted a Phase I study of topotecan (a topoisomerase I inhibitor) followed by doxorubicin (a topoisomerase II inhibitor) in patients with advanced malignancies. Thirty-three patients with advanced malignancies or malignancies for whom no standard therapy exists were entered into the study. Topotecan was administered in escalating doses by 72-h continuous infusion on days 1, 2, and 3, followed by a bolus of doxorubicin given on day 5. To explore the hematological toxicity associated with this sequence, bone marrow aspirates were obtained both prior to the topotecan infusion and immediately prior to the doxorubicin in 10 patients to determine by fluorescence-activated cell sorting analysis whether CD34+ cell synchronization was occurring using this sequential schedule. Dose-limiting hematological toxicity occurred at the first dose-level in three of six patients. Therefore, we defined the maximum-tolerated dose (MTD) below our starting dose-level. Further dose-escalation and a new MTD were defined with the addition of granulocyte-colony stimulating factor (G-CSF). The MTD was, therefore, topotecan 0.35 mg/m2/day continuous i.v. infusion on days 1, 2, and 3, followed by doxorubicin 45 mg/m2 on day 5 without G-CSF, whereas the MTD with G-CSF was topotecan 0.75 mg/m2/day by 72-h continuous i.v. infusion, followed by doxorubicin 45 mg/m2 i.v. bolus on day 5. Ten patients with paired bone marrow aspirates obtained before topotecan and before doxorubicin administrations were available for evaluation. In 7 of 10 patients, there was an increase (16.6 +/- 2.9% to 25.0 +/- 3.5%; P < 0.02) in the proportion of CD34+ cells in S-phase 24 h after the topotecan infusion and prior to doxorubicin compared to the pretreatment values, whereas 1 patient had a decrease in the proportion of CD34+ cells in S phase and 2 patients had no change. Topotecan and doxorubicin with this sequence and schedule can be given safely; the dose-limiting toxicity is hematological toxicity. Alterations in the fraction of hematopoietic progenitor CD34+ cells in S-phase may account for the increased granulocytopenia and thrombocytopenia observed at relatively low dose levels of the combination with and without G-CSF. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Tolcher, A W AU - O'Shaughnessy, J A AU - Weiss, R B AU - Zujewski, J AU - Myhand, R C AU - Schneider, E AU - Hakim, F AU - Gress, R AU - Goldspiel, B AU - Noone, M H AU - Brewster, L R AU - Gossard, M R AU - Cowan, K H AD - Medicine Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 755 EP - 760 VL - 3 IS - 5 SN - 1078-0432, 1078-0432 KW - Topoisomerase I Inhibitors KW - 0 KW - Topoisomerase II Inhibitors KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Topotecan KW - 7M7YKX2N15 KW - Doxorubicin KW - 80168379AG KW - Index Medicus KW - Drug Administration Schedule KW - Infusions, Intravenous KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Female KW - Topotecan -- adverse effects KW - Neoplasms -- drug therapy KW - Doxorubicin -- adverse effects KW - Granulocyte Colony-Stimulating Factor -- therapeutic use KW - Topotecan -- administration & dosage KW - Doxorubicin -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79639620?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=A+phase+I+study+of+topotecan+followed+sequentially+by+doxorubicin+in+patients+with+advanced+malignancies.&rft.au=Tolcher%2C+A+W%3BO%27Shaughnessy%2C+J+A%3BWeiss%2C+R+B%3BZujewski%2C+J%3BMyhand%2C+R+C%3BSchneider%2C+E%3BHakim%2C+F%3BGress%2C+R%3BGoldspiel%2C+B%3BNoone%2C+M+H%3BBrewster%2C+L+R%3BGossard%2C+M+R%3BCowan%2C+K+H&rft.aulast=Tolcher&rft.aufirst=A&rft.date=1997-05-01&rft.volume=3&rft.issue=5&rft.spage=755&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-12 N1 - Date created - 1999-02-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The carcinogenicity of metals in humans. AN - 79569774; 9498900 AB - Epidemiologic evidence on the relation between exposure to metals and cancer is reviewed. Human exposure to metals is common, with wide use in industry and long-term environmental persistence. Historically, the heaviest metal exposures occurred in the workplace or in environmental settings in close proximity to industrial sources. Among the general population, exposure to a number of metals is widespread but generally at substantially lower levels than have been found in industry. The carcinogenicity of arsenic, chromium, and nickel has been established. Occupational and environmental arsenic exposure is linked to increased lung cancer risk in humans, although experimental studies remain inconclusive. Experimental studies clearly demonstrate the malignant potential of hexavalent(VI) chromium compounds, with solubility being an important determining factor. Epidemiologic studies of workers in chromium chemical production and use link exposure to lung and nasal cancer. Experimental and epidemiologic data show that sparingly-soluble nickel compounds and possibly also the soluble compounds are carcinogens linked to lung and nasal cancer in humans. Some experimental and epidemiologic studies suggest that lead may be a human carcinogen, but the evidence is inconclusive. Although epidemiologic data are less extensive for beryllium and cadmium, the findings in humans of excess cancer risk are supported by the clear demonstration of carcinogenicity in experimental studies. Other metals, including antimony and cobalt, may be human carcinogens, but the experimental and epidemiologic data are limited. JF - Cancer causes & control : CCC AU - Hayes, R B AD - Division of Cancer Epidemiology and Genetics, US National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 371 EP - 385 VL - 8 IS - 3 SN - 0957-5243, 0957-5243 KW - Carcinogens KW - 0 KW - Metals KW - Cadmium KW - 00BH33GNGH KW - Chromium KW - 0R0008Q3JB KW - Lead KW - 2P299V784P KW - Cobalt KW - 3G0H8C9362 KW - Nickel KW - 7OV03QG267 KW - Antimony KW - 9IT35J3UV3 KW - Arsenic KW - N712M78A8G KW - Beryllium KW - OW5102UV6N KW - Index Medicus KW - Occupational Exposure KW - Arsenic -- adverse effects KW - Animals KW - Solubility KW - Chromium -- chemistry KW - Humans KW - Cobalt -- adverse effects KW - Disease Models, Animal KW - Antimony -- adverse effects KW - Nose Neoplasms -- epidemiology KW - Lead -- adverse effects KW - Cadmium -- adverse effects KW - Lung Neoplasms -- epidemiology KW - Neoplasms, Experimental -- chemically induced KW - Risk Factors KW - Nose Neoplasms -- chemically induced KW - Environmental Exposure KW - Nickel -- adverse effects KW - Beryllium -- adverse effects KW - Lung Neoplasms -- chemically induced KW - Nickel -- chemistry KW - Chemical Industry KW - Industry KW - Chromium -- adverse effects KW - Metals -- adverse effects KW - Neoplasms -- chemically induced KW - Neoplasms -- epidemiology KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79569774?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+carcinogenicity+of+metals+in+humans.&rft.au=Hayes%2C+R+B&rft.aulast=Hayes&rft.aufirst=R&rft.date=1997-05-01&rft.volume=8&rft.issue=3&rft.spage=371&rft.isbn=&rft.btitle=&rft.title=Cancer+causes+%26+control+%3A+CCC&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-10 N1 - Date created - 1998-03-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drinking water and cancer. AN - 79569465; 9498894 AB - Epidemiologic evidence on the relation between contaminants in drinking water and cancer is reviewed. The reviewed studies cover exposure to: disinfection byproducts; nitrate; arsenic and other metals; volatiles and contaminants from hazardous waste sites; asbestiform fibers; radionuclides; and fluoride. Most investigations are ecologic, with some confirmation of elevated risk from individual-based studies. In the case of waterborne arsenic, and possibly chlorination byproducts, there is a consistent but small body of epidemiologic evidence of an association with one or more types of cancer. Nitrate in groundwater has increased greatly over the years, and the demonstration of endogenous nitrosation among highly exposed subjects raises concern of elevated cancer risk. However, the epidemiologic data are not yet sufficient to draw a conclusion. There is a diversity of studies among populations exposed to water contaminated with pesticides, volatile organics, or mixtures from hazardous waste sites. Studies of asbestiform fibers and radionuclides in water are not conclusive, but there are suggested elevations of several cancer sites in highly exposed populations. There is no suggestion that fluoride in drinking water is linked with elevated risk of cancer. As topics for epidemiologic evaluation, drinking water contaminants pose methodologic problems common to studies designed to detect relatively small elevations in risk, with the added challenge of assessing exposures for many years in the past. Nevertheless, epidemiologic assessment is valuable and clearly warranted, given the potential public health impact of small risk elevations among very large exposed populations, and the limitations of toxicologic experiments in assessing carcinogenic risk of complex mixtures or of compounds for which appropriate animal models are not available. JF - Cancer causes & control : CCC AU - Cantor, K P AD - Occupational Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 292 EP - 308 VL - 8 IS - 3 SN - 0957-5243, 0957-5243 KW - Carcinogens KW - 0 KW - Chlorine Compounds KW - Disinfectants KW - Hazardous Waste KW - Metals KW - Nitrates KW - Organic Chemicals KW - Pesticides KW - Radioisotopes KW - Asbestos KW - 1332-21-4 KW - Arsenic KW - N712M78A8G KW - Fluorides KW - Q80VPU408O KW - Index Medicus KW - Pesticides -- analysis KW - Asbestos -- analysis KW - Arsenic -- adverse effects KW - Organic Chemicals -- adverse effects KW - Water Pollution, Radioactive -- adverse effects KW - Animals KW - Humans KW - Disease Models, Animal KW - Organic Chemicals -- analysis KW - Carcinogens -- analysis KW - Pesticides -- adverse effects KW - Metals -- analysis KW - Disinfectants -- adverse effects KW - Public Health KW - Water Pollution, Radioactive -- analysis KW - Asbestos -- adverse effects KW - Disinfectants -- analysis KW - Nitrates -- analysis KW - Arsenic -- analysis KW - Hazardous Waste -- adverse effects KW - Water Pollution, Radioactive -- statistics & numerical data KW - Chlorine Compounds -- adverse effects KW - Radioisotopes -- analysis KW - Nitrates -- adverse effects KW - Metals -- adverse effects KW - Radioisotopes -- adverse effects KW - Hazardous Waste -- analysis KW - Risk Factors KW - Chlorine Compounds -- analysis KW - Environmental Exposure KW - Fluorides -- analysis KW - Fluorides -- adverse effects KW - Carcinogens -- adverse effects KW - Water Supply -- analysis KW - Neoplasms -- epidemiology KW - Water Pollution, Chemical -- statistics & numerical data KW - Water Pollution, Chemical -- adverse effects KW - Water Pollution, Chemical -- analysis KW - Neoplasms -- etiology KW - Water Supply -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79569465?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Drinking+water+and+cancer.&rft.au=Cantor%2C+K+P&rft.aulast=Cantor&rft.aufirst=K&rft.date=1997-05-01&rft.volume=8&rft.issue=3&rft.spage=292&rft.isbn=&rft.btitle=&rft.title=Cancer+causes+%26+control+%3A+CCC&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-10 N1 - Date created - 1998-03-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reactive chemicals and cancer. AN - 79566920; 9498905 AB - Epidemiologic evidence on the relation between reactive chemicals and cancer is reviewed. These highly reactive chemicals (acrylonitrile; bis[chloromethyl]ether and chloromethyl methyl ether; 1,3-butadiene, ethylene oxide; formaldehyde; mustard gas; sulfuric acid; and vinyl chloride) vary in use and exposure. All are animal carcinogens that also have received considerable epidemiologic attention. Acrylonitrile is a chemical of current economic importance. The epidemiologic evidence is quite weak, but the available studies were very small. Epidemiologic studies clearly demonstrate that bis (chloromethyl) ether and chloromethyl methyl ether cause lung cancer. Continued follow-up of exposed workers is encouraged to provide information on risks for other cancers. Results from epidemiologic studies of butadiene-exposed workers are somewhat inconsistent, but the largest study with the best exposure assessment found the largest relative risk for leukemia. The failure of several larger studies to replicate the early Swedish findings of a very strong association between leukemia and ethylene oxide has not been adequately explained. Epidemiologic studies of formaldehyde provide limited evidence for an association with cancer of the nasopharynx and possibly with nasal cancer. These very rare tumors, however, are difficult to study epidemiologically. Mustard gas is a well-established lung carcinogen, but a recent follow-up of the English cohort suggests that other sites also may be affected. Sulfuric acid appears to cause laryngeal cancer. A suggested relationship with lung cancer in a few studies is of concern because of the widespread opportunity for exposure from ambient air pollution. Vinyl chloride causes angiosarcoma of the liver, but a large, multi-country study provided no clear evidence that other sites are affected. JF - Cancer causes & control : CCC AU - Blair, A AU - Kazerouni, N AD - Occupational Studies Section at the National Cancer Institute, Rockville, MD 20892-7364, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 473 EP - 490 VL - 8 IS - 3 SN - 0957-5243, 0957-5243 KW - Air Pollutants KW - 0 KW - Butadienes KW - Carcinogens KW - Methyl Ethers KW - Organic Chemicals KW - Sulfuric Acids KW - Formaldehyde KW - 1HG84L3525 KW - chloromethyl methyl ether KW - 334G5B96VG KW - Bis(Chloromethyl) Ether KW - 77382IHE37 KW - Ethylene Oxide KW - JJH7GNN18P KW - 1,3-butadiene KW - JSD5FGP5VD KW - Acrylonitrile KW - MP1U0D42PE KW - sulfuric acid KW - O40UQP6WCF KW - Mustard Gas KW - T8KEC9FH9P KW - Vinyl Chloride KW - WD06X94M2D KW - Index Medicus KW - Occupational Exposure KW - Methyl Ethers -- adverse effects KW - Animals KW - Leukemia -- chemically induced KW - Humans KW - Nasopharyngeal Neoplasms -- epidemiology KW - Sulfuric Acids -- adverse effects KW - Occupational Diseases -- chemically induced KW - Air Pollutants -- adverse effects KW - Laryngeal Neoplasms -- chemically induced KW - Lung Neoplasms -- epidemiology KW - Leukemia -- epidemiology KW - Nose Neoplasms -- chemically induced KW - Butadienes -- adverse effects KW - Formaldehyde -- adverse effects KW - Mustard Gas -- adverse effects KW - Occupational Diseases -- epidemiology KW - Lung Neoplasms -- chemically induced KW - Bis(Chloromethyl) Ether -- adverse effects KW - Nasopharyngeal Neoplasms -- chemically induced KW - Acrylonitrile -- adverse effects KW - Vinyl Chloride -- adverse effects KW - Ethylene Oxide -- adverse effects KW - Liver Neoplasms -- chemically induced KW - Laryngeal Neoplasms -- epidemiology KW - Hemangiosarcoma -- chemically induced KW - Liver Neoplasms -- epidemiology KW - Nose Neoplasms -- epidemiology KW - Neoplasms, Experimental -- chemically induced KW - England -- epidemiology KW - Risk Factors KW - Cohort Studies KW - Environmental Exposure KW - Sweden -- epidemiology KW - Follow-Up Studies KW - Hemangiosarcoma -- epidemiology KW - Organic Chemicals -- adverse effects KW - Neoplasms -- chemically induced KW - Neoplasms -- epidemiology KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79566920?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Reactive+chemicals+and+cancer.&rft.au=Blair%2C+A%3BKazerouni%2C+N&rft.aulast=Blair&rft.aufirst=A&rft.date=1997-05-01&rft.volume=8&rft.issue=3&rft.spage=473&rft.isbn=&rft.btitle=&rft.title=Cancer+causes+%26+control+%3A+CCC&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-10 N1 - Date created - 1998-03-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Occupational and environmental radiation and cancer. AN - 79566883; 9498895 AB - Epidemiologic evidence on the relation between occupational and environmental radiation and cancer is reviewed. Studies of pioneering radiation workers, underground miners, and radium dial painters revealed excess cancer deaths and contributed to the setting of radiation protection standards and to theories of carcinogenesis. Occupational exposures today are generally much lower than in the past, thus any associated increases in cancer will be difficult to detect. Pooling investigations of these more recently exposed workers, however, has the potential to validate current estimates of risk used in radiation protection. New information on the effects of chronic radiation exposure also may come from studies in the former Soviet Union of Chernobyl clean-up workers and of workers at the Mayak nuclear facilities. Studies of environmental radiation exposures, other than radon, are largely inconclusive, due mainly to the difficulties in detecting the low risks associated with low dose exposures. Thyroid cancer, however, has been linked to environmental radiation from the Chernobyl accident and from nuclear weapons tests. Low-level radiation released during normal operations at nuclear plants has not been found to increase cancer rates in surrounding populations. Radon, a human carcinogen, is the most ubiquitous exposure to human populations; remediating high residential-radon levels is recommended, recognizing that the exposure can never be removed completely because it occurs naturally. JF - Cancer causes & control : CCC AU - Boice, J D AU - Lubin, J H AD - Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, US National Cancer Institute, Bethesda, Maryland, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 309 EP - 322 VL - 8 IS - 3 SN - 0957-5243, 0957-5243 KW - Air Pollutants, Radioactive KW - 0 KW - Radon KW - Q74S4N8N1G KW - Radium KW - W90AYD6R3Q KW - Index Medicus KW - Radiation Dosage KW - Radium -- adverse effects KW - Reproducibility of Results KW - Radiation Protection KW - Radioactive Hazard Release KW - Humans KW - Ukraine KW - Occupational Diseases -- etiology KW - Thyroid Neoplasms -- etiology KW - Air Pollutants, Radioactive -- adverse effects KW - Radon -- adverse effects KW - Radiology KW - Air Pollution, Indoor -- adverse effects KW - Power Plants KW - Risk Factors KW - Nuclear Warfare KW - Mining KW - Occupational Exposure KW - Neoplasms, Radiation-Induced -- etiology KW - Environmental Exposure KW - Radiation, Ionizing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79566883?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Occupational+and+environmental+radiation+and+cancer.&rft.au=Boice%2C+J+D%3BLubin%2C+J+H&rft.aulast=Boice&rft.aufirst=J&rft.date=1997-05-01&rft.volume=8&rft.issue=3&rft.spage=309&rft.isbn=&rft.btitle=&rft.title=Cancer+causes+%26+control+%3A+CCC&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-10 N1 - Date created - 1998-03-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Liver transplantation for alcoholic liver disease: a survey of transplantation programs in the United States. AN - 79358921; 9346743 JF - Liver transplantation and surgery : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society AU - Everhart, J E AU - Beresford, T P AD - Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892-6600, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 220 EP - 226 VL - 3 IS - 3 SN - 1074-3022, 1074-3022 KW - Index Medicus KW - Humans KW - Adult KW - Data Collection KW - Patient Selection KW - United States -- epidemiology KW - Liver Diseases, Alcoholic -- surgery KW - Liver Transplantation -- statistics & numerical data KW - Liver Diseases, Alcoholic -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79358921?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Liver+transplantation+and+surgery+%3A+official+publication+of+the+American+Association+for+the+Study+of+Liver+Diseases+and+the+International+Liver+Transplantation+Society&rft.atitle=Liver+transplantation+for+alcoholic+liver+disease%3A+a+survey+of+transplantation+programs+in+the+United+States.&rft.au=Everhart%2C+J+E%3BBeresford%2C+T+P&rft.aulast=Everhart&rft.aufirst=J&rft.date=1997-05-01&rft.volume=3&rft.issue=3&rft.spage=220&rft.isbn=&rft.btitle=&rft.title=Liver+transplantation+and+surgery+%3A+official+publication+of+the+American+Association+for+the+Study+of+Liver+Diseases+and+the+International+Liver+Transplantation+Society&rft.issn=10743022&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-20 N1 - Date created - 1997-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The etiology, consequences, and treatment of alcoholism. AN - 79358144; 9346740 JF - Liver transplantation and surgery : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society AU - Gordis, E AD - National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892-7003, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 199 EP - 205 VL - 3 IS - 3 SN - 1074-3022, 1074-3022 KW - Index Medicus KW - Animals KW - Humans KW - Adult KW - Alcoholism -- etiology KW - Alcoholism -- therapy KW - Alcoholism -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79358144?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Liver+transplantation+and+surgery+%3A+official+publication+of+the+American+Association+for+the+Study+of+Liver+Diseases+and+the+International+Liver+Transplantation+Society&rft.atitle=The+etiology%2C+consequences%2C+and+treatment+of+alcoholism.&rft.au=Gordis%2C+E&rft.aulast=Gordis&rft.aufirst=E&rft.date=1997-05-01&rft.volume=3&rft.issue=3&rft.spage=199&rft.isbn=&rft.btitle=&rft.title=Liver+transplantation+and+surgery+%3A+official+publication+of+the+American+Association+for+the+Study+of+Liver+Diseases+and+the+International+Liver+Transplantation+Society&rft.issn=10743022&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-20 N1 - Date created - 1997-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Definition and diagnosis of relapse to drinking. AN - 79354432; 9346749 JF - Liver transplantation and surgery : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society AU - Fuller, R K AD - National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892-7003, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 258 EP - 262 VL - 3 IS - 3 SN - 1074-3022, 1074-3022 KW - Index Medicus KW - Humans KW - Temperance KW - Liver Function Tests KW - Alcohol Drinking -- epidemiology KW - Recurrence KW - Breath Tests KW - Alcoholism -- epidemiology KW - Alcoholism -- diagnosis KW - Liver Diseases, Alcoholic -- psychology KW - Liver Diseases, Alcoholic -- surgery KW - Alcoholism -- psychology KW - Liver Transplantation KW - Liver Diseases, Alcoholic -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79354432?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Liver+transplantation+and+surgery+%3A+official+publication+of+the+American+Association+for+the+Study+of+Liver+Diseases+and+the+International+Liver+Transplantation+Society&rft.atitle=Definition+and+diagnosis+of+relapse+to+drinking.&rft.au=Fuller%2C+R+K&rft.aulast=Fuller&rft.aufirst=R&rft.date=1997-05-01&rft.volume=3&rft.issue=3&rft.spage=258&rft.isbn=&rft.btitle=&rft.title=Liver+transplantation+and+surgery+%3A+official+publication+of+the+American+Association+for+the+Study+of+Liver+Diseases+and+the+International+Liver+Transplantation+Society&rft.issn=10743022&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-20 N1 - Date created - 1997-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Liver transplantation for alcoholic liver disease: executive statement and recommendations. Summary of a National Institutes of Health workshop held December 6-7, 1996, Bethesda, Maryland. AN - 79354405; 9346762 JF - Liver transplantation and surgery : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society AU - Hoofnagle, J H AU - Kresina, T AU - Fuller, R K AU - Lake, J R AU - Lucey, M R AU - Sorrell, M F AU - Beresford, T P Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 347 EP - 350 VL - 3 IS - 3 KW - Index Medicus KW - United States KW - Alcoholism -- epidemiology KW - Humans KW - National Institutes of Health (U.S.) KW - Adult KW - Patient Selection KW - Recurrence KW - Liver Diseases, Alcoholic -- surgery KW - Liver Transplantation KW - Liver Diseases, Alcoholic -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79354405?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Liver+transplantation+and+surgery+%3A+official+publication+of+the+American+Association+for+the+Study+of+Liver+Diseases+and+the+International+Liver+Transplantation+Society&rft.atitle=Liver+transplantation+for+alcoholic+liver+disease%3A+executive+statement+and+recommendations.+Summary+of+a+National+Institutes+of+Health+workshop+held+December+6-7%2C+1996%2C+Bethesda%2C+Maryland.&rft.au=Hoofnagle%2C+J+H%3BKresina%2C+T%3BFuller%2C+R+K%3BLake%2C+J+R%3BLucey%2C+M+R%3BSorrell%2C+M+F%3BBeresford%2C+T+P&rft.aulast=Hoofnagle&rft.aufirst=J&rft.date=1997-05-01&rft.volume=3&rft.issue=3&rft.spage=347&rft.isbn=&rft.btitle=&rft.title=Liver+transplantation+and+surgery+%3A+official+publication+of+the+American+Association+for+the+Study+of+Liver+Diseases+and+the+International+Liver+Transplantation+Society&rft.issn=10743022&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-20 N1 - Date created - 1997-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Delivery of antigens to the MHC class I pathway using bacterial toxins. AN - 79282729; 9297531 AB - Cytotoxic T lymphocytes (CTL) recognize antigens derived from endogenously expressed proteins presented on the cell surface in the context of major histocompatibility complex (MHC) class I molecules. Because CTL are effective in antiviral and antitumor responses, the delivery of antigens to the class I pathway has been the focus of numerous efforts. Generating CTL by immunization with exogenous proteins is often ineffective because these antigens typically enter the MHC class II pathway. This review focuses on the usefulness of bacterial toxins for delivering antigens to the MHC class I pathway. Several toxins naturally translocate into the cytosol, where they mediate their cytopathic effects, and the mechanisms by which this occurs has been elucidated. Molecular characterization of these toxins identified the functional domains and enabled the generation of modified proteins that were no longer toxic but retained the ability to translocate into the cytosol. Thus, these modified toxins could be examined for their ability to carry peptides or whole proteins into the cytosolic processing pathway. Of the toxins studied-diphtheria, pertussis, Pseudomonas, and anthrax-the anthrax toxin appears the most promising in its ability to deliver large protein antigens and its efficiency of translocation. JF - Human immunology AU - Goletz, T J AU - Klimpel, K R AU - Leppla, S H AU - Keith, J M AU - Berzofsky, J A AD - Molecular Immunogenetics and Vaccine Research Section, National Cancer Institute, National Institutes of Health, Bethasda, Maryland 20892, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 129 EP - 136 VL - 54 IS - 2 SN - 0198-8859, 0198-8859 KW - Antigens, Bacterial KW - 0 KW - Bacterial Toxins KW - Diphtheria Toxin KW - Exotoxins KW - Histocompatibility Antigens Class I KW - Virulence Factors, Bordetella KW - anthrax toxin KW - Peptide Hydrolases KW - EC 3.4.- KW - Index Medicus KW - Diphtheria Toxin -- immunology KW - Virulence Factors, Bordetella -- immunology KW - Humans KW - Peptide Hydrolases -- metabolism KW - Exotoxins -- immunology KW - Antigen Presentation KW - Histocompatibility Antigens Class I -- immunology KW - Bacterial Toxins -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79282729?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+immunology&rft.atitle=Delivery+of+antigens+to+the+MHC+class+I+pathway+using+bacterial+toxins.&rft.au=Goletz%2C+T+J%3BKlimpel%2C+K+R%3BLeppla%2C+S+H%3BKeith%2C+J+M%3BBerzofsky%2C+J+A&rft.aulast=Goletz&rft.aufirst=T&rft.date=1997-05-01&rft.volume=54&rft.issue=2&rft.spage=129&rft.isbn=&rft.btitle=&rft.title=Human+immunology&rft.issn=01988859&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-23 N1 - Date created - 1997-10-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sexual behavior and injection drug use during pregnancy and vertical transmission of HIV-1. AN - 79127690; 9215658 AB - We evaluated maternal sexual behavior and injection drug use practices as possible risk factors for vertical transmission of human immunodeficiency virus type 1 (HIV-1). Data were analyzed from the Mothers and Infants Cohort Study, a prospective study in Brooklyn and the Bronx, New York. A total of 207 mother-infant sets were enrolled between 1986 and 1991 and followed for up to 4 years after the enrollment visit during pregnancy. HIV-1 transmission occurred in 49 of 201 mother-infant sets, yielding an overall transmission rate of 24.4% (95% confidence interval (CI) = 18.7% to 31.0%). Increased frequency of vaginal intercourse after the first trimester of pregnancy was positively associated with vertical transmission of HIV-1 (trend p = 0.03). A lifetime history of injection drug use was not associated with vertical transmission. However, a history of combined cocaine and heroin injection after the first trimester of pregnancy was associated with vertical HIV-1 transmission, particularly among women with CD4+ lymphocyte levels of 20% or higher (risk ratio = 4.0; 95% CI = 2.0 to 8.1). Cocaine and heroin injection drug use after the first trimester accounted for most of the relation between preterm birth and vertical HIV-1 transmission in this cohort. Maternal coinfection with hepatitis C virus or human T-cell lymphotropic virus types I and II could not explain these observations, because coinfection with these viruses had no detectable effect on HIV-1 transmission. These results suggest that maternal sexual behavior and injection drug use practices during the second and third trimester of pregnancy may modify the risk of vertical HIV-1 transmission. JF - Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association AU - Bulterys, M AU - Landesman, S AU - Burns, D N AU - Rubinstein, A AU - Goedert, J J AD - Viral Epidemiology Branch, National Cancer Institute, Rockville, Maryland 20852, USA. Y1 - 1997/05/01/ PY - 1997 DA - 1997 May 01 SP - 76 EP - 82 VL - 15 IS - 1 SN - 1077-9450, 1077-9450 KW - Index Medicus KW - AIDS/HIV KW - Risk Factors KW - Humans KW - Infant, Newborn KW - CD4 Lymphocyte Count KW - Female KW - Pregnancy KW - Infectious Disease Transmission, Vertical KW - Sexual Behavior KW - Acquired Immunodeficiency Syndrome -- transmission KW - Substance Abuse, Intravenous -- complications KW - HIV-1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79127690?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+acquired+immune+deficiency+syndromes+and+human+retrovirology+%3A+official+publication+of+the+International+Retrovirology+Association&rft.atitle=Sexual+behavior+and+injection+drug+use+during+pregnancy+and+vertical+transmission+of+HIV-1.&rft.au=Bulterys%2C+M%3BLandesman%2C+S%3BBurns%2C+D+N%3BRubinstein%2C+A%3BGoedert%2C+J+J&rft.aulast=Bulterys&rft.aufirst=M&rft.date=1997-05-01&rft.volume=15&rft.issue=1&rft.spage=76&rft.isbn=&rft.btitle=&rft.title=Journal+of+acquired+immune+deficiency+syndromes+and+human+retrovirology+%3A+official+publication+of+the+International+Retrovirology+Association&rft.issn=10779450&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-24 N1 - Date created - 1997-07-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Resistance to 3-mercaptopropionic acid-induced seizures in hepatic encephalopathy. AN - 79123597; 9222686 AB - To determine if a model of hepatic encephalopathy (HE) exhibits decreased sensitivity to the neuronal effects of a drug that induces seizures as a consequence of decreasing GABA-mediated inhibitory neurotransmission. 3-Mercaptopropionic Acid (MPA) is an inhibitor of L-glutamate decarboxylase which catalyzes the synthesis of GABA from glutamate. MPA was administered, either by intraperitoneal or intracerebroventricular injection, into rats with stage III HE due to thioacetamide-induced fulminant hepatic failure and into normal control rats. When MPA was administered by intraperitoneal injection, seizure-inducing doses were similar for rats with HE and control rats. However, when a constant dose of MPA (330 micrograms) was administered by intracerebroventricular injection, rats with HE took significantly longer to develop seizures than control rats (16.2 vs. 7.3 minutes; p < 0.0005). In a model of HE: (i) There is increased resistance to the convulsive effects of MPA; and (ii) This phenomenon is apparent when MPA is given centrally, but not when it is given peripherally. Increased resistance to the development of a complication of reduced GABA-mediated neurotransmission induced by MPA in the model provides support for the hypothesis that HE is associated with increased GABA-mediated inhibitory neurotransmission. JF - Hepato-gastroenterology AU - Ferreira, M R AU - Gammal, S H AU - Jones, E A AD - Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA. PY - 1997 SP - 766 EP - 769 VL - 44 IS - 15 SN - 0172-6390, 0172-6390 KW - Convulsants KW - 0 KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - 3-Mercaptopropionic Acid KW - B03TJ3QU9M KW - Glutamate Decarboxylase KW - EC 4.1.1.15 KW - Index Medicus KW - Rats KW - Injections, Intraperitoneal KW - Animals KW - Rats, Sprague-Dawley KW - Glutamate Decarboxylase -- antagonists & inhibitors KW - gamma-Aminobutyric Acid -- metabolism KW - Synaptic Transmission KW - Injections, Intraventricular KW - Seizures -- chemically induced KW - Seizures -- complications KW - Seizures -- physiopathology KW - Hepatic Encephalopathy -- physiopathology KW - 3-Mercaptopropionic Acid -- administration & dosage KW - Convulsants -- administration & dosage KW - Hepatic Encephalopathy -- metabolism KW - Hepatic Encephalopathy -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79123597?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepato-gastroenterology&rft.atitle=Resistance+to+3-mercaptopropionic+acid-induced+seizures+in+hepatic+encephalopathy.&rft.au=Ferreira%2C+M+R%3BGammal%2C+S+H%3BJones%2C+E+A&rft.aulast=Ferreira&rft.aufirst=M&rft.date=1997-05-01&rft.volume=44&rft.issue=15&rft.spage=766&rft.isbn=&rft.btitle=&rft.title=Hepato-gastroenterology&rft.issn=01726390&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-11 N1 - Date created - 1997-09-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A model of the lutropin/choriogonadotropin receptor: insights into the structural and functional effects of constitutively activating mutations. AN - 79120522; 9215568 AB - A model of the seven transmembrane helical domain (7-TM) of the human lutropin receptor was constructed from the 2D electron density map of bovine rhodopsin and a set of geometric parameters derived from a published analysis of 204 G-protein coupled receptor sequences. The Self-Consistent Ensemble Optimization method was applied to predict overall side chain packing. The model is consistent with the general helical packing properties expected of transmembrane proteins and suggests possible structural and functional effects of constitutively activating mutations. A tightly packed hydrophobic cluster formed between the intracellular halves of TM5 and TM6, as well as a specific H-bonding network formed between the central regions of TM6 and TM7, is proposed to be critical for stabilizing the inactive form of the receptor. The model suggests that single activating mutations perturb the specific interactions of TM6 with TM5 and TM7, either by disrupting the hydrophobic packing between TM5 and TM6, or by weakening the H-bonds between TM6 and TM7. JF - Protein engineering AU - Lin, Z AU - Shenker, A AU - Pearlstein, R AD - Center for Molecular Modeling, Laboratory of Structural Biology, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 501 EP - 510 VL - 10 IS - 5 SN - 0269-2139, 0269-2139 KW - Receptors, LH KW - 0 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Protein Structure, Secondary KW - Cattle KW - Sequence Alignment KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Receptors, LH -- chemistry KW - Models, Molecular KW - Receptors, LH -- genetics KW - Protein Conformation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79120522?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+engineering&rft.atitle=A+model+of+the+lutropin%2Fchoriogonadotropin+receptor%3A+insights+into+the+structural+and+functional+effects+of+constitutively+activating+mutations.&rft.au=Lin%2C+Z%3BShenker%2C+A%3BPearlstein%2C+R&rft.aulast=Lin&rft.aufirst=Z&rft.date=1997-05-01&rft.volume=10&rft.issue=5&rft.spage=501&rft.isbn=&rft.btitle=&rft.title=Protein+engineering&rft.issn=02692139&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-02 N1 - Date created - 1997-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Society for Research on Nicotine and Tobacco. AN - 79119070; 9219386 AB - The proceedings of the second annual scientific conference of the Society for Research on Nicotine and Tobacco are summarized. The goal of the annual conference was to disseminate information about ongoing nicotine research from biological, behavioral and social perspectives. Data were presented describing our current understanding of the structure and function of neuronal nicotinic acetylcholine receptors, by which nicotine exerts most, if not all, of its effects in the brain. The conformational complexity of receptor subunits expressed in different brain areas contributes significantly to the complexity of responses observed to nicotinic agonists. Nicotine is being developed as a medication that might be used to maintain smoking cessation and to treat various medical diseases. The potential toxicity of nicotine, apart from cigarette smoking, is an important variable in assessing the benefits and risks of such therapeutic applications. The risks of nicotine-containing medications appear to be far less than those associated with tobacco use. Recent data indicate that cigarette smoking is increasing among young in the United States. Adolescent smokers are interested in quitting and make frequent quit attempts, but are usually not successful. Effective methods are needed to manage adolescent smokers before they become heavily addicted. Nicotine replacement as a pharmacological treatment for smoking cessation has made a significant contribution in improving quit rates. New medications have been developed that target specific populations of smokers. JF - Addiction (Abingdon, England) AU - Heishman, S J AU - Balfour, D J AU - Benowitz, N L AU - Hatsukami, D K AU - Lindstrom, J M AU - Ockene, J K Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 615 EP - 633 VL - 92 IS - 5 KW - Receptors, Nicotinic KW - 0 KW - Nicotine KW - 6M3C89ZY6R KW - Index Medicus KW - Humans KW - Smoking Cessation -- methods KW - Receptors, Nicotinic -- physiology KW - Adolescent KW - Smoking -- therapy KW - Nicotine -- pharmacology KW - Brain -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79119070?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Addiction+%28Abingdon%2C+England%29&rft.atitle=Society+for+Research+on+Nicotine+and+Tobacco.&rft.au=Heishman%2C+S+J%3BBalfour%2C+D+J%3BBenowitz%2C+N+L%3BHatsukami%2C+D+K%3BLindstrom%2C+J+M%3BOckene%2C+J+K&rft.aulast=Heishman&rft.aufirst=S&rft.date=1997-05-01&rft.volume=92&rft.issue=5&rft.spage=615&rft.isbn=&rft.btitle=&rft.title=Addiction+%28Abingdon%2C+England%29&rft.issn=09652140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-24 N1 - Date created - 1997-07-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Heterogeneity in recombinant HIV-1 integrase corrected by site-directed mutagenesis: the identification and elimination of a protease cleavage site. AN - 79108935; 9215579 AB - Purified recombinant human immunodeficiency virus type 1 (HIV-1) integrase and certain deletion mutants exhibit heterogeneity consistent with proteolysis at a site close to the C-terminus. Electrospray ionization mass spectrometric analysis indicated that proteolytic cleavage generated a protein missing five residues from the C-terminus. PCR mutagenesis of amino acids on either side of the cleavage site identified two changes which were subsequently shown to prevent clipping when proteins were expressed and purified from Escherichia coli: the substitution of Arg284, the residue on the C-terminal side of the cleavage site, by either glycine or lysine. The introduction of either of these mutations into full-length integrase did not affect in vitro 3' processing or strand transfer activities. Thus, the incorporation of either of these mutations is likely to be beneficial when homogeneity of HIV-1 integrase is a concern, as in crystallographic or nuclear magnetic resonance spectroscopic experiments. JF - Protein engineering AU - Hickman, A B AU - Dyda, F AU - Craigie, R AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 601 EP - 606 VL - 10 IS - 5 SN - 0269-2139, 0269-2139 KW - HIV Integrase KW - EC 2.7.7.- KW - HIV Protease KW - EC 3.4.23.- KW - Index Medicus KW - AIDS/HIV KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Chromatography, Gel KW - Humans KW - Escherichia coli KW - Crystallography, X-Ray KW - Binding Sites -- genetics KW - Protein Conformation KW - Magnetic Resonance Spectroscopy KW - HIV Integrase -- genetics KW - HIV Protease -- metabolism KW - HIV Integrase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79108935?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+engineering&rft.atitle=Heterogeneity+in+recombinant+HIV-1+integrase+corrected+by+site-directed+mutagenesis%3A+the+identification+and+elimination+of+a+protease+cleavage+site.&rft.au=Hickman%2C+A+B%3BDyda%2C+F%3BCraigie%2C+R&rft.aulast=Hickman&rft.aufirst=A&rft.date=1997-05-01&rft.volume=10&rft.issue=5&rft.spage=601&rft.isbn=&rft.btitle=&rft.title=Protein+engineering&rft.issn=02692139&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-02 N1 - Date created - 1997-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Body weight-tumor incidence correlations in long-term rodent carcinogenicity studies. AN - 79105734; 9210256 AB - Associations between body weight and tumor incidence and among the incidences of selected site-specific tumors were examined for more than 4,000 male and female Fischer-344 rats and B6C3F1 mice in the National Toxicology Program historical control database. Incidences of certain site-specific tumors, most notably mammary gland and pituitary gland tumors in rats and liver tumors in mice, were shown to have a strong positive correlation with 52-wk body weight. Using individual animal data, logistic regression models were derived for predicting site-specific tumor incidence as a function of 52-wk body weight, age, and other factors. This association between body weight and tumor incidence can explain many of the decreased tumor incidences observed in National Toxicology Program carcinogenicity studies. Body weight differences between dosed and control groups can also mask carcinogenic effects for those sites sensitive to body weight changes. Thus, when designing long-term rodent carcinogenicity studies, measures should be taken to minimize potential body weight differences between dosed and control groups. There were a number of small but significant negative correlations among tumor incidences, reflecting primarily the lethality of the tumors in question. None of these correlations (nor the 2 small positive correlations found) are likely to have any impact on the interpretation of experimental results. However, the high negative correlation between pituitary gland and testis tumors in male Fischer-344 rats cannot be dismissed so easily, does not reflect tumor lethality, and is currently being studied further. JF - Toxicologic pathology AU - Haseman, J K AU - Young, E AU - Eustis, S L AU - Hailey, J R AD - Statistics and Biomathematics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. PY - 1997 SP - 256 EP - 263 VL - 25 IS - 3 SN - 0192-6233, 0192-6233 KW - Index Medicus KW - Pituitary Neoplasms -- epidemiology KW - Mammary Neoplasms, Animal -- physiopathology KW - Animals KW - Testicular Neoplasms -- physiopathology KW - Liver Neoplasms -- epidemiology KW - Mice KW - Pituitary Neoplasms -- physiopathology KW - Rats KW - Rats, Inbred F344 KW - Organ Specificity -- drug effects KW - Mice, Inbred C3H KW - Mice, Inbred C57BL KW - Crosses, Genetic KW - Incidence KW - Liver Neoplasms -- physiopathology KW - Mammary Neoplasms, Animal -- epidemiology KW - Testicular Neoplasms -- epidemiology KW - Female KW - Male KW - Neoplasms, Experimental -- epidemiology KW - Body Weight -- drug effects KW - Neoplasms, Experimental -- physiopathology KW - Carcinogenicity Tests -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79105734?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Body+weight-tumor+incidence+correlations+in+long-term+rodent+carcinogenicity+studies.&rft.au=Haseman%2C+J+K%3BYoung%2C+E%3BEustis%2C+S+L%3BHailey%2C+J+R&rft.aulast=Haseman&rft.aufirst=J&rft.date=1997-05-01&rft.volume=25&rft.issue=3&rft.spage=256&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 - 1997-08-21 N1 - Date created - 1997-08-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Min mouse: a genetic model for intestinal carcinogenesis. AN - 79104772; 9210266 JF - Toxicologic pathology AU - Thompson, M B AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. PY - 1997 SP - 329 EP - 332 VL - 25 IS - 3 SN - 0192-6233, 0192-6233 KW - Index Medicus KW - Animals KW - Humans KW - Disease Models, Animal KW - Mice KW - Genes, APC KW - Mice, Mutant Strains KW - Intestinal Neoplasms -- pathology KW - Intestinal Neoplasms -- etiology KW - Carcinoma -- etiology KW - Carcinoma -- pathology KW - Models, Genetic KW - Intestinal Neoplasms -- genetics KW - Carcinoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79104772?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Min+mouse%3A+a+genetic+model+for+intestinal+carcinogenesis.&rft.au=Thompson%2C+M+B&rft.aulast=Thompson&rft.aufirst=M&rft.date=1997-05-01&rft.volume=25&rft.issue=3&rft.spage=329&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 - 1997-08-21 N1 - Date created - 1997-08-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Absence of tetrodotoxins in a captive-raised riparian frog, Atelopus varius. AN - 79099602; 9203295 AB - Bufonid frogs of the genus Atelopus contain two classes of skin toxins, namely the steroidal bufadienolides and the water-soluble tetrodotoxins. Frogs of the Panamanian species Atelopus varius have now been raised in captivity and levels in skin extracts of bufadienolides and of tetrodotoxin-like compounds assessed, using inhibition of [3H]ouabain binding and inhibition of [3H]saxitoxin binding, respectively. Levels of ouabain equivalents, corresponding to bufadienolides, were comparable to those found in wild-caught frogs from the same population in Panama, while tetrodotoxin-like activity was undetectable. The results strongly implicate environmental factors, perhaps symbiotic microorganisms, in the genesis of tetrodotoxins in the skin of frogs of the genus Atelopus, while indicating that the frog itself produces the skin bufadienolides. JF - Toxicon : official journal of the International Society on Toxinology AU - Daly, J W AU - Padgett, W L AU - Saunders, R L AU - Cover, J F AD - Laboratory of Bioorganic Chemistry, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 705 EP - 709 VL - 35 IS - 5 SN - 0041-0101, 0041-0101 KW - Amphibian Venoms KW - 0 KW - Bufanolides KW - Tetrodotoxin KW - 4368-28-9 KW - Index Medicus KW - Animals KW - Male KW - Female KW - Pregnancy KW - Bufanolides -- metabolism KW - Skin -- chemistry KW - Tetrodotoxin -- analysis KW - Amphibian Venoms -- analysis KW - Skin -- metabolism KW - Anura KW - Bufanolides -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79099602?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicon+%3A+official+journal+of+the+International+Society+on+Toxinology&rft.atitle=Absence+of+tetrodotoxins+in+a+captive-raised+riparian+frog%2C+Atelopus+varius.&rft.au=Daly%2C+J+W%3BPadgett%2C+W+L%3BSaunders%2C+R+L%3BCover%2C+J+F&rft.aulast=Daly&rft.aufirst=J&rft.date=1997-05-01&rft.volume=35&rft.issue=5&rft.spage=705&rft.isbn=&rft.btitle=&rft.title=Toxicon+%3A+official+journal+of+the+International+Society+on+Toxinology&rft.issn=00410101&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-11 N1 - Date created - 1997-08-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of HIV1 infection status by HIV1 PCR and culture methodologies in a small cohort of intravenous drug users. AN - 79090854; 9201812 AB - A small cohort of high-risk intravenous drug users (IVDU) from the Baltimore, MD, area was evaluated for HIV1 infection status and viral load. Quantitative dilution endpoint HIV1 DNA polymerase chain reaction (PCR) results, from HIV proviral DNA from quantitated peripheral blood mononuclear cell (PBMC) lysates, were compared to the dilution endpoint results for HIV PBMC micrococulture. The quantitative dilution endpoint HIV1 PCR was more rapid, sensitive and reproducible. In addition, an HIV1 capture RT-PCR technique was used to qualitatively detect the presence or absence of intact HIV1 virus in IVDU plasma and was compared with plasma culture detection, for HIV1 viraemia. Using the results of the PCR techniques, a rapid molecular assessment of the HIV1 infection status can be attained, which is important, as the IVDU population can be difficult to study prospectively. The PCR techniques can also be used to assess HIV1 burden as well as the potential effectiveness of antiviral therapies. These molecular techniques can be used to monitor the progression of HIV in patients and to evaluate the clinical effects of concurrent substance abuse. JF - Research in virology AU - Contoreggi, C S AU - Jones, S W AU - Lange, W R AU - Meyer, W A AD - National Institutes of Health, National Institute on Drug Abuse, Baltimore, MD 21224, USA. PY - 1997 SP - 215 EP - 224 VL - 148 IS - 3 SN - 0923-2516, 0923-2516 KW - DNA, Viral KW - 0 KW - RNA, Viral KW - Index Medicus KW - AIDS/HIV KW - Leukocytes, Mononuclear -- virology KW - Humans KW - Cohort Studies KW - DNA, Viral -- blood KW - RNA, Viral -- blood KW - Polymerase Chain Reaction KW - HIV-1 -- genetics KW - HIV Infections -- virology KW - HIV Infections -- complications KW - HIV Infections -- blood KW - HIV-1 -- isolation & purification KW - Substance Abuse, Intravenous -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79090854?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Research+in+virology&rft.atitle=Evaluation+of+HIV1+infection+status+by+HIV1+PCR+and+culture+methodologies+in+a+small+cohort+of+intravenous+drug+users.&rft.au=Contoreggi%2C+C+S%3BJones%2C+S+W%3BLange%2C+W+R%3BMeyer%2C+W+A&rft.aulast=Contoreggi&rft.aufirst=C&rft.date=1997-05-01&rft.volume=148&rft.issue=3&rft.spage=215&rft.isbn=&rft.btitle=&rft.title=Research+in+virology&rft.issn=09232516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-19 N1 - Date created - 1997-08-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Translocation of a UV-damaged DNA binding protein into a tight association with chromatin after treatment of mammalian cells with UV light. AN - 79090100; 9191040 AB - A UV-damaged DNA binding protein (UV-DDB) is the major source of UV-damaged DNA binding activity in mammalian cell extracts. This activity is defective in at least some xeroderma pigmentosum group E (XP-E) patients; microinjection of the UV-DDB protein into their fibroblasts corrects nucleotide excision repair (NER). In an in vitro reconstituted NER system, small amounts of UV-DDB stimulate repair synthesis a few fold. After exposure to UV, mammalian cells show an early dose-dependent inhibition of the extractable UV-DDB activity; this inhibition may reflect a tight association of the binding protein with UV-damaged genomic DNA. To investigate the dynamics and location of UV-DDB with respect to damaged chromatin in vivo, we utilized nuclear fractionation and specific antibodies and detected translocation of the p127 component of UV-DDB from a loose to a tight association with chromatinized DNA immediately after UV treatment. A similar redistribution was found for other NER proteins, i.e. XPA, RP-A and PCNA, suggesting their tighter association with genomic DNA after UV. These studies revealed a specific protein-protein interaction between UV-DDB/p127 and RP-A that appears to enhance binding of both proteins to UV-damaged DNA in vitro, providing evidence for the involvement of UV-DDB in the damage-recognition step of NER. Moreover, the kinetics of the reappearance of extractable UV-DDB activity after UV treatment of human cells with differing repair capacities positively correlate with the cell's capacity to repair 6-4 pyrimidine dimers (6-4 PD) in the whole genome, a result consistent with an in vivo role for UV-DDB in recognizing this type of UV lesion. JF - Journal of cell science AU - Otrin, V R AU - McLenigan, M AU - Takao, M AU - Levine, A S AU - Protić, M AD - Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 1159 EP - 1168 VL - 110 ( Pt 10) SN - 0021-9533, 0021-9533 KW - Chromatin KW - 0 KW - DNA-Binding Proteins KW - RPA1 protein, human KW - Replication Protein A KW - XPA protein, human KW - Xeroderma Pigmentosum Group A Protein KW - Index Medicus KW - Clone Cells KW - Animals KW - DNA Repair KW - DNA Damage KW - Kinetics KW - Humans KW - Cercopithecus aethiops KW - Xeroderma Pigmentosum -- metabolism KW - Biological Transport, Active KW - Cell Line KW - Chromatin -- radiation effects KW - Chromatin -- metabolism KW - Ultraviolet Rays -- adverse effects KW - DNA-Binding Proteins -- radiation effects KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79090100?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Translocation+of+a+UV-damaged+DNA+binding+protein+into+a+tight+association+with+chromatin+after+treatment+of+mammalian+cells+with+UV+light.&rft.au=Otrin%2C+V+R%3BMcLenigan%2C+M%3BTakao%2C+M%3BLevine%2C+A+S%3BProti%C4%87%2C+M&rft.aulast=Otrin&rft.aufirst=V&rft.date=1997-05-01&rft.volume=110+%28+Pt+10%29&rft.issue=&rft.spage=1159&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 - 1997-08-13 N1 - Date created - 1997-08-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Three steps in the regulation of transcription by the thyroid hormone receptor: establishment of a repressive chromatin structure, disruption of chromatin and transcriptional activation. AN - 79088690; 9191166 JF - Biochemical Society transactions AU - Wolffe, A P AU - Wong, J AU - Li, Q AU - Levi, B Z AU - Shi, Y B AD - Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892-5431, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 612 EP - 615 VL - 25 IS - 2 SN - 0300-5127, 0300-5127 KW - Chromatin KW - 0 KW - Receptors, Retinoic Acid KW - Receptors, Thyroid Hormone KW - Recombinant Proteins KW - Retinoid X Receptors KW - Transcription Factors KW - Index Medicus KW - Receptors, Retinoic Acid -- metabolism KW - Mutagenesis, Site-Directed KW - Animals KW - Recombinant Proteins -- metabolism KW - Dimerization KW - Xenopus KW - Oocytes -- physiology KW - Transcription Factors -- metabolism KW - Receptors, Thyroid Hormone -- metabolism KW - Chromatin -- physiology KW - Transcription, Genetic KW - Gene Expression Regulation KW - Chromatin -- ultrastructure KW - Transcriptional Activation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79088690?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+Society+transactions&rft.atitle=Three+steps+in+the+regulation+of+transcription+by+the+thyroid+hormone+receptor%3A+establishment+of+a+repressive+chromatin+structure%2C+disruption+of+chromatin+and+transcriptional+activation.&rft.au=Wolffe%2C+A+P%3BWong%2C+J%3BLi%2C+Q%3BLevi%2C+B+Z%3BShi%2C+Y+B&rft.aulast=Wolffe&rft.aufirst=A&rft.date=1997-05-01&rft.volume=25&rft.issue=2&rft.spage=612&rft.isbn=&rft.btitle=&rft.title=Biochemical+Society+transactions&rft.issn=03005127&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-04 N1 - Date created - 1997-08-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interactive effects of nitric oxide and the p53 tumor suppressor gene in carcinogenesis and tumor progression. AN - 79088239; 9194524 AB - The tumor suppressor gene product p53 plays an important role in the cellular response to DNA damage. DNA damage can lead to p53-mediated growth arrest and apoptosis. High concentrations of nitric oxide (NO) and NO metabolites such as peroxynitrite and NO2 cause DNA damage and have been shown to be mutagenic. Furthermore, NO induces p53 accumulation and, as part of a feedback loop, p53 mediates transcriptional transrepression of inducible nitric oxide synthase. Recent studies have shown increased expression and activity of nitric oxide synthase isoforms in human cancer. NO has both genotoxic and angiogenic properties, so that increased NO production may select mutant p53 cells and contribute to human carcinogenesis and tumor progression. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Ambs, S AU - Hussain, S P AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 443 EP - 448 VL - 11 IS - 6 SN - 0892-6638, 0892-6638 KW - Nitric Oxide KW - 31C4KY9ESH KW - Index Medicus KW - Animals KW - Humans KW - Disease Progression KW - Genes, p53 -- physiology KW - Nitric Oxide -- physiology KW - Neoplasms -- genetics KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79088239?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.atitle=Interactive+effects+of+nitric+oxide+and+the+p53+tumor+suppressor+gene+in+carcinogenesis+and+tumor+progression.&rft.au=Ambs%2C+S%3BHussain%2C+S+P%3BHarris%2C+C+C&rft.aulast=Ambs&rft.aufirst=S&rft.date=1997-05-01&rft.volume=11&rft.issue=6&rft.spage=443&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=08926638&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-03 N1 - Date created - 1997-07-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The N-domain of the signal recognition particle 54-kDa subunit promotes efficient signal sequence binding. AN - 79064179; 9183011 AB - The signal recognition particle 54-kDa subunit (SRP54) binds to the signal sequences of nascent presecretory and transmembrane proteins. Previous studies have shown that signal sequences bind to the C-terminal methionine-rich domain of the protein (M-domain), but have raised the possibility that either the N-terminal domain (N-domain) or the central guanosine triphosphatase module (GTPase-domain) also contribute to signal-sequence-binding activity. We have generated a series of N-domain and GTPase-domain mutants to investigate this issue further. Mutations in a conserved N-domain motif (ALLEADV) produced significant defects in signal sequence binding that correlate with the severity of the mutation. The magnitude of the defect was independent of the preprotein substrate, which suggested that the mutations do not alter the specificity of signal sequence recognition. The N-domain mutants also showed defects in promoting the translocation of presecretory proteins across the membrane of microsomal vesicles, but these defects appeared to be a direct consequence of the reduction in signal-sequence-binding activity and not separate effects of the mutations. By contrast, mutations in the guanosine triphosphatase consensus sequence had no effect on signal sequence binding, but instead severely impaired protein translocation activity. These results indicate that a principal function of the SRP54 N-domain is to promote efficient signal sequence binding. These data also suggest that the SRP54 GTPase regulates the cycle of signal sequence binding and release, perhaps by modulating the relative orientation of the N- and M-domains. JF - European journal of biochemistry AU - Newitt, J A AU - Bernstein, H D AD - Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1810, USA. Y1 - 1997/05/01/ PY - 1997 DA - 1997 May 01 SP - 720 EP - 729 VL - 245 IS - 3 SN - 0014-2956, 0014-2956 KW - Signal Recognition Particle KW - 0 KW - GTP Phosphohydrolases KW - EC 3.6.1.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Peptide Mapping KW - Protein Processing, Post-Translational KW - Plasmids KW - Binding Sites KW - GTP Phosphohydrolases -- chemistry KW - GTP Phosphohydrolases -- genetics KW - GTP Phosphohydrolases -- metabolism KW - Signal Recognition Particle -- metabolism KW - Signal Recognition Particle -- genetics KW - Signal Recognition Particle -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79064179?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+biochemistry&rft.atitle=The+N-domain+of+the+signal+recognition+particle+54-kDa+subunit+promotes+efficient+signal+sequence+binding.&rft.au=Newitt%2C+J+A%3BBernstein%2C+H+D&rft.aulast=Newitt&rft.aufirst=J&rft.date=1997-05-01&rft.volume=245&rft.issue=3&rft.spage=720&rft.isbn=&rft.btitle=&rft.title=European+journal+of+biochemistry&rft.issn=00142956&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-01 N1 - Date created - 1997-07-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant RFB4 single-chain immunotoxin that is cytotoxic towards CD22-positive cells. AN - 79059466; 9191188 JF - Biochemical Society transactions AU - Mansfield, E AU - Chiron, M F AU - Amlot, P AU - Pastan, I AU - FitzGerald, D J AD - Laboratory of Molecular Biology, DBS, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 709 EP - 714 VL - 25 IS - 2 SN - 0300-5127, 0300-5127 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD KW - Antigens, Differentiation, B-Lymphocyte KW - Bacterial Toxins KW - CD22 protein, human KW - Cell Adhesion Molecules KW - DNA Primers KW - Exotoxins KW - Immunoglobulin G KW - Immunoglobulin Heavy Chains KW - Immunoglobulin Light Chains KW - Immunotoxins KW - Lectins KW - Recombinant Fusion Proteins KW - Sialic Acid Binding Ig-like Lectin 2 KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - Humans KW - Recombinant Fusion Proteins -- toxicity KW - Immunoglobulin Heavy Chains -- biosynthesis KW - Cloning, Molecular KW - Immunoglobulin Light Chains -- biosynthesis KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Burkitt Lymphoma KW - Leukemia, T-Cell KW - Cell Line KW - Antibodies, Monoclonal -- biosynthesis KW - Antigens, CD -- physiology KW - Immunotoxins -- toxicity KW - Exotoxins -- biosynthesis KW - Antigens, Differentiation, B-Lymphocyte -- physiology KW - Exotoxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79059466?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+Society+transactions&rft.atitle=Recombinant+RFB4+single-chain+immunotoxin+that+is+cytotoxic+towards+CD22-positive+cells.&rft.au=Mansfield%2C+E%3BChiron%2C+M+F%3BAmlot%2C+P%3BPastan%2C+I%3BFitzGerald%2C+D+J&rft.aulast=Mansfield&rft.aufirst=E&rft.date=1997-05-01&rft.volume=25&rft.issue=2&rft.spage=709&rft.isbn=&rft.btitle=&rft.title=Biochemical+Society+transactions&rft.issn=03005127&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-04 N1 - Date created - 1997-08-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Perspectives on integrating experimental and epidemiologic research on diet, anthropometry and breast cancer. AN - 79037027; 9164268 AB - Three perspectives on the integration of experimental and epidemiologic research on diet, anthropometry and breast cancer are presented. 1) Although body weight and height have been linked to breast cancer risk by epidemiologic research, their roles have not been directly explored with animal models. However, basic, clinical and epidemiologic research on obesity and associated metabolic alterations may be pertinent. Individual differences in the timing and magnitude of weight gain and loss during adult life need to be considered in epidemiologic studies of adiposity and breast cancer, along with individual differences in the pattern of body fat deposition, the hormonal and metabolic changes that accompany the adiposity, and family history of obesity-related chronic diseases. Animal models with genetic predispositions to obesity, diabetes and breast cancer merit further exploration, as well as models that can evaluate exposures occurring after puberty. 2) The synergy between experimental and epidemiologic studies on fat and energy intake and breast carcinogenesis has been productive because each discipline has had to incorporate recent findings of the other. Dietary studies utilizing animals with different genetic profiles are promising, but require identification of the critical genes in human carcinogenesis. 3) Controlled dietary intervention studies with human participants using intermediate endpoints can bridge the gap between animal and epidemiologic studies, but generally accepted intermediate endpoints for breast cancer need to be developed. Such studies would permit better control of diet than large clinical trials and the opportunity to explore mechanisms. JF - The Journal of nutrition AU - Ballard-Barbash, R AU - Birt, D F AU - Kestin, M AU - King, I B AD - Applied Research Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 936S EP - 939S VL - 127 IS - 5 Suppl SN - 0022-3166, 0022-3166 KW - Dietary Fats KW - 0 KW - Index Medicus KW - Body Weight KW - Animals KW - Body Height KW - Humans KW - Adult KW - Dietary Fats -- administration & dosage KW - Middle Aged KW - Female KW - Anthropometry KW - Mammary Neoplasms, Experimental KW - Diet KW - Breast Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79037027?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+nutrition&rft.atitle=Perspectives+on+integrating+experimental+and+epidemiologic+research+on+diet%2C+anthropometry+and+breast+cancer.&rft.au=Ballard-Barbash%2C+R%3BBirt%2C+D+F%3BKestin%2C+M%3BKing%2C+I+B&rft.aulast=Ballard-Barbash&rft.aufirst=R&rft.date=1997-05-01&rft.volume=127&rft.issue=5+Suppl&rft.spage=936S&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+nutrition&rft.issn=00223166&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-13 N1 - Date created - 1997-06-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - New nonpurified diet (NTP-2000) for rodents in the National Toxicology Program's toxicology and carcinogenesis studies. AN - 79036991; 9164250 AB - The NIH-07 open-formula nonpurified diet was the selected diet for rodents in the National Toxicology Program's toxicology and carcinogenesis studies from 1980 to 1994. Protein and mineral concentrations of the NIH-07 diet may have increased some diet- and age-associated lesions such as nephropathy. A number of experimental nonpurified diets with lower protein and higher fat and fiber (approximately 15% protein, 7-8.5% fat, and 9-14% crude fiber) than the NIH-07 diet were formulated and evaluated in Fischer 344 (F344) rats. Decreasing protein content of the diet decreased protein consumption by approximately 30% and decreased severity of nephropathy without affecting growth. Increased fat intake seemed to have decreased the incidence or severity of leukemia, a lethal neoplasm of F344 rats. Increasing fiber content without decreasing the caloric density lowered body weight gain and slowed growth of mammary tumors. Higher fat and/or fiber intake decreased the incidences of adrenal pheochromocytomas and medullary hyperplasia in male rats. Nonpurified diets with lower protein and higher fat and fiber concentrations than the NIH-07 diet decreased or delayed diet- and age-associated lesions and increased survivals in 2-y studies. On the basis of these results, a new cereal-based nonpurified diet, designated as NTP-2000, was formulated with approximately 14.5% protein, approximately 8.2% fat, approximately 9.3% fiber and a calcium:phosphorus molar ratio of approximately 1.3. The NTP-2000 diet was compared with the NIH-07 diet in a 13-wk study in F344 rats. The NTP-2000 diet was adequate for growth, did not affect the hematological parameters and did not cause substantial changes in blood chemistry, serum enzyme or serum electrolyte values. The NTP-2000 diet decreased liver and kidney weights, prevented nephrocalcinosis and decreased the severity of diet- and possibly age-associated lesions. JF - The Journal of nutrition AU - Rao, G N AD - National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 842S EP - 846S VL - 127 IS - 5 Suppl SN - 0022-3166, 0022-3166 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Male KW - Female KW - Animal Feed KW - Neoplasms, Experimental -- chemically induced KW - Food, Formulated KW - Diet KW - Rodentia KW - Toxicology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79036991?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+nutrition&rft.atitle=New+nonpurified+diet+%28NTP-2000%29+for+rodents+in+the+National+Toxicology+Program%27s+toxicology+and+carcinogenesis+studies.&rft.au=Rao%2C+G+N&rft.aulast=Rao&rft.aufirst=G&rft.date=1997-05-01&rft.volume=127&rft.issue=5+Suppl&rft.spage=842S&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+nutrition&rft.issn=00223166&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-13 N1 - Date created - 1997-06-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular genetic events in the development and progression of ovarian cancer in humans. AN - 79034299; 9176883 AB - Ovarian tumor development is characterized by specific clinical and pathological features that provide an interesting model of carcinogenesis: first, the pre-invasive and even invasive lesions are difficult to detect; second, a group of cases with a known familial predilection constitute an important heredltary model of carcinogenesis; and third, the category of morphologically borderline ovarian tumors (tumors of low malignant potential) poses several unanswered questions such as: what histologic criteria should be used for their diagnosis; what is their natural history; and what is their molecular relationship to invasive tumors? Recently, molecular studies have contributed to a better understanding of the biology of these tumors, their behavior in vivo, and their response to therapy. This article summarizes the most recent molecular advances. JF - Molecular medicine today AU - Chuaqui, R F AU - Zhuang, Z AU - Merino, M J AD - Laboratory of Pathology, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 207 EP - 213 VL - 3 IS - 5 SN - 1357-4310, 1357-4310 KW - Growth Substances KW - 0 KW - Receptors, Cell Surface KW - Receptors, Growth Factor KW - Index Medicus KW - Genetic Linkage KW - Breast Neoplasms -- genetics KW - Chromosome Deletion KW - Disease Susceptibility KW - Genes, Tumor Suppressor KW - Receptors, Growth Factor -- physiology KW - Humans KW - Family KW - Receptors, Cell Surface -- physiology KW - Growth Substances -- physiology KW - Chromosome Mapping KW - Female KW - Ovarian Neoplasms -- physiopathology KW - Ovarian Neoplasms -- genetics KW - Ovarian Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79034299?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+today&rft.atitle=Molecular+genetic+events+in+the+development+and+progression+of+ovarian+cancer+in+humans.&rft.au=Chuaqui%2C+R+F%3BZhuang%2C+Z%3BMerino%2C+M+J&rft.aulast=Chuaqui&rft.aufirst=R&rft.date=1997-05-01&rft.volume=3&rft.issue=5&rft.spage=207&rft.isbn=&rft.btitle=&rft.title=Molecular+medicine+today&rft.issn=13574310&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-21 N1 - Date created - 1997-07-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chromatin studies by DNA-protein cross-linking. AN - 79033133; 9169193 AB - Our current level of understanding of chromatin structure was to a large extent achieved with the help of DNA-protein cross-linking. The versatile inventory of cross-linking techniques allows the identification of the contacts between DNA and proteins with a single nucleotide-single amino acid precision, to detect minor components of the complex nucleoprotein systems, to reveal the interactions of the flexible protein domains with DNA, and to assay for conformational changes in the nucleosomes. JF - Methods (San Diego, Calif.) AU - Pruss, D AU - Bavykin, S G AD - Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 36 EP - 47 VL - 12 IS - 1 SN - 1046-2023, 1046-2023 KW - Chromatin KW - 0 KW - Cross-Linking Reagents KW - DNA-Binding Proteins KW - Histones KW - Nucleosomes KW - Purines KW - Sulfuric Acid Esters KW - Transcription Factor TFIIIA KW - Transcription Factors KW - DNA KW - 9007-49-2 KW - dimethyl sulfate KW - JW5CW40Z50 KW - Index Medicus KW - Purines -- metabolism KW - Animals KW - Transcription Factors -- metabolism KW - Sulfuric Acid Esters -- metabolism KW - Electrophoresis, Polyacrylamide Gel KW - Models, Molecular KW - Histones -- chemistry KW - Nucleic Acid Conformation KW - Binding Sites KW - DNA Methylation KW - DNA Footprinting KW - Histones -- metabolism KW - Xenopus KW - Crystallography, X-Ray KW - Purines -- chemistry KW - DNA-Binding Proteins -- metabolism KW - Protein Conformation KW - Chromatin -- metabolism KW - DNA -- metabolism KW - Chromatin -- chemistry KW - DNA -- chemistry KW - Cross-Linking Reagents -- metabolism KW - Nucleosomes -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79033133?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+%28San+Diego%2C+Calif.%29&rft.atitle=Chromatin+studies+by+DNA-protein+cross-linking.&rft.au=Pruss%2C+D%3BBavykin%2C+S+G&rft.aulast=Pruss&rft.aufirst=D&rft.date=1997-05-01&rft.volume=12&rft.issue=1&rft.spage=36&rft.isbn=&rft.btitle=&rft.title=Methods+%28San+Diego%2C+Calif.%29&rft.issn=10462023&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-17 N1 - Date created - 1997-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Continuous hyperthermic peritoneal perfusion with cisplatin for the treatment of peritoneal mesothelioma. AN - 79030555; 9161783 AB - Peritoneal mesothelioma remains a difficult therapeutic challenge. Aggressive debulking combined with continuous hyperthermic peritoneal perfusion (CHPP) using cisplatin (CDDP) is a novel strategy for the treatment of peritoneal mesothelioma, allowing high regional delivery of chemotherapeutics and hyperthermia while minimizing systemic toxicity. From June 1993 to May 1996, 10 patients with peritoneal mesothelioma (six men, four women; mean age 40 years, range 15-57) underwent tumor debulking followed by a 90-minute CHPP. CHPP parameters included mean initial CDDP of 120 micrograms/mL (range 81-166), perfusate volume 5.2 L (range 4-7), flow 1.5 L/min, intraperitoneal temperature at three locations-41.5 degrees C, 40.5 degrees C, 41.1 degrees C, and core temperature 38.4 degrees C (range 37.2 degrees C-39.5 degrees C). Nine of 10 patients had malignant peritoneal mesothelioma, eight with associated ascites, while the tenth had a symptomatic, multiply recurrent benign peritoneal mesothelioma. Nine of 10 patients were optimally debulked. Pharmacokinetics were performed on blood and perfusate samples on nine patients; CDDP levels were quantitated by atomic absorption spectroscopy. Total perfusate cisplatin AUC was a mean of 21-fold higher (range 2- to 116-fold) than total serum cisplatin AUC, and serum CDDP behaved similarly to systemically administered CDDP. Median follow-up after CHPP is 10 months (range 2-32), with no treatment-related mortality. In eight optimally debulked patients there is no evidence of recurrent disease clinically or by CT or MRI. Seven patients with symptomatic ascites have been completely palliated. CHPP with CDDP is well tolerated with no significant regional toxicity. Because favorable CDDP pharmacokinetics suggest the potential for enhanced CDDP tumoricidal effect during CHPP, tumor debulking and CHPP may represent an effective strategy for the treatment of peritoneal mesothelioma. JF - The cancer journal from Scientific American AU - Ma, G Y AU - Bartlett, D L AU - Reed, E AU - Figg, W D AU - Lush, R M AU - Lee, K B AU - Libutti, S K AU - Alexander, H R AD - Metabolism Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1997 SP - 174 EP - 179 VL - 3 IS - 3 SN - 1081-4442, 1081-4442 KW - Antineoplastic Agents KW - 0 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Combined Modality Therapy KW - Humans KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Mesothelioma -- drug therapy KW - Cisplatin -- therapeutic use KW - Mesothelioma -- surgery KW - Cisplatin -- toxicity KW - Chemotherapy, Cancer, Regional Perfusion KW - Hyperthermia, Induced KW - Antineoplastic Agents -- toxicity KW - Peritoneal Neoplasms -- surgery KW - Peritoneal Neoplasms -- drug therapy KW - Antineoplastic Agents -- blood KW - Cisplatin -- blood KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79030555?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Continuous+hyperthermic+peritoneal+perfusion+with+cisplatin+for+the+treatment+of+peritoneal+mesothelioma.&rft.au=Ma%2C+G+Y%3BBartlett%2C+D+L%3BReed%2C+E%3BFigg%2C+W+D%3BLush%2C+R+M%3BLee%2C+K+B%3BLibutti%2C+S+K%3BAlexander%2C+H+R&rft.aulast=Ma&rft.aufirst=G&rft.date=1997-05-01&rft.volume=3&rft.issue=3&rft.spage=174&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 - 1997-07-15 N1 - Date created - 1997-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carboxypeptidase-G2, thymidine, and leucovorin rescue in cancer patients with methotrexate-induced renal dysfunction. AN - 79028366; 9164227 AB - Methotrexate nephrotoxicity can lead to delayed methotrexate elimination and the development of life-threatening toxicity, which may not be preventable with the standard rescue agent leucovorin. In preclinical studies, we previously demonstrated that carboxypetidase-G2 (CPDG2) rapidly hydrolyzes methotrexate to nontoxic metabolites. A protocol for the compassionate use of CPDG2 in patients who develop nephrotoxicity while receiving high-dose methotrexate was therefore developed. The pharmacologic and clinical outcome of CPDG2 rescue administered with thymidine and leucovorin in 20 patients is presented here. Patients with high-dose methotrexate-induced renal dysfunction received one to three doses of CPDG2, 50 U/kg body weight intravenously (i.v.), thymidine 8 g/m2/d by continuous i.v. infusion, and standard pharmacokinetically guided leucovorin rescue. Plasma concentrations of methotrexate and its inactive metabolite 4-deoxy-4-amino-N10-methylpteroic acid (DAMPA) were measured before and after CPDG2 using high-pressure liquid chromatography (HPLC). Tolerance of CPDG2 and thymidine, development of methotrexate toxicities, and recovery of renal function were monitored. Twenty patients who received high-dose methotrexate for osteosarcoma (n = 11), lymphoid cancers (n = 8), and gastric cancer (n = 1) developed nephrotoxicity (median serum creatinine, 3.2 mg/dL) and elevated plasma methotrexate concentrations (median, 201 mumol/L at hour 46). CPDG2 and thymidine rescue was well tolerated and resulted in a rapid 95.6% to 99.6% reduction in the plasma methotrexate concentration. Methotrexate-related toxicity was mild to moderate. Serum creatinine returned to normal values at a median of 22 days. CPDG2, thymidine, and leucovorin rescue was highly effective in 20 patients at high risk for developing life-threatening methotrexate toxicity after the onset of methotrexate-induced nephrotoxicity and delayed methotrexate excretion. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Widemann, B C AU - Balis, F M AU - Murphy, R F AU - Sorensen, J M AU - Montello, M J AU - O'Brien, M AU - Adamson, P C AD - Pediatric Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1928, USA. widemanb@pbmac.nci.nih.gov Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 2125 EP - 2134 VL - 15 IS - 5 SN - 0732-183X, 0732-183X KW - Antidotes KW - 0 KW - Antimetabolites, Antineoplastic KW - Carboxypeptidases KW - EC 3.4.- KW - Leucovorin KW - Q573I9DVLP KW - Thymidine KW - VC2W18DGKR KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Lymphoma, Non-Hodgkin -- blood KW - Humans KW - Child KW - Sarcoma -- drug therapy KW - Child, Preschool KW - Infant KW - Lymphoma, Non-Hodgkin -- drug therapy KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- blood KW - Adult KW - Middle Aged KW - Adolescent KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- drug therapy KW - Female KW - Male KW - Sarcoma -- blood KW - Antimetabolites, Antineoplastic -- administration & dosage KW - Kidney -- metabolism KW - Methotrexate -- blood KW - Antimetabolites, Antineoplastic -- adverse effects KW - Kidney -- drug effects KW - Antidotes -- therapeutic use KW - Thymidine -- therapeutic use KW - Carboxypeptidases -- adverse effects KW - Thymidine -- adverse effects KW - Kidney Diseases -- metabolism KW - Carboxypeptidases -- therapeutic use KW - Methotrexate -- adverse effects KW - Antimetabolites, Antineoplastic -- blood KW - Kidney Diseases -- prevention & control KW - Methotrexate -- administration & dosage KW - Kidney Diseases -- chemically induced KW - Leucovorin -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79028366?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Carboxypeptidase-G2%2C+thymidine%2C+and+leucovorin+rescue+in+cancer+patients+with+methotrexate-induced+renal+dysfunction.&rft.au=Widemann%2C+B+C%3BBalis%2C+F+M%3BMurphy%2C+R+F%3BSorensen%2C+J+M%3BMontello%2C+M+J%3BO%27Brien%2C+M%3BAdamson%2C+P+C&rft.aulast=Widemann&rft.aufirst=B&rft.date=1997-05-01&rft.volume=15&rft.issue=5&rft.spage=2125&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-16 N1 - Date created - 1997-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ontogeny of lactoferrin in the developing mouse uterus: a marker of early hormone response. AN - 79025224; 9160713 AB - Lactoferrin (LF) was mapped during organogenesis of the murine reproductive tract, starting on fetal Day 12, as a marker of estrogen responsiveness. To induce LF expression, pregnant outbred CD-1 mice were injected s.c. with diethylstilbestrol (DES; 100 microg/kg maternal body weight), and fetal genital tract tissues were removed; neonatal and immature mice received s.c. injections of DES (2 microg/pup per day). Corn oil-treated and untreated mice at corresponding ages provided the controls. Immunocytochemical techniques using a polyclonal antibody showed no detectable LF in control genital tract tissues until late gestation. However, after DES treatment, LF was localized in uterine epithelial cells as early as fetal Day 14; the intensity of LF staining increased with age and number of DES treatments. Control uterine tissues responded to the rise of circulating estrogens at parturition (fetal Day 19) by producing LF, although the magnitude of response was lower than that of DES-treated tissues. Uterine tissue homogenates from control and DES mice were analyzed by SDS-PAGE and Western blots, verifying the protein to be LF. Isolation of mRNA and Northern blot analysis further showed that LF mRNA was present in the developing Mullerian duct and that DES stimulated early induction of the LF gene. The early appearance of LF suggests that it may play an important role in the hormonal regulation of growth and differentiation of developing uterine tissues. JF - Biology of reproduction AU - Newbold, R R AU - Hanson, R B AU - Jefferson, W N AD - Environmental Toxicology Program, Division of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. newbold1@niehs.nih.gov Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 1147 EP - 1157 VL - 56 IS - 5 SN - 0006-3363, 0006-3363 KW - Biomarkers KW - 0 KW - Estrogens, Non-Steroidal KW - RNA, Messenger KW - Receptors, Estrogen KW - Diethylstilbestrol KW - 731DCA35BT KW - Lactoferrin KW - EC 3.4.21.- KW - Index Medicus KW - Animals KW - Receptors, Estrogen -- drug effects KW - Gestational Age KW - Mice KW - Receptors, Estrogen -- metabolism KW - RNA, Messenger -- genetics KW - Pregnancy KW - In Situ Hybridization KW - RNA, Messenger -- metabolism KW - Diethylstilbestrol -- pharmacology KW - Estrogens, Non-Steroidal -- pharmacology KW - Immunohistochemistry KW - Female KW - Uterus -- metabolism KW - Lactoferrin -- genetics KW - Lactoferrin -- metabolism KW - Uterus -- embryology KW - Uterus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79025224?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biology+of+reproduction&rft.atitle=Ontogeny+of+lactoferrin+in+the+developing+mouse+uterus%3A+a+marker+of+early+hormone+response.&rft.au=Newbold%2C+R+R%3BHanson%2C+R+B%3BJefferson%2C+W+N&rft.aulast=Newbold&rft.aufirst=R&rft.date=1997-05-01&rft.volume=56&rft.issue=5&rft.spage=1147&rft.isbn=&rft.btitle=&rft.title=Biology+of+reproduction&rft.issn=00063363&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-28 N1 - Date created - 1997-07-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacokinetics of elemental platinum (ultrafiltrate and total) after a thirty minute intravenous infusion of ormaplatin. AN - 79024092; 9158882 AB - Preclinical data suggest that ormaplatin (tetrachloro-(dl-trans)-1, 2-diamminocyclohexaneplatinum) has substantial activity in cisplatin-resistant tumor models and may be less nephrotoxic than cisplatin. Based on these data we initiated a phase I clinical trial in patients with refractory metastatic cancer. This report characterizes the pharmacokinetic profile of both the total plasma concentrations of elemental platinum and the unbound ultrafiltrate concentrations of elemental platinum, following a 30 min intravenous infusion of ormaplatin. Platinum concentrations were determined by AAS, and pharmacokinetic parameters for both the total plasma concentration and the ultrafiltrate concentration of elemental platinum were determined using both compartmental and noncompartmental methods. Twenty-eight patients (14 males and 14 females; median age, 58) received ormaplatin. There was a linear relationship between Cmax and dose (r2 = 0.945) and AUC and dose (r2 = 0.976). Ormaplatin is more accurately described by a two-compartment model than by a one-compartment model. The distribution half-life (t1/2 alpha) was 0.3 h and the terminal half-life (t1/2 beta) was 39.1 h. The volume of the central compartment (V) was 68.6 L and the volume of distribution at steady state (Vdss) was 183 L. Like total plasma platinum, unbound platinum is also best characterized by a two-compartment model. The elimination of free platinum is also biphasic with a distribution half-life (t1/2 alpha) of 0.3 h and a terminal half-life (t1/2 beta) of 19.3 h. The mean volume of the central compartment (V) was 200.5 L, and the mean volume of distribution at steady state (Vdss) was 560.5 L. Clinical development of ormaplatin has been terminated due to increased frequency of neurological complications noted over other platinum agents; however, the pharmacokinetics are, in general, similar to those of other clinically used platinum compounds. JF - Biopharmaceutics & drug disposition AU - Figg, W D AU - Christian, M C AU - Lush, R AU - Link, C J AU - Davis, P AU - Kohn, E AU - Sarosy, G AU - Rothenberg, M L AU - Weiss, R B AU - Ryan, N AU - Jacobs, J AU - Reed, E AD - Clinical Pharmacological Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 347 EP - 359 VL - 18 IS - 4 SN - 0142-2782, 0142-2782 KW - Antineoplastic Agents KW - 0 KW - Organoplatinum Compounds KW - Platinum KW - 49DFR088MY KW - ormaplatin KW - SFK1SGY8V1 KW - Index Medicus KW - Neoplasms -- drug therapy KW - Infusions, Intravenous KW - Humans KW - Neoplasms -- blood KW - Adult KW - Hemofiltration KW - Aged KW - Middle Aged KW - Male KW - Female KW - Organoplatinum Compounds -- pharmacokinetics KW - Platinum -- blood KW - Organoplatinum Compounds -- administration & dosage KW - Antineoplastic Agents -- administration & dosage KW - Antineoplastic Agents -- pharmacokinetics KW - Organoplatinum Compounds -- therapeutic use KW - Antineoplastic Agents -- blood KW - Organoplatinum Compounds -- blood KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79024092?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biopharmaceutics+%26+drug+disposition&rft.atitle=Pharmacokinetics+of+elemental+platinum+%28ultrafiltrate+and+total%29+after+a+thirty+minute+intravenous+infusion+of+ormaplatin.&rft.au=Figg%2C+W+D%3BChristian%2C+M+C%3BLush%2C+R%3BLink%2C+C+J%3BDavis%2C+P%3BKohn%2C+E%3BSarosy%2C+G%3BRothenberg%2C+M+L%3BWeiss%2C+R+B%3BRyan%2C+N%3BJacobs%2C+J%3BReed%2C+E&rft.aulast=Figg&rft.aufirst=W&rft.date=1997-05-01&rft.volume=18&rft.issue=4&rft.spage=347&rft.isbn=&rft.btitle=&rft.title=Biopharmaceutics+%26+drug+disposition&rft.issn=01422782&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-18 N1 - Date created - 1997-07-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Familial aggregation of DSM-IV alcohol use disorders: examination of the primary-secondary distinction in a general population sample. AN - 79023587; 9171811 AB - This study examined the familial aggregation of alcoholism in subgroups of respondents classified with respect to the primary-secondary distinction as it is related to DSM-IV major depression and alcohol use disorders. Rates of alcoholism among specific first- and second-degree relatives of male and female probands with primary, secondary, and concurrent depression (i.e., the comorbid groups) and with major depression only were compared with one another and with a normal control group. The results of this general population survey that uses a large representative sample of the U.S. were at variance with some findings from the clinical literature with regard to familial aggregation. Greater rates of alcoholism were found among first- and second-degree relatives of the major depression only group compared with normal controls. Male and female probands of all three comorbid groups were not shown to convey a greater risk of alcoholism to their offspring compared with the normal control group or the major depression only group. The discrepancy between clinical research findings and those of this general population study were discussed in terms of methodological considerations. JF - The Journal of nervous and mental disease AU - Grant, B F AU - Pickering, R P AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892-7003, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 335 EP - 343 VL - 185 IS - 5 SN - 0022-3018, 0022-3018 KW - Abridged Index Medicus KW - Index Medicus KW - Age Factors KW - Sex Factors KW - Humans KW - Depressive Disorder -- genetics KW - Comorbidity KW - Depressive Disorder -- epidemiology KW - Risk Factors KW - Adult KW - Health Surveys KW - Depressive Disorder -- diagnosis KW - Adolescent KW - Psychiatric Status Rating Scales -- statistics & numerical data KW - United States -- epidemiology KW - Female KW - Male KW - Alcoholism -- epidemiology KW - Alcoholism -- diagnosis KW - Family KW - Alcoholism -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79023587?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+nervous+and+mental+disease&rft.atitle=Familial+aggregation+of+DSM-IV+alcohol+use+disorders%3A+examination+of+the+primary-secondary+distinction+in+a+general+population+sample.&rft.au=Grant%2C+B+F%3BPickering%2C+R+P&rft.aulast=Grant&rft.aufirst=B&rft.date=1997-05-01&rft.volume=185&rft.issue=5&rft.spage=335&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+nervous+and+mental+disease&rft.issn=00223018&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-12 N1 - Date created - 1997-06-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protection against methoxyacetic-acid-induced spermatocyte apoptosis with calcium channel blockers in cultured rat seminiferous tubules: possible mechanisms. AN - 79022216; 9169075 AB - A calcium-mediated mechanism underlying spermatocyte apoptosis induced by 2-methoxyethanol (2-ME) has been previously proposed. This hypothesis was tested in vitro in the present study using cultured juvenile (25 days old) and adult rat seminiferous tubules (JRST and ARST, respectively) with methoxyacetic acid (MAA, the active metabolite of 2-ME). In JRST, spermatocyte degeneration was morphologically obvious 19 hr after a 5-hr exposure to 5 mM MAA. The lesion was unaffected by the presence or absence of extratubular Ca2+. However, MAA-induced cell death was significantly prevented by cotreatment with the dihydropyridines (DHP) nifedipine (50 microM) and nicardipine (20 microM), as well as verapamil (50 microM) and TMB-8 (50 microM), all of which are able to inhibit calcium movement through plasma membranes. However, neither ryanodine, dantrolene, nor cyclosporin A and ruthenium red, which inhibit Ca2+ mobilization from intracellular stores (endoplasmic reticulum and mitochondria), affected the MAA-induced cell death. Inhibition of calcium mobilization through IP3-sensitive pathways by blocking the product of IP3 with manoalide, neomycin, and U73122 did not block the MAA-induced lesion. The protective effects of 50 microM nifedipine and 50 microM TMB-8 were also observed in ARSTs treated with 10 mM MAA for 5 hr. However, when rat testicular sections were immunohistochemically stained with monoclonal antibodies specific for the alpha 1 (the DHP receptor) or the alpha 2 subunits of DHP-sensitive calcium channels, no positive staining was found. Finally, in an attempt to see whether the intracellular free calcium concentrations ([Ca2+]i) in germ cells were increased after the MAA treatment, intact seminiferous tubules were loaded with indo-1 and were measured using laser-scanning confocal microscopy. No detectable increase in the signal in MA A-sensitive spermatocytes was observed, while a 34-54% increase in the signal could be detected in the same cell types when tubules were exposed to 10 microM of the calcium ionophore 4-bromo-A23187 for 5 min. Collectively, these data suggest that the protective effect of calcium channel blockers against the MAA-induced spermatocyte apoptosis is probably not through their blocking effect on DHP-sensitive calcium channels. We postulate alternate mechanisms based on stabilization of cells membranes, or interactions with calmodulin or protein kinase C. JF - Toxicology and applied pharmacology AU - Li, L H AU - Wine, R N AU - Miller, D S AU - Reece, J M AU - Smith, M AU - Chapin, R E AD - National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 105 EP - 119 VL - 144 IS - 1 SN - 0041-008X, 0041-008X KW - Acetates KW - 0 KW - Calcium Channel Blockers KW - Potassium Channel Blockers KW - Tetraethylammonium Compounds KW - Tetraethylammonium KW - 66-40-0 KW - 4-Aminopyridine KW - BH3B64OKL9 KW - methoxyacetic acid KW - F11T1H7Q7W KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Rats KW - Calcium -- metabolism KW - Animals KW - Rats, Sprague-Dawley KW - 4-Aminopyridine -- pharmacology KW - Tetraethylammonium Compounds -- pharmacology KW - Male KW - Spermatocytes -- cytology KW - Seminiferous Tubules -- metabolism KW - Calcium Channel Blockers -- pharmacology KW - Seminiferous Tubules -- drug effects KW - Spermatocytes -- metabolism KW - Seminiferous Tubules -- cytology KW - Apoptosis -- drug effects KW - Spermatocytes -- drug effects KW - Acetates -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79022216?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Protection+against+methoxyacetic-acid-induced+spermatocyte+apoptosis+with+calcium+channel+blockers+in+cultured+rat+seminiferous+tubules%3A+possible+mechanisms.&rft.au=Li%2C+L+H%3BWine%2C+R+N%3BMiller%2C+D+S%3BReece%2C+J+M%3BSmith%2C+M%3BChapin%2C+R+E&rft.aulast=Li&rft.aufirst=L&rft.date=1997-05-01&rft.volume=144&rft.issue=1&rft.spage=105&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=0041008X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-18 N1 - Date created - 1997-06-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I trial of micronized formulation carboxyamidotriazole in patients with refractory solid tumors: pharmacokinetics, clinical outcome, and comparison of formulations. AN - 79018234; 9164210 AB - Cytostatic agents targeted against angiogenesis and tumor cell invasive potential form a new class of investigational drugs. Orally administered carboxyamidotriazole (CAI) (NSC609974) is both antiangiogenic and antimetastatic. An encapsulated micronized powder formulation has been developed to optimize CAI administration. A phase I dose escalation trial with pharmacokinetic analysis has been performed. Twenty-one patients with refractory solid tumors and good end organ function and performance status were enrolled onto the study. Patients received a test dose followed 1 week later by daily administration of CAI in the encapsulated micronized formulation at doses of 100 to 350 mg/m2. Patients remained on CAI until disease progression or dose-limiting toxicity. Plasma samples were taken to characterize the pharmacokinetic parameters of this formulation of CAI. All patients were assessable for toxicity and 18 were assessable for pharmacokinetics and response analysis. Grade 1 and 2 gastrointestinal side effects were observed in up to 50% of patients. Dose-limiting toxicity was observed in both patients treated at 350 mg/m2/d, consisting of reversible grade 2 to 3 cerebellar ataxia (n = 1) and confusion (n = 1). One minor response (MR) was observed in a patient with renal cell carcinoma and another nine patients had disease stabilization (MR + SD = 47%). Pharmacokinetic analysis demonstrated reduced bioavailability (58% reduction) compared with the PEG-400 liquid formulation previously reported. The better toxicity profile of encapsulated micronized CAI with similar frequency of disease stabilization and ease of administration compared with the liquid or gelatin capsule, suggests that the micronized formulation is a preferable formulation for subsequent studies. A dose of 300 mg/m2/d is proposed for phase II investigations. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Kohn, E C AU - Figg, W D AU - Sarosy, G A AU - Bauer, K S AU - Davis, P A AU - Soltis, M J AU - Thompkins, A AU - Liotta, L A AU - Reed, E AD - Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA. eckohn@helix.nih.gov Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 1985 EP - 1993 VL - 15 IS - 5 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents KW - 0 KW - Triazoles KW - carboxyamido-triazole KW - 99519-84-3 KW - Index Medicus KW - Drug Administration Schedule KW - Drug Compounding KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Female KW - Neoplasms -- drug therapy KW - Neoplasms -- pathology KW - Antineoplastic Agents -- administration & dosage KW - Antineoplastic Agents -- pharmacokinetics KW - Triazoles -- adverse effects KW - Triazoles -- pharmacokinetics KW - Triazoles -- administration & dosage KW - Neoplasms -- metabolism KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79018234?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Phase+I+trial+of+micronized+formulation+carboxyamidotriazole+in+patients+with+refractory+solid+tumors%3A+pharmacokinetics%2C+clinical+outcome%2C+and+comparison+of+formulations.&rft.au=Kohn%2C+E+C%3BFigg%2C+W+D%3BSarosy%2C+G+A%3BBauer%2C+K+S%3BDavis%2C+P+A%3BSoltis%2C+M+J%3BThompkins%2C+A%3BLiotta%2C+L+A%3BReed%2C+E&rft.aulast=Kohn&rft.aufirst=E&rft.date=1997-05-01&rft.volume=15&rft.issue=5&rft.spage=1985&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-16 N1 - Date created - 1997-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High-dose oral dextromethorphan versus placebo in painful diabetic neuropathy and postherpetic neuralgia. AN - 79015112; 9153445 AB - N-methyl-D-aspartate (NMDA) receptor antagonists relieve neuropathic pain in animal models, but side effects of dissociative anesthetic channel blockers, such as ketamine, have discouraged clinical application. Based on the hypothesis that low-affinity NMDA channel blockers might have a better therapeutic ratio, we carried out two randomized, double-blind, crossover trials comparing six weeks of oral dextromethorphan to placebo in two groups, made up of 14 patients with painful distal symmetrical diabetic neuropathy and 18 with postherpetic neuralgia. Thirteen patients with each diagnosis completed the comparison. Dosage was titrated in each patient to the highest level reached without disrupting normal activities; mean doses were 381 mg/day in diabetics and 439 mg/day in postherpetic neuralgia patients. In diabetic neuropathy, dextromethorphan decreased pain by a mean of 24% (95% CI: 6% to 42%, p = 0.01), relative to placebo. In postherpetic neuralgia, dextromethorphan did not reduce pain (95% CI: 10% decrease in pain to 14% increase in pain, p = 0.72). Five of 31 patients who took dextromethorphan dropped out due to sedation or ataxia during dose escalation, but the remaining patients all reached a reasonably well-tolerated maintenance dose. We conclude that dextromethorphan or other low-affinity NMDA channel blockers may have promise in the treatment of painful diabetic neuropathy. JF - Neurology AU - Nelson, K A AU - Park, K M AU - Robinovitz, E AU - Tsigos, C AU - Max, M B AD - Pain and Neurosensory Mechanisms Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892-1258, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 1212 EP - 1218 VL - 48 IS - 5 SN - 0028-3878, 0028-3878 KW - Placebos KW - 0 KW - Dextromethorphan KW - 7355X3ROTS KW - Abridged Index Medicus KW - Index Medicus KW - Administration, Oral KW - Double-Blind Method KW - Dose-Response Relationship, Drug KW - Humans KW - Palliative Care KW - Aged KW - Pain KW - Adult KW - Cross-Over Studies KW - Follow-Up Studies KW - Middle Aged KW - Female KW - Male KW - Neuralgia -- physiopathology KW - Neuralgia -- drug therapy KW - Neuralgia -- etiology KW - Dextromethorphan -- administration & dosage KW - Diabetic Neuropathies -- physiopathology KW - Dextromethorphan -- adverse effects KW - Dextromethorphan -- therapeutic use KW - Herpesviridae Infections -- complications KW - Diabetic Neuropathies -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79015112?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=High-dose+oral+dextromethorphan+versus+placebo+in+painful+diabetic+neuropathy+and+postherpetic+neuralgia.&rft.au=Nelson%2C+K+A%3BPark%2C+K+M%3BRobinovitz%2C+E%3BTsigos%2C+C%3BMax%2C+M+B&rft.aulast=Nelson&rft.aufirst=K&rft.date=1997-05-01&rft.volume=48&rft.issue=5&rft.spage=1212&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-11 N1 - Date created - 1997-06-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacokinetic studies with recombinant cytokines. Scientific issues and practical considerations. AN - 79014104; 9160171 AB - Advances in molecular biology and recombinant DNA technology have led to the development of cytokines as therapeutic agents for a variety of disease states. The pharmacokinetic analysis of cytokines involves the understanding of analytical methods capable of detecting these agents in biological fluids and recognition of several factors which may have an impact on the cytokine concentration-time curves. Enzyme-linked immunosorbent assays (ELISA) have become the most common method of detection and commercial kits are available for a wide variety of cytokines. Monoclonal antibody products are sensitive, have minimal cross-reactivity and are relatively inexpensive when compared with high performance liquid chromatography (HPLC). However, the primary limitation of these assays is their inability to measure biologically active protein. Conversely, bioassays do measure a biological event (i.e. proliferation or cytotoxicity) but are generally not used for cytokine analysis because of their high cost, long assay completion time, lack of specificity, poor sensitivity and influence of environmental conditions on the outcome. The pharmacokinetic profile of recombinant cytokines is influenced by a number of variables: endogenous production, circulating soluble receptors and cell-associated receptors, immunocompetence and antibody production against the cytokine all may influence the disposition of the agent. Thus, pharmacokinetic modelling of cytokines may involve complex models capable of characterising these nonlinear processes and resulting effects. The route of administration is an important variable since cytokines administered by subcutaneous injection may be partially metabolised by proteases present in the subcutaneous tissue. Other methods to simplify cytokine delivery are being actively investigated and include formulations for inhalation, topical and oral administration. A variety of cytokines (including interferon-alpha, interleukin-6 and tumour necrosis factor) are capable of inhibiting cytochrome P450 hepatic enzymes and, therefore, possess the potential to cause drug-cytokine interactions. Inhibition has been demonstrated in several in vitro systems and animal models, although clinical data are currently limited. An increased understanding of the many factors which can alter the analysis and pharmacokinetics of cytokines is essential to the design of optimal dosage regimens. JF - Clinical pharmacokinetics AU - Piscitelli, S C AU - Reiss, W G AU - Figg, W D AU - Petros, W P AD - Department of Pharmacy, National Institutes of Health, Bethesda, Maryland, USA. spisc@nih.gov Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 368 EP - 381 VL - 32 IS - 5 SN - 0312-5963, 0312-5963 KW - Cytokines KW - 0 KW - Recombinant Proteins KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Animals KW - Drug Interactions KW - Recombinant Proteins -- metabolism KW - Humans KW - Recombinant Proteins -- pharmacokinetics KW - Enzyme-Linked Immunosorbent Assay KW - Cytochrome P-450 Enzyme System -- metabolism KW - Recombinant Proteins -- analysis KW - Drug Administration Routes KW - Cytokines -- analysis KW - Cytokines -- pharmacokinetics KW - Cytokines -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79014104?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+pharmacokinetics&rft.atitle=Pharmacokinetic+studies+with+recombinant+cytokines.+Scientific+issues+and+practical+considerations.&rft.au=Piscitelli%2C+S+C%3BReiss%2C+W+G%3BFigg%2C+W+D%3BPetros%2C+W+P&rft.aulast=Piscitelli&rft.aufirst=S&rft.date=1997-05-01&rft.volume=32&rft.issue=5&rft.spage=368&rft.isbn=&rft.btitle=&rft.title=Clinical+pharmacokinetics&rft.issn=03125963&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-04 N1 - Date created - 1997-08-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Efficacy of treatment after measurable diabeticlike retinopathy in galactose-fed rats. AN - 79010491; 9152226 AB - To determine whether the diabeticlike retinal microangiopathies of the galactose-fed rat model could be ameliorated if intervention by withdrawal of the galactose diet or treatment with the aldose reductase inhibitor AL-3152 was initiated after quantifiable microangiopathies had occurred. Weanling male Sprague-Dawley rats were randomized into five groups and fed for up to 24 months Purina laboratory chow (#5001) plus 50% starch (control [CON]), 50% D-galactose (galactose [GAL]), 50% D-galactose with AL-3152 (approximately 14 mg/kg per day) (prevention [PRV]), 50% D-galactose for 6 months followed by intervention with the inhibitor (intervention [INT]), or 50% D-galactose for 6 months followed by replacement with the 50% starch diet (withdrawal [GWD]). In rats on experimental diets and killed after 6, 18, and 24 months, one retina was prepared for transmission electron microscopy; the other was used for vessel wholemounts using elastase digestion. Capillary images were analyzed by computer morphometry. At 6 months, the GAL rats exhibited statistically significant (P < 0.05) increases over CON rats in mean capillary basement membrane thickness, capillary density, and dilated channels. These parameters tended to increase with time in most groups, and the differences between GAL and age-matched CON rats were maintained at the 18- and 24-month endpoints. Although the microangiopathies were ameliorated by AL-3152 treatment from the onset (PRV), intervention after 6 months of galactosemia with either galactose withdrawal (GWD) or addition of inhibitor (INT) showed amelioration in only some parameters at 18 months and no statistically significant benefit at the 24-month endpoint. Amelioration of galactose-induced retinal microangiopathies with AL-3152 in the prevention group suggests an efficacious application of aldose reductase inhibitors in treating diabetic retinopathy, provided treatment can begin soon after the onset of diabetes. Intervention after some of the earliest microscopic lesions neither halted progression of the angiopathy nor provided appreciable benefit at the 24-month follow-up. JF - Investigative ophthalmology & visual science AU - Robison, W G AU - Laver, N M AU - Jacot, J L AU - Chandler, M L AU - York, B M AU - Glover, J P AD - National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-2740, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 1066 EP - 1073 VL - 38 IS - 6 SN - 0146-0404, 0146-0404 KW - Enzyme Inhibitors KW - 0 KW - Fluorenes KW - Hydantoins KW - AL 3152 KW - 126048-33-7 KW - Aldehyde Reductase KW - EC 1.1.1.21 KW - Galactose KW - X2RN3Q8DNE KW - Index Medicus KW - Animals KW - Reference Values KW - Retina -- ultrastructure KW - Enzyme Inhibitors -- therapeutic use KW - Fluorenes -- therapeutic use KW - Rats KW - Rats, Sprague-Dawley KW - Hydantoins -- therapeutic use KW - Aldehyde Reductase -- antagonists & inhibitors KW - Microscopy, Electron KW - Diet KW - Image Processing, Computer-Assisted KW - Male KW - Retinal Vessels -- pathology KW - Diabetic Retinopathy -- diet therapy KW - Diabetic Retinopathy -- chemically induced KW - Galactose -- administration & dosage KW - Diabetic Retinopathy -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79010491?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Efficacy+of+treatment+after+measurable+diabeticlike+retinopathy+in+galactose-fed+rats.&rft.au=Robison%2C+W+G%3BLaver%2C+N+M%3BJacot%2C+J+L%3BChandler%2C+M+L%3BYork%2C+B+M%3BGlover%2C+J+P&rft.aulast=Robison&rft.aufirst=W&rft.date=1997-05-01&rft.volume=38&rft.issue=6&rft.spage=1066&rft.isbn=&rft.btitle=&rft.title=Investigative+ophthalmology+%26+visual+science&rft.issn=01460404&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-09 N1 - Date created - 1997-06-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Of snails and holy grails... AN - 79010283; 9161778 JF - The cancer journal from Scientific American AU - Yang, J C AD - Surgery Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. PY - 1997 SP - 142 EP - 143 VL - 3 IS - 3 SN - 1081-4442, 1081-4442 KW - Cytokines KW - 0 KW - Interferon-alpha KW - Interleukin-2 KW - Index Medicus KW - Drug Therapy, Combination KW - Cytokines -- pharmacology KW - Clinical Trials, Phase II as Topic KW - Aged, 80 and over KW - Immunotherapy KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Follow-Up Studies KW - Male KW - Female KW - Interferon-alpha -- toxicity KW - Kidney Neoplasms -- drug therapy KW - Interferon-alpha -- therapeutic use KW - Interleukin-2 -- therapeutic use KW - Carcinoma, Renal Cell -- secondary KW - Carcinoma, Renal Cell -- drug therapy KW - Interleukin-2 -- toxicity KW - Kidney Neoplasms -- secondary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79010283?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Of+snails+and+holy+grails...&rft.au=Yang%2C+J+C&rft.aulast=Yang&rft.aufirst=J&rft.date=1997-05-01&rft.volume=3&rft.issue=3&rft.spage=142&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 - 1997-07-15 N1 - Date created - 1997-07-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Cancer J Sci Am. 1997 May-Jun;3(3):157-62 [9161781] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacometric analysis of the effect of furosemide on suramin pharmacokinetics. AN - 79007989; 9165547 AB - To characterize the effects of furosemide on the pharmacokinetics of suramin, a renally eliminated investigational antineoplastic agent. Retrospective population pharmacokinetic analysis. Government biomedical research facility. Twenty-six men with hormone-refractory prostate cancer and one with adrenocortical carcinoma. Patients received suramin by continuous or intermittent infusion with and without concomitant furosemide. Optimum suramin regimens were achieved by adaptive feedback control, and pharmacokinetic data were collected both in the presence and absence of furosemide. Suramin concentrations were determined by high-performance liquid chromatography (coefficient of variation < 8%). Suramin concentrations were fit to a three-compartment linear model with six coefficients and two rate inputs, which allowed furosemide to affect suramin pharmacokinetics. Individual and population parameter estimates were determined using the iterative two-stage approach. Concomitant furosemide was associated with a median decrease in total body clearance of suramin by 36% (range 0-63%, p < 0.0001). No other parameter was significantly altered, and there was no trend for change in any pharmacokinetic value with time. Suramin plasma concentrations were simulated with and without prolonged furosemide therapy in 26 patients for 12 weeks. The average suramin concentration increased by greater than 33% in 12 patients; 2 patients had a greater than 67% increase in this extreme case model. Coadministration of furosemide with suramin can cause an increase in suramin concentrations; however, due to suramin's long half-life, its rate of accumulation is very slow. Nonetheless, in individuals receiving suramin by nonadaptive control, appropriate precautions should be taken when prolonged furosemide therapy is begun. JF - Pharmacotherapy AU - Piscitelli, S C AU - Forrest, A AU - Lush, R M AU - Ryan, N AU - Whitfield, L R AU - Figg, W D AD - Clinical Center Pharmacy Department, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1997 SP - 431 EP - 437 VL - 17 IS - 3 SN - 0277-0008, 0277-0008 KW - Antineoplastic Agents KW - 0 KW - Diuretics KW - Suramin KW - 6032D45BEM KW - Furosemide KW - 7LXU5N7ZO5 KW - Index Medicus KW - Prostatic Neoplasms -- metabolism KW - Drug Interactions KW - Adrenocortical Carcinoma -- metabolism KW - Humans KW - Retrospective Studies KW - Aged KW - Adrenal Cortex Neoplasms -- drug therapy KW - Middle Aged KW - Drug Resistance, Neoplasm KW - Prostatic Neoplasms -- drug therapy KW - Adrenal Cortex Neoplasms -- metabolism KW - Male KW - Adrenocortical Carcinoma -- drug therapy KW - Diuretics -- therapeutic use KW - Antineoplastic Agents -- pharmacokinetics KW - Diuretics -- pharmacology KW - Suramin -- pharmacokinetics KW - Furosemide -- therapeutic use KW - Furosemide -- pharmacology KW - Antineoplastic Agents -- therapeutic use KW - Suramin -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79007989?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacotherapy&rft.atitle=Pharmacometric+analysis+of+the+effect+of+furosemide+on+suramin+pharmacokinetics.&rft.au=Piscitelli%2C+S+C%3BForrest%2C+A%3BLush%2C+R+M%3BRyan%2C+N%3BWhitfield%2C+L+R%3BFigg%2C+W+D&rft.aulast=Piscitelli&rft.aufirst=S&rft.date=1997-05-01&rft.volume=17&rft.issue=3&rft.spage=431&rft.isbn=&rft.btitle=&rft.title=Pharmacotherapy&rft.issn=02770008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-15 N1 - Date created - 1997-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemoprevention of spontaneous tumorigenesis in nullizygous p53-deficient mice by dehydroepiandrosterone and its analog 16alpha-fluoro-5-androsten-17-one. AN - 79007723; 9163685 AB - Transgenic mice with both alleles of the p53 tumor suppressor gene product 'knocked out' by gene targeting are susceptible to early development of tumors, chiefly lymphomas and sarcomas. Compared with the control group, administration of dehydroepiandrosterone (DHEA) at 0.3% of the diet to male p53-deficient mice extended their lifespan by delaying death due to neoplasms (from 105 to 166 days on study, P = 0.002), primarily by suppressing lymphoblastic lymphoma (from 45 to 6% of neoplastic deaths, P = 0.010). Treatment with a synthetic DHEA analog, 16alpha-fluoro-5-androsten-17-one (compound 8354), at 0.15% of the diet also increased lifespan, to 140 days for mice that developed tumors (P = 0.037). The effects of these steroids on lifespan and tumor development did not appear to be strongly related to inhibition of food consumption and weight gain, in that a group pair-fed with control diet to the reduced food consumption of the DHEA-treated group developed and died of the same types of neoplasms at the same rate as the controls fed ad libitum. The chemopreventive effect of these steroids has been proposed to be due to suppression of DNA synthesis by inhibition of glucose 6-phosphate dehydrogenase, the rate-limiting enzyme of the pentose phosphate pathway. Although DHEA and its analog are strong non-competitive inhibitors of this enzyme in vitro, treatment with DHEA did not deplete cellular nucleotide pools in the liver, as would have been predicted. The chemopreventive effect of DHEA in this model may be due to steroid-induced thymic atrophy and suppression of T cell lymphoma, permitting these mice to survive long enough to develop tumors with longer latency. JF - Carcinogenesis AU - Perkins, S N AU - Hursting, S D AU - Haines, D C AU - James, S J AU - Miller, B J AU - Phang, J M AD - Laboratory of Nutritional and Molecular Regulation, SAIC, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 989 EP - 994 VL - 18 IS - 5 SN - 0143-3334, 0143-3334 KW - Androstenes KW - 0 KW - Antineoplastic Agents KW - Nucleotides KW - 16-fluoro-5-androsten-17-one KW - 112859-71-9 KW - Dehydroepiandrosterone KW - 459AG36T1B KW - Index Medicus KW - Nucleotides -- metabolism KW - Animals KW - Longevity -- drug effects KW - Body Weight -- drug effects KW - Liver -- metabolism KW - Mice KW - Male KW - Survival Analysis KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- etiology KW - Mice, Knockout KW - Genes, p53 KW - Androstenes -- pharmacology KW - Dehydroepiandrosterone -- pharmacology KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79007723?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chemoprevention+of+spontaneous+tumorigenesis+in+nullizygous+p53-deficient+mice+by+dehydroepiandrosterone+and+its+analog+16alpha-fluoro-5-androsten-17-one.&rft.au=Perkins%2C+S+N%3BHursting%2C+S+D%3BHaines%2C+D+C%3BJames%2C+S+J%3BMiller%2C+B+J%3BPhang%2C+J+M&rft.aulast=Perkins&rft.aufirst=S&rft.date=1997-05-01&rft.volume=18&rft.issue=5&rft.spage=989&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-12 N1 - Date created - 1997-06-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of three different methods for radiolabelling human activated T lymphocytes. AN - 79004040; 9142729 AB - One approach in the treatment of ovarian cancer patients involves the infusion of autologous T lymphocytes coupled with a bispecific monoclonal antibody MOv18/anti-CD3 (biMAb OC/TR), which recognizes a 38-kDa glycoprotein expressed on ovarian carcinomas and the CD3 T cell receptor. However, little is known about the in vivo biodistribution of injected activated lymphocytes, information that could be obtained by scintigraphic imaging of radiolabelled T cells in order to visualize the migratory pattern. We compared the efficiency, stability and toxicity of technetium-99m hexamethylpropylene amine oxime (HMPAO), indium-111 oxine and fluorine-18 2-fluoro-2-deoxy-d-glucose (FDG) in radiolabelling activated lymphocytes targeted with biMAb OC/TR. The mean labelling efficiencies of 111In-oxine and 18F-FDG using 2.5x10(8) lymphocytes (68% and 64%, respectively) were more than twice that of 99mTc-HMPAO (31%). Retention of the radionuclide in the cell was highest in the case of 111In-oxine labelling (less than 25% of the initial cell-bound activity released after 240 min, as compared with 44% of the 99mTc label in the same period and 45% of 18F radionuclide released after 150 min). None of the three radiolabelling reagents induced any significant alteration in cell viability or immunophenotype. However, both 111In-oxine and 18F-FDG induced a loss of cytotoxic activity of lymphocytes against the ovarian carcinoma cell line IGROV1, and all three radiolabelling reagents caused a significant reduction in the proliferative ability of labelled lymphocytes compared to controls, with cell death occurring after 8-9 days. Radiolabelling with the more stable 111In-oxine reagent using a higher number of lymphocytes (1.4x10(9)) but the same total activity (around 55.5 MBq) resulted in improved labelled T cell viability and proliferative ability, although the mean labelling efficiency decreased (35.8%). Together the data suggest that 111In-oxine at low activity per cell is the most appropriate reagent for radiolabelling activated retargeted T lymphocytes useful for in vivo biodistribution studies. JF - European journal of nuclear medicine AU - Botti, C AU - Negri, D R AU - Seregni, E AU - Ramakrishna, V AU - Arienti, F AU - Maffioli, L AU - Lombardo, C AU - Bogni, A AU - Pascali, C AU - Crippa, F AU - Massaron, S AU - Remonti, F AU - Nerini-Molteni, S AU - Canevari, S AU - Bombardieri, E AD - Nuclear Medicine Department, National Cancer Institute, Milano, Italy. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 497 EP - 504 VL - 24 IS - 5 SN - 0340-6997, 0340-6997 KW - Fluorine Radioisotopes KW - 0 KW - Indium Radioisotopes KW - Organometallic Compounds KW - Organotechnetium Compounds KW - Oximes KW - Fluorodeoxyglucose F18 KW - 0Z5B2CJX4D KW - indium oxine KW - 14514-42-2 KW - Technetium Tc 99m Exametazime KW - 3B744AG22N KW - Oxyquinoline KW - 5UTX5635HP KW - Deoxyglucose KW - 9G2MP84A8W KW - Index Medicus KW - Lymphocyte Activation KW - Tumor Cells, Cultured KW - Cells, Cultured KW - Humans KW - Cell Death KW - Ovarian Neoplasms -- immunology KW - Female KW - Cell Survival KW - Isotope Labeling -- methods KW - Oxyquinoline -- analogs & derivatives KW - Deoxyglucose -- analogs & derivatives KW - T-Lymphocytes -- physiology KW - T-Lymphocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79004040?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+nuclear+medicine&rft.atitle=Comparison+of+three+different+methods+for+radiolabelling+human+activated+T+lymphocytes.&rft.au=Botti%2C+C%3BNegri%2C+D+R%3BSeregni%2C+E%3BRamakrishna%2C+V%3BArienti%2C+F%3BMaffioli%2C+L%3BLombardo%2C+C%3BBogni%2C+A%3BPascali%2C+C%3BCrippa%2C+F%3BMassaron%2C+S%3BRemonti%2C+F%3BNerini-Molteni%2C+S%3BCanevari%2C+S%3BBombardieri%2C+E&rft.aulast=Botti&rft.aufirst=C&rft.date=1997-05-01&rft.volume=24&rft.issue=5&rft.spage=497&rft.isbn=&rft.btitle=&rft.title=European+journal+of+nuclear+medicine&rft.issn=03406997&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-07 N1 - Date created - 1997-07-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of alpha-fetoprotein and stem cell factor/c-kit system in bile duct ligated young rats. AN - 78993882; 9141427 AB - The existence of a facultative hepatic stem cell compartment in bile ductules that participates in the renewal process of epithelial cell populations in the liver is well documented. The present study was undertaken to determine whether the immature bile epithelium responds differently to growth stimulus induced by bile stasis to that seen in the adult animal. In addition, the possible involvement of the growth factor/receptor systems associated with early activation of hepatic stem cells in bile duct proliferation was also examined. Bile duct ligation was used to induce the proliferation of bile epithelial cells. The expression of full-length alpha-fetoprotein (AFP) was used as an indicator for activation of the stem cell compartment. AFP was highly and selectively expressed in small bile ducts 7 days after bile duct ligation in immature rats up to 5 weeks of age. Although no significant increase in the expression of stem cell factor (SCF) c-kit, hepatocyte growth factor (HGF), and transforming growth factor-alpha (TGF-alpha) was observed 7 days after bile duct ligation in adult rats, the expression of all these growth factors was increased in bile duct ligated rats up to 5 weeks of age. These results suggest that the bile ductular epithelium in the young rats responds to bile stasis in a fashion that is phenotypically similar to that seen during early activation of hepatic stem cells in adult liver. JF - Hepatology (Baltimore, Md.) AU - Omori, M AU - Evarts, R P AU - Omori, N AU - Hu, Z AU - Marsden, E R AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, DBS, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 1115 EP - 1122 VL - 25 IS - 5 SN - 0270-9139, 0270-9139 KW - Stem Cell Factor KW - 0 KW - Transforming Growth Factor alpha KW - alpha-Fetoproteins KW - Proto-Oncogene Proteins c-kit KW - EC 2.7.10.1 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Age Factors KW - Epithelium -- metabolism KW - Transforming Growth Factor alpha -- metabolism KW - Epithelium -- pathology KW - Immunohistochemistry KW - Male KW - Cell Division KW - Cholestasis -- pathology KW - alpha-Fetoproteins -- biosynthesis KW - Cholestasis -- metabolism KW - Proto-Oncogene Proteins c-kit -- biosynthesis KW - Stem Cell Factor -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78993882?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepatology+%28Baltimore%2C+Md.%29&rft.atitle=Expression+of+alpha-fetoprotein+and+stem+cell+factor%2Fc-kit+system+in+bile+duct+ligated+young+rats.&rft.au=Omori%2C+M%3BEvarts%2C+R+P%3BOmori%2C+N%3BHu%2C+Z%3BMarsden%2C+E+R%3BThorgeirsson%2C+S+S&rft.aulast=Omori&rft.aufirst=M&rft.date=1997-05-01&rft.volume=25&rft.issue=5&rft.spage=1115&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 - 1997-05-28 N1 - Date created - 1997-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of uveitis by oral administration of retinal antigens: results of a phase I/II randomized masked trial. AN - 78993307; 9152063 AB - To evaluate the effect and safety of the oral administration of retinal antigens as a treatment of ocular inflammation. In a phase I/II randomized masked trial, patients with endogenous uveitis who were dependent on immunosuppressive agents were randomly assigned to receive either retinal S antigen alone (10 patients), retinal S antigen and a mixture of soluble retinal antigens (10 patients), a mixture of soluble retinal antigens alone (10 patients), or placebo (15 patients). An attempt was then made to taper patients completely off their standard immunosuppressive therapy over an 8 week period. The primary study endpoint was time to ocular inflammatory attack. The secondary study endpoint was the ability to taper patients completely off their immunosuppressive or cytotoxic medication within 8 weeks. Time to development of the main study endpoint was not statistically significantly different for any of the four treatment groups. However, the group receiving the purified S antigen alone appeared to be tapered off their immunosuppressive medication more successfully compared with patients given placebo (P = .08), whereas all the other groups appeared to do worse than did those receiving placebo. No toxic effects attributable to any treatment were observed. This phase I/II study is the first to test the use of orally administered S antigen in the treatment of uveitis. Although not statistically significant, patients given S antigen were more likely to be tapered off their chronically administered systemic immunosuppressive therapy than were the other groups tested. JF - American journal of ophthalmology AU - Nussenblatt, R B AU - Gery, I AU - Weiner, H L AU - Ferris, F L AU - Shiloach, J AU - Remaley, N AU - Perry, C AU - Caspi, R R AU - Hafler, D A AU - Foster, C S AU - Whitcup, S M AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1858, USA. rnq@helix.nih.gov Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 583 EP - 592 VL - 123 IS - 5 SN - 0002-9394, 0002-9394 KW - Antigens KW - 0 KW - Arrestin KW - Immunosuppressive Agents KW - Abridged Index Medicus KW - Index Medicus KW - Administration, Oral KW - Animals KW - Double-Blind Method KW - Humans KW - Safety KW - Aged KW - Child KW - Child, Preschool KW - Drug Therapy, Combination KW - Drug Evaluation KW - Life Tables KW - Cattle KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Adolescent KW - Immunosuppressive Agents -- therapeutic use KW - Male KW - Female KW - Arrestin -- therapeutic use KW - Antigens -- adverse effects KW - Uveitis -- therapy KW - Arrestin -- adverse effects KW - Antigens -- therapeutic use KW - Uveitis -- physiopathology KW - Retina -- immunology KW - Arrestin -- administration & dosage KW - Antigens -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78993307?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+ophthalmology&rft.atitle=Treatment+of+uveitis+by+oral+administration+of+retinal+antigens%3A+results+of+a+phase+I%2FII+randomized+masked+trial.&rft.au=Nussenblatt%2C+R+B%3BGery%2C+I%3BWeiner%2C+H+L%3BFerris%2C+F+L%3BShiloach%2C+J%3BRemaley%2C+N%3BPerry%2C+C%3BCaspi%2C+R+R%3BHafler%2C+D+A%3BFoster%2C+C+S%3BWhitcup%2C+S+M&rft.aulast=Nussenblatt&rft.aufirst=R&rft.date=1997-05-01&rft.volume=123&rft.issue=5&rft.spage=583&rft.isbn=&rft.btitle=&rft.title=American+journal+of+ophthalmology&rft.issn=00029394&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-28 N1 - Date created - 1997-05-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Am J Ophthalmol. 1997 May;123(5):684-7 [9152074] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A single amino acid in the p58 killer cell inhibitory receptor controls the ability of natural killer cells to discriminate between the two groups of HLA-C allotypes. AN - 78989325; 9126959 AB - To examine the structural basis for the specific recognition of the MHC class I allotypes HLA-Cw*0401 and HLA-Cw*0304 by the killer cell inhibitory receptors (KIR) cl42 and cl43, respectively, mutant KIR-Ig fusion proteins were tested by direct binding to cells transfected with single HLA-C alleles. The putative loop region at position 44-46 of KIR contained amino acids that were necessary for the discrimination between HLA-Cw*0401 and HLA-Cw*0304. Surprisingly, exchanging the methionine at position 44 in cl42 with the lysine at position 44 in cl43 was sufficient to switch the specificity of cl42 from HLA-Cw*0401 to HLA-Cw*0304, and vice versa. Thus, a single amino acid in the first Ig domain of these KIR determines their ability to discriminate between the two groups of HLA-C allotypes. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Winter, C C AU - Long, E O AD - Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA. Y1 - 1997/05/01/ PY - 1997 DA - 1997 May 01 SP - 4026 EP - 4028 VL - 158 IS - 9 SN - 0022-1767, 0022-1767 KW - HLA-C Antigens KW - 0 KW - KIR2DL3 protein, human KW - Receptors, Immunologic KW - Receptors, KIR KW - Receptors, KIR2DL3 KW - Recombinant Fusion Proteins KW - Abridged Index Medicus KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Alleles KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Consensus Sequence KW - Structure-Activity Relationship KW - Receptors, Immunologic -- chemistry KW - HLA-C Antigens -- immunology KW - Killer Cells, Natural -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78989325?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=A+single+amino+acid+in+the+p58+killer+cell+inhibitory+receptor+controls+the+ability+of+natural+killer+cells+to+discriminate+between+the+two+groups+of+HLA-C+allotypes.&rft.au=Winter%2C+C+C%3BLong%2C+E+O&rft.aulast=Winter&rft.aufirst=C&rft.date=1997-05-01&rft.volume=158&rft.issue=9&rft.spage=4026&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-19 N1 - Date created - 1997-05-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Influence of other maternal variables on the relationship between maternal virus load and mother-to-infant transmission of human immunodeficiency virus type 1. AN - 78974792; 9129087 AB - To assess the relationship between maternal human immunodeficiency virus (HIV) type 1 RNA level, other important covariates, and mother-to-infant (vertical) transmission of HIV-1, third trimester repository specimens from 160 HIV-1-seropositive women enrolled in the Mothers and Infants Cohort Study between 1986 and 1991 were assayed in batch for HIV-1 RNA. A significant association between peripheral blood HIV-1 RNA level and vertical transmission remained after controlling for CD4 cell level, duration of ruptured membranes, "hard" drug (cocaine and heroin) use, and frequency of sexual activity during pregnancy. However, the association was attenuated among women with advanced HIV infection and those with a high frequency of sexual activity during pregnancy. In these settings, interventions that target risk factors other than virus load may be particularly important for preventing vertical transmission of HIV-1. JF - The Journal of infectious diseases AU - Burns, D N AU - Landesman, S AU - Wright, D J AU - Waters, D AU - Mitchell, R M AU - Rubinstein, A AU - Willoughby, A AU - Goedert, J J AD - Pediatric, Adolescent, and Maternal AIDS Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-7510, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 1206 EP - 1210 VL - 175 IS - 5 SN - 0022-1899, 0022-1899 KW - HIV Core Protein p24 KW - 0 KW - RNA, Viral KW - Cocaine KW - I5Y540LHVR KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Pregnancy Trimester, Third KW - Heroin Dependence KW - Humans KW - Retrospective Studies KW - Infant, Newborn KW - HIV Core Protein p24 -- analysis KW - CD4 Lymphocyte Count KW - Opioid-Related Disorders KW - Pregnancy KW - Sexual Behavior KW - Risk Factors KW - Cohort Studies KW - Female KW - RNA, Viral -- blood KW - Infectious Disease Transmission, Vertical -- statistics & numerical data KW - HIV-1 -- genetics KW - Acquired Immunodeficiency Syndrome -- epidemiology KW - HIV Seropositivity KW - HIV-1 -- isolation & purification KW - Pregnancy Complications, Infectious KW - Acquired Immunodeficiency Syndrome -- transmission UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78974792?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Influence+of+other+maternal+variables+on+the+relationship+between+maternal+virus+load+and+mother-to-infant+transmission+of+human+immunodeficiency+virus+type+1.&rft.au=Burns%2C+D+N%3BLandesman%2C+S%3BWright%2C+D+J%3BWaters%2C+D%3BMitchell%2C+R+M%3BRubinstein%2C+A%3BWilloughby%2C+A%3BGoedert%2C+J+J&rft.aulast=Burns&rft.aufirst=D&rft.date=1997-05-01&rft.volume=175&rft.issue=5&rft.spage=1206&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 - 1997-06-02 N1 - Date created - 1997-06-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Involvement of a tissue-specific RNA recognition motif protein in Drosophila spermatogenesis. AN - 78974405; 9111341 AB - RNA binding proteins mediate posttranscriptional regulation of gene expression via their roles in nuclear and cytoplasmic mRNA metabolism. Many of the proteins involved in these processes have a common RNA binding domain, the RNA recognition motif (RRM). We have characterized the Testis-specific RRM protein gene (Tsr), which plays an important role in spermatogenesis in Drosophila melanogaster. Disruption of Tsr led to a dramatic reduction in male fertility due to the production of spermatids with abnormalities in mitochondrial morphogenesis. Tsr is located on the third chromosome at 87F, adjacent to the nuclear pre-mRNA binding protein gene Hrb87F. A 1.7-kb Tsr transcript was expressed exclusively in the male germ line. It encoded a protein containing two RRMs similar to those found in HRB87F as well as a unique C-terminal domain. TSR protein was located in the cytoplasm of spermatocytes and young spermatids but was absent from mature sperm. The cellular proteins expressed in premeiotic primary spermatocytes from Tsr mutant and wild-type males were assessed by two-dimensional gel electrophoresis. Lack of TSR resulted in the premature expression of a few proteins prior to meiosis; this was abolished by a transgenic copy of Tsr. These data demonstrate that TSR negatively regulated the expression of some testis proteins and, in combination with its expression pattern and subcellular localization, suggest that TSR regulates the stability or translatability of some mRNAs during spermatogenesis. JF - Molecular and cellular biology AU - Haynes, S R AU - Cooper, M T AU - Pype, S AU - Stolow, D T AD - Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-2785, USA. sh4i@nih.gov Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 2708 EP - 2715 VL - 17 IS - 5 SN - 0270-7306, 0270-7306 KW - Drosophila Proteins KW - 0 KW - Microfilament Proteins KW - RNA, Messenger KW - RNA-Binding Proteins KW - twinstar protein, Drosophila KW - RNA KW - 63231-63-0 KW - Index Medicus KW - Phenotype KW - Mutagenesis, Site-Directed KW - Animals KW - Base Sequence KW - Testis -- metabolism KW - RNA, Messenger -- metabolism KW - Cytoplasm -- metabolism KW - Drosophila melanogaster KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Male KW - Spermatogenesis -- genetics KW - Microfilament Proteins -- metabolism KW - RNA-Binding Proteins -- metabolism KW - RNA-Binding Proteins -- genetics KW - RNA -- metabolism KW - Microfilament Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78974405?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Involvement+of+a+tissue-specific+RNA+recognition+motif+protein+in+Drosophila+spermatogenesis.&rft.au=Haynes%2C+S+R%3BCooper%2C+M+T%3BPype%2C+S%3BStolow%2C+D+T&rft.aulast=Haynes&rft.aufirst=S&rft.date=1997-05-01&rft.volume=17&rft.issue=5&rft.spage=2708&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-15 N1 - Date created - 1997-05-15 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U18401; GENBANK N1 - SuppNotes - Cited By: Development. 1989 Jun;106(2):367-73 [2512111] Mol Biol Cell. 1996 Jul;7(7):1059-73 [8862520] Mol Cell Biol. 1990 Nov;10(11):5937-44 [1700276] EMBO J. 1990 Dec;9(13):4519-25 [2124974] Mol Gen Genet. 1990 Dec;224(3):450-8 [2125114] Dev Biol. 1991 Mar;144(1):65-77 [1704862] Genes Dev. 1991 Mar;5(3):403-15 [1900493] J Cell Biol. 1991 Nov;115(3):587-96 [1717489] Mol Cell Biol. 1993 Jan;13(1):174-83 [8417324] Nucleic Acids Res. 1993 May 11;21(9):2229-35 [8502565] Genes Dev. 1993 Jun;7(6):948-60 [7684991] J Biol Chem. 1993 Jun 5;268(16):12213-20 [8505341] Dev Biol. 1993 Jul;158(1):99-100 [8330676] Annu Rev Biochem. 1993;62:289-321 [8352591] Genetics. 1993 Oct;135(2):489-505 [8244010] Cell. 1993 Dec 31;75(7):1287-95 [8269511] Nucleic Acids Res. 1993 Dec 25;21(25):5803-16 [8290338] Dev Genet. 1993;14(6):449-59 [8111973] FEBS Lett. 1994 Feb 28;340(1-2):1-8 [7509757] Curr Opin Cell Biol. 1993 Dec;5(6):950-4 [7907491] Science. 1994 Jul 29;265(5172):615-21 [8036511] Bioessays. 1994 Aug;16(8):533-5 [8086000] Mol Gen Genet. 1995 Feb 6;246(3):334-41 [7854318] Biochimie. 1994;76(9):867-79 [7880904] Nucleic Acids Res. 1995 Mar 11;23(5):725-8 [7535921] Nucleic Acids Res. 1995 Mar 11;23(5):835-43 [7708500] Cell. 1995 Apr 21;81(2):171-8 [7736569] Dev Genet. 1995;16(2):95-103 [7736670] Recent Prog Horm Res. 1995;50:275-86 [7740161] Trends Biochem Sci. 1995 Jun;20(6):235-40 [7543225] Nat Genet. 1995 Aug;10(4):383-93 [7670487] Dev Biol. 1995 Dec;172(2):344-52 [8612956] Mol Cell Biol. 1996 Jun;16(6):3023-34 [8649414] Nature. 1996 Jun 27;381(6585):740-1 [8657275] Nature. 1996 Jun 27;381(6585):783-5 [8657280] Mutat Res. 1965 Aug;2(4):366-80 [5878312] Biochemistry. 1981 Aug 18;20(17):4871-7 [6170318] Dev Biol. 1983 Feb;95(2):512-7 [6402401] Nucleic Acids Res. 1984 Jul 11;12(13):5495-513 [6087289] Cell. 1985 Jan;40(1):37-43 [3917855] Cell. 1985 Nov;43(1):97-104 [3935320] Mol Cell Biol. 1988 May;8(5):2237-41 [3386636] Biotechnology. 1988;10:437-56 [2850048] Biochemistry. 1988 Nov 15;27(23):8509-15 [3064814] Mol Cell Biol. 1990 Jan;10(1):316-23 [2104660] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Case study: risperidone-induced hepatotoxicity in pediatric patients. AN - 78973226; 9136506 AB - The purpose of this case study is to document hepatic adverse effects associated with long-term risperidone use in pediatric populations. Charts of all patients admitted to the National Institute of Mental Health (NIMH) from December 1993 to April 1996 who had been treated with risperidone were screened for hepatotoxicity and weight gain. From the medical records of 13 psychotic children admitted to the NIMH and treated with risperidone, 2 children (both male) who presented with obesity, liver enzyme abnormalities, and confirmatory evidence of fatty liver were identified. In each case liver damage was reversed after discontinuation of risperidone and/or associated weight loss. The observations suggest that long-term risperidone therapy is possibly associated with hepatotoxicity in male pediatric patients. It is recommended that pediatric patients treated with risperidone have baseline liver function tests, careful monitoring of weight, and periodic monitoring of liver function tests during the maintenance phase of therapy. JF - Journal of the American Academy of Child and Adolescent Psychiatry AU - Kumra, S AU - Herion, D AU - Jacobsen, L K AU - Briguglia, C AU - Grothe, D AD - Department of Child Psychiatry, NIMH, Bethesda, MD 20892-1600, USA. kumra@helix.nih.gov Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 701 EP - 705 VL - 36 IS - 5 SN - 0890-8567, 0890-8567 KW - Antipsychotic Agents KW - 0 KW - Risperidone KW - L6UH7ZF8HC KW - Index Medicus KW - Humans KW - Retrospective Studies KW - Child KW - Adolescent KW - Male KW - Female KW - Chemical and Drug Induced Liver Injury -- etiology KW - Schizophrenia -- drug therapy KW - Risperidone -- adverse effects KW - Antipsychotic Agents -- adverse effects KW - Obesity -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78973226?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Academy+of+Child+and+Adolescent+Psychiatry&rft.atitle=Case+study%3A+risperidone-induced+hepatotoxicity+in+pediatric+patients.&rft.au=Kumra%2C+S%3BHerion%2C+D%3BJacobsen%2C+L+K%3BBriguglia%2C+C%3BGrothe%2C+D&rft.aulast=Kumra&rft.aufirst=S&rft.date=1997-05-01&rft.volume=36&rft.issue=5&rft.spage=701&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Academy+of+Child+and+Adolescent+Psychiatry&rft.issn=08908567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-24 N1 - Date created - 1997-06-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Am Acad Child Adolesc Psychiatry. 1998 Mar;37(3):246-7 [9519624] J Am Acad Child Adolesc Psychiatry. 1998 Oct;37(10):1007-8 [9785708] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of NFAT-family proteins in normal human T cells. AN - 78967866; 9111316 AB - NFAT proteins constitute a family of transcription factors involved in mediating signal transduction. Using a panel of specific antisera in immunoprecipitation assays, we found that NFATp (135 kDa) is constitutively expressed in normal human T cells, while synthesis of NFATc (predominant form of 86 kDa) is induced by ionomycin treatment. NFAT4/x was very weakly expressed in unstimulated cells, and its level did not increase upon treatment with activating agents. NFAT3 protein was not observed under any conditions. Higher-molecular-weight species of NFATc (of 110 and 140 kDa) were also detected. In addition, translation of NFATc mRNA apparently initiates at two different AUG codons, giving rise to proteins that differ in size by 36 amino acids. Additional size heterogeneity of both NFATc and NFATp results from phosphorylation. In contrast to ionomycin treatment, exposure of cells to phorbol myristate acetate (PMA) plus anti-CD28 did not induce NFATc, indicating that under these conditions, interleukin-2 synthesis by these cells is apparently independent of NFATc. In DNA binding assays, both PMA plus anti-CD28 and PMA plus ionomycin resulted in nuclear NFAT. Surprisingly, the PMA-ionomycin-induced synthesis of NFATc that was detected by immunoprecipitation was not mirrored in the DNA binding assays: nearly all of the activity was due to NFATp. This is the first study of expression of all family members at the protein level in normal human T cells. JF - Molecular and cellular biology AU - Lyakh, L AU - Ghosh, P AU - Rice, N R AD - Molecular Basis of Carcinogenesis Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 2475 EP - 2484 VL - 17 IS - 5 SN - 0270-7306, 0270-7306 KW - Antigens, CD28 KW - 0 KW - DNA-Binding Proteins KW - Immune Sera KW - NFATC Transcription Factors KW - NFATC2 protein, human KW - NFATC3 protein, human KW - NFATC4 protein, human KW - Nuclear Proteins KW - Phosphoproteins KW - Transcription Factors KW - DNA KW - 9007-49-2 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Electrophoresis, Polyacrylamide Gel KW - Humans KW - DNA -- metabolism KW - Jurkat Cells KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Molecular Weight KW - Antigens, CD28 -- immunology KW - Lymphocyte Activation KW - T-Lymphocytes -- metabolism KW - Transcription Factors -- metabolism KW - Nuclear Proteins -- metabolism KW - Phosphoproteins -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78967866?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Expression+of+NFAT-family+proteins+in+normal+human+T+cells.&rft.au=Lyakh%2C+L%3BGhosh%2C+P%3BRice%2C+N+R&rft.aulast=Lyakh&rft.aufirst=L&rft.date=1997-05-01&rft.volume=17&rft.issue=5&rft.spage=2475&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-15 N1 - Date created - 1997-05-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1993 Feb 15;268(5):3747-52 [7679116] Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8907-12 [8799126] Mol Cell Biol. 1993 Aug;13(8):4793-805 [8336717] J Exp Med. 1993 Oct 1;178(4):1365-79 [8376940] EMBO J. 1993 Dec;12(12):4685-95 [8223478] Science. 1993 Oct 29;262(5134):750-4 [8235597] Mol Cell Biol. 1993 Dec;13(12):7399-407 [8246960] Nucleic Acids Res. 1993 Dec 11;21(24):5694-704 [8284217] Nature. 1994 Jun 9;369(6480):497-502 [8202141] Immunol Today. 1994 Jun;15(6):274-81 [8068174] J Biol Chem. 1994 Nov 11;269(45):28181-6 [7961754] Annu Rev Biochem. 1994;63:1045-83 [7979236] J Biol Chem. 1994 Dec 2;269(48):30445-50 [7982959] J Biol Chem. 1995 Feb 24;270(8):4138-45 [7876165] Immunity. 1994 Jun;1(3):179-87 [7889406] Immunity. 1994 Jun;1(3):189-96 [7889407] Mol Cell Biol. 1995 Apr;15(4):2071-9 [7891702] Mol Cell Biol. 1995 May;15(5):2697-706 [7739550] Immunity. 1995 May;2(5):461-72 [7749981] Immunity. 1995 May;2(5):473-83 [7749982] J Immunol. 1995 Jun 1;154(11):6112-9 [7751652] J Biol Chem. 1995 Aug 25;270(34):19898-907 [7650004] Biochemistry. 1979 Feb 20;18(4):690-3 [84683] Nucleic Acids Res. 1987 Oct 26;15(20):8125-48 [3313277] Proc Natl Acad Sci U S A. 1989 Feb;86(4):1333-7 [2465550] J Biol Chem. 1990 Sep 15;265(26):15788-95 [2394747] Cell. 1992 Oct 16;71(2):243-53 [1423592] J Exp Med. 1995 Sep 1;182(3):801-10 [7650486] J Biol Chem. 1995 Sep 1;270(35):20653-9 [7657645] J Biol Chem. 1995 Sep 22;270(38):22602-7 [7545680] Biochim Biophys Acta. 1995 Sep 19;1263(3):181-200 [7548205] Ann N Y Acad Sci. 1995 Sep 7;766:182-94 [7486655] Curr Opin Immunol. 1995 Jun;7(3):333-42 [7546397] Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):11205-9 [7479966] J Biol Chem. 1996 Jan 19;271(3):1274-7 [8576111] Immunity. 1996 Apr;4(4):397-405 [8612134] J Biol Chem. 1996 Mar 29;271(13):7700-4 [8631809] J Biol Chem. 1996 May 3;271(18):10884-91 [8631904] Science. 1996 May 10;272(5263):892-5 [8629027] Mol Cell Biol. 1996 Jul;16(7):3945-54 [8668212] Mol Cell Biol. 1996 Jul;16(7):3955-66 [8668213] Nature. 1996 Jul 25;382(6589):370-3 [8684469] J Exp Med. 1996 Jul 1;184(1):141-7 [8691127] J Biol Chem. 1996 Aug 23;271(34):20914-21 [8702849] J Biol Chem. 1993 Jul 5;268(19):14285-93 [8314792] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thrombospondin 1 and type I repeat peptides of thrombospondin 1 specifically induce apoptosis of endothelial cells. AN - 78966093; 9135017 AB - Thrombospondin 1 (TSP1) inhibits angiogenesis and modulates endothelial cell adhesion, motility, and growth. The antiproliferative activity of TSP1 is mimicked by synthetic peptides derived from the type I repeats of TSP1 that antagonize fibroblast growth factor 2 and activate latent transforming growth factor beta. These TSP1 analogues induced programmed cell death in bovine aortic endothelial cells based on morphological changes, assessment of DNA fragmentation, and internucleosomal DNA cleavage. Intact TSP1 also induced DNA fragmentation. The endothelial cell response was specific because no DNA fragmentation was induced in MDA-MB-435S breast carcinoma cells, although TSP1 and the peptide conjugates inhibited the growth of both cell types. Apoptosis did not depend on activation of latent transforming growth factor beta because peptides lacking the activating sequence RFK were active. Apoptosis was not sensitive to inhibitors of ceramide generation but was inhibited by the phosphatase inhibitor vanadate. Induction of DNA fragmentation by the peptides was decreased when endothelial cell cultures reached confluence. Growth of the cells on a fibronectin substrate also suppressed induction of apoptosis by TSP1 or the peptides. Differential sensitivities to kinase inhibitors suggest that apoptosis and inhibition of proliferation are mediated by distinct signal transduction pathways. These results demonstrate that induction of apoptosis by the TSP1 analogues is not a general cytotoxic effect and is conditional on a lack of strong survival-promoting signals, such as those provided by a fibronectin matrix. The antitumor activity of TSP1 may therefore result from an increased sensitivity to apoptosis in endothelial cells adjacent to a provisional matrix during formation of vascular beds in tumors expressing TSP1. JF - Cancer research AU - Guo, N AU - Krutzsch, H C AU - Inman, J K AU - Roberts, D D AD - Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, Maryland 20892-1500, USA. Y1 - 1997/05/01/ PY - 1997 DA - 1997 May 01 SP - 1735 EP - 1742 VL - 57 IS - 9 SN - 0008-5472, 0008-5472 KW - Fibronectins KW - 0 KW - Membrane Glycoproteins KW - Peptides KW - Thrombospondins KW - Transforming Growth Factor beta KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Extracellular Matrix -- physiology KW - Cell Division -- drug effects KW - Amino Acid Sequence KW - Peptides -- pharmacology KW - Cattle KW - Phosphorylation KW - Cells, Cultured KW - Fibronectins -- physiology KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Peptides -- chemistry KW - Protein Kinase C -- physiology KW - Repetitive Sequences, Nucleic Acid KW - Transforming Growth Factor beta -- metabolism KW - DNA Fragmentation KW - Cell Adhesion KW - Membrane Glycoproteins -- chemistry KW - Apoptosis KW - Endothelium, Vascular -- cytology KW - Membrane Glycoproteins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78966093?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Thrombospondin+1+and+type+I+repeat+peptides+of+thrombospondin+1+specifically+induce+apoptosis+of+endothelial+cells.&rft.au=Guo%2C+N%3BKrutzsch%2C+H+C%3BInman%2C+J+K%3BRoberts%2C+D+D&rft.aulast=Guo&rft.aufirst=N&rft.date=1997-05-01&rft.volume=57&rft.issue=9&rft.spage=1735&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-21 N1 - Date created - 1997-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hypermutability of homonucleotide runs in mismatch repair and DNA polymerase proofreading yeast mutants. AN - 78949163; 9111358 AB - Homonucleotide runs in coding sequences are hot spots for frameshift mutations and potential sources of genetic changes leading to cancer in humans having a mismatch repair defect. We examined frameshift mutations in homonucleotide runs of deoxyadenosines ranging from 4 to 14 bases at the same position in the LYS2 gene of the yeast Saccharomyces cerevisiae. In the msh2 mismatch repair mutant, runs of 9 to 14 deoxyadenosines are 1,700-fold to 51,000-fold, respectively, more mutable for single-nucleotide deletions than are runs of 4 deoxyadenosines. These frameshift mutations can account for up to 99% of all forward mutations inactivating the 4-kb LYS2 gene. Based on results with single and double mutations of the POL2 and MSH2 genes, both DNA polymerase epsilon proofreading and mismatch repair are efficient for short runs while only the mismatch repair system prevents frameshift mutations in runs of > or = 8 nucleotides. Therefore, coding sequences containing long homonucleotide runs are likely to be at risk for mutational inactivation in cells lacking mismatch repair capability. JF - Molecular and cellular biology AU - Tran, H T AU - Keen, J D AU - Kricker, M AU - Resnick, M A AU - Gordenin, D A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 2859 EP - 2865 VL - 17 IS - 5 SN - 0270-7306, 0270-7306 KW - DNA, Fungal KW - 0 KW - DNA-Binding Proteins KW - Deoxyadenosines KW - Fungal Proteins KW - Nucleic Acid Heteroduplexes KW - Saccharomyces cerevisiae Proteins KW - DNA Polymerase II KW - EC 2.7.7.- KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - MSH2 protein, S cerevisiae KW - EC 3.6.1.3 KW - MutS Homolog 2 Protein KW - Index Medicus KW - Frameshift Mutation KW - Base Sequence KW - Humans KW - DNA Polymerase II -- metabolism KW - Molecular Sequence Data KW - DNA-Binding Proteins -- genetics KW - Deoxyadenosines -- metabolism KW - Saccharomyces cerevisiae KW - Mutagenesis KW - DNA-Binding Proteins -- metabolism KW - DNA Repair -- genetics KW - Nucleic Acid Heteroduplexes -- genetics KW - DNA, Fungal -- metabolism KW - DNA-Directed DNA Polymerase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78949163?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hypermutability+of+homonucleotide+runs+in+mismatch+repair+and+DNA+polymerase+proofreading+yeast+mutants.&rft.au=Tran%2C+H+T%3BKeen%2C+J+D%3BKricker%2C+M%3BResnick%2C+M+A%3BGordenin%2C+D+A&rft.aulast=Tran&rft.aufirst=H&rft.date=1997-05-01&rft.volume=17&rft.issue=5&rft.spage=2859&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-15 N1 - Date created - 1997-05-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cold Spring Harb Symp Quant Biol. 1966;31:77-84 [5237214] Mol Cell Biol. 1997 May;17(5):2851-8 [9111357] Genetics. 1985 Apr;109(4):633-59 [3988038] Genetics. 1985 Aug;110(4):609-46 [3896926] J Biol Chem. 1986 Oct 15;261(29):13581-7 [3759982] J Mol Biol. 1986 Oct 20;191(4):601-13 [3806675] Proc Natl Acad Sci U S A. 1987 May;84(9):2838-42 [3554248] Nucleic Acids Res. 1987 Jul 10;15(13):5323-38 [3299269] Proc Natl Acad Sci U S A. 1987 Sep;84(17):6220-4 [3306672] J Biol Chem. 1989 May 5;264(13):7720-5 [2708388] Proc Natl Acad Sci U S A. 1989 Oct;86(19):7465-9 [2552445] Cancer Res. 1991 Jun 15;51(12):3075-9 [2039987] Crit Rev Biochem Mol Biol. 1991;26(3-4):377-95 [1935171] Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9473-7 [1658784] Genetics. 1991 Oct;129(2):317-26 [1660424] EMBO J. 1992 Feb;11(2):733-40 [1537345] Genomics. 1992 Apr;12(4):627-31 [1572635] Genetics. 1992 Dec;132(4):975-85 [1334021] EMBO J. 1993 Apr;12(4):1467-73 [8385605] Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6424-8 [8341649] Nature. 1993 Sep 16;365(6443):274-6 [8371783] Annu Rev Biochem. 1996;65:101-33 [8811176] Genetics. 1996 Aug;143(4):1579-87 [8844147] Genetics. 1996 Mar;142(3):717-26 [8849882] Cell. 1996 Oct 4;87(1):65-73 [8858149] Cell. 1996 Oct 18;87(2):159-70 [8861899] Nat Genet. 1996 Nov;14(3):255-7 [8896552] Mol Cell Biol. 1997 Feb;17(2):1027-36 [9001255] Prog Nucleic Acid Res Mol Biol. 1993;46:93-120 [8234788] Mol Cell Biol. 1994 Jan;14(1):407-15 [8264608] Mol Gen Genet. 1994 Feb;242(3):289-96 [8107676] Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6319-23 [8022779] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):6830-4 [8041704] Oncogene. 1995 Jan 5;10(1):33-7 [7824277] Somat Cell Mol Genet. 1994 Sep;20(5):409-21 [7825063] Mol Cell Biol. 1995 Apr;15(4):2173-9 [7891712] Curr Opin Oncol. 1995 Jan;7(1):83-9 [7696368] Mol Endocrinol. 1994 Dec;8(12):1656-66 [7708054] Cancer Res. 1995 Jun 1;55(11):2304-9 [7757980] Science. 1995 Jun 2;268(5215):1336-8 [7761852] Science. 1995 Jul 14;269(5221):238-40 [7618086] J Biol Chem. 1995 Aug 18;270(33):19516-23 [7543900] J Biol Chem. 1995 Sep 15;270(37):22044-9 [7665626] Mol Cell Biol. 1995 Oct;15(10):5607-17 [7565712] Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10418-21 [7479796] Cancer Res. 1995 Dec 1;55(23):5548-50 [7585632] Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12017-20 [8618835] Biochemistry. 1996 Jan 23;35(3):1046-53 [8547240] Hum Mol Genet. 1995 Nov;4(11):2057-64 [8589681] Endocrinology. 1996 Apr;137(4):1349-57 [8625910] Genes Dev. 1996 Feb 15;10(4):407-20 [8600025] Mutat Res. 1996 Feb 19;350(1):201-5 [8657182] Oncogene. 1996 Apr 4;12(7):1425-32 [8622858] J Biol Chem. 1996 Mar 29;271(13):7285-8 [8631743] J Bacteriol. 1996 Apr;178(8):2388-96 [8636043] Mutat Res. 1996 May;316(5-6):249-59 [8649458] Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):9049-54 [8799152] Mol Cell Biol. 1997 May;17(5):2844-50 [9111356] J Mol Biol. 1981 Jul 5;149(3):337-76 [6273585] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Applications of genetic technologies to cancer screening, prevention, diagnosis, prognosis, and treatment. AN - 78944567; 9114474 AB - To help oncology nurses to appreciate genetic contributions to carcinogenesis; to learn how genetic changes are connected to biological mechanisms underlying cancer initiation, promotion, and progression; and to become familiar with new genetic technologies being incorporated into clinical oncology practice. Review of published professional journals and oncology textbooks. Molecular genetic approaches with high sensitivity and specificity offer new hope for the improved evaluation of potential carcinogens, cancer prevention, early and accurate diagnosis, more reliable prognosis, and effective treatment and monitoring of cancer. Effective translation of molecular technologies will require development of improved methods, clinical validation studies, high-quality control, multisite clinical outcome studies, and development of multidisciplinary collaborations. Oncology nurses are incorporating new genetic technologies into the following areas of practice: patient education, cancer prevention and control, diagnostic and prognostic testing, and treatment. JF - Seminars in oncology nursing AU - Peters, J A AD - Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-1852, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 74 EP - 81 VL - 13 IS - 2 SN - 0749-2081, 0749-2081 KW - Index Medicus KW - Nursing KW - Sensitivity and Specificity KW - Mass Screening KW - Cocarcinogenesis KW - Reproducibility of Results KW - Humans KW - Prognosis KW - Genetic Therapy KW - Neoplasms -- diagnosis KW - Molecular Biology KW - Genetic Techniques KW - Neoplasms -- therapy KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78944567?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+oncology+nursing&rft.atitle=Applications+of+genetic+technologies+to+cancer+screening%2C+prevention%2C+diagnosis%2C+prognosis%2C+and+treatment.&rft.au=Peters%2C+J+A&rft.aulast=Peters&rft.aufirst=J&rft.date=1997-05-01&rft.volume=13&rft.issue=2&rft.spage=74&rft.isbn=&rft.btitle=&rft.title=Seminars+in+oncology+nursing&rft.issn=07492081&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-26 N1 - Date created - 1997-06-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alcohol consumption and breast cancer risk among women under age 45 years. AN - 78942744; 9115015 AB - In a population-based case-control study of women younger than 45 years of age, we obtained a detailed lifetime history of alcohol use to evaluate the effects of drinking during different periods of life in relation to breast cancer risk. This analysis focused on interviews obtained from 1,645 cases and 1,497 controls. Breast cancer risk was not influenced by drinking during the teenage years or early adulthood. Contemporary drinking (that is, average intake during the recent 5-year interval) was directly associated with risk, but the adverse effect of recent drinking was restricted to women who consumed > or = 14 drinks per week [relative risk (RR) = 1.7; 95% confidence interval (CI) = 1.2-2.5]. The effect of alcohol was most pronounced among women with advanced disease. Compared with nondrinkers, the risk estimate associated with recent consumption of > or = 14 drinks per week was 2.4 (95% CI = 1.6-3.8) for women with regional/distant disease. Our data add support to the accumulating evidence that alcohol consumption is associated with increased risk of breast cancer and further indicate that alcohol acts at a late stage in breast carcinogenesis. JF - Epidemiology (Cambridge, Mass.) AU - Swanson, C A AU - Coates, R J AU - Malone, K E AU - Gammon, M D AU - Schoenberg, J B AU - Brogan, D J AU - McAdams, M AU - Potischman, N AU - Hoover, R N AU - Brinton, L A AD - Nutritional Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892-7374, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 231 EP - 237 VL - 8 IS - 3 SN - 1044-3983, 1044-3983 KW - Index Medicus KW - Risk KW - Risk Factors KW - Humans KW - Adult KW - Case-Control Studies KW - Confidence Intervals KW - Middle Aged KW - Female KW - Multivariate Analysis KW - Breast Neoplasms -- etiology KW - Alcohol Drinking -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78942744?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epidemiology+%28Cambridge%2C+Mass.%29&rft.atitle=Alcohol+consumption+and+breast+cancer+risk+among+women+under+age+45+years.&rft.au=Swanson%2C+C+A%3BCoates%2C+R+J%3BMalone%2C+K+E%3BGammon%2C+M+D%3BSchoenberg%2C+J+B%3BBrogan%2C+D+J%3BMcAdams%2C+M%3BPotischman%2C+N%3BHoover%2C+R+N%3BBrinton%2C+L+A&rft.aulast=Swanson&rft.aufirst=C&rft.date=1997-05-01&rft.volume=8&rft.issue=3&rft.spage=231&rft.isbn=&rft.btitle=&rft.title=Epidemiology+%28Cambridge%2C+Mass.%29&rft.issn=10443983&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-27 N1 - Date created - 1997-06-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Epidemiology. 1997 May;8(3):225-7 [9115012] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of discounting certain tumor types/sites on evaluations of carcinogenicity in laboratory animals. AN - 78941343; 9099349 AB - It has been suggested that, for mechanistic reasons, certain tumors found in experimental animals should be discounted when evaluating carcinogenic effects. The questioned tumors are: mouse liver, rat thyroid follicular cell, bladder and kidney (male rat), forestomach (mouse and rat, gavage route), and lung (mouse and rat, inhalation of particles). We sought to determine the effects of discounting those tumors on classification of chemicals as carcinogens in animals. We looked at carcinogenicity data for chemicals studied in NCI-NTP bioassays and/or reviewed in IARC monographs and we found that deleting the questioned tumors would have significant impact on evaluations of carcinogenicity in animals. Fifty-six of 234 (24%) chemicals determined to be carcinogenic in the NCI-NTP bioassay program would no longer be considered carcinogenic: 102 (44%) would have weaker evidence of carcinogenic effects. Thirty-three of 361 (9%) chemicals determined by IARC to have "limited" or "sufficient" evidence of carcinogenicity would no longer be considered carcinogenic; 119 (33%) would have weaker evidence of carcinogenic effects. Because such a large number of chemicals currently considered carcinogenic would be affected by categorical deletion of tumors and because we are not aware of data that would justify such categorical deletions, it would be preferable to consider mechanistic justifications for discounting tumors on a case-by-case basis for each individual chemical. Deletion of tumors on a categorical basis has serious implications for regulation of toxic chemicals and for public health. JF - American journal of industrial medicine AU - Karstadt, M AU - Haseman, J K AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 485 EP - 494 VL - 31 IS - 5 SN - 0271-3586, 0271-3586 KW - Carcinogens KW - 0 KW - Index Medicus KW - Rats KW - Animals KW - Neoplasms, Experimental -- chemically induced KW - Carcinogenicity Tests KW - Biological Assay KW - Mice KW - Carcinogens -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78941343?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=Effect+of+discounting+certain+tumor+types%2Fsites+on+evaluations+of+carcinogenicity+in+laboratory+animals.&rft.au=Karstadt%2C+M%3BHaseman%2C+J+K&rft.aulast=Karstadt&rft.aufirst=M&rft.date=1997-05-01&rft.volume=31&rft.issue=5&rft.spage=485&rft.isbn=&rft.btitle=&rft.title=American+journal+of+industrial+medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-08 N1 - Date created - 1997-07-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The A34R glycoprotein gene is required for induction of specialized actin-containing microvilli and efficient cell-to-cell transmission of vaccinia virus. AN - 78940855; 9094667 AB - The mechanisms allowing vaccinia virus to spread from cell to cell are incompletely understood. The A34R gene of vaccinia virus encodes a glycoprotein that is localized in the outer membranes of extracellular virions. The small-plaque phenotype of an A34R deletion mutant was similar to that of mutants with deletions in other envelope genes that fail to produce extracellular vaccinia virions. Transmission electron microscopy, however, revealed that the A34R mutant produced numerous extracellular particles that were labeled with antibodies to other outer-envelope proteins and with protein A-colloidal gold. Fluorescence and scanning electron microscopy indicated that expression of the A34R protein was necessary for detection of vaccinia virus-induced actin tails, which provide motility to the intracellular enveloped form of vaccinia virus, and of virus-tipped specialized microvilli that project from the cell. The ability of vaccinia virus-infected cells to form syncytia after a brief exposure to a pH below 6, known as fusion from within, failed to occur in the absence of expression of the A34R protein; nevertheless, purified A34R- virions were capable of mediating low-pH-induced fusion from without. The present study provides genetic and microscopic evidence for the involvement of a specific viral protein in the formation or stability of actin-containing microvilli and for a role of these structures in cell-to-cell spread rather than in formation of extracellular virions. JF - Journal of virology AU - Wolffe, E J AU - Katz, E AU - Weisberg, A AU - Moss, B AD - Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0445, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 3904 EP - 3915 VL - 71 IS - 5 SN - 0022-538X, 0022-538X KW - A34R protein, Vaccina virus KW - 0 KW - Actins KW - Glycoproteins KW - Viral Envelope Proteins KW - Phalloidine KW - 17466-45-4 KW - Index Medicus KW - Microvilli -- chemistry KW - Virion -- ultrastructure KW - HeLa Cells KW - Hydrogen-Ion Concentration KW - Humans KW - Phalloidine -- analysis KW - Microscopy, Electron KW - Vaccinia virus -- genetics KW - Vaccinia virus -- physiology KW - Vaccinia virus -- ultrastructure KW - Glycoproteins -- genetics KW - Actins -- analysis KW - Viral Envelope Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78940855?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=The+A34R+glycoprotein+gene+is+required+for+induction+of+specialized+actin-containing+microvilli+and+efficient+cell-to-cell+transmission+of+vaccinia+virus.&rft.au=Wolffe%2C+E+J%3BKatz%2C+E%3BWeisberg%2C+A%3BMoss%2C+B&rft.aulast=Wolffe&rft.aufirst=E&rft.date=1997-05-01&rft.volume=71&rft.issue=5&rft.spage=3904&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-25 N1 - Date created - 1997-04-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1976 May;18(2):636-43 [1271521] Virology. 1994 Oct;204(1):376-90 [8091668] J Virol. 1978 Jul;27(1):28-37 [691112] Virology. 1979 Oct 15;98(1):142-53 [573519] Exp Cell Res. 1981 Mar;132(1):81-7 [7193591] Virology. 1981 Sep;113(2):556-64 [7269254] J Virol. 1981 Sep;39(3):903-13 [7288920] J Virol. 1982 Nov;44(2):647-57 [6890583] Arch Virol. 1982;74(1):11-20 [6891579] Arch Virol. 1983;75(3):213-8 [6838377] J Electron Microsc (Tokyo). 1983;32(2):125-40 [6644226] J Virol. 1985 Sep;55(3):651-9 [4020961] Virology. 1986 Apr 30;150(2):451-62 [3008418] J Virol. 1986 Jun;58(3):757-64 [3701927] Virology. 1990 Apr;175(2):372-84 [2183466] Virology. 1990 Sep;178(1):81-91 [2389560] J Virol. 1990 Oct;64(10):4884-92 [2398531] J Virol. 1991 Jul;65(7):3598-606 [2041086] J Virol. 1991 Sep;65(9):4598-608 [1870190] J Virol. 1991 Nov;65(11):5910-20 [1920620] J Virol. 1991 Nov;65(11):6101-10 [1920628] Virology. 1992 Mar;187(1):251-60 [1736527] J Virol. 1992 Mar;66(3):1610-21 [1738204] Virology. 1992 Jun;188(2):801-10 [1585649] J Virol. 1992 Jul;66(7):4170-9 [1602540] J Virol. 1992 Dec;66(12):7217-24 [1433514] J Cell Biol. 1993 May;121(3):521-41 [8486734] J Virol. 1993 Jun;67(6):3319-25 [8497053] Virology. 1993 Jun;194(2):627-37 [8503178] J Virol. 1993 Aug;67(8):4732-41 [8331727] Virology. 1995 Aug 1;211(1):53-63 [7645236] Virology. 1995 Oct 20;213(1):19-27 [7483262] Nature. 1995 Dec 7;378(6557):636-8 [8524400] J Virol. 1996 Jan;70(1):272-81 [8523536] J Virol. 1996 May;70(5):2797-808 [8627754] J Virol. 1996 Jun;70(6):3753-62 [8648710] Curr Biol. 1996 May 1;6(5):504-7 [8805268] J Cell Sci. 1996 Jul;109 ( Pt 7):1739-47 [8832396] J Virol. 1997 Apr;71(4):3178-87 [9060681] J Biophys Biochem Cytol. 1961 Aug;10:475-503 [13719413] Virology. 1976 Aug;73(1):43-58 [960564] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Scrapie infectivity correlates with converting activity, protease resistance, and aggregation of scrapie-associated prion protein in guanidine denaturation studies. AN - 78908577; 9094691 AB - Denaturation studies with guanidine HCl (GdnHCl) were performed to test the relationship between scrapie infectivity and properties of scrapie-associated prion protein (PrP(Sc)). Large GdnHCl-induced reductions in infectivity were associated with the irreversible elimination of both the proteinase K resistance and apparent self-propagating converting activity of PrP(Sc). In intermediate GdnHCl concentrations that stimulate converting activity and partially disaggregate PrP(Sc), both scrapie infectivity and converting activity were associated with residual partially protease-resistant multimers of PrP(Sc). JF - Journal of virology AU - Caughey, B AU - Raymond, G J AU - Kocisko, D A AU - Lansbury, P T AD - Laboratory of Persistent Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana 59840, USA. Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 4107 EP - 4110 VL - 71 IS - 5 SN - 0022-538X, 0022-538X KW - Guanidines KW - 0 KW - PrPSc Proteins KW - Endopeptidase K KW - EC 3.4.21.64 KW - Guanidine KW - JU58VJ6Y3B KW - Index Medicus KW - Endopeptidase K -- pharmacology KW - Animals KW - Protein Denaturation KW - Mesocricetus KW - Cricetinae KW - PrPSc Proteins -- drug effects KW - PrPSc Proteins -- toxicity KW - Guanidines -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78908577?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Scrapie+infectivity+correlates+with+converting+activity%2C+protease+resistance%2C+and+aggregation+of+scrapie-associated+prion+protein+in+guanidine+denaturation+studies.&rft.au=Caughey%2C+B%3BRaymond%2C+G+J%3BKocisko%2C+D+A%3BLansbury%2C+P+T&rft.aulast=Caughey&rft.aufirst=B&rft.date=1997-05-01&rft.volume=71&rft.issue=5&rft.spage=4107&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-25 N1 - Date created - 1997-04-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1967 Sep 2;215(5105):1043-4 [4964084] Cell. 1993 Jun 18;73(6):1055-8 [8513491] Protein Sci. 1993 Dec;2(12):2206-16 [7905316] Ann N Y Acad Sci. 1994 Jun 6;724:282-9 [8030948] Nature. 1994 Aug 11;370(6489):471-4 [7913989] J Biol Chem. 1995 Feb 17;270(7):3299-305 [7852415] Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):3923-7 [7732006] Proc Natl Acad Sci U S A. 1995 May 23;92(11):5124-8 [7761460] Nature. 1995 Jun 22;375(6533):698-700 [7791905] FEBS Lett. 1996 Jun 24;389(1):3-11 [8682199] Biochemistry. 1996 Oct 15;35(41):13434-42 [8873612] Chem Biol. 1995 Jan;2(1):1-5 [9383397] Cell. 1983 Nov;35(1):57-62 [6414721] Nature. 1983 Dec 1-7;306(5942):476-8 [6685822] J Virol. 1987 Dec;61(12):3688-93 [2446004] J Neuroimmunol. 1988 Dec;20(2-3):95-110 [3143742] J Virol. 1989 Mar;63(3):1212-22 [2492609] Proc Natl Acad Sci U S A. 1990 Aug;87(16):6373-7 [1974720] Proc Natl Acad Sci U S A. 1990 Sep;87(18):7240-4 [2119503] J Virol. 1991 Jul;65(7):3667-75 [1710287] Science. 1991 Jun 14;252(5012):1515-22 [1675487] Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):1-5 [8419912] J Biol Chem. 1993 Sep 25;268(27):20276-84 [8104185] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Extracting protein alignment models from the sequence database. AN - 19500160; 8729064 AB - Biologists often gain structural and functional insights into a protein sequence by constructing a multiple alignment model of the family. Here a program called Probe fully automates this process of model construction starting from a single sequence. Central to this program is a powerful new method to locate and align only those, often subtly, conserved patterns essential to the family as a whole. When applied to randomly chosen proteins, Probe found on average about four times as many relationships as a pairwise search and yielded many new discoveries. These include: an obscure subfamily of globins in the roundworm Caenorhabditis elegans ; two new superfamilies of metallohydrolases; a lipoyl/biotin swinging arm domain in bacterial membrane fusion proteins; and a DH domain in the yeast Bud3 and Fus2 proteins. By identifying distant relationships and merging families into superfamilies in this way, this analysis further confirms the notion that proteins evolved from relatively few ancient sequences. Moreover, this method automatically generates models of these ancient conserved regions for rapid and sensitive screening of sequences. JF - Nucleic Acids Research AU - Neuwald, A F AU - Liu, J S AU - Lipman, D J AU - Lawrence, C E AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA, neuwald@ncbi.nlm.nih.gov Y1 - 1997/05/01/ PY - 1997 DA - 1997 May 01 SP - 1665 EP - 1677 PB - Oxford University Press, Oxford Journals, Great Clarendon Street VL - 25 IS - 9 SN - 0305-1048, 0305-1048 KW - Microbiology Abstracts B: Bacteriology; Microbiology Abstracts C: Algology, Mycology & Protozoology; Biochemistry Abstracts 2: Nucleic Acids KW - Computer programs KW - Databases KW - Automate KW - Structure-function relationships KW - Membrane fusion KW - Caenorhabditis elegans KW - Probes KW - Membrane proteins KW - Biotin KW - Models KW - Amino acid sequence KW - J 02310:Genetics & Taxonomy KW - K 03300:Methods KW - N 14810:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19500160?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+Acids+Research&rft.atitle=Extracting+protein+alignment+models+from+the+sequence+database.&rft.au=Neuwald%2C+A+F%3BLiu%2C+J+S%3BLipman%2C+D+J%3BLawrence%2C+C+E&rft.aulast=Neuwald&rft.aufirst=A&rft.date=1997-05-01&rft.volume=25&rft.issue=9&rft.spage=1665&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-12-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Databases; Computer programs; Membrane fusion; Structure-function relationships; Probes; Membrane proteins; Biotin; Amino acid sequence; Models; Automate; Caenorhabditis elegans ER - TY - JOUR T1 - Isolation and characterization of new anti-HIV and cytotoxic leads from plants, marine, and microbial organisms AN - 16223415; 4218603 AB - New cytotoxic isomalabaricane triterpenes have been isolated from a sponge Stelletta sp. (1-7); anti-HIV pterocarpans (8 and 9) and isoflavanoids (12-16 and 18) were elucidated from two tropical plants in the genus Erythrina; and anti-HIV enniatins (20 and 22-23) were characterized from fungi in the genera Fusarium and Alternaria. The enniatins were evaluated for in vivo anti-HIV activity in the hollow fiber assay. JF - Journal of Natural Products AU - McKee, T C AU - Bokesch, H R AU - McCormick, J L AU - Rashid, MA AU - Spielvogel, D AU - Gustafson, K R AU - Alavanja, M M AU - Cardellina, JH II AU - Boyd, M R AD - Laboratory of Drug Discovery Research and Development, Developmental Therapeutics Program, Division of Cancer Treatment, Diagnosis and Centers, National Cancer Institute, Frederick, Maryland 21702-1201, USA Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 431 EP - 438 VL - 60 IS - 5 SN - 0163-3864, 0163-3864 KW - Alternaria KW - Erythrina KW - antiviral agents KW - enniatins KW - fusarium KW - human immunodeficiency virus KW - isoflavanoids KW - isomalabaricane triterpenes KW - pterocarpans KW - stelletta KW - Biotechnology and Bioengineering Abstracts; ASFA Marine Biotechnology Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - V 22002:AIDS: Molecular and in vitro aspects KW - A 01068:Antiviral & viricidal KW - Q4 27380:Pharmaceuticals KW - W3 33372:Antiviral agents KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16223415?accountid=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+Natural+Products&rft.atitle=Isolation+and+characterization+of+new+anti-HIV+and+cytotoxic+leads+from+plants%2C+marine%2C+and+microbial+organisms&rft.au=McKee%2C+T+C%3BBokesch%2C+H+R%3BMcCormick%2C+J+L%3BRashid%2C+MA%3BSpielvogel%2C+D%3BGustafson%2C+K+R%3BAlavanja%2C+M+M%3BCardellina%2C+JH+II%3BBoyd%2C+M+R&rft.aulast=McKee&rft.aufirst=T&rft.date=1997-05-01&rft.volume=60&rft.issue=5&rft.spage=431&rft.isbn=&rft.btitle=&rft.title=Journal+of+Natural+Products&rft.issn=01633864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Relative mutagenicities of gaseous nitrogen oxides in the supF gene of pSP189 AN - 16086790; 4112141 AB - Gaseous nitric oxide (NO), an environmental pollutant found in cigarette smoke and diesel exhaust, has been shown to generate mutations in aerobic in vitro assays. The objective of this study was to identify which oxides of nitrogen, formed in the gaseous phase from NO, possess mutagenic activity. Samples of the plasmid pSP189, in 1 M HEPES buffer, pH 7.4, were exposed to preparations of nitrogen dioxide (NO sub(2)), dinitrogen trioxide (N sub(2)O sub(3)) or an air control. The gas mixtures were formed in a gas-tight syringe and were then introduced into 1 l flasks. The plasmid solution was introduced immediately afterwards. Transformation of Escherichia coli strain MBM7070 with the treated plasmids allowed analysis of mutation frequencies and the types of mutations induced in the target supF gene. The mutation frequency resulting from NO sub(2) exposure was not different from that of the control. However, N sub(2)O sub(3) produced a substantial number of mutations. The mutation frequency and the types of mutations were found to depend on the length of time that the gases were allowed to incubate in the syringe prior to introduction into the 1 l flasks (mutation frequency was maximal at similar to 2 min). The most prevalent mutations were AT arrow right GC transitions (68%), followed by GC arrow right AT transitions (30%), similar to previous findings when pure NO was bubbled through pSP189 solutions. These results suggest that it is N sub(2)O sub(3), rather than NO sub(2), that is the most likely source of mutagenic potential from gaseous nitrogen oxides. JF - Carcinogenesis AU - Kelman, D J AU - Christodoulou, D AU - Wink, DA AU - Keefer, L K AU - Srinivasan, A AU - Dipple, A AD - Chemistry of Carcinogenesis Laboratory, ABL-Basic Research Program and NCI Laboratory of Comparative Carcinogenesis, NCI-Frederick Cancer Research and Development Center, Frederick, MD 21702, USA Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 1045 EP - 1048 VL - 18 IS - 5 SN - 0143-3334, 0143-3334 KW - nitrogen oxides KW - plasmid pSP189 KW - supF gene KW - Toxicology Abstracts KW - Escherichia coli KW - mutagenicity KW - X 24155:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16086790?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Relative+mutagenicities+of+gaseous+nitrogen+oxides+in+the+supF+gene+of+pSP189&rft.au=Kelman%2C+D+J%3BChristodoulou%2C+D%3BWink%2C+DA%3BKeefer%2C+L+K%3BSrinivasan%2C+A%3BDipple%2C+A&rft.aulast=Kelman&rft.aufirst=D&rft.date=1997-05-01&rft.volume=18&rft.issue=5&rft.spage=1045&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; mutagenicity ER - TY - JOUR T1 - Sequence changes at the V-D junction of the V sub(H)1 heavy chain of anti-phosphocholine antibodies alter binding to and protection against Streptococcus pneumoniae AN - 16074777; 4111889 AB - X-linked immune deficient (Xid) mice fail to produce anti-phosphocholine (PC) antibodies even after immunization with Streptococcus pneumoniae. Consequently, Xid mice are extremely susceptible to infection with S. pneumoniae. PC-specific B cells appear to undergo clonal deletion in Xid mice; however, a new thymus-dependent form of PC, 6-(O-phosphocholine)hydroxyhexanoate (EPC), can rescue PC-specific B cells from the bone marrow presumably by providing T cell help before clonal deletion. Analysis of PC-specific IgG hybridomas from Xid mice revealed utilization of several V-D junctional variants of the V sub(H)1 gene segment rearranged to different D and J sub(H) gene segments. The majority of Xid anti-PC antibodies exhibit an Asp arrow right Gly95H replacement at the V-D junction. These Gly95H V sub(H)1 variants associate with Kappa 1C L chains to produce anti-PC antibodies that: (i) have low relative affinity for PC, (ii) are heteroclitic for nitrophenylphosphocholine and (iii) fail to bind to or provide protection against S. pneumoniae. Single prototypic V-D variants of the T15 idiotype (Asp95H), M603 idiotype (Asn95H) and M167 idiotype (Asp95H-Ala96H) were also induced in Xid mice. The M603-like and M167-like antibodies bound to and protected against S. pneumoniae even though they exhibited K sub(a)s for PC which were lower than T15 idiotype super(+) antibodies. These data demonstrate that small changes in the V-D junctional sequence of the T15 (V sub(H)1) heavy chain alter L chain usage and the structure of the PC binding site so that the PC expressed on S. pneumoniae is no longer recognized. JF - International Immunology AU - Guo, Wei-Xing AU - Burger, A M AU - Fischer, R T AU - Sieckmann, D G AU - Longo, D L AU - Kenny, J J AD - National Institutes of Health, National Institute on Aging, Gerontology Research Center, 4940 Eastern Avenue, Baltimore, MD 21224, USA Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 665 EP - 677 VL - 9 IS - 5 SN - 0953-8178, 0953-8178 KW - Xid mice KW - heavy chains KW - variable region KW - phosphocholine KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Streptococcus pneumoniae KW - antibody response KW - J 02833:Immune response and immune mechanisms KW - F 06065:Genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16074777?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Immunology&rft.atitle=Sequence+changes+at+the+V-D+junction+of+the+V+sub%28H%291+heavy+chain+of+anti-phosphocholine+antibodies+alter+binding+to+and+protection+against+Streptococcus+pneumoniae&rft.au=Guo%2C+Wei-Xing%3BBurger%2C+A+M%3BFischer%2C+R+T%3BSieckmann%2C+D+G%3BLongo%2C+D+L%3BKenny%2C+J+J&rft.aulast=Guo&rft.aufirst=Wei-Xing&rft.date=1997-05-01&rft.volume=9&rft.issue=5&rft.spage=665&rft.isbn=&rft.btitle=&rft.title=International+Immunology&rft.issn=09538178&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Streptococcus pneumoniae; antibody response ER - TY - JOUR T1 - Evaluation of monoclonal antibodies to human immunodeficiency virus type 1 primary isolates by neutralization assays: Performance criteria for selecting candidate antibodies for clinical trials AN - 16073755; 4108742 AB - A collaborative study was organized to identify monoclonal antibodies (MAbs) that may be broadly and potently neutralizing for a panel of human immunodeficiency virus type 1 (HIV-1) low-passaged adult and pediatric primary isolates in peripheral blood mononuclear cells. Five laboratories evaluated a coded panel of seven human MAbs to HIV-1 subtype B envelope V3, CD4 binding region, gp41, and other conformationally sensitive determinants. Each laboratory measured neutralizing activity of the MAbs against the laboratory isolate HIV sub(MN) and a panel of 9 subtype B primary isolates. Antibodies were classified as suitable candidates for future clinical studies if they could neutralize at least half of the 9 primary isolates at a concentration of less than or equal to 25 mu g/mL for 90% viral inhibition. The study identified three MAbs that met stated performance criteria: IgG1b12, 2G12, and 2F5. These results may provide a rationale for examining the clinical efficacy, either singly or in combination, of the three MAbs. JF - Journal of Infectious Diseases AU - D'Souza, M P AU - Livnat, D AU - Bradac, JA AU - Bridges, SH AD - Div. AIDS, NIAID, 6003 Executive Blvd. Rm. 2C35, Rockville, MD 20852, USA Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 1056 EP - 1062 VL - 175 IS - 5 SN - 0022-1899, 0022-1899 KW - Human immunodificiency virus KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts; Virology & AIDS Abstracts KW - neutralization KW - human immunodeficiency virus KW - monoclonal antibodies KW - W3 33375:Antibodies KW - F 06711:Monoclonal antibodies, hybridomas, antigens and antisera KW - V 22003:AIDS: Immunological aspects KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16073755?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Infectious+Diseases&rft.atitle=Evaluation+of+monoclonal+antibodies+to+human+immunodeficiency+virus+type+1+primary+isolates+by+neutralization+assays%3A+Performance+criteria+for+selecting+candidate+antibodies+for+clinical+trials&rft.au=D%27Souza%2C+M+P%3BLivnat%2C+D%3BBradac%2C+JA%3BBridges%2C+SH&rft.aulast=D%27Souza&rft.aufirst=M&rft.date=1997-05-01&rft.volume=175&rft.issue=5&rft.spage=1056&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - neutralization; monoclonal antibodies; human immunodeficiency virus ER - TY - JOUR T1 - The ability of activated clay for the adsorption of dyes from aqueous solutions AN - 16054529; 4102476 AB - A low-cost inorganic acid-activated clay was used as adsorbent for the adsorption of six dyes (two basic, one acidic, one disperse, one direct dye, and one reactive) from aqueous solutions. The adsorption capacity was comparatively high for basic dyes and was lower for disperse, direct, and reactive dyes. The equilibrium data could be well described by the Langmuir equation over the entire range of concentration (50 similar to 500 mg dm super(-3)). In addition, the effect of temperature on the adsorption was examined and the thermodynamic data were determined. Based on the adsorption capacity only, it was generally shown that activated clay was more effective compared to other commonly used adsorbents. JF - Environmental Technology AU - Juang, R S AU - Wu, F C AU - Tseng, R L AD - Dep. Chem. Eng., Yuan-Ze Inst. Technol., Nei-Li, Taoyuan 320, Taiwan Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 525 EP - 531 VL - 18 IS - 5 SN - 0959-3330, 0959-3330 KW - clay KW - industrial effluents KW - clays KW - industrial wastewater KW - Water Resources Abstracts; Pollution Abstracts KW - color removal KW - wastewater treatment KW - adsorption KW - dyes KW - thermodynamics KW - P 3000:SEWAGE & WASTEWATER TREATMENT KW - SW 3040:Wastewater treatment processes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16054529?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Apollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Technology&rft.atitle=The+ability+of+activated+clay+for+the+adsorption+of+dyes+from+aqueous+solutions&rft.au=Juang%2C+R+S%3BWu%2C+F+C%3BTseng%2C+R+L&rft.aulast=Juang&rft.aufirst=R&rft.date=1997-05-01&rft.volume=18&rft.issue=5&rft.spage=525&rft.isbn=&rft.btitle=&rft.title=Environmental+Technology&rft.issn=09593330&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 - color removal; dyes; adsorption; thermodynamics; wastewater treatment; clays; industrial wastewater; clay; industrial effluents ER - TY - JOUR T1 - Temporal production of streptococcal erythrogenic toxin B (streptococcal cysteine proteinase) in response to nutrient depletion AN - 16006249; 4082997 AB - The effects of various growth conditions on the production of streptococcal erythrogenic toxin B (streptococcal pyrogenic exotoxin B [SPE B]) by Streptococcus pyogenes were analyzed. SPE B was detected in broth culture supernatant fluid only during the stationary phase of growth when glucose and other potential carbon sources were depleted from the medium. Additionally, SPE B production was inhibited when the concentration of glucose in the medium was maintained. These results suggest that SPE B is secreted under conditions of starvation and may be involved in nutrient acquisition. JF - Infection and Immunity AU - Chaussee AU - Phillips, E R AU - Ferretti, J J AD - Lab. Microbial Struct. and Function, Rocky Mountain Labs., NIAID, NIH, Hamilton, MT 59840, USA Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 1956 EP - 1959 VL - 65 IS - 5 SN - 0019-9567, 0019-9567 KW - cysteine proteinase KW - erythrogenic toxin B KW - Toxicology Abstracts; Microbiology Abstracts B: Bacteriology KW - starvation KW - exotoxins KW - nutrient deficiency KW - Streptococcus pyogenes KW - J 02822:Biosynthesis and physicochemical properties KW - X 24171:Microbial UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16006249?accountid=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=Temporal+production+of+streptococcal+erythrogenic+toxin+B+%28streptococcal+cysteine+proteinase%29+in+response+to+nutrient+depletion&rft.au=Chaussee%3BPhillips%2C+E+R%3BFerretti%2C+J+J&rft.aulast=Chaussee&rft.aufirst=&rft.date=1997-05-01&rft.volume=65&rft.issue=5&rft.spage=1956&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 - Streptococcus pyogenes; exotoxins; nutrient deficiency; starvation ER - TY - JOUR T1 - Interaction of MutS protein with the major and minor grooves of a heteroduplex DNA AN - 15975116; 4070360 AB - Thermus aquaticus MutS protein is a DNA mismatch repair protein that recognizes and binds to heteroduplex DNAs containing mispaired or unpaired bases. Using enzymatic and chemical probe methods, we have examined the binding of Taq MutS protein to a heteroduplex DNA having a single unpaired thymidine residue. DNase I footprinting identifies a symmetrical region of protection 24-28 nucleotides long centered on the unpaired base. Methylation protection and interference studies establish that Taq MutS protein makes contacts with the major groove of the heteroduplex in the immediate vicinity of the unpaired base. Hydroxyl radical and 1,10-phenanthroline-copper footprinting experiments indicate that MutS also interacts with the minor groove near the unpaired base. Together with the identification of key phosphate groups detected by ethylation interference, these data reveal critical contact points residing in the major and minor grooves of the heteroduplex DNA. JF - Journal of Biological Chemistry AU - Biswas, I AU - Hsieh, P AD - National Institutes of Health, Bldg. 10 Room 9D04, 10 Center Dr. MSC 1810, Bethesda, MD 20892-1810, USA Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 13355 EP - 13364 VL - 272 IS - 20 SN - 0021-9258, 0021-9258 KW - DNA KW - MutS protein KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Thermus aquaticus KW - DNA repair KW - J 02725:DNA KW - N 14652:DNA repair UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15975116?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Interaction+of+MutS+protein+with+the+major+and+minor+grooves+of+a+heteroduplex+DNA&rft.au=Biswas%2C+I%3BHsieh%2C+P&rft.aulast=Biswas&rft.aufirst=I&rft.date=1997-05-01&rft.volume=272&rft.issue=20&rft.spage=13355&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Thermus aquaticus; DNA repair; DNA ER - TY - JOUR T1 - Reverse gyrase from Methanopyrus kandleri: Reconstitution of an active extremozyme from its two recombinant subunits AN - 15974980; 4070356 AB - Reverse gyrases are ATP-dependent type I 5'-topoisomerases that positively supercoil DNA. Reverse gyrase from Methanopyrus kandleri is unique as the first heterodimeric type I 5'-topoisomerase described, consisting of a 138-kDa subunit involved in the hydrolysis of ATP (RgyB) and a 43-kDa subunit that forms the covalent complex with DNA during the topoisomerase reaction (RgyA). Here we report the reconstitution of active reverse gyrase from the two recombinant proteins over-expressed in Escherichia coli. Both proteins have been purified by column chromatography to >90% homogeneity. RgyB has a DNA-dependent ATPase activity at high temperature (80 degree C) and is independent of the presence of RgyA. RgyA alone has no detectable activity. The addition of RgyA to RgyB reconstitutes positive supercoiling activity, but the RgyB and RgyA subunits form a stable heterodimer only after being heated together. This is the first case in which it has been possible to reconstitute an active heterodimeric enzyme of a hyperthermophilic prokaryote from recombinant proteins. JF - Journal of Biological Chemistry AU - Krah, R AU - O'Dea, M H AU - Gellert, M AD - Laboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892-0540, USA Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 13986 EP - 13990 VL - 272 IS - 21 SN - 0021-9258, 0021-9258 KW - DNA KW - ATP KW - RgyB protein KW - RgyA protein KW - reverse gyrase KW - adenosinetriphosphatase KW - DNA topoisomerase KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Methanopyrus kandleri KW - J 02725:DNA KW - N 14731:DNA-unwinding enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15974980?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Reverse+gyrase+from+Methanopyrus+kandleri%3A+Reconstitution+of+an+active+extremozyme+from+its+two+recombinant+subunits&rft.au=Krah%2C+R%3BO%27Dea%2C+M+H%3BGellert%2C+M&rft.aulast=Krah&rft.aufirst=R&rft.date=1997-05-01&rft.volume=272&rft.issue=21&rft.spage=13986&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Methanopyrus kandleri; DNA ER - TY - JOUR T1 - Genotoxicity and mitochondrial damage in human lymphocytic cells chronically exposed to 3'-azido-2',3'-dideoxythymidine AN - 15934438; 4053360 AB - AZT (3'-azido-2',3'-dideoxythymidine), the first nucleoside analog approved for the treatment of AIDS (acquired immunodeficiency syndrome), induces significant toxic effects in humans exposed to therapeutic doses. As an inhibitor of the HIV-1 (human immunodeficiency virus 1) reverse transcriptase, AZT blocks the incorporation of nucleotides into the host's newly synthesized DNA. Incorporation of AZT into mammalian DNA as well as specific localization of the drug into telomeric DNA, has been previously documented by immunohistochemistry. As with other nucleoside analogs, AZT has affinity for polymerase- gamma , the enzyme responsible for the replication of mitochondrial DNA. In order to examine the mechanisms of toxic events induced by long-term AZT exposure, human T-lymphocytic H9 cells were cultured with 25 mu M AZT for 7 months. In the resulting H9-AZT cells, incorporation of AZT into DNA was demonstrated by radioimmunoassay and immunohistochemistry, chromosomal aberrations and micronuclei were scored and intracellular lipid distribution was determined. Two pmol of AZT per microgram of DNA were detected by radioimmunoassay in H9-AZT cells. Control cells showed negative values in the radioimmunoassay. Cytogenetic observations on H9-AZT cells showed an increase in chromosomal aberrations and nuclear fragmentation when compared with unexposed H9 cells. Electron microscopy revealed mitochondrial damage and an elevated accumulation of neutral intracellular lipid deposits probably as a consequence of a distortion in the beta -oxidation of fatty acids normally carried out by this organelle. The toxicities explored here suggest that the mechanisms of AZT induced cytotoxicity in bone marrow of the patients chronically exposed to the drug in vivo may involve both chromosomal and mitochondrial DNA damage. JF - Mutation Research-Genetic Toxicology and Environmental Mutagenesis AU - Agarwal, R P AU - Olivero, O A AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, NIH, Bethesda, MD 20892, USA Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 223 EP - 231 PB - ELSEVIER SCIENCE B.V. VL - 390 IS - 3 SN - 1383-5718, 1383-5718 KW - radioimmunoassay KW - lymphocytes T KW - man KW - mitochondria KW - lipids KW - DNA KW - zidovudine KW - Genetics Abstracts; Toxicology Abstracts KW - antiviral agents KW - genotoxicity KW - chromosome aberrations KW - micronuclei KW - X 24117:Biochemistry KW - G 07221:Specific chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15934438?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+Research-Genetic+Toxicology+and+Environmental+Mutagenesis&rft.atitle=Genotoxicity+and+mitochondrial+damage+in+human+lymphocytic+cells+chronically+exposed+to+3%27-azido-2%27%2C3%27-dideoxythymidine&rft.au=Agarwal%2C+R+P%3BOlivero%2C+O+A&rft.aulast=Agarwal&rft.aufirst=R&rft.date=1997-05-01&rft.volume=390&rft.issue=3&rft.spage=223&rft.isbn=&rft.btitle=&rft.title=Mutation+Research-Genetic+Toxicology+and+Environmental+Mutagenesis&rft.issn=13835718&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 - genotoxicity; mitochondria; antiviral agents; DNA; chromosome aberrations; micronuclei; lipids ER - TY - JOUR T1 - Aromatic amine DNA adduct formation in chronically-exposed mice: Considerations for human comparison AN - 15930254; 4053316 AB - Lifetime chronic exposure of mice to the aromatic amines 4-aminobiphenyl (ABP) and 2-acetylaminofluorene (AAF) produces liver and urinary bladder tumors. In parallel experiments, DNA adduct levels in target tissues reach a steady-state (a balance between adduct formation and removal) after about four weeks of either AAF or ABP ingestion. For these and other carcinogens, steady-state DNA adduct levels most frequently increase linearly with dose, but the formation of tumors also depends upon a variety of factors, including the proliferative capacity of the target tissue, the sex of the animal, genotoxic properties of the specific adducts formed, and other unknown events. Chronic dosing experiments in animal models are of interest for human risk assessment because human exposure is typically intermittent, involving repeated exposures. However, it is to be expected that in a genetically-diverse human population, where the lifetime averages >70 years, the relationship between tumorigenesis and DNA adduct formation will be relatively more complex than that observed in mice. From our studies of chronic ABP exposure in male mice, we have obtained the daily dose of ABP and the steady-state level of N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-ABP) adduct associated with a 50% mouse bladder tumor incidence. Our attempt at a human extrapolation for adducts and urinary bladder cancer in smoking males (20-40 cigarettes/day) is based on the ABP dose per cigarette, values for the dG-C8-ABP adduct in bladder biopsies of lifetime heavy smokers at age similar to 70, and the smoking-related bladder tumor incidence (absolute lifetime risk) for Caucasian males in the United States aged 65-84 years. The extrapolation has produced two major predictions, one related to adduct formation and the other related to tumorigenesis. First, the observed level of smoking-related dG-C8-ABP in DNA of human bladder epithelium, expressed as a function of daily ABP intake, is about 3500-times higher than similar data for mice, which suggests that humans may perform the biotransformation of ABP more efficiently than mice. Second, at a similar bladder tumor incidence, mouse bladder contained adduct concentrations that were much higher than those observed in human bladder; for example, at a 2.6% tumor incidence, mouse bladder contained an average of 55.5 fmol dG-C8-ABP/ mu g DNA (1850 adducts/108 nucleotides), while bladders from Caucasian male smokers contained an average of 0.036 fmol dG-C8-ABP/ mu g DNA (1.2 adducts/108 nucleotides). This suggests that factors other than ABP-DNA adducts, such as adducts of other carcinogens, the influence of promoters and synergistic effects of all of these factors contribute substantially to smoking-related bladder cancer in humans. JF - Mutation Research AU - Poirier, M C AU - Beland, F A AD - National Cancer Institute, Bldg. 37 Rm. 3B25, MSC-4255, 37 Convent Drive, NIH, Bethesda, MD 20892-4255, USA Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 177 EP - 184 PB - ELSEVIER SCIENCE B.V. VL - 376 IS - 1-2 SN - 0027-5107, 0027-5107 KW - mice KW - man KW - aromatic amines KW - p-biphenylamine KW - N-2-fluorenylacetamide KW - urinary bladder carcinoma KW - Toxicology Abstracts; Genetics Abstracts KW - DNA adducts KW - cigarette smoking KW - aromatic compounds KW - X 24200:Nitrosamines & related compounds KW - G 07221:Specific chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15930254?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+Research&rft.atitle=Aromatic+amine+DNA+adduct+formation+in+chronically-exposed+mice%3A+Considerations+for+human+comparison&rft.au=Poirier%2C+M+C%3BBeland%2C+F+A&rft.aulast=Poirier&rft.aufirst=M&rft.date=1997-05-01&rft.volume=376&rft.issue=1-2&rft.spage=177&rft.isbn=&rft.btitle=&rft.title=Mutation+Research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - DNA adducts; cigarette smoking; aromatic compounds ER - TY - JOUR T1 - Metabolism of food-derived heterocyclic amines in nonhuman primates AN - 15926093; 4053319 AB - During the cooking of meats, several highly mutagenic heterocyclic amines (HCAs) are produced. Three HCAs, IQ, MeIQx, and PhIP have been under study for carcinogenicity in cynomolgus monkeys, and to date, IQ has been shown to be a potent hepatocarcinogen. Concomitantly, the metabolic processing of these HCAs has been examined. Metabolism studies show that the potent hepatocarcinogenicity of IQ is associated with the in vivo metabolic activation of IQ via N-hydroxylation and the formation of DNA adducts. In monkeys undergoing carcinogen bioassay with IQ, N-hydroxylation was confirmed by the presence of the N-hydroxy-N-glucuronide conjugate of IQ in urine. The N-hydroxylation of IQ appears to be carried out largely by hepatic CYP3A4 and/or CYP2C9/10, and not by CYP1A2, an isoform not expressed in liver of this species. Notably MeIQx is poorly activated in cynomolgus monkeys and lacks the potency of IQ to induce hepatocellular carcinoma after a 5-year dosing period. The poor activation of MeIQx appears to be due to the lack of constitutive expression of CYP1A2 and an inability of other cytochromes P450, such as CYP3A4 and CYP2C9/10, to N-hydroxylate the quinoxalines. MeIQx is detoxified in monkeys largely by conjugation with glucuronide at the N-1 position. Although the carcinogenicity of PhIP is not yet known, the metabolic data suggest that PhIP will be carcinogenic in this species. PhIP is metabolically activated in vivo in monkeys by N-hydroxylation, as discerned by the presence of the N-hydroxy-N-glucuronide conjugate in urine, bile, and plasma. PhIP also produces DNA adducts that are widely distributed in tissues. The results from these studies support the importance of N-hydroxylation in the carcinogenicity of HCAs in nonhuman primates and by analogy, the importance of this metabolic activation step in the possible carcinogenicity of dietary HCAs in humans. JF - Mutation Research AU - Snyderwine, E G AU - Turesky, R J AU - Turteltaub, K W AU - Davis, C D AU - Sadrieh, N AU - Schut, HAJ AU - Nagao, M AU - Sugimura, T AU - Thorgeirsson, U P AU - Adamson, R H AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, Building 37, Room 3C28, National Cancer Institute, Bethesda, MD 20892-4255, USA Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 203 EP - 210 PB - ELSEVIER SCIENCE B.V. VL - 376 IS - 1-2 SN - 0027-5107, 0027-5107 KW - heterocyclic amines KW - CYP1A2 gene KW - CYP3A4 gene KW - Genetics Abstracts; Toxicology Abstracts KW - DNA adducts KW - metabolism KW - gene expression KW - X 24120:Food, additives & contaminants KW - G 07221:Specific chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15926093?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+Research&rft.atitle=Metabolism+of+food-derived+heterocyclic+amines+in+nonhuman+primates&rft.au=Snyderwine%2C+E+G%3BTuresky%2C+R+J%3BTurteltaub%2C+K+W%3BDavis%2C+C+D%3BSadrieh%2C+N%3BSchut%2C+HAJ%3BNagao%2C+M%3BSugimura%2C+T%3BThorgeirsson%2C+U+P%3BAdamson%2C+R+H%3BThorgeirsson%2C+S+S&rft.aulast=Snyderwine&rft.aufirst=E&rft.date=1997-05-01&rft.volume=376&rft.issue=1-2&rft.spage=203&rft.isbn=&rft.btitle=&rft.title=Mutation+Research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - DNA adducts; gene expression; metabolism ER - TY - JOUR T1 - Exposure assessment of heterocyclic amines (HCAs) in epidemiologic studies AN - 15925768; 4053318 AB - The carcinogenic potential of heterocyclic amines (HCAs) in humans has yet to be established. Epidemiologic studies of colon cancer using crude surrogates for HCAs exposure (e.g., doneness of meat) have produced inconsistent results. To improve exposure assessment of HCAs, we have developed a database of HCA concentrations in commonly consumed meat items cooked by various techniques and degrees of doneness. HCA type and level are dependent on multiple factors, including type of meat (e.g., steak, chicken, bacon), cooking technique (with substantial variability present even within high temperature cooking methods), place of preparation (e.g., home, restaurant, or `fast-food' restaurant), as well as the degree of doneness and surface browning/charring. We have developed a questionnaire with meat photographs linked to this database, which we are using in a variety of case-control and cohort studies of cancer etiology. In addition, we have carried out a metabolic study of HCA exposure among 66 subjects to identify biomarkers of HCA exposure which may be useful in epidemiologic studies. These studies should help clarify the role of HCAs in human carcinogenesis, and eventually allow an estimation of the cancer burden in the population attributable to these compounds. JF - Mutation Research AU - Sinha, R AU - Rothman, N AD - Division of Cancer Epidemiology and Genetics, NCI, Rm. 443, EPN, 6130 Executive Blvd, Bethesda, MD 20892-7374, USA Y1 - 1997/05// PY - 1997 DA - May 1997 SP - 195 EP - 202 PB - ELSEVIER SCIENCE B.V. VL - 376 IS - 1-2 SN - 0027-5107, 0027-5107 KW - man KW - epidemiology KW - heterocyclic amines KW - colon cancer KW - Toxicology Abstracts KW - meat KW - X 24120:Food, additives & contaminants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15925768?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+Research&rft.atitle=Exposure+assessment+of+heterocyclic+amines+%28HCAs%29+in+epidemiologic+studies&rft.au=Sinha%2C+R%3BRothman%2C+N&rft.aulast=Sinha&rft.aufirst=R&rft.date=1997-05-01&rft.volume=376&rft.issue=1-2&rft.spage=195&rft.isbn=&rft.btitle=&rft.title=Mutation+Research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - meat ER - TY - JOUR T1 - The social, economic and political impact of the global HIV/AIDS epidemic AN - 1372060733; 18142970 AB - OBJECTIVES: This paper reviews the themes emerging from reports of the many social, economic and political effects of the HIV/AIDS epidemic on individuals, nations and the world. The impact of the global HIV/AIDS epidemic has been felt in every facet of society. APPROACH: The impact of the epidemic is described in five areas: (1) challenges and changes to traditional public health approaches to infectious diseases and sexually transmitted diseases; (2) adjustments to 'standard' clinical research and drug regulatory practices; (3) emphasis on the importance of personal behaviors and behavioral approaches in controlling the epidemic; (4) revealing the complexity of and recognizing the need to monitor the impacts of HIV/AIDS; and (5) highlighting the difficulties of, and need for, the international responsiveness to address HIV/AIDS. The oral health community's response to the epidemic is briefly described. CONCLUSIONS: Although in its second decade, the epidemic is still in its early stages of evolution. The challenges lie in the development and perpetual evolution of strategies to respond to the epidemic locally while thinking and acting globally. The international oral health community is one of many that has played and must continue to play an active role in a multi-disciplinary effort needed to curb this epidemic. JF - Oral Diseases AU - Kleinman, D V AD - National Institute of Dental Research, National Institutes of Health, Bethesda, MD, USA Y1 - 1997/05// PY - 1997 DA - May 1997 SP - S7 EP - S12 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 3 IS - S1 SN - 1354-523X, 1354-523X KW - Virology & AIDS Abstracts; Health & Safety Science Abstracts KW - Acquired immune deficiency syndrome KW - Epidemics KW - Sexually-transmitted diseases KW - Politics KW - Clinical trials KW - Public health KW - Infectious diseases KW - Human immunodeficiency virus KW - Reviews KW - Economics KW - Drugs KW - Sexually transmitted diseases KW - Evolution KW - International standardization KW - V 22360:AIDS and HIV KW - H 11000:Diseases/Injuries/Trauma UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1372060733?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oral+Diseases&rft.atitle=The+social%2C+economic+and+political+impact+of+the+global+HIV%2FAIDS+epidemic&rft.au=Kleinman%2C+D+V&rft.aulast=Kleinman&rft.aufirst=D&rft.date=1997-05-01&rft.volume=3&rft.issue=S1&rft.spage=S7&rft.isbn=&rft.btitle=&rft.title=Oral+Diseases&rft.issn=1354523X&rft_id=info:doi/10.1111%2Fj.1601-0825.1997.tb00378.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2013-06-01 N1 - Last updated - 2013-09-09 N1 - SubjectsTermNotLitGenreText - Acquired immune deficiency syndrome; Epidemics; Sexually-transmitted diseases; Infectious diseases; Economics; Drugs; Evolution; Public health; Politics; Human immunodeficiency virus; Reviews; Clinical trials; Sexually transmitted diseases; International standardization DO - http://dx.doi.org/10.1111/j.1601-0825.1997.tb00378.x ER - TY - JOUR T1 - Reduced RNA polymerase II transcription in intact and permeabilized Cockayne syndrome group B cells. AN - 78990927; 9113985 AB - Cockayne syndrome (CS) is characterized by increased photosensitivity, growth retardation, and neurological and skeletal abnormalities. The recovery of RNA synthesis is abnormally delayed in CS cells after exposure to UV radiation. Gene-specific repair studies have shown a defect in the transcription-coupled repair (TCR) of active genes in CS cells from genetic complementation groups A and B (CS-A and CS-B). We have analyzed transcription in vivo in intact and permeabilized CS-B cells. Uridine pulse labeling in intact CS-B fibroblasts and lymphoblasts shows a reduction of approximately 50% compared with various normal cells and with cells from a patient with xeroderma pigmentosum (XP) group A. In permeabilized CS-B cells transcription in chromatin isolated under physiological conditions is reduced to about 50% of that in normal chromatin and there is a marked reduction in fluorescence intensity in transcription sites in interphase nuclei. Transcription in CS-B cells is sensitive to alpha-amanitin, suggesting that it is RNA polymerase II-dependent. The reduced transcription in CS-B cells is complemented in chromatin by the addition of normal cell extract, and in intact cells by transfection with the CSB gene. CS-B may be a primary transcription deficiency. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Balajee, A S AU - May, A AU - Dianov, G L AU - Friedberg, E C AU - Bohr, V A AD - Laboratory of Molecular Genetics, National Institute on Aging, the National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 1997/04/29/ PY - 1997 DA - 1997 Apr 29 SP - 4306 EP - 4311 VL - 94 IS - 9 SN - 0027-8424, 0027-8424 KW - Amanitins KW - 0 KW - Chromatin KW - Nucleic Acid Synthesis Inhibitors KW - RNA Polymerase II KW - EC 2.7.7.- KW - Index Medicus KW - DNA Repair KW - Amanitins -- pharmacology KW - Humans KW - Hematopoietic Stem Cells -- cytology KW - Genetic Complementation Test KW - Lymphocytes -- cytology KW - Fibroblasts -- cytology KW - Cell Membrane Permeability KW - Chromatin -- genetics KW - Cell Line KW - RNA Polymerase II -- metabolism KW - Cockayne Syndrome -- genetics KW - Transcription, Genetic KW - Cockayne Syndrome -- enzymology KW - Cockayne Syndrome -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78990927?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Reduced+RNA+polymerase+II+transcription+in+intact+and+permeabilized+Cockayne+syndrome+group+B+cells.&rft.au=Balajee%2C+A+S%3BMay%2C+A%3BDianov%2C+G+L%3BFriedberg%2C+E+C%3BBohr%2C+V+A&rft.aulast=Balajee&rft.aufirst=A&rft.date=1997-04-29&rft.volume=94&rft.issue=9&rft.spage=4306&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-27 N1 - Date created - 1997-05-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Cell Biol. 1993 Jul;122(2):283-93 [8320255] Nature. 1993 May 13;363(6425):114-5 [8483493] Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10499-503 [8248136] Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1950-4 [8127913] Mutat Res. 1994 May;314(3):221-31 [7513055] EMBO J. 1995 Jan 16;14(2):360-7 [7835346] J Biol Chem. 1995 Jul 7;270(27):15915-8 [7608140] Cell. 1995 Aug 25;82(4):555-64 [7664335] Cell. 1996 Jan 26;84(2):235-44 [8565069] Biochemistry. 1996 Feb 20;35(7):2157-67 [8652557] J Biol Chem. 1996 Apr 12;271(15):8903-10 [8621533] J Biol Chem. 1996 Jul 5;271(27):15898-904 [8663148] Mol Cell Biol. 1996 Aug;16(8):4436-44 [8754844] Annu Rev Biochem. 1996;65:15-42 [8811173] Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10718-22 [8855246] Nucleic Acids Res. 1996 Oct 1;24(19):3685-92 [8871545] Mutat Res. 1996 Dec 2;364(3):183-92 [8960130] J Biol Chem. 1997 Jan 17;272(3):1885-90 [8999876] Pediatrics. 1977 Aug;60(2):135-9 [887325] Proc Natl Acad Sci U S A. 1978 Apr;75(4):1984-8 [273925] Cell. 1980 Feb;19(2):527-36 [7357619] Proc Natl Acad Sci U S A. 1980 Jul;77(7):3855-9 [6933441] Cell. 1982 Jan;28(1):99-106 [7066988] EMBO J. 1984 Aug;3(8):1837-42 [6479149] Cell. 1985 Feb;40(2):359-69 [3838150] J Mol Biol. 1986 Nov 5;192(1):77-86 [3820307] Dermatol Clin. 1987 Jan;5(1):109-21 [3549072] Cell. 1988 Apr 8;53(1):97-106 [3349527] J Cell Sci. 1988 Jul;90 ( Pt 3):365-78 [3075613] Proc Natl Acad Sci U S A. 1990 Jun;87(12):4707-11 [2352945] Mutat Res. 1991 May;254(3):217-24 [2052011] Exp Cell Res. 1992 Aug;201(2):373-9 [1322316] Cell. 1992 Dec 11;71(6):939-53 [1339317] Science. 1993 Apr 2;260(5104):58-63 [8465201] Am J Med Genet. 1992 Jan 1;42(1):68-84 [1308368] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Peptide-specific killing of antigen-presenting cells by a recombinant antibody-toxin fusion protein targeted to major histocompatibility complex/peptide class I complexes with T cell receptor-like specificity. AN - 78972765; 9114042 AB - Specificity in the immune system is dictated and regulated by specific recognition of peptide/major histocompatibility complex (MHC) complexes by the T cell receptor. Such peptide/MHC complexes are a desirable target for novel approaches in immunotherapy because of their highly restricted fine specificity. Recently, phage display was used to isolate an antibody that has T cell receptor-like specificity. It recognizes mouse MHC class I H-2Kk molecules complexed with a H-2Kk-restricted influenza virus-derived hemagglutinin peptide (Ha255-262) but does not bind to class I H-2Kk alone, peptide alone, or H-2Kk complexed with other peptides. We have used this antibody to make a recombinant antibody-toxin fusion protein (immunotoxin) and show herein that it specifically kills antigen-presenting cells in a peptide-dependent manner and with T cell receptor-like specificity. We find a striking correlation between the fine specificity of binding of the antibody and the cytotoxic activity of the recombinant immunotoxin. We also show specific killing of influenza virus-infected target cells. The results suggest that it should be possible to develop novel immunotherapeutic strategies against human cancer by making recombinant antibodies that will recognize cancer-related peptides complexed with MHC class I molecules on the surface of cancer cells and using these to deliver toxins, radioisotopes, or cytotoxic drugs to the cancer cells. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Reiter, Y AU - Di Carlo, A AU - Fugger, L AU - Engberg, J AU - Pastan, I AD - Laboratory of Molecular Biology, Division of Basic Sciences, National Cancer Institute, Building 37, Room 4E16, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1997/04/29/ PY - 1997 DA - 1997 Apr 29 SP - 4631 EP - 4636 VL - 94 IS - 9 SN - 0027-8424, 0027-8424 KW - Antibodies KW - 0 KW - Bacterial Toxins KW - Exotoxins KW - H-2 Antigens KW - H-2K(K) antigen KW - Histocompatibility Antigens Class I KW - Immunotoxins KW - Peptides KW - Receptors, Antigen, T-Cell KW - Recombinant Fusion Proteins KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Sensitivity and Specificity KW - Animals KW - Humans KW - Receptors, Antigen, T-Cell -- metabolism KW - Peptides -- immunology KW - Mice KW - Influenza A virus -- drug effects KW - Protein Binding KW - Immunotherapy -- methods KW - Recombinant Fusion Proteins -- metabolism KW - Cytotoxicity, Immunologic KW - Pseudomonas aeruginosa KW - Exotoxins -- pharmacology KW - Bacterial Toxins -- metabolism KW - Antibodies -- metabolism KW - Histocompatibility Antigens Class I -- metabolism KW - Antibodies -- pharmacology KW - Exotoxins -- metabolism KW - Bacterial Toxins -- pharmacology KW - Immunotoxins -- metabolism KW - Immunotoxins -- pharmacology KW - Antigen-Presenting Cells -- drug effects KW - Poly(ADP-ribose) Polymerases -- metabolism KW - Poly(ADP-ribose) Polymerases -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78972765?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Peptide-specific+killing+of+antigen-presenting+cells+by+a+recombinant+antibody-toxin+fusion+protein+targeted+to+major+histocompatibility+complex%2Fpeptide+class+I+complexes+with+T+cell+receptor-like+specificity.&rft.au=Reiter%2C+Y%3BDi+Carlo%2C+A%3BFugger%2C+L%3BEngberg%2C+J%3BPastan%2C+I&rft.aulast=Reiter&rft.aufirst=Y&rft.date=1997-04-29&rft.volume=94&rft.issue=9&rft.spage=4631&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-27 N1 - Date created - 1997-05-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1994 Jan 14;76(1):39-50 [7506996] J Exp Med. 1993 Aug 1;178(2):489-95 [8340755] Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3515-9 [8170938] Science. 1994 Apr 29;264(5159):716-9 [7513441] Eur J Immunol. 1994 Jun;24(6):1404-9 [8206101] J Exp Med. 1994 Jul 1;180(1):347-52 [7516411] Annu Rev Immunol. 1994;12:433-55 [8011287] Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6458-62 [8022805] Nat Med. 1995 Aug;1(8):837-9 [7585190] Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2253-6 [8637858] Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2264-71 [8637861] Annu Rev Med. 1996;47:481-91 [8712798] Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):1820-4 [8700842] Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10338-42 [8816801] Nat Biotechnol. 1996 Oct;14(10):1239-45 [9631086] Nature. 1987 Oct 8-14;329(6139):512-8 [2443855] Nature. 1990 Aug 2;346(6283):476-80 [2198471] Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8616-20 [1924323] Science. 1991 Nov 22;254(5035):1173-7 [1683495] Science. 1991 Dec 13;254(5038):1643-7 [1840703] Annu Rev Biochem. 1992;61:331-54 [1497314] Science. 1992 Aug 14;257(5072):919-27 [1323877] J Exp Med. 1994 Mar 1;179(3):921-30 [8113684] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The mouse mammary tumor associated gene INT3 is a unique member of the NOTCH gene family (NOTCH4). AN - 79002619; 9150355 AB - The INT3 gene is frequently rearranged in mouse mammary tumor virus (MMTV)-induced mammary tumors of the CzechII mouse strain. We have completed the nucleotide sequence of the normal 6.5 Kb INT3 RNA and defined the intron/exon boundaries of the gene. The open reading frame of INT3 RNA should encode a 200 kd protein which shares 60% homology with the mouse homologue of Drosophila NOTCH. INT3 is unique among other members of the NOTCH family by containing 29 instead of 36 EGF-like repeats in the extracellular domain of the gene product. Five novel EGF-like repeats have been created as consequence of apparent small deletions which have occurred within the coding region for the extracellular domain during evolution. Nucleotide sequence analysis of host-viral junction fragments from nine independent MMTV-induced mammary tumors containing a rearranged INT3 gene reveals that all of the integration events occur within a 174 bp region 3' of the sequences encoding the LIN12 repeats in the INT3 extracellular domain and 5' of the sequences encoding the transmembrane domain. Therefore, the only tumorigenic INT3 mutations resulting from MMTV proviral insertions are those which results in the expression of the intracellular domain. This strongly suggests that MMTV-induced activation of INT3 is manifest in the absence of the regulatory action of the extracellular domain, including the LIN12 repeat sequences, leaving the expressed intracellular domain constitutively free to function in its role in mammary tumorigenesis. JF - Oncogene AU - Gallahan, D AU - Callahan, R AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1997/04/24/ PY - 1997 DA - 1997 Apr 24 SP - 1883 EP - 1890 VL - 14 IS - 16 SN - 0950-9232, 0950-9232 KW - DNA Primers KW - 0 KW - Proto-Oncogene Proteins KW - Receptors, Cell Surface KW - Receptors, Notch KW - Recombinant Proteins KW - Notch4 protein, mouse KW - 146991-60-8 KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Multigene Family KW - Amino Acid Sequence KW - Mice KW - Proto-Oncogenes KW - Cloning, Molecular KW - Rats KW - Polymerase Chain Reaction KW - Base Sequence KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Sequence Homology, Amino Acid KW - Repetitive Sequences, Nucleic Acid KW - Drosophila -- genetics KW - Female KW - Mutagenesis, Insertional KW - Proto-Oncogene Proteins -- biosynthesis KW - Proto-Oncogene Proteins -- chemistry KW - Tumor Virus Infections -- genetics KW - Mammary Tumor Virus, Mouse KW - Mammary Neoplasms, Experimental -- genetics KW - Proto-Oncogene Proteins -- genetics KW - Retroviridae Infections -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79002619?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=The+mouse+mammary+tumor+associated+gene+INT3+is+a+unique+member+of+the+NOTCH+gene+family+%28NOTCH4%29.&rft.au=Gallahan%2C+D%3BCallahan%2C+R&rft.aulast=Gallahan&rft.aufirst=D&rft.date=1997-04-24&rft.volume=14&rft.issue=16&rft.spage=1883&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-03 N1 - Date created - 1997-06-03 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - M80456; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pentoxifylline decreases brain levels of platelet activating factor in murine AIDS. AN - 78995605; 9151942 AB - Tumor necrosis factor-alpha (TNF-alpha) and platelet-activating factor (PAF) have been implicated in the pathogenesis of human immunodeficiency virus (HIV)-associated encephalopathy. The effects of pentoxifylline on brain PAF levels were examined in mice infected with the LP-BM5 murine leukemia virus (MuLV). Seven weeks after viral inoculation, significant increases in serum TNF-alpha and brain PAF levels were observed. One week of treatment with pentoxifylline initiated 6 weeks postinfection significantly reduced both serum TNF-alpha and brain PAF levels. A significant positive correlation was observed between the levels of these substances (r = 0.62; P < 0.01). This study demonstrates that pentoxifylline treatment was effective in decreasing the levels of TNF-alpha in the serum and PAF levels in the brain of mice infected with the LP-BM5 MuLV. JF - European journal of pharmacology AU - Sei, Y AU - Nishida, K AU - Kustova, Y AU - Markey, S P AU - Morse, H C AU - Basile, A S AD - Laboratory of Neuroscience, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA. sei@helix.nih.gov Y1 - 1997/04/23/ PY - 1997 DA - 1997 Apr 23 SP - 81 EP - 84 VL - 325 IS - 1 SN - 0014-2999, 0014-2999 KW - Phosphodiesterase Inhibitors KW - 0 KW - Platelet Activating Factor KW - Tumor Necrosis Factor-alpha KW - Pentoxifylline KW - SD6QCT3TSU KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Leukemia Virus, Murine KW - Tumor Virus Infections -- metabolism KW - Mice, Inbred C57BL KW - Mice KW - Tumor Necrosis Factor-alpha -- metabolism KW - Retroviridae Infections -- metabolism KW - Retroviridae Infections -- complications KW - Tumor Virus Infections -- complications KW - Phosphodiesterase Inhibitors -- pharmacology KW - Brain Diseases -- virology KW - Pentoxifylline -- pharmacology KW - Murine Acquired Immunodeficiency Syndrome -- complications KW - Murine Acquired Immunodeficiency Syndrome -- blood KW - Platelet Activating Factor -- toxicity KW - Platelet Activating Factor -- metabolism KW - Murine Acquired Immunodeficiency Syndrome -- metabolism KW - Brain -- drug effects KW - Brain -- metabolism KW - Brain Diseases -- metabolism KW - Brain Diseases -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78995605?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+pharmacology&rft.atitle=Pentoxifylline+decreases+brain+levels+of+platelet+activating+factor+in+murine+AIDS.&rft.au=Sei%2C+Y%3BNishida%2C+K%3BKustova%2C+Y%3BMarkey%2C+S+P%3BMorse%2C+H+C%3BBasile%2C+A+S&rft.aulast=Sei&rft.aufirst=Y&rft.date=1997-04-23&rft.volume=325&rft.issue=1&rft.spage=81&rft.isbn=&rft.btitle=&rft.title=European+journal+of+pharmacology&rft.issn=00142999&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-11 N1 - Date created - 1997-08-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cholinergic stimulation increases thrombin activity and gene expression in cultured mouse muscle. AN - 78944907; 9125468 AB - Activity-dependent synapse reduction is a major determinant of neuromuscular innervation. Previous research has shown that nanomolar concentrations of hirudin, a specific thrombin antagonist, significantly attenuates this reduction, and protease nexin 1 (PN1), an endogenous thrombin inhibitor closely localized to the neuromuscular synapse, can inhibit synapse reduction at similar concentrations. Protease inhibitors which do not inhibit thrombin, including cystatin and aprotinin, had no effect on synapse reduction. We present a series of experiments examining whether prothrombin and/or PN1 gene expression, as well as thrombin activity, are regulated in muscle cultures by acetylcholine (ACh) receptor activation. We also studied the effect of exogenous thrombin on synapse elimination in co-cultures of muscle and cholinergic neurons. Cultured muscle cells were electrically blocked with tetrodotoxin (TTX), or co-treated with ACh in order to isolate ACh receptor activation. Electrical blockade resulted in a decrease in thrombin release to about two-thirds of control values. The application of ACh to electrically blocked muscle cultures resulted in a 2.5-fold increase in thrombin activity released into the medium and a 2-fold increase in prothrombin gene expression. In contrast, ACh treatment in the presence of TTX had no effect on PN1 gene expression compared to treatment with TTX alone. In addition, exogenous thrombin significantly increased synapse elimination in unstimulated muscle/cholinergic neuron co-cultures. These results suggest that thrombin or a thrombin-like molecule released from muscle is required for activity-dependent synapse elimination and is regulated by neuromuscular activity. JF - Brain research. Developmental brain research AU - Glazner, G W AU - Yadav, K AU - Fitzgerald, S AU - Coven, E AU - Brenneman, D E AU - Nelson, P G AD - Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-4480, USA. Y1 - 1997/04/18/ PY - 1997 DA - 1997 Apr 18 SP - 148 EP - 154 VL - 99 IS - 2 SN - 0165-3806, 0165-3806 KW - Amyloid beta-Protein Precursor KW - 0 KW - Antithrombins KW - Carrier Proteins KW - Hirudins KW - Plasminogen Inactivators KW - Protease Nexins KW - RNA, Messenger KW - Receptors, Cell Surface KW - SERPINE2 protein, human KW - Serpin E2 KW - Tetrodotoxin KW - 4368-28-9 KW - Prothrombin KW - 9001-26-7 KW - Endodeoxyribonucleases KW - EC 3.1.- KW - Thrombin KW - EC 3.4.21.5 KW - Amino Acid Isomerases KW - EC 5.1.1.- KW - Peptidylprolyl Isomerase KW - EC 5.2.1.8 KW - Acetylcholine KW - N9YNS0M02X KW - Index Medicus KW - Gene Expression -- drug effects KW - Animals KW - Hirudins -- pharmacology KW - Synapses -- drug effects KW - Antithrombins -- pharmacology KW - Superior Cervical Ganglion -- cytology KW - Carrier Proteins -- genetics KW - Endodeoxyribonucleases -- genetics KW - Mice KW - Prothrombin -- genetics KW - Electric Stimulation KW - Plasminogen Inactivators -- genetics KW - RNA, Messenger -- metabolism KW - Amino Acid Isomerases -- genetics KW - Cells, Cultured KW - Synapses -- enzymology KW - Tetrodotoxin -- pharmacology KW - Muscle, Skeletal -- cytology KW - Muscle, Skeletal -- innervation KW - Acetylcholine -- pharmacology KW - Muscle, Skeletal -- enzymology KW - Thrombin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78944907?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research.+Developmental+brain+research&rft.atitle=Cholinergic+stimulation+increases+thrombin+activity+and+gene+expression+in+cultured+mouse+muscle.&rft.au=Glazner%2C+G+W%3BYadav%2C+K%3BFitzgerald%2C+S%3BCoven%2C+E%3BBrenneman%2C+D+E%3BNelson%2C+P+G&rft.aulast=Glazner&rft.aufirst=G&rft.date=1997-04-18&rft.volume=99&rft.issue=2&rft.spage=148&rft.isbn=&rft.btitle=&rft.title=Brain+research.+Developmental+brain+research&rft.issn=01653806&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-16 N1 - Date created - 1997-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The inducibly expressed GTPase localizes to the endoplasmic reticulum, independently of GTP binding. AN - 78914149; 9099712 AB - The inducibly expressed GTPase (IGTP) is representative of a newly identified group of interferon gamma-inducible GTPases, whose functions are currently unknown. We have begun to address the cellular function of IGTP by examining its subcellular distribution and its guanine nucleotide binding status. Using immunofluorescence, electron microscopy, and subcellular fractionation, IGTP was localized predominantly to the endoplasmic reticulum of both RAW 264. 7 macrophages and C127 fibroblasts. In the immunostaining experiments, staining of discrete cytoplasmic structures on the periphery of the endoplasmic reticulum was also evident. Using polyethyleneimine-cellulose thin layer chromatography, the guanine nucleotides that complexed to immunoprecipitated IGTP, in both control and interferon gamma-stimulated cells, were 90-95% GTP and 5-10% GDP, suggesting that the protein was in an active state. A mutant IGTP protein was created that had no detectable complexed GTP, and in both subcellular fractionation and IGTP-green fluorescent protein fusion studies, this mutant also localized to the endoplasmic reticulum. These results suggested that the GTP binding status of IGTP is independent of its capacity to localize to the endoplasmic reticulum. Given these results, we propose that IGTP is representative of a new family of endoplasmic reticulum GTPases that may be involved in protein processing or trafficking. JF - The Journal of biological chemistry AU - Taylor, G A AU - Stauber, R AU - Rulong, S AU - Hudson, E AU - Pei, V AU - Pavlakis, G N AU - Resau, J H AU - Vande Woude, G F AD - ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA. Y1 - 1997/04/18/ PY - 1997 DA - 1997 Apr 18 SP - 10639 EP - 10645 VL - 272 IS - 16 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - Luminescent Proteins KW - Oligopeptides KW - Peptides KW - Recombinant Fusion Proteins KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Guanosine Triphosphate KW - 86-01-1 KW - FLAG peptide KW - 98849-88-8 KW - GTP Phosphohydrolases KW - EC 3.6.1.- KW - Igtp protein, mouse KW - Index Medicus KW - Macrophages KW - Recombinant Fusion Proteins -- biosynthesis KW - Animals KW - Amino Acid Sequence KW - Fibroblasts KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Base Sequence KW - Molecular Sequence Data KW - Enzyme Induction KW - Microscopy, Immunoelectron KW - Luminescent Proteins -- biosynthesis KW - Mutagenesis, Insertional KW - Cell Line KW - Endoplasmic Reticulum -- metabolism KW - GTP Phosphohydrolases -- chemistry KW - GTP Phosphohydrolases -- metabolism KW - Endoplasmic Reticulum -- ultrastructure KW - GTP Phosphohydrolases -- biosynthesis KW - Guanosine Triphosphate -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78914149?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+inducibly+expressed+GTPase+localizes+to+the+endoplasmic+reticulum%2C+independently+of+GTP+binding.&rft.au=Taylor%2C+G+A%3BStauber%2C+R%3BRulong%2C+S%3BHudson%2C+E%3BPei%2C+V%3BPavlakis%2C+G+N%3BResau%2C+J+H%3BVande+Woude%2C+G+F&rft.aulast=Taylor&rft.aufirst=G&rft.date=1997-04-18&rft.volume=272&rft.issue=16&rft.spage=10639&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-09 N1 - Date created - 1997-05-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mammalian Raf-1 is activated by mutations that restore Raf signaling in Drosophila. AN - 79023653; 9155021 AB - An interaction with the Ras proto-oncogene product is a requirement for Raf-1 activation in many signaling cascades. The significance of this interaction is demonstrated by the fact that a mutation preventing the Ras-Raf interaction severely impairs the function of both mammalian (Raf-1) and Drosophila (D-Raf) Raf proteins. In D-Raf, however, dominant intragenic mutations have been identified that suppress the effect of the Ras-binding site (RBS) mutation. To address the mechanism by which these mutations restore Raf signaling, we have introduced the suppressor mutations into the analogous residues of mammalian Raf-1. Here, we show that rather than compensating for the RBS mutation by restoring the Ras-Raf-1 interaction, the suppressor mutations increase the enzymatic and biological activity of Raf-1, allowing Raf-1 to signal in the absence of Ras binding. Surprisingly, we find that while one of the suppressor mutations (P181L) increases the basal kinase activity of Raf-1, it also abolishes the ability of wild-type Raf-1 to become activated by Ras. This mutation occurs in the cysteine-rich domain (CRD) of Raf-1 and demonstrates the importance of this region for a productive Ras-Raf interaction. Finally, we present evidence that the most activating suppressor mutation (G498S) increases Raf-1 activity by introducing a novel phosphorylation site into the L12 activation loop of the Raf-1 kinase domain. JF - The EMBO journal AU - Cutler, R E AU - Morrison, D K AD - Molecular Basis of Carcinogenesis Laboratory, ABL-Basic Research Program, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702, USA. Y1 - 1997/04/15/ PY - 1997 DA - 1997 Apr 15 SP - 1953 EP - 1960 VL - 16 IS - 8 SN - 0261-4189, 0261-4189 KW - 14-3-3 Proteins KW - 0 KW - Proteins KW - Proto-Oncogene Proteins KW - Phosphoserine KW - 17885-08-4 KW - Aspartic Acid KW - 30KYC7MIAI KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Proto-Oncogene Proteins c-raf KW - Oncogene Protein p21(ras) KW - EC 3.6.5.2 KW - Glycine KW - TE7660XO1C KW - Index Medicus KW - Aspartic Acid -- metabolism KW - Animals KW - Enzyme Activation KW - Glycine -- metabolism KW - Humans KW - Phosphoserine -- analysis KW - Proteins -- metabolism KW - Binding Sites KW - Meiosis KW - Kidney KW - Xenopus KW - Oocytes KW - Drosophila -- physiology KW - Drosophila -- genetics KW - Cell Line KW - Signal Transduction -- physiology KW - Protein-Serine-Threonine Kinases -- metabolism KW - Oncogene Protein p21(ras) -- genetics KW - Oncogene Protein p21(ras) -- metabolism KW - Proto-Oncogene Proteins -- metabolism KW - Suppression, Genetic -- physiology KW - Protein-Serine-Threonine Kinases -- genetics KW - Proto-Oncogene Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79023653?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+EMBO+journal&rft.atitle=Mammalian+Raf-1+is+activated+by+mutations+that+restore+Raf+signaling+in+Drosophila.&rft.au=Cutler%2C+R+E%3BMorrison%2C+D+K&rft.aulast=Cutler&rft.aufirst=R&rft.date=1997-04-15&rft.volume=16&rft.issue=8&rft.spage=1953&rft.isbn=&rft.btitle=&rft.title=The+EMBO+journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-27 N1 - Date created - 1997-06-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1994 Jun 3;264(5164):1463-7 [7811320] Genes Dev. 1996 Nov 1;10(21):2684-95 [8946910] Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):5982-6 [8016101] Science. 1994 Aug 12;265(5174):966-70 [8052857] J Biol Chem. 1994 Sep 2;269(35):22340-6 [8071362] Science. 1994 Sep 16;265(5179):1713-6 [8085158] Science. 1994 Sep 16;265(5179):1716-9 [8085159] Nature. 1994 Oct 13;371(6498):612-4 [7935795] Cell. 1978 Jul;14(3):725-31 [210957] Cell. 1985 Dec;43(3 Pt 2):615-21 [2416466] Mol Cell Biol. 1990 Oct;10(10):5324-32 [2118994] Methods Enzymol. 1991;201:110-49 [1943760] Methods Enzymol. 1991;200:62-81 [1956339] Cell. 1992 Mar 20;68(6):1041-50 [1312393] Nature. 1992 Dec 10;360(6404):600-3 [1461284] Biochem J. 1994 Oct 1;303 ( Pt 1):105-12 [7945229] Cell. 1995 Apr 7;81(1):63-71 [7720074] J Biol Chem. 1995 Apr 28;270(17):9809-12 [7730360] Mol Cell Biol. 1995 Jun;15(6):3390-7 [7760835] Nature. 1993 May 13;363(6425):133-40 [8483497] Science. 1993 Jun 11;260(5114):1658-61 [8503013] Nature. 1993 Jul 22;364(6435):308-13 [8332187] Cell. 1993 Jul 16;74(1):205-14 [8334704] J Cell Biol. 1993 Aug;122(3):645-52 [8335690] J Biol Chem. 1993 Aug 15;268(23):17309-16 [8349614] Development. 1993 May;118(1):127-38 [8375330] Mol Cell Biol. 1993 Nov;13(11):7170-9 [7692235] J Biol Chem. 1994 Feb 11;269(6):3913-6 [8307946] Nature. 1994 Feb 24;367(6465):686 [8107861] Nature. 1994 Feb 24;367(6465):704-11 [8107865] J Biol Chem. 1994 Apr 1;269(13):10000-7 [8144497] EMBO J. 1994 Apr 1;13(7):1610-9 [8157000] Trends Genet. 1994 Feb;10(2):44-8 [8191584] Curr Opin Genet Dev. 1994 Feb;4(1):82-9 [8193545] J Biol Chem. 1995 Jun 9;270(23):14100-6 [7539798] Nature. 1995 Jun 15;375(6532):554-60 [7791872] J Biol Chem. 1996 Jan 5;271(1):233-7 [8550565] Nat Struct Biol. 1996 Mar;3(3):244-51 [8605626] Mol Reprod Dev. 1995 Dec;42(4):507-14 [8607983] Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8312-7 [8710867] Cell Growth Differ. 1996 Feb;7(2):243-50 [8822208] EMBO J. 1994 Jun 1;13(11):2592-9 [8013459] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - FHIT mutations in human primary gastric cancer. AN - 78964385; 9108441 AB - Allelic deletion of multiple regions on the short arm of chromosome 3 (3p) implies the presence of multiple important tumor suppressor genes in human carcinogenesis. The FHIT gene, identified recently in chromosome 3p14.2, shows frequent allelic deletion and aberrant transcripts in gastrointestinal tumors. After determining the intron sequences flanking each of the coding exons of the FHIT gene and designing intron primers to facilitate mutation analysis of genomic DNA samples, we analyzed the complete coding sequences in matched cancer and normal tissues from 40 cases with primary gastric cancer using intron primers, PCR-single-strand conformation polymorphism analysis, and direct sequencing. A somatic missense mutation in exon 6, codon 61, ACG (threonine) --> ATG (methionine) was found in a signet ring cell adenocarcinoma. We also evaluated allelic deletion in these tumors by PCR-based microsatellite analysis; allelic deletion occurred in 42.1% (16 of 38) of evaluable cases. This is the first report of a somatic missense mutation of the FHIT gene in a primary tumor. Presence of a point mutation and frequent allelic deletions are consistent with the hypothesis that FHIT gene alterations are involved in the development of primary gastric cancers. JF - Cancer research AU - Gemma, A AU - Hagiwara, K AU - Ke, Y AU - Burke, L M AU - Khan, M A AU - Nagashima, M AU - Bennett, W P AU - Harris, C C AD - Laboratory of Human Carcinogenesis, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 1997/04/15/ PY - 1997 DA - 1997 Apr 15 SP - 1435 EP - 1437 VL - 57 IS - 8 SN - 0008-5472, 0008-5472 KW - Neoplasm Proteins KW - 0 KW - Proteins KW - fragile histidine triad protein KW - Acid Anhydride Hydrolases KW - EC 3.6.- KW - Index Medicus KW - Polymerase Chain Reaction KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Polymorphism, Single-Stranded Conformational KW - Exons -- genetics KW - Genes, Tumor Suppressor -- genetics KW - Stomach Neoplasms -- genetics KW - Neoplasm Proteins -- genetics KW - Proteins -- genetics KW - Open Reading Frames -- genetics KW - Gene Deletion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78964385?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=FHIT+mutations+in+human+primary+gastric+cancer.&rft.au=Gemma%2C+A%3BHagiwara%2C+K%3BKe%2C+Y%3BBurke%2C+L+M%3BKhan%2C+M+A%3BNagashima%2C+M%3BBennett%2C+W+P%3BHarris%2C+C+C&rft.aulast=Gemma&rft.aufirst=A&rft.date=1997-04-15&rft.volume=57&rft.issue=8&rft.spage=1435&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-01 N1 - Date created - 1997-05-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunohistochemical expression of pi-class glutathione S-transferase is down-regulated in adenocarcinoma of the prostate. AN - 78956029; 9118044 AB - Glutathione S-transferase is often up-regulated in neoplastic tissues. A single previous study found a loss of expression associated with carcinogenesis of the prostate. To extend these results, the authors performed immunohistochemical staining for the pi-class of glutathione S-transferase (GSTpi) on 74 archival sequential prostate specimens. The antibody used was derived from rabbits immunized against purified human GSTpi. Paraffin blocks containing both benign tissue and adenocarcinoma were studied. Heterogeneous expression of GSTpi in benign acini was found in 96% of cases, but GSTpi was not expressed in 95% of invasive adenocarcinomas of the prostate, nor was it expressed in any of the foci of high grade prostatic intraepithelial neoplasia. Basal cells of benign acini showed strong, diffuse staining for GSTpi, whereas the secretory luminal epithelium expressed GSTpi weakly and focally. This study confirms the down-regulation of GSTpi in adenocarcinoma of the prostate and shows that the loss of GSTpi expression is a phenotype associated with malignant transformation. JF - Cancer AU - Moskaluk, C A AU - Duray, P H AU - Cowan, K H AU - Linehan, M AU - Merino, M J AD - Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1997/04/15/ PY - 1997 DA - 1997 Apr 15 SP - 1595 EP - 1599 VL - 79 IS - 8 SN - 0008-543X, 0008-543X KW - Antibodies KW - 0 KW - Neoplasm Proteins KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Humans KW - Rabbits KW - Immunohistochemistry KW - Male KW - Adenocarcinoma -- enzymology KW - Down-Regulation KW - Neoplasm Proteins -- immunology KW - Glutathione Transferase -- metabolism KW - Prostatic Neoplasms -- enzymology KW - Glutathione Transferase -- immunology KW - Neoplasm Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78956029?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Immunohistochemical+expression+of+pi-class+glutathione+S-transferase+is+down-regulated+in+adenocarcinoma+of+the+prostate.&rft.au=Moskaluk%2C+C+A%3BDuray%2C+P+H%3BCowan%2C+K+H%3BLinehan%2C+M%3BMerino%2C+M+J&rft.aulast=Moskaluk&rft.aufirst=C&rft.date=1997-04-15&rft.volume=79&rft.issue=8&rft.spage=1595&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-24 N1 - Date created - 1997-04-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of m-chlorophenylpiperazine on regional brain glucose utilization: a positron emission tomographic comparison of alcoholic and control subjects. AN - 78933862; 9092601 AB - m-Chlorophenylpiperazine (mCPP) is a mixed serotonin agonist/antagonist used extensively in psychiatric research. Alcoholics show blunted neuroendocrine responses to mCPP, and in some settings mCPP can induce craving for alcohol, particularly among early onset alcoholics. We used 2-[18F]-2-deoxy-D-glucose positron emission tomography to examine the effects of intravenously administered mCPP (0.08 mg/kg) on brain glucose utilization in a group of 18 male alcoholics and 12 healthy male control subjects. Differences between two sequential scans (the first followed placebo and the second followed mCPP) were evaluated statistically with a Gaussian random field-based method. Among healthy volunteers mCPP significantly increased brain glucose metabolism in the right medial and posterior orbital gyrus, the cerebellar hemispheres bilaterally, the left nucleus accumbens, the head of the caudate nucleus bilaterally, the anterior and medial-dorsal nuclei of the thalamus bilaterally, the middle frontal gyrus, the left insular cortex, the left middle temporal gyrus, and the posterior cingulate gyrus. Among alcoholic subjects mCPP significantly increased brain glucose metabolism in larger areas of the cerebellum and posterior cingulate than it did in healthy volunteers, but compared with the healthy volunteers, alcoholics showed a smaller area of mCPP-induced activation in the thalamus, almost no activation in the orbital cortices, and no activation at all in the head of the caudate nucleus or the middle frontal gyrus. These results suggest that a serotoninergic challenge activates basal ganglia circuits involving orbital and prefrontal cortices among healthy volunteers but that the response of these circuits is blunted among alcoholics. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Hommer, D AU - Andreasen, P AU - Rio, D AU - Williams, W AU - Ruttimann, U AU - Momenan, R AU - Zametkin, A AU - Rawlings, R AU - Linnoila, M AD - Laboratory of Clinical Studies, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-1256, USA. Y1 - 1997/04/15/ PY - 1997 DA - 1997 Apr 15 SP - 2796 EP - 2806 VL - 17 IS - 8 SN - 0270-6474, 0270-6474 KW - Fluorine Radioisotopes KW - 0 KW - Piperazines KW - Serotonin Receptor Agonists KW - Fluorodeoxyglucose F18 KW - 0Z5B2CJX4D KW - Deoxyglucose KW - 9G2MP84A8W KW - Glucose KW - IY9XDZ35W2 KW - 1-(3-chlorophenyl)piperazine KW - REY0CNO998 KW - Index Medicus KW - Magnetic Resonance Imaging KW - Regression Analysis KW - Reference Values KW - Humans KW - Adult KW - Tomography, Emission-Computed KW - Middle Aged KW - Male KW - Serotonin Receptor Agonists -- pharmacology KW - Fluorine Radioisotopes -- pharmacokinetics KW - Glucose -- metabolism KW - Brain -- drug effects KW - Deoxyglucose -- analogs & derivatives KW - Alcoholism -- metabolism KW - Deoxyglucose -- pharmacokinetics KW - Brain -- metabolism KW - Piperazines -- pharmacology KW - Brain -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78933862?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Effects+of+m-chlorophenylpiperazine+on+regional+brain+glucose+utilization%3A+a+positron+emission+tomographic+comparison+of+alcoholic+and+control+subjects.&rft.au=Hommer%2C+D%3BAndreasen%2C+P%3BRio%2C+D%3BWilliams%2C+W%3BRuttimann%2C+U%3BMomenan%2C+R%3BZametkin%2C+A%3BRawlings%2C+R%3BLinnoila%2C+M&rft.aulast=Hommer&rft.aufirst=D&rft.date=1997-04-15&rft.volume=17&rft.issue=8&rft.spage=2796&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 - 1997-04-28 N1 - Date created - 1997-04-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytokine-in-adjuvant steering of the immune response phenotype to HIV-1 vaccine constructs: granulocyte-macrophage colony-stimulating factor and TNF-alpha synergize with IL-12 to enhance induction of cytotoxic T lymphocytes. AN - 78912193; 9103465 AB - To enhance and steer immune responses to synthetic peptide vaccines toward selected functional types and to understand the cooperative action of cytokines in fine-tuning the immune response, we attempted to influence the in vivo cytokine environment by delivering cytokines directly to the microenvironment in which the immune response is initiated. Here we study the effects of IL-2, IL-4, IL-7, IL-1beta, IL-12, IFN-gamma, TNF-alpha, and granulocyte-macrophage CSF (GM-CSF) incorporated with peptide in adjuvant on a variety of responses elicited: CTL, T cell proliferation, cytokine production and message, and Ab isotype. We show GM-CSF to be the single most effective cytokine for enhancing both cellular and humoral immunity to two previously characterized HIV-1 MN vaccine constructs. Novel synergies were also detected. GM-CSF synergized with IL-12 for CTL induction in BALB/c mice concomitant with suppression of Th2 cytokines IL-4 and IL-10. TNF-alpha also synergized with IL-12, but by a different mechanism, inducing IFN-gamma production in BALB/c mice and thus shifting the response to a Th1 phenotype. The results presented here suggest that in addition to IL-2, optimum induction of CD8+ CTL in vivo requires a combination of cytokines, including GM-CSF (probably acting to enhance Ag presentation and CD4+ cell help) and IL-12 (steering the Th response toward Th1 cytokines). JF - Journal of immunology (Baltimore, Md. : 1950) AU - Ahlers, J D AU - Dunlop, N AU - Alling, D W AU - Nara, P L AU - Berzofsky, J A AD - Molecular Immunogenetics and Vaccine Research Section Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/04/15/ PY - 1997 DA - 1997 Apr 15 SP - 3947 EP - 3958 VL - 158 IS - 8 SN - 0022-1767, 0022-1767 KW - AIDS Vaccines KW - 0 KW - Adjuvants, Immunologic KW - Cytokines KW - Peptides KW - Tumor Necrosis Factor-alpha KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Interleukin-12 KW - 187348-17-0 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Interleukin-12 -- immunology KW - Animals KW - Tumor Necrosis Factor-alpha -- administration & dosage KW - Interleukin-12 -- administration & dosage KW - Peptides -- administration & dosage KW - Humans KW - Tumor Necrosis Factor-alpha -- immunology KW - Peptides -- immunology KW - Amino Acid Sequence KW - Mice KW - Mice, Inbred BALB C KW - Granulocyte Colony-Stimulating Factor -- immunology KW - Cytokines -- administration & dosage KW - Adjuvants, Immunologic -- administration & dosage KW - Molecular Sequence Data KW - Granulocyte Colony-Stimulating Factor -- administration & dosage KW - Drug Synergism KW - Female KW - Lymphocyte Activation -- drug effects KW - CD8-Positive T-Lymphocytes -- immunology KW - AIDS Vaccines -- immunology KW - CD4-Positive T-Lymphocytes -- immunology KW - Immunity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78912193?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Cytokine-in-adjuvant+steering+of+the+immune+response+phenotype+to+HIV-1+vaccine+constructs%3A+granulocyte-macrophage+colony-stimulating+factor+and+TNF-alpha+synergize+with+IL-12+to+enhance+induction+of+cytotoxic+T+lymphocytes.&rft.au=Ahlers%2C+J+D%3BDunlop%2C+N%3BAlling%2C+D+W%3BNara%2C+P+L%3BBerzofsky%2C+J+A&rft.aulast=Ahlers&rft.aufirst=J&rft.date=1997-04-15&rft.volume=158&rft.issue=8&rft.spage=3947&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-05 N1 - Date created - 1997-05-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA methylation and the association between genetic and epigenetic changes: relation to carcinogenesis. AN - 78975679; 9129674 AB - This paper examines the relationship between DNA mutagenic lesions, DNA methylation and the involvement of these changes in the process of carcinogenesis. Many types of DNA damage (oxidative lesions, alkylation of bases, abasic sites, photodimers, etc.) interfere with the ability of mammalian cell DNA to be methylated at CpG dinucleotides by DNA-methyltransferases (DNA-MTases). This can result in altered patterns in the distribution of 5-methylcytosine (5MeC) residues at CpG sites. Methylation of DNA is an epigenetic change that by definition is heritable, can result in changes in chromatin structure, and is often accompanied by modified patterns of gene expression. The presence of 5MeC in DNA, as well as oxidative stress induced by the free radical nitric oxide, can interefere with the repair of alkylation damage, thereby increasing the level of potentially mutagenic lesions. CpG sites in DNA represent mutational hotspots, with both the presence of 5MeC in DNA and the catalytic activity of DNA-MTases being intrinsically mutagenic. The process of carcinogenesis has frequently been associated with an increased expression of DNA-MTase activity, accompanied by either hypermethylation or hypomethylation of target cell (progenitor tumor cell) DNA. In addition, there is evidence that overexpression of DNA-MTase activity could result in increased cytosine methylation at non-CpG sites. A variety of chemicals can alter the extent of DNA methylation in mammalian cells. These include inhibitors of topoisomerase II, as well as inhibitors of DNA synthesis, microtubule formation, histone deacetylation, transmethylation, etc. Genetic and epigenetic changes in DNA have a profound influence on one another and could play a major role in the process of carcinogenesis, by modulating both the extent and the pattern of gene expression. JF - Mutation research AU - Wachsman, J T AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1997/04/14/ PY - 1997 DA - 1997 Apr 14 SP - 1 EP - 8 VL - 375 IS - 1 SN - 0027-5107, 0027-5107 KW - Alkylating Agents KW - 0 KW - Enzyme Inhibitors KW - Nucleic Acid Synthesis Inhibitors KW - Topoisomerase II Inhibitors KW - 5-Methylcytosine KW - 6R795CQT4H KW - Cytosine KW - 8J337D1HZY KW - DNA Modification Methylases KW - EC 2.1.1.- KW - Index Medicus KW - Nucleic Acid Synthesis Inhibitors -- pharmacology KW - Animals KW - DNA Repair KW - Humans KW - Alkylating Agents -- pharmacology KW - Oxidative Stress KW - Enzyme Inhibitors -- pharmacology KW - Cytosine -- analogs & derivatives KW - Cytosine -- metabolism KW - DNA Modification Methylases -- metabolism KW - DNA Damage KW - DNA Methylation -- drug effects KW - Mutation KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78975679?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=DNA+methylation+and+the+association+between+genetic+and+epigenetic+changes%3A+relation+to+carcinogenesis.&rft.au=Wachsman%2C+J+T&rft.aulast=Wachsman&rft.aufirst=J&rft.date=1997-04-14&rft.volume=375&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-15 N1 - Date created - 1997-05-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Quantitative and qualitative comparisons of spontaneous and radiation-induced specific-locus mutation in the ad-3 region of heterokaryon 12 of Neurospora crassa. AN - 78957824; 9129678 AB - The data from forward-mutation experiments to obtain specific-locus mutations at two closely linked loci in the adenine-3 (ad-3) region of heterokaryon 12 (H-12) of Neurospora crassa have been used to determine the relative frequencies and mutational spectra of ad-3 mutants occurring spontaneously and those induced by 7 different radiation treatments. Previous studies have demonstrated that specific-locus mutants at these two loci result from 5 major genotypic classes, namely two classes of gene/point mutations (ad-3AR and ad-3BR), and 3 classes of multilocus deletion mutations ([ad-3A]IR, [ad-3B]IR and [ad-3A ad-3B]IR). Two different approaches were used to compare spontaneous mutation in the ad-3 region with that induced by 7 different radiation treatments (UV, 32P, 447 MeV protons, 85Sr, 250 kVp X-rays, 39 MeV helium ions, and 101 MeV carbon ions). These comparisons included X2-tests on the numbers of ad-3 mutants resulting in the following two sets of ratios: (1) gene/point mutations and multilocus deletion mutations; and (2) complementing and non-complementing ad-3BR mutants. Combination of the data from these two methods of comparison has demonstrated that each of the 7 radiation treatments induced a spectrum of ad-3 mutants that is statistically different from the spontaneous spectrum. In addition, these same two methods of comparison have been used to compare the mutagenic effects of each of the 7 radiation treatments with each other. Combination of the data from these two methods of comparison demonstrated that the majority of radiation-induced specific-locus mutations: (90.5% (19/21 of the pairwise combinations)) are qualitatively different from each other. We conclude that the mechanisms by which various radiations modify DNA tend to exhibit fundamental differences from each other and from the processes involved in spontaneous mutation. JF - Mutation research AU - de Serres, F J AU - Webber, B B AD - Laboratory of Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709-2233, USA. deserres@niehs.nih.gov Y1 - 1997/04/14/ PY - 1997 DA - 1997 Apr 14 SP - 37 EP - 52 VL - 375 IS - 1 SN - 0027-5107, 0027-5107 KW - Index Medicus KW - Alleles KW - Models, Genetic KW - Point Mutation KW - Genetic Complementation Test KW - Models, Statistical KW - Dose-Response Relationship, Radiation KW - Risk Assessment KW - Gene Deletion KW - Neurospora crassa -- genetics KW - Neurospora crassa -- radiation effects KW - Genes, Fungal KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78957824?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Quantitative+and+qualitative+comparisons+of+spontaneous+and+radiation-induced+specific-locus+mutation+in+the+ad-3+region+of+heterokaryon+12+of+Neurospora+crassa.&rft.au=de+Serres%2C+F+J%3BWebber%2C+B+B&rft.aulast=de+Serres&rft.aufirst=F&rft.date=1997-04-14&rft.volume=375&rft.issue=1&rft.spage=37&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-15 N1 - Date created - 1997-05-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Further in vivo studies on attenuating morphine withdrawal: isoform-selective nitric oxide synthase inhibitors differ in efficacy. AN - 78991645; 9137908 AB - The N-methyl-D-aspartate (NMDA) receptor-nitric oxide (NO) pathway has been linked to opiate withdrawal. Pretreatments with four inhibitors of NO synthase, 7-nitro indazole, 3-bromo-7-nitro indazole, S-methyl-L-thiocitrulline and aminoguanidine, which exhibit different isoform selectivity in vitro, were evaluated for their ability to attenuate signs of naloxone-precipitated morphine withdrawal. In separate experiments, effects of NO synthase inhibitors on blood pressure were measured in naive and morphine-dependent rats. 7-Nitro indazole, 3-bromo-7-nitro indazole and S-methyl-L-thiocitrulline, which are specific inhibitors of the constitutive isoforms, produced dose-dependent reductions of several signs of withdrawal. Blood pressure was unaffected by the indazoles, whereas S-methyl-L-thiocitrulline produced a strong vasoconstrictor response. Aminoguanidine, which selectively inhibits inducible NO synthase, reduced fewer signs of opioid withdrawal, had a lower relative potency and exhibited no vasopressor activity. These data suggest that constitutive isoforms, but not the inducible isoform of NO synthase, have a primary role in NO-mediated processes that modulate the opioid withdrawal syndrome in the rat. JF - European journal of pharmacology AU - Vaupel, D B AU - Kimes, A S AU - London, E D AD - Brain Imaging Section, National Institute on Drug Abuse, Baltimore, MD 21224, USA. Y1 - 1997/04/11/ PY - 1997 DA - 1997 Apr 11 SP - 11 EP - 20 VL - 324 IS - 1 SN - 0014-2999, 0014-2999 KW - 3-bromo-7-nitroindazole KW - 0 KW - Enzyme Inhibitors KW - Guanidines KW - Indazoles KW - Isoenzymes KW - Narcotic Antagonists KW - S-methylthiocitrulline KW - 156719-41-4 KW - Citrulline KW - 29VT07BGDA KW - Naloxone KW - 36B82AMQ7N KW - Morphine KW - 76I7G6D29C KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Thiourea KW - GYV9AM2QAG KW - pimagedine KW - SCQ4EZQ113 KW - 7-nitroindazole KW - UX0N37CMVH KW - Index Medicus KW - Animals KW - Naloxone -- administration & dosage KW - Drug Interactions KW - Analysis of Variance KW - Indazoles -- pharmacology KW - Disease Models, Animal KW - Thiourea -- analogs & derivatives KW - Citrulline -- therapeutic use KW - Guanidines -- pharmacology KW - Rats KW - Rats, Inbred F344 KW - Heart Rate -- drug effects KW - Guanidines -- therapeutic use KW - Enzyme Induction -- drug effects KW - Naloxone -- therapeutic use KW - Thiourea -- administration & dosage KW - Male KW - Naloxone -- pharmacology KW - Citrulline -- analogs & derivatives KW - Guanidines -- administration & dosage KW - Dose-Response Relationship, Drug KW - Indazoles -- therapeutic use KW - Citrulline -- administration & dosage KW - Narcotic Antagonists -- administration & dosage KW - Indazoles -- administration & dosage KW - Narcotic Antagonists -- therapeutic use KW - Thiourea -- pharmacology KW - Thiourea -- therapeutic use KW - Blood Pressure -- drug effects KW - Citrulline -- pharmacology KW - Narcotic Antagonists -- pharmacology KW - Enzyme Inhibitors -- therapeutic use KW - Enzyme Inhibitors -- administration & dosage KW - Morphine -- adverse effects KW - Nitric Oxide Synthase -- antagonists & inhibitors KW - Substance Withdrawal Syndrome -- drug therapy KW - Enzyme Inhibitors -- pharmacology KW - Nitric Oxide Synthase -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78991645?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+pharmacology&rft.atitle=Further+in+vivo+studies+on+attenuating+morphine+withdrawal%3A+isoform-selective+nitric+oxide+synthase+inhibitors+differ+in+efficacy.&rft.au=Vaupel%2C+D+B%3BKimes%2C+A+S%3BLondon%2C+E+D&rft.aulast=Vaupel&rft.aufirst=D&rft.date=1997-04-11&rft.volume=324&rft.issue=1&rft.spage=11&rft.isbn=&rft.btitle=&rft.title=European+journal+of+pharmacology&rft.issn=00142999&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-24 N1 - Date created - 1997-07-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Arylamide inhibitors of HIV-1 integrase. AN - 78944108; 9111292 AB - Based on data derived from a large number of HIV-1 integrase inhibitors, similar structural features can be observed, which consist of two aryl units separated by a central linker. For many inhibitors fitting this pattern, at least one aryl ring also requires ortho bis-hydroxylation for significant inhibitory potency. The ability of such catechol species to undergo in situ oxidation to reactive quinones presents one potential limitation to their utility. In an effort to address this problem, a series of inhibitors were prepared which did not contain ortho bishydroxyls. None of these analogues exhibited significant inhibition. Therefore an alternate approach was taken, whose aim was to increase potency rather than eliminate catechol substructures. In this latter study, naphthyl nuclei were utilized as aryl components, since a previous report had indicated that fused bicyclic rings may afford higher affinity relative to monocyclic phenyl-based systems. In preliminary work with monomeric units, it was found that the 6,7-dihydroxy-2-naphthoic acid (17) (IC50 = 4.7 microM) was approximately 10-fold more potent than its 5,6-dihydroxy isomer 19 (IC50 = 62.4 microM). Of particular note was the dramatic difference in potency between free acid 17 and its methyl ester 21 (IC50 > 200 microM). The nearly total loss of activity induced by esterification strongly indicates that the free carboxylic -OH is important for high potency of this compound. This contrasts with the isomeric 5,6-dihydroxy species 19, where esterification had no effect on inhibitory potency (23, IC50 = 52.7 microM). These data provide evidence that the monomeric 6,7- and 5,6-dihydroxynaphthalenes may be interacting with the enzyme in markedly different fashions. However, when these naphthyl nuclei were incorporated into dimeric structures, significant enhancements in potencies each relative to the monomeric acids were observed, with bis-6,7-dihydroxy analogue 49 and bis-5,6-dihydroxy analogue 51 both exhibiting approximately equal potencies (IC50 values of 0.81 and 0.11 microM, respectively). JF - Journal of medicinal chemistry AU - Zhao, H AU - Neamati, N AU - Mazumder, A AU - Sunder, S AU - Pommier, Y AU - Burke, T R AD - Laboratory of Medicinal Chemistry, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/04/11/ PY - 1997 DA - 1997 Apr 11 SP - 1186 EP - 1194 VL - 40 IS - 8 SN - 0022-2623, 0022-2623 KW - Caffeic Acids KW - 0 KW - Cytotoxins KW - Enzyme Inhibitors KW - HIV Integrase Inhibitors KW - NF-kappa B KW - Quinones KW - HIV Integrase KW - EC 2.7.7.- KW - caffeic acid phenethyl ester KW - G960R9S5SK KW - Curcumin KW - IT942ZTH98 KW - Phenylethyl Alcohol KW - ML9LGA7468 KW - Index Medicus KW - AIDS/HIV KW - Curcumin -- chemistry KW - Dose-Response Relationship, Drug KW - Quinones -- metabolism KW - Chromatography, High Pressure Liquid KW - Structure-Activity Relationship KW - Curcumin -- pharmacology KW - Caffeic Acids -- chemistry KW - Cytotoxins -- chemistry KW - Phenylethyl Alcohol -- analogs & derivatives KW - Phenylethyl Alcohol -- chemistry KW - Cytotoxins -- pharmacology KW - HIV Integrase Inhibitors -- chemical synthesis KW - Phenylethyl Alcohol -- pharmacology KW - Caffeic Acids -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - HIV Integrase Inhibitors -- pharmacology KW - Enzyme Inhibitors -- chemical synthesis KW - HIV Integrase -- metabolism KW - NF-kappa B -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78944108?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Arylamide+inhibitors+of+HIV-1+integrase.&rft.au=Zhao%2C+H%3BNeamati%2C+N%3BMazumder%2C+A%3BSunder%2C+S%3BPommier%2C+Y%3BBurke%2C+T+R&rft.aulast=Zhao&rft.aufirst=H&rft.date=1997-04-11&rft.volume=40&rft.issue=8&rft.spage=1186&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 - 1997-05-09 N1 - Date created - 1997-05-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Depletion of T lymphocytes with immunotoxin retards the progress of experimental allergic encephalomyelitis in rhesus monkeys. AN - 78972287; 9140093 AB - FN18-CRM9 is an anti-rhesus anti-CD3 immunotoxin that can transiently deplete T cells to 1% of initial values in both the blood and lymph node compartments and can induce long-term tolerance to mismatched renal allografts. We have investigated the ability of this immunotoxin to interdict the course of an experimental rhesus T-cell-driven autoimmune disease, experimental allergic encephalomyelitis (EAE) induced by myelin basic protein. Monkeys showing CSF pleocytosis were then treated with FN18-CRM9 alone or in combination with cranial irradiation (325 or 650 cGy). EAE in nontreated control monkeys progressed rapidly. Paralysis occurred 4-6 days after CSF pleocytosis. Paralysis was either delayed or never occurred in treated monkeys, and histopathology revealed few inflammatory plaques that were notable for their low or absent T cell content. While T cells repopulate in the periphery posttreatment, they do not return to the CNS in large numbers, suggesting that the newly repopulated T cells have lost their previously acquired CNS homing capability. Anti-CD3 immunotoxin may be useful in treating clinical T-cell-driven autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. JF - Cellular immunology AU - Hu, H AU - Stavrou, S AU - Cairns Baker, B AU - Tornatore, C AU - Scharff, J AU - Okunieff, P AU - Neville, D M AD - Laboratory of Molecular Biology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 28092-4034, USA. Y1 - 1997/04/10/ PY - 1997 DA - 1997 Apr 10 SP - 26 EP - 34 VL - 177 IS - 1 SN - 0008-8749, 0008-8749 KW - Antigens, CD3 KW - 0 KW - Immunotoxins KW - Myelin Basic Protein KW - Index Medicus KW - Antigens, CD3 -- immunology KW - Animals KW - Macaca mulatta KW - Immunohistochemistry KW - Myelin Basic Protein -- immunology KW - Encephalomyelitis, Autoimmune, Experimental -- prevention & control KW - Lymphocyte Depletion KW - T-Lymphocytes -- physiology KW - Immunotoxins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78972287?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+immunology&rft.atitle=Depletion+of+T+lymphocytes+with+immunotoxin+retards+the+progress+of+experimental+allergic+encephalomyelitis+in+rhesus+monkeys.&rft.au=Hu%2C+H%3BStavrou%2C+S%3BCairns+Baker%2C+B%3BTornatore%2C+C%3BScharff%2C+J%3BOkunieff%2C+P%3BNeville%2C+D+M&rft.aulast=Hu&rft.aufirst=H&rft.date=1997-04-10&rft.volume=177&rft.issue=1&rft.spage=26&rft.isbn=&rft.btitle=&rft.title=Cellular+immunology&rft.issn=00088749&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-21 N1 - Date created - 1997-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mouse glucocorticoid receptor phosphorylation status influences multiple functions of the receptor protein. AN - 78916631; 9083064 AB - Although studies have shown that the mouse glucocorticoid receptor (mGR) contains eight phosphorylation sites (Bodwell, J. E., Ortí, E. , Coull, J. M., Pappin, D. J. C., Smith, L. I., and Swift, F. (1991) J. Biol. Chem. 266, 7549-7555), the effect of phosphorylation on receptor function is unclear. We have examined the consequences of single or multiple phosphorylation site mutations on several properties of mGR including receptor expression, ligand-dependent nuclear translocation, hormone-mediated transactivation, ligand-dependent down-regulation of mGR, and receptor protein half-life. Mutations had little effect on receptor expression, subcellular distribution, ligand-dependent nuclear translocation, or on the ability to activate hormone-mediated transcription from a complex (murine mammary tumor virus) promoter. In contrast, the phosphorylation status of the mGR had a profound effect on the ability to transactivate a minimal promoter containing simple glucocorticoid response elements after hormone administration. Similarly, ligand-dependent down-regulation by glucocorticoids of both receptor mRNA and protein was abrogated in mutants containing three or more phosphorylation site alterations. Finally, we show that the phosphorylation status of mGR has a profound effect on the stability of the glucocorticoid receptor protein. Receptors containing seven or eight mutated sites have a markedly extended half-life and do not show the ligand-dependent destabilization seen with wild type receptor. These data show that receptor phosphorylation may play a crucial role in regulating receptor levels and hence control receptor functions. JF - The Journal of biological chemistry AU - Webster, J C AU - Jewell, C M AU - Bodwell, J E AU - Munck, A AU - Sar, M AU - Cidlowski, J A AD - Molecular Endocrinology Group, the Laboratory of Signal Transduction, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/04/04/ PY - 1997 DA - 1997 Apr 04 SP - 9287 EP - 9293 VL - 272 IS - 14 SN - 0021-9258, 0021-9258 KW - Glucocorticoids KW - 0 KW - RNA, Messenger KW - Receptors, Glucocorticoid KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Glucocorticoids -- metabolism KW - Animals KW - RNA, Messenger -- metabolism KW - Phosphorylation KW - Half-Life KW - COS Cells KW - Transfection KW - Cell Nucleus -- metabolism KW - Transcription, Genetic KW - Mice KW - Receptors, Glucocorticoid -- metabolism KW - Receptors, Glucocorticoid -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78916631?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Mouse+glucocorticoid+receptor+phosphorylation+status+influences+multiple+functions+of+the+receptor+protein.&rft.au=Webster%2C+J+C%3BJewell%2C+C+M%3BBodwell%2C+J+E%3BMunck%2C+A%3BSar%2C+M%3BCidlowski%2C+J+A&rft.aulast=Webster&rft.aufirst=J&rft.date=1997-04-04&rft.volume=272&rft.issue=14&rft.spage=9287&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-08 N1 - Date created - 1997-05-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA secondary structures and the evolution of hypervariable tandem arrays. AN - 78904130; 9083093 AB - Tandem repeats are ubiquitous in nature and constitute a major source of genetic variability in populations. This variability is associated with a number of genetic disorders in humans including triplet expansion diseases such as Fragile X syndrome and Huntington's disease. The mechanism responsible for the variability/instability of these tandem arrays remains contentious. We show here that formation of secondary structures, in particular intrastrand tetraplexes, is an intrinsic property of some of the more unstable arrays. Tetraplexes block DNA polymerase progression and may promote instability of tandem arrays by increasing the likelihood of reiterative strand slippage. In the course of doing this work we have shown that some of these tetraplexes involve unusual base interactions. These interactions not only generate tetraplexes with novel properties but also lead us to conclude that the number of sequences that can form stable tetraplexes might be much larger than previously thought. JF - The Journal of biological chemistry AU - Weitzmann, M N AU - Woodford, K J AU - Usdin, K AD - Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-0830, USA. Y1 - 1997/04/04/ PY - 1997 DA - 1997 Apr 04 SP - 9517 EP - 9523 VL - 272 IS - 14 SN - 0021-9258, 0021-9258 KW - Sulfuric Acid Esters KW - 0 KW - DNA KW - 9007-49-2 KW - dimethyl sulfate KW - JW5CW40Z50 KW - Potassium KW - RWP5GA015D KW - Index Medicus KW - Animals KW - Fragile X Syndrome -- genetics KW - Humans KW - Mice KW - Potassium -- metabolism KW - DNA Replication KW - Huntington Disease -- genetics KW - DNA -- chemistry KW - Repetitive Sequences, Nucleic Acid KW - Nucleic Acid Conformation KW - Evolution, Molecular UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78904130?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=DNA+secondary+structures+and+the+evolution+of+hypervariable+tandem+arrays.&rft.au=Weitzmann%2C+M+N%3BWoodford%2C+K+J%3BUsdin%2C+K&rft.aulast=Weitzmann&rft.aufirst=M&rft.date=1997-04-04&rft.volume=272&rft.issue=14&rft.spage=9517&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-08 N1 - Date created - 1997-05-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A familial amyotrophic lateral sclerosis-associated A4V Cu, Zn-superoxide dismutase mutant has a lower Km for hydrogen peroxide. Correlation between clinical severity and the Km value. AN - 78887371; 9083002 AB - Point mutations of Cu,Zn-superoxide dismutase (Cu,Zn-SOD) have been linked to familial amyotrophic lateral sclerosis (FALS). We reported that Cu,Zn-SOD can catalyze free radical generation and a FALS mutant, G93A, exhibits an enhanced free radical-generating activity, while its dismutation activity is identical to that of the wild-type enzyme (Yim, M. B., Kang, J.-H., Yim, H.-S., Kwak, H.-S., Chock, P. B., and Stadtman, E. R. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 5709-5714). The A4V mutation is both the most commonly detected of FALS-associated SOD1 mutations and among the most clinically severe (Rosen, D. R., Bowling, A. C., Patterson, D., Usdin, T. B., Sapp, P., Mezey, E., McKenna-Yasek, D., O'Regan, J. P., Rahmani, Z., Ferrante, R. J., Brownstein, M. J., Kowall, N. W., Beal, M. F., Horvitz, H. R., and Brown, R. H., Jr. (1994) Hum. Mol. Genet. 3, 981-987). We cloned the cDNA for the FALS A4V mutant, overexpressed the protein in Sf9 insect cells, purified the protein, and studied its enzymic activities. Our results show that the mutant and wild-type enzymes contain one copper ion per subunit and have identical dismutation activities. However, the free radical-generating activity of the mutant, as measured by the spin trapping method at low H2O2 concentration, is enhanced relative to that of the wild-type and G93A enzyme (wild-type G93A > A4V, while the kcat is identical for these enzymes. Thus, the FALS symptoms are not associated with the reduction in the dismutation activity of the mutant enzyme. The fact that the A4V mutant has the lowest Km for H2O2 is correlated to the clinical severity observed with the A4V patients, if FALS is associated with a differential gain of the free radical-generating function of the Cu,Zn-SOD mutant. JF - The Journal of biological chemistry AU - Yim, H S AU - Kang, J H AU - Chock, P B AU - Stadtman, E R AU - Yim, M B AD - Laboratory of Biochemistry, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/04/04/ PY - 1997 DA - 1997 Apr 04 SP - 8861 EP - 8863 VL - 272 IS - 14 SN - 0021-9258, 0021-9258 KW - Free Radicals KW - 0 KW - Recombinant Proteins KW - Hydrogen Peroxide KW - BBX060AN9V KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Humans KW - Electron Spin Resonance Spectroscopy KW - Recombinant Proteins -- genetics KW - Amyotrophic Lateral Sclerosis -- enzymology KW - Amyotrophic Lateral Sclerosis -- genetics KW - Hydrogen Peroxide -- metabolism KW - Superoxide Dismutase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78887371?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=A+familial+amyotrophic+lateral+sclerosis-associated+A4V+Cu%2C+Zn-superoxide+dismutase+mutant+has+a+lower+Km+for+hydrogen+peroxide.+Correlation+between+clinical+severity+and+the+Km+value.&rft.au=Yim%2C+H+S%3BKang%2C+J+H%3BChock%2C+P+B%3BStadtman%2C+E+R%3BYim%2C+M+B&rft.aulast=Yim&rft.aufirst=H&rft.date=1997-04-04&rft.volume=272&rft.issue=14&rft.spage=8861&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-08 N1 - Date created - 1997-05-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gene transfer by biolistic process AN - 954576077; 13859648 AB - Gene transfer into somatic tissues is a tool for both the study of gene function in the basic science laboratory and for gene therapy and genetic immunization in the clinic. Biolistic processes can be used to deliver both viral and nonviral vectors into somatic tissues. This review discusses the advantages and disadvantages of three biolistic processes: jet injection, microparticle bombardment, and needle and syringe injection. Jet injection and needle and syringe injection can be used to deliver both viral and nonviral vectors. Both jet injection and microparticle bombardment can be used to target a broad range of tissues. Needle and syringe injection has been most widely used in muscle tissue. The choice of which biolistic process to use is dependent on the specific application. JF - Molecular Biotechnology AU - Furth, Priscilla A AD - Division of Infectious Diseases, Department of Medicine, University of Maryland Medical School, the Baltimore Veterans Affairs Medical Center, 725 West Lombard Street, Room 545, 21201, Baltimore, MD, USA, furth@nih.gov Y1 - 1997/04// PY - 1997 DA - Apr 1997 SP - 139 EP - 143 PB - Humana Press Inc., 999 Riverview Dr., Ste. 208 Totowa NJ 07512 USA VL - 7 IS - 2 SN - 1073-6085, 1073-6085 KW - Genetics Abstracts; Biotechnology and Bioengineering Abstracts KW - microparticles KW - Gene therapy KW - Muscles KW - Syringes KW - Immunization KW - G 07720:Immunogenetics KW - W 30905:Medical Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/954576077?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Biotechnology&rft.atitle=Gene+transfer+by+biolistic+process&rft.au=Furth%2C+Priscilla+A&rft.aulast=Furth&rft.aufirst=Priscilla&rft.date=1997-04-01&rft.volume=7&rft.issue=2&rft.spage=139&rft.isbn=&rft.btitle=&rft.title=Molecular+Biotechnology&rft.issn=10736085&rft_id=info:doi/10.1007%2FBF02761749 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-03-01 N1 - Last updated - 2012-03-30 N1 - SubjectsTermNotLitGenreText - Gene therapy; microparticles; Muscles; Syringes; Immunization DO - http://dx.doi.org/10.1007/BF02761749 ER - TY - JOUR T1 - Lateralization and behavioral correlation of changes in regional cerebral blood flow with classical conditioning of the human eyeblink response. AN - 85244624; pmid-9114262 AB - Laterality of changes in regional cerebral blood flow (rCBF) during classical conditioning of the human eyeblink response was studied and changes in rCBF were correlated with conditioned responses. In 10 normal volunteers, rCBF was mapped with positron emission tomography and H2(15)O during pairings of a binaural tone conditioned stimulus and an air puff unconditioned stimulus to the left eye. Control conditions consisted of explicitly unpaired presentations of the tone and air puff before (control) and after (extinction) pairings. During pairings, rCBF increased significantly in right primary auditory cortex (contralateral to air puff) and decreased significantly in left and right cerebellar cortex. There were also increases in rCBF in right auditory association cortex and left temporoccipital cortex. Decreases in rCBF were noted bilaterally in the temporal poles and in the left prefrontal cortex. Positive correlations between changes in rCBF and percent conditioned responses were located in middle cerebellum, right superior temporal cortex, left dorsal premotor cortex, right middle cingulate, and right superior temporal cortex. There were negative correlations in left inferior prefrontal cortex, left middle prefrontal cortex, and right inferior parietal cortex. The data replicate our previous findings of lateralized changes in rCBF following presentations of a binaural tone and air puff to the right eye and indicate that there are pairing-specific changes in primary auditory cortex and cerebellum that are not unique to the left or right hemisphere but are a function of the side of training. The commonalities as well as differences in regional involvement in our present and previous experiment as well as in other eyeblink studies illustrate the advantage of functional neuroimaging to quantify different strategies used by the brain to perform seemingly similar functions. Indeed, the data support the notion that learning-related changes can be detected in a number of specific, but not necessarily invariant, brain regions, and that the involvement of any one region is dependent on the characteristics of the particular learning situation. JF - Journal of Neurophysiology AU - Schreurs, B G AU - McIntosh, A R AU - Bahro, M AU - Herscovitch, P AU - Sunderland, T AU - Molchan, S E AD - Laboratory of Adaptive Systems, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1997 SP - 2153 EP - 2163 VL - 77 IS - 4 SN - 0022-3077, 0022-3077 KW - Brain Mapping KW - Analysis of Variance KW - Reference Values KW - Comparative Study KW - Conditioning, Classical KW - Human KW - Adult KW - Blinking KW - Tomography, Emission-Computed KW - Acoustic Stimulation KW - Physical Stimulation KW - Cerebrovascular Circulation KW - Laterality KW - Image Processing, Computer-Assisted KW - Female KW - Reaction Time UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85244624?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Neurophysiology&rft.atitle=Lateralization+and+behavioral+correlation+of+changes+in+regional+cerebral+blood+flow+with+classical+conditioning+of+the+human+eyeblink+response.&rft.au=Schreurs%2C+B+G%3BMcIntosh%2C+A+R%3BBahro%2C+M%3BHerscovitch%2C+P%3BSunderland%2C+T%3BMolchan%2C+S+E&rft.aulast=Schreurs&rft.aufirst=B&rft.date=1997-04-01&rft.volume=77&rft.issue=4&rft.spage=2153&rft.isbn=&rft.btitle=&rft.title=Journal+of+Neurophysiology&rft.issn=00223077&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Brain incorporation of [1-11C]arachidonate in normocapnic and hypercapnic monkeys, measured with positron emission tomography. AN - 85229063; pmid-9163542 AB - Positron emission tomography (PET) was used to determine brain incorporation coefficients k* of [1-11C]arachidonate in isoflurane-anesthetized rhesus monkeys, as well as cerebral blood flow (CBF) using [15O]water. Intravenously injected [1-11C]arachidonate disappeared from plasma with a half-life of 1.1 min, whereas brain radioactivity reached a steady-state by 10 min. Mean values of k* were the same whether calculated by a single-time point method at 20 min after injection began, or by least-squares fitting of an equation for total brain radioactivity to data at all time points. k* equalled 1.1-1.2 x 10(-4) ml x s(-1) x g(-1) in gray matter and was unaffected by a 2.6-fold increase in CBF caused by hypercapnia. These results indicate that brain incorporation of [1-11C]arachidonate can be quantified in the primate using PET, and that incorporation is flow-independent. JF - Brain Research AU - Chang, M C AU - Arai, T AU - Freed, L M AU - Wakabayashi, S AU - Channing, M A AU - Dunn, B B AU - Der, M G AU - Bell, J M AU - Sasaki, T AU - Herscovitch, P AU - Eckelman, W C AU - Rapoport, S I AD - Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1997 SP - 74 EP - 83 VL - 755 IS - 1 SN - 0006-8993, 0006-8993 KW - Carbon Radioisotopes KW - Reference Values KW - Hypercapnia KW - Animal KW - Brain KW - Cerebrovascular Circulation KW - Radioligand Assay KW - Tomography, Emission-Computed KW - Least-Squares Analysis KW - Macaca mulatta KW - Male KW - Arachidonic Acid KW - Female KW - Phospholipids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85229063?accountid=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+Research&rft.atitle=Brain+incorporation+of+%5B1-11C%5Darachidonate+in+normocapnic+and+hypercapnic+monkeys%2C+measured+with+positron+emission+tomography.&rft.au=Chang%2C+M+C%3BArai%2C+T%3BFreed%2C+L+M%3BWakabayashi%2C+S%3BChanning%2C+M+A%3BDunn%2C+B+B%3BDer%2C+M+G%3BBell%2C+J+M%3BSasaki%2C+T%3BHerscovitch%2C+P%3BEckelman%2C+W+C%3BRapoport%2C+S+I&rft.aulast=Chang&rft.aufirst=M&rft.date=1997-04-01&rft.volume=755&rft.issue=1&rft.spage=74&rft.isbn=&rft.btitle=&rft.title=Brain+Research&rft.issn=00068993&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Patterns of DNA ploidy and S-phase fraction associated with breast cancer survival in blacks and whites. AN - 79647281; 9815724 AB - A significant survival difference between black and white breast cancer patients has been observed in the United States. Evaluation of the prognostic value of DNA ploidy and S-phase fraction (SPF) in black and white breast cancer patients may contribute to our understanding of the mechanisms of racial disparity in survival. A sample of 98 patients (50 blacks and 48 whites) who participated in the Black/White Cancer Survival Study was selected for DNA flow cytometry analysis. Patients were followed between 4.5 and 6.5 years. The impacts of DNA ploidy and SPF on breast cancer survival were examined. Kaplan-Meier survival curves, log rank statistics, and Cox proportional hazards regression were used for survival analyses. Black patients were more likely than white patients to have tumors with high SPF (P < 0.05), but there was no difference in DNA ploidy (P = 0.79). Because there were significant interactions of both DNA ploidy and SPF with race, survival was examined separately for blacks and whites. Significantly poorer survival was observed for white patients with class A ploidy (hypodiploidy, hypotetraploidy, and hypertetraploidy; P = 0.001) and with high SPF (P = 0.025). The elevated hazard ratios remained significant after adjusting for age and stage. Further adjustment for adjuvant therapy and histopathological characteristics of tumor reduced the hazard ratios of SPF to a nonsignificant level. No significant associations were found between survival and DNA ploidy or SPF among blacks. DNA ploidy and SPF are prognostic factors for breast cancer survival in white patients but not in blacks. This may have clinical implication in breast cancer management. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Shiao, Y H AU - Chen, V W AU - Lehmann, H P AU - Wu, X C AU - Correa, P AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute-Frederick Cancer Research and Development Center, NIH, Frederick, Maryland 21702, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 587 EP - 592 VL - 3 IS - 4 SN - 1078-0432, 1078-0432 KW - Receptors, Estrogen KW - 0 KW - Receptors, Progesterone KW - Index Medicus KW - Polyploidy KW - Neoplasm Staging KW - Humans KW - Prognosis KW - S Phase KW - Receptors, Estrogen -- analysis KW - Receptors, Progesterone -- analysis KW - Follow-Up Studies KW - Middle Aged KW - Time Factors KW - Female KW - Survival Analysis KW - Diploidy KW - Louisiana -- epidemiology KW - Breast Neoplasms -- genetics KW - Breast Neoplasms -- mortality KW - Breast Neoplasms -- pathology KW - African Continental Ancestry Group -- genetics KW - Breast Neoplasms -- therapy KW - Ploidies KW - European Continental Ancestry Group -- genetics KW - Cell Cycle UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79647281?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Patterns+of+DNA+ploidy+and+S-phase+fraction+associated+with+breast+cancer+survival+in+blacks+and+whites.&rft.au=Shiao%2C+Y+H%3BChen%2C+V+W%3BLehmann%2C+H+P%3BWu%2C+X+C%3BCorrea%2C+P&rft.aulast=Shiao&rft.aufirst=Y&rft.date=1997-04-01&rft.volume=3&rft.issue=4&rft.spage=587&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-18 N1 - Date created - 1999-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Detection of in vivo P-glycoprotein inhibition by PSC 833 using Tc-99m sestamibi. AN - 79646140; 9815718 AB - Tc-99m sestamibi is a substrate of P-glycoprotein (Pgp) that has been proposed for use as a functional imaging agent for the multidrug resistance-1 phenotype. In vitro, retention of sestamibi by cells that overexpress Pgp can be modified by the presence of Pgp antagonists. In a Phase I trial of the Pgp reversal agent PSC 833, we show that the effects of this reversal agent can also be demonstrated in patients. Nine patients with metastatic renal carcinoma were studied three times: at baseline, approximately 1 day after vinblastine infusion, and while on PSC 833. One patient with metastatic adrenocortical cancer was also studied. Time activity curves and areas under the curve (AUCs) were obtained for tumor, liver, lung, and myocardium, and organ:heart AUC ratios were generated. With PSC 833, tumor visualization was enhanced, and statistically significant increases were found in AUC ratios for tumor and liver compared to baseline. For the liver, significant differences were also found between the vinblastine versus PSC 833 scans but not between the baseline versus vinblastine scans. This study demonstrates that sestamibi retention by tumor and liver is altered in the presence of the reversal agent PSC 833, presumably reflecting inhibition of Pgp. Thus, sestamibi may be useful in vivo as a means of monitoring the effects of this and other reversal agents on various tumors and normal tissues that express Pgp. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Chen, C C AU - Meadows, B AU - Regis, J AU - Kalafsky, G AU - Fojo, T AU - Carrasquillo, J A AU - Bates, S E AD - Department of Nuclear Medicine, Warren G. Magnuson Clinical Center, Division of Clinical Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 545 EP - 552 VL - 3 IS - 4 SN - 1078-0432, 1078-0432 KW - Antineoplastic Agents KW - 0 KW - Cyclosporins KW - P-Glycoprotein KW - Radiopharmaceuticals KW - Vinblastine KW - 5V9KLZ54CY KW - Technetium Tc 99m Sestamibi KW - 971Z4W1S09 KW - valspodar KW - Q7ZP55KF3X KW - Index Medicus KW - Humans KW - Adult KW - Vinblastine -- administration & dosage KW - Neoplasm Metastasis KW - Middle Aged KW - Tissue Distribution KW - Male KW - Female KW - Radionuclide Imaging KW - Carcinoma, Renal Cell -- pathology KW - Cyclosporins -- adverse effects KW - Kidney Neoplasms -- pathology KW - Kidney Neoplasms -- drug therapy KW - P-Glycoprotein -- analysis KW - Antineoplastic Agents -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacokinetics KW - Antineoplastic Agents -- pharmacokinetics KW - Cyclosporins -- pharmacokinetics KW - Carcinoma, Renal Cell -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Kidney Neoplasms -- diagnostic imaging KW - Cyclosporins -- administration & dosage KW - P-Glycoprotein -- antagonists & inhibitors KW - Antineoplastic Agents -- adverse effects KW - P-Glycoprotein -- metabolism KW - Carcinoma, Renal Cell -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79646140?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Detection+of+in+vivo+P-glycoprotein+inhibition+by+PSC+833+using+Tc-99m+sestamibi.&rft.au=Chen%2C+C+C%3BMeadows%2C+B%3BRegis%2C+J%3BKalafsky%2C+G%3BFojo%2C+T%3BCarrasquillo%2C+J+A%3BBates%2C+S+E&rft.aulast=Chen&rft.aufirst=C&rft.date=1997-04-01&rft.volume=3&rft.issue=4&rft.spage=545&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-18 N1 - Date created - 1999-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Quantification of diazeniumdiolate mutagenicity in four different in vitro assays. AN - 79612742; 9701054 AB - Diazeniumdiolates are under investigation as possible prodrugs of the multifaceted bioregulatory agent nitric oxide. This study was undertaken to assess further the mutagenic potential of two diazeniumdiolates, DEA/NO (Et2N[N(O)NO]Na) and SPER/NO ([H2N(CH2)3NH(CH2)4N[N(O)NO-](CH2)3 NH3+]), which generate NO spontaneously with half-lives at 37 degrees C and pH 7.4 of 2 and 39 min, respectively. The genotoxic potential of these compounds was investigated with the Ames bacterial reverse mutation assay, two mammalian cell gene mutation assays (CHO/HGPRT and L5178Y TK+/-), and an assay for sister chromatid exchange (SCE) using Chinese hamster ovary (CHO) cells. Both diazeniumdiolates had previously been shown to be mutagenic in the Ames Salmonella plate assay. In the experiments reported here, Salmonella typhimurium strain TA1535 was exposed to the compounds in a liquid incubation assay for either 15 min or 48 h without an S-9 fraction. With the 15-min exposure, DEA/NO was mutagenic at concentrations of 0.625 mM (3.5 x control) and greater, while SPER/NO was mutagenic at 0.5 mM (2.7 x control) and above. In the CHO/HGPRT assay, DEA/NO was weakly mutagenic only at the highest concentration used, 20 mM, inducing a mutant frequency per survivor that was 2.5 x control, while SPER/NO was mutagenic at 0.5 mM with a mutant frequency of 2.5 x control. When the CHO cells were given 10 repetitive 20 mM DEA/NO exposures (3 min each), HGPRT mutant frequency was 4.1 x control. In the L5178Y mouse lymphoma cell TK+/- assay, DEA/NO doubled the mutation rate at 1.82 mM, while SPER/NO's mutation frequency was more than twice that of control at 0.63 mM. DEA/NO was positive in the SCE assay without metabolic activation, yielding significant SCE at 1.25, 2.5, and 5 mM that was 1.8, 2.2, and 2.6 times control, respectively. SPER/NO increased the SCE by 1.2, 1.4, and 1.3 times at 1.5, 2.0, and 2.5 mM. The results suggest that the two diazeniumdiolates, although mutagenic in the bacteria, are much weaker mutagens in mammalian cells. JF - Nitric oxide : biology and chemistry AU - Donovan, P J AU - Smith, G T AU - Lawlor, T E AU - Cifone, M A AU - Murli, H AU - Keefer, L K AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702-1201, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 158 EP - 166 VL - 1 IS - 2 SN - 1089-8603, 1089-8603 KW - Mutagens KW - 0 KW - Prodrugs KW - Nitric Oxide KW - 31C4KY9ESH KW - Hypoxanthine Phosphoribosyltransferase KW - EC 2.4.2.8 KW - Index Medicus KW - Animals KW - Mutagenicity Tests KW - Tumor Cells, Cultured KW - Hypoxanthine Phosphoribosyltransferase -- genetics KW - Sister Chromatid Exchange KW - CHO Cells KW - Mice KW - Salmonella typhimurium -- genetics KW - Cricetinae KW - Nitric Oxide -- toxicity KW - Prodrugs -- toxicity KW - Mutagens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79612742?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nitric+oxide+%3A+biology+and+chemistry&rft.atitle=Quantification+of+diazeniumdiolate+mutagenicity+in+four+different+in+vitro+assays.&rft.au=Donovan%2C+P+J%3BSmith%2C+G+T%3BLawlor%2C+T+E%3BCifone%2C+M+A%3BMurli%2C+H%3BKeefer%2C+L+K&rft.aulast=Donovan&rft.aufirst=P&rft.date=1997-04-01&rft.volume=1&rft.issue=2&rft.spage=158&rft.isbn=&rft.btitle=&rft.title=Nitric+oxide+%3A+biology+and+chemistry&rft.issn=10898603&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-28 N1 - Date created - 1998-08-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pesticides and cancer. AN - 79121305; 9220486 AB - The authors discuss pesticide exposure in both agricultural and nonagricultural occupations, referring to a variety of studies on the cancer risks of specific pesticides. Adult and childhood cancer are addressed, and direction for future research efforts is offered. JF - Occupational medicine (Philadelphia, Pa.) AU - Zahm, S H AU - Ward, M H AU - Blair, A AD - Occupational Epidemiology Branch, National Cancer Institute, Rockville, Maryland 20892-7364, USA. PY - 1997 SP - 269 EP - 289 VL - 12 IS - 2 SN - 0885-114X, 0885-114X KW - Pesticides KW - 0 KW - Index Medicus KW - Animals KW - Survival Rate KW - Humans KW - Adult KW - Incidence KW - Child KW - Environmental Exposure -- adverse effects KW - United States -- epidemiology KW - Risk Assessment KW - Child, Preschool KW - Neoplasms -- diagnosis KW - Neoplasms -- chemically induced KW - Neoplasms -- epidemiology KW - Occupational Exposure -- adverse effects KW - Pesticides -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79121305?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+medicine+%28Philadelphia%2C+Pa.%29&rft.atitle=Pesticides+and+cancer.&rft.au=Zahm%2C+S+H%3BWard%2C+M+H%3BBlair%2C+A&rft.aulast=Zahm&rft.aufirst=S&rft.date=1997-04-01&rft.volume=12&rft.issue=2&rft.spage=269&rft.isbn=&rft.btitle=&rft.title=Occupational+medicine+%28Philadelphia%2C+Pa.%29&rft.issn=0885114X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-04 N1 - Date created - 1997-09-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Suppression of retrovirial replication: inactivation of murine leukemia virus by compounds reacting with the zinc finger in the viral nucleocapsid protein. AN - 79118466; 9209313 AB - All retroviral nucleocapsid (NC) proteins, except those of spumaretroviruses, contain one or two zinc fingers, consisting of the sequence C-X2-C-X4-H-X4-C. Rice et al. (Science 270:1194-1197, 1995) have described a series of compounds which inactivate HIV-1 particles and oxidize the sulfur atoms in the NC zinc finger. We have characterized the effects of three such compounds on Moloney murine leukemia virus (MuLV). We find that, as with HIV-1, the compounds inactivate cell-free MuLV particles and induce disulfide cross-linking of NC in these particles. In contrast, the compounds have no effect on the infectivity of human foamy virus, a spumaretrovirus lacking zinc fingers in its NC protein. The resistance of foamy virus supports the hypothesis that the zinc fingers are the targets for inactivation of MuLV and HIV-1 by the compounds. The absolute conservation of the zinc finger motif among oncoretroviruses and lentiviruses, and the lethality of all known mutations altering the zinc-binding residues, suggest that only the normal, wild-type structure can efficiently perform all of its functions. This possibility would make the zinc finger an ideal target for antiretroviral agents. JF - Leukemia AU - Rein, A AU - Ott, D E AU - Mirro, J AU - Arthur, L O AU - Rice, W G AU - Henderson, L E AD - Retroviral Genetics Section, SAIC-Frederick, NCI-Frederick Cancer Research and Development Center, MD 21702-1201, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 106 EP - 108 VL - 11 Suppl 3 SN - 0887-6924, 0887-6924 KW - Antiviral Agents KW - 0 KW - Cross-Linking Reagents KW - Disulfides KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Humans KW - Zinc Fingers KW - Mice KW - Amino Acid Sequence KW - Mutagenesis KW - Virus Replication -- drug effects KW - Nucleocapsid -- drug effects KW - Cross-Linking Reagents -- pharmacology KW - Antiviral Agents -- pharmacology KW - Moloney murine leukemia virus -- physiology KW - Moloney murine leukemia virus -- drug effects KW - Spumavirus -- physiology KW - Virus Replication -- physiology KW - Nucleocapsid -- chemistry KW - HIV-1 -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79118466?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Leukemia&rft.atitle=Suppression+of+retrovirial+replication%3A+inactivation+of+murine+leukemia+virus+by+compounds+reacting+with+the+zinc+finger+in+the+viral+nucleocapsid+protein.&rft.au=Rein%2C+A%3BOtt%2C+D+E%3BMirro%2C+J%3BArthur%2C+L+O%3BRice%2C+W+G%3BHenderson%2C+L+E&rft.aulast=Rein&rft.aufirst=A&rft.date=1997-04-01&rft.volume=11+Suppl+3&rft.issue=&rft.spage=106&rft.isbn=&rft.btitle=&rft.title=Leukemia&rft.issn=08876924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-07 N1 - Date created - 1997-08-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - MuLV-insertional mutagenesis of c-myb and Mml1 in a murine model for promonocytic leukemia. AN - 79097702; 9209355 AB - Analysis of retroviral integration sites in MuLV-induced promonocytic leukemias has determined that two genetic loci, c-myb and Mml1, can contribute to disease development but not in the same leukemia. Recent studies aimed at understanding the function of Myb in leukemia development have focused on the consequences of ectopic Myb expression on monocytic and granulocytic differentiation in vitro. In all instances Myb was shown to block growth arrest but not commitment to differentiation, a result which is consistent with observed effects of Myb in leukemia development. No effect of Myb protein truncation was observed in these studies although similar truncations are produced as a result of insertional mutagenesis. Common integration site, Mml1, was recently identified and mapped to mouse chromosome 10 within 1cM of c-myb. Despite its linkage to c-myb, Myb mRNA and protein expression appear to be unaffected in leukemias with Mml1 integrations. JF - Leukemia AU - Bies, J AU - Koller, R AU - Hoffman, B AU - Amanullah, A AU - Mock, B AU - Wolff, L AD - Laboratory of Genetics, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 247 EP - 250 VL - 11 Suppl 3 SN - 0887-6924, 0887-6924 KW - Proto-Oncogene Proteins KW - 0 KW - Proto-Oncogene Proteins c-myb KW - Trans-Activators KW - Index Medicus KW - Macrophages -- cytology KW - Animals KW - Monocytes -- cytology KW - Disease Models, Animal KW - Cell Differentiation KW - Mice KW - Mutagenesis, Insertional KW - Cell Line KW - Granulocytes -- cytology KW - Proto-Oncogene Proteins -- biosynthesis KW - Leukemia Virus, Murine -- genetics KW - Trans-Activators -- biosynthesis KW - Trans-Activators -- genetics KW - Leukemia, Myeloid -- genetics KW - Virus Integration KW - Proto-Oncogenes KW - Proto-Oncogene Proteins -- genetics KW - Leukemia, Myeloid -- virology KW - Chromosome Mapping UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79097702?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Leukemia&rft.atitle=MuLV-insertional+mutagenesis+of+c-myb+and+Mml1+in+a+murine+model+for+promonocytic+leukemia.&rft.au=Bies%2C+J%3BKoller%2C+R%3BHoffman%2C+B%3BAmanullah%2C+A%3BMock%2C+B%3BWolff%2C+L&rft.aulast=Bies&rft.aufirst=J&rft.date=1997-04-01&rft.volume=11+Suppl+3&rft.issue=&rft.spage=247&rft.isbn=&rft.btitle=&rft.title=Leukemia&rft.issn=08876924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-07 N1 - Date created - 1997-08-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase II trial of suramin, leuprolide, and flutamide in previously untreated metastatic prostate cancer. AN - 79083340; 9193342 AB - To assess the efficacy and toxicity of suramin, hydrocortisone, leuprolide, and flutamide in previously untreated metastatic prostate cancer. Patients with stage D2 and poor-prognosis stage D1 prostate cancer were given suramin on a pharmacokinetically derived dosing schedule to maintain suramin concentrations between 175 and 300 micrograms/mL. Additionally, all patients received flutamide 250 mg orally three times daily, initiated on day 1 and continued until disease progression; depot leuprolide 7.5 mg intramuscularly begun on day 5 and repeated every 4 weeks indefinitely; and replacement doses of hydrocortisone. Fifty patients were entered onto the study: 48 with stage D2 and two with stage D1 disease. The median age was 59 years (range, 42 to 79) and 31 patients had a Karnofsky performance status (KPS) of 100%. Forty-five patients had bone metastases and 25 had measurable soft tissue disease. Forty-one (82%) had severe disease. The overall response rate in 49 assessable patients was three complete responses (CRs) and 30 partial responses (PRs) for an overall response rate of 67%. Eighteen patients have died. The median survival time has not been reached, with a median potential follow-up duration of 44 months. Grade 3 to 4 toxicity was seen in 38% of patients and was predominantly hematologic and reversible. The high response rate and prolonged survival in a poor-prognosis group of patients with metastatic prostate cancer warrant a phase III randomized comparison of this regimen versus hormonal therapy alone. Toxicity was moderate and reversible. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Dawson, N A AU - Figg, W D AU - Cooper, M R AU - Sartor, O AU - Bergan, R C AU - Senderowicz, A M AU - Steinberg, S M AU - Tompkins, A AU - Weinberger, B AU - Sausville, E A AU - Reed, E AU - Myers, C E AD - Division of Clinical Sciences, National Cancer Institute, Bethesda, MD, USA. nancy_a.dawson@wramaa.chcs.amedd.army.mil Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 1470 EP - 1477 VL - 15 IS - 4 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents, Hormonal KW - 0 KW - Suramin KW - 6032D45BEM KW - Flutamide KW - 76W6J0943E KW - Prostate-Specific Antigen KW - EC 3.4.21.77 KW - Leuprolide KW - EFY6W0M8TG KW - Index Medicus KW - Drug Administration Schedule KW - Humans KW - Disease Progression KW - Aged KW - Leuprolide -- administration & dosage KW - Adult KW - Antineoplastic Agents, Hormonal -- administration & dosage KW - Prostate-Specific Antigen -- blood KW - Treatment Outcome KW - Suramin -- administration & dosage KW - Middle Aged KW - Male KW - Survival Analysis KW - Flutamide -- administration & dosage KW - Prostatic Neoplasms -- pathology KW - Prostatic Neoplasms -- immunology KW - Prostatic Neoplasms -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79083340?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Phase+II+trial+of+suramin%2C+leuprolide%2C+and+flutamide+in+previously+untreated+metastatic+prostate+cancer.&rft.au=Dawson%2C+N+A%3BFigg%2C+W+D%3BCooper%2C+M+R%3BSartor%2C+O%3BBergan%2C+R+C%3BSenderowicz%2C+A+M%3BSteinberg%2C+S+M%3BTompkins%2C+A%3BWeinberger%2C+B%3BSausville%2C+E+A%3BReed%2C+E%3BMyers%2C+C+E&rft.aulast=Dawson&rft.aufirst=N&rft.date=1997-04-01&rft.volume=15&rft.issue=4&rft.spage=1470&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-10 N1 - Date created - 1997-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression and characterization of a cytotoxic human-frog chimeric ribonuclease: potential for cancer therapy. AN - 79073909; 9194172 AB - Onconase is a cytotoxic ribonuclease with antitumor properties. A semisynthetic gene encoding the entire protein sequence was constructed by fusing oligonucleotides coding for the first 15 and last six of the 104 amino acid residues to a genomic clone that encoded the remaining amino acid residues. Additionally, the 15 N-terminal amino acid residues of onconase were replaced with the first 21 amino acid residues of the homologous human RNase, eosinophil-derived neurotoxin, EDN. Two versions of the hybrid EDN-onconase protein were cloned, expressed and purified. The chimera that contained a glycine in lieu of the aspartic acid present in native onconase (position 26 in the chimera) exhibited enzymatic activity more characteristic of EDN than native onconase and was considerably more active with respect to both RNase activity and cellular cytotoxicity than recombinant onconase. In contrast to native or recombinant onconase, the EDN chimera was recognized by anti-EDN polyclonal antibodies, demonstrating that the chimera also shared structural antigenic determinants to the human enzyme. These results demonstrate that a chimeric ribonuclease has cytotoxicity comparable to onconase in two out of four cell lines tested. The implications with regard to cancer therapy are presented. JF - Protein engineering AU - Newton, D L AU - Xue, Y AU - Boqué, L AU - Wlodawer, A AU - Kung, H F AU - Rybak, S M AD - Intramural Research Support Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 463 EP - 470 VL - 10 IS - 4 SN - 0269-2139, 0269-2139 KW - Antineoplastic Agents KW - 0 KW - Egg Proteins KW - Neurotoxins KW - Recombinant Fusion Proteins KW - Methionine KW - AE28F7PNPL KW - Eosinophil-Derived Neurotoxin KW - EC 3.1.- KW - Ribonucleases KW - ranpirnase KW - ZE15FIT23E KW - Index Medicus KW - Rana pipiens KW - Software KW - Animals KW - Drug Screening Assays, Antitumor KW - Electrophoresis, Polyacrylamide Gel KW - Models, Molecular KW - Humans KW - Methionine -- metabolism KW - Amino Acid Sequence KW - Recombinant Fusion Proteins -- chemistry KW - Cloning, Molecular KW - Recombinant Fusion Proteins -- metabolism KW - Tumor Cells, Cultured KW - Molecular Sequence Data KW - Models, Chemical KW - Methionine -- chemistry KW - Egg Proteins -- therapeutic use KW - Neurotoxins -- metabolism KW - Neurotoxins -- genetics KW - Ribonucleases -- therapeutic use KW - Antineoplastic Agents -- metabolism KW - Egg Proteins -- genetics KW - Ribonucleases -- chemistry KW - Neurotoxins -- therapeutic use KW - Ribonucleases -- metabolism KW - Egg Proteins -- chemistry KW - Ribonucleases -- genetics KW - Egg Proteins -- metabolism KW - Antineoplastic Agents -- chemistry KW - Neurotoxins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79073909?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+engineering&rft.atitle=Expression+and+characterization+of+a+cytotoxic+human-frog+chimeric+ribonuclease%3A+potential+for+cancer+therapy.&rft.au=Newton%2C+D+L%3BXue%2C+Y%3BBoqu%C3%A9%2C+L%3BWlodawer%2C+A%3BKung%2C+H+F%3BRybak%2C+S+M&rft.aulast=Newton&rft.aufirst=D&rft.date=1997-04-01&rft.volume=10&rft.issue=4&rft.spage=463&rft.isbn=&rft.btitle=&rft.title=Protein+engineering&rft.issn=02692139&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-18 N1 - Date created - 1997-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I trial of docetaxel administered as a 1-hour infusion in children with refractory solid tumors: a collaborative pediatric branch, National Cancer Institute and Children's Cancer Group trial. AN - 79067193; 9193350 AB - A phase I trial of docetaxel was performed to determine the maximum-tolerated dose (MTD), the dose-limiting toxicities, and the incidence and severity of other toxicities in children with refractory solid tumors. Forty-four children received 103 courses of docetaxel administered as a 1-hour intravenous infusion every 21 days. Doses ranged from 55 to 150 mg/m2, MTD was defined in heavily pretreated and less heavily pretreated ( or = 100 mg/m2. The recommended phase II dose of docetaxel administered as a 1-hour intravenous infusion in children with solid tumors in 125 mg/m2. Because neutropenia was the dose-limiting toxicity and thrombocytopenia was mild, further escalation of the dose should be attempted with granulocyte colony-stimulating factor (G-CSF) support. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Blaney, S M AU - Seibel, N L AU - O'Brien, M AU - Reaman, G H AU - Berg, S L AU - Adamson, P C AU - Poplack, D G AU - Krailo, M D AU - Mosher, R AU - Balis, F M AD - Pediatric Branch, National Cancer Institute, Bethesda, MD, USA. blaney@nsmail.his.tch.tmc.edu Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 1538 EP - 1543 VL - 15 IS - 4 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Taxoids KW - docetaxel KW - 15H5577CQD KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Severity of Illness Index KW - Drug Administration Schedule KW - Infusions, Intravenous KW - Humans KW - Neutropenia -- chemically induced KW - Child KW - Child, Preschool KW - Infant KW - Adult KW - Treatment Outcome KW - Incidence KW - Adolescent KW - Female KW - Male KW - Paclitaxel -- administration & dosage KW - Neoplasms -- drug therapy KW - Paclitaxel -- adverse effects KW - Antineoplastic Agents, Phytogenic -- adverse effects KW - Paclitaxel -- analogs & derivatives KW - Antineoplastic Agents, Phytogenic -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79067193?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Phase+I+trial+of+docetaxel+administered+as+a+1-hour+infusion+in+children+with+refractory+solid+tumors%3A+a+collaborative+pediatric+branch%2C+National+Cancer+Institute+and+Children%27s+Cancer+Group+trial.&rft.au=Blaney%2C+S+M%3BSeibel%2C+N+L%3BO%27Brien%2C+M%3BReaman%2C+G+H%3BBerg%2C+S+L%3BAdamson%2C+P+C%3BPoplack%2C+D+G%3BKrailo%2C+M+D%3BMosher%2C+R%3BBalis%2C+F+M&rft.aulast=Blaney&rft.aufirst=S&rft.date=1997-04-01&rft.volume=15&rft.issue=4&rft.spage=1538&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-10 N1 - Date created - 1997-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Diversified prime and boost protocols using recombinant vaccinia virus and recombinant non-replicating avian pox virus to enhance T-cell immunity and antitumor responses. AN - 79045918; 9178479 AB - Recombinant vaccinia viruses containing tumor associated genes represent an attractive vector to induce immune responses to weak immunogens in cancer immunotherapy protocols. The property of intense immunogenicity of vaccinia proteins, however, also serves to limit the number of inoculations of recombinant vaccinia viruses. Host immune responses to the first immunization have been shown to limit the replication of subsequent vaccinations and thus reduce effectiveness of boost inoculations. The use of recombinant avian pox viruses (avipox) such as the canarypox (ALVAC) or fowlpox are potential candidates for immunization protocols in that they can infect mammalian cells and express the inserted transgene, but do not replicate in mammalian cells. We report here the construction and characterization of a canarypox (ALVAC) recombinant expressing the human carcinoembryonic antigen (CEA) gene (designated ALVAC-CEA). Antibody, lymphoproliferative and cytolytic T-cell responses as well as tumor inhibition were shown to be elicited by the ALVAC-CEA recombinant in a murine model. The utilization of a diversified immunization scheme using a recombinant vaccinia virus followed by recombinant avian pox virus was shown to be far superior than the use of either one alone in eliciting CEA-specific T-cell responses. Experiments were conducted to determine if the use of a diversified immunization scheme using a recombinant vaccinia virus (rV-CEA) and ALVAC-CEA would be superior to the use of either one alone in eliciting CEA-specific T-cell responses. When mice were immunized with rV-CEA and then ALVAC-CEA. CEA-specific T-cell responses were at least four times greater, and for superior to those achieved with three immunizations of ALVAC-CEA. Multiple boosts of ALVAC-CEA following rV-CEA immunization further potentiated anti-tumor effects and CEA specific T-cell responses. These studies demonstrate the proof of concept of the advantage of diversified immunization protocols employing both recombinant vaccinia and recombinant avipox vectors. JF - Vaccine AU - Hodge, J W AU - McLaughlin, J P AU - Kantor, J A AU - Schlom, J AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1997 SP - 759 EP - 768 VL - 15 IS - 6-7 SN - 0264-410X, 0264-410X KW - Antibodies, Neoplasm KW - 0 KW - Cancer Vaccines KW - Carcinoembryonic Antigen KW - Vaccines, Synthetic KW - Index Medicus KW - Virus Replication KW - Animals KW - Antibodies, Neoplasm -- analysis KW - Humans KW - T-Lymphocytes, Cytotoxic -- immunology KW - Mice KW - Immunization, Secondary KW - Immunization KW - Genetic Vectors KW - Cercopithecus aethiops KW - Mice, Inbred C57BL KW - Cytotoxicity Tests, Immunologic KW - Cell Line KW - Female KW - Cancer Vaccines -- immunology KW - Vaccinia virus KW - Carcinoembryonic Antigen -- immunology KW - Vaccines, Synthetic -- immunology KW - Avipoxvirus -- physiology KW - Adenocarcinoma -- prevention & control KW - T-Lymphocytes -- immunology KW - Carcinoembryonic Antigen -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79045918?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vaccine&rft.atitle=Diversified+prime+and+boost+protocols+using+recombinant+vaccinia+virus+and+recombinant+non-replicating+avian+pox+virus+to+enhance+T-cell+immunity+and+antitumor+responses.&rft.au=Hodge%2C+J+W%3BMcLaughlin%2C+J+P%3BKantor%2C+J+A%3BSchlom%2C+J&rft.aulast=Hodge&rft.aufirst=J&rft.date=1997-04-01&rft.volume=15&rft.issue=6-7&rft.spage=759&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-31 N1 - Date created - 1997-07-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adjuvant therapy for resectable colorectal carcinoma with 5-fluorouracil portal vein infusion. AN - 79042146; 9176762 JF - Journal of chemotherapy (Florence, Italy) AU - Cremona, F AU - Izzo, F AU - Ruffolo, F AU - Palaia, R AU - Parisi, V AD - Division of Surgical Oncology C, National Cancer Institute of Naples, Italy. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 140 EP - 141 VL - 9 IS - 2 SN - 1120-009X, 1120-009X KW - Antimetabolites, Antineoplastic KW - 0 KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Infusions, Intravenous KW - Humans KW - Treatment Outcome KW - Retrospective Studies KW - Portal Vein KW - Postoperative Period KW - Chemotherapy, Adjuvant KW - Fluorouracil -- therapeutic use KW - Fluorouracil -- administration & dosage KW - Fluorouracil -- adverse effects KW - Colorectal Neoplasms -- radiotherapy KW - Carcinoma -- surgery KW - Antimetabolites, Antineoplastic -- administration & dosage KW - Colorectal Neoplasms -- surgery KW - Antimetabolites, Antineoplastic -- adverse effects KW - Carcinoma -- radiotherapy KW - Carcinoma -- drug therapy KW - Colorectal Neoplasms -- drug therapy KW - Antimetabolites, Antineoplastic -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79042146?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+chemotherapy+%28Florence%2C+Italy%29&rft.atitle=Adjuvant+therapy+for+resectable+colorectal+carcinoma+with+5-fluorouracil+portal+vein+infusion.&rft.au=Cremona%2C+F%3BIzzo%2C+F%3BRuffolo%2C+F%3BPalaia%2C+R%3BParisi%2C+V&rft.aulast=Cremona&rft.aufirst=F&rft.date=1997-04-01&rft.volume=9&rft.issue=2&rft.spage=140&rft.isbn=&rft.btitle=&rft.title=Journal+of+chemotherapy+%28Florence%2C+Italy%29&rft.issn=1120009X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-31 N1 - Date created - 1997-07-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modification of oral contraceptive relationships on breast cancer risk by selected factors among younger women. AN - 79041191; 9179450 AB - In a case-control study of 1647 breast cancer cases and 1501 population controls under 45 years of age, potential modifying effects of other risk factors on the relationship of oral contraceptives to breast cancer were examined. Among the total series of study subjects, the relationship of extended pill usage was greater in non-white than white women. Oral contraceptive associations, however, did not appear to be substantially modified by other risk factors, including parity, body size, or family history of breast cancer (apart from a somewhat enhanced relationship among subjects who reported a sister with breast cancer. Further, oral contraceptive relationships did not vary by a history of benign breast disease, although the majority of subjects began pill usage prior to the development of benign breast disease. Among the women under the age of 35, in whom oral contraceptive relationships were heightened (over a twofold excess risk for use of 5 years or longer), pill relationships were less modified by race than in the total series. Although among these younger subjects there was no effect of pill usage in heavy women, and an enhanced relationship among heavier consumers of alcoholic beverages, these interactive effects were not statistically significant. The findings of this study generally support no substantial variation in oral contraceptive relationships by other breast cancer risk factors, although some further attention might be warranted regarding possible modifying effects of race, body size, type of relative with breast cancer, and alcohol consumption. JF - Contraception AU - Brinton, L A AU - Gammon, M D AU - Malone, K E AU - Schoenberg, J B AU - Daling, J R AU - Coates, R J AD - Environmental Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892, USA. brinton@epndce.nci.nih.gov Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 197 EP - 203 VL - 55 IS - 4 SN - 0010-7824, 0010-7824 KW - Contraceptives, Oral KW - 0 KW - Index Medicus KW - Population KW - United States KW - Research Methodology KW - Breast Cancer KW - Oral Contraceptives KW - Contraceptive Methods KW - Developed Countries KW - Risk Assessment KW - Evaluation KW - Whites--women KW - Population Characteristics KW - Demographic Factors KW - Diseases KW - Family Planning KW - North America KW - Americas KW - Oral Contraceptives, Combined KW - Blacks--women KW - Research Report KW - Studies KW - Cancer KW - Case Control Studies KW - Northern America KW - Neoplasms KW - Contraception KW - Ethnic Groups KW - Cultural Background KW - Risk Factors KW - Humans KW - European Continental Ancestry Group KW - Continental Population Groups KW - Adult KW - Menarche KW - Case-Control Studies KW - Biopsy KW - Body Mass Index KW - African Continental Ancestry Group KW - Female KW - Contraceptives, Oral -- adverse effects KW - Breast Neoplasms -- pathology KW - Breast Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79041191?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Contraception&rft.atitle=Modification+of+oral+contraceptive+relationships+on+breast+cancer+risk+by+selected+factors+among+younger+women.&rft.au=Brinton%2C+L+A%3BGammon%2C+M+D%3BMalone%2C+K+E%3BSchoenberg%2C+J+B%3BDaling%2C+J+R%3BCoates%2C+R+J&rft.aulast=Brinton&rft.aufirst=L&rft.date=1997-04-01&rft.volume=55&rft.issue=4&rft.spage=197&rft.isbn=&rft.btitle=&rft.title=Contraception&rft.issn=00107824&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-29 N1 - Date created - 1997-07-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Breast cancer and pesticides in Hawaii: the need for further study. AN - 79038219; 9168014 AB - Only 30% of all breast cancer can be explained by known risk factors. Increases in breast cancer incidence rates in Hawaii over the past few decades cannot be attributed solely to improvements in screening and detection. Avoidable environmental factors may contribute to a proportion of the unexplained cases. Emerging evidence on endocrine disruption suggests that environmental chemicals may play a role in the development of breast cancer. Agricultural chemicals, including endocrine disruptors, have been used intensively in Hawaii's island ecosystem over the past 40 years leaching into groundwater, and leading to unusually widespread occupational and general population exposures. This paper discusses breast cancer patterns in Hawaii in the context of documented episodes of exposure to two endocrine-disrupting chemicals, chlordane/heptachlor and 1,2-dibromo-3-chloropropane (DBCP), at levels that sometimes exceeded federal standards by several orders of magnitude. In light of this history, detailed geographic-based studies should be undertaken in Hawaii to elucidate the potential role of environmental factors in the development of breast cancer and other diseases. JF - Environmental health perspectives AU - Allen, R H AU - Gottlieb, M AU - Clute, E AU - Pongsiri, M J AU - Sherman, J AU - Obrams, G I AD - Extramural Epidemiology and Genetics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892-7105, USA. allenr@epndce.nci.nih.gov Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 679 EP - 683 VL - 105 Suppl 3 SN - 0091-6765, 0091-6765 KW - Insecticides KW - 0 KW - Pesticides KW - Water Pollutants, Chemical KW - Chlordan KW - 12789-03-6 KW - Heptachlor KW - 7GLS9ACN3L KW - 1,2-dibromo-3-chloropropane KW - 96K0FD4803 KW - Propane KW - T75W9911L6 KW - Index Medicus KW - Insecticides -- toxicity KW - Chlordan -- toxicity KW - Environmental Health KW - Water Pollutants, Chemical -- toxicity KW - Hawaii -- epidemiology KW - Humans KW - Propane -- analogs & derivatives KW - Aged KW - Heptachlor -- toxicity KW - Neoplasms, Hormone-Dependent -- epidemiology KW - Propane -- toxicity KW - Risk Factors KW - Endocrine Glands -- drug effects KW - Adult KW - Environmental Exposure KW - Middle Aged KW - Neoplasms, Hormone-Dependent -- etiology KW - Female KW - Breast Neoplasms -- etiology KW - Breast Neoplasms -- epidemiology KW - Pesticides -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79038219?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Breast+cancer+and+pesticides+in+Hawaii%3A+the+need+for+further+study.&rft.au=Allen%2C+R+H%3BGottlieb%2C+M%3BClute%2C+E%3BPongsiri%2C+M+J%3BSherman%2C+J%3BObrams%2C+G+I&rft.aulast=Allen&rft.aufirst=R&rft.date=1997-04-01&rft.volume=105+Suppl+3&rft.issue=&rft.spage=679&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 - 1997-08-11 N1 - Date created - 1997-08-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Epidemiol. 1981 Apr;113(4):413-22 [7211826] Toxicol Appl Pharmacol. 1961 Sep;3:545-59 [13777510] Environ Health Perspect. 1991 May;92:167-73 [1935846] J Natl Cancer Inst. 1993 Apr 21;85(8):648-52 [8468722] J Am Diet Assoc. 1993 Sep;93(9):994-9 [8395546] Epidemiol Rev. 1993;15(1):7-16 [8405214] J Natl Cancer Inst. 1994 Feb 2;86(3):232-4 [8283497] Environ Health Perspect. 1993 Oct;101(5):372-7 [8119245] Environ Health Perspect. 1993 Oct;101(5):378-84 [8080506] J Natl Cancer Inst. 1994 Apr 20;86(8):589-99 [8145274] Environ Health Perspect. 1994 Apr;102(4):380-3 [7925178] Toxicol Ind Health. 1994 May-Jun;10(3):163-79 [7855866] Cancer Causes Control. 1995 Mar;6(2):135-44 [7749053] Environ Health Perspect. 1995 Apr;103(4):346-51 [7607134] J Natl Cancer Inst. 1996 May 15;88(10):650-60 [8627641] Science. 1996 Jun 7;272(5267):1489-92 [8633243] J Occup Med. 1986 Nov;28(11):1145-50 [3097279] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lack of correlation between phenotype and genotype for the polymorphically expressed dihydropyrimidine dehydrogenase in a family of Pakistani origin. AN - 79037115; 9170156 AB - Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in pyrimidine catabolism. DPD deficiency is associated with an increased risk of toxicity in cancer patients receiving 5-fluorouracil (5-PU) treatment. DPD deficiency causes an inborn error of metabolism called thymine-uraciluria that is in some instances associated with convulsive disorders and developmental delay in children. We have studied the molecular mechanism accounting for DPD deficiency in a Pakistani pedigree having 2-year-old child with thymine-uraciluria and exhibiting some degree of motor impairment and developmental delay. A common splice mutation was found in the patient's dihydropyrimidine dehydrogenase (DPYD) gene that produces a mutant mRNA resulting in the complete lack of DPD protein and activity in lymphocytes and primary fibroblast. This trait segregated in the family following a typical Mendelian distribution. Surprisingly, the patient's brother also had thymine-uraciluria and was homozygous for the splicing mutation but was clinically asymptomatic. Sequence tagged sites (STS) linkage analyses within 5 megabases of telomeric and centromeric DNA surrounding the DPYD gene revealed no allelic polymorphism between the two brothers. These results suggest that DPD deficiency might not be the only cause of the more severe clinical phenotypes observed in certain thymine-uraciluria patients and that an incomplete correlation between phenotype and genotype is present in the population. JF - Pharmacogenetics AU - Fernandez-Salguero, P M AU - Sapone, A AU - Wei, X AU - Holt, J R AU - Jones, S AU - Idle, J R AU - Gonzalez, F J AD - Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 161 EP - 163 VL - 7 IS - 2 SN - 0960-314X, 0960-314X KW - Uracil KW - 56HH86ZVCT KW - Oxidoreductases KW - EC 1.- KW - Dihydrouracil Dehydrogenase (NADP) KW - EC 1.3.1.2 KW - Thymine KW - QR26YLT7LT KW - Index Medicus KW - Phenotype KW - Genotype KW - RNA Splicing KW - Humans KW - Molecular Sequence Data KW - Sequence Tagged Sites KW - Pakistan -- ethnology KW - Mutation KW - Male KW - Child, Preschool KW - Thymine -- urine KW - Polymorphism, Restriction Fragment Length KW - Oxidoreductases -- deficiency KW - Purine-Pyrimidine Metabolism, Inborn Errors -- genetics KW - Uracil -- urine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79037115?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacogenetics&rft.atitle=Lack+of+correlation+between+phenotype+and+genotype+for+the+polymorphically+expressed+dihydropyrimidine+dehydrogenase+in+a+family+of+Pakistani+origin.&rft.au=Fernandez-Salguero%2C+P+M%3BSapone%2C+A%3BWei%2C+X%3BHolt%2C+J+R%3BJones%2C+S%3BIdle%2C+J+R%3BGonzalez%2C+F+J&rft.aulast=Fernandez-Salguero&rft.aufirst=P&rft.date=1997-04-01&rft.volume=7&rft.issue=2&rft.spage=161&rft.isbn=&rft.btitle=&rft.title=Pharmacogenetics&rft.issn=0960314X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-29 N1 - Date created - 1997-07-29 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U57655; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antinociceptive effects of dynorphin peptides in a model of inflammatory pain. AN - 79002343; 9150287 AB - Dynorphin A (DYN) peptides, administered into the central nervous system, have produced inconsistent analgesic actions in tests using thermal stimuli. This study examined antinociceptive effects of intravenous and intraplantar DYN-(2-17) against noxious pressure in rats with Freund's adjuvant-induced unilateral hindpaw inflammation. The effects of DYN-(2-17) were compared to those of the opioid agonists morphine. (D-Ala2,N-Methyl-Phe4,Gly-ol5)-enkephalin (DAMGO) and DYN-(1-17). Intravenous DYN-(2-17) (0.188-10 mg/kg) produced dose-dependent elevations of paw pressure thresholds in inflamed and in non-inflamed paws. These effects were similar in magnitude to those of subcutaneous morphine (2 mg/kg), at doses of 0.375-1.5 mg/kg they were significantly greater on the inflamed (right) than on the non-inflamed (left) paw, and they were not reversible by intravenous naloxone (1-10 mg/kg). Intraplantar Dyn-(2-17)(0.001-0.3 mg) was ineffective, whereas both intraplantar DYN-(1-17)(0.15-0.3 mg) and DAMGO (0.008-0.016 mg) produced dose-dependent and naloxone-reversible elevations of paw pressure thresholds. The intraplantar injection of both Dyn peptides produced a transient increase in the volume of non-inflamed paws. These findings suggest that intravenous DYN-(2-17) produces possibly centrally mediated, non-opioid antinociceptive effects against noxious pressure. At certain doses these effects are more potent in inflamed than in non-inflamed paws. In contrast to the opioid peptides DYN-(1-17) and DAMGO, DYN-(2-17) does not appear to have no peripheral antinociceptive actions. JF - Pain AU - Beyer, A AU - Schäfer, M AU - Stein, C AD - Division of Intramural Research, National Institute on Drug Abuse, Baltimore, MD 21224, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 141 EP - 147 VL - 70 IS - 2-3 SN - 0304-3959, 0304-3959 KW - Analgesics KW - 0 KW - Analgesics, Opioid KW - Enkephalins KW - Peptide Fragments KW - Enkephalin, Ala(2)-MePhe(4)-Gly(5)- KW - 100929-53-1 KW - Dynorphins KW - 74913-18-1 KW - dynorphin (2-17) KW - 83608-80-4 KW - Index Medicus KW - Rats KW - Edema -- chemically induced KW - Animals KW - Enkephalins -- therapeutic use KW - Rats, Wistar KW - Analgesics -- therapeutic use KW - Male KW - Inflammation -- physiopathology KW - Peptide Fragments -- therapeutic use KW - Peptide Fragments -- adverse effects KW - Dynorphins -- adverse effects KW - Foot KW - Analgesics, Opioid -- therapeutic use KW - Dynorphins -- therapeutic use KW - Analgesics, Opioid -- adverse effects KW - Nociceptors -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79002343?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pain&rft.atitle=Antinociceptive+effects+of+dynorphin+peptides+in+a+model+of+inflammatory+pain.&rft.au=Beyer%2C+A%3BSch%C3%A4fer%2C+M%3BStein%2C+C&rft.aulast=Beyer&rft.aufirst=A&rft.date=1997-04-01&rft.volume=70&rft.issue=2-3&rft.spage=141&rft.isbn=&rft.btitle=&rft.title=Pain&rft.issn=03043959&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-15 N1 - Date created - 1997-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Surgically debulked malignant pleural mesothelioma: results and prognostic factors. AN - 78996765; 9142382 AB - We analyzed morbidity and mortality, sites of recurrence, and possible prognostic factors in 95 (78 male, 17 female) patients with MPM on phase I-III trials since 1990. A debulking resection to a requisite, residual tumor thickness of < or = 5 mm was required for inclusion. Preoperative tumor volumes were determined by three-dimensional reconstruction of chest computerized tomograms. Pleurectomy (n = 39) or extrapleural pneumonectomy (EPP; n = 39) was performed. Seventeen patients could not be debulked. Preoperative EPP platelet counts (404,000) and mean tumor volume (491 cm3) were greater than that seen for pleurectomy (344,000, 114 cm3). Median survival for all patients was 11.2 months, with that for pleurectomy 14.5 months, that for EPP 9.4 months, and that for unresectable patients 5.0 months. Arrhythmia (n = 14; 15%) was the most common complication, and there were two deaths related to surgery (2.0%). Tumor volume of > 100 ml, biphasic histology, male sex, and elevated platelet count were associated with decreased survival (p < 0.05). Both EPP and pleurectomy had equivalent recurrence rates (27 of 39 [69%] and 31 of 39 [79%], respectively); however, 17 of 27 EPP recurrences as opposed to 28 of 31 pleurectomy recurrences were locoregional (p2 = 0.013). Debulking resections for MPM can be performed with low operative mortality. Size and platelet count are important preoperative prognostic parameters for MPM. Patients with poor prognostic indicators should probably enter nonsurgical, innovative trials where toxicity or response to therapy can be evaluated. JF - Annals of surgical oncology AU - Pass, H I AU - Kranda, K AU - Temeck, B K AU - Feuerstein, I AU - Steinberg, S M AD - Thoracic Oncology Section, National Cancer Institute/National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1997 SP - 215 EP - 222 VL - 4 IS - 3 SN - 1068-9265, 1068-9265 KW - Index Medicus KW - Pneumonectomy -- adverse effects KW - Combined Modality Therapy KW - Humans KW - Immunotherapy KW - Prognosis KW - Aged KW - Recurrence KW - Survival Rate KW - Postoperative Complications KW - Risk Factors KW - Adult KW - Pneumonectomy -- mortality KW - Middle Aged KW - Phototherapy KW - United States -- epidemiology KW - Female KW - Male KW - Survival Analysis KW - Proportional Hazards Models KW - Mesothelioma -- epidemiology KW - Mesothelioma -- surgery KW - Pleural Neoplasms -- epidemiology KW - Pleural Neoplasms -- surgery UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78996765?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+surgical+oncology&rft.atitle=Surgically+debulked+malignant+pleural+mesothelioma%3A+results+and+prognostic+factors.&rft.au=Pass%2C+H+I%3BKranda%2C+K%3BTemeck%2C+B+K%3BFeuerstein%2C+I%3BSteinberg%2C+S+M&rft.aulast=Pass&rft.aufirst=H&rft.date=1997-04-01&rft.volume=4&rft.issue=3&rft.spage=215&rft.isbn=&rft.btitle=&rft.title=Annals+of+surgical+oncology&rft.issn=10689265&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-17 N1 - Date created - 1997-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An update on the clinical use of methadone for cancer pain. AN - 78994930; 9150283 AB - Methadone is a synthetic opioid agonist considered a second choice drug in the management of cancer pain. Methadone has a number of unique characteristics including excellent oral and rectal absorption, no known active metabolites, high potency, low cost, and longer administration intervals, as well as an incomplete cross-tolerance with respect to other mu-opioid receptor agonist drugs. For these reasons, methadone has the potential of playing a major role in the treatment of cancer pain. However, its use is limited by the remarkably long and unpredictable half-life, large inter-individual variations in pharmacokinetics, the potential for delayed toxicity, and above all by the limited knowledge of correct administration intervals and the equianalgesic ratio with other opioids when administered chronically. Recent findings suggest that standard equianalgesic tables are unreliable for methadone titration in patients tolerant to high doses of opioid agonists and that switchovers should take place slowly and should be personalized. Future research has to better define the variation in both bioavailability and elimination of methadone in different patient populations, the interaction between methadone and the most commonly used drugs in cancer patients, the type and activity of potential methadone metabolites, and the equianalgesic doses between methadone and the most commonly used opioids. JF - Pain AU - Ripamonti, C AU - Zecca, E AU - Bruera, E AD - Pain Therapy and Palliative Care Division, National Cancer Institute of Milan, Milano, Italy. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 109 EP - 115 VL - 70 IS - 2-3 SN - 0304-3959, 0304-3959 KW - Analgesics, Opioid KW - 0 KW - Methadone KW - UC6VBE7V1Z KW - Index Medicus KW - Evaluation Studies as Topic KW - Administration, Oral KW - Humans KW - Administration, Rectal KW - Neoplasms -- drug therapy KW - Methadone -- adverse effects KW - Methadone -- therapeutic use KW - Analgesics, Opioid -- therapeutic use KW - Palliative Care -- trends KW - Methadone -- administration & dosage KW - Analgesics, Opioid -- adverse effects KW - Analgesics, Opioid -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78994930?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pain&rft.atitle=An+update+on+the+clinical+use+of+methadone+for+cancer+pain.&rft.au=Ripamonti%2C+C%3BZecca%2C+E%3BBruera%2C+E&rft.aulast=Ripamonti&rft.aufirst=C&rft.date=1997-04-01&rft.volume=70&rft.issue=2-3&rft.spage=109&rft.isbn=&rft.btitle=&rft.title=Pain&rft.issn=03043959&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-15 N1 - Date created - 1997-07-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Pain. 1997 Oct;73(1):114-5 [9414068] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased cyclic AMP response to forskolin in Epstein-Barr virus-transformed human B-lymphocytes derived from schizophrenics. AN - 78991895; 9151357 AB - Phorbol 12-myristate-13-acetate (PMA), a protein kinase C (PKC) activator, elevated basal cyclic AMP levels and enhanced isoproterenol-, prostaglandin E1- (PGE1), forskolin- and cholera toxin-stimulated cyclic AMP accumulation in Epstein-Barr virus (EBV)-transformed human B-lymphocytes. Staurosporine, a PKC inhibitor, significantly antagonized the increase in cyclic AMP accumulation produced by PMA, whereas the inactive phorbol ester, 4 alpha-phorbol 12,13-didecanoate (4 alpha PDD), had no effect. Basal levels of cyclic AMP and the accumulation of cyclic AMP produced by PMA, isoproterenol, PGE1, cholera toxin and the combination of these compounds with PMA were not significantly different between schizophrenics and controls. The cyclic AMP response to forskolin in the presence and absence of PMA was significantly greater in EBV-transformed human B-lymphocytes from schizophrenics. These results suggest that activation of adenylyl cyclase by forskolin is elevated in EBV-transformed B-lymphocytes derived from schizophrenics and that this elevation is further enhanced through a PKC-dependent phosphorylation mechanism. JF - Psychopharmacology AU - Natsukari, N AU - Kulaga, H AU - Baker, I AU - Wyatt, R J AU - Masserano, J M AD - National Institute of Mental Health, Neuropsychiatry Branch, Washington, DC 20032, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 235 EP - 241 VL - 130 IS - 3 SN - 0033-3158, 0033-3158 KW - Colforsin KW - 1F7A44V6OU KW - Cholera Toxin KW - 9012-63-9 KW - Cyclic AMP KW - E0399OZS9N KW - Alprostadil KW - F5TD010360 KW - Isoproterenol KW - L628TT009W KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Lymphocyte Activation -- drug effects KW - Alprostadil -- pharmacology KW - Humans KW - Adult KW - Cholera Toxin -- pharmacology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Herpesvirus 4, Human KW - Male KW - Isoproterenol -- pharmacology KW - Female KW - Cyclic AMP -- biosynthesis KW - B-Lymphocytes -- drug effects KW - Colforsin -- pharmacology KW - Schizophrenia -- metabolism KW - B-Lymphocytes -- metabolism KW - Cell Transformation, Viral -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78991895?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology&rft.atitle=Increased+cyclic+AMP+response+to+forskolin+in+Epstein-Barr+virus-transformed+human+B-lymphocytes+derived+from+schizophrenics.&rft.au=Natsukari%2C+N%3BKulaga%2C+H%3BBaker%2C+I%3BWyatt%2C+R+J%3BMasserano%2C+J+M&rft.aulast=Natsukari&rft.aufirst=N&rft.date=1997-04-01&rft.volume=130&rft.issue=3&rft.spage=235&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-07 N1 - Date created - 1997-07-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lessons from Chernobyl: the event, the aftermath fallout: radioactive, political, social. AN - 78987713; 9133682 AB - The accident at the Chernobyl nuclear power station on April 26, 1986, released about 300 MCi of radioactive substances, including about 40 MCi of 131I and 100 MCi of short-lived radioiodines. In the immediate surroundings there were 143 cases of acute radiation syndrome, 34 deaths, and hundreds of thousands of people displaced from their homes, many permanently. The social and psychologic stresses that followed have been enormous and long-lasting. This article focuses on the rising incidence of thyroid cancer in exposed children. Radiation-induced thyroid cancer following external radiation is well documented but there is little evidence in humans of thyroid cancer from internal radiation and the risk coefficient for radioiodine exposure is known. To achieve this, thyroid dose reconstruction and prospective follow-up of about 50,000 persons who were children in 1986 will be required. Thyroid cancer in children of southern Belarus began to increase in 1990 and there now are about 1,000 cases in Belarus and northern Ukraine. These aggressively growing tumors, almost all variants of papillary thyroid cancer, are typical for thyroid cancer in children not exposed to radiation, and a low mortality rate is to be expected. It also is expected, however, that malignant as well as benign thyroid neoplasms will continue to arise in these exposed children well into their adult life. JF - Thyroid : official journal of the American Thyroid Association AU - Robbins, J AD - Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1766, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 189 EP - 192 VL - 7 IS - 2 SN - 1050-7256, 1050-7256 KW - Radioactive Fallout KW - 0 KW - Index Medicus KW - Power Plants KW - Humans KW - Ukraine KW - Adult KW - Neoplasms, Radiation-Induced KW - Carcinoma, Papillary KW - Thyroid Neoplasms -- etiology KW - Child KW - Nuclear Reactors KW - Republic of Belarus KW - Radioactive Hazard Release KW - Politics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78987713?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Thyroid+%3A+official+journal+of+the+American+Thyroid+Association&rft.atitle=Lessons+from+Chernobyl%3A+the+event%2C+the+aftermath+fallout%3A+radioactive%2C+political%2C+social.&rft.au=Robbins%2C+J&rft.aulast=Robbins&rft.aufirst=J&rft.date=1997-04-01&rft.volume=7&rft.issue=2&rft.spage=189&rft.isbn=&rft.btitle=&rft.title=Thyroid+%3A+official+journal+of+the+American+Thyroid+Association&rft.issn=10507256&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-19 N1 - Date created - 1997-06-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of various pretreatments on the hepatotoxicity of inhaled styrene in the B6C3F1 mouse. AN - 78984227; 9149379 AB - 1. The roles of cytochrome P450 monooxygenases (P450) and glutathione (GSH) in styrene hepatotoxicity were investigated in mice by pretreating with either phenobarbital (PB; P450 inducer), SKF 525A (P450 inhibitor), N-acetylcysteine (NAC; GSH precursor), or saline (vehicle control) prior to a 6-h exposure to either 500 ppm styrene on air. 2. Styrene caused hepatocellular degeneration or necrosis in all groups; these changes were more extensive and severe in mice pretreated with PB. Styrene significantly increased relative liver weights and serum ALT and SDH levels only in mice pretreated with PB. NAC did not prevent GSH depletion or hepatotoxicity. 3. In the fat of SKF 525A-pretreated mice a slight but statistically significant increase in styrene levels was observed, suggesting that metabolism was decreased; the SO/styrene ratio in the fat of PB-pretreated mice showed a slight, but statistically significant, increase indicating a slight increase in styrene metabolism. Neither SKF 525A nor PB caused changes in microsomal enzyme activity in vitro. 4. These results suggest that styrene may be activated by a pathway not totally dependent upon P450 enzyme activity, or more likely that PB and SKF 525A are not specific for the P450 enzymes involved in activation and detoxification of styrene. JF - Xenobiotica; the fate of foreign compounds in biological systems AU - Morgan, D L AU - Mahler, J F AU - Wilson, R E AU - Moorman, M P AU - Price, H C AU - Patrick, K R AU - Richards, J H AU - O'Connor, R W AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 401 EP - 411 VL - 27 IS - 4 SN - 0049-8254, 0049-8254 KW - Cytochrome P-450 Enzyme Inhibitors KW - 0 KW - Styrenes KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Epoxide Hydrolases KW - EC 3.3.2.- KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Animals KW - Epoxide Hydrolases -- metabolism KW - Organ Size -- physiology KW - Glutathione -- metabolism KW - Body Weight -- physiology KW - Cytochrome P-450 Enzyme System -- metabolism KW - Liver -- metabolism KW - Mice KW - Epoxide Hydrolases -- antagonists & inhibitors KW - Liver Function Tests KW - Epoxide Hydrolases -- biosynthesis KW - Mice, Inbred Strains KW - Adipose Tissue -- metabolism KW - Enzyme Induction -- drug effects KW - Microsomes, Liver -- enzymology KW - Administration, Inhalation KW - Male KW - Styrenes -- administration & dosage KW - Chemical and Drug Induced Liver Injury -- pathology KW - Styrenes -- pharmacokinetics KW - Styrenes -- toxicity KW - Chemical and Drug Induced Liver Injury -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78984227?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Xenobiotica%3B+the+fate+of+foreign+compounds+in+biological+systems&rft.atitle=Effects+of+various+pretreatments+on+the+hepatotoxicity+of+inhaled+styrene+in+the+B6C3F1+mouse.&rft.au=Morgan%2C+D+L%3BMahler%2C+J+F%3BWilson%2C+R+E%3BMoorman%2C+M+P%3BPrice%2C+H+C%3BPatrick%2C+K+R%3BRichards%2C+J+H%3BO%27Connor%2C+R+W&rft.aulast=Morgan&rft.aufirst=D&rft.date=1997-04-01&rft.volume=27&rft.issue=4&rft.spage=401&rft.isbn=&rft.btitle=&rft.title=Xenobiotica%3B+the+fate+of+foreign+compounds+in+biological+systems&rft.issn=00498254&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-05 N1 - Date created - 1997-08-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Correlation of 2,3,7,8-tetrachlorodibenzo-p-dioxin induction of cytochrome P4501A in vascular endothelium with toxicity in early life stages of lake trout. AN - 78977260; 9144443 AB - Edema and cardiovascular dysfunction occur in vertebrates exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during early development. This study examined cytochrome P4501A (CYP1A) induction in endothelium and its possible association with mortality due to the edema and vascular effects of TCDD in lake trout early life stages. Lake trout (Salvelinus namaycush) eggs were injected at 24-50 hr postfertilization with 0.2 microl of 50 mM phosphatidylcholine liposomes or liposomes containing TCDD to give seven doses ranging from 11 to 176 pg TCDD/g egg. Doses of TCDD greater than 44 pg/g egg elicited hemorrhages; yolk sac, pericardial, and meningial edema; craniofacial malformations; regional ischemia; growth retardation; and mortality at the sac fry stage of development. Expression of CYP1A was assessed at four developmental stages, by immunohistochemical analysis of serial sections of individual fish with monoclonal antibody 1-12-3 to teleost CYP1A. CYP1A staining occurred in endothelial cells of many organs of TCDD-exposed but not vehicle-exposed embryos at 1 week prehatch and sac fry at 2 weeks posthatch. Earlier developmental stages examined were negative for CYP1A expression at any dose of TCDD. The strongest response occurred in sac fry at TCDD doses greater than 88 pg TCDD/g egg but was detected at doses as low as 22 pg TCDD/g egg. CYP1A staining in endothelium appeared at lower doses and was stronger than that in other cell types, in both prehatch embryos and posthatch sac fry. Thus, the vascular system is a major initial site affected by TCDD in lake trout early life stages, and the vascular endothelium is a cell type uniquely sensitive to induction of CYP1A in these developing animals. Based on an index of immunohistochemical staining of CYP1A, endothelial CYP1A induction in sac fry by TCDD occurred with an ED50 of 64-69 pg TCDD/g egg, similar to the dose-response for mortality occurring during the sac fry stage of development (LD50 = 47 pg TCDD/g egg). The correlations seen here suggest that CYP1A or aryl hydrocarbon receptor (AhR) in the endothelium may be linked to early lesions that result in TCDD-induced vascular derangements leading to yolk sac, pericardial, and meningial edema that is associated with lake trout sac fry mortality, but the precise mechanism remains to be determined. JF - Toxicology and applied pharmacology AU - Guiney, P D AU - Smolowitz, R M AU - Peterson, R E AU - Stegeman, J J AD - Department of Biological Sciences and NIEHS Marine and Freshwater Biomedical Core Center, University of Wisconsin, Milwaukee 53204, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 256 EP - 273 VL - 143 IS - 2 SN - 0041-008X, 0041-008X KW - Drug Carriers KW - 0 KW - Liposomes KW - Polychlorinated Dibenzodioxins KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - Index Medicus KW - Animals KW - Animals, Newborn -- metabolism KW - Ovum -- drug effects KW - Ovum -- enzymology KW - Embryo, Nonmammalian -- enzymology KW - Yolk Sac -- pathology KW - Yolk Sac -- enzymology KW - Enzyme Induction -- drug effects KW - Yolk Sac -- drug effects KW - Embryo, Nonmammalian -- pathology KW - Embryo, Nonmammalian -- drug effects KW - Female KW - Male KW - Endothelium, Vascular -- enzymology KW - Endothelium, Vascular -- drug effects KW - Trout -- embryology KW - Polychlorinated Dibenzodioxins -- toxicity KW - Trout -- metabolism KW - Cytochrome P-450 CYP1A1 -- biosynthesis KW - Cytochrome P-450 CYP1A1 -- drug effects KW - Cytochrome P-450 CYP1A1 -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78977260?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Correlation+of+2%2C3%2C7%2C8-tetrachlorodibenzo-p-dioxin+induction+of+cytochrome+P4501A+in+vascular+endothelium+with+toxicity+in+early+life+stages+of+lake+trout.&rft.au=Guiney%2C+P+D%3BSmolowitz%2C+R+M%3BPeterson%2C+R+E%3BStegeman%2C+J+J&rft.aulast=Guiney&rft.aufirst=P&rft.date=1997-04-01&rft.volume=143&rft.issue=2&rft.spage=256&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=0041008X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-02 N1 - Date created - 1997-06-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Decoupling of DNA excision repair and RNA transcription in translocation breaksite regions of plasmacytoma-susceptible BALB/cAnPt mice. AN - 78964157; 9111201 AB - Preferential repair of pyrimidine dimers in rodent cells is thought to be directly coupled to the RNA transcription machinery. The most compelling evidence for this notion is the finding that excision repair occurs more rapidly in the template strand of DNA of transcribed genes than in the non-template strand. A thorough test of this coupling concept by careful comparison of the rate of repair to the rate of transcription of a gene and its regulatory region has not been reported. In the present study, we used nuclear run-on as a measure of transcription in the c-myc and Pvt1 genes in normal B-lymphoblasts from plasmacytoma-susceptible (BALB/cAnPt) and plasmacytoma-resistant (DBA/2N) strains of mice. Previous studies have shown that these loci, but not c-abl or Dhfr are repaired differently in mouse strains: poorly in BALB/cAnPt but efficiently in DBA/2N. The results presented here indicate that in DBA/2N cells, run-on transcription from both DNA strands can be readily detected in the regions of c-myc and Pvt1 that were efficiently repaired. Unexpectedly, however, in BALB/cAnPt lymphoblasts, transcription was equivalent to that of DBA/2N, despite a dramatic reduction in efficiency of excision repair. This finding indicates that, in BALB/cAnPt lymphoblasts, DNA repair 5' to c-myc and in Pvt1 is decoupled from the RNA transcription machinery. We postulate that this dissociation of repair and transcription represents a BALB/cAnPt-specific defect in a component of the transcription/repair complex that specifically compromises repair activity but not transcription. This defect may be responsible for the inability of normal BALB/cAnPt lymphoblasts to repair DNA sequences in the c-myc 5' flank and the Pvt1 gene, inducing gene-specific instability that predisposes these loci to genetic accidents, including chromosomal translocation, retroviral integration and other mutations. JF - Carcinogenesis AU - Beecham, E J AU - Owens, J D AU - Shaughnessy, J D AU - Huppi, K AU - Bohr, V A AU - Mushinski, J F AD - Laboratory of Molecular Pharmacology, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 687 EP - 694 VL - 18 IS - 4 SN - 0143-3334, 0143-3334 KW - RNA KW - 63231-63-0 KW - Index Medicus KW - Animals KW - DNA Methylation KW - Polymorphism, Restriction Fragment Length KW - Genes, myc KW - Mice KW - Genetic Predisposition to Disease KW - Mice, Inbred BALB C KW - Species Specificity KW - Female KW - Mice, Inbred DBA KW - Plasmacytoma -- genetics KW - DNA Repair KW - Transcription, Genetic KW - Translocation, Genetic KW - RNA -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78964157?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Decoupling+of+DNA+excision+repair+and+RNA+transcription+in+translocation+breaksite+regions+of+plasmacytoma-susceptible+BALB%2FcAnPt+mice.&rft.au=Beecham%2C+E+J%3BOwens%2C+J+D%3BShaughnessy%2C+J+D%3BHuppi%2C+K%3BBohr%2C+V+A%3BMushinski%2C+J+F&rft.aulast=Beecham&rft.aufirst=E&rft.date=1997-04-01&rft.volume=18&rft.issue=4&rft.spage=687&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-09 N1 - Date created - 1997-05-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Proposed recommendations for research on biochemical markers for problematic drinking. AN - 78963623; 9113259 AB - Biochemical markers can serve as valuable tools in screening for problematic drinking, determining whether a health problem is likely alcohol related, and monitoring alcoholics for relapse during and after treatment. Furthermore, biochemical markers can assist in forensic investigations; in identification of public health, safety, and transportation workers who may drink excessively and who, as a result, may put others at risk; in evaluation of efficacy of treatments for alcohol abuse; and in recognition of early phase alcohol-related tissue damage. Within all of these contexts, a biochemical marker or set of markers may corroborate verbal reports or may provide valuable independent information on alcohol use when an individual is unable or unwilling to offer valid data about alcohol consumption. JF - Alcoholism, clinical and experimental research AU - Allen, J P AU - Fertig, J B AU - Litten, R Z AU - Sillanaukee, P AU - Anton, R F AD - National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 244 EP - 247 VL - 21 IS - 2 SN - 0145-6008, 0145-6008 KW - Biomarkers KW - 0 KW - Index Medicus KW - Reference Values KW - Humans KW - Predictive Value of Tests KW - Follow-Up Studies KW - Liver Function Tests KW - Alcoholism -- rehabilitation KW - Alcoholism -- enzymology KW - Alcoholism -- diagnosis KW - Biomarkers -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78963623?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Proposed+recommendations+for+research+on+biochemical+markers+for+problematic+drinking.&rft.au=Allen%2C+J+P%3BFertig%2C+J+B%3BLitten%2C+R+Z%3BSillanaukee%2C+P%3BAnton%2C+R+F&rft.aulast=Allen&rft.aufirst=J&rft.date=1997-04-01&rft.volume=21&rft.issue=2&rft.spage=244&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 - 1997-07-22 N1 - Date created - 1997-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Percent 131I uptake and post-therapy 131I scans: their role in the management of thyroid cancer. AN - 78958376; 9133701 AB - This short review focuses on two questions commonly asked about 131I therapy of thyroid cancer. The first relates to radiation dosimetry. What percentage of 131I uptake is needed for effective therapy? Studies have shown that 131I uptake and therapeutic outcome may not be closely related. A more powerful relationship, however, occurs by using percent uptake per gram. A rearrangement of the basic dosimetry equation shows that for a specific level of radiation, percent uptake per gram and effective half-life are inversely related. Formulas developed from this relationship are useful in determining whether uptake is satisfactory but require estimates of effective half-life and tumor mass. The second question is whether post-therapy 131I scans are useful. Because the sensitivity of 131I scanning is related directly to the amount of radioactivity administered, imaging after therapy may show previously undetected lesions that not infrequently are distant metastases. Thus, information from post-therapy scans may 1) after therapy, 2) direct new diagnostic studies, 3) lead to formal dosimetry studies when maximal 131I doses are needed to treat distant metastases, and 4) be necessary to obtain when 131I therapy is administered to patients with elevated thyroglobulin and negative diagnostic scans. Should post-therapy scans always be performed? They are easy to perform and are clinically useful but may be inconvenient to patients and costly overall. At this time, however, there is not a simple paradigm for selecting patients who may forego these scans. JF - Thyroid : official journal of the American Thyroid Association AU - Reynolds, J C AD - Nuclear Medicine Department, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 281 EP - 284 VL - 7 IS - 2 SN - 1050-7256, 1050-7256 KW - Iodine Radioisotopes KW - 0 KW - Index Medicus KW - Neoplasm Metastasis -- diagnostic imaging KW - Half-Life KW - Humans KW - Radionuclide Imaging KW - Iodine Radioisotopes -- therapeutic use KW - Radiation Dosage KW - Thyroid Neoplasms -- diagnostic imaging KW - Thyroid Neoplasms -- surgery KW - Thyroid Neoplasms -- radiotherapy KW - Iodine Radioisotopes -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78958376?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Thyroid+%3A+official+journal+of+the+American+Thyroid+Association&rft.atitle=Percent+131I+uptake+and+post-therapy+131I+scans%3A+their+role+in+the+management+of+thyroid+cancer.&rft.au=Reynolds%2C+J+C&rft.aulast=Reynolds&rft.aufirst=J&rft.date=1997-04-01&rft.volume=7&rft.issue=2&rft.spage=281&rft.isbn=&rft.btitle=&rft.title=Thyroid+%3A+official+journal+of+the+American+Thyroid+Association&rft.issn=10507256&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-19 N1 - Date created - 1997-06-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Progress in clinical chemoprevention. AN - 78956732; 9129692 AB - Chemoprevention has four goals: (1) inhibition of carcinogens, (2) logical intervention for persons at genetic risk for cancer, (3) treatment of precancerous lesions, and (4) confirmation and translation of leads from dietary epidemiology into intervention strategies. The National Cancer Institute has described a multidisciplinary, cancer science-based program for chemopreventive drug development that addresses these objectives, and has collaborated with the US Food and Drug Administration to provide consensus guidance for applying this approach. A critical component is the identification and characterization of intermediate biomarkers of cancer and their validation as surrogate end points for cancer incidence in clinical chemoprevention trials. More than 40 agents in the program are currently on the clinical development path (preclinical toxicology and phase I clinical safety studies or phase II/III efficacy trials), with the major effort in phase II studies to identify and characterize intermediate biomarkers. The continually advancing knowledge of molecular and tissue-based carcinogenesis mechanisms will provide leads to new chemopreventive agents with increased specificity for carcinogenesis-related activities and, hence, reduced toxicity by virtue of minimal effects on normal cell and tissue functions. Results from the Human Genome Project will help identify and evaluate the potential for chemopreventive intervention in cohorts at genetic risk and will provide specific target lesions for intervention strategies. JF - Seminars in oncology AU - Kelloff, G J AU - Hawk, E T AU - Karp, J E AU - Crowell, J A AU - Boone, C W AU - Steele, V E AU - Lubet, R A AU - Sigman, C C AD - Division of Cancer Prevention and Control, Chemoprevention Branch, National Cancer Institute, Bethesda, MD 20852, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 241 EP - 252 VL - 24 IS - 2 SN - 0093-7754, 0093-7754 KW - Anticarcinogenic Agents KW - 0 KW - Drugs, Investigational KW - Index Medicus KW - Evaluation Studies as Topic KW - Humans KW - Clinical Trials as Topic KW - Pharmacology, Clinical KW - Drugs, Investigational -- therapeutic use KW - Drugs, Investigational -- pharmacology KW - Anticarcinogenic Agents -- therapeutic use KW - Anticarcinogenic Agents -- pharmacology KW - Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78956732?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+oncology&rft.atitle=Progress+in+clinical+chemoprevention.&rft.au=Kelloff%2C+G+J%3BHawk%2C+E+T%3BKarp%2C+J+E%3BCrowell%2C+J+A%3BBoone%2C+C+W%3BSteele%2C+V+E%3BLubet%2C+R+A%3BSigman%2C+C+C&rft.aulast=Kelloff&rft.aufirst=G&rft.date=1997-04-01&rft.volume=24&rft.issue=2&rft.spage=241&rft.isbn=&rft.btitle=&rft.title=Seminars+in+oncology&rft.issn=00937754&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-06 N1 - Date created - 1997-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical safety of serial monthly administrations of gadopentetate dimeglumine in patients with multiple sclerosis: implications for natural history and early-phase treatment trials. AN - 78955581; 9109864 AB - Serial contrast magnetic resonance imaging (MRI) has played an increasingly important role in understanding natural-history and early-treatment trials of multiple sclerosis patients. The purpose of this study is to determine whether the serial administration of gadopentetate dimeglumine at the conventional dose has any demonstrable effect on routine hematologic or serum chemistries. This study followed 56 patients with multiple sclerosis in a longitudinal natural-history trial using contrast-enhanced MRI scans over a four-year period between 1988 and 1993. Patients received between 3 and 53 doses of gadopentetate dimeglumine at 0.1 mmol/kg intravenously. A retrospective review of regular blood screening tests over this period identified no significant effect either on routine hematologic studies, as defined by complete blood count (hemoglobin, hematocrit, platelet and white blood cell counts, and mean corpuscular volume); standard serum chemistry studies, including electrolytes (sodium, potassium, chloride) and renal and liver function tests; or serum iron profiles. We conclude, therefore, that serial contrast-enhanced MRIs can be used safely as an outcome measure for Phase I/II evaluations of new therapies for multiple sclerosis. JF - Neurology AU - Tresley, R M AU - Stone, L A AU - Fields, N AU - Maloni, H AU - McFarland, H AU - Frank, J A AD - National Institutes of Health, Bethesda, MD 20892-1074, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 832 EP - 835 VL - 48 IS - 4 SN - 0028-3878, 0028-3878 KW - Contrast Media KW - 0 KW - Hemoglobins KW - Organometallic Compounds KW - Pentetic Acid KW - 7A314HQM0I KW - Gadolinium DTPA KW - K2I13DR72L KW - Abridged Index Medicus KW - Index Medicus KW - Drug Administration Schedule KW - Clinical Trials, Phase II as Topic KW - Humans KW - Safety KW - Retrospective Studies KW - Longitudinal Studies KW - Hemoglobins -- analysis KW - Clinical Trials, Phase I as Topic KW - Adult KW - Middle Aged KW - Female KW - Male KW - Contrast Media -- adverse effects KW - Organometallic Compounds -- administration & dosage KW - Pentetic Acid -- analogs & derivatives KW - Pentetic Acid -- adverse effects KW - Pentetic Acid -- administration & dosage KW - Contrast Media -- administration & dosage KW - Organometallic Compounds -- adverse effects KW - Multiple Sclerosis -- diagnosis KW - Multiple Sclerosis -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78955581?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Clinical+safety+of+serial+monthly+administrations+of+gadopentetate+dimeglumine+in+patients+with+multiple+sclerosis%3A+implications+for+natural+history+and+early-phase+treatment+trials.&rft.au=Tresley%2C+R+M%3BStone%2C+L+A%3BFields%2C+N%3BMaloni%2C+H%3BMcFarland%2C+H%3BFrank%2C+J+A&rft.aulast=Tresley&rft.aufirst=R&rft.date=1997-04-01&rft.volume=48&rft.issue=4&rft.spage=832&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-15 N1 - Date created - 1997-05-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antisense oligonucleotides as therapeutics for malignant diseases. AN - 78951872; 9129689 AB - The continued progress in our understanding of the biology of neoplasia and in the identification, cloning, and sequencing of genes critical to tumor cell function permits the exploitation of this information to develop specific agents that may directly modulate the function of these genes or their protein products. Antisense oligonucleotides are being investigated as a potential therapeutic modality that takes direct advantage of molecular sequencing. The antisense approach uses short oligonucleotides designed to hybridize to a target mRNA transcript through Watson-Crick base pairing. The formation of this oligonucleotide: RNA heteroduplex results in mRNA inactivation and consequent inhibition of synthesis of the protein product. A fundamental attraction of the antisense approach is that this method potentially may be applied to any gene product, in theory, for the treatment of malignant and non-malignant diseases. However, this simple and attractive model has proven to be much more complex in practice. A number of important challenges in the preclinical development of antisense oligonucleotides have been identified, including stability, sequence length, cellular uptake, target sequence selection, appropriate negative controls, oligonucleotide: protein interactions, and cost of manufacture. Although the biological activity of an oligonucleotide against its molecular target is theoretically sequence-dependent, the animal pharmacokinetics and toxicology of phosphorothioate analogues directed against vastly disparate gene products appear relatively non-sequence-specific. In oncology, a number of clinical trials have been initiated with antisense oligonucleotides directed against molecular targets including: p53; bcl-2; raf kinase; protein kinase C-alpha; c-myb. The experience gained from these early clinical trials will be applicable to the next generation of antisense agents in development. These may include molecules with novel backbones or other structural modifications, chimeric oligonucleotides, or peptide nucleic acids. Continued progress in this arena will require that many of the preclinical challenges confronting antisense development are satisfactory resolved. JF - Seminars in oncology AU - Ho, P T AU - Parkinson, D R AD - Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Rockville, MD 20852, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 187 EP - 202 VL - 24 IS - 2 SN - 0093-7754, 0093-7754 KW - Antineoplastic Agents KW - 0 KW - Drugs, Investigational KW - Oligonucleotides, Antisense KW - Index Medicus KW - Neoplasms -- drug therapy KW - Animals KW - Humans KW - Clinical Trials as Topic KW - Drug Design KW - Oligonucleotides, Antisense -- therapeutic use KW - Oligonucleotides, Antisense -- pharmacology KW - Antineoplastic Agents -- therapeutic use KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78951872?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+oncology&rft.atitle=Antisense+oligonucleotides+as+therapeutics+for+malignant+diseases.&rft.au=Ho%2C+P+T%3BParkinson%2C+D+R&rft.aulast=Ho&rft.aufirst=P&rft.date=1997-04-01&rft.volume=24&rft.issue=2&rft.spage=187&rft.isbn=&rft.btitle=&rft.title=Seminars+in+oncology&rft.issn=00937754&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-06 N1 - Date created - 1997-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antigen-specific agents in development. AN - 78951831; 9129688 AB - Differences in antigen expression between tumor cells and normal cells can be exploited to develop a variety of therapeutic anticancer agents. For example, vaccines containing tumor antigens can be administered to patients to elicit an immune-mediated attack against the tumor. Tumor antigens can also be targeted by passive transfer of monoclonal antibodies (MoAbs), or MoAbs that have been modified to carry toxin molecules. A large number of these antigen-specific agents are currently in clinical or late preclinical development. For the anticancer vaccines, much of the current development is focused on determining optimum immunization approaches. In the case of antibody-based reagents, second- and third-generation constructs are being developed to improve potency, decrease immunogenicity, and increase distribution to tumor. JF - Seminars in oncology AU - Sznol, M AU - Holmlund, J AD - Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Rockville, MD 20852, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 173 EP - 186 VL - 24 IS - 2 SN - 0093-7754, 0093-7754 KW - Antibodies, Bispecific KW - 0 KW - Antibodies, Monoclonal KW - Antigens, Neoplasm KW - Antineoplastic Agents KW - Cancer Vaccines KW - Drugs, Investigational KW - Immunotoxins KW - Index Medicus KW - Neoplasms -- drug therapy KW - Animals KW - Humans KW - Cancer Vaccines -- pharmacology KW - Immunotoxins -- pharmacology KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78951831?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+oncology&rft.atitle=Antigen-specific+agents+in+development.&rft.au=Sznol%2C+M%3BHolmlund%2C+J&rft.aulast=Sznol&rft.aufirst=M&rft.date=1997-04-01&rft.volume=24&rft.issue=2&rft.spage=173&rft.isbn=&rft.btitle=&rft.title=Seminars+in+oncology&rft.issn=00937754&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-06 N1 - Date created - 1997-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Long-term follow-up of patients with chronic uveitis affecting the posterior pole treated with combination cyclosporine and ketoconazole. AN - 78943963; 9111267 AB - Combined treatment with cyclosporine (CsA) and ketoconazole in autoimmune diseases has received little attention. This article reports the outcome of a pilot study in patients receiving combination therapy for chronic uveitis affecting the posterior pole. Six patients initially treated with CsA and oral prednisone were observed prospectively on a combination of CsA, prednisone, and ketoconazole. Data were analyzed for visual acuity, number of flare-ups, and signs of systemic toxicity. Patients were treated with CsA for a mean of 13 months and CsA-ketoconazole for a mean of 33 months. Although patients had a number of flare-ups before combination therapy, only two flare-ups in two patients were noted during combined therapy (P = 0.055). Three patients showed signs of renal toxicity on CsA, and two continued to show signs of toxicity on CsA-ketoconazone. One patient stabilized and maintained normal renal parameters. Using CsA, three of six patients showed elevations of systolic and diastolic pressure. After switching to CsA-ketoconazole, the patient's systolic pressure remained unchanged, and the diastolic pressure returned to normal in all patients (P = 0.03). No toxicity related to ketoconazole alone was observed. A combination of CsA and ketoconazole is effective in the treatment of chronic uveitis affecting the posterior pole. It appears to be more effective in preventing recurrences than does CsA alone and does not lead to an increased risk of renal toxicity. JF - Ophthalmology AU - Ramadan, A M AU - Nussenblatt, R B AU - de Smet, M D AD - Clinical Immunology Section, National Eye Institute, Bethesda, MD 20892-1858, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 706 EP - 711 VL - 104 IS - 4 SN - 0161-6420, 0161-6420 KW - Anti-Inflammatory Agents KW - 0 KW - Immunosuppressive Agents KW - Cyclosporine KW - 83HN0GTJ6D KW - Ketoconazole KW - R9400W927I KW - Prednisone KW - VB0R961HZT KW - Index Medicus KW - Drug Therapy, Combination KW - Prospective Studies KW - Double-Blind Method KW - Prednisone -- therapeutic use KW - Humans KW - Adult KW - Anti-Inflammatory Agents -- therapeutic use KW - Pilot Projects KW - Middle Aged KW - Follow-Up Studies KW - Chronic Disease KW - Longitudinal Studies KW - Cyclosporine -- adverse effects KW - Ketoconazole -- therapeutic use KW - Cyclosporine -- therapeutic use KW - Ketoconazole -- adverse effects KW - Immunosuppressive Agents -- therapeutic use KW - Uveitis -- drug therapy KW - Immunosuppressive Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78943963?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ophthalmology&rft.atitle=Long-term+follow-up+of+patients+with+chronic+uveitis+affecting+the+posterior+pole+treated+with+combination+cyclosporine+and+ketoconazole.&rft.au=Ramadan%2C+A+M%3BNussenblatt%2C+R+B%3Bde+Smet%2C+M+D&rft.aulast=Ramadan&rft.aufirst=A&rft.date=1997-04-01&rft.volume=104&rft.issue=4&rft.spage=706&rft.isbn=&rft.btitle=&rft.title=Ophthalmology&rft.issn=01616420&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-14 N1 - Date created - 1997-05-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Farnesyl protein transferase inhibitors as potential cancer chemopreventives. AN - 78938655; 9107432 AB - Among the most important targets for chemopreventive intervention and drug development are deregulated signal transduction pathways. Ras proteins serve as central connectors between signals generated at the plasma membrane and nuclear effectors; thus, disrupting the Ras signaling pathway could have significant potential as a cancer chemopreventive strategy. Target organs for Ras-based chemopreventive strategies include those associated with activating ras mutations (e.g., colorectum, pancreas, and lung) and those carrying aberrations in upstream element(s), such as growth factors and their receptors. Ras proteins require posttranslational modification with a farnesyl moiety for both normal and oncogenic activity. Inhibitors of the enzyme that catalyzes this reaction, farnesyl protein transferase (FPT) should, therefore, inhibit Ras-dependent proliferative activity in cancerous and precancerous lesions (J. B. Gibbs et al., Cell, 77: 175-178, 1994). Because growth factor networks are redundant, selective inhibition of signaling pathways activated in precancerous and cancerous cells should be possible. Requirements for Ras farnesylation inhibitors include: specificity for FPT compared with other prenyl transferases; specificity for FPT compared with other farnesyl PPi-utilizing enzymes; ability to specifically inhibit processing of mutant K-ras (the most commonly mutated ras gene in human cancers); high potency; selective activity in intact cells; activity in vivo; and lack of toxicity. Numerous FPT inhibitors have been identified through random screening of natural products and by rational design of analogues of the two substrates, farnesyl PPi and the COOH-terminal CAAX motif of Ras tetrapeptides. A possible testing strategy for developing FPT inhibitors as chemopreventive agents includes the following steps: (a) determine FPT inhibitory activity in vitro; (b) evaluate selectivity (relative to other protein prenyl transferases and FPT-utilizing enzymes); (c) determine inhibition of Ras-mediated effects in intact cells; (d) determine inhibition of Ras-mediated effects in vivo (e.g., in nude mouse tumor xenografts); and (e) determine chemopreventive efficacy in vivo (e.g., in carcinogen-induced A/J mouse lung, rat colon, or hamster pancreas). JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Kelloff, G J AU - Lubet, R A AU - Fay, J R AU - Steele, V E AU - Boone, C W AU - Crowell, J A AU - Sigman, C C AD - Chemoprevention Branch, National Cancer Institute, Bethesda, Maryland, Rockville, MD 20852, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 267 EP - 282 VL - 6 IS - 4 SN - 1055-9965, 1055-9965 KW - Anticarcinogenic Agents KW - 0 KW - Transferases KW - EC 2.- KW - Alkyl and Aryl Transferases KW - EC 2.5.- KW - Farnesyltranstransferase KW - EC 2.5.1.29 KW - HRAS protein, human KW - EC 3.6.5.2 KW - Proto-Oncogene Proteins p21(ras) KW - Index Medicus KW - Rats KW - Animals KW - Humans KW - Signal Transduction -- drug effects KW - Mice KW - Structure-Activity Relationship KW - Cricetinae KW - Transferases -- antagonists & inhibitors KW - Anticarcinogenic Agents -- pharmacology KW - Cell Division -- drug effects KW - Cell Transformation, Neoplastic -- drug effects KW - Proto-Oncogene Proteins p21(ras) -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78938655?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Farnesyl+protein+transferase+inhibitors+as+potential+cancer+chemopreventives.&rft.au=Kelloff%2C+G+J%3BLubet%2C+R+A%3BFay%2C+J+R%3BSteele%2C+V+E%3BBoone%2C+C+W%3BCrowell%2C+J+A%3BSigman%2C+C+C&rft.aulast=Kelloff&rft.aufirst=G&rft.date=1997-04-01&rft.volume=6&rft.issue=4&rft.spage=267&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-17 N1 - Date created - 1997-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Coexpression of flt-3 ligand/flt-3 and SCF/c-kit signal transduction system in bile-duct-ligated SI and W mice. AN - 78938264; 9094974 AB - Stem cell factor (SCF) and its receptor c-kit constitute an important signal transduction system regulating cell growth and differentiation in hematopoiesis, gametogenesis, and melanogenesis. Recently, we have demonstrated that both SCF and c-kit are expressed in the bile duct epithelial cells of the rat liver and are highly up-regulated during activation of the normally dormant hepatic stem cell compartment. In the present study, we used sl/sld and w/wv mice, which have mutation of either SCF or c-kit, to study the possible involvement of the SCF/c-kit system in the bile duct proliferation. Bile duct ligation was performed to induce the proliferation of bile duct epithelial cells. The transcripts for both SCF and c-kit were clearly increased after bile duct ligation in both control and mutant mice. Moreover, both Sl and W mice responded to the bile duct ligation, similar to the control mice, by developing new bile ducts. Recently, a novel tyrosine kinase receptor, flt-3 receptor, has been identified in the fetal liver. It has been reported that the flt-3 ligand (FL)/flt-3 system can synergize with the SCF/c-kit system and stimulate the proliferation of hematopoietic cells. Therefore, we hypothesized that the FL/flt-3 system might compensate for the compromised SCF/c-kit system in the liver of Sl and W mice. The expression of both FL and flt-3 were significantly increased in bile duct-ligated liver from both normal and mutant mice, and the transcripts for the flt-3 receptor were selectively located on bile duct epithelial cells. Based on these results, we postulate the existence of a compensatory/additive function between the FL/flt-3 and the SCF/c-kit signal transduction systems in hepatic cell biology. JF - The American journal of pathology AU - Omori, M AU - Omori, N AU - Evarts, R P AU - Teramoto, T AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 1179 EP - 1187 VL - 150 IS - 4 SN - 0002-9440, 0002-9440 KW - Membrane Proteins KW - 0 KW - Proto-Oncogene Proteins KW - Stem Cell Factor KW - flt3 ligand protein KW - Flt3 protein, mouse KW - EC 2.7.10.1 KW - Proto-Oncogene Proteins c-kit KW - Receptor Protein-Tyrosine Kinases KW - fms-Like Tyrosine Kinase 3 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Liver -- pathology KW - Mice, Inbred C57BL KW - Ligation KW - Mice KW - Staining and Labeling KW - Immunohistochemistry KW - Mice, Knockout KW - Bile Ducts -- chemistry KW - Bile Ducts -- metabolism KW - Hematopoiesis KW - Stem Cell Factor -- biosynthesis KW - Proto-Oncogene Proteins -- biosynthesis KW - Receptor Protein-Tyrosine Kinases -- immunology KW - Stem Cell Factor -- immunology KW - Bile Ducts -- pathology KW - Membrane Proteins -- biosynthesis KW - Proto-Oncogene Proteins c-kit -- biosynthesis KW - Receptor Protein-Tyrosine Kinases -- chemistry KW - Receptor Protein-Tyrosine Kinases -- biosynthesis KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78938264?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Coexpression+of+flt-3+ligand%2Fflt-3+and+SCF%2Fc-kit+signal+transduction+system+in+bile-duct-ligated+SI+and+W+mice.&rft.au=Omori%2C+M%3BOmori%2C+N%3BEvarts%2C+R+P%3BTeramoto%2C+T%3BThorgeirsson%2C+S+S&rft.aulast=Omori&rft.aufirst=M&rft.date=1997-04-01&rft.volume=150&rft.issue=4&rft.spage=1179&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+pathology&rft.issn=00029440&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-29 N1 - Date created - 1997-04-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Development. 1995 Mar;121(3):731-42 [7536655] Blood. 1995 Feb 1;85(3):641-9 [7530502] Blood. 1995 Sep 1;86(5):1661-70 [7544638] J Exp Med. 1995 Dec 1;182(6):1931-42 [7500039] Blood. 1996 Feb 15;87(4):1317-25 [8608220] Exp Cell Res. 1996 May 1;224(2):243-50 [8612701] Blood. 1996 May 1;87(9):3563-70 [8611678] Br J Exp Pathol. 1976 Feb;57(1):85-94 [1268043] Adv Genet. 1979;20:357-459 [390999] Nucleic Acids Res. 1985 Mar 11;13(5):1431-42 [2987824] Carcinogenesis. 1987 Nov;8(11):1737-40 [3664968] Blood. 1988 Aug;72(2):463-8 [3401590] Nature. 1988 Sep 1;335(6185):88-9 [2457811] Genes Dev. 1989 Jun;3(6):816-26 [2473008] EMBO J. 1990 Jun;9(6):1805-13 [1693331] Cancer Res. 1990 Jul 1;50(13):3811-5 [1693878] Gastroenterology. 1990 Aug;99(2):466-77 [1694804] Cell. 1990 Oct 5;63(1):167-74 [1698553] Cell. 1990 Oct 5;63(1):195-201 [2208278] Cell. 1990 Oct 5;63(1):225-33 [1698557] Cell. 1991 Mar 8;64(5):1025-35 [1705866] Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4671-4 [1711207] Cell. 1991 Jun 28;65(7):1143-52 [1648448] EMBO J. 1991 Sep;10(9):2425-35 [1714375] Am J Pathol. 1991 Sep;139(3):535-52 [1716045] Oncogene. 1991 Sep;6(9):1641-50 [1656368] Development. 1991 Dec;113(4):1207-21 [1811937] Mol Cell Biol. 1993 Oct;13(10):6572-85 [7692230] Proc Soc Exp Biol Med. 1993 Dec;204(3):242-52 [7694303] Cell. 1993 Dec 17;75(6):1157-67 [7505204] Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):459-63 [7507245] Nature. 1994 Apr 14;368(6472):643-8 [8145851] Lab Invest. 1994 Apr;70(4):511-6 [7513770] Blood. 1994 May 15;83(10):2795-801 [8180375] Dev Suppl. 1993;:125-37 [7519481] Am J Pathol. 1994 Aug;145(2):409-22 [8053498] Cell Mol Biol (Noisy-le-grand). 1994 May;40(3):443-56 [7920189] Oncogene. 1995 Jan 5;10(1):149-57 [7824267] Immunity. 1995 Jul;3(1):147-61 [7621074] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oral contraceptives, reproductive factors and p53 gene expression in colorectal cancer. AN - 78938010; 9111225 AB - Protective effects of oral contraceptives and high parity on the development of colorectal cancer have been hypothesized. However, the epidemiological data are inconsistent. This inconsistency may be due in part to the biological heterogeneity of colorectal tumors. A recent investigation of hepatocellular carcinoma demonstrated an association between lack of p53 expression and oral contraceptive use. We investigated the relationship between oral contraceptive use and other reproductive factors with p53 over-expression in 64 post-menopausal women, 45-86 years of age, with non-familial colorectal adenocarcinoma. Fifty per cent (32/64) of colorectal tumors displayed nuclear over-expression of p53 protein. Women with a history of oral contraceptive use were significantly less likely to have p53 positive (+) tumors than women who never used oral contraceptives (P = 0.02). In contrast, tumors from women who had never been pregnant were more likely to be p53 + compared to tumors from parous women (P = 0.10). These data suggest that oral contraceptive use and pregnancy are associated with a p53 independent pathway in the development of colorectal cancer. JF - Carcinogenesis AU - Freedman, A N AU - Michalek, A M AU - Troisi, R AU - Mettlin, C J AU - Petrelli, N J AU - Asirwatham, J E AU - Caporaso, N AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 855 EP - 856 VL - 18 IS - 4 SN - 0143-3334, 0143-3334 KW - Contraceptives, Oral KW - 0 KW - Index Medicus KW - Population KW - United States KW - Cancer--women KW - Fertility KW - Population Dynamics KW - Physiology KW - Pregnancy History KW - Oral Contraceptives KW - Contraceptive Methods KW - Developed Countries KW - Genetics KW - Demographic Factors KW - Diseases KW - Family Planning KW - North America KW - Americas KW - Research Report KW - Northern America KW - Neoplasms KW - Contraception KW - Gastrointestinal Effects--women KW - Reproduction KW - Fertility Measurements KW - Menopause KW - Biology KW - Aged, 80 and over KW - Humans KW - Aged KW - Middle Aged KW - Male KW - Female KW - Gene Expression Regulation, Neoplastic KW - Genes, p53 KW - Pregnancy -- physiology KW - Contraceptives, Oral -- pharmacology KW - Colorectal Neoplasms -- physiopathology KW - Colorectal Neoplasms -- genetics KW - Colorectal Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78938010?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Oral+contraceptives%2C+reproductive+factors+and+p53+gene+expression+in+colorectal+cancer.&rft.au=Freedman%2C+A+N%3BMichalek%2C+A+M%3BTroisi%2C+R%3BMettlin%2C+C+J%3BPetrelli%2C+N+J%3BAsirwatham%2C+J+E%3BCaporaso%2C+N&rft.aulast=Freedman&rft.aufirst=A&rft.date=1997-04-01&rft.volume=18&rft.issue=4&rft.spage=855&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-09 N1 - Date created - 1997-05-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of pineal alpha1B-adrenergic receptor mRNA: day/night rhythm and beta-adrenergic receptor/cyclic AMP control. AN - 78931205; 9106618 AB - Mammalian pineal function is regulated by norepinephrine acting through alpha1beta- and beta1-adrenergic receptors (ARs). Noradrenergic stimulation of alpha1beta-ARs potentiates the beta1-AR-driven increase in cAMP, serotonin N-acetyltransferase, and melatonin production. In the present study, we describe a 3-fold daily rhythm in mRNA-encoding alpha1beta-ARs in the pineal gland, with a peak at midnight. Pharmacological studies indicate that this increase in alpha1beta-AR mRNA is due to activation of beta-ARs. Second messenger studies indicate that alpha1beta-AR mRNA is increased by agents that increase cAMP, including dibutyryl cAMP, cholera toxin, forskolin, or vasoactive intestinal peptide. These observations indicate that alpha1beta-AR mRNA can be physiologically regulated by a beta-AR-dependent enhancement of cAMP. It also was observed that in vivo and in vitro changes in alpha1beta-AR mRNA are not accompanied by similar changes in alpha1beta-AR binding, indicating that turnover of alpha1beta-AR protein is significantly slower than that of alpha1beta-AR mRNA and that post-transcriptional mechanisms play an important role in regulating alpha1beta-AR binding. JF - Molecular pharmacology AU - Coon, S L AU - McCune, S K AU - Sugden, D AU - Klein, D C AD - Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 551 EP - 557 VL - 51 IS - 4 SN - 0026-895X, 0026-895X KW - ADRA1B protein, human KW - 0 KW - Adrenergic alpha-Agonists KW - Adrenergic beta-Agonists KW - RNA, Messenger KW - Receptors, Adrenergic, alpha-1 KW - Colforsin KW - 1F7A44V6OU KW - Phenylephrine KW - 1WS297W6MV KW - Vasoactive Intestinal Peptide KW - 37221-79-7 KW - Cholera Toxin KW - 9012-63-9 KW - Cyclic AMP KW - E0399OZS9N KW - Isoproterenol KW - L628TT009W KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Vasoactive Intestinal Peptide -- pharmacology KW - Animals KW - Adrenergic alpha-Agonists -- pharmacology KW - Norepinephrine -- pharmacology KW - Cholera Toxin -- pharmacology KW - Vasoactive Intestinal Peptide -- physiology KW - Isoproterenol -- pharmacology KW - Rats KW - Adrenergic beta-Agonists -- pharmacology KW - Colforsin -- pharmacology KW - Rats, Sprague-Dawley KW - Female KW - Male KW - Phenylephrine -- pharmacology KW - Receptors, Adrenergic, alpha-1 -- metabolism KW - Cyclic AMP -- biosynthesis KW - Pineal Gland -- metabolism KW - Circadian Rhythm -- physiology KW - RNA, Messenger -- metabolism KW - Cyclic AMP -- metabolism KW - Pineal Gland -- ultrastructure KW - Receptors, Adrenergic, alpha-1 -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78931205?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=Regulation+of+pineal+alpha1B-adrenergic+receptor+mRNA%3A+day%2Fnight+rhythm+and+beta-adrenergic+receptor%2Fcyclic+AMP+control.&rft.au=Coon%2C+S+L%3BMcCune%2C+S+K%3BSugden%2C+D%3BKlein%2C+D+C&rft.aulast=Coon&rft.aufirst=S&rft.date=1997-04-01&rft.volume=51&rft.issue=4&rft.spage=551&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 - 1997-05-06 N1 - Date created - 1997-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular mechanism of antifolate transport-deficiency in a methotrexate-resistant MOLT-3 human leukemia cell line. AN - 78910209; 9116294 AB - Ohnuma et al reported a series of methotrexate-resistant MOLT-3 human T-cell acute lymphoblastic leukemia cell lines that showed decreasing methotrexate (MTX) uptake as the sublines acquired increasing MTX resistance (Cancer Res 45:1815, 1985). The alteration of MTX uptake kinetics in these cells, the intermediately resistant MOLT-3/MTX200 and the highly resistant MOLT-3/MTX10,000 cell lines, was attributed to a change in Vmax for methotrexate transport, without an apparent change in affinity of the transporter for MTX. We studied these cell lines to determine whether alteration of transcription or translation of the recently isolated reduced folate carrier gene (RFC1) was the cause of MTX transport deficiency in these cell lines. Reconstitution of RFC activity in MOLT-3/MTX10,000 cells by transduction with a murine RFC retroviral vector reversed MTX resistance and trimetrexate sensitivity. Although RFC1 RNA levels were unchanged in the resistant cell lines, FACS analysis using a polyclonal anti-RFC1 antibody showed no detectable RFC1 protein in the MOLT-3/MTX10,000 cells. Determination of the nucleotide sequence of RFC1 genes from MOLT-3/MTX10,000 cells revealed that this cell line contained 3 RFC1 alleles: a wild-type allele, an allele containing the premature stop codon at codon 40 and a third allele containing another mutation, which resulted in a premature stop codon at codon 25. We examined the relative expression of these alleles by determining the nucleotide sequence of 24 RFC1 cDNA subclones from MOLT-3/MTX10,000 cells and found that only one-third of these clones contained the wild-type sequence. Determination of the genomic sequence of RFC1 in MOLT-3/ MTX200 cells demonstrated that these cells were heterozygous for a mutation at codon 40, but were homozygous for the wild-type sequence at codon 25. Thus, the acquisition of MTX transport-deficiency in MOLT-3/MTX10,000 cells results from inactivating mutations of RFC1 gene alleles. JF - Blood AU - Gong, M AU - Yess, J AU - Connolly, T AU - Ivy, S P AU - Ohnuma, T AU - Cowan, K H AU - Moscow, J A AD - Medicine and Pediatric Branches, National Cancer Institute, Bethesda, MD 20892,USA. Y1 - 1997/04/01/ PY - 1997 DA - 1997 Apr 01 SP - 2494 EP - 2499 VL - 89 IS - 7 SN - 0006-4971, 0006-4971 KW - Antimetabolites, Antineoplastic KW - 0 KW - Carrier Proteins KW - Codon KW - Membrane Proteins KW - Membrane Transport Proteins KW - Neoplasm Proteins KW - SLC19A2 protein, human KW - Methotrexate KW - YL5FZ2Y5U1 KW - Abridged Index Medicus KW - Index Medicus KW - Terminator Regions, Genetic KW - Alleles KW - Codon -- genetics KW - Tumor Cells, Cultured -- drug effects KW - Transfection KW - Humans KW - Biological Transport KW - Drug Resistance, Neoplasm KW - Gene Expression Regulation, Leukemic KW - Methotrexate -- pharmacology KW - Carrier Proteins -- genetics KW - Neoplasm Proteins -- deficiency KW - Leukemia-Lymphoma, Adult T-Cell -- genetics KW - Membrane Proteins -- genetics KW - Antimetabolites, Antineoplastic -- metabolism KW - Antimetabolites, Antineoplastic -- pharmacology KW - Leukemia-Lymphoma, Adult T-Cell -- pathology KW - Neoplasm Proteins -- physiology KW - Neoplasm Proteins -- genetics KW - Carrier Proteins -- physiology KW - Methotrexate -- metabolism KW - Membrane Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78910209?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Molecular+mechanism+of+antifolate+transport-deficiency+in+a+methotrexate-resistant+MOLT-3+human+leukemia+cell+line.&rft.au=Gong%2C+M%3BYess%2C+J%3BConnolly%2C+T%3BIvy%2C+S+P%3BOhnuma%2C+T%3BCowan%2C+K+H%3BMoscow%2C+J+A&rft.aulast=Gong&rft.aufirst=M&rft.date=1997-04-01&rft.volume=89&rft.issue=7&rft.spage=2494&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-22 N1 - Date created - 1997-04-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Wortmannin-sensitive and -insensitive steps in calcium-controlled exocytosis in pituitary gonadotrophs: evidence that myosin light chain kinase mediates calcium-dependent and wortmannin-sensitive gonadotropin secretion. AN - 78908904; 9075700 AB - In cultured rat pituitary cells, increases in the cytosolic calcium concentration ([Ca2+]i) and LH release are induced by activation of GnRH receptors as well as by nonreceptor-mediated stimuli. Treatment of pituitary cells with the myosin light chain kinase (MLCK) inhibitor, wortmannin, attenuated GnRH-induced LH release. Wortmannin also reduced the LH responses to nonreceptor-mediated elevation of [Ca2+]i by ionomycin and activation of voltage-sensitive Ca2+ channels by Bay K 8644 or high K+, as well as Ca2+-induced LH release in permeabilized pituitary cells. The [Ca2+]i responses to these stimuli were unaltered in wortmannin-treated pituitary cells, indicating that this compound inhibits a Ca2+-dependent step in exocytosis without affecting Ca2+ signaling. In perifused pituitary cells, the GnRH-induced early spike phase of LH release was not affected by wortmannin, whereas the subsequent plateau phase was almost completely inhibited. No significant changes in GnRH-induced phospholipase D activity and diacylglycerol production were observed in wortmannin-treated pituitary cells during the sustained phase of agonist stimulation. Wortmannin also had no effect on LH responses to the protein kinase C activator, phorbol 12-myristate 13-acetate, further indicating that the attenuation of agonist-induced LH release is not related to inhibition of the diacylglycerol/protein kinase C pathway. In addition, agonist-induced LH release was attenuated by two other MLCK inhibitors, MS-347a and KT5926. These data suggest that MLCK mediates the downstream effects of Ca2+ on exocytosis, an action supported by the finding of wortmannin-sensitive phosphorylation of a 20-kDa protein in pituitary cells and alphaT3-1 gonadotrophs treated with GnRH, K+, and Bay K 8644. This protein was coprecipitated from pituitary extracts with a specific antibody to nonmuscle myosin IIB and comigrated with 20-kDa smooth muscle myosin light chain on SDS-PAGE. These results demonstrate that Ca2+ controls exocytosis through an initial wortmannin-insensitive step and a sustained wortmannin-sensitive step and suggest that the latter event in the cascade of cellular responses is dependent on phosphorylation of nonmuscle myosin IIB light chain by MLCK. JF - Endocrinology AU - Rao, K AU - Paik, W Y AU - Zheng, L AU - Jobin, R M AU - Tomić, M AU - Jiang, H AU - Nakanishi, S AU - Stojilkovic, S S AD - Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 1440 EP - 1449 VL - 138 IS - 4 SN - 0013-7227, 0013-7227 KW - Androstadienes KW - 0 KW - Calcium Channel Agonists KW - Enzyme Inhibitors KW - Gonadotropins, Pituitary KW - Inositol Phosphates KW - Phorbol Esters KW - Receptors, LHRH KW - Ionomycin KW - 56092-81-0 KW - 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester KW - 71145-03-4 KW - Luteinizing Hormone KW - 9002-67-9 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Myosin-Light-Chain Kinase KW - EC 2.7.11.18 KW - Calcium KW - SY7Q814VUP KW - wortmannin KW - XVA4O219QW KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Protein Kinase C -- metabolism KW - Phorbol Esters -- pharmacology KW - Animals KW - Inositol Phosphates -- metabolism KW - Enzyme Activation KW - Luteinizing Hormone -- metabolism KW - 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester -- pharmacology KW - Ionomycin -- pharmacology KW - Calcium Channel Agonists -- pharmacology KW - Receptors, LHRH -- metabolism KW - Gonadotropins, Pituitary -- secretion KW - Exocytosis -- drug effects KW - Calcium -- metabolism KW - Pituitary Gland, Anterior -- drug effects KW - Myosin-Light-Chain Kinase -- metabolism KW - Pituitary Gland, Anterior -- metabolism KW - Androstadienes -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Pituitary Gland, Anterior -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78908904?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Wortmannin-sensitive+and+-insensitive+steps+in+calcium-controlled+exocytosis+in+pituitary+gonadotrophs%3A+evidence+that+myosin+light+chain+kinase+mediates+calcium-dependent+and+wortmannin-sensitive+gonadotropin+secretion.&rft.au=Rao%2C+K%3BPaik%2C+W+Y%3BZheng%2C+L%3BJobin%2C+R+M%3BTomi%C4%87%2C+M%3BJiang%2C+H%3BNakanishi%2C+S%3BStojilkovic%2C+S+S&rft.aulast=Rao&rft.aufirst=K&rft.date=1997-04-01&rft.volume=138&rft.issue=4&rft.spage=1440&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-17 N1 - Date created - 1997-04-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Genetic analyses of complex behavioral disorders. AN - 78907529; 9096294 JF - Proceedings of the National Academy of Sciences of the United States of America AU - Uhl, G R AU - Gold, L H AU - Risch, N Y1 - 1997/04/01/ PY - 1997 DA - 1997 Apr 01 SP - 2785 EP - 2786 VL - 94 IS - 7 KW - Membrane Glycoproteins KW - 0 KW - Membrane Transport Proteins KW - Neuropeptides KW - Receptors, Dopamine D1 KW - Receptors, Dopamine D2 KW - Vesicular Biogenic Amine Transport Proteins KW - Index Medicus KW - Animals KW - Receptors, Dopamine D1 -- genetics KW - Humans KW - Mice KW - Receptors, Dopamine D2 -- genetics KW - Substance-Related Disorders -- genetics KW - Behavior, Animal KW - Membrane Glycoproteins -- genetics KW - Mental Disorders -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78907529?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Genetic+analyses+of+complex+behavioral+disorders.&rft.au=Uhl%2C+G+R%3BGold%2C+L+H%3BRisch%2C+N&rft.aulast=Uhl&rft.aufirst=G&rft.date=1997-04-01&rft.volume=94&rft.issue=7&rft.spage=2785&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-08 N1 - Date created - 1997-05-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1988 Jul;85(14):5274-8 [2899326] Science. 1994 Jun 17;264(5166):1715-23 [8209252] Science. 1996 Sep 13;273(5281):1516-7 [8801636] Neuroreport. 1995 Nov 27;6(17):2314-6 [8747144] Cell. 1994 Nov 18;79(4):729-42 [7954836] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selegiline in ADHD adults: plasma monoamines and monoamine metabolites. AN - 78906122; 9094145 AB - Plasma monoamines and monoamine metabolites were assessed before and during selegiline treatment in adults with attention deficit/hyperactivity disorder (ADHD). Selegiline, at low dose, is a selective monoamine oxidase inhibitor type B (MAOI-B). After 2-week placebo baseline, 36 ADHD adults were randomized to 6-week placebo or 20 mg/day or 60 mg/day selegiline, followed by 2-week posttreatment placebo. Twenty-seven subjects continued into a 6-week 20-mg/day or 60-mg/day selegiline period. Behavioral variables included self-rated scores on the Conners' Abbreviated Teacher Rating Scale (Conners-ATRS) and performance on a Continuous Performance Task (CPT). Plasma samples were assayed for amines (dopamine, norepinephrine, epinephrine), precursor (DOPA), and metabolites (HVA, DOPAC, DHPG, normetanephrine, metanephrine, 5-HIAA). Selegiline produced dose-dependent changes in monoamine metabolites and DOPA plasma levels. Dopaminergic indices were associated with ADHD symptom severity (Conners-ATRS) and noradrenergic indices with CPT performance. Serotonergic metabolism, challenged by selegiline, correlated with clinical changes. These findings support a multisystem dysfunction underlying ADHD pathophysiology. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Ernst, M AU - Liebenauer, L L AU - Tebeka, D AU - Jons, P H AU - Eisenhofer, G AU - Murphy, D L AU - Zametkin, A J AD - Child Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 276 EP - 284 VL - 16 IS - 4 SN - 0893-133X, 0893-133X KW - Biogenic Monoamines KW - 0 KW - Monoamine Oxidase Inhibitors KW - Selegiline KW - 2K1V7GP655 KW - Serotonin KW - 333DO1RDJY KW - Dopamine KW - VTD58H1Z2X KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Psychomotor Performance -- drug effects KW - Double-Blind Method KW - Dose-Response Relationship, Drug KW - Norepinephrine -- blood KW - Humans KW - Serotonin -- blood KW - Adult KW - Dopamine -- blood KW - Male KW - Female KW - Monoamine Oxidase Inhibitors -- adverse effects KW - Attention Deficit Disorder with Hyperactivity -- psychology KW - Selegiline -- adverse effects KW - Selegiline -- therapeutic use KW - Attention Deficit Disorder with Hyperactivity -- metabolism KW - Biogenic Monoamines -- metabolism KW - Monoamine Oxidase Inhibitors -- therapeutic use KW - Attention Deficit Disorder with Hyperactivity -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78906122?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Selegiline+in+ADHD+adults%3A+plasma+monoamines+and+monoamine+metabolites.&rft.au=Ernst%2C+M%3BLiebenauer%2C+L+L%3BTebeka%2C+D%3BJons%2C+P+H%3BEisenhofer%2C+G%3BMurphy%2C+D+L%3BZametkin%2C+A+J&rft.aulast=Ernst&rft.aufirst=M&rft.date=1997-04-01&rft.volume=16&rft.issue=4&rft.spage=276&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 - 1997-06-13 N1 - Date created - 1997-06-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Blocking both E-selectin and P-selectin inhibits endotoxin-induced leukocyte infiltration into the eye. AN - 78905396; 9073535 AB - The initial contact between leukocytes and the vascular endothelium at sites of inflammation is mediated by selectins. The purpose of this study was to investigate the role of the two selectins expressed on the vascular endothelium, E-selectin and P-selectin, in the pathogenesis of endotoxin-induced uveitis. Endotoxin-induced uveitis was produced in female C3H/HeN mice using Salmonella typhimurium endotoxin injected into one hind footpad. At the time of endotoxin injection mice were treated with an intraperitoneal injection of a monoclonal antibody against E-selectin or P-selectin, a combination of both anti-selectin antibodies, or isotype-matched control antibodies. In a second set of experiments, antibody treatment was administered 6 hr after endotoxin injection, when inflammatory cells are already entering the eye. Ocular inflammation was graded histologically by a masked observer. When administered at the time of endotoxin injection, anti-P-selectin antibody decreased ocular inflammation by 37% compared to control animals (P = 0.05). There was no statistical decrease in ocular inflammation in animals treated with anti-E-selectin antibody. The combination of anti-P-selectin and anti-E-selectin antibodies decreased infiltrating inflammatory cells by 61% (P < 0.01). When treatment was delayed until 6 hr after endotoxin injection, the combination of anti-P-selectin and anti-E-selectin antibodies again decreased ocular inflammation by 60% (P < 0.01). Immunohistochemical staining showed decreased ICAM-1 expression in the eyes of animals treated with the combination of anti-P-and anti-E-selectin antibodies. Blocking both P-selectin and E-selectin resulted in a significant decrease in endotoxin-induced intraocular inflammation. JF - Clinical immunology and immunopathology AU - Whitcup, S M AU - Kozhich, A T AU - Lobanoff, M AU - Wolitzky, B A AU - Chan, C C AD - National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 45 EP - 52 VL - 83 IS - 1 SN - 0090-1229, 0090-1229 KW - Antibodies KW - 0 KW - Antibodies, Monoclonal KW - E-Selectin KW - Endotoxins KW - P-Selectin KW - Intercellular Adhesion Molecule-1 KW - 126547-89-5 KW - Index Medicus KW - Animals KW - Disease Models, Animal KW - Mice KW - Antibodies, Monoclonal -- pharmacology KW - Antibodies, Monoclonal -- therapeutic use KW - Neutrophils -- drug effects KW - Intercellular Adhesion Molecule-1 -- physiology KW - Antibodies -- therapeutic use KW - Eye -- immunology KW - Antibodies -- pharmacology KW - Mice, Inbred C3H KW - Immunohistochemistry KW - Female KW - Uveitis -- prevention & control KW - P-Selectin -- immunology KW - E-Selectin -- physiology KW - E-Selectin -- immunology KW - P-Selectin -- physiology KW - Uveitis -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78905396?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+immunology+and+immunopathology&rft.atitle=Blocking+both+E-selectin+and+P-selectin+inhibits+endotoxin-induced+leukocyte+infiltration+into+the+eye.&rft.au=Whitcup%2C+S+M%3BKozhich%2C+A+T%3BLobanoff%2C+M%3BWolitzky%2C+B+A%3BChan%2C+C+C&rft.aulast=Whitcup&rft.aufirst=S&rft.date=1997-04-01&rft.volume=83&rft.issue=1&rft.spage=45&rft.isbn=&rft.btitle=&rft.title=Clinical+immunology+and+immunopathology&rft.issn=00901229&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-29 N1 - Date created - 1997-04-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential sensitivity of thyroid hormone receptor isoform homodimers and mutant heterodimers to hormone-induced dissociation from deoxyribonucleic acid: its role in dominant negative action. AN - 78904581; 9075702 AB - General resistance to thyroid hormone is an inheritable disease with resistance of peripheral tissues to elevated levels of thyroid hormone. Genetic studies have shown that it is due to interference in the functions of wild-type thyroid hormone nuclear receptors (wTRs) via the dominant negative effect of mutant TRs (mTRs). The present study compared the heterodimerization of the two TR isoforms, TR beta1 and TR alpha1, with mutant TRs to understand if mTRs had isoform-dependent dominant negative action. Using electrophoresis gel mobility shift assay, we have demonstrated that mutant PV, S, ED, and OK form heterodimers with wTR alpha1 and deltaTR beta1 (in which the A/B domain of wTR beta1 has been deleted), on the F2-thyroid hormone response element (TRE). In the presence of T3, both homo- and heterodimer complexes are dissociated in a T3 concentration dependent manner. The ED50 for deltaTR beta1 homodimers was 3-fold higher than that of wTR alpha1 homodimers. ED50s for deltaTR beta1/mTR heterodimers were 10- to 40-fold higher than the corresponding wTR alpha1/mTR heterodimers. Mutant ED and OK homodimers were only partially dissociated at the highest T3 concentrations used (100 nM), whereas no dissociation could be detected for PV and S homodimers, indicating differential sensitivity of the F2-bound TR dimers to the T3-induced dissociation. We presented a model that indicates the dissociation of any particular TR dimer from F2 is determined by competition of T3 for both of its constituent TRs. By transfection assays, we showed that the potency of the dominant negative action of PV on TR alpha1 and TR beta1 inversely correlated with the sensitivity of the appropriate mTR/wTR heterodimer to T3-induced dissociation from F2. The differential dominant negative action of mutants on the two TR isoforms could play an important role in the heterogeneity of tissue-specific manifestations in patients with resistance to thyroid hormone. JF - Endocrinology AU - Zhu, X G AU - McPhie, P AU - Cheng, S Y AD - Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 1456 EP - 1463 VL - 138 IS - 4 SN - 0013-7227, 0013-7227 KW - Receptors, Thyroid Hormone KW - 0 KW - Triiodothyronine KW - 06LU7C9H1V KW - DNA KW - 9007-49-2 KW - Abridged Index Medicus KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Triiodothyronine -- pharmacology KW - Transfection KW - Electrophoresis, Polyacrylamide Gel KW - Cells, Cultured KW - Structure-Activity Relationship KW - Protein Conformation KW - DNA -- metabolism KW - Receptors, Thyroid Hormone -- metabolism KW - Receptors, Thyroid Hormone -- genetics KW - Receptors, Thyroid Hormone -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78904581?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Endocrinology&rft.atitle=Differential+sensitivity+of+thyroid+hormone+receptor+isoform+homodimers+and+mutant+heterodimers+to+hormone-induced+dissociation+from+deoxyribonucleic+acid%3A+its+role+in+dominant+negative+action.&rft.au=Zhu%2C+X+G%3BMcPhie%2C+P%3BCheng%2C+S+Y&rft.aulast=Zhu&rft.aufirst=X&rft.date=1997-04-01&rft.volume=138&rft.issue=4&rft.spage=1456&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-17 N1 - Date created - 1997-04-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Subcutaneous administration of interleukin-2 in human immunodeficiency virus type 1-infected persons. AN - 78901384; 9086130 AB - The safety and efficacy were assessed of 5-day cycles of subcutaneous (sc) interleukin-2 (IL-2) every 8 weeks in human immunodeficiency virus type 1-infected outpatients with >200 CD4 cells/mm3. Immunologic, virologic, and toxicity parameters were measured in 18 patients receiving standard antiretrovirals plus 5-day courses of sc IL-2 (3-18 MIU/day) every 2 months. Systemic toxicities established the maximally tolerated dose (MTD) of IL-2 as 15 MIU/day. CD4 cell responses appeared to correlate directly with baseline CD4 cell counts, with several patients experiencing a dramatic rise after 3 cycles. Virus load increased only transiently in the peri-injection period. It was concluded that serial cycles of outpatient sc IL-2 can be administered safely, with an MTD of 15 MIU/day. Patients with higher baseline counts appear to have a greater CD4 cell response to sc IL-2 therapy. JF - The Journal of infectious diseases AU - Davey, R T AU - Chaitt, D G AU - Piscitelli, S C AU - Wells, M AU - Kovacs, J A AU - Walker, R E AU - Falloon, J AU - Polis, M A AU - Metcalf, J A AU - Masur, H AU - Fyfe, G AU - Lane, H C AD - National Institute of Allergy and Infectious Diseases, Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland 20892-1880, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 781 EP - 789 VL - 175 IS - 4 SN - 0022-1899, 0022-1899 KW - Interleukin-2 KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Humans KW - Adult KW - Injections, Subcutaneous KW - Middle Aged KW - Follow-Up Studies KW - CD4 Lymphocyte Count KW - Male KW - Female KW - Acquired Immunodeficiency Syndrome -- therapy KW - Interleukin-2 -- adverse effects KW - Interleukin-2 -- administration & dosage KW - Acquired Immunodeficiency Syndrome -- immunology KW - Interleukin-2 -- pharmacokinetics KW - HIV-1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78901384?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Subcutaneous+administration+of+interleukin-2+in+human+immunodeficiency+virus+type+1-infected+persons.&rft.au=Davey%2C+R+T%3BChaitt%2C+D+G%3BPiscitelli%2C+S+C%3BWells%2C+M%3BKovacs%2C+J+A%3BWalker%2C+R+E%3BFalloon%2C+J%3BPolis%2C+M+A%3BMetcalf%2C+J+A%3BMasur%2C+H%3BFyfe%2C+G%3BLane%2C+H+C&rft.aulast=Davey&rft.aufirst=R&rft.date=1997-04-01&rft.volume=175&rft.issue=4&rft.spage=781&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 - 1997-04-17 N1 - Date created - 1997-04-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The complexity of Raf-1 regulation. AN - 78890825; 9069260 AB - The activation of the serine/threonine kinase Raf-1 is proving to be an intricate multistep process. Recent advances in elucidating how Raf-1 becomes activated in response to signaling events have emphasized the role of phosphorylation and protein interactions in Raf-1 regulation. The picture clearly emerging is that Raf-1 activity can be regulated by multiple mechanisms. JF - Current opinion in cell biology AU - Morrison, D K AU - Cutler, R E AD - Molecular Basis of Carcinogenesis Laboratory, ABL-Basic Research Program, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, MD 21702, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 174 EP - 179 VL - 9 IS - 2 SN - 0955-0674, 0955-0674 KW - Proto-Oncogene Proteins KW - 0 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Proto-Oncogene Proteins c-raf KW - ras Proteins KW - EC 3.6.5.2 KW - Index Medicus KW - Animals KW - Phosphorylation KW - Enzyme Activation KW - Humans KW - ras Proteins -- metabolism KW - Protein-Serine-Threonine Kinases -- metabolism KW - Proto-Oncogene Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78890825?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cell+biology&rft.atitle=The+complexity+of+Raf-1+regulation.&rft.au=Morrison%2C+D+K%3BCutler%2C+R+E&rft.aulast=Morrison&rft.aufirst=D&rft.date=1997-04-01&rft.volume=9&rft.issue=2&rft.spage=174&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+cell+biology&rft.issn=09550674&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-23 N1 - Date created - 1997-04-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The ability of C/EBP beta but not C/EBP alpha to synergize with an Sp1 protein is specified by the leucine zipper and activation domain. AN - 78887378; 9121452 AB - The rat CYP2D5 P-450 gene is activated in the liver during postnatal development. We previously showed that liver-specific transcription of the CYP2D5 gene is dictated by a proximal promoter element, termed 2D5, that is composed of a binding site for Sp1 or a related factor, and an adjacent cryptic C/EBP (CCAAT/enhancer-binding protein) site. Despite the fact that both C/EBP alpha and C/EBP beta are expressed abundantly in liver, only C/EBP beta is capable of stimulating the 2D5 promoter in HepG2 hepatocarcinoma cells. In addition, activation of the 2D5 promoter by C/EBP beta is completely dependent on the presence of the Sp1 site. Domain switch experiments reveal that C/EBP beta proteins containing either the leucine zipper or the activation domain of C/EBP alpha are unable to stimulate the 2D5 promoter yet are fully capable of transactivating an artificial promoter bearing a high-affinity C/EBP site. Thus, the leucine zipper and the activation domain of C/EBP beta are absolutely required to support transactivation of the 2D5 promoter. Using Drosophila cells that lack endogenous Sp1 activity, we show that the serine/threonine- and glutamine-rich activation domains A and B of Sp1 are required for efficient cooperatively with C/EBP beta. Furthermore, analysis of c/ebp beta-deficient mice shows that mutant animals are defective in expression of a murine CYP2D5 homolog in hepatic cells, confirming the selective ability of C/EBP beta to activate this liver-specific P-450 gene in vivo. Our findings illustrate that two members of a transcription factor family can achieve distinct target gene specificities through differential interactions with a cooperating Sp1 protein. JF - Molecular and cellular biology AU - Lee, Y H AU - Williams, S C AU - Baer, M AU - Sterneck, E AU - Gonzalez, F J AU - Johnson, P F AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 2038 EP - 2047 VL - 17 IS - 4 SN - 0270-7306, 0270-7306 KW - CCAAT-Enhancer-Binding Proteins KW - 0 KW - DNA Primers KW - DNA-Binding Proteins KW - Nuclear Proteins KW - Sp1 Transcription Factor KW - DNA KW - 9007-49-2 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Molecular Structure KW - Animals KW - Cytochrome P-450 Enzyme System -- genetics KW - DNA Primers -- genetics KW - DNA -- metabolism KW - Gene Expression KW - Liver -- metabolism KW - Mice KW - Transcriptional Activation KW - Leucine Zippers KW - Binding Sites KW - Rats KW - Promoter Regions, Genetic KW - Base Sequence KW - DNA -- genetics KW - Drosophila KW - Cell Line KW - Nuclear Proteins -- deficiency KW - DNA-Binding Proteins -- chemistry KW - Sp1 Transcription Factor -- metabolism KW - Nuclear Proteins -- chemistry KW - Nuclear Proteins -- metabolism KW - Sp1 Transcription Factor -- chemistry KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78887378?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=The+ability+of+C%2FEBP+beta+but+not+C%2FEBP+alpha+to+synergize+with+an+Sp1+protein+is+specified+by+the+leucine+zipper+and+activation+domain.&rft.au=Lee%2C+Y+H%3BWilliams%2C+S+C%3BBaer%2C+M%3BSterneck%2C+E%3BGonzalez%2C+F+J%3BJohnson%2C+P+F&rft.aulast=Lee&rft.aufirst=Y&rft.date=1997-04-01&rft.volume=17&rft.issue=4&rft.spage=2038&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-24 N1 - Date created - 1997-04-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell Biol. 1994 Oct;14(10):6570-83 [7935378] J Biol Chem. 1994 May 20;269(20):14375-8 [8182041] Cell. 1995 Jan 27;80(2):353-61 [7530603] Mol Cell Biol. 1995 May;15(5):2437-47 [7739528] EMBO J. 1995 May 1;14(9):1932-41 [7744000] EMBO J. 1995 Jul 3;14(13):3170-83 [7621830] Annu Rev Biochem. 1995;64:533-61 [7574492] Cell. 1996 Feb 23;84(4):575-85 [8598044] EMBO J. 1990 Jun;9(6):1897-906 [2112087] Virology. 1973 Apr;52(2):456-67 [4705382] Mol Cell Biol. 1982 Sep;2(9):1044-51 [6960240] Mol Cell Biol. 1987 Feb;7(2):725-37 [3821727] Proc Natl Acad Sci U S A. 1988 Jan;85(2):382-6 [3124106] Cell. 1988 Dec 2;55(5):887-98 [3142690] J Biol Chem. 1989 Feb 15;264(5):2920-7 [2914938] Cell. 1989 May 5;57(3):443-8 [2566384] Annu Rev Biochem. 1989;58:799-839 [2673023] Genes Dev. 1989 Sep;3(9):1314-22 [2558052] Nature. 1990 May 24;345(6273):359-61 [2188137] Nature. 1990 May 24;345(6273):361-4 [2160609] Mol Cell Biol. 1990 Dec;10(12):6172-80 [2123290] Genes Dev. 1990 Sep;4(9):1541-51 [2253878] Cell. 1991 Feb 8;64(3):585-93 [1899357] New Biol. 1990 Dec;2(12):1063-70 [2088498] Genes Dev. 1991 Sep;5(9):1553-67 [1884998] Trends Biochem Sci. 1991 Nov;16(11):417-22 [1776171] Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8145-9 [1518839] Mol Cell Biol. 1992 Oct;12(10):4251-61 [1341900] Genes Dev. 1993 Feb;7(2):173-9 [8436289] Pharmacogenetics. 1993 Feb;3(1):51-7 [8387380] Mol Cell Biol. 1993 Jul;13(7):3964-74 [8321203] J Biol Chem. 1993 Nov 15;268(32):23915-23 [8226931] Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10193-7 [8234276] EMBO J. 1993 Sep;12(9):3551-8 [8253080] Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):225-6 [8278369] Mol Cell Biol. 1994 Feb;14(2):1383-94 [8289814] EMBO J. 1994 Jan 1;13(1):147-57 [8306958] Genes Dev. 1994 Feb 1;8(3):350-62 [8314088] Genes Dev. 1994 Nov 15;8(22):2781-91 [7958933] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Specificity of p47phox SH3 domain interactions in NADPH oxidase assembly and activation. AN - 78886508; 9121467 AB - The delineation of molecular structures that dictate Src homology 3 (SH3) domain recognition of specific proline-rich ligands is key to understanding unique functions of diverse SH3 domain-containing signalling molecules. We recently established that assembly of the phagocyte NADPH oxidase involves multiple SH3 domain interactions between several oxidase components (p47phox, p67phox, and p22phox). p47phox was shown to play a central role in oxidase activation in whole cells by mediating interactions with both the transmembrane component p22phox and cytosolic p67phox. To understand the specific roles of each SH3 domain of p47phox in oxidase assembly and activation, we mutated critical consensus residues (Tyr167 or Tyr237-->Leu [Y167L or Y237L], W193R or W263R, and P206L or P276L) on each of their binding surfaces. The differential effects of these mutations indicated that the first SH3 domain is responsible for the p47phox-p22phox interaction and plays a predominant role in oxidase activity and p47phox membrane assembly, while the second p47phox SH3 domain interacts with the NH2-terminal domain of p67phox. Binding experiments using the isolated first SH3 domain also demonstrated its involvement in intramolecular interactions within p47phox and showed a requirement for five residues (residues 151 to 155) on its N-terminal boundary for binding to p22phox. The differential effects of nonconserved-site mutations (W204A or Y274A and E174Q or E244Q) on whole-cell oxidase activity suggested that unique contact residues within the third binding pocket of each SH3 domain influence their ligand-binding specificities. JF - Molecular and cellular biology AU - de Mendez, I AU - Homayounpour, N AU - Leto, T L AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. imendez@atlas.niaid.hin.gov Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 2177 EP - 2185 VL - 17 IS - 4 SN - 0270-7306, 0270-7306 KW - Ligands KW - 0 KW - Membrane Transport Proteins KW - Phosphoproteins KW - neutrophil cytosol factor 67K KW - Superoxides KW - 11062-77-4 KW - CYBA protein, human KW - EC 1.6.3.1 KW - NADPH Oxidase KW - neutrophil cytosolic factor 1 KW - NADPH Dehydrogenase KW - EC 1.6.99.1 KW - Index Medicus KW - Molecular Structure KW - NADPH Dehydrogenase -- genetics KW - Enzyme Activation KW - Humans KW - Amino Acid Sequence KW - Models, Biological KW - src Homology Domains KW - Mutagenesis, Site-Directed KW - NADPH Dehydrogenase -- metabolism KW - Superoxides -- metabolism KW - NADPH Dehydrogenase -- chemistry KW - Molecular Sequence Data KW - Binding Sites -- genetics KW - Sequence Homology, Amino Acid KW - Cell Line KW - NADPH Oxidase -- metabolism KW - Phosphoproteins -- genetics KW - Phosphoproteins -- chemistry KW - Phosphoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78886508?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Specificity+of+p47phox+SH3+domain+interactions+in+NADPH+oxidase+assembly+and+activation.&rft.au=de+Mendez%2C+I%3BHomayounpour%2C+N%3BLeto%2C+T+L&rft.aulast=de+Mendez&rft.aufirst=I&rft.date=1997-04-01&rft.volume=17&rft.issue=4&rft.spage=2177&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-24 N1 - Date created - 1997-04-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nat Struct Biol. 1994 Apr;1(4):221-5 [7656049] Nat Struct Biol. 1994 Dec;1(12):898-907 [7773779] Mol Cell Biol. 1995 Oct;15(10):5627-34 [7565714] EMBO J. 1995 Oct 16;14(20):5006-15 [7588629] Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):10909-13 [7479908] J Biol Chem. 1996 Jul 19;271(29):17013-20 [8663333] J Biol Chem. 1996 Sep 6;271(36):22152-8 [8703027] Blood. 1989 May 1;73(6):1686-94 [2469497] Science. 1989 Jul 28;245(4916):409-12 [2547247] J Biol Chem. 1990 Nov 15;265(32):19910-5 [2246268] J Clin Invest. 1991 Jan;87(1):352-6 [1985107] J Biol Chem. 1991 Oct 15;266(29):19812-8 [1918085] Nature. 1992 Mar 26;356(6367):340-4 [1372395] Science. 1993 Feb 19;259(5098):1157-61 [8438166] Cell. 1993 May 21;73(4):813-22 [7684655] Mol Cell Biol. 1993 Sep;13(9):5225-32 [7689147] Cell. 1994 Mar 11;76(5):933-45 [7510218] J Biol Chem. 1994 May 13;269(19):13752-5 [8188650] Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5345-9 [8202490] J Biol Chem. 1994 Jun 10;269(23):16326-32 [8206939] J Biol Chem. 1994 Sep 23;269(38):23431-6 [8089108] Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10650-4 [7938008] J Exp Med. 1994 Dec 1;180(6):2329-34 [7964505] Science. 1994 Nov 18;266(5188):1241-7 [7526465] Cell. 1995 Jan 27;80(2):237-48 [7834743] Blood. 1995 Feb 15;85(4):1104-10 [7849298] Nature. 1995 Feb 16;373(6515):573-80 [7531822] EMBO J. 1995 Mar 1;14(5):963-75 [7534229] J Biol Chem. 1995 May 12;270(19):11216-21 [7744754] Nat Struct Biol. 1994 Dec;1(12):835-7 [7773767] Nat Struct Biol. 1994 Dec;1(12):891-7 [7773778] Nat Struct Biol. 1994 Aug;1(8):546-51 [7664083] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adoptive transfer of anti-CD3-activated CD4+ T cells plus cyclophosphamide and liposome-encapsulated interleukin-2 cure murine MC-38 and 3LL tumors and establish tumor-specific immunity. AN - 78881710; 9116299 AB - The infusion of anti-CD3-activated murine T cells plus interleukin-2 (IL-2) exerts antitumor effects against several tumors in murine immunotherapy models. This study compares the therapeutic efficacy of anti-CD3-activated CD4+ or CD8+ T-cell subsets, when given with cyclophosphamide (Cy) and liposome-encapsulated IL-2 (L-IL2) in a murine model. C57BL/6 mice bearing subcutaneous (S.C.) MC-38 colon adenocarcinoma, 3LL Lewis lung carcinoma, or 38C13 lymphoma for 7 to 14 days were pretreated with low-dose intraperitoneal (I.P.) Cy before intravenous (I.V.) injection of anti-CD3-activated T cells or T-cell subsets. Cell administration was followed by I.P. administration of L-IL2 for 5 days. Mice receiving activated CD4+ T cells showed significantly reduced tumor growth or complete remissions with prolonged disease-free survival in MC-38, 3LL, and 38C13. The timing of Cy doses in relation to adoptive transfer was critical in obtaining the optimal antitumor effect by CD4+ cells. Injecting Cy 4 days before the infusion of CD4+ cells greatly enhanced the antitumor effect of the CD4+ cells and improved survival of the mice compared with other Cy regimens. C57BL/6 mice cured of MC-38 after treatment with CD4+ T cells developed tumor-type immunologic memory as demonstrated by their ability to reject rechallenges with MC-38, but not 3LL. Similarly, mice cured of 3LL tumors rejected rechallenges of 3LL, but not MC-38. The immunologic memory could be transferred with an I.V. injection of splenocytes from mice cured of MC-38 or 3LL. No cytotoxic T-lymphocyte activity was detected in T cells or T-cell subsets from mice cured of MC-38 or 3LL. Increased IL-2 and interferon-gamma (IFN-gamma) production was observed from CD4+ subsets in cured animals when stimulated in vitro with the original tumor, but not with an unrelated syngeneic tumor. These results suggest that tumor-specific immunity can be achieved in vivo with anti-CD3-stimulated CD4+ T cells in this cellular therapy model. JF - Blood AU - Saxton, M L AU - Longo, D L AU - Wetzel, H E AU - Tribble, H AU - Alvord, W G AU - Kwak, L W AU - Leonard, A S AU - Ullmann, C D AU - Curti, B D AU - Ochoa, A C AD - Biological Response Modifiers Program, National Cancer Institute, Frederick Cancer Research and Development Center, MD, USA. Y1 - 1997/04/01/ PY - 1997 DA - 1997 Apr 01 SP - 2529 EP - 2536 VL - 89 IS - 7 SN - 0006-4971, 0006-4971 KW - Antineoplastic Agents, Alkylating KW - 0 KW - Immunosuppressive Agents KW - Interleukin-2 KW - Liposomes KW - Cyclophosphamide KW - 8N3DW7272P KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Drug Administration Schedule KW - Combined Modality Therapy KW - Mice, Inbred C57BL KW - Mice, Inbred C3H KW - Immunologic Memory KW - Mice KW - Female KW - Interleukin-2 -- administration & dosage KW - Antineoplastic Agents, Alkylating -- therapeutic use KW - Carcinoma, Lewis Lung -- drug therapy KW - Carcinoma, Lewis Lung -- immunology KW - Adenocarcinoma -- immunology KW - Adenocarcinoma -- therapy KW - Colonic Neoplasms -- immunology KW - Cyclophosphamide -- therapeutic use KW - Carcinoma, Lewis Lung -- therapy KW - Colonic Neoplasms -- therapy KW - Interleukin-2 -- therapeutic use KW - Colonic Neoplasms -- drug therapy KW - Immunotherapy, Adoptive KW - CD4-Positive T-Lymphocytes -- transplantation KW - Adenocarcinoma -- drug therapy KW - Immunosuppressive Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78881710?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Adoptive+transfer+of+anti-CD3-activated+CD4%2B+T+cells+plus+cyclophosphamide+and+liposome-encapsulated+interleukin-2+cure+murine+MC-38+and+3LL+tumors+and+establish+tumor-specific+immunity.&rft.au=Saxton%2C+M+L%3BLongo%2C+D+L%3BWetzel%2C+H+E%3BTribble%2C+H%3BAlvord%2C+W+G%3BKwak%2C+L+W%3BLeonard%2C+A+S%3BUllmann%2C+C+D%3BCurti%2C+B+D%3BOchoa%2C+A+C&rft.aulast=Saxton&rft.aufirst=M&rft.date=1997-04-01&rft.volume=89&rft.issue=7&rft.spage=2529&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-22 N1 - Date created - 1997-04-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutational analysis of the adeno-associated virus Rep68 protein: identification of critical residues necessary for site-specific endonuclease activity. AN - 78869681; 9060625 AB - The Rep68 and Rep78 proteins of adeno-associated virus type 2 (AAV) are multifunctional proteins which contain overlapping amino acid sequences. They are required for viral replication and preferential integration of the AAV genome into a region of human chromosome 19. During the terminal resolution process of AAV DNA replication, these proteins make a site-specific and strand-specific endonuclease cut within the AAV inverted terminal repeat DNA. The Rep68 and Rep78 proteins also have helicase and DNA-binding activities. The endonuclease activity is believed to involve the covalent attachment of Rep68 or Rep78 at the cut site via a phosphotyrosine linkage. In an attempt to identify the active-site tyrosine residue of Rep78 and Rep68, tyrosine residues were site specifically mutated to phenylalanines by overlap extension PCR, and the resulting PCR fragments were cloned into a maltose binding protein-Rep68 fusion (MBP-Rep68delta) expression vector. The mutant MBP-Rep68delta proteins were expressed in Escherichia coli cells, purified with amylose resin, and assayed in vitro for Rep68-specific activities. Although several of the mutations disrupted the endonuclease activity, only the mutation of tyrosine 152 abrogated the endonuclease activity with no discernible effect on the helicase or DNA-binding activities. Our data therefore suggest that there are distinct active sites for the helicase and endonuclease activities. JF - Journal of virology AU - Walker, S L AU - Wonderling, R S AU - Owens, R A AD - Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 2722 EP - 2730 VL - 71 IS - 4 SN - 0022-538X, 0022-538X KW - Carrier Proteins KW - 0 KW - DNA-Binding Proteins KW - Escherichia coli Proteins KW - Maltose-Binding Proteins KW - Monosaccharide Transport Proteins KW - Recombinant Fusion Proteins KW - Viral Proteins KW - maltose transport system, E coli KW - rep proteins, Adeno-associated virus 2 KW - 137750-19-7 KW - Tyrosine KW - 42HK56048U KW - Phenylalanine KW - 47E5O17Y3R KW - Endonucleases KW - EC 3.1.- KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - DNA Helicases KW - EC 3.6.4.- KW - Index Medicus KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Phenylalanine -- metabolism KW - DNA Helicases -- metabolism KW - Humans KW - Carrier Proteins -- genetics KW - Recombinant Fusion Proteins -- genetics KW - Molecular Sequence Data KW - Adenosine Triphosphatases -- metabolism KW - Amino Acid Sequence KW - Tyrosine -- metabolism KW - Viral Proteins -- genetics KW - Viral Proteins -- isolation & purification KW - Dependovirus -- enzymology KW - DNA-Binding Proteins -- genetics KW - Dependovirus -- genetics KW - Endonucleases -- genetics KW - Endonucleases -- metabolism KW - Viral Proteins -- metabolism KW - ATP-Binding Cassette Transporters KW - DNA-Binding Proteins -- isolation & purification KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78869681?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Mutational+analysis+of+the+adeno-associated+virus+Rep68+protein%3A+identification+of+critical+residues+necessary+for+site-specific+endonuclease+activity.&rft.au=Walker%2C+S+L%3BWonderling%2C+R+S%3BOwens%2C+R+A&rft.aulast=Walker&rft.aufirst=S&rft.date=1997-04-01&rft.volume=71&rft.issue=4&rft.spage=2722&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-11 N1 - Date created - 1997-04-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Gene. 1989 Apr 15;77(1):51-9 [2744487] Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7966-72 [8755586] Cell. 1990 Jan 12;60(1):105-13 [2153052] Proc Natl Acad Sci U S A. 1976 Mar;73(3):742-6 [1062784] Virology. 1977 May 15;78(2):488-99 [867815] Proc Natl Acad Sci U S A. 1980 May;77(5):2482-6 [6446713] J Virol. 1983 Feb;45(2):555-64 [6300419] Cell. 1983 Dec;35(3 Pt 2):795-803 [6317202] J Virol. 1984 Aug;51(2):329-39 [6086948] Cell. 1983 May;33(1):135-43 [6088052] J Virol. 1984 Sep;51(3):611-9 [6088786] J Mol Biol. 1984 Oct 15;179(1):1-20 [6094825] J Virol. 1986 Feb;57(2):656-69 [3502703] J Virol. 1986 Dec;60(3):823-32 [3023672] Virology. 1987 Nov;161(1):18-28 [2823460] J Biol Chem. 1988 Jun 5;263(16):7678-85 [2836392] Proc Natl Acad Sci U S A. 1990 Mar;87(6):2211-5 [2156265] Cell. 1990 May 4;61(3):447-57 [2159383] J Virol. 1990 Dec;64(12):6204-13 [2173787] Nature. 1991 May 2;351(6321):78-80 [1851252] Virology. 1991 Sep;184(1):14-22 [1651588] Genomics. 1991 Jul;10(3):831-4 [1653762] J Virol. 1992 Feb;66(2):1119-28 [1309894] Mol Cell Biol. 1992 May;12(5):2331-8 [1314954] J Virol. 1992 Nov;66(11):6361-9 [1404595] EMBO J. 1992 Dec;11(13):5071-8 [1334463] J Virol. 1993 Feb;67(2):989-96 [8380474] J Virol. 1993 Feb;67(2):997-1005 [8380475] J Virol. 1994 Feb;68(2):797-804 [8289383] Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):942-6 [8302872] Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):5808-12 [8016070] Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6654-8 [7912831] J Virol. 1994 Aug;68(8):4998-5006 [8035499] Virology. 1994 Oct;204(1):304-11 [8091661] Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):10039-43 [7937833] Virology. 1995 Jan 10;206(1):448-56 [7831800] J Virol. 1995 Apr;69(4):2038-46 [7884849] J Virol. 1995 Jun;69(6):3542-8 [7538173] Virology. 1995 May 10;209(1):122-35 [7747462] Virology. 1995 Oct 1;212(2):562-73 [7571426] Virology. 1995 Dec 20;214(2):360-70 [8553536] J Virol. 1996 Apr;70(4):2440-8 [8642672] Biochem Biophys Res Commun. 1996 Mar 18;220(2):294-9 [8645299] J Virol. 1989 Jul;63(7):3034-9 [2542611] J Virol. 1989 Jul;63(7):3095-104 [2542617] Virology. 1989 Jul;171(1):239-47 [2545030] J Virol. 1996 Jul;70(7):4783-6 [8676507] Virology. 1989 Nov;173(1):120-8 [2554565] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - EGF-related peptides and their receptors in mammary gland development. AN - 78708823; 10882297 AB - The discovery of multiple EGF-like ligands and erbB receptors offers the potential for a highly diverse signaling system allowing specific ligand/receptor complexes to be created in response to a certain hormone(s) or stage of mammary development. The known erbB receptors and several of the erbB-related ligands are synthesized by the normal mammary gland and have different temporal and spatial expression patterns. For instance, cumulative findings support the concepts that the EGF receptor has an essential role in morphogenesis of the mammary gland and that activation of this receptor occurs in response to estradiol-stimulated synthesis of an EGF receptor ligand in mammary stromal cells. The importance of both epithelial and stromal mammary cells in the hormonal activation of erbB-related pathways is underscored in this review. Current experimental protocols that utilize erbB mutant mice or enable detection of phosphorylated erbB members and their proximal substrates should permit more precise identification of the pathways operative in the mammary gland. JF - Journal of mammary gland biology and neoplasia AU - DiAugustine, R P AU - Richards, R G AU - Sebastian, J AD - Hormones and Cancer Section, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 109 EP - 117 VL - 2 IS - 2 SN - 1083-3021, 1083-3021 KW - Ligands KW - 0 KW - Epidermal Growth Factor KW - 62229-50-9 KW - Receptor Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Receptor, Epidermal Growth Factor KW - Receptor, ErbB-2 KW - Index Medicus KW - Animals KW - Mice KW - Receptor Protein-Tyrosine Kinases -- metabolism KW - Female KW - Receptor, ErbB-2 -- physiology KW - Mammary Glands, Animal -- physiology KW - Receptor, Epidermal Growth Factor -- physiology KW - Epidermal Growth Factor -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78708823?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+mammary+gland+biology+and+neoplasia&rft.atitle=EGF-related+peptides+and+their+receptors+in+mammary+gland+development.&rft.au=DiAugustine%2C+R+P%3BRichards%2C+R+G%3BSebastian%2C+J&rft.aulast=DiAugustine&rft.aufirst=R&rft.date=1997-04-01&rft.volume=2&rft.issue=2&rft.spage=109&rft.isbn=&rft.btitle=&rft.title=Journal+of+mammary+gland+biology+and+neoplasia&rft.issn=10833021&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-14 N1 - Date created - 2000-07-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Insulin receptor knock-out mice. AN - 734283524; 18406794 AB - Targeted mutagenesis of the insulin receptor gene in mice has yielded unexpected results. This article reviews recent findings and analyzes this animal model can further our understanding of the mechanism of insulin action and its impairment in non-insulin-dependent diabetes mellitus is analyzed. (Trends Endocrinol Metab 1997;8:101-104). Published 1997 by Elsevier Science Inc. JF - Trends in endocrinology and metabolism: TEM AU - Accili, D AD - Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892USA. Y1 - 1997/04// PY - 1997 DA - April 1997 SP - 101 EP - 104 VL - 8 IS - 3 SN - 1043-2760, 1043-2760 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/734283524?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+endocrinology+and+metabolism%3A+TEM&rft.atitle=Insulin+receptor+knock-out+mice.&rft.au=Accili%2C+D&rft.aulast=Accili&rft.aufirst=D&rft.date=1997-04-01&rft.volume=8&rft.issue=3&rft.spage=101&rft.isbn=&rft.btitle=&rft.title=Trends+in+endocrinology+and+metabolism%3A+TEM&rft.issn=10432760&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2012-10-02 N1 - Date created - 2008-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mitochondrial and cellular toxicity induced by fialuridine in human muscle in vitro AN - 16428351; 4328917 AB - Fialuridine (FIAU), when used experimentally in the treatment of patients with chronic hepatitis B, caused irreversible acute hepatic failure, myopathy, myoglobinuria, severe lactic acidosis, neuropathy, and death. To investigate the primary cellular elements involved in the neuromuscular toxicity of FIAU, we examined its effects on human myotubes in cultures and searched for signs of recovery. From a total of 75 flasks of normal myotubes prepared from human muscle biopsies, 63 were exposed to various concentrations of FIAU (0.01 mu M, 0.1 mu M, 1 mu M, 10 mu M, 50 mu M, and 100 mu M) for 1 to 3 weeks, whereas 12 served as controls. After 3 weeks of FIAU treatment, 27 flasks were observed for 3 additional weeks to assess spontaneous recovery. All cultures were evaluated with: (a) light microscopy; (b) quantitative immunocytochemistry examining the number of myotubes immunostained for neural-cell adhesion molecule (N-CAM); (c) Oil-Red-O stain, to assess the lipid droplet accumulation; and d) electron microscopy with morphometric measurements of the volumetric density of each organelle per unit volume of tissue (magnification, x24,000). After 3 weeks of FIAU treatment, we found a severe reduction in the number of N-CAM-positive myotubes that varied according to the concentration of FIAU and the duration of treatment. Electron microscopy demonstrated a varying degree of destruction of the myotubes with significant increase in lipid droplets, lysosomes, and the rough endoplasmic reticulum. Major changes in mitochondria were noted even early in the treatment and consisted of concentric lamellar structures, paracrystalline inclusions, and vacuolization. These abnormalities remained unchanged without signs of recovery for up to 3 weeks after withdrawal of FIAU. We conclude that FIAU induces mitochondrial changes and intracellular lipid accumulations similar, but more severe, to those described with the other nucleoside analogues, such as zidovudine. In contrast to zidovudine, however, the FIAU-induced abnormalities do not improve or reverse after withdrawal of the drug. The observations are consistent with the irreversible mitochondrial changes noted in the FIAU-treated patients due to defective mitochondrial DNA replication. JF - Laboratory Investigation AU - Semino-Mora, C AU - Leon-Monzon, M AU - Dalakas, M C AD - Neuromuscular Diseases Section, National Institutes of Neurological Diseases and Stroke, National Institutes of Health, Building 10, Room 4N248, Bethesda, MD 20892, USA Y1 - 1997/04// PY - 1997 DA - Apr 1997 SP - 487 EP - 496 VL - 76 IS - 4 SN - 0023-6837, 0023-6837 KW - fialuridine KW - man KW - morphometry KW - Toxicology Abstracts KW - X 24117:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16428351?accountid=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=Laboratory+Investigation&rft.atitle=Mitochondrial+and+cellular+toxicity+induced+by+fialuridine+in+human+muscle+in+vitro&rft.au=Semino-Mora%2C+C%3BLeon-Monzon%2C+M%3BDalakas%2C+M+C&rft.aulast=Semino-Mora&rft.aufirst=C&rft.date=1997-04-01&rft.volume=76&rft.issue=4&rft.spage=487&rft.isbn=&rft.btitle=&rft.title=Laboratory+Investigation&rft.issn=00236837&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Rickettsia peacockii sp. nov., a new species infecting wood ticks, Dermacentor andersoni, in western Montana AN - 16100141; 4201569 AB - Rickettsia peacockii, a new species of spotted fever group rickettsiae, was identified from Rocky Mountain wood ticks (Dermacentor andersoni) collected in the Sapphire Mountain Range on the eastern side of Bitterroot Valley, Montana. DNA from R. peacockii Skalkaho super(T) (T = type strain) in naturally infected tick tissue was amplified by a PCR assay with primer sets derived from eubacterial 16S ribosomal DNA (rDNA), rickettsial citrate synthase, and 190-kDa surface antigen (rOmpA) genes. Partial 16S rDNA and rOmpA gene sequences exhibited levels of similarity of 99.7 and 93.2%, respectively, with the sequences of the spotted fever agent Rickettsia rickettsii R. By using Gimenez staining, fluorescent antibody tests, a PCR assay, and a restriction fragment length polymorphism analysis, 76 of 115 female ticks (minimal field infection rate, 66.1%) collected between 1992 and 1995 were found to be infected. The organism is passed transstadially and transovarially (minimal vertical transmission rate, 73.3%), and infections are localized in ovarial tissues. Attempts to cultivate R. peacockii were unsuccessful. JF - International Journal of Systematic Bacteriology AU - Niebylski, M L AU - Schrumpf, ME AU - Burgdorfer, W AU - Fischer, E R AU - Gage, K L AU - Schwan, T G AD - Rokcy Mountain Labs., NIAID-NIH, 903 S. Fourth St., Hamilton, MT 59840, USA Y1 - 1997/04// PY - 1997 DA - Apr 1997 SP - 446 EP - 452 VL - 47 IS - 2 SN - 0020-7713, 0020-7713 KW - nucleotide sequence KW - rRNA 16S KW - Entomology Abstracts; Microbiology Abstracts B: Bacteriology KW - Rickettsia peacockii KW - genes KW - Ixodidae KW - spotted fevers KW - restriction fragment length polymorphism KW - Dermacentor andersoni KW - DNA KW - taxonomy KW - polymerase chain reaction KW - Z 05206:Medical & veterinary entomology KW - J 02710:Identification, taxonomy and typing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16100141?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Systematic+Bacteriology&rft.atitle=Rickettsia+peacockii+sp.+nov.%2C+a+new+species+infecting+wood+ticks%2C+Dermacentor+andersoni%2C+in+western+Montana&rft.au=Niebylski%2C+M+L%3BSchrumpf%2C+ME%3BBurgdorfer%2C+W%3BFischer%2C+E+R%3BGage%2C+K+L%3BSchwan%2C+T+G&rft.aulast=Niebylski&rft.aufirst=M&rft.date=1997-04-01&rft.volume=47&rft.issue=2&rft.spage=446&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Systematic+Bacteriology&rft.issn=00207713&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Rickettsia peacockii; Dermacentor andersoni; Ixodidae; taxonomy; genes; DNA; restriction fragment length polymorphism; polymerase chain reaction; spotted fevers ER - TY - JOUR T1 - Infection of mucosal epithelial cells by Neisseria gonorrhoeae AN - 16086356; 4115182 AB - The bacterial pathogen Neisseria gonorrhoeae (gonococcus) is able to colonize and penetrate the human mucosa, to avoid the host's defences and to persist in various anatomical niches. Molecular analyses of recovered gonococci suggest that bacterial survival during the course of an infection is accompanied by dramatic alterations in the bacterial phenotype, including the variable expression of pili, opacity outer membrane proteins and lipo-oligosaccharides. These findings have led to the hypothesis that gonococcal surface variations may reflect bacterial adaptations that are essential to establish infection. Recent insights into the molecular mechanisms behind the early events in gonococcal pathogenesis support the concept that phenotypic transitions direct bacterial attachment and entry into mucosal cells. JF - Reviews in Medical Microbiology AU - Van Putten, JPM AU - Duensing, T D AD - Rocky Mountain Labs., NIAID, NIH, 903 South 4th St., Hamilton, MT 59840-2999, USA Y1 - 1997/04// PY - 1997 DA - Apr 1997 SP - 51 EP - 59 VL - 8 IS - 2 SN - 0954-139X, 0954-139X KW - Microbiology Abstracts B: Bacteriology KW - mucosa KW - gonorrhea KW - pili KW - epithelium KW - Neisseria gonorrhoeae KW - J 02832:Antigenic properties and virulence UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16086356?accountid=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=Reviews+in+Medical+Microbiology&rft.atitle=Infection+of+mucosal+epithelial+cells+by+Neisseria+gonorrhoeae&rft.au=Van+Putten%2C+JPM%3BDuensing%2C+T+D&rft.aulast=Van+Putten&rft.aufirst=JPM&rft.date=1997-04-01&rft.volume=8&rft.issue=2&rft.spage=51&rft.isbn=&rft.btitle=&rft.title=Reviews+in+Medical+Microbiology&rft.issn=0954139X&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 - Neisseria gonorrhoeae; mucosa; epithelium; pili; gonorrhea ER - TY - JOUR T1 - Effects of the carcinogen, acrylonitrile, on forestomach cell proliferation and apoptosis in the rat: Comparison with methacrylonitrile AN - 16083043; 4112152 AB - Acrylonitrile (AN) and methacrylonitrile (MAN) are two major industrial nitriles used in the production of plastics and acrylic fibers. Whereas AN is a potent acute toxin and carcinogenic in rats, little is known regarding MAN. Current work is part of an overall effort designed to assess the potential toxicity /carcinogenicity of MAN. The present study compares the ability of the two chemicals to induce epithelial proliferation and apoptosis in the forestomach (FS; a target of AN carcinogenicity), liver and glandular stomach (non-targets of AN carcinogenicity) of male F344 rats. AN was administered to rats daily, by gavage, for 6 weeks, at 0.43 and 0.22 mmol/kg. MAN was administered at 0.87 and 0.43 mmol /kg. Both AN and MAN induced a dose-dependent increase in epithelial cell proliferation in the FS of male F344 rats as determined by bromodeoxy-uridine (BrdU) incorporation into DNA. In contrast, AN, but not MAN caused a dose-dependent increase in the thickness of the forestomach squamous mucosa. This increased thickness (hyperplasia) was reflected by an increase in the number of total epithelial cells per unit length of mucosa. At doses of AN and MAN which induced a 2.3-fold increase in BrdU incorporation, apoptosis was 5- and 18-fold greater than controls, respectively. Although both MAN and AN caused a similar increase in cell proliferation, the relatively more prominent increase in the apoptotic index of the squamous epithelium of rats exposed to MAN may explain the lack of a detectable increase in the thickness of the mucosa compared to that seen with AN. The disruption of the balance between FS mucosal cell proliferation and apoptosis in favor of a net increase in the number of FS epithelial cells per unit length may contribute to the carcinogenicity of AN. In conclusion, present work demonstrated that AN selectively induced a net enhancement in FS cell proliferation, a site of its carcinogenicity. On the other hand, MAN-induced FS cell proliferation was associated with a parallel increase in apoptosis. The relatively greater increase in apoptosis by MAN may have compensated for the increase in FS mucosal cell proliferation and the lack of observable change in the FS thickness. JF - Carcinogenesis AU - Ghanayem, B I AU - Elwell, M R AU - Eldridge AD - NIH/NIEHS, RTP, NC 27709, USA Y1 - 1997/04// PY - 1997 DA - Apr 1997 SP - 675 EP - 680 VL - 18 IS - 4 SN - 0143-3334, 0143-3334 KW - rats KW - acrylonitrile KW - methacrylonitrile KW - Toxicology Abstracts KW - cell proliferation KW - apoptosis KW - stomach KW - X 24154:Pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16083043?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Effects+of+the+carcinogen%2C+acrylonitrile%2C+on+forestomach+cell+proliferation+and+apoptosis+in+the+rat%3A+Comparison+with+methacrylonitrile&rft.au=Ghanayem%2C+B+I%3BElwell%2C+M+R%3BEldridge&rft.aulast=Ghanayem&rft.aufirst=B&rft.date=1997-04-01&rft.volume=18&rft.issue=4&rft.spage=675&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - cell proliferation; apoptosis; stomach ER - TY - JOUR T1 - Both K-ras and H-ras protooncogene mutations are associated with Harderian gland tumorigenesis in B6C3F1 mice exposed to isoprene for 26 weeks AN - 16055526; 4103317 AB - Isoprene is the 2-methyl analog of 1,3-butadiene, a genotoxic and carcinogenic compound in rats and mice. Male B6C3F1 mice were exposed to 0,2200 or 7000 ppm isoprene by inhalation (6 h/day; 5 days/week) for 26 weeks. Following a 26-week recovery period, an increased incidence of Harderian gland (HG) neoplasms was observed at both concentrations. The present study was designed to characterize genetic alterations in the K-ras and H-ras protooncogenes in HG neoplasms. Mutations in K-ras and H-ras were identified by single-strand conformational analysis and direct sequencing of polymerase chain reaction (PCR) amplified DNA, isolated from paraffin-embedded sections of HG neoplasms. A higher frequency of ras mutations, in particular K-ras mutations, was detected in isoprene-induced neoplasms than in 1,3-butadiene-induced or control HG neoplasms. All of the isoprene-induced HG neoplasms exhibited activated K-ras (60%) or H-ras (40%) mutations. In contrast, ras mutations were detected in 69% of HG neoplasms from 1,3-butadiene exposed mice (14% K-ras and 55% H-ras) and in 56% of HG neoplasms obtained from control B6C3F1 mice (8% K-ras and 48% H-ras). The predominant mutations in isoprene-induced HG neoplasms, but not in previously or newly analysed 1,3-butadiene-induced HG neoplasms, consisted of A arrow right T transversions (CAA arrow right CTA) at K-ras codon 61 (15/30) and C arrow right A transversions (CAA arrow right AAA) at H-ras codon 61 (8/30). Two-thirds of the K-ras CTA mutations were detected in HG neoplasms from the 2200 ppm exposure group while one-third was present in the 7000 ppm group. Isoprene-induced HG neoplasms with K-ras or H-ras mutations had an elevated proliferating cell nuclear antigen (PCNA) index, compared to spontaneous HG neoplasms without ras mutations. The high frequency and specificity of the ras mutation profile suggest that ras protooncogene activation contributes to isoprene-induced HG tumorigenesis. JF - Carcinogenesis AU - Hong, H L AU - Devereux, T R AU - Melnick, R L AU - Eldridge AU - Greenwell, A AU - Haseman, J AU - Boorman, G A AU - Sills, R C AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1997/04// PY - 1997 DA - Apr 1997 SP - 783 EP - 789 VL - 18 IS - 4 SN - 0143-3334, 0143-3334 KW - mice KW - K-ras gene KW - H-ras gene KW - isoprene KW - proliferating cell nuclear antigen KW - Toxicology Abstracts; Oncogenes & Growth Factors Abstracts KW - tumorigenesis KW - Harderian gland KW - mutation KW - X 24155:Biochemistry KW - B 26130:Ras and Ras related oncogenes (Rho/Rac/Ral) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16055526?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Both+K-ras+and+H-ras+protooncogene+mutations+are+associated+with+Harderian+gland+tumorigenesis+in+B6C3F1+mice+exposed+to+isoprene+for+26+weeks&rft.au=Hong%2C+H+L%3BDevereux%2C+T+R%3BMelnick%2C+R+L%3BEldridge%3BGreenwell%2C+A%3BHaseman%2C+J%3BBoorman%2C+G+A%3BSills%2C+R+C&rft.aulast=Hong&rft.aufirst=H&rft.date=1997-04-01&rft.volume=18&rft.issue=4&rft.spage=783&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - mutation; Harderian gland; tumorigenesis ER - TY - JOUR T1 - Chlamydia psittaci IncA is phosphorylated by the host cell and is exposed on the cytoplasmic face of the developing inclusion AN - 16019547; 4090716 AB - Chlamydiae are obligate intracellular bacteria that replicate within a non-acidified vacuole called an inclusion. Chlamydia psittaci (strain GPIC) produces a 39 kDa protein (IncA) that is localized to the inclusion membrane. While IncA is present as a single 39 kDa species in purified reticulate bodies, two additional higher M sub(r) forms are found in C. psittaci-infected cells. This finding suggested that IncA may be post-translationally modified in the host cell. Here we present evidence that IncA is a serine/threonine phosphoprotein that is phosphorylated by host cell enzymes. This conclusion is supported by the following experimental findings: (i) treatment of infected cells with inhibitors of host cell phosphatases or kinases altered the electrophoretic migration pattern of IncA; (ii) treatment with calf intestinal alkaline phosphatase eliminated the multiple-banding pattern of IncA, leaving only the protein band with the lowest relative molecular weight; and (iii) radioimmunoprecipitation of lysates of [ super(32)P]-orthophosphate-labelled infected HeLa cells with anti-IncA antisera demonstrated that the two highest M sub(r) IncA bands were phosphorylated. A vaccinia-virus recombinant expressing incA was used to determine if HeLa cells can phosphorylate IncA in the absence of a chlamydial background. IncA in lysates of these cells migrated identically to that seen in C. psittaci-infected cells, indicating the host cell was responsible for the phosphorylation of the protein. Microinjection of fluorescently labelled anti-IncA antibodies into C. psittaci-infected HeLa cells resulted in immunostaining of the outer face of the inclusion membrane. Collectively, these results demonstrate that IncA is phosphorylated by the host cell, and regions of IncA are exposed at the cytoplasmic face of the inclusion. JF - Molecular Microbiology AU - Rockey, D D AU - Grosenbach, D AU - Hruby, DE AU - Peacock, M G AU - Heinzen, R A AU - Hackstadt, T AD - Rocky Mountain Labs., NIH, NIAID Hamilton, MT 59840, USA Y1 - 1997/04// PY - 1997 DA - Apr 1997 SP - 217 EP - 228 VL - 24 IS - 1 SN - 0950-382X, 0950-382X KW - IncA protein KW - Microbiology Abstracts B: Bacteriology KW - Chlamydia psittaci KW - phosphorylation KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16019547?accountid=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=Chlamydia+psittaci+IncA+is+phosphorylated+by+the+host+cell+and+is+exposed+on+the+cytoplasmic+face+of+the+developing+inclusion&rft.au=Rockey%2C+D+D%3BGrosenbach%2C+D%3BHruby%2C+DE%3BPeacock%2C+M+G%3BHeinzen%2C+R+A%3BHackstadt%2C+T&rft.aulast=Rockey&rft.aufirst=D&rft.date=1997-04-01&rft.volume=24&rft.issue=1&rft.spage=217&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 N1 - SubjectsTermNotLitGenreText - Chlamydia psittaci; phosphorylation ER - TY - JOUR T1 - In vivo retrovirus-mediated gene transfer into multiple hematopoietic lineages in rabbits without preconditioning AN - 16019524; 4093461 AB - Hematopoietic progenitor cells are attractive targets for gene therapy of inherited and acquired disorders. We have developed a novel procedure for mediating gene transfer into hematopoietic cells using an in vivo approach. The procedure involves injection of irradiated retroviral producer cells into the femoral bone marrow cavity in rabbits without preconditioning. The emergence of vector-marked cells in multiple peripheral blood hematopoietic lineages was detected 1 week post-injection and persisted until the animals were sacrificed up to 20 months later. Vector-marked cells were also detected in different hematopoietic tissues including bone marrow, spleen, thymus, and lymph node. Expression of retrovirus-specific messages by reverse transcription polymerase chain reaction was detected at multiple time points up to 20 months. Retrovirally encoded protein was detected by enzyme-linked immunosorbent assay in supernatant from cultures of granulocytes isolated 14 months after the procedure. This work demonstrates the feasibility of effecting gene transfer into hematopoietic progenitor cells in vivo. JF - Human Gene Therapy AU - Nelson, D M AU - Metzger, ME AU - Donahue, R E AU - Morgan, R A AD - Gene Transfer Technology Section, Clinical Gene Therapy Branch, National Center for Human Genome Research, 10 Center Drive, Bldg. 10, Rm. 10C103, Bethesda, MD 20892, USA Y1 - 1997/04// PY - 1997 DA - Apr 1997 SP - 747 EP - 754 VL - 8 IS - 6 SN - 1043-0342, 1043-0342 KW - hematopoiesis KW - rabbits KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - gene transfer KW - retrovirus KW - stem cells KW - bone marrow 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/16019524?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=In+vivo+retrovirus-mediated+gene+transfer+into+multiple+hematopoietic+lineages+in+rabbits+without+preconditioning&rft.au=Nelson%2C+D+M%3BMetzger%2C+ME%3BDonahue%2C+R+E%3BMorgan%2C+R+A&rft.aulast=Nelson&rft.aufirst=D&rft.date=1997-04-01&rft.volume=8&rft.issue=6&rft.spage=747&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 - 2011-12-14 N1 - SubjectsTermNotLitGenreText - gene transfer; retrovirus; stem cells; bone marrow ER - TY - JOUR T1 - Cytochrome P4502C11 is a target of diclofenac covalent binding in rats AN - 16009493; 4073951 AB - Diclofenac antiserum was previously developed and used to detect protein adducts of metabolites of dichlofenac in livers of mice and rats. In this study, the antibody has been used to facilitate the purification of a major 51 kDa microsomal adduct of diclofenac from the liver microsomes of male rats that were treated with diclofenac. The adduct was identified as male-specific cytochrome P4502C11 based on its N-terminal amino acid sequence, reaction with a cytochrome P4502C11 antibody, and by its absence from liver microsomes of diclofenac-treated female rats. When diclofenac was incubated with liver microsomes of control rats in the presence of NADPH, only the 51 kDa adduct was produced. The formation of the adduct was inhibited by a cytochrome P4502C11 monoclonal antibody, but not by reduced glutathione or N- alpha -acetyl-L-lysine. No adduct was detected when diclofenac was incubated with liver microsomes from female rats. Moreover, adduct formation in vivo appeared to lead to a 72% decrease in the activity of cytochrome P4502C11. The results indicate that cytochrome P4502C11 metabolizes diclofenac into a highly reactive product that covalently binds to this enzyme before it can diffuse away and react with other proteins. JF - Chemical Research in Toxicology AU - Shen, S AU - Hargus, S J AU - Martin, B M AU - Pohl, L R AD - Mol. and Cell. Toxicol. Sect., NHLBI, NIH, Bldg. 10, Rm. 8N110, Bethesda, MD 20892-1760, USA Y1 - 1997/04// PY - 1997 DA - Apr 1997 SP - 420 EP - 423 VL - 10 IS - 4 SN - 0893-228X, 0893-228X KW - rats KW - cytochrome P4502C11 KW - diclofenac KW - Toxicology Abstracts KW - microsomes KW - antiinflammatory agents KW - liver KW - monoclonal antibodies KW - X 24117:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16009493?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+Research+in+Toxicology&rft.atitle=Cytochrome+P4502C11+is+a+target+of+diclofenac+covalent+binding+in+rats&rft.au=Shen%2C+S%3BHargus%2C+S+J%3BMartin%2C+B+M%3BPohl%2C+L+R&rft.aulast=Shen&rft.aufirst=S&rft.date=1997-04-01&rft.volume=10&rft.issue=4&rft.spage=420&rft.isbn=&rft.btitle=&rft.title=Chemical+Research+in+Toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - antiinflammatory agents; monoclonal antibodies; liver; microsomes ER - TY - JOUR T1 - Unfolding of the bacterial nucleoid both in vivo and in vitro as a result of exposure to camphor AN - 15994154; 4075244 AB - Both prokaryotic and eukaryotic cells are sensitive to killing by camphor; however, the mechanism by which camphor kills has not been elucidated. We report here that camphor unfolds the nucleoid of Escherichia coli and that unfolding does not require DNA replication, translation, or cell division. We show that exposure of isolated nucleoids to camphor results in unfolding of the chromosome. JF - Journal of Bacteriology AU - Harrington, E W AU - Trun, N J AD - NCI, Building 37, Room 2D21, 37 Convent Dr., MSC4255, Bethesda, MD 20892-4255, USA Y1 - 1997/04// PY - 1997 DA - Apr 1997 SP - 2435 EP - 2439 VL - 179 IS - 7 SN - 0021-9193, 0021-9193 KW - unfolding KW - camphor KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - chromosomes KW - Escherichia coli KW - nucleoids KW - G 07320:Bacterial genetics KW - J 02812:Antibacterial Agents: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15994154?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=Unfolding+of+the+bacterial+nucleoid+both+in+vivo+and+in+vitro+as+a+result+of+exposure+to+camphor&rft.au=Harrington%2C+E+W%3BTrun%2C+N+J&rft.aulast=Harrington&rft.aufirst=E&rft.date=1997-04-01&rft.volume=179&rft.issue=7&rft.spage=2435&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; nucleoids; unfolding; chromosomes ER - TY - JOUR T1 - Characterization of DNA adducts formed by the four configurationally isomeric 5,6-dimethylchrysene 1,2-dihydrodiol 3,4-epoxides AN - 15991884; 4074682 AB - The DNA adducts formed from the racemic syn and anti dihydrodiol epoxides of 5,6-dimethylchrysene were characterized through various spectroscopic methods. Substantial reaction with the amino groups of both deoxyadenosine and deoxyguanosine residues were detected with both the syn and anti derivatives. The chemical shifts and coupling constants for the cis and trans opened adducts from the syn dihydrodiol epoxide were distinctly different, whereas for the anti dihydrodiol epoxide these properties were fairly similar for cis and trans adducts. In the latter case, assignment of trans and cis configurations was less obvious, and the finding that trans adducts have always predominated over cis adducts for all dihydrodiol epoxides studied to date was helpful in making these assignments. The preferential formation of cis adducts in DNA by the syn dihydrodiol epoxide is more like the chemistry of the dihydrodiol epoxide of benzo[c]phenanthrene than of benzo[g]chrysene, although both of these, like 5,6-dimethylchrysene, are non-planar compounds. JF - Chemical Research in Toxicology AU - Szeliga, J AU - Hilton, B D AU - Chmurny, G N AU - Krzeminski, J AU - Amin, S AU - Dipple, A AD - Chem. Carcinogenesis Lab., ABL-Basic Res. Prog., NCI-Frederick Cancer Res. and Dev. Cent., Frederick, MD 21702, USA Y1 - 1997/04// PY - 1997 DA - Apr 1997 SP - 378 EP - 385 VL - 10 IS - 4 SN - 0893-228X, 0893-228X KW - 5,6-dimethylchrysene KW - 1,2-dihydrodiol 3,4-epoxide KW - Biochemistry Abstracts 2: Nucleic Acids; Toxicology Abstracts KW - DNA adducts KW - polycyclic aromatic hydrocarbons 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/15991884?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+Research+in+Toxicology&rft.atitle=Characterization+of+DNA+adducts+formed+by+the+four+configurationally+isomeric+5%2C6-dimethylchrysene+1%2C2-dihydrodiol+3%2C4-epoxides&rft.au=Szeliga%2C+J%3BHilton%2C+B+D%3BChmurny%2C+G+N%3BKrzeminski%2C+J%3BAmin%2C+S%3BDipple%2C+A&rft.aulast=Szeliga&rft.aufirst=J&rft.date=1997-04-01&rft.volume=10&rft.issue=4&rft.spage=378&rft.isbn=&rft.btitle=&rft.title=Chemical+Research+in+Toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - DNA adducts; polycyclic aromatic hydrocarbons ER - TY - JOUR T1 - Formation of 8-hydroxy-2'-deoxyguanosine following treatment of 2'-deoxyguanosine or DNA by hydrogen peroxide or glutathione AN - 15930329; 4053339 AB - We have demonstrated that free radicals generated by hydrogen peroxide (H2O2), in the presence of divalent iron (Fe2+) and a chelator (EDTA), oxidize 2'-deoxyguanosine (dG) to 8-hydroxy-2'-deoxyguanosine (8-OHdG). The 8-OHdG formed by this reaction was isolated and quantitated using reverse-phase HPLC with UV and electrochemical detection. A 1-h incubation of dG with H2O2 caused a 50% increase in 8-OHdG over background, which increased to 100% after 2 h. However, when an H2O2-generating system [glutathione (GSH), Fe2+, EDTA] was used, there was no increase in 8-OHdG yield after the 1-h incubation, but up to a 50% increase over background was observed with GSH after 2-h incubation. Attempts to detect increased levels of 8-OHdG after H2O2- or GSH-treatment of purified calf thymus or rat DNA, or purified Salmonella typhimurium DNA were not successful. This may have been because the treatment procedures used generated 8-OHdG in the control samples at sufficiently high levels to mask any H2O2-induced responses that may have been present. This artifactual production of 8-OHdG has presented a problem in all in vitro studies to date. In contrast, treatment of Salmonella cells (strain TA104) with increasing concentrations of H2O2, caused a doubling in the 8-OHdG yield. GSH-treatment of strain TA104 cells under the same conditions did not result in an increase of 8-OHdG. The study presented here shows that the ubiquitous molecule H2O2 can play a major role in DNA oxidation, mutation, and damage. JF - Mutation Research-Genetic Toxicology and Environmental Mutagenesis AU - Abu-Shakra, A AU - Zeiger, E AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA Y1 - 1997/04// PY - 1997 DA - Apr 1997 SP - 45 EP - 50 PB - ELSEVIER SCIENCE B.V. VL - 390 IS - 1-2 SN - 1383-5718, 1383-5718 KW - 2'-deoxyguanosine KW - 8-hydroxy-2'-deoxyguanosine KW - hydrogen peroxide KW - glutathione KW - Biochemistry Abstracts 2: Nucleic Acids; Toxicology Abstracts KW - DNA damage KW - oxidation KW - mutation KW - free radicals KW - N 14630:Chemical reactions & interactions, including effects of radiation KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15930329?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+Research-Genetic+Toxicology+and+Environmental+Mutagenesis&rft.atitle=Formation+of+8-hydroxy-2%27-deoxyguanosine+following+treatment+of+2%27-deoxyguanosine+or+DNA+by+hydrogen+peroxide+or+glutathione&rft.au=Abu-Shakra%2C+A%3BZeiger%2C+E&rft.aulast=Abu-Shakra&rft.aufirst=A&rft.date=1997-04-01&rft.volume=390&rft.issue=1-2&rft.spage=45&rft.isbn=&rft.btitle=&rft.title=Mutation+Research-Genetic+Toxicology+and+Environmental+Mutagenesis&rft.issn=13835718&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - DNA damage; free radicals; mutation; oxidation ER - TY - JOUR T1 - HIV accessory proteins as therapeutic targets. Viral regulatory proteins represent new targets for therapeutic and prevention strategies against HIV AN - 15905195; 4036428 AB - HIV-1 is a member of the lentiviruses, a subgroup of the retrovirus family. As such, the virus shares the major genetic elements common to all retroviruses. Since the essential enzymes - reverse transcriptase (RT), ribonuclease H (RNase H), protease (PR) and integrase (IN) - are unique to the virus, they represent attractive targets to suppress HIV replication without impinging on normal cell function. As of this writing, a total of nine HIV drugs (six RT and three PR inhibitors) have been approved by the Food and Drug Administration (FDA) for clinical use, and others are in advanced preclinical development. However, it is sobering that, unlike RT and PR, RNase H and IN have thus far proven intransigent for targeted inhibition, notwithstanding the intense effort in these areas expended by academic, pharmaceutical and government sectors. The lentiviruses exhibit genomic complexity far beyond that of a prototypic retrovirus, with six additional genes (in addition to gag, pol and env) identified in HIV. Tat and rev are two regulatory genes absolutely required for virus replication: the Tat protein is required early in replication with a primary role in transcriptional activation of the viral promoter. The Rev protein acts as a temporal gatekeeper later in the replication cycle, allowing transport of late mRNAs from the nucleus to the cytoplasm. To date, only two anti-Tat agents have been evaluated clinically: one was subsequently withdrawn because of lack of clinical efficacy; the other is currently in phase II clinical studies in Canada. Conventional anti-Rev drugs are still not available for clinical studies. JF - Nature Medicine AU - Miller, R H AU - Sarver, N AD - DAIDS, NIAID, Solar Bldg., Rm. 2C36A, 6003 Executive Blvd., MSC 7620, Bethesda, MD 20892-7620, USA Y1 - 1997/04// PY - 1997 DA - Apr 1997 SP - 389 EP - 394 VL - 3 IS - 4 SN - 1078-8956, 1078-8956 KW - Nef protein KW - Vif protein KW - Vpr protein KW - Vpu protein KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - reviews KW - antiviral agents KW - human immunodeficiency virus KW - V 22002:AIDS: Molecular and in vitro aspects KW - W 30965:Miscellaneous, Reviews KW - W3 33000:General topics and reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15905195?accountid=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=HIV+accessory+proteins+as+therapeutic+targets.+Viral+regulatory+proteins+represent+new+targets+for+therapeutic+and+prevention+strategies+against+HIV&rft.au=Miller%2C+R+H%3BSarver%2C+N&rft.aulast=Miller&rft.aufirst=R&rft.date=1997-04-01&rft.volume=3&rft.issue=4&rft.spage=389&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 - 2011-12-14 N1 - SubjectsTermNotLitGenreText - reviews; antiviral agents; human immunodeficiency virus ER - TY - JOUR T1 - A Francisella tularensis DNA clone complements Escherichia coli defective for the production of Era, an essential Ras-like GTP-binding protein AN - 15891503; 4035088 AB - We cloned the era gene of Francisella tularensis from a plasmid library by heterologous genetic complementation of an Escherichia coli mutant conditionally defective for the production of Era, an essential protein for cell growth. Nucleotide sequence analysis indicated that, in F. tularensis, era constitutes a single gene operon. ORFs aspC and mdh encoding aspartate aminotransferase and malate dehydrogenase, respectively, flank era in F. tularensis. Although classified as Gram-, the flanking regions and the relative location of era in F. tularensis are distinctly different from those of typical Gram- and Gram+ bacteria. Computer analysis of bacterial Era protein sequences identified conserved domains in addition to the common G domains of most GTP-binding proteins. JF - Gene AU - Zuber, M AU - Hoover, T A AU - Dertzbaugh, M T AU - Court, D L AD - Molecular Control and Genetics Section, Gene Regulation and Chromosome Biology Laboratory, ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702-1201, USA Y1 - 1997/04// PY - 1997 DA - Apr 1997 SP - 31 EP - 34 PB - ELSEVIER SCIENCE B.V. VL - 189 IS - 1 SN - 0378-1119, 0378-1119 KW - nucleotide sequence KW - era gene KW - Era protein KW - guanine nucleotide-binding protein KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - complementation KW - Escherichia coli KW - Francisella tularensis KW - N 14640:Structure & sequence KW - G 07321:GENERAL KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15891503?accountid=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=Gene&rft.atitle=A+Francisella+tularensis+DNA+clone+complements+Escherichia+coli+defective+for+the+production+of+Era%2C+an+essential+Ras-like+GTP-binding+protein&rft.au=Zuber%2C+M%3BHoover%2C+T+A%3BDertzbaugh%2C+M+T%3BCourt%2C+D+L&rft.aulast=Zuber&rft.aufirst=M&rft.date=1997-04-01&rft.volume=189&rft.issue=1&rft.spage=31&rft.isbn=&rft.btitle=&rft.title=Gene&rft.issn=03781119&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 - Francisella tularensis; Escherichia coli; complementation ER - TY - JOUR T1 - The spirit of Dakar: A call for action on malaria AN - 15890038; 4033960 AB - Malaria has been a problem for too long. More than a million people still die from it every year, most of them young children. Nine out of ten of these deaths occur in Africa, where resistance to chloroquine is spreading, diminishing the impact of a drug which in the past has helped to limit the damage wreaked by the disease. Resistance is also increasing to Fansidar, the only other drug affordable for widespread use in Africa. This grim situation prompted an unprecedented meeting earlier this year in Dakar, Senegal, where, for the first time, scientists from both French- and English-speaking parts of Africa and scientists from the North came together to confront malaria. The challenge is enormous. New approaches are needed to control malaria and its mosquito vectors. New drugs must be found to prevent and treat the disease, and vaccines need to be developed. JF - Nature AU - Bruno, J-M AU - Feachem, R AU - Godal, T AU - Nchinda, T AU - Ogilvie, B AU - Mons, B AU - Mshana, R AU - Radda, G AU - Samba, E AU - Schwartz, M AU - Varmus, H AU - Diallo, S AU - Doumbo, O AU - Greenwood, B AU - Miller, L H AD - Build. 4, Rm. 126, NIAID, NIH, Bethesda, MD 20892, USA Y1 - 1997/04// PY - 1997 DA - Apr 1997 SP - 541 EP - 542 VL - 386 IS - 6625 SN - 0028-0836, 0028-0836 KW - antimalarial agents KW - biological vectors KW - ASFA 3: Aquatic Pollution & Environmental Quality; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - vaccines KW - drugs KW - Freshwater KW - disease control KW - vectors KW - Plasmodium KW - Senegal KW - malaria KW - drug resistance KW - Africa KW - public health KW - K 03090:Protozoa: human KW - Q5 08524:Public health, medicines, dangerous organisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15890038?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=The+spirit+of+Dakar%3A+A+call+for+action+on+malaria&rft.au=Bruno%2C+J-M%3BFeachem%2C+R%3BGodal%2C+T%3BNchinda%2C+T%3BOgilvie%2C+B%3BMons%2C+B%3BMshana%2C+R%3BRadda%2C+G%3BSamba%2C+E%3BSchwartz%2C+M%3BVarmus%2C+H%3BDiallo%2C+S%3BDoumbo%2C+O%3BGreenwood%2C+B%3BMiller%2C+L+H&rft.aulast=Bruno&rft.aufirst=J-M&rft.date=1997-04-01&rft.volume=386&rft.issue=6625&rft.spage=541&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2014-05-06 N1 - SubjectsTermNotLitGenreText - vectors; biological vectors; vaccines; drugs; malaria; drug resistance; disease control; public health; antimalarial agents; Plasmodium; Senegal; Africa; Freshwater ER - TY - JOUR T1 - Quantitative and qualitative comparisons of spontaneous and radiation-induced specific-locus mutation in the ad-3 region of heterokaryon 12 of Neurospora crassa AN - 15885566; 4035308 AB - The data from forward-mutation experiments to obtain specific-locus mutations at two closely linked loci in the adenine-3 (ad-3) region of heterokaryon 12 (H-12) of Neurospora crassa have been used to determine the relative frequencies and mutational spectra of ad-3 mutants occurring spontaneously and those induced by 7 different radiation treatments. Previous studies have demonstrated that specific-locus mutants at these two loci result from 5 major genotypic classes, namely two classes of gene/point mutations (ad-3AR and ad-3BR), and 3 classes of multilocus deletion mutations ([ad-3A]IR, [ad-3B]IR and [ad-3A ad-3B]IR). Two different approaches were used to compare spontaneous mutation in the ad-3 region with that induced by 7 different radiation treatments (UV, 32P, 447 MeV protons, 85Sr, 250 kVp X-rays, 39 MeV helium ions, and 101 MeV carbon ions). These comparisons included chi 2-tests on the numbers of ad-3 mutants resulting in the following two sets of ratios: (1) gene/point mutations and multilocus deletion mutations; and (2) complementing and non-complementing ad-3BR mutants. Combination of the data from these two methods of comparison has demonstrated that each of the 7 radiation treatments induced a spectrum of ad-3 mutants that is statistically different from the spontaneous spectrum. In addition, these same two methods of comparison have been used to compare the mutagenic effects of each of the 7 radiation treatments with each other. Combination of the data from these two methods of comparison demonstrated that the majority of radiation-induced specific-locus mutations: (90.5% (19 /21 of the pairwise combinations)) are qualitatively different from each other. We conclude that the mechanisms by which various radiations modify DNA tend to exhibit fundamental differences from each other and from the processes involved in spontaneous mutation. JF - Mutation Research AU - de Serres, FJ AU - Webber, B B AD - Laboratory of Toxicology, Environmental Toxicology Program, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709-2233, USA Y1 - 1997/04// PY - 1997 DA - Apr 1997 SP - 37 EP - 52 PB - ELSEVIER SCIENCE B.V. VL - 375 IS - 1 SN - 0027-5107, 0027-5107 KW - Toxicology Abstracts; Genetics Abstracts KW - deletion KW - Neurospora crassa KW - X radiation KW - U.V. radiation KW - point mutation KW - X 24210:Radiation & radioactive materials KW - G 07233:Radiation (U.V.) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15885566?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+Research&rft.atitle=Quantitative+and+qualitative+comparisons+of+spontaneous+and+radiation-induced+specific-locus+mutation+in+the+ad-3+region+of+heterokaryon+12+of+Neurospora+crassa&rft.au=de+Serres%2C+FJ%3BWebber%2C+B+B&rft.aulast=de+Serres&rft.aufirst=FJ&rft.date=1997-04-01&rft.volume=375&rft.issue=1&rft.spage=37&rft.isbn=&rft.btitle=&rft.title=Mutation+Research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Neurospora crassa; point mutation; deletion; U.V. radiation; X radiation ER - TY - JOUR T1 - Construction of four double gene substitution human x bovine rotavirus reassortant vaccine candidates: Each bears two outer capsid human rotavirus genes, one encoding P serotype 1A and the other encoding G serotype 1, 2, 3, or 4 specificity AN - 15880919; 4031577 AB - Previously, four human x bovine rotavirus reassortant candidate vaccines, each of which derived ten genes from bovine rotavirus UK strain and only the outer capsid protein VP7-gene from human rotavirus strain D (G serotype 1), DS-1 (G serotype 2), P (G serotype 3), or ST3 (G serotype 4), were developed. Such human x bovine reassortant vaccines should theoretically provide antigenic coverage for the four epidemiologically most important VP7(G) serotype 1, 2, 3, and 4. In an attempt to increase the antigenicity of VP7-based human x animal reassortant rotavirus vaccines which derive a single VP7-encoding gene from the human strain and the remaining ten genes from the animal strain, we generated double gene substitution reassortants. This was done by incorporating another protective antigen (VP4) of an epidemiologically important human rotavirus by crossing human rotavirus Wa strain (P serotype 1A), with each of the human x bovine single VP7-gene substitution rotavirus reassortants. In this way four separate double gene substitution rotavirus reassortants were generated. Each of these reassortants bears the VP4-encoding gene from human rotavirus Wa strain, the VP7-encoding gene from human rotavirus strain D, DS-1, P, or ST3, and the remaining nine genes from bovine rotavirus strain UK. The safety, antigenicity, and protective efficacy of individual components as well as combinations of strains are currently under evaluation. JF - Journal of Medical Virology AU - Hoshino, Y AU - Jones, R W AU - Chanock, R M AU - Kapikian, A Z AD - ES/LID/NIAID/NIH, Build. 7, Rm. 105, 7 Center Dr. MSC 0720, Bethesda, MD 20892-0720, USA Y1 - 1997/04// PY - 1997 DA - Apr 1997 SP - 319 EP - 325 PB - JOHN WILEY & SONS VL - 51 IS - 4 SN - 0146-6615, 0146-6615 KW - VP7 gene KW - Immunology Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology; Genetics Abstracts; Virology & AIDS Abstracts KW - cell culture KW - rotavirus KW - vaccines KW - immunogenicity KW - capsids KW - V 22050:Viral genetics including virus reactivation KW - F 06807:Active immunization KW - G 07313:Viruses KW - A 01097:Viruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15880919?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Medical+Virology&rft.atitle=Construction+of+four+double+gene+substitution+human+x+bovine+rotavirus+reassortant+vaccine+candidates%3A+Each+bears+two+outer+capsid+human+rotavirus+genes%2C+one+encoding+P+serotype+1A+and+the+other+encoding+G+serotype+1%2C+2%2C+3%2C+or+4+specificity&rft.au=Hoshino%2C+Y%3BJones%2C+R+W%3BChanock%2C+R+M%3BKapikian%2C+A+Z&rft.aulast=Hoshino&rft.aufirst=Y&rft.date=1997-04-01&rft.volume=51&rft.issue=4&rft.spage=319&rft.isbn=&rft.btitle=&rft.title=Journal+of+Medical+Virology&rft.issn=01466615&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - rotavirus; capsids; vaccines; immunogenicity; cell culture ER - TY - JOUR T1 - Regional changes in constitutive, but not inducible NOS expression in the brains of mice infected with the LP-BM5 leukemia virus. AN - 78956370; 9106446 AB - Potential neurotoxins such as nitric oxide have been implicated in the pathogenesis of acquired immunodeficiency syndrome (AIDS) dementia complex. The LP-BM5 murine leukemia-infected mice, which develop immunological and cognitive deficits reminiscent of human HIV-1 infection, were employed to investigate the changes in brain constitutive nitric oxide synthase (cNOS) and inducible nitric oxide synthase (iNOS) expression. Cerebellar and striatal cNOS enzymatic activity increased approximately 70% as early as 2 weeks after infection, declining to control levels by 12-16 weeks. In contrast, cNOS protein expression in the striatum and cerebellum was decreased 30% at 4 weeks, declining to 50% of control levels by 16 weeks post-infection. Staining intensity for cNOS, but not neuron number was reduced in the cerebral cortex, striatum, ventromedial hypothalamic nucleus and amygdala. Although iNOS protein expression was elevated in splenic monocytes, neither iNOS activity, mRNA nor protein was detected in the brains of mice 12 weeks after infection. These results indicate that neurons decrease cNOS protein expression to compensate for chronic cNOS activation, probably resulting from glutamatergic stimulation. The cNOS activation is contemporaneous with microglial activation in LP-BM5-infected mice, and precedes the development of cognitive deficits. Moreover, the lack of iNOS induction in either infected macrophages or glial elements suggests that iNOS is not necessary for the development of these cognitive deficits. JF - Brain research AU - Li, Y AU - Kustova, Y AU - Sei, Y AU - Basile, A S AD - Laboratory of Neuroscience, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/03/28/ PY - 1997 DA - 1997 Mar 28 SP - 107 EP - 116 VL - 752 IS - 1-2 SN - 0006-8993, 0006-8993 KW - RNA, Messenger KW - 0 KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Index Medicus KW - AIDS/HIV KW - Polymerase Chain Reaction KW - Animals KW - Blotting, Western KW - RNA, Messenger -- metabolism KW - Mice, Inbred C57BL KW - Mice KW - Tissue Distribution KW - Time Factors KW - Immunohistochemistry KW - Male KW - Tumor Virus Infections -- enzymology KW - Brain -- enzymology KW - Leukemia Virus, Murine KW - Retroviridae Infections -- enzymology KW - Nitric Oxide Synthase -- genetics KW - Nitric Oxide Synthase -- metabolism KW - Leukemia, Experimental -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78956370?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research&rft.atitle=Regional+changes+in+constitutive%2C+but+not+inducible+NOS+expression+in+the+brains+of+mice+infected+with+the+LP-BM5+leukemia+virus.&rft.au=Li%2C+Y%3BKustova%2C+Y%3BSei%2C+Y%3BBasile%2C+A+S&rft.aulast=Li&rft.aufirst=Y&rft.date=1997-03-28&rft.volume=752&rft.issue=1-2&rft.spage=107&rft.isbn=&rft.btitle=&rft.title=Brain+research&rft.issn=00068993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-23 N1 - Date created - 1997-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risk of secondary leukemia after treatment with etoposide (VP-16) for Langerhans' cell histiocytosis in Italian and Austrian-German populations. AN - 78944119; 9096658 AB - To estimate the risk of secondary leukemias after treatment with etoposide (VP-16), we evaluated subjects treated for Langerhans' cell histiocytosis (LCH) according to cooperative protocols in Italy or in Austria, Germany, Holland and Switzerland (AGDS). For each subject, information was collected on the cumulative dosages of chemotherapy and radiotherapy received, vital status and occurrence of secondary leukemia. The expected number of leukemias was estimated using age-specific incidence rates from the cancer registries in Italy and Germany. Standardized incidence ratios (SIR) were used to measure the risk of secondary leukemia among LCH patients. Five leukemias occurred among the 241 Italian study patients (SIR 520), whereas no cases were reported among the 363 AGDS patients. Interestingly, and in contrast to previous descriptions of epipodophyllotoxin-related leukemias which are mostly FAB M4 or M5, these leukemias showed typical FAB M3 features, and received a dose of VP-16 > 4,000 mg/m2. Among the AGDS cohort, very few subjects were exposed to high doses of VP-16. The risk of secondary acute non-lymphoblastic leukemia (s-ANLL) among the Italian subjects exposed to VP-16 was more than 1,000 times greater than expected. The study suggests that high doses of VP-16 appear to increase the risk of s-ANLL in LCH patients. The fact that all the leukemias described in the Italian LCH cohort were promyelocytic, and evidence of a higher incidence of promyelocytic leukemias among Italians and Latinos, suggest that high doses of etoposide in subjects of Latino origin may lead to aberrations on chromosomes 15 and 17. JF - International journal of cancer AU - Haupt, R AU - Fears, T R AU - Heise, A AU - Gadner, H AU - Loiacono, G AU - De Terlizzi, M AU - Tucker, M A AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 1997/03/28/ PY - 1997 DA - 1997 Mar 28 SP - 9 EP - 13 VL - 71 IS - 1 SN - 0020-7136, 0020-7136 KW - Etoposide KW - 6PLQ3CP4P3 KW - Index Medicus KW - Netherlands -- epidemiology KW - Chromosomes, Human, Pair 17 KW - Age Factors KW - Chromosomes, Human, Pair 15 KW - Sex Factors KW - Humans KW - Austria -- ethnology KW - Germany -- epidemiology KW - Infant, Newborn KW - Child KW - Translocation, Genetic KW - Risk Assessment KW - Child, Preschool KW - Infant KW - Switzerland -- epidemiology KW - Adult KW - Cohort Studies KW - Follow-Up Studies KW - Italy -- epidemiology KW - Adolescent KW - Male KW - Female KW - Histiocytosis, Langerhans-Cell -- drug therapy KW - Leukemia, Myeloid, Acute -- epidemiology KW - Leukemia, Myeloid, Acute -- chemically induced KW - Etoposide -- adverse effects KW - Histiocytosis, Langerhans-Cell -- radiotherapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78944119?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Risk+of+secondary+leukemia+after+treatment+with+etoposide+%28VP-16%29+for+Langerhans%27+cell+histiocytosis+in+Italian+and+Austrian-German+populations.&rft.au=Haupt%2C+R%3BFears%2C+T+R%3BHeise%2C+A%3BGadner%2C+H%3BLoiacono%2C+G%3BDe+Terlizzi%2C+M%3BTucker%2C+M+A&rft.aulast=Haupt&rft.aufirst=R&rft.date=1997-03-28&rft.volume=71&rft.issue=1&rft.spage=9&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-01 N1 - Date created - 1997-05-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risk of adenocarcinoma of the stomach and esophagus with meat cooking method and doneness preference. AN - 78909116; 9096659 AB - Meats cooked at high temperatures (frying, grilling) and for a long duration contain heterocyclic amines (HCAs), which are both mutagens and animal carcinogens. Additionally, barbecuing/grilling of meats produces polycyclic aromatic hydrocarbons (PAHs). Consumption of well-done meat has been associated with an increased risk of colon cancer but has not been evaluated as a risk factor for stomach or esophageal cancers. We conducted a population-based case-control study in 66 counties of eastern Nebraska. Telephone interviews were conducted with white men and women diagnosed with adenocarcinoma of the stomach (n = 176) and esophagus (n = 143) between July 1988 and June 1993 and 502 controls. The dietary assessment included several questions about usual cooking methods for meats and doneness preference for beef. High intake of red meat was associated with increased risks for both stomach and esophageal cancers. Overall, broiling or frying of beef, chicken or pork was not associated with the risk of these tumors. Barbecuing/grilling, reported as the usual cooking method for a small number of study participants, was associated with an elevated risk of stomach and esophageal cancers. After excluding those who reported usually barbecuing/grilling, a source of both PAHs and HCAs, we evaluated doneness level as a surrogate for HCA exposure. Compared to a preference for rare/medium rare beef, odds ratios were 2.4 for medium, 2.4 for medium well and 3.2 for well done, a significant positive trend. Doneness level was not associated with a significant trend in risk of esophageal cancer. JF - International journal of cancer AU - Ward, M H AU - Sinha, R AU - Heineman, E F AU - Rothman, N AU - Markin, R AU - Weisenburger, D D AU - Correa, P AU - Zahm, S H AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7364, USA. Y1 - 1997/03/28/ PY - 1997 DA - 1997 Mar 28 SP - 14 EP - 19 VL - 71 IS - 1 SN - 0020-7136, 0020-7136 KW - Index Medicus KW - Swine KW - Animals KW - Age Factors KW - Odds Ratio KW - Sex Factors KW - Humans KW - Aged KW - Cattle KW - Chickens KW - Risk Factors KW - Adult KW - Case-Control Studies KW - Middle Aged KW - Female KW - Male KW - Meat KW - Adenocarcinoma -- etiology KW - Cooking -- methods KW - Stomach Neoplasms -- etiology KW - Esophageal Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78909116?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Risk+of+adenocarcinoma+of+the+stomach+and+esophagus+with+meat+cooking+method+and+doneness+preference.&rft.au=Ward%2C+M+H%3BSinha%2C+R%3BHeineman%2C+E+F%3BRothman%2C+N%3BMarkin%2C+R%3BWeisenburger%2C+D+D%3BCorrea%2C+P%3BZahm%2C+S+H&rft.aulast=Ward&rft.aufirst=M&rft.date=1997-03-28&rft.volume=71&rft.issue=1&rft.spage=14&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-01 N1 - Date created - 1997-05-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - TPA induces transglutaminase C and inhibits cell growth in the colon carcinoma cell line SW620. AN - 78978414; 9126346 AB - In contrast to most other systems, TPA induced TGc activity and protein in SW620 human colon carcinoma cells. This induction was accompanied by cell growth inhibition and increased apoptosis. The general protein kinase-C inhibitor GF-109203X blocked the induction of TGc by TPA, whereas the specific inhibitor of the PKC alpha isoform, the indocarbazole Go6976, reduced it by 40%. These PKC inhibitors had similar inhibitory effects on TPA increased apoptosis and inhibition of cell growth, suggesting that the observed actions of TPA are mediated by PKC, and a close connection between TGc activity, increased apoptosis and cell growth inhibition. We conclude that TPA may offer new approaches in the management of colon cancer cell growth. JF - Biochemical and biophysical research communications AU - Kósa, K AU - Rosenberg, M I AU - Chiantore, M V AU - De Luca, L M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1997/03/27/ PY - 1997 DA - 1997 Mar 27 SP - 737 EP - 741 VL - 232 IS - 3 SN - 0006-291X, 0006-291X KW - Transglutaminases KW - EC 2.3.2.13 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Thymidine KW - VC2W18DGKR KW - Index Medicus KW - Thymidine -- metabolism KW - Protein Kinase C -- metabolism KW - Tumor Cells, Cultured KW - Enzyme Induction -- drug effects KW - Dose-Response Relationship, Drug KW - Humans KW - Apoptosis -- drug effects KW - Enzyme Activation -- drug effects KW - Colonic Neoplasms -- drug therapy KW - Cell Division -- drug effects KW - Transglutaminases -- biosynthesis KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Tetradecanoylphorbol Acetate -- administration & dosage KW - Colonic Neoplasms -- pathology KW - Colonic Neoplasms -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78978414?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=TPA+induces+transglutaminase+C+and+inhibits+cell+growth+in+the+colon+carcinoma+cell+line+SW620.&rft.au=K%C3%B3sa%2C+K%3BRosenberg%2C+M+I%3BChiantore%2C+M+V%3BDe+Luca%2C+L+M&rft.aulast=K%C3%B3sa&rft.aufirst=K&rft.date=1997-03-27&rft.volume=232&rft.issue=3&rft.spage=737&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-19 N1 - Date created - 1997-05-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Solid cancers after bone marrow transplantation. AN - 78862358; 9070469 AB - The late effects of bone marrow transplantation, including cancer, need to be determined in a large population at risk. We studied 19,229 patients who received allogeneic transplants (97.2 percent) or syngeneic transplants (2.8 percent) between 1964 and 1992 at 235 centers to evaluate the risk of the development of a new solid cancer. Risk factors relating to the patient, the transplant, and the course after transplantation were evaluated. The transplant recipients were at significantly higher risk of new solid cancers than the general population (observed cases, 80; ratio of observed to expected cases, 2.7; P<0.001). The risk was 8.3 times higher than expected among those who survived 10 or more years after transplantation. The cumulative incidence rate was 2.2 percent (95 percent confidence interval, 1.5 to 3.0 percent) at 10 years and 6.7 percent (95 percent confidence interval, 3.7 to 9.6 percent) at 15 years. The risk was significantly elevated (P<0.05) for malignant melanoma (ratio of observed to expected cases, 5.0) and cancers of the buccal cavity (11.1), liver (7.5), brain or other parts of the central nervous system (7.6), thyroid (6.6), bone (13.4), and connective tissue (8.0). The risk was higher for recipients who were younger at the time of transplantation than for those who were older (P for trend <0.001). In multivariate analyses, higher doses of total-body irradiation were associated with a higher risk of solid cancers. Chronic graft-versus-host disease and male sex were strongly linked with an excess risk of squamous-cell cancers of the buccal cavity and skin. Patients undergoing bone marrow transplantation have an increased risk of new solid cancers later in life. The trend toward an increased risk over time after transplantation and the greater risk among younger patients indicate the need for life-long surveillance. JF - The New England journal of medicine AU - Curtis, R E AU - Rowlings, P A AU - Deeg, H J AU - Shriner, D A AU - Socíe, G AU - Travis, L B AU - Horowitz, M M AU - Witherspoon, R P AU - Hoover, R N AU - Sobocinski, K A AU - Fraumeni, J F AU - Boice, J D AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1997/03/27/ PY - 1997 DA - 1997 Mar 27 SP - 897 EP - 904 VL - 336 IS - 13 SN - 0028-4793, 0028-4793 KW - Abridged Index Medicus KW - Index Medicus KW - Regression Analysis KW - Radiation Dosage KW - Age Factors KW - Analysis of Variance KW - Leukemia -- therapy KW - Neoplasms, Radiation-Induced -- etiology KW - Humans KW - Whole-Body Irradiation -- adverse effects KW - Child KW - Risk Factors KW - Adult KW - Incidence KW - Follow-Up Studies KW - Hematologic Diseases -- therapy KW - Adolescent KW - Time Factors KW - Male KW - Female KW - Graft vs Host Disease -- complications KW - Neoplasms, Second Primary -- epidemiology KW - Neoplasms, Second Primary -- etiology KW - Bone Marrow Transplantation -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78862358?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+journal+of+medicine&rft.atitle=Solid+cancers+after+bone+marrow+transplantation.&rft.au=Curtis%2C+R+E%3BRowlings%2C+P+A%3BDeeg%2C+H+J%3BShriner%2C+D+A%3BSoc%C3%ADe%2C+G%3BTravis%2C+L+B%3BHorowitz%2C+M+M%3BWitherspoon%2C+R+P%3BHoover%2C+R+N%3BSobocinski%2C+K+A%3BFraumeni%2C+J+F%3BBoice%2C+J+D&rft.aulast=Curtis&rft.aufirst=R&rft.date=1997-03-27&rft.volume=336&rft.issue=13&rft.spage=897&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=00284793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-27 N1 - Date created - 1997-03-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: N Engl J Med. 1997 Mar 27;336(13):949-50 [9070477] N Engl J Med. 1997 Jul 31;337(5):345-6 [9235499] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evidence for the involvement of Glu-355 in the catalytic action of human beta-hexosaminidase B. AN - 78882657; 9065471 AB - In a previous study the photoactivable affinity probe, 3-azi-1-[([6-3H]2-acetamido-2-deoxy-1-beta-D-galactopyranosyl)thio ]-b utane, was used to identify the active site of beta-hexosaminidase B, a beta-subunit dimer (Liessem, B., Glombitza, G. J., Knoll, F., Lehmann, J., Kellermann, J., Lottspeich, F., and Sandhoff, K. (1995) J. Biol. Chem. 270, 23693-23699). The probe predominately labeled Glu-355, a highly conserved residue among hexosaminidases. To determine if Glu-355 has a role in catalysis, beta-subunit mutants were prepared with the Glu-355 codon altered to either Ala, Gln, Asp, or Trp. After expression of mutant proteins using recombinant baculovirus, the enzyme activity associated with the beta-subunits was found to be reduced to background levels. Although catalytic activity was lost, the mutations did not otherwise affect the folding or assembly of the subunits. The mutant beta-subunits could be isolated using substrate affinity chromatography, indicating they contained intact substrate binding sites. As shown by cross-linking with disuccinimidyl suberate, the mutant beta-subunits were properly assembled. They could also participate in the formation of functional beta-hexosaminidase A activity as indicated by activator-dependent GM2 ganglioside degradation activity produced by co-expression of the mutant beta-subunits with the alpha-subunit. Finally, the mutant subunits showed normal lysosomal processing in COS-1 cells, demonstrating that a transport-competent protein conformation had been attained. Collectively the results provide strong support for the intimate involvement of Glu-355 in beta-hexosaminidase B-mediated catalysis. JF - The Journal of biological chemistry AU - Pennybacker, M AU - Schuette, C G AU - Liessem, B AU - Hepbildikler, S T AU - Kopetka, J A AU - Ellis, M R AU - Myerowitz, R AU - Sandhoff, K AU - Proia, R L AD - Section on Biochemical Genetics, Genetics and Biochemistry Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/03/21/ PY - 1997 DA - 1997 Mar 21 SP - 8002 EP - 8006 VL - 272 IS - 12 SN - 0021-9258, 0021-9258 KW - Affinity Labels KW - 0 KW - Recombinant Proteins KW - Glutamic Acid KW - 3KX376GY7L KW - beta-N-Acetylhexosaminidases KW - EC 3.2.1.52 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Chromatography, Affinity KW - Animals KW - COS Cells KW - Recombinant Proteins -- metabolism KW - Humans KW - Substrate Specificity KW - Recombinant Proteins -- chemistry KW - Recombinant Proteins -- genetics KW - Catalysis KW - Glutamic Acid -- metabolism KW - beta-N-Acetylhexosaminidases -- metabolism KW - beta-N-Acetylhexosaminidases -- chemistry KW - beta-N-Acetylhexosaminidases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78882657?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Evidence+for+the+involvement+of+Glu-355+in+the+catalytic+action+of+human+beta-hexosaminidase+B.&rft.au=Pennybacker%2C+M%3BSchuette%2C+C+G%3BLiessem%2C+B%3BHepbildikler%2C+S+T%3BKopetka%2C+J+A%3BEllis%2C+M+R%3BMyerowitz%2C+R%3BSandhoff%2C+K%3BProia%2C+R+L&rft.aulast=Pennybacker&rft.aufirst=M&rft.date=1997-03-21&rft.volume=272&rft.issue=12&rft.spage=8002&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-18 N1 - Date created - 1997-04-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Importance of conserved and variable C-terminal residues for the activity and thermal stability of the beta subunit of tryptophan synthase. AN - 78871815; 9065452 AB - To assess the functional roles of helix 13 and of the conserved and variable residues in the C-terminal region (residues 378-397) of the tryptophan synthase beta subunit, we have constructed four C-terminal truncations and 12 point mutations. The effects of these mutations on kinetic and spectroscopic properties and thermal stability are reported here. The mutant beta subunits all form stable alpha2beta2 complexes that have been purified to homogeneity. The mutant alpha2beta2 complexes are divided into two classes on the basis of activity in the reaction of L-serine with indole to form tryptophan. Class I enzymes, which have mutations at Arg-379 or Asp-381 or truncations (384-397 or 385-397), exhibit significant activity (1-38% of wild type). Class II enzymes, which have mutations at Lys-382 or Asp-383 or truncations (382-397 or 383-397), exhibit very low activity (<1% of wild type). Although Class II enzymes have drastically reduced activity in the reaction of L-serine with indole and an altered distribution of enzyme-substrate intermediates in the reaction of L-serine with beta-mercaptoethanol, they retain activity in the reaction of beta-chloro-L-alanine with indole. Correlation of the results with the three-dimensional structure of the alpha2beta2 complex suggests that Lys-382 and Asp-383 serve important roles in a proposed "open" to "closed" conformational change that occurs in the reactions of L-serine. Because mutant beta subunits having C-terminal truncations (383-397 or 384-397) undergo much more rapid thermal inactivation at 60 degrees C than the wild type beta subunit, the C-terminal helix 13 stabilizes the beta subunit. JF - The Journal of biological chemistry AU - Yang, L AU - Ahmed, S A AU - Rhee, S AU - Miles, E W AD - Enzyme Structure and Function Section, Laboratory of Biochemical Pharmacology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/03/21/ PY - 1997 DA - 1997 Mar 21 SP - 7859 EP - 7866 VL - 272 IS - 12 SN - 0021-9258, 0021-9258 KW - beta-Alanine KW - 11P2JDE17B KW - 3-chloroalanine KW - 3981-36-0 KW - Serine KW - 452VLY9402 KW - Tryptophan Synthase KW - EC 4.2.1.20 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - beta-Alanine -- analogs & derivatives KW - Spectrometry, Fluorescence KW - Enzyme Stability KW - Temperature KW - Molecular Sequence Data KW - beta-Alanine -- metabolism KW - Amino Acid Sequence KW - Protein Binding KW - Serine -- metabolism KW - Protein Conformation KW - Tryptophan Synthase -- metabolism KW - Tryptophan Synthase -- chemistry KW - Conserved Sequence KW - Tryptophan Synthase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78871815?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Importance+of+conserved+and+variable+C-terminal+residues+for+the+activity+and+thermal+stability+of+the+beta+subunit+of+tryptophan+synthase.&rft.au=Yang%2C+L%3BAhmed%2C+S+A%3BRhee%2C+S%3BMiles%2C+E+W&rft.aulast=Yang&rft.aufirst=L&rft.date=1997-03-21&rft.volume=272&rft.issue=12&rft.spage=7859&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-18 N1 - Date created - 1997-04-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional interaction of ADP-ribosylation factor 1 with phosphatidylinositol 4,5-bisphosphate. AN - 78867106; 9065426 AB - The relationship between ADP-ribosylation factor (Arf) 1 and phosphoinositides, which have been independently implicated as regulators of membrane traffic, was examined. Because both Arf-dependent phospholipase D and Arf1 GTPase-activating protein (GAP) require phosphatidylinositol 4,5-bisphosphate (PIP2), Arf1 complexed with PIP2 has been proposed to interact with target proteins. This hypothesis was tested using Arf1 GAP as a model system. Arf1 was shown to bind to PIP2 in Triton X-100 micelles with a Kd of 45 +/- 13 microM. Arf1 also bound phosphatidic acid but with 10-fold lower affinity. PIP2 binding was specifically disrupted by mutating lysines 15, 16, and 181 and arginine 178 to leucines. Decreased PIP2 binding resulted in an increased EC50 of PIP2 for activation of Arf GAP. None of the mutations that decreased PIP2 binding affected binding to or activation of GAP by phosphatidic acid, which acts at a functionally distinct site. These data support the hypothesis that PIP2 binding to Arf1 promotes interaction with Arf GAP. The implications of lipid-directed protein-protein interactions for membrane traffic are discussed. JF - The Journal of biological chemistry AU - Randazzo, P A AD - Laboratory of Biological Chemistry, Division of Basic Sciences, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. randazzo@helix.nih.gov Y1 - 1997/03/21/ PY - 1997 DA - 1997 Mar 21 SP - 7688 EP - 7692 VL - 272 IS - 12 SN - 0021-9258, 0021-9258 KW - Phosphatidylinositol 4,5-Diphosphate KW - 0 KW - Phospholipids KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - ADP-Ribosylation Factor 1 KW - EC 3.6.5.2 KW - ADP-Ribosylation Factors KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Humans KW - Phospholipids -- metabolism KW - GTP-Binding Proteins -- metabolism KW - Phosphatidylinositol 4,5-Diphosphate -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78867106?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Functional+interaction+of+ADP-ribosylation+factor+1+with+phosphatidylinositol+4%2C5-bisphosphate.&rft.au=Randazzo%2C+P+A&rft.aulast=Randazzo&rft.aufirst=P&rft.date=1997-03-21&rft.volume=272&rft.issue=12&rft.spage=7688&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-18 N1 - Date created - 1997-04-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reciprocal size-effect relationship of the key residues in determining regio- and stereospecificities of DHEA hydroxylase activity in P450 2a5. AN - 78899274; 9115996 AB - Collectively, the P450 2a4/2a5 system hyrdoxylates DHEA in at least three positions (7alpha, 7beta, and 2alpha). An individual P450, however, exhibits high specificity to one of these products. Using site-directed mutagenesis of mP450 2a5 from the wild mouse Mus minutoides and bacterial expression, we have associated the function of residues 117, 209, and 481 with the respective specificity observed in each P450. Ala at position 117 determines the 7beta-hydroxylase activity, whereas Val at this position defines the 2alpha-hydroxylase activity. Leu at position 209 is essential for high DHEA 7alpha-hydroxylase activity. The substitutions of residue 481 with various hydrophobic amino acids elicited a profound alteration of the specific hydroxylation rates, but did not influence the regio- and stereospecificities at either of the three positions of DHEA. The alterations caused by residue 481 also depended on the residue identity at position 117 or 209. The results indicate that the sizes of several key residues obey a concerted reciprocal relationship whereby the substrate pocket of the P450s adjusts to accommodate DHEA. A limited molecular modeling study successfully correlates DHEA binding to experimental DHEA hydroxylase activities for a series of mutants at key positions. JF - Biochemistry AU - Uno, T AU - Mitchell, E AU - Aida, K AU - Lambert, M H AU - Darden, T A AU - Pedersen, L G AU - Negishi, M AD - Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/03/18/ PY - 1997 DA - 1997 Mar 18 SP - 3193 EP - 3198 VL - 36 IS - 11 SN - 0006-2960, 0006-2960 KW - Oligodeoxyribonucleotides KW - 0 KW - Recombinant Proteins KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - Cytochrome P-450 CYP2A6 KW - Index Medicus KW - Muridae KW - Animals KW - Stereoisomerism KW - Liver -- enzymology KW - Amino Acid Sequence KW - Binding Sites KW - Cloning, Molecular KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Escherichia coli KW - Molecular Sequence Data KW - Substrate Specificity KW - Recombinant Proteins -- chemistry KW - Mixed Function Oxygenases -- chemistry KW - Mixed Function Oxygenases -- metabolism KW - Cytochrome P-450 Enzyme System -- chemistry KW - Cytochrome P-450 Enzyme System -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78899274?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Reciprocal+size-effect+relationship+of+the+key+residues+in+determining+regio-+and+stereospecificities+of+DHEA+hydroxylase+activity+in+P450+2a5.&rft.au=Uno%2C+T%3BMitchell%2C+E%3BAida%2C+K%3BLambert%2C+M+H%3BDarden%2C+T+A%3BPedersen%2C+L+G%3BNegishi%2C+M&rft.aulast=Uno&rft.aufirst=T&rft.date=1997-03-18&rft.volume=36&rft.issue=11&rft.spage=3193&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-21 N1 - Date created - 1997-04-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential interaction of erythromycin with cytochromes P450 3A1/2 in the endoplasmic reticulum: a CO flash photolysis study. AN - 78895275; 9116001 AB - The kinetics of CO binding to cytochromes P450, measured by the flash photolysis technique, were used to probe the interaction of erythromycin with cytochromes P450 in rat liver microsomes. Addition of erythromycin generates substrate difference spectra using microsomes from rats treated with phenobarbital or dexamethasone but not from untreated rats, showing that it binds to P450s induced by these agents. In contrast, erythromycin and/or a monoclonal antibody to P450 3A1/2 accelerated CO binding to microsomes from rats treated with phenobarbital but had no effect on microsomes from untreated or dexamethasone-treated rats. Based on the differential amounts and inducibilities of the P450 3A1 and 3A2 forms in these microsomal samples, these results indicate that erythromycin increased the rate for P450 3A2 but not P450 3A1. The divergent effects of erythromycin on these P450s, which exhibit 89% sequence similarity, were consistent with a model of the P450 substrate binding site in which erythromycin forms a more rigid complex with P450 3A1 than P450 3A2. These results demonstrate the sensitivity of P450 conformation/dynamics to substrate binding, and show that CO binding kinetics can distinguish among closely related P450s in a microsomal environment. JF - Biochemistry AU - Koley, A P AU - Dai, R AU - Robinson, R C AU - Markowitz, A AU - Friedman, F K AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/03/18/ PY - 1997 DA - 1997 Mar 18 SP - 3237 EP - 3241 VL - 36 IS - 11 SN - 0006-2960, 0006-2960 KW - Antibodies, Monoclonal KW - 0 KW - Erythromycin KW - 63937KV33D KW - Dexamethasone KW - 7S5I7G3JQL KW - Carbon Monoxide KW - 7U1EE4V452 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - Steroid Hydroxylases KW - EC 1.14.- KW - CYP3A protein, human KW - EC 1.14.14.1 KW - Cytochrome P-450 CYP3A KW - steroid hormone 6-beta-hydroxylase KW - Index Medicus KW - Endoplasmic Reticulum -- enzymology KW - Animals KW - Photolysis KW - Models, Molecular KW - Dexamethasone -- pharmacology KW - Antibodies, Monoclonal -- pharmacology KW - Binding Sites KW - Rats KW - Rats, Sprague-Dawley KW - Kinetics KW - Enzyme Induction KW - Male KW - Protein Conformation KW - Steroid Hydroxylases -- metabolism KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Cytochrome P-450 Enzyme System -- metabolism KW - Erythromycin -- metabolism KW - Steroid Hydroxylases -- chemistry KW - Erythromycin -- pharmacology KW - Steroid Hydroxylases -- biosynthesis KW - Mixed Function Oxygenases -- chemistry KW - Mixed Function Oxygenases -- metabolism KW - Mixed Function Oxygenases -- biosynthesis KW - Microsomes, Liver -- enzymology KW - Cytochrome P-450 Enzyme System -- chemistry KW - Carbon Monoxide -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78895275?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=Differential+interaction+of+erythromycin+with+cytochromes+P450+3A1%2F2+in+the+endoplasmic+reticulum%3A+a+CO+flash+photolysis+study.&rft.au=Koley%2C+A+P%3BDai%2C+R%3BRobinson%2C+R+C%3BMarkowitz%2C+A%3BFriedman%2C+F+K&rft.aulast=Koley&rft.aufirst=A&rft.date=1997-03-18&rft.volume=36&rft.issue=11&rft.spage=3237&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-21 N1 - Date created - 1997-04-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A highly conserved nucleotide in the Alu domain of SRP RNA mediates translation arrest through high affinity binding to SRP9/14. AN - 78934670; 9092618 AB - Binding of the signal recognition particle (SRP) to signal sequences during translation leads to an inhibition of polypeptide elongation known as translation arrest. The arrest activity is mediated by a discrete domain comprised of the Alu portion of SRP RNA and a 9 and 14 kDa polypeptide heterodimer (SRP9/14). Although very few nucleotides in SRP RNA are conserved throughout evolution, the remarkable conservation of G24, which resides in the region of SRP9/14 interaction, suggests that it is essential for translation arrest. To understand the functional significance of the G24 residue, we made single base substitutions in SRP RNA at this position and analyzed the ability of the mutants to bind SRP9/14 and to reconstitute functional SRPs. Mutation of G24 to C reduced binding to SRP9/14 by at least 50-fold, whereas mutation to A and U reduced binding approximately 2- and 5-fold respectively. The mutant RNAs could nevertheless assemble into SRPs at high subunit concentrations. SRPs reconstituted with mutant RNAs were not significantly defective in translation arrest assays, indicating that the conserved guanosine does not interact directly with the translational machinery. Taken together, these results demonstrate that G24 plays an important role in the translation arrest function of SRP by mediating high affinity binding of SRP9/14. JF - Nucleic acids research AU - Chang, D Y AU - Newitt, J A AU - Hsu, K AU - Bernstein, H D AU - Maraia, R J AD - Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/03/15/ PY - 1997 DA - 1997 Mar 15 SP - 1117 EP - 1122 VL - 25 IS - 6 SN - 0305-1048, 0305-1048 KW - DNA Primers KW - 0 KW - RNA-Binding Proteins KW - Recombinant Proteins KW - Signal Recognition Particle KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Base Sequence KW - RNA-Binding Proteins -- metabolism KW - Conserved Sequence KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Dimerization KW - Point Mutation KW - Nucleic Acid Conformation KW - Binding Sites KW - Protein Biosynthesis KW - Signal Recognition Particle -- isolation & purification KW - Signal Recognition Particle -- metabolism KW - Signal Recognition Particle -- chemistry KW - Repetitive Sequences, Nucleic Acid UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78934670?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+highly+conserved+nucleotide+in+the+Alu+domain+of+SRP+RNA+mediates+translation+arrest+through+high+affinity+binding+to+SRP9%2F14.&rft.au=Chang%2C+D+Y%3BNewitt%2C+J+A%3BHsu%2C+K%3BBernstein%2C+H+D%3BMaraia%2C+R+J&rft.aulast=Chang&rft.aufirst=D&rft.date=1997-03-15&rft.volume=25&rft.issue=6&rft.spage=1117&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-30 N1 - Date created - 1997-04-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Cell Biol. 1985 Jun;100(6):1913-21 [2581979] Nucleic Acids Res. 1983 Nov 11;11(21):7363-74 [6196719] Nature. 1986 Mar 6-12;320(6057):81-4 [2419765] Nature. 1986 Apr 17-23;320(6063):634-6 [3010127] Proc Natl Acad Sci U S A. 1986 Nov;83(22):8604-8 [3095839] Annu Rev Cell Biol. 1986;2:499-516 [3030381] Cell. 1988 Jan 15;52(1):39-49 [2830980] Proc Natl Acad Sci U S A. 1988 Mar;85(6):1801-5 [2450348] EMBO J. 1988 Jun;7(6):1769-75 [3169004] Nature. 1989 May 25;339(6222):280-6 [2566918] Proc Natl Acad Sci U S A. 1989 Oct;86(20):7706-10 [2479010] Mol Cell Biol. 1990 Feb;10(2):777-84 [2153922] Cell. 1990 Nov 2;63(3):591-600 [2171778] Science. 1990 Nov 23;250(4984):1111-7 [1701272] EMBO J. 1991 Apr;10(4):767-77 [1706993] Nucleic Acids Res. 1991 Jan 25;19(2):209-15 [1707519] J Biol Chem. 1991 May 15;266(14):8675-8 [1709156] Mol Cell Biol. 1991 Aug;11(8):3949-59 [1712900] Nucleic Acids Res. 1991 Oct 25;19(20):5695-702 [1945845] Methods Enzymol. 1991;208:103-17 [1779832] Nature. 1992 May 7;357(6373):47-52 [1315422] Nucleic Acids Res. 1992 Apr 11;20(7):1607-15 [1315954] Biochemistry. 1992 Jun 30;31(25):5830-40 [1377027] Nucleic Acids Res. 1992 Nov 25;20(22):5919-25 [1281314] J Cell Biol. 1993 Mar;120(5):1113-21 [8382204] J Biol Chem. 1993 Mar 25;268(9):6423-8 [7681065] Mol Cell Biol. 1993 Jul;13(7):4233-41 [7686619] Cell. 1993 Nov 19;75(4):615-30 [8242738] Mol Cell Biol. 1994 Jun;14(6):3949-59 [8196634] Nucleic Acids Res. 1994 Jun 11;22(11):1933-47 [7518075] Nucleic Acids Res. 1994 Jul 11;22(13):2557-67 [8041618] Annu Rev Cell Biol. 1994;10:87-119 [7888184] Mol Cell Biol. 1995 Apr;15(4):2109-16 [7534378] J Biol Chem. 1995 Apr 28;270(17):10179-86 [7730321] Mol Biol Cell. 1995 Apr;6(4):471-84 [7542942] Science. 1996 Mar 15;271(5255):1519-26 [8599107] Curr Biol. 1996 Mar 1;6(3):331-8 [8805251] Nucleic Acids Res. 1996 Nov 1;24(21):4165-70 [8932367] Anal Biochem. 1981 Nov 1;117(2):307-10 [6172996] Cell. 1983 Sep;34(2):525-33 [6413076] J Cell Biol. 1983 Dec;97(6):1693-9 [6196367] Nature. 1985 Nov 28-Dec 4;318(6044):371-4 [2415825] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Aberrant expression and regulation of hepatic epidermal growth factor receptor in a c-myc transgenic mouse model. AN - 78911567; 9093914 AB - In an attempt to elucidate the mechanism by which c-myc and transforming growth factor-alpha (TGF-alpha) cooperate in hepatocyte tumor development, we have analyzed signaling by the epidermal growth factor (EGF) receptor and the consequent regulation of receptor number in transgenic mice bearing the c-myc transgene under the control of the albumin enhancer/promoter. 125I-EGF binding and Scatchard analysis indicated a single class of high affinity receptors with the total number of binding sites of 1.2 X 10(4) +/- 600 and 2.5 X 10(5) +/- 1000 sites/cell in the normal and c-myc hepatocytes in primary culture, respectively. After 72 h of EGF exposure in culture, the number of detectable EGF receptors on the cell surface of the c-myc hepatocytes was not reduced, whereas the number of EGF receptors on normal hepatocytes was reduced to 32% that of untreated hepatocytes. Nuclear run-on experiments done with nuclei isolated from intact livers demonstrated that transcription of the EGF receptor was 4.9-fold higher in c-myc mice. Increased levels of the transcriptional factor SP1 in the c-myc hepatocytes in vivo and in primary culture, suggest a mechanism for the increased transcription of the EGF receptor. c-myc also increases the expression of TGF-alpha; a consequent increase in tyrosine phosphorylation is also detected in vivo. Thus, the increased number of EGF receptors in c-myc expressing hepatocytes, even after prolonged exposure to EGF, or TGF-alpha in vivo, may allow greater triggering of the EGF receptor signaling cascade. JF - Journal of cellular biochemistry AU - Woitach, J T AU - Conner, E A AU - Wirth, P J AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1997/03/15/ PY - 1997 DA - 1997 Mar 15 SP - 651 EP - 660 VL - 64 IS - 4 SN - 0730-2312, 0730-2312 KW - Transforming Growth Factor alpha KW - 0 KW - Epidermal Growth Factor KW - 62229-50-9 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Animals KW - Signal Transduction -- genetics KW - Gene Expression KW - Transforming Growth Factor alpha -- pharmacology KW - Mice KW - Epidermal Growth Factor -- pharmacology KW - Mice, Transgenic KW - Receptor, Epidermal Growth Factor -- genetics KW - Genes, myc KW - Liver -- metabolism KW - Gene Expression Regulation KW - Receptor, Epidermal Growth Factor -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78911567?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+biochemistry&rft.atitle=Aberrant+expression+and+regulation+of+hepatic+epidermal+growth+factor+receptor+in+a+c-myc+transgenic+mouse+model.&rft.au=Woitach%2C+J+T%3BConner%2C+E+A%3BWirth%2C+P+J%3BThorgeirsson%2C+S+S&rft.aulast=Woitach&rft.aufirst=J&rft.date=1997-03-15&rft.volume=64&rft.issue=4&rft.spage=651&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+biochemistry&rft.issn=07302312&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-03 N1 - Date created - 1997-06-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Positions of chromosome 3p14.2 fragile sites (FRA3B) within the FHIT gene. AN - 78887211; 9067288 AB - The FHIT gene spans approximately 1 Mb of DNA at chromosome band 3p14.2, which includes the familial renal cell carcinoma chromosome translocation breakpoint (between FHIT exons 3 and 4), the most frequently expressed human constitutive chromosomal fragile site (FRA3B, telomeric to the t(3;8) translocation), and numerous homozygous deletions in various human cancers, frequently involving FHIT exon 5. The FRA3B has previously been shown to represent more than one specific site, and some specific representatives of FRA3B breaks have been shown to fall in two regions, which we know to be in FHIT introns 4 and intron 5. Because breakage and integration of exogenous DNA in this chromosome region is frequent in aphidicolin-treated somatic cell hybrids, cancer cells, and, presumably, aphidicolin-treated normal lymphocytes that exhibit gaps or breaks, we determined by one- and two color fluorescence in situ hybridization, using cosmids covering specific regions of the FHIT gene, that most of the aphidicolin-induced gaps at FRA3B fall within the FHIT gene, with the highest frequency of gaps falling in intron 5 of the FHIT gene, less than 30 kb telomeric to FHIT exon 5. Gaps also occur in intron 4, where a human papillomavirus 16 integration site has been localized, and in intron 3, where the t(3;8) break point is located. These results suggest that the cancer-specific deletions, which frequently involve introns 4 and 5, originated through breaks in fragile sites. JF - Cancer research AU - Zimonjic, D B AU - Druck, T AU - Ohta, M AU - Kastury, K AU - Croce, C M AU - Popescu, N C AU - Huebner, K AD - Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1997/03/15/ PY - 1997 DA - 1997 Mar 15 SP - 1166 EP - 1170 VL - 57 IS - 6 SN - 0008-5472, 0008-5472 KW - DNA Probes KW - 0 KW - Neoplasm Proteins KW - Proteins KW - fragile histidine triad protein KW - Aphidicolin KW - 38966-21-1 KW - Acid Anhydride Hydrolases KW - EC 3.6.- KW - Index Medicus KW - Exons -- genetics KW - Chromosome Walking KW - Aphidicolin -- pharmacology KW - Humans KW - Chromosome Fragile Sites KW - Molecular Sequence Data KW - In Situ Hybridization, Fluorescence KW - Lymphocytes -- ultrastructure KW - Lymphocytes -- drug effects KW - Chromosome Mapping KW - Kidney Neoplasms -- genetics KW - Chromosomes, Human, Pair 3 -- ultrastructure KW - Chromosome Fragility KW - Chromosomes, Human, Pair 3 -- genetics KW - Proteins -- genetics KW - Carcinoma, Renal Cell -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78887211?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Positions+of+chromosome+3p14.2+fragile+sites+%28FRA3B%29+within+the+FHIT+gene.&rft.au=Zimonjic%2C+D+B%3BDruck%2C+T%3BOhta%2C+M%3BKastury%2C+K%3BCroce%2C+C+M%3BPopescu%2C+N+C%3BHuebner%2C+K&rft.aulast=Zimonjic&rft.aufirst=D&rft.date=1997-03-15&rft.volume=57&rft.issue=6&rft.spage=1166&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-09 N1 - Date created - 1997-04-09 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U76283; GENBANK; U39804; U39799 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The rat arylalkylamine N-acetyltransferase gene promoter. cAMP activation via a cAMP-responsive element-CCAAT complex. AN - 78853313; 9054387 AB - A 10-100-fold rhythm in the activity of arylalkylamine N-acetyltransferase (AA-NAT; EC 2.3.1.87) controls the rhythm in melatonin synthesis in the pineal gland. In some mammals, including the rat, the high nocturnal level of AA-NAT activity is preceded by an approximately 100-fold increase in AA-NAT mRNA. The increase in AA-NAT mRNA is generated by norepinephrine acting through a cAMP mechanism. Indirect evidence has suggested that cAMP enhances AA-NAT gene expression by stimulating phosphorylation of a DNA-binding protein (cAMP-responsive element (CRE)-binding protein) bound to a CRE. The nature of the sites involved in cAMP activation was investigated in this report by analyzing the AA-NAT promoter. An approximately 3700-base pair fragment of the 5'-flanking region of the rat AA-NAT gene was isolated, and the major transcription start points were mapped. The results of deletion analysis and site-directed mutagenesis indicate that cAMP activation requires a CRE.CCAAT complex consisting of a near-perfect CRE and an inverted CCAAT box located within two helical turns. JF - The Journal of biological chemistry AU - Baler, R AU - Covington, S AU - Klein, D C AD - Section on Neuroendocrinology, Laboratory of Developmental Neurobiology, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/03/14/ PY - 1997 DA - 1997 Mar 14 SP - 6979 EP - 6985 VL - 272 IS - 11 SN - 0021-9258, 0021-9258 KW - Cyclic AMP KW - E0399OZS9N KW - Arylamine N-Acetyltransferase KW - EC 2.3.1.5 KW - Index Medicus KW - Rats KW - Animals KW - Base Sequence KW - Molecular Sequence Data KW - Pineal Gland -- enzymology KW - Sequence Analysis, DNA KW - Cyclic AMP -- genetics KW - Gene Expression Regulation, Enzymologic KW - Promoter Regions, Genetic -- genetics KW - Arylamine N-Acetyltransferase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78853313?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+rat+arylalkylamine+N-acetyltransferase+gene+promoter.+cAMP+activation+via+a+cAMP-responsive+element-CCAAT+complex.&rft.au=Baler%2C+R%3BCovington%2C+S%3BKlein%2C+D+C&rft.aulast=Baler&rft.aufirst=R&rft.date=1997-03-14&rft.volume=272&rft.issue=11&rft.spage=6979&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-17 N1 - Date created - 1997-04-17 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U77455; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutation analysis of coding sequences of the entire transforming growth factor beta type II receptor gene in sporadic human colon cancer using genomic DNA and intron primers. AN - 78908433; 9121777 AB - Mutations in the transforming growth factor beta type II receptor (TGFbeta RII) gene have been detected in several human cancers exhibiting microsatellite instability. To extend analyses of this gene, we previously investigated the exon-intron organization of the TGFbeta RII gene and defined seven exons and flanking intron sequences. In this study, we further determined the nucleotide sequences surrounding these seven exons and designed eight sets of intron-based primers to examine the entire coding region of the TGFbeta RII gene. Using these primers, we screened genomic DNA sequences from 30 sporadic colorectal cancers for mutations of the TGFbeta RII gene. TGFbeta RII mutations were detected in two of 30 tumors and both displayed microsatellite instability. One had a deletion in a polyadenine tract in exon 3 and the other had a point mutation in the kinase domain located in exon 7. There were no mutations in exons 1, 2, 4, 5 and 6. These results further implicate the polyadenine tract and kinase domain as mutational hotspots in the TGFbeta RII gene in cells with genomic instability and suggest that TGFbeta RII gene mutations occur rarely in cells lacking genomic instability. JF - Oncogene AU - Takenoshita, S AU - Tani, M AU - Nagashima, M AU - Hagiwara, K AU - Bennett, W P AU - Yokota, J AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institute of Health, Bethesda, MD 20892, USA. Y1 - 1997/03/13/ PY - 1997 DA - 1997 Mar 13 SP - 1255 EP - 1258 VL - 14 IS - 10 SN - 0950-9232, 0950-9232 KW - DNA Primers KW - 0 KW - DNA, Neoplasm KW - Receptors, Transforming Growth Factor beta KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - transforming growth factor-beta type II receptor KW - EC 2.7.11.30 KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - Base Sequence KW - Humans KW - DNA Mutational Analysis KW - Molecular Sequence Data KW - Receptors, Transforming Growth Factor beta -- genetics KW - Colonic Neoplasms -- genetics KW - Introns KW - DNA, Neoplasm -- genetics KW - Colonic Neoplasms -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78908433?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Mutation+analysis+of+coding+sequences+of+the+entire+transforming+growth+factor+beta+type+II+receptor+gene+in+sporadic+human+colon+cancer+using+genomic+DNA+and+intron+primers.&rft.au=Takenoshita%2C+S%3BTani%2C+M%3BNagashima%2C+M%3BHagiwara%2C+K%3BBennett%2C+W+P%3BYokota%2C+J%3BHarris%2C+C+C&rft.aulast=Takenoshita&rft.aufirst=S&rft.date=1997-03-13&rft.volume=14&rft.issue=10&rft.spage=1255&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-24 N1 - Date created - 1997-04-24 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U52246; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of BCL2 family member MCL1 as an early response to DNA damage. AN - 78886761; 9070651 AB - When ML-1 human myeloid leukemia cells are exposed to DNA damaging agents, they exhibit dramatic changes in the expression of a variety of gene products. This includes an increase in p53 (wild-type), a decrease in BCL2, a p53-dependent increase in the BCL2 family member BAX, and increases in Growth Arrest and DNA Damage-inducible (GADD) genes such as GADD45; these changes occur as early events in a sequence that culminates in DNA damage-induced apoptosis. DNA damaging agents have now been tested for effects on expression of another BCL2 family member, MCL1, a gene expressed during ML-1 cell differentiation. Expression of MCL1 was found to increase upon exposure of ML-1 cells to various types of DNA damaging agents, including ionizing radiation, ultraviolet radiation, and alkylating drugs. The increase in MCL1 occurred rapidly and was transient, levels of the MCL1 mRNA being elevated within 4 h and having returned to near baseline within 24 h. An increase in the Mcl1 protein was also seen, with the maximal increase occurring at an intermediate dose of IR (5 Gray) and lesser increases occurring at either lower or higher doses. The increase in expression of MCL1 was further studied using a panel of human cell lines that includes cells containing or not containing alterations in p53 as well as cells sensitive or insensitive to the apoptosis-inducing effects of DNA damage. The DNA damage-induced increase in MCL1 mRNA did not depend upon p53 as it was seen in cells lacking functional p53. However, the increase did depend upon susceptibility to apoptosis as it was not seen in cells insensitive to apoptosis-induction by DNA damaging agents. These findings demonstrate that cytotoxic DNA damage causes an increase in the expression of MCL1 along with increases in GADD45 and BAX and a decrease in BCL2. Furthermore, while the increase in GADD45 is seen both in cells that undergo growth arrest and in cells that undergo apoptosis in response to DNA damage, alterations in the profile of expression of BCL2 family members occur exclusively in cells that undergo the apoptotic response, with some family members increasing through p53-dependent (BAX) and others through p53-independent (MCL1) pathways. Overall, expression MCL1 can increase during the induction of cell death as well as during the induction of differentiation. JF - Oncogene AU - Zhan, Q AU - Bieszczad, C K AU - Bae, I AU - Fornace, A J AU - Craig, R W AD - Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1997/03/06/ PY - 1997 DA - 1997 Mar 06 SP - 1031 EP - 1039 VL - 14 IS - 9 SN - 0950-9232, 0950-9232 KW - BAX protein, human KW - 0 KW - DNA, Neoplasm KW - GADD45 protein KW - Intracellular Signaling Peptides and Proteins KW - Myeloid Cell Leukemia Sequence 1 Protein KW - Neoplasm Proteins KW - Proteins KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - RNA, Messenger KW - bcl-2-Associated X Protein KW - Methyl Methanesulfonate KW - AT5C31J09G KW - Index Medicus KW - Ultraviolet Rays KW - Humans KW - RNA, Messenger -- analysis KW - Proto-Oncogene Proteins -- metabolism KW - Leukemia, Myeloid -- genetics KW - Dose-Response Relationship, Radiation KW - Proteins -- genetics KW - Proteins -- metabolism KW - Proto-Oncogene Proteins -- radiation effects KW - Proteins -- drug effects KW - Tumor Cells, Cultured KW - Proto-Oncogene Proteins -- drug effects KW - Leukemia, Myeloid -- metabolism KW - Cell Survival -- radiation effects KW - Proto-Oncogene Proteins -- genetics KW - Time Factors KW - Proteins -- radiation effects KW - Radiation, Ionizing KW - Neoplasm Proteins -- drug effects KW - DNA Damage KW - Neoplasm Proteins -- radiation effects KW - Neoplasm Proteins -- genetics KW - Neoplasm Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78886761?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Induction+of+BCL2+family+member+MCL1+as+an+early+response+to+DNA+damage.&rft.au=Zhan%2C+Q%3BBieszczad%2C+C+K%3BBae%2C+I%3BFornace%2C+A+J%3BCraig%2C+R+W&rft.aulast=Zhan&rft.aufirst=Q&rft.date=1997-03-06&rft.volume=14&rft.issue=9&rft.spage=1031&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-11 N1 - Date created - 1997-04-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A glucose-6-phosphate dehydrogenase (G6PD) splice site consensus sequence mutation associated with G6PD enzyme deficiency. AN - 78868389; 9067418 AB - A glucose-6-phosphate dehydrogenase (G6PD) deficient strain of mouse (GPDX) which was developed using the ethylating agent ethylnitrosourea (ENU) has been used to study clonality in epithelial tissues. While the biochemical defect has been quantified, the genetic basis of the deficiency is unknown. The G6PD gene is composed of 13 exons. Exon 1 is not translated, and the ATG start site is near the 5' end of exon 2. Direct sequencing of the exonic regions of the gene from GPDX, C3H, 101, C57BL/6 and BALB/c mice was carried out. The coding region, in which (with a single exception) all mutations found to cause G6PD deficiency in man are situated, showed identical sequences in three of the four strains studied (101 coding region sequence was not examined). However, the G6PD gene in the GPDX mouse showed a single base difference from the other four strains and from the published mouse G6PD sequence (BALB/c) in the 5' splice site consensus sequence at the 3' end of exon 1, part of the untranslated region. The difference was confirmed in four different GPDX mice. This mutation was of the type (A to T transversion) that is known to be induced by ENU; its effect is likely to be exerted through a defect in transcription, splicing or translation, leading to a reduction in protein levels. By Western blot we have found a marked decrease in the G6PD protein levels in the GPDX mouse, with the C3H X GPDX heterozygote showing a lesser decrease. Recently, an increasing number of mutations in the untranslated regions of genes have been found which have effects on protein levels. We believe that the reduced enzyme activity in the GPDX mouse is due to the mutation in the 5' untranslated region (UTR), and that similar mutations may be relevant in other inherited conditions. JF - Mutation research AU - Sanders, S AU - Smith, D P AU - Thomas, G A AU - Williams, E D AD - Department of Histopathology, Addenbrooke's Hospital, Cambridge, UK. sean-sanders@nih.gov Y1 - 1997/03/04/ PY - 1997 DA - 1997 Mar 04 SP - 79 EP - 87 VL - 374 IS - 1 SN - 0027-5107, 0027-5107 KW - Glucosephosphate Dehydrogenase KW - EC 1.1.1.49 KW - Ethylnitrosourea KW - P8M1T4190R KW - Index Medicus KW - Animals KW - Exons KW - Mice KW - Mice, Inbred BALB C KW - Liver -- chemistry KW - Mutagenesis KW - Phenotype KW - Polymerase Chain Reaction KW - Promoter Regions, Genetic KW - Base Sequence KW - Blotting, Western KW - Mice, Inbred C57BL KW - Molecular Sequence Data KW - Ethylnitrosourea -- pharmacology KW - Male KW - Glucosephosphate Dehydrogenase Deficiency -- genetics KW - Alternative Splicing KW - Consensus Sequence KW - Glucosephosphate Dehydrogenase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78868389?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+glucose-6-phosphate+dehydrogenase+%28G6PD%29+splice+site+consensus+sequence+mutation+associated+with+G6PD+enzyme+deficiency.&rft.au=Sanders%2C+S%3BSmith%2C+D+P%3BThomas%2C+G+A%3BWilliams%2C+E+D&rft.aulast=Sanders&rft.aufirst=S&rft.date=1997-03-04&rft.volume=374&rft.issue=1&rft.spage=79&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-08 N1 - Date created - 1997-04-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A new 85 kDa, breast tumour associated antigen -- A potential diagnostic and prognostic agent AN - 867732184; 13835850 AB - In an attempt to develop measures for early diagnosis and prognosis of the disease and to explore association of murine mammary tumour virus (MuMTV) or related virus in breast cancer, we purified a breast tumour associated antigen (BTAA) from the breast tumour tissues of untreated female cancer patients. The BTAA purified by DEAE discontinuous column chromatography followed by SE-HPLC was an 85 kDa glycoprotein. A high level of circulating antibodies against this antigen was observed, using ELISA, in all the untreated female breast cancer patients. The BTAA was not immunologically related to MuMTV antigens but strongly resembled an 83 kDa glycoprotein tumour associated antigen, purified from MuMTV induced mouse mammary tumour. In patients after surgical removal of the breast tumour, the circulating antibodies to the BTAA decreased gradually, but reappeared in the patients with secondary metastasis. In healthy age matched women or in female patients with carcinoma of tissues other than breast, no significant titre of the BTAA antibodies was observed. JF - Journal of Biosciences (Bangalore) AU - Chattopadhyay, Utpala AU - Pal, Saumitra AD - Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, 700 026, Calcutta, India Y1 - 1997/03// PY - 1997 DA - Mar 1997 SP - 69 EP - 75 PB - Springer-Verlag (Heidelberg), Tiergartenstrasse 17 Heidelberg 69121 Germany VL - 22 IS - 1 SN - 0250-5991, 0250-5991 KW - Biotechnology and Bioengineering Abstracts KW - Metastases KW - Antibodies KW - Enzyme-linked immunosorbent assay KW - Prognosis KW - Breast cancer KW - Column chromatography KW - Glycoproteins KW - Carcinoma KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/867732184?accountid=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+Biosciences+%28Bangalore%29&rft.atitle=A+new+85+kDa%2C+breast+tumour+associated+antigen+--+A+potential+diagnostic+and+prognostic+agent&rft.au=Chattopadhyay%2C+Utpala%3BPal%2C+Saumitra&rft.aulast=Chattopadhyay&rft.aufirst=Utpala&rft.date=1997-03-01&rft.volume=22&rft.issue=1&rft.spage=69&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biosciences+%28Bangalore%29&rft.issn=02505991&rft_id=info:doi/10.1007%2FBF02703619 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-05-01 N1 - Last updated - 2012-03-29 N1 - SubjectsTermNotLitGenreText - Metastases; Enzyme-linked immunosorbent assay; Antibodies; Prognosis; Column chromatography; Breast cancer; Glycoproteins; Carcinoma DO - http://dx.doi.org/10.1007/BF02703619 ER - TY - JOUR T1 - Characteristics of vocal fold adduction related to voice onset. AN - 85236295; pmid-9075172 AB - This study examined whether vocal fold kinematics prior to phonation differed between hard (glottal), normal, or breathy onsets in men and women. Glottal landmarks were identified and digitized from videotape recorded with a rigid laryngoscope during different voice onset types. Significant linear relationships (p < or = 0.0055) were found among onset types on measures of (a) gesture duration when moving from 80% to 20% of maximum distance during adduction, (b) maximum velocity, (c) duration between the completion of adduction and phonation onset, and (d) ratios of maximum velocity to maximum distance between the vocal processes, an estimate of stiffness. The gesture duration was greatest for breathy onsets and least for hard onsets, while the maximum velocity, latency between adduction and phonation onset, and estimated stiffness were greatest for hard onsets and least for breathy onsets. The results suggest that one trajectory seems to be used with increases in gesture duration being accompanied by decreases in articulator stiffness when moving from hard to normal to breathy voice onset types. JF - Journal of Voice AU - Cooke, A AU - Ludlow, C L AU - Hallett, N AU - Selbie, W S AD - Voice and Speech Section, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892-1416, USA. PY - 1997 SP - 12 EP - 22 VL - 11 IS - 1 SN - 0892-1997, 0892-1997 KW - Vocal Cords KW - Sex Factors KW - Human KW - Voice KW - Adult KW - Larynx KW - Time Factors KW - Female KW - Male UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85236295?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Voice&rft.atitle=Characteristics+of+vocal+fold+adduction+related+to+voice+onset.&rft.au=Cooke%2C+A%3BLudlow%2C+C+L%3BHallett%2C+N%3BSelbie%2C+W+S&rft.aulast=Cooke&rft.aufirst=A&rft.date=1997-03-01&rft.volume=11&rft.issue=1&rft.spage=12&rft.isbn=&rft.btitle=&rft.title=Journal+of+Voice&rft.issn=08921997&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - The role of posterior parietal cortex in visually guided reaching movements in humans. AN - 85235180; pmid-9125463 AB - Positron emission tomography (PET) was used to identify the brain areas involved in visually guided reaching by measuring regional cerebral blood flow (rCBF) in six normal volunteers while they were fixating centrally and reaching with the left or right arm to targets presented in either the right or the left visual field. The PET images were registered with magnetic resonance images from each subject so that increases in rCBF could be localized with anatomical precision in individual subjects. Increased neural activity was examined in relation to the hand used to reach, irrespective of field of reach (hand effect), and the effects of target field of reach, irrespective of hand used (field effect). A separate analysis on intersubject, averaged PET data was also performed. A comparison of the results of the two analyses showed close correspondence in the areas of activation that were identified. We did not find a strict segregation of regions associated exclusively with either hand or field. Overall, significant rCBF increases in the hand and field conditions occurred bilaterally in the supplementary motor area, premotor cortex, cuneus, lingual gyrus, superior temporal cortex, insular cortex, thalamus, and putamen. Primary motor cortex, postcentral gyrus, and the superior parietal lobule (intraparietal sulcus) showed predominantly a contralateral hand effect, whereas the inferior parietal lobule showed this effect for the left hand only. Greater contralateral responses for the right hand were observed in the secondary motor areas. Only the anterior and posterior cingulate cortices exhibited strong ipsilateral hand effects. Field of reach was more commonly associated with bilateral patterns of activation in the areas with contralateral or ipsilateral hand effects. These results suggest that the visual and motor components of reaching may have a different functional organization and that many brain regions represent both limb of reach and field of reach. However, since posterior parietal cortex is connected with all of these regions, we suggest that it plays a crucial role in the integration of limb and field coordinates. JF - Experimental Brain Research AU - Kertzman, C AU - Schwarz, U AU - Zeffiro, T A AU - Hallett, M AD - Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20891-1428, USA. PY - 1997 SP - 170 EP - 183 VL - 114 IS - 1 SN - 0014-4819, 0014-4819 KW - Magnetic Resonance Imaging KW - Brain Mapping KW - Vision KW - Human KW - Adult KW - Tomography, Emission-Computed KW - Hand KW - Arm KW - Parietal Lobe KW - Visual Fields KW - Male KW - Female KW - Psychomotor Performance KW - Movement UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85235180?accountid=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=Experimental+Brain+Research&rft.atitle=The+role+of+posterior+parietal+cortex+in+visually+guided+reaching+movements+in+humans.&rft.au=Kertzman%2C+C%3BSchwarz%2C+U%3BZeffiro%2C+T+A%3BHallett%2C+M&rft.aulast=Kertzman&rft.aufirst=C&rft.date=1997-03-01&rft.volume=114&rft.issue=1&rft.spage=170&rft.isbn=&rft.btitle=&rft.title=Experimental+Brain+Research&rft.issn=00144819&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Treatment of inclusion-body myositis with IVIg: a double-blind, placebo-controlled study. AN - 85170905; pmid-9065553 AB - We randomized 19 patients with inclusion-body myositis (IBM) to a double-blind, placebo-controlled, crossover study using monthly infusions of 2 g/kg intravenous immunoglobulin (IVIg) or placebo for 3 months. Patients crossed over to the alternate treatment after a washout period. We evaluated responses at baseline and at the end of each treatment period using expanded (0-10) MRC scales, the Maximum Voluntary Isometric Contraction (MVIC) method, symptom and disability scores, and quantitative swallowing studies. We calculated the differences in scores between IVIg and placebo from baseline to end of treatment. Of the 19 patients, 9 (mean age, 61.2 years; mean disease duration, 5.6 years) were randomized to IVIg and 10 (mean age, 66.1 years; mean disease duration, 7.4 years) to placebo. During IVIg the patients gained a mean of 4.2 (-16 to +39.8) MRC points, and during placebo lost 2.7 (-10 to +8) points (p < 0.1). These gains were not significant. Similar results were obtained with the MRC and MVIC scores when the patients crossed to the alternate treatment. Six patients had a functionally important improvement by more than 10 MRC points that declined when crossed over to placebo. Limb-by-limb analysis demonstrated that during IVIg the muscle strength in 39% of the lower extremity limbs significantly increased compared with placebo (p < 0.05), while a simultaneous decrease in 28% of other limbs was detected. The clinical importance of these minor gains is unclear. The duration of swallowing functions measured in seconds with ultrasound improved statistically in the IVIg-randomized patients (p < 0.05) compared with placebo. Although the study did not establish efficacy of IVIg, possibly because of the small sample size, the drug induced functionally important improvement in 6 (28%) of the 19 patients. Whether the modest gains noted in certain muscle groups justify the high cost of trying IVIg in IBM patients at a given stage of the disease remains unclear. JF - Neurology AU - Dalakas, M C AU - Sonies, B AU - Dambrosia, J AU - Sekul, E AU - Cupler, E AU - Sivakumar, K AD - Neuromuscular Diseases Section, Medical Neurology Branch, NINDS, National Institutes of Health, Bethesda, MD 20892-1382, USA. PY - 1997 SP - 712 EP - 716 VL - 48 IS - 3 SN - 0028-3878, 0028-3878 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85170905?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=Treatment+of+inclusion-body+myositis+with+IVIg%3A+a+double-blind%2C+placebo-controlled+study.&rft.au=Dalakas%2C+M+C%3BSonies%2C+B%3BDambrosia%2C+J%3BSekul%2C+E%3BCupler%2C+E%3BSivakumar%2C+K&rft.aulast=Dalakas&rft.aufirst=M&rft.date=1997-03-01&rft.volume=48&rft.issue=3&rft.spage=712&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Paclitaxel cytotoxicity against human lung cancer cell lines increases with prolonged exposure durations. AN - 79648771; 9815704 AB - Paclitaxel blocks cells in G2-M, and this may result in a schedule-dependent effect on paclitaxel cytotoxicity. To test this hypothesis, we evaluated paclitaxel cytotoxicity in 28 human lung cancer cell lines. Fourteen of the cell lines were derived from patients with non-small cell lung cancer (NSCLC), and 14 were from patients with small cell lung cancer (SCLC). All cell lines were exposed to a range of paclitaxel concentrations for durations of 3, 24, and 120 h, and cytotoxicity was measured with a tetrazolium-based assay. The median IC50 values for all 28 cell lines at exposure durations of 3, 24, and 120 h were >32 microM, 23 microM, and 0.38 microM, respectively. The median IC50 values for the NSCLC cell lines were >32 microM, 9.4 microM, and 0.027 microM at exposure durations of 3, 24, and 120 h, respectively. For the 14 SCLC cell lines, the median IC50 values were >32 microM, 25 microM, and 5.0 microM, respectively. Five of the 14 SCLC cell lines had IC50 values at 120 h of paclitaxel exposure that were 1000-fold less than the remaining SCLC cell lines. The median IC50 values for these five sensitive SCLC cell lines at 3-, 24-, and 120-h exposures were >32 microM, 23 microM, and <0.0032 microM, respectively. These in vitro cytotoxicity results were independent of the paclitaxel diluent, a 1:1 solution of ethanol and Cremophor EL. We conclude that longer durations of paclitaxel exposure result in an increase in the chemosensitivity of some human lung cancer cell lines and that this phenomenon is more consistent within NSCLC cell lines than in SCLC cell lines. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Georgiadis, M S AU - Russell, E K AU - Gazdar, A F AU - Johnson, B E AD - National Cancer Institute-Navy Medical Oncology Branch, Division of Hematology/Oncology, Department of Internal Medicine, National Naval Medical Center, Bethesda, Maryland 20889, USA. georgiam@navmed.nci.nih.gov Y1 - 1997/03// PY - 1997 DA - March 1997 SP - 449 EP - 454 VL - 3 IS - 3 SN - 1078-0432, 1078-0432 KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Tumor Cells, Cultured KW - Mitosis KW - Humans KW - G2 Phase KW - Time Factors KW - Carcinoma, Small Cell -- pathology KW - Paclitaxel -- toxicity KW - Cell Survival -- drug effects KW - Cell Cycle -- drug effects KW - Lung Neoplasms -- pathology KW - Carcinoma, Non-Small-Cell Lung -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79648771?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Paclitaxel+cytotoxicity+against+human+lung+cancer+cell+lines+increases+with+prolonged+exposure+durations.&rft.au=Georgiadis%2C+M+S%3BRussell%2C+E+K%3BGazdar%2C+A+F%3BJohnson%2C+B+E&rft.aulast=Georgiadis&rft.aufirst=M&rft.date=1997-03-01&rft.volume=3&rft.issue=3&rft.spage=449&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-18 N1 - Date created - 1999-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Wheel Project. Women Helping to Empower and Enhance Lives. AN - 79210346; 9258855 AB - The Women Helping to Empower and Enhance Lives (WHEEL) Project focused on female sexual partners of injection drug users (i.d.u.s). It was conducted in five sites, three within and two outside the continental United States. The study's two main intervention goals were to (a) reduce HIV-related sexual risk behaviors and (b) reduce HIV-related drug risk behaviors. The Project also featured needs assessment, planning, and staff training components. Baseline data were collected on 2,794 women, which made this the largest study of noninjecting female sexual partners of i.d.u.s in the United States. Six-month follow-up data were obtained on 1,953 women. The Wheel Project tested two interventions: an individual intervention and a group intervention. The study found significant reductions in drug use and risky sexual behaviors for the 6-month follow-up sample for both interventions. These changes were substantial and point to the viability of both interventions for this population of sexual partners of injection drug users. JF - Journal of substance abuse treatment AU - Ashery, R S AU - Wild, J AU - Zhao, Z AU - Rosenshine, N AU - Young, P AD - National Institute on Drug Abuse, Prevention Research Branch, Rockville, MD, USA. PY - 1997 SP - 113 EP - 121 VL - 14 IS - 2 SN - 0740-5472, 0740-5472 KW - Index Medicus KW - AIDS/HIV KW - United States KW - Life Style KW - Humans KW - Adult KW - Health Knowledge, Attitudes, Practice KW - Health Behavior KW - Pilot Projects KW - Middle Aged KW - Follow-Up Studies KW - Health Education KW - Adolescent KW - Female KW - Acquired Immunodeficiency Syndrome -- prevention & control KW - HIV Infections -- transmission KW - Substance Abuse, Intravenous -- rehabilitation KW - Power (Psychology) KW - HIV Infections -- prevention & control KW - Acquired Immunodeficiency Syndrome -- transmission KW - Acquired Immunodeficiency Syndrome -- psychology KW - Sexual Partners -- psychology KW - HIV Infections -- psychology KW - Substance Abuse, Intravenous -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79210346?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+substance+abuse+treatment&rft.atitle=The+Wheel+Project.+Women+Helping+to+Empower+and+Enhance+Lives.&rft.au=Ashery%2C+R+S%3BWild%2C+J%3BZhao%2C+Z%3BRosenshine%2C+N%3BYoung%2C+P&rft.aulast=Ashery&rft.aufirst=R&rft.date=1997-03-01&rft.volume=14&rft.issue=2&rft.spage=113&rft.isbn=&rft.btitle=&rft.title=Journal+of+substance+abuse+treatment&rft.issn=07405472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-10 N1 - Date created - 1997-10-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prenatal and perinatal risk factors for breast cancer in young women. AN - 79147834; 9229211 AB - There is increasing interest in the role of early life exposures in breast carcinogenesis, especially estrogen exposure in utero. Estrogen levels during pregnancy may be higher in twin pregnancies and among older women and slightly lower among smokers. We analyzed early life risk factors in a population-based case-control study in the United States of 2,202 breast cancer cases and 2,009 controls under age 55 years. Twins were at an increased risk of breast cancer compared with singletons (relative risk = 1.62; 95% confidence interval = 1.0-2.7), particularly women with a twin brother (relative risk = 2.06), a finding consistent with the observation of high estrogen levels in dizygotic twin pregnancies. Little association was seen between maternal age at birth and breast cancer risk. We carried out further analyses for 534 cases and 497 controls under age 45 years, using data from a questionnaire completed by their mothers relating to the daughters' early life exposures. There was no evidence of an effect of smoking or diethylstilbestrol exposure during pregnancy on daughters' breast cancer risk. A reduced breast cancer risk was seen among women who had been breastfed (relative risk = 0.74; 95% confidence interval = 0.6-1.0). These findings indicate some effect of early life exposures on breast cancer risk, although the role of estrogen exposure may be less central than previously suggested. JF - Epidemiology (Cambridge, Mass.) AU - Weiss, H A AU - Potischman, N A AU - Brinton, L A AU - Brogan, D AU - Coates, R J AU - Gammon, M D AU - Malone, K E AU - Schoenberg, J B AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1997/03// PY - 1997 DA - March 1997 SP - 181 EP - 187 VL - 8 IS - 2 SN - 1044-3983, 1044-3983 KW - Estrogens KW - 0 KW - Index Medicus KW - Perinatal Care KW - Random Allocation KW - Breast Feeding KW - Humans KW - Age Distribution KW - Pregnancy KW - Registries KW - Twins KW - Logistic Models KW - Risk Factors KW - Maternal Age KW - Adult KW - Surveys and Questionnaires KW - Case-Control Studies KW - Confidence Intervals KW - Middle Aged KW - United States -- epidemiology KW - Female KW - Pregnancy, Multiple KW - Breast Neoplasms -- physiopathology KW - Breast Neoplasms -- etiology KW - Estrogens -- biosynthesis KW - Breast Neoplasms -- epidemiology KW - Estrogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79147834?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epidemiology+%28Cambridge%2C+Mass.%29&rft.atitle=Prenatal+and+perinatal+risk+factors+for+breast+cancer+in+young+women.&rft.au=Weiss%2C+H+A%3BPotischman%2C+N+A%3BBrinton%2C+L+A%3BBrogan%2C+D%3BCoates%2C+R+J%3BGammon%2C+M+D%3BMalone%2C+K+E%3BSchoenberg%2C+J+B&rft.aulast=Weiss&rft.aufirst=H&rft.date=1997-03-01&rft.volume=8&rft.issue=2&rft.spage=181&rft.isbn=&rft.btitle=&rft.title=Epidemiology+%28Cambridge%2C+Mass.%29&rft.issn=10443983&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-04 N1 - Date created - 1997-09-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A simple risk estimates study for oral cavity cancer: practical approach in Indian context. AN - 79115005; 9212572 AB - A study was conducted on 131 cases of oral cavity cancer (OCC), 145 cases of oral leucoplakia and 704 subjects without any oral lesions to investigate risk factors associated with the development of carcinoma of oral cavity in a hospital based cancer registry. Personal interviews, as well as physical examinations of the subjects enabled evaluation of a variety of potential risk factors. Potential risk factors like tobacco chewing, tobacco smoking, snuff dipping, alcohol consumption, bad oral and dental hygiene and age were given each certain numerical values. Each subject was first given a scoring and then analysed and correlated with the presenting lesions, when present. The study revealed that tobacco chewing and bad oral and dental hygiene contributed mainly to higher scoring. Among the subjects in high risk group (scoring more than 400) 63% had OCC, 21% had oral leucoplakia and 16% had no clinical oral lesions. Among the medium risk group (scoring between 100 and 400) 6% had OCC, 21% had leucoplakia and 73% had no oral lesions. In low risk group (scoring below 100) 8% had leucoplakia and 92% had no clinical oral lesions. Using the scoring system, it is suggested that the high risk group for OCC could be identified from general population and cancer detection tests could be specially directed towards this target group to detect maximum number of cases with minimum possible resources. JF - Journal of the Indian Medical Association AU - Datta, K AU - Saha, R K AU - Chakrabarti, R N AD - Chittaranjan National Cancer Institute, Calcutta. Y1 - 1997/03// PY - 1997 DA - March 1997 SP - 70 EP - 71 VL - 95 IS - 3 SN - 0019-5847, 0019-5847 KW - Index Medicus KW - Leukoplakia, Oral -- etiology KW - Oral Health KW - Humans KW - Alcohol Drinking -- adverse effects KW - Smoking -- adverse effects KW - Aged KW - Predictive Value of Tests KW - India KW - Plants, Toxic KW - Risk Factors KW - Adult KW - Tobacco, Smokeless -- adverse effects KW - Middle Aged KW - Female KW - Male KW - Mouth Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79115005?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+Indian+Medical+Association&rft.atitle=A+simple+risk+estimates+study+for+oral+cavity+cancer%3A+practical+approach+in+Indian+context.&rft.au=Datta%2C+K%3BSaha%2C+R+K%3BChakrabarti%2C+R+N&rft.aulast=Datta&rft.aufirst=K&rft.date=1997-03-01&rft.volume=95&rft.issue=3&rft.spage=70&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+Indian+Medical+Association&rft.issn=00195847&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-04 N1 - Date created - 1997-09-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A behavior-genetic approach to multiple chemical sensitivity. AN - 79036471; 9167987 AB - This report emphasizes the application of behavior-genetic designs to the study of sensitivity to toxic chemicals, and features of multiple chemical sensitivity and substance abuse that are polar opposites. The implications of these issues for future research are discussed in relation to twin, adoption, and sibling pair studies, as well as in relation to the degree to which genetically selected lines of rodents that have been developed in the alcoholism field are applicable to multiple chemical sensitivity. JF - Environmental health perspectives AU - Newlin, D B AD - National Institute on Drug Abuse, Intramural Research Program, Baltimore, Maryland 21224, USA. dnewlin@irp.nida.nih.gov Y1 - 1997/03// PY - 1997 DA - March 1997 SP - 505 EP - 508 VL - 105 Suppl 2 SN - 0091-6765, 0091-6765 KW - Index Medicus KW - Animals KW - Orientation KW - Environmental Health KW - Humans KW - Substance-Related Disorders -- etiology KW - Temperament KW - Diseases in Twins KW - Disease Models, Animal KW - Adoption KW - Substance-Related Disorders -- psychology KW - Research Design KW - Substance-Related Disorders -- genetics KW - Multiple Chemical Sensitivity -- genetics KW - Genetics, Behavioral KW - Multiple Chemical Sensitivity -- etiology KW - Multiple Chemical Sensitivity -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79036471?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=A+behavior-genetic+approach+to+multiple+chemical+sensitivity.&rft.au=Newlin%2C+D+B&rft.aulast=Newlin&rft.aufirst=D&rft.date=1997-03-01&rft.volume=105+Suppl+2&rft.issue=&rft.spage=505&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 - 1997-08-11 N1 - Date created - 1997-08-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Arch Gen Psychiatry. 1973 Feb;28(2):238-43 [4684290] Environ Health Perspect. 1997 Mar;105 Suppl 2:445-53 [9167978] Toxicol Appl Pharmacol. 1981 Nov;61(2):260-8 [7324068] Science. 1984 Jul 6;225(4657):78-80 [6539502] Psychopharmacology (Berl). 1985;86(3):274-80 [2994144] Arch Gen Psychiatry. 1986 Dec;43(12):1131-6 [3778110] Psychol Rev. 1984 Apr;91(2):251-68 [6571424] Arch Gen Psychiatry. 1991 Jan;48(1):19-28 [1984758] Arch Gen Psychiatry. 1992 Nov;49(11):876-80 [1345133] Arch Gen Psychiatry. 1992 Nov;49(11):881-7 [1444726] Am J Hum Genet. 1994 Jun;54(6):1092-103 [8198132] Nature. 1994 Sep 8;371(6493):161-4 [8072544] Science. 1994 Oct 14;266(5183):276-9 [7939663] J Clin Psychiatry. 1995 Apr;56(4):151-60 [7713854] Am J Hum Genet. 1995 Dec;57(6):1476-85 [8533778] Arch Gen Psychiatry. 1995 Nov;52(11):895-9 [7487337] Toxicol Appl Pharmacol. 1979 Aug;50(1):157-62 [494294] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gene therapy for Parkinson's disease: an approach to the prevention or palliation of levodopa-associated motor complications. AN - 78974699; 9126152 AB - Gene therapy holds considerable potential for the treatment of central nervous system disease. The introduction of functional genes into the brain of patients with Parkinson's disease may, for example, prove useful as a means to replace a defective gene, introduce a potentially neuroprotective or neurorestorative protein, or permit the physiological delivery of a deficient neurotransmitter. Recent observations suggest that the oral administration of currently available dopaminomimetics to relatively advanced parkinsonian patients leads to nonphysiologic intermittent stimulation of striatal neurons that express dopamine receptors. Resultant activation of signal transduction pathways from these dopaminergic receptors on medium-sized GABAergic neurons apparently induces long-term potentiation of adjacent glutamatergic receptors of the N-methyl-D-aspartate subtype. The effects of dopaminergic drugs thus become modified in ways that favor the clinical appearance of response fluctuations and peak-dose dyskinesias. In parkinsonian models was well as in patients with Parkinson's disease, continuous dopaminergic replacement tends to prevent or alleviate these adverse effects. By continuously maintaining appropriate cerebral dopamine concentrations, molecular techniques which stimulate an increase in the intrastriatal activity of tyrosine hydroxylase, the rate-limiting enzyme for dopamine synthesis, might be expected to palliate parkinsonian symptoms with less risk of the disabling consequences of current therapy. Clinical study of these approaches could also serve as initial, relatively simple, proof-of-principle evaluations of the safety and efficacy of genetic approaches to the treatment of basic disease processes in Parkinson's disease and related neurodegenerative disorders. JF - Experimental neurology AU - Mouradian, M M AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/03// PY - 1997 DA - March 1997 SP - 51 EP - 57 VL - 144 IS - 1 SN - 0014-4886, 0014-4886 KW - Levodopa KW - 46627O600J KW - Index Medicus KW - Humans KW - Dyskinesia, Drug-Induced -- therapy KW - Parkinson Disease -- therapy KW - Dyskinesia, Drug-Induced -- prevention & control KW - Levodopa -- therapeutic use KW - Genetic Therapy KW - Levodopa -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78974699?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+neurology&rft.atitle=Gene+therapy+for+Parkinson%27s+disease%3A+an+approach+to+the+prevention+or+palliation+of+levodopa-associated+motor+complications.&rft.au=Mouradian%2C+M+M%3BChase%2C+T+N&rft.aulast=Mouradian&rft.aufirst=M&rft.date=1997-03-01&rft.volume=144&rft.issue=1&rft.spage=51&rft.isbn=&rft.btitle=&rft.title=Experimental+neurology&rft.issn=00144886&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-20 N1 - Date created - 1997-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Incorporating environmental sciences and nursing research: an NINR initiative. AN - 78971047; 9127346 JF - Nursing outlook AU - Grady, P A AU - Harden, J T AU - Moritz, P AU - Amende, L M AD - National Institute of Nursing Research, National Institutes of Health, Bethesda, Md., USA. PY - 1997 SP - 73 EP - 75 VL - 45 IS - 2 SN - 0029-6554, 0029-6554 KW - Abridged Index Medicus KW - Index Medicus KW - Nursing KW - United States KW - Humans KW - National Institutes of Health (U.S.) KW - Adult KW - Aged KW - Child KW - Interprofessional Relations KW - Female KW - Nursing Research -- organization & administration KW - Occupational Exposure -- prevention & control KW - Environmental Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78971047?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nursing+outlook&rft.atitle=Incorporating+environmental+sciences+and+nursing+research%3A+an+NINR+initiative.&rft.au=Grady%2C+P+A%3BHarden%2C+J+T%3BMoritz%2C+P%3BAmende%2C+L+M&rft.aulast=Grady&rft.aufirst=P&rft.date=1997-03-01&rft.volume=45&rft.issue=2&rft.spage=73&rft.isbn=&rft.btitle=&rft.title=Nursing+outlook&rft.issn=00296554&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-07 N1 - Date created - 1997-07-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Diagnostic criteria for degenerative, inflammatory, proliferative nonneoplastic and neoplastic liver lesions in medaka (Oryzias latipes): consensus of a National Toxicology Program Pathology Working Group. AN - 78969759; 9125779 AB - Diagnostic criteria are presented for degenerative, inflammatory, nonneoplastic proliferative, and neoplastic lesions in the liver of medaka (Oryzias latipes), a small fish species frequently used in carcinogenesis studies. The criteria are the consensus of a Pathology Working Group (PWG) convened by the National Toxicology Program. The material examined by the PWG was from Medaka exposed to N-nitrosodiethylamine for 28 days, removed to clean water, and sacrificed 4, 6, or 9 mo after initiation of exposure. Degenerative lesions included hepatocellular intracytoplasmic vacuolation, hepatocellular necrosis, spongiosis hepatis, hepatic cysts, and hepatocellular hyalinization. Inflammatory lesions consisted of granulomas, chronic inflammation, macrophage aggregates, and focal lymphocytic infiltration. Nonneoplastic proliferative lesions comprised foci of cellular alteration (basophilic focus, eosinophilic focus, vacuolated focus, and clear cell focus) and bile duct hyperplasia. Neoplastic lesions included hepatocellular adenoma, hepatocellular carcinoma, cholangioma, and cholangiocarcinoma. Two lesions composed mainly of spindle cells were noted, hemangiopericytoma and spindle cell proliferation. Rather than being an exhaustive treatment of medaka liver lesions, this report draws from the published literature on carcinogen-induced liver lesions in medaka and other fish species and attempts to consolidate lesion criteria into a simplified scheme that might be useful to pathologists and other researchers using medaka lesions for risk assessment or regulatory purposes. JF - Toxicologic pathology AU - Boorman, G A AU - Botts, S AU - Bunton, T E AU - Fournie, J W AU - Harshbarger, J C AU - Hawkins, W E AU - Hinton, D E AU - Jokinen, M P AU - Okihiro, M S AU - Wolfe, M J AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. boorman@niehs.nih.gov PY - 1997 SP - 202 EP - 210 VL - 25 IS - 2 SN - 0192-6233, 0192-6233 KW - Index Medicus KW - United States KW - Oryzias KW - Cell Movement KW - Animals KW - Vacuoles -- pathology KW - Chemical and Drug Induced Liver Injury KW - Cysts -- pathology KW - Cell Division -- drug effects KW - Hemangiopericytoma -- pathology KW - Basophils -- pathology KW - Lymphocytes -- pathology KW - Necrosis KW - Hyperplasia KW - Macrophages -- pathology KW - Adenoma, Bile Duct -- pathology KW - Eosinophils -- pathology KW - Bile Ducts -- pathology KW - Carcinoma, Hepatocellular -- pathology KW - Chronic Disease KW - Adenoma -- pathology KW - Cell Aggregation KW - Inflammation -- pathology KW - Liver Neoplasms -- pathology KW - Toxicology -- standards KW - Liver Diseases -- pathology KW - Liver Neoplasms -- chemically induced KW - Liver Neoplasms -- diagnosis KW - Liver Diseases -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78969759?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Diagnostic+criteria+for+degenerative%2C+inflammatory%2C+proliferative+nonneoplastic+and+neoplastic+liver+lesions+in+medaka+%28Oryzias+latipes%29%3A+consensus+of+a+National+Toxicology+Program+Pathology+Working+Group.&rft.au=Boorman%2C+G+A%3BBotts%2C+S%3BBunton%2C+T+E%3BFournie%2C+J+W%3BHarshbarger%2C+J+C%3BHawkins%2C+W+E%3BHinton%2C+D+E%3BJokinen%2C+M+P%3BOkihiro%2C+M+S%3BWolfe%2C+M+J&rft.aulast=Boorman&rft.aufirst=G&rft.date=1997-03-01&rft.volume=25&rft.issue=2&rft.spage=202&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 - 1997-07-03 N1 - Date created - 1997-07-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Behavioral, physiological and neuroendocrine responses in healthy volunteers to m-chlorophenylpiperazine (m-CPP) with and without ondansetron pretreatment. AN - 78956480; 9106905 AB - Several serotonin3 (5-HT3) antagonists have been shown to attenuate the anxiogenic effects of the serotonergic agent, m-chlorophenylpiperazine (m-CPP), in animal models, but little data regarding possible effects of 5-HT3 antagonists on responses to m-CPP are available from studies in humans. Therefore, we studied the behavioral, physiological and neuroendocrine responses of 12 healthy volunteers to i.v. administered placebo and m-CPP (0.08 mg/kg), with and without i.v. pretreatment with the selective 5-HT3 antagonist, ondansetron (0.15 mg/kg). Compared to placebo, m-CPP given alone significantly increased ratings of anxiety and several other behavioral measures. m-CPP also produced statistically significant increases in temperature, systolic and diastolic blood pressure, heart rate, and in plasma concentrations of adrenocorticotropic hormone, cortisol, prolactin and norepinephrine. Responses to ondansetron given alone were no different from those of placebo. Pretreatment with ondansetron did not affect peak behavioral responses to m-CPP, but was associated with a significantly earlier return to baseline levels of ratings of anxiety and functional deficit as well as a summary measure of overall behavioral effects. Following ondansetron pretreatment, the increases produced by m-CPP in systolic and diastolic blood pressure and heart rate were no longer significantly different from placebo. Ondansetron pretreatment significantly reduced their plasma cortisol response to m-CPP without affecting the other plasma hormone responses. Plasma concentrations of m-CPP were unaffected by ondansetron pretreatment. These findings suggest that in normal human subjects some behavioral, cardiovascular and neuroendocrine effects of m-CPP may be partially modulated by 5-HT3 receptor-mediated mechanisms. JF - Psychopharmacology AU - Broocks, A AU - Briggs, N C AU - Pigott, T A AU - Hill, J L AU - Canter, S K AU - Tolliver, T J AU - Baldemore, D AU - Murphy, D L AD - Laboratory of Clinical Science, National Institute of Mental Health, NIH Clinical Science Center, Bethesda, MD 20892, USA. Y1 - 1997/03// PY - 1997 DA - March 1997 SP - 91 EP - 103 VL - 130 IS - 2 SN - 0033-3158, 0033-3158 KW - Piperazines KW - 0 KW - Serotonin Antagonists KW - Serotonin Receptor Agonists KW - Ondansetron KW - 4AF302ESOS KW - 1-(3-chlorophenyl)piperazine KW - REY0CNO998 KW - Index Medicus KW - Euphoria -- drug effects KW - Heart Rate -- drug effects KW - Anxiety -- psychology KW - Injections, Intravenous KW - Body Temperature -- drug effects KW - Humans KW - Adult KW - Self-Assessment KW - Blood Pressure -- drug effects KW - Male KW - Female KW - Serotonin Receptor Agonists -- pharmacology KW - Serotonin Receptor Agonists -- adverse effects KW - Serotonin Receptor Agonists -- administration & dosage KW - Ondansetron -- administration & dosage KW - Serotonin Antagonists -- pharmacology KW - Neurosecretory Systems -- drug effects KW - Serotonin Antagonists -- adverse effects KW - Piperazines -- adverse effects KW - Piperazines -- pharmacology KW - Piperazines -- administration & dosage KW - Behavior -- drug effects KW - Serotonin Antagonists -- administration & dosage KW - Ondansetron -- pharmacology KW - Ondansetron -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78956480?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology&rft.atitle=Behavioral%2C+physiological+and+neuroendocrine+responses+in+healthy+volunteers+to+m-chlorophenylpiperazine+%28m-CPP%29+with+and+without+ondansetron+pretreatment.&rft.au=Broocks%2C+A%3BBriggs%2C+N+C%3BPigott%2C+T+A%3BHill%2C+J+L%3BCanter%2C+S+K%3BTolliver%2C+T+J%3BBaldemore%2C+D%3BMurphy%2C+D+L&rft.aulast=Broocks&rft.aufirst=A&rft.date=1997-03-01&rft.volume=130&rft.issue=2&rft.spage=91&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-26 N1 - Date created - 1997-06-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Precipitation of overt encephalopathy in the portacaval shunted rat: towards the development of an adequate model of chronic portal systemic encephalopathy. AN - 78946216; 9096433 AB - To assess the feasibility of developing a model of overt portal-systemic encephalopathy (PSE) in rats with a surgically constructed portacaval anastomosis (PCA). The ability of increasing the load of nitrogenous substances in the gastrointestinal tract and/or further decreasing hepatocellular function to induce overt encephalopathy in rats with a PCA was determined. The load of nitrogenous substances in the gastrointestinal tract was increased by feeding a pure horse-meat diet or by gavaging with blood. Partial hepatectomy and the induction of cirrhosis were used to decrease hepatocellular function further. The severity of encephalopathy was assessed using a neurobehavioural scale. Overt encephalopathy was not induced in rats by a PCA alone, by a PCA plus a horse-meat diet, by a PCA plus induction of cirrhosis, or by a PCA plus a 50% hepatectomy. Predominantly mild, but overt, encephalopathy was induced in rats with a PCA alone by gavaging with blood and a higher incidence of more severe overt encephalopathy was induced in rats with a PCA combined with either cirrhosis or partial hepatectomy by gavaging with blood. Although these models of PSE were associated in some instances with plasma ammonia concentrations about 25 times higher than normal, no seizures were observed. A syndrome that resembles overt PSE in humans can be induced in the rat with a PCA by further reducing hepatocellular function and also gavaging with blood. Although the rat with a PCA has been. extensively used as a model in studies relating to the pathogenesis of PSE, a syndrome resembling overt PSE in humans cannot readily be induced in rats with a PCA. JF - European journal of gastroenterology & hepatology AU - Mullen, K D AU - Roessle, M AU - Jones, D B AU - Grun, M AU - Jones, E A AD - Digestive Diseases Branch, NIDDK, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1997/03// PY - 1997 DA - March 1997 SP - 293 EP - 298 VL - 9 IS - 3 SN - 0954-691X, 0954-691X KW - Ammonia KW - 7664-41-7 KW - Index Medicus KW - Rats KW - Liver Cirrhosis, Experimental -- chemically induced KW - Body Weight KW - Animals KW - Rats, Sprague-Dawley KW - Feasibility Studies KW - Ammonia -- blood KW - Hepatectomy KW - Blood Urea Nitrogen KW - Organ Size KW - Male KW - Portacaval Shunt, Surgical KW - Hepatic Encephalopathy -- etiology KW - Disease Models, Animal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78946216?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Precipitation+of+overt+encephalopathy+in+the+portacaval+shunted+rat%3A+towards+the+development+of+an+adequate+model+of+chronic+portal+systemic+encephalopathy.&rft.au=Mullen%2C+K+D%3BRoessle%2C+M%3BJones%2C+D+B%3BGrun%2C+M%3BJones%2C+E+A&rft.aulast=Mullen&rft.aufirst=K&rft.date=1997-03-01&rft.volume=9&rft.issue=3&rft.spage=293&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 - 1997-09-05 N1 - Date created - 1997-09-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interleukin 1 receptor antagonist gene expression in rat pituitary in the systemic inflammatory response syndrome: pathophysiological implications. AN - 78934922; 9106226 AB - The systemic inflammatory response syndrome (SIRS) is characterized by endothelial cell activation causing a generalized inflammatory response and cytokine-mediated pathophysiological alterations. The pathophysiology of SIRS involves changes in the functioning of several endocrine glands, including the pituitary. SIRS-induced alterations in pituitary function include activation of the hypothalamic-pituitary adrenal (HPA) axis causing hypercortisolemia, the euthyroid sick syndrome, and cessation of reproductive function. These changes are in part mediated by cytokines, such as tumor necrosis factor alpha (TNF-alpha) and interleukin 1 (IL-1). IL-1 function depends on the local ratio of bioactive IL-1 and IL-1 receptor antagonist. Here we review our studies on IL-1 beta and IL-1ra mRNA levels in the pituitary in a rat model of SIRS. We have found that IL-1 beta mRNA peaked at 2 h after lipopolysaccharide (LPS) administration, increasing twelvefold over control values in the posterior pituitary and fivefold over controls in the anterior pituitary. IL-1ra mRNA levels peaked at 6 h post-LPS administration, later than those of IL-1 beta mRNA. IL-1ra mRNA levels increased tenfold in the anterior pituitary, but were induced only threefold in the posterior pituitary. IL-1ra gene expression is profoundly induced in the pituitary in vivo during systemic inflammation and its induction follows that of IL-1 beta, but it is differentially regulated and tissue-specific, occurring predominantly in the anterior pituitary. Future studies of the effects of IL-1 in the pituitary should take into account the local levels of IL-1ra. JF - Molecular psychiatry AU - Licinio, J AU - Wong, M L AD - Clinical Neuroendocrinology Branch, Intramural Research Program, NIMH, NIH, Bethesda, Maryland 20892-1284, USA. Y1 - 1997/03// PY - 1997 DA - March 1997 SP - 99 EP - 103 VL - 2 IS - 2 SN - 1359-4184, 1359-4184 KW - Interleukin 1 Receptor Antagonist Protein KW - 0 KW - Interleukin-1 KW - Lipopolysaccharides KW - Nerve Tissue Proteins KW - RNA, Messenger KW - Sialoglycoproteins KW - Index Medicus KW - Specific Pathogen-Free Organisms KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - In Situ Hybridization KW - Interleukin-1 -- biosynthesis KW - Syndrome KW - Lipopolysaccharides -- toxicity KW - Interleukin-1 -- genetics KW - RNA, Messenger -- biosynthesis KW - Male KW - Densitometry KW - Inflammation -- physiopathology KW - Sialoglycoproteins -- genetics KW - Sialoglycoproteins -- biosynthesis KW - Inflammation -- genetics KW - Nerve Tissue Proteins -- biosynthesis KW - Gene Expression Regulation KW - Pituitary Gland -- metabolism KW - Nerve Tissue Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78934922?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+psychiatry&rft.atitle=Interleukin+1+receptor+antagonist+gene+expression+in+rat+pituitary+in+the+systemic+inflammatory+response+syndrome%3A+pathophysiological+implications.&rft.au=Licinio%2C+J%3BWong%2C+M+L&rft.aulast=Licinio&rft.aufirst=J&rft.date=1997-03-01&rft.volume=2&rft.issue=2&rft.spage=99&rft.isbn=&rft.btitle=&rft.title=Molecular+psychiatry&rft.issn=13594184&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-30 N1 - Date created - 1997-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An automated radiopharmaceutical dispenser. AN - 78919110; 9116653 AB - An automated radiopharmaceutical dispenser, that offers several advantages over manual procedures, has been developed. It employs a personal computer interfaced to a precision syringe drive module, a dose calibrator, and a printer. The operating program provides menu-selection operation and documentation of procedures and individual doses delivered. All materials in contact with the radiopharmaceutical are sterile and disposable. A novel transport safe is employed to further reduce radiation exposure. JF - Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine AU - Plascjak, P S AU - Kim, K AU - Meyer, W AU - Divel, J AU - Der, M AU - Eckelman, W C AD - PET Department, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/03// PY - 1997 DA - March 1997 SP - 345 EP - 348 VL - 48 IS - 3 SN - 0969-8043, 0969-8043 KW - Fluorine Radioisotopes KW - 0 KW - Radiopharmaceuticals KW - Fluorodeoxyglucose F18 KW - 0Z5B2CJX4D KW - Deoxyglucose KW - 9G2MP84A8W KW - Index Medicus KW - Radiation Protection KW - Quality Control KW - Drug Delivery Systems -- instrumentation KW - Radiopharmaceuticals -- administration & dosage KW - Deoxyglucose -- administration & dosage KW - Fluorine Radioisotopes -- administration & dosage KW - Deoxyglucose -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78919110?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Applied+radiation+and+isotopes+%3A+including+data%2C+instrumentation+and+methods+for+use+in+agriculture%2C+industry+and+medicine&rft.atitle=An+automated+radiopharmaceutical+dispenser.&rft.au=Plascjak%2C+P+S%3BKim%2C+K%3BMeyer%2C+W%3BDivel%2C+J%3BDer%2C+M%3BEckelman%2C+W+C&rft.aulast=Plascjak&rft.aufirst=P&rft.date=1997-03-01&rft.volume=48&rft.issue=3&rft.spage=345&rft.isbn=&rft.btitle=&rft.title=Applied+radiation+and+isotopes+%3A+including+data%2C+instrumentation+and+methods+for+use+in+agriculture%2C+industry+and+medicine&rft.issn=09698043&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-23 N1 - Date created - 1997-04-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phenotypic heterogeneity and disease course in three murine strains with mutations in genes encoding for alpha 1 and beta glycine receptor subunits. AN - 78905796; 9087981 AB - Impaired glycinergic inhibition causes human hyperekplexia, and may be involved in the pathogenesis of movement disorders associated with uremia, spinal cord lesions, DDT poisoning, and tetanus. Three autosomal recessive mutant mouse strains with single-gene mutations affecting either the alpha 1 (spasmodic and oscillator) or beta (spastic) subunits of the glycine receptor were studied. Serial videotaped examinations assessed the severity of hyperkinetic features. Homozygote oscillator mice appeared normal until postnatal day (P) 11-14, when decreased exploratory movements, spastic gait, stimulus-induced myoclonic bouts, rigidity, and tremor were noticeable. All symptoms gradually worsened until death by P21-P23. In contrast, spastic and spasmodic mice were most severely affected by the 3rd-5th week of life and had a lessening of symptom severity in adulthood. Within each mutant strain, there was marked interanimal variation of severity of the other motor abnormalities, possibly because of stochastic variability in developmental processes. These mutants represent good animal models for elucidation of molecular and cellular issues regarding the glycine receptor and for the study of pathogenetic mechanisms of movement disorders. JF - Movement disorders : official journal of the Movement Disorder Society AU - Simon, E S AD - Laboratory of Neural Control, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1997/03// PY - 1997 DA - March 1997 SP - 221 EP - 228 VL - 12 IS - 2 SN - 0885-3185, 0885-3185 KW - Receptors, Glycine KW - 0 KW - Index Medicus KW - Spinal Cord -- physiopathology KW - Animals KW - Chromosome Aberrations -- genetics KW - Genes, Recessive -- genetics KW - Humans KW - Chromosome Disorders KW - Mice KW - Motor Activity -- physiology KW - Heterozygote Detection KW - Mice, Neurologic Mutants KW - Species Specificity KW - Female KW - Male KW - Phenotype KW - Receptors, Glycine -- physiology KW - DNA Mutational Analysis KW - Receptors, Glycine -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78905796?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.atitle=Phenotypic+heterogeneity+and+disease+course+in+three+murine+strains+with+mutations+in+genes+encoding+for+alpha+1+and+beta+glycine+receptor+subunits.&rft.au=Simon%2C+E+S&rft.aulast=Simon&rft.aufirst=E&rft.date=1997-03-01&rft.volume=12&rft.issue=2&rft.spage=221&rft.isbn=&rft.btitle=&rft.title=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.issn=08853185&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-17 N1 - Date created - 1997-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Long-term morbidity associated with delayed treatment of first admission schizophrenic patients: a re-analysis of the Camarillo State Hospital data. AN - 78904054; 9089819 AB - The authors examined data from a follow-up study of first admission schizophrenic patients treated with and without antipsychotic medications, who were discharged from the hospital within 6 months. It was predicted that patients who did not require antipsychotic medications for discharge would have a more favourable long-term outcome. The subjects were part of the Camarillo State Hospital study conducted by May and colleagues in the late 1950s and early 1960s. Patients had been randomly assigned to treatment with and without antipsychotic medications. The number of rehospitalization days and total prescribed chlorpromazine equivalents were calculated for each patient for the 2 years following discharge. In order to assess patients' continuing ability to function, 11 patients from each group who met DSM-IV criteria for schizophrenia were matched for age, educational status at first admission, race, and gender; their Global Assessment of Functioning Scale (GAF) score was estimated across a period of 6-7 years following discharge. During the second year following discharge, patients initially treated with antipsychotic medications required fewer rehospitalization days than the initially non-medicated patients. Furthermore, 6-7 years following initial discharge, those patients initially treated with medications were functioning at a higher level, as measured by GAF scores, than patients not initially treated with antipsychotic medications. The results of this study suggest that, at least for this subgroup of patients, early treatment with antipsychotic medications both decreases the immediate morbidity associated with schizophrenia, and prevents detrimental changes possibly related to prolonged untreated psychosis. JF - Psychological medicine AU - Wyatt, R J AU - Green, M F AU - Tuma, A H AD - Neuropsychiatry Branch, IRP, National Institute of Mental Health, NIMH Neuropsychiatric Hospital, Washington, DC 20032, USA. Y1 - 1997/03// PY - 1997 DA - March 1997 SP - 261 EP - 268 VL - 27 IS - 2 SN - 0033-2917, 0033-2917 KW - Antipsychotic Agents KW - 0 KW - Chlorpromazine KW - U42B7VYA4P KW - Index Medicus KW - Drug Administration Schedule KW - Humans KW - Chlorpromazine -- adverse effects KW - Hospitals, State KW - Psychiatric Status Rating Scales KW - Patient Discharge -- statistics & numerical data KW - Adult KW - Treatment Outcome KW - Chlorpromazine -- therapeutic use KW - Follow-Up Studies KW - Middle Aged KW - Adolescent KW - California -- epidemiology KW - Female KW - Male KW - Patient Readmission -- statistics & numerical data KW - Antipsychotic Agents -- therapeutic use KW - Schizophrenia -- diagnosis KW - Schizophrenic Psychology KW - Schizophrenia -- drug therapy KW - Schizophrenia -- epidemiology KW - Antipsychotic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78904054?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychological+medicine&rft.atitle=Long-term+morbidity+associated+with+delayed+treatment+of+first+admission+schizophrenic+patients%3A+a+re-analysis+of+the+Camarillo+State+Hospital+data.&rft.au=Wyatt%2C+R+J%3BGreen%2C+M+F%3BTuma%2C+A+H&rft.aulast=Wyatt&rft.aufirst=R&rft.date=1997-03-01&rft.volume=27&rft.issue=2&rft.spage=261&rft.isbn=&rft.btitle=&rft.title=Psychological+medicine&rft.issn=00332917&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-27 N1 - Date created - 1997-06-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhanced sensitivity to tumor growth and development in multistage skin carcinogenesis by transforming growth factor-alpha-induced epidermal growth factor receptor activation but not p53 inactivation. AN - 78903654; 9115586 AB - Transforming growth factor-alpha (TGF alpha) can stimulate keratinocyte proliferation and function as an autocrine tumor promoter in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated TGF alpha-transgenic mouse skin. In this study, we examined the effect of ectopic TGF alpha transgene expression on skin tumor growth and progression after DMBA initiation in the presence of 12-O-tetradecanoylphorbol-13-acetate (TPA). Both the multiplicity and size of skin tumors arising in TGF alpha-transgenic mice were significantly higher than those of the nontransgenic parental CD-1 strain. There were more dysplastic papillomas and squamous cell carcinomas (SCCs) in the transgenic animals as well. ProTGF alpha protein was expressed in transgenic papillomas, but mature TGF alpha was not detected. The epidermal growth factor receptor (EGFR) appeared to be downregulated and was associated with enhanced tyrosine phosphorylation of several substrates in TGF alpha-transgenic mouse tumors. Characteristic codon 61 mutations in the Ha-ras gene were found in most of the papillomas and SCCs induced by DMBA and TPA in transgenic as well as nontransgenic mice. However, no p53 gene mutations were found in any skin tumors from either transgenic or control animals. Analysis of cellular proliferation in both DMBA-TPA-induced papillomas and in skin 48 h after TPA treatment alone revealed significantly more DNA synthesis in TGF alpha-transgenic mice relative to controls. These results demonstrate that TGF alpha, through EGFR overstimulation, can act synergistically with TPA to induce the formation, growth, and development of DMBA-initiated skin tumors containing classic Ha-ras gene mutations but not p53 gene inactivation. JF - Molecular carcinogenesis AU - Shibata, M A AU - Ward, J M AU - Green, J E AU - Merlino, G AD - Veterinary and Tumor Pathology Section, National Cancer Institute, Frederick, Maryland 21702-1201, USA. Y1 - 1997/03// PY - 1997 DA - March 1997 SP - 160 EP - 170 VL - 18 IS - 3 SN - 0899-1987, 0899-1987 KW - Carcinogens KW - 0 KW - Recombinant Proteins KW - Transforming Growth Factor alpha KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Exons KW - Skin -- metabolism KW - Humans KW - Skin -- pathology KW - Mice KW - Mice, Transgenic KW - Polymorphism, Single-Stranded Conformational KW - Cloning, Molecular KW - Polymerase Chain Reaction KW - Skin -- cytology KW - Papilloma -- pathology KW - Carcinoma, Squamous Cell -- chemically induced KW - Skin Neoplasms -- pathology KW - Papilloma -- genetics KW - Receptor, Epidermal Growth Factor -- biosynthesis KW - Skin Neoplasms -- genetics KW - Transforming Growth Factor alpha -- genetics KW - Genes, p53 KW - Carcinoma, Squamous Cell -- pathology KW - Skin Neoplasms -- chemically induced KW - Carcinoma, Squamous Cell -- genetics KW - Transforming Growth Factor alpha -- biosynthesis KW - Papilloma -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78903654?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Enhanced+sensitivity+to+tumor+growth+and+development+in+multistage+skin+carcinogenesis+by+transforming+growth+factor-alpha-induced+epidermal+growth+factor+receptor+activation+but+not+p53+inactivation.&rft.au=Shibata%2C+M+A%3BWard%2C+J+M%3BGreen%2C+J+E%3BMerlino%2C+G&rft.aulast=Shibata&rft.aufirst=M&rft.date=1997-03-01&rft.volume=18&rft.issue=3&rft.spage=160&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 - 1997-04-24 N1 - Date created - 1997-04-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Histopathologic changes associated with fialuridine hepatotoxicity. AN - 78903106; 9071726 AB - Chronic hepatitis B is a widespread viral illness with the serious sequelae of cirrhosis and hepatocellular carcinoma. Current therapy with interferon is not universally efficacious, and this has led to the evaluation of other antiviral agents. A recent Phase II trial of the nucleoside analogue, fluoroiodoarabinofuranosyluracil (fialuridine, FIAU) was halted because of the sudden development of severe multisystem toxicity characterized by hepatic failure, lactic acidosis, and pancreatitis, which resulted in the deaths of five patients. We systematically evaluated pre- and post-therapy biopsy, explant, and autopsy specimens from the 15 patients involved in this trial to define the hepatic changes of fialuridine toxicity and to determine whether the degree of pre-existing hepatitis contributed to the severity of toxicity. Severe hepatotoxicity from fialuridine was characterized by hepatomegaly with diffuse, predominantly microvesicular steatosis, hepatocellular glycogen depletion, marked bile ductular proliferation, and cholestasis. Ultrastructural examination revealed intracytoplasmic lipid droplets and marked mitochondrial injury. Patients in whom severe toxicity did not develop mainly showed changes caused by the underlying chronic hepatitis B alone. There was a subtle increase in the amount of microvesicular steatosis in two of six patients with mild or no symptoms of toxicity. The microscopic and ultrastructural pattern of injury and systemic symptoms in patients with fialuridine toxicity are consistent with severe mitochondrial and metabolic derangements. Similar hepatic pathologic findings have been reported rarely for other antiviral nucleoside analogues, which suggests that the mechanisms of toxicity might be related. JF - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc AU - Kleiner, D E AU - Gaffey, M J AU - Sallie, R AU - Tsokos, M AU - Nichols, L AU - McKenzie, R AU - Straus, S E AU - Hoofnagle, J H AD - Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/03// PY - 1997 DA - March 1997 SP - 192 EP - 199 VL - 10 IS - 3 SN - 0893-3952, 0893-3952 KW - Antiviral Agents KW - 0 KW - Arabinofuranosyluracil KW - 3083-77-0 KW - fialuridine KW - 53T7IN77LC KW - Index Medicus KW - Randomized Controlled Trials as Topic KW - Hepatitis B -- complications KW - Hepatitis B -- pathology KW - Clinical Trials, Phase II as Topic KW - Humans KW - Adult KW - Middle Aged KW - Chronic Disease KW - Hepatitis B -- drug therapy KW - Male KW - Female KW - Liver -- ultrastructure KW - Arabinofuranosyluracil -- therapeutic use KW - Antiviral Agents -- therapeutic use KW - Liver -- pathology KW - Chemical and Drug Induced Liver Injury -- etiology KW - Chemical and Drug Induced Liver Injury -- pathology KW - Liver -- drug effects KW - Arabinofuranosyluracil -- adverse effects KW - Arabinofuranosyluracil -- analogs & derivatives KW - Antiviral Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78903106?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Modern+pathology+%3A+an+official+journal+of+the+United+States+and+Canadian+Academy+of+Pathology%2C+Inc&rft.atitle=Histopathologic+changes+associated+with+fialuridine+hepatotoxicity.&rft.au=Kleiner%2C+D+E%3BGaffey%2C+M+J%3BSallie%2C+R%3BTsokos%2C+M%3BNichols%2C+L%3BMcKenzie%2C+R%3BStraus%2C+S+E%3BHoofnagle%2C+J+H&rft.aulast=Kleiner&rft.aufirst=D&rft.date=1997-03-01&rft.volume=10&rft.issue=3&rft.spage=192&rft.isbn=&rft.btitle=&rft.title=Modern+pathology+%3A+an+official+journal+of+the+United+States+and+Canadian+Academy+of+Pathology%2C+Inc&rft.issn=08933952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-13 N1 - Date created - 1997-05-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The safety and pharmacokinetics of single-agent and combination therapy with megestrol acetate and dronabinol for the treatment of HIV wasting syndrome. The DATRI 004 Study Group. Division of AIDS Treatment Research Initiative. AN - 78902807; 9071430 AB - This randomized, open-labeled, multicenter study was designed to assess safety and pharmacokinetics of dronabinol (Marinol) tablets and megestrol acetate (Megace) micronized tablets, alone and in combination, for treatment of HIV wasting syndrome. Weight and quality of life data were also collected. Fifty-two patients (mean CD4+ count, 59 cells/microliter) were randomized to one of four treatment arms: dronabinol 2.5 mg twice/day (D); megestrol acetate 750 mg/day (M750); megestrol acetate 750 mg/day+dronabinol 2.5 mg twice/day (M750+D); or megestrol acetate 250 mg/day+dronabinol 2.5 mg twice/day (M250+D). After therapy initiation, 47 patients returned for at least one visit, and 39 completed the planned 12 weeks of study visits. Occurrence of adverse events, drug discontinuation, new AIDS-defining conditions, or CD4+ T lymphocyte changes were not statistically significantly different among arms. Serious adverse events assessed as related to dronabinol included CNS events (e.g., confusion, anxiety, emotional lability, euphoria, hallucinations) and those assessed as related to megestrol acetate included dyspnea, liver enzyme changes, and hyperglycemia. The mean weight change +/- SE over 12 weeks was as follows: D, -2.0 +/- 1.3 kg; M750, +6.5 +/- 1.1 kg; M750+D, +6.0 +/- 1.0 kg; and M250+D, -0.3 +/- 1.0 kg (difference among treatment arms, p = 0.0001). Pharmacokinetic parameters measured after 2 weeks of therapy for M750 were Cmax = 985 ng/ml and AUC = 22,487 ng x hr/ml, and for dronabinol and its active metabolite (HO-THC), respectively, were Cmax = 2.01; 4.61 ng/ml and AUC = 5.3; 23.7 ng x hr/ml. For megestrol acetate, but not dronabinol, there was a positive correlation at week 2 between both Cmax and AUC with each of the following: (1) weight change, (2) breakfast visual analog scale for hunger (VASH) score, and (3) dinner VASH score. JF - AIDS research and human retroviruses AU - Timpone, J G AU - Wright, D J AU - Li, N AU - Egorin, M J AU - Enama, M E AU - Mayers, J AU - Galetto, G AD - Division of AIDS, NIAID, NIH, Bethesda, Maryland 20892, USA. Y1 - 1997/03/01/ PY - 1997 DA - 1997 Mar 01 SP - 305 EP - 315 VL - 13 IS - 4 SN - 0889-2229, 0889-2229 KW - Dronabinol KW - 7J8897W37S KW - Megestrol Acetate KW - TJ2M0FR8ES KW - Index Medicus KW - AIDS/HIV KW - Drug Therapy, Combination KW - Body Weight KW - Humans KW - Adult KW - Quality of Life KW - Middle Aged KW - Adolescent KW - Dronabinol -- therapeutic use KW - Megestrol Acetate -- therapeutic use KW - Dronabinol -- pharmacokinetics KW - HIV Wasting Syndrome -- drug therapy KW - Megestrol Acetate -- pharmacokinetics KW - Megestrol Acetate -- adverse effects KW - HIV Wasting Syndrome -- mortality KW - Dronabinol -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78902807?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+research+and+human+retroviruses&rft.atitle=The+safety+and+pharmacokinetics+of+single-agent+and+combination+therapy+with+megestrol+acetate+and+dronabinol+for+the+treatment+of+HIV+wasting+syndrome.+The+DATRI+004+Study+Group.+Division+of+AIDS+Treatment+Research+Initiative.&rft.au=Timpone%2C+J+G%3BWright%2C+D+J%3BLi%2C+N%3BEgorin%2C+M+J%3BEnama%2C+M+E%3BMayers%2C+J%3BGaletto%2C+G&rft.aulast=Timpone&rft.aufirst=J&rft.date=1997-03-01&rft.volume=13&rft.issue=4&rft.spage=305&rft.isbn=&rft.btitle=&rft.title=AIDS+research+and+human+retroviruses&rft.issn=08892229&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-15 N1 - Date created - 1997-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enzyme/prodrug gene therapy approach for breast cancer using a recombinant adenovirus expressing Escherichia coli cytosine deaminase. AN - 78899808; 9080120 AB - A recombinant adenovirus expressing Escherichia coli cytosine deaminase (AdCD) was constructed with the purpose of exploring its utility for the treatment of breast cancer. Infection of the human breast cancer cell line, MDA-MB-231, with AdCD resulted in high levels of cytosine deaminase enzyme activity. MDA-MB-231 cells infected with AdCD were 1000-fold more sensitive to 5-fluorocytosine (5-FC) than cells infected with a control adenovirus. Cell mixing experiments indicated that only 10% of AdCD-infected cells in a population were needed to induce complete cytotoxicity of noninfectious cells exposed to 5-FC. This suggests that bystander effects play an important role in AdCD-mediated cytotoxicities. Direct injection of AdCD into human breast MDA-MB-231-derived tumors grown as xenografts in nude mice, followed by daily intraperitoneal injection 5-FC was sufficient to inhibit tumor growth. These results suggest that in vivo gene therapy for breast cancer using AdCD is feasible. JF - Cancer gene therapy AU - Li, Z AU - Shanmugam, N AU - Katayose, D AU - Huber, B AU - Srivastava, S AU - Cowan, K AU - Seth, P AD - Medical Breast Cancer Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1997 SP - 113 EP - 117 VL - 4 IS - 2 SN - 0929-1903, 0929-1903 KW - Antimetabolites KW - 0 KW - Prodrugs KW - Recombinant Proteins KW - Flucytosine KW - D83282DT06 KW - Nucleoside Deaminases KW - EC 3.5.4.- KW - Cytosine Deaminase KW - EC 3.5.4.1 KW - Index Medicus KW - Antimetabolites -- pharmacology KW - Flucytosine -- pharmacology KW - Drug Screening Assays, Antitumor KW - Animals KW - Recombinant Proteins -- pharmacology KW - Tumor Cells, Cultured KW - Prodrugs -- pharmacology KW - Neoplasms, Experimental -- genetics KW - Humans KW - Transplantation, Heterologous KW - Mice, Nude KW - Mice KW - Neoplasms, Experimental -- drug therapy KW - Recombinant Proteins -- genetics KW - Breast Neoplasms -- drug therapy KW - Nucleoside Deaminases -- genetics KW - Breast Neoplasms -- pathology KW - Genetic Therapy -- methods KW - Breast Neoplasms -- virology KW - Escherichia coli -- enzymology KW - Nucleoside Deaminases -- pharmacology KW - Adenoviridae -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78899808?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Enzyme%2Fprodrug+gene+therapy+approach+for+breast+cancer+using+a+recombinant+adenovirus+expressing+Escherichia+coli+cytosine+deaminase.&rft.au=Li%2C+Z%3BShanmugam%2C+N%3BKatayose%2C+D%3BHuber%2C+B%3BSrivastava%2C+S%3BCowan%2C+K%3BSeth%2C+P&rft.aulast=Li&rft.aufirst=Z&rft.date=1997-03-01&rft.volume=4&rft.issue=2&rft.spage=113&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 - 1997-06-12 N1 - Date created - 1997-06-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synergistic effect and possible mechanisms of tumor necrosis factor and cisplatin cytotoxicity under moderate hyperthermia against gastric cancer cells. AN - 78895204; 9084851 AB - Peritoneal carcinomatosis is a difficult management problem, and intraperitoneal treatment approaches may provide an opportunity to intensify dose and minimize toxicity. The current experiments were conducted to characterize the cytotoxic effects of cisplatin (cDDP), tumor necrosis factor (TNF), and hyperthermia (HT) on a gastric cancer cell line in vitro under conditions achievable with intraperitoneal treatment. Seoul National University gastric cancer cell line (SNU-5), a poorly differentiated gastric cancer cell line, was tested for sensitivity to various doses of cDDP, TNF, or combinations of the two at normothermia (37 degrees C) or HT (42.5 degrees C). The effect of TNF on cellular rates of cDDP accumulation, efflux, and cDDP-DNA adduct formation were evaluated using atomic absorbance spectrometry with Zeemen background correction. During a 2-h exposure to various doses of cDDP HT, we observed a supraadditive cytotoxicity of SNU-5 with 1 to 50 micrograms/ml of TNF (p2 = 0.0001). In the presence of the three-agent combination (HT, TNF, and cDDP) we observed statistically significant increases in total cellular accumulation of cisplatin (p2 = 0.016); a nonsignificant decrease in cellular efflux of drug (p2 = 0.098); and a 40% increase in persistent cisplatin DNA damage as measured by atomic absorption spectrophotometry (p2 = 0.06). These patterns were specifically not seen with the combinations of cDDP and HT, or cDDP and TNF. These data provide the experimental basis for the use of TNF and cDDP with HT in the treatment of gastric cancer and support the investigation of these agents in vivo in the regional treatment of peritoneal carcinomatosis. JF - Annals of surgical oncology AU - Buell, J F AU - Reed, E AU - Lee, K B AU - Parker, R J AU - Venzon, D J AU - Amikura, K AU - Arnold, S AU - Fraker, D L AU - Alexander, H R AD - Surgical Metabolism Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. USA. Y1 - 1997/03// PY - 1997 DA - March 1997 SP - 141 EP - 148 VL - 4 IS - 2 SN - 1068-9265, 1068-9265 KW - Antineoplastic Agents KW - 0 KW - Tumor Necrosis Factor-alpha KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Tumor Cells, Cultured KW - Combined Modality Therapy KW - Humans KW - Spectrophotometry, Atomic KW - Drug Synergism KW - Stomach Neoplasms -- pathology KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Hyperthermia, Induced KW - Cisplatin -- pharmacology KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78895204?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+surgical+oncology&rft.atitle=Synergistic+effect+and+possible+mechanisms+of+tumor+necrosis+factor+and+cisplatin+cytotoxicity+under+moderate+hyperthermia+against+gastric+cancer+cells.&rft.au=Buell%2C+J+F%3BReed%2C+E%3BLee%2C+K+B%3BParker%2C+R+J%3BVenzon%2C+D+J%3BAmikura%2C+K%3BArnold%2C+S%3BFraker%2C+D+L%3BAlexander%2C+H+R&rft.aulast=Buell&rft.aufirst=J&rft.date=1997-03-01&rft.volume=4&rft.issue=2&rft.spage=141&rft.isbn=&rft.btitle=&rft.title=Annals+of+surgical+oncology&rft.issn=10689265&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-13 N1 - Date created - 1997-06-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of the IGF-I receptor in mutagenesis and tumor promotion. AN - 78893754; 9071953 JF - The Journal of endocrinology AU - Blakesley, V A AU - Stannard, B S AU - Kalebic, T AU - Helman, L J AU - LeRoith, D AD - Section on Molecular and Cellular Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/03// PY - 1997 DA - March 1997 SP - 339 EP - 344 VL - 152 IS - 3 SN - 0022-0795, 0022-0795 KW - Receptor, IGF Type 1 KW - EC 2.7.10.1 KW - Index Medicus KW - Rats KW - Animals KW - Oncogenes KW - Genes, Tumor Suppressor KW - Gene Expression KW - Mice KW - Signal Transduction KW - Receptor, IGF Type 1 -- physiology KW - Mutagenesis -- physiology KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78893754?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+endocrinology&rft.atitle=Role+of+the+IGF-I+receptor+in+mutagenesis+and+tumor+promotion.&rft.au=Blakesley%2C+V+A%3BStannard%2C+B+S%3BKalebic%2C+T%3BHelman%2C+L+J%3BLeRoith%2C+D&rft.aulast=Blakesley&rft.aufirst=V&rft.date=1997-03-01&rft.volume=152&rft.issue=3&rft.spage=339&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+endocrinology&rft.issn=00220795&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-02 N1 - Date created - 1997-04-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo characterization of extracellular GABA release in the caudate nucleus and prefrontal cortex of the rhesus monkey. AN - 78881644; 9068127 AB - Extracellular gamma amino butyric acid (GABA) levels were measured in the caudate nucleus and the prefrontal cortex of the rhesus monkey brain using in vivo microdialysis under isofluorane gas anesthesia. Evoked GABA release was investigated for voltage sensitivity and calcium (Ca2+) dependency. There was a multifold increase in extracellular GABA levels following local perfusion with: (1) high potassium (50 mM, KCI), (2) veratridine (10 microM), and (3) the GABA releasing agent and uptake blocker, (-) nipecotic acid (1 mM). Release of GABA was significantly reduced when veratridine or (-) nipecotic acid were coinfused in Ca(2+)-free cerebrospinal fluid (CSF). Coinfusion of nipecotic acid with TTX (10 microM) also resulted in attenuation of evoked GABA release. These results suggest that GABA levels recovered using in vivo microdialysis, from the caudate nucleus and the prefrontal cortex in the rhesus monkey, derive in significant part from vesicular pools and the exocytotic process is both Ca(2+)-dependent and voltage-sensitive. JF - Synapse (New York, N.Y.) AU - Kolachana, B S AU - Saunders, R C AU - Weinberger, D R AD - Clinical Brain Disorders Branch, NIMH/NIH, St. Elizabeths, Washington, D.C. 20032, USA. Y1 - 1997/03// PY - 1997 DA - March 1997 SP - 285 EP - 292 VL - 25 IS - 3 SN - 0887-4476, 0887-4476 KW - GABA Agents KW - 0 KW - Nipecotic Acids KW - nipecotic acid KW - 1U1QTN40SY KW - Tetrodotoxin KW - 4368-28-9 KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - Veratridine KW - 71-62-5 KW - Proline KW - 9DLQ4CIU6V KW - homoproline KW - C7315YL6ZG KW - Potassium KW - RWP5GA015D KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Microdialysis KW - Animals KW - Nipecotic Acids -- pharmacology KW - Potassium -- pharmacology KW - Membrane Potentials -- drug effects KW - Macaca mulatta KW - Tetrodotoxin -- pharmacology KW - GABA Agents -- pharmacology KW - Veratridine -- pharmacology KW - Infusions, Parenteral KW - Caudate Nucleus -- metabolism KW - Prefrontal Cortex -- metabolism KW - Calcium -- physiology KW - Caudate Nucleus -- drug effects KW - gamma-Aminobutyric Acid -- metabolism KW - Cerebrospinal Fluid -- physiology KW - Prefrontal Cortex -- drug effects KW - Proline -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78881644?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=In+vivo+characterization+of+extracellular+GABA+release+in+the+caudate+nucleus+and+prefrontal+cortex+of+the+rhesus+monkey.&rft.au=Kolachana%2C+B+S%3BSaunders%2C+R+C%3BWeinberger%2C+D+R&rft.aulast=Kolachana&rft.aufirst=B&rft.date=1997-03-01&rft.volume=25&rft.issue=3&rft.spage=285&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 - 1997-05-27 N1 - Date created - 1997-05-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A comparison of the effects of intravenous pentagastrin on patients with social phobia, panic disorder and healthy controls. AN - 78863977; 9138439 AB - The present study sought to determine whether social phobics, like patients with panic disorder, have increased sensitivity to the panicogenic effects of pentagastrin. Intravenous pentagastrin and placebo were administered in a double-blind fashion to 19 social phobics, 11 patients with panic disorder, and 19 healthy controls while they participated in a structured social interaction task. Behavioral, cardiovascular, and neuroendocrine responses were obtained. Pentagastrin led to panic attacks in 47% of the social phobics, 64% of the panic disorder patients, and 11% of the healthy controls. The social interaction itself increased anxiety, blood pressure, and pulse in all three groups. These findings suggest that the panicogenic effects of pentagastrin are not limited to patients with panic disorder and provide further evidence for shared neurobiology in social phobia and panic disorder. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - McCann, U D AU - Slate, S O AU - Geraci, M AU - Roscow-Terrill, D AU - Uhde, T W AD - Unit on Anxiety Disorders, Biological Psychiatry Branch, NIMH, NIH, Bethesda, MD 20892-1272, USA. Y1 - 1997/03// PY - 1997 DA - March 1997 SP - 229 EP - 237 VL - 16 IS - 3 SN - 0893-133X, 0893-133X KW - Pentagastrin KW - EF0NX91490 KW - Index Medicus KW - Hemodynamics -- drug effects KW - Psychiatric Status Rating Scales KW - Double-Blind Method KW - Humans KW - Adult KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Panic Disorder -- chemically induced KW - Phobic Disorders -- complications KW - Pentagastrin -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78863977?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+comparison+of+the+effects+of+intravenous+pentagastrin+on+patients+with+social+phobia%2C+panic+disorder+and+healthy+controls.&rft.au=McCann%2C+U+D%3BSlate%2C+S+O%3BGeraci%2C+M%3BRoscow-Terrill%2C+D%3BUhde%2C+T+W&rft.aulast=McCann&rft.aufirst=U&rft.date=1997-03-01&rft.volume=16&rft.issue=3&rft.spage=229&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 - 1997-05-08 N1 - Date created - 1997-05-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regional binding to corticotropin releasing factor receptors in brain of rats exposed to chronic cocaine and cocaine withdrawal. AN - 78863666; 9068125 AB - Cocaine, as does exposure to other physiological stressors, releases brain corticotropin releasing factor (CRF), and this release habituates during the course of repeated cocaine administration in animals. Due to the many signs of anxiety and responses to stress that are produced by cocaine withdrawal in humans, the present study was designed to assess the effects of chronic cocaine and its withdrawal on regional 125I-Tyr-oCRF binding to the CRF1 receptor in brains of male Lewis rats. Cocaine or saline was intravenously infused for 10 days in a regimen that resembled a self-administration paradigm (1 mg/kg every 12 min for 2 h each day). Tissues were harvested either 15 min after or 10 days after the last cocaine infusion, and the brains were sectioned and prepared for CRF1 receptor autoradiography. Compared with findings in saline controls, there was a 31% lower level of CRF binding sites in the basolateral nucleus of the amygdala immediately after the last cocaine infusion, but not 10 days later. Neuroendocrine and non-neuroendocrine mechanisms associated with CRF1 receptors do not appear to contribute to long-term withdrawal effects. JF - Synapse (New York, N.Y.) AU - Ambrosio, E AU - Sharpe, L G AU - Pilotte, N S AD - National Institute on Drug Abuse, Division of Intramural Research, Baltimore, Maryland 21224, USA. Y1 - 1997/03// PY - 1997 DA - March 1997 SP - 272 EP - 276 VL - 25 IS - 3 SN - 0887-4476, 0887-4476 KW - Receptors, Corticotropin-Releasing Hormone KW - 0 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred Lew KW - Drug Administration Schedule KW - Infusions, Intravenous KW - Radioligand Assay KW - Male KW - Substance Withdrawal Syndrome -- metabolism KW - Receptors, Corticotropin-Releasing Hormone -- metabolism KW - Brain -- metabolism KW - Cocaine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78863666?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Regional+binding+to+corticotropin+releasing+factor+receptors+in+brain+of+rats+exposed+to+chronic+cocaine+and+cocaine+withdrawal.&rft.au=Ambrosio%2C+E%3BSharpe%2C+L+G%3BPilotte%2C+N+S&rft.aulast=Ambrosio&rft.aufirst=E&rft.date=1997-03-01&rft.volume=25&rft.issue=3&rft.spage=272&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 - 1997-05-27 N1 - Date created - 1997-05-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - O6-alkylguanine DNA alkyltransferase activity in student embalmers. AN - 78853052; 9055960 AB - O6-Alkylguanine-DNA alkyltransferase (AGT) activity was assessed in peripheral blood lymphocytes among 23 mortuary science students before and after 9 weeks in a laboratory course in techniques of embalming. Formaldehyde exposure was established by environmental monitoring. The average air concentration of formaldehyde during embalming was about 1.5 ppm. At the pre-exposure sampling, baseline DNA repair capacity tended to be reduced in subjects who reported a prior history of embalming (p = 0.08). From pre- to post-exposure, 17 subjects decreased in DNA repair capacity, while only 6 increased (p < 0.05). Analysis of variance, including adjustment for age, sex, and smoking status, confirmed these findings. Among the eight subjects who had no embalming experience during the 90 days before study, seven had decreased and one had increased AGT activity during the period of study (p < 0.05). For those with prior embalming experience, 10 subjects decreased in AGT activity, while 5 increased (p < 0.05). Although the major chemical exposure in embalming practice was to formaldehyde, no clear link was established between amount of formaldehyde exposure and AGT activity. JF - American journal of industrial medicine AU - Hayes, R B AU - Klein, S AU - Suruda, A AU - Schulte, P AU - Boeniger, M AU - Stewart, P AU - Livingston, G K AU - Oesch, F AD - Environmental Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1997/03// PY - 1997 DA - March 1997 SP - 361 EP - 365 VL - 31 IS - 3 SN - 0271-3586, 0271-3586 KW - Air Pollutants, Occupational KW - 0 KW - Formaldehyde KW - 1HG84L3525 KW - Methyltransferases KW - EC 2.1.1.- KW - O(6)-Methylguanine-DNA Methyltransferase KW - EC 2.1.1.63 KW - Index Medicus KW - Air Pollutants, Occupational -- analysis KW - Humans KW - Air Pollutants, Occupational -- adverse effects KW - Adult KW - Lymphocytes -- enzymology KW - Male KW - Female KW - DNA Repair -- drug effects KW - Methyltransferases -- drug effects KW - Embalming KW - Occupational Exposure -- adverse effects KW - Formaldehyde -- adverse effects KW - Methyltransferases -- metabolism KW - Formaldehyde -- analysis KW - Occupational Exposure -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78853052?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=O6-alkylguanine+DNA+alkyltransferase+activity+in+student+embalmers.&rft.au=Hayes%2C+R+B%3BKlein%2C+S%3BSuruda%2C+A%3BSchulte%2C+P%3BBoeniger%2C+M%3BStewart%2C+P%3BLivingston%2C+G+K%3BOesch%2C+F&rft.aulast=Hayes&rft.aufirst=R&rft.date=1997-03-01&rft.volume=31&rft.issue=3&rft.spage=361&rft.isbn=&rft.btitle=&rft.title=American+journal+of+industrial+medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-15 N1 - Date created - 1997-05-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of tissue inhibitor of metalloproteinase-1 and type IV collagenase/gelatinase messenger RNAs in human breast cancer. AN - 78843319; 9042802 AB - The relationship between malignant epithelial cell growth and the formation of tumor stroma is poorly understood. To investigate the roles of type IV collagenases/gelatinases and tissue inhibitor of metalloproteinase-1 (TIMP-1) in human breast cancer, we localized their messenger RNAs (mRNAs) in normal and malignant breast tissue. Type IV collagenase/gelatinase mRNAs were expressed at low levels by some tumor cells. High levels of TIMP-1 mRNA were found in all areas where tissue remodeling was evident, particularly in cells at the tumor-stromal interface. Small blood vessels in both the tumor and stroma were often outlined by high levels of TIMP-1 mRNA. These results indicate that TIMP-1 and type IV collagenases/gelatinases are expressed independently in breast cancer. JF - Human pathology AU - Lindsay, C K AU - Thorgeirsson, U P AU - Tsuda, H AU - Hirohashi, S AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/03// PY - 1997 DA - March 1997 SP - 359 EP - 366 VL - 28 IS - 3 SN - 0046-8177, 0046-8177 KW - Antigens, CD34 KW - 0 KW - Glycoproteins KW - Protease Inhibitors KW - RNA, Messenger KW - Tissue Inhibitor of Metalloproteinases KW - Collagenases KW - EC 3.4.24.- KW - Gelatinases KW - Metalloendopeptidases KW - Matrix Metalloproteinase 2 KW - EC 3.4.24.24 KW - Matrix Metalloproteinase 9 KW - EC 3.4.24.35 KW - Index Medicus KW - In Situ Hybridization KW - RNA, Messenger -- metabolism KW - Humans KW - Gene Expression KW - Metalloendopeptidases -- metabolism KW - Gelatinases -- metabolism KW - Immunohistochemistry KW - Antigens, CD34 -- metabolism KW - Collagenases -- genetics KW - Breast Neoplasms -- genetics KW - Protease Inhibitors -- metabolism KW - Breast Neoplasms -- pathology KW - Glycoproteins -- metabolism KW - Breast Neoplasms -- metabolism KW - Glycoproteins -- genetics KW - Breast Neoplasms -- blood supply KW - Collagenases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78843319?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+pathology&rft.atitle=Expression+of+tissue+inhibitor+of+metalloproteinase-1+and+type+IV+collagenase%2Fgelatinase+messenger+RNAs+in+human+breast+cancer.&rft.au=Lindsay%2C+C+K%3BThorgeirsson%2C+U+P%3BTsuda%2C+H%3BHirohashi%2C+S&rft.aulast=Lindsay&rft.aufirst=C&rft.date=1997-03-01&rft.volume=28&rft.issue=3&rft.spage=359&rft.isbn=&rft.btitle=&rft.title=Human+pathology&rft.issn=00468177&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-17 N1 - Date created - 1997-03-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Detection of a tyrosine-phosphorylated form of cyclin A during liver regeneration. AN - 78838670; 9056672 AB - Cyclin A functions in both the S and G2-M phases of the cell cycle. The expression of cyclin A during liver regeneration was compared with that of cyclin B1 and p34cdc2. Liver regeneration was followed at 2-h intervals from 12 to 48 h after partial hepatectomy (PH). Immunohistochemical staining using proliferating cell nuclear antigen revealed DNA synthesis peaks at 18 h after PH. The most intense nuclear staining of hepatocytes with cyclins A and B1 and p34cdc2 antibodies occurred at 26 h post-PH, which corresponds with the onset of mitosis. Quantitative mRNA expression of cyclins A and B1 and p34cdc2 was determined by competitive reverse transcription-PCR. Construction of mRNA internal standards and coamplification during reverse transcription-PCR allowed quantitation of all three cell cycle genes. At 24 h post-PH, cyclin A mRNA levels were approximately 5 fg/100 ng total RNA. In contrast, cyclin B1 and p34cdc2 levels were 20-fold higher, 100 fg/100 ng total RNA. Cyclin B1 and p34cdc2 mRNA levels showed two peaks, at 26 and 38-44 h post-PH, whereas the levels of cyclin A were constant during this interval. Immunoblots revealed the presence of cyclin A in normal liver, and significant amounts were present as early as 12 h post-PH. At 26 h post-PH, tyrosine-phosphorylated forms of cyclin A were detected. Cyclin B1 and p34cdc2 protein were not present until 22-24 h post-PH, and two peaks were observed, at 26 and 38-44 h, coinciding with the mRNA pattern. Histone H1 kinase activity was associated with the two peaks of cyclin B1 and p34cdc2 expression. The unique pattern of cyclin A expression and detection of tyrosine-phosphorylated forms suggest a different mechanism for the regulation of cyclin A during liver regeneration. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Spiewak Rinaudo, J A AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 1997/03// PY - 1997 DA - March 1997 SP - 301 EP - 309 VL - 8 IS - 3 SN - 1044-9523, 1044-9523 KW - Ccnb1 protein, rat KW - 0 KW - Cyclin B KW - Cyclin B1 KW - Cyclins KW - Phosphoproteins KW - Proliferating Cell Nuclear Antigen KW - RNA, Messenger KW - Protein Kinases KW - EC 2.7.- KW - histone H1 kinase KW - EC 2.7.1.- KW - Index Medicus KW - Animals KW - Immunoblotting KW - Protein Kinases -- analysis KW - Rats KW - Protein Kinases -- metabolism KW - Polymerase Chain Reaction KW - Rats, Inbred F344 KW - RNA, Messenger -- metabolism KW - Phosphorylation KW - Hepatectomy KW - Time Factors KW - Cell Cycle KW - Immunohistochemistry KW - Male KW - Proliferating Cell Nuclear Antigen -- metabolism KW - Phosphoproteins -- metabolism KW - Liver -- enzymology KW - Cyclins -- chemistry KW - Liver -- metabolism KW - Cyclins -- metabolism KW - Liver Regeneration -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78838670?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Detection+of+a+tyrosine-phosphorylated+form+of+cyclin+A+during+liver+regeneration.&rft.au=Spiewak+Rinaudo%2C+J+A%3BThorgeirsson%2C+S+S&rft.aulast=Spiewak+Rinaudo&rft.aufirst=J&rft.date=1997-03-01&rft.volume=8&rft.issue=3&rft.spage=301&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 - 1997-06-27 N1 - Date created - 1997-06-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Homologous segments in three subunits of the guanine nucleotide exchange factor eIF2B mediate translational regulation by phosphorylation of eIF2. AN - 78824165; 9032257 AB - eIF2B is a five-subunit guanine nucleotide exchange factor that is negatively regulated by phosphorylation of the alpha subunit of its substrate, eIF2, leading to inhibition of translation initiation. To analyze this regulatory mechanism, we have characterized 29 novel mutations in the homologous eIF2B subunits encoded by GCD2, GCD7, and GCN3 that reduce or abolish inhibition of eIF2B activity by eIF2 phosphorylated on its alpha subunit [eIF2(alphaP)]. Most, if not all, of the mutations decrease sensitivity to eIF2(alphaP) without excluding GCN3, the nonessential subunit, from eIF2B; thus, all three proteins are critical for regulation of eIF2B by eIF2(alphaP). The mutations are clustered at both ends of the homologous region of each subunit, within two segments each of approximately 70 amino acids in length. Several mutations alter residues at equivalent positions in two or all three subunits. These results imply that structurally similar segments in GCD2, GCD7, and GCN3 perform related functions in eIF2B regulation. We propose that these segments form a single domain in eIF2B that makes multiple contacts with the alpha subunit of eIF2, around the phosphorylation site, allowing eIF2B to detect and respond to phosphoserine at residue 51. Most of the eIF2 is phosphorylated in certain mutants, suggesting that these substitutions allow eIF2B to accept phosphorylated eIF2 as a substrate for nucleotide exchange. JF - Molecular and cellular biology AU - Pavitt, G D AU - Yang, W AU - Hinnebusch, A G AD - Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/03// PY - 1997 DA - March 1997 SP - 1298 EP - 1313 VL - 17 IS - 3 SN - 0270-7306, 0270-7306 KW - DNA-Binding Proteins KW - 0 KW - Eukaryotic Initiation Factor-2 KW - Eukaryotic Initiation Factor-2B KW - Fungal Proteins KW - GCD2 protein, S cerevisiae KW - GCD6 protein, S cerevisiae KW - GCD7 protein, S cerevisiae KW - GCN3 protein, S cerevisiae KW - Guanine Nucleotide Exchange Factors KW - Proteins KW - Repressor Proteins KW - Saccharomyces cerevisiae Proteins KW - Protein Kinases KW - EC 2.7.- KW - Index Medicus KW - Protein Kinases -- metabolism KW - Sequence Alignment KW - Phosphorylation KW - Protein Kinases -- genetics KW - Molecular Sequence Data KW - Suppression, Genetic KW - Protein Biosynthesis -- genetics KW - Amino Acid Sequence KW - Mutation KW - Mutagenesis KW - Saccharomyces cerevisiae -- genetics KW - Fungal Proteins -- metabolism KW - Repressor Proteins -- metabolism KW - Eukaryotic Initiation Factor-2 -- metabolism KW - Fungal Proteins -- genetics KW - Gene Expression Regulation, Fungal -- genetics KW - Repressor Proteins -- genetics KW - Proteins -- metabolism KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78824165?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Homologous+segments+in+three+subunits+of+the+guanine+nucleotide+exchange+factor+eIF2B+mediate+translational+regulation+by+phosphorylation+of+eIF2.&rft.au=Pavitt%2C+G+D%3BYang%2C+W%3BHinnebusch%2C+A+G&rft.aulast=Pavitt&rft.aufirst=G&rft.date=1997-03-01&rft.volume=17&rft.issue=3&rft.spage=1298&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-14 N1 - Date created - 1997-03-14 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - P34604; GENBANK; P12754; P14741; Z48225; U05821; P32502 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1978 Jan;75(1):204-8 [272635] Proc Natl Acad Sci U S A. 1989 Jun;86(12):4579-83 [2660141] Genetics. 1989 Jul;122(3):543-50 [2668116] Mol Cell Biol. 1990 Jun;10(6):2820-31 [2188100] J Mol Biol. 1990 Oct 5;215(3):403-10 [2231712] Proc Natl Acad Sci U S A. 1990 Nov;87(21):8622-6 [2236073] Methods Enzymol. 1991;194:195-230 [2005788] Mol Cell Biol. 1991 Jun;11(6):3217-28 [2038327] Cell. 1992 Feb 7;68(3):585-96 [1739968] Gene. 1992 Jan 2;110(1):119-22 [1544568] EMBO J. 1992 Apr;11(4):1553-62 [1348691] Microbiol Rev. 1992 Jun;56(2):291-315 [1620067] Science. 1992 Sep 18;257(5077):1685-9 [1382315] Cell. 1992 Oct 30;71(3):359-62 [1423600] Mol Cell Biol. 1992 Dec;12(12):5700-10 [1333044] Mol Cell Biol. 1992 Dec;12(12):5801-15 [1448107] Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):232-6 [7678339] PCR Methods Appl. 1992 Aug;2(1):28-33 [1490172] Mol Cell Biol. 1993 Mar;13(3):1920-32 [8441423] Proc Natl Acad Sci U S A. 1993 May 15;90(10):4616-20 [8099443] Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5350-4 [8506384] Mol Cell Biol. 1993 Aug;13(8):4618-31 [8336705] Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7215-9 [8102207] Nature. 1993 Dec 16;366(6456):643-54 [8259209] Mol Cell Biol. 1994 May;14(5):3208-22 [8164676] Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6288-92 [7912826] Mol Cell Biol. 1995 Jan;15(1):365-78 [7799945] Trends Biochem Sci. 1994 Oct;19(10):409-14 [7817398] Biochem J. 1995 Aug 1;309 ( Pt 3):1009-14 [7639677] EMBO J. 1995 Aug 1;14(15):3828-34 [7641700] Mol Cell Biol. 1995 Nov;15(11):6351-63 [7565788] Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):7-12 [8552677] Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):13-20 [8552589] Mol Cell Biol. 1996 Nov;16(11):6603-16 [8887689] J Mol Biol. 1975 Nov 5;98(3):503-17 [1195397] J Biol Chem. 1983 Mar 10;258(5):3402-8 [6826566] Proc Natl Acad Sci U S A. 1983 Sep;80(17):5374-8 [6351059] Mol Cell Biol. 1986 Nov;6(11):3990-8 [3540603] Genetics. 1987 Aug;116(4):541-5 [3305158] Methods Enzymol. 1987;154:164-75 [3323810] Gene. 1987;60(2-3):237-43 [3327750] J Biol Chem. 1988 Apr 25;263(12):5526-33 [3356695] Microbiol Rev. 1988 Jun;52(2):248-73 [3045517] Mol Cell Biol. 1988 Nov;8(11):4808-20 [3062370] Genetics. 1989 May;122(1):19-27 [2659436] J Bacteriol. 1983 Jan;153(1):163-8 [6336730] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Contexts as Moderators of Observed Interactions: A Study of Costa Rican Mothers and Infants from Differing Socioeconomic Backgrounds AN - 61539412; 9813051 AB - Infants from low- & middle-socioeconomic status families (N = 20 each) in San Jose, Costa Rica, were observed at age 14 weeks to study the impact of length of observation & context on measures of interactional engagement & to compare the interactional experiences of the infants in the two groups in various functional & social contexts. Results indicate that attuned & disharmonious interactions, as well as the frequency of positive affect, soothing, & vocalization, vary considerably across the functional contexts. Disharmonious interaction increases & interactional engagement decreases when mothers & infants are joined by others. Highly unstable measures of individual differences are obtained when observations are limited to 45-minute intervals but stability increases significantly as the duration of the observations expands. The groups do not differ with respect to the amount of time spent in various functional & social contexts, in attuned or disharmonious states, or in high levels of interactional engagmement. However, in some functional contexts, significant group differences in levels of attuned interactions, infant vocalization, & maternal response vocalization are reported. Overall, functional & social contexts moderate interactional experiences, while socioeconomic status effects interactional measures are limited to some contexts & may not represent the infant's overall experiences. It is concluded that comparisons based on a single context may be inadequate for studies of subjects from different socioeconomic backgrounds. 7 Tables, 2 Appendixes, 7 References. Adapted from the source document. JF - International Journal of Behavioral Development AU - Leyendecker, Birgit AU - Lamb, Michael E AU - Scholmerich, Axel AU - Fricke, Delia Miranda AD - c/o Lamb -- Section Social & Emotional Development National Instit Child Health & Human Development, 9190 Rockville Pike Bethesda MD 20814 Y1 - 1997/03// PY - 1997 DA - March 1997 SP - 15 EP - 34 VL - 21 IS - 1 SN - 0165-0254, 0165-0254 KW - Mothers KW - Costa Rica KW - Socioeconomic Status KW - Parent Child Relations KW - Infants KW - article KW - 1941: the family and socialization; sociology of the family, marriage, & divorce UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61539412?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocabs&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Behavioral+Development&rft.atitle=Contexts+as+Moderators+of+Observed+Interactions%3A+A+Study+of+Costa+Rican+Mothers+and+Infants+from+Differing+Socioeconomic+Backgrounds&rft.au=Leyendecker%2C+Birgit%3BLamb%2C+Michael+E%3BScholmerich%2C+Axel%3BFricke%2C+Delia+Miranda&rft.aulast=Leyendecker&rft.aufirst=Birgit&rft.date=1997-03-01&rft.volume=21&rft.issue=1&rft.spage=15&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Behavioral+Development&rft.issn=01650254&rft_id=info:doi/ LA - English DB - Sociological Abstracts N1 - Date revised - 2007-04-01 N1 - Last updated - 2016-09-28 N1 - CODEN - IJBDDY N1 - SubjectsTermNotLitGenreText - Socioeconomic Status; Costa Rica; Parent Child Relations; Infants; Mothers ER - TY - JOUR T1 - New evidence that Candida albicans possesses additional ATP-binding cassette MDR-like genes: implications for antifungal azole resistance AN - 20169580; 7385296 AB - Emergence of resistance of Candida albicans to antifungal triazoles is increasingly recognized as an important cause of refractory mucosal candidiasis in HIV-infected patients. Recently, CDR1, which is thought to be analogous to the human MDR-1 P-glycoprotein, has been cloned in C. albicans. It has been proposed that its expression is partially responsible for fluconazole resistance in C. albicans. This gene is characterized by the presence of an ATP binding cassette (ABC) region and is distinct from the BENr gene which does not encode such a functional domain. As the molecular basis for fluconazole resistance appears to be multifactorial, we considered that there may be other ATP binding cassette-containing MDR genes that may potentially contribute to antifungal azole resistance in C. albicans. We therefore sought to identify potential target sequences that may be derived from candidate genes that share homology with the ATP binding cassette region of the human MDR-1 P-glycoprotein. Degenerate oligonucleotide primers based on the known sequence from the ATP binding cassette region of the human MDR-1 P-glycoprotein were used to amplify PCR products within the range of 100 bp in length from C. albicans isolates (3 fluconazole-susceptible and 3 fluconazole-resistant). Sequence analysis of individually subcloned PCR products, derived from the six isolates revealed 34 sequences in total. The results of our study identified 14 clones (with at least one per isolate) with a high degree of homology to the ATP binding cassette of the human MDR-1 P-glycoprotein. The BLAST search did not disclose homology of these new sequences to the C. albicans CDR1 gene, suggesting that C. albicans may possess more than one MDR-like gene. We conclude that C. albicans may possess one or more additional genes encoding ATP binding cassette MDR-like proteins that are distinct from CDR1 and which could participate in the development of fluconazole resistance. JF - Medical Mycology AU - Walsh, T J AU - Kasai, M AU - Francesconi, A AU - Landsman, D AU - Chanock, S J AD - Infectious Diseases Section, Pediatric Branch, National Cancer Institute, Bethesda, MD 20892 Y1 - 1997/03/01/ PY - 1997 DA - 1997 Mar 01 SP - 133 EP - 137 PB - Taylor & Francis Ltd., 11 New Fetter Lane London EC4P 4EE UK, [mailto:info@tandf.co.uk], [URL:http://www.tandf.co.uk] VL - 35 IS - 2 SN - 1369-3786, 1369-3786 KW - HIV KW - Genetics Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts C: Algology, Mycology & Protozoology; Biotechnology and Bioengineering Abstracts KW - ATP binding cassette KW - C. albicans KW - MDR-like proteins KW - Candidiasis KW - complementarity-determining region 1 KW - Mucosa KW - ATP KW - Candida albicans KW - Oligonucleotides KW - P-Glycoprotein KW - fluconazole KW - Homology KW - Human immunodeficiency virus KW - triazoles KW - CDR1 gene KW - Polymerase chain reaction KW - Primers KW - azoles KW - A 01340:Antibiotics & Antimicrobials KW - W 30900:Methods KW - K 03310:Genetics & Taxonomy KW - G 07780:Fungi UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20169580?accountid=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=Medical+Mycology&rft.atitle=New+evidence+that+Candida+albicans+possesses+additional+ATP-binding+cassette+MDR-like+genes%3A+implications+for+antifungal+azole+resistance&rft.au=Walsh%2C+T+J%3BKasai%2C+M%3BFrancesconi%2C+A%3BLandsman%2C+D%3BChanock%2C+S+J&rft.aulast=Walsh&rft.aufirst=T&rft.date=1997-03-01&rft.volume=35&rft.issue=2&rft.spage=133&rft.isbn=&rft.btitle=&rft.title=Medical+Mycology&rft.issn=13693786&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-06-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Candidiasis; complementarity-determining region 1; Mucosa; ATP; Oligonucleotides; P-Glycoprotein; fluconazole; Homology; triazoles; Polymerase chain reaction; CDR1 gene; Primers; azoles; Human immunodeficiency virus; Candida albicans ER - TY - JOUR T1 - Intermediate Markers and Molecular Genetics of Lung Carcinogenesis. AN - 1859316201; 10763008 AB - BACKGROUND: Various options are available for the local control of cancer in the breast - mastectomy, conservation therapy, and mastectomy with reconstruction. METHODS: To evaluate the benefits and drawbacks of the available management options, the authors combine their extensive experience with a review of the literature on outcomes from these approaches. RESULTS: Conservation therapy provides survival outcomes similar to those from mastectomy. Differences in local recurrence rates can be minimized by close adherence to guidelines for patient selection, operative approach, and radiation technique. CONCLUSIONS: The role of the physician in selecting a local therapy for breast cancer has changed from one of informing the patient of the treatment to assessing the presence of medical contraindications to any of the treatments, educating the patients on each treatment approach, providing access to multidisciplinary consultation, and allowing the patient to choose an appropriate treatment approach. JF - Cancer control : journal of the Moffitt Cancer Center AU - Szabo AU - Shaw AD - Division of Clinical Sciences, National Cancer Institute, Rockville, Maryland 20850, USA. Y1 - 1997/03// PY - 1997 DA - March 1997 SP - 109 EP - 117 VL - 4 IS - 2 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859316201?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+control+%3A+journal+of+the+Moffitt+Cancer+Center&rft.atitle=Intermediate+Markers+and+Molecular+Genetics+of+Lung+Carcinogenesis.&rft.au=Szabo%3BShaw&rft.aulast=Szabo&rft.aufirst=&rft.date=1997-03-01&rft.volume=4&rft.issue=2&rft.spage=109&rft.isbn=&rft.btitle=&rft.title=Cancer+control+%3A+journal+of+the+Moffitt+Cancer+Center&rft.issn=1526-2359&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2000-04-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer Prevention: The Roles of Diet and Chemoprevention. AN - 1859316085; 10763009 AB - BACKGROUND: Reduction of cancer risk by either preventing carcinogenesis or stopping carcinogenesis in its early stages is a logical approach for reducing the cancer burden, both for high-risk individuals and for the general population. The areas of dietary modification and chemoprevention show considerable promise as effective approaches for cancer prevention and are a focus of research efforts. RESULTS: Diet and cancer studies show that, generally, vegetables and fruits, dietary fiber, and certain nutrients seem to be protective against cancer, whereas fat, excessive calories, and alcohol seem to increase cancer risk. Chemoprevention research is closely linked to diet and cancer research and represents a logical research progression. CONCLUSIONS: Dietary epidemiologic studies have helped to identify many naturally occurring chemopreventive agents. Currently, randomized clinical prevention trials sponsored by the NCI include dietary interventions (eg, low-fat and/or high-fiber vegetables and fruits) targeting breast and colorectal cancer, chemoprevention trials using micronutrients (eg, vitamin E, calcium, vitamin D) aimed at lung and colorectal cancer, and chemoprevention trials testing the effectiveness of pharmaceutical agents (eg, tamoxifen, finasteride, aspirin) for breast, prostate, and colorectal cancer. JF - Cancer control : journal of the Moffitt Cancer Center AU - Greenwald AU - McDonald AD - Division of Cancer Prevention and Control, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1997/03// PY - 1997 DA - March 1997 SP - 118 EP - 127 VL - 4 IS - 2 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859316085?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+control+%3A+journal+of+the+Moffitt+Cancer+Center&rft.atitle=Cancer+Prevention%3A+The+Roles+of+Diet+and+Chemoprevention.&rft.au=Greenwald%3BMcDonald&rft.aulast=Greenwald&rft.aufirst=&rft.date=1997-03-01&rft.volume=4&rft.issue=2&rft.spage=118&rft.isbn=&rft.btitle=&rft.title=Cancer+control+%3A+journal+of+the+Moffitt+Cancer+Center&rft.issn=1526-2359&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2000-04-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Volume and ion regulation during repeated exposure to temperature change: Physiological divergence in trans-Isthmian cognate pairs and latitudinally distant populations of decapod Crustacea AN - 16318993; 4256512 AB - When the Isthmus of Panama emerged as a land bridge, it set the stage for allopatric speciation in the marine fauna. In the present study Pacific and Atlantic populations of three cognate pairs of crabs were used to discern whether physiological divergence has occurred as a result of exposure to different thermal regimes in habitats and in the putative absence of gene flow. Additional comparison was made with Belize and Florida populations of the Atlantic Panama cognate. This was done to test the strength of correlation between physiological divergence and exposure to different thermal regimes in populations that potentially form a common genetic pool. Water temperatures decrease periodically in Pacific Panama and Florida but not in Atlantic Panama or Belize. Physiological divergence in volume and ion regulation was assessed in response to repeated exposure to either control and decreased temperature or to control and increased temperature. Results indicate that exposure to naturally occurring decreased temperatures in habitats has resulted in divergence. This divergence is demonstrated both in enhanced ability to regulate volume at decreased temperature and impaired ability to regulate volume at elevated temperature. JF - Marine Ecology AU - Ferraris, J D AU - Norenburg, J L AD - LKEM/NHLBI/NIH, 10 Cent. DR MSC 1598, Bldg. 10, Rm 6N307, Bethesda, MD 20892-1598, USA Y1 - 1997/03// PY - 1997 DA - Mar 1997 SP - 193 EP - 209 VL - 18 IS - 3 SN - 0173-9565, 0173-9565 KW - Crabs KW - Crayfishes KW - Lobsters KW - Prawns KW - Shrimp KW - electrolyte balance KW - ion exchange KW - water temperature KW - Ecology Abstracts KW - D 04665:Crustaceans UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16318993?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Marine+Ecology&rft.atitle=Volume+and+ion+regulation+during+repeated+exposure+to+temperature+change%3A+Physiological+divergence+in+trans-Isthmian+cognate+pairs+and+latitudinally+distant+populations+of+decapod+Crustacea&rft.au=Ferraris%2C+J+D%3BNorenburg%2C+J+L&rft.aulast=Ferraris&rft.aufirst=J&rft.date=1997-03-01&rft.volume=18&rft.issue=3&rft.spage=193&rft.isbn=&rft.btitle=&rft.title=Marine+Ecology&rft.issn=01739565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - A novel malaria protein, Pfs28, and Pfs25 are genetically linked and synergistic as falciparum malaria transmission-blocking vaccines AN - 16240623; 4225577 AB - Antibodies to Pfs28 block Plasmodium falciparum transmission and when combined with antibodies to Pfs25 provide synergy in blocking transmission. Pfs28 and Pfs25 are immunogenic, have limited antigenic diversity, and are structurally similar and genetically linked on chromosome 10. Pfs28 may prove a useful addition to Pfs25 in an effective transmission-blocking vaccine. JF - Infection and Immunity AU - Duffy, P E AU - Kaslow, D C AD - Malaria Vaccines Section, Laboratory of Parasitic Diseases, NIAID, Building 4, Room B1-31, NIH, Bethesda, MD 20892-0425, USA Y1 - 1997/03// PY - 1997 DA - Mar 1997 SP - 1109 EP - 1113 VL - 65 IS - 3 SN - 0019-9567, 0019-9567 KW - Antigenic determinants KW - Immunogenicity KW - Malaria KW - Pfs25 protein KW - Pfs28 protein KW - Plasmodium falciparum KW - Synergism KW - Vaccines KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - W3 33365:Vaccines (other) KW - K 03086:Immunology & vaccination KW - F 06807:Active immunization KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16240623?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=A+novel+malaria+protein%2C+Pfs28%2C+and+Pfs25+are+genetically+linked+and+synergistic+as+falciparum+malaria+transmission-blocking+vaccines&rft.au=Duffy%2C+P+E%3BKaslow%2C+D+C&rft.aulast=Duffy&rft.aufirst=P&rft.date=1997-03-01&rft.volume=65&rft.issue=3&rft.spage=1109&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 - Viral vectors for gene therapy of hematopoietic cells AN - 16220162; 4222071 AB - Hematopoietic cells, in particular hematopoietic stem cells, are important targets for the development of gene therapy for hematological and other disorders. So far, simple retroviral vectors based on Murine Leukemia Virus (MLV) have been the main delivery vehicles for the transfer of corrective genes into primary hematopoietic cells. While the gene transfer efficiency of progenitor cells has been very efficient using these vectors, it has been much more problematic to obtain efficient gene transfer into repopulating human hematopoietic stem cells. The main reason for this is due to the quiescent nature of these cells and the fact that MLV-based vectors require dividing target cells. It may be that efficient gene transfer into hematopoietic stem cells can be accomplished by stimulating the cells to divide in vitro or by developing new vector systems that can isolate transduced cells or that can deliver genes permanently into nondividing target cells. This review will discuss the progress and problems of these approaches in developing effective gene therapy for hematopoietic cells. JF - Immunotechnology AU - Medin, JA AU - Karlsson, S AD - Dev. and Metabolic Neurol. Branch, NINDS, NIH, Bethesda, MD 20892, USA Y1 - 1997/03// PY - 1997 DA - Mar 1997 SP - 3 EP - 19 VL - 3 IS - 1 SN - 1380-2933, 1380-2933 KW - gene therapy KW - gene transfer KW - hematopoiesis KW - reviews KW - stem cells KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33181:Gene therapy vectors KW - F 06840:Immunotherapy of immune diseases KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16220162?accountid=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=Immunotechnology&rft.atitle=Viral+vectors+for+gene+therapy+of+hematopoietic+cells&rft.au=Medin%2C+JA%3BKarlsson%2C+S&rft.aulast=Medin&rft.aufirst=JA&rft.date=1997-03-01&rft.volume=3&rft.issue=1&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Immunotechnology&rft.issn=13802933&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 - Oxygen uptake during repeated exposure to temperature change: Physiological divergence in Panamanian cognate pairs and latitudinally distant populations of decapod Crustacea AN - 16100804; 4206898 AB - The emergence of the Isthmus of Panama subdivided the amphi-American biota. In the present study, Pacific and Atlantic populations of four cognate pairs of crabs were used to discern whether exposure to different thermal regimes in habitats, in the putative absence of gene flow, has resulted in physiological divergence. Populations that potentially form a common genetic pool were also used; these were populations of the Atlantic Panama cognate that occur in Belize and Florida. Decreases in water temperature occur periodically in Pacific Panama and Florida, but not in Atlantic Panama or Belize. In this study, physiological divergence in oxygen uptake was assessed in response to repeated exposure to either control and decreased temperature or control and increased temperature. Results indicate that, in only some of the genera tested, exposure to decreases in habitat temperature has resulted in divergence. Partial support is found for the corollary that adaptation to an environment with periods of decreased temperature results in reduced compensation during exposure to elevated temperature. JF - Marine ecology. Berlin AU - Ferraris, J D AU - Norenburg, J L AD - LKEM/NHLBI/NIH, 10 Center DR MSC 1598, Bldg. 10, Rm. 6N307, Bethesda, MD 208920-1598, USA Y1 - 1997/03// PY - 1997 DA - Mar 1997 SP - 127 EP - 146 VL - 18 IS - 2 SN - 0173-9565, 0173-9565 KW - Crabs KW - Crayfishes KW - Lobsters KW - Prawns KW - Shrimp KW - Ecology Abstracts KW - Western Hemisphere KW - Decapoda KW - marine environment KW - speciation KW - water temperature KW - oxygen consumption KW - D 04665:Crustaceans UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16100804?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Marine+ecology.+Berlin&rft.atitle=Oxygen+uptake+during+repeated+exposure+to+temperature+change%3A+Physiological+divergence+in+Panamanian+cognate+pairs+and+latitudinally+distant+populations+of+decapod+Crustacea&rft.au=Ferraris%2C+J+D%3BNorenburg%2C+J+L&rft.aulast=Ferraris&rft.aufirst=J&rft.date=1997-03-01&rft.volume=18&rft.issue=2&rft.spage=127&rft.isbn=&rft.btitle=&rft.title=Marine+ecology.+Berlin&rft.issn=01739565&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 - Decapoda; Western Hemisphere; oxygen consumption; water temperature; speciation; marine environment ER - TY - JOUR T1 - Vitronectin mediates internalization of Neisseria gonorrhoeae by Chinese hamster ovary cells AN - 16068621; 4109147 AB - Gonococci producing a distinct opacity protein (OpaA in strain MS11) adhere to and are efficiently internalized by cultured epithelial cells such as the Chang conjunctiva cell line. Both adherence and uptake require interactions between OpaA and heparan sulfate proteoglycans on the mammalian cell surface. Chinese hamster ovary (CHO) cells also support adherence of gonococci through interactions of OpaA with cell surface heparan sulfate proteoglycans. However, despite this similarity in the requirements for adherence, CHO cells are not capable of internalizing gonococci. In this report, we characterized this apparent deficiency and identified a factor in fetal calf serum (FCS) which is capable of mediating uptake of gonococci by CHO cells. In the absence of FCS, OpaA super(+) gonococci adhered to but were not internalized by CHO cells, whereas in the presence of up to 15% FCS, the bacteria were efficiently internalized by the cells. Preincubation of bacteria, but not cells, with FCS also stimulated internalization, suggesting that a factor present in FCS was binding to the surface of gonococci and subsequently stimulating entry. Using a combination of chromatographic purification procedures, we identified the adhesive glycoprotein vitronectin as the serum factor which mediates the internalization of gonococci by CHO cells. Vitronectin-depleted serum did not support gonococcal entry, and this deficiency was restored by the addition of purified vitronectin. Further experiments using a set of gonococcal recombinants, each expressing a single member of the family of Opa outer membrane proteins, demonstrated that vitronectin bound to the surface of OpaA-producing gonococci only and that the vitronectin-mediated uptake by the CHO cells was limited to this bacterial phenotype. To our knowledge, our data are the first example that vitronectin can serve as a molecule that drives bacterial entry into epithelial cells. JF - Infection and Immunity AU - Duensing, T D AU - Van-Putten, JPM AD - Rocky Mountain Labs., LMSF, NIAID, NIH, 903 South 4th St., Hamilton, MT 59840-2999, USA Y1 - 1997/03// PY - 1997 DA - Mar 1997 SP - 964 EP - 970 VL - 65 IS - 3 SN - 0019-9567, 0019-9567 KW - vitronectin KW - Microbiology Abstracts B: Bacteriology KW - CHO cells KW - gonorrhea KW - cell adhesion KW - Neisseria gonorrhoeae KW - J 02721:Cell cycle, morphology and motility UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16068621?accountid=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=Vitronectin+mediates+internalization+of+Neisseria+gonorrhoeae+by+Chinese+hamster+ovary+cells&rft.au=Duensing%2C+T+D%3BVan-Putten%2C+JPM&rft.aulast=Duensing&rft.aufirst=T&rft.date=1997-03-01&rft.volume=65&rft.issue=3&rft.spage=964&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 - Neisseria gonorrhoeae; CHO cells; cell adhesion; gonorrhea ER - TY - JOUR T1 - Mechanism of `bystander effect' killing in the herpes simplex thymidine kinase gene therapy model of cancer treatment AN - 16031235; 4097927 AB - `Bystander' killing of adjacent wild-type tumor cells was seen when tumors transduced with the herpes thymidine kinase gene were treated with the antiviral agent ganciclovir (GCV). Some tumors were `bystander-sensitive' while others were `bystander-resistant'. Mixtures of different `sensitive' tumor lines showed cross-transfer of bystander killing, while in mixtures of `resistant' with `sensitive' tumors, the resistant phenotype was predominant. Using super(3)H-GCV with `sensitive' mixtures, phosphorylated super(3)H-GCV was found in both herpes thymidine kinase transduced and unmodified cells, while `resistant' cell combinations showed little or no transfer of phosphorylated GCV between cells. The capacity of intracellularly produced nucleotide toxin to spread from cell to cell within a tumor mass effectively amplifies the apparent efficiency of gene transfer in the tumor and makes feasible the use of this system for therapy of localized cancer. JF - Gene Therapy AU - Ishii-Morita, H AU - Agbaria, R AU - Mullen, CA AU - Hirano, H AU - Koeplin, DA AU - Ram, Z AU - Oldfield, E H AU - Johns, D G AU - Blaese, R M AD - Building 10, Room 10C103, National Institutes of Health, Bethesda, MD 20892-1852, USA Y1 - 1997/03// PY - 1997 DA - Mar 1997 SP - 244 EP - 251 VL - 4 IS - 3 SN - 0969-7128, 0969-7128 KW - bystander effect KW - ganciclovir KW - suicide gene KW - thymidine kinase KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Genetics Abstracts KW - gene therapy KW - gene transfer KW - herpes simplex virus 1 KW - tumors 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/16031235?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gene+Therapy&rft.atitle=Mechanism+of+%60bystander+effect%27+killing+in+the+herpes+simplex+thymidine+kinase+gene+therapy+model+of+cancer+treatment&rft.au=Ishii-Morita%2C+H%3BAgbaria%2C+R%3BMullen%2C+CA%3BHirano%2C+H%3BKoeplin%2C+DA%3BRam%2C+Z%3BOldfield%2C+E+H%3BJohns%2C+D+G%3BBlaese%2C+R+M&rft.aulast=Ishii-Morita&rft.aufirst=H&rft.date=1997-03-01&rft.volume=4&rft.issue=3&rft.spage=244&rft.isbn=&rft.btitle=&rft.title=Gene+Therapy&rft.issn=09697128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - gene transfer; gene therapy; tumors; herpes simplex virus 1 ER - TY - JOUR T1 - Three-dimensional model of sensory rhodopsin I reveals important restraints between the protein and the chromophore AN - 16008249; 4084536 AB - A structural model is constructed for the integral membrane protein, sensory rhodopsin I (SRI), the phototaxis receptor of the archaeon Halobacterium salinarium. The model is built on the template of the homologous bacteriorhodopsin (BR). The modeling procedure includes sequence alignment, a side chain rotamer search and simulated annealing by restricted molecular dynamics. The structure is in general agreement with previous results from mutagenesis experiments, chromophore substitution and room and cryogenic temperature spectroscopy. In particular, a residue near the beta -ionone ring of the retinylidene chromophore is found to be critical in maintaining the proper isomeric conformation of the chromophore; a layer of residues lying on the cytoplasmic side of the chromophore pocket is found to modulate the restraints around the C sub(13) region of the chromophore, affecting the isomerizations around its 13=14 bond that are important to the protein's activity. The restraints in these regions are more stringent in SRI than in BR. The tightened restraints are chiefly due to van der Waals interactions, where the attractive and repulsive components play separable roles. Aromatic residues account for a majority of the restrictive interactions. It is hypothesized that the enhanced barriers due to these restrictions regulate the progress of SRI's photocycle, so that it can couple with the phototaxis reaction chain in the bacterium. A possibility is also suggested that conformational changes of the protein provide the signal recognized by the transducer. JF - Protein Engineering AU - Lin, S L AU - Yan, B AD - Lab. Math. Biol., NCI-FCRDC, Bldg. 469, Rm. 151, Frederick, MD 21702, USA Y1 - 1997/03// PY - 1997 DA - Mar 1997 SP - 197 EP - 206 VL - 10 IS - 3 SN - 0269-2139, 0269-2139 KW - Halobacterium salinarium KW - rhodopsin I KW - bacteriorhodopsin KW - sensory rhodopsin I KW - Microbiology Abstracts B: Bacteriology KW - phototaxis KW - J 02723:Photosynthesis, electron transport and related phenomena UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16008249?accountid=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=Protein+Engineering&rft.atitle=Three-dimensional+model+of+sensory+rhodopsin+I+reveals+important+restraints+between+the+protein+and+the+chromophore&rft.au=Lin%2C+S+L%3BYan%2C+B&rft.aulast=Lin&rft.aufirst=S&rft.date=1997-03-01&rft.volume=10&rft.issue=3&rft.spage=197&rft.isbn=&rft.btitle=&rft.title=Protein+Engineering&rft.issn=02692139&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - phototaxis ER - TY - JOUR T1 - Characterization of DinR, the Bacillus subtilis SOS repressor AN - 15967128; 4067965 AB - In Bacillus subtilis, exposure to DNA damage and the development of natural competence lead to the induction of the SOS regulon. It has been hypothesized that the DinR protein is the cellular repressor of the B. subtilis SOS system due to its homology to the Escherichia coli LexA transcriptional repressor. Indeed, comparison of DinR and its homologs from gram-negative and -positive bacteria revealed conserved structural motifs within the carboxyl-terminal domain that are believed to be important for autocatalysis of the protein. In contrast, regions within the DNA binding domain were conserved only within gram-negative or -positive genera, which possibly explains the differences in the sequence specificities between gram-negative and gram-positive SOS boxes. The hypothesis that DinR is the repressor of the SOS regulon in B. subtilis has been tested through overexpression, purification, and characterization of the DinR protein. Like E. coli LexA, B. subtilis DinR undergoes an autocatalytic reaction at alkaline pH at a siscile Ala super(91)-Gly super(92) bond. The cleavage reaction can also be mediated in vitro under more physiological conditions by the E. coli RecA protein. By using electrophoretic mobility shift assays, we demonstrated that DinR interacts with the previously characterized SOS box of the B. subtilis recA gene, but not with sequences containing single base pair mutations within the SOS box. Together, these observations strongly suggest that DinR is the repressor of the SOS regulon in B. subtilis. JF - Journal of Bacteriology AU - Winterling, K W AU - Levine, A S AU - Yasbin, R E AU - Woodgate, R AD - Bldg. 6, Rm. 1A13, NICHD, NIH, 9000 Rockville Pike, Bethesda, MD 20892-2725, USA Y1 - 1997/03// PY - 1997 DA - Mar 1997 SP - 1698 EP - 1703 VL - 179 IS - 5 SN - 0021-9193, 0021-9193 KW - DinR protein KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Bacillus subtilis KW - repressors KW - DNA repair KW - SOS repair KW - J 02725:DNA KW - N 14930:Transcription factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15967128?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=Characterization+of+DinR%2C+the+Bacillus+subtilis+SOS+repressor&rft.au=Winterling%2C+K+W%3BLevine%2C+A+S%3BYasbin%2C+R+E%3BWoodgate%2C+R&rft.aulast=Winterling&rft.aufirst=K&rft.date=1997-03-01&rft.volume=179&rft.issue=5&rft.spage=1698&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bacillus subtilis; DNA repair; SOS repair; repressors ER - TY - JOUR T1 - Is there an association between preconception paternal X-ray exposure and birth outcome? AN - 15914225; 4043250 AB - Diagnostic x-rays are performed commonly on men of reproductive age, yet little is known about the potential effects of these x-rays on the future unborn children of such men. This study examines the possibility that preconception diagnostic x-ray studies of fathers may adversely effect their newborns. The authors used prospectively collected data from the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC) for 7,678 birth records for women who gave birth in the County of Avon, England, in 1991-1992. Birth weight, gestational age, and fetal growth of infants whose fathers received diagnostic x-ray examinations likely to deliver significant gonadal doses within one year prior to conception were compared with infants whose fathers did not receive such x-rays. The mean birth weight of babies of exposed fathers was 3,358 g compared with a mean of 3,437 g in the unexposed group (p = 0.055). A similar difference was noted for intrauterine growth, 3,374 g exposed versus 3,437 g unexposed (p = 0.078). The downward trend in birth weight and fetal growth (birth weight adjusted for gestational age) persisted despite control for infants' sex and important parental variables such as age, height, race, education, occupational exposure, parity, and maternal smoking. Because medical x-rays are the largest controllable source of man-made ionizing radiation, more detailed study of the potential effect of paternal x-irradiation on progeny seems justified. JF - American Journal of Epidemiology AU - Shea, K M AU - Little, R E AD - NIEHS, P.O, Box 12233, Bldg. 101, MD A3-05, 111 T. W. Alexander Drive, Research Triangle Park, NC 27709, USA Y1 - 1997/03// PY - 1997 DA - Mar 1997 SP - 546 EP - 551 VL - 145 IS - 6 SN - 0002-9262, 0002-9262 KW - British Isles, England, Avon Cty. KW - birth weight KW - Toxicology Abstracts; Risk Abstracts; Health & Safety Science Abstracts KW - irradiation KW - fetuses KW - reproduction KW - radiology KW - ionizing radiation KW - infants KW - X radiation KW - males KW - prenatal experience KW - H SM7.3:HAZARD DETERMINATION KW - X 24210:Radiation & radioactive materials KW - R2 23020:Technological risks UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15914225?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Epidemiology&rft.atitle=Is+there+an+association+between+preconception+paternal+X-ray+exposure+and+birth+outcome%3F&rft.au=Shea%2C+K+M%3BLittle%2C+R+E&rft.aulast=Shea&rft.aufirst=K&rft.date=1997-03-01&rft.volume=145&rft.issue=6&rft.spage=546&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - ionizing radiation; X radiation; prenatal experience; infants; fetuses; irradiation; males; reproduction; radiology; birth weight ER - TY - JOUR T1 - Genotoxic potential of estrogens AN - 15895724; 4035340 AB - A genotoxicity evaluation of three commonly used estrogens - ethinyl estradiol, cyclotriol and cyclodiol was undertaken using short-term in vitro and in vivo assays. None of the drugs caused significantly increased or decreased number of His+ mutants to appear in the Ames Salmonella assay, either with or without S9 mix or in a modified host-mediated version of this assay. However, the clastogenic potential of these drugs became evident from the increased number or chromosome aberrations and sister chromatid exchanges (SCEs) induced by these drugs in human lymphocyte cultures both in the presence and absence of S9 mix. Increased frequencies of micronuclei and of sister chromatid exchanges in mice confirmed their clastogenic potential. JF - Mutation Research-Genetic Toxicology and Environmental Mutagenesis AU - Hundal, B S AU - Dhillon, V S AU - Sidhu, I S AD - Department of Public Health, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 1997/03// PY - 1997 DA - Mar 1997 SP - 173 EP - 181 PB - ELSEVIER SCIENCE B.V. VL - 389 IS - 2-3 SN - 1383-5718, 1383-5718 KW - estrogens KW - ethinyl estradiol KW - cyclotriol KW - cyclodiol KW - Genetics Abstracts; Toxicology Abstracts KW - sister chromatid exchange KW - genotoxicity KW - chromosome aberrations KW - Ames test KW - micronuclei KW - X 24117:Biochemistry KW - G 07221:Specific chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15895724?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+Research-Genetic+Toxicology+and+Environmental+Mutagenesis&rft.atitle=Genotoxic+potential+of+estrogens&rft.au=Hundal%2C+B+S%3BDhillon%2C+V+S%3BSidhu%2C+I+S&rft.aulast=Hundal&rft.aufirst=B&rft.date=1997-03-01&rft.volume=389&rft.issue=2-3&rft.spage=173&rft.isbn=&rft.btitle=&rft.title=Mutation+Research-Genetic+Toxicology+and+Environmental+Mutagenesis&rft.issn=13835718&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 - genotoxicity; Ames test; chromosome aberrations; sister chromatid exchange; micronuclei ER - TY - JOUR T1 - Interleukin-10 immunoadhesin production by a replication-defective adenovirus AN - 15887497; 4035112 AB - The present study examined the use of replication-defective adenovirus for in vitro production of an immunoadhesin. A recombinant adenovirus, rendered replication defective by deletion of the E1 gene, was constructed to contain the murine interleukin-10 gene fused in frame with the hinge, CH2, and CH3 domains of the murine immunoglobulin gamma 1 heavy chain constant region gene under the control of the human cytomegalovirus promoter. The resultant recombinant virus, Ad5.hCMV.mIL-10:HFc, was used to transduce several cell types. The expressed protein, mIL-10:HFc, is secreted as a disulfide-bonded homodimer. In vitro, a murine pro-B-cell line expressing transfected recombinant murine interleukin-10 receptor proliferated in response to purified mIL-10:HFc. The results obtained demonstrate the relative ease of production of an immunoadhesin using replication-defective adenovirus. JF - Journal of Immunological Methods AU - Anglade, E AU - Sullivan, D M AU - Csaky, K G AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Building 10, Room 10N-119, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1997/03// PY - 1997 DA - Mar 1997 SP - 41 EP - 48 PB - ELSEVIER SCIENCE B.V. VL - 202 IS - 1 SN - 0022-1759, 0022-1759 KW - immunoadhesin KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - adenovirus KW - interleukin 10 KW - F 06731:Other methods KW - W 30965:Miscellaneous, Reviews KW - W3 33250:Methods: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15887497?accountid=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=Interleukin-10+immunoadhesin+production+by+a+replication-defective+adenovirus&rft.au=Anglade%2C+E%3BSullivan%2C+D+M%3BCsaky%2C+K+G&rft.aulast=Anglade&rft.aufirst=E&rft.date=1997-03-01&rft.volume=202&rft.issue=1&rft.spage=41&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunological+Methods&rft.issn=00221759&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - interleukin 10; adenovirus ER - TY - JOUR T1 - Production of recombinant MART-1 proteins and specific antiMART-1 polyclonal and monoclonal antibodies: Use in the characterization of the human melanoma antigen MART-1 AN - 15884902; 4035109 AB - Recombinant human MART-1 protein was produced by bacterial and baculoviral-insect cell expression systems. By immunization with bacterial MBP-MART-1 fusion protein or MBP cleaved MART-1 protein, a rabbit polyclonal and two murine monoclonal antibodies specific for MART-1 were produced. These antibodies specifically detected MART-1 in immuno-precipitation, Western blotting, flow cytometric assays and in immunohistochemical analysis of tissue sections. They also stained cytoplasmic components in melanocytes and most melanoma cells in frozen or paraffin embedded tissue sections, indicating that these antibodies may be useful for the diagnosis of melanoma. One of the monoclonal antibodies M2-7 C10 recognized only human MART-1, but the other monoclonal antibody M2-9 E3 recognized both human and murine MART-1. The size of the human MART-1 molecule detected by SDS-PAGE with these antibodies was approximately 18 kDa, suggesting possible posttranslational modifications in the MART-1 protein. Subcellular fractionation studies suggested that MART-1 was present in melanosomes and endoplasmic reticulum, although known melanogenic enzymatic activities were not detected in the MART-1 protein. These reagents may be useful for biological studies on melanocytes and melanoma cells as well as for the development and monitoring of immunotherapy for patients with melanoma. JF - Journal of Immunological Methods AU - Kawakami, Y AU - Battles, J K AU - Kobayashi, T AU - Ennis, W AU - Wang, Xiang AU - Tupesis, J P AU - Marincola, F M AU - Robbins, P F AU - Hearing, V J AU - Gonda, MA AU - Rosenberg, SA AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 1997/03// PY - 1997 DA - Mar 1997 SP - 13 EP - 25 PB - ELSEVIER SCIENCE B.V. VL - 202 IS - 1 SN - 0022-1759, 0022-1759 KW - MART-1 antigen KW - man KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - immunotherapy KW - melanoma KW - monoclonal antibodies KW - F 06711:Monoclonal antibodies, hybridomas, antigens and antisera KW - W3 33120:Receptor based (antibodies, etc.) KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15884902?accountid=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=Production+of+recombinant+MART-1+proteins+and+specific+antiMART-1+polyclonal+and+monoclonal+antibodies%3A+Use+in+the+characterization+of+the+human+melanoma+antigen+MART-1&rft.au=Kawakami%2C+Y%3BBattles%2C+J+K%3BKobayashi%2C+T%3BEnnis%2C+W%3BWang%2C+Xiang%3BTupesis%2C+J+P%3BMarincola%2C+F+M%3BRobbins%2C+P+F%3BHearing%2C+V+J%3BGonda%2C+MA%3BRosenberg%2C+SA&rft.aulast=Kawakami&rft.aufirst=Y&rft.date=1997-03-01&rft.volume=202&rft.issue=1&rft.spage=13&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunological+Methods&rft.issn=00221759&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - immunotherapy; melanoma; monoclonal antibodies ER - TY - JOUR T1 - Nitric oxide increases tumor necrosis factor production in differentiated U937 cells by decreasing cyclic AMP. AN - 78836336; 9038216 AB - Nitric oxide (NO) increases tumor necrosis factor (TNF) synthesis in human peripheral blood mononuclear cells by a cGMP-independent mechanism. NO has been shown to inhibit adenylate cyclase in cell membranes. Since cAMP down-regulates TNF transcription, we examined the possibility that NO enhances TNF synthesis by decreasing cAMP. U937 cells were induced to differentiate using phorbol myristate acetate (100 nM for 48 h) and then were incubated for 24 h with sodium nitroprusside (SNP) or S-nitroso-N-acetylpenicillamine (SNAP). These NO donors increased TNF production (7.0- and 15.6-fold, respectively, at 500 microM) in a dose-dependent manner (p = 0.002). However, SNP and SNAP did not elevate cGMP levels in U937 cell cultures, and the cGMP analog, 8-bromo-cGMP, had no effect on TNF production. In contrast, SNP (p = 0.001) and SNAP (p = 0.009) decreased intracellular cAMP levels by up to 51.5% over 24 h and, in the presence of a phosphodiesterase inhibitor, blunted isoproterenol-stimulated increases in cAMP by 21.8% (p = 0.004) and 27.6% (p = 0.008), respectively. H89, an inhibitor of cAMP-dependent protein kinase, dose dependently increased TNF production in phorbol myristate acetate-differentiated U937 cells in the absence (6.5-fold at 30 microM; p = 0.035), but not in the presence (p = 0.77) of SNAP. Conversely, the cAMP analog dibutyryl cAMP (Bt2cAMP) blocked SNAP-induced TNF production (p = 0.001). SNP and SNAP (500 microM) increased relative TNF mRNA levels by 57.5% (p = 0.045) and 66.2% (p = 0.001), respectively. This effect was prevented by Bt2cAMP. These results indicate that NO up-regulates TNF production by decreasing intracellular cAMP. JF - The Journal of biological chemistry AU - Wang, S AU - Yan, L AU - Wesley, R A AU - Danner, R L AD - Critical Care Medicine Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/02/28/ PY - 1997 DA - 1997 Feb 28 SP - 5959 EP - 5965 VL - 272 IS - 9 SN - 0021-9258, 0021-9258 KW - RNA, Messenger KW - 0 KW - Tumor Necrosis Factor-alpha KW - Vasodilator Agents KW - Nitric Oxide KW - 31C4KY9ESH KW - Bucladesine KW - 63X7MBT2LQ KW - S-Nitroso-N-Acetylpenicillamine KW - 79032-48-7 KW - Cyclic AMP KW - E0399OZS9N KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Penicillamine KW - GNN1DV99GX KW - Cyclic GMP KW - H2D2X058MU KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Penicillamine -- analogs & derivatives KW - Cyclic GMP -- pharmacology KW - RNA, Messenger -- metabolism KW - Penicillamine -- pharmacology KW - Humans KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Differentiation KW - Bucladesine -- pharmacology KW - Cyclic GMP -- analogs & derivatives KW - Vasodilator Agents -- pharmacology KW - Cyclic AMP -- metabolism KW - Nitric Oxide -- pharmacology KW - Tumor Necrosis Factor-alpha -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78836336?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Nitric+oxide+increases+tumor+necrosis+factor+production+in+differentiated+U937+cells+by+decreasing+cyclic+AMP.&rft.au=Wang%2C+S%3BYan%2C+L%3BWesley%2C+R+A%3BDanner%2C+R+L&rft.aulast=Wang&rft.aufirst=S&rft.date=1997-02-28&rft.volume=272&rft.issue=9&rft.spage=5959&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-15 N1 - Date created - 1997-04-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Site-directed mutation of Nm23-H1. Mutations lacking motility suppressive capacity upon transfection are deficient in histidine-dependent protein phosphotransferase pathways in vitro. AN - 78830474; 9038158 AB - We previously compared the structure and motility suppressive capacity of nm23-H1 by transfection of wild type and site-directed mutant forms into breast carcinoma cells. Wild type nm23-H1 and an nm23-H1(S44A) (serine 44 to alanine) mutant suppressed motility, whereas the nm23-H1(P96S), nm23-H1(S120G), and to a lesser extent, nm23-H1(S120A) mutant forms failed to do so. In the present study wild type and mutant recombinant Nm23-H1 proteins have been produced, purified, and assayed for phosphorylation and phosphotransfer activities. We report the first association of Nm23-H1 mutations lacking motility suppressive capacity with decreased in vitro activity in histidine-dependent protein phosphotransferase assays. Nm23-H1(P96S), a Drosophila developmental mutation homolog, exhibited normal autophosphorylation and nucleoside-diphosphate kinase (NDPK) characteristics but deficient phosphotransfer activity in three histidine protein kinase assays, using succinic thiokinase, Nm23-H2, and GST-Nm23-H1 as substrates. Nm23-H1(S120G), found in advanced human neuroblastomas, exhibited deficient activity in several histidine-dependent protein phosphotransfer reactions, including histidine autophosphorylation, downstream phosphorylation on serines, and slightly decreased histidine protein kinase activity; significant NDPK activity was observed. The Nm23-H1(S120A) mutant was deficient in only histidine-dependent serine autophosphorylation. Nm23-H1 and Nm23-H1(S44A) exhibited normal activity in all assays conducted. Based on this correlation, we hypothesize that a histidine-dependent protein phosphotransfer activity of Nm23-H1 may be responsible for its biological suppressive effects. JF - The Journal of biological chemistry AU - Freije, J M AU - Blay, P AU - MacDonald, N J AU - Manrow, R E AU - Steeg, P S AD - Women's Cancers Section, Laboratory of Pathology, Division of Clinical Sciences, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/02/28/ PY - 1997 DA - 1997 Feb 28 SP - 5525 EP - 5532 VL - 272 IS - 9 SN - 0021-9258, 0021-9258 KW - NM23 Nucleoside Diphosphate Kinases KW - 0 KW - Recombinant Proteins KW - Transcription Factors KW - Serine KW - 452VLY9402 KW - Histidine KW - 4QD397987E KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Protein Kinases KW - EC 2.7.- KW - Phosphoenolpyruvate Sugar Phosphotransferase System KW - EC 2.7.1.- KW - protein-N-pi-phosphohistidine - sugar phosphotransferase KW - EC 2.7.1.69 KW - Histidine Kinase KW - EC 2.7.13.1 KW - NME1 protein, human KW - EC 2.7.4.6 KW - Nucleoside-Diphosphate Kinase KW - Monomeric GTP-Binding Proteins KW - EC 3.6.5.2 KW - Index Medicus KW - Dose-Response Relationship, Drug KW - Humans KW - Glutathione Transferase -- metabolism KW - Models, Biological KW - Mutagenesis, Site-Directed KW - Protein Kinases -- metabolism KW - Recombinant Proteins -- isolation & purification KW - Phosphorylation KW - Transfection KW - Recombinant Proteins -- metabolism KW - Phosphoenolpyruvate Sugar Phosphotransferase System -- metabolism KW - Transcription Factors -- genetics KW - Nucleoside-Diphosphate Kinase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78830474?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Site-directed+mutation+of+Nm23-H1.+Mutations+lacking+motility+suppressive+capacity+upon+transfection+are+deficient+in+histidine-dependent+protein+phosphotransferase+pathways+in+vitro.&rft.au=Freije%2C+J+M%3BBlay%2C+P%3BMacDonald%2C+N+J%3BManrow%2C+R+E%3BSteeg%2C+P+S&rft.aulast=Freije&rft.aufirst=J&rft.date=1997-02-28&rft.volume=272&rft.issue=9&rft.spage=5525&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-15 N1 - Date created - 1997-04-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Subcellular distribution of normal and mutant vitamin D receptors in living cells. Studies with a novel fluorescent ligand. AN - 78817041; 9038191 AB - To understand the subcellular localization of the vitamin D receptor (VDR) and to measure VDR content in single cells, we recently developed a fluorescent labeled ligand, 4,4-difluoro-4-bora-3a, 4a-diaza-s-indacene (BODIPY)-calcitriol. This tagged hormone has intact biological activity, high affinity and specific binding to the receptor, and enhanced fluorescent emission upon receptor binding. Using BODIPY-calcitriol, here we monitored the subcellular distribution of VDR in living cultured cells by microscopy. Time course studies showed that an equilibrium between the cytoplasmic and nuclear hormone binding developed within 5 min and was maintained thereafter. We found a substantial proportion of VDR residing in the cytoplasm, colocalized with endoplasmic reticulum, the Golgi complex, and microtubules. Confocal microscopy clarified the presence of VDR within discrete regions of the nucleus and along the nuclear envelope. There was no VDR in the plasma membrane. Low affinity BODIPY-calcitriol binding sites were in the mitochondria. Mutations in the VDR gene selectively and specifically altered BODIPY-calcitriol distribution. Defects in the hormone binding region of VDR prevented both nuclear and cytoplasmic hormone binding. Defects in the DNA binding region decreased the nuclear retention of VDR and prevented localization to nuclear foci. These results with BODIPY-calcitriol reveal cytoplasmic VDR localization in living cells and open the possibility of studying the three-dimensional architecture of intranuclear target sites. JF - The Journal of biological chemistry AU - Barsony, J AU - Renyi, I AU - McKoy, W AD - Laboratory of Cell Biochemistry and Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. jul@helix.nih.gov Y1 - 1997/02/28/ PY - 1997 DA - 1997 Feb 28 SP - 5774 EP - 5782 VL - 272 IS - 9 SN - 0021-9258, 0021-9258 KW - 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene KW - 0 KW - Boron Compounds KW - Receptors, Calcitriol KW - Thapsigargin KW - 67526-95-8 KW - Calcitriol KW - FXC9231JVH KW - Index Medicus KW - Thapsigargin -- pharmacology KW - Microscopy, Confocal KW - Cells, Cultured KW - Cell Nucleus -- metabolism KW - Humans KW - Fibroblasts -- chemistry KW - Subcellular Fractions -- metabolism KW - Mutagenesis KW - Boron Compounds -- metabolism KW - Receptors, Calcitriol -- genetics KW - Receptors, Calcitriol -- metabolism KW - Calcitriol -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78817041?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Subcellular+distribution+of+normal+and+mutant+vitamin+D+receptors+in+living+cells.+Studies+with+a+novel+fluorescent+ligand.&rft.au=Barsony%2C+J%3BRenyi%2C+I%3BMcKoy%2C+W&rft.aulast=Barsony&rft.aufirst=J&rft.date=1997-02-28&rft.volume=272&rft.issue=9&rft.spage=5774&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-15 N1 - Date created - 1997-04-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p21(Waf1/Cip1) protects against p53-mediated apoptosis of human melanoma cells. AN - 78869230; 9050992 AB - The tumor suppressive effect of p53 is believed to be rooted in its two primary functions: the implementation of cellular growth arrest and the execution of apoptotic cell death. While p53-regulated expression of the cyclin-dependent kinase inhibitor p21(Waf1/Cip1) appears to be central for the implementation of G1 arrest, the participation of p21(Waf1/Cip1) in p53-triggered cell death remains controversial. In the present study, overexpression of p53 in human melanoma SK-MEL-110 cells through use of an adenoviral expression vector (AdCMV.p53) was found to result in apoptosis, while similar infection of primary vascular smooth muscle cells (VSMC) instead resulted in a moderate inhibition of growth. Expression of p21(Waf1/Cip1) was strongly elevated in VSMC, but showed little change in SK-MEL-110 cells, although expression of another p53-regulated gene (GADD45) was comparable in both AdCMV.p53-infected cell types. Evidence that p21(Waf1/Cip1) expression may be required for surviving p53-induced cell death was further supported by the finding that p53 overexpression was highly toxic for p21-deficient mouse embryonal fibroblasts (p21-/- MEFs). In both SK-MEL-110 and p21-/- MEFs, adenovirus-driven ectopic expression of p21(Waf1/Cip1) resulted in a substantial protection against p53-induced apoptosis, indicating that p21(Waf1/Cip1) rescued cells from a path of programmed cell death to one of enhanced survival. JF - Oncogene AU - Gorospe, M AU - Cirielli, C AU - Wang, X AU - Seth, P AU - Capogrossi, M C AU - Holbrook, N J AD - Laboratory of Cellular and Molecular Biology, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1997/02/27/ PY - 1997 DA - 1997 Feb 27 SP - 929 EP - 935 VL - 14 IS - 8 SN - 0950-9232, 0950-9232 KW - CDKN1A protein, human KW - 0 KW - Cdkn1a protein, mouse KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - GADD45 protein KW - Intracellular Signaling Peptides and Proteins KW - Proteins KW - RNA, Messenger KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured KW - Cells, Cultured KW - Humans KW - Gene Expression KW - Mice KW - RNA, Messenger -- genetics KW - Proteins -- genetics KW - Mice, Knockout KW - Cyclins -- physiology KW - Tumor Suppressor Protein p53 -- physiology KW - Melanoma -- pathology KW - Apoptosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78869230?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=p21%28Waf1%2FCip1%29+protects+against+p53-mediated+apoptosis+of+human+melanoma+cells.&rft.au=Gorospe%2C+M%3BCirielli%2C+C%3BWang%2C+X%3BSeth%2C+P%3BCapogrossi%2C+M+C%3BHolbrook%2C+N+J&rft.aulast=Gorospe&rft.aufirst=M&rft.date=1997-02-27&rft.volume=14&rft.issue=8&rft.spage=929&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-31 N1 - Date created - 1997-03-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vitro effect of gallium nitrate when combined with ketoconazole in the prostate cancer cell line PC-3. AN - 78888090; 9065809 AB - Secondary hormonal manipulations are common following the failure of combined androgen blockade in patients with metastatic prostate cancer. Ketoconazole has been shown to have activity in this disease by inhibiting cytochrome P450 steroid hormone biosynthesis, thus inducing androgen deprivation. Gallium nitrate has been reported to target tumor tissue in vitro and some preliminary data suggests activity in patients with prostate cancer. Thus, we conducted a Phase II study of gallium nitrate in patients with androgen-independent prostate cancer. Two patients with progressive prostate cancer were removed from this study and subsequently placed on ketoconazole, as a palliative agent. Surprisingly, both of these patients had a greater than 50% decline in their prostate specific antigen (PSA) with this secondary endocrine maneuver. Based on this clinical observation, we conducted the following in vitro study to determine if there was a substantial additive effect of gallium nitrate followed by ketoconazole. Gallium nitrate or ketoconazole was added to the androgen-independent prostatic epithelial cell line, PC-3. One hundred and twenty hours (120 h) following the addition of one of the agents, the media was aspirated and the second agent was added to the wells. One plate was assayed every 24 h for cell viability using a non-isotopic cell proliferation assay kit. Cells treated with gallium nitrate followed by ketoconazole were 70-100% of control at the end of the gallium nitrate treatment; ketoconazole was then added and viability either remained constant or dropped steadily. Gallium nitrate by itself had a weak inhibitory effect on cell viability that only became apparent at the highest concentration evaluated. Ketoconazole, on the other hand, showed a substantial growth inhibition that was concentration-dependent. Cells treated with this agent alone showed a pronounced steady decrease in viability. Exposure to ketoconazole for 120 h followed by incubation in culture medium alone for 120 h caused a decrease in cell viability to 26.0% of control. Our in vitro results suggest that the combination of gallium nitrate and ketoconazole has no additive activity in the PC-3 cell line. Furthermore, this study confirms that ketoconazole added to prostate cancer cells has antiproliferative activity. The in vitro activity of ketoconazole has traditionally been thought to result from its inhibition of cytochrome P450-dependent enzymes responsible for steroidogenesis; however, an alternative hypothesis is necessary to explain the cytotoxic effect in the absence of adrenal and testicular androgen production as found in an in vitro system. JF - Cancer letters AU - Dixon, S C AU - Zalles, A AU - Giordano, C AU - Lush, R M AU - Venzon, D AU - Reed, E AU - Figg, W D AD - Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1997/02/26/ PY - 1997 DA - 1997 Feb 26 SP - 111 EP - 116 VL - 113 IS - 1-2 SN - 0304-3835, 0304-3835 KW - Antifungal Agents KW - 0 KW - Gallium KW - CH46OC8YV4 KW - Ketoconazole KW - R9400W927I KW - gallium nitrate KW - VRA0C6810N KW - Index Medicus KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Humans KW - Drug Synergism KW - Time Factors KW - Male KW - Gallium -- pharmacology KW - Antifungal Agents -- pharmacology KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacology KW - Prostatic Neoplasms -- drug therapy KW - Ketoconazole -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78888090?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=In+vitro+effect+of+gallium+nitrate+when+combined+with+ketoconazole+in+the+prostate+cancer+cell+line+PC-3.&rft.au=Dixon%2C+S+C%3BZalles%2C+A%3BGiordano%2C+C%3BLush%2C+R+M%3BVenzon%2C+D%3BReed%2C+E%3BFigg%2C+W+D&rft.aulast=Dixon&rft.aufirst=S&rft.date=1997-02-26&rft.volume=113&rft.issue=1-2&rft.spage=111&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-07 N1 - Date created - 1997-04-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synthesis and nicotinic activity of epiboxidine: an isoxazole analogue of epibatidine. AN - 78875553; 9063687 AB - Synthetic (+/-)-epiboxidine (exo-2-(3-methyl-5-isoxazolyl)-7-azabicyclo[2.2.1]heptane) is a methylisoxazole analog of the alkaloid epibatidine, itself a potent nicotinic receptor agonist with antinociceptive activity. Epiboxidine contains a methylisoxazolyl ring replacing the chloropyridinyl ring of epibatidine. Thus, it is also an analog of another nicotinic receptor agonist, ABT 418 ((S)-3-methyl-5-(1-methyl-2-pyrrolidinyl)isoxazole), in which the pyridinyl ring of nicotine has been replaced by the methylisoxazolyl ring. Epiboxidine was about 10-fold less potent than epibatidine and about 17-fold more potent than ABT 418 in inhibiting [3H]nicotine binding to alpha 4 beta 2 nicotinic receptors in rat cerebral cortical membranes. In cultured cells with functional ion flux assays, epiboxidine was nearly equipotent to epibatidine and 200-fold more potent than ABT 418 at alpha 3 beta 4(5) nicotinic receptors in PC12 cells. Epiboxidine was about 5-fold less potent than epibatidine and about 30-fold more potent than ABT 418 in TE671 cells with alpha 1 beta 1 gamma delta nicotinic receptors. In a hot-plate antinociceptive assay with mice, epiboxidine was about 10-fold less potent than epibatidine. However, epiboxidine was also much less toxic than epibatidine in mice. JF - European journal of pharmacology AU - Badio, B AU - Garraffo, H M AU - Plummer, C V AU - Padgett, W L AU - Daly, J W AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/02/26/ PY - 1997 DA - 1997 Feb 26 SP - 189 EP - 194 VL - 321 IS - 2 SN - 0014-2999, 0014-2999 KW - Anti-Anxiety Agents KW - 0 KW - Isoxazoles KW - Nicotinic Agonists KW - Pyrrolidines KW - Receptors, Nicotinic KW - epiboxidine KW - Tritium KW - 10028-17-8 KW - 3-methyl-5-(1-methyl-2-pyrrolidinyl)isoxazole KW - 147402-53-7 KW - Nicotine KW - 6M3C89ZY6R KW - Index Medicus KW - Animals KW - Cerebral Cortex -- drug effects KW - Cerebral Cortex -- ultrastructure KW - Mice KW - Nociceptors -- drug effects KW - Rats KW - Anti-Anxiety Agents -- pharmacology KW - Kinetics KW - Ganglia -- ultrastructure KW - Receptors, Nicotinic -- drug effects KW - Pyrrolidines -- pharmacology KW - Ganglia -- drug effects KW - Male KW - PC12 Cells KW - Isoxazoles -- chemical synthesis KW - Nicotine -- pharmacology KW - Nicotine -- metabolism KW - Nicotinic Agonists -- pharmacology KW - Isoxazoles -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78875553?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+pharmacology&rft.atitle=Synthesis+and+nicotinic+activity+of+epiboxidine%3A+an+isoxazole+analogue+of+epibatidine.&rft.au=Badio%2C+B%3BGarraffo%2C+H+M%3BPlummer%2C+C+V%3BPadgett%2C+W+L%3BDaly%2C+J+W&rft.aulast=Badio&rft.aufirst=B&rft.date=1997-02-26&rft.volume=321&rft.issue=2&rft.spage=189&rft.isbn=&rft.btitle=&rft.title=European+journal+of+pharmacology&rft.issn=00142999&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-01 N1 - Date created - 1997-07-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vitro mutagenicity of the plasmacytomagenic agent pristane (2,6,10,14-tetramethylpentadecane). AN - 78866401; 9065804 AB - Pristane is known to induce a distinct type of B-cell-derived malignant lymphoma, plasmacytoma, after administration into the peritoneal cavity of genetically susceptible BALB/cAnPt mice. Since the mechanism of pristane-induced plasmacytoma development is poorly understood, we chose to examine the possibility that pristane is mutagenic in rodent cells and decided to use bacteriophage lambda-derived lacI/lacZ genes as target/reporter to quantitate mutagenesis. Here we show that in vitro exposure to micromolar amounts of pristane, delivered as an inclusion complex with beta-cyclodextrin, resulted in 1.7-fold and 6.2-fold increases of mutant frequencies over controls in a cell line of rat fibroblasts and primary mouse B lymphocytes, respectively. We conclude that pristane can be mutagenic to mammalian cells, yet are currently unable to explain the mechanism of mutagenicity. It is suggested that B-cell mutagenesis contributes to the plasmacytomagenic activity of pristane in vivo. JF - Cancer letters AU - Felix, K AU - Potter, M AU - Bornkamm, G W AU - Janz, S AD - Institut für Klinische Molekularbiologie and Tumorgenetik, München, Germany. felixk@dc37a.nci.nih.gov Y1 - 1997/02/26/ PY - 1997 DA - 1997 Feb 26 SP - 71 EP - 76 VL - 113 IS - 1-2 SN - 0304-3835, 0304-3835 KW - Carcinogens KW - 0 KW - Mutagens KW - Terpenes KW - pristane KW - 26HZV48DT1 KW - Index Medicus KW - Rats KW - Fibroblasts -- drug effects KW - B-Lymphocytes -- drug effects KW - Animals KW - Base Sequence KW - Mutagenicity Tests -- methods KW - Cells, Cultured KW - Mice KW - Amino Acid Sequence KW - Terpenes -- toxicity KW - Carcinogens -- toxicity KW - Mutagens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78866401?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=In+vitro+mutagenicity+of+the+plasmacytomagenic+agent+pristane+%282%2C6%2C10%2C14-tetramethylpentadecane%29.&rft.au=Felix%2C+K%3BPotter%2C+M%3BBornkamm%2C+G+W%3BJanz%2C+S&rft.aulast=Felix&rft.aufirst=K&rft.date=1997-02-26&rft.volume=113&rft.issue=1-2&rft.spage=71&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-07 N1 - Date created - 1997-04-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drug-drug interactions: effect of quinidine on nifedipine binding to human cytochrome P450 3A4. AN - 78954568; 9105395 AB - Quinidine is a known inhibitor of cytochrome P450-mediated nifedipine metabolism. The interactions of nifedipine and quinidine with human cytochrome P450 3A4, which metabolizes these drugs, were examined using the kinetics of CO binding to this P450 as a rapid kinetic probe of protein conformation and dynamics. This approach showed that nifedipine and quinidine bind to different P450 3A4 species, respectively termed species I and II, with distinct conformations. When both drugs were present simultaneously, nifedipine interacted with the quinidine-bound P450 species II, but not species I. These findings indicate that quinidine acts as an allosteric inhibitor by switching nifedipine binding from nifedipine-metabolizing species I to the nonmetabolizing species II. JF - Biochemical pharmacology AU - Koley, A P AU - Robinson, R C AU - Markowitz, A AU - Friedman, F K AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/02/21/ PY - 1997 DA - 1997 Feb 21 SP - 455 EP - 460 VL - 53 IS - 4 SN - 0006-2952, 0006-2952 KW - Anti-Arrhythmia Agents KW - 0 KW - Calcium Channel Blockers KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - CYP3A protein, human KW - EC 1.14.14.1 KW - Cytochrome P-450 CYP3A KW - Nifedipine KW - I9ZF7L6G2L KW - Quinidine KW - ITX08688JL KW - Index Medicus KW - Drug Interactions KW - Humans KW - Mixed Function Oxygenases -- metabolism KW - Calcium Channel Blockers -- metabolism KW - Quinidine -- pharmacology KW - Cytochrome P-450 Enzyme System -- metabolism KW - Nifedipine -- metabolism KW - Anti-Arrhythmia Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78954568?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Drug-drug+interactions%3A+effect+of+quinidine+on+nifedipine+binding+to+human+cytochrome+P450+3A4.&rft.au=Koley%2C+A+P%3BRobinson%2C+R+C%3BMarkowitz%2C+A%3BFriedman%2C+F+K&rft.aulast=Koley&rft.aufirst=A&rft.date=1997-02-21&rft.volume=53&rft.issue=4&rft.spage=455&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 - 1997-05-01 N1 - Date created - 1997-05-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evidence for generation of oxidative stress in brain by MPTP: in vitro and in vivo studies in mice. AN - 78889989; 9070626 AB - The role of oxidative stress in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-mediated neurotoxicity is as yet unclear and the evidence for generation of oxygen free radicals as a primary event in the neurotoxicity is yet to be demonstrated. The present study was undertaken to ascertain the potential role of oxidative damage, and the protective role, if any, of the antioxidant, glutathione (GSH), in MPTP-induced neurotoxicity. Exposure of sagittal slices of mouse brain to MPTP resulted in significant increases of reactive oxygen species (ROS) and malondialdehyde (MDA, the product of lipid peroxidation) and decreases in GSH content. Pretreatment of mouse brain slices, in vitro, with GSH or GSH isopropyl ester attenuated MPTP toxicity as assessed by the tissue activity of the mitochondrial enzyme, NADH-dehydrogenase (NADH-DH), and by leakage of the cytosolic enzyme, lactate dehydrogenase (LDH), from the slice into the medium. In vivo administration of MPTP (30 mg/kg body weight, s.c.), to mice resulted in significant lowering of GSH in the striatum and midbrain, 2 h after dosage; ROS levels in the striatum and midbrain increased after 4 and 8 h, respectively. In the striatum significant inhibition of rotenone-sensitive NADH ubiquinone-1 oxido-reductase (Complex 1) was observed transiently 1 h after MPTP administration. The enzyme activity recovered thereafter; significant inhibition of mitochondrial Complex I was observed in the striatum only 18 h after MPTP dose. In the midbrain, mitochondrial Complex I was inhibited only 18 h after MPTP dose; no change was observed at the early time points examined. Thus, the depletion of GSH and increased ROS formation preceded the inhibition of the mitochondrial enzyme in the midbrain. Evidence presented herein from both in vitro and in vivo studies support that MPTP exposure generates ROS resulting in oxidative stress. JF - Brain research AU - Sriram, K AU - Pai, K S AU - Boyd, M R AU - Ravindranath, V AD - Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bangalore, India. Y1 - 1997/02/21/ PY - 1997 DA - 1997 Feb 21 SP - 44 EP - 52 VL - 749 IS - 1 SN - 0006-8993, 0006-8993 KW - Dopamine Agents KW - 0 KW - Malondialdehyde KW - 4Y8F71G49Q KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - NADH, NADPH Oxidoreductases KW - EC 1.6.- KW - Electron Transport Complex I KW - EC 1.6.5.3 KW - Index Medicus KW - Malondialdehyde -- metabolism KW - Animals KW - In Vitro Techniques KW - NADH, NADPH Oxidoreductases -- metabolism KW - Mice KW - Male KW - L-Lactate Dehydrogenase -- metabolism KW - Dopamine Agents -- toxicity KW - MPTP Poisoning KW - Brain Chemistry -- drug effects KW - Oxidative Stress -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78889989?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Evidence+for+generation+of+oxidative+stress+in+brain+by+MPTP%3A+in+vitro+and+in+vivo+studies+in+mice.&rft.au=Sriram%2C+K%3BPai%2C+K+S%3BBoyd%2C+M+R%3BRavindranath%2C+V&rft.aulast=Sriram&rft.aufirst=K&rft.date=1997-02-21&rft.volume=749&rft.issue=1&rft.spage=44&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 - 1997-06-10 N1 - Date created - 1997-06-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thymidylate synthase expression and response to neoadjuvant chemotherapy in patients with advanced head and neck cancer. AN - 78829695; 9048835 AB - Thymidylate synthase (TS), an essential enzyme in DNA synthesis, is a target for the fluoropyrimidines, an important group of antineoplastic agents used widely in the treatment of head and neck cancer. We evaluated relationships between the level and/or pattern of tumor TS expression and response to fluorouracil (5-FU)-based neoadjuvant chemotherapy in patients with advanced head and neck cancer. Tumor specimens from 86 patients were available for this retrospective analysis. The patients were enrolled in four consecutive phase II studies that tested combinations of 5-FU, leucovorin, and cisplatin with or without added methotrexate plus piritrexim or interferon alfa-2b (IFN alpha-2b). TS protein expression in the tumors was assessed by use of the TS 106 monoclonal antibody and standard immunohistochemical staining techniques. TS immunostaining was classified according to its level of intensity (TS 0-1 = low, TS 2 = intermediate, and TS 3 = high) and according to its extent (focal pattern = less than 25% of tumor cells positive; diffuse pattern = greater than or equal to 25% of tumor cells positive). Data from 79 patients were available for an analysis of tumor TS expression and patient/tumor characteristics; 70 patients were assessable for their response to neoadjuvant chemotherapy. There was a statistically significant association between the level of tumor TS expression and the degree of tumor differentiation; a higher proportion of patients whose tumors exhibited TS 0-1 immunostaining had undifferentiated or poorly differentiated tumors than patients whose tumors exhibited TS 2 or TS 3 immunostaining (P = .04, Jonckheere-Terpstra trend test). Among the 70 patients who were assessable for response to neoadjuvant chemotherapy, TS 3 tumor immunostaining was associated with a lower rate of complete response (i.e., complete disappearance of clinically detectable disease for a minimum of 4 weeks from time of initial determination) than was TS 2 or TS 0-1 immunostaining, but this association was not statistically significant (P = .09, exact trend test); among the 39 patients who were treated with regimens that included 5-FU, leucovorin, cisplatin, and IFN alpha-2b, this inverse association between TS immunostaining intensity and response was statistically significant (P = .02, exact trend test). Tumor TS immunostaining intensity and overall survival were not found to be associated. Patients with tumors exhibiting a focal pattern of TS immunostaining have experienced significantly longer survival than patients with tumors exhibiting a diffuse pattern; for the 53 patients with diffuse tumor TS immunostaining, the median survival was 24.7 months, whereas the median survival has not yet been reached for the 22 patients with focal tumor TS immunostaining (P = .04, two-tailed logrank test). However, the survival advantage for the focal versus diffuse TS immunostaining pattern was limited to patients whose tumors also exhibited a TS 3 level of immunostaining intensity. Characterization of tumor TS expression may be of value in identifying patients with advanced head and neck cancer who would benefit from fluoropyrimidine-based neoadjuvant chemotherapy. JF - Journal of the National Cancer Institute AU - Johnston, P G AU - Mick, R AU - Recant, W AU - Behan, K A AU - Dolan, M E AU - Ratain, M J AU - Beckmann, E AU - Weichselbaum, R R AU - Allegra, C J AU - Vokes, E E AD - NCI-Navy Medical Oncology Branch, USA. Y1 - 1997/02/19/ PY - 1997 DA - 1997 Feb 19 SP - 308 EP - 313 VL - 89 IS - 4 SN - 0027-8874, 0027-8874 KW - Antimetabolites, Antineoplastic KW - 0 KW - Interferon-alpha KW - Recombinant Proteins KW - interferon alfa-2b KW - 43K1W2T1M6 KW - Oxidoreductases KW - EC 1.- KW - Dihydrouracil Dehydrogenase (NADP) KW - EC 1.3.1.2 KW - Thymidylate Synthase KW - EC 2.1.1.45 KW - Cisplatin KW - Q20Q21Q62J KW - Leucovorin KW - Q573I9DVLP KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Antimetabolites, Antineoplastic -- administration & dosage KW - Interferon-alpha -- administration & dosage KW - Humans KW - Leucovorin -- administration & dosage KW - Retrospective Studies KW - Predictive Value of Tests KW - Fluorouracil -- blood KW - Cisplatin -- administration & dosage KW - Fluorouracil -- administration & dosage KW - Oxidoreductases -- blood KW - Treatment Outcome KW - Immunohistochemistry KW - Chemotherapy, Adjuvant KW - Remission Induction KW - Head and Neck Neoplasms -- blood KW - Head and Neck Neoplasms -- enzymology KW - Thymidylate Synthase -- drug effects KW - Head and Neck Neoplasms -- pathology KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Thymidylate Synthase -- biosynthesis KW - Head and Neck Neoplasms -- drug therapy KW - Gene Expression Regulation, Neoplastic -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78829695?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Thymidylate+synthase+expression+and+response+to+neoadjuvant+chemotherapy+in+patients+with+advanced+head+and+neck+cancer.&rft.au=Johnston%2C+P+G%3BMick%2C+R%3BRecant%2C+W%3BBehan%2C+K+A%3BDolan%2C+M+E%3BRatain%2C+M+J%3BBeckmann%2C+E%3BWeichselbaum%2C+R+R%3BAllegra%2C+C+J%3BVokes%2C+E+E&rft.aulast=Johnston&rft.aufirst=P&rft.date=1997-02-19&rft.volume=89&rft.issue=4&rft.spage=308&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-20 N1 - Date created - 1997-03-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dependence of intracellular signaling and neurosecretion on phospholipase D activation in immortalized gonadotropin-releasing hormone neurons. AN - 78815359; 9037095 AB - The excitability of gonadotropin-releasing hormone (GnRH) neurons is essential for episodic neuropeptide release, but the mechanism by which electrical activity controls GnRH secretion is not well characterized. The role of phospholipase D (PLD) in mediating the activity-dependent secretory pathway was investigated in immortalized GT1 neurons, which both secrete GnRH and express GnRH receptors. Activation of these Ca2+-mobilizing receptors was associated with transient hyperpolarization of GT1 cells, followed by sustained firing of action potentials. This was accompanied by an increase in PLD activity, as indicated by elevated phosphatidylethanol (PEt) production. GnRH-induced PEt production was reduced by inhibition of phospholipase C-dependent phosphoinositide hydrolysis by U73122 and neomycin, suggesting that signaling from phospholipase C led to activation of PLD. The intermediate role of protein kinase C (PKC) in this process was indicated by the ability of phorbol 12-myristate 13-acetate to induce time- and dose-dependent increases in PEt and diacylglycerol, but not inositol trisphosphate, and by reduction of GnRH-induced PEt accumulation in PKC-depleted cells. Consistent with the role of action potential-driven Ca2+ entry in this process, agonist-induced PLD activity was also reduced by nifedipine and low extracellular Ca2+. Inhibition of the PLD pathway by ethanol and propranolol reduced diacylglycerol production and caused a concomitant fall in GnRH release. These data indicate that voltage-gated Ca2+ entry and PKC act in an independent but cooperative manner to regulate PLD activity, which contributes to the secretory response in GT1 cells. Thus, the electrical activity of the GnRH-secreting neuron participates in the functional coupling between GnRH receptors and PLD pathway. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Zheng, L AU - Krsmanovic, L Z AU - Vergara, L A AU - Catt, K J AU - Stojilkovic, S S AD - Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/02/18/ PY - 1997 DA - 1997 Feb 18 SP - 1573 EP - 1578 VL - 94 IS - 4 SN - 0027-8424, 0027-8424 KW - Calcium Channels KW - 0 KW - Enzyme Inhibitors KW - Glycerophospholipids KW - Neuropeptides KW - Phosphatidic Acids KW - Receptors, LHRH KW - phosphatidylethanol KW - Gonadotropin-Releasing Hormone KW - 33515-09-2 KW - Ethanol KW - 3K9958V90M KW - Propranolol KW - 9Y8NXQ24VQ KW - Protein Kinase C KW - EC 2.7.11.13 KW - Phospholipase D KW - EC 3.1.4.4 KW - Nifedipine KW - I9ZF7L6G2L KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Ion Channel Gating KW - Phosphatidic Acids -- metabolism KW - Calcium Channels -- metabolism KW - Neurons -- metabolism KW - Dose-Response Relationship, Drug KW - Enzyme Activation KW - Ethanol -- pharmacology KW - Propranolol -- pharmacology KW - Neurons -- drug effects KW - Models, Biological KW - Protein Kinase C -- metabolism KW - Calcium -- metabolism KW - Nifedipine -- pharmacology KW - Protein Kinase C -- antagonists & inhibitors KW - Cells, Cultured KW - Enzyme Inhibitors -- pharmacology KW - Receptors, LHRH -- metabolism KW - Phospholipase D -- metabolism KW - Hypothalamus -- drug effects KW - Hypothalamus -- metabolism KW - Hypothalamus -- cytology KW - Neuropeptides -- secretion KW - Gonadotropin-Releasing Hormone -- secretion KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78815359?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dependence+of+intracellular+signaling+and+neurosecretion+on+phospholipase+D+activation+in+immortalized+gonadotropin-releasing+hormone+neurons.&rft.au=Zheng%2C+L%3BKrsmanovic%2C+L+Z%3BVergara%2C+L+A%3BCatt%2C+K+J%3BStojilkovic%2C+S+S&rft.aulast=Zheng&rft.aufirst=L&rft.date=1997-02-18&rft.volume=94&rft.issue=4&rft.spage=1573&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-27 N1 - Date created - 1997-03-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8462-6 [1326758] Endocrinology. 1984 May;114(5):1941-3 [6370671] Proc Natl Acad Sci U S A. 1993 May 1;90(9):3908-12 [8387201] J Biol Chem. 1993 Jun 15;268(17):12560-4 [8509396] FEBS Lett. 1990 Dec 17;277(1-2):7-10 [2269371] Endocrinology. 1991 Mar;128(3):1404-8 [1999162] Endocrinology. 1991 Sep;129(3):1207-14 [1874166] Endocrinology. 1991 Sep;129(3):1575-83 [1874189] Biochem Soc Trans. 1991 Apr;19(2):324-9 [1653733] Biochem Soc Trans. 1991 Apr;19(2):402-7 [1889622] J Steroid Biochem Mol Biol. 1991;40(1-3):143-54 [1958514] FEBS Lett. 1991 Dec 16;295(1-3):107-9 [1765140] Neuroendocrinology. 1984 Sep;39(3):256-60 [6504270] Proc Soc Exp Biol Med. 1985 May;179(1):132-5 [3921973] Brain Res. 1985 Oct 21;345(2):332-6 [3899285] J Biol Chem. 1986 Jul 5;261(19):8597-600 [3013856] Proc Natl Acad Sci U S A. 1987 Dec;84(23):8745-9 [3317420] Pharmacol Ther. 1988;38(3):387-417 [2848266] J Biol Chem. 1989 Jul 15;264(20):11762-7 [2663840] J Biol Chem. 1989 Oct 15;264(29):17069-77 [2793844] Am J Obstet Gynecol. 1990 Nov;163(5 Pt 2):1721-7 [2122728] Endocrinology. 1990 Dec;127(6):2884-90 [2123444] Science. 1992 Jan 24;255(5043):462-4 [1734523] Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1852-5 [1542682] J Biol Chem. 1992 Apr 15;267(11):7199-202 [1559964] Proc Natl Acad Sci U S A. 1992 May 1;89(9):4081-5 [1373893] Proc Natl Acad Sci U S A. 1992 May 1;89(9):4149-53 [1570341] Endocrinology. 1993 Oct;133(4):1624-32 [8404603] Endocrinology. 1993 Nov;133(5):2399-402 [8104781] Endocrinology. 1993 Dec;133(6):2481-7 [8243268] Endocr Rev. 1993 Oct;14(5):507-38 [8262004] J Membr Biol. 1993 Oct;136(1):85-96 [7505828] Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):395-9 [8278400] J Biol Chem. 1994 Feb 18;269(7):4860-5 [8106457] Neuroendocrinology. 1993 Nov;58(5):485-92 [8115017] Endocrinology. 1994 Mar;134(3):1446-54 [8119185] J Biol Chem. 1994 Apr 8;269(14):10511-6 [8144636] Mol Biol Cell. 1994 Jan;5(1):17-27 [8186462] Endocrinology. 1994 Jul;135(1):113-8 [7912182] J Cell Biochem. 1994 Apr;54(4):478-86 [8014197] J Neuroendocrinol. 1994 Apr;6(2):127-30 [7914132] Trends Neurosci. 1994 Dec;17(12):531-6 [7532338] J Neurophysiol. 1995 Jan;73(1):56-64 [7714589] Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3416-20 [7724577] Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):3918-22 [7537379] Eur J Pharmacol. 1995 Feb 15;288(3):231-50 [7774668] Endocrinology. 1995 Aug;136(8):3398-405 [7628375] Cell Mol Neurobiol. 1995 Feb;15(1):141-64 [7648606] Mol Biol Cell. 1995 Aug;6(8):1037-47 [7579706] Physiol Rev. 1995 Oct;75(4):865-85 [7480165] Neuroendocrinology. 1995 Sep;62(3):248-58 [8538862] Can J Biochem Physiol. 1959 Aug;37(8):911-7 [13671378] Science. 1992 Oct 23;258(5082):607-14 [1411571] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protein composition and morphology of human foamy virus intracellular cores and extracellular particles. AN - 78888810; 9123838 AB - Characterization of human foamy virus (HFV) gag-encoded precursors and the search for a Gag-Pol polyprotein and mature proteins derived from proteolytic processing were carried out in HFV-infected cells and with purified preassembled cores and extracellular virus by Western blotting and radioimmunoprecipitation using antisera against synthetic peptides corresponding to putative Gag and protease proteins. Precursor proteins, Pr78gag/74gag and Pr135pol, were found in the nucleus of epithelial and fibroblast cells 3-4 days after HFV infection. Kinetic analysis of HFV Pr78gag and Pr74gag indicated that Pr78gag is a precursor to Pr74gag. South-Western blot analysis indicated that Pr78gag and Pr74gag have properties associated with nucleic acid binding protein although they lack the typical zinc-finger motifs found in retroviral nucleocapsid proteins. Western blot analyses of preassembled HFV cores isolated from the cytoplasm of infected cells and purified by sucrose gradient centrifugation demonstrated the presence of Pr78gag/74gag and Pr135pol, but no proteolytically processed Gag proteins were observed. The majority of extracellular HFV particles were found to have pentagon-shaped cores, as observed intracellularly, and are believed to be the immature extracellular form of the virus. The highest concentration of extracellular particles, estimated by EM, Western blot, and reverse transcriptase assays were found in sucrose gradient fractions having a density of 1.21-1.24 g/cm3. Western blot analysis revealed that Pr78gag/74gag and Pr135pol were the major viral proteins associated with these extracellular particles, as only small amounts of putative proteolytically cleaved capsid (p32) were observed. Our results support the notion that Pol is translated independent of Gag in HFV-infected cells. JF - Virology AU - Morozov, V A AU - Copeland, T D AU - Nagashima, K AU - Gonda, M A AU - Oroszlan, S AD - Laboratory of Molecular Virology and Carcinogenesis, SAIC Frederick, NCI-Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1997/02/17/ PY - 1997 DA - 1997 Feb 17 SP - 307 EP - 317 VL - 228 IS - 2 SN - 0042-6822, 0042-6822 KW - DNA-Binding Proteins KW - 0 KW - Gene Products, gag KW - Gene Products, pol KW - Protein Precursors KW - Viral Core Proteins KW - Index Medicus KW - AIDS/HIV KW - Virus Assembly KW - Animals KW - Humans KW - Viral Core Proteins -- biosynthesis KW - DNA-Binding Proteins -- biosynthesis KW - Protein Precursors -- genetics KW - Amino Acid Sequence KW - Rabbits KW - Virion -- ultrastructure KW - Blotting, Western KW - Tumor Cells, Cultured KW - Protein Precursors -- biosynthesis KW - Molecular Sequence Data KW - Radioimmunoprecipitation Assay KW - Spumavirus -- metabolism KW - Gene Products, gag -- genetics KW - Gene Products, pol -- biosynthesis KW - Spumavirus -- ultrastructure KW - Gene Products, gag -- biosynthesis KW - Spumavirus -- chemistry KW - Gene Products, pol -- genetics KW - Spumavirus -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78888810?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Protein+composition+and+morphology+of+human+foamy+virus+intracellular+cores+and+extracellular+particles.&rft.au=Morozov%2C+V+A%3BCopeland%2C+T+D%3BNagashima%2C+K%3BGonda%2C+M+A%3BOroszlan%2C+S&rft.aulast=Morozov&rft.aufirst=V&rft.date=1997-02-17&rft.volume=228&rft.issue=2&rft.spage=307&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-21 N1 - Date created - 1997-04-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Malignant transformation of human prostate epithelial cells by N-nitroso-N-methylurea. AN - 78802257; 9044828 AB - We report the malignant transformation of adult human prostate epithelial cells after multiple exposures to the chemical carcinogen N-nitroso-N-methylurea. Such transformants showed morphological alterations and anchorage-independent growth in soft agar and induced carcinomas when transplanted into nude mice. No p53 or ras mutations were observed. Stepwise chromosomal changes in the progression to tumorigenicity were observed. Loss of the p arms of chromosome 8 (p10>pter) and chromosome 10 (p10>pter) and gain of the q arm of chromosome 8 (q10>qter) were only observed in the tumor outgrows. These findings provide the first evidence of malignant transformation of human prostate epithelial cells exposed to a chemical carcinogen. JF - Cancer research AU - Rhim, J S AU - Jin, S AU - Jung, M AU - Thraves, P J AU - Kuettel, M R AU - Webber, M M AU - Hukku, B AD - Laboratory of Biochemical Physiology, National Cancer Institute, Frederick, Maryland 21702, USA. Y1 - 1997/02/15/ PY - 1997 DA - 1997 Feb 15 SP - 576 EP - 580 VL - 57 IS - 4 SN - 0008-5472, 0008-5472 KW - Carcinogens KW - 0 KW - Neoplasm Proteins KW - Tumor Suppressor Protein p53 KW - Methylnitrosourea KW - 684-93-5 KW - ras Proteins KW - EC 3.6.5.2 KW - Index Medicus KW - Karyotyping KW - Animals KW - Tumor Suppressor Protein p53 -- analysis KW - ras Proteins -- analysis KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Adult KW - Chromosome Disorders KW - Tumor Cells, Cultured -- pathology KW - Mice, Nude KW - Mice KW - Neoplasm Proteins -- analysis KW - Male KW - Prostate -- drug effects KW - Chromosome Aberrations -- chemically induced KW - Cell Transformation, Neoplastic -- pathology KW - Cell Transformation, Neoplastic -- chemically induced KW - Prostate -- pathology KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78802257?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Malignant+transformation+of+human+prostate+epithelial+cells+by+N-nitroso-N-methylurea.&rft.au=Rhim%2C+J+S%3BJin%2C+S%3BJung%2C+M%3BThraves%2C+P+J%3BKuettel%2C+M+R%3BWebber%2C+M+M%3BHukku%2C+B&rft.aulast=Rhim&rft.aufirst=J&rft.date=1997-02-15&rft.volume=57&rft.issue=4&rft.spage=576&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-05 N1 - Date created - 1997-03-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tissue-specific stabilization of the thyroid hormone beta1 nuclear receptor by phosphorylation. AN - 78818590; 9020124 AB - The present study evaluated the expression and regulation of endogenous thyroid hormone receptors (TRs) in cultured cells. In COS-1 cells, the endogenous TR, subtype beta1 (TRbeta1), but not subtype beta2 or alpha1, was induced to express by okadaic acid (OA) in a concentration-dependent manner. The induced TRbeta1 had immunoreactivity and partial V8 proteolytic maps similar to those of the transfected and in vitro translated human TRbeta1 (h-TRbeta1). The OA-induced expression of endogenous TRbeta1 was, however, not observed in a variety of other cultured cell lines tested, indicating that the induction was cell type-dependent. TRbeta1 induced by OA was a multisite phosphorylated protein, in which serine and threonine in a ratio of 10:1 were phosphorylated. The induced TRbeta1 was functional as it could mediate the thyroid hormone-dependent transcriptional activity via several thyroid hormone response elements. The induction of endogenous TRbeta1 expression by OA was not accompanied by an increase in mRNA levels but was the result of an increase in the stability of the TRbeta1 protein. This is the first report to indicate that one of the mechanisms by which the TR isoforms are differentially expressed is via the tissue-specific stabilization of the TR isoform proteins. Furthermore, this selective stability of TRbeta1 could be conferred by phosphorylation. JF - The Journal of biological chemistry AU - Ting, Y T AU - Bhat, M K AU - Wong, R AU - Cheng, S y AD - Laboratory of Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1997/02/14/ PY - 1997 DA - 1997 Feb 14 SP - 4129 EP - 4134 VL - 272 IS - 7 SN - 0021-9258, 0021-9258 KW - Phosphoproteins KW - 0 KW - RNA, Messenger KW - Receptors, Thyroid Hormone KW - Okadaic Acid KW - 1W21G5Q4N2 KW - Index Medicus KW - Animals KW - Transcription, Genetic -- drug effects KW - Phosphoproteins -- genetics KW - RNA, Messenger -- metabolism KW - Phosphorylation KW - COS Cells KW - Humans KW - Okadaic Acid -- pharmacology KW - RNA, Messenger -- genetics KW - Cell Line KW - Phosphoproteins -- metabolism KW - Receptors, Thyroid Hormone -- metabolism KW - Receptors, Thyroid Hormone -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78818590?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Tissue-specific+stabilization+of+the+thyroid+hormone+beta1+nuclear+receptor+by+phosphorylation.&rft.au=Ting%2C+Y+T%3BBhat%2C+M+K%3BWong%2C+R%3BCheng%2C+S+y&rft.aulast=Ting&rft.aufirst=Y&rft.date=1997-02-14&rft.volume=272&rft.issue=7&rft.spage=4129&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-14 N1 - Date created - 1997-03-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interaction of the GTP-binding and GTPase-activating domains of ARD1 involves the effector region of the ADP-ribosylation factor domain. AN - 78818555; 9020091 AB - ADP-ribosylation factors (ARFs) are a family of approximately 20-kDa guanine nucleotide-binding proteins and members of the Ras superfamily, originally identified and purified by their ability to enhance the ADP-ribosyltransferase activity of cholera toxin and more recently recognized as critical participants in vesicular trafficking pathways and phospholipase D activation. ARD1 is a 64-kDa protein with an 18-kDa carboxyl-terminal ARF domain (p3) and a 46-kDa amino-terminal extension (p5) that is widely expressed in mammalian tissues. Using recombinant proteins, we showed that p5, the amino-terminal domain of ARD1, stimulates the GTPase activity of p3, the ARF domain, and appears to be the GTPase-activating protein (GAP) component of this bifunctional protein, whereas in other members of the Ras superfamily a separate GAP molecule interacts with the effector region of the GTP-binding protein. p5 stimulated the GTPase activity of p3 but not of ARF1, which differs from p3 in several amino acids in the effector domain. After substitution of 7 amino acids from p3 in the appropriate position in ARF1, the chimeric protein ARF1(39-45p3) bound to p5, which increased its GTPase activity. Specifically, after Gly40 and Thr45 in the putative effector domain of ARF1 were replaced with the equivalent Asp and Pro, respectively, from p3, functional interaction of the chimeric ARF1 with p5 was increased. Thus, Asp25 and Pro30 of the ARF domain (p3) of ARD1 are involved in its functional and physical interaction with the GTPase-activating (p5) domain of ARD1. After deletion of the amino-terminal 15 amino acids from ARF1(39-45p3), its interaction with p5 was essentially equivalent to that of p3, suggesting that the amino terminus of ARF1(39-45p3) may interfere with binding to p5. These results are consistent with the conclusion that the GAP domain of ARD1 interacts with the effector region of the ARF domain and thereby stimulates GTP hydrolysis. JF - The Journal of biological chemistry AU - Vitale, N AU - Moss, J AU - Vaughan, M AD - Pulmonary-Critical Care Medicine Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/02/14/ PY - 1997 DA - 1997 Feb 14 SP - 3897 EP - 3904 VL - 272 IS - 7 SN - 0021-9258, 0021-9258 KW - Phospholipids KW - 0 KW - Recombinant Proteins 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 - Acetyltransferases KW - EC 2.3.1.- KW - protein N-terminal acetyltransferase KW - GTP Phosphohydrolases KW - EC 3.6.1.- KW - GTP-Binding Proteins KW - ADP-Ribosylation Factor 1 KW - EC 3.6.5.2 KW - ADP-Ribosylation Factors KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- metabolism KW - Phospholipids -- metabolism KW - Guanosine 5'-O-(3-Thiotriphosphate) -- metabolism KW - Recombinant Proteins -- genetics KW - Protein Binding KW - Cholera Toxin -- metabolism KW - Binding Sites KW - Acetyltransferases -- metabolism KW - GTP-Binding Proteins -- metabolism KW - GTP Phosphohydrolases -- metabolism KW - Acetyltransferases -- genetics KW - Guanosine Triphosphate -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78818555?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Interaction+of+the+GTP-binding+and+GTPase-activating+domains+of+ARD1+involves+the+effector+region+of+the+ADP-ribosylation+factor+domain.&rft.au=Vitale%2C+N%3BMoss%2C+J%3BVaughan%2C+M&rft.aulast=Vitale&rft.aufirst=N&rft.date=1997-02-14&rft.volume=272&rft.issue=7&rft.spage=3897&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-14 N1 - Date created - 1997-03-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant DNA research: proposed actions under the guidelines; notice. AN - 78718933; 11654870 JF - Federal register AU - U.S. National Institutes of Health AD - U.S. National Institutes of Health Y1 - 1997/02/14/ PY - 1997 DA - 1997 Feb 14 SP - 7108 EP - 7123 VL - 62 IS - 31 SN - 0097-6326, 0097-6326 KW - DNA, Recombinant KW - 0 KW - Hazardous Substances KW - Bioethics KW - Recombinant DNA Advisory Committee KW - Biomedical and Behavioral Research KW - Genetics and Reproduction KW - National Institutes of Health KW - NIH Guidelines KW - Legal Approach KW - Office of Recombinant DNA Activities KW - United States KW - Financing, Government KW - Organization and Administration KW - Ethics Committees KW - United States Food and Drug Administration KW - Humans KW - Guidelines as Topic KW - Committee Membership KW - Ethics Committees, Research KW - Organisms, Genetically Modified KW - Industry KW - Containment of Biohazards KW - Government Regulation KW - Government KW - Social Control, Formal KW - National Institutes of Health (U.S.) KW - Human Experimentation KW - Genetic Therapy KW - Federal Government KW - Public Policy KW - Advisory Committees UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78718933?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Federal+register&rft.atitle=Recombinant+DNA+research%3A+proposed+actions+under+the+guidelines%3B+notice.&rft.au=U.S.+National+Institutes+of+Health&rft.aulast=U.S.+National+Institutes+of+Health&rft.aufirst=&rft.date=1997-02-14&rft.volume=62&rft.issue=31&rft.spage=7108&rft.isbn=&rft.btitle=&rft.title=Federal+register&rft.issn=00976326&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-01-07 N1 - Date created - 1998-01-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular basis of receptor/G protein coupling selectivity studied by coexpression of wild type and mutant m2 muscarinic receptors with mutant G alpha(q) subunits. AN - 78806193; 9063897 AB - The molecular basis of receptor/G protein coupling selectivity was studied by using the m2 muscarinic receptor, a prototypical G(i/o)-coupled receptor as a model system. We could recently show that the m2 receptor can efficiently interact with mutant G protein alpha(q) subunits in which the last five amino acids were replaced with alpha(i2) or alpha(o) sequence [Liu, J., Conklin, B. R., Blin, N., Yun, J., & Wess, J. (1995) Proc. Natl. Acad. Sci. U.S.A. 92, 11642-11646]. Additional mutagenesis studies led to the identification of a four-amino-acid motif on the m2 receptor (Val385, Thr386, Ile389, and Leu390) that is predicted to functionally interact with the C-terminal portion of alpha(i/o) subunits. To further investigate the structural requirements for this interaction to occur, these four m2 receptor residues were replaced, either individually or in combination, with the corresponding residues present in the G(q/11)-coupled muscarinic receptors (m1, m3, and m5). The ability of the resulting mutant m2 receptors to interact with a mutant alpha(q) subunit (qo5) in which the last five amino acids were replaced with alpha(o) sequence was investigated in co-transfected COS-7 cells [studied biochemical response: stimulation of phosphatidyl inositol (PI) hydrolysis]. Our data suggest that the presence of three of the four targeted m2 receptor residues (Val385, Thr386, and Ile389) is essential for efficient recognition of C-terminal alpha(i/o) sequences. To study which specific amino acids within the C-terminal segment of alpha(i/o) subunits are critical for this interaction to occur, the wild type m2 receptor was co-expressed with a series of mutant alpha(q) subunits containing single or multiple alpha(q) --> alpha(i1,2) point mutations at their C-terminus. Remarkably, the wild type m2 receptor, while unable to efficiently stimulate wild type alpha(q), gained the ability to productively interact with three alpha(q) single-point mutants, providing the first example that the receptor coupling selectivity of G protein alpha subunits can be switched by single amino acid substitutions. Given the high degree of structural homology among different G protein-coupled receptors and among different classes of G protein alpha subunits, our results should be of broad general relevance. JF - Biochemistry AU - Kostenis, E AU - Conklin, B R AU - Wess, J AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA. Y1 - 1997/02/11/ PY - 1997 DA - 1997 Feb 11 SP - 1487 EP - 1495 VL - 36 IS - 6 SN - 0006-2960, 0006-2960 KW - Phosphoproteins KW - 0 KW - RGS Proteins KW - Receptor, Muscarinic M2 KW - Receptor, Muscarinic M3 KW - Receptors, Muscarinic KW - regulator of G-protein signalling 19 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - COS Cells KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Protein Conformation KW - Receptors, Muscarinic -- genetics KW - Receptors, Muscarinic -- metabolism KW - Phosphoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78806193?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=Molecular+basis+of+receptor%2FG+protein+coupling+selectivity+studied+by+coexpression+of+wild+type+and+mutant+m2+muscarinic+receptors+with+mutant+G+alpha%28q%29+subunits.&rft.au=Kostenis%2C+E%3BConklin%2C+B+R%3BWess%2C+J&rft.aulast=Kostenis&rft.aufirst=E&rft.date=1997-02-11&rft.volume=36&rft.issue=6&rft.spage=1487&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-17 N1 - Date created - 1997-03-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential mechanisms of cytochrome P450 inhibition and activation by alpha-naphthoflavone. AN - 78797202; 9013547 AB - The anticarcinogenicity of some flavonoids has been attributed to modulation of the cytochrome P450 enzymes, which metabolize procarcinogens to their activated forms. However, the mechanism by which flavonoids inhibit some P450-mediated activities while activating others is a longstanding, intriguing question. We employed flash photolysis to measure carbon monoxide binding to P450 as a rapid kinetic technique to probe the interaction of the prototype flavonoid alpha-naphthoflavone with human cytochrome P450s 1A1 and 3A4, whose benzo[a]pyrene hydroxylation activities are respectively inhibited and stimulated by this compound. This flavonoid inhibited P450 1A1 binding to benzo[a]pyrene via a classical competitive mechanism. In contrast, alpha-naphthoflavone stimulated P450 3A4 by selectively binding and activating an otherwise inactive subpopulation of this P450 and promoting benzo[a]pyrene binding to the latter. These data indicate that flavonoids enhance activity by increasing the pool of active P450 molecules within this P450 macrosystem. Activators in other biological systems may similarly exert their effect by expanding the population of active receptor molecules. JF - The Journal of biological chemistry AU - Koley, A P AU - Buters, J T AU - Robinson, R C AU - Markowitz, A AU - Friedman, F K AD - Laboratory of Molecular Carcinogenesis, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/02/07/ PY - 1997 DA - 1997 Feb 07 SP - 3149 EP - 3152 VL - 272 IS - 6 SN - 0021-9258, 0021-9258 KW - Benzoflavones KW - 0 KW - Cytochrome P-450 Enzyme Inhibitors KW - Benzo(a)pyrene KW - 3417WMA06D KW - alpha-naphthoflavone KW - 604-59-1 KW - Carbon Monoxide KW - 7U1EE4V452 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - CYP3A protein, human KW - EC 1.14.14.1 KW - Cytochrome P-450 CYP3A KW - Index Medicus KW - Photolysis KW - Mixed Function Oxygenases -- metabolism KW - Enzyme Activation KW - Kinetics KW - Humans KW - Cytochrome P-450 Enzyme System -- metabolism KW - Models, Chemical KW - Carbon Monoxide -- metabolism KW - Benzo(a)pyrene -- metabolism KW - Benzoflavones -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78797202?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Differential+mechanisms+of+cytochrome+P450+inhibition+and+activation+by+alpha-naphthoflavone.&rft.au=Koley%2C+A+P%3BButers%2C+J+T%3BRobinson%2C+R+C%3BMarkowitz%2C+A%3BFriedman%2C+F+K&rft.aulast=Koley&rft.aufirst=A&rft.date=1997-02-07&rft.volume=272&rft.issue=6&rft.spage=3149&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-02 N1 - Date created - 1997-04-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparative enzymatic study of HIV-1 reverse transcriptase resistant to 2',3'-dideoxynucleotide analogs using the single-nucleotide incorporation assay. AN - 78814455; 9033399 AB - Employing the single-nucleotide incorporation assay using a heteropolymeric RNA template and DNA primers, we defined enzymatic profiles of recombinant human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) containing a set of five mutations [A62V, V75I, F77L, F116Y, and Q151M] which confers resistance to multiple 2',3'-dideoxynucleosides (ddNs) on HIV-1. RTs containing other drug-resistance-associated mutations were also examined. The K(m) for dNTPs, the kcat, and the kcat/ K(m) ratios of mutant RTs were all comparable to those of wild-type RT (RTwt). The processive primer extension activity of mutant RTs was also comparable to that of RTwt as examined in the presence of saturating concentrations of dNTPs and heparin. Determination of the Ki values toward 5'-triphosphates (TP) of various ddNs [3'-azido-2',3'-dideoxythymidine (AZT), 2',3'-didehydro-2',3'-dideoxythymidine (D4T), 2',3'-dideoxycytidine (ddC), (-)-beta-L-2',3'-dideoxy-3'-thiacytidine (3TC), (-)-beta-L-2',3'-dideoxy-5-fluorocytidine (FddC), 2',3'-dideoxyadenosine (ddA), and 2'-beta-fluoro-2',3'-dideoxyadenosine (FddA)] and 9-(2-phosphonylmethoxyethyl)adenine diphosphate (PMEApp) revealed that RTA62V/V75I/F77L/F116Y/Q151M was insensitive to ddATP, AZTTP, D4TTP, FddATP, and ddCTP, but was sensitive to PMEApp, 3TCTP, and FddCTP. RTK65R was less sensitive to ddATP, FddATP, PMEApp, ddCTP, and 3TCTP, while RTM184V was less sensitive only to 3TCTP and ddCTP. The determination of Ki(ddNTP)/K(m)(dNTP) ratios showed that AZTTP, D4TTP, and ddCTP are, as substrates, as efficient for RTwt as their corresponding dNTPs, that ddATP, PMEApp, and 3TCTP are moderately efficient substrates for RTwt, and that FddATP is the least efficient substrate among ddNTPs examined. The observed cross-resistance of HIV-1 RT to various ddNTPs should reflect the alteration of RT's substrate recognition and should provide insights into the molecular mechanism of RT discrimination of ddNTPs from natural substrates. JF - Biochemistry AU - Ueno, T AU - Mitsuya, H AD - Experimental Retrovirology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/02/04/ PY - 1997 DA - 1997 Feb 04 SP - 1092 EP - 1099 VL - 36 IS - 5 SN - 0006-2960, 0006-2960 KW - Anti-HIV Agents KW - 0 KW - DNA Primers KW - Deoxyribonucleotides KW - Recombinant Proteins KW - Reverse Transcriptase Inhibitors KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - Index Medicus KW - AIDS/HIV KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Kinetics KW - Humans KW - Point Mutation KW - Templates, Genetic KW - Recombinant Proteins -- antagonists & inhibitors KW - Structure-Activity Relationship KW - Reverse Transcriptase Inhibitors -- pharmacology KW - Anti-HIV Agents -- pharmacology KW - HIV Reverse Transcriptase -- metabolism KW - HIV-1 -- enzymology KW - Deoxyribonucleotides -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78814455?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Comparative+enzymatic+study+of+HIV-1+reverse+transcriptase+resistant+to+2%27%2C3%27-dideoxynucleotide+analogs+using+the+single-nucleotide+incorporation+assay.&rft.au=Ueno%2C+T%3BMitsuya%2C+H&rft.aulast=Ueno&rft.aufirst=T&rft.date=1997-02-04&rft.volume=36&rft.issue=5&rft.spage=1092&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-17 N1 - Date created - 1997-03-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of tyrosinase-related protein 2 as a tumor rejection antigen for the B16 melanoma. AN - 78825316; 9053445 AB - Recently, major advances have been made in the identification of antigens from human melanoma which are recognized by T cells. In spite of this, little is known about the optimal ways to use these antigens to treat patients with cancer. Progress in this area is likely to require accurate preclinical animal models, but the availability of such models has lagged behind developments in human tumor immunology. Whereas many of the identified human melanoma antigens are normal tissue differentiation proteins, analogous murine tumor antigens have not yet been identified. In this paper we identify a normal tissue differentiation antigen, tyrosinase-related protein 2 (TRP-2), expressed by the murine B16 melanoma which was found by screening a cDNA library from B16 with tumor-reactive cytotoxic T lymphocytes (CTL). A peptide conforming to the predicted MHC class I H2-Kb binding motif, TRP-2181-188, was identified as the major reactive epitope within TRP-2 recognized by these anti-B16 CTLs. By site-directed mutagenesis, it was shown that alteration of this epitope eliminated recognition of TRP-2. It was further demonstrated that a CTL line raised from splenocytes by repeated stimulation in vitro with this peptide could recognize B16 tumor and was therapeutic against 3-d-old established pulmonary metastases. The use of TRP-2 in a preclinical model of tumor immunotherapy may be helpful in suggesting optimal vaccination strategies for cancer therapy in patients. JF - The Journal of experimental medicine AU - Bloom, M B AU - Perry-Lalley, D AU - Robbins, P F AU - Li, Y AU - el-Gamil, M AU - Rosenberg, S A AU - Yang, J C AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/02/03/ PY - 1997 DA - 1997 Feb 03 SP - 453 EP - 459 VL - 185 IS - 3 SN - 0022-1007, 0022-1007 KW - Antigens, Neoplasm KW - 0 KW - Isomerases KW - EC 5.- KW - Intramolecular Oxidoreductases KW - EC 5.3.- KW - dopachrome isomerase KW - EC 5.3.3.12 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Base Sequence KW - Tumor Cells, Cultured KW - Molecular Sequence Data KW - Mice, Inbred C57BL KW - Mice KW - Vaccination KW - T-Lymphocytes -- immunology KW - Female KW - Structure-Activity Relationship KW - Isomerases -- immunology KW - Antigens, Neoplasm -- analysis KW - Melanoma, Experimental -- therapy KW - Melanoma, Experimental -- immunology KW - Isomerases -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78825316?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Identification+of+tyrosinase-related+protein+2+as+a+tumor+rejection+antigen+for+the+B16+melanoma.&rft.au=Bloom%2C+M+B%3BPerry-Lalley%2C+D%3BRobbins%2C+P+F%3BLi%2C+Y%3Bel-Gamil%2C+M%3BRosenberg%2C+S+A%3BYang%2C+J+C&rft.aulast=Bloom&rft.aufirst=M&rft.date=1997-02-03&rft.volume=185&rft.issue=3&rft.spage=453&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 - 1997-03-13 N1 - Date created - 1997-03-13 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - UNKNOWN; GENBANK N1 - SuppNotes - Cited By: J Mol Biol. 1990 Oct 5;215(3):403-10 [2231712] J Exp Med. 1996 Dec 1;184(6):2207-16 [8976176] Science. 1991 Dec 13;254(5038):1643-7 [1840703] Int J Cancer. 1992 Jan 21;50(2):289-97 [1730522] EMBO J. 1992 Feb;11(2):527-35 [1537334] Eur J Immunol. 1992 Sep;22(9):2283-8 [1381312] J Exp Med. 1993 Aug 1;178(2):489-95 [8340755] J Exp Med. 1994 Mar 1;179(3):921-30 [8113684] Nature. 1994 May 5;369(6475):67-71 [8164742] Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3515-9 [8170938] Cancer Res. 1994 Jun 15;54(12):3124-6 [8205528] Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6458-62 [8022805] J Natl Cancer Inst. 1994 Aug 3;86(15):1159-66 [8028037] Eur J Immunol. 1994 Nov;24(11):2740-5 [7525302] J Exp Med. 1995 Feb 1;181(2):799-804 [7836932] Immunogenetics. 1995;41(4):178-228 [7890324] Immunity. 1995 Feb;2(2):167-75 [7895173] Biol Cell. 1994;81(3):195-203 [7696973] Behring Inst Mitt. 1994 Dec;(95):7-13 [7538751] J Exp Med. 1995 Sep 1;182(3):689-98 [7544395] Science. 1995 Sep 1;269(5228):1281-4 [7652577] J Exp Med. 1996 Mar 1;183(3):1185-92 [8642260] J Exp Med. 1996 Aug 1;184(2):647-57 [8760818] J Exp Med. 1991 Jun 1;173(6):1373-84 [1903428] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I trial with fixed-dose carboplatin and escalating doses of paclitaxel in advanced ovarian cancer. AN - 85262856; pmid-9045331 AB - A dose-finding study involving 27 untreated patients with ovarian cancer was performed to define the maximum tolerated dose of a 3-hour infusion of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) combined with a fixed dose of carboplatin. The median age of the study patients was 55 years (age range, 30 to 74 years), the median Eastern Cooperative Oncology Group performance status was 0 (range, 0 to 2), and residual tumor to first surgery was > or = 1 cm in 14 patients and less than 1 cm in 13 patients. All patients received carboplatin at a fixed dose of 300 mg/m2 over 1 hour. Paclitaxel was administered at five dose levels starting at 150 mg/m2 and increasing in 25-mg/m2 increments to 250 mg/m2. In the absence of toxicity, courses were repeated every 4 weeks for a total of six cycles. World Health Organization grade 1 hypersensitivity and cardiotoxicity were observed in 7.4% and 14.8% of patients, respectively. Moderate peripheral neuropathy was experienced by 29.6% of patients. Grades 3 and 4 neutropenia lasted less than 7 days; no patient required hospitalization for sepsis or febrile neutropenia, and no supportive treatment with granulocyte or granulocyte-macrophage colony-stimulating factor was needed. The maximum tolerated paclitaxel dose was not achieved. JF - Seminars in Oncology AU - Bolis, G AU - Scarfone, G AU - Villa, A AU - Acerboni, S AU - Siliprandi, V AU - Guarnerio, P AD - National Cancer Institute, 1st Department of Obstetrics and Gynecology, University of Milan, Italy. PY - 1997 SP - S2 EP - 23 VL - 24 IS - 1 Suppl 2 SN - 0093-7754, 0093-7754 KW - Drug Administration Schedule KW - Ovarian Neoplasms KW - Paclitaxel KW - Human KW - Antineoplastic Combined Chemotherapy Protocols KW - Aged KW - Middle Age KW - Pilot Projects KW - Carboplatin KW - Female UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85262856?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+Oncology&rft.atitle=A+phase+I+trial+with+fixed-dose+carboplatin+and+escalating+doses+of+paclitaxel+in+advanced+ovarian+cancer.&rft.au=Bolis%2C+G%3BScarfone%2C+G%3BVilla%2C+A%3BAcerboni%2C+S%3BSiliprandi%2C+V%3BGuarnerio%2C+P&rft.aulast=Bolis&rft.aufirst=G&rft.date=1997-02-01&rft.volume=24&rft.issue=1+Suppl+2&rft.spage=S2&rft.isbn=&rft.btitle=&rft.title=Seminars+in+Oncology&rft.issn=00937754&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Auditory working memory and Wisconsin Card Sorting Test performance in schizophrenia. AN - 85254538; pmid-9040284 AB - BACKGROUND: Impaired Wisconsin Card Sorting Test (WCST) performance has been one critical piece of evidence suggesting frontal lobe dysfunction in schizophrenia. However, the specific cognitive processes underlying impaired performance have not been identified. Impaired WCST performance in schizophrenia might in part reflect a fundamental working memory deficit. METHODS: We examined the performance of 30 normal subjects and 36 patients with schizophrenia on a neuropsychological battery including a novel measure of working memory-letter-number (LN) span. RESULTS: Patients with schizophrenia were impaired on LN span performance, which was also highly correlated with WCST performance (r = 0.74). Between-group WCST differences were eliminated when we covaried LN span. Regression analyses suggested that LN span performance predicted the WCST category achieved score, whereas measures of set shifting, verbal fluency, and attention were predictive of perseveration. CONCLUSION: Working memory may be a critical determinant of one aspect of WCST performance in schizophrenia. JF - Archives of General Psychiatry AU - Gold, J M AU - Carpenter, C AU - Randolph, C AU - Goldberg, T E AU - Weinberger, D R AD - Clinical Research Services Branch, National Institute of Mental Health, Washington, DC, USA. PY - 1997 SP - 159 EP - 165 VL - 54 IS - 2 SN - 0003-990X, 0003-990X KW - Frontal Lobe KW - Schizophrenia KW - Wechsler Scales KW - Regression Analysis KW - Hospitalization KW - Human KW - Adult KW - Memory KW - Neuropsychological Tests KW - Auditory Perception UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85254538?accountid=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+General+Psychiatry&rft.atitle=Auditory+working+memory+and+Wisconsin+Card+Sorting+Test+performance+in+schizophrenia.&rft.au=Gold%2C+J+M%3BCarpenter%2C+C%3BRandolph%2C+C%3BGoldberg%2C+T+E%3BWeinberger%2C+D+R&rft.aulast=Gold&rft.aufirst=J&rft.date=1997-02-01&rft.volume=54&rft.issue=2&rft.spage=159&rft.isbn=&rft.btitle=&rft.title=Archives+of+General+Psychiatry&rft.issn=0003990X&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Microsporidium-associated sinusitis. AN - 85234011; pmid-9046697 AB - Two cases of biopsy-proven Microsporidium-associated chronic sinusitis in HIV-seropositive patients are presented. Spores of Septata intestinalis were identified by light microscopy and confirmed by electron microscopy in each case. Both patients displayed severe deficiencies of nasal mucosa CD4-positive cells, demonstrated by immunohistochemical methods. Only two other cases of Septata intestinalis-associated sinusitis have been reported previously. Our observations agree with the theory that functional defects in local mucosal immunity may partially explain the acquisition of opportunistic mucosal infections in many HIV-seropositive patients. JF - Ear, Nose, and Throat Journal AU - Moss, R B AU - Beaudet, L M AU - Wenig, B M AU - Nelson, A M AU - Firpo, A AU - Punja, U AU - Scott, T S AU - Kaliner, M A AD - Allergic Disease Section, NIAID, NIH, Bethesda, Maryland, USA. PY - 1997 SP - 95 EP - 101 VL - 76 IS - 2 SN - 0145-5613, 0145-5613 KW - Fatal Outcome KW - Human KW - Tomography, X-Ray Computed KW - Animal KW - Biopsy KW - Sinusitis KW - HIV Seropositivity KW - Microsporida KW - AIDS-Related Opportunistic Infections KW - Adult KW - Nasal Mucosa KW - Immunocompromised Host KW - Case Report KW - Immunohistochemistry KW - Microsporidiosis KW - Male UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85234011?accountid=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=Ear%2C+Nose%2C+and+Throat+Journal&rft.atitle=Microsporidium-associated+sinusitis.&rft.au=Moss%2C+R+B%3BBeaudet%2C+L+M%3BWenig%2C+B+M%3BNelson%2C+A+M%3BFirpo%2C+A%3BPunja%2C+U%3BScott%2C+T+S%3BKaliner%2C+M+A&rft.aulast=Moss&rft.aufirst=R&rft.date=1997-02-01&rft.volume=76&rft.issue=2&rft.spage=95&rft.isbn=&rft.btitle=&rft.title=Ear%2C+Nose%2C+and+Throat+Journal&rft.issn=01455613&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Semantic, phonological, and perceptual changes following left and right intracarotid injection (Wada) with a low amytal dosage. AN - 85211394; pmid-9056278 AB - Intracarotid injection of a low dosage of amobarbital (75 mg, 5% solution) was studied in 30 temporal lobectomy candidates while naming achromatic, incongruously, and congruously colored pictorial objects and reading real, nonsense, and embedded words. Semantic errors and phonological alexia followed the left injection, while the right injection induced visuoperceptual errors. When the contralateral hemisphere was anesthetized, the left brain formulated supraordinate categories for words and objects, while the right brain applied concrete labels. The basic language proficiency of patients influenced recovery and outcome; left temporal patients who were interictally anomic performed especially poorly after both injections. Codifying phonological and perceptual changes during the intracarotid amobarbital procedure can improve interpretations about language laterality and organization. JF - Brain and Cognition AU - Fedio, P AU - August, A AU - Patronas, N AU - Sato, S AU - Kufta, C AD - Department of Neuropsychology, National Institute of Neurological Disorders and Stroke and Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1997 SP - 98 EP - 117 VL - 33 IS - 1 SN - 0278-2626, 0278-2626 KW - Injections, Intra-Arterial KW - Human KW - Adult KW - Language Disorders KW - Laterality KW - Memory Disorders KW - Perceptual Disorders KW - Male KW - Female KW - Amobarbital KW - Carotid Artery, Internal KW - Phonetics KW - Semantics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85211394?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+and+Cognition&rft.atitle=Semantic%2C+phonological%2C+and+perceptual+changes+following+left+and+right+intracarotid+injection+%28Wada%29+with+a+low+amytal+dosage.&rft.au=Fedio%2C+P%3BAugust%2C+A%3BPatronas%2C+N%3BSato%2C+S%3BKufta%2C+C&rft.aulast=Fedio&rft.aufirst=P&rft.date=1997-02-01&rft.volume=33&rft.issue=1&rft.spage=98&rft.isbn=&rft.btitle=&rft.title=Brain+and+Cognition&rft.issn=02782626&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Nitric oxide and some nitric oxide donor compounds enhance the cytotoxicity of cisplatin. AN - 79616800; 9701048 AB - A major emphasis in cancer therapy research is finding mechanisms to enhance the effectiveness of clinically used chemotherapeutic agents. In this report, we show the effects of direct NO exposure or NO delivery agents such as NONOate NO donors, DEA/NO ((C2H5)2N[N(O)NO]-Na+) and PAPA/ NO (NH2(C3H6)(N[N(O)NO]C3H7)), or S-nitrosothiol NO donors (GSNO, S-nitrosoglutathione, and SNAP, S-nitroso-N-acetylpenicillamine) on the cytotoxicity of cisplatin with Chinese hamster V79 lung fibroblast cells. Cells pretreated with bolus NO or NO delivered from NONOate NO donors were markedly sensitized to subsequent cisplatin treatment, whereas S-nitrosothiol NO donors exerted little effect. The enhancement in cisplatin cytotoxicity from pretreatment with DEA/NO and PAPA/ NO persisted for approximately 180 and 240 min, respectively; thereafter cytotoxicity returned to a level consistent with cisplatin treatment alone. Pretreatment of cells with GSNO or SNAP did not enhance cisplatin cytotoxity. To discern why there were differential effects among the different NO donors, formation of NO over the time course of the experiment was assessed by the nitrosation of 2,3-diaminonaphthylene. Bolus NO, DEA/NO, and PAPA/NO produced more reactive nitrogen oxide species (RNOS) than did treatment with GSNO or SNAP. Previously reported electrochemical studies revealed that temporal NO concentrations measured from DEA/NO and PAPA/NO (1 mM) were greater than 5 microM. It appears that the flux of NO, as well as the amount of RNOS, is important in the NO-mediated enhancement of cisplatin cytotoxicity. Our results demonstrate the importance of NO delivery systems in the enhancement of cisplatin cytotoxicity and may provide insights into strategies for participation of NO donors and nitric oxide synthase with cisplatin therapy. JF - Nitric oxide : biology and chemistry AU - Wink, D A AU - Cook, J A AU - Christodoulou, D AU - Krishna, M C AU - Pacelli, R AU - Kim, S AU - DeGraff, W AU - Gamson, J AU - Vodovotz, Y AU - Russo, A AU - Mitchell, J B AD - Radiation Biology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1997/02// PY - 1997 DA - February 1997 SP - 88 EP - 94 VL - 1 IS - 1 SN - 1089-8603, 1089-8603 KW - Antineoplastic Agents KW - 0 KW - Nitric Oxide KW - 31C4KY9ESH KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Animals KW - Spectrometry, Fluorescence KW - Cricetulus KW - Mice KW - Nitric Oxide Synthase -- analysis KW - Drug Synergism KW - Cell Line KW - Cricetinae KW - Cisplatin -- pharmacology KW - Nitric Oxide -- pharmacology KW - Nitric Oxide -- chemistry KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79616800?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nitric+oxide+%3A+biology+and+chemistry&rft.atitle=Nitric+oxide+and+some+nitric+oxide+donor+compounds+enhance+the+cytotoxicity+of+cisplatin.&rft.au=Wink%2C+D+A%3BCook%2C+J+A%3BChristodoulou%2C+D%3BKrishna%2C+M+C%3BPacelli%2C+R%3BKim%2C+S%3BDeGraff%2C+W%3BGamson%2C+J%3BVodovotz%2C+Y%3BRusso%2C+A%3BMitchell%2C+J+B&rft.aulast=Wink&rft.aufirst=D&rft.date=1997-02-01&rft.volume=1&rft.issue=1&rft.spage=88&rft.isbn=&rft.btitle=&rft.title=Nitric+oxide+%3A+biology+and+chemistry&rft.issn=10898603&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 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 - Alcohol's impact upon glycobiology. AN - 79356629; 9343953 AB - This report reviews and illustrates ways in which some of the problems linked to excessive alcohol intake may develop from alcohol-induced alterations of eukaryotic cell surface molecules. Alcohol is the number one drug of abuse in the US, affecting at least 15 million Americans and causing annual losses of more than $80 billion and 100,000 lives. An estimated 20-40% of all persons admitted to general hospitals have alcohol-related problems and are often undiagnosed alcoholics being treated for the consequences of their drinking. Chronic alcohol-related cirrhosis of the liver is the ninth leading cause of death in the US, with over 28,000 deaths annually. Alcohol has harmful effects on almost every organ system in the body, producing cardiovascular disorders, liver disease, neuropathological illness and fetal injury. The etiologic mechanisms for these effects of alcohol is a research area of considerable importance to the National Institute for Alcohol Abuse and Alcoholism. JF - Indian journal of biochemistry & biophysics AU - Lands, W E AD - Division of Basic Research, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD 20892-7003, USA. PY - 1997 SP - 212 EP - 213 VL - 34 IS - 1-2 SN - 0301-1208, 0301-1208 KW - Glycoconjugates KW - 0 KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Liver Diseases, Alcoholic -- metabolism KW - Cell Membrane -- drug effects KW - Humans KW - Alcoholism -- metabolism KW - Cell Membrane -- metabolism KW - Signal Transduction KW - Liver Diseases, Alcoholic -- etiology KW - Glycoconjugates -- metabolism KW - Ethanol -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79356629?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Indian+journal+of+biochemistry+%26+biophysics&rft.atitle=Alcohol%27s+impact+upon+glycobiology.&rft.au=Lands%2C+W+E&rft.aulast=Lands&rft.aufirst=W&rft.date=1997-02-01&rft.volume=34&rft.issue=1-2&rft.spage=212&rft.isbn=&rft.btitle=&rft.title=Indian+journal+of+biochemistry+%26+biophysics&rft.issn=03011208&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-23 N1 - Date created - 1997-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Changes in cigarette smoking not observed following repeated cocaine self-administration. AN - 79158673; 9234039 AB - Acute administration of some psychoactive drugs (e.g., cocaine, heroin, methadone d-amphetamine) has been found to increase spontaneous cigarette smoking for 1-3 hr, but the effects of chronic drug administration have not been systematically studied. Computerized cigarette dispensers were used to study the effects of multiple daily cocaine administrations on cigarette smoking. Participants were 8 (5 male) cocaine-dependent cigarette smokers who resided on a closed clinical research ward and smoked an average of 16.7 cigarettes per day during the week prior to starting the study. During test sessions on Monday, Wednesday, and Friday of each week, participants could obtain either cocaine (25 mg i.v.) on 2 days or saline (1 ml i.v.) on the other day, 3 times per day at 2-hr intervals under double-blind conditions. The number of cigarettes dispensed during study days was analyzed in 2-hr increments. No significant cocaine effect was found. These findings fail to show a change in the number of cigarettes smoked after chronic cocaine self-administration over time intervals longer than 1-3 hr. JF - Experimental and clinical psychopharmacology AU - Radzius, A AU - Carriero, N J AU - Weinhold, L L AU - Gorelick, D A AU - Henningfield, J E AD - Clinical Pharmacology Branch, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. Y1 - 1997/02// PY - 1997 DA - February 1997 SP - 51 EP - 53 VL - 5 IS - 1 SN - 1064-1297, 1064-1297 KW - Narcotics KW - 0 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Double-Blind Method KW - Humans KW - Adult KW - Substance-Related Disorders -- psychology KW - Male KW - Female KW - Smoking -- psychology KW - Cocaine -- pharmacology KW - Narcotics -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79158673?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Changes+in+cigarette+smoking+not+observed+following+repeated+cocaine+self-administration.&rft.au=Radzius%2C+A%3BCarriero%2C+N+J%3BWeinhold%2C+L+L%3BGorelick%2C+D+A%3BHenningfield%2C+J+E&rft.aulast=Radzius&rft.aufirst=A&rft.date=1997-02-01&rft.volume=5&rft.issue=1&rft.spage=51&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 - 1997-09-12 N1 - Date created - 1997-09-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recent update on the PPAR alpha-null mouse. AN - 79103425; 9209711 AB - Short-term treatment of rats and mice with peroxisome proliferators (PP) results in an increase in liver peroxisome number, marked hepatomegaly and induction of several genes encoding peroxisomal and other microsomal and mitochondrial enzymes involved in fatty acid metabolism. Chronic treatment of rodents with PP results in hepatocellular carcinoma. Species differences in PP responses have been found. For example, PP such as clofibrate and gemfibrozil, are highly effective lipid and cholesterol lowering drugs in humans but do not cause peroxisome proliferation and there is no evidence for increased liver cancers in patients receiving these drugs. A receptor, designated PP-activated receptor alpha (PPAR alpha) is capable of trans-activating reporter genes containing a PP response (PPRE), but requires the presence of both PP, 9-cis retinoic acid and another receptor called RXR alpha. However, PP may not directly bind to PPAR alpha but probably indirectly disturb cellular metabolism to liberate an endogenous ligand. Subsequent to the first identification of a PPAR alpha, other members of this receptor family were found and designated PPAR alpha, PPAR beta (also called NUC1 and PPAR delta) and PPAR gamma. The alpha form is most abundant in liver and kidney, sites of peroxisome proliferation while the other two receptors are not significantly expressed in these tissues. On the basis of tissue-specific localization and spectrum of target gene activation, the physiological function of PPAR alpha and PPAR gamma appear to be related to fatty acid metabolism and regulation of adipogenesis, respectively. To gain insight into the function of PPAR alpha and its role in the peroxisome proliferator response and hepatocellular carcinogenesis, gene targeting was used to develop a PPAR alpha-deficient mouse. These animals are resistant to the pleiotropic effects of PP and no induction of any known target gene has been found. Recent studies on the phenotypes of these mice have led to an understanding of the mechanism of action of PP. They have also provided a useful model to establish the physiological role of PPAR alpha in fatty acid homeostasis and inflammation. JF - Biochimie AU - Gonzalez, F J AD - Laboratory of Metabolism, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. PY - 1997 SP - 139 EP - 144 VL - 79 IS - 2-3 SN - 0300-9084, 0300-9084 KW - RNA, Messenger KW - 0 KW - Receptors, Cytoplasmic and Nuclear KW - Sulfates KW - Transcription Factors KW - Dehydroepiandrosterone KW - 459AG36T1B KW - Index Medicus KW - Rats KW - Animals KW - Inflammation -- physiopathology KW - Humans KW - Mice KW - RNA, Messenger -- genetics KW - Dehydroepiandrosterone -- analogs & derivatives KW - Dehydroepiandrosterone -- pharmacology KW - Mice, Knockout KW - Cell Division KW - Receptors, Cytoplasmic and Nuclear -- physiology KW - Transcription Factors -- physiology KW - Transcription Factors -- deficiency KW - Microbodies -- ultrastructure KW - Receptors, Cytoplasmic and Nuclear -- deficiency KW - Microbodies -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79103425?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochimie&rft.atitle=Recent+update+on+the+PPAR+alpha-null+mouse.&rft.au=Gonzalez%2C+F+J&rft.aulast=Gonzalez&rft.aufirst=F&rft.date=1997-02-01&rft.volume=79&rft.issue=2-3&rft.spage=139&rft.isbn=&rft.btitle=&rft.title=Biochimie&rft.issn=03009084&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-14 N1 - Date created - 1997-08-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Conservation genetics of the koala (Phascolarctos cinereus): low mitochondrial DNA variation amongst southern Australian populations. AN - 79010638; 9164173 AB - Koala (Phascolarctos cinereus) populations in southern Australia have a history of bottlenecks-earlier this century the species became extinct in South Australia, and almost so in Victoria. Subsequently large numbers of animals from island populations (founded from very few animals) have been translocated back to mainland sites and to other islands in the region. As part of a larger study of the genetic structure of koala populations in southern Australia, we have undertaken a survey of mitochondrial DNA restriction fragment length polymorphism (mtDNA-RFLP) variability. Genomic DNA from 91 koalas from five populations was examined using 23 restriction enzymes, and mtDNA fragments were detected using a domestic cat full-length mtDNA clone. Only one of the enzymes, TaqI, revealed polymorphism-a relatively low amount of variation compared with other mammals, although low mtDNA-RFLP variation has also been reported in Queensland koalas. French Island and populations established predominantly from French Island immigrant koalas, either directly or via other island populations, were indistinguishable by haplotype frequencies. The mtDNA data are thus consistent with the interpretation that the koala translocation programme has homogenized gene frequencies amongst those populations involved. South Gippsland is not recorded as having received translocated koalas directly, and has significantly different mtDNA-RFLP haplotype frequencies from all other populations examined. The fact that this distinction was not previously observed in nuclear gene frequencies may reflect predominantly male-mediated dispersal in koalas. JF - Genetical research AU - Taylor, A C AU - Graves, J M AU - Murray, N D AU - O'Brien, S J AU - Yuhki, N AU - Sherwin, B AD - Laboratory of Viral Carcinogenesis, National Institutes of Health Frederick, MD 21702-1201, USA. ataylor@rna.bio.mq.edu.au Y1 - 1997/02// PY - 1997 DA - February 1997 SP - 25 EP - 33 VL - 69 IS - 1 KW - DNA, Mitochondrial KW - 0 KW - Deoxyribonucleases, Type II Site-Specific KW - EC 3.1.21.4 KW - TCGA-specific type II deoxyribonucleases KW - Index Medicus KW - Animals KW - Haplotypes KW - Genetics, Population KW - Deoxyribonucleases, Type II Site-Specific -- genetics KW - South Australia KW - Genetic Variation KW - Marsupialia -- genetics KW - DNA, Mitochondrial -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79010638?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genetical+research&rft.atitle=Conservation+genetics+of+the+koala+%28Phascolarctos+cinereus%29%3A+low+mitochondrial+DNA+variation+amongst+southern+Australian+populations.&rft.au=Taylor%2C+A+C%3BGraves%2C+J+M%3BMurray%2C+N+D%3BO%27Brien%2C+S+J%3BYuhki%2C+N%3BSherwin%2C+B&rft.aulast=Taylor&rft.aufirst=A&rft.date=1997-02-01&rft.volume=69&rft.issue=1&rft.spage=25&rft.isbn=&rft.btitle=&rft.title=Genetical+research&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-23 N1 - Date created - 1997-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reproductive assessment by continuous breeding: evolving study design and summaries of ninety studies. AN - 78965042; 9114287 AB - The Reproductive Assessment by Continuous Breeding (RACB) design has been used by the National Toxicology Program for approximately 15 years. This article details the evolutions in the thinking behind the design and the end points used in the identification of hazards to reproduction. Means of nominating chemicals are provided, and both early and current designs are described as well as some proposed changes for the future. This introduction is followed by a text and tabular summary of each study performed to date. We hope that this will not only be an explicit presentation of the findings of this testing program to date, but will help stimulate thinking about new ways to detect and measure reproductive toxicity in rodents, and help identify new relationships among the end points that are measured in such studies. JF - Environmental health perspectives AU - Chapin, R E AU - Sloane, R A AD - National Institute of Environmental Health Sciences and National Toxicology Program, Research Triangle Park, North Carolina 27709, USA. chapin@niehs.nih.gov Y1 - 1997/02// PY - 1997 DA - February 1997 SP - 199 EP - 205 VL - 105 Suppl 1 SN - 0091-6765, 0091-6765 KW - Acrylamides KW - 0 KW - Environmental Pollutants KW - Ethers KW - Phthalic Acids KW - Index Medicus KW - Rats KW - Animals KW - Ethers -- toxicity KW - Humans KW - Acrylamides -- toxicity KW - Animal Husbandry KW - Research Design KW - Toxicology KW - Phthalic Acids -- toxicity KW - Male KW - Female KW - Pregnancy KW - Environmental Pollutants -- toxicity KW - Reproduction -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78965042?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Reproductive+assessment+by+continuous+breeding%3A+evolving+study+design+and+summaries+of+ninety+studies.&rft.au=Chapin%2C+R+E%3BSloane%2C+R+A&rft.aulast=Chapin&rft.aufirst=R&rft.date=1997-02-01&rft.volume=105+Suppl+1&rft.issue=&rft.spage=199&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-09 N1 - Date created - 1997-07-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Arch Toxicol. 1981 Jun;47(3):179-89 [7271446] Environ Health Perspect. 1984 Aug;57:97-103 [6541999] Fundam Appl Toxicol. 1991 Aug;17(2):270-9 [1765220] Exp Cell Res. 1990 Apr;187(2):328-34 [2318269] Exp Mol Pathol. 1990 Jun;52(3):279-90 [2369934] Fundam Appl Toxicol. 1989 Nov;13(4):747-77 [2620795] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vaginal colonization or infection with Candida albicans in human immunodeficiency virus-infected women during pregnancy and during the postpartum period. Women and Infants Transmission Study Group. AN - 78940159; 9114148 AB - We evaluated the relationship between immunologic status and vaginal colonization or infection with Candida albicans for 605 women enrolled in a multicenter, prospective cohort study of mother-to-infant transmission of human immunodeficiency virus type 1 (HIV-1). A low CD4+ lymphocyte level ( or = 14%, which corresponds to an absolute count of approximately 200 x 10(6)/L) was associated with a two- to fivefold increased likelihood of vaginal colonization (odds ratio [OR], 2.28; 95% confidence interval [CI], 1.01-5.19) and vaginal candidiasis (OR, 3.08; 95% CI, 1.21-7.71) during pregnancy and during the postpartum period (OR, 2.98; 95% CI, 1.51-5.88 and OR, 5.45; 95% CI, 1.73-16.6, respectively). These associations persisted in multivariate logistic regression analyses. No associations with CD8+ lymphocyte levels or CD8+ CD38+ or other lymphocyte subset levels were found after adjustment for CD4+ cell level and other covariates. However, postpartum (but not antepartum) antibiotic use and pregnancy were also associated with vaginal colonization and candidiasis (P < or = .001 for each). Vaginal candidiasis was not associated with an increased risk of mother-to-infant transmission of HIV-1; however, a related, more inclusive variable, clinical vaginitis or vaginosis of any etiology at the last antepartum visit, was associated with mother-to-infant transmission (OR, 1.92; 95% CI, 1.07-3.43). These findings emphasize the complex, multifactorial nature of vaginal candidiasis and highlight the need for safe and effective treatment and prevention strategies for women with advanced HIV infection. JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America AU - Burns, D N AU - Tuomala, R AU - Chang, B H AU - Hershow, R AU - Minkoff, H AU - Rodriguez, E AU - Zorrilla, C AU - Hammill, H AU - Regan, J AD - Pediatric, Adolescent, and Maternal AIDS Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-7510, USA. Y1 - 1997/02// PY - 1997 DA - February 1997 SP - 201 EP - 210 VL - 24 IS - 2 SN - 1058-4838, 1058-4838 KW - Anti-Bacterial Agents KW - 0 KW - Index Medicus KW - AIDS/HIV KW - Infectious Disease Transmission, Vertical KW - Prospective Studies KW - Humans KW - Anti-Bacterial Agents -- adverse effects KW - Adult KW - CD4 Lymphocyte Count KW - Female KW - Pregnancy KW - HIV Infections -- complications KW - Puerperal Infection -- etiology KW - Pregnancy Complications, Infectious KW - Candida albicans -- isolation & purification KW - Candidiasis, Vulvovaginal -- etiology KW - Vagina -- microbiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78940159?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Vaginal+colonization+or+infection+with+Candida+albicans+in+human+immunodeficiency+virus-infected+women+during+pregnancy+and+during+the+postpartum+period.+Women+and+Infants+Transmission+Study+Group.&rft.au=Burns%2C+D+N%3BTuomala%2C+R%3BChang%2C+B+H%3BHershow%2C+R%3BMinkoff%2C+H%3BRodriguez%2C+E%3BZorrilla%2C+C%3BHammill%2C+H%3BRegan%2C+J&rft.aulast=Burns&rft.aufirst=D&rft.date=1997-02-01&rft.volume=24&rft.issue=2&rft.spage=201&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 - 1997-06-19 N1 - Date created - 1997-06-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cyclosporine A-induced contractions and prostacyclin release are maintained by extracellular calcium in rat aortic rings: role of protein kinase C. AN - 78863176; 9051725 AB - Chronic treatment with the immunosuppressive drug, Cyclosporine A (CsA), is associated with increased intracellular calcium in vascular smooth muscle cells, which may cause vasoconstriction and/or activate phospholipase A2. We used rat aortic rings to investigate the role of protein kinase C (PKC) in CsA-induced contractions and secondary prostacyclin (PGI2) release. CsA (10(-9) M) produced a sustained contraction in rat aortic rings. Both CsA-induced contractions and PGI2 release were inhibited 84 to 89% by 10(-9) M, and 99 to 100% by 10(-6) M pretreatment doses of any of three different PKC inhibitors, i.e. 1-(5-isoquinolinesulfonylmethyl) piperazine (H7), staurosporine or 1-(5-isoquinolinesulfonyl) piperazine. Pretreatment with (10(-9) M) of diltiazem (a voltage-sensitive L-type calcium channel blocker) completely inhibited both CsA-induced contractions and PGI2 release. Conversely, pretreatment with (10(-9) M) of thapsigargin (an intracellular calcium channel blocker) did not alter the action of CsA. These results strongly suggest that PKC, in association with an influx of extracellular calcium mediates CsA-induced contractions and secondary PGI2 release in rat aortic rings. JF - Prostaglandins, leukotrienes, and essential fatty acids AU - Oriji, G K AU - Keiser, H R AD - Hypertension-Endocrine Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/02// PY - 1997 DA - February 1997 SP - 151 EP - 156 VL - 56 IS - 2 SN - 0952-3278, 0952-3278 KW - Calcium Channel Blockers KW - 0 KW - Enzyme Inhibitors KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - Thapsigargin KW - 67526-95-8 KW - Cyclosporine KW - 83HN0GTJ6D KW - 1-(5-isoquinolinesulfonyl)piperazine KW - 84468-24-6 KW - 1-(5-isoquinolinylsulfonyl)-3-methylpiperazine KW - 84477-73-6 KW - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine KW - 84477-87-2 KW - Epoprostenol KW - DCR9Z582X0 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Diltiazem KW - EE92BBP03H KW - Staurosporine KW - H88EPA0A3N KW - Index Medicus KW - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine -- pharmacology KW - Animals KW - Cytosol -- metabolism KW - Aorta KW - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine -- analogs & derivatives KW - Phorbol 12,13-Dibutyrate -- pharmacology KW - Thapsigargin -- pharmacology KW - Rats KW - Staurosporine -- pharmacology KW - Diltiazem -- pharmacology KW - Calcium Channel Blockers -- pharmacology KW - In Vitro Techniques KW - Muscle Contraction -- drug effects KW - Enzyme Inhibitors -- pharmacology KW - Cell Membrane -- metabolism KW - Male KW - Protein Kinase C -- metabolism KW - Muscle, Smooth, Vascular -- physiology KW - Protein Kinase C -- antagonists & inhibitors KW - Cyclosporine -- pharmacology KW - Epoprostenol -- metabolism KW - Muscle, Smooth, Vascular -- drug effects KW - Muscle, Smooth, Vascular -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78863176?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Prostaglandins%2C+leukotrienes%2C+and+essential+fatty+acids&rft.atitle=Cyclosporine+A-induced+contractions+and+prostacyclin+release+are+maintained+by+extracellular+calcium+in+rat+aortic+rings%3A+role+of+protein+kinase+C.&rft.au=Oriji%2C+G+K%3BKeiser%2C+H+R&rft.aulast=Oriji&rft.aufirst=G&rft.date=1997-02-01&rft.volume=56&rft.issue=2&rft.spage=151&rft.isbn=&rft.btitle=&rft.title=Prostaglandins%2C+leukotrienes%2C+and+essential+fatty+acids&rft.issn=09523278&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-15 N1 - Date created - 1997-05-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulation of the inhibitory effect of phenylethylamine on spontaneous motor activity in mice by CPP-(+/-)-3-(2-carboxypiperazin-4-YL)-propyl-1-phosphonic acid. AN - 78854944; 9050075 AB - Beta-phenyl-ethylamine (PEA) at dose of 50 mg/kg inhibits spontaneous, motor activity in mice. CPP- (+/-)-3-(2-Carboxypiperazin-4-yl)-propyl-1-phosphonic acid, a selective and competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, in doses of 0.2-10 mg/kg dose-dependently antagonizes this inhibitory effect of PEA. This effect of CPP appeared to be selective because the inhibitory action of PEA was not altered by pretreament with noncompetitive antagonists of NMDA receptors, such as dizocilpine (MK-801), phencyclidine (PCP), 1-phenylcyclohexylamine (PCA) or by antagonists of other behavioral effects of PEA such as haloperidol, baclofen and phenibut (beta-phenyl-GABA). CPP failed to antagonize the inhibitory effect of other tested drugs such as diazepam, haloperidol, baclofen and phenibut. Intracerebroventricularly administered NMDA (0.2 microM), an agonist of NMDA receptors, suppressed the antagonistic effects of CPP against PEA. This suggests that anti-PEA effect of CPP is related to NMDA receptors. Anti-PEA effect of CPP is not due to accelerated deamination of PEA in CPP-treated mice. When small doses of PEA (5 and 10 mg/kg) and CPP (0.2 and 1 mg/kg) were used, the synergism of two drugs was observed. CPP (1 mg/kg) and deprenyl (0.5 mg/kg) an inhibitor monoamine oxidase of B type (MAO-B), had additive effects on PEA-induced inhibition of locomotion. This effect was not associated with any further inhibition of activity of brain MAO-B (over the inhibition induced by deprenyl alone-by 65%) under high (80 microM) or low (4.3 microM) concentration of PEA as a substrate in the medium. Mechanism of the interaction of CPP and PEA, two drugs belonging to different groups of biologically active compounds, deserves further studies. JF - Pharmacology, biochemistry, and behavior AU - Lapin, I P AU - Yuwiler, A AD - Neuronal Excitability Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/02// PY - 1997 DA - February 1997 SP - 199 EP - 204 VL - 56 IS - 2 SN - 0091-3057, 0091-3057 KW - Excitatory Amino Acid Agonists KW - 0 KW - Excitatory Amino Acid Antagonists KW - Monoamine Oxidase Inhibitors KW - Phenethylamines KW - Piperazines KW - Selegiline KW - 2K1V7GP655 KW - phenethylamine KW - 327C7L2BXQ KW - N-Methylaspartate KW - 6384-92-5 KW - 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid KW - 98Y1I8ZD4M KW - Monoamine Oxidase KW - EC 1.4.3.4 KW - Index Medicus KW - Brain -- enzymology KW - Animals KW - Selegiline -- pharmacology KW - N-Methylaspartate -- pharmacology KW - Dose-Response Relationship, Drug KW - Brain -- drug effects KW - Excitatory Amino Acid Agonists -- pharmacology KW - Mice KW - Monoamine Oxidase -- metabolism KW - Drug Synergism KW - Monoamine Oxidase Inhibitors -- pharmacology KW - Male KW - Phenethylamines -- antagonists & inhibitors KW - Motor Activity -- drug effects KW - Piperazines -- pharmacology KW - Excitatory Amino Acid Antagonists -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78854944?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacology%2C+biochemistry%2C+and+behavior&rft.atitle=Modulation+of+the+inhibitory+effect+of+phenylethylamine+on+spontaneous+motor+activity+in+mice+by+CPP-%28%2B%2F-%29-3-%282-carboxypiperazin-4-YL%29-propyl-1-phosphonic+acid.&rft.au=Lapin%2C+I+P%3BYuwiler%2C+A&rft.aulast=Lapin&rft.aufirst=I&rft.date=1997-02-01&rft.volume=56&rft.issue=2&rft.spage=199&rft.isbn=&rft.btitle=&rft.title=Pharmacology%2C+biochemistry%2C+and+behavior&rft.issn=00913057&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-01 N1 - Date created - 1997-05-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selected pharmacokinetics of theophylline ethylenediamine in pre-term and term goat kids. AN - 78848321; 9049952 JF - Journal of veterinary pharmacology and therapeutics AU - Lidl, G M AU - Jernigan, A D AU - Haibel, G K AD - Office of Laboratory Animal Science, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-2471, USA. Y1 - 1997/02// PY - 1997 DA - February 1997 SP - 69 EP - 72 VL - 20 IS - 1 SN - 0140-7783, 0140-7783 KW - Phosphodiesterase Inhibitors KW - 0 KW - Aminophylline KW - 27Y3KJK423 KW - Index Medicus KW - Administration, Oral KW - Animals KW - Injections, Intravenous -- veterinary KW - Half-Life KW - Birth Weight -- drug effects KW - Male KW - Female KW - Phosphodiesterase Inhibitors -- administration & dosage KW - Phosphodiesterase Inhibitors -- pharmacology KW - Aminophylline -- administration & dosage KW - Goats -- metabolism KW - Aminophylline -- pharmacokinetics KW - Phosphodiesterase Inhibitors -- pharmacokinetics KW - Animals, Newborn -- metabolism KW - Aminophylline -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78848321?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+veterinary+pharmacology+and+therapeutics&rft.atitle=Selected+pharmacokinetics+of+theophylline+ethylenediamine+in+pre-term+and+term+goat+kids.&rft.au=Lidl%2C+G+M%3BJernigan%2C+A+D%3BHaibel%2C+G+K&rft.aulast=Lidl&rft.aufirst=G&rft.date=1997-02-01&rft.volume=20&rft.issue=1&rft.spage=69&rft.isbn=&rft.btitle=&rft.title=Journal+of+veterinary+pharmacology+and+therapeutics&rft.issn=01407783&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-13 N1 - Date created - 1997-05-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxidative DNA base damage and its repair in kidneys and livers of nickel(II)-treated male F344 rats. AN - 78844354; 9054618 AB - DNA base damage was assayed using gas chromatography/ mass spectrometry with selected ion monitoring (GC/MS-SIM) in renal and hepatic chromatin of male F344 rats up to 14 days after a single i.p. injection of 90 micromol Ni(II) acetate/kg body wt. Ten different damaged bases were quantified. No damage was found in either organ 12 h after Ni(II) treatment. The damage became significant only from day 1, with magnitude and persistence depending on the organ and base. In livers, levels of five DNA base products were significantly elevated over those in control rats. They were: 8-oxoguanine (by 46% at day 1 postinjection); 2,6-diamino-4-hydroxy-5-formamidopyrimidine (by 107% at day 1); 5-(hydroxymethyl)uracil (by 94% at day 1); 5,6-dihydroxyuracil (by 128% at day 1); and 5-hydroxyhydantoin (by 39% in terms of the overall adjusted means for days 1-14 post-injection). The elevation was highest at day 1 post-injection followed by a decrease at later days, except for 5-hydroxyhydantoin. In kidneys, the levels of only three damaged bases, 8-oxoguanine, 5-hydroxyhydantoin and 5,6-dihydroxyuracil were increased significantly (by 31, 73 and 60%, respectively) and one base, 8-oxoadenine, was increased by 26%, just below significance, all in terms of overall adjusted means for days 1-14 post-injection. Hence, unlike those in the liver, the renal increases persisted for 14 days. The results reveal a tissue specific response to Ni(II)-mediated oxidative DNA base damage with apparently faster DNA repair in liver than in kidney, the main target of Ni(II) carcinogenicity. JF - Carcinogenesis AU - Kasprzak, K S AU - Jaruga, P AU - Zastawny, T H AU - North, S L AU - Riggs, C W AU - Olinski, R AU - Dizdaroglu, M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, FCRDC, Frederick, MD 21702, USA. Y1 - 1997/02// PY - 1997 DA - February 1997 SP - 271 EP - 277 VL - 18 IS - 2 SN - 0143-3334, 0143-3334 KW - Acetates KW - 0 KW - Nickel KW - 7OV03QG267 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Rats KW - Oxidation-Reduction KW - Animals KW - Rats, Inbred F344 KW - Male KW - DNA Repair KW - Liver -- drug effects KW - DNA Damage KW - Kidney -- drug effects KW - Nickel -- toxicity KW - Acetates -- toxicity KW - DNA -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78844354?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Oxidative+DNA+base+damage+and+its+repair+in+kidneys+and+livers+of+nickel%28II%29-treated+male+F344+rats.&rft.au=Kasprzak%2C+K+S%3BJaruga%2C+P%3BZastawny%2C+T+H%3BNorth%2C+S+L%3BRiggs%2C+C+W%3BOlinski%2C+R%3BDizdaroglu%2C+M&rft.aulast=Kasprzak&rft.aufirst=K&rft.date=1997-02-01&rft.volume=18&rft.issue=2&rft.spage=271&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-24 N1 - Date created - 1997-03-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Involvement of protein kinase C in nerve growth factor- and K-252a-stimulated calcium uptake into PC12 cells. AN - 78840167; 9039649 AB - Both nerve growth factor (NGF) and K-252a stimulate the uptake of calcium into PC12 cells. Stimulation by either is prevented by pretreatment of the cells with the tumor promoter phorbol 12-myristate 13-acetate (PMA), suggesting an involvement of protein kinase C in the stimulation. The effect of PMA is specific in that the calcium uptake stimulated by either the L-type channel agonist BAY K 8644 or by ATP is not altered in PMA-pretreated cells. An involvement of kinase C is also suggested by the inhibition of NGF- or K-252a-stimulated calcium uptake by the kinase C inhibitors staurosporine and calphostin C. Inhibition by the isoform-specific agents GO 6976 and thymeleatoxin implicates one of the classic calcium-sensitive isoforms of kinase C. The close similarity in the profiles of inhibition of NGF-stimulated and K-252a-stimulated calcium uptake by the various effectors suggests that NGF and K-252a act on calcium uptake through some of the same signaling elements. JF - Journal of neuroscience research AU - Dickens, G AU - Lavarreda, M AU - Zheng, W H AU - Guroff, G AD - Section on Growth Factors, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA. Y1 - 1997/02/01/ PY - 1997 DA - 1997 Feb 01 SP - 271 EP - 276 VL - 47 IS - 3 SN - 0360-4012, 0360-4012 KW - Calcium Channel Agonists KW - 0 KW - Carbazoles KW - Carcinogens KW - Enzyme Inhibitors KW - Indole Alkaloids KW - Indoles KW - Isoenzymes KW - Naphthalenes KW - Nerve Growth Factors KW - Phorbol Esters KW - Receptors, Nerve Growth Factor KW - Go 6976 KW - 136194-77-9 KW - 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester KW - 71145-03-4 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - thymeleatoxin KW - 94482-56-1 KW - staurosporine aglycone KW - 97161-97-2 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Protein Kinase C-alpha KW - Staurosporine KW - H88EPA0A3N KW - calphostin C KW - I271P23G24 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Naphthalenes -- pharmacology KW - Animals KW - Carcinogens -- pharmacology KW - 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester -- pharmacology KW - PC12 Cells -- enzymology KW - Calcium Channel Agonists -- pharmacology KW - Rats KW - Phorbol Esters -- pharmacology KW - Staurosporine -- pharmacology KW - Signal Transduction -- drug effects KW - Adenosine Triphosphate -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Indoles -- pharmacology KW - Receptors, Nerve Growth Factor -- antagonists & inhibitors KW - PC12 Cells -- chemistry KW - Protein Kinase C -- metabolism KW - Isoenzymes -- antagonists & inhibitors KW - Protein Kinase C -- antagonists & inhibitors KW - Nerve Growth Factors -- pharmacology KW - Carbazoles -- pharmacology KW - Calcium -- pharmacokinetics KW - Enzyme Inhibitors -- pharmacology KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78840167?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Involvement+of+protein+kinase+C+in+nerve+growth+factor-+and+K-252a-stimulated+calcium+uptake+into+PC12+cells.&rft.au=Dickens%2C+G%3BLavarreda%2C+M%3BZheng%2C+W+H%3BGuroff%2C+G&rft.aulast=Dickens&rft.aufirst=G&rft.date=1997-02-01&rft.volume=47&rft.issue=3&rft.spage=271&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 - 1997-04-28 N1 - Date created - 1997-04-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of mutant amyloid precursor proteins induces apoptosis in PC12 cells. AN - 78840110; 9039647 AB - The cause of neuronal loss in Alzheimer disease is unknown. We investigated the effects on survival of PC12 cells expressing A692G, E693Q, and V717F mutant amyloid precursor proteins (APP). Differentiated cells expressing mutant APPs exhibited somal shrinkage, followed by cell detachment from the plates. Increased levels of oligonucleosome-sized DNA ladders and TUNEL-positive nuclei were observed, and electron microscopy revealed extensive plasma membrane blebbing, margination of condensed chromatin, and well-preserved organelles in these transfectants. The levels of TUNEL-positive cells, analyzed by a flow-cytometric method, were increased by four- to sevenfold in mutant APP transfectants, but less than twofold in wild-type APP transfectants relative to untransfected cells. Our results provide evidence that expression of mutant APPs in differentiated PC12 cells induces cell death via an apoptotic pathway. JF - Journal of neuroscience research AU - Zhao, B AU - Chrest, F J AU - Horton, W E AU - Sisodia, S S AU - Kusiak, J W AD - Molecular Neurobiology Unit/LBC, National Institute on Aging, Baltimore, Maryland 21224, USA. Y1 - 1997/02/01/ PY - 1997 DA - 1997 Feb 01 SP - 253 EP - 263 VL - 47 IS - 3 SN - 0360-4012, 0360-4012 KW - Amyloid beta-Protein Precursor KW - 0 KW - Deoxyuracil Nucleotides KW - Biotin KW - 6SO6U10H04 KW - Index Medicus KW - Animals KW - Mutagenesis -- physiology KW - Rats KW - Phenotype KW - Polymerase Chain Reaction KW - Blotting, Western KW - Cell Differentiation -- physiology KW - Transfection KW - Flow Cytometry KW - Microscopy, Electron KW - Gene Expression -- physiology KW - Staining and Labeling KW - DNA Fragmentation KW - Microscopy, Electron, Scanning KW - PC12 Cells -- cytology KW - PC12 Cells -- ultrastructure KW - Apoptosis -- physiology KW - Amyloid beta-Protein Precursor -- analysis KW - Amyloid beta-Protein Precursor -- genetics KW - PC12 Cells -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78840110?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Expression+of+mutant+amyloid+precursor+proteins+induces+apoptosis+in+PC12+cells.&rft.au=Zhao%2C+B%3BChrest%2C+F+J%3BHorton%2C+W+E%3BSisodia%2C+S+S%3BKusiak%2C+J+W&rft.aulast=Zhao&rft.aufirst=B&rft.date=1997-02-01&rft.volume=47&rft.issue=3&rft.spage=253&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 - 1997-04-28 N1 - Date created - 1997-04-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Achievement and safety of a low blood pressure goal in chronic renal disease. The Modification of Diet in Renal Disease Study Group. AN - 78836510; 9040451 AB - The Modification of Diet in Renal Disease Study showed a beneficial effect of a lower-than-usual blood pressure (BP) goal on the progression of renal disease in patients with proteinuria. The purpose of the present analyses was to examine the achieved BP, baseline characteristics that helped or hindered achievement of the BP goals, and safety of the BP interventions. Five hundred eighty-five patients with baseline glomerular filtration rate between 13 and 55 mL/min per 1.73 m2 (0.22 to 0.92 mL/s per 1.73 m2) were randomly assigned to either a usual or low BP goal (mean arterial pressure 92 mm Hg, a diagnosis of polycystic kidney disease or glomerular diseases, baseline urinary protein excretion > 1 g/d, age > or = 61 years, and black race. The frequency of medication changes and incidence of symptoms of low BP were greater in the low BP group, but there were no significant differences between BP groups in stop points, hospitalizations, or death. When data from both groups were combined, each 1-mm Hg increase in follow-up systolic BP was associated with a 1.35-times greater risk of hospitalization for cardiovascular or cerebrovascular disease. Lower BP than usually recommended for the prevention of cardiovascular disease is achievable by several medication regimens without serious adverse effects in patients with chronic renal disease without cardiovascular disease. For patients with urinary protein excretion > 1 g/d, target BP should be a mean arterial pressure of < or = 92 mm Hg, equivalent to 125/75 mm Hg. JF - Hypertension (Dallas, Tex. : 1979) AU - Lazarus, J M AU - Bourgoignie, J J AU - Buckalew, V M AU - Greene, T AU - Levey, A S AU - Milas, N C AU - Paranandi, L AU - Peterson, J C AU - Porush, J G AU - Rauch, S AU - Soucie, J M AU - Stollar, C AD - National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Md, USA. Y1 - 1997/02// PY - 1997 DA - February 1997 SP - 641 EP - 650 VL - 29 IS - 2 SN - 0194-911X, 0194-911X KW - Antihypertensive Agents KW - 0 KW - Index Medicus KW - Humans KW - Safety KW - Antihypertensive Agents -- adverse effects KW - Aged KW - Hypertension -- diagnosis KW - Proteinuria -- diagnosis KW - Adult KW - Antihypertensive Agents -- therapeutic use KW - Chronic Disease KW - Follow-Up Studies KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - Blood Pressure -- drug effects KW - Diet, Protein-Restricted -- adverse effects KW - Kidney Diseases -- diet therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78836510?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hypertension+%28Dallas%2C+Tex.+%3A+1979%29&rft.atitle=Achievement+and+safety+of+a+low+blood+pressure+goal+in+chronic+renal+disease.+The+Modification+of+Diet+in+Renal+Disease+Study+Group.&rft.au=Lazarus%2C+J+M%3BBourgoignie%2C+J+J%3BBuckalew%2C+V+M%3BGreene%2C+T%3BLevey%2C+A+S%3BMilas%2C+N+C%3BParanandi%2C+L%3BPeterson%2C+J+C%3BPorush%2C+J+G%3BRauch%2C+S%3BSoucie%2C+J+M%3BStollar%2C+C&rft.aulast=Lazarus&rft.aufirst=J&rft.date=1997-02-01&rft.volume=29&rft.issue=2&rft.spage=641&rft.isbn=&rft.btitle=&rft.title=Hypertension+%28Dallas%2C+Tex.+%3A+1979%29&rft.issn=0194911X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-13 N1 - Date created - 1997-03-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Taxonomy and function of C1 protein kinase C homology domains. AN - 78832620; 9041654 AB - C1 domains are compact alpha/beta structural units of about 50 amino acids which tightly bind two zinc ions. These domains were first discovered as the loci of phorbol ester and diacylglycerol binding to conventional protein kinase C isozymes, which contain 2 C1 domains (C1A and C1B) in their N-terminal regulatory regions. We present a comprehensive list of 54 C1 domains occurring singly or doubly in 34 different proteins. Many C1 domains and C1 domain-containing proteins bind phorbol esters, but many others do not. By combining analysis of 54 C1 domain sequences with information from previously reported solution and crystal structure determinations and site-directed mutagenesis, profiles are derived and used to classify C1 domains. Twenty-six C1 domains fit the profile for phorbol-ester binding and are termed "typical." Twenty-eight other domains fit the profile for the overall C1 domain fold but do not fit the profile for phorbol ester binding, and are termed "atypical." Proteins containing typical C1 domains are predicted to be regulated by diacylglycerol, whereas those containing only atypical domains are not. JF - Protein science : a publication of the Protein Society AU - Hurley, J H AU - Newton, A C AU - Parker, P J AU - Blumberg, P M AU - Nishizuka, Y AD - Laboratory of Molecular Biology, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0580, USA. Hurley@tove.niddk.nih.gov Y1 - 1997/02// PY - 1997 DA - February 1997 SP - 477 EP - 480 VL - 6 IS - 2 SN - 0961-8368, 0961-8368 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Animals KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Protein Kinase C -- metabolism KW - Protein Kinase C -- chemistry KW - Protein Kinase C -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78832620?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+science+%3A+a+publication+of+the+Protein+Society&rft.atitle=Taxonomy+and+function+of+C1+protein+kinase+C+homology+domains.&rft.au=Hurley%2C+J+H%3BNewton%2C+A+C%3BParker%2C+P+J%3BBlumberg%2C+P+M%3BNishizuka%2C+Y&rft.aulast=Hurley&rft.aufirst=J&rft.date=1997-02-01&rft.volume=6&rft.issue=2&rft.spage=477&rft.isbn=&rft.btitle=&rft.title=Protein+science+%3A+a+publication+of+the+Protein+Society&rft.issn=09618368&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-03 N1 - Date created - 1997-06-03 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U43584; GENBANK; D14815; X75756; U49379; U43195; U28495; D73409; U51477; M94883; P15882; SWISSPROT; 49619; Q02111; P04411; P04409; P49621; P40809; P41743; P05130; P15498; P14056; P16054; P49025; P28867; P27715; P34125; P05697; P24723; Q04982; Q05513; Q03070 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1989 Jul;86(13):4868-71 [2500657] Biochem J. 1996 Sep 1;318 ( Pt 2):583-90 [8809050] Methods Enzymol. 1990;183:146-59 [2314273] J Biol Chem. 1991 Sep 25;266(27):18330-8 [1917958] Biochem J. 1991 Nov 15;280 ( Pt 1):233-41 [1660266] Mol Cell Biol. 1992 Nov;12(11):5111-22 [1406685] Cell Signal. 1993 Sep;5(5):495-503 [8312127] J Biol Chem. 1994 Apr 15;269(15):11590-4 [8157692] J Biol Chem. 1994 Jul 29;269(30):19200-2 [8034680] Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8572-6 [8078925] Cell. 1995 Jun 16;81(6):917-24 [7781068] J Biochem. 1995 Mar;117(3):566-74 [7629023] J Biol Chem. 1995 Aug 4;270(31):18388-95 [7629163] Nat Struct Biol. 1994 Jun;1(6):383-7 [7664052] Curr Biol. 1995 Sep 1;5(9):973-6 [8542286] Mol Cell Biol. 1996 Jan;16(1):105-14 [8524286] EMBO J. 1995 Dec 1;14(23):5931-8 [8846785] FEBS Lett. 1995 Dec 18;377(2):243-8 [8543060] J Biol Chem. 1996 Apr 19;271(16):9193-6 [8621575] EMBO J. 1996 Apr 15;15(8):1885-93 [8617235] J Biol Chem. 1996 Apr 5;271(14):8472-80 [8626548] Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8312-7 [8710867] J Biol Chem. 1996 Aug 2;271(31):18299-301 [8702464] Cell. 1996 Sep 6;86(5):777-86 [8797824] Annu Rev Biochem. 1989;58:31-44 [2549852] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The relationship between drinking and heart disease morbidity in the United States: results from the National Health Interview Survey. AN - 78830416; 9046382 AB - This study, based on data drawn from the responses of 18,323 males and 25,440 females to the 1988 National Health Interview Survey, a nationally representative, multistage probability sample of the United States, attempts to define more precisely the level of drinking at which the relationship between heart disease and alcohol consumption is a protective one. Its attempt at precision derives from (1) using drinking categories that represent various points within the range of moderate drinking (1-6 drinks) defined in the literature as protective; (2) adjusting for underreporting that commonly occurs in population surveys by using consumption at time of heaviest drinking; and (3) controlling for age, body mass, smoking, former drinker, and former smoker status, duration of drinking, and sociodemographic factors. It also examines whether the relationship derived from these levels conforms to the U-shaped curve that demonstrates the protective effect of moderate drinking when abstainers are not used as the reference group. Relative to infrequent drinkers (less than 1 drink per day), men report more heart disease at the level of more than five drinks per day. However, black men also report more heart disease, relative to infrequent drinkers, at the greater than two drinks per day level; and women report more heart disease at the level of more than two drinks per day at the time of their heaviest drinking. Former drinkers of both genders, considered as an independent variable in the regression analysis, were more likely to report having heart disease. Abstainers, light drinkers, and infrequent drinkers were not significantly different in their reports of heart disease. Our results are consistent with studies that suggest protection from heart disease occurs only at lower levels of drinking. JF - Alcoholism, clinical and experimental research AU - Hanna, E Z AU - Chou, S P AU - Grant, B F AD - National Institute on Alcohol Abuse and Alcoholism, Division of Biometry and Epidemiology, Bethesda, Maryland 20892-7003, USA. Y1 - 1997/02// PY - 1997 DA - February 1997 SP - 111 EP - 118 VL - 21 IS - 1 SN - 0145-6008, 0145-6008 KW - Index Medicus KW - Humans KW - Aged KW - Cross-Sectional Studies KW - Hispanic Americans -- statistics & numerical data KW - Risk Factors KW - European Continental Ancestry Group KW - Adult KW - Sampling Studies KW - Incidence KW - Middle Aged KW - Adolescent KW - United States -- epidemiology KW - African Continental Ancestry Group KW - Female KW - Male KW - Coronary Disease -- prevention & control KW - Alcoholism -- epidemiology KW - Alcohol Drinking -- ethnology KW - Cardiomyopathy, Alcoholic -- ethnology KW - Alcoholism -- ethnology KW - Alcohol Drinking -- adverse effects KW - Coronary Disease -- epidemiology KW - Alcohol Drinking -- epidemiology KW - Coronary Disease -- ethnology KW - Alcoholism -- prevention & control KW - Cardiomyopathy, Alcoholic -- epidemiology KW - Cardiomyopathy, Alcoholic -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78830416?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=The+relationship+between+drinking+and+heart+disease+morbidity+in+the+United+States%3A+results+from+the+National+Health+Interview+Survey.&rft.au=Hanna%2C+E+Z%3BChou%2C+S+P%3BGrant%2C+B+F&rft.aulast=Hanna&rft.aufirst=E&rft.date=1997-02-01&rft.volume=21&rft.issue=1&rft.spage=111&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 - 1997-05-21 N1 - Date created - 1997-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential inhibition of murine prostaglandin synthase-1 and -2 by nonsteroidal anti-inflammatory drugs using exogenous and endogenous sources of arachidonic acid. AN - 78828405; 9023270 AB - Mouse embryonic fibroblasts (10T1/2) and Chinese hamster ovary (AS52) cell lines that stably express murine prostaglandin G/H synthase (PGHS)-1 or -2 were used to compare the effects of exogenous and endogenous arachidonic acid (AA) on isozyme-selective inhibition by acetylsalicylic acid, indomethacin, and N-[2-cyclohexyloxyl-4-nitrophenyl] methanesulfonamide (NS-398). The rationale for developing in vitro systems that identify PGHS-2-selective inhibitors is the belief that inhibition of this isoform accounts for the therapeutic benefits of nonsteroidal anti-inflammatory drugs (NSAIDs). Conversely, inhibition of PGHS-1 is believed to cause the toxic effects of NSAIDs, such as gastric and renal damage. When exogenous AA was used, acetylsalicylic acid was a 5- to 10-fold more potent inhibitor of PGHS-1, whereas indomethacin was a 4- to 5-fold more potent inhibitor of PGHS-2. Within the dose range tested (1 x 10(-6) microM to 100 microM), NS-398 was highly selective for PGHS-2. When calcium ionophore A23187 was used to mobilize endogenous AA, acetylsalicylic acid and indomethacin equipotently inhibited both PGHS-1 and PGHS-2 isozymes. NS-398 remained highly selective for PGHS-2 in 10T1/2 and AS52 cells but also effectively (100%) inhibited PGHS-1 in AS52 cells. Pharmacological data derived using endogenous AA correlated better with the anti-inflammatory efficacy of these NSAIDs in laboratory animals and with the therapeutic/toxic activities of these NSAIDs in rheumatoid arthritic patients. Therefore, screening for PGHS-selective NSAIDs may best be conducted in intact cells that express high levels of each isozyme using endogenous sources of AA. JF - The Journal of pharmacology and experimental therapeutics AU - Chulada, P C AU - Langenbach, R AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/02// PY - 1997 DA - February 1997 SP - 606 EP - 613 VL - 280 IS - 2 SN - 0022-3565, 0022-3565 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Cyclooxygenase 2 Inhibitors KW - Cyclooxygenase Inhibitors KW - Isoenzymes KW - Membrane Proteins KW - Nitrobenzenes KW - Sulfonamides KW - N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide KW - 123653-11-2 KW - Arachidonic Acid KW - 27YG812J1I KW - Calcimycin KW - 37H9VM9WZL KW - Cyclooxygenase 1 KW - EC 1.14.99.1 KW - Cyclooxygenase 2 KW - Prostaglandin-Endoperoxide Synthases KW - Ptgs1 protein, mouse KW - Aspirin KW - R16CO5Y76E KW - Indomethacin KW - XXE1CET956 KW - Index Medicus KW - Animals KW - Nitrobenzenes -- pharmacology KW - Mice KW - Calcimycin -- pharmacology KW - Indomethacin -- pharmacology KW - Cell Survival -- drug effects KW - Sulfonamides -- pharmacology KW - Kinetics KW - CHO Cells KW - Aspirin -- pharmacology KW - Cell Line KW - Cricetinae KW - Prostaglandin-Endoperoxide Synthases -- metabolism KW - Isoenzymes -- metabolism KW - Arachidonic Acid -- metabolism KW - Cyclooxygenase Inhibitors -- pharmacology KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78828405?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Differential+inhibition+of+murine+prostaglandin+synthase-1+and+-2+by+nonsteroidal+anti-inflammatory+drugs+using+exogenous+and+endogenous+sources+of+arachidonic+acid.&rft.au=Chulada%2C+P+C%3BLangenbach%2C+R&rft.aulast=Chulada&rft.aufirst=P&rft.date=1997-02-01&rft.volume=280&rft.issue=2&rft.spage=606&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-17 N1 - Date created - 1997-03-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of activating and inactivating mutations of Gs- and Gi2-alpha protein subunits on growth and differentiation of 3T3-L1 preadipocytes. AN - 78826281; 9027585 AB - Previous investigations have demonstrated that both Gs- and the Gi-family of GTP-binding proteins are implicated in differentiation of the 3T3-L1 preadipocyte. In order to further analyze the role of Gs alpha vs. Gi2 alpha, which are both involved in adenylate cyclase modulation, we transfected undifferentiated 3T3-L1 cells with two sets of G-protein cDNA: the pZEM vector with either wild type, the activating (i.e., GTP-ase inhibiting) R201C-Gs alpha or the inactivating G226A(H21a)-Gs alpha point mutations, or the pZIPNeoSV(X) retroviral vector constructs containing the Gi2 alpha wild type or the missense mutations R179E-Gi2 alpha, Q205L-Gi2 alpha, and G204A(H21a)-Gi2 alpha. The activating [R201C]Gs alpha-mutant did not significantly affect the differentiation process, i.e., increase in the steady-state levels of G-protein subunits, gross appearance, or insulin-elicited deoxy-glucose uptake into 3T3-L1 adipocytes, despite a marked initial increase in hormone-elicited adenylate cyclase activity. The [H21a]Gs alpha-mutant, on the other hand, enhanced the degree of differentiation slightly, as evidenced by an augmented production of lipid vesicles and insulin-stimulated deoxy-glucose uptake. However, an expected increase in mRNA for hormone-sensitive lipase was not seen. Secondly, it appeared that both activating [R179E]Gi2 alpha or [Q205L]Gi2 alpha mutants reduced cell doubling time in non-confluent 3T3-L1 cell cultures, while [H21a]Gi2 alpha slowed proliferation rate. Furthermore, it seemed that cell proliferation, as evidenced by thymidine incorporation, ceased at a much earlier stage prior to cell confluency when cultures were transfected with the [R179E]Gi2 alpha or [Q205L]Gi2 alpha mutants. Upon differentiation with insulin, dexamethasone, and iBuMeXan, the following cell characteristics emerged: the [R179E]Gi2 alpha and [Q205L]Gi2 alpha mutants consistently enhanced adenylate cyclase activation and cAMP accumulation stimulated by isoproterenol and corticotropin over controls. Deoxy-glucose uptake was also super-activated by the [R179E]Gi2 alpha and [Q205L]Gi2 alpha mutants. Finally, steady-state levels of hormone sensitive lipase mRNA were dramatically increased by [R179E]Gi2 alpha and [Q205L]Gi2 alpha over differentiated controls. The inactivating [H21a]Gi2 alpha-mutant obliterated all signs of preadipocyte differentiation. It is concluded that Gi2 plays a positive and much more important role than Gs in 3T3-L1 preadipocyte differentiation. Cyclic AMP appears to play no role in this process. JF - Journal of cellular biochemistry AU - Gordeladze, J O AU - Høvik, K E AU - Merendino, J J AU - Hermouet, S AU - Gutkind, S AU - Accili, D AD - Molecular Pathophysiology Branch, NIH, NIDDK, Bethesda, Maryland, USA. Y1 - 1997/02// PY - 1997 DA - February 1997 SP - 242 EP - 257 VL - 64 IS - 2 SN - 0730-2312, 0730-2312 KW - Deoxyglucose KW - 9G2MP84A8W KW - Cyclic AMP KW - E0399OZS9N KW - Sterol Esterase KW - EC 3.1.1.13 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Adenylyl Cyclases KW - EC 4.6.1.1 KW - Thymidine KW - VC2W18DGKR KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Enzyme Activation KW - Adenylyl Cyclases -- metabolism KW - Mice KW - Transcription, Genetic KW - Mutagenesis, Site-Directed KW - Rats KW - Thymidine -- metabolism KW - Sterol Esterase -- genetics KW - Transfection KW - Cyclic AMP -- metabolism KW - Deoxyglucose -- metabolism KW - Adipocytes -- enzymology KW - GTP-Binding Proteins -- metabolism KW - Cell Differentiation -- genetics KW - GTP-Binding Proteins -- genetics KW - Cell Division -- genetics KW - Adipocytes -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78826281?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+biochemistry&rft.atitle=Effect+of+activating+and+inactivating+mutations+of+Gs-+and+Gi2-alpha+protein+subunits+on+growth+and+differentiation+of+3T3-L1+preadipocytes.&rft.au=Gordeladze%2C+J+O%3BH%C3%B8vik%2C+K+E%3BMerendino%2C+J+J%3BHermouet%2C+S%3BGutkind%2C+S%3BAccili%2C+D&rft.aulast=Gordeladze&rft.aufirst=J&rft.date=1997-02-01&rft.volume=64&rft.issue=2&rft.spage=242&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+biochemistry&rft.issn=07302312&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-09 N1 - Date created - 1997-04-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Diarylsulfones, a novel class of human immunodeficiency virus type 1 integrase inhibitors. AN - 78820459; 9021196 AB - A majority of reported human immunodeficiency virus type 1 integrase (HIV-1 IN) inhibitors are polyhydroxylated aromatic compounds containing two phenyl rings separated by aliphatic or aromatic linkers. Most inhibitors possessing a catechol moiety exhibit considerable toxicity in cellular assays. In an effort to identify nonhydroxylated analogs, a series of aromatic sulfones were tested for their ability to inhibit the 3' processing and strand transfer steps that are necessary for HIV replication. Several aromatic sulfones have previously been shown to have moderate activity against HIV-1 reverse transcriptase in cellular assays; however, their inhibitory potencies against IN have not been explored. In the present study, the inhibitory effect of a series of sulfones and sulfonamides against IN was determined. Among 52 diaryl sulfones tested, 4 were determined to be highly potent (50% inhibitory concentration [IC50], 0.8 to 10 micrograms/ml), 5 had good potencies (IC50, 11 to 50 micrograms/ml), 10 showed moderate potencies (IC50, 51 to 100 micrograms/ml), and 33 were inactive (IC50, > 100 micrograms/ml) against IN. All of the active compounds exhibited similar potencies against HIV-2 IN. Sulfa drugs, used extensively in treating Pneumocystis carinii pneumonia, a leading cause of morbidity and mortality in AIDs patients, were also examined. Among 19 sulfonamides tested, sulfasalazine (IC50, 50 micrograms/ml) was the most potent. We conclude that potent inhibitors of IN can be designed based on the results presented in this study. JF - Antimicrobial agents and chemotherapy AU - Neamati, N AU - Mazumder, A AU - Zhao, H AU - Sunder, S AU - Burke, T R AU - Schultz, R J AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1997/02// PY - 1997 DA - February 1997 SP - 385 EP - 393 VL - 41 IS - 2 SN - 0066-4804, 0066-4804 KW - HIV Integrase Inhibitors KW - 0 KW - Sulfonamides KW - Sulfones KW - HIV Integrase KW - EC 2.7.7.- KW - Index Medicus KW - AIDS/HIV KW - Virus Replication -- drug effects KW - Sulfonamides -- pharmacology KW - Cell Line KW - Structure-Activity Relationship KW - Sulfones -- pharmacology KW - HIV Integrase Inhibitors -- pharmacology KW - HIV-1 -- enzymology KW - HIV Integrase -- chemistry KW - HIV-1 -- physiology KW - HIV-1 -- drug effects KW - HIV Integrase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78820459?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+agents+and+chemotherapy&rft.atitle=Diarylsulfones%2C+a+novel+class+of+human+immunodeficiency+virus+type+1+integrase+inhibitors.&rft.au=Neamati%2C+N%3BMazumder%2C+A%3BZhao%2C+H%3BSunder%2C+S%3BBurke%2C+T+R%3BSchultz%2C+R+J%3BPommier%2C+Y&rft.aulast=Neamati&rft.aufirst=N&rft.date=1997-02-01&rft.volume=41&rft.issue=2&rft.spage=385&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+agents+and+chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-05 N1 - Date created - 1997-05-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochem Pharmacol. 1994 Aug 3;48(3):595-608 [7520698] J Biol Chem. 1994 Aug 26;269(34):21635-8 [8063805] J Med Chem. 1995 Feb 3;38(3):443-52 [7853337] Antimicrob Agents Chemother. 1995 Feb;39(2):320-4 [7726489] Biochem Pharmacol. 1995 Apr 18;49(8):1165-70 [7748198] J Med Chem. 1995 Jul 7;38(14):2491-517 [7543152] Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8861-5 [7568032] J Med Chem. 1995 Oct 13;38(21):4171-8 [7473544] Biochemistry. 1995 Nov 21;34(46):15111-22 [7578125] Adv Pharmacol. 1995;33:389-438 [7495676] Antimicrob Agents Chemother. 1995 Aug;39(8):1756-63 [7486915] J Med Chem. 1996 Jan 19;39(2):522-30 [8558522] Mol Pharmacol. 1996 Apr;49(4):621-8 [8609889] J Med Chem. 1996 Jun 21;39(13):2472-81 [8691444] Biochem Pharmacol. 1996 Aug 9;52(3):475-80 [8687502] Curr Opin Struct Biol. 1996 Feb;6(1):76-83 [8696976] J Med Chem. 1987 May;30(5):900-6 [3572979] J Natl Cancer Inst. 1989 Apr 19;81(8):577-86 [2495366] Free Radic Biol Med. 1990;8(4):415-23 [2199344] Prog Drug Res. 1991;36:361-417 [1876709] Science. 1992 Feb 7;255(5045):723-6 [1738845] Antimicrob Agents Chemother. 1993 Apr;37(4):754-60 [7684215] Arch Biochem Biophys. 1993 Sep;305(2):606-10 [8373200] Annu Rev Biochem. 1994;63:133-73 [7526778] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Agricultural Health Study: factors affecting completion and return of self-administered questionnaires in a large prospective cohort study of pesticide applicators. AN - 78820010; 9028440 AB - Response rates were examined in a prospective epidemiologic study of individuals, mostly farmers, from Iowa and North Carolina seeking a pesticide applicator license during the period from 1994 through 1996. In the first year of enrollment 16,535 farmers (representing 77% of eligible farmer applicators) enrolled in the study by completing a 17-page questionnaire administered at a pesticide training session; 47% of the enrolled farmers completed and returned a much longer take-home questionnaire. The characteristics of farmers who completed only the enrollment questionnaire were quite similar to those of farmers who also completed and returned the take-home questionnaire. The most notable difference was the increased age of responders. Thus, the study population might have slightly higher cumulative farm exposures and slightly lower current farm exposures than the base population of all farmer applicators. The lack of evidence for substantial selection bias is reassuring for the Agricultural Health Study, and provides a measure of reassurance for other studies depending on the voluntary completion of self-administered questionnaires. JF - American journal of industrial medicine AU - Tarone, R E AU - Alavanja, M C AU - Zahm, S H AU - Lubin, J H AU - Sandler, D P AU - McMaster, S B AU - Rothman, N AU - Blair, A AD - Epidemiology and Biostatistics Program, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1997/02// PY - 1997 DA - February 1997 SP - 233 EP - 242 VL - 31 IS - 2 SN - 0271-3586, 0271-3586 KW - Pesticides KW - 0 KW - Index Medicus KW - Family Characteristics KW - Educational Status KW - Humans KW - Aged KW - Alcohol Drinking -- epidemiology KW - Feeding Behavior KW - Iowa KW - Smoking -- epidemiology KW - Marital Status KW - Prospective Studies KW - Adult KW - North Carolina KW - Occupational Diseases -- epidemiology KW - Middle Aged KW - Bias (Epidemiology) KW - Agriculture KW - Surveys and Questionnaires UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78820010?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=The+Agricultural+Health+Study%3A+factors+affecting+completion+and+return+of+self-administered+questionnaires+in+a+large+prospective+cohort+study+of+pesticide+applicators.&rft.au=Tarone%2C+R+E%3BAlavanja%2C+M+C%3BZahm%2C+S+H%3BLubin%2C+J+H%3BSandler%2C+D+P%3BMcMaster%2C+S+B%3BRothman%2C+N%3BBlair%2C+A&rft.aulast=Tarone&rft.aufirst=R&rft.date=1997-02-01&rft.volume=31&rft.issue=2&rft.spage=233&rft.isbn=&rft.btitle=&rft.title=American+journal+of+industrial+medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-28 N1 - Date created - 1997-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Paclitaxel by 96-hour continuous infusion in combination with cisplatin: a phase I trial in patients with advanced lung cancer. AN - 78816148; 9053499 AB - To determine the maximum-tolerated dose (MTD) of paclitaxel administered by 96-hour continuous infusion in combination with cisplatin, to determine if the addition of granulocyte colony-stimulating factor (G-CSF) permits significant paclitaxel dose escalation, and to assess the toxicity and preliminary activity of this combination in patients with advanced lung cancer. Fifty patients with untreated lung cancer were enrolled: 42 had advanced non-small-cell lung cancer (NSCLC) and eight had extensive-stage small-cell lung cancer (SCLC). Patients received paclitaxel doses of 100 to 180 mg/m2/96 hours and cisplatin doses of 60 to 80 mg/m2 as a single 30-minute bolus injection at the end of the paclitaxel infusion. Two of six patients experienced dose-limiting neutropenia at a dose of paclitaxel 140 mg/m2/96 hours and cisplatin 80 mg/m2. With G-CSF support, one of three patients experienced both dose-limiting mucositis and fatal neutropenic sepsis at a dose of paclitaxel 180 mg/m2/96 hours and cisplatin 80 mg/m2. Significant peripheral neuropathy developed in five patients and occurred after six or more cycles of therapy. Thirty-three of 42 patients with NSCLC had measurable disease; the objective response rate was 55%, with two complete responses and 16 partial responses. For all 42 patients with NSCLC, the median time to progression and median survival duration were 5 months and 10 months, respectively. The actuarial 1-year survival rate was 41%. Of eight SCLC patients, four responded to therapy, and the median survival duration for all SCLC patients was 11 months. The MTD without G-CSF is paclitaxel 120 mg/m2/96 hours and cisplatin 80 mg/m2, and the MTD with G-CSF is paclitaxel 160 mg/m2/96 hours and cisplatin 80 mg/m2. Infusional paclitaxel with cisplatin is well tolerated and active in patients with advanced NSCLC. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Georgiadis, M S AU - Schuler, B S AU - Brown, J E AU - Kieffer, L V AU - Steinberg, S M AU - Wilson, W H AU - Takimoto, C H AU - Kelley, M J AU - Johnson, B E AD - National Cancer Institute-Navy Medical Oncology Branch, National Cancer Institute, Bethesda, MD, USA. georgiam@navmed.nci.nih.gov Y1 - 1997/02// PY - 1997 DA - February 1997 SP - 735 EP - 743 VL - 15 IS - 2 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents KW - 0 KW - Antineoplastic Agents, Phytogenic KW - Paclitaxel KW - P88XT4IS4D KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Paclitaxel -- administration & dosage KW - Disease-Free Survival KW - Antineoplastic Agents -- administration & dosage KW - Infusions, Intravenous KW - Injections, Intravenous KW - Paclitaxel -- pharmacokinetics KW - Humans KW - Aged KW - Cisplatin -- administration & dosage KW - Antineoplastic Agents, Phytogenic -- pharmacokinetics KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Antineoplastic Agents, Phytogenic -- administration & dosage KW - Female KW - Male KW - Carcinoma, Non-Small-Cell Lung -- blood KW - Carcinoma, Small Cell -- blood KW - Lung Neoplasms -- blood KW - Lung Neoplasms -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Carcinoma, Small Cell -- drug therapy KW - Carcinoma, Non-Small-Cell Lung -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78816148?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Paclitaxel+by+96-hour+continuous+infusion+in+combination+with+cisplatin%3A+a+phase+I+trial+in+patients+with+advanced+lung+cancer.&rft.au=Georgiadis%2C+M+S%3BSchuler%2C+B+S%3BBrown%2C+J+E%3BKieffer%2C+L+V%3BSteinberg%2C+S+M%3BWilson%2C+W+H%3BTakimoto%2C+C+H%3BKelley%2C+M+J%3BJohnson%2C+B+E&rft.aulast=Georgiadis&rft.aufirst=M&rft.date=1997-02-01&rft.volume=15&rft.issue=2&rft.spage=735&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-10 N1 - Date created - 1997-03-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thyroid nodularity and cancer among Chernobyl cleanup workers from Estonia. AN - 78812957; 9008215 AB - Thyroid examinations, including palpation, ultrasound and, selectively, fine-needle aspiration biopsy, were conducted on nearly 2,000 Chernobyl cleanup workers from Estonia to evaluate the occurrence of thyroid cancer and nodular thyroid disease among men with protracted exposure to ionizing radiation. The examinations were conducted in four cities in Estonia during March-April 1995, 9 years after the reactor accident. The study population was selected from a predefined cohort of 4,833 cleanup workers from Estonia under surveillance for cancer incidence. These men had been sent to Chernobyl between 1986 and 1991 to entomb the damaged reactor, remove radioactive debris and perform related cleanup activities. A total of 2,997 men were invited for thyroid screening and 1,984 (66%) were examined. Estimates of radiation dose from external sources were obtained from military or other institutional records, and details about service dates and types of work performed while at Chernobyl were obtained from a self-administered questionnaire. Blood samples were collected for assay of chromosomal translocations in circulating lymphocytes and loss of expression of the glycophorin A (GPA) gene in erythrocytes. The primary outcome measure was the presence or absence of thyroid nodules as determined by the ultrasound examination. Of the screened workers, 1,247 (63%) were sent to Chernobyl in 1986, including 603 (30%) sent in April or May, soon after the accident. Workers served at Chernobyl for an average of 3 months. The average age was 32 years at the time of arrival at Chernobyl and 40 years at the time of thyroid examination. The mean documented radiation dose from external sources was 10.8 cGy. Biological indicators of exposure showed low correlations with documented dose, but did not indicate that the mean dose for the population was higher than the average documented dose. Ultrasound examinations revealed thyroid nodules in 201 individuals (10.2%). The prevalence of nodules increased with age at examination, but no significant associations were observed with recorded dose, date of first duty at Chernobyl, duration of service at Chernobyl, building the sarcophagus or working on the roof of neighboring buildings or close to the damaged reactor. Nodularity showed a nonsignificant (p(1) = 0.10) positive association with the proportion of lymphocytes with chromosome translocations, but associations with the frequency of variant erythrocytes in the GPA assay were weak and unstable (p(1) > or = 0.46). The majority of fine-needle biopsies taken on 77 study participants indicated benign nodular disease. However, two cases of papillary carcinoma and three benign follicular neoplasms were identified and referred for treatment. Both men with thyroid cancer had been sent to Chernobyl in May of 1986, when the potential for exposure to radioactive iodines was greatest. Chernobyl cleanup workers from Estonia did not experience a markedly increased risk of nodular thyroid disease associated with exposure to external radiation. Possible reasons for the apparent absence of effect include low radiation doses, the protracted nature of the exposure, errors in dose measurement, low sensitivity of the adult thyroid gland or the insufficient passage of time for a radiation effect to be expressed. JF - Radiation research AU - Inskip, P D AU - Hartshorne, M F AU - Tekkel, M AU - Rahu, M AU - Veidebaum, T AU - Auvinen, A AU - Crooks, L A AU - Littlefield, L G AU - McFee, A F AU - Salomaa, S AU - Makinen, S AU - Tucker, J D AU - Sorensen, K J AU - Bigbee, W L AU - Boice, J D AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland 20892, USA. Y1 - 1997/02// PY - 1997 DA - February 1997 SP - 225 EP - 235 VL - 147 IS - 2 SN - 0033-7587, 0033-7587 KW - Glycophorin KW - 0 KW - Index Medicus KW - Space life sciences KW - Glycophorin -- genetics KW - Adenocarcinoma, Follicular -- epidemiology KW - Humans KW - Carcinoma, Papillary -- epidemiology KW - Ukraine KW - Adenocarcinoma, Follicular -- etiology KW - Erythrocyte Membrane -- chemistry KW - Carcinoma, Papillary -- etiology KW - Biopsy, Needle KW - Ultrasonography KW - Translocation, Genetic KW - Thyroid Gland -- radiation effects KW - Population Surveillance KW - Chromosomes, Human -- radiation effects KW - Estonia -- epidemiology KW - Adult KW - Cohort Studies KW - Adenocarcinoma, Follicular -- pathology KW - Middle Aged KW - Carcinoma, Papillary -- pathology KW - Lymphocytes -- ultrastructure KW - Radiation Monitoring KW - Male KW - Prevalence KW - Occupational Exposure KW - Neoplasms, Radiation-Induced -- etiology KW - Radioactive Hazard Release KW - Neoplasms, Radiation-Induced -- epidemiology KW - Thyroid Nodule -- epidemiology KW - Thyroid Neoplasms -- etiology KW - Thyroid Nodule -- diagnostic imaging KW - Thyroid Neoplasms -- epidemiology KW - Neoplasms, Radiation-Induced -- diagnostic imaging KW - Power Plants KW - Neoplasms, Radiation-Induced -- pathology KW - Thyroid Neoplasms -- diagnostic imaging KW - Thyroid Neoplasms -- pathology KW - Thyroid Nodule -- pathology KW - Thyroid Nodule -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78812957?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Thyroid+nodularity+and+cancer+among+Chernobyl+cleanup+workers+from+Estonia.&rft.au=Inskip%2C+P+D%3BHartshorne%2C+M+F%3BTekkel%2C+M%3BRahu%2C+M%3BVeidebaum%2C+T%3BAuvinen%2C+A%3BCrooks%2C+L+A%3BLittlefield%2C+L+G%3BMcFee%2C+A+F%3BSalomaa%2C+S%3BMakinen%2C+S%3BTucker%2C+J+D%3BSorensen%2C+K+J%3BBigbee%2C+W+L%3BBoice%2C+J+D&rft.aulast=Inskip&rft.aufirst=P&rft.date=1997-02-01&rft.volume=147&rft.issue=2&rft.spage=225&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 - 1997-02-20 N1 - Date created - 1997-02-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of alterations in calcium homeostasis on apoptosis during neoplastic progression. AN - 78811743; 9012487 AB - Our previous studies showed that early, stage I preneoplastic cells (sup+ I) are highly susceptible to apoptosis, whereas the later, stage II preneoplastic cells (sup- II) are relatively resistant. To examine possible mechanisms that might explain these differences in the regulation of apoptosis, Ca2+ homeostasis was analyzed and comparisons were made between these two Syrian hamster embryo cell lines. The Ca2+ indicator, fura-2, and fluorescent microscopy were used to measure intracellular free calcium concentrations, [Ca2+]i. The results indicated that the [Ca2+]i level in logarithmically growing sup+ I cells (approximately 100 nM) was considerably lower than that observed in sup- II cells (approximately 260 nM). Serum removal resulted in a reduction of [Ca2+]i in the sup+ I cells (approximately 82 nM), whereas the [Ca2+]i level in sup- II cells did not change. Endoplasmic reticulum (ER) calcium levels were determined by measuring thapsigargin-releasable Ca2+. Reduced ER calcium was consistently observed in cells induced to undergo apoptosis. Specifically, thapsigargin-releasable Ca2+ was greatly reduced in sup+ I cells (45 nM) as compared to sup- II cells (190 nNM) after 4 h in low serum. When sup- II cells were placed under conditions that resulted in apoptosis (thapsigargin or okadaic acid), decreased ER calcium was observed. To determine whether reduced ER calcium had a causative effect in apoptosis, ER calcium levels were exogenously increased in sup+ I cells by raising extracellular Ca2+ to 3 mM; ER calcium levels were maintained, and apoptosis was blocked. Studies were performed to determined whether the decrease in ER calcium could be attributed to reduced Ca2+ influx at the plasma membrane. To measure directly whether Ca2+ entry was decreased in sup+ I cells in 0.2% serum, Mn2+ uptake was used to monitor Ca2+ influx. The data show that in low serum, the rate of thapsigargin-induced Mn2+ entry in sup+ I cells was approximately 50% lower than that of sup- II cells, demonstrating that capacitative entry is reduced in sup+ I cells. In further support of this hypothesis, thapsigargin-treated sup+ I cells (0.2% serum) showed decreased Ca2+ entry upon raising extracellular Ca2+ from 0 to 2 mM. We report the novel finding that early preneoplastic cells, which exhibit a high propensity to undergo apoptosis, have decreased calcium entry at the plasma membrane, resulting in decreased ER calcium pools. This study provides new insight into mechanisms that can be involved in the regulation/dysregulation of apoptosis during neoplastic progression. Furthermore, the data imply that preneoplastic cells, which have developed a mechanism to maintain ER calcium, would be less susceptible to apoptosis and would thus have an increased potential for becoming transformed. JF - Cancer research AU - Preston, G A AU - Barrett, J C AU - Biermann, J A AU - Murphy, E AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/02/01/ PY - 1997 DA - 1997 Feb 01 SP - 537 EP - 542 VL - 57 IS - 3 SN - 0008-5472, 0008-5472 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Endoplasmic Reticulum -- metabolism KW - Animals KW - Cell Line KW - Cricetinae KW - Calcium -- metabolism KW - Apoptosis KW - Homeostasis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78811743?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effects+of+alterations+in+calcium+homeostasis+on+apoptosis+during+neoplastic+progression.&rft.au=Preston%2C+G+A%3BBarrett%2C+J+C%3BBiermann%2C+J+A%3BMurphy%2C+E&rft.aulast=Preston&rft.aufirst=G&rft.date=1997-02-01&rft.volume=57&rft.issue=3&rft.spage=537&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-20 N1 - Date created - 1997-02-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adrenomedullin receptor expression in human lung and in pulmonary tumors. AN - 78811071; 9016306 AB - Adrenomedullin (AM) is a multifunctional regulatory peptide that stimulates cyclic AMP production in many target tissues and is highly expressed in the lung. Analysis of the distribution of the recently cloned AM receptor (AM-R) by non-radioactive in situ hybridization revealed abundant expression in the basal cells of the airway epithelium and Type II pneumocytes. The expression of AM-R in the two cell types involved in epithelial regeneration of the lung suggests that AM may be relevant in such functions as organ development, wound repair, and epithelial turnover. AM-Rs are also synthesized in vivo and in vitro by a variety of tumor cells that also express the ligand, suggesting the existence of an autocrine loop that may be involved in tumor growth stimulation. The present findings suggest that the AM/AM-R regulatory system plays a major role in respiratory physiology and lung carcinogenesis and that new functions for AM remain to be identified. JF - The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society AU - Martínez, A AU - Miller, M J AU - Catt, K J AU - Cuttitta, F AD - Biomarkers and Prevention Research Branch, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20850-3300, USA. Y1 - 1997/02// PY - 1997 DA - February 1997 SP - 159 EP - 164 VL - 45 IS - 2 SN - 0022-1554, 0022-1554 KW - Membrane Proteins KW - 0 KW - Receptors, Adrenomedullin KW - Receptors, Peptide KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Rats KW - Polymerase Chain Reaction KW - Animals KW - Adenocarcinoma -- metabolism KW - In Situ Hybridization KW - Tumor Cells, Cultured KW - Carcinoma, Small Cell -- metabolism KW - Blotting, Southern KW - Humans KW - Carcinoma, Squamous Cell -- metabolism KW - Carcinoma, Large Cell -- metabolism KW - Membrane Proteins -- metabolism KW - GTP-Binding Proteins -- metabolism KW - Lung -- metabolism KW - Lung Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78811071?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+histochemistry+and+cytochemistry+%3A+official+journal+of+the+Histochemistry+Society&rft.atitle=Adrenomedullin+receptor+expression+in+human+lung+and+in+pulmonary+tumors.&rft.au=Mart%C3%ADnez%2C+A%3BMiller%2C+M+J%3BCatt%2C+K+J%3BCuttitta%2C+F&rft.aulast=Mart%C3%ADnez&rft.aufirst=A&rft.date=1997-02-01&rft.volume=45&rft.issue=2&rft.spage=159&rft.isbn=&rft.btitle=&rft.title=The+journal+of+histochemistry+and+cytochemistry+%3A+official+journal+of+the+Histochemistry+Society&rft.issn=00221554&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-03 N1 - Date created - 1997-03-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Serum ionized magnesium in chronic alcoholism: is it really decreased? AN - 78810583; 9023146 AB - Chronic alcoholism is associated with a marked deficit in total magnesium (tMg). However, little is known about the status of the physiologically active form, ionized magnesium (iMg). We assessed serum iMg (measured with two ion-selective electrodes, AVL 988-4 and NOVA CRT) and tMg concentrations in chronic alcoholics at admission (n = 31) and after abstinence (n = 13) and compared these results with those for a control group (n = 40). At admission, the tMg and NOVA iMg concentrations in alcoholics (0.78 +/- 0.020 and 0.38 +/- 0.016 mmol/L, respectively) were significantly less (P 0.05). The mean iMg between the two analyzers differed significantly in both groups (P <0.001). After 3 weeks of abstinence, the alcoholics showed a significant increase in tMg (P <0.001) and in both NOVA and AVL iMg values (P <0.01 for each). tMg concentrations were positively correlated with the AVL iMg values in both alcoholics and controls but correlated positively with the NOVA iMg results only in the controls. Thus, the altered status of iMg is instrument-dependent, and the usefulness of the measurement in alcoholics is yet to be determined. JF - Clinical chemistry AU - Hristova, E N AU - Rehak, N N AU - Cecco, S AU - Ruddel, M AU - Herion, D AU - Eckardt, M AU - Linnoila, M AU - Elin, R J AD - Clinical Chemistry Service, Clinical Pathology Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. ehristova@nih.gov Y1 - 1997/02// PY - 1997 DA - February 1997 SP - 394 EP - 399 VL - 43 IS - 2 SN - 0009-9147, 0009-9147 KW - Keto Acids KW - 0 KW - Ethanol KW - 3K9958V90M KW - Magnesium KW - I38ZP9992A KW - Index Medicus KW - Reference Values KW - Ethanol -- pharmacology KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Keto Acids -- pharmacology KW - Male KW - Female KW - Ion-Selective Electrodes KW - Magnesium -- blood KW - Alcoholism -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78810583?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Serum+ionized+magnesium+in+chronic+alcoholism%3A+is+it+really+decreased%3F&rft.au=Hristova%2C+E+N%3BRehak%2C+N+N%3BCecco%2C+S%3BRuddel%2C+M%3BHerion%2C+D%3BEckardt%2C+M%3BLinnoila%2C+M%3BElin%2C+R+J&rft.aulast=Hristova&rft.aufirst=E&rft.date=1997-02-01&rft.volume=43&rft.issue=2&rft.spage=394&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 - 1997-03-06 N1 - Date created - 1997-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Acute effects of bromocriptine, cyproheptadine, and valproic acid on plasma adrenocorticotropin secretion in Nelson's syndrome. AN - 78808684; 9024246 AB - Previous studies have found that bromocriptine, cyproheptadine, and valproic acid can reduce ACTH secretion in Nelson's syndrome, but none of these agents has achieved widespread use due to their failure to normalize ACTH in most patients. The current study was undertaken to determine whether these three agents, which act through different mechanisms, decrease plasma ACTH synergistically when administered together. Six adult female patients (mean age, 41 yr) with Nelson's syndrome were studied. ACTH was measured every 20 min for 8 h, 2 h before and 6 h after each of the following six treatments: placebo, bromocriptine (2.5 mg), cyproheptadine (8 mg), valproic acid (1 g), cyproheptadine plus valproic acid, and the combination of all three drugs. The sequence of treatments was determined randomly, and there was an interval of at least 2 days between each treatment. The hourly ACTH values were averaged, and the percent maximal suppression of plasma ACTH, relative to the baseline values before drug administration, was compared among the six treatments. Basal plasma ACTH levels in the six patients ranged from 40-3324 pmol/L (normal range, 1-8). The percent maximal suppression of ACTH after administration of placebo (6 +/- 11%), cyproheptadine (17 +/- 15%), valproic acid (37 +/- 10%) or the combination of cyproheptadine and valproic acid (19 +/- 14%) did not achieve statistical significance. Bromocriptine, on the other hand, caused a significant decrease in plasma ACTH (52 +/- 8%; P < 0.05), as did the combination of bromocriptine, cyproheptadine, and valproic acid (58 +/- 12%; P < 0.05). However, the combined effect of the three drugs did not significantly exceed the effect of bromocriptine alone. We conclude that at the doses studied, bromocriptine had the greatest acute effect in suppressing ACTH secretion in Nelson's syndrome, and that combined administration with valproic acid and cyproheptadine did not further increase this acute ACTH-suppressive effect. JF - The Journal of clinical endocrinology and metabolism AU - Mercado-Asis, L B AU - Yanovski, J A AU - Tracer, H L AU - Chik, C L AU - Cutler, G B AD - Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/02// PY - 1997 DA - February 1997 SP - 514 EP - 517 VL - 82 IS - 2 SN - 0021-972X, 0021-972X KW - Drug Combinations KW - 0 KW - Cyproheptadine KW - 2YHB6175DO KW - Bromocriptine KW - 3A64E3G5ZO KW - Valproic Acid KW - 614OI1Z5WI KW - Adrenocorticotropic Hormone KW - 9002-60-2 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Adult KW - Middle Aged KW - Drug Synergism KW - Time Factors KW - Female KW - Nelson Syndrome -- drug therapy KW - Bromocriptine -- adverse effects KW - Nelson Syndrome -- blood KW - Bromocriptine -- therapeutic use KW - Cyproheptadine -- therapeutic use KW - Valproic Acid -- adverse effects KW - Cyproheptadine -- adverse effects KW - Valproic Acid -- therapeutic use KW - Adrenocorticotropic Hormone -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78808684?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+endocrinology+and+metabolism&rft.atitle=Acute+effects+of+bromocriptine%2C+cyproheptadine%2C+and+valproic+acid+on+plasma+adrenocorticotropin+secretion+in+Nelson%27s+syndrome.&rft.au=Mercado-Asis%2C+L+B%3BYanovski%2C+J+A%3BTracer%2C+H+L%3BChik%2C+C+L%3BCutler%2C+G+B&rft.aulast=Mercado-Asis&rft.aufirst=L&rft.date=1997-02-01&rft.volume=82&rft.issue=2&rft.spage=514&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+endocrinology+and+metabolism&rft.issn=0021972X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-11 N1 - Date created - 1997-03-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of refractory chronic lymphocytic leukemia with fludarabine phosphate via the group C protocol mechanism of the National Cancer Institute: five-year follow-up report. AN - 78805893; 9053466 AB - To provide fludarabine to physicians for the management of patients with advanced refractory chronic lymphocytic leukemia (CLL) and to determine the response rate and duration, toxicity, and survival with this agent. This phase II protocol was open to all eligible patients whose local physicians obtained written permission from the National Cancer Institute (NCI) to register patients onto this protocol. Of 791 national and international enrolled patients, 724 with a median age of 65 years received fludarabine, of which 703 were assessable for response. Thirty-two percent of assessable patients responded (95% confidence interval [CI], 29% to 36%), with 21 patients (3%) obtaining a complete response and 205 (29%) a partial response. The median duration of response was 13.1 months and the median survival time from registration was 12.6 months. Age, performance status (PS), and Rai stage correlated with survival (P < .01). Grade 4 hematologic toxicity was reported in 43% and was associated with infection in 22%. Neurotoxicity (primarily grade 1 motor dysfunction) was reported in 14% patients and correlated with age. This study describes the toxicity and activity of fludarabine in refractory CLL in a setting that more closely resembles clinical practice than most published trials. The low response rate may be related to advanced stage (89% Rai high-risk), disease-related symptoms (63% had B symptoms), and/or degree of prior treatment. Other contributing factors inherent in a group C treatment protocol included lack of central pathology review, variable supportive care, and a tendency to use this mechanism at a later stage in the disease. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Sorensen, J M AU - Vena, D A AU - Fallavollita, A AU - Chun, H G AU - Cheson, B D AD - Division of Cancer Treatment, Diagnosis and Centers, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/02// PY - 1997 DA - February 1997 SP - 458 EP - 465 VL - 15 IS - 2 SN - 0732-183X, 0732-183X KW - Antimetabolites, Antineoplastic KW - 0 KW - Vidarabine Phosphate KW - 106XV160TZ KW - fludarabine phosphate KW - 1X9VK9O1SC KW - Index Medicus KW - United States KW - Drug Administration Schedule KW - Disease-Free Survival KW - Humans KW - National Institutes of Health (U.S.) KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Follow-Up Studies KW - Male KW - Female KW - Clinical Protocols KW - Survival Analysis KW - Antimetabolites, Antineoplastic -- administration & dosage KW - Vidarabine Phosphate -- therapeutic use KW - Leukemia, Lymphocytic, Chronic, B-Cell -- drug therapy KW - Vidarabine Phosphate -- adverse effects KW - Antimetabolites, Antineoplastic -- adverse effects KW - Vidarabine Phosphate -- administration & dosage KW - Antimetabolites, Antineoplastic -- therapeutic use KW - Vidarabine Phosphate -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78805893?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Treatment+of+refractory+chronic+lymphocytic+leukemia+with+fludarabine+phosphate+via+the+group+C+protocol+mechanism+of+the+National+Cancer+Institute%3A+five-year+follow-up+report.&rft.au=Sorensen%2C+J+M%3BVena%2C+D+A%3BFallavollita%2C+A%3BChun%2C+H+G%3BCheson%2C+B+D&rft.aulast=Sorensen&rft.aufirst=J&rft.date=1997-02-01&rft.volume=15&rft.issue=2&rft.spage=458&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-10 N1 - Date created - 1997-03-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Epidemiology of acute leukemia in children and adults. AN - 78805570; 9045302 AB - The epidemiologic features of acute leukemia in children and adults are reviewed and suggestions are made for new research directions. Similarities in risk factors exist for adults and children, but differences in tumor biology suggest that the etiological factors may not be the same. Many unifying hypotheses have been proposed for childhood leukemia based on well-designed studies. Two recent theories, both involving an unusual response to childhood infection, attempt to explain the 2- to 5-year age peak. The etiology of infant leukemia may be related to chromosomal damage sustained in utero, analogous to the damage in adults with treatment-related leukemia. Although much is known about risk for treatment-related leukemias in adults, environmental, occupational, and other risk factors are less well studied. More homogeneous populations are needed for study including populations where distinction is made between acute myleloid leukemia patients with and without antecedent hematologic disorders. JF - Seminars in oncology AU - Sandler, D P AU - Ross, J A AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1997/02// PY - 1997 DA - February 1997 SP - 3 EP - 16 VL - 24 IS - 1 SN - 0093-7754, 0093-7754 KW - Index Medicus KW - Infant KW - Acute Disease KW - Leukemia, Radiation-Induced -- epidemiology KW - Humans KW - Adult KW - Incidence KW - Child KW - United States -- epidemiology KW - Male KW - Female KW - Child, Preschool KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- epidemiology KW - Leukemia, Myeloid -- epidemiology KW - Leukemia, Myeloid -- etiology KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78805570?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+oncology&rft.atitle=Epidemiology+of+acute+leukemia+in+children+and+adults.&rft.au=Sandler%2C+D+P%3BRoss%2C+J+A&rft.aulast=Sandler&rft.aufirst=D&rft.date=1997-02-01&rft.volume=24&rft.issue=1&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Seminars+in+oncology&rft.issn=00937754&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-03 N1 - Date created - 1997-03-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Estimating lung cancer mortality from residential radon using data for low exposures of miners. AN - 78804421; 9008203 AB - Some recent estimates of lung cancer risk from exposure to radon progeny in homes have been based on models developed from a pooled analysis of 11 cohorts of underground miners exposed to radon. While some miners were exposed to over 10,000 working level months (WLM), mean exposure among exposed miners was 162 WLM, about 10 times the exposure from lifetime residence in an average house and about three times the exposure from lifetime residence at the "action level" suggested by the U.S. Environmental Protection Agency. The extrapolation of lung cancer risk from the higher exposures in the miners to the generally lower exposures in the home is a substantial source of uncertainty in the assessment of the risk of indoor radon. Using the pooled data for the miners, analyses of lung cancer risk were carried out on data restricted to lower exposures, either <50 WLM or <100 WLM. In the pooled data, there were 115 lung cancer cases among workers with no occupational WLM exposure and 2,674 among exposed miners, with 353 and 562 lung cancer cases in miners with <50 WLM and <100 WLM, respectively. Relative risks (RRs) for categories of WLM based on deciles exhibited a statistically significant increasing trend with exposure in each of the restricted data sets. In the restricted data, there was little evidence of departures from a linear excess relative risk model in cumulative exposure, although power to assess alternative exposure-response trends was limited. The general patterns of declining excess RR per WLM with attained age, time since exposure and exposure rate seen in the unrestricted data were similar to the patterns found in the restricted data. Risk models based on the unrestricted data for miners provided an excellent fit to the restricted data, suggesting substantial internal validity in the projection of risk from miners with high exposures to those with low exposures. Estimates of attributable risk for lung cancer (10-14%) in the U.S. from residential radon based on models from the unrestricted data were similar to estimates based on the data for miners receiving low exposures. JF - Radiation research AU - Lubin, J H AU - Tomásek, L AU - Edling, C AU - Hornung, R W AU - Howe, G AU - Kunz, E AU - Kusiak, R A AU - Morrison, H I AU - Radford, E P AU - Samet, J M AU - Tirmarche, M AU - Woodward, A AU - Yao, S X AD - Biostatistics Branch, Epidemiology and Biostatistics Program, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1997/02// PY - 1997 DA - February 1997 SP - 126 EP - 134 VL - 147 IS - 2 SN - 0033-7587, 0033-7587 KW - Air Pollutants, Radioactive KW - 0 KW - Uranium KW - 4OC371KSTK KW - Radon KW - Q74S4N8N1G KW - Index Medicus KW - Space life sciences KW - Risk KW - Humans KW - Cohort Studies KW - Middle Aged KW - Dose-Response Relationship, Radiation KW - Risk Assessment KW - Occupational Exposure KW - Lung Neoplasms -- etiology KW - Air Pollutants, Radioactive -- administration & dosage KW - Neoplasms, Radiation-Induced -- etiology KW - Housing KW - Environmental Exposure KW - Neoplasms, Radiation-Induced -- mortality KW - Lung Neoplasms -- mortality KW - Air Pollutants, Radioactive -- adverse effects KW - Radon -- administration & dosage KW - Mining KW - Radon -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78804421?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Estimating+lung+cancer+mortality+from+residential+radon+using+data+for+low+exposures+of+miners.&rft.au=Lubin%2C+J+H%3BTom%C3%A1sek%2C+L%3BEdling%2C+C%3BHornung%2C+R+W%3BHowe%2C+G%3BKunz%2C+E%3BKusiak%2C+R+A%3BMorrison%2C+H+I%3BRadford%2C+E+P%3BSamet%2C+J+M%3BTirmarche%2C+M%3BWoodward%2C+A%3BYao%2C+S+X&rft.aulast=Lubin&rft.aufirst=J&rft.date=1997-02-01&rft.volume=147&rft.issue=2&rft.spage=126&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 - 1997-02-20 N1 - Date created - 1997-02-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Radiat Res. 1997 Feb;147(2):135-7 [9008204] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The molecular pathogenesis of treatment-induced (secondary) leukemias: foundations for treatment and prevention. AN - 78803212; 9045296 AB - Acute myeloid leukemia (AML) developing after exposure to genotoxic agents has been recognized as a distinctive entity for more than 40 years. Secondary, or therapy-related, AML accounts for 10% to 20% of all AML cases. The basic and clinical investigation of these complex malignancies can be approached from four major vantage points: (I) dissection of the molecular structure of the induced genetic lesions and identification of the functional consequences of these changes, thereby providing clues to the pathogenesis of secondary AML and potentially serving as a basis for innovative therapeutic interventions; (2) identification and characterization of mechanisms of DNA damage and the orderly repair of such damage; (3) identification and application of accurate biomarkers of leukemogenesis for the purpose of risk prediction and quantification, potentially allowing recognition of patients especially susceptible to the leukemogenic effects of chemotherapy (for genetic or acquired reasons) and allowing their treatment for cancer to be modified based on this susceptibility; and (4) design and implementation of longitudinal clinical and genetic monitoring of high-risk populations (ie, individuals undergoing cytotoxic therapies for primary malignancies). In this article, we build on these themes, and attempt to integrate these seemingly disparate areas of research so that they can be more effectively used together to address the problem of secondary AML. Ultimately, the evaluation of these areas will inform our understanding of de novo leukemia and serve as a springboard for the development of new concepts of therapy and prevention. JF - Seminars in oncology AU - Karp, J E AU - Smith, M A AD - Division of Cancer Prevention and Control, National Cancer Institute, Bethesda, MD, USA. Y1 - 1997/02// PY - 1997 DA - February 1997 SP - 103 EP - 113 VL - 24 IS - 1 SN - 0093-7754, 0093-7754 KW - Antineoplastic Agents, Alkylating KW - 0 KW - Podophyllotoxin KW - L36H50F353 KW - Index Medicus KW - Acute Disease KW - Molecular Epidemiology KW - Humans KW - Neoplasms, Second Primary -- therapy KW - Leukemia, Myeloid -- chemically induced KW - DNA Repair KW - DNA Damage KW - Neoplasms, Second Primary -- genetics KW - Leukemia, Myeloid -- genetics KW - Leukemia, Myeloid -- therapy KW - Antineoplastic Agents, Alkylating -- adverse effects KW - Podophyllotoxin -- adverse effects KW - Neoplasms, Second Primary -- prevention & control KW - Neoplasms, Second Primary -- chemically induced KW - Leukemia, Myeloid -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78803212?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+oncology&rft.atitle=The+molecular+pathogenesis+of+treatment-induced+%28secondary%29+leukemias%3A+foundations+for+treatment+and+prevention.&rft.au=Karp%2C+J+E%3BSmith%2C+M+A&rft.aulast=Karp&rft.aufirst=J&rft.date=1997-02-01&rft.volume=24&rft.issue=1&rft.spage=103&rft.isbn=&rft.btitle=&rft.title=Seminars+in+oncology&rft.issn=00937754&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-03 N1 - Date created - 1997-03-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Integrity of p53 in hepatitis B x antigen-positive and -negative hepatocellular carcinomas. AN - 78801432; 9012469 AB - Inactivation of the tumor suppressor p53 seems to be important to the pathogenesis of hepatocellular carcinoma (HCC) associated with chronic hepatitis B virus infection. Although this inactivation may be due to mutations in the p53 gene, recent evidence suggests that the hepatitis B virus-encoded X antigen (HBxAg) binds to and inactivates wild-type p53. Hence, experiments were designed to test the hypothesis that there is a low frequency of p53 mutations in HBxAg-positive HCC. HBxAg and p53 were assayed by immunohistochemistry (IHC) in HCC and nontumor liver from 16 Chinese patients, half of whom were hepatitis B surface antigen carriers. HBxAg was detectable in tumor and/or nontumor cells from all patients by IHC; six of these samples also had detectable p53. To determine whether p53 detection by IHC, and hence stabilization, is associated with mutation, sequencing of p53 exons 5-8 was performed with each patient sample. Wild-type sequences were found in 13 of 16 HBxAg-positive cases (81%). Hence, HBxAg is a common marker of HCC that correlates with the persistence of wild-type p53 among both carriers and noncarriers. The low frequency of p53 mutations in HCC in these patients implies that p53 inactivation may occur predominantly by complex formation with HBxAg. JF - Cancer research AU - Greenblatt, M S AU - Feitelson, M A AU - Zhu, M AU - Bennett, W P AU - Welsh, J A AU - Jones, R AU - Borkowski, A AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1997/02/01/ PY - 1997 DA - 1997 Feb 01 SP - 426 EP - 432 VL - 57 IS - 3 SN - 0008-5472, 0008-5472 KW - Hepatitis B Antigens KW - 0 KW - Trans-Activators KW - Tumor Suppressor Protein p53 KW - hepatitis B virus X protein KW - Index Medicus KW - Humans KW - Mutation KW - Immunohistochemistry KW - Tumor Suppressor Protein p53 -- analysis KW - Carcinoma, Hepatocellular -- etiology KW - Hepatitis B Antigens -- analysis KW - Trans-Activators -- analysis KW - Liver Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78801432?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Integrity+of+p53+in+hepatitis+B+x+antigen-positive+and+-negative+hepatocellular+carcinomas.&rft.au=Greenblatt%2C+M+S%3BFeitelson%2C+M+A%3BZhu%2C+M%3BBennett%2C+W+P%3BWelsh%2C+J+A%3BJones%2C+R%3BBorkowski%2C+A%3BHarris%2C+C+C&rft.aulast=Greenblatt&rft.aufirst=M&rft.date=1997-02-01&rft.volume=57&rft.issue=3&rft.spage=426&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-20 N1 - Date created - 1997-02-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Infectious complications of patients undergoing therapy for acute leukemia: current status and future prospects. AN - 78800978; 9045299 AB - The success of managing the infectious complications of acute leukemia has permitted oncologists to develop new approaches to induction and high-dose therapy. The single most important risk factor for infection is the duration of absolute neutropenia. Historically, most attention was directed towards gram negative aerobes, especially Pseudomonas aeruginosa, but in recent years gram positive bacteria, generally considered to be less virulent, have become the most frequent isolates in most centers. A recent disturbing trend is the isolation of vancomycin-resistant enterococci. A recent controversy has been whether to use empirical vancomycin; the Centers for Disease Control has issued a formal recommendation discouraging empirical vancomycin in the febrile neutropenic patient. Empirical monotherapy has replaced combination therapy in many institutions except where there has been an increase in resistant isolates. In patients who remain profoundly neutropenic, fungal infections represent a serious source of secondary infection, especially species of Candida and Aspergillus. Recently lipid-based formulations of amphotericin B have offered reduced nephrotoxicity. Less toxic antifungals, the azoles, which include fluconazole and itraconazole, offer an attractive alternative to amphotericin B. New patterns of invasive mycoses have emerged, as for example hepatosplenic candidiasis, presenting new problems in diagnosis and therapy. The successful management of virus infections with herpes simplex, cytomegalovirus, varicella zoster, and Epstein Barr virus is based on early recognition and careful attention to prevention. JF - Seminars in oncology AU - Chanock, S J AU - Pizzo, P A AD - Pediatric Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1997/02// PY - 1997 DA - February 1997 SP - 132 EP - 140 VL - 24 IS - 1 SN - 0093-7754, 0093-7754 KW - Hematopoietic Cell Growth Factors KW - 0 KW - Index Medicus KW - Acute Disease KW - Hematopoietic Cell Growth Factors -- therapeutic use KW - Humans KW - Immunocompromised Host KW - Leukemia -- therapy KW - Bacterial Infections -- microbiology KW - Neutropenia -- complications KW - Mycoses -- microbiology KW - Virus Diseases -- virology KW - Neutropenia -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78800978?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+oncology&rft.atitle=Infectious+complications+of+patients+undergoing+therapy+for+acute+leukemia%3A+current+status+and+future+prospects.&rft.au=Chanock%2C+S+J%3BPizzo%2C+P+A&rft.aulast=Chanock&rft.aufirst=S&rft.date=1997-02-01&rft.volume=24&rft.issue=1&rft.spage=132&rft.isbn=&rft.btitle=&rft.title=Seminars+in+oncology&rft.issn=00937754&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-03 N1 - Date created - 1997-03-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cyclophilin A is present in rat germ cells and is associated with spermatocyte apoptosis. Reproductive Toxicology Group. AN - 78798947; 9116144 AB - Recent investigations in our laboratory revealed divalent cation-dependent endonuclease activity in testes from 2-methoxyethanol-treated rats, which was able to cleave substrate DNA into a pattern of DNA fragmentation consisting of approximately 180-200 base pairs. Further studies were undertaken to characterize the active nuclease. F344 rats were treated with 2-methoxyethanol, a glycol ether that causes the death of pachytene spermatocytes in juvenile and adult rats. The active nuclease was found in nuclear extract from treated animals, but not controls. A radioactive gel nuclease assay, which detects degradation and loss of 32P-labeled DNA from a DNA-containing polyacrylamide gel, localized the nuclease activity to a band of approximately 18 kDa. This activity was dependent on calcium and was inhibited by both zinc and aurintricarboxylic acid. Amino acid sequence data showed that this protein was identical to cyclophilin A. Immunohistochemistry using antibodies against cyclophilin A found specific staining in pachytene spermatocytes, spermatids, interstitial cells, and Sertoli cell nuclei. Cyclophilin A staining was present in both control and 2-methoxyethanol-treated rat testes in a stage-dependent manner, with pachytene spermatocytes in stage-VIII-XIV seminiferous tubules most heavily stained. These data demonstrate that rat testis germ cells contain relatively high levels of cyclophilin A whose nuclease activity is associated with spermatocyte apoptosis induced by 2-methoxyethanol. JF - Biology of reproduction AU - Wine, R N AU - Ku, W W AU - Li, L H AU - Chapin, R E AD - National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. wine@niehs.nih.gov Y1 - 1997/02// PY - 1997 DA - February 1997 SP - 439 EP - 446 VL - 56 IS - 2 SN - 0006-3363, 0006-3363 KW - Carrier Proteins KW - 0 KW - Ethylene Glycols KW - Peptide Fragments KW - Endodeoxyribonucleases KW - EC 3.1.- KW - Amino Acid Isomerases KW - EC 5.1.1.- KW - Peptidylprolyl Isomerase KW - EC 5.2.1.8 KW - methyl cellosolve KW - EK1L6XWI56 KW - Index Medicus KW - Animals KW - Testis -- metabolism KW - Amino Acid Sequence KW - Rats KW - Rats, Sprague-Dawley KW - Blotting, Western KW - Rats, Inbred F344 KW - Peptide Fragments -- chemistry KW - Testis -- drug effects KW - Kinetics KW - Molecular Sequence Data KW - Ethylene Glycols -- pharmacology KW - Testis -- chemistry KW - DNA Fragmentation KW - Male KW - Amino Acid Isomerases -- metabolism KW - Spermatozoa -- physiology KW - Carrier Proteins -- metabolism KW - Apoptosis -- physiology KW - Endodeoxyribonucleases -- metabolism KW - Carrier Proteins -- analysis KW - Amino Acid Isomerases -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78798947?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biology+of+reproduction&rft.atitle=Cyclophilin+A+is+present+in+rat+germ+cells+and+is+associated+with+spermatocyte+apoptosis.+Reproductive+Toxicology+Group.&rft.au=Wine%2C+R+N%3BKu%2C+W+W%3BLi%2C+L+H%3BChapin%2C+R+E&rft.aulast=Wine&rft.aufirst=R&rft.date=1997-02-01&rft.volume=56&rft.issue=2&rft.spage=439&rft.isbn=&rft.btitle=&rft.title=Biology+of+reproduction&rft.issn=00063363&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-22 N1 - Date created - 1997-04-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Multiple widely spaced elements determine the efficiency with which a distal cistron is expressed from the polycistronic pregenomic RNA of figwort mosaic caulimovirus. AN - 78795487; 8995683 AB - The polycistronic expression mechanism of the plant pararetrovirus figwort mosaic caulimovirus (FMV) depends upon cis-acting elements present in its pregenomic RNA and a trans-acting protein (P6) which is expressed from a monocistronic subgenomic RNA. Using transient expression of FMV-derived polycistronic reporter constructs in Nicotiana edwardsonii cell suspension protoplasts, we further analyzed the cis-acting elements involved in polycistronic expression. A cis-acting element located within the first 74 nucleotides of the 7,954-nucleotide pregenomic RNA appears to be essential for P6 to transactivate expression of an internal cistron. Expression of this internal cistron, in the presence of P6, is greatly enhanced by the combined presence of two cis-acting elements located at the 3' end of the polycistronic RNA. Surprisingly, deletion of the most upstream of these two 3' cis-acting elements exposed a negative-acting element located internally on the polycistronic RNA, at the 3' end of open reading frame I. The action of both this negative-acting internal element and the positive-acting 3' elements is more pronounced when the large 5' untranslated leader region is present. This indicates that the 5' untranslated leader region is central to regulation of the FMV gene expression mechanism. Although a limited set of elements suffices to direct polycistronic expression in this eukaryotic system, a complex interplay between elements is involved in the spatial regulation of the genes present on the pregenomic RNA of FMV. JF - Journal of virology AU - Edskes, H K AU - Kiernan, J M AU - Shepherd, R J AD - Tobacco and Health Research Institute and Department of Plant Pathology, University of Kentucky, Lexington 40546-0091, USA. Edskes@Helix.NIH.gov Y1 - 1997/02// PY - 1997 DA - February 1997 SP - 1567 EP - 1575 VL - 71 IS - 2 SN - 0022-538X, 0022-538X KW - RNA, Viral KW - 0 KW - Viral Structural Proteins KW - Index Medicus KW - Plants, Toxic KW - Caulimovirus -- genetics KW - Gene Expression Regulation, Viral KW - Tobacco -- virology KW - Genome, Viral KW - Genes, Viral KW - Viral Structural Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78795487?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Multiple+widely+spaced+elements+determine+the+efficiency+with+which+a+distal+cistron+is+expressed+from+the+polycistronic+pregenomic+RNA+of+figwort+mosaic+caulimovirus.&rft.au=Edskes%2C+H+K%3BKiernan%2C+J+M%3BShepherd%2C+R+J&rft.aulast=Edskes&rft.aufirst=H&rft.date=1997-02-01&rft.volume=71&rft.issue=2&rft.spage=1567&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-18 N1 - Date created - 1997-02-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: EMBO J. 1993 Aug;12(8):3305-14 [8344266] Cell. 1993 May 21;73(4):789-802 [8500171] Mol Cell Biol. 1993 Dec;13(12):7476-86 [8246965] Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):370-4 [8278396] J Biol Chem. 1994 Jun 24;269(25):17166-73 [8006024] Curr Opin Genet Dev. 1994 Apr;4(2):305-9 [8032209] Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8314-8 [8078879] Nucleic Acids Res. 1994 Oct 11;22(20):4163-6 [7937142] Adv Virus Res. 1994;44:1-67 [7817872] J Biol Chem. 1995 Jun 2;270(22):13446-52 [7768947] Mol Cell Biol. 1995 Jul;15(7):3864-9 [7791793] EMBO J. 1995 Jul 17;14(14):3552-62 [7628455] RNA. 1995 May;1(3):246-59 [7489497] Virology. 1996 Oct 15;224(2):564-7 [8874519] Virology. 1968 Sep;36(1):150-2 [5669985] Virology. 1977 Jul 15;80(2):362-75 [329557] Cell. 1982 Jun;29(2):395-402 [7116445] Proc Natl Acad Sci U S A. 1987 Sep;84(17):6030-4 [3476924] Nucleic Acids Res. 1987 Oct 26;15(20):8451-66 [3671088] Mol Cell Biol. 1987 Oct;7(10):3438-45 [3683388] EMBO J. 1987 Dec 20;6(13):3901-7 [3327686] Mol Biol Evol. 1985 Nov;2(6):455-68 [2835576] Nucleic Acids Res. 1988 Sep 12;16(17):8377-90 [3419922] Virology. 1988 Nov;167(1):125-35 [3188393] Proc Natl Acad Sci U S A. 1989 Dec;86(23):9203-7 [2594762] Cell. 1989 Dec 22;59(6):1135-43 [2598263] J Virol. 1990 Jun;64(6):2594-8 [2186173] EMBO J. 1991 Dec;10(12):3887-96 [1935908] Virology. 1991 Sep;184(1):290-8 [1871973] EMBO J. 1990 Jun;9(6):1697-707 [2347303] Trends Biochem Sci. 1991 Sep;16(9):346-50 [1949157] Virology. 1991 Dec;185(2):867-71 [1962457] J Virol. 1992 May;66(5):3131-9 [1560539] Nucleic Acids Res. 1992 Aug 11;20(15):3851-7 [1508670] Virology. 1992 Sep;190(1):403-12 [1529539] Semin Cell Biol. 1992 Aug;3(4):279-88 [1384772] Annu Rev Cell Biol. 1992;8:197-225 [1335743] J Biol Chem. 1993 May 5;268(13):9504-10 [8486640] Mol Cell Biol. 1993 Jun;13(6):3340-9 [8497255] Cell. 1993 Oct 22;75(2):329-39 [8402916] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Acute lymphoblastic leukemia in children: nonrandomized comparison of conventional vs. intensive chemotherapy at the National Cancer Institute of Colombia. AN - 78794682; 8986146 AB - This study aimed to compare the therapeutic efficacy of two treatments for childhood acute lymphoblastic leukemia (ALL), and to evaluate the feasibility of intensive chemotherapy in a developing country. The study was conducted at the National Cancer Institute in Bogota, Colombia. Untreated ALL patients under 16 years of age were divided into two groups: a historical control cohort (HC) of 141 patients treated with conventional chemotherapy and an intensive chemotherapy cohort (IC) of 130 patients treated with a modified Berlin-Frankfurt-Münster protocol (m-BFM). Patients were clinically classified into risk categories for relapse, and followed through July 31, 1995. Disease-free survival (DFS) curves were obtained using the Kaplan-Meier method and were compared by the log rank test. Therapy groups had similar clinical baseline characteristics. Nonresponse rate to induction was higher in the HC group (16.3%) than in the IC cohort (7.6%) (P = 0.047), but deaths during induction were more frequent among m-BFM patients (13.8%) than in the HC group (6.4%) (P = 0.064). Bone marrow relapses after complete remission were less common in the IC group than in the HC group (19.4% and 45.9%, respectively; P = 0.0001), but central nervous system relapses showed no difference (12.8% in the HC and 16.3% under IC; P = 0.6). The DFS rates at 10 years were higher for the IC group, regardless of the baseline risk. IC reduces the frequency of relapses in ALL children in developing countries, when compared to previous therapy. A highly effective therapy such as m-BFM seems to be the most important predictor of outcome in children. JF - Medical and pediatric oncology AU - Buendia, M T AU - Terselich, G AU - Lozano, J M AU - Viscaino, M P AD - Pediatric Oncology Section, National Cancer Institute, Bogota, Colombia. Y1 - 1997/02// PY - 1997 DA - February 1997 SP - 108 EP - 116 VL - 28 IS - 2 SN - 0098-1532, 0098-1532 KW - Cytarabine KW - 04079A1RDZ KW - Vincristine KW - 5J49Q6B70F KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - 6-Mercaptopurine KW - E7WED276I5 KW - Asparaginase KW - EC 3.5.1.1 KW - Prednisone KW - VB0R961HZT KW - Methotrexate KW - YL5FZ2Y5U1 KW - Daunorubicin KW - ZS7284E0ZP KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Daunorubicin -- administration & dosage KW - Drug Administration Schedule KW - Combined Modality Therapy KW - Humans KW - Vincristine -- administration & dosage KW - Asparaginase -- administration & dosage KW - Child KW - Doxorubicin -- administration & dosage KW - Cytarabine -- administration & dosage KW - Child, Preschool KW - Infant KW - Feasibility Studies KW - Risk Factors KW - Treatment Outcome KW - 6-Mercaptopurine -- administration & dosage KW - Adolescent KW - Methotrexate -- administration & dosage KW - Prednisone -- administration & dosage KW - Male KW - Female KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- radiotherapy KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78794682?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Medical+and+pediatric+oncology&rft.atitle=Acute+lymphoblastic+leukemia+in+children%3A+nonrandomized+comparison+of+conventional+vs.+intensive+chemotherapy+at+the+National+Cancer+Institute+of+Colombia.&rft.au=Buendia%2C+M+T%3BTerselich%2C+G%3BLozano%2C+J+M%3BViscaino%2C+M+P&rft.aulast=Buendia&rft.aufirst=M&rft.date=1997-02-01&rft.volume=28&rft.issue=2&rft.spage=108&rft.isbn=&rft.btitle=&rft.title=Medical+and+pediatric+oncology&rft.issn=00981532&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-24 N1 - Date created - 1997-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retinoid X receptor (RXR) within the RXR-retinoic acid receptor heterodimer binds its ligand and enhances retinoid-dependent gene expression. AN - 78789458; 9001218 AB - Retinoic acid receptor (RAR) and retinoid X receptor (RXR) form heterodimers and regulate retinoid-mediated gene expression. We studied binding of RXR- and RAR-selective ligands to the RXR-RAR heterodimer and subsequent transcription. In limited proteolysis analyses, both RXR and RAR in the heterodimer bound their respective ligands and underwent a conformational change in the presence of a retinoic acid-responsive element. In reporter analyses, the RAR ligand (but not the RXR ligand), when added singly, activated transcription, but coaddition of the two ligands led to synergistic activation of transcription. This activation required the AF-2 domain of both RXR and RAR. Genomic footprinting analysis was performed with P19 embryonal carcinoma cells, in which transcription of the RARbeta gene is induced upon retinoid addition. Paralleling the reporter activation data, only the RAR ligand induced in vivo occupancy of the RARbeta2 promoter when added singly. However, at suboptimal concentrations of RAR ligand, coaddition of the RXR ligand increased the stability of promoter occupancy. Thus, liganded RXR and RAR both participate in transcription. Finally, when these ligands were tested for teratogenic effects on zebra fish and Xenopus embryos, we found that coadministration of the RXR and RAR ligands caused more severe abnormalities in these embryos than either ligand alone, providing biological support for the synergistic action of the two ligands. JF - Molecular and cellular biology AU - Minucci, S AU - Leid, M AU - Toyama, R AU - Saint-Jeannet, J P AU - Peterson, V J AU - Horn, V AU - Ishmael, J E AU - Bhattacharyya, N AU - Dey, A AU - Dawid, I B AU - Ozato, K AD - Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/02// PY - 1997 DA - February 1997 SP - 644 EP - 655 VL - 17 IS - 2 SN - 0270-7306, 0270-7306 KW - Ligands KW - 0 KW - Peptide Fragments KW - Receptors, Retinoic Acid KW - Recombinant Fusion Proteins KW - Retinoid X Receptors KW - Retinoids KW - Teratogens KW - Transcription Factors KW - retinoic acid receptor beta KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Xenopus -- embryology KW - Blastocyst KW - Neoplastic Stem Cells KW - DNA -- metabolism KW - Humans KW - Mice KW - Protein Conformation -- drug effects KW - Transcriptional Activation KW - Teratogens -- pharmacology KW - Promoter Regions, Genetic -- genetics KW - Zebrafish -- embryology KW - Embryo, Nonmammalian -- drug effects KW - Embryonal Carcinoma Stem Cells KW - Receptors, Retinoic Acid -- metabolism KW - Receptors, Retinoic Acid -- genetics KW - Transcription Factors -- metabolism KW - Receptors, Retinoic Acid -- chemistry KW - Transcription Factors -- chemistry KW - Gene Expression Regulation -- drug effects KW - Retinoids -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78789458?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Retinoid+X+receptor+%28RXR%29+within+the+RXR-retinoic+acid+receptor+heterodimer+binds+its+ligand+and+enhances+retinoid-dependent+gene+expression.&rft.au=Minucci%2C+S%3BLeid%2C+M%3BToyama%2C+R%3BSaint-Jeannet%2C+J+P%3BPeterson%2C+V+J%3BHorn%2C+V%3BIshmael%2C+J+E%3BBhattacharyya%2C+N%3BDey%2C+A%3BDawid%2C+I+B%3BOzato%2C+K&rft.aulast=Minucci&rft.aufirst=S&rft.date=1997-02-01&rft.volume=17&rft.issue=2&rft.spage=644&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-18 N1 - Date created - 1997-02-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochemistry. 1996 Mar 26;35(12):3816-24 [8620004] Proc Natl Acad Sci U S A. 1990 Jul;87(14):5392-6 [2164682] Mol Cell Biol. 1996 Jul;16(7):3807-13 [8668198] Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):1803-7 [8700839] Mol Cell Biol. 1996 Aug;16(8):4137-46 [8754812] Nature. 1996 Aug 29;382(6594):819-22 [8752277] FASEB J. 1996 Jul;10(9):940-54 [8801176] FASEB J. 1996 Jul;10(9):1071-7 [8801169] Mol Endocrinol. 1996 Jul;10(7):781-93 [8813719] EMBO J. 1996 Aug 15;15(16):4142-55 [8861943] Curr Opin Genet Dev. 1996 Oct;6(5):567-74 [8939720] Genes Cells. 1996 Feb;1(2):209-21 [9140065] Genes Dev. 1995 May 1;9(9):1033-45 [7744246] J Biol Chem. 1993 Dec 15;268(35):26625-33 [8253793] Mol Cell Biol. 1994 Jan;14(1):287-98 [8264595] Mol Cell Biol. 1994 Jan;14(1):360-72 [8264603] J Steroid Biochem Mol Biol. 1993 Dec;46(6):643-61 [8274399] J Biol Chem. 1994 May 13;269(19):14175-81 [8188700] EMBO J. 1994 Jul 1;13(13):3039-49 [8039499] Endocr Rev. 1994 Jun;15(3):391-407 [8076589] Mol Cell Biol. 1994 Nov;14(11):7105-10 [7935425] Nature. 1994 Oct 6;371(6497):528-31 [7935766] EMBO J. 1994 Nov 15;13(22):5370-82 [7957103] Annu Rev Biochem. 1994;63:451-86 [7979245] Genes Dev. 1994 Dec 15;8(24):3068-79 [8001825] Mol Cell Biol. 1995 Jan;15(1):255-63 [7799932] Cancer Res. 1995 Jan 15;55(2):232-6 [7812950] J Biol Chem. 1995 Feb 17;270(7):3001-11 [7852380] Nature. 1992 Jan 23;355(6358):359-61 [1309942] Cell. 1992 Jan 24;68(2):397-406 [1310260] Cell. 1992 May 15;69(4):703-13 [1586949] Biochemistry. 1992 Jun 16;31(23):5303-11 [1606154] Genes Dev. 1995 Apr 1;9(7):769-82 [7705655] Cell. 1995 May 19;81(4):541-50 [7758108] Cell. 1995 Jun 2;81(5):687-93 [7774010] Mol Cell Biol. 1995 Jul;15(7):3540-51 [7791761] J Biol Chem. 1995 Aug 4;270(31):18672-7 [7629199] Genes Dev. 1995 Aug 1;9(15):1811-6 [7649469] Nature. 1995 Oct 5;377(6548):397-404 [7566114] Nature. 1995 Oct 5;377(6548):451-4 [7566126] Nature. 1995 Oct 5;377(6548):454-7 [7566127] Mol Cell Biol. 1995 Dec;15(12):6481-7 [8524212] J Biol Chem. 1995 Dec 22;270(51):30765-72 [8530518] Cell. 1995 Dec 15;83(6):835-9 [8521507] Cell. 1995 Dec 15;83(6):841-50 [8521508] Cell. 1995 Dec 15;83(6):859-69 [8521510] Blood. 1996 Jan 1;87(1):227-37 [8547646] EMBO J. 1996 Feb 15;15(4):888-99 [8631309] Mol Cell Biol. 1992 Aug;12(8):3590-9 [1630463] Nature. 1992 Aug 13;358(6387):587-91 [1323763] Nature. 1992 Aug 27;358(6389):771-4 [1324435] J Biol Chem. 1992 Sep 25;267(27):19513-20 [1326555] J Biol Chem. 1992 Nov 5;267(31):22010-3 [1331043] Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11750-4 [1465392] Science. 1992 Dec 18;258(5090):1944-6 [1335166] Nucleic Acids Res. 1992 Dec 11;20(23):6393-9 [1335571] Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):30-4 [8380496] Biochem Biophys Res Commun. 1993 Aug 31;195(1):385-92 [8363616] Nature. 1993 Dec 2;366(6454):476-9 [8247157] Nature. 1989 Jul 13;340(6229):140-4 [2739735] J Biol Chem. 1989 Aug 25;264(24):14493-7 [2503518] Nature. 1990 Jan 11;343(6254):177-80 [2153268] Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):6197-202 [8650243] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Degradation of the Met tyrosine kinase receptor by the ubiquitin-proteasome pathway. AN - 78788410; 9001234 AB - The Met tyrosine kinase receptor is a widely expressed molecule which mediates pleiotropic cellular responses following activation by its ligand, hepatocyte growth factor/scatter factor (HGF/SF). In this communication we demonstrate that significant Met degradation is induced by HGF/SF and that this degradation can be blocked by lactacystin, an inhibitor of proteasome activity. We also show that Met is rapidly polyubiquitinated in response to ligand and that polyubiquitinated Met molecules, which are normally unstable, are stabilized by lactacystin. Both HGF/SF-induced degradation and polyubiquitination of Met were shown to be dependent on the receptor possessing intact tyrosine kinase activity. Finally, we found that a normally highly labile 55-kDa fragment of the Met receptor is stabilized by lactacystin and demonstrate that it represents a cell-associated remnant that is generated following the ligand-independent proteolytic cleavage of the Met receptor in its extracellular domain. This truncated Met molecule encompasses the kinase domain of the receptor and is itself tyrosine phosphorylated. We conclude that the ubiquitin-proteasome pathway plays a significant role in the degradation of the Met tyrosine kinase receptor as directed by ligand-dependent and -independent signals. We propose that this proteolytic pathway may be important for averting cellular transformation by desensitizing Met signaling following ligand stimulation and by eliminating potentially oncogenic fragments generated via extracellular cleavage of the Met receptor. JF - Molecular and cellular biology AU - Jeffers, M AU - Taylor, G A AU - Weidner, K M AU - Omura, S AU - Vande Woude, G F AD - ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1997/02// PY - 1997 DA - February 1997 SP - 799 EP - 808 VL - 17 IS - 2 SN - 0270-7306, 0270-7306 KW - Cyclopentanes KW - 0 KW - Cysteine Proteinase Inhibitors KW - Ligands KW - Multienzyme Complexes KW - Nerve Growth Factors KW - Peptide Fragments KW - Protein Synthesis Inhibitors KW - Recombinant Fusion Proteins KW - Ubiquitins KW - lactacystin KW - 133343-34-7 KW - Brefeldin A KW - 20350-15-6 KW - Hepatocyte Growth Factor KW - 67256-21-7 KW - Proto-Oncogene Proteins c-met KW - EC 2.7.10.1 KW - Receptor Protein-Tyrosine Kinases KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Acetylcysteine KW - WYQ7N0BPYC KW - Index Medicus KW - Peptide Fragments -- metabolism KW - Animals KW - Acetylcysteine -- analogs & derivatives KW - Nerve Growth Factors -- pharmacology KW - Humans KW - Acetylcysteine -- pharmacology KW - Molecular Weight KW - Cysteine Proteinase Inhibitors -- pharmacology KW - Cyclopentanes -- pharmacology KW - Peptide Fragments -- chemistry KW - Protein Synthesis Inhibitors -- pharmacology KW - Phosphorylation KW - Transfection KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Membrane -- metabolism KW - Cell Line KW - Multienzyme Complexes -- metabolism KW - Ubiquitins -- metabolism KW - Receptor Protein-Tyrosine Kinases -- genetics KW - Hepatocyte Growth Factor -- pharmacology KW - Cysteine Endopeptidases -- metabolism KW - Receptor Protein-Tyrosine Kinases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78788410?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Degradation+of+the+Met+tyrosine+kinase+receptor+by+the+ubiquitin-proteasome+pathway.&rft.au=Jeffers%2C+M%3BTaylor%2C+G+A%3BWeidner%2C+K+M%3BOmura%2C+S%3BVande+Woude%2C+G+F&rft.aulast=Jeffers&rft.aufirst=M&rft.date=1997-02-01&rft.volume=17&rft.issue=2&rft.spage=799&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-18 N1 - Date created - 1997-02-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: EXS. 1993;65:225-49 [8422545] EXS. 1993;65:351-68 [8380742] J Clin Invest. 1994 May;93(5):2056-65 [8182137] Oncogene. 1994 Jun;9(6):1583-9 [7514283] Oncogene. 1994 Jun;9(6):1691-7 [8183564] Dev Biol. 1994 Jun;163(2):525-9 [8200486] Oncogene. 1994 Jul;9(7):2019-27 [8208547] Biochem J. 1994 Jun 1;300 ( Pt 2):281-90 [8002928] Cell. 1994 Oct 7;79(1):13-21 [7923371] J Biol Chem. 1994 Dec 16;269(50):31991-8 [7527401] J Biol Chem. 1995 Jan 13;270(2):551-7 [7822279] J Cell Biol. 1995 Jan;128(1-2):171-84 [7822413] Mol Cell Biol. 1995 Feb;15(2):731-41 [7823941] Nature. 1995 Feb 23;373(6516):699-702 [7854452] Nature. 1995 Feb 23;373(6516):702-5 [7854453] Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2597-601 [7708691] Development. 1995 Mar;121(3):813-24 [7720585] Science. 1995 May 5;268(5211):726-31 [7732382] J Cell Sci. 1995 Feb;108 ( Pt 2):413-30 [7768990] Biochem Biophys Res Commun. 1995 Aug 4;213(1):32-9 [7639752] Nature. 1995 Aug 31;376(6543):768-71 [7651534] J Cell Biol. 1995 Oct;131(1):1-5 [7559768] Oncogene. 1995 Nov 16;11(10):1979-87 [7478516] J Biol Chem. 1995 Dec 8;270(49):29447-52 [7493983] J Cell Biol. 1995 Dec;131(6 Pt 1):1573-86 [8522613] Oncogene. 1995 Dec 21;11(12):2649-55 [8545122] Oncogene. 1996 Aug 15;13(4):853-6 [8761307] J Mol Med (Berl). 1996 Sep;74(9):505-13 [8892055] J Virol. 1978 May;26(2):291-8 [26810] J Mol Appl Genet. 1982;1(4):327-41 [6286831] J Biol Chem. 1986 Aug 25;261(24):11398-403 [2426273] Nature. 1987 May 21-27;327(6119):239-42 [2952888] Cell. 1987 Oct 23;51(2):199-209 [3499230] Mol Cell Biol. 1988 Dec;8(12):5126-31 [2854192] Mol Cell Biol. 1989 Jul;9(7):2890-6 [2528680] Oncogene. 1989 Nov;4(11):1383-8 [2554238] J Cell Biol. 1992 Nov;119(3):629-41 [1383237] Mol Cell Biol. 1992 Nov;12(11):5152-8 [1406687] Science. 1990 Feb 23;247(4945):962-4 [2305263] Cell. 1990 Apr 20;61(2):203-12 [2158859] Science. 1991 Feb 15;251(4995):802-4 [1846706] J Cell Biol. 1991 Feb;112(3):469-78 [1846866] J Antibiot (Tokyo). 1991 Jan;44(1):113-6 [1848215] J Antibiot (Tokyo). 1991 Jan;44(1):117-8 [2001981] EMBO J. 1991 Apr;10(4):877-83 [1826254] Oncogene. 1991 Apr;6(4):639-43 [1674366] EMBO J. 1991 Oct;10(10):2867-78 [1655405] Mol Cell Biol. 1991 Dec;11(12):5954-62 [1944272] Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1937-41 [7680481] J Cell Biol. 1993 Apr;121(1):145-54 [8384622] J Biol Chem. 1993 Jul 5;268(19):14189-201 [7686152] J Cell Biol. 1993 Oct;123(1):223-35 [8408200] Oncogene. 1993 Nov;8(11):2917-23 [8105438] Biochim Biophys Acta. 1993 Dec 23;1155(3):357-71 [8268192] Science. 1994 Jan 7;263(5143):98-101 [7505952] Blood. 1994 Jan 1;83(1):137-45 [7506076] Annu Rev Cell Biol. 1993;9:129-61 [8280459] J Biol Chem. 1994 Jan 21;269(3):1750-5 [8294424] Symp Soc Exp Biol. 1993;47:163-81 [8165564] Cell. 1991 Nov 29;67(5):901-8 [1835669] Crit Rev Oncog. 1992;3(1-2):27-54 [1312869] J Biol Chem. 1992 Mar 25;267(9):6429-34 [1313434] Oncogene. 1992 Jun;7(6):1149-57 [1317541] Science. 1992 Aug 28;257(5074):1258-61 [1387731] J Biol Chem. 1993 Jan 5;268(1):577-83 [8380168] EXS. 1993;65:107-30 [8380734] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ovarian luteal cell toxicity of ethylene glycol monomethyl ether and methoxy acetic acid in vivo and in vitro AN - 16081871; 4115271 AB - These studies define the site and mechanisms of reproductive toxicity of ethylene glycol monomethyl ether (EGME) in a non-gravid female animal model using in vivo and in vitro methods. In vivo studies assessed vaginal cytology and histology, ovarian histology, and serum hormones in 80- to 90-day-old, adult, regularly cycling, female Sprague-Dawley rats treated daily with EGME or vehicle by oral gavage. Dose-response and time-course studies (four to nine rats per group per treatment) determined that 300 mg/kg EGME suppressed cyclicity without systemic toxicity within 3 to 8 days, and doses less than 100 mg/kg had no effect. Pathogenesis studies (six to nine rats per time and treatment) determined that 300 mg/kg EGME elevated serum progesterone within 32 hr after dosing, while serum estradiol, FSH, LH, and prolactin remained at baseline levels. In EGME-treated rats, cyclicity was suppressed, ovulation was inhibited, and corpora lutea were hypertrophied. Thus, EGME appeared to target the ovarian luteal cell. To further examine the toxicity in vitro, luteal cells were recovered from 23-day-old, hCG-primed Sprague-Dawley rats and treated with 0-10 mM methoxy acetic acid (MAA), the proximate toxic metabolite of EGME. MAA (1-10 mM) maintained elevated progesterone levels as production declined in untreated cells at 24 and 48 hr of culture. Progesterone production was maintained independent of LH-stimulated cAMP levels. MAA decreased ATP, but only at 48 hr and at 2.5 mM or greater concentrations. Thus, these studies establish that the ovarian luteal cell is a target of EGME and MAA in vivo and in vitro and that the effect on luteal cell progesterone production is likely independent of LH-stimulated cAMP pathways. JF - Toxicology and Applied Pharmacology AU - Davis, B J AU - Almekinder, J L AU - Flagler, N AU - Travlos, G AU - Wilson, R AU - Maronpot, R R AD - NIEHS, MD B3-06, P.O. Box 12233, RTP, NC 27709, USA Y1 - 1997/02// PY - 1997 DA - Feb 1997 SP - 328 EP - 337 VL - 142 IS - 2 SN - 0041-008X, 0041-008X KW - rats KW - ovarian luteal cells KW - histology KW - ethylene glycol monomethyl ether KW - methoxy acetic acid KW - Toxicology Abstracts KW - vagina KW - serum KW - reproduction KW - ovaries KW - hormones KW - X 24151:Acute exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16081871?accountid=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=Ovarian+luteal+cell+toxicity+of+ethylene+glycol+monomethyl+ether+and+methoxy+acetic+acid+in+vivo+and+in+vitro&rft.au=Davis%2C+B+J%3BAlmekinder%2C+J+L%3BFlagler%2C+N%3BTravlos%2C+G%3BWilson%2C+R%3BMaronpot%2C+R+R&rft.aulast=Davis&rft.aufirst=B&rft.date=1997-02-01&rft.volume=142&rft.issue=2&rft.spage=328&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 - reproduction; vagina; hormones; serum; ovaries ER - TY - JOUR T1 - Anti-tumor activity of synthetic peptide fragments of the human interferon- alpha sub(2) AN - 15966837; 4068787 AB - We have studied an influence of nine overlapping peptides from the region between amino acid residues 124 and 144 of the human interferon (FIN)- alpha sub(2) molecule on the growth of human lymphoid tumor cell lines in vitro. It was found that several, but not all, synthetic peptides inhibited proliferation of the same cell lines that IFN did. One of peptides, corresponding to the 124-138 amino acid residues of the IFN molecule (124-138) was most active. Using a human-mouse somatic hybrid cell line, we have shown that antiproliferative activity of the peptide 124-138 and IFN depended on the presence of human chromosome 21. Receptor binding studies also demonstrated that the peptide specifically interacted with membrane receptors on hybrid human-mouse cells carrying human chromosome 21, but not on parental mouse cells. Displacement experiments confirm that IFN and the peptide 124-138 compete for the same binding sites. Taken together, the data presented support a hypothesis that the C-terminal part of the IFN molecule contributes to antiproliferative activity possessed by IFN. Synthetic peptides studied in the present work may serve as a tool for studying tumor cell growth regulation by IFN and may be considered as potential nontoxic anti-tumor agents. JF - Hybridoma AU - Danilkovitch, A AU - Freze, K AU - Romashkova, J AU - Makarov, E AD - Immunopathology Sect., Lab. Immunobiology, NCI-FCROC, Bldg. 560, Frederick, MD 21702, USA Y1 - 1997/02// PY - 1997 DA - Feb 1997 SP - 69 EP - 76 VL - 16 IS - 1 SN - 0272-457X, 0272-457X KW - man KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - alpha -interferon KW - immunotherapy KW - peptides KW - antitumor agents KW - F 06818:Cancer immunotherapy KW - W3 33150:Cytokine based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15966837?accountid=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=Hybridoma&rft.atitle=Anti-tumor+activity+of+synthetic+peptide+fragments+of+the+human+interferon-+alpha+sub%282%29&rft.au=Danilkovitch%2C+A%3BFreze%2C+K%3BRomashkova%2C+J%3BMakarov%2C+E&rft.aulast=Danilkovitch&rft.aufirst=A&rft.date=1997-02-01&rft.volume=16&rft.issue=1&rft.spage=69&rft.isbn=&rft.btitle=&rft.title=Hybridoma&rft.issn=0272457X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Selected Papers from Immunological Approaches to Tumor Therapy: III Int. Meeting on Idiotypic Network and Tumor Therapy by Gene Therapy, Bonn, Germany, Feb 29-M N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - alpha -interferon; immunotherapy; peptides; antitumor agents ER - TY - JOUR T1 - Lack of correlation between the inducibility of metallothionein mRNA and metallothionein protein in cadmium-exposed rodents AN - 15963193; 4062871 AB - Cadmium (Cd) is carcinogenic in humans and laboratory animals. Depending on the duration and route of exposure, Cd can also induce damage in the liver, kidneys and lungs. In certain tissues, metallothionein (MT) proteins are induced by Cd exposure and associated with native and acquired tolerance to the metal. Rats are generally more sensitive than mice to Cd carcinogenicity; however, sensitivity can vary markedly between different strains of the same rodent species. To further define the role of MT in Cd toxicity and carcinogenesis, adult male Wistar rats and adult male C57 and DBA mice were treated with CdCl sub(2) and liver, kidney, and lung were analyzed for Cd, MT mRNA, and MT protein 24 h later. Dose-related increases in Cd were detected in the livers and kidneys of all animals tested; however, increases in pulmonary Cd were observed only in C57 mice, and only at the highest CdCl sub(2) dose. While hepatic Cd concentrations were similar in the rats and mice, renal Cd concentrations were similar in the rats and DBA mice but were nearly 2-fold higher in C57 mice at the highest CdCl sub(2) dose. Dose-related increases in MT mRNA occurred in the livers and lungs of all animals tested. Hepatic MT mRNA concentrations were highest in the rats, and C57 mice exhibited the greatest magnitude of hepatic MT mRNA induction. Dose-related increases in renal MT mRNA were also detected in both strains of mice, but between the two strains, C57 mice exhibited substantially higher levels of renal MT mRNA induction. Basal levels of renal MT mRNA were higher in the rats than in the mice, and transcription of the MT gene was not inducible in the rat kidney at any of the CdCl sub(2) doses used. In comparison, basal levels of pulmonary MT mRNA were similar in the rats and DBA mice, were substantially lower in C57 mice, and increases in pulmonary MT mRNA were most pronounced in the rats. Analysis of MT protein revealed dose-related increases in the livers and kidneys of all animals tested. C57 mice had the lowest basal and induced levels of hepatic MT, and basal levels of renal MT were much higher in the rats than in mice of either strain. Although dose-related increases in pulmonary MT were similar in both strains of mice, pulmonary MT levels were much lower and not inducible in the rats. Overall our experiments revealed complex profiles of Cd distribution and MT expression that varied between tissues, species and strains, and often did not directly correlate with sensitivity to damage. The results suggest that Cd distribution, inducibility of the MT gene, and levels of MT protein, must all be considered when predicting susceptibility to Cd toxicity and carcinogenicity at particular target sites. JF - Toxicology AU - Misra, R R AU - Crance, KA AU - Bare, R M AU - Waalkes, M P AD - Bldg. 538, Rm. 205E, NCI-FCRDC, Frederick, MD 21702-1201, USA Y1 - 1997/02// PY - 1997 DA - Feb 1997 SP - 99 EP - 109 VL - 117 IS - 2-3 SN - 0300-483X, 0300-483X KW - rats KW - mice KW - cadmium KW - heavy metals KW - metallothionein KW - Toxicology Abstracts KW - carcinogenesis KW - proteins KW - X 24163:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15963193?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=Lack+of+correlation+between+the+inducibility+of+metallothionein+mRNA+and+metallothionein+protein+in+cadmium-exposed+rodents&rft.au=Misra%2C+R+R%3BCrance%2C+KA%3BBare%2C+R+M%3BWaalkes%2C+M+P&rft.aulast=Misra&rft.aufirst=R&rft.date=1997-02-01&rft.volume=117&rft.issue=2-3&rft.spage=99&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - carcinogenesis; proteins ER - TY - JOUR T1 - The effects of dietary boron on bone strength in rats AN - 15963123; 4064750 AB - Previous studies from our laboratory found that when boric acid (BA) was administered in the diet to rats, boron levels in bone were approximately fourfold greater than serum levels. The current studies were undertaken to determine if these elevations produced adverse effects on several bone-related measures, including serum electrolyte levels, bone structure, and bone strength. Data from two studies are presented: in the first study, young adult male rats consumed a powdered diet containing 0, 3000, 4500, 6000, or 9000 ppm BA for 9 weeks. Endpoints were serum calcium, phosphorous, potassium, and chloride, as well as blood and bone boron concentrations ([B]) measured weekly during the 9-week exposure period, and at 8, 16, 24, and 32 weeks after the end of exposure. In the second study, the male and female young adult rats diet contained 0, 200, 1000, 3000, or 9000 ppm BA for 12 weeks; endpoints measured weekly were serum levels of calcium, phosphorous, and magnesium, bone [B], and bone structure (humerus) and strength (tibia, femur, and lumbar vertebrae). In treated rats, calcium was reduced in the first study but not the second. Serum phosphorous was reduced in both studies; potassium was unchanged, chloride was increased by 1%, and magnesium was reduced in all BA-exposed groups in the second study, to a maximal 19% reduction. Bone [B] was consistently increased in all treated groups, to concentrations approximately fourfold those of serum. After cessation of exposure, serum and urinary boron concentrations dropped to within control values within a week. However, even 32 weeks after the end of exposure, bone [B] remained threefold greater than controls. Male tibia and femur resistance to bending was unchanged. However, vertebral strength in compression was significantly increased by 5-10% in all dose groups (200 to 9000 ppm). The pattern was substantially similar in females. Only the humerus was examined by light microscopy and was found to be unchanged at any level of BA consumption. These data show that, despite a reduction in some serum electrolyte levels, BA consumption increased vertebral resistance to crush force, without detectably altering the microscopic structure of the humerus or the resistance of femur and tibia to a bending load. This increase in compression resistance occurred at exposure levels substantially below those that were previously reported to be reproductively toxic. JF - Fundamental and Applied Toxicology AU - Chapin, R E AU - Ku, W W AU - Kenney, MA AU - McCoy, H AU - Gladen, B AU - Wine, R N AU - Wilson, R AU - Elwell, M R AD - Reproductive Toxicology Group, NIEHS, Research Triangle Park, NC 27709, USA Y1 - 1997/02// PY - 1997 DA - Feb 1997 SP - 205 EP - 215 VL - 35 IS - 2 SN - 0272-0590, 0272-0590 KW - rats KW - boric acid KW - boron KW - calcium KW - phosphorus KW - potassium KW - chloride KW - Calcium & Calcified Tissue Abstracts; Toxicology Abstracts KW - dietary intake KW - bone KW - bone strength KW - T 20083:Trace elements KW - X 24154:Pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15963123?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+Applied+Toxicology&rft.atitle=The+effects+of+dietary+boron+on+bone+strength+in+rats&rft.au=Chapin%2C+R+E%3BKu%2C+W+W%3BKenney%2C+MA%3BMcCoy%2C+H%3BGladen%2C+B%3BWine%2C+R+N%3BWilson%2C+R%3BElwell%2C+M+R&rft.aulast=Chapin&rft.aufirst=R&rft.date=1997-02-01&rft.volume=35&rft.issue=2&rft.spage=205&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+Applied+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - dietary intake; bone; bone strength ER - TY - JOUR T1 - Protein-disulfide isomerase-mediated reduction of the A subunit of cholera toxin in a human intestinal cell line AN - 15937643; 4046654 AB - A key step in the action of cholera toxin (CT) is the reduction of its A subunit to the A sub(1) peptide. The latter is an ADP-ribosyltransferase, which activates the alpha -subunit of the stimulatory G protein of adenylyl cyclase. In this study, the enzymatic reduction of membrane-bound CT in CaCo-2 human intestinal epithelial cells was characterized. Whereas diphtheria toxin was found to be reduced by a cell surface population of protein-disulfide isomerase (PDI) and its cytotoxicity was inhibited by p-chloromercuribenzenesulfonic acid, bacitracin, or anti-PDI antibodies, these inhibitors had no effect on CT reduction or activity in intact cells. In contrast, the reduction of CT in vitro by either postnuclear supernatants (PNS) or microsomal membranes in the presence of Triton X-100 was significantly inhibited by p-chloromercuribenzenesulfonic acid and bacitracin. Anti-PDI monoclonal antibodies likewise inhibited the in vitro reduction of CT and also were effective in depleting reductase activity from PNS. Since inhibition and depletion were not observed in the absence of detergent, these results suggested that the reductase activity was a soluble component localized to the lumen of microsomal vesicles and correlated with the presence of protein-disulfide isomerase. This was further confirmed by showing a corresponding depletion of reductase activity and PDI in alkali-treated microsomes. This activity was restored when purified bovine PDI was added back to alkali-treated microsomes in a redox buffer that reflected conditions found in the lumen of the endoplasmic reticulum (ER). When the CT-related reductase activity was assayed in subcellular fractions of PNS-derived membranes isolated on a 9-30% Iodixanol gradient, the activity, as measured by CT-A sub(1) peptide formation localized to those fractions containing PDI. Likewise CT-A sub(1) peptide formed in intact cells co-localized to those membrane fractions containing the majority of cellular PDI. Furthermore, the banding density corresponded to a region of the gradient containing ER-derived membranes. These results indicated that CT was a substrate for PDI-catalyzed reduction in intact cells and supported the hypothesis that CT reduction and activation occurs in the ER. JF - Journal of Biological Chemistry AU - Orlandi, P A AD - Bldg. 49, Room 2A28, National Institutes of Health, Bethesda, MD 20892-4440, USA Y1 - 1997/02// PY - 1997 DA - Feb 1997 SP - 4591 EP - 4599 VL - 272 IS - 7 SN - 0021-9258, 0021-9258 KW - man KW - protein disulfide-isomerase KW - cholera toxin KW - Microbiology Abstracts B: Bacteriology; Toxicology Abstracts KW - Vibrio cholerae KW - toxins KW - intestine KW - X 24171:Microbial KW - J 02823:In vitro and in vivo effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15937643?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Protein-disulfide+isomerase-mediated+reduction+of+the+A+subunit+of+cholera+toxin+in+a+human+intestinal+cell+line&rft.au=Orlandi%2C+P+A&rft.aulast=Orlandi&rft.aufirst=P&rft.date=1997-02-01&rft.volume=272&rft.issue=7&rft.spage=4591&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Vibrio cholerae; toxins; intestine ER - TY - JOUR T1 - Metabolic activation of benzo[g]chrysene in the human mammary carcinoma cell line MCF-7 AN - 15914410; 4043505 AB - Benzo[g]chrysene (BgC) is an environmental pollutant, and recent studies have demonstrated that anti-BgC-11,12-dihydrodiol 13,14-epoxide (anti-BgCDE) is a potent mammary carcinogen in rats. To determine whether BgC can be metabolically activated to anti-BgCDE in human cells, the human mammary carcinoma cell line MCF-7 was treated with BgC and with the racemic trans-3,4- and 11,12-dihydrodiols. The DNA adducts formed in these experiments were examined using super(32)P-postlabeling, and specific adducts were identified through comparisons with adducts obtained by the reaction of the racemic syn- and anti-BgCDEs with calf thymus DNA and with purine deoxyribonucleoside-3'-phosphates in vitro. It was found that BgC is metabolically activated in MCF-7 cells to form major DNA adducts through both the syn- and anti-11,12-dihydrodiol 13,14-epoxide metabolites. BgC is therefore a potential environmental risk to humans. The major BgC-DNA adducts formed from both the dihydrodiol-epoxide diastereomers were deoxyadenosine adducts. Thus, BgC has DNA-binding properties that are very similar to those of the potent mammary carcinogens 7,12-dimethylbenz[a]anthracene and dibenzo[a,l]pyrene. JF - Cancer Research AU - Agarwal, R AU - Coffing, S L AU - Baird, WM AU - Kiselyov, A S AU - Harvey, R G AU - Dipple, A AD - ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research & Development Center, P.O. Box B, Frederick, MD 21702-1201, USA Y1 - 1997/02// PY - 1997 DA - Feb 1997 SP - 415 EP - 419 VL - 57 IS - 3 SN - 0008-5472, 0008-5472 KW - MCF-7 cells KW - benzo(g)chrysene KW - Toxicology Abstracts KW - breast KW - tumor cell lines KW - polycyclic aromatic hydrocarbons KW - cancer KW - X 24190:Polycyclic hydrocarbons UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15914410?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Research&rft.atitle=Metabolic+activation+of+benzo%5Bg%5Dchrysene+in+the+human+mammary+carcinoma+cell+line+MCF-7&rft.au=Agarwal%2C+R%3BCoffing%2C+S+L%3BBaird%2C+WM%3BKiselyov%2C+A+S%3BHarvey%2C+R+G%3BDipple%2C+A&rft.aulast=Agarwal&rft.aufirst=R&rft.date=1997-02-01&rft.volume=57&rft.issue=3&rft.spage=415&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 - breast; cancer; tumor cell lines; polycyclic aromatic hydrocarbons ER - TY - JOUR T1 - The iteron bases and spacers of the P1 replication origin contain information that specifies the formation of a complex structure involved in initiation AN - 15881791; 4028850 AB - The origin of replication of the P1 plasmid contains five direct, imperfect repeats (iterons) of a 19 bp sequence that binds the P1-encoded RepA initiator protein. RepA binding to these iterons triggers origin initiation and represses transcription from the repA promoter that is nested within the iterons. The origin iterons were replaced with ligated oligonucleotides that insert five perfect 19 bp repeats with identical spacer sequences. This eliminates the natural variation in the iteron and spacer sequences and removes the repA promoter. The reconstructed origin is functional, showing that the repA promoter is not essential for origin function. The method used to make the reconstructed origin allows substitution of identical iterons with altered sequence or spacer length. Single changes of conserved iteron bases gave reduced or non-existent origin activity, as did an increase in spacer length. Like the wild type, most of these mutant arrays retain avid primary binding activity for the RepA protein. However, although the wild-type arrays readily form a mature complex in which all iterons are saturated, the most replication-defective mutants were completely unable to do this, even at very high RepA concentrations. It appears that iteron spacing and contacts involving at least three of the conserved iteron bases play an important role in the assembly of the mature structure in which all sites are occupied. A model is presented in which an allosteric interaction between the DNA site and protein is needed for the saturated, mature complex required for initiation. JF - Molecular Microbiology AU - Brendler, T G AU - Abeles, AL AU - Reaves, L D AU - Austin, S J AD - Gene Regulation and Chromosome Biol. Lab., ABL-Basic Res. Program, NCI-Frederick Cancer Res. and Dev. Cent., Frederick, MD 21702-1201, USA Y1 - 1997/02// PY - 1997 DA - Feb 1997 SP - 559 EP - 567 VL - 23 IS - 3 SN - 0950-382X, 0950-382X KW - plasmid P1 KW - repA protein KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - replication KW - J 02760:Plasmids KW - N 14650:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15881791?accountid=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=The+iteron+bases+and+spacers+of+the+P1+replication+origin+contain+information+that+specifies+the+formation+of+a+complex+structure+involved+in+initiation&rft.au=Brendler%2C+T+G%3BAbeles%2C+AL%3BReaves%2C+L+D%3BAustin%2C+S+J&rft.aulast=Brendler&rft.aufirst=T&rft.date=1997-02-01&rft.volume=23&rft.issue=3&rft.spage=559&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 N1 - SubjectsTermNotLitGenreText - replication ER - TY - JOUR T1 - Membrane fusion with cationic liposomes: Effects of target membrane lipid composition AN - 15876170; 4026488 AB - Determination of the mechanisms by which cationic liposomes adhere to and fuse with biological membranes is important to understanding how these lipid vesicles mediate cellular transfection. To determine what role the lipid composition of "target" membranes might have in promoting fusion with cationic liposomes, we have examined the ability of large unilamellar vesicles composed of 1,2-dioleoyl-sn-phosphatidylethanolamine (DOPE) and N,N-dimethyl-N,N-di-9-cis-octadecenylammonium chloride (DODAC) (1:1) to fuse with target liposomes of varying composition in the absence of DNA. Membrane fusion was promoted by increased negative surface charge and, for liquid crystalline lipids, by increased acyl chain unsaturation in target liposomes. However, the presence of disaturated phospholipids promoted fusion below the gel to liquid crystalline transition temperature, an effect which was eliminated by the addition of cholesterol. It was also shown that DOPE/DODAC (1:1) LUVs fused with erythrocyte ghosts and that this fusion was blocked by the presence of serum. Membrane fusion was determined by a quantitative fluorescent lipid mixing assay and qualitatively by freeze-fracture electron microscopy and fluorescence microscopy. JF - Biochemistry (Washington) AU - Bailey, AL AU - Cullis, PR AD - Lab. Cell. and Mol. Biophys., NICHD, Natl. Institutes Health, 10 Cent. Dr., Rm. 10D-07, Bethesda, MD 20892-1855, USA Y1 - 1997/02// PY - 1997 DA - Feb 1997 SP - 1628 EP - 1634 VL - 36 IS - 7 SN - 0006-2960, 0006-2960 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - liposomes KW - lipids KW - cell membranes KW - W 30965:Miscellaneous, Reviews KW - W3 33390:Products: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15876170?accountid=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=Biochemistry+%28Washington%29&rft.atitle=Membrane+fusion+with+cationic+liposomes%3A+Effects+of+target+membrane+lipid+composition&rft.au=Bailey%2C+AL%3BCullis%2C+PR&rft.aulast=Bailey&rft.aufirst=AL&rft.date=1997-02-01&rft.volume=36&rft.issue=7&rft.spage=1628&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 - 2011-12-14 N1 - SubjectsTermNotLitGenreText - liposomes; lipids; cell membranes ER - TY - JOUR T1 - Selection of Opa super(+) Neisseria gonorrhoeae by limited availability of normal human serum AN - 15855827; 4021443 AB - Experimental infections of human male volunteers with Neisseria gonorrhoeae have provided valuable insights into the early stages of gonorrheal disease. Bacterial variants expressing outer membrane opacity (Opa) proteins appear to be selected from the inoculum during a period in which total recoverable numbers of bacteria decrease rapidly. This apparent survival advantage occurs simultaneously with the onset of an inflammatory response, characterized by local production of interleukin 6 (IL-6) and IL-8 and the appearance of leukocytes in urine. Since the inflammatory response may also result in the presence of serum factors on the mucosal surface, we investigated the possibility that killing in normal human serum (NHS) leads to the selection of Opa super(+) variants. We therefore studied killing of separate populations and mixtures of Opa super(-) and Opa super(+) N. gonorrhoeae MS11mk in NHS. Expression of an Opa protein conferred a survival advantage upon the organism; i.e., the Opa super(+) variants were more serum resistant than their isogenic Opa super(-) counterparts, resulting in a selection for Opa super(+) phenotypes when a mixture of Opa super(+) and Opa super(-) gonococci (GC) was exposed to submaximal doses of NHS. This selection was observed in three different lipooligosaccharide (LOS) backgrounds, indicating that it was not due to a difference in LOS expression between Opa super(-) and Opa super(+) phenotypes. Incubation in NHS of sialylated GC resulted in a similar selection for Opa super(+) variants. The presence of normal human urine during the serum killing assay had no effect on the selection phenomenon but drastically depleted NHS of bactericidal activity, which was found to be at least partly due to complement inhibition. The results suggest that serum killing may contribute to the transition from Opa super(-) to Opa super(+) phenotypes during the early stages of infection of the male urethra. JF - Infection and Immunity AU - Bos, M P AU - Hogan, D AU - Belland, R J AD - Rocky Mountain Labs., NIH, NIAID, 903 South 4th St., Hamilton, MT 59840, USA Y1 - 1997/02// PY - 1997 DA - Feb 1997 SP - 645 EP - 650 VL - 65 IS - 2 SN - 0019-9567, 0019-9567 KW - Opa protein KW - Microbiology Abstracts B: Bacteriology KW - gonorrhea KW - gene expression KW - serum bactericidal activity KW - Neisseria gonorrhoeae KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15855827?accountid=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=Selection+of+Opa+super%28%2B%29+Neisseria+gonorrhoeae+by+limited+availability+of+normal+human+serum&rft.au=Bos%2C+M+P%3BHogan%2C+D%3BBelland%2C+R+J&rft.aulast=Bos&rft.aufirst=M&rft.date=1997-02-01&rft.volume=65&rft.issue=2&rft.spage=645&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 - Neisseria gonorrhoeae; gene expression; serum bactericidal activity; gonorrhea ER - TY - JOUR T1 - Mammalian germ cell mutagenicity of ENU, IPMS and MMS, chemicals selected for a transgenic mouse collaborative study AN - 15851601; 4017298 AB - A collaborative study to systematically assess transgenic mouse mutation assays as screens for germ cell mutagens has been conducted. Three male mouse germ cell mutagens (ENU, iPMS and MMS) were selected for testing. This paper provides a brief review of the effects reported for those 3 chemicals in the most commonly used non-transgenic germ cell mutagenicity assays, namely the dominant lethal, heritable translocation, and specific locus tests. Additionally, information on the DNA reactivity and the molecular nature of mutations induced by these chemicals is summarized. JF - Mutation Research-Genetic Toxicology and Environmental Mutagenesis AU - Shelby, MD AU - Tindall, K R AD - Reproductive Toxicology Group, NIEHS, P.O. Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1997/02// PY - 1997 DA - Feb 1997 SP - 99 EP - 109 PB - ELSEVIER SCIENCE B.V. VL - 388 IS - 2-3 SN - 1383-5718, 1383-5718 KW - transgenic mice KW - DNA KW - N-ethyl-N-nitrosourea KW - isopropyl methanesulfonate KW - methyl methanesulfonate KW - Toxicology Abstracts; Genetics Abstracts KW - reviews KW - mutagenicity testing KW - X 24200:Nitrosamines & related compounds KW - X 24221:Toxicity testing KW - G 07221:Specific chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15851601?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+Research-Genetic+Toxicology+and+Environmental+Mutagenesis&rft.atitle=Mammalian+germ+cell+mutagenicity+of+ENU%2C+IPMS+and+MMS%2C+chemicals+selected+for+a+transgenic+mouse+collaborative+study&rft.au=Shelby%2C+MD%3BTindall%2C+K+R&rft.aulast=Shelby&rft.aufirst=MD&rft.date=1997-02-01&rft.volume=388&rft.issue=2-3&rft.spage=99&rft.isbn=&rft.btitle=&rft.title=Mutation+Research-Genetic+Toxicology+and+Environmental+Mutagenesis&rft.issn=13835718&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 - mutagenicity testing; reviews; DNA ER - TY - JOUR T1 - Slow dendritic transport of dissociated mouse hippocampal neurons exposed to aluminum AN - 15847180; 4016782 AB - We determined the influence of aluminum on dendritic transport, using an in vitro system of dissociated mouse hippocampal neurons. Newly synthesized RNA from dissociated mouse hippocampal neurons was more slowly transported into dendrites in the presence of aluminum chloride when compared to those without the addition of aluminum chloride to the culture medium. Suppression of dendritic transport of newly synthesized RNA may be responsible for the dendritic degeneration observed in aluminum neurotoxicity, eventually leading to neuronal degeneration. JF - Brain Research AU - Wakayama, I AU - Song, Ki-Joon AU - Nerurkar, V R AU - Yoshida, S AU - Garruto, R M AD - Building 376, National Institute of Neurological Disorders and Stroke, Frederick Cancer Research and Development Center, P.O. Box B, Frederick, MD 21702-1201, USA Y1 - 1997/02// PY - 1997 DA - Feb 1997 SP - 237 EP - 240 PB - ELSEVIER SCIENCE B.V. VL - 748 IS - 1-2 SN - 0006-8993, 0006-8993 KW - cell culture KW - Guam KW - mice KW - aluminum KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - amyotrophic lateral sclerosis KW - neurotoxins KW - Parkinson's disease KW - Alzheimer's disease KW - axonal transport KW - RNA KW - hippocampus KW - dementia disorders KW - N3 11126:Alzheimer's disease and other dementias KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15847180?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+Research&rft.atitle=Slow+dendritic+transport+of+dissociated+mouse+hippocampal+neurons+exposed+to+aluminum&rft.au=Wakayama%2C+I%3BSong%2C+Ki-Joon%3BNerurkar%2C+V+R%3BYoshida%2C+S%3BGarruto%2C+R+M&rft.aulast=Wakayama&rft.aufirst=I&rft.date=1997-02-01&rft.volume=748&rft.issue=1-2&rft.spage=237&rft.isbn=&rft.btitle=&rft.title=Brain+Research&rft.issn=00068993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - dementia disorders; RNA; Alzheimer's disease; amyotrophic lateral sclerosis; Parkinson's disease; axonal transport; neurotoxins; hippocampus ER - TY - JOUR T1 - An udder way of making lambs AN - 15834694; 4008351 AB - A hoary old question that has interested developmental biologists for years has been the continuity of the genome during animal development. Put another way -- do growth, differentiation and development of the embryo involve irreversible modifications to the genome in somatic cells? On page 810 of this issue, Wilmut and colleagues extend their previous findings that viable lambs can be produced by transplanting nuclei from cell lines that have been established from very early sheep embryos (blastocysts) to enucleated eggs. They now show that the same procedure can be used to obtain viable lambs from cell lines that have been established from older, more mature embryos and, remarkably, one viable lamb has been derived from a cell line that was established from the udder of a six-year-old ewe. The results are of profound significance. Not only do they confirm that the genome (with the exception of the immunoglobulin and T-cell-receptor genes) does not undergo irreversible modifications, but they will open up a range of new ways to think about the questions that are of current interest, as well as providing the impetus to develop novel approaches for the genetic manipulation of mammals. JF - Nature AU - Stewart, C AD - Cancer and Dev. Biol. Lab., ABL-Basic Res. Program, NCI-Frederick Cancer Res. and Dev. Cent., Frederick, MD 21702, USA Y1 - 1997/02// PY - 1997 DA - Feb 1997 SP - 769 EP - 771 VL - 385 IS - 6619 SN - 0028-0836, 0028-0836 KW - cloning KW - sheep KW - Biotechnology and Bioengineering Abstracts; Agricultural and Environmental Biotechnology Abstracts; Genetics Abstracts KW - reviews KW - eggs KW - embryos KW - udder KW - transplantation KW - differentiation KW - genomes KW - nuclei KW - mammary gland KW - G 07415:Domestic animals (sheep, goats) KW - W2 32435:Animal breeding KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15834694?accountid=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&rft.atitle=An+udder+way+of+making+lambs&rft.au=Stewart%2C+C&rft.aulast=Stewart&rft.aufirst=C&rft.date=1997-02-01&rft.volume=385&rft.issue=6619&rft.spage=769&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - reviews; embryos; eggs; udder; differentiation; transplantation; genomes; nuclei; mammary gland ER - TY - JOUR T1 - Possible relation between hypertension and cancers of the renal pelvis and ureter. AN - 78828906; 9033625 AB - To evaluate the relationship of selected medical conditions and medications with cancers of the renal pelvis and ureter, we interviewed 308 subjects with renal pelvis cancer, 194 subjects with ureter cancer and 496 control subjects in 3 areas of the United States. After controlling for the effects of smoking, age, gender and geographic residence, a history of hypertension (reported to have been diagnosed more than 5 years before interview) was associated with a small but significantly increased risk (odds ratio [OR] = 1.3; 95% confidence interval [CI], 1.0-1.8), whereas no relationship was observed with a variety of other medical conditions or medications. Stratified analysis showed that the risk associated with hypertension was twice as high among users of diuretics or other antihypertensive drugs (OR = 2.4; 95% CI, 1.1-4.9) as it was among those who never used these medications (OR = 1.2; 95% CI, 0.8-1.7). Our findings suggest that the association previously reported between hypertension and renal cell cancer may extend to cancers of the renal pelvis and ureter. JF - International journal of cancer AU - Liaw, K L AU - Linet, M S AU - McLaughlin, J K AU - Yu, M C AU - Schoenberg, J B AU - Lynch, C F AU - Niwa, S AU - Fraumeni, J F AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. LIAWK@EPNDCE.NCI.NIH.GOV Y1 - 1997/01/27/ PY - 1997 DA - 1997 Jan 27 SP - 265 EP - 268 VL - 70 IS - 3 SN - 0020-7136, 0020-7136 KW - Antihypertensive Agents KW - 0 KW - Diuretics KW - Index Medicus KW - Diuretics -- adverse effects KW - Odds Ratio KW - Humans KW - Antihypertensive Agents -- adverse effects KW - Adult KW - Case-Control Studies KW - Confidence Intervals KW - Aged KW - Middle Aged KW - Male KW - Female KW - Hypertension -- complications KW - Ureteral Neoplasms -- complications KW - Ureteral Neoplasms -- epidemiology KW - Hypertension -- epidemiology KW - Kidney Neoplasms -- complications KW - Kidney Neoplasms -- epidemiology KW - Kidney Pelvis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78828906?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Possible+relation+between+hypertension+and+cancers+of+the+renal+pelvis+and+ureter.&rft.au=Liaw%2C+K+L%3BLinet%2C+M+S%3BMcLaughlin%2C+J+K%3BYu%2C+M+C%3BSchoenberg%2C+J+B%3BLynch%2C+C+F%3BNiwa%2C+S%3BFraumeni%2C+J+F&rft.aulast=Liaw&rft.aufirst=K&rft.date=1997-01-27&rft.volume=70&rft.issue=3&rft.spage=265&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-06 N1 - Date created - 1997-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The E. coli signal recognition particle is required for the insertion of a subset of inner membrane proteins. AN - 78804318; 9008159 AB - E. coli homologs of the signal recognition particle (SRP) and its receptor are essential for viability, but their role in protein export is unclear. To elucidate their function, we devised a genome-wide screen to identify genes that encode SRP substrates. Inhibition of the SRP pathway sharply blocked the membrane insertion of several polytopic inner membrane proteins (IMPs) that were predicted to be SRP substrates, but had a smaller effect on the insertion of other IMPs and no significant effect on preprotein translocation. Our results suggest that whereas most E. coli preproteins and some IMPs can utilize SRP-independent targeting pathways effectively, the structural features of a subset of IMPs have required the conservation of an SRP-based targeting machinery. JF - Cell AU - Ulbrandt, N D AU - Newitt, J A AU - Bernstein, H D AD - Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/01/24/ PY - 1997 DA - 1997 Jan 24 SP - 187 EP - 196 VL - 88 IS - 2 SN - 0092-8674, 0092-8674 KW - Bacterial Proteins KW - 0 KW - Escherichia coli Proteins KW - Ffh protein, E coli KW - FtsY protein, Bacteria KW - Membrane Proteins KW - Protein Precursors KW - Receptors, Cytoplasmic and Nuclear KW - Recombinant Fusion Proteins KW - Signal Recognition Particle KW - Index Medicus KW - Recombinant Fusion Proteins -- metabolism KW - Phenotype KW - Mutagenesis, Site-Directed KW - Transformation, Bacterial KW - Genes, Bacterial KW - Protein Precursors -- metabolism KW - Recombinant Fusion Proteins -- genetics KW - Biological Transport KW - Escherichia coli -- metabolism KW - Bacterial Proteins -- genetics KW - Receptors, Cytoplasmic and Nuclear -- metabolism KW - Membrane Proteins -- metabolism KW - Bacterial Proteins -- metabolism KW - Signal Recognition Particle -- metabolism KW - Signal Recognition Particle -- genetics KW - Escherichia coli -- genetics KW - Receptors, Cytoplasmic and Nuclear -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78804318?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell&rft.atitle=The+E.+coli+signal+recognition+particle+is+required+for+the+insertion+of+a+subset+of+inner+membrane+proteins.&rft.au=Ulbrandt%2C+N+D%3BNewitt%2C+J+A%3BBernstein%2C+H+D&rft.aulast=Ulbrandt&rft.aufirst=N&rft.date=1997-01-24&rft.volume=88&rft.issue=2&rft.spage=187&rft.isbn=&rft.btitle=&rft.title=Cell&rft.issn=00928674&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-18 N1 - Date created - 1997-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Peroxidation of a specific tryptophan of metmyoglobin by hydrogen peroxide. AN - 78789965; 8999946 AB - Globin-centered radicals at tyrosine and tryptophan residues and a peroxyl radical at an unknown location have been reported previously as products of the reaction of metmyoglobin with hydrogen peroxide. The peroxyl radical is shown here to be localized on tryptophan through the use of recombinant sperm whale myoglobin labeled with 13C at the indole ring C-3. Peroxyl radical formation was not prevented by site-directed mutations that replaced all three tyrosines, the distal histidine, or tryptophan 7 with non-oxidizable residues. In contrast, mutation of tryptophan 14 prevents peroxyl radical formation, implicating tryptophan 14 as the specific site of the peroxidation. JF - The Journal of biological chemistry AU - DeGray, J A AU - Gunther, M R AU - Tschirret-Guth, R AU - Ortiz de Montellano, P R AU - Mason, R P AD - Laboratory of Pharmacology and Chemistry, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/01/24/ PY - 1997 DA - 1997 Jan 24 SP - 2359 EP - 2362 VL - 272 IS - 4 SN - 0021-9258, 0021-9258 KW - Free Radicals KW - 0 KW - Metmyoglobin KW - 12772-23-5 KW - Tryptophan KW - 8DUH1N11BX KW - Hydrogen Peroxide KW - BBX060AN9V KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Electron Spin Resonance Spectroscopy KW - Crystallography, X-Ray KW - Free Radicals -- metabolism KW - Whales KW - Protein Conformation KW - Metmyoglobin -- genetics KW - Hydrogen Peroxide -- metabolism KW - Tryptophan -- metabolism KW - Metmyoglobin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78789965?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Peroxidation+of+a+specific+tryptophan+of+metmyoglobin+by+hydrogen+peroxide.&rft.au=DeGray%2C+J+A%3BGunther%2C+M+R%3BTschirret-Guth%2C+R%3BOrtiz+de+Montellano%2C+P+R%3BMason%2C+R+P&rft.aulast=DeGray&rft.aufirst=J&rft.date=1997-01-24&rft.volume=272&rft.issue=4&rft.spage=2359&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-21 N1 - Date created - 1997-02-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sequential modification of serines 621 and 624 in the Raf-1 carboxyl terminus produces alterations in its electrophoretic mobility. AN - 78782399; 8999914 AB - The Raf-1 serine/threonine protein kinase plays a central role in many of the mitogenic signaling pathways regulating cell growth and differentiation. The regulation of Raf-1 is complex, and involves protein-protein interactions as well as changes in the phosphorylation state of Raf-1 that are accompanied by alterations in its electrophoretic mobility. We have previously shown that a 33-kDa COOH-terminal, kinase-inactive fragment of Raf-1 underwent a mobility shift in response to the stimulation of cells with serum or phorbol esters. Here we demonstrate that treatment of NIH 3T3 cells or Sf9 cells with hydrogen peroxide (H2O2) also induces the mobility shift of the kinase-inactive Raf-1 fragment. A series of deletion mutants of the Raf-1 COOH terminus were analyzed, and the region required for the mobility shift was localized to a 78-amino acid fragment (residues 566-643). Metabolic labeling revealed that the slower migrating forms of the 33-kDa and of the smaller fragment contained phosphorus. Mutation of a previously characterized phosphorylation site, serine 621, to alanine prevented the mobility shift as well as phosphate incorporation or Src and Ras-dependent kinase activation in Sf9 cells when this mutation was engineered into the full-length Raf-1. Mutation of 621 to aspartate yielded a protein that existed in both the shifted and unshifted forms, demonstrating that a negative charge at 621 was necessary, but not sufficient, for the mobility shift to occur; however, its full-length form was still resistant to activation in the Sf9 system. Additional mutation of nearby serine 624 to alanine blocked the shift, implicating this residue as the site of the second of a two-step modification process leading to the slower migrating form. Co-expression of the 33-kDa fragment with an activated form of mitogen-activated protein kinase kinase in NIH 3T3 led to the appearance of the shifted form in a serum-independent manner. These results demonstrate that a mitogen-activated protein kinase kinase-induced event involving modification of serines 621 and 624 leads to the mobility shift of Raf-1. JF - The Journal of biological chemistry AU - Ferrier, A F AU - Lee, M AU - Anderson, W B AU - Benvenuto, G AU - Morrison, D K AU - Lowy, D R AU - DeClue, J E AD - Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, Maryland 20892-4040, USA. Y1 - 1997/01/24/ PY - 1997 DA - 1997 Jan 24 SP - 2136 EP - 2142 VL - 272 IS - 4 SN - 0021-9258, 0021-9258 KW - Proto-Oncogene Proteins KW - 0 KW - Serine KW - 452VLY9402 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Proto-Oncogene Proteins c-raf KW - Zinc KW - J41CSQ7QDS KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - 3T3 Cells KW - Zinc -- pharmacology KW - Phosphorylation KW - Transfection KW - Electrophoresis, Polyacrylamide Gel KW - Hydrogen Peroxide -- pharmacology KW - Point Mutation KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Mice KW - Protein-Serine-Threonine Kinases -- chemistry KW - Proto-Oncogene Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78782399?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Sequential+modification+of+serines+621+and+624+in+the+Raf-1+carboxyl+terminus+produces+alterations+in+its+electrophoretic+mobility.&rft.au=Ferrier%2C+A+F%3BLee%2C+M%3BAnderson%2C+W+B%3BBenvenuto%2C+G%3BMorrison%2C+D+K%3BLowy%2C+D+R%3BDeClue%2C+J+E&rft.aulast=Ferrier&rft.aufirst=A&rft.date=1997-01-24&rft.volume=272&rft.issue=4&rft.spage=2136&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-21 N1 - Date created - 1997-02-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cleavage of syntaxin prevents G-protein regulation of presynaptic calcium channels. AN - 78798606; 9002518 AB - Neurotransmitter release into the synapse is stimulated by calcium influx through ion channels that are closely associated with the transmitter release sites. This link may involve the membrane protein syntaxin, which is known to be associated with the release sites and to bind to the calcium channels. There is evidence that presynaptic calcium channels are downregulated by second messenger pathways involving G proteins. Here we use the patch-clamp technique to test whether calcium current is regulated by G proteins in a vertebrate presynaptic nerve terminal, and whether this regulation is affected by the linkage to syntaxin. The calcium current in the nerve terminal showed typical G-protein-mediated changes in amplitude and activation kinetics which were reversed by a preceding depolarization. These effects of the G protein were virtually eliminated if syntaxin was first cleaved with botulinum toxin C1. Our findings indicate that this sensitivity of the current to modulation by G proteins requires the association of the presynaptic calcium channel with elements of the transmitter release site, which may ensure that channels tethered at release sites are preferentially regulated by the G-protein second messenger pathway. JF - Nature AU - Stanley, E F AU - Mirotznik, R R AD - Synaptic Mechanisms Section, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. elis@helix.nih.gov Y1 - 1997/01/23/ PY - 1997 DA - 1997 Jan 23 SP - 340 EP - 343 VL - 385 IS - 6614 SN - 0028-0836, 0028-0836 KW - Calcium Channels KW - 0 KW - Membrane Proteins KW - Nerve Tissue Proteins KW - Qa-SNARE Proteins KW - Guanosine 5'-O-(3-Thiotriphosphate) KW - 37589-80-3 KW - Botulinum Toxins KW - EC 3.4.24.69 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Microscopy, Fluorescence KW - Animals KW - Chickens KW - Patch-Clamp Techniques KW - Botulinum Toxins -- pharmacology KW - Guanosine 5'-O-(3-Thiotriphosphate) -- metabolism KW - Presynaptic Terminals -- drug effects KW - Calcium Channels -- metabolism KW - Membrane Proteins -- metabolism KW - GTP-Binding Proteins -- metabolism KW - Nerve Tissue Proteins -- metabolism KW - Synaptic Membranes -- metabolism KW - Presynaptic Terminals -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78798606?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=Cleavage+of+syntaxin+prevents+G-protein+regulation+of+presynaptic+calcium+channels.&rft.au=Stanley%2C+E+F%3BMirotznik%2C+R+R&rft.aulast=Stanley&rft.aufirst=E&rft.date=1997-01-23&rft.volume=385&rft.issue=6614&rft.spage=340&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-05 N1 - Date created - 1997-02-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of phenylalanine in structure-function relationships of phenylalanine hydroxylase revealed by radiation target analysis. AN - 78809043; 9012811 AB - The activity of rat liver phenylalanine hydroxylase (PAH; phenylalanine 4-monooxygenase, EC 1.14.16.1) is regulated by interaction with its substrate, phenylalanine, and its coenzyme, BH4 [tetrahydrobiopterin (6R-dihydroxypropyl-L-erythro-5,6,7,8-tetrahydropterin)]. The structural changes accompanying these interactions have been studied by radiation target analysis. PAH purified from rat liver was incubated with 2 mM phenylalanine to achieve complete activation of the enzyme. Frozen samples were irradiated with various doses of high energy electrons; samples were subsequently thawed, and several surviving properties of the enzyme were determined. Each parameter decreased as a single exponential function of radiation dose. Radiation target analysis of enzymatic activity yielded a dimeric target size. Similar radiation effects on subunit monomers and on tetrameric structure were observed. Together with results from unactivated enzyme, these data show that phenylalanine increases the interactions between the subunits in a dimer and weakens the interactions between dimers in a tetramer. These alterations prevent the natural cofactor, a tetrahydrobiopterin, from exerting a negative effect on activity. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Davis, M D AU - Parniak, M A AU - Kaufman, S AU - Kempner, E AD - National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/01/21/ PY - 1997 DA - 1997 Jan 21 SP - 491 EP - 495 VL - 94 IS - 2 SN - 0027-8424, 0027-8424 KW - Macromolecular Substances KW - 0 KW - Biopterin KW - 22150-76-1 KW - Phenylalanine KW - 47E5O17Y3R KW - Phenylalanine Hydroxylase KW - EC 1.14.16.1 KW - sapropterin KW - EGX657432I KW - Index Medicus KW - Rats KW - Biopterin -- analogs & derivatives KW - Animals KW - Liver -- enzymology KW - Enzyme Activation KW - Dose-Response Relationship, Radiation KW - Biopterin -- chemistry KW - Chromatography, High Pressure Liquid KW - Phenylalanine -- chemistry KW - Phenylalanine Hydroxylase -- chemistry KW - Phenylalanine Hydroxylase -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78809043?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+role+of+phenylalanine+in+structure-function+relationships+of+phenylalanine+hydroxylase+revealed+by+radiation+target+analysis.&rft.au=Davis%2C+M+D%3BParniak%2C+M+A%3BKaufman%2C+S%3BKempner%2C+E&rft.aulast=Davis&rft.aufirst=M&rft.date=1997-01-21&rft.volume=94&rft.issue=2&rft.spage=491&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-06 N1 - Date created - 1997-03-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Eur J Biochem. 1969 Jan;7(3):360-9 [5791581] Biochemistry. 1991 Aug 20;30(33):8151-7 [1907851] J Biol Chem. 1970 Sep 25;245(18):4751-9 [5456148] Biochim Biophys Acta. 1971 Aug 20;242(2):345-54 [5160150] J Biol Chem. 1973 Jun 25;248(12):4345-53 [4145799] J Biol Chem. 1978 Oct 10;253(19):6657-9 [690116] J Biol Chem. 1979 Nov 25;254(22):11300-6 [500646] J Biol Chem. 1980 May 25;255(10):4793-800 [7372612] J Biol Chem. 1981 Jul 10;256(13):6876-82 [7240248] J Biol Chem. 1982 Oct 10;257(19):11213-6 [6981644] J Biol Chem. 1984 Jan 10;259(1):271-7 [6706937] Biochemistry. 1984 Aug 14;23(17):3836-42 [6487579] J Biol Chem. 1984 Dec 10;259(23):14560-6 [6501308] Methods Enzymol. 1985;117:65-94 [4079816] J Biol Chem. 1986 Mar 25;261(9):4148-53 [2869038] J Biol Chem. 1987 Jul 15;262(20):9433-6 [3298256] Methods Enzymol. 1987;142:3-17 [3600372] J Biol Chem. 1988 Jan 25;263(3):1223-30 [3335542] Adv Enzymol Relat Areas Mol Biol. 1993;67:77-264 [8322620] Trends Biochem Sci. 1993 Jul;18(7):236-9 [8212129] Anal Biochem. 1994 Feb 1;216(2):451-5 [8179203] J Biol Chem. 1994 Oct 7;269(40):24647-56 [7929136] J Biol Chem. 1995 Dec 22;270(51):30532-44 [8530485] Arch Biochem Biophys. 1996 Jan 15;325(2):235-41 [8561502] Adv Enzymol Relat Areas Mol Biol. 1988;61:107-47 [3281417] J Biol Chem. 1990 Jul 15;265(20):11633-42 [2365689] Nature. 1970 Aug 15;227(5259):680-5 [5432063] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intronic enhancer activity of the eosinophil-derived neurotoxin (RNS2) and eosinophil cationic protein (RNS3) genes is mediated by an NFAT-1 consensus binding sequence. AN - 78779056; 8999843 AB - The eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) are both small, cationic ribonuclease toxins that are stored in and secreted by activated human eosinophilic leukocytes. We have previously shown that optimal expression of the EDN gene is dependent on an interaction between an intronic enhancer element or elements and the 5' promoter region. Here we present evidence demonstrating that the gene encoding ECP is regulated in an analogous fashion and that an intronic enhancer element functioning in both genes is a consensus binding sequence for the transcription factor NFAT-1. Our initial results demonstrate that one or more nuclear proteins isolated from human promyelocytic leukemia (HL-60) cells bind specifically at this consensus site (5'-GGAGAA-3') within the intron of the EDN gene and that disruption of this sequence reduced the characteristic 20-30-fold increase in reporter gene activity observed with the tandem EDN promoter/exon 1/intron construct to background levels. The NFAT-1 consensus site in the ECP gene differs from that found in the EDN gene by a single nucleotide (5'-GGAGAG-3'); the conversion of the 3' G to an A resulted in a further enhancement of the reporter gene activity supported by the ECP promoter/exon 1/intron construct. Interestingly, no "supershift" was observed in gel shift assays performed in the presence of anti-NFAT-1 antiserum, suggesting that a nuclear protein other than NFAT-1 may be acting at this consensus site. JF - The Journal of biological chemistry AU - Handen, J S AU - Rosenberg, H F AD - Laboratory of Host Defenses, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/01/17/ PY - 1997 DA - 1997 Jan 17 SP - 1665 EP - 1669 VL - 272 IS - 3 SN - 0021-9258, 0021-9258 KW - DNA-Binding Proteins KW - 0 KW - NFATC Transcription Factors KW - Nuclear Proteins KW - Proteins KW - Transcription Factors KW - DNA KW - 9007-49-2 KW - Eosinophil-Derived Neurotoxin KW - EC 3.1.- KW - Ribonucleases KW - RNASE2 protein, human KW - EC 3.1.27.5 KW - Index Medicus KW - Base Sequence KW - Tumor Cells, Cultured KW - Sequence Homology, Nucleic Acid KW - Humans KW - Molecular Sequence Data KW - Introns KW - Consensus Sequence KW - Protein Binding KW - Gene Expression Regulation -- genetics KW - Transcription Factors -- metabolism KW - Enhancer Elements, Genetic KW - Proteins -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78779056?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Intronic+enhancer+activity+of+the+eosinophil-derived+neurotoxin+%28RNS2%29+and+eosinophil+cationic+protein+%28RNS3%29+genes+is+mediated+by+an+NFAT-1+consensus+binding+sequence.&rft.au=Handen%2C+J+S%3BRosenberg%2C+H+F&rft.aulast=Handen&rft.aufirst=J&rft.date=1997-01-17&rft.volume=272&rft.issue=3&rft.spage=1665&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-13 N1 - Date created - 1997-02-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Loss of hippocampal CA1 neurons and learning impairment in subicular lesioned rats. AN - 78817524; 9037400 AB - 30-Day-old male Wistar rats were tested for acquisition and retention of operant conditioned behavior after bilateral subicular lesions made either electrolytically or chemically (ibotenic acid). The acquisition of operant learning was carried out in lesioned rats by assessing the number of sessions required to learn the operant task, whereas the retention test was performed after lesions by assessing performance on a previously learnt operant task. The acquisition of pedal press operant learning was significantly delayed in both types of lesioned rats, without any impairment in the retention of the previously learned task after lesioning. In these animals the cell densities were quantified in cresyl violet-stained sections in different subfields of hippocampus. Following the lesion of subiculum, selective degeneration of CA1 cells without the involvement of other hippocampal subfields was observed. This might be due to the loss of target area (subiculum) through which hippocampus is connected with neocortical and subcortical structures. This, in turn, might have resulted in behavioral deficits. The data suggest that the subiculum might be involved in the acquisition of new information rather than in retention. JF - Brain research AU - Govindaiah AU - Rao, B S AU - Raju, T R AU - Meti, B L AD - Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Bangalore, India. Y1 - 1997/01/16/ PY - 1997 DA - 1997 Jan 16 SP - 121 EP - 126 VL - 745 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Excitatory Amino Acid Antagonists KW - 0 KW - Ibotenic Acid KW - 2552-55-8 KW - Index Medicus KW - Animals KW - Nerve Degeneration -- drug effects KW - Cell Count KW - Conditioning, Operant -- physiology KW - Memory -- drug effects KW - Memory -- physiology KW - Nerve Degeneration -- physiology KW - Axons -- physiology KW - Rats KW - Excitatory Amino Acid Antagonists -- toxicity KW - Rats, Wistar KW - Electroshock KW - Ibotenic Acid -- toxicity KW - Male KW - Stereotaxic Techniques KW - Neurons -- physiology KW - Hippocampus -- injuries KW - Hippocampus -- pathology KW - Learning Disorders -- etiology KW - Learning Disorders -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78817524?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Loss+of+hippocampal+CA1+neurons+and+learning+impairment+in+subicular+lesioned+rats.&rft.au=Govindaiah%3BRao%2C+B+S%3BRaju%2C+T+R%3BMeti%2C+B+L&rft.aulast=Govindaiah&rft.aufirst=&rft.date=1997-01-16&rft.volume=745&rft.issue=1-2&rft.spage=121&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 - 1997-04-29 N1 - Date created - 1997-04-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oncogenic activation of c-Myb by carboxyl-terminal truncation leads to decreased proteolysis by the ubiquitin-26S proteasome pathway. AN - 78813252; 9010222 AB - c-myb activation by insertional mutagenesis in murine myeloid leukemias can lead to amino (NH2)-terminal or carboxyl (COOH)-terminal truncation of its protein product. We observed that in these leukemias, the steady state level of the protein truncated at the COOH terminus was remarkably higher than that of the protein truncated at the NH2-terminus or full length wild-type protein. To examine the rate of proteolysis of different forms of Myb in a uniform cellular background, the proteins were constitutively expressed in the myeloblast cell line M1, using the retrovirus vector LXSN. In pulse chase experiments, using metabolically 35S-labeled proteins, it was determined that COOH-terminal truncation of c-Myb by 248 aa (CT-c-Myb) substantially increases protein stability, resulting in a t1/2 of about 140 min, as compared to 50 min for full length c-Myb (FL-c-Myb). In an investigation of the mechanism involved in the in vivo degradation of this short lived transcription factor, inhibitors of the lysosomal (chloroquine), proteasomal (ALLM, ALLN, lactacystin) and calpains (EGTA, E-64d, BAPTA/AM) pathways were utilized. Results of this experiment identified the 26S proteasome as a major pathway responsible for rapid breakdown of the protein in hematopoietic cells. Further experiments carried out in vitro demonstrated that c-Myb can be ubiquitinated, suggesting that this process may be involved in the targeting of wild-type c-Myb to degradation by the 26S proteasome. In addition, it was demonstrated that CT-c-Myb was less efficiently ubiquitinated than wild-type protein indicating that defects in modification account for its escape from rapid turnover. We speculate that the increased half-life of c-Myb resulting from truncation could contribute to its transforming potential. JF - Oncogene AU - Bies, J AU - Wolff, L AD - Laboratory of Cellular Oncology, National Cancer Institute, NIH, Bethesda, Maryland 20892-40255, USA. Y1 - 1997/01/16/ PY - 1997 DA - 1997 Jan 16 SP - 203 EP - 212 VL - 14 IS - 2 SN - 0950-9232, 0950-9232 KW - Peptide Fragments KW - 0 KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-myb KW - Trans-Activators KW - Transcription Factors KW - Ubiquitins KW - Peptide Hydrolases KW - EC 3.4.- KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - ATP dependent 26S protease KW - EC 3.4.99.- KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured KW - Half-Life KW - Transcription Factors -- metabolism KW - Genetic Vectors KW - Transcription, Genetic KW - Mice KW - Peptide Fragments -- metabolism KW - Peptide Hydrolases -- chemistry KW - Trans-Activators -- metabolism KW - Leukemia, Myeloid -- genetics KW - Proto-Oncogene Proteins -- metabolism KW - Trans-Activators -- chemistry KW - Ubiquitins -- metabolism KW - Trans-Activators -- genetics KW - Peptide Hydrolases -- metabolism KW - Proto-Oncogene Proteins -- chemistry KW - Leukemia, Myeloid -- metabolism KW - Proto-Oncogene Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78813252?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Oncogenic+activation+of+c-Myb+by+carboxyl-terminal+truncation+leads+to+decreased+proteolysis+by+the+ubiquitin-26S+proteasome+pathway.&rft.au=Bies%2C+J%3BWolff%2C+L&rft.aulast=Bies&rft.aufirst=J&rft.date=1997-01-16&rft.volume=14&rft.issue=2&rft.spage=203&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-21 N1 - Date created - 1997-02-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of serotonin depletion on the play of juvenile rats. AN - 78872334; 9071373 JF - Annals of the New York Academy of Sciences AU - Knutson, B AU - Panksepp, J AD - Department of Psychology, Bowling Green State University, Ohio 43402, USA. knutson@odin.niaaa.nih.gov Y1 - 1997/01/15/ PY - 1997 DA - 1997 Jan 15 SP - 475 EP - 477 VL - 807 SN - 0077-8923, 0077-8923 KW - Neurotoxins KW - 0 KW - 5,7-Dihydroxytryptamine KW - 31363-74-3 KW - Serotonin KW - 333DO1RDJY KW - Index Medicus KW - Rats KW - Animals KW - Neurons -- drug effects KW - 5,7-Dihydroxytryptamine -- administration & dosage KW - Neurons -- physiology KW - 5,7-Dihydroxytryptamine -- toxicity KW - Dominance, Cerebral KW - Time Factors KW - Play and Playthings KW - Injections, Intraventricular KW - Serotonin -- physiology KW - Cerebral Ventricles -- physiology KW - Social Behavior KW - Cerebral Ventricles -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78872334?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effects+of+serotonin+depletion+on+the+play+of+juvenile+rats.&rft.au=Knutson%2C+B%3BPanksepp%2C+J&rft.aulast=Knutson&rft.aufirst=B&rft.date=1997-01-15&rft.volume=807&rft.issue=&rft.spage=475&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-10 N1 - Date created - 1997-04-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HTLV-I Tax self-association in optimal trans-activation function. AN - 78816817; 9016568 AB - HTLV-I Tax protein is a potent transcriptional activator of viral and cellular genes. Tax does not bind DNA directly but interacts through protein-protein contact with host cell factors that recognize the viral long terminal repeat (LTR). Domains within Tax needed for protein-protein interaction have not been fully characterized. In studying transcriptional function in yeast cells, we unexpectedly found that Tax functions optimally not as a monomer, but as a homodimer. Here we have used the one hybrid and two hybrid genetic approaches in yeast to investigate the region(s) within Tax necessary for self-association. Dimer formation was also confirmed biochemically by using electrophoretic mobility shift (EMSA) and supershift assays. Twenty two Tax point mutants were utilized to map relevant residues. Genetic results from this series of mutants revealed that a necessary region for dimerization is contained within a previously characterized zinc finger domain. Two loss-of-function Tax mutants, each poorly active when assayed individually, were found to have complementing activity when co-expressed together. This genetic complementation suggests a mechanism fortrans-activation resulting from simultaneous but non-identical contact with a responsive target by each of two Tax monomers in a dimer. JF - Nucleic acids research AU - Jin, D Y AU - Jeang, K T AD - Molecular Virology Section, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0460, USA. Y1 - 1997/01/15/ PY - 1997 DA - 1997 Jan 15 SP - 379 EP - 387 VL - 25 IS - 2 SN - 0305-1048, 0305-1048 KW - Gene Products, tax KW - 0 KW - Viral Proteins KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Index Medicus KW - AIDS/HIV KW - Point Mutation -- genetics KW - Electrophoresis, Polyacrylamide Gel KW - Dimerization KW - Mutagenesis, Site-Directed -- genetics KW - Viral Proteins -- chemistry KW - Chloramphenicol O-Acetyltransferase -- metabolism KW - Cloning, Molecular KW - Saccharomyces cerevisiae -- genetics KW - Chloramphenicol O-Acetyltransferase -- genetics KW - beta-Galactosidase -- metabolism KW - Gene Expression -- genetics KW - Zinc Fingers -- genetics KW - Sequence Deletion -- genetics KW - Genetic Complementation Test KW - Viral Proteins -- metabolism KW - beta-Galactosidase -- genetics KW - Models, Chemical KW - Gene Products, tax -- chemistry KW - Gene Products, tax -- metabolism KW - Transcriptional Activation -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78816817?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=HTLV-I+Tax+self-association+in+optimal+trans-activation+function.&rft.au=Jin%2C+D+Y%3BJeang%2C+K+T&rft.aulast=Jin&rft.aufirst=D&rft.date=1997-01-15&rft.volume=25&rft.issue=2&rft.spage=379&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-28 N1 - Date created - 1997-02-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Anal Biochem. 1976 May 7;72:248-54 [942051] Mol Cell Biol. 1995 Oct;15(10):5757-61 [7565728] Science. 1985 Jul 5;229(4708):54-8 [2990037] Science. 1985 Aug 16;229(4714):675-9 [2992082] EMBO J. 1986 Nov;5(11):2883-8 [3024966] J Virol. 1987 Jul;61(7):2175-81 [3035218] Proc Natl Acad Sci U S A. 1987 Aug;84(15):5389-93 [3037548] Cell. 1988 Jun 3;53(5):827-36 [2836068] J Virol. 1988 Dec;62(12):4499-509 [3263510] Proc Natl Acad Sci U S A. 1988 Nov;85(21):8291-5 [2847157] Proc Natl Acad Sci U S A. 1988 Nov;85(22):8526-30 [2847164] Mol Cell Biol. 1988 Dec;8(12):5581-7 [2854202] Nature. 1989 Jul 20;340(6230):245-6 [2547163] J Mol Biol. 1989 Oct 5;209(3):423-32 [2511324] Science. 1990 Mar 2;247(4946):1082-4 [2309119] Science. 1990 Jun 29;248(4963):1646-50 [2194289] AIDS Res Hum Retroviruses. 1990 Nov;6(11):1305-9 [2078411] J Virol. 1991 May;65(5):2612-21 [2016773] Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11445-9 [1763059] Nucleic Acids Res. 1992 Mar 25;20(6):1425 [1561104] Virology. 1992 Jun;188(2):754-64 [1585646] J Virol. 1992 Dec;66(12):7183-92 [1433511] J Virol. 1992 Dec;66(12):7253-61 [1433517] Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):610-4 [8421695] N Engl J Med. 1993 Apr 22;328(16):1173-82 [8455685] FASEB J. 1993 Jul;7(10):957-63 [8344494] Science. 1993 Oct 15;262(5132):395-9 [8211160] EMBO J. 1993 Nov;12(11):4269-78 [8223437] Cell. 1993 Nov 19;75(4):805-16 [8242751] Oncogene. 1994 Jan;9(1):337-40 [8302601] Trends Biochem Sci. 1994 Jan;19(1):38-42 [8140620] Trends Microbiol. 1993 Jul;1(4):131-5 [8143128] Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3584-8 [8170951] Nature. 1994 May 19;369(6477):252-5 [8183347] J Biol Chem. 1994 Sep 9;269(36):22466-9 [8077190] J Biol Chem. 1994 Sep 9;269(36):22492-5 [8077196] Mol Cell Biol. 1994 Nov;14(11):7377-84 [7935451] Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12634-8 [7809091] J Virol. 1995 Mar;69(3):1827-33 [7853523] J Virol. 1995 Mar;69(3):1834-41 [7853524] Mol Cell Biol. 1995 Mar;15(3):1234-43 [7862117] J Virol. 1995 Aug;69(8):5077-86 [7609077] J Virol. 1995 Sep;69(9):5806-11 [7637025] Virology. 1995 Dec 1;214(1):3-11 [8525633] Trends Biochem Sci. 1995 Dec;20(12):517-21 [8571454] Virology. 1996 Mar 1;217(1):373-9 [8599225] Nature. 1996 Apr 18;380(6575):642-6 [8602268] Mol Cell Biol. 1996 May;16(5):2174-82 [8628284] Cell. 1996 Feb 9;84(3):331-4 [8608586] J Biol Chem. 1996 Apr 19;271(16):9730-8 [8621651] EMBO J. 1996 Apr 1;15(7):1607-14 [8612584] Mol Cell Biol. 1996 Jul;16(7):3567-75 [8668173] Nature. 1996 May 23;381(6580):328-31 [8692272] J Virol. 1996 Sep;70(9):6347-57 [8709263] Science. 1996 Aug 16;273(5277):951-3 [8688078] Mol Cell Biol. 1996 Sep;16(9):4656-64 [8756622] Nature. 1995 Aug 17;376(6541):602-5 [7637811] Nature. 1995 Aug 17;376(6541):606-8 [7637812] Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8283-7 [7545299] Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9445-9 [7568151] Science. 1985 Jun 21;228(4706):1430-4 [2990028] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction and prevention of colonic inflammation in IL-2-deficient mice. AN - 78778873; 8992969 AB - Gene-targeted mice deficient for IL-2 (IL-2 -/- mice) are free of apparent disease when maintained under germfree conditions but develop colitis and autoimmunity in a conventional environment. Here we show that colitis can be reproducibly induced in IL-2 -/- mice, but not in IL-2 +/+ mice, by i.p. immunization with Ag in CFA; thus enabling the systematic study of the immunopathogenesis of the colitis. We found that TNP-KLH or TNP-OVA had the most significant effect in inducing colitis, and while TNP-KLH immunization leads to the early appearance of activated T cells in the colons of both IL-2 -/- and IL-2 +/+ mice, only lamina propria cells of IL-2 -/- mice produced high amounts of INF-gamma. Moreover, both infiltrating colon CD4+ (69%) and CD8+ (6%) T cells secrete large amounts of IFN-gamma; however, only the depletion of CD4+ T cells leads to abrogation of the inflammation. In further analysis, we showed that the high IFN-gamma production is IL-12 driven, since colonic tissues of IL-2 -/- mice but not IL-2 +/+ mice show the presence of heterodimeric IL-12 and co-administration of anti-IL-12 with TNP-KLH completely prevented colitis and significantly reduced IFN-gamma production. Finally, we demonstrate that IL-2 -/- mice are deficient in their ability to induce Th2 responses after TNP-KLH challenge and that such immunization also leads to autoimmune-like phenomena in other organs of IL-2 -/- mice. These findings suggest that in the absence of IL-2 systemic administration of Ag induces primarily Th1 cells driven by overexpression of heterodimeric IL-12. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Ehrhardt, R O AU - Lúdvíksson, B R AU - Gray, B AU - Neurath, M AU - Strober, W AD - Mucosal Immunity Section, Laboratory of Clinical Investigation, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/01/15/ PY - 1997 DA - 1997 Jan 15 SP - 566 EP - 573 VL - 158 IS - 2 SN - 0022-1767, 0022-1767 KW - Antigens, T-Independent KW - 0 KW - Haptens KW - Interleukin-2 KW - Trinitrobenzenes KW - trinitrophenyl keyhole limpet hemocyanin KW - trinitrophenyl-ovalbumin KW - Interleukin-12 KW - 187348-17-0 KW - Interleukin-4 KW - 207137-56-2 KW - Interferon-gamma KW - 82115-62-6 KW - Ovalbumin KW - 9006-59-1 KW - Hemocyanin KW - 9013-72-3 KW - Abridged Index Medicus KW - Index Medicus KW - Ovalbumin -- immunology KW - Animals KW - Ovalbumin -- toxicity KW - Interferon-gamma -- toxicity KW - Mutagenesis, Site-Directed -- genetics KW - Interferon-gamma -- biosynthesis KW - Interleukin-4 -- biosynthesis KW - Intestinal Mucosa -- metabolism KW - Mice KW - Hemocyanin -- toxicity KW - Immunization KW - T-Lymphocytes -- metabolism KW - Mice, Mutant Strains KW - Interleukin-12 -- biosynthesis KW - Mice, Inbred C57BL KW - Haptens -- immunology KW - Antigens, T-Independent -- immunology KW - Immunophenotyping KW - Colitis -- prevention & control KW - Trinitrobenzenes -- immunology KW - Colitis -- immunology KW - Colitis -- chemically induced KW - Trinitrobenzenes -- toxicity KW - Interleukin-2 -- genetics KW - Interleukin-2 -- deficiency UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78778873?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Induction+and+prevention+of+colonic+inflammation+in+IL-2-deficient+mice.&rft.au=Ehrhardt%2C+R+O%3BL%C3%BAdv%C3%ADksson%2C+B+R%3BGray%2C+B%3BNeurath%2C+M%3BStrober%2C+W&rft.aulast=Ehrhardt&rft.aufirst=R&rft.date=1997-01-15&rft.volume=158&rft.issue=2&rft.spage=566&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-11 N1 - Date created - 1997-02-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chick pineal clock regulates serotonin N-acetyltransferase mRNA rhythm in culture. AN - 78780268; 8990204 AB - Melatonin production in the chick pineal gland is high at night and low during the day. This rhythm reflects circadian changes in the activity of serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AA-NAT; EC 2.3.1.87), the penultimate enzyme in melatonin synthesis. In contrast to the external regulation of pineal rhythms in mammals by the suprachiasmatic nucleus, rhythmic changes in AA-NAT activity in cultured chick pineal cells are controlled by an oscillator located in the pineal cells themselves. Here we present evidence that the chick pineal clock generates a rhythm in the abundance of AA-NAT mRNA in cultured cells that parallels the rhythm in AA-NAT activity. In contrast, elevating cAMP by forskolin treatment markedly increases AA-NAT activity without producing strong changes in AA-NAT mRNA levels, and lowering cAMP by norepinephrine treatment decreases enzyme activity without markedly decreasing mRNA. These results suggest that clock-controlled changes in AA-NAT activity occur primarily through changes at the mRNA level, whereas cAMP-controlled changes occur primarily through changes at the protein level. Related studies indicate that the clock-dependent nocturnal increase in AA-NAT mRNA requires gene expression but not de novo protein synthesis, and that AA-NAT mRNA levels are suppressed at all times of the day by a rapidly turning over protein. Further analysis of the regulation of chick pineal AA-NAT mRNA is likely to enhance our understanding of the molecular basis of vertebrate circadian rhythms. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Bernard, M AU - Klein, D C AU - Zatz, M AD - Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-4480, USA. Y1 - 1997/01/07/ PY - 1997 DA - 1997 Jan 07 SP - 304 EP - 309 VL - 94 IS - 1 SN - 0027-8424, 0027-8424 KW - Protein Synthesis Inhibitors KW - 0 KW - RNA, Messenger KW - Colforsin KW - 1F7A44V6OU KW - Cycloheximide KW - 98600C0908 KW - Cyclic AMP KW - E0399OZS9N KW - Arylamine N-Acetyltransferase KW - EC 2.3.1.5 KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Animals, Newborn KW - Animals KW - Drug Interactions KW - Colforsin -- pharmacology KW - Chickens KW - Protein Synthesis Inhibitors -- pharmacology KW - Cells, Cultured KW - Norepinephrine -- metabolism KW - Cycloheximide -- pharmacology KW - Cyclic AMP -- metabolism KW - Light KW - Time Factors KW - Circadian Rhythm -- physiology KW - Pineal Gland -- cytology KW - Circadian Rhythm -- radiation effects KW - Biological Clocks -- physiology KW - Circadian Rhythm -- drug effects KW - Biological Clocks -- drug effects KW - Pineal Gland -- drug effects KW - Biological Clocks -- radiation effects KW - Pineal Gland -- physiology KW - Arylamine N-Acetyltransferase -- biosynthesis KW - RNA, Messenger -- biosynthesis KW - Pineal Gland -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78780268?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chick+pineal+clock+regulates+serotonin+N-acetyltransferase+mRNA+rhythm+in+culture.&rft.au=Bernard%2C+M%3BKlein%2C+D+C%3BZatz%2C+M&rft.aulast=Bernard&rft.aufirst=M&rft.date=1997-01-07&rft.volume=94&rft.issue=1&rft.spage=304&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-13 N1 - Date created - 1997-02-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Recent Prog Horm Res. 1989;45:279-348; discussion 348-52 [2682842] Brain Res. 1988 Jun 21;453(1-2):51-62 [2841014] J Comp Physiol A. 1990 Jul;167(2):187-92 [1976805] Trends Neurosci. 1990 Nov;13(11):457-64 [1701579] J Biol Rhythms. 1992 Winter;7(4):301-11 [1337482] Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1824-8 [8127888] Brain Res. 1995 Oct 23;696(1-2):37-48 [8574683] Endocrinology. 1996 Jul;137(7):3033-45 [8770929] J Neurochem. 1997 Jan;68(1):213-24 [8978728] Science. 1970 Sep 11;169(3950):1093-5 [4915470] Brain Res. 1974 May 10;71(1):17-33 [4595289] Science. 1978 Dec 15;202(4373):1198-20 [214852] Science. 1979 Feb 16;203(4381):656-8 [569904] J Neurochem. 1979 Jul;33(1):45-51 [222883] Nature. 1979 Nov 1;282(5734):94-6 [503196] Brain Res. 1983 Aug 8;272(2):311-7 [6616205] Life Sci. 1986 Nov 24;39(21):2025-32 [2878334] Brain Res. 1988 Jan 12;438(1-2):199-215 [3345427] Brain Res. 1988 May 31;450(1-2):137-43 [3401707] J Neurochem. 1990 Jun;54(6):1953-60 [2159978] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Insulin-like growth factor 1 inhibits apoptosis using the phosphatidylinositol 3'-kinase and mitogen-activated protein kinase pathways. AN - 78793291; 8995241 AB - The role of insulin-like growth factor 1 (IGF-1) in preventing apoptosis was examined in differentiated PC12 cells. Induction of differentiation was achieved using nerve growth factor, and apoptosis was provoked by serum withdrawal. After 4-6 h of serum deprivation, apoptosis was initiated, concomitant with a 30% decrease in cell number and a 75% decrease in MTT activity. IGF-1 was capable of preventing apoptosis at concentrations as low as 10(-9) M and as early as 4 h. The phosphatidylinositol 3' (PI3')-kinase inhibitors wortmannin (at concentrations of 10(-8) M) and LY294002 (10(-6) M) blocked the effect of IGF-1. The pp70 S6 kinase (pp70S6K) inhibitor rapamycin (10(-8) M) was, however, less effective in blocking IGF-1 action. Moreover, stable transfection of a dominant-negative p85 (subunit of PI3'-kinase) construct in PC12 cells enhanced apoptosis provoked by serum deprivation. Interestingly, in the cells overexpressing the dominant-negative p85 protein, IGF-1 was still capable of inhibiting apoptosis, suggesting the existence of a second pathway involved in the IGF-1 effect. Blocking the mitogen-activated protein kinase pathway with the specific mitogen-activated protein kinase/extracellular-response kinase kinase inhibitor PD098059 (10(-5) M) inhibited the IGF-1 effect. When wortmannin and PD098059 were given together, the effect was synergistic. The results presented here suggest that IGF-1 is capable of preventing apoptosis by activation of multiple signal transduction pathways. JF - The Journal of biological chemistry AU - Párrizas, M AU - Saltiel, A R AU - LeRoith, D AD - Diabetes Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/01/03/ PY - 1997 DA - 1997 Jan 03 SP - 154 EP - 161 VL - 272 IS - 1 SN - 0021-9258, 0021-9258 KW - 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one KW - 0 KW - Androstadienes KW - Chromones KW - Enzyme Inhibitors KW - Flavonoids KW - Morpholines KW - Polyenes KW - 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one KW - 31M2U1DVID KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Phosphotransferases (Alcohol Group Acceptor) KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Ribosomal Protein S6 Kinases KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Sirolimus KW - W36ZG6FT64 KW - wortmannin KW - XVA4O219QW KW - Index Medicus KW - Animals KW - Morpholines -- pharmacology KW - Androstadienes -- pharmacology KW - Polyenes -- pharmacology KW - Protein-Serine-Threonine Kinases -- antagonists & inhibitors KW - Rats KW - Chromones -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Flavonoids -- pharmacology KW - Drug Synergism KW - Signal Transduction KW - PC12 Cells KW - Phosphotransferases (Alcohol Group Acceptor) -- antagonists & inhibitors KW - Insulin-Like Growth Factor I -- physiology KW - Apoptosis KW - Phosphotransferases (Alcohol Group Acceptor) -- physiology KW - Calcium-Calmodulin-Dependent Protein Kinases -- antagonists & inhibitors KW - Calcium-Calmodulin-Dependent Protein Kinases -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78793291?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+inhibits+apoptosis+using+the+phosphatidylinositol+3%27-kinase+and+mitogen-activated+protein+kinase+pathways.&rft.au=P%C3%A1rrizas%2C+M%3BSaltiel%2C+A+R%3BLeRoith%2C+D&rft.aulast=P%C3%A1rrizas&rft.aufirst=M&rft.date=1997-01-03&rft.volume=272&rft.issue=1&rft.spage=154&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-18 N1 - Date created - 1997-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The catalytic domain of protein kinase C-delta in reciprocal delta and epsilon chimeras mediates phorbol ester-induced macrophage differentiation of mouse promyelocytes. AN - 78789483; 8995230 AB - The overexpression of protein kinase C-delta (PKC-delta), but not PKC-epsilon, enables the mouse myeloid cell line 32D to differentiate into macrophages when treated with phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA). To determine the domain of PKC-delta that is responsible for this isotype-specific function, cDNAs that encode reciprocal chimeras of PKC-delta and -epsilon (PKC-delta epsilon and PKC-epsilon delta) were constructed by exchanging regulatory and kinase domains using polymerase chain reaction technology. Both chimeras were stably expressed in 32D cells using the pLTR expression vector and displayed protein kinase activity upon TPA treatment. TPA treatment of L epsilon delta, cells that overexpressed the PKC-epsilon delta chimera, induced a dramatically increased cell volume, surface adherence, surface expression of Mac-1 and Mac-3, lysozyme production, and phagocytosis. These are the characteristics of the macrophage phenotype found in TPA-treated 32D cells that overexpressed PKC-delta. In contrast, little effect was seen in L delta epsilon, 32D cells that overexpressed PKC-delta epsilon, with or without TPA treatment. A PKC inhibitor directed toward the catalytic domain of PKC, GF109203X, and a selective inhibitor of PKC-delta, Rottlerin, blocked the TPA-induced differentiation of PKC-epsilon delta-overexpressing 32D cells. These results demonstrate that the catalytic domain of PKC-delta contains the primary determinants for its activity in phorbol ester-induced macrophage differentiation. JF - The Journal of biological chemistry AU - Wang, Q J AU - Acs, P AU - Goodnight, J AU - Giese, T AU - Blumberg, P M AU - Mischak, H AU - Mushinski, J F AD - Laboratory of Genetics, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1997/01/03/ PY - 1997 DA - 1997 Jan 03 SP - 76 EP - 82 VL - 272 IS - 1 SN - 0021-9258, 0021-9258 KW - Antigens, Differentiation KW - 0 KW - Isoenzymes KW - Macrophage-1 Antigen KW - Recombinant Fusion Proteins KW - monocyte-macrophage differentiation antigen KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - Prkcd protein, mouse KW - EC 2.7.1.- KW - Prkce protein, mouse KW - Protein Kinase C KW - EC 2.7.11.13 KW - Protein Kinase C-delta KW - Protein Kinase C-epsilon KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Antigens, Differentiation -- metabolism KW - Phorbol 12,13-Dibutyrate -- metabolism KW - Macrophage Activation KW - Mice KW - Macrophage-1 Antigen -- metabolism KW - Hematopoiesis -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Differentiation -- drug effects KW - Phagocytosis KW - Cell Line KW - Cell Adhesion KW - Macrophages -- cytology KW - Isoenzymes -- chemistry KW - Protein Kinase C -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78789483?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=The+catalytic+domain+of+protein+kinase+C-delta+in+reciprocal+delta+and+epsilon+chimeras+mediates+phorbol+ester-induced+macrophage+differentiation+of+mouse+promyelocytes.&rft.au=Wang%2C+Q+J%3BAcs%2C+P%3BGoodnight%2C+J%3BGiese%2C+T%3BBlumberg%2C+P+M%3BMischak%2C+H%3BMushinski%2C+J+F&rft.aulast=Wang&rft.aufirst=Q&rft.date=1997-01-03&rft.volume=272&rft.issue=1&rft.spage=76&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-18 N1 - Date created - 1997-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Conversation and Sentence-Hood AN - 85661504; 9812386 AB - What Y. R. Chao in his Grammar of Spoken Chinese (1970) classified as minor sentences in Chinese are used to illustrate that the direction of syntactic analysis, from word to sentence, although possibly appropriate for European languages, is inappropriate for Chinese. These sentences, composed of adverbial phrases, adjectival phrases, & particles that can act as a subject or predicate in Indo-European languages, may often serve (1) a backward function, responding to the situation or intrapersonal needs; (2) a forward, or initiating, function; & (3) a downward function, affecting the next move. Chinese is maintained to be predominately conversational, & its sentences fossilized dialogues that evolved to accompany Chinese sociocultural development. Particles are singled out as maintaining coherence. 1 Table, 20 References. Adapted from the source document JF - Text AU - Shen, Jiaxuan AU - Gu, Yueguo AD - Instit Linguistics Chinese Academy Social Sciences, 5 Jianguomen Nei Da Jie 5 Hao Beijing People's Republic China Y1 - 1997///0, PY - 1997 DA - 0, 1997 SP - 477 EP - 489 VL - 17 IS - 4 SN - 0165-4888, 0165-4888 KW - Grice, H. Paul (29720) KW - Discourse Analysis (19200) KW - Chinese (12100) KW - Syntax (86800) KW - Sentences (77450) KW - article KW - 4610: discourse analysis/text linguistics; discourse analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85661504?accountid=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=Text&rft.atitle=Conversation+and+Sentence-Hood&rft.au=Shen%2C+Jiaxuan%3BGu%2C+Yueguo&rft.aulast=Shen&rft.aufirst=Jiaxuan&rft.date=1997-01-01&rft.volume=17&rft.issue=4&rft.spage=477&rft.isbn=&rft.btitle=&rft.title=Text&rft.issn=01654888&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 - TXTHDF N1 - SubjectsTermNotLitGenreText - Chinese (12100); Sentences (77450); Syntax (86800); Grice, H. Paul (29720); Discourse Analysis (19200) ER - TY - JOUR T1 - Stochastic resonance in non-dynamical systems without response thresholds. AN - 85228765; pmid-9002515 AB - The addition of noise to a system can sometimes improve its ability to transfer information reliably. This phenomenon--known as stochastic resonance--was originally proposed to account for periodicity in the Earth's ice ages, but has now been shown to occur in many systems in physics and biology. Recent experimental and theoretical work has shown that the simplest system exhibiting 'stochastic resonance' consists of nothing more than signal and noise with a threshold-triggered device (when the signal plus noise exceeds the threshold, the system responds momentarily, then relaxes to equilibrium to await the next triggering event). Here we introduce a class of non-dynamical and threshold-free systems that also exhibit stochastic resonance. We present and analyse a general mathematical model for such systems, in which a sequence of pulses is generated randomly with a probability (per unit time) that depends exponentially on an input. When this input is a sine-wave masked by additive noise, we observe an increase in the output signal-to-noise ratio as the level of noise increases. This result shows that stochastic resonance can occur in a broad class of thermally driven physico-chemical systems, such as semiconductor p-n junctions, mesoscopic electronic devices and voltage-dependent ion channels, in which reaction rates are controlled by activation barriers. JF - Nature AU - Bezrukov, S M AU - Vodyanoy, I AD - Division of Computer Research and Technology, National Institutes of Health, Bethesda, Maryland 29892-0580, USA. PY - 1997 SP - 319 EP - 321 VL - 385 IS - 6614 SN - 0028-0836, 0028-0836 KW - Support, U.S. Gov't, Non-P.H.S. KW - Stochastic Processes KW - Systems Theory KW - Models, Theoretical UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85228765?accountid=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=Stochastic+resonance+in+non-dynamical+systems+without+response+thresholds.&rft.au=Bezrukov%2C+S+M%3BVodyanoy%2C+I&rft.aulast=Bezrukov&rft.aufirst=S&rft.date=1997-01-01&rft.volume=385&rft.issue=6614&rft.spage=319&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 - Human prostate carcinogenesis. AN - 79606184; 9622052 AB - Prostate cancer is a major medical problem that is expected to affect over 300,000 American men and cause over 40,000 deaths in 1997. Despite its widespread prevalence and because of the difficulties in clinical diagnosis and treatment of the disease, the etiological mechanism underlying prostate carcinogenesis remains poorly understood. Elucidation of the mechanism of prostate tumorigenesis has been slowed by a lack of tumor tissues and the limited number of human cell lines available for study. In vitro human cell models to study the molecular biology of prostate cancer progression are urgently needed. Normal human prostate cells require immortalization to provide a practical system for transformation studies. Neoplastic transformation of human prostate epithelial cells in culture has been achieved recently in a stepwise fashion--immortalization of primary cells in culture and conversion of the immortalized cells to a tumorigenic state. Reviewed here are the steps involved in the neoplastic transformation of human prostate cells. To provide an insight into the molecular and genetic mechanisms involved in the conversion of normal cells to a neoplastic state of growth, the authors have attempted to put into perspective the history of human prostate epithelial cell transformation by a combination of carcinogenic agents, and to discuss the current state-of-the-art in transformation of human prostate epithelial cells in culture. JF - Critical reviews in oncogenesis AU - Rhim, J S AU - Kung, H F AD - Laboratory of Biochemical Physiology, National Cancer Institute, Frederick, Maryland 21702, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 305 EP - 328 VL - 8 IS - 4 SN - 0893-9675, 0893-9675 KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured KW - Humans KW - Cell Line, Transformed KW - United States -- epidemiology KW - Male KW - Prostatic Neoplasms -- etiology KW - Prostatic Neoplasms -- pathology KW - Prostatic Neoplasms -- epidemiology KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79606184?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Critical+reviews+in+oncogenesis&rft.atitle=Human+prostate+carcinogenesis.&rft.au=Rhim%2C+J+S%3BKung%2C+H+F&rft.aulast=Rhim&rft.aufirst=J&rft.date=1997-01-01&rft.volume=8&rft.issue=4&rft.spage=305&rft.isbn=&rft.btitle=&rft.title=Critical+reviews+in+oncogenesis&rft.issn=08939675&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 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 - DNA topoisomerase I inhibitors. AN - 79601897; 9551210 JF - Cancer chemotherapy and biological response modifiers AU - Takimoto, C H AU - Kieffer, L V AU - Arbuck, S G AD - Navy Medical Oncology Branch, National Cancer Institute, Naval Hospital Bethesda, MD 20889-5105, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 80 EP - 113 VL - 17 SN - 0921-4410, 0921-4410 KW - Antineoplastic Agents KW - 0 KW - Antiviral Agents KW - Enzyme Inhibitors KW - Topoisomerase I Inhibitors KW - irinotecan KW - 0H43101T0J KW - 9-aminocamptothecin KW - 5MB77ICE2Q KW - Topotecan KW - 7M7YKX2N15 KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Animals KW - Neoplasms -- drug therapy KW - Camptothecin -- pharmacology KW - DNA Damage KW - Humans KW - Camptothecin -- adverse effects KW - Camptothecin -- therapeutic use KW - Topotecan -- therapeutic use KW - DNA Topoisomerases, Type I -- genetics KW - Camptothecin -- pharmacokinetics KW - Topotecan -- pharmacokinetics KW - Topotecan -- pharmacology KW - Antiviral Agents -- pharmacology KW - Camptothecin -- analogs & derivatives KW - Enzyme Inhibitors -- therapeutic use KW - Enzyme Inhibitors -- pharmacology KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79601897?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+biological+response+modifiers&rft.atitle=DNA+topoisomerase+I+inhibitors.&rft.au=Takimoto%2C+C+H%3BKieffer%2C+L+V%3BArbuck%2C+S+G&rft.aulast=Takimoto&rft.aufirst=C&rft.date=1997-01-01&rft.volume=17&rft.issue=&rft.spage=80&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+biological+response+modifiers&rft.issn=09214410&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-20 N1 - Date created - 1998-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Taxanes. AN - 79601857; 9551209 JF - Cancer chemotherapy and biological response modifiers AU - Sackett, D AU - Fojo, T AD - Department of Health and Human Services, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 59 EP - 79 VL - 17 SN - 0921-4410, 0921-4410 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Animals KW - Drug Administration Schedule KW - Humans KW - Apoptosis -- drug effects KW - Drug Resistance, Neoplasm KW - Paclitaxel -- toxicity KW - Antineoplastic Agents, Phytogenic -- pharmacology KW - Paclitaxel -- therapeutic use KW - Paclitaxel -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79601857?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+biological+response+modifiers&rft.atitle=Taxanes.&rft.au=Sackett%2C+D%3BFojo%2C+T&rft.aulast=Sackett&rft.aufirst=D&rft.date=1997-01-01&rft.volume=17&rft.issue=&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+biological+response+modifiers&rft.issn=09214410&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-20 N1 - Date created - 1998-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phenylacetate and phenylbutyrate as novel, nontoxic differentiation inducers. AN - 79600283; 9547596 AB - Phenylacetate and analogs represent a new class of pleiotropic growth regulators that alter tumor cell biology by affecting gene expression at both the transcriptional and post transcriptional levels. Based on these findings, NaPA and NaPB entered clinical trials at the National Cancer Institute. Ongoing phase I studies with NaPA, involving adults with prostate and brain cancer, have confirmed that therapeutic levels can be achieved with no significant toxicities, and provide preliminary evidence for benefit to patients with advanced disease (Thibault et al., submitted). JF - Advances in experimental medicine and biology AU - Samid, D AU - Hudgins, W R AU - Shack, S AU - Liu, L AU - Prasanna, P AU - Myers, C E AD - Clinical Pharmacology Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 501 EP - 505 VL - 400A SN - 0065-2598, 0065-2598 KW - Antimetabolites, Antineoplastic KW - 0 KW - Phenylacetates KW - Phenylbutyrates KW - phenylacetic acid KW - ER5I1W795A KW - Index Medicus KW - Neoplasms -- drug therapy KW - Transcription, Genetic -- drug effects KW - Brain Neoplasms -- drug therapy KW - Tumor Cells, Cultured KW - Humans KW - Clinical Trials, Phase I as Topic KW - Adult KW - Prostatic Neoplasms -- drug therapy KW - Male KW - Phenylbutyrates -- therapeutic use KW - Phenylacetates -- pharmacology KW - Phenylbutyrates -- pharmacology KW - Cell Differentiation -- drug effects KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Antimetabolites, Antineoplastic -- therapeutic use KW - Phenylacetates -- therapeutic use KW - Antimetabolites, Antineoplastic -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79600283?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+experimental+medicine+and+biology&rft.atitle=Phenylacetate+and+phenylbutyrate+as+novel%2C+nontoxic+differentiation+inducers.&rft.au=Samid%2C+D%3BHudgins%2C+W+R%3BShack%2C+S%3BLiu%2C+L%3BPrasanna%2C+P%3BMyers%2C+C+E&rft.aulast=Samid&rft.aufirst=D&rft.date=1997-01-01&rft.volume=400A&rft.issue=&rft.spage=501&rft.isbn=&rft.btitle=&rft.title=Advances+in+experimental+medicine+and+biology&rft.issn=00652598&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-28 N1 - Date created - 1998-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cloning and sequencing of prostaglandin H synthetase from rat tracheal epithelial cells: structural evidence that a TPA regulated mRNA codes for the rat ortholog of murine PHS-1. AN - 79595181; 9547538 JF - Advances in experimental medicine and biology AU - Kitzler, J AU - Hardman, R AU - Hill, E AU - Reddy, N AU - Philpot, R AU - Eling, T E AD - Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 65 EP - 70 VL - 400A SN - 0065-2598, 0065-2598 KW - RNA, Messenger KW - 0 KW - Prostaglandin-Endoperoxide Synthases KW - EC 1.14.99.1 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Amino Acid Sequence KW - Mice KW - RNA, Messenger -- biosynthesis KW - Cloning, Molecular KW - Rats KW - Base Sequence KW - Sequence Alignment KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Consensus Sequence KW - Sequence Homology, Amino Acid KW - Cell Line KW - Gene Library KW - Transcription, Genetic -- drug effects KW - Epithelial Cells -- enzymology KW - Gene Expression Regulation, Enzymologic -- drug effects KW - Prostaglandin-Endoperoxide Synthases -- chemistry KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Trachea -- enzymology KW - Prostaglandin-Endoperoxide Synthases -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79595181?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+experimental+medicine+and+biology&rft.atitle=Cloning+and+sequencing+of+prostaglandin+H+synthetase+from+rat+tracheal+epithelial+cells%3A+structural+evidence+that+a+TPA+regulated+mRNA+codes+for+the+rat+ortholog+of+murine+PHS-1.&rft.au=Kitzler%2C+J%3BHardman%2C+R%3BHill%2C+E%3BReddy%2C+N%3BPhilpot%2C+R%3BEling%2C+T+E&rft.aulast=Kitzler&rft.aufirst=J&rft.date=1997-01-01&rft.volume=400A&rft.issue=&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Advances+in+experimental+medicine+and+biology&rft.issn=00652598&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-28 N1 - Date created - 1998-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evolution of tobacco control studies at the National Cancer Institute. AN - 79594943; 9583644 JF - Tobacco control AU - Klausner, R AD - klausner@helix.nih.gov Y1 - 1997 PY - 1997 DA - 1997 SP - S1 EP - S2 VL - 6 Suppl 2 SN - 0964-4563, 0964-4563 KW - Index Medicus KW - United States KW - Neoplasms KW - Humans KW - Research KW - Health Promotion KW - Plants, Toxic KW - Tobacco KW - Academies and Institutes KW - Tobacco Use Disorder -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79594943?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Tobacco+control&rft.atitle=Evolution+of+tobacco+control+studies+at+the+National+Cancer+Institute.&rft.au=Klausner%2C+R&rft.aulast=Klausner&rft.aufirst=R&rft.date=1997-01-01&rft.volume=6+Suppl+2&rft.issue=&rft.spage=S1&rft.isbn=&rft.btitle=&rft.title=Tobacco+control&rft.issn=09644563&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-30 N1 - Date created - 1998-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The American Stop Smoking Intervention Study for cancer prevention: an overview. AN - 79592215; 9583646 AB - The American Stop Smoking Intervention Study (ASSIST) is a programme to implement proven interventions in 17 states across the United States. ASSIST applies all that we have learned in 10 years of research on tobacco use prevention and control. The goal of this seven-year project is to reduce the prevalence of smoking and cigarette consumption in the ASSIST states. The scientific basis for ASSIST is described, followed by a general description of the project and its current status in the 17 targeted states. JF - Tobacco control AU - Manley, M AU - Lynn, W AU - Payne Epps, R AU - Grande, D AU - Glynn, T AU - Shopland, D AD - Cancer Control Science Program, Division of Cancer Prevention and Control, National Cancer Institute, Bethesda, Maryland, USA. mm112h@nih.gov Y1 - 1997 PY - 1997 DA - 1997 SP - S5 EP - 11 VL - 6 Suppl 2 SN - 0964-4563, 0964-4563 KW - Tobacco Smoke Pollution KW - 0 KW - Index Medicus KW - United States KW - Tobacco Smoke Pollution -- prevention & control KW - Humans KW - Advertising as Topic -- economics KW - Social Support KW - Employment KW - Male KW - Female KW - Lung Neoplasms -- prevention & control KW - Lung Neoplasms -- etiology KW - Tobacco Use Disorder -- prevention & control KW - Tobacco Use Disorder -- complications KW - Health Promotion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79592215?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Tobacco+control&rft.atitle=The+American+Stop+Smoking+Intervention+Study+for+cancer+prevention%3A+an+overview.&rft.au=Manley%2C+M%3BLynn%2C+W%3BPayne+Epps%2C+R%3BGrande%2C+D%3BGlynn%2C+T%3BShopland%2C+D&rft.aulast=Manley&rft.aufirst=M&rft.date=1997-01-01&rft.volume=6+Suppl+2&rft.issue=&rft.spage=S5&rft.isbn=&rft.btitle=&rft.title=Tobacco+control&rft.issn=09644563&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 - Impact of the American Stop Smoking Intervention Study on cigarette consumption. AN - 79591237; 9583647 AB - To obtain an early estimate of the effectiveness of the American Stop Smoking Intervention Study (ASSIST). Seventeen American states funded through ASSIST are compared with 32 others regarding per capita cigarette consumption from 1989 to 1995. California, which already had an extensive tobacco control programme, was omitted. ASSIST states were selected competitively (not randomly) based on their proposals' merit, state smoking prevalence, and geographical distribution. Comprehensive tobacco control programmes, emphasising policy interventions, were implemented in the ASSIST states beginning in 1993. Trends in aggregated per capita cigarette consumption and inflation-adjusted average price/pack of cigarettes in the intervention states were compared. Percentage change in per capita consumption is also compared with percentage change in inflation-adjusted cigarette price by state in each group from 1992 to 1994. Per capita consumption and inflation-adjusted cigarette price were nearly identical in both groups of states before 1993, when full funding for the ASSIST interventions began. However, by 1996 smokers in the intervention states were consuming about 7% less cigarettes per capita (P<0.05, beginning in 1994), and in 1994 the average price was over $0.12/pack higher in the intervention states. All but three states (all intervention) showed decreases in cigarette price. Nonetheless, 76% of the intervention and 55% of the comparison states showed some decrease in consumption despite decreases in price. The relationship between changes in price and consumption was considerably diminished in the intervention group. These interim results suggest that the ASSIST programme is associated with a substantial difference in tobacco consumption in a third of the United States, and that increased price from taxation may not be the only programme influence. JF - Tobacco control AU - Manley, M W AU - Pierce, J P AU - Gilpin, E A AU - Rosbrook, B AU - Berry, C AU - Wun, L M AD - Division of Cancer Prevention and Control, National Cancer Institute, Bethesda, Maryland, USA. mm112h@nih.gov Y1 - 1997 PY - 1997 DA - 1997 SP - S12 EP - S16 VL - 6 Suppl 2 SN - 0964-4563, 0964-4563 KW - Index Medicus KW - United States KW - Humans KW - Tobacco Use Disorder -- prevention & control KW - Smoking -- economics KW - Health Promotion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79591237?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Tobacco+control&rft.atitle=Impact+of+the+American+Stop+Smoking+Intervention+Study+on+cigarette+consumption.&rft.au=Manley%2C+M+W%3BPierce%2C+J+P%3BGilpin%2C+E+A%3BRosbrook%2C+B%3BBerry%2C+C%3BWun%2C+L+M&rft.aulast=Manley&rft.aufirst=M&rft.date=1997-01-01&rft.volume=6+Suppl+2&rft.issue=&rft.spage=S12&rft.isbn=&rft.btitle=&rft.title=Tobacco+control&rft.issn=09644563&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 - Pathogenesis and prevention of doxorubicin cardiomyopathy. AN - 79562566; 9505340 AB - A review is presented of the various types of cardiotoxicity associated with the clinical use of doxorubicin, a highly effective antineoplastic agent of the anthracycline family. Acute toxicity is related to rapid intravenous administration of the drug and is manifested by vasodilatation, hypotension and cardiac arrhythmias. Subacute toxicity is very uncommon. It develops early in the course of therapy and is characterized by myocarditis and pericarditis. Chronic toxicity is the most common form of doxorubicin-induced cardiac toxicity. It is manifested by chronic dilated cardiomyopathy, which develops late in the course of therapy or shortly after its termination. Morphologic changes are characteristic and consist of myofibrillar loss and cytoplasmic vacuolization (which is due to dilatation of the sarcoplasmic reticulum) of the myocytes. The damaging effects of reactive oxygen species, generated by the interaction of doxorubicin with iron, play a critically important role in the pathogenesis of the chronic cardiotoxicity. Other factors related to this toxicity include inhibition of DNA topoisomerase II, stimulation of certain immune responses and a diversity of other biochemical effects on various cellular organelles. Doxorubicin induces apoptosis in a variety of cell types, but not in cardiac myocytes. The chronic cardiotoxicity of doxorubicin is significantly attenuated by chelation of iron by ICRF-187 (dexrazoxane). A greatly delayed type of doxorubicin cardiotoxicity has been recently found to occur in survivors of childhood cancers who were treated with doxorubicin without any immediate adverse effects, but develop chronic cardiomyopathy at periods of time ranging up to 15 years later. The pathogenesis of this type of toxicity remains to be determined. JF - Tsitologiia AU - Ferrans, V J AU - Clark, J R AU - Zhang, J AU - Yu, Z X AU - Herman, E H AD - Pathology Section, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 928 EP - 937 VL - 39 IS - 10 SN - 0041-3771, 0041-3771 KW - Antibiotics, Antineoplastic KW - 0 KW - Cardiovascular Agents KW - Doxorubicin KW - 80168379AG KW - Index Medicus KW - Humans KW - Doxorubicin -- adverse effects KW - Cardiovascular Agents -- therapeutic use KW - Cardiomyopathies -- classification KW - Cardiomyopathies -- prevention & control KW - Cardiomyopathies -- chemically induced KW - Antibiotics, Antineoplastic -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79562566?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Tsitologiia&rft.atitle=Pathogenesis+and+prevention+of+doxorubicin+cardiomyopathy.&rft.au=Ferrans%2C+V+J%3BClark%2C+J+R%3BZhang%2C+J%3BYu%2C+Z+X%3BHerman%2C+E+H&rft.aulast=Ferrans&rft.aufirst=V&rft.date=1997-01-01&rft.volume=39&rft.issue=10&rft.spage=928&rft.isbn=&rft.btitle=&rft.title=Tsitologiia&rft.issn=00413771&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-06 N1 - Date created - 1998-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Age at onset of alcohol use and its association with DSM-IV alcohol abuse and dependence: results from the National Longitudinal Alcohol Epidemiologic Survey. AN - 79561750; 9494942 AB - Data from 27,616 current and former drinkers interviewed in the 1992 National Longitudinal Alcohol Epidemiologic Survey were used to examine the relationship between age at first use of alcohol and the prevalence of lifetime alcohol abuse and alcohol dependence, among all U.S. adults 18 years of age and over and within subgroups defined by sex and race. The rates of lifetime dependence declined from more than 40% among individuals who started drinking at ages 14 or younger to roughly 10% among those who started drinking at ages 20 and older. The rates of lifetime abuse declined from just over 11% among those who initiated use of alcohol at ages 16 or younger to approximately 4% among those whose onset of use was at ages 20 or older. After using multivariate logistic regression models to adjust for potential confounders, the odds of dependence decreased by 14% with each increasing year of age at onset of use, and the odds of abuse decreased by 8%. These findings are discussed with respect to their implications for prevention policies and the need to integrate epidemiological and intervention research. JF - Journal of substance abuse AU - Grant, B F AU - Dawson, D A AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20852-7003, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 103 EP - 110 VL - 9 SN - 0899-3289, 0899-3289 KW - Index Medicus KW - Regression Analysis KW - Age of Onset KW - Humans KW - Disease Progression KW - Aged KW - Longitudinal Studies KW - Multivariate Analysis KW - Cross-Sectional Studies KW - Risk Factors KW - Adult KW - Health Surveys KW - Sampling Studies KW - Middle Aged KW - Adolescent KW - United States -- epidemiology KW - Female KW - Male KW - Prevalence KW - Alcohol Drinking -- epidemiology KW - Alcohol-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79561750?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+substance+abuse&rft.atitle=Age+at+onset+of+alcohol+use+and+its+association+with+DSM-IV+alcohol+abuse+and+dependence%3A+results+from+the+National+Longitudinal+Alcohol+Epidemiologic+Survey.&rft.au=Grant%2C+B+F%3BDawson%2C+D+A&rft.aulast=Grant&rft.aufirst=B&rft.date=1997-01-01&rft.volume=9&rft.issue=&rft.spage=103&rft.isbn=&rft.btitle=&rft.title=Journal+of+substance+abuse&rft.issn=08993289&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Convergent validity of DSM-III-R and DSM-IV alcohol dependence: results from the National Longitudinal Alcohol Epidemiologic Survey. AN - 79561654; 9494941 AB - The purpose of this study was to separately examine the associations between ethanol intake and alcohol dependence, as defined in the DSM-III-R and DSM-IV, in conjunction with an identical set of external correlates, with a view toward assessing the convergent validity of the two diagnostic definitions of dependence. Although the sociodemographic, alcohol, drug and comorbid profiles of respondents classified as DSM-III-R and DSM-IV dependent were similar, the results of the linear logistic regression analyses differed for each of the diagnostic definitions. The risk of DSM-III-R dependence was reduced among blacks and increased among early onset drinkers. Given equivalent levels of ethanol intake, the risk of DSM-III-R dependence was greater for these respondents who had experienced a recent death of close relative compared to those who had not. In contrast, the risk of DSM-IV dependence was greatest among respondents with a current alcoholic spouse or partner relative to those without an alcoholic spouse or partner. Major differences in the content and structure of the two definitions of dependence were useful in predicting the observed discrepancies between the risk gradients associated with the DSM-III-R and DSM-IV classifications. Implications of these findings were discussed in terms of differential coverage of the DSM-III-R and DSM-IV diagnostic categories and the impact of the absence of complete convergent validity on epidemiologic research. JF - Journal of substance abuse AU - Grant, B F AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892-7003, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 89 EP - 102 VL - 9 SN - 0899-3289, 0899-3289 KW - Index Medicus KW - Regression Analysis KW - Odds Ratio KW - Reproducibility of Results KW - Humans KW - Aged KW - Longitudinal Studies KW - Comorbidity KW - Multivariate Analysis KW - Depressive Disorder -- epidemiology KW - Risk Factors KW - Adult KW - Health Surveys KW - Sampling Studies KW - Confidence Intervals KW - Middle Aged KW - Adolescent KW - United States -- epidemiology KW - Male KW - Substance-Related Disorders -- epidemiology KW - Prevalence KW - Alcohol-Related Disorders -- diagnosis KW - Manuals as Topic -- standards KW - Alcohol Drinking -- epidemiology KW - Alcohol-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79561654?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+substance+abuse&rft.atitle=Convergent+validity+of+DSM-III-R+and+DSM-IV+alcohol+dependence%3A+results+from+the+National+Longitudinal+Alcohol+Epidemiologic+Survey.&rft.au=Grant%2C+B+F&rft.aulast=Grant&rft.aufirst=B&rft.date=1997-01-01&rft.volume=9&rft.issue=&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=Journal+of+substance+abuse&rft.issn=08993289&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Is quantitative urinalysis more sensitive? AN - 79561283; 9467804 JF - NIDA research monograph AU - Li, S H AU - Chiang, N AU - Tai, B AU - Marschke, C K AU - Hawks, R L AD - Clinical Trials Branch, National Institute on Drug Abuse, NIH, Rockville, MD 20857, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 265 EP - 286 VL - 175 SN - 1046-9516, 1046-9516 KW - Narcotics KW - 0 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Computer Simulation KW - Humans KW - Substance-Related Disorders -- urine KW - Models, Biological KW - Substance Abuse Detection -- standards KW - Cocaine -- urine KW - Urinalysis -- standards KW - Narcotics -- urine KW - Narcotics -- pharmacokinetics KW - Cocaine -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79561283?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NIDA+research+monograph&rft.atitle=Is+quantitative+urinalysis+more+sensitive%3F&rft.au=Li%2C+S+H%3BChiang%2C+N%3BTai%2C+B%3BMarschke%2C+C+K%3BHawks%2C+R+L&rft.aulast=Li&rft.aufirst=S&rft.date=1997-01-01&rft.volume=175&rft.issue=&rft.spage=265&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-17 N1 - Date created - 1998-03-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effect of positive and negative health behavior during gestation on pregnancy outcome. AN - 79560705; 9494939 AB - This study examined the effects of substance use (alcohol, tobacco and/or drugs (cocaine and/or marijuana)) and healthy maternal behavior (prenatal care, prenatal class, vitamins, regular exercise) during gestation on pregnancy outcome. Live births from the nationally representative 1988 National Maternal and Infant Health Survey were analyzed. Pregnancy outcomes (infant birth weight, weeks gestation, one and five minute Apgar scores, whether or not the infant was transferred to another hospital after delivery and whether or not the infant was rehospitalized) were studied in multiple linear regression and logistic regression models. The relationship of the interaction of substance use and healthy behaviors and outcome was studied in all models. It was found that women engaging in substance use while pregnant were less likely to engage in healthy behavior. However, in general, engaging in healthy behaviors had the largest positive effects on outcome for those women who engaged in multiple substance use while pregnant. Significant interactions between healthy and unhealthy behavior were found for birth weight, weeks gestation and five minute Apgar scores, indicating that engaging in positive health behavior may help moderate some of the deleterious consequences of substance use during pregnancy. JF - Journal of substance abuse AU - Faden, V B AU - Hanna, E AU - Graubard, B I AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892-7003, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 63 EP - 76 VL - 9 SN - 0899-3289, 0899-3289 KW - Index Medicus KW - Birth Weight KW - Odds Ratio KW - Humans KW - Marijuana Smoking -- epidemiology KW - Gestational Age KW - Linear Models KW - Cocaine-Related Disorders -- epidemiology KW - Alcohol Drinking -- epidemiology KW - Smoking -- epidemiology KW - Pregnancy KW - Prenatal Care -- utilization KW - Apgar Score KW - Logistic Models KW - Risk Factors KW - Adult KW - Health Surveys KW - Databases, Factual KW - Confidence Intervals KW - United States -- epidemiology KW - Female KW - Maternal Behavior KW - Pregnancy Outcome -- epidemiology KW - Health Behavior KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79560705?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+substance+abuse&rft.atitle=The+effect+of+positive+and+negative+health+behavior+during+gestation+on+pregnancy+outcome.&rft.au=Faden%2C+V+B%3BHanna%2C+E%3BGraubard%2C+B+I&rft.aulast=Faden&rft.aufirst=V&rft.date=1997-01-01&rft.volume=9&rft.issue=&rft.spage=63&rft.isbn=&rft.btitle=&rft.title=Journal+of+substance+abuse&rft.issn=08993289&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Issues in the treatment of women with bipolar illness. AN - 79505621; 9427871 AB - Gender differences in bipolar illness have been relatively neglected, but the course of the illness does appear to differ between men and women. Compared with bipolar men, bipolar women are clearly more likely to develop the rapid cycling form of the illness and may also suffer from more episodes of depression. Therefore, the literature concerning the treatment of rapid cycling bipolar disorder and of bipolar depression is reviewed. In addition, effects of bipolar illness on the female reproductive cycle are discussed. Since bipolar women are at high risk to develop postpartum episodes, the use of mood stabilizers in pregnancy is discussed. JF - The Journal of clinical psychiatry AU - Leibenluft, E AD - Clinical Psychobiology Branch, National Institute of Mental Health, Bethesda, Md., USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 5 EP - 11 VL - 58 Suppl 15 SN - 0160-6689, 0160-6689 KW - Antidepressive Agents, Second-Generation KW - 0 KW - Antidepressive Agents, Tricyclic KW - Monoamine Oxidase Inhibitors KW - Serotonin Uptake Inhibitors KW - Bupropion KW - 01ZG3TPX31 KW - Valproic Acid KW - 614OI1Z5WI KW - Index Medicus KW - Depression, Postpartum -- psychology KW - Sex Factors KW - Antidepressive Agents, Second-Generation -- therapeutic use KW - Bupropion -- therapeutic use KW - Serotonin Uptake Inhibitors -- therapeutic use KW - Humans KW - Antidepressive Agents, Tricyclic -- therapeutic use KW - Antidepressive Agents, Tricyclic -- adverse effects KW - Serotonin Uptake Inhibitors -- adverse effects KW - Pregnancy KW - Monoamine Oxidase Inhibitors -- adverse effects KW - Depression, Postpartum -- epidemiology KW - Antidepressive Agents, Second-Generation -- adverse effects KW - Reproduction KW - Valproic Acid -- therapeutic use KW - Monoamine Oxidase Inhibitors -- therapeutic use KW - Female KW - Male KW - Prevalence KW - Depression, Postpartum -- drug therapy KW - Bipolar Disorder -- epidemiology KW - Bipolar Disorder -- drug therapy KW - Bipolar Disorder -- psychology KW - Bipolar Disorder -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79505621?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+psychiatry&rft.atitle=Issues+in+the+treatment+of+women+with+bipolar+illness.&rft.au=Leibenluft%2C+E&rft.aulast=Leibenluft&rft.aufirst=E&rft.date=1997-01-01&rft.volume=58+Suppl+15&rft.issue=&rft.spage=5&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+psychiatry&rft.issn=01606689&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-01-20 N1 - Date created - 1998-01-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Deficient DNA repair in chronic ulcerative colitis. AN - 79453781; 9398994 AB - Carcinoma of the colon is a serious complication of chronic ulcerative colitis (CUC), a disease of unknown etiology. Peripheral blood lymphocytes from nine patients with CUC showed deficient repair of radiation-induced DNA damage compared with a group of healthy controls. DNA repair was measured indirectly by quantifying chromatid breaks after irradiation of cells with X-rays or ultraviolet during G2 phase of the cell cycle. Such breaks represent unrepaired DNA strand breaks that may arise directly from the damaging agent or indirectly during repair processes. Two types of deficiency were revealed. One was an abnormally high frequency of chromatid breaks after G2-phase X-irradiation. These may reflect deficient strand-break repair. The second deficiency was manifest as a low frequency of breaks not increased by addition of the DNA repair inhibitor araC. This low frequency apparently results from negligible incision activity. Deficient DNA repair in CUC may thus be a requisite predisposing factor for genomic instability and the potential development of colon carcinoma. JF - Cancer detection and prevention AU - Sanford, K K AU - Price, F M AU - Brodeur, C AU - Makrauer, F L AU - Parshad, R AD - Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 540 EP - 545 VL - 21 IS - 6 SN - 0361-090X, 0361-090X KW - Index Medicus KW - Ultraviolet Rays KW - Chromatids -- physiology KW - Humans KW - Adult KW - Lymphocytes -- radiation effects KW - Aged KW - Middle Aged KW - Chronic Disease KW - Lymphocytes -- physiology KW - Radiation Effects KW - Male KW - Female KW - DNA Repair KW - Colitis, Ulcerative -- physiopathology KW - Colitis, Ulcerative -- genetics KW - Chromosome Breakage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79453781?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+detection+and+prevention&rft.atitle=Deficient+DNA+repair+in+chronic+ulcerative+colitis.&rft.au=Sanford%2C+K+K%3BPrice%2C+F+M%3BBrodeur%2C+C%3BMakrauer%2C+F+L%3BParshad%2C+R&rft.aulast=Sanford&rft.aufirst=K&rft.date=1997-01-01&rft.volume=21&rft.issue=6&rft.spage=540&rft.isbn=&rft.btitle=&rft.title=Cancer+detection+and+prevention&rft.issn=0361090X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-31 N1 - Date created - 1997-12-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Seizures and schizophrenia. AN - 79409666; 9365998 AB - Patients with epilepsy develop psychosis or schizophrenia at a rate exceeding that expected if the two disorders were independent. Similarly, patients with schizophrenia are more prone to seizures than the general population. This excess vulnerability may be conferred by the neuropathological substrate of schizophrenia itself or by the secondary effects of the illness, including exposure to psychotropic medications that lower the seizure threshold. Neuropathological investigations into the anatomic substrate of seizures in patients with psychosis or schizophrenia are consistent with the notion that there are neurodevelopmental abnormalities involving the mesial temporal lobe. Finally, clinical recommendations for the evaluation and pharmacological management of patients with schizophrenia who have one or more seizures are described. JF - Schizophrenia bulletin AU - Hyde, T M AU - Weinberger, D R AD - Clinical Brain Disorders Branch, NIMH Neuroscience Ctr., St. Elizabeths Hospital, Washington, DC 20032, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 611 EP - 622 VL - 23 IS - 4 SN - 0586-7614, 0586-7614 KW - Anticonvulsants KW - 0 KW - Antipsychotic Agents KW - Index Medicus KW - Epilepsy, Temporal Lobe -- physiopathology KW - Epilepsy, Complex Partial -- epidemiology KW - Humans KW - Electroencephalography KW - Epilepsy, Temporal Lobe -- epidemiology KW - Anticonvulsants -- therapeutic use KW - Epilepsy, Complex Partial -- physiopathology KW - Psychotic Disorders -- epidemiology KW - Comorbidity KW - Risk Factors KW - Incidence KW - Antipsychotic Agents -- adverse effects KW - Psychotic Disorders -- physiopathology KW - Temporal Lobe -- physiopathology KW - Seizures -- chemically induced KW - Seizures -- physiopathology KW - Seizures -- epidemiology KW - Schizophrenia -- drug therapy KW - Schizophrenia -- epidemiology KW - Schizophrenia -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79409666?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+bulletin&rft.atitle=Seizures+and+schizophrenia.&rft.au=Hyde%2C+T+M%3BWeinberger%2C+D+R&rft.aulast=Hyde&rft.aufirst=T&rft.date=1997-01-01&rft.volume=23&rft.issue=4&rft.spage=611&rft.isbn=&rft.btitle=&rft.title=Schizophrenia+bulletin&rft.issn=05867614&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-16 N1 - Date created - 1997-12-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of tardive dyskinesia. AN - 79408448; 9365997 AB - Although the new generation of atypical antipsychotic agents could some day eliminate concerns about tardive dyskinesia (TD), this disorder remains a significant clinical problem for both patients and physicians. Fortunately, many, if not most, cases of TD are mild. For patients with mild to moderate TD, therapeutic efforts are primarily directed at minimizing neuroleptic exposure or, when possible, changing to atypical agents. Most cases of TD do not seem to progress, suggesting that the risk of remaining on typical neuroleptics is probably small. Patients with moderate to severe forms of TD present greater challenges. These patients frequently require medication to suppress their dyskinesias. A variety of suppressive agents have been tried with limited success. No treatment strategy has emerged that is clearly superior or even successful in most patients. Increasing doses of typical neuroleptics may be useful for short-term suppression; however, the long-term efficacy and risk of this strategy have not been studied carefully. Data on atypical neuroleptics are scant. Clozapine's short-term suppressive effects seem, at best, weak, but patients may improve with long-term treatment. Medications with relatively few side effects that may have suppressive efficacy for some patients include calcium channel blockers, adrenergic antagonists, and vitamin E. Gamma-amino-butyric acid agonists agents and dopamine depleters are frequently useful, but have troubling side effects of their own. A variety of other medications have been employed, but are not well studied. For patients with tardive dystonia, anticholinergic agents or botulinum toxin has been particularly effective. Efforts to understand the neurobiology of TD may shed light on this persistent clinical conundrum. JF - Schizophrenia bulletin AU - Egan, M F AU - Apud, J AU - Wyatt, R J AD - Neuropsychiatry Branch, NIMH Neuroscience Ctr., St. Elizabeths Hospital, Washington, DC 20032, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 583 EP - 609 VL - 23 IS - 4 SN - 0586-7614, 0586-7614 KW - Antioxidants KW - 0 KW - Antipsychotic Agents KW - Calcium Channel Blockers KW - Cholinergic Antagonists KW - Dopamine Agents KW - GABA Agonists KW - Botulinum Toxins KW - EC 3.4.24.69 KW - Index Medicus KW - Dopamine Agents -- therapeutic use KW - Drug Administration Schedule KW - Dose-Response Relationship, Drug KW - Botulinum Toxins -- therapeutic use KW - Humans KW - GABA Agonists -- therapeutic use KW - Dystonia -- chemically induced KW - Antioxidants -- therapeutic use KW - Cholinergic Antagonists -- therapeutic use KW - Dystonia -- drug therapy KW - Calcium Channel Blockers -- therapeutic use KW - Antipsychotic Agents -- administration & dosage KW - Dyskinesia, Drug-Induced -- drug therapy KW - Antipsychotic Agents -- therapeutic use KW - Dyskinesia, Drug-Induced -- prevention & control KW - Schizophrenia -- drug therapy KW - Antipsychotic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79408448?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+bulletin&rft.atitle=Treatment+of+tardive+dyskinesia.&rft.au=Egan%2C+M+F%3BApud%2C+J%3BWyatt%2C+R+J&rft.aulast=Egan&rft.aufirst=M&rft.date=1997-01-01&rft.volume=23&rft.issue=4&rft.spage=583&rft.isbn=&rft.btitle=&rft.title=Schizophrenia+bulletin&rft.issn=05867614&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-16 N1 - Date created - 1997-12-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of peroxisome proliferator activated receptor alpha in peroxisome proliferation, physiological homeostasis, and chemical carcinogenesis. AN - 79402215; 9361819 JF - Advances in experimental medicine and biology AU - Gonzalez, F J AD - Laboratory of Metabolism, National Cancer Institute, National Insitutes of Health, Bethesda, Maryland 20892, USA. fjgonz@helix.nih.gov Y1 - 1997 PY - 1997 DA - 1997 SP - 109 EP - 125 VL - 422 SN - 0065-2598, 0065-2598 KW - Carcinogens KW - 0 KW - Receptors, Cytoplasmic and Nuclear KW - Transcription Factors KW - Index Medicus KW - Animals KW - Gene Expression Regulation -- physiology KW - Humans KW - Mice KW - Forecasting KW - Microbodies -- physiology KW - Microbodies -- drug effects KW - Homeostasis KW - Liver Neoplasms -- etiology KW - Species Specificity KW - Risk Assessment KW - Receptors, Cytoplasmic and Nuclear -- physiology KW - Transcription Factors -- physiology KW - Carcinogens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79402215?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+experimental+medicine+and+biology&rft.atitle=The+role+of+peroxisome+proliferator+activated+receptor+alpha+in+peroxisome+proliferation%2C+physiological+homeostasis%2C+and+chemical+carcinogenesis.&rft.au=Gonzalez%2C+F+J&rft.aulast=Gonzalez&rft.aufirst=F&rft.date=1997-01-01&rft.volume=422&rft.issue=&rft.spage=109&rft.isbn=&rft.btitle=&rft.title=Advances+in+experimental+medicine+and+biology&rft.issn=00652598&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-23 N1 - Date created - 1997-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tempol inhibits neutrophil and hydrogen peroxide-mediated DNA damage. AN - 79397077; 9378367 AB - Inflammatory conditions characterized by neutrophil activation are associated with a variety of chronic diseases. Reactive oxygen species are produced by activated neutrophils and produce DNA damage which may lead to tissue damage. Previous studies have shown that activated murine neutrophils induce DNA strand breaks in a target plasmacytoma cell, RIMPC 2394. We studied the effect of a water soluble nitroxide anti-oxidant, Tempol, on murine neutrophil induction of DNA strand breaks in this system. Murine neutrophils were isolated from the peritoneal cavity of BALB/cAn mice after an i.p. injection of pristane oil. Neutrophils were activated by the phorbol ester PMA and co-incubated with RIMPC 2394 cells. Control alkaline elution studies revealed progressive DNA strand breaks in RIMPC cells with time. The addition of Tempol to the incubation mixture prevented DNA damage in a dose dependent fashion. Five mM Tempol provided complete protection. Tempol protection against DNA strand breaks was similar for both stimulated neutrophils and exogenously added hydrogen peroxide. Measurement of hydrogen peroxide produced by stimulated neutrophils demonstrated that Tempol did not decrease hydrogen peroxide concentration. Oxidation of reduced metals, thereby interfering with the production of hydroxyl radical, is the most likely mechanism of nitroxide protection, although superoxide dismutase (SOD) like activity and scavenging of carbon-based free radicals may also account for a portion of the observed protection. The anti-oxidant activity of Tempol inhibited DNA damage by activated neutrophils. The nitroxides as a class of compounds may have a role in the investigation and modification of inflammatory conditions. JF - Free radical biology & medicine AU - Hahn, S M AU - Mitchell, J B AU - Shacter, E AD - Radiation Biology Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 879 EP - 884 VL - 23 IS - 6 SN - 0891-5849, 0891-5849 KW - Antioxidants KW - 0 KW - Cyclic N-Oxides KW - Reactive Oxygen Species KW - Spin Labels KW - Hydrogen Peroxide KW - BBX060AN9V KW - tempol KW - U78ZX2F65X KW - Index Medicus KW - Respiratory Burst -- drug effects KW - Reactive Oxygen Species -- metabolism KW - Animals KW - Peritoneal Cavity -- cytology KW - Neutrophil Activation -- drug effects KW - Tumor Cells, Cultured KW - Plasmacytoma KW - Cells, Cultured KW - Mice KW - Mice, Inbred BALB C KW - Neutrophils -- metabolism KW - Neutrophils -- drug effects KW - Hydrogen Peroxide -- toxicity KW - Antioxidants -- pharmacology KW - Cyclic N-Oxides -- pharmacology KW - DNA Damage -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79397077?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+radical+biology+%26+medicine&rft.atitle=Tempol+inhibits+neutrophil+and+hydrogen+peroxide-mediated+DNA+damage.&rft.au=Hahn%2C+S+M%3BMitchell%2C+J+B%3BShacter%2C+E&rft.aulast=Hahn&rft.aufirst=S&rft.date=1997-01-01&rft.volume=23&rft.issue=6&rft.spage=879&rft.isbn=&rft.btitle=&rft.title=Free+radical+biology+%26+medicine&rft.issn=08915849&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-12 N1 - Date created - 1997-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular adaptations to psychostimulants in striatal neurons: toward a pathophysiology of addiction. AN - 79394574; 9361300 JF - Neurobiology of disease AU - Genova, L AU - Berke, J AU - Hyman, S E AD - Section of Molecular Plasticity, NINDS, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 239 EP - 246 VL - 4 IS - 3-4 SN - 0969-9961, 0969-9961 KW - Psychotropic Drugs KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Substance-Related Disorders -- physiopathology KW - Neurons -- metabolism KW - Adaptation, Physiological -- physiology KW - Psychotropic Drugs -- pharmacology KW - Corpus Striatum -- metabolism KW - Corpus Striatum -- drug effects KW - Corpus Striatum -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79394574?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurobiology+of+disease&rft.atitle=Molecular+adaptations+to+psychostimulants+in+striatal+neurons%3A+toward+a+pathophysiology+of+addiction.&rft.au=Genova%2C+L%3BBerke%2C+J%3BHyman%2C+S+E&rft.aulast=Genova&rft.aufirst=L&rft.date=1997-01-01&rft.volume=4&rft.issue=3-4&rft.spage=239&rft.isbn=&rft.btitle=&rft.title=Neurobiology+of+disease&rft.issn=09699961&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-10 N1 - Date created - 1997-12-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Issues involving biomarkers in the study of the genetics of human cancer. AN - 79376036; 9354923 AB - The investigation of hereditary factors in human cancer was suggested from kindreds that exhibited aggregations of cancer consistent with Mendelian inheritance. A subset of cancer that exhibits strong familial tendencies is due to single genes that 'cause' cancer; more commonly, hereditary factors may influence tumorigenesis in a stepwise probabilistic rather than deterministic manner through a variety of mechanisms, e.g. influencing the disposition of carcinogens. The roles of both common susceptibility genes and rare 'familial' cancer genes are receiving increasing attention in the general population. Population-based studies designed to examine more common genetic variants differ from linkage-based studies. Candidate susceptibility genes may be studied by phenotype or genotype approaches, and the relative advantages and disadvantages of each approach are considered. The issue of gene-environment interaction, implicit in the concept of susceptibility genes, is considered. The influence of genetic factors on individual and attributable risk is addressed. JF - IARC scientific publications AU - Caporaso, N AU - Goldstein, A AD - Genetic Epidemiology Branch National Cancer Institute, Rockville, MD 20892, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 237 EP - 250 IS - 142 SN - 0300-5038, 0300-5038 KW - Biomarkers, Tumor KW - 0 KW - Index Medicus KW - Disease Susceptibility KW - Humans KW - Genetic Diseases, Inborn -- genetics KW - Family Health KW - Male KW - Female KW - Biomarkers, Tumor -- genetics KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79376036?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=IARC+scientific+publications&rft.atitle=Issues+involving+biomarkers+in+the+study+of+the+genetics+of+human+cancer.&rft.au=Caporaso%2C+N%3BGoldstein%2C+A&rft.aulast=Caporaso&rft.aufirst=N&rft.date=1997-01-01&rft.volume=&rft.issue=142&rft.spage=237&rft.isbn=&rft.btitle=&rft.title=IARC+scientific+publications&rft.issn=03005038&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-09 N1 - Date created - 1997-12-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of major depression: selection of initial drug. AN - 79358025; 9344366 JF - Modern problems of pharmacopsychiatry AU - Potter, W Z AU - Schmidt, M E AD - National Institute of Mental Health, Bethesda, Md., USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 1 EP - 16 VL - 25 SN - 0077-0094, 0077-0094 KW - Antidepressive Agents KW - 0 KW - Serotonin Uptake Inhibitors KW - Index Medicus KW - Randomized Controlled Trials as Topic KW - Serotonin Uptake Inhibitors -- therapeutic use KW - Humans KW - Treatment Outcome KW - Serotonin Uptake Inhibitors -- classification KW - Serotonin Uptake Inhibitors -- adverse effects KW - Depressive Disorder, Major -- diagnosis KW - Depressive Disorder, Major -- drug therapy KW - Depressive Disorder, Major -- psychology KW - Antidepressive Agents -- therapeutic use KW - Antidepressive Agents -- adverse effects KW - Antidepressive Agents -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79358025?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Modern+problems+of+pharmacopsychiatry&rft.atitle=Treatment+of+major+depression%3A+selection+of+initial+drug.&rft.au=Potter%2C+W+Z%3BSchmidt%2C+M+E&rft.aulast=Potter&rft.aufirst=W&rft.date=1997-01-01&rft.volume=25&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Modern+problems+of+pharmacopsychiatry&rft.issn=00770094&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-02 N1 - Date created - 1997-12-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Algorithms for bipolar mania. AN - 79356762; 9344373 JF - Modern problems of pharmacopsychiatry AU - Post, R M AU - Denicoff, K D AU - Frye, M A AU - Leverich, G S AD - Biological Psychiatry Branch, NIMH, NIH, Bethesda, Md. 20892-1272, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 114 EP - 145 VL - 25 SN - 0077-0094, 0077-0094 KW - Anti-Anxiety Agents KW - 0 KW - Anticonvulsants KW - Antimanic Agents KW - Antipsychotic Agents KW - Benzodiazepines KW - 12794-10-4 KW - Lithium Carbonate KW - 2BMD2GNA4V KW - Carbamazepine KW - 33CM23913M KW - Valproic Acid KW - 614OI1Z5WI KW - Index Medicus KW - Drug Administration Schedule KW - Anti-Anxiety Agents -- administration & dosage KW - Humans KW - Anticonvulsants -- adverse effects KW - Anticonvulsants -- administration & dosage KW - Anti-Anxiety Agents -- classification KW - Lithium Carbonate -- administration & dosage KW - Valproic Acid -- administration & dosage KW - Antipsychotic Agents -- classification KW - Drug Therapy, Combination KW - Antipsychotic Agents -- administration & dosage KW - Carbamazepine -- adverse effects KW - Lithium Carbonate -- adverse effects KW - Anticonvulsants -- classification KW - Anti-Anxiety Agents -- adverse effects KW - Carbamazepine -- administration & dosage KW - Valproic Acid -- adverse effects KW - Antipsychotic Agents -- adverse effects KW - Bipolar Disorder -- diagnosis KW - Antimanic Agents -- classification KW - Bipolar Disorder -- drug therapy KW - Bipolar Disorder -- classification KW - Antimanic Agents -- adverse effects KW - Antimanic Agents -- administration & dosage KW - Algorithms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79356762?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Modern+problems+of+pharmacopsychiatry&rft.atitle=Algorithms+for+bipolar+mania.&rft.au=Post%2C+R+M%3BDenicoff%2C+K+D%3BFrye%2C+M+A%3BLeverich%2C+G+S&rft.aulast=Post&rft.aufirst=R&rft.date=1997-01-01&rft.volume=25&rft.issue=&rft.spage=114&rft.isbn=&rft.btitle=&rft.title=Modern+problems+of+pharmacopsychiatry&rft.issn=00770094&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-02 N1 - Date created - 1997-12-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selection of initial treatment for bipolar disorder, manic phase. AN - 79353858; 9344372 JF - Modern problems of pharmacopsychiatry AU - Frye, M A AU - Altshuler, L L AD - Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, Md., USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 88 EP - 113 VL - 25 SN - 0077-0094, 0077-0094 KW - Anticonvulsants KW - 0 KW - Antimanic Agents KW - Lithium Carbonate KW - 2BMD2GNA4V KW - Index Medicus KW - Treatment Failure KW - Psychiatric Status Rating Scales KW - Lithium Carbonate -- adverse effects KW - Humans KW - Anticonvulsants -- classification KW - Clinical Trials as Topic KW - Anticonvulsants -- adverse effects KW - Anticonvulsants -- administration & dosage KW - Lithium Carbonate -- administration & dosage KW - Bipolar Disorder -- diagnosis KW - Antimanic Agents -- classification KW - Bipolar Disorder -- drug therapy KW - Antimanic Agents -- adverse effects KW - Antimanic Agents -- administration & dosage KW - Bipolar Disorder -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79353858?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Modern+problems+of+pharmacopsychiatry&rft.atitle=Selection+of+initial+treatment+for+bipolar+disorder%2C+manic+phase.&rft.au=Frye%2C+M+A%3BAltshuler%2C+L+L&rft.aulast=Frye&rft.aufirst=M&rft.date=1997-01-01&rft.volume=25&rft.issue=&rft.spage=88&rft.isbn=&rft.btitle=&rft.title=Modern+problems+of+pharmacopsychiatry&rft.issn=00770094&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-02 N1 - Date created - 1997-12-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Overview of experimental approaches for study of drug metabolism and drug-drug interactions. AN - 79346241; 9342181 JF - Advances in pharmacology (San Diego, Calif.) AU - Gonzalez, F J AD - National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 255 EP - 277 VL - 43 SN - 1054-3589, 1054-3589 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Pharmaceutical Preparations KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Animals KW - Paclitaxel -- metabolism KW - Cells, Cultured KW - Humans KW - Animals, Genetically Modified KW - Species Specificity KW - Antineoplastic Agents, Phytogenic -- metabolism KW - Pharmaceutical Preparations -- metabolism KW - Drug Interactions KW - Liver -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Drug Evaluation, Preclinical -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79346241?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+pharmacology+%28San+Diego%2C+Calif.%29&rft.atitle=Overview+of+experimental+approaches+for+study+of+drug+metabolism+and+drug-drug+interactions.&rft.au=Gonzalez%2C+F+J&rft.aulast=Gonzalez&rft.aufirst=F&rft.date=1997-01-01&rft.volume=43&rft.issue=&rft.spage=255&rft.isbn=&rft.btitle=&rft.title=Advances+in+pharmacology+%28San+Diego%2C+Calif.%29&rft.issn=10543589&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-01 N1 - Date created - 1997-12-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacologic challenges in Alzheimer disease and normal controls: cognitive modeling in humans. AN - 79340601; 9339269 AB - Alzheimer disease (AD) is a progressive disorder characterized by cognitive and behavioral dysfunction, central to which are deficits in the cholinergic and other neurotransmitter systems. These results in the essential symptoms of dementia, including impairment of memory, judgment, and abstract thinking. The pharmacologic relationships among the various neurotransmitters (e.g., cholinergic, serotonergic, nicotinic, and dopaminergic) are highly complex and are still being investigated. Information on the pharmacologic basis of cognitive and behavioral dysfunction in AD has applications to drug therapy. One method of obtaining this information is by pharmacomodeling, using individual or combined drugs. Joint cholinergic antagonism with both muscarinic and nicotinic blockade combines to produce short-term memory impairment, which approximates to mild AD in normal elderly people. This effect is better than that achieved with either agent alone. Mixed cholinergic and serotonergic antagonism has an effect on the cognitive function of AD patients and on depression-related behavior. Dopaminergic dysfunction is linked with the development of hallucinatory and psychotic symptoms and may also be involved in dysfunction of verbal fluency. Combination pharmacomodeling allows the various behavioral and cognitive deficits in AD to be studied and allows models for drug trials to be developed. JF - Alzheimer disease and associated disorders AU - Sunderland, T AU - Molchan, S E AU - Little, J T AU - Bahro, M AU - Putnam, K T AU - Weingartner, H AD - National Institute of Mental Health, Geriatric Psychiatry Branch, Bethesda, Maryland 20892, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - S23 EP - S26 VL - 11 Suppl 4 SN - 0893-0341, 0893-0341 KW - Neurotransmitter Agents KW - 0 KW - Psychotropic Drugs KW - Receptors, Cholinergic KW - Receptors, Dopamine KW - Receptors, Muscarinic KW - Receptors, Nicotinic KW - Receptors, Serotonin KW - Index Medicus KW - Receptors, Serotonin -- physiology KW - Receptors, Serotonin -- drug effects KW - Receptors, Dopamine -- drug effects KW - Humans KW - Aged KW - Receptors, Nicotinic -- physiology KW - Memory, Short-Term -- physiology KW - Memory, Short-Term -- drug effects KW - Receptors, Dopamine -- physiology KW - Receptors, Cholinergic -- drug effects KW - Receptors, Cholinergic -- physiology KW - Receptors, Muscarinic -- drug effects KW - Receptors, Nicotinic -- drug effects KW - Drug Synergism KW - Receptors, Muscarinic -- physiology KW - Brain -- physiopathology KW - Neurotransmitter Agents -- physiology KW - Brain -- drug effects KW - Alzheimer Disease -- physiopathology KW - Alzheimer Disease -- drug therapy KW - Psychotropic Drugs -- therapeutic use KW - Models, Neurological UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79340601?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alzheimer+disease+and+associated+disorders&rft.atitle=Pharmacologic+challenges+in+Alzheimer+disease+and+normal+controls%3A+cognitive+modeling+in+humans.&rft.au=Sunderland%2C+T%3BMolchan%2C+S+E%3BLittle%2C+J+T%3BBahro%2C+M%3BPutnam%2C+K+T%3BWeingartner%2C+H&rft.aulast=Sunderland&rft.aufirst=T&rft.date=1997-01-01&rft.volume=11+Suppl+4&rft.issue=&rft.spage=S23&rft.isbn=&rft.btitle=&rft.title=Alzheimer+disease+and+associated+disorders&rft.issn=08930341&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-09 N1 - Date created - 1997-12-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alternative approaches to refractory depression in bipolar illness. AN - 79340325; 9338110 AB - Thus, there appears to be a large variety of approaches to refractory bipolar depression. In contrast to several decades ago, wherein augmentation of lithium with antidepressants and neuroleptics was essentially the only treatment mode available, a panoply of treatment options now exist. However, their relative efficacy in different illness subtypes and stages remains to be better delineated, as do their optimal sequencing and use in combination in individual patients. It is the opinion of these authors and many of our colleagues in the field that initial use of several mood stabilizer drugs in combination may have a preferable long-term outcome in some rapid cycling patients, compared with the immediate use of a unimodal antidepressant with an inadequate single mood stabilizer, although this remains to be systematically studied. The use of thyroid augmentation strategies would appear to have merit in relationship to not only the potential treatment of lithium-related hypothyroidism, but also in augmenting antimanic and antidepressant effects. As one moves toward some of the complex combination treatment strategies discussed in this chapter, one has to be particularly careful about drug interactions and their potential for toxicity as well as therapeutic effects. Perhaps a prevailing guideline would be to use these agents more carefully in combination therapy than in monotherapy, with slow upward titration of dose to individual patients' side effects thresholds, even in preference to targeting of conventional blood level windows. In this way, side effects can be avoided during the assessment of complex combination regimens. In addition, one should be aware of potential pharmacokinetic interactions. For example, with the addition of valproate to carbamazenine, one should reduce the dose of carbamazepine, as valproate will not only increase the free fraction of carbamazepine based on displacement of protein binding, but will lead to increased accumulation of carbamazepine-10,11-epoxide. This epoxide is not measured in conventional assays but could contribute to the side effects profile (Ketter and Post, 1994). Similarly, valproate will markedly increase blood levels of lamotrigine; the starting dose of this agent should be substantially lower than conventional dosage when these two drugs are used in combination. We suggest the utility of detailed mapping with a formal system-such as the Life Chart Methodology (LCM) (Leverich and Post, 1996)-of mood fluctuation vs. medications in order to optimize and rationalize complex combination therapy. In this way, not only can the nuances of partial response be better defined, but also basic decisions about the therapeutic index and relative likelihood of response can be more readily assessed. We have discussed the other merits of the life chart method as an important clinical treatment tool as well as a research tool in other venues, but reemphasize its potential great importance in the treatment of refractory cyclic bipolar patients, in whom an initial period of remission of depression may, in many instances, be as likely attributable to the natural course of illness as the current intervention being offered. As such, it behooves the clinician to have a systematic database for the more subtle issues of dose titration and sequential addition of medications in complex combination regimens. In the face of inefficiency to one combination strategy, how one moves to the next strategy remains a highly individualized, clinically-based algorithm. We suggest the potential utility of moving towards a new set of mood stabilizers and then repeating some of the unimodal antidepressant additions and augmentation trials in an attempt to overcome refractory depression. Refractory depression in bipolar patients should be viewed as a medical emergency in light of the high potential for suicide in the illness in general (Chen and Dilsaver, 1996) and in patients who have either sustained or episodic refracto JF - Depression and anxiety AU - Post, R M AU - Leverich, G S AU - Denicoff, K D AU - Frye, M A AU - Kimbrell, T A AU - Dunn, R AD - Biological Psychiatry Branch, National Institute of Mental Health, NIH, Bethesda, MD 20892-1272, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 175 EP - 189 VL - 5 IS - 4 SN - 1091-4269, 1091-4269 KW - Psychotropic Drugs KW - 0 KW - Lithium KW - 9FN79X2M3F KW - Index Medicus KW - Drug Therapy, Combination KW - Drug Interactions KW - Drug Administration Schedule KW - Combined Modality Therapy KW - Humans KW - Psychotropic Drugs -- therapeutic use KW - Drug Resistance KW - Electroconvulsive Therapy KW - Case Management KW - Depression -- therapy KW - Bipolar Disorder -- drug therapy KW - Lithium -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79340325?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Depression+and+anxiety&rft.atitle=Alternative+approaches+to+refractory+depression+in+bipolar+illness.&rft.au=Post%2C+R+M%3BLeverich%2C+G+S%3BDenicoff%2C+K+D%3BFrye%2C+M+A%3BKimbrell%2C+T+A%3BDunn%2C+R&rft.aulast=Post&rft.aufirst=R&rft.date=1997-01-01&rft.volume=5&rft.issue=4&rft.spage=175&rft.isbn=&rft.btitle=&rft.title=Depression+and+anxiety&rft.issn=10914269&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-01-15 N1 - Date created - 1998-01-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification and further characterization of a locus coding for a hypothetical 33.6-kDa protein involved in intrageneric coaggregation of oral streptococci. AN - 79335397; 9331746 JF - Advances in experimental medicine and biology AU - Whittaker, C J AU - Kolenbrander, P E AD - National Institute for Dental Research, National Institutes of Health, Bethesda, Maryland 20892-4350, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 695 EP - 698 VL - 418 SN - 0065-2598, 0065-2598 KW - Bacterial Proteins KW - 0 KW - Index Medicus KW - Actinomyces -- pathogenicity KW - Plasmids -- genetics KW - Transformation, Genetic KW - Humans KW - Restriction Mapping KW - Species Specificity KW - Mouth -- microbiology KW - Mutagenesis, Insertional KW - Molecular Weight KW - Streptococcus -- pathogenicity KW - Streptococcus -- genetics KW - Genes, Bacterial KW - Bacterial Proteins -- genetics KW - Bacterial Adhesion -- genetics KW - Bacterial Proteins -- chemistry KW - Bacterial Proteins -- physiology KW - Bacterial Adhesion -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79335397?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+experimental+medicine+and+biology&rft.atitle=Identification+and+further+characterization+of+a+locus+coding+for+a+hypothetical+33.6-kDa+protein+involved+in+intrageneric+coaggregation+of+oral+streptococci.&rft.au=Whittaker%2C+C+J%3BKolenbrander%2C+P+E&rft.aulast=Whittaker&rft.aufirst=C&rft.date=1997-01-01&rft.volume=418&rft.issue=&rft.spage=695&rft.isbn=&rft.btitle=&rft.title=Advances+in+experimental+medicine+and+biology&rft.issn=00652598&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-09 N1 - Date created - 1997-12-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Disruption of the mouse cyclooxygenase 1 gene. Characteristics of the mutant and areas of future study. AN - 79317879; 9321936 AB - Surprisingly, disruption of the COX-1 gene resulted in generally healthy mice. This is in spite of the fact that prostaglandin levels in the tissues examined were reduced by greater than 99%. The results obtained to date with the COX-1 deficient mice indicate that some of the physiological roles previously attributed to COX-1 may not be entirely correct. Ongoing studies with the COX deficient mice are aimed at better defining the physiological roles of the cyclooxygenases and concomitantly the mechanisms by which NSAIDs cause their biological effects. JF - Advances in experimental medicine and biology AU - Langenbach, R AU - Morham, S G AU - Tiano, H F AU - Loftin, C D AU - Ghanayem, B I AU - Chulada, P C AU - Mahler, J F AU - Davis, B J AU - Lee, C A AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 87 EP - 92 VL - 407 SN - 0065-2598, 0065-2598 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Cyclooxygenase Inhibitors KW - Isoenzymes KW - Membrane Proteins KW - Cyclooxygenase 1 KW - EC 1.14.99.1 KW - Prostaglandin-Endoperoxide Synthases KW - Ptgs1 protein, mouse KW - Index Medicus KW - Animals KW - Anti-Inflammatory Agents, Non-Steroidal -- therapeutic use KW - Cyclooxygenase Inhibitors -- toxicity KW - Inflammation -- drug therapy KW - Cell Transformation, Neoplastic -- drug effects KW - Anti-Inflammatory Agents, Non-Steroidal -- toxicity KW - Stomach Ulcer -- chemically induced KW - Mice, Knockout KW - Cyclooxygenase Inhibitors -- therapeutic use KW - Genotype KW - Mice, Mutant Strains KW - Reproduction -- physiology KW - Genes KW - Gene Targeting KW - Male KW - Cell Transformation, Neoplastic -- genetics KW - Female KW - Prostaglandin-Endoperoxide Synthases -- physiology KW - Isoenzymes -- physiology KW - Mice -- genetics KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Isoenzymes -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79317879?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+experimental+medicine+and+biology&rft.atitle=Disruption+of+the+mouse+cyclooxygenase+1+gene.+Characteristics+of+the+mutant+and+areas+of+future+study.&rft.au=Langenbach%2C+R%3BMorham%2C+S+G%3BTiano%2C+H+F%3BLoftin%2C+C+D%3BGhanayem%2C+B+I%3BChulada%2C+P+C%3BMahler%2C+J+F%3BDavis%2C+B+J%3BLee%2C+C+A&rft.aulast=Langenbach&rft.aufirst=R&rft.date=1997-01-01&rft.volume=407&rft.issue=&rft.spage=87&rft.isbn=&rft.btitle=&rft.title=Advances+in+experimental+medicine+and+biology&rft.issn=00652598&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-30 N1 - Date created - 1997-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Generation of immunoglobulin/c-myc recombinations in murine Peyer's patch follicles. AN - 79299776; 9308248 JF - Current topics in microbiology and immunology AU - Müller, J R AU - Mushinski, E B AU - Jones, G M AU - Williams, J A AU - Janz, S AU - Hausner, P F AU - Potter, M AD - Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 251 EP - 255 VL - 224 SN - 0070-217X, 0070-217X KW - Carcinogens KW - 0 KW - Terpenes KW - pristane KW - 26HZV48DT1 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Terpenes -- toxicity KW - Animals KW - Peyer's Patches -- immunology KW - Plasmacytoma -- chemically induced KW - Carcinogens -- toxicity KW - Mice KW - Mice, Inbred BALB C KW - Polymerase Chain Reaction KW - Mice, Inbred Strains KW - Base Sequence KW - Plasmacytoma -- genetics KW - Peyer's Patches -- metabolism KW - DNA -- genetics KW - Plasmacytoma -- immunology KW - Genes, myc KW - Recombination, Genetic KW - Genes, Immunoglobulin UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79299776?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+topics+in+microbiology+and+immunology&rft.atitle=Generation+of+immunoglobulin%2Fc-myc+recombinations+in+murine+Peyer%27s+patch+follicles.&rft.au=M%C3%BCller%2C+J+R%3BMushinski%2C+E+B%3BJones%2C+G+M%3BWilliams%2C+J+A%3BJanz%2C+S%3BHausner%2C+P+F%3BPotter%2C+M&rft.aulast=M%C3%BCller&rft.aufirst=J&rft.date=1997-01-01&rft.volume=224&rft.issue=&rft.spage=251&rft.isbn=&rft.btitle=&rft.title=Current+topics+in+microbiology+and+immunology&rft.issn=0070217X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-28 N1 - Date created - 1997-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetics of Parkinson's disease. AN - 79287926; 9300660 AB - For the past 40 years, research into Parkinson's disease (PD) has been predominantly the province of epidemiologists interested in pursuing the connection between the disease and environmental factors such as viral infection or neurotoxins. Hereditary influences were actually discounted because of a high monozygotic twin discordance rate found in studies that were later shown to be inadequate and inconclusive. There has recently been a resurgence of interest in investigating hereditary factors in PD when it became more and more apparent that a positive family history was a major risk factor for the disease. Meanwhile, it also became increasingly apparent from neuropathological studies that the common, idiopathic form of Parkinson's disease had, in fact, a pathological correlate, i.e., the existence of Lewy bodies, an eosinophilic cytoplasmic inclusion body, distributed diffusely throughout the substantia nigra, hypothalamus, hippocampus, autonomic ganglia and olfactory tracts. Although candidate gene approaches to linkage in PD families have not been rewarding, a genome wide scan mapped PD to 4q21-23 in one large family with PD with diffuse Lewy bodies, where a candidate gene, alpha-synuclein, resides. This gene encodes a presynaptic protein of which a peptide fragment is known to be a constituent of Alzheimer's disease plaques. The identification of a missense mutation in the alpha-synuclein gene in four independent PD families suggests that at least some fraction of familial PD with diffuse Lewy bodies is the result of an abnormal protein that interferes with normal protein degradation leading to the development of inclusions and ultimately neuronal cell death. There may be common pathogenetic mechanisms involved in alpha-synuclein mutations in PD and beta-amyloid and presenilin gene mutations in Alzheimer's disease. JF - Human molecular genetics AU - Nussbaum, R L AU - Polymeropoulos, M H AD - Laboratory of Genetic Diseases Research, National Human Genome Research Institute, Bethesda, MD 20892-4472, USA. rlnuss@nhgri.nih.gov Y1 - 1997 PY - 1997 DA - 1997 SP - 1687 EP - 1691 VL - 6 IS - 10 SN - 0964-6906, 0964-6906 KW - Nerve Tissue Proteins KW - 0 KW - SNCA protein, human KW - Synucleins KW - alpha-Synuclein KW - Index Medicus KW - Genetic Linkage KW - Risk Factors KW - Humans KW - Family KW - Chromosome Mapping KW - Point Mutation KW - Nerve Tissue Proteins -- genetics KW - Parkinson Disease -- genetics KW - Chromosomes, Human, Pair 4 KW - Parkinson Disease -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79287926?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+molecular+genetics&rft.atitle=Genetics+of+Parkinson%27s+disease.&rft.au=Nussbaum%2C+R+L%3BPolymeropoulos%2C+M+H&rft.aulast=Nussbaum&rft.aufirst=R&rft.date=1997-01-01&rft.volume=6&rft.issue=10&rft.spage=1687&rft.isbn=&rft.btitle=&rft.title=Human+molecular+genetics&rft.issn=09646906&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-16 N1 - Date created - 1997-10-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interactions between D1 and D2 dopamine receptor family agonists and antagonists: the effects of chronic exposure on behavior and receptor binding in rats and their clinical implications. AN - 79280133; 9295170 AB - Functional interactions between dopamine receptor subtypes may affect behavioral and biochemical responses which serve as models for neuropsychiatric illnesses and the clinical effects of drug therapy. We evaluated the effects of chronic exposure to the selective D1 receptor antagonist SCH 23390, and the selective D2 receptor antagonist metoclopramide, on spontaneous and drug-induced behavior and receptor density in rats, and then determined how these effects would be modified by concurrent administration of antagonists or agonists [SKF 38393, LY 171555 (quinpirole)] selective for the complementary receptor subtype. Administered alone, both the D1 and D2 antagonists had acute cataleptic effects to which animals became tolerant following chronic treatment, but the selective antagonists had opposing effects on spontaneous locomotor activity. Both antagonists produced equivalent, supersensitive behavioral responses to apomorphine, and resulted in an increase in D2 receptor density. Coadministration of the D1 and D2 antagonists had a synergistic effect on catalepsy, attenuated the effects on spontaneous locomotor activity observed with either drug alone, and had an additive effect on both apomorphine-induced stereotypic behavior and D2 receptor proliferation. On the other hand, when either selective antagonist was combined with the agonist selective for the complementary receptor subtype, both D2 receptor proliferation and behavioral supersensitivity were completely blocked. Combined antagonist-agonist treatments had opposing effects on the development of tolerance to antagonist-induced catalepsy. D2 - but not D1 - receptor densities were correlated with animals' behavioral responses to apomorphine. There results support and extend the notion that complex functional interactions between D1 and D2 receptor families occur within the central nervous system, and suggest that novel effects might be derived from combined administration of receptor selective agonists and antagonists. JF - Journal of neural transmission (Vienna, Austria : 1996) AU - Braun, A R AU - Laruelle, M AU - Mouradian, M M AD - Language Section, Voice Speech and Language Branch, NIDCD, National Institutes of Health, Bethesda, Maryland 20892, U.S.A. Y1 - 1997 PY - 1997 DA - 1997 SP - 341 EP - 362 VL - 104 IS - 4-5 SN - 0300-9564, 0300-9564 KW - Dopamine Agents KW - 0 KW - Dopamine D2 Receptor Antagonists KW - Receptors, Dopamine D1 KW - Receptors, Dopamine D2 KW - Apomorphine KW - N21FAR7B4S KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Drug Interactions KW - Catalepsy -- chemically induced KW - Corpus Striatum -- metabolism KW - Apomorphine -- pharmacology KW - Stereotyped Behavior KW - Motor Activity -- drug effects KW - Male KW - Behavior, Animal -- drug effects KW - Receptors, Dopamine D1 -- agonists KW - Receptors, Dopamine D1 -- antagonists & inhibitors KW - Receptors, Dopamine D2 -- agonists KW - Dopamine Agents -- pharmacology KW - Receptors, Dopamine D1 -- metabolism KW - Receptors, Dopamine D2 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79280133?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neural+transmission+%28Vienna%2C+Austria+%3A+1996%29&rft.atitle=Interactions+between+D1+and+D2+dopamine+receptor+family+agonists+and+antagonists%3A+the+effects+of+chronic+exposure+on+behavior+and+receptor+binding+in+rats+and+their+clinical+implications.&rft.au=Braun%2C+A+R%3BLaruelle%2C+M%3BMouradian%2C+M+M&rft.aulast=Braun&rft.aufirst=A&rft.date=1997-01-01&rft.volume=104&rft.issue=4-5&rft.spage=341&rft.isbn=&rft.btitle=&rft.title=Journal+of+neural+transmission+%28Vienna%2C+Austria+%3A+1996%29&rft.issn=03009564&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-21 N1 - Date created - 1997-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Direct enhancement of GABA-ergic neurotransmission by ammonia. AN - 79269652; 9286428 JF - Advances in experimental medicine and biology AU - Ha, J H AU - Knauer, S AU - Moody, E AU - Jones, E A AU - Basile, A S AD - Laboratory of Neuroscience, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 85 EP - 94 VL - 420 SN - 0065-2598, 0065-2598 KW - Barbiturates KW - 0 KW - Receptors, GABA-A KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - Ammonia KW - 7664-41-7 KW - Index Medicus KW - Animals KW - Neurons -- drug effects KW - Humans KW - Barbiturates -- pharmacology KW - Receptors, GABA-A -- drug effects KW - Membrane Potentials -- drug effects KW - Ammonia -- toxicity KW - gamma-Aminobutyric Acid -- physiology KW - Synaptic Transmission -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79269652?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+experimental+medicine+and+biology&rft.atitle=Direct+enhancement+of+GABA-ergic+neurotransmission+by+ammonia.&rft.au=Ha%2C+J+H%3BKnauer%2C+S%3BMoody%2C+E%3BJones%2C+E+A%3BBasile%2C+A+S&rft.aulast=Ha&rft.aufirst=J&rft.date=1997-01-01&rft.volume=420&rft.issue=&rft.spage=85&rft.isbn=&rft.btitle=&rft.title=Advances+in+experimental+medicine+and+biology&rft.issn=00652598&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-11-24 N1 - Date created - 1997-11-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alcoholism and gene polymorphisms related to central dopaminergic transmission in the Japanese population. AN - 79260884; 9285967 AB - We examined the association between gene polymorphisms related to central dopaminergic transmission and alcoholism in the Japanese population. Polymorphic gene loci examined included those encoding the dopamine D2 receptor (NcoI site and Ser-Cys site), the dopamine D3 receptor (BalI site), the dopamine D4 receptor (48 bp tandem repeat) and the dopamine transporter (40 bp tandem repeat). The genotype distribution at the NcoI site in the dopamine D2 receptor gene differed significantly (p < 0.5) between alcoholic patients and control subjects. The frequency of 7 repeats at the 40 bp/DAT tended to be higher (p < 0.1), and that of 9 repeats tended to be lower (p < 0.1) in alcoholic patients than in control subjects. The possible effects of dopamine-related gene polymorphisms, which might predispose individuals to alcoholism, are discussed. JF - Psychiatric genetics AU - Dobashi, I AU - Inada, T AU - Hadano, K AD - National Institute of Mental Health, National Center of Neurology and Psychiatry, Chiba, Japan. Y1 - 1997 PY - 1997 DA - 1997 SP - 87 EP - 91 VL - 7 IS - 2 SN - 0955-8829, 0955-8829 KW - Carrier Proteins KW - 0 KW - DRD3 protein, human KW - Dopamine Plasma Membrane Transport Proteins KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Receptors, Dopamine D2 KW - Receptors, Dopamine D3 KW - SLC6A3 protein, human KW - Serine KW - 452VLY9402 KW - Cysteine KW - K848JZ4886 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Reference Values KW - Humans KW - Dopamine -- metabolism KW - Amino Acid Sequence KW - Genotype KW - Polymerase Chain Reaction KW - Restriction Mapping KW - Repetitive Sequences, Nucleic Acid KW - Japan KW - Polymorphism, Genetic KW - Carrier Proteins -- genetics KW - Receptors, Dopamine D2 -- genetics KW - Alcoholism -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79260884?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychiatric+genetics&rft.atitle=Alcoholism+and+gene+polymorphisms+related+to+central+dopaminergic+transmission+in+the+Japanese+population.&rft.au=Dobashi%2C+I%3BInada%2C+T%3BHadano%2C+K&rft.aulast=Dobashi&rft.aufirst=I&rft.date=1997-01-01&rft.volume=7&rft.issue=2&rft.spage=87&rft.isbn=&rft.btitle=&rft.title=Psychiatric+genetics&rft.issn=09558829&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-16 N1 - Date created - 1997-10-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronic administration of a partial agonist at strychnine-insensitive glycine receptors: a novel experimental approach to the treatment of ischemias. AN - 79232875; 9266432 AB - During the past decade, converging lines of evidence have linked the abnormal release or leak of excitatory amino acids to the neurodegeneration associated with a wide range of pathologies including cerebral ischemias, Huntington's disease, and AIDS dementia (Coyle and Robinson, 1987; Lipton, 1994; Meldrum, 1994). Pharmacological studies indicate that activation of both ionotropic and metabotropic glutamate receptors can substantially contribute to excitotoxic cell damage (Choi, 1992; Pizzi et al., 1993; Sheardown et al., 1993; Xue et al., 1994). Based on these findings, therapeutic strategies based on blunting or blocking glutamatergic transmission may be useful in treating a variety of neurodegenerative disorders. JF - Journal of neural transmission. Supplementum AU - Fossom, L H AU - Skolnick, P AD - Laboratory of Neuroscience, NIDDK, National Institutes of Health, Bethesda, MD, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 235 EP - 244 VL - 49 SN - 0303-6995, 0303-6995 KW - Amino Acids KW - 0 KW - Amino Acids, Cyclic KW - Neuroprotective Agents KW - Receptors, Glycine KW - Receptors, N-Methyl-D-Aspartate KW - 1-aminocyclopropane-1-carboxylic acid KW - 3K9EJ633GL KW - Strychnine KW - H9Y79VD43J KW - Index Medicus KW - AIDS/HIV KW - Huntington Disease -- physiopathology KW - Animals KW - Humans KW - Neurons -- drug effects KW - Huntington Disease -- drug therapy KW - AIDS Dementia Complex -- physiopathology KW - AIDS Dementia Complex -- pathology KW - Nerve Degeneration KW - Receptors, N-Methyl-D-Aspartate -- physiology KW - AIDS Dementia Complex -- drug therapy KW - Neurons -- physiology KW - Strychnine -- pharmacology KW - Huntington Disease -- pathology KW - Brain Ischemia -- drug therapy KW - Receptors, Glycine -- agonists KW - Brain Ischemia -- pathology KW - Amino Acids -- therapeutic use KW - Amino Acids -- pharmacology KW - Receptors, Glycine -- antagonists & inhibitors KW - Neuroprotective Agents -- therapeutic use KW - Brain Ischemia -- physiopathology KW - Neuroprotective Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79232875?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neural+transmission.+Supplementum&rft.atitle=Chronic+administration+of+a+partial+agonist+at+strychnine-insensitive+glycine+receptors%3A+a+novel+experimental+approach+to+the+treatment+of+ischemias.&rft.au=Fossom%2C+L+H%3BSkolnick%2C+P&rft.aulast=Fossom&rft.aufirst=L&rft.date=1997-01-01&rft.volume=49&rft.issue=&rft.spage=235&rft.isbn=&rft.btitle=&rft.title=Journal+of+neural+transmission.+Supplementum&rft.issn=03036995&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-03 N1 - Date created - 1997-10-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Central nervous system cytokines and their relevance for neurotoxicity and apoptosis. AN - 79228010; 9266426 AB - Cytokines are molecules that are synthesized not only by the immune system, but also by cells in the central nervous system, including neurons, glia, and brain vascular cells. In the brain, cytokines can be neuroprotective or they can contribute to neurodegeneration. The role of cytokines in the regulation of normal and abnormal brain function represents a rapidly growing frontier in neuroscience. Cytokines are pleiotropic and redundant, and they can modulate the effects of neurotransmitters and neuropeptides; thus, in order to understand the effects of brain cytokines on apoptosis and toxicity, it is necessary to study the temporal and spatial expression of complex networks of cytokines, growth factors, neuropeptides, and neurotransmitters. This effort is currently in progress in many centers. Modulation of cytokine function in the central nervous system represents a new therapeutic strategy for neurodegeneration. JF - Journal of neural transmission. Supplementum AU - Licinio, J AD - Clinical Neuroendocrinology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 169 EP - 175 VL - 49 SN - 0303-6995, 0303-6995 KW - Cytokines KW - 0 KW - Neurotoxins KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Caspase 1 KW - EC 3.4.22.36 KW - Index Medicus KW - Neuroglia -- cytology KW - Nerve Degeneration KW - Animals KW - Necrosis KW - Humans KW - Cysteine Endopeptidases -- metabolism KW - Neuroglia -- immunology KW - Cerebrovascular Circulation KW - Neuroglia -- physiology KW - Apoptosis KW - Brain -- cytology KW - Neurons -- cytology KW - Neurons -- physiology KW - Cytokines -- physiology KW - Brain -- immunology KW - Neurons -- immunology KW - Brain -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79228010?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neural+transmission.+Supplementum&rft.atitle=Central+nervous+system+cytokines+and+their+relevance+for+neurotoxicity+and+apoptosis.&rft.au=Licinio%2C+J&rft.aulast=Licinio&rft.aufirst=J&rft.date=1997-01-01&rft.volume=49&rft.issue=&rft.spage=169&rft.isbn=&rft.btitle=&rft.title=Journal+of+neural+transmission.+Supplementum&rft.issn=03036995&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-10-03 N1 - Date created - 1997-10-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicokinetics in the National Toxicology Program. AN - 79218978; 9260193 AB - Toxic responses to test chemicals are known to be dependent on the exposure route, the kinetic behavior of the chemical, and the dose used in the toxicology study. Therefore, knowledge of internal dose is indispensable for the interpretation of toxicology study results, for the facilitation of interspecies scaling, and for risk assessment. By monitoring the blood and/or tissue concentrations of test chemical and/or metabolites versus time after administration of study chemicals by different routes, the bioavailability and kinetic characteristic of test chemicals can be readily obtained. This data can define the so-called linear dose range using area under the plasma concentration versus time curve, clearance, or other related toxicokinetic parameters, and can also be used to predict the possible bioaccumulation under multiple dose regimes. Changes in kinetic parameters after multiple exposures indicate alteration in how the animal handles the chemical (e.g., that there was enzyme induction or inhibition). A recommended approach for conducting toxicokinetic studies generally involves three steps. Step 1 is a preliminary study, which uses a minimum number of animals to estimate the range of blood/tissue concentrations, the required quantitation limit for the analytical method, and the optimal sampling times for the definitive toxicokinetic studies. Step 2 is the definitive study and generates blood and/or tissue concentration data for calculating the toxicokinetic parameters. Step 3 is the toxicokinetic study conducted in conjunction with the toxicology study to determine the internal dose and the effects of age and continuous exposure on kinetic parameters. Examples of the application of NTP toxicokinetic evaluations were also presented in this chapter, demonstrating their use in the design and interpretation of toxicology studies. JF - NIDA research monograph AU - Goehl, T J AD - National Institute of Environmental Health Sciences, National Toxicology Program, Research Triangle Park, NC 27560, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 273 EP - 304 VL - 173 SN - 1046-9516, 1046-9516 KW - Index Medicus KW - Animals KW - Humans KW - Toxicology KW - Pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79218978?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NIDA+research+monograph&rft.atitle=Toxicokinetics+in+the+National+Toxicology+Program.&rft.au=Goehl%2C+T+J&rft.aulast=Goehl&rft.aufirst=T&rft.date=1997-01-01&rft.volume=173&rft.issue=&rft.spage=273&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-18 N1 - Date created - 1997-09-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of transforming growth factor-beta 1 and phorbol ester on PAI-1 and PA genes in human lung cells. AN - 79189429; 9255608 AB - Transforming growth factor-beta (TGF-beta) mediates the production of extracellular matrix proteins, proteases and protease inhibitors in epithelial cells. Both TGF-beta and phorbol-12-myristate-13-acetate (PMA) exert both positive and negative effects on mitogenesis in these as well as other cell types. Phorbol esters act through stimulation of protein kinase C (PKC) and are among the most potent tumor promoters known. The present study was conducted to determine whether the effect of TGF-beta in human non-small cell lung cancer (NSCLC) and normal human bronchial epithelial (NHBE) cells parallels that of the phorbol esters and whether this effect of TGF-beta involves PKC. TGF-beta 1 and PMA increased expression of TGF-beta 1 mRNA 24 hr after their addition to both NSCLC and NHBE cells. The effects of these agents on expression of the mRNAs for TGF-beta 2 and TGF-beta 3 were more complex; while TGF-beta 2 and TGF-beta 3 mRNAs increased transiently in response to TGF-beta 1 in NHBE cells and TGF-beta 3 mRNA increased transiently in some NSCLC cells, expression of these mRNAs decreased in most of these cells in response to PMA with the exception of the carcinoid NCI-H727 where TGF-beta 2 mRNA increased dramatically, TGF-beta 1 and PMA both caused a persistent increase in expression of the mRNAs for both plasminogen activator inhibitor-1 (PAI-1) and plasminogen activator (PA) up to 24 hr in most NSCLC cells, with the increase in PAI-1 mRNA beginning several hours before that of PA mRNA. In contrast, while TGF-beta 1 also increased expression of PAI-1 mRNA in NHBE cells, the expression of PA mRNA decreased simultaneously. The effect of PMA on PAI-1 and PA mRNAs was opposite of TGF-beta 1 in these cells, with expression of PAI-1 mRNA decreasing and PA mRNA increasing after addition of PMA. These data show that there is parallel regulation of the genes for TGF-beta 1, PAI-1 and PA by TGF-beta 1 and PMA in NSCLC, but differential regulation of the genes for PAI-1 and PA by these agents in NHBE cells. The responses of the mRNAs and proteins of TGF-beta 1, PAI-1 and PA to TGF-beta 1 and PMA were inhibited by the serine/ threonine kinase inhibitor H7 in NSCLC cells. Treatment of NSCLC cells with TGF-beta 1 and PMA resulted in a persistent increase in the expression of fibronectin mRNA and protein. This response was blocked by the addition of H7. Inhibition of these effects by H7 in NSCLC cells suggests that H7 blocks TGF-beta responses by inhibiting a protein serine/threonine kinase(s). Because the effects of TGF-beta and PMA on the different TGF-beta isoforms, PA, PAI and fibronectin in NHBE and NSCLC cells are complex, our data suggest that there are distinct mechanisms for controlling the different TGF-beta isoforms, PA, PAI and extracellular matrix proteins in normal lung and lung cancer cells. JF - Growth factors (Chur, Switzerland) AU - Jakowlew, S B AU - Mariano, J M AU - You, L AD - National Cancer Institute, Biomarkers and Prevention Research Branch, Rockville, Maryland 20850, USA. jakowlews@bprb.nci.nih.gov Y1 - 1997 PY - 1997 DA - 1997 SP - 177 EP - 197 VL - 14 IS - 2-3 SN - 0897-7194, 0897-7194 KW - DNA Probes KW - 0 KW - Enzyme Inhibitors KW - Fibronectins KW - Plasminogen Activator Inhibitor 1 KW - RNA, Messenger KW - Transforming Growth Factor beta KW - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine KW - 84477-87-2 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Plasminogen Activators KW - EC 3.4.21.- KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine -- pharmacology KW - Blotting, Northern KW - Extracellular Matrix -- metabolism KW - Humans KW - Fibronectins -- metabolism KW - Fibronectins -- genetics KW - Protein-Serine-Threonine Kinases -- antagonists & inhibitors KW - RNA, Messenger -- genetics KW - Extracellular Matrix -- drug effects KW - Gene Expression Regulation, Neoplastic KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - Cells, Cultured KW - Enzyme Inhibitors -- pharmacology KW - Gene Expression Regulation KW - Transforming Growth Factor beta -- pharmacology KW - Carcinoma, Non-Small-Cell Lung -- metabolism KW - Plasminogen Activator Inhibitor 1 -- genetics KW - Plasminogen Activator Inhibitor 1 -- metabolism KW - Carcinoma, Non-Small-Cell Lung -- pathology KW - Plasminogen Activators -- genetics KW - Bronchi -- cytology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Bronchi -- metabolism KW - Transforming Growth Factor beta -- genetics KW - Transforming Growth Factor beta -- metabolism KW - Lung Neoplasms -- metabolism KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79189429?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Growth+factors+%28Chur%2C+Switzerland%29&rft.atitle=Effects+of+transforming+growth+factor-beta+1+and+phorbol+ester+on+PAI-1+and+PA+genes+in+human+lung+cells.&rft.au=Jakowlew%2C+S+B%3BMariano%2C+J+M%3BYou%2C+L&rft.aulast=Jakowlew&rft.aufirst=S&rft.date=1997-01-01&rft.volume=14&rft.issue=2-3&rft.spage=177&rft.isbn=&rft.btitle=&rft.title=Growth+factors+%28Chur%2C+Switzerland%29&rft.issn=08977194&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-09 N1 - Date created - 1997-09-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Csk-like proteins Lsk, Hyl, and Matk represent the same Csk homologous kinase (Chk) and are regulated by stem cell factor in the megakaryoblastic cell line MO7e. AN - 79187502; 9255603 AB - Recently, the cDNAs for Lsk, Matk and Hyl, three Csk-related protein tyrosine kinases, have been cloned. We have examined the relationship of Lsk, Matk and Hyl, and found that the gene for each of these proteins is localized to the same region of human chromosome 19. Further, the proteins encoded by Lsk and Matk cDNAs are immunologically similar. These data strongly suggest that Lsk, Hyl and Matk are the same gene product. Previous reports demonstrating expression of Hyl and Matk in hematopoietic lineages led us to investigate the regulation of Lsk expression in response to stem cell factor (SCF) and granulocyte-macrophage colony stimulating factor (GM-CSF) in M07e, a human leukemic cell line. Induction of Lsk/Hyl/Matk protein and mRNA was observed after treatment with SCF but not with GM-CSF. GM-CSF and IL-3, potent mitogens, had no effect on Lsk/Hyl/Matk expression. In contrast, PMA induced Lsk/Hyl/Matk but did not stimulate proliferation. Therefore, induction of Lsk/ Hyl/Matk does not correlate with the capacity to stimulate proliferation. None of the stimuli examined increased Csk protein or mRNA expression. These data demonstrate differential regulation of Csk family members by cytokines and suggest a role for Lsk/ Hyl/Matk in responses mediated by SCF and PMA. Further, our data demonstrate that, as has been seen in blood monocytes, cytokine driven translational control of Lsk/Hyl/ Matk is likely a critical mode of regulation. Lastly, since our studies strongly suggest that the Lsk, Hyl and Matk kinases are related and regulated distinctly from Csk, we and several of the original authors have agreed to rename this kinase the Csk homologous kinase (Chk). JF - Growth factors (Chur, Switzerland) AU - Grgurevich, S AU - Linnekin, D AU - Musso, T AU - Zhang, X AU - Modi, W AU - Varesio, L AU - Ruscetti, F W AU - Ortaldo, J R AU - McVicar, D W AD - Laboratory of Experimental Immunology, National Cancer Institute, Frederick, MD, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 103 EP - 115 VL - 14 IS - 2-3 SN - 0897-7194, 0897-7194 KW - Interleukin-3 KW - 0 KW - RNA, Messenger KW - Stem Cell Factor KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - MATK protein, human KW - EC 2.7.10.2 KW - Proto-Oncogene Proteins pp60(c-src) KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Humans KW - Interleukin-3 -- pharmacology KW - In Situ Hybridization, Fluorescence KW - Cell Differentiation -- genetics KW - Chromosomes, Human, Pair 19 -- genetics KW - Granulocyte-Macrophage Colony-Stimulating Factor -- pharmacology KW - Precipitin Tests KW - Chromosome Mapping KW - Cloning, Molecular KW - Blotting, Western KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Enzyme Induction KW - Signal Transduction KW - Protein-Tyrosine Kinases -- immunology KW - Protein-Tyrosine Kinases -- genetics KW - Stem Cell Factor -- pharmacology KW - Megakaryocytes -- enzymology KW - Protein-Tyrosine Kinases -- biosynthesis KW - Megakaryocytes -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79187502?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Growth+factors+%28Chur%2C+Switzerland%29&rft.atitle=The+Csk-like+proteins+Lsk%2C+Hyl%2C+and+Matk+represent+the+same+Csk+homologous+kinase+%28Chk%29+and+are+regulated+by+stem+cell+factor+in+the+megakaryoblastic+cell+line+MO7e.&rft.au=Grgurevich%2C+S%3BLinnekin%2C+D%3BMusso%2C+T%3BZhang%2C+X%3BModi%2C+W%3BVaresio%2C+L%3BRuscetti%2C+F+W%3BOrtaldo%2C+J+R%3BMcVicar%2C+D+W&rft.aulast=Grgurevich&rft.aufirst=S&rft.date=1997-01-01&rft.volume=14&rft.issue=2-3&rft.spage=103&rft.isbn=&rft.btitle=&rft.title=Growth+factors+%28Chur%2C+Switzerland%29&rft.issn=08977194&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-09 N1 - Date created - 1997-09-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nitric oxide enhancement of melphalan-induced cytotoxicity. AN - 79183653; 9252199 AB - The effects of the diatomic radical, nitric oxide (NO), on melphalan-induced cytotoxicity in Chinese hamster V79 and human MCF-7 breast cancer cells were studied using clonogenic assays. NO delivered by the NO-releasing agent (C2H5)2N[N(O)NO]- Na+ (DEA/NO; 1 mM) resulted in enhancement of melphalan-mediated toxicity in Chinese hamster V79 lung fibroblasts and human breast cancer (MCF-7) cells by 3.6- and 4.3-fold, respectively, at the IC50 level. Nitrite/nitrate and diethylamine, the ultimate end products of DEA/NO decomposition, had little effect on melphalan cytotoxicity, which suggests that NO was responsible for the sensitization. Whereas maximal sensitization of melphalan cytotoxicity by DEA/NO was observed for simultaneous exposure of DEA/NO and melphalan, cells pretreated with DEA/NO were sensitized to melphalan for several hours after NO exposure. Reversing the order of treatment also resulted in a time-dependent enhancement in melphalan cytotoxicity. To explore possible mechanisms of NO enhancement of melphalan cytotoxicity, the effects of DEA/NO on three factors that might influence melphalan toxicity were examined, namely NO-mediated cell cycle perturbations, intracellular glutathione (GSH) levels and melphalan uptake. NO pretreatment resulted in a delayed entry into S phase and a G2/M block for both V79 and MCF-7 cells; however, cell cycle redistribution for V79 cells occurred after the cells returned to a level of cell survival, consistent with treatment with melphalan alone. After 15 min exposure of V79 cells to DEA/NO (1 mM), GSH levels were reduced to 40% of control values; however, GSH levels recovered fully after 1 h and were elevated 2 h after DEA/NO incubation. In contrast, DEA/NO (1 mM) incubation did not reduce GSH levels significantly in MCF-7 cells (approximately 10%). Melphalan uptake was increased by 33% after DEA/NO exposure in V79 cells. From these results enhancement of melphalan cytotoxicity mediated by NO appears to be complex and may involve several pathways, including possibly alteration of the repair of melphalan-induced lesions. Our observations may give insights for improving tumour kill with melphalan using either exogenous or possibly endogenous sources of NO. JF - British journal of cancer AU - Cook, J A AU - Krishna, M C AU - Pacelli, R AU - DeGraff, W AU - Liebmann, J AU - Mitchell, J B AU - Russo, A AU - Wink, D A AD - Radiation Biology Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 325 EP - 334 VL - 76 IS - 3 SN - 0007-0920, 0007-0920 KW - Nitric Oxide KW - 31C4KY9ESH KW - Buthionine Sulfoximine KW - 5072-26-4 KW - Glutathione KW - GAN16C9B8O KW - Melphalan KW - Q41OR9510P KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured KW - Humans KW - Glutathione -- metabolism KW - Buthionine Sulfoximine -- pharmacology KW - Drug Synergism KW - DNA Repair -- drug effects KW - Cricetinae KW - Melphalan -- metabolism KW - Melphalan -- administration & dosage KW - Nitric Oxide -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79183653?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Nitric+oxide+enhancement+of+melphalan-induced+cytotoxicity.&rft.au=Cook%2C+J+A%3BKrishna%2C+M+C%3BPacelli%2C+R%3BDeGraff%2C+W%3BLiebmann%2C+J%3BMitchell%2C+J+B%3BRusso%2C+A%3BWink%2C+D+A&rft.aulast=Cook&rft.aufirst=J&rft.date=1997-01-01&rft.volume=76&rft.issue=3&rft.spage=325&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 - 1997-09-03 N1 - Date created - 1997-09-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer Res. 1984 Nov;44(11):5427-31 [6488194] Biochem Pharmacol. 1985 Jul 15;34(14):2583-6 [4040369] Int J Radiat Oncol Biol Phys. 1986 Jul;12(7):1187-9 [3744938] J Immunol. 1987 Jan 15;138(2):550-65 [2432129] Biochem Pharmacol. 1987 Jan 1;36(1):147-53 [3801051] Cancer Res. 1987 Mar 15;47(6):1593-7 [3815359] Cancer Res. 1988 May 15;48(10):2764-7 [3359437] Cancer Res. 1989 Apr 15;49(8):1970-6 [2495172] J Exp Med. 1989 May 1;169(5):1543-55 [2497225] Cancer Res. 1991 Mar 15;51(6):1606-12 [1998951] J Med Chem. 1991 Nov;34(11):3242-7 [1956043] J Leukoc Biol. 1992 Sep;52(3):255-61 [1522385] Cancer Chemother Pharmacol. 1993;32(1):73-7 [8462127] Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):9813-7 [8234317] Cancer Res. 1993 Dec 15;53(24):5845-8 [8261391] J Neurochem. 1994 Jan;62(1):315-21 [7505314] Carcinogenesis. 1994 Mar;15(3):443-7 [8118926] Biochem Biophys Res Commun. 1994 Apr 29;200(2):1105-10 [8179589] Cancer Res. 1994 Jul 1;54(13):3365-8 [7516820] Biochem Biophys Res Commun. 1994 Aug 30;203(1):209-18 [7521161] Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):10089-93 [7524082] Carcinogenesis. 1994 Oct;15(10):2125-9 [7955043] Pediatr Res. 1995 Jan;37(1):41-9 [7700733] Proc Natl Acad Sci U S A. 1995 May 9;92(10):4452-6 [7538671] Arch Biochem Biophys. 1995 Jun 1;319(2):402-7 [7786021] J Clin Oncol. 1996 Jan;14(1):249-56 [8558205] Anal Biochem. 1996 Jul 1;238(2):150-8 [8660604] Methods Enzymol. 1996;268:69-83 [8782574] Chem Res Toxicol. 1996 Jan-Feb;9(1):326-32 [8924612] Cancer Res. 1994 Mar 1;54(5):1352-4 [7509718] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential effects of flavonoids on testosterone-metabolizing cytochrome P450s. AN - 79181850; 9252251 AB - Flavonoids are widely distributed phytochemicals, whose modulation of cytochrome P450 mediated carcinogen metabolism is well established. Less well studied is their effect on P450 dependent metabolism of endogenous substrates. To address this question we evaluated a series of twelve flavonoids and hematoxylin for their effect on P450-mediated steroid hydroxylation by rat liver microsomes. Site-specific 7alpha-, 6beta- and 2alpha-hydroxylation of testosterone by P450s 2A1, 3A2 and 2C11, respectively, was measured. Highly selective patterns of inhibition or activation of these P450s were observed. 3,6-dichloro-2'-isopropyloxy-4'-methylflavone was the most potent inhibitor of P450 2C11 while cyanidin chloride most potently inhibited P450s 2A1 and 3A2. The flavonoid analogue hematoxylin was unique in that it activated 2C11 (by 2.5 fold) yet inhibited both 2A1 and 3A2 (by 60%). These results indicate that consumption of dietary flavonoids may likewise alter the metabolite profile of steroids and other physiological P450 substrates. JF - Life sciences AU - Dai, R AU - Jacobson, K A AU - Robinson, R C AU - Friedman, F K AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - PL75 EP - PL80 VL - 61 IS - 7 SN - 0024-3205, 0024-3205 KW - Cytochrome P-450 Enzyme Inhibitors KW - 0 KW - Flavonoids KW - Isoenzymes KW - Testosterone KW - 3XMK78S47O KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Male KW - Isoenzymes -- antagonists & inhibitors KW - Testosterone -- metabolism KW - Microsomes, Liver -- enzymology KW - Microsomes, Liver -- drug effects KW - Cytochrome P-450 Enzyme System -- metabolism KW - Isoenzymes -- drug effects KW - Flavonoids -- pharmacology KW - Cytochrome P-450 Enzyme System -- drug effects KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79181850?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Life+sciences&rft.atitle=Differential+effects+of+flavonoids+on+testosterone-metabolizing+cytochrome+P450s.&rft.au=Dai%2C+R%3BJacobson%2C+K+A%3BRobinson%2C+R+C%3BFriedman%2C+F+K&rft.aulast=Dai&rft.aufirst=R&rft.date=1997-01-01&rft.volume=61&rft.issue=7&rft.spage=PL75&rft.isbn=&rft.btitle=&rft.title=Life+sciences&rft.issn=00243205&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-29 N1 - Date created - 1997-08-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of self-reported drug use with quantitative and qualitative urinalysis for assessment of drug use in treatment studies. AN - 79167944; 9243560 AB - The effectiveness of substance abuse treatment programs can be monitored by self-reported drug use and objectively measured by qualitative and quantitative urinalysis. The advantages and disadvantages of each of these three methods of assessing drug use are reviewed. Data collected in a clinical trial of a behavioral treatment for cocaine abuse are used to evaluate the relationships among qualitative and quantitative urinalysis for cocaine metabolite and self-reported cocaine use. Qualitative and quantitative urine testing showed greater rates of drug use than that shown by self-report, though there were significant correlations between self-reported use and urine toxicology results. Benzoylecgonine concentrations in urine specimens supported the suggestions that rates of drug use as determined by qualitative urinalysis are artificially high due to carryover and were informative about subjects' patterns of use. JF - NIDA research monograph AU - Preston, K L AU - Silverman, K AU - Schuster, C R AU - Cone, E J AD - Clinical Trials Section, National Institute on Drug Abuse, Baltimore, MD 21224, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 130 EP - 145 VL - 167 SN - 1046-9516, 1046-9516 KW - Street Drugs KW - 0 KW - Index Medicus KW - Evaluation Studies as Topic KW - Reproducibility of Results KW - Humans KW - Treatment Outcome KW - Substance-Related Disorders -- therapy KW - Self Disclosure KW - Surveys and Questionnaires KW - Street Drugs -- urine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79167944?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NIDA+research+monograph&rft.atitle=Comparison+of+self-reported+drug+use+with+quantitative+and+qualitative+urinalysis+for+assessment+of+drug+use+in+treatment+studies.&rft.au=Preston%2C+K+L%3BSilverman%2C+K%3BSchuster%2C+C+R%3BCone%2C+E+J&rft.aulast=Preston&rft.aufirst=K&rft.date=1997-01-01&rft.volume=167&rft.issue=&rft.spage=130&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-05 N1 - Date created - 1997-09-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - New developments in biological measures of drug prevalence. AN - 79167892; 9243559 AB - Drug use among different populations such as household members, students, and arrestees vary substantially and the accuracy of their self-reports may be questionable. The accuracy of prevalence estimates based on self-report data can be monitored by chemical drug testing of biological specimens such as urine, saliva, sweat, and hair. Each biological specimen is unique and offers a somewhat different pattern of information regarding drug use over time. Also, each specimen has unique strengths and weaknesses regarding the type of information obtained from drug testing. The performance characteristics of the assay methodology may also be important. The validation of self-report data by drug testing must be performed with careful consideration of the limitations imposed by the testing methodology and the biological specimen. JF - NIDA research monograph AU - Cone, E J AD - Chemistry and Drug Metabolism Section, National Institute on Drug Abuse, Baltimore, MD 21224, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 108 EP - 129 VL - 167 SN - 1046-9516, 1046-9516 KW - Street Drugs KW - 0 KW - Index Medicus KW - Sweat -- metabolism KW - Saliva -- chemistry KW - Humans KW - Hair -- chemistry KW - Biological Assay KW - Prevalence KW - Substance-Related Disorders -- diagnosis KW - Street Drugs -- blood KW - Street Drugs -- metabolism KW - Street Drugs -- urine KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79167892?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NIDA+research+monograph&rft.atitle=New+developments+in+biological+measures+of+drug+prevalence.&rft.au=Cone%2C+E+J&rft.aulast=Cone&rft.aufirst=E&rft.date=1997-01-01&rft.volume=167&rft.issue=&rft.spage=108&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-05 N1 - Date created - 1997-09-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment for drug addiction: it won't work if they don't receive it. AN - 79165749; 9243543 JF - NIDA research monograph AU - Onken, L S AU - Blaine, J D AU - Boren, J J AD - Treatment Research Branch, National Institute on Drug Abuse, Rockville, MD 20857, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 1 EP - 3 VL - 165 SN - 1046-9516, 1046-9516 KW - Index Medicus KW - Patient Compliance KW - Humans KW - Patient Dropouts KW - Substance-Related Disorders -- therapy KW - Substance-Related Disorders -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79165749?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NIDA+research+monograph&rft.atitle=Treatment+for+drug+addiction%3A+it+won%27t+work+if+they+don%27t+receive+it.&rft.au=Onken%2C+L+S%3BBlaine%2C+J+D%3BBoren%2C+J+J&rft.aulast=Onken&rft.aufirst=L&rft.date=1997-01-01&rft.volume=165&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-24 N1 - Date created - 1997-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Estrogen in geriatric psychopharmacology. AN - 79146531; 9230644 JF - Psychopharmacology bulletin AU - Lebowitz, B D AU - Pollock, B G AU - Schneider, L S AD - Mental Disorders of the Aging Research Branch, National Institute of Mental Health, Rockville, MD 20857, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 287 EP - 288 VL - 33 IS - 2 SN - 0048-5764, 0048-5764 KW - Estrogens KW - 0 KW - Psychotropic Drugs KW - Index Medicus KW - Estrogen Replacement Therapy KW - Drug Interactions KW - Humans KW - Aged KW - Female KW - Estrogens -- therapeutic use KW - Psychotropic Drugs -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79146531?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology+bulletin&rft.atitle=Estrogen+in+geriatric+psychopharmacology.&rft.au=Lebowitz%2C+B+D%3BPollock%2C+B+G%3BSchneider%2C+L+S&rft.aulast=Lebowitz&rft.aufirst=B&rft.date=1997-01-01&rft.volume=33&rft.issue=2&rft.spage=287&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology+bulletin&rft.issn=00485764&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-20 N1 - Date created - 1997-08-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Histological, histochemical and autoradiographic evidence of in vitro neurotoxic effects of the novel antitumor agent, 9-methoxy-N2-methylellipticinium acetate. AN - 79129008; 9215991 AB - 9-Methoxy-N2-methylellipticinium acetate (MMEA) exhibits selective cytotoxicity towards glial-derived human brain tumor cell lines comprising the U.S. National Cancer Institute preclinical drug screen. Neurotoxic potential of MMEA has been demonstrated in an in vitro model employing sagittal slices of rat brain. Histochemical staining of rat brain slices for lactate dehydrogenase (LDH) activity revealed decreased staining intensity following incubation with increasing concentrations of MMEA (0.1-100 microM). Cytological evaluation of paraffin sections stained with Cresyl Fast Violet revealed neuronal damage delineated by cytoplasmic vacuolation, and distention and fraying of the plasma membrane. No glial or vascular pathology could be discerned. Autoradiography, following exposure to 14C-MMEA, revealed distinct labelling of the large neurons of the brain stem, neurons in the thalamus and pyramidal neurons of the hippocampus, indicating neuronal uptake of the drug. JF - Neurotoxicology AU - Shankar, L AU - Ravindranath, V AU - Boyd, M R AU - Vistica, D T AU - Shankar, S K AD - Department of Neuropathology, National Institute of Mental Health and Neuroscience, Bangalore, India. Y1 - 1997 PY - 1997 DA - 1997 SP - 89 EP - 95 VL - 18 IS - 1 SN - 0161-813X, 0161-813X KW - Antineoplastic Agents KW - 0 KW - Ellipticines KW - Neurotoxins KW - 9-methoxy-N(2)-methylellipticinium KW - 70173-20-5 KW - Index Medicus KW - Rats KW - Animals KW - In Vitro Techniques KW - Rats, Wistar KW - Histocytochemistry KW - Autoradiography KW - Male KW - Neurons -- metabolism KW - Brain -- pathology KW - Brain -- drug effects KW - Ellipticines -- toxicity KW - Antineoplastic Agents -- toxicity KW - Brain -- metabolism KW - Neurotoxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79129008?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicology&rft.atitle=Histological%2C+histochemical+and+autoradiographic+evidence+of+in+vitro+neurotoxic+effects+of+the+novel+antitumor+agent%2C+9-methoxy-N2-methylellipticinium+acetate.&rft.au=Shankar%2C+L%3BRavindranath%2C+V%3BBoyd%2C+M+R%3BVistica%2C+D+T%3BShankar%2C+S+K&rft.aulast=Shankar&rft.aufirst=L&rft.date=1997-01-01&rft.volume=18&rft.issue=1&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=Neurotoxicology&rft.issn=0161813X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-09 N1 - Date created - 1997-09-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antiproliferative effects of cyclopentenyl cytosine (NSC 375575) in human glioblastoma cells. AN - 79119297; 9220496 AB - Cyclopentenyl cytosine (CPEC) exerts an antiproliferative effect against a wide variety of human and murine tumor lines, including a panel of human gliosarcoma and astrocytoma lines. This effect is produced primarily by the 5'-triphosphate metabolite CPEC-TP, an inhibitor of cytidine-5'-triphosphate (CTP) synthase (EC 6.3.4.2). Because previous studies with human glioma cell lines utilized cells in long-term tissue culture, we have undertaken to determine whether the activity of CPEC in such model systems is also demonstrable in freshly excised human glioblastoma cells. Glioma cells obtained at surgery and in log phase growth were exposed to the drug at levels ranging from 0.01 to 1 microM for 24 h, and CPEC-TP and CTP levels were determined by HPLC. Dose-dependent accumulation of CPEC-TP was accompanied by a concomitant decrease in CTP pools, with 50% depletion of the latter being achieved at a CPEC level of ca. 0.1 microM. Human glioma cell proliferation was inhibited 50% by 24-h exposure to 0.07 microM CPEC. Postexposure decay of CPEC-TP was slow, with a half-time of 30 h. DNA cytometry showed a dose-dependent shift in cell cycle distribution, with an accumulation of cells in S-phase. The pharmacological effects of CPEC on freshly excised glioblastoma cells are quantitatively similar to those seen in a range of established tissue culture lines, including human glioma, colon carcinoma, and MOLT-4 lymphoblasts, supporting the recommendation that the drug may be advantageous for the treatment of human glioblastoma. JF - Oncology research AU - Agbaria, R AU - Kelley, J A AU - Jackman, J AU - Viola, J J AU - Ram, Z AU - Oldfield, E AU - Johns, D G AD - Laboratory of Medical Chemistry, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 111 EP - 118 VL - 9 IS - 3 SN - 0965-0407, 0965-0407 KW - Antimetabolites, Antineoplastic KW - 0 KW - Growth Inhibitors KW - Nucleotides KW - Cytidine KW - 5CSZ8459RP KW - Cytidine Triphosphate KW - 65-47-4 KW - cyclopentenyl cytosine KW - 69MO0NDN8K KW - Index Medicus KW - Nucleotides -- metabolism KW - Tumor Cells, Cultured KW - Dose-Response Relationship, Drug KW - Cytidine Triphosphate -- metabolism KW - Humans KW - Adult KW - Cell Division -- drug effects KW - Male KW - Glioblastoma -- pathology KW - Growth Inhibitors -- pharmacology KW - Cytidine -- pharmacology KW - Cytidine -- analogs & derivatives KW - Antimetabolites, Antineoplastic -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79119297?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncology+research&rft.atitle=Antiproliferative+effects+of+cyclopentenyl+cytosine+%28NSC+375575%29+in+human+glioblastoma+cells.&rft.au=Agbaria%2C+R%3BKelley%2C+J+A%3BJackman%2C+J%3BViola%2C+J+J%3BRam%2C+Z%3BOldfield%2C+E%3BJohns%2C+D+G&rft.aulast=Agbaria&rft.aufirst=R&rft.date=1997-01-01&rft.volume=9&rft.issue=3&rft.spage=111&rft.isbn=&rft.btitle=&rft.title=Oncology+research&rft.issn=09650407&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-13 N1 - Date created - 1997-08-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vitro neurotoxicity of the antitumor agent 9-methoxy-N2-methylellipticinium acetate (MMEA): role of brain cytochrome P-450. AN - 79111188; 9215992 AB - 9-methoxy-N2-methylellipticinium acetate (MMEA) is representative of a series of quaternized ellipticine derivatives that are selectively cytotoxic to human brain tumor cell lines derived from non-neuronal (glial) cells (Acton et al, 1994). In an attempt to determine whether MMEA may exhibit toxicity to normal brain cells, we have examined the effect of the drug, in vitro, using sagittal slices of rat brain. Incubation of rat brain slices in an artificial cerebrospinal fluid medium containing MMEA resulted in dose-dependent leakage of lactate dehydrogenase (LDH) into the surrounding medium. However, other subcellular marker enzymes such as Na(+)-K+ATPase (plasma membrane), cytochrome c oxidase, isocitrate dehydrogenase, NADH-dehydrogenase (mitochondrial), N-acetylglucosaminidase, acid phosphate (lysosomal), glyceraldehyde-3-phosphate dehydrogenase and enolase (glycolytic enzymes) were unaffected even at the highest tested concentrations of MMEA (10 and 100 microM). Preincubation of slices with reserpine (1 nM) or, dopamine or serotonin-specific reuptake inhibitors abolished MMEA-induced toxicity in brain slices. Pretreatment of slices with piperonyl butoxide and metyrapone, inhibitor of cytochrome P-450, also prevented the toxicity of MMEA. Further, brain slices prepared from phenobarbital-treated rats showed enhanced sensitivity to MMEA; significant leakage of LDH was observed at MMEA concentrations as low as 1 nM. The present studies demonstrate the toxicity of MMEA in rat brain slices, in vitro, and suggest a role for brain cytochrome P-450 in the neurotoxicity of MMEA [corrected]. JF - Neurotoxicology AU - Sriram, K AU - Boyd, M R AU - Vistica, D T AU - Ravindranath, R AD - Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bangalore, India. Y1 - 1997 PY - 1997 DA - 1997 SP - 97 EP - 104 VL - 18 IS - 1 SN - 0161-813X, 0161-813X KW - Antineoplastic Agents KW - 0 KW - Ellipticines KW - Neurotoxins KW - 9-methoxy-N(2)-methylellipticinium KW - 70173-20-5 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Rats KW - Animals KW - In Vitro Techniques KW - Rats, Wistar KW - Drug Evaluation, Preclinical KW - Male KW - Brain -- enzymology KW - Brain -- pathology KW - Brain -- drug effects KW - Cytochrome P-450 Enzyme System -- physiology KW - Ellipticines -- toxicity KW - Antineoplastic Agents -- toxicity KW - Neurotoxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79111188?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicology&rft.atitle=In+vitro+neurotoxicity+of+the+antitumor+agent+9-methoxy-N2-methylellipticinium+acetate+%28MMEA%29%3A+role+of+brain+cytochrome+P-450.&rft.au=Sriram%2C+K%3BBoyd%2C+M+R%3BVistica%2C+D+T%3BRavindranath%2C+R&rft.aulast=Sriram&rft.aufirst=K&rft.date=1997-01-01&rft.volume=18&rft.issue=1&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=Neurotoxicology&rft.issn=0161813X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-09 N1 - Date created - 1997-09-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Neurotoxicology 1998 Feb;19(1):167 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Trans-rearrangements and the risk of lymphoid malignancy. AN - 79110789; 9209640 AB - Antigen receptor 'trans-rearrangements' occur in all individuals and represent a particular type of genetic instability whose mechanism, V(D)J recombination, is the same as that required for the development of a normal immune response. We have measured the level of trans-rearrangements in a variety of populations characterized by increased risk for the development of lymphoid malignancy. The human populations studied include those with an inherited predisposition to lymphomagenesis (ataxia-telangiectasia patients), as well as populations at increased risk because of an occupational (agriculture workers) or iatrogenic (Hodgkin's disease patients) exposure. In addition, we have developed a mouse model for the more controlled analysis of these events. There is a correlation between the absolute number of trans-rearrangements (as a population mean or median) and risk of lymphoma, whether that risk is based on an inherited predisposition or acquired exposure. This assay may serve as an easily measurable biomarker of lymphoma risk. If so, it is more than a fortuitous biomarker since the same mechanism responsible for the formation of trans-rearrangement is, at least in part, responsible for the majority of presumably 'malevolent' translocations associated with the transformation of lymphocytes. JF - Annals of oncology : official journal of the European Society for Medical Oncology AU - Kirsch, I R AD - National Cancer Institute-Navy Medical Oncology Branch, National Institutes of Health, Bethesda, MD, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 45 EP - 48 VL - 8 Suppl 2 SN - 0923-7534, 0923-7534 KW - Receptors, Antigen, T-Cell KW - 0 KW - Index Medicus KW - Polymerase Chain Reaction KW - Ataxia Telangiectasia -- genetics KW - Animals KW - Hodgkin Disease -- genetics KW - Agricultural Workers' Diseases -- genetics KW - Risk Factors KW - Humans KW - Recombination, Genetic KW - Hodgkin Disease -- drug therapy KW - Mice KW - Receptors, Antigen, T-Cell -- genetics KW - Gene Rearrangement UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79110789?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+oncology+%3A+official+journal+of+the+European+Society+for+Medical+Oncology&rft.atitle=Trans-rearrangements+and+the+risk+of+lymphoid+malignancy.&rft.au=Kirsch%2C+I+R&rft.aulast=Kirsch&rft.aufirst=I&rft.date=1997-01-01&rft.volume=8+Suppl+2&rft.issue=&rft.spage=45&rft.isbn=&rft.btitle=&rft.title=Annals+of+oncology+%3A+official+journal+of+the+European+Society+for+Medical+Oncology&rft.issn=09237534&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-05 N1 - Date created - 1997-09-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Radioprotection of hematopoietic tissue by fibroblast growth factors in fractionated radiation experiments. AN - 79108592; 9208907 AB - Acidic and basic fibroblast growth factors (FGF(1/2)) myeloprotect mice in single dose total body irradiation (TBI) experiments with a dose modification factor (DMF) of approximately 1.15. CFU-C assay suggests that one of the mechanisms is augmentation of the shoulder of the radiation dose response curve, and thus protection could be greater with fractionation. Four equal fractions of TBI were delivered to C3H/He mice at times 0 h, 8 h, 24 h, and 32 h. FGF(1/2) dose was 3 microg per i.v. injection given 24 and 4 hrs before the first radiation dose. FGF2 treated mice had a significant survival advantage over saline-treated mice with a DMF of 1.22 +/- 0.07 (p < 0.01). Adding a third dose of FGF2, had no additional benefit on LD(50/30) (dose of radiation lethal to 50% of animals measured at day 30) (DMF = 1.23 +/- 0.06, p < 0.01). FGF1 was not as effective with fractionation (DMF = 1.04 +/- 0.03). Increased survival in FGF2 treated mice was due to the a more rapid recovery of bone marrow hematopoietic cells and peripheral WBC, RBC and platelets. FGF2 may prove a useful treatment response modifier in clinical fractionated irradiation. JF - Acta oncologica (Stockholm, Sweden) AU - Ding, I AU - Huang, K AU - Wang, X AU - Greig, J R AU - Miller, R W AU - Okunieff, P AD - Radiation Oncology Branch, National Cancer Institute, Bethesda, MD 20892-1002, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 337 EP - 340 VL - 36 IS - 3 SN - 0284-186X, 0284-186X KW - Radiation-Protective Agents KW - 0 KW - Recombinant Proteins KW - Fibroblast Growth Factor 2 KW - 103107-01-3 KW - Fibroblast Growth Factor 1 KW - 104781-85-3 KW - Index Medicus KW - Animals KW - Whole-Body Irradiation KW - Recombinant Proteins -- pharmacology KW - Dose-Response Relationship, Drug KW - Mice, Inbred C3H KW - Mice KW - Dose-Response Relationship, Radiation KW - Female KW - Fibroblast Growth Factor 2 -- pharmacology KW - Fibroblast Growth Factor 1 -- pharmacology KW - Hematopoietic System -- drug effects KW - Radiation-Protective Agents -- pharmacology KW - Hematopoietic System -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79108592?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Acta+oncologica+%28Stockholm%2C+Sweden%29&rft.atitle=Radioprotection+of+hematopoietic+tissue+by+fibroblast+growth+factors+in+fractionated+radiation+experiments.&rft.au=Ding%2C+I%3BHuang%2C+K%3BWang%2C+X%3BGreig%2C+J+R%3BMiller%2C+R+W%3BOkunieff%2C+P&rft.aulast=Ding&rft.aufirst=I&rft.date=1997-01-01&rft.volume=36&rft.issue=3&rft.spage=337&rft.isbn=&rft.btitle=&rft.title=Acta+oncologica+%28Stockholm%2C+Sweden%29&rft.issn=0284186X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-17 N1 - Date created - 1997-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of comorbid schizophrenia and substance abuse disorders. AN - 79102019; 9200909 JF - New directions for mental health services AU - Hansell, S AD - NIMH Center for Research on the Organization and Financing of Care for the Severely Mentally Ill, Rutgers University, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 65 EP - 73 IS - 73 SN - 0193-9416, 0193-9416 KW - Index Medicus KW - Humans KW - Comorbidity KW - Substance-Related Disorders -- therapy KW - Schizophrenia -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79102019?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=New+directions+for+mental+health+services&rft.atitle=Treatment+of+comorbid+schizophrenia+and+substance+abuse+disorders.&rft.au=Hansell%2C+S&rft.aulast=Hansell&rft.aufirst=S&rft.date=1997-01-01&rft.volume=&rft.issue=73&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=New+directions+for+mental+health+services&rft.issn=01939416&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-21 N1 - Date created - 1997-07-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular cloning and characterization of lymphocyte and muscle ADP-ribosyltransferases. AN - 79098113; 9193645 AB - Mono-ADP-ribosylation, catalyzed by ADP-ribosyltransferases, is a posttranslational modification of proteins in which the ADP-ribose moiety of NAD is transferred to an acceptor protein(arginine). Several of the bacterial toxin ADP-ribosyltransferases have been well characterized in their ability to alter cellular metabolism. It has been postulated that these bacterial toxins mimic the actions of transferases from mammalian cells. We have cloned and characterized ADP-ribosyltransferases from rabbit and human skeletal muscle, and mouse lymphocytes. The muscle transferases are glycosylphosphatidylinositol (GPI)-anchored proteins that are conserved among species. Two distinct transferases, termed Yac-1 and Yac-2 were cloned from mouse lymphoma (Yac-1) cells. The Yac-1 transferase, like the muscle enzymes, is a GPI-linked exoenzyme. The Yac-2 transferase, on the other hand, is membrane-associated but appears not to be GPI-linked. In contrast to Yac-1, the Yac-2 enzyme had significant NAD glycohydrolase activity and may preferentially hydrolyze NAD. The bacterial toxin ADP-ribosyltransferases contain three noncontiguous regions of sequence similarity, which are involved in formation of the catalytic site. Alignment of the deduced amino acid sequences of the mammalian transferases and the rodent RT6 enzymes, along with results from site-directed mutagenesis of the muscle enzyme, are consistent with the notion of a common mechanism of NAD binding and catalysis among ADP-ribosyltransferases. JF - Advances in experimental medicine and biology AU - Okazaki, I J AU - Kim, H J AU - Moss, J AD - Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 129 EP - 136 VL - 419 SN - 0065-2598, 0065-2598 KW - Glycosylphosphatidylinositols KW - 0 KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured KW - Humans KW - Rabbits KW - Mice KW - Glycosylphosphatidylinositols -- metabolism KW - Cloning, Molecular KW - ADP Ribose Transferases -- chemistry KW - Lymphocytes -- enzymology KW - ADP Ribose Transferases -- metabolism KW - Muscle, Skeletal -- enzymology KW - ADP Ribose Transferases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79098113?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+experimental+medicine+and+biology&rft.atitle=Molecular+cloning+and+characterization+of+lymphocyte+and+muscle+ADP-ribosyltransferases.&rft.au=Okazaki%2C+I+J%3BKim%2C+H+J%3BMoss%2C+J&rft.aulast=Okazaki&rft.aufirst=I&rft.date=1997-01-01&rft.volume=419&rft.issue=&rft.spage=129&rft.isbn=&rft.btitle=&rft.title=Advances+in+experimental+medicine+and+biology&rft.issn=00652598&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-04 N1 - Date created - 1997-09-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of iron metabolism in eukaryotes. AN - 79083206; 9192174 AB - Iron metabolism is regulated in cells to ensure that iron supplies are adequate and nontoxic. The expression of iron metabolism is regulated primarily by posttranscriptional mechanisms. Ferritin, eALAS, SDHb of Drosophila, and mammalian mitochondrial aconitase are translationally regulated. The TfR is regulated at the level of mRNA stability. Iron regulatory proteins are regulated either by assembly or by disassembly of an iron-sulfur cluster (IRP1) or by rapid degradation in the presence of iron (IRP2). The list of targets for IRP-mediated regulation is growing longer, and a range of possibilities for versatile regulation exists, as each IRP can bind to unique targets that differ from the consensus IRE. The reactivity of iron with oxygen and the creation of toxic by-products may be the evolutionary stimulus that produced this system of tight posttranscriptional gene regulation. JF - Current topics in cellular regulation AU - Rouault, T AU - Klausner, R AD - Cell Biology and Metabolism National Institutes of Child and Human Disease, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 1 EP - 19 VL - 35 SN - 0070-2137, 0070-2137 KW - Iron-Regulatory Proteins KW - 0 KW - Iron-Sulfur Proteins KW - RNA, Messenger KW - RNA-Binding Proteins KW - Receptors, Transferrin KW - Ferritins KW - 9007-73-2 KW - Iron KW - E1UOL152H7 KW - Aconitate Hydratase KW - EC 4.2.1.3 KW - Iron Regulatory Protein 1 KW - Iron Regulatory Protein 2 KW - Index Medicus KW - Animals KW - RNA-Binding Proteins -- genetics KW - RNA-Binding Proteins -- metabolism KW - Humans KW - Gene Expression KW - Iron-Sulfur Proteins -- genetics KW - RNA, Messenger -- genetics KW - Models, Biological KW - Receptors, Transferrin -- metabolism KW - Iron-Sulfur Proteins -- metabolism KW - Aconitate Hydratase -- chemistry KW - Ferritins -- metabolism KW - Ferritins -- genetics KW - Protein Biosynthesis KW - Models, Molecular KW - RNA-Binding Proteins -- chemistry KW - Evolution, Molecular KW - Binding Sites KW - Iron-Sulfur Proteins -- chemistry KW - Base Sequence KW - Receptors, Transferrin -- genetics KW - Mutation KW - Eukaryotic Cells -- metabolism KW - Iron -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79083206?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+topics+in+cellular+regulation&rft.atitle=Regulation+of+iron+metabolism+in+eukaryotes.&rft.au=Rouault%2C+T%3BKlausner%2C+R&rft.aulast=Rouault&rft.aufirst=T&rft.date=1997-01-01&rft.volume=35&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Current+topics+in+cellular+regulation&rft.issn=00702137&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-13 N1 - Date created - 1997-08-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retinoic acid-induced alteration of cell surface topography and other changes in an oral carcinoma cell line in culture. AN - 79082282; 9201279 AB - Nature of antiproliferative action of retinoic acid (RA) on KB cells was studied by using monolayer and agar culture techniques. RA-treated cultures showed increased requirement of serum for their growth. Growth of colonies in agar culture was significantly retarded when cells were treated with 40 mumol RA. RA-induced growth inhibitions in both monolayer and agar cultures were independent of cell seeding densities. Cortisone and hydrocortisone showed no reversal of the inhibitory effects induced by RA on KB cells. Scanning electron microscopy study revealed a significant alteration in cell surface topography of RA-treated cells in monolayer culture. The results demonstrate that RA has a potential of reversing some of the properties which are associated with transformed state of oral carcinoma cells. JF - Neoplasma AU - Sarkar, R AU - Das, S K AD - Chittaranjan National Cancer Institute, Calcutta, India. Y1 - 1997 PY - 1997 DA - 1997 SP - 37 EP - 43 VL - 44 IS - 1 SN - 0028-2685, 0028-2685 KW - Antineoplastic Agents KW - 0 KW - Tretinoin KW - 5688UTC01R KW - Cortisone KW - V27W9254FZ KW - Hydrocortisone KW - WI4X0X7BPJ KW - Index Medicus KW - Hydrocortisone -- pharmacology KW - Drug Interactions KW - Cortisone -- pharmacology KW - Cell Membrane -- drug effects KW - Humans KW - Cell Division -- drug effects KW - Microscopy, Electron, Scanning KW - Tretinoin -- pharmacology KW - KB Cells -- drug effects KW - KB Cells -- ultrastructure KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79082282?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neoplasma&rft.atitle=Retinoic+acid-induced+alteration+of+cell+surface+topography+and+other+changes+in+an+oral+carcinoma+cell+line+in+culture.&rft.au=Sarkar%2C+R%3BDas%2C+S+K&rft.aulast=Sarkar&rft.aufirst=R&rft.date=1997-01-01&rft.volume=44&rft.issue=1&rft.spage=37&rft.isbn=&rft.btitle=&rft.title=Neoplasma&rft.issn=00282685&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-18 N1 - Date created - 1997-07-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The treatment of pediatric lymphomas: paradigms to plagiarize? AN - 79075343; 9187422 AB - The excellent results in pediatric lymphomas presented at the Sixth International Conference on Malignant Lymphoma in Lugano encompass several emerging themes and provide paradigms which it may be possible to extrapolate to at least some adult lymphomas. In pediatric Hodgkin's disease, there is mounting evidence that radiation adds nothing except toxicity to effective chemotherapy regimens, with the possible exception that patients with bulky disease, particularly in the mediastinum, may benefit from involved-field radiation. This is of particular importance in view of the recently recognized high rate of late-occurring second solid tumors and cardiac infarction, largely referable to radiotherapy. It is likely that there will be greater efforts to eliminate radiation from treatment protocols wherever possible. In pediatric non-Hodgkin's lymphomas, the intensive regimens used by several cooperative groups in Europe and the United States have resulted in very high event-free survival rates--90% in B-cell lymphomas, and only slightly lower in T-cell lymphomas. These results stand in striking contrast to those obtained in adults with the same diseases, except those treated with the same treatment protocols, who appear to have a similar prognosis. Finally, progress in the characterization of the molecular abnormalities and viral association of pediatric lymphomas is leading to new approaches to diagnosis and the detection of minimal residual disease, as well as to the development of targeted treatment approaches. JF - Annals of oncology : official journal of the European Society for Medical Oncology AU - Magrath, I T AD - Lymphoma Biology Section, National Cancer Institute, Bethesda, MD, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 7 EP - 14 VL - 8 Suppl 1 SN - 0923-7534, 0923-7534 KW - Index Medicus KW - Lymphoma, B-Cell -- drug therapy KW - Combined Modality Therapy KW - Lymphoma, T-Cell -- drug therapy KW - Humans KW - Adult KW - Clinical Trials as Topic KW - Child KW - Lymphoma, Non-Hodgkin -- drug therapy KW - Hodgkin Disease -- radiotherapy KW - Hodgkin Disease -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79075343?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+oncology+%3A+official+journal+of+the+European+Society+for+Medical+Oncology&rft.atitle=The+treatment+of+pediatric+lymphomas%3A+paradigms+to+plagiarize%3F&rft.au=Magrath%2C+I+T&rft.aulast=Magrath&rft.aufirst=I&rft.date=1997-01-01&rft.volume=8+Suppl+1&rft.issue=&rft.spage=7&rft.isbn=&rft.btitle=&rft.title=Annals+of+oncology+%3A+official+journal+of+the+European+Society+for+Medical+Oncology&rft.issn=09237534&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-31 N1 - Date created - 1997-07-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation of toxin ADP-ribosyltransferases by the family of ADP-ribosylation factors. AN - 79070717; 9193671 AB - ADP-ribosylation factors or ARFs are 20-kDa guanine nucleotide-binding proteins, initially identified as stimulators of cholera toxin-catalyzed ADP-ribosylation of Gs alpha. We now know that ARFs play a critical role in many vesicular trafficking events and ARF activation of a membrane-associated phospholipase D (PLD) has been recognized. ARF is active and associates with membranes when GTP is bound. The active state is terminated by hydrolysis of bound GTP, producing inactive ARF-GDP. The nucleotide effect on ARF association with membranes is related to alteration in orientation of the N-terminal myristoyl moiety that is important for ARF function. Cycling of ARF between active and inactive states involves guanine nucleotide-exchange proteins (GEPs) that accelerate replacement of bound GDP with GTP and GTPase-activating proteins (GAPS) that are responsible for ARF inactivation. Six mammalian ARFs have been identified by cDNA cloning. Class I ARFs 1 and 3 have been studied most extensively. Their activation (GTP binding) is catalyzed by a GEP now purified from spleen cytosol. In crude preparations, GEP was inhibited by brefeldin A (BFA), which in cells causes apparent disintegration of Golgi. Demonstration that the approximately 60 kDa purified GEP was not inhibited by BFA means that contrary to earlier belief, there must be another protein to mediate BFA inhibition. GEP activity was greatly enhanced by phosphatidyl serine. The purified GEP, equally active with ARFs 1 and 3, was inactive with ARFs 5 and 6 (Classes II and III); myristoylated ARFs were better substrates than were their non-myristoylated counterparts. ARF GAP purified from bovine spleen cytosol in our laboratory had much broader substrate specificity than the GEP. It used both ARFs 5 and 6 at least as well as ARFs 1 and 3; myristoylation was without effect. It also accelerated GTP hydrolysis by certain ARF mutants and an ARF-like protein (ARL1) that does not have ARF activity. The purified GAP also differed from the GEP in its rather specific requirement for phosphatidylinositol bisphosphate. This was also observed with a seemingly different ARF GAP that was purified and subsequently cloned in Cassel's laboratory. Activation and inactivation of ARFs present many potential sites for physiological regulation and, therefore, for pathological disruption of ARF function. JF - Advances in experimental medicine and biology AU - Vaughan, M AU - Moss, J AD - Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institute of Health, Bethesda, Maryland, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 315 EP - 320 VL - 419 SN - 0065-2598, 0065-2598 KW - Cholera Toxin KW - 9012-63-9 KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - ADP-Ribosylation Factors KW - EC 3.6.5.2 KW - Index Medicus KW - Animals KW - Enzyme Activation KW - GTP-Binding Proteins -- metabolism KW - Poly(ADP-ribose) Polymerases -- physiology KW - Poly(ADP-ribose) Polymerases -- metabolism KW - Cholera Toxin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79070717?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+experimental+medicine+and+biology&rft.atitle=Activation+of+toxin+ADP-ribosyltransferases+by+the+family+of+ADP-ribosylation+factors.&rft.au=Vaughan%2C+M%3BMoss%2C+J&rft.aulast=Vaughan&rft.aufirst=M&rft.date=1997-01-01&rft.volume=419&rft.issue=&rft.spage=315&rft.isbn=&rft.btitle=&rft.title=Advances+in+experimental+medicine+and+biology&rft.issn=00652598&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-04 N1 - Date created - 1997-09-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Determinants of cytotoxicity with prolonged exposure to fluorouracil in human colon cancer cells. AN - 79009690; 9167189 AB - To explore the determinants of cytotoxicity during prolonged exposure to pharmacologically relevant concentrations of 5-fluorouracil (FUra), we studied the effects of FUra at concentrations ranging from 0.1 to 1 microM in HCT 116 and HT 29 colon cancer cells grown in the presence of physiologic levels of leucovorin. A 5- and 7-day exposure to 1 microM FUra reduced cell growth to 46% and 20% of control in HT 29 cells and to 74% and 38% of control in HCT 116 cells. Concurrent exposure to thymidine (10 or 20 microM) or uridine (1 mM) provided partial protection against FUra toxicity in HT 29 cells, but did not protect HCT 116 cells. After a 24-h exposure to 1 microM [3H]FUra, free 5-fluoro-2'-deoxyuridine-5' -monophosphate (FdUMP) and FUDP. + FUTP levels were 0.7 and 144 pmol/10(6) cells in HT 29 cells, respectively, and 3.9 and 178 pmol/10(6) cells in HCT 116 cells. FdUMP and FUDP + FUTP pools increased by 5.7- and 2.0-fold in HT 29 cells and by 1.7- and 3.3-fold in HCT 116 cells over the next 48 h, but did not accumulate thereafter. After a 24-h exposure to 1 microM [3H]FUra, FUra-RNA levels were 158 and 280 fmol/microgram in HT 29 and HCT 116 cells, respectively; FUra-RNA levels increased over time, and reached 700 and 1156 fmol/microgram at day 5. Concurrent exposure to 1 mM uridine for 72 h did not diminish [3H]FUra-RNA incorporation. Upon removal of [3H]FUra following a 24-h exposure, FUra-RNA levels remained relatively stable with 57-78% retained at 120 h. A low level of [3H]FUra-DNA incorporation was detected in HT 29 cells. Thymidylate synthase (TS) catalytic activity in control cells was 2-fold higher in HCT 116 cells compared to HT 29 cells (47 vs. 23 pmol/min/mg). Total TS content increased 1.5- to 3-fold over control in both cell lines during FUra exposure, and ternary complex formation was evident for up to 96 h-dTTP pools were not depleted in FUra-treated cells, suggesting that residual TS catalytic activity was sufficient to maintain dTTP pools relative to demand. Surprisingly, the partial inhibition of TS was accompanied by a striking accumulation of immunoreactive "dUMP" pools in both lines; dUTP pools also increased 2-to 3-fold. In summary, the gradual and stable accumulation of FUra in RNA noted in both lines may account for the thymidine-insensitive component of FUra toxicity. Because dTTP pools were not appreciably diminished, the interference with nascent DNA chain elongation and induction of single-strand breaks in newly synthesized DNA in both cell lines may be due to misincorporation of deoxyuridine nucleotides. JF - Oncology research AU - Ren, Q AU - Van Groeningen, C J AU - Hardcastle, A AU - Aherne, G W AU - Geoffroy, F AU - Allegra, C J AU - Johnston, P G AU - Grem, J L AD - Developmental Therapeutics Department, National Cancer Institute, National Naval Medical Center, Bethesda, MD 20889-5105, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 77 EP - 88 VL - 9 IS - 2 SN - 0965-0407, 0965-0407 KW - 5-fluoro-2'-deoxyuridine-5'-diphosphate KW - 0 KW - DNA, Neoplasm KW - Deoxyribonucleotides KW - Deoxyuracil Nucleotides KW - Fluorodeoxyuridylate KW - 134-46-3 KW - 5-fluorouridine 5'-triphosphate KW - 3828-96-4 KW - Thymidylate Synthase KW - EC 2.1.1.45 KW - Leucovorin KW - Q573I9DVLP KW - Fluorouracil KW - U3P01618RT KW - Uridine Triphosphate KW - UT0S826Z60 KW - Index Medicus KW - Dose-Response Relationship, Drug KW - Humans KW - Cell Division -- drug effects KW - Deoxyuracil Nucleotides -- metabolism KW - Uridine Triphosphate -- metabolism KW - DNA, Neoplasm -- drug effects KW - Thymidylate Synthase -- antagonists & inhibitors KW - Tumor Cells, Cultured KW - Gene Expression Regulation, Enzymologic -- drug effects KW - Fluorodeoxyuridylate -- metabolism KW - Deoxyribonucleotides -- metabolism KW - Uridine Triphosphate -- analogs & derivatives KW - Colonic Neoplasms KW - Thymidylate Synthase -- biosynthesis KW - Cell Survival -- drug effects KW - Fluorouracil -- toxicity KW - DNA Damage KW - Leucovorin -- pharmacology KW - Fluorouracil -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79009690?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncology+research&rft.atitle=Determinants+of+cytotoxicity+with+prolonged+exposure+to+fluorouracil+in+human+colon+cancer+cells.&rft.au=Ren%2C+Q%3BVan+Groeningen%2C+C+J%3BHardcastle%2C+A%3BAherne%2C+G+W%3BGeoffroy%2C+F%3BAllegra%2C+C+J%3BJohnston%2C+P+G%3BGrem%2C+J+L&rft.aulast=Ren&rft.aufirst=Q&rft.date=1997-01-01&rft.volume=9&rft.issue=2&rft.spage=77&rft.isbn=&rft.btitle=&rft.title=Oncology+research&rft.issn=09650407&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-10 N1 - Date created - 1997-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The human health effects of DDT (dichlorodiphenyltrichloroethane) and PCBS (polychlorinated biphenyls) and an overview of organochlorines in public health. AN - 79007236; 9143718 AB - Organochlorines are a diverse group of persistent synthetic compounds, some of which are detectable in nearly everyone. Many organochlorines are endocrine disruptors or carcinogens in experimental assays. p,p'-DDE (dichlorodiphenyl-dichloroethene) and PCBs (polychlorinated biphenyls) comprise the bulk of organochlorine residues in human tissues. We reviewed relevant human data cited in the 1991-1995 Medline database and elsewhere. High-level exposure to selected organochlorines appears to cause abnormalities of liver function, skin (chloracne), and the nervous system. Of more general interest, however, is evidence suggesting insidious effects of background exposure. Of particular concern is the finding of neonatal hypotonia or hyporeflexia in relation to PCB exposure. The epidemiologic data reviewed, considered in isolation, provide no convincing evidence that organochlorines cause a large excess number of cancers. A recent risk assessment that considered animal data, however, gives a cancer risk estimate for background exposure to dioxin and dioxin-like compounds (e.g. some PCBs) with an upper bound in the range of 10(-4) per year. JF - Annual review of public health AU - Longnecker, M P AU - Rogan, W J AU - Lucier, G AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. longnecker@niehs.nih.gov Y1 - 1997 PY - 1997 DA - 1997 SP - 211 EP - 244 VL - 18 SN - 0163-7525, 0163-7525 KW - Dioxins KW - 0 KW - Insecticides KW - DDT KW - CIW5S16655 KW - Polychlorinated Biphenyls KW - DFC2HB4I0K KW - Index Medicus KW - Dioxins -- adverse effects KW - Humans KW - Adult KW - Infant, Newborn KW - Risk Assessment KW - Insecticides -- adverse effects KW - Public Health KW - Environmental Health KW - DDT -- adverse effects KW - Morbidity KW - Polychlorinated Biphenyls -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79007236?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annual+review+of+public+health&rft.atitle=The+human+health+effects+of+DDT+%28dichlorodiphenyltrichloroethane%29+and+PCBS+%28polychlorinated+biphenyls%29+and+an+overview+of+organochlorines+in+public+health.&rft.au=Longnecker%2C+M+P%3BRogan%2C+W+J%3BLucier%2C+G&rft.aulast=Longnecker&rft.aufirst=M&rft.date=1997-01-01&rft.volume=18&rft.issue=&rft.spage=211&rft.isbn=&rft.btitle=&rft.title=Annual+review+of+public+health&rft.issn=01637525&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-27 N1 - Date created - 1997-06-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The influence of comorbid major depression and substance use disorders on alcohol and drug treatment: results of a national survey. AN - 79005235; 9154262 JF - NIDA research monograph AU - Grant, B F AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892-7003, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 4 EP - 15 VL - 172 SN - 1046-9516, 1046-9516 KW - Index Medicus KW - Random Allocation KW - Humans KW - Adult KW - Surveys and Questionnaires KW - Data Collection KW - Adolescent KW - United States -- epidemiology KW - Comorbidity KW - Prevalence KW - Ambulatory Care KW - Depressive Disorder -- epidemiology KW - Substance-Related Disorders -- therapy KW - Alcoholism -- epidemiology KW - Alcoholism -- therapy KW - Substance Abuse Treatment Centers -- utilization KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79005235?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NIDA+research+monograph&rft.atitle=The+influence+of+comorbid+major+depression+and+substance+use+disorders+on+alcohol+and+drug+treatment%3A+results+of+a+national+survey.&rft.au=Grant%2C+B+F&rft.aulast=Grant&rft.aufirst=B&rft.date=1997-01-01&rft.volume=172&rft.issue=&rft.spage=4&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-06 N1 - Date created - 1997-06-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Absence of systemic in vivo genotoxicity after dermal exposure to ethyl acrylate and tripropylene glycol diacrylate in Tg.AC (v-Ha-ras) mice. AN - 79003701; 9142166 AB - Acrylates may be polymerized to stable surface coatings (paints, lacquers, inks, etc.) by alkylation via the Michaelis-type addition reaction. Thus, acrylates have an inherent potential as electrophiles to be genotoxic, limited in their biological activity by their physicochemical properties. To evaluate their systemic genotoxicity, ethyl acrylate (EA), tripropylene glycol diacrylate (TPGDA), or Lacquer A, an ultraviolet radiation curable lacquer containing TPGDA as the active ingredient, were applied dermally to Tg.AC mice (3 times a week for 20 weeks). Peripheral blood leukocytes were evaluated for DNA damage (single-strand breaks, alkali labile sites, DNA crosslinking) at weeks 4, 8, 12, 16, and 20 by using the alkaline (pH: 13) single cell gel (SCG) assay. Peripheral blood polychromatic erythrocytes (PCE) and normochromatic erythrocytes (NCE) were evaluated for the presence of micronuclei at week 20. The extent of DNA migration in leukocytes and the frequency of micronucleated erythrocytes was not significantly altered by treatment with TPGDA when administered alone or in Lacquer A or with EA, at doses that induced cell proliferation in keratinocytes. The absence of genotoxicity in these two cell populations suggests that these acrylates are not genotoxic or that they are not absorbed systemically when applied dermally. However, a significant, dose-dependent increase in the percentage of PCE relative to the vehicle control was present in mice treated with TPGDA, while a dose-dependent, but nonsignificant, increase in the percentage of PCE was observed in mice treated with Lacquer A. This observed increase in the rate of erythropoiesis may reflect bone marrow/blood toxicity, a homeostatic mechanism in response to the treatment-induced tumor burden, and/or a hematopoietic response to epidermal keratinocyte cytokines induced by tissue injury. JF - Environmental and molecular mutagenesis AU - Tice, R R AU - Nylander-French, L A AU - French, J E AD - Integrated Laboratory Systems, Research Triangle Park, NC 27709, USA. tice@niehs.nih.gov Y1 - 1997 PY - 1997 DA - 1997 SP - 240 EP - 249 VL - 29 IS - 3 SN - 0893-6692, 0893-6692 KW - Acrylates KW - 0 KW - Propylene Glycols KW - tripropylene glycol diacrylate KW - 42978-66-5 KW - ethyl acrylate KW - 71E6178C9T KW - Index Medicus KW - Animals KW - Erythrocytes, Abnormal KW - Micronucleus Tests KW - DNA Damage KW - Mice KW - Mice, Transgenic KW - Female KW - Administration, Topical KW - Propylene Glycols -- administration & dosage KW - Propylene Glycols -- toxicity KW - Acrylates -- toxicity KW - Acrylates -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79003701?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+and+molecular+mutagenesis&rft.atitle=Absence+of+systemic+in+vivo+genotoxicity+after+dermal+exposure+to+ethyl+acrylate+and+tripropylene+glycol+diacrylate+in+Tg.AC+%28v-Ha-ras%29+mice.&rft.au=Tice%2C+R+R%3BNylander-French%2C+L+A%3BFrench%2C+J+E&rft.aulast=Tice&rft.aufirst=R&rft.date=1997-01-01&rft.volume=29&rft.issue=3&rft.spage=240&rft.isbn=&rft.btitle=&rft.title=Environmental+and+molecular+mutagenesis&rft.issn=08936692&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-02 N1 - Date created - 1997-06-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevalence and distribution of dental restorative materials in US Air Force veterans. AN - 78988265; 9150058 AB - Millions of restorative procedures are performed annually in the United States, yet very little is known about their distribution in the general population. With increasing concern about potential adverse health effects of some restorative materials, a better understanding of the extent of exposure to these materials in the population is important. The purpose of this study is to report the prevalence, patterns, and distribution of dental restorative materials in a population of male veterans. This collaborative study with the US Air Force examined 1,166 male veterans to assess exposure to dental amalgam and other restorative materials. An inventory of dental materials in the study population was obtained through oral examinations. Dental materials were classified into five categories: (1) amalgam; (2) resin; (3) porcelain, cement, or temporary, including ionomer (PCT); (4) cast gold alloys/direct filling gold; and (5) other metals (OM). The mean age of the study participants was 52.9 years. Over 94 percent of the study participants were dentate. The study participants averaged 45.8 restored/replaced surfaces. Restored/replaced surfaces increased with age while the number of teeth decreased with age. The most frequently used restorative material was amalgam, averaging 19.89 surfaces per subject, followed by PCT (9.38), resins (8.99), OM (5.52), and gold (4.91). The distributions of restorative materials varied by age, arch type, and location in the mouth. The study population experienced substantial exposure to dental materials. JF - Journal of public health dentistry AU - Albertini, T F AU - Kingman, A AU - Brown, L J AD - Division of Intramural Research, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892, USA. albertinit@de45.nidr.nih.gov Y1 - 1997 PY - 1997 DA - 1997 SP - 5 EP - 10 VL - 57 IS - 1 SN - 0022-4006, 0022-4006 KW - Dental Alloys KW - 0 KW - Dental Cements KW - Dental Materials KW - Glass Ionomer Cements KW - Gold Alloys KW - Resins, Synthetic KW - Dental Porcelain KW - 12001-21-7 KW - Dental Amalgam KW - 8049-85-2 KW - Dentistry KW - Index Medicus KW - Aviation KW - Resins, Synthetic -- adverse effects KW - Jaw, Edentulous -- epidemiology KW - Age Factors KW - Dental Cements -- adverse effects KW - Humans KW - Aged KW - Gold Alloys -- adverse effects KW - Dental Alloys -- adverse effects KW - Dental Restoration, Temporary -- adverse effects KW - Adult KW - Glass Ionomer Cements -- adverse effects KW - Dental Amalgam -- adverse effects KW - Dental Restoration, Temporary -- statistics & numerical data KW - Dentition KW - Environmental Exposure KW - Tooth Loss -- epidemiology KW - Middle Aged KW - Dental Porcelain -- adverse effects KW - United States -- epidemiology KW - Male KW - Prevalence KW - Dental Restoration, Permanent -- statistics & numerical data KW - Dental Materials -- adverse effects KW - Veterans -- statistics & numerical data KW - Dental Restoration, Permanent -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78988265?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+public+health+dentistry&rft.atitle=Prevalence+and+distribution+of+dental+restorative+materials+in+US+Air+Force+veterans.&rft.au=Albertini%2C+T+F%3BKingman%2C+A%3BBrown%2C+L+J&rft.aulast=Albertini&rft.aufirst=T&rft.date=1997-01-01&rft.volume=57&rft.issue=1&rft.spage=5&rft.isbn=&rft.btitle=&rft.title=Journal+of+public+health+dentistry&rft.issn=00224006&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-17 N1 - Date created - 1997-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recent advances in the molecular genetics of hereditary breast and ovarian cancer. AN - 78972627; 9108588 JF - Progress in clinical and biological research AU - Lancaster, J M AU - Wiseman, R W AD - Laboratory of Molecular Carcinogenesis, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 31 EP - 51 VL - 396 SN - 0361-7742, 0361-7742 KW - Index Medicus KW - Causality KW - Genetic Testing KW - Genes, Tumor Suppressor KW - Humans KW - Genes, BRCA1 KW - Proto-Oncogenes KW - Female KW - Breast Neoplasms -- genetics KW - Ovarian Neoplasms -- genetics KW - Breast Neoplasms -- epidemiology KW - Ovarian Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78972627?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Progress+in+clinical+and+biological+research&rft.atitle=Recent+advances+in+the+molecular+genetics+of+hereditary+breast+and+ovarian+cancer.&rft.au=Lancaster%2C+J+M%3BWiseman%2C+R+W&rft.aulast=Lancaster&rft.aufirst=J&rft.date=1997-01-01&rft.volume=396&rft.issue=&rft.spage=31&rft.isbn=&rft.btitle=&rft.title=Progress+in+clinical+and+biological+research&rft.issn=03617742&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-14 N1 - Date created - 1997-07-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tamoxifen Breast Cancer Prevention Trial--an update. AN - 78960428; 9108604 JF - Progress in clinical and biological research AU - Ford, L G AU - Johnson, K A AD - Division of Cancer Prevention and Control, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 271 EP - 282 VL - 396 SN - 0361-7742, 0361-7742 KW - Antineoplastic Agents, Hormonal KW - 0 KW - Estrogen Antagonists KW - Placebos KW - Tamoxifen KW - 094ZI81Y45 KW - Index Medicus KW - Uterine Neoplasms -- epidemiology KW - Uterine Neoplasms -- chemically induced KW - Risk Factors KW - Humans KW - Follow-Up Studies KW - Female KW - Chemotherapy, Adjuvant KW - Tamoxifen -- therapeutic use KW - Breast Neoplasms -- prevention & control KW - Estrogen Antagonists -- therapeutic use KW - Breast Neoplasms -- epidemiology KW - Antineoplastic Agents, Hormonal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78960428?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Progress+in+clinical+and+biological+research&rft.atitle=Tamoxifen+Breast+Cancer+Prevention+Trial--an+update.&rft.au=Ford%2C+L+G%3BJohnson%2C+K+A&rft.aulast=Ford&rft.aufirst=L&rft.date=1997-01-01&rft.volume=396&rft.issue=&rft.spage=271&rft.isbn=&rft.btitle=&rft.title=Progress+in+clinical+and+biological+research&rft.issn=03617742&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-14 N1 - Date created - 1997-07-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modification of proteins in endothelial cell death during oxidative stress. AN - 78947790; 9098102 AB - Exposure of bovine aortic endothelial cells in vitro to oxidative stress causes a cascade of changes in cell function, culminating in cell death if the stress is sufficiently severe. Oxidative modification of proteins, as measured by the reaction of 2,4-dinitrophenylhydrazine with carbonyl groups of oxidized proteins, increased three- to fourfold in endothelial cells exposed to hydrogen peroxide or to a xanthine/xanthine oxidase system. The increase in oxidative modification of protein occurred rapidly, preceding loss of cellular ATP and eventual cell death. Oxidative modification of protein was paralleled by loss of activity of the key metabolic enzymes, glucose-6-phosphate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase. The finding that oxidative modification of protein is an early event following oxidative stress suggests that oxidative modification of protein is not only a marker for oxidative damage but also a causal factor in oxidative injury. JF - Free radical biology & medicine AU - Ciolino, H P AU - Levine, R L AD - Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-0320, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 1277 EP - 1282 VL - 22 IS - 7 SN - 0891-5849, 0891-5849 KW - Chlorides KW - 0 KW - Ferric Compounds KW - Phenylhydrazines KW - Proteins KW - Chromium KW - 0R0008Q3JB KW - 2,4-dinitrophenylhydrazine KW - 1N39KD7QPJ KW - Oxyquinoline KW - 5UTX5635HP KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Hydrogen Peroxide KW - BBX060AN9V KW - Glucosephosphate Dehydrogenase KW - EC 1.1.1.49 KW - Glyceraldehyde-3-Phosphate Dehydrogenases KW - EC 1.2.1.- KW - ferric chloride KW - U38V3ZVV3V KW - Index Medicus KW - Animals KW - Glyceraldehyde-3-Phosphate Dehydrogenases -- metabolism KW - Aorta KW - Ferric Compounds -- toxicity KW - Hydrogen Peroxide -- pharmacology KW - Phenylhydrazines -- pharmacology KW - Ferric Compounds -- metabolism KW - Chromium -- metabolism KW - Oxyquinoline -- metabolism KW - Glucosephosphate Dehydrogenase -- metabolism KW - Cattle KW - Cells, Cultured KW - Adenosine Triphosphate -- metabolism KW - Endothelium, Vascular -- metabolism KW - Endothelium, Vascular -- cytology KW - Oxidative Stress KW - Cell Death KW - Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78947790?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+radical+biology+%26+medicine&rft.atitle=Modification+of+proteins+in+endothelial+cell+death+during+oxidative+stress.&rft.au=Ciolino%2C+H+P%3BLevine%2C+R+L&rft.aulast=Ciolino&rft.aufirst=H&rft.date=1997-01-01&rft.volume=22&rft.issue=7&rft.spage=1277&rft.isbn=&rft.btitle=&rft.title=Free+radical+biology+%26+medicine&rft.issn=08915849&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-29 N1 - Date created - 1997-07-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Radiation and breast cancer risk. AN - 78946823; 9108593 JF - Progress in clinical and biological research AU - Land, C E AD - Radiation Epidemiology Branch, National Cancer Institute, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 115 EP - 124 VL - 396 SN - 0361-7742, 0361-7742 KW - Carcinogens, Environmental KW - 0 KW - Index Medicus KW - North America -- epidemiology KW - Nuclear Warfare KW - Humans KW - Survival KW - Incidence KW - Europe -- epidemiology KW - Female KW - Radiation, Ionizing KW - Carcinogens, Environmental -- adverse effects KW - Breast Neoplasms -- etiology KW - Breast Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78946823?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Progress+in+clinical+and+biological+research&rft.atitle=Radiation+and+breast+cancer+risk.&rft.au=Land%2C+C+E&rft.aulast=Land&rft.aufirst=C&rft.date=1997-01-01&rft.volume=396&rft.issue=&rft.spage=115&rft.isbn=&rft.btitle=&rft.title=Progress+in+clinical+and+biological+research&rft.issn=03617742&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-14 N1 - Date created - 1997-07-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronic immunosuppressive therapy for systemic vasculitis. AN - 78941312; 9110133 AB - Treatment with glucocorticoids and cytotoxic agents has markedly improved the outcome in patients with systemic vasculitis. As more patients survive with these disorders, the long-term risks of these therapies have become increasingly apparent. An understanding of therapeutic toxicities is important because in some instances they can be minimized by the use of treatment strategies and monitoring techniques. Pneumocystis carinii pneumonia is associated with a high mortality rate in immunosuppressed patients but can be prevented by prophylaxis. Glucocorticoid-related avascular necrosis can incur morbidity affecting employment and daily function. Although treatment options remain limited, investigation into joint salvage procedures has continued. The frequency and longevity of urologic toxicity associated with cyclophosphamide therapy have recently been addressed. Identification of this risk has led to the development of long-term monitoring strategies in cyclophosphamide-treated patients. JF - Current opinion in rheumatology AU - Langford, C A AD - Immunologic Diseases Section, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/01// PY - 1997 DA - January 1997 SP - 41 EP - 47 VL - 9 IS - 1 SN - 1040-8711, 1040-8711 KW - Glucocorticoids KW - 0 KW - Immunosuppressive Agents KW - Cyclophosphamide KW - 8N3DW7272P KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Pneumocystis Infections -- etiology KW - Cyclophosphamide -- therapeutic use KW - Methotrexate -- adverse effects KW - Humans KW - Methotrexate -- therapeutic use KW - Glucocorticoids -- adverse effects KW - Glucocorticoids -- therapeutic use KW - Cyclophosphamide -- adverse effects KW - Vasculitis -- complications KW - Vasculitis -- drug therapy KW - Vasculitis -- immunology KW - Immunosuppressive Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78941312?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+rheumatology&rft.atitle=Chronic+immunosuppressive+therapy+for+systemic+vasculitis.&rft.au=Langford%2C+C+A&rft.aulast=Langford&rft.aufirst=C&rft.date=1997-01-01&rft.volume=9&rft.issue=1&rft.spage=41&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+rheumatology&rft.issn=10408711&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-18 N1 - Date created - 1997-06-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - New developments in the treatment of Wegener's granulomatosis, polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome. AN - 78941229; 9110130 AB - With the opportunity for long-term follow-up, it has been appreciated that disease severity may vary considerably in patients with Wegener's granulomatosis, polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome. Although combined therapy with cyclophosphamide and glucocorticoids continues to be the foundation of treatment, concerns have increased about the toxicities of this regimen. As illustrated by studies on Wegener's-related subglottic stenosis and endobronchial involvement, it has also become apparent that some disease manifestations may not respond to this therapy. Recent therapeutic investigations have therefore focused on identifying approaches that are less toxic and that are based on anatomic involvement and disease severity. The study of polyarteritis nodosa has additionally been affected by proposed changes in classification that would make this condition a separate entity from microscopic polyangiitis. As progress is made in defining the clinical significance of this nomenclature, the prognostic factors in these patients have also been examined, which may be helpful in guiding therapeutic decisions. JF - Current opinion in rheumatology AU - Langford, C A AU - Sneller, M C AD - Immunologic Diseases Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/01// PY - 1997 DA - January 1997 SP - 26 EP - 30 VL - 9 IS - 1 SN - 1040-8711, 1040-8711 KW - Index Medicus KW - Humans KW - Churg-Strauss Syndrome -- therapy KW - Granulomatosis with Polyangiitis -- therapy KW - Vasculitis -- therapy KW - Polyarteritis Nodosa -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78941229?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+rheumatology&rft.atitle=New+developments+in+the+treatment+of+Wegener%27s+granulomatosis%2C+polyarteritis+nodosa%2C+microscopic+polyangiitis%2C+and+Churg-Strauss+syndrome.&rft.au=Langford%2C+C+A%3BSneller%2C+M+C&rft.aulast=Langford&rft.aufirst=C&rft.date=1997-01-01&rft.volume=9&rft.issue=1&rft.spage=26&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+rheumatology&rft.issn=10408711&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-18 N1 - Date created - 1997-06-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selection of transfected cells. Magnetic affinity cell sorting. AN - 78932332; 9108532 JF - Methods in molecular biology (Clifton, N.J.) AU - Padmanabhan, R AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 343 EP - 358 VL - 62 SN - 1064-3745, 1064-3745 KW - Colloids KW - 0 KW - P-Glycoprotein KW - Recombinant Proteins KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Index Medicus KW - Recombinant Proteins -- isolation & purification KW - Animals KW - Plasmids -- genetics KW - Lymphoma -- genetics KW - HeLa Cells KW - Humans KW - Hybrid Cells KW - Gene Expression KW - P-Glycoprotein -- isolation & purification KW - Mammals -- genetics KW - beta-Galactosidase -- isolation & purification KW - Transfection -- methods KW - Immunomagnetic Separation KW - Selection, Genetic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78932332?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.atitle=Selection+of+transfected+cells.+Magnetic+affinity+cell+sorting.&rft.au=Padmanabhan%2C+R%3BThorgeirsson%2C+S+S&rft.aulast=Padmanabhan&rft.aufirst=R&rft.date=1997-01-01&rft.volume=62&rft.issue=&rft.spage=343&rft.isbn=&rft.btitle=&rft.title=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.issn=10643745&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-12 N1 - Date created - 1997-06-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo drug-selectable genes: a new concept in gene therapy. AN - 78907325; 9090786 AB - Chemoresistance genes, initially considered to be a major impediment to the successful treatment of cancer, may become useful tools for gene therapy of cancer and of genetically determined disorders. Various target cells are rendered resistant to anticancer drugs by transfer of chemoresistance genes encoding P-glycoprotein, the multidrug resistance-associated protein-transporter, dihydrofolate reductase, glutathione-S-transferase, O6-alkylguanine DNA alkyltransferase, or aldehyde reductase. These genes can be used for selection in vivo because of the pharmacology and pharmacokinetics of their substrates. In contrast, several other selectable marker genes conferring resistance to substrates like neomycin or hygromycin can only be utilized in tissue culture. Possible applications for chemoresistance genes include protection of bone marrow and other organs from adverse effects caused by the toxicity of chemotherapy. Strategies have also been developed to introduce and overexpress nonselectable genes in target cells by cotransduction with chemoresistance genes. Thereby expression of both transgenes can be increased following selection with drugs. Moreover, treatment with chemotherapeutic agents should restore transgene expression when or if expression levels decrease after several weeks or months. This approach may improve the efficacy of somatic gene therapy of hematopoietic disorders which is hampered by low or unstable gene expression in progenitor cells. In this article we review preclinical studies in tissue culture and animal models, and ongoing clinical trials on transfer of chemoresistance genes to hematopoietic precursor cells of cancer patients. JF - Stem cells (Dayton, Ohio) AU - Licht, T AU - Herrmann, F AU - Gottesman, M M AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 104 EP - 111 VL - 15 IS - 2 SN - 1066-5099, 1066-5099 KW - Index Medicus KW - Animals KW - Humans KW - Drug Resistance, Neoplasm KW - Animals, Genetically Modified KW - Genetic Therapy -- methods KW - Genes, MDR UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78907325?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Stem+cells+%28Dayton%2C+Ohio%29&rft.atitle=In+vivo+drug-selectable+genes%3A+a+new+concept+in+gene+therapy.&rft.au=Licht%2C+T%3BHerrmann%2C+F%3BGottesman%2C+M+M%3BPastan%2C+I&rft.aulast=Licht&rft.aufirst=T&rft.date=1997-01-01&rft.volume=15&rft.issue=2&rft.spage=104&rft.isbn=&rft.btitle=&rft.title=Stem+cells+%28Dayton%2C+Ohio%29&rft.issn=10665099&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-18 N1 - Date created - 1997-06-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hepatic tumor induction in c-myc mono-transgenic and TGF-alpha/c-myc double-transgenic mice. AN - 78896757; 9079223 AB - Double transgenic mice bearing fusion genes consisting of mouse albumin enhancer/promoter-mouse c-myc cDNA and mouse metallothionein 1 promoter-human TGF-alpha cDNA were generated to investigate the interaction of these genes in hepatic oncogenesis and to provide a general paradigm for characterizing both the interaction of nuclear oncogenes and growth factors in tumorigenesis as well as to produce an experimental model to test how environmental chemicals might interact with these genes during the neoplastic process. Coexpression of c-myc and TGF-alpha as transgenes in the mouse liver resulted in a tremendous acceleration of neoplastic development in this organ as compared to expression of either of these transgenes alone. The two distinct cellular reactions that occurred in the liver of the double transgenic mice prior to the appearance of liver tumors were dysplastic and apoptotic changes in the existing hepatocytes followed by emergence of multiple focal lesions composed of both hyperplastic and dysplastic cell populations. These observations suggest that the interaction of c-myc and TGF-alpha, during development of hepatic neoplasia contributes to the selection and expansion of the preneoplastic cell populations which consequently increases the probability of malignant conversion. Treatment of the double transgenic mice with both genotoxic agents such as diethylnitrosamine and IQ as well as the tumor promoter phenobarbital greatly accelerated the neoplastic process. These results suggest that selective transgenic mouse models may provide important tools for testing both the carcinogenic potential of environmental chemicals and the interaction/cooperation of these compounds with specific genes during the neoplastic process. JF - Archives of toxicology. Supplement. = Archiv fur Toxikologie. Supplement AU - Thorgeirsson, S S AU - Santoni-Rugiu, E AU - Davis, C D AU - Snyderwine, E G AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 359 EP - 366 VL - 19 SN - 0171-9750, 0171-9750 KW - Carcinogens KW - 0 KW - Proto-Oncogene Proteins c-myc KW - Quinolines KW - Transforming Growth Factor alpha KW - 2-amino-3-methylimidazo(4,5-f)quinoline KW - 30GL3D3T0G KW - Diethylnitrosamine KW - 3IQ78TTX1A KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Quinolines -- toxicity KW - Diethylnitrosamine -- toxicity KW - Animals KW - Carcinogens -- toxicity KW - Mice KW - Phenobarbital -- toxicity KW - Mice, Transgenic KW - Liver Neoplasms, Experimental -- genetics KW - Transforming Growth Factor alpha -- genetics KW - Liver Neoplasms, Experimental -- pathology KW - Proto-Oncogene Proteins c-myc -- genetics KW - Liver Neoplasms, Experimental -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78896757?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+toxicology.+Supplement.+%3D+Archiv+fur+Toxikologie.+Supplement&rft.atitle=Hepatic+tumor+induction+in+c-myc+mono-transgenic+and+TGF-alpha%2Fc-myc+double-transgenic+mice.&rft.au=Thorgeirsson%2C+S+S%3BSantoni-Rugiu%2C+E%3BDavis%2C+C+D%3BSnyderwine%2C+E+G&rft.aulast=Thorgeirsson&rft.aufirst=S&rft.date=1997-01-01&rft.volume=19&rft.issue=&rft.spage=359&rft.isbn=&rft.btitle=&rft.title=Archives+of+toxicology.+Supplement.+%3D+Archiv+fur+Toxikologie.+Supplement&rft.issn=01719750&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-12 N1 - Date created - 1997-06-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structural basis of receptor/G protein coupling selectivity studied with muscarinic receptors as model systems. AN - 78884488; 9121341 AB - Different muscarinic acetylcholine receptor subtypes were used as model systems to study the structural basis of receptor/G protein coupling selectivity. Extensive mutagenesis studies have previously led to the identification of single amino acids on the m3 muscarinic receptor protein (located in the second intracellular loop (i2) and at the N- and C-terminus of the third intracellular loop (i3)) that dictate selective recognition of Gq/11 proteins by this receptor subtype. Based on these results, we proposed a model of the intracellular m3 receptor surface in which the functionally critical residues project into the interior of the transmembrane receptor core. To identify specific regions on the G protein(s) that are contacted by these different, functionally critical receptor sites, we recently employed a novel experimental strategy involving the coexpression of hybrid m2/m3 muscarinic receptors with hybrid G alpha-subunits. Using this approach, we could demonstrate that the C-terminus of G protein alpha i/o-subunits is recognized by a short sequence element in the m2 muscarinic receptor ("VTIL") that is located at the junction between the sixth transmembrane domain (TM VI) and the i3 loop. We could show that this interaction is critically involved in determining coupling selectivity and triggering G protein activation. By using a similar strategy (coexpression of mutant muscarinic receptors with hybrid G alpha-subunits), other major receptor/G protein contact sites are currently being identified. These studies, complemented by biochemical and biophysical approaches, should eventually lead to a detailed structural model of the ligand-receptor-G protein complex. JF - Life sciences AU - Wess, J AU - Liu, J AU - Blin, N AU - Yun, J AU - Lerche, C AU - Kostenis, E AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 1007 EP - 1014 VL - 60 IS - 13-14 SN - 0024-3205, 0024-3205 KW - Receptors, Muscarinic KW - 0 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Humans KW - Structure-Activity Relationship KW - GTP-Binding Proteins -- chemistry KW - GTP-Binding Proteins -- physiology KW - Receptors, Muscarinic -- chemistry KW - Receptors, Muscarinic -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78884488?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Life+sciences&rft.atitle=Structural+basis+of+receptor%2FG+protein+coupling+selectivity+studied+with+muscarinic+receptors+as+model+systems.&rft.au=Wess%2C+J%3BLiu%2C+J%3BBlin%2C+N%3BYun%2C+J%3BLerche%2C+C%3BKostenis%2C+E&rft.aulast=Wess&rft.aufirst=J&rft.date=1997-01-01&rft.volume=60&rft.issue=13-14&rft.spage=1007&rft.isbn=&rft.btitle=&rft.title=Life+sciences&rft.issn=00243205&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-23 N1 - Date created - 1997-04-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Complications of cyclophosphamide therapy. AN - 78879842; 9065658 AB - Cyclophosphamide is a powerful immunosuppressive agent that is commonly used clinically to treat neoplastic and inflammatory diseases affecting various sites, including the head and neck. The pharmacology of cyclophosphamide is reviewed with an emphasis on its toxicities and strategies for minimizing therapeutic adverse effects. Principles of therapy are discussed and illustrated by the use of cyclophosphamide in the treatment of Wegener's granulomatosis, a form of systemic vasculitis with prominent head and neck manifestations. JF - European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery AU - Langford, C A AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 65 EP - 72 VL - 254 IS - 2 SN - 0937-4477, 0937-4477 KW - Immunosuppressive Agents KW - 0 KW - Cyclophosphamide KW - 8N3DW7272P KW - Index Medicus KW - Neoplasms -- drug therapy KW - Humans KW - Lung -- drug effects KW - Bone Marrow -- drug effects KW - Granulomatosis with Polyangiitis -- drug therapy KW - Clinical Protocols KW - Inflammation KW - Cyclophosphamide -- therapeutic use KW - Immunosuppressive Agents -- therapeutic use KW - Immunosuppressive Agents -- pharmacology KW - Immunosuppressive Agents -- adverse effects KW - Cyclophosphamide -- pharmacology KW - Cyclophosphamide -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78879842?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+archives+of+oto-rhino-laryngology+%3A+official+journal+of+the+European+Federation+of+Oto-Rhino-Laryngological+Societies+%28EUFOS%29+%3A+affiliated+with+the+German+Society+for+Oto-Rhino-Laryngology+-+Head+and+Neck+Surgery&rft.atitle=Complications+of+cyclophosphamide+therapy.&rft.au=Langford%2C+C+A&rft.aulast=Langford&rft.aufirst=C&rft.date=1997-01-01&rft.volume=254&rft.issue=2&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=European+archives+of+oto-rhino-laryngology+%3A+official+journal+of+the+European+Federation+of+Oto-Rhino-Laryngological+Societies+%28EUFOS%29+%3A+affiliated+with+the+German+Society+for+Oto-Rhino-Laryngology+-+Head+and+Neck+Surgery&rft.issn=09374477&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-29 N1 - Date created - 1997-05-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reproductive toxicity of di-n-butylphthalate in a continuous breeding protocol in Sprague-Dawley rats. AN - 78878854; 9074889 AB - The phthalate ester di-n-butylphthalate (DBP) is used extensively in the manufacture of plastics; its reproductive toxicity was tested in rats by the National Toxicology Program's Reproductive Assessment by Continuous Breeding protocol. Levels of 0.1, 0.5, and 1.0% DBP in the diet were selected, and this dosing design yielded average daily DBP intakes of 52, 256, and 509 mg/kg for males and 80, 385, and 794 mg/kg for females, respectively. DBP consumption by F0 rats reduced the total number of live pups per litter in all treated groups by 8-17% and live pup weights in the 0.5% and 1.0% dose groups by < 13%. In tests to determine the affected sex, the number of offspring was unchanged, but the weights of pups from treated females were significantly decreased and offspring from treated males were unchanged. At necropsy, high-dose F0 females had a 14% reduction in body weight, and both sexes had approximately 10-15% increased kidney and liver to body weight ratios compared to controls. Sperm parameters and estrous cyclicity were not affected. In the F1 mating trial, indices of mating, pregnancy, and fertility in the 1.0% dose group were all sharply decreased (one live litter was delivered out of 20 cohabited pairs), concomitant with a 13% decrease in dam body weight. Live F2 pup weights were 6-8% lower in all dose groups. F1 necropsy results revealed that epididymal sperm counts and testicular spermatid head counts were significantly decreased in the 1.0% dose group. Histopathologic investigation showed that 8 of 10 F1 males consuming 1.0% DBP had degenerated seminiferous tubules and 5 of 10 had underdeveloped or otherwise defective epididymides. No ovarian or uterine lesions were observed. In conclusion, this study showed that DBP is a reproductive/developmental toxicant in Sprague-Dawley rats exposed both as adults and during development; it also indicates that the adverse reproductive/developmental effects of DBP on the second generation were greater than on the first generation. JF - Environmental health perspectives AU - Wine, R N AU - Li, L H AU - Barnes, L H AU - Gulati, D K AU - Chapin, R E AD - National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1997/01// PY - 1997 DA - January 1997 SP - 102 EP - 107 VL - 105 IS - 1 SN - 0091-6765, 0091-6765 KW - Dibutyl Phthalate KW - 2286E5R2KE KW - Index Medicus KW - Rats KW - Animals KW - Sperm Count -- drug effects KW - Rats, Sprague-Dawley KW - Body Weight -- drug effects KW - Male KW - Female KW - Pregnancy KW - Testis -- abnormalities KW - Penis -- abnormalities KW - Dibutyl Phthalate -- toxicity KW - Abnormalities, Drug-Induced -- etiology KW - Fertility -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78878854?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Reproductive+toxicity+of+di-n-butylphthalate+in+a+continuous+breeding+protocol+in+Sprague-Dawley+rats.&rft.au=Wine%2C+R+N%3BLi%2C+L+H%3BBarnes%2C+L+H%3BGulati%2C+D+K%3BChapin%2C+R+E&rft.aulast=Wine&rft.aufirst=R&rft.date=1997-01-01&rft.volume=105&rft.issue=1&rft.spage=102&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 - 1997-06-13 N1 - Date created - 1997-06-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Toxicol Appl Pharmacol. 1973 Oct;26(2):253-9 [4751104] Contact Dermatitis. 1995 Sep;33(3):157-64 [8565455] Toxicol Appl Pharmacol. 1977 Sep;41(3):609-18 [918990] Biochem Pharmacol. 1979 Jun 15;28(12):1865-77 [454458] Toxicol Appl Pharmacol. 1980 Jul;54(3):392-8 [7394794] Toxicol Lett. 1980 May;5(6):413-6 [7394838] Environ Health Perspect. 1982 Nov;45:3-9 [6754362] Toxicol Lett. 1983 Feb;15(2-3):265-71 [6829050] Crit Rev Toxicol. 1984;13(4):283-317 [6386344] Environ Health Perspect. 1986 Mar;65:229-35 [3709446] Environ Health Perspect. 1986 Mar;65:243-8 [3709448] Biometrics. 1986 Mar;42(1):183-6 [3719054] Exp Mol Pathol. 1987 Jun;46(3):357-71 [3595805] J Urol. 1987 Dec;138(6):1446-50 [3682076] Toxicol Appl Pharmacol. 1987 Dec;91(3):315-25 [2892284] Toxicol Appl Pharmacol. 1988 Aug;95(1):104-21 [3413790] J Appl Toxicol. 1989 Aug;9(4):277-83 [2506265] Fundam Appl Toxicol. 1989 Nov;13(4):747-77 [2620795] Fundam Appl Toxicol. 1991 Aug;17(2):270-9 [1765220] Exp Mol Pathol. 1993 Jun;58(3):179-93 [8519345] Leuk Res. 1993 Jul;17(7):557-60 [8326736] Environ Health Perspect. 1993 Apr;100:269-82 [8354175] J Appl Toxicol. 1993 Jul-Aug;13(4):241-6 [8376724] Toxicology. 1994 Feb 7;86(3):163-74 [8128502] J Am Mosq Control Assoc. 1994 Dec;10(4):565-71 [7707065] Arch Environ Contam Toxicol. 1995 Feb;28(2):223-8 [7710290] Biol Pharm Bull. 1994 Dec;17(12):1609-12 [7735204] Acta Odontol Scand. 1995 Apr;53(2):75-80 [7610779] Leuk Res. 1995 Aug;19(8):557-60 [7658702] Environ Health Perspect. 1995 Jun;103(6):582-7 [7556011] Biometrics. 1977 Jun;33(2):386-9 [884197] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transplacental cisplatin exposure induces persistent fetal mitochondrial and genomic DNA damage in patas monkeys. AN - 78871053; 9138639 AB - A previous attempt to model transplacental cisplatin exposure and genotoxicity employed several pregnant Erythrocebus patas monkeys; most of the animals were exposed near the end of gestation and cisplatin-DNA adduct analyses included only genomic DNA. Here, both genomic and mitochondrial DNA adduct formation have been determined in fetuses from two pregnant monkeys exposed at the end of the second trimester of gestation. Multiple fetal tissues were obtained after doses of 0.315 mg cisplatin/kg body weight (5.3 mg/m2 total) on days 101 and 106 of gestation. Cesarean sections were performed 24 h after exposure and 27 d after exposure. Cisplatin genomic (g)-DNA adducts were observed in fetal adrenal, brain, heart, kidney, liver, skin, spleen, and thymus. When placentas from the two animals were divided into four concentric regions at increasing distances from the umbilical cord, and g-DNA was assayed, cisplatin DNA adduct levels were similar in all four regions. Mitochondrial (mt)-DNA adducts were higher than g-DNA adducts in maternal liver and fetal liver, brain and kidney, suggesting that the mitochondria may constitute a particular target for cisplatin genotoxicity. The study demonstrates significant fetal genotoxicity in g-DNA and mt-DNA of patas monkeys exposed to cisplatin in utero, suggesting that similarly exposed human fetuses may also sustain drug-induced DNA damage. JF - Reproductive toxicology (Elmsford, N.Y.) AU - Giurgiovich, A J AU - Anderson, L M AU - Jones, A B AU - Dove, L F AU - Moskal, T J AU - Rice, J M AU - Olivero, O A AU - Poirier, M C AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. PY - 1997 SP - 95 EP - 100 VL - 11 IS - 1 SN - 0890-6238, 0890-6238 KW - DNA Adducts KW - 0 KW - DNA, Mitochondrial KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Animals KW - Organ Specificity -- genetics KW - Organ Specificity -- drug effects KW - Erythrocebus patas KW - DNA Adducts -- drug effects KW - Female KW - Prenatal Exposure Delayed Effects KW - Pregnancy KW - DNA, Mitochondrial -- drug effects KW - Maternal-Fetal Exchange -- drug effects KW - DNA Damage KW - Cisplatin -- toxicity KW - Embryonic and Fetal Development -- genetics KW - Placenta -- drug effects KW - Placenta -- metabolism KW - Embryonic and Fetal Development -- drug effects KW - Cisplatin -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78871053?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Reproductive+toxicology+%28Elmsford%2C+N.Y.%29&rft.atitle=Transplacental+cisplatin+exposure+induces+persistent+fetal+mitochondrial+and+genomic+DNA+damage+in+patas+monkeys.&rft.au=Giurgiovich%2C+A+J%3BAnderson%2C+L+M%3BJones%2C+A+B%3BDove%2C+L+F%3BMoskal%2C+T+J%3BRice%2C+J+M%3BOlivero%2C+O+A%3BPoirier%2C+M+C&rft.aulast=Giurgiovich&rft.aufirst=A&rft.date=1997-01-01&rft.volume=11&rft.issue=1&rft.spage=95&rft.isbn=&rft.btitle=&rft.title=Reproductive+toxicology+%28Elmsford%2C+N.Y.%29&rft.issn=08906238&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-08 N1 - Date created - 1997-05-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Acidic fibroblast growth factor (FGF1) increases survival and haematopoietic recovery in total body irradiated C3H/HeNCr mice. AN - 78862445; 9067097 AB - Basic fibroblast growth factor is known to stimulate the proliferation of bone marrow stem and/or progenitor cells in vitro and in vivo. We examined a similar cytokine, acidic fibroblast growth factor (FGF1), for its in vivo radiomodifying effects. Female C3H/HeNCr mice were given human recombinant FGF1 intravenously at doses ranging from 1 to 24 micrograms. FGF1 was delivered in two equal doses 24 and 4 h before or 24 h after otherwise lethal total body irradiation (TBI). In vivo FGF1 radioprotection of C3H mice was maximized at a total dose of 12 micrograms/mouse given before TBI. The radiomodification was 1.16 +/- 0.03 (+/- 1 SD) with an increase of LD50/30 from 736 +/- 9 to 854 +/- 16 cGy (P < 0.01). Some retroactive radiomodification was observed even when FGF1 was given 24 h after irradiation (P < 0.05). FGF1 radioprotected mice by improving the repopulation of haematopoietic progenitor cells of bone marrow. The radioprotection was not associated with an increase in S-phase fraction or detectable circulating IL-3, TNF-alpha or GM-CSF, suggesting that other mechanisms of protection were responsible. JF - Cytokine AU - Ding, I AU - Wu, T AU - Matsubara, H AU - Magae, J AU - Shou, M AU - Cook, J AU - Okunieff, P AD - Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997/01// PY - 1997 DA - January 1997 SP - 59 EP - 65 VL - 9 IS - 1 SN - 1043-4666, 1043-4666 KW - Radiation-Protective Agents KW - 0 KW - Recombinant Proteins KW - Fibroblast Growth Factor 1 KW - 104781-85-3 KW - Index Medicus KW - Animals KW - Survival Rate KW - Dose-Response Relationship, Drug KW - Humans KW - Mice, Inbred C3H KW - Lethal Dose 50 KW - Mice KW - Cell Cycle -- radiation effects KW - Bone Marrow Examination KW - Drug Evaluation, Preclinical KW - Recombinant Proteins -- therapeutic use KW - Female KW - Cell Cycle -- drug effects KW - Whole-Body Irradiation KW - Hematopoiesis -- radiation effects KW - Hematopoiesis -- drug effects KW - Radiation-Protective Agents -- pharmacology KW - Fibroblast Growth Factor 1 -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78862445?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytokine&rft.atitle=Acidic+fibroblast+growth+factor+%28FGF1%29+increases+survival+and+haematopoietic+recovery+in+total+body+irradiated+C3H%2FHeNCr+mice.&rft.au=Ding%2C+I%3BWu%2C+T%3BMatsubara%2C+H%3BMagae%2C+J%3BShou%2C+M%3BCook%2C+J%3BOkunieff%2C+P&rft.aulast=Ding&rft.aufirst=I&rft.date=1997-01-01&rft.volume=9&rft.issue=1&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=Cytokine&rft.issn=10434666&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-29 N1 - Date created - 1997-05-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pradimicins: a novel class of broad-spectrum antifungal compounds. AN - 78861614; 9063679 AB - Pradimicins are a new class of antifungal compounds currently undergoing preclinical and early phase I clinical trials. The pradimicin structure is characterized by an aglycone of dihydrobenzo (alpha) naphthacenequinone with substitutions by a D-amino acid and hexose sugar. Pradimicins possess a novel mechanism of action consisting of a specific binding recognition to terminal D-mannosides of the cell wall of Candida albicans, resulting in the formation of a ternary complex consisting of D-mannoside, pradimicin, and calcium that leads to disruption of the integrity of the fungal cell membrane. Pradimicin in the form of BMS-181184 has broad-spectrum in vitro antifungal activity against Candida spp., Cryptococcus neoformans, Aspergillus spp., dematiaceous molds, and the Zygomycetes. Fusarium spp. are comparatively resistant to high concentrations of pradimicin. Initial vivo studies indicate that pradimicins have antifungal activity against experimental murine disseminated candidiasis and disseminated aspergillosis. Early studies indicate an excellent therapeutic index with no major end-organ toxicity. Pradimicins warrant further investigation for treatment of opportunistic mycoses in immuno-compromised hosts. JF - European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology AU - Walsh, T J AU - Giri, N AD - Immunocompromised Host Section, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1997/01// PY - 1997 DA - January 1997 SP - 93 EP - 97 VL - 16 IS - 1 SN - 0934-9723, 0934-9723 KW - Antibiotics, Antineoplastic KW - 0 KW - Antifungal Agents KW - Index Medicus KW - Chemistry KW - Humans KW - Chemical Phenomena KW - Mycoses -- drug therapy KW - Structure-Activity Relationship KW - Antifungal Agents -- adverse effects KW - Antifungal Agents -- pharmacology KW - Antibiotics, Antineoplastic -- pharmacology KW - Antifungal Agents -- therapeutic use KW - Antibiotics, Antineoplastic -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78861614?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+clinical+microbiology+%26+infectious+diseases+%3A+official+publication+of+the+European+Society+of+Clinical+Microbiology&rft.atitle=Pradimicins%3A+a+novel+class+of+broad-spectrum+antifungal+compounds.&rft.au=Walsh%2C+T+J%3BGiri%2C+N&rft.aulast=Walsh&rft.aufirst=T&rft.date=1997-01-01&rft.volume=16&rft.issue=1&rft.spage=93&rft.isbn=&rft.btitle=&rft.title=European+journal+of+clinical+microbiology+%26+infectious+diseases+%3A+official+publication+of+the+European+Society+of+Clinical+Microbiology&rft.issn=09349723&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-03 N1 - Date created - 1997-07-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Upregulation of Gfi-1, a gene involved in IL-2-independent growth of T cells, in a murine retrovirus-induced immunodeficiency syndrome. AN - 78858990; 9067766 AB - A prominent feature of retrovirus-induced immunodeficiency in mice (MAIDS) is early polyclonal activation of CD4+ T cells followed by the appearance of monoclonal lymphomas marked by clonal proviral integrations. These events appear to occur independent of interleukin-2 (IL-2), suggesting the activity of an alternative growth-promoting pathway. We studied the possible contributions to T cell expansion of a gene, Gfi-1, previously shown to confer IL-2 independence to rat T cell lymphomas. We studied 17 mice with MAIDS that had clonal populations of T cells. Proviral integrations at Gfi-1 were detected in two animals. These integrations were associated with enhanced transcription of Gfi-1. Unexpectedly, elevated levels of Gfi-1 transcripts were also observed in four T cell lymphomas without detectable integrations at this locus. This suggests that IL-2-independent T cell growth in MAIDS may be driven by transcriptional activation of Gfi-1 by proviral insertion or transactivation. JF - In vivo (Athens, Greece) AU - Liao, X AU - Tang, Y AU - Chattopadhyay, S K AU - Hartley, J W AU - Morse, H C AD - Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0760, USA. PY - 1997 SP - 9 EP - 12 VL - 11 IS - 1 SN - 0258-851X, 0258-851X KW - DNA, Viral KW - 0 KW - DNA-Binding Proteins KW - Gfi1 protein, mouse KW - Gfi1 protein, rat KW - Interleukin-2 KW - Transcription Factors KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Interleukin-2 -- pharmacology KW - Gene Expression Regulation -- immunology KW - Cell Division -- drug effects KW - Gene Rearrangement KW - Transcription, Genetic -- immunology KW - Mice KW - Blotting, Southern KW - Cell Division -- immunology KW - DNA, Viral -- analysis KW - Zinc Fingers -- genetics KW - Mice, Inbred C57BL KW - Promoter Regions, Genetic -- genetics KW - Mice, SCID KW - Mutagenesis -- immunology KW - CD4-Positive T-Lymphocytes -- cytology KW - Murine Acquired Immunodeficiency Syndrome -- immunology KW - CD4-Positive T-Lymphocytes -- virology KW - DNA-Binding Proteins -- genetics KW - CD4-Positive T-Lymphocytes -- drug effects KW - Murine Acquired Immunodeficiency Syndrome -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78858990?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=In+vivo+%28Athens%2C+Greece%29&rft.atitle=Upregulation+of+Gfi-1%2C+a+gene+involved+in+IL-2-independent+growth+of+T+cells%2C+in+a+murine+retrovirus-induced+immunodeficiency+syndrome.&rft.au=Liao%2C+X%3BTang%2C+Y%3BChattopadhyay%2C+S+K%3BHartley%2C+J+W%3BMorse%2C+H+C&rft.aulast=Liao&rft.aufirst=X&rft.date=1997-01-01&rft.volume=11&rft.issue=1&rft.spage=9&rft.isbn=&rft.btitle=&rft.title=In+vivo+%28Athens%2C+Greece%29&rft.issn=0258851X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-28 N1 - Date created - 1997-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Research in schizophrenia and the discontinuation of antipsychotic medications. AN - 78858098; 9050108 AB - This article, and the accompanying one by Dr. Carpenter, discuss the benefits and risks associated with taking patients with schizophrenia off medications for research purposes. This article reviews the concept that at least some forms of schizophrenia are progressive. Evidence for this view is provided by studies examining the impact of early intervention with antipsychotic medications on the long-term morbidity of schizophrenia, as well as the few studies examining the long-term risks of discontinuing antipsychotic medications in patients with schizophrenia. While there is evidence that early intervention improves the long-term course of the illness, it is not known whether withdrawal of antipsychotic medications increases long-term morbidity. This is an area where further information is needed for clinical practice and research. JF - Schizophrenia bulletin AU - Wyatt, R J AD - Neuropsychiatry Branch, NIMH Neuropsychiatric Research Hospital, Washington, DC 20032, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 3 EP - 9 VL - 23 IS - 1 SN - 0586-7614, 0586-7614 KW - Antipsychotic Agents KW - 0 KW - Bioethics KW - Index Medicus KW - Biomedical and Behavioral Research KW - Mental Health Therapies KW - Psychiatric Status Rating Scales KW - Humans KW - Neurologic Examination -- drug effects KW - Ethics, Medical KW - Antipsychotic Agents -- administration & dosage KW - Substance Withdrawal Syndrome -- etiology KW - Schizophrenic Psychology KW - Schizophrenia -- drug therapy KW - Antipsychotic Agents -- adverse effects KW - Clinical Trials as Topic -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78858098?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+bulletin&rft.atitle=Research+in+schizophrenia+and+the+discontinuation+of+antipsychotic+medications.&rft.au=Wyatt%2C+R+J&rft.aulast=Wyatt&rft.aufirst=R&rft.date=1997-01-01&rft.volume=23&rft.issue=1&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Schizophrenia+bulletin&rft.issn=05867614&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-21 N1 - Date created - 1997-05-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Schizophr Bull. 1998;24(1):34-5 [9502545] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of human hepatic cytochrome P450 1A2 and 3A4 in the metabolic activation of estrone. AN - 78857218; 9054608 AB - The metabolic activation of estrone (E1), a potent estrogen was investigated using recombinant human cytochrome P450 enzymes, 1A2, 2B6, 2C8, 2C9, 2C9R144C, 2E1, 3A4, 3A5 and liver microsomes from 14 human organ donors. At least five products of E1 were detected and quantitated by HPLC and gas chromatography-mass spectrometry (GC-MS). Among these metabolites, 16alpha-OH-E1, 2-OH-E1 and 4-OH-E1, which are believed to be associated with estrogen carcinogenesis in animals, were definitively identified. Of all P450s examined, 1A2 and 3A4 exhibited the highest activities with turnovers of 3.4 and 2.5 nmol/min/nmol P450 for the total metabolism of E1, respectively, while 3A5, 2C9 and 2C9R144C showed moderate activities. 2B6, 2E1 and 2C8 did not produce any significant amount of products. 1A2 formed almost exclusively the 2-OH-E1 at a rate of 3.3 nmol/min/nmol but 3A4 preferentially formed the metabolite X1 (an unknown hydroxylation product) and 16alpha-OH-E1. Kinetic characterization showed that the Km values of 1A2, 3A4 and 3A5 were 14, 95 and 64 microM and Vmax were 5.43, 0.68 and 0.35 min(-1), respectively. All human liver microsomes were capable of metabolizing estrone and a 4-fold variation was seen between individuals. The relative amount of metabolites formed was generally 2-OH-E1 > metabolite X1 > 4-OH-E1 > 16alpha-OH-E1 > metabolite X2. 3A4/5 enzyme complex was assessed by inhibitory monoclonal antibody specific for 3A4/5 to contribute 60-88% to the formation of individual metabolites in human liver except for 2-OH-E1 (3%). The formation of 2-OH-E1 and 16alpha-OH-E1 by 14 human liver microsomes was significantly correlated with caffeine 3-demethylation supported by 1A2 (r2 = 0.87) and with testosterone 6beta-hydroxylation by 3A4 (r2 = 0.66), respectively. Thus the metabolic patterns exhibited by human liver are likely due to the combined activities of the P450 1A2 and 3A4 enzymes. JF - Carcinogenesis AU - Shou, M AU - Korzekwa, K R AU - Brooks, E N AU - Krausz, K W 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 - 1997/01// PY - 1997 DA - January 1997 SP - 207 EP - 214 VL - 18 IS - 1 SN - 0143-3334, 0143-3334 KW - Estrone KW - 2DI9HA706A KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - CYP3A protein, human KW - EC 1.14.14.1 KW - Cytochrome P-450 CYP1A2 KW - Cytochrome P-450 CYP3A KW - Index Medicus KW - Vaccinia virus -- genetics KW - Biotransformation KW - Humans KW - Adult KW - Middle Aged KW - Genetic Vectors -- genetics KW - Male KW - Female KW - Chromatography, High Pressure Liquid KW - Mixed Function Oxygenases -- metabolism KW - Estrone -- pharmacokinetics KW - Cytochrome P-450 CYP1A2 -- genetics KW - Cytochrome P-450 Enzyme System -- genetics KW - Cytochrome P-450 CYP1A2 -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Mixed Function Oxygenases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78857218?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Role+of+human+hepatic+cytochrome+P450+1A2+and+3A4+in+the+metabolic+activation+of+estrone.&rft.au=Shou%2C+M%3BKorzekwa%2C+K+R%3BBrooks%2C+E+N%3BKrausz%2C+K+W%3BGonzalez%2C+F+J%3BGelboin%2C+H+V&rft.aulast=Shou&rft.aufirst=M&rft.date=1997-01-01&rft.volume=18&rft.issue=1&rft.spage=207&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-21 N1 - Date created - 1997-03-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Radon and lung carcinogenesis: mutability of p53 codons 249 and 250 to 238Pu alpha-particles in human bronchial epithelial cells. AN - 78854911; 9054598 AB - Radon-222, a decay product of uranium-238 and a source of high linear energy transfer (LET) alpha-particles, has been implicated in the increased risk of lung cancer in uranium miners as well as non-miners. p53 mutation spectrum studies of radon-associated lung cancer have failed to show any specific mutational hot spot with the exception of a single study in which 31% of squamous cell and large cell lung cancers from uranium miners showed a p53 codon 249 AGGarg --> ATGmet mutation. Although the results of laboratory studies indicate that double-strand breaks and deletions are the principal genetic alterations caused by alpha-particles, uncertainty still prevails in the description of DNA damage in radon-associated human lung cancer. In the present study, we have evaluated the mutability of p53 codons 249 and 250 to alpha-particles in normal human bronchial epithelial (NHBE) cells using a highly sensitive genotypic mutation assay. Exposure of NHBE cells to a total dose of 4 Gy (equivalent to approximately 1460 working level months in uranium mining) of high LET alpha-radiation induced codon 249 AGG --> AAG transitions and codon 250 CCC --> ACC transversions with absolute mutation frequencies of 3.6 x 10(-7) and 3.8 x 10(-7) respectively. This mutation spectrum is consistent with our previous report of radon-associated human lung cancer. JF - Carcinogenesis AU - Hussain, S P AU - Kennedy, C H AU - Amstad, P AU - Lui, H AU - Lechner, J F AU - Harris, C C AD - Laboratory of Human Carcinogenesis, NCI, NIH, Bethesda, MD 20892-4255, USA. Y1 - 1997/01// PY - 1997 DA - January 1997 SP - 121 EP - 125 VL - 18 IS - 1 SN - 0143-3334, 0143-3334 KW - Codon KW - 0 KW - Radon KW - Q74S4N8N1G KW - Index Medicus KW - Space life sciences KW - Mutagenicity Tests KW - Humans KW - Adolescent KW - Male KW - Codon -- radiation effects KW - Genes, p53 -- radiation effects KW - Codon -- genetics KW - Genes, p53 -- genetics KW - Lung Neoplasms -- genetics KW - Neoplasms, Radiation-Induced -- genetics KW - Radon -- toxicity KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78854911?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Radon+and+lung+carcinogenesis%3A+mutability+of+p53+codons+249+and+250+to+238Pu+alpha-particles+in+human+bronchial+epithelial+cells.&rft.au=Hussain%2C+S+P%3BKennedy%2C+C+H%3BAmstad%2C+P%3BLui%2C+H%3BLechner%2C+J+F%3BHarris%2C+C+C&rft.aulast=Hussain&rft.aufirst=S&rft.date=1997-01-01&rft.volume=18&rft.issue=1&rft.spage=121&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-21 N1 - Date created - 1997-03-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Elevated mitochondrial cisplatin-DNA adduct levels in rat tissues after transplacental cisplatin exposure. AN - 78853879; 9054594 AB - Although there is evidence that the toxic effects of cis-diamminedichloroplatinum(II) (cisplatin) include morphologically abnormal mitochondria, direct demonstrations of mitochondrial DNA damage by this chemotherapeutic agent have rarely been reported. Here we show that, in rats exposed to a single dose of cisplatin during gestation, cisplatin-DNA binding levels in both maternal and fetal liver and brain mitochondrial DNA are higher than those observed in genomic DNA. Pregnant F344/NCr rats were injected i.p. with either 5 or 15 mg cisplatin/kg body wt at 18 days of gestation and killed 24 h later. Cisplatin-DNA adducts were determined by dissociation-enhanced lanthanide fluoroimmunoassay using a cisplatin-DNA standard modified in the same range as the biological samples. Values for genomic cisplatin-DNA adducts in multiple maternal and fetal tissues have been presented elsewhere. Here, genomic DNA adduct levels for liver, brain, kidney and placenta are reported again for comparison with mitochondrial DNA adduct levels in the same tissues. In maternal and fetal brain, mitochondrial DNA adduct levels were approximately 7- to 50-fold higher than genomic DNA adduct levels, and in fetal liver they were approximately 2- to 16-fold higher than genomic DNA adduct levels. These studies demonstrate extensive cisplatin-DNA adduct formation in brain and liver mitochondria of fetal rats exposed transplacentally and suggest that mitochondrial DNA in some organs may be a particular target for cisplatin genotoxicity. JF - Carcinogenesis AU - Giurgiovich, A J AU - Diwan, B A AU - Olivero, O A AU - Anderson, L M AU - Rice, J M AU - Poirier, M C AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, NIH, Bethesda, MD 20892-4255, USA. Y1 - 1997/01// PY - 1997 DA - January 1997 SP - 93 EP - 96 VL - 18 IS - 1 SN - 0143-3334, 0143-3334 KW - DNA Adducts KW - 0 KW - DNA, Mitochondrial KW - cisplatin-DNA adduct KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Kidney -- metabolism KW - Dose-Response Relationship, Drug KW - Placenta -- metabolism KW - Female KW - Pregnancy KW - Maternal-Fetal Exchange KW - DNA, Mitochondrial -- metabolism KW - Cisplatin -- metabolism KW - DNA Adducts -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78853879?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Elevated+mitochondrial+cisplatin-DNA+adduct+levels+in+rat+tissues+after+transplacental+cisplatin+exposure.&rft.au=Giurgiovich%2C+A+J%3BDiwan%2C+B+A%3BOlivero%2C+O+A%3BAnderson%2C+L+M%3BRice%2C+J+M%3BPoirier%2C+M+C&rft.aulast=Giurgiovich&rft.aufirst=A&rft.date=1997-01-01&rft.volume=18&rft.issue=1&rft.spage=93&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-21 N1 - Date created - 1997-03-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhancement of cellular immunity in melanoma patients immunized with a peptide from MART-1/Melan A. AN - 78852338; 9072306 AB - In this study, we tested the effectiveness of a melanoma-associated antigen-derived peptide, MART-1(27-35), in eliciting cellular immune responses in vivo in the context of a phase I active immunization protocol. This peptide (AAGIGILTV) corresponds to residues 27-35 from the nonmutated melanoma-associated antigen MART-1/Melan A and is recognized by most melanoma-specific, HLA-A*0201-restricted, tumor-infiltrating lymphocytes. To test the in vivo induction of cytotoxic T lymphocyte (CTL) sensitization, we compared CTL reactivity in vitro from peripheral blood mononuclear cell (PBMC) pools obtained before and after vaccination. MART-1(27-35) was administered to HLA-A*0201 melanoma patients subcutaneously in an emulsification with incomplete Freund's adjuvant. A vaccination course included four inoculations of peptide at 3-week intervals. PBMC collected by leukapheresis and separated by Ficoll-Hypaque gradient before and after vaccination were analyzed in 18 patients by in vitro sensitization with MART-1(27-35). To induce MART-1(27-35)-specific CTL, PBMC were incubated with 1 microM peptide (on day 0) and interleukin-2 (IL-2) (300 IU/mL, on days 1 and 4 after each stimulation). At weekly intervals, cells were harvested and an aliquot was cryopreserved for later analysis. The remaining cells were replated and restimulated using irradiated autologous PBMC pulsed with 1 microM of relevant peptide. After three restimulations, all samples from one patient were tested simultaneously for HLA-A*0201-restricted anti-MART-1(27-35) reactivity by microcytotoxicity and cytokine (IFN-gamma) release assays. Toxicities were minimal and consisted of local irritation at the site of vaccine administration. None of the patients sustained a clinical response. The first eight patients were monitored by inducing CTL reactivity from PBMC obtained preimmunization and after two and four vaccinations. Only two prevaccination cultures were reactive to MART-1, compared with five and seven cultures from PBMC obtained after two and four vaccinations, respectively. Thus, an enhancement in cytotoxic activity could be detected in postvaccination CTL cultures, and serial vaccine administrations appeared to boost the detectability of cytotoxicity in vitro. For completeness, the analysis compared prevaccination with postvaccination PBMC cultures. Specific anti-MART-1(27-35) cytotoxicity (> or = 10 lytic units) could be detected in two prevaccination and 12 postvaccination cultures after two in vitro stimulations. In 15 postvaccination CTL cultures, a more than threefold increase in specific release of IFN-gamma was noted, compared with prevaccination. In vivo administration of a melanoma-associated antigen peptide, emulsified in incomplete Freund's adjuvant, could safely augment CTL reactivity against epitopes commonly expressed by melanoma cells. Although the enhancement of CTL reactivity did not achieve tumor regression, it is possible that the use of recombinant immunogens with increased immunomodulatory capabilities in future clinical trials could reach the threshold of CTL activation necessary for tumor regression. JF - The cancer journal from Scientific American AU - Cormier, J N AU - Salgaller, M L AU - Prevette, T AU - Barracchini, K C AU - Rivoltini, L AU - Restifo, N P AU - Rosenberg, S A AU - Marincola, F M AD - Surgery Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. PY - 1997 SP - 37 EP - 44 VL - 3 IS - 1 SN - 1081-4442, 1081-4442 KW - Antigens, Neoplasm KW - 0 KW - MART-1 Antigen KW - MLANA protein, human KW - Neoplasm Proteins KW - Interferon-gamma KW - 82115-62-6 KW - Index Medicus KW - Cytotoxicity, Immunologic KW - Leukocytes, Mononuclear KW - Cells, Cultured KW - Humans KW - Adult KW - Interferon-gamma -- metabolism KW - Aged KW - Middle Aged KW - Male KW - Female KW - Neoplasm Proteins -- administration & dosage KW - Antigens, Neoplasm -- adverse effects KW - Immunity, Cellular -- drug effects KW - Neoplasm Proteins -- adverse effects KW - Melanoma -- immunology KW - Antigens, Neoplasm -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78852338?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Enhancement+of+cellular+immunity+in+melanoma+patients+immunized+with+a+peptide+from+MART-1%2FMelan+A.&rft.au=Cormier%2C+J+N%3BSalgaller%2C+M+L%3BPrevette%2C+T%3BBarracchini%2C+K+C%3BRivoltini%2C+L%3BRestifo%2C+N+P%3BRosenberg%2C+S+A%3BMarincola%2C+F+M&rft.aulast=Cormier&rft.aufirst=J&rft.date=1997-01-01&rft.volume=3&rft.issue=1&rft.spage=37&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 - 1997-03-27 N1 - Date created - 1997-03-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Immunol. 1994 Aug 1;153(3):1225-37 [8027550] Cancer Res. 1994 Aug 1;54(15):4155-61 [7518351] Eur J Immunol. 1994 Dec;24(12):3038-43 [7805731] J Clin Invest. 1995 Jan;95(1):341-9 [7814635] J Immunol. 1995 Jan 15;154(2):762-71 [7814882] J Immunol. 1995 Mar 1;154(5):2257-65 [7868898] Proc Natl Acad Sci U S A. 1995 Mar 14;92(6):2219-23 [7892250] Cancer Res. 1995 Jul 15;55(14):3149-57 [7541714] Immunol Today. 1995 Oct;16(10):487-94 [7576053] Cancer Res. 1995 Nov 1;55(21):4972-9 [7585538] J Immunol. 1996 May 15;156(10):3882-91 [8621927] J Immunother Emphasis Tumor Immunol. 1996 May;19(3):192-205 [8811494] J Immunother Emphasis Tumor Immunol. 1996 Jul;19(4):266-77 [8877721] Cancer J Sci Am. 1996 Jan-Feb;2(1):16-8 [9166492] Nature. 1992 Apr 2;356(6368):443-6 [1557127] Int J Cancer. 1992 Jan 21;50(2):289-97 [1730522] J Immunol. 1991 May 15;146(10):3674-81 [1902860] Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2283-7 [1848698] Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6458-62 [8022805] J Exp Med. 1994 Jul 1;180(1):35-42 [8006593] J Exp Med. 1993 Aug 1;178(2):489-95 [8340755] Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3515-9 [8170938] J Exp Med. 1994 Jul 1;180(1):347-52 [7516411] J Exp Med. 1992 Dec 1;176(6):1739-44 [1460429] Comment In: Cancer J Sci Am. 1997 Jan-Feb;3(1):4-5 [9072307] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lack of p53 and ras mutations in Helicobacter hepaticus-induced liver tumors in A/JCr mice. AN - 78843910; 9054612 AB - Helicobacter hepaticus is a recently discovered bacterium that invades mouse liver causing chronic active hepatitis followed by development of preneoplastic hepatocellular foci, hepatocellular adenomas and carcinomas. This establishes a unique animal model for study of the mechanisms of cancer development due to a chronic bacterial infection. A possible mechanism of bacteria-associated tumorigenesis is mutation of oncogenes or tumor suppressor genes. Since mutations in ras oncogenes have been widely detected in a variety of chemically induced and spontaneous mouse liver tumors and specific mutations in the p53 tumor suppressor gene have been associated with human bladder cancers attributed to chronic schistosomal infection, we studied exons 1 and 2 of the N-, K- and H-ras genes and exons 5-8 of the p53 gene for the presence of point mutations in 25 liver tumors from 10 naturally infected A/JCr mice, ranging in age from 16 to 24 months. The 20 adenomas and five carcinomas varied in size from 0.1 to 2.3 cm and arose in livers characterized by a wide assortment of pathological profiles, including hepatitis, inflammation, hyperplasia, hypertrophy, leukocyte infiltration, necrosis and focal phenotypic alteration. DNA samples extracted from formalin-fixed paraffin-embedded tissues were screened by PCR/SSCP analysis and showed no mutations in the analyzed genes. Complete absence of mutations in ras genes in 25 mouse liver tumors is unusual. Other genes may be targeted or H. hepaticus infection causes liver cancer through other pathways than direct damage to DNA. JF - Carcinogenesis AU - Sipowicz, M A AU - Weghorst, C M AU - Shiao, Y H AU - Buzard, G S AU - Calvert, R J AU - Anver, M R AU - Anderson, L M AU - Rice, J M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute-FCRDC, Frederick, MD 21702, USA. Y1 - 1997/01// PY - 1997 DA - January 1997 SP - 233 EP - 236 VL - 18 IS - 1 SN - 0143-3334, 0143-3334 KW - Index Medicus KW - Mice, Inbred A KW - Animals KW - Helicobacter Infections -- microbiology KW - Mice KW - Adenoma -- microbiology KW - Carcinoma -- microbiology KW - Adenoma -- genetics KW - Helicobacter Infections -- genetics KW - Gene Amplification KW - Carcinoma -- genetics KW - Point Mutation -- genetics KW - Liver Neoplasms, Experimental -- genetics KW - Genes, ras -- genetics KW - Liver Neoplasms, Experimental -- microbiology KW - Genes, p53 -- genetics KW - Genes, Bacterial -- genetics KW - Helicobacter -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78843910?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Lack+of+p53+and+ras+mutations+in+Helicobacter+hepaticus-induced+liver+tumors+in+A%2FJCr+mice.&rft.au=Sipowicz%2C+M+A%3BWeghorst%2C+C+M%3BShiao%2C+Y+H%3BBuzard%2C+G+S%3BCalvert%2C+R+J%3BAnver%2C+M+R%3BAnderson%2C+L+M%3BRice%2C+J+M&rft.aulast=Sipowicz&rft.aufirst=M&rft.date=1997-01-01&rft.volume=18&rft.issue=1&rft.spage=233&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-21 N1 - Date created - 1997-03-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Avoided and avoidable risks of cancer. AN - 78843862; 9054595 AB - Despite the considerable efforts and funds devoted to cancer research over several decades, cancer still remains a mainly lethal disease. Cancer incidence and mortality have not declined at the same rate as other major causes of death, indicating that primary prevention remains a most valuable approach to decrease mortality. There is general agreement that environmental exposures are variously involved in the causation of the majority of cancer cases and that at least half of all cancers could be avoided by applying existing etiologic knowledge. There is disagreement, however, regarding the proportion of cancer risks attributable to specific etiological factors, including diet, occupation and pollution. Estimates of attributable risks are largely based today on unverified assumptions and the calculation of attributable risks involves taking very unequal evidence of various types of factors and treating them equally. Effective primary prevention resulting in a reduction of cancer risk can be obtained by: (i) a reduction in the number of carcinogens to which humans are exposed; or (ii) a reduction of the exposure levels to carcinogens. Exposure levels that could be seen as sufficiently low when based on single agents, may actually not be safe in the context of the many other concomitant carcinogenic and mutagenic exposures. The list of human carcinogens and of their target organs might be quite different if: (i) epidemiological data were available for a larger proportion of human exposures for which there is experimental evidence of carcinogenicity; (ii) more attention was paid to epidemiological evidence that is suggestive of an exposure-cancer association, but is less than sufficient, particularly in identifying target organs; and (iii) experimental evidence of carcinogenicity, supported by mechanistic considerations, were more fully accepted as predictions of human risk. JF - Carcinogenesis AU - Tomatis, L AU - Huff, J AU - Hertz-Picciotto, I AU - Sandler, D P AU - Bucher, J AU - Boffetta, P AU - Axelson, O AU - Blair, A AU - Taylor, J AU - Stayner, L AU - Barrett, J C AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709-2233, USA. Y1 - 1997/01// PY - 1997 DA - January 1997 SP - 97 EP - 105 VL - 18 IS - 1 SN - 0143-3334, 0143-3334 KW - Carcinogens, Environmental KW - 0 KW - Index Medicus KW - Dose-Response Relationship, Drug KW - Humans KW - Carcinogenicity Tests KW - Incidence KW - Environmental Exposure -- prevention & control KW - Risk Assessment KW - Carcinogens, Environmental -- adverse effects KW - Neoplasms -- mortality KW - Neoplasms -- epidemiology KW - Neoplasms -- prevention & control KW - Carcinogens, Environmental -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78843862?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Avoided+and+avoidable+risks+of+cancer.&rft.au=Tomatis%2C+L%3BHuff%2C+J%3BHertz-Picciotto%2C+I%3BSandler%2C+D+P%3BBucher%2C+J%3BBoffetta%2C+P%3BAxelson%2C+O%3BBlair%2C+A%3BTaylor%2C+J%3BStayner%2C+L%3BBarrett%2C+J+C&rft.aulast=Tomatis&rft.aufirst=L&rft.date=1997-01-01&rft.volume=18&rft.issue=1&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-21 N1 - Date created - 1997-03-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alterations in pharmacodynamics of anxiolytics in abstinent alcoholic men: subjective responses, abuse liability, and electroencephalographic effects of alprazolam, diazepam, and buspirone. AN - 78841849; 9048275 AB - Subjective responses, including those associated with abuse liability and changes in frontal electroencephalographic activity, were assessed in abstinent alcoholic men and control subjects after administration of alprazolam, diazepam, buspirone, and placebo. Plasma concentrations of alprazolam, diazepam, and desmethyldiazepam also were determined. Abuse liability scales were elevated for alcoholic participants above control levels after alprazolam and diazepam. Areas under the concentration-time curve differed only for desmethyldiazepam, which was lower for the alcoholic participants. Compared with control subjects, alcoholic participants had greater declines in the absolute power of the alpha band after diazepam challenge. Alcoholic participants, unlike control subjects, had areas under the effect-time curve for alpha and theta bands that were lower after administration of alprazolam or diazepam than they were after receiving placebo. These results suggest that alprazolam and diazepam are more likely to be abused by alcoholic men than by nonalcoholic men and that alcoholic men have enhanced sensitivity to the effects of benzodiazepines on alpha and theta activity. JF - Journal of clinical pharmacology AU - Ciraulo, D A AU - Barnhill, J G AU - Ciraulo, A M AU - Sarid-Segal, O AU - Knapp, C AU - Greenblatt, D J AU - Shader, R I AD - National Institute on Drug Abuse/Veterans Affairs Medication Development Research Unit, Boston Veterans Affairs Medical Center, Massachusetts, USA. Y1 - 1997/01// PY - 1997 DA - January 1997 SP - 64 EP - 73 VL - 37 IS - 1 SN - 0091-2700, 0091-2700 KW - Anti-Anxiety Agents KW - 0 KW - Diazepam KW - Q3JTX2Q7TU KW - Buspirone KW - TK65WKS8HL KW - Alprazolam KW - YU55MQ3IZY KW - Index Medicus KW - Affect -- drug effects KW - Alprazolam -- pharmacokinetics KW - Humans KW - Adult KW - Diazepam -- pharmacokinetics KW - Buspirone -- pharmacokinetics KW - Male KW - Electrocardiography -- drug effects KW - Substance-Related Disorders -- physiopathology KW - Anti-Anxiety Agents -- pharmacokinetics KW - Alcoholism -- metabolism KW - Substance-Related Disorders -- metabolism KW - Alcoholism -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78841849?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+pharmacology&rft.atitle=Alterations+in+pharmacodynamics+of+anxiolytics+in+abstinent+alcoholic+men%3A+subjective+responses%2C+abuse+liability%2C+and+electroencephalographic+effects+of+alprazolam%2C+diazepam%2C+and+buspirone.&rft.au=Ciraulo%2C+D+A%3BBarnhill%2C+J+G%3BCiraulo%2C+A+M%3BSarid-Segal%2C+O%3BKnapp%2C+C%3BGreenblatt%2C+D+J%3BShader%2C+R+I&rft.aulast=Ciraulo&rft.aufirst=D&rft.date=1997-01-01&rft.volume=37&rft.issue=1&rft.spage=64&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+pharmacology&rft.issn=00912700&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-01 N1 - Date created - 1997-05-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of androgen synthesis: the late steroidogenic pathway. AN - 78837557; 9029727 AB - Studies of the regulation of androgen synthesis in steroidogenic cells have focused on both transcriptional and post-translational regulation of the proteins that catalyze these reactions: the P450c17 that catalyzes the production of DHEA or androstenedione in consecutive hydroxylase and lyase activities, and the 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) that catalyzes the conversion of androstenedione to testosterone. Our studies of the regulation of the CYP17 lyase activity at the molecular level have utilized species- and tissue-specific differences to identify target regulatory sequences. Adenovirus infection of rat CYP17 promoter/luciferase reporter gene constructs in primary cultures of rat adrenal and rat Leydig cells revealed a rat-specific domain between-1 and -108 bp that cause inhibition of both basal and cAMP-induced CYP17 transcription in the adrenal, but not the Leydig cell. In contrast, similar promoter constructs from other species exhibited substantial cAMP-induced transcriptional activity in the rat adrenal. Mutagenesis of the conserved region of the rat and human proteins reveals significant differences in the amino acid domains required for hydroxylase and lyase activities within and between the two species, consistent with their differential regulation of lyase activity. The 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) reaction requires a viable glucose transporter system for optimal activity, and a high-energy phosphate was discovered to be the requisite product of glucose metabolism in 17 beta-HSD activation. These studies have provided insight into potential mechanisms of control of androgen synthesis in the late steroidogenic pathway, at the transcriptional and post-translational levels. JF - Steroids AU - Dufau, M L AU - Miyagawa, Y AU - Takada, S AU - Khanum, A AU - Miyagawa, H AU - Buczko, E AD - Section on Molecular Endocrinology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1997/01// PY - 1997 DA - January 1997 SP - 128 EP - 132 VL - 62 IS - 1 SN - 0039-128X, 0039-128X KW - Androgens KW - 0 KW - DNA-Binding Proteins KW - Fushi Tarazu Transcription Factors KW - Homeodomain Proteins KW - Receptors, Cytoplasmic and Nuclear KW - Steroidogenic Factor 1 KW - Transcription Factors KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - 17-Hydroxysteroid Dehydrogenases KW - EC 1.1.- KW - Steroid 17-alpha-Hydroxylase KW - EC 1.14.14.19 KW - Index Medicus KW - Animals KW - Transcription Factors -- metabolism KW - Humans KW - Protein Processing, Post-Translational KW - Transcription, Genetic KW - Amino Acid Sequence KW - Binding Sites KW - Cloning, Molecular KW - Rats KW - Conserved Sequence KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Mutation KW - DNA-Binding Proteins -- metabolism KW - Cytochrome P-450 Enzyme System -- genetics KW - Androgens -- biosynthesis KW - 17-Hydroxysteroid Dehydrogenases -- metabolism KW - Steroid 17-alpha-Hydroxylase -- metabolism KW - Steroid 17-alpha-Hydroxylase -- genetics KW - Cytochrome P-450 Enzyme System -- metabolism KW - 17-Hydroxysteroid Dehydrogenases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78837557?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Steroids&rft.atitle=Regulation+of+androgen+synthesis%3A+the+late+steroidogenic+pathway.&rft.au=Dufau%2C+M+L%3BMiyagawa%2C+Y%3BTakada%2C+S%3BKhanum%2C+A%3BMiyagawa%2C+H%3BBuczko%2C+E&rft.aulast=Dufau&rft.aufirst=M&rft.date=1997-01-01&rft.volume=62&rft.issue=1&rft.spage=128&rft.isbn=&rft.btitle=&rft.title=Steroids&rft.issn=0039128X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-29 N1 - Date created - 1997-05-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Eight-week toxicity study of 60 Hz magnetic fields in F344 rats and B6C3F1 mice. AN - 78822504; 9024673 AB - Toxicity studies were performed by exposing F344/N rats and B6C3F1 mice (10 animals per sex per species per group) to transient-free, linearly polarized 60 Hz magnetic fields for 8 weeks. Targeted magnetic fields strengths used were 0 gauss (G; sham control fields did not exceed 0.001 G), 0.02 G, 2 G, and 10 G. Exposure was whole-body and continuous for 18.5 hr per day, 7 days per week. An additional group of rats and mice was exposed intermittently (1 hr on/1 hr off) to 10 G fields for the same period of time. Endpoints evaluated included morbidity, mortality, gross pathology, histopathology, body/organ weights, clinical chemistry (rats only), and hematology (rats only). All mice and all male rats survived until the end of the study. One female rat (2-G exposure group) died during Week 7 of the study; the death was not attributed to magnetic field exposure. In both studies, the mean body weight gains of exposed animals were similar to those of the respective controls. There were no gross, histological, hematological, or biochemical lesions attributed to magnetic field exposure. Statistically significant increases in liver weight and liver to body weight ratio occurred in female rats of all exposure groups but only at the termination. These data suggest that, for the variables evaluated in these studies, an 8-week exposure to linear-polarized, transient-free 60 Hz magnetic fields at field intensities of up to 10 G is not associated with significant toxicity in F344/N rats and B6C3F1 mice. Furthermore, there was no toxicity observed in animals receiving intermittent (1 hr on/1 hr off) exposures to 10-G fields. A 2-year study in F344/N rats and B6C3F1 mice is nearing completion of the in-life phase without overt toxicity in any exposed group. It is premature, however, to make any prediction concerning the possible influence of exposure to 60 Hz magnetic fields on cancer rates. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Boorman, G A AU - Gauger, J R AU - Johnson, T R AU - Tomlinson, M J AU - Findlay, J C AU - Travlos, G S AU - McCormick, D L AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1997/01// PY - 1997 DA - January 1997 SP - 55 EP - 63 VL - 35 IS - 1 SN - 0272-0590, 0272-0590 KW - Index Medicus KW - Rats KW - Hematologic Tests KW - Animals KW - Rats, Inbred F344 KW - Blood Chemical Analysis KW - Body Weight -- radiation effects KW - Survival Rate KW - Mice KW - Organ Size -- radiation effects KW - Male KW - Female KW - Electromagnetic Fields -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78822504?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Eight-week+toxicity+study+of+60+Hz+magnetic+fields+in+F344+rats+and+B6C3F1+mice.&rft.au=Boorman%2C+G+A%3BGauger%2C+J+R%3BJohnson%2C+T+R%3BTomlinson%2C+M+J%3BFindlay%2C+J+C%3BTravlos%2C+G+S%3BMcCormick%2C+D+L&rft.aulast=Boorman&rft.aufirst=G&rft.date=1997-01-01&rft.volume=35&rft.issue=1&rft.spage=55&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-14 N1 - Date created - 1997-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional properties of cultured endothelial cells derived from large microvessels of human brain. AN - 78817379; 9038829 AB - This report describes the fractional separation of microvessels from human brain for establishment of segmentally derived endothelial cell (EC) cultures. The investigation comprised evaluation of media constituents and purity of the cell culture and focused on functional biochemical characterization of endothelium derived from large microvessels (EC) Cells contained endothelial marker factor VIII (von Willebrand antigen), secreted endothelin-1 (ET-1) and prostaglandins, and took up 86Rb+ as a measure of K+. Exogenous ET-1 stimulated phosphatidylinositol hydrolysis and K+ uptake; BQ-123 (selective ETA receptor antagonist) but not IRL-1038 or BQ-788 (selective ETB receptor antagonists) inhibited both. Ouabain (inhibitor of Na(+)-K(+)-ATPase) and bumetanide (inhibitor of Na(+)-K(+)-Cl- cotransport) reduced (74-80 and 20-40%, respectively) the ET-1-stimulated K+ uptake. Staurosporine [protein kinase C (PKC) inhibitor] selectively reduced Na(+)-K(+)-Cl- cotransport, whereas verapamil but not nifedipine (L-type voltage-dependent Ca2+ channel blockers) decreased Na(+)-K(+)-ATPase activity induced by ET-1. Phorbol 12-myristate 13-acetate (PMA; activator of PKC) stimulated K+ uptake, which was only decreased with bumetanide. N-ethylisopropylamiloride (inhibitor of Na+/H+ exchange) reduced the ET-1-stimulated but not the PMA-induced K+ uptake. Results indicate that phosphatidylinositol hydrolysis and ion transport systems in large microvascular EC are stimulated by ET-1 through activation of ETA receptors. The findings also suggest that the ET-1-stimulated Na(+)-K(+)-ATPase activity, in contrast to Na(+)-K(+)-Cl- cotransport, is not mediated by PKC. In addition, the data suggest a linkage between Na(+)-K(+)-ATPase activity and Na+/H+ exchange. JF - The American journal of physiology AU - Spatz, M AU - Kawai, N AU - Merkel, N AU - Bembry, J AU - McCarron, R M AD - Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-4128, USA. Y1 - 1997/01// PY - 1997 DA - January 1997 SP - C231 EP - C239 VL - 272 IS - 1 Pt 1 SN - 0002-9513, 0002-9513 KW - Carrier Proteins KW - 0 KW - Endothelin-1 KW - Enzyme Inhibitors KW - Sodium-Potassium-Chloride Symporters KW - Ouabain KW - 5ACL011P69 KW - Amiloride KW - 7DZO8EB0Z3 KW - Inositol 1,4,5-Trisphosphate KW - 85166-31-0 KW - Sodium-Potassium-Exchanging ATPase KW - EC 3.6.3.9 KW - Staurosporine KW - H88EPA0A3N KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Potassium KW - RWP5GA015D KW - Thymidine KW - VC2W18DGKR KW - ethylisopropylamiloride KW - VW50CE070T KW - Index Medicus KW - Carrier Proteins -- metabolism KW - Humans KW - Inositol 1,4,5-Trisphosphate -- biosynthesis KW - Potassium -- pharmacokinetics KW - Amiloride -- pharmacology KW - Amiloride -- analogs & derivatives KW - Thymidine -- metabolism KW - Staurosporine -- pharmacology KW - Sodium-Potassium-Exchanging ATPase -- metabolism KW - Cells, Cultured KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Microcirculation KW - Endothelin-1 -- pharmacology KW - Ouabain -- pharmacology KW - Cell Division KW - Endothelium, Vascular -- metabolism KW - Endothelium, Vascular -- cytology KW - Cerebrovascular Circulation KW - Endothelium, Vascular -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78817379?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+physiology&rft.atitle=Functional+properties+of+cultured+endothelial+cells+derived+from+large+microvessels+of+human+brain.&rft.au=Spatz%2C+M%3BKawai%2C+N%3BMerkel%2C+N%3BBembry%2C+J%3BMcCarron%2C+R+M&rft.aulast=Spatz&rft.aufirst=M&rft.date=1997-01-01&rft.volume=272&rft.issue=1+Pt+1&rft.spage=C231&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+physiology&rft.issn=00029513&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-28 N1 - Date created - 1997-03-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A nonhuman primate model of excessive alcohol intake. Personality and neurobiological parallels of type I- and type II-like alcoholism. AN - 78814053; 9122496 AB - Developmental, biochemical, and behavioral concomitants of voluntary excessive alcohol consumption were investigated using a nonhuman primate model. Studies were designed to investigate potential neurobiological and behavioral parallels of Cloninger's subtypes of type I and type II alcoholism in nonhuman primates. The studies have shown that a subpopulation of primates chronically consume intoxicating amounts of alcohol. Subjects that chronically consume intoxicating amounts of alcohol often exhibit neurobiological and behavioral features that were predicted by Cloninger's model for subtypes of alcoholism among humans. Investigations showed that behavior patterns and biological indices that characterize high anxiety, whether constitutionally or stress induced, were correlated with high rates of alcohol consumption, consistent with predictions for type I alcoholism. Early untoward rearing experiences that increased anxiety increased the probability that subjects would chronically drink alcohol to intoxication. Investigations of type II-like alcohol consumption patterns focused on subjects with low central nervous system (CNS) serotonin functioning [as measured by reduced cerebrospinal fluid (CSF) concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA)]. CSF 5-HIAA in infancy was shown to be a relatively stable neurobiological trait across development into adulthood. An individual CSF 5-HIAA concentration in infancy was shown to be a consequence of paternal and maternal genetic influences. Early parental neglect reduced CSF 5-HIAA concentrations. Low CSF 5-HIAA and CNS norepinephrine functioning were shown to predict excessive alcohol consumption in adolescence. Behaviorally, subjects with low CSF 5-HIAA demonstrated impaired impulse control, which resulted in excessive and inappropriate aggression, infrequent and inept social behaviors, low social status, social isolation and expulsion from social groups at an early age, and high rates of early mortality. With some exceptions, these findings were consistent with predictions from Cloninger's type II model of excessive alcohol consumption among men who exhibit impaired impulse control and violent and antisocial behaviors. JF - Recent developments in alcoholism : an official publication of the American Medical Society on Alcoholism, the Research Society on Alcoholism, and the National Council on Alcoholism AU - Higley, J D AU - Linnoila, M AD - Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, Poolesville, Maryland 20837, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 191 EP - 219 VL - 13 SN - 0738-422X, 0738-422X KW - Serotonin KW - 333DO1RDJY KW - Hydroxyindoleacetic Acid KW - 54-16-0 KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Brain -- physiopathology KW - Norepinephrine -- physiology KW - Animals KW - Serotonin -- physiology KW - Arousal -- drug effects KW - Humans KW - Arousal -- physiology KW - Hydroxyindoleacetic Acid -- cerebrospinal fluid KW - Disease Models, Animal KW - Macaca mulatta KW - Species Specificity KW - Male KW - Female KW - Social Environment KW - Alcoholic Intoxication -- psychology KW - Alcoholic Intoxication -- physiopathology KW - Alcoholism -- classification KW - Alcoholic Intoxication -- classification KW - Personality -- genetics KW - Alcoholism -- physiopathology KW - Alcoholism -- genetics KW - Alcoholic Intoxication -- genetics KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78814053?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Recent+developments+in+alcoholism+%3A+an+official+publication+of+the+American+Medical+Society+on+Alcoholism%2C+the+Research+Society+on+Alcoholism%2C+and+the+National+Council+on+Alcoholism&rft.atitle=A+nonhuman+primate+model+of+excessive+alcohol+intake.+Personality+and+neurobiological+parallels+of+type+I-+and+type+II-like+alcoholism.&rft.au=Higley%2C+J+D%3BLinnoila%2C+M&rft.aulast=Higley&rft.aufirst=J&rft.date=1997-01-01&rft.volume=13&rft.issue=&rft.spage=191&rft.isbn=&rft.btitle=&rft.title=Recent+developments+in+alcoholism+%3A+an+official+publication+of+the+American+Medical+Society+on+Alcoholism%2C+the+Research+Society+on+Alcoholism%2C+and+the+National+Council+on+Alcoholism&rft.issn=0738422X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-22 N1 - Date created - 1997-04-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Definition by specific antisense oligonucleotides of a role for protein kinase C alpha in expression of differentiation markers in normal and neoplastic mouse epidermal keratinocytes. AN - 78810664; 9022812 AB - Epidermal keratinocyte differentiation is a tightly regulated, stepwise process that requires protein kinase C (PKC) activation. Studies using cultured mouse keratinocytes induced to differentiate with Ca2+ have indirectly implicated the alpha isoform of PKC in upregulation of "late" (granular cell) epidermal differentiation markers. Activation of this isoform is also implicated in the suppression of "early" differentiation markers keratin (K) 1 and 10 that characterizes the neoplastic phenotype produced by the v-Ha-ras oncogene. We used antisense oligonucleotides (AS) to directly address the role of PKC alpha in regulating expression of these markers in normal and v-Ha-ras-transduced primary keratinocytes and a keratinocyte cell line (SP-1) containing an activating mutation of the c-Ha-ras gene. Transfection of PKC alpha AS reduced the PKC alpha protein level in a dose-dependent manner, with a maximum effect at doses of 100 nM or higher. Immunoblot analysis with antibodies against PKC alpha, PKC delta, PKC epsilon, and PKC eta confirmed that PKC alpha AS selectively reduced the level of PKC alpha but not the other isoforms. In vitro kinase assays also revealed suppression of Ca(2+)-dependent PKC activity, which is the PKC alpha activity in this cell type, after transfection of PKC alpha AS. When PKC alpha AS-treated normal keratinocytes were stimulated to terminally differentiate with Ca2+, induction of the late differentiation markers loricrin, filaggrin, and SPR-1, as well as transglutaminase K mRNA, was suppressed when compared with their induction in scrambled AS-treated controls. In neoplastic v-Ha-ras-transduced keratinocytes and SP-1 cells, transfection of PKC alpha AS, but not the scrambled AS control, selectively downregulated PKC alpha and restored differentiation-specific expression of K1. These findings directly confirm that PKC alpha is an important component of the signaling pathway regulating terminal differentiation of normal keratinocytes and that activation of PKC alpha contributes to the altered differentiation program of neoplastic murine keratinocytes. JF - Molecular carcinogenesis AU - Lee, Y S AU - Dlugosz, A A AU - McKay, R AU - Dean, N M AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1997/01// PY - 1997 DA - January 1997 SP - 44 EP - 53 VL - 18 IS - 1 SN - 0899-1987, 0899-1987 KW - Antigens, Differentiation KW - 0 KW - Enzyme Inhibitors KW - Isoenzymes KW - Oligonucleotides, Antisense KW - Keratins KW - 68238-35-7 KW - Prkca protein, mouse KW - EC 2.7.11.13 KW - Protein Kinase C KW - Protein Kinase C-alpha KW - Ornithine Decarboxylase KW - EC 4.1.1.17 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Solubility KW - Cytoskeleton -- metabolism KW - Epidermis -- cytology KW - Oligonucleotides, Antisense -- pharmacology KW - Mice KW - Mice, Inbred BALB C KW - Keratins -- biosynthesis KW - Ornithine Decarboxylase -- metabolism KW - Calcium -- metabolism KW - Genes, ras KW - Tumor Cells, Cultured KW - Cell Differentiation -- physiology KW - Cells, Cultured KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Enzyme Induction KW - Enzyme Inhibitors -- pharmacology KW - Cell Line, Transformed KW - Isoenzymes -- antagonists & inhibitors KW - Protein Kinase C -- antagonists & inhibitors KW - Isoenzymes -- physiology KW - Keratinocytes -- enzymology KW - Isoenzymes -- biosynthesis KW - Protein Kinase C -- genetics KW - Antigens, Differentiation -- biosynthesis KW - Keratinocytes -- cytology KW - Protein Kinase C -- biosynthesis KW - Protein Kinase C -- physiology KW - Isoenzymes -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78810664?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Definition+by+specific+antisense+oligonucleotides+of+a+role+for+protein+kinase+C+alpha+in+expression+of+differentiation+markers+in+normal+and+neoplastic+mouse+epidermal+keratinocytes.&rft.au=Lee%2C+Y+S%3BDlugosz%2C+A+A%3BMcKay%2C+R%3BDean%2C+N+M%3BYuspa%2C+S+H&rft.aulast=Lee&rft.aufirst=Y&rft.date=1997-01-01&rft.volume=18&rft.issue=1&rft.spage=44&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 - 1997-02-27 N1 - Date created - 1997-02-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The relationship of alcohol to injury in assault cases. AN - 78808850; 9122504 AB - Little is known about the precise role of alcohol in the escalation of interactions from threats into physical violence or its contribution to the risk of injury. Experimental studies indicate that intoxicated subjects (allegedly) give markedly higher electric shocks than sober subjects and are less sensitive to their cries of pain. However, few studies in a naturalistic setting have examined whether aggressive acts become more serious and result in higher injury rates when the assailants have been drinking than when they are sober. This chapter reviews the two bodies of research on the effects of alcohol on interpersonal aggression and violence; presents new data on the escalation of threatening interactions to assaults and the likelihood of victim injury given an assault, using data from the National Crime Victimization Survey for the years 1992 and 1993; and suggests future directions for research based on our findings that alcohol's impact on both escalation and injury differed according to the victim-assailant relationship. JF - Recent developments in alcoholism : an official publication of the American Medical Society on Alcoholism, the Research Society on Alcoholism, and the National Council on Alcoholism AU - Martin, S E AU - Bachman, R AD - Prevention Research Branch, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland 20892-7003, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 41 EP - 56 VL - 13 SN - 0738-422X, 0738-422X KW - Index Medicus KW - Causality KW - Humans KW - Aged KW - Child KW - Dominance-Subordination KW - Aggression -- psychology KW - Risk Factors KW - Adult KW - Crime -- statistics & numerical data KW - Middle Aged KW - Adolescent KW - United States -- epidemiology KW - Crime -- psychology KW - Female KW - Male KW - Wounds and Injuries -- epidemiology KW - Alcoholic Intoxication -- psychology KW - Alcoholic Intoxication -- epidemiology KW - Violence -- statistics & numerical data KW - Alcoholism -- epidemiology KW - Alcoholism -- psychology KW - Violence -- psychology KW - Wounds and Injuries -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78808850?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Recent+developments+in+alcoholism+%3A+an+official+publication+of+the+American+Medical+Society+on+Alcoholism%2C+the+Research+Society+on+Alcoholism%2C+and+the+National+Council+on+Alcoholism&rft.atitle=The+relationship+of+alcohol+to+injury+in+assault+cases.&rft.au=Martin%2C+S+E%3BBachman%2C+R&rft.aulast=Martin&rft.aufirst=S&rft.date=1997-01-01&rft.volume=13&rft.issue=&rft.spage=41&rft.isbn=&rft.btitle=&rft.title=Recent+developments+in+alcoholism+%3A+an+official+publication+of+the+American+Medical+Society+on+Alcoholism%2C+the+Research+Society+on+Alcoholism%2C+and+the+National+Council+on+Alcoholism&rft.issn=0738422X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-22 N1 - Date created - 1997-04-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reduced renal medullary water channel expression in puromycin aminonucleoside--induced nephrotic syndrome. AN - 78808012; 9013444 AB - The aquaporins are molecular water channels that mediate transcellular water transport across water-permeable epithelia. To investigate the cause of the concentrating defect in the nephrotic syndrome, immunoblotting using membrane fractions from inner medulla was utilized to assess the level of expression of four aquaporin water channels in vehicle-treated versus puromycin aminonucleoside (PAN)-treated rats. Scanning electron microscopy demonstrating loss of glomerular foot processes and measurements of urinary protein excretion confirmed the efficacy of the PAN treatment. In rats receiving PAN, there was an increase in plasma vasopressin, without a change in plasma sodium concentration. Inner medullary tissue hypertonicity was sustained in PAN-treated rats while the urinary osmolality was low, pointing to defective osmotic equilibration across the collecting ducts in PAN-nephrosis. Among collecting duct aquaporins, there was an 87% decrease in aquaporin-2 expression and a 70% decrease in aquaporin-3 expression in the inner medulla, whereas aquaporin-4 expression was unaltered. Transmission electron microscopy of the inner medullary collecting ducts of PAN-treated rats showed normal-appearing cells. Thus, PAN-nephrosis is associated with an extensive downregulation of collecting duct water channel expression despite increased circulating vasopressin, providing an explanation for the concentrating defect associated with the nephrotic syndrome. JF - Journal of the American Society of Nephrology : JASN AU - Apostol, E AU - Ecelbarger, C A AU - Terris, J AU - Bradford, A D AU - Andrews, P AU - Knepper, M A AD - Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892-0951, USA. Y1 - 1997/01// PY - 1997 DA - January 1997 SP - 15 EP - 24 VL - 8 IS - 1 SN - 1046-6673, 1046-6673 KW - Antimetabolites, Antineoplastic KW - 0 KW - Aqp2 protein, rat KW - Aquaporin 2 KW - Aquaporin 6 KW - Aquaporins KW - Ion Channels KW - Puromycin Aminonucleoside KW - 58-60-6 KW - Index Medicus KW - Kidney Tubules, Collecting -- metabolism KW - Animals KW - Immunoblotting KW - Dose-Response Relationship, Drug KW - Kidney Tubules, Collecting -- drug effects KW - Microscopy, Electron, Scanning Transmission KW - Kidney Tubules, Collecting -- ultrastructure KW - Rats KW - Rats, Sprague-Dawley KW - Down-Regulation KW - Kidney Concentrating Ability KW - Male KW - Densitometry KW - Antimetabolites, Antineoplastic -- administration & dosage KW - Puromycin Aminonucleoside -- toxicity KW - Kidney Medulla -- metabolism KW - Kidney Medulla -- ultrastructure KW - Puromycin Aminonucleoside -- administration & dosage KW - Nephrotic Syndrome -- metabolism KW - Kidney Medulla -- drug effects KW - Nephrotic Syndrome -- pathology KW - Antimetabolites, Antineoplastic -- toxicity KW - Nephrotic Syndrome -- chemically induced KW - Ion Channels -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78808012?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Society+of+Nephrology+%3A+JASN&rft.atitle=Reduced+renal+medullary+water+channel+expression+in+puromycin+aminonucleoside--induced+nephrotic+syndrome.&rft.au=Apostol%2C+E%3BEcelbarger%2C+C+A%3BTerris%2C+J%3BBradford%2C+A+D%3BAndrews%2C+P%3BKnepper%2C+M+A&rft.aulast=Apostol&rft.aufirst=E&rft.date=1997-01-01&rft.volume=8&rft.issue=1&rft.spage=15&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Society+of+Nephrology+%3A+JASN&rft.issn=10466673&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-17 N1 - Date created - 1997-04-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Progesterone pretreatment enhances cellular sensitivity to cadmium despite a marked activation of the metallothionein gene. AN - 78803991; 9007047 AB - Previously, we found that in vivo pretreatment with progesterone markedly increased cadmium lethality in rats, apparently by enhancing cadmium-induced hepatonecrosis. Therefore, the present study was designed to investigate this phenomenon at the molecular level in an in vitro system. TRL-1215 rat liver cells were exposed to various concentrations of progesterone (0, 1, 10, and 100 microM) for 24 hr and subsequently exposed to cadmium (0, 1, 5, 10, and 50 microM; as CdCl2) for an additional 24 hr. Although the levels of progesterone used were essentially nontoxic, progesterone pretreatment resulted in a concentration-dependent increase in sensitivity to cadmium as assessed by loss of mitochondrial enzyme activity (tetrazolium-based dye assay) and loss of cytosolic enzyme activity (glutamic oxaloacetic transaminase). The effects of progesterone treatment on intracellular levels of metallothionein (MT), an inducible metal-binding protein generally associated with cadmium tolerance, were also measured. Progesterone (100 microM) alone increased MT levels 2.4-fold, while cadmium (10 microM) alone resulted in a 7-fold increase over control. Progesterone pretreatment followed by cadmium exposure caused a marked, 16-fold induction in MT synthesis, a level of activity that has been associated with acquired tolerance to cadmium. In addition, progesterone pretreatment clearly induced transcription of the MT gene as evidenced by enhanced cadmium-induced accumulation of cellular MT mRNA. Progesterone pretreatment had no effect on the level of glutathione, a cellular thiol thought to be important in detoxication of cadmium prior to MT gene activation and MT protein accumulation, or on cellular accumulation of cadmium during the initial 3 hr of exposure to the metal. The proportion of total cellular cadmium bound to MT in cells pretreated with progesterone was greater than that in the cells treated with cadmium alone, indicating an enhanced sequestration of the metal by MT after pretreatment. These results indicate that progesterone, at nontoxic levels, markedly exacerbates cadmium toxicity at the cellular level in liver cells. This is in accord with the observed progesterone-induced enhancement of the hepatotoxic effects of cadmium in vivo. The observed facilitation of cytotoxicity is not based in altered toxicokinetics of cadmium and occurs despite a pronounced activation of the MT gene resulting in an enhanced sequestration of cadmium by MT. The mechanism by which progesterone enhances cadmium toxicity deserves further study. JF - Toxicology and applied pharmacology AU - Shimada, H AU - Hochadel, J F AU - Waalkes, M P AD - Laboratory of Comparative Carcinogenesis, SAIC Frederick, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702-1201, USA. Y1 - 1997/01// PY - 1997 DA - January 1997 SP - 178 EP - 185 VL - 142 IS - 1 SN - 0041-008X, 0041-008X KW - RNA, Messenger KW - 0 KW - Progesterone KW - 4G7DS2Q64Y KW - Metallothionein KW - 9038-94-2 KW - Aspartate Aminotransferases KW - EC 2.6.1.1 KW - Glutathione KW - GAN16C9B8O KW - Cadmium Chloride KW - J6K4F9V3BA KW - Index Medicus KW - Rats KW - Aspartate Aminotransferases -- metabolism KW - Animals KW - Rats, Inbred F344 KW - Mitochondria, Liver -- enzymology KW - Glutathione -- metabolism KW - Mitochondria, Liver -- drug effects KW - Cells, Cultured -- drug effects KW - Drug Synergism KW - Transcriptional Activation KW - RNA, Messenger -- biosynthesis KW - Liver -- pathology KW - Metallothionein -- biosynthesis KW - Liver -- drug effects KW - Progesterone -- pharmacology KW - Cadmium Chloride -- toxicity KW - Cadmium Chloride -- pharmacology KW - Metallothionein -- genetics KW - Gene Expression Regulation -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78803991?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Progesterone+pretreatment+enhances+cellular+sensitivity+to+cadmium+despite+a+marked+activation+of+the+metallothionein+gene.&rft.au=Shimada%2C+H%3BHochadel%2C+J+F%3BWaalkes%2C+M+P&rft.aulast=Shimada&rft.aufirst=H&rft.date=1997-01-01&rft.volume=142&rft.issue=1&rft.spage=178&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=0041008X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-24 N1 - Date created - 1997-02-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacologic treatments for temporomandibular disorders. AN - 78802411; 9007937 AB - Drugs are widely used in the management of acute and chronic orofacial pain. Whereas the use of analgesics for acute orofacial pain is well documented through hundreds of controlled clinical trials, the use of a broad spectrum of drugs for chronic pain is based on very few studies. In the absence of data supporting a therapeutic benefit for a drug used chronically for pain, toxicity associated with the drug can still occur. It is critical, therefore, to assess the balance between therapeutic benefit and safety. This article reviews current evidence supporting the use of several drug classes for temporomandibular disorders (TMD) and identifies therapeutic controversies in need of further research. JF - Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics AU - Dionne, R A AD - Neurobiology and Anesthesiology Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD, USA. Y1 - 1997/01// PY - 1997 DA - January 1997 SP - 134 EP - 142 VL - 83 IS - 1 SN - 1079-2104, 1079-2104 KW - Adrenal Cortex Hormones KW - 0 KW - Analgesics, Non-Narcotic KW - Analgesics, Opioid KW - Anti-Inflammatory Agents, Non-Steroidal KW - Antidepressive Agents KW - Muscle Relaxants, Central KW - Benzodiazepines KW - 12794-10-4 KW - Dentistry KW - Index Medicus KW - Benzodiazepines -- therapeutic use KW - Adrenal Cortex Hormones -- therapeutic use KW - Anti-Inflammatory Agents, Non-Steroidal -- therapeutic use KW - Analgesics, Non-Narcotic -- therapeutic use KW - Humans KW - Muscle Relaxants, Central -- therapeutic use KW - Analgesics, Opioid -- therapeutic use KW - Antidepressive Agents -- therapeutic use KW - Facial Pain -- drug therapy KW - Chronic Disease KW - Temporomandibular Joint Dysfunction Syndrome -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78802411?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oral+surgery%2C+oral+medicine%2C+oral+pathology%2C+oral+radiology%2C+and+endodontics&rft.atitle=Pharmacologic+treatments+for+temporomandibular+disorders.&rft.au=Dionne%2C+R+A&rft.aulast=Dionne&rft.aufirst=R&rft.date=1997-01-01&rft.volume=83&rft.issue=1&rft.spage=134&rft.isbn=&rft.btitle=&rft.title=Oral+surgery%2C+oral+medicine%2C+oral+pathology%2C+oral+radiology%2C+and+endodontics&rft.issn=10792104&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-13 N1 - Date created - 1997-02-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dihydropyrimidine dehydrogenase deficiency: a pharmacogenetic defect causing severe adverse reactions to 5-fluorouracil-based chemotherapy. AN - 78798315; 9007910 AB - To describe the pharmacogenetic syndrome of dihydropyrimidine dehydrogenase (DPD) deficiency, which predisposes patients with cancer to potentially lethal adverse reactions following 5-fluorouracil (5-FU)-based chemotherapy. Published articles, abstracts, and conference proceedings. Genetic deficiencies in DPD, the rate-limiting enzyme responsible for 5-FU catabolism, may occur in 3% or more of patients with cancer putting them at increased risk for unusually severe adverse reactions (e.g., diarrhea, stomatitis, mucositis, myelosuppression, neurotoxicity) to standard doses of 5-FU. Diagnosis of DPD deficiency must be confirmed by specialized laboratory tests. The principle treatment for DPD-deficient patients with severe acute 5-FU reactions is supportive care; however, the administration of thymidine potentially may reverse severe 5-FU-induced neurologic symptoms such as encephalopathy and coma. Early recognition of this serious pharmacogenetic syndrome may allow for the modification of future chemotherapy, thus avoiding further life-threatening toxicities. Nurses must understand the pharmacology, mechanism of action, clinical presentation, potentially lethal risks, and traumatic psychosocial stresses experienced by DPD-deficient patients with cancer receiving 5-FU therapy in order to develop timely interventions and alternative plans of care. JF - Oncology nursing forum AU - Morrison, G B AU - Bastian, A AU - Dela Rosa, T AU - Diasio, R B AU - Takimoto, C H AD - NCI-Navy Medical Oncology Branch, National Cancer Institute in Bethesda, MD, USA. PY - 1997 SP - 83 EP - 88 VL - 24 IS - 1 SN - 0190-535X, 0190-535X KW - Antimetabolites, Antineoplastic KW - 0 KW - Oxidoreductases KW - EC 1.- KW - Dihydrouracil Dehydrogenase (NADP) KW - EC 1.3.1.2 KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Nursing KW - Severity of Illness Index KW - Liver Neoplasms -- pathology KW - Carcinoma, Hepatocellular -- drug therapy KW - Liver Neoplasms -- drug therapy KW - Humans KW - Carcinoma, Hepatocellular -- secondary KW - Adult KW - Pleural Neoplasms -- secondary KW - Pleural Neoplasms -- drug therapy KW - Middle Aged KW - Male KW - Female KW - Neoplasms -- drug therapy KW - Fluorouracil -- adverse effects KW - Antimetabolites, Antineoplastic -- adverse effects KW - Metabolism, Inborn Errors -- complications KW - Oxidoreductases -- deficiency KW - Fluorouracil -- metabolism KW - Antimetabolites, Antineoplastic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78798315?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+nursing+forum&rft.atitle=Dihydropyrimidine+dehydrogenase+deficiency%3A+a+pharmacogenetic+defect+causing+severe+adverse+reactions+to+5-fluorouracil-based+chemotherapy.&rft.au=Morrison%2C+G+B%3BBastian%2C+A%3BDela+Rosa%2C+T%3BDiasio%2C+R+B%3BTakimoto%2C+C+H&rft.aulast=Morrison&rft.aufirst=G&rft.date=1997-01-01&rft.volume=24&rft.issue=1&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=Oncology+nursing+forum&rft.issn=0190535X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-05 N1 - Date created - 1997-06-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Influence of endosome-destabilizing peptides on efficacy of anti-HIV immunotoxins. AN - 78795857; 9026033 AB - The effects on immunotoxin efficacy of fusogenic peptides derived from influenza virus hemagglutinin have been studied. These peptides have an amphipathic nature and change conformation from random at pH 7 to helical at pH 5. Fusogenic peptides are reported to destabilize endosomal membranes, resulting in the release of contents into the cytoplasm. The use of two related fusogenic peptides to enhance the efficacy of anti-HIV immunotoxins is described. The direct toxicity of the peptides was tested on HIV-infected H9/NL4-3 cells. Peptide HA24 was considerably more toxic than HA23. The peptides were mixed with two different immunotoxins. Immunotoxin action was enhanced by both peptides, with HA24 providing greater enhancement than HA23. Immunotoxins were then constructed by coupling HA23 or HA24 to the targeting antibody with disulfide-containing linkers. Peptide HA23 enhanced the activity of the immunotoxin 4-5-fold. Surprisingly, HA24 significantly inhibited immunotoxin activity. Coupling the peptides to the immunotoxin had no effect on antigen binding characteristics or the activity of the toxic moiety. Bafilomycin A1, an agent that inhibits vacuolar acidification, markedly potentiated the effects of all immunotoxins. These results demonstrate that amphipathic peptides can influence the efficacy of immunotoxins, but in sometimes unpredictable ways. JF - Bioconjugate chemistry AU - Tolstikov, V V AU - Cole, R AU - Fang, H AU - Pincus, S H 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. PY - 1997 SP - 38 EP - 43 VL - 8 IS - 1 SN - 1043-1802, 1043-1802 KW - Anti-Bacterial Agents KW - 0 KW - CD4 Immunoadhesins KW - Enzyme Inhibitors KW - HIV Envelope Protein gp120 KW - Immunotoxins KW - Macrolides KW - Peptides KW - bafilomycin A1 KW - 88899-55-2 KW - Alkaline Phosphatase KW - EC 3.1.3.1 KW - Proton-Translocating ATPases KW - EC 3.6.3.14 KW - Index Medicus KW - AIDS/HIV KW - Animals KW - CD4 Immunoadhesins -- therapeutic use KW - Guinea Pigs KW - Models, Molecular KW - Humans KW - Anti-Bacterial Agents -- pharmacology KW - Rabbits KW - Alkaline Phosphatase -- metabolism KW - Amino Acid Sequence KW - Proton-Translocating ATPases -- antagonists & inhibitors KW - Molecular Sequence Data KW - Enzyme Inhibitors -- pharmacology KW - Enzyme-Linked Immunosorbent Assay KW - CD4 Immunoadhesins -- metabolism KW - Cell Line KW - HIV Envelope Protein gp120 -- immunology KW - Peptides -- metabolism KW - Immunotoxins -- therapeutic use KW - Endosomes -- metabolism KW - HIV-1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78795857?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioconjugate+chemistry&rft.atitle=Influence+of+endosome-destabilizing+peptides+on+efficacy+of+anti-HIV+immunotoxins.&rft.au=Tolstikov%2C+V+V%3BCole%2C+R%3BFang%2C+H%3BPincus%2C+S+H&rft.aulast=Tolstikov&rft.aufirst=V&rft.date=1997-01-01&rft.volume=8&rft.issue=1&rft.spage=38&rft.isbn=&rft.btitle=&rft.title=Bioconjugate+chemistry&rft.issn=10431802&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-22 N1 - Date created - 1997-05-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sporadic and Thorotrast-induced angiosarcomas of the liver manifest frequent and multiple point mutations in K-ras-2. AN - 78795806; 9010458 AB - Hepatic angiosarcoma (HA) is an uncommon neoplasm associated with known etiologic factors in 25% to 42% of cases. It is, however, one of the most common sarcomas found in the liver. The aim of this study was to find was to find mutations in the K-ras-2 oncogene in sporadic and Thorotrast (TT)-induced HA. Point mutations in K-ras-2 were sought in archival, formalin-fixed tissue blocks from 24 patients with angiosarcoma. Of these, 19 cases were sporadic and 5 were TT-induced. Mutational analysis was performed by topographic microdissection with PCR amplification followed by genotyping. Specific mutations were determined by two independent methods: (a) direct sequencing of the PCR product confirmed by rePCR and by using a different sequencing primer, and (b) PCR-based selective enrichment of mutant DNA by endonuclease digestion followed by heteroduplex DNA analysis using denaturing gradient gel electrophoresis. Eleven K-ras-2 point mutations were detected in 7 of 24 (29%) tumors, including 5 of 19 (26%) sporadic HA and 2 of 5 (40%) TT-induced HA. There were seven G:C > A:T and four G:C > T:A mutations. All seven mutated tumors contained a codon 12-aspartate amino acid substitution. In addition, a second codon 12-cysteine mutant cell population was present in one of two codon 12-aspartate mutated TT-induced HA and in three of five codon 12-aspartate sporadic tumors. Of these four tumors, three contained both aspartate and cysteine mutations and were composed of multiple nodules; the fourth was a single mass. Seventeen tumors had multiple nodules; whereas 5 had a K-ras-2 mutation, 12 were wild-type. The molecular pathology of both sporadic and TT-induced HA is characterized by a high rate of K-ras-2 mutations characteristic of oxidative damage (ie, G:C > A:T and G:C > T:A mutations) resulting in two mutated population sets: codon 12 GGT > GAT and GGT > TGT (glycine to aspartic acid and cysteine). This is, to date, the first study to characterize the K-ras-2 gene mutations within human sporadic and TT-induced HA by direct sequence analysis and denaturing gradient gel electrophoresis. These data further support the hypothesis linking adduct-forming vinyl chloride exposure to HA containing a much higher frequency of K-ras-2 mutations and a mutational spectrum characteristic of chloroethylene oxide, a carcinogenic metabolite of vinyl chloride. JF - Laboratory investigation; a journal of technical methods and pathology AU - Przygodzki, R M AU - Finkelstein, S D AU - Keohavong, P AU - Zhu, D AU - Bakker, A AU - Swalsky, P A AU - Soini, Y AU - Ishak, K G AU - Bennett, W P AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1997/01// PY - 1997 DA - January 1997 SP - 153 EP - 159 VL - 76 IS - 1 SN - 0023-6837, 0023-6837 KW - Carcinogens KW - 0 KW - Thorium Dioxide KW - 9XA7X17UQC KW - Index Medicus KW - Occupational Exposure KW - Polymerase Chain Reaction KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Female KW - Genes, ras KW - Liver Neoplasms -- pathology KW - Hemangiosarcoma -- etiology KW - Neoplasms, Radiation-Induced -- etiology KW - Hemangiosarcoma -- genetics KW - Hemangiosarcoma -- pathology KW - Point Mutation KW - Neoplasms, Radiation-Induced -- genetics KW - Liver Neoplasms -- etiology KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78795806?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Laboratory+investigation%3B+a+journal+of+technical+methods+and+pathology&rft.atitle=Sporadic+and+Thorotrast-induced+angiosarcomas+of+the+liver+manifest+frequent+and+multiple+point+mutations+in+K-ras-2.&rft.au=Przygodzki%2C+R+M%3BFinkelstein%2C+S+D%3BKeohavong%2C+P%3BZhu%2C+D%3BBakker%2C+A%3BSwalsky%2C+P+A%3BSoini%2C+Y%3BIshak%2C+K+G%3BBennett%2C+W+P&rft.aulast=Przygodzki&rft.aufirst=R&rft.date=1997-01-01&rft.volume=76&rft.issue=1&rft.spage=153&rft.isbn=&rft.btitle=&rft.title=Laboratory+investigation%3B+a+journal+of+technical+methods+and+pathology&rft.issn=00236837&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-24 N1 - Date created - 1997-02-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of transforming growth factor beta-1 in endotoxin-induced uveitis. AN - 78794927; 9008650 AB - Transforming growth factor beta-1 (TGF beta-1) can modulate inflammation. Endotoxin-induced uveitis (EIU) is characterized by acute ocular inflammation related to the release of cytokines, including interleukin (IL)-6. The authors investigated the effect of TGF beta-1 on EIU in mice. Three independent experiments were performed. Endotoxin-induced uveitis was induced in C3H/HeN mice by an injection of 200 micrograms of lipopolysaccharide (LPS). Two micrograms of TGF beta-1 in 0.1 ml phosphate-buffered saline (PBS) or 0.1 ml PBS alone was administered intraperitoneally at 8 hours after LPS injection. Twenty-four hours after LPS injection, the aqueous humor of the right eyes was collected for leukocyte count, protein concentration, and IL-6 assay. Left eyes were processed for routine histology. TGF beta-1-treated mice showed less ocular inflammation histologically than to the animals that were given PBS. This was confirmed by decreases in leukocyte count, protein concentration, and IL-6 level in the aqueous humor. TGF beta-1 inhibits the development of EIU. TGF beta-1 may be useful for the modulation of uveitis in humans. JF - Investigative ophthalmology & visual science AU - Peng, B AU - Li, Q AU - Roberge, F G AU - Chan, C C AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-1858, USA. Y1 - 1997/01// PY - 1997 DA - January 1997 SP - 257 EP - 260 VL - 38 IS - 1 SN - 0146-0404, 0146-0404 KW - Endotoxins KW - 0 KW - Transforming Growth Factor beta KW - Index Medicus KW - Animals KW - Aqueous Humor -- immunology KW - Leukocytes -- immunology KW - Mice, Inbred C3H KW - Mice KW - Leukocyte Count KW - Female KW - Transforming Growth Factor beta -- pharmacology KW - Uveitis, Anterior -- prevention & control KW - Uveitis, Anterior -- chemically induced KW - Uveitis, Anterior -- immunology KW - Uveitis, Anterior -- pathology KW - Salmonella typhimurium KW - Endotoxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78794927?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+transforming+growth+factor+beta-1+in+endotoxin-induced+uveitis.&rft.au=Peng%2C+B%3BLi%2C+Q%3BRoberge%2C+F+G%3BChan%2C+C+C&rft.aulast=Peng&rft.aufirst=B&rft.date=1997-01-01&rft.volume=38&rft.issue=1&rft.spage=257&rft.isbn=&rft.btitle=&rft.title=Investigative+ophthalmology+%26+visual+science&rft.issn=01460404&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-11 N1 - Date created - 1997-02-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lung cancer risk from residential radon: meta-analysis of eight epidemiologic studies. AN - 78794570; 8978406 AB - Studies of underground miners exposed to radioactive radon and its decay products have found that exposure increases risk of lung cancer. Consequently, when radon was found to accumulate in houses, there was concern about the public health impact from exposure to a known carcinogen. Estimates on the basis of studies of underground miners suggest that indoor radon may account for 6000-36,000 lung cancer deaths each year in the United States. Because of differences between working in underground mines and living in houses, estimates are subject to major uncertainties. Numerous case-control studies were launched to assess directly the lung cancer risk from indoor radon. Some studies report positive or weakly positive findings, while others report no increased risk. Thus, the potential hazard from indoor radon remains answered only indirectly through miner studies, experimental animal studies, and cellular studies. To provide more information on the risk of lung cancer from indoor radon, we conducted a meta-analysis of all case-control studies that included at least 200 case subjects each and that used long-term indoor radon measurements. Eight studies were available and included a total of 4263 lung cancer case subjects and 6612 control subjects. From the published results of each study, confounder-adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) for categories of radon concentration were obtained, and weighted linear regression analyses were performed. The combined trend in the RR was significantly different from zero (two-sided P = .03), and an estimated RR of 1.14 (95% CI = 1.0-1.3) at 150 Bq/m3 was found. An influence analysis indicated that no single study dominated the combined results. The exposure-response trend was similar to model-based extrapolations from miners and to RRs computed directly from miners with low cumulative exposures. However, there were significant differences in the study-specific estimates of the exposure response (two-sided P < .001), which were not explained by study differences in percent of the defined exposure interval covered by radon measurements, mean number of residences per subject, and other factors. Meta-analyses are valuable for identifying differences among studies and for summarizing results, but they should be interpreted cautiously when expected RRs are low as with indoor radon exposure, when there is study heterogeneity and where there is the potential for confounding and exposure misclassification. Nonetheless, the results of this meta-analysis suggest that the risk from indoor radon is not likely to be markedly greater than that predicted from miners and indicate that the negative exposure response reported in some ecologic studies is likely due to model misspecification or uncontrolled confounding and can be rejected. Until ongoing case-control studies of indoor radon are completed and the data are pooled and analyzed, the studies of underground miners remain the best source of data to use to assess risk from indoor radon. This meta-analysis provides support for their general validity. JF - Journal of the National Cancer Institute AU - Lubin, J H AU - Boice, J D AD - Epidemiology and Biostatistics Program, National Cancer Institute, Bethesda, MD, USA. Y1 - 1997/01/01/ PY - 1997 DA - 1997 Jan 01 SP - 49 EP - 57 VL - 89 IS - 1 SN - 0027-8874, 0027-8874 KW - Radon KW - Q74S4N8N1G KW - Index Medicus KW - Canada -- epidemiology KW - Risk KW - Missouri -- epidemiology KW - New Jersey -- epidemiology KW - Humans KW - China -- epidemiology KW - Case-Control Studies KW - Sweden -- epidemiology KW - Finland -- epidemiology KW - Air Pollution, Indoor -- adverse effects KW - Lung Neoplasms -- epidemiology KW - Lung Neoplasms -- chemically induced KW - Radon -- adverse effects KW - Environmental Exposure -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78794570?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Lung+cancer+risk+from+residential+radon%3A+meta-analysis+of+eight+epidemiologic+studies.&rft.au=Lubin%2C+J+H%3BBoice%2C+J+D&rft.aulast=Lubin&rft.aufirst=J&rft.date=1997-01-01&rft.volume=89&rft.issue=1&rft.spage=49&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-17 N1 - Date created - 1997-01-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Natl Cancer Inst. 1997 Jan 1;89(1):4-6 [8978397] J Natl Cancer Inst. 1997 May 7;89(9):664; author reply 664-5 [9150198] J Natl Cancer Inst. 1997 May 7;89(9):663-4; author reply 664-5 [9150197] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phorbol esters increase dopamine transporter phosphorylation and decrease transport Vmax. AN - 78794088; 8978729 AB - Sodium- and chloride-coupled transport of dopamine from synapses into presynaptic terminals plays a key role in terminating dopaminergic neurotransmission. Regulation of the function of the dopamine transporter, the molecule responsible for this translocation, is thus of interest. The primary sequence of the dopamine transporter contains multiple potential phosphorylation sites, suggesting that the function of the transporter could be regulated by phosphorylation. Previous work from this laboratory has documented that phorbol ester activation of protein kinase C (PKC) decreases dopamine transport Vmax in transiently expressing COS cells. In the present report, we document in vivo phosphorylation of the rat dopamine transporter stably expressed in LLC-PK1, cells and show that phosphorylation is increased threefold by phorbol esters. Dopamine uptake is also regulated by phorbol esters in these cells; phorbol 12-myristate 13-acetate (PMA) reduces transport Vmax by 35%. Parallels between the time course, concentration dependency, and staurosporine sensitivity of alterations in transporter phosphorylation and transporter Vmax suggest that dopamine transporter phosphorylation involving PKC could contribute to this decreased transporter function. Phosphorylation of the dopamine transporter by PKC or by a PKC-activated kinase could be involved in rapid neuroadaptive processes in dopaminergic neurons. JF - Journal of neurochemistry AU - Huff, R A AU - Vaughan, R A AU - Kuhar, M J AU - Uhl, G R AD - Molecular Neurobiology Branch, National Institute on Drug Abuse, Baltimore, MD 21224, USA. Y1 - 1997/01// PY - 1997 DA - January 1997 SP - 225 EP - 232 VL - 68 IS - 1 SN - 0022-3042, 0022-3042 KW - Carrier Proteins KW - 0 KW - Dopamine Plasma Membrane Transport Proteins KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Leucine KW - GMW67QNF9C KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Alanine KW - OF5P57N2ZX KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Swine KW - Rats KW - Animals KW - Leucine -- pharmacokinetics KW - LLC-PK1 Cells KW - Alanine -- pharmacokinetics KW - Phosphorylation -- drug effects KW - Biological Transport -- drug effects KW - Carrier Proteins -- metabolism KW - Dopamine -- pharmacokinetics KW - Tetradecanoylphorbol Acetate -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78794088?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=Phorbol+esters+increase+dopamine+transporter+phosphorylation+and+decrease+transport+Vmax.&rft.au=Huff%2C+R+A%3BVaughan%2C+R+A%3BKuhar%2C+M+J%3BUhl%2C+G+R&rft.aulast=Huff&rft.aufirst=R&rft.date=1997-01-01&rft.volume=68&rft.issue=1&rft.spage=225&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-27 N1 - Date created - 1997-01-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pigment epithelium-derived factor protects cultured cerebellar granule cells against glutamate-induced neurotoxicity. AN - 78793903; 8978706 AB - Pigment epithelium-derived factor (PEDF) is a survival factor for cerebellar granule cells in culture. In the present study, we have investigated the ability of a recombinant form of PEDF (rPEDF) to protect against glutamate neurotoxicity. When rPEDF was added to cerebellar granule cell cultures 30 min before addition of 100 microM glutamate, glutamate-induced neuronal death was significantly reduced. The protective effect of rPEDF was dose-dependent in the range from 0.023 to 7.0 nM (1-500 ng/ml), with a half-maximal dose of 0.47 nM. An antibody to rPEDF blocked this protective effect. Measurement of intraneuronal free calcium levels demonstrated that rPEDF raised the basal calcium content. However, after the elevation of intracellular calcium in response to administration of glutamate, rPEDF reduced the plateau level seen in the presence of glutamate. These data show that PEDF can protect neurons against glutamate-induced neurotoxicity, possibly via a calcium-related pathway. The finding that only 30 min of preincubation is required for the neuroprotective effect, significantly faster than other known neurotrophic factors, suggests that PEDF may be useful clinically as a neuroprotective agent in the CNS. JF - Journal of neurochemistry AU - Taniwaki, T AU - Hirashima, N AU - Becerra, S P AU - Chader, G J AU - Etcheberrigaray, R AU - Schwartz, J P AD - Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland 20892-1279, USA. Y1 - 1997/01// PY - 1997 DA - January 1997 SP - 26 EP - 32 VL - 68 IS - 1 SN - 0022-3042, 0022-3042 KW - Eye Proteins KW - 0 KW - Immune Sera KW - Nerve Growth Factors KW - Neuroprotective Agents KW - Neurotoxins KW - Proteins KW - Recombinant Proteins KW - Serpins KW - pigment epithelium-derived factor KW - Glutamic Acid KW - 3KX376GY7L KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Rats KW - Calcium -- metabolism KW - Animals, Newborn KW - Animals KW - Rats, Sprague-Dawley KW - Cells, Cultured KW - Intracellular Membranes -- drug effects KW - Immune Sera -- immunology KW - Intracellular Membranes -- metabolism KW - Proteins -- pharmacology KW - Cerebellum -- cytology KW - Neurons -- metabolism KW - Serpins -- pharmacology KW - Neurons -- drug effects KW - Cerebellum -- drug effects KW - Neurotoxins -- pharmacology KW - Serpins -- immunology KW - Glutamic Acid -- pharmacology KW - Proteins -- immunology KW - Neuroprotective Agents -- pharmacology KW - Cerebellum -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78793903?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=Pigment+epithelium-derived+factor+protects+cultured+cerebellar+granule+cells+against+glutamate-induced+neurotoxicity.&rft.au=Taniwaki%2C+T%3BHirashima%2C+N%3BBecerra%2C+S+P%3BChader%2C+G+J%3BEtcheberrigaray%2C+R%3BSchwartz%2C+J+P&rft.aulast=Taniwaki&rft.aufirst=T&rft.date=1997-01-01&rft.volume=68&rft.issue=1&rft.spage=26&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-27 N1 - Date created - 1997-01-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of an RNA sequence within an intracisternal-A particle element able to replace Rev-mediated posttranscriptional regulation of human immunodeficiency virus type 1. AN - 78792018; 8985327 AB - Human immunodeficiency virus type 1 (HIV-1) replication depends on the posttranscriptional regulation by the viral Rev protein and can be replaced with the posttranscriptional RNA control element (CTE) of the type D simian retroviruses. We have identified a sequence which shares only nucleotide sequences of the internal loops and secondary structure with the CTE and which is part of a novel murine intracisternal-A particle (IAP) retroelement, inserted within the transcribed mouse osteocalcin-related gene. This sequence, named CTE(IAP), can replace the Rev-mediated regulation of HIV-1, hence it is a posttranscriptional regulatory element. Related elements have been identified in other IAPs. These results suggest that insertional mutagenesis can affect gene expression by providing a functional posttranscriptional control element. The CTE(IAP) and CTEs of the type D simian retroviruses represent a novel class of RNA elements characterized by unique sequences within the internal loops which are predicted to represent the interaction site with cellular factor(s). These findings suggest that such elements may be involved in posttranscriptional regulation of cellular mRNAs. JF - Journal of virology AU - Tabernero, C AU - Zolotukhin, A S AU - Bear, J AU - Schneider, R AU - Karsenty, G AU - Felber, B K AD - Human Retrovirus Pathogenesis Group, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201, USA. Y1 - 1997/01// PY - 1997 DA - January 1997 SP - 95 EP - 101 VL - 71 IS - 1 SN - 0022-538X, 0022-538X KW - Gene Products, rev KW - 0 KW - rev Gene Products, Human Immunodeficiency Virus KW - Osteocalcin KW - 104982-03-8 KW - RNA KW - 63231-63-0 KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Base Sequence KW - Sequence Homology, Nucleic Acid KW - Humans KW - Molecular Sequence Data KW - Databases, Factual KW - Mice KW - Amino Acid Sequence KW - Cell Line, Transformed KW - Regulatory Sequences, Nucleic Acid KW - HIV-1 -- genetics KW - Gene Expression Regulation, Viral KW - Gene Products, rev -- genetics KW - Genes, Intracisternal A-Particle KW - RNA Processing, Post-Transcriptional UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78792018?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Identification+of+an+RNA+sequence+within+an+intracisternal-A+particle+element+able+to+replace+Rev-mediated+posttranscriptional+regulation+of+human+immunodeficiency+virus+type+1.&rft.au=Tabernero%2C+C%3BZolotukhin%2C+A+S%3BBear%2C+J%3BSchneider%2C+R%3BKarsenty%2C+G%3BFelber%2C+B+K&rft.aulast=Tabernero&rft.aufirst=C&rft.date=1997-01-01&rft.volume=71&rft.issue=1&rft.spage=95&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-31 N1 - Date created - 1997-01-31 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U53817; GENBANK; U53816; U53815; U53814; U53819; U53818; U53820; U53813 N1 - SuppNotes - Cited By: J Virol. 1994 Dec;68(12):7944-52 [7966585] Proc Natl Acad Sci U S A. 1989 Mar;86(5):1495-9 [2784208] J Virol. 1995 May;69(5):2932-45 [7707519] Mol Cell Biol. 1995 Jun;15(6):2962-71 [7760794] Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11940-4 [8524879] J Virol. 1989 May;63(5):1959-66 [2704072] Cell. 1989 Jun 30;57(7):1155-65 [2736624] Cell. 1989 Dec 1;59(5):789-95 [2686839] Genes Dev. 1989 Oct;3(10):1534-44 [2482226] Science. 1986 Mar 28;231(4745):1567-72 [3006247] J Virol. 1986 Aug;59(2):284-91 [3016298] Cell. 1986 Sep 12;46(6):807-17 [3638988] J Virol. 1990 Jun;64(6):2519-29 [2335812] Proc Natl Acad Sci U S A. 1990 Oct;87(19):7497-501 [2170981] Proc Natl Acad Sci U S A. 1990 Oct;87(19):7598-602 [2217190] New Biol. 1989 Dec;1(3):318-28 [2562124] Genes Dev. 1991 May;5(5):808-19 [1827422] Gene. 1991 Apr;100:139-46 [2055466] J Virol. 1991 Nov;65(11):5702-9 [1920613] J Virol. 1992 Jan;66(1):150-9 [1727477] Mol Cell Biol. 1992 Mar;12(3):1375-86 [1545819] New Biol. 1991 Dec;3(12):1220-32 [1725960] Microbiol Rev. 1992 Sep;56(3):375-94 [1406488] Endocrinology. 1993 Dec;133(6):3050-3 [8243336] Mol Cell Biol. 1993 Dec;13(12):7476-86 [8246965] J Biol Chem. 1994 Jan 14;269(2):1183-90 [8288580] Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1256-60 [8108397] Virology. 1994 Feb 15;199(1):47-55 [8116254] J Virol. 1994 May;68(5):3193-9 [8151782] J Virol. 1995 Sep;69(9):5607-20 [7637007] Oncogene. 1995 Jul 6;11(1):81-7 [7624135] J Virol. 1996 Jun;70(6):3834-43 [8648719] J Virol. 1996 Sep;70(9):5998-6011 [8709222] FEBS Lett. 1986 Dec 15;209(2):187-90 [3025015] Proc Natl Acad Sci U S A. 1987 Jun;84(11):3653-7 [3035544] Science. 1988 May 13;240(4854):916-9 [2834826] EMBO J. 1988 Feb;7(2):519-23 [2835230] Nature. 1988 Sep 8;335(6186):181-3 [3412474] Proc Natl Acad Sci U S A. 1988 Oct;85(19):7124-8 [3174625] Adv Cancer Res. 1988;51:183-276 [3146900] Nature. 1989 Mar 16;338(6212):254-7 [2784194] Mol Cell Biol. 1995 Apr;15(4):1858-69 [7891679] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neurotrophin protection against toxicity induced by low potassium and nitroprusside in cultured cerebellar granule neurons. AN - 78789469; 8978711 AB - Long-term survival of cultured rat cerebellar granule neurons requires depolarizing concentrations of potassium (high potassium; 25 mM KCl). A high-potassium culturing condition has been reported to increase the intracellular calcium concentration ([Ca2+]i) and the expression of brain-derived neurotrophic factor (BDNF), which in turn induces the expression of neurotrophin-3 (NT-3) in these neurons. We therefore examined the neurotrophic effect of these two neurotrophins in low-potassium (5 mM) cultures and their neuroprotective capabilities against sodium nitroprusside-induced neurotoxicity in both low- and high-potassium cultures. Neuronal survival and neurotrophic effects were monitored by [3H]ouabain binding and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. In low-potassium cultures, the neurotrophic effect of BDNF approached that found in high-potassium cultures but was much more robust than that of NT-3. In contrast, undifferentiated neurons cultured in high-potassium medium were much less responsive to BDNF and not responsive at all to NT-3. Induction of nitroprusside neurotoxicity occurred more readily in low- than in high-potassium cultures. BDNF, NT-3, and a high potassium concentration, alone or in combination, were unable to protect neurons treated with nitroprusside at 50 or 100 microM. However, the neurotoxicity of a lower dose of nitroprusside (10 microM) was reversed by the combined actions of these two neurotrophins in low-potassium cultures and by BDNF alone in high-potassium cultures. Because nitroprusside neurotoxicity is less robust in high-potassium cultures, high-potassium-induced BDNF expression and subsequent NT-3 expression may participate in its neuroprotection and neurotrophism in these cultures. Also, we found that toxic doses of nitroprusside antagonized KCl- and NMDA-induced rises in [Ca2+]i, suggesting that this effect is related to nitroprusside-induced neurotoxicity. JF - Journal of neurochemistry AU - Yu, O AU - Chuang, D M AD - Section on Molecular Neurobiology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1272, USA. Y1 - 1997/01// PY - 1997 DA - January 1997 SP - 68 EP - 77 VL - 68 IS - 1 SN - 0022-3042, 0022-3042 KW - Brain-Derived Neurotrophic Factor KW - 0 KW - Culture Media KW - Nerve Growth Factors KW - Neuroprotective Agents KW - Neurotrophin 3 KW - Fibroblast Growth Factor 2 KW - 103107-01-3 KW - Nitroprusside KW - 169D1260KM KW - Potassium KW - RWP5GA015D KW - Index Medicus KW - Rats KW - Osmolar Concentration KW - Fibroblast Growth Factor 2 -- pharmacology KW - Animals KW - Rats, Sprague-Dawley KW - Cells, Cultured KW - Neurons -- drug effects KW - Cell Death KW - Neurons -- physiology KW - Cerebellum -- cytology KW - Nerve Growth Factors -- pharmacology KW - Brain-Derived Neurotrophic Factor -- pharmacology KW - Cerebellum -- drug effects KW - Potassium -- pharmacology KW - Nitroprusside -- pharmacology KW - Potassium -- administration & dosage KW - Nitroprusside -- administration & dosage KW - Neuroprotective Agents -- pharmacology KW - Cerebellum -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78789469?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=Neurotrophin+protection+against+toxicity+induced+by+low+potassium+and+nitroprusside+in+cultured+cerebellar+granule+neurons.&rft.au=Yu%2C+O%3BChuang%2C+D+M&rft.aulast=Yu&rft.aufirst=O&rft.date=1997-01-01&rft.volume=68&rft.issue=1&rft.spage=68&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-27 N1 - Date created - 1997-01-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Raf-1 protein is required for growth factor-induced proliferation of primitive hematopoietic progenitors stimulated with synergistic combinations of cytokines. AN - 78789004; 9007224 AB - Raf-1 is a serine/threonine kinase that has been identified as a component of growth factor-activated signal transduction pathways, and is required for growth factor-induced proliferation of leukemic cell lines and colony formation of hematopoietic progenitors stimulated with single colony-stimulating factors, which promote the growth of committed hematopoietic progenitor cells. However, it is known that the most primitive progenitors in the bone marrow require stimulation with multiple cytokines to promote cell growth. We have determined that c-raf antisense oligonucleotides inhibit the growth of murine lineage-negative progenitors stimulated with two-, three- and four-factor combinations of growth factors, including GM-CSF + interleukin (IL)- 1, IL-3 + steel factor (SLF), IL-3 + IL-11 + SLF and IL-3 + IL-11 + SLF + G-CSF. In addition, c-raf antisense oligonucleotides inhibit the synergistic response of the MO7e human progenitor cell line induced to proliferate with IL-3 + SLF (99%) or GM-CSF + SLF (99%). In contrast, c-raf antisense oligonucleotides only partially inhibited day 14 colony formation of CD34+ human progenitors stimulated with IL-3 + SLF (50%) or GM-CSF + SLF (55%) but completely inhibited day 7 colony formation. However, pulsing CD34+ cells with additional oligonucleotides on day 7 of the colony assay further inhibited day 14 colony formation (70%-80%). Furthermore, a comparison of the effect of c-raf antisense oligonucleotides on the synergistic response of normal human fetal liver cells in [3H]thymidine incorporation assays and colony assays showed strong inhibition in short-term proliferation assays and partial inhibition in 14-day colony assays. Taken together, these results demonstrate that partial inhibition of colony formation of primitive human progenitors stimulated with multiple growth factors is a result of the length (14 days) of the human colony assay and does not represent a differential requirement of primitive progenitors for Raf-1. Thus Raf-1 is required for the proliferation and differentiation of primitive hematopoietic progenitor cells stimulated with synergistic combinations of cytokines. JF - Stem cells (Dayton, Ohio) AU - Muszynski, K W AU - Ruscetti, F W AU - Gooya, J M AU - Linnekin, D M AU - Keller, J R AD - Intramural Research Support Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 63 EP - 72 VL - 15 IS - 1 SN - 1066-5099, 1066-5099 KW - Antigens, CD34 KW - 0 KW - Cytokines KW - Growth Substances KW - Interleukin-3 KW - Oligonucleotides, Antisense KW - Proto-Oncogene Proteins KW - Stem Cell Factor KW - Erythropoietin KW - 11096-26-7 KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Proto-Oncogene Proteins c-raf KW - Index Medicus KW - Animals KW - Liver -- cytology KW - Humans KW - Interleukin-3 -- pharmacology KW - Cell Division -- drug effects KW - Fetus -- cytology KW - Oligonucleotides, Antisense -- pharmacology KW - Mice KW - Mice, Inbred BALB C KW - Granulocyte-Macrophage Colony-Stimulating Factor -- pharmacology KW - Liver -- embryology KW - Erythropoietin -- pharmacology KW - Stem Cell Factor -- pharmacology KW - Antigens, CD34 -- analysis KW - Drug Synergism KW - Cell Line KW - Protein-Serine-Threonine Kinases -- biosynthesis KW - Proto-Oncogene Proteins -- biosynthesis KW - Protein-Serine-Threonine Kinases -- pharmacology KW - Hematopoietic Stem Cells -- immunology KW - Cytokines -- pharmacology KW - Growth Substances -- pharmacology KW - Proto-Oncogene Proteins -- pharmacology KW - Hematopoietic Stem Cells -- cytology KW - Protein-Serine-Threonine Kinases -- genetics KW - Proto-Oncogene Proteins -- genetics KW - Hematopoietic Stem Cells -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78789004?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Stem+cells+%28Dayton%2C+Ohio%29&rft.atitle=Raf-1+protein+is+required+for+growth+factor-induced+proliferation+of+primitive+hematopoietic+progenitors+stimulated+with+synergistic+combinations+of+cytokines.&rft.au=Muszynski%2C+K+W%3BRuscetti%2C+F+W%3BGooya%2C+J+M%3BLinnekin%2C+D+M%3BKeller%2C+J+R&rft.aulast=Muszynski&rft.aufirst=K&rft.date=1997-01-01&rft.volume=15&rft.issue=1&rft.spage=63&rft.isbn=&rft.btitle=&rft.title=Stem+cells+%28Dayton%2C+Ohio%29&rft.issn=10665099&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-08 N1 - Date created - 1997-05-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ongoing immunologic activity after short courses of pulse cyclophosphamide in the NZB/W murine model of systemic lupus erythematosus. AN - 78788619; 9002012 AB - Short courses of intermittent pulse cyclophosphamide (CY) have mitigated ovarian toxicity but have also led to incomplete or unsustained remissions of active systemic lupus erythematosus (SLE) in many patients, prompting an evaluation of the immunologic effects of this regimen in the NZB/W female mouse (B/W) model of human SLE. Phenotypic and functional characteristics of spleen lymphocytes from B/W mice treated with short courses of intraperitoneal (i.p.) CY were compared to those from untreated control B/W mice. After a single dose (250 mg/kg) of i.p. CY, spleen lymphocyte subpopulations fell abruptly but recovered within 4 weeks. Four monthly doses of i.p. CY (starting at 5 months of age) led to a sustained reduction in spleen lymphocyte subpopulations and a parallel decrease in the number of spleen cells spontaneously secreting immunoglobulin and anti-DNA antibody to about 30% of the number seen in untreated control B/W mice. Lipopolysaccharide induced secretion of total IgG and IgG anti-DNA by cultured spleen cells was not diminished one month after the 4 month course of i.p. CY. The 4 month course of i.p. CY produced a marked reduction in the number of activated B cells producing autoantibody, but did not achieve sustained immunomodulation judged by the unaltered proportion of spleen B cells spontaneously secreting immunoglobulin and anti-DNA, as well as the response to polyclonal activators of B cells. These results suggest a continued susceptibility to flares of SLE activity after brief courses of intensive immunosuppressive therapy. JF - The Journal of rheumatology AU - Austin, H A AU - Patel, A D AU - Cadena, C A AU - Boumpas, D T AU - Balow, J E AD - Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1268, USA. Y1 - 1997/01// PY - 1997 DA - January 1997 SP - 61 EP - 68 VL - 24 IS - 1 SN - 0315-162X, 0315-162X KW - Adjuvants, Immunologic KW - 0 KW - Antibodies, Antinuclear KW - Cyclophosphamide KW - 8N3DW7272P KW - Index Medicus KW - Injections, Intraperitoneal KW - Animals KW - Drug Administration Schedule KW - Adjuvants, Immunologic -- administration & dosage KW - Spleen -- cytology KW - Lymphocyte Subsets -- drug effects KW - Disease Models, Animal KW - Antibody Formation KW - Mice KW - Antibodies, Antinuclear -- immunology KW - Female KW - Cyclophosphamide -- administration & dosage KW - Lupus Erythematosus, Systemic -- immunology KW - Lupus Erythematosus, Systemic -- drug therapy KW - Mice, Inbred NZB -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78788619?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+rheumatology&rft.atitle=Ongoing+immunologic+activity+after+short+courses+of+pulse+cyclophosphamide+in+the+NZB%2FW+murine+model+of+systemic+lupus+erythematosus.&rft.au=Austin%2C+H+A%3BPatel%2C+A+D%3BCadena%2C+C+A%3BBoumpas%2C+D+T%3BBalow%2C+J+E&rft.aulast=Austin&rft.aufirst=H&rft.date=1997-01-01&rft.volume=24&rft.issue=1&rft.spage=61&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+rheumatology&rft.issn=0315162X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-26 N1 - Date created - 1997-03-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Minimal effects of dextroamphetamine on scopolamine-induced cognitive impairments in humans. AN - 78787118; 8988795 AB - The central anticholinergic drug scopolamine has been used to model aspects of the memory impairment that occurs in Alzheimer's disease and in aging. To determine whether nonspecific stimulant effects can attenuate the cognitive impairment induced by scopolamine, we studied the effects of scopolamine and the stimulant dextroamphetamine in 17 young normal volunteers. After a baseline day of cognitive testing, subjects participated in two study days, in which they received dextroamphetamine (d-AMP) (0.25 mg/kg p.o.) + scopolamine (0.5 mg i.v.) and placebo + scopolamine, in randomized order under double-blind conditions. There were no statistically significant differences in cognitive test performance between the two drug conditions with the exception of one of the category retrieval tasks. Stimulant effects were documented to occur by other measures. We conclude that d-AMP at the dose used does not attenuate the memory impairment induced by scopolamine. JF - Biological psychiatry AU - Martinez, R AU - Molchan, S E AU - Lawlor, B A AU - Thompson, K AU - Martinson, H AU - Latham, G AU - Weingartner, H AU - Sunderland, T AD - Section on Geriatric Psychopharmacology, National Institute of Mental Health, Bethesda, Maryland, USA. Y1 - 1997/01/01/ PY - 1997 DA - 1997 Jan 01 SP - 50 EP - 57 VL - 41 IS - 1 SN - 0006-3223, 0006-3223 KW - Central Nervous System Stimulants KW - 0 KW - Scopolamine Hydrobromide KW - 451IFR0GXB KW - Dextroamphetamine KW - TZ47U051FI KW - Index Medicus KW - Reaction Time -- drug effects KW - Double-Blind Method KW - Humans KW - Alzheimer Disease -- psychology KW - Adult KW - Middle Aged KW - Attention -- drug effects KW - Neuropsychological Tests KW - Male KW - Female KW - Central Nervous System Stimulants -- pharmacology KW - Cognition -- drug effects KW - Scopolamine Hydrobromide -- toxicity KW - Dextroamphetamine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78787118?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biological+psychiatry&rft.atitle=Minimal+effects+of+dextroamphetamine+on+scopolamine-induced+cognitive+impairments+in+humans.&rft.au=Martinez%2C+R%3BMolchan%2C+S+E%3BLawlor%2C+B+A%3BThompson%2C+K%3BMartinson%2C+H%3BLatham%2C+G%3BWeingartner%2C+H%3BSunderland%2C+T&rft.aulast=Martinez&rft.aufirst=R&rft.date=1997-01-01&rft.volume=41&rft.issue=1&rft.spage=50&rft.isbn=&rft.btitle=&rft.title=Biological+psychiatry&rft.issn=00063223&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-02 N1 - Date created - 1997-04-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lack of a role for Jun kinase and AP-1 in Fas-induced apoptosis. AN - 78786794; 8972197 AB - Cross-linking of Fas (CD95) induces apoptosis, a response that has been reported to depend upon the Ras activation pathway. Since many examples of apoptosis have been reported to involve AP-1 and/or the AP-1-activation pathway. Since many examples of apoptosis have been reported to involve AP-1 and/or the AP-1-activating enzyme Jun kinase (JNK), downstream effectors of Ras or Ras-like small GTP-binding proteins, we evaluated the role of these molecules in Fas-mediated apoptosis. Although cross-linking of Fas on Jurkat T cells did result in JNK activation, increased activity was observed relatively late, being detectable only after 60 min of stimulation. Expression of a dominant negative form of SEK1 that blocked Fas-mediated induction of JNK activity had no effect on Fas-mediated apoptosis. Furthermore, maximally effective concentrations of anti-Fas did not cause JNK activation if apoptosis was blocked by a cysteine protease inhibitor, suggesting that under these conditions, activation of JNK may be secondary to the stress of apoptosis rather than a direct result of Fas engagement. Despite the activation of JNK, there was no induction of AP-1 activity as determined by gel shift assay or induction of an AP-1-responsive reporter. The lack of a requirement for AP-1 induction in Fas-mediated death was further substantiated with Jurkat cells that were stably transfected with a dominant negative cJun, TAM-67. While TAM-67 effectively prevented AP-1-dependent transcription of both the interleukin-2 and cJun genes, it had no effect on Fas-induced cell death, even at limiting levels of Fas signaling. Thus, induction of JNK activity in Jurkat cells by ligation of Fas at levels sufficient to cause cell death is likely a result, rather than a cause, of the apoptotic response, and AP-1 function is not required for Fas-induced apoptosis. JF - Molecular and cellular biology AU - Lenczowski, J M AU - Dominguez, L AU - Eder, A M AU - King, L B AU - Zacharchuk, C M AU - Ashwell, J D AD - Laboratory of Immune Cell Biology, National Institutes of Health, Bethesda, Maryland 20892-1152, USA. Y1 - 1997/01// PY - 1997 DA - January 1997 SP - 170 EP - 181 VL - 17 IS - 1 SN - 0270-7306, 0270-7306 KW - Amino Acid Chloromethyl Ketones KW - 0 KW - Antigens, CD95 KW - Cysteine Proteinase Inhibitors KW - DNA-Binding Proteins KW - Interleukin-2 KW - Ionophores KW - NFATC Transcription Factors KW - Nuclear Proteins KW - Proto-Oncogene Proteins c-jun KW - Transcription Factor AP-1 KW - Transcription Factors KW - benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone KW - Ionomycin KW - 56092-81-0 KW - DNA KW - 9007-49-2 KW - Protein Kinases KW - EC 2.7.- KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - JNK Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinases KW - MAP Kinase Kinase 4 KW - EC 2.7.12.2 KW - MAP2K4 protein, human KW - Mitogen-Activated Protein Kinase Kinases KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Protein Kinases -- physiology KW - Enzyme Activation KW - Jurkat Cells -- metabolism KW - DNA -- metabolism KW - Humans KW - DNA-Binding Proteins -- genetics KW - Interleukin-2 -- biosynthesis KW - Proto-Oncogene Proteins c-jun -- metabolism KW - Ionomycin -- pharmacology KW - Proto-Oncogene Proteins c-jun -- biosynthesis KW - Transcription Factors -- genetics KW - Cysteine Proteinase Inhibitors -- pharmacology KW - Ionophores -- pharmacology KW - Jurkat Cells -- cytology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Amino Acid Chloromethyl Ketones -- pharmacology KW - Signal Transduction -- physiology KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Transcription Factor AP-1 -- metabolism KW - Apoptosis -- physiology KW - Antigens, CD95 -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78786794?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Lack+of+a+role+for+Jun+kinase+and+AP-1+in+Fas-induced+apoptosis.&rft.au=Lenczowski%2C+J+M%3BDominguez%2C+L%3BEder%2C+A+M%3BKing%2C+L+B%3BZacharchuk%2C+C+M%3BAshwell%2C+J+D&rft.aulast=Lenczowski&rft.aufirst=J&rft.date=1997-01-01&rft.volume=17&rft.issue=1&rft.spage=170&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - 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Last updated - 2017-01-18 ER - TY - CONF T1 - Naturally occurring selenium compounds in cancer chemoprevention trials: a workshop summary. AN - 78786026; 8993799 AB - Evidence from epidemiological studies and a human intervention trial indicates that selenium (Se) may have chemopreventive activity in humans. This report summarizes a workshop held by the National Cancer Institute to address the use of naturally occurring Se compounds in future cancer chemoprevention trials. Differences in the metabolism of inorganic and organic Se compounds can be seen both in the biochemical handling of these forms and in their kinetics in humans. Long-term supplementation could result in greater increases in muscle stores for organic rather than inorganic forms. Because of long half-lives, trials may have to be of long duration to assess efficacy and safety. The optimal size of dose for supplementation is controversial with respect to both efficacy and safety. In China, selenosis was observed in some individuals with a sustained intake of at least 750 micrograms/day but was not observed among others with intakes exceeding 1 mg. These levels exceed the reference dose, a measure of the maximal safe intake, which is 350 micrograms/day. A large-scale Se human intervention trial in the United States suggests no harm due to long-term Se intake of more than 200 micrograms/day. Se deficiency has been shown to have deleterious effects on the immune system, allowing, for example, a benign form of the Coxsackievirus to become virulent in mice. These recent results may provide an explanation of earlier findings showing a protective effect of elevated Se intakes against a mouse mammary tumor virus. Additional studies on the use of Se as a chemopreventive agent in man seem warranted. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Patterson, B H AU - Levander, O A Y1 - 1997/01// PY - 1997 DA - January 1997 SP - 63 EP - 69 VL - 6 IS - 1 KW - Selenium KW - H6241UJ22B KW - Index Medicus KW - Nutritional Requirements KW - Animals KW - Maximum Allowable Concentration KW - Humans KW - Mice KW - Time Factors KW - Selenium -- deficiency KW - Selenium -- metabolism KW - Selenium -- therapeutic use KW - Selenium -- pharmacokinetics KW - Clinical Trials as Topic KW - Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78786026?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=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=Naturally+occurring+selenium+compounds+in+cancer+chemoprevention+trials%3A+a+workshop+summary.&rft.au=Patterson%2C+B+H%3BLevander%2C+O+A&rft.aulast=Patterson&rft.aufirst=B&rft.date=1997-01-01&rft.volume=6&rft.issue=1&rft.spage=63&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-20 N1 - Date created - 1997-03-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Two-dimensional polyacrylamide gel electrophoresis of cancer-associated proteins. AN - 78785895; 8912417 JF - Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer AU - Wirth, P J AU - Luo, L D AU - Hoang, T AU - Benjamin, T AD - Biopolymer Chemistry Section, National Cancer Institute, Bethesda, MD 20893, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 145 EP - 160 VL - 143 SN - 0080-0015, 0080-0015 KW - Carcinogens KW - 0 KW - Neoplasm Proteins KW - Phosphoproteins KW - Phosphorus Radioisotopes KW - Tropomyosin KW - Aflatoxin B1 KW - 9N2N2Y55MH KW - Index Medicus KW - Animals KW - Electrophoresis, Polyacrylamide Gel -- methods KW - Amino Acid Sequence KW - Autoradiography KW - Rats KW - Rats, Inbred F344 KW - Isoelectric Focusing -- methods KW - Liver KW - Molecular Sequence Data KW - Epithelium KW - Cell Line, Transformed KW - Sequence Homology, Amino Acid KW - Female KW - Neoplasm Proteins -- biosynthesis KW - Phosphoproteins -- chemistry KW - Oncogenes KW - Phosphoproteins -- biosynthesis KW - Neoplasm Proteins -- isolation & purification KW - Carcinogens -- toxicity KW - Aflatoxin B1 -- toxicity KW - Neoplasm Proteins -- chemistry KW - Tropomyosin -- chemistry KW - Tropomyosin -- biosynthesis KW - Phosphoproteins -- isolation & purification KW - Tropomyosin -- isolation & purification KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78785895?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Recent+results+in+cancer+research.+Fortschritte+der+Krebsforschung.+Progres+dans+les+recherches+sur+le+cancer&rft.atitle=Two-dimensional+polyacrylamide+gel+electrophoresis+of+cancer-associated+proteins.&rft.au=Wirth%2C+P+J%3BLuo%2C+L+D%3BHoang%2C+T%3BBenjamin%2C+T&rft.aulast=Wirth&rft.aufirst=P&rft.date=1997-01-01&rft.volume=143&rft.issue=&rft.spage=145&rft.isbn=&rft.btitle=&rft.title=Recent+results+in+cancer+research.+Fortschritte+der+Krebsforschung.+Progres+dans+les+recherches+sur+le+cancer&rft.issn=00800015&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-18 N1 - Date created - 1997-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Developmental differences determine larval susceptibility to nitric oxide-mediated killing in a murine model of vaccination against Schistosoma mansoni. AN - 78785691; 8975915 AB - A persistent paradox in our understanding of protective immunity against Schistosoma mansoni infection in animals vaccinated with attenuated parasites has been that attrition of challenge parasites occurs during migration through the lungs in vivo, although parasites recovered from the lungs appear to be relatively resistant to cytotoxic effector mechanisms in vitro. We have compared the susceptibilities of different stages of larvae to killing by nitric oxide (NO), which was previously shown to be involved in the larvicidal function of cytokine-activated cytotoxic effector cells. Lung-stage larvae obtained 1 week after infection were not killed in vitro by NO generated either by a chemical NO donor or by activated cells. In contrast, parasites obtained from the portal system of control mice or from the lungs of vaccinated mice 2.5 weeks following challenge infection were killed by NO. As previously shown for mammalian cell targets, the effects of NO in susceptible larval stages may involve enzymes required for aerobic energy metabolism, since similar cytotoxicity was demonstrated by chemical inhibitors of the citric acid cycle or mitochondrial respiration. Taken together with previous observations of enhanced Th1 activity and expression of NO synthase in the lungs of vaccinated mice at 2.5 weeks after challenge infection, these observations elucidate the immune mechanism of vaccine-induced resistance to S. mansoni infection. Moreover, they suggest that conversion to a less metabolically active state may allow pathogens to escape the effects of the important effector molecule NO. JF - Infection and immunity AU - Ahmed, S F AU - Oswald, I P AU - Caspar, P AU - Hieny, S AU - Keefer, L AU - Sher, A AU - James, S L AD - Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1997/01// PY - 1997 DA - January 1997 SP - 219 EP - 226 VL - 65 IS - 1 SN - 0019-9567, 0019-9567 KW - Anthelmintics KW - 0 KW - Enzyme Inhibitors KW - Nitric Oxide KW - 31C4KY9ESH KW - Index Medicus KW - Animals KW - Age Factors KW - Macrophages -- immunology KW - Dose-Response Relationship, Drug KW - Portal System -- parasitology KW - Mice KW - Endothelium, Vascular -- immunology KW - Lung -- parasitology KW - Schistosoma KW - Mice, Inbred C57BL KW - Cytotoxicity Tests, Immunologic KW - Enzyme Inhibitors -- pharmacology KW - Female KW - Larva -- drug effects KW - Schistosoma mansoni -- drug effects KW - Anthelmintics -- pharmacology KW - Nitric Oxide -- pharmacology KW - Schistosomiasis mansoni -- prevention & control KW - Vaccination UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78785691?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Developmental+differences+determine+larval+susceptibility+to+nitric+oxide-mediated+killing+in+a+murine+model+of+vaccination+against+Schistosoma+mansoni.&rft.au=Ahmed%2C+S+F%3BOswald%2C+I+P%3BCaspar%2C+P%3BHieny%2C+S%3BKeefer%2C+L%3BSher%2C+A%3BJames%2C+S+L&rft.aulast=Ahmed&rft.aufirst=S&rft.date=1997-01-01&rft.volume=65&rft.issue=1&rft.spage=219&rft.isbn=&rft.btitle=&rft.title=Infection+and+immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-03 N1 - Date created - 1997-02-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Trop Med Hyg. 1992 Aug;47(2):238-48 [1503191] Infect Immun. 1994 May;62(5):1761-7 [8168938] J Immunol. 1992 Dec 1;149(11):3654-8 [1431135] Science. 1992 Dec 18;258(5090):1898-902 [1281928] Mol Biochem Parasitol. 1993 Jul;60(1):93-104 [8396206] Immunol Ser. 1994;60:179-95 [8251567] Immunol Ser. 1994;60:461-73 [8251586] J Immunol. 1994 Dec 1;153(11):5200-9 [7525727] J Immunol. 1995 May 1;154(9):4693-700 [7722322] J Cardiovasc Pharmacol. 1995 Apr;25(4):674-8 [7596138] Parasitology. 1965 Nov;55(4):695-700 [4957633] Am J Pathol. 1981 Jan;102(1):121-6 [7468755] Exp Parasitol. 1982 Feb;53(1):39-44 [6276213] J Immunol. 1982 Apr;128(4):1876-9 [7061853] Parasitology. 1983 Aug;87 (Pt 1):87-102 [6622067] Am J Trop Med Hyg. 1984 Jan;33(1):89-96 [6696190] Parasitology. 1984 Feb;88 ( Pt 1):179-98 [6424084] Mol Biochem Parasitol. 1984 Sep;13(1):39-51 [6513987] Parasite Immunol. 1985 May;7(3):315-31 [3892433] Parasitology. 1985 Apr;90 ( Pt 4):675-85 [4011323] Parasite Immunol. 1986 Sep;8(5):513-27 [3534695] Parasitol Res. 1988;75(1):31-5 [3144712] Exp Parasitol. 1989 Jul;69(1):44-53 [2499487] J Immunol. 1989 Dec 15;143(12):4208-12 [2592772] Proc Natl Acad Sci U S A. 1990 Feb;87(4):1620-4 [2154753] Immunol Invest. 1992 Aug;21(5):477-93 [1428021] Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):999-1003 [7508126] Am J Trop Med Hyg. 1992 Aug;47(2):231-7 [1503190] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ibogaine: a potent noncompetitive blocker of ganglionic/neuronal nicotinic receptors. AN - 78785488; 9016339 AB - Ibogaine noncompetitively blocked (IC50 approximately 20 nM) 22NaCl influx through ganglionic-type nicotinic receptor channels of rat pheochromocytoma PC12 cells. The major metabolite O-des-methylibogaine was 75-fold less active, and O-t-butyl-O-des-methylibogaine was 20-fold less active. Ibogaine was relatively weak as a blocker (IC50 approximately 2000 nM) of the neuromuscular-type nicotinic receptor channels in human medulloblastoma TE671 cells. The blockade of nicotinic responses by ibogaine was only partially reversible in PC12 cells. In vivo, ibogaine at 10 mg/kg completely blocked epibatidine-elicited antinociception in mice, a response that is mediated by central nicotinic receptor channels. There was no significant blockade of the epibatidine response at 24 hr after the administration of 40 mg/kg ibogaine. The blockade of nicotinic channels could contribute to the antiaddictive properties of ibogaine. JF - Molecular pharmacology AU - Badio, B AU - Padgett, W L AU - Daly, J W AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0820, USA. Y1 - 1997/01// PY - 1997 DA - January 1997 SP - 1 EP - 5 VL - 51 IS - 1 SN - 0026-895X, 0026-895X KW - Ganglionic Blockers KW - 0 KW - Nicotinic Antagonists KW - Receptors, N-Methyl-D-Aspartate KW - Ibogaine KW - 3S814I130U KW - Carbachol KW - 8Y164V895Y KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Dopamine -- secretion KW - Animals KW - Humans KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Mice KW - Opioid-Related Disorders -- drug therapy KW - Carbachol -- pharmacology KW - Male KW - PC12 Cells KW - Ganglionic Blockers -- pharmacology KW - Nicotinic Antagonists -- pharmacology KW - Ibogaine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78785488?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Ibogaine%3A+a+potent+noncompetitive+blocker+of+ganglionic%2Fneuronal+nicotinic+receptors.&rft.au=Badio%2C+B%3BPadgett%2C+W+L%3BDaly%2C+J+W&rft.aulast=Badio&rft.aufirst=B&rft.date=1997-01-01&rft.volume=51&rft.issue=1&rft.spage=1&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 - 1997-02-27 N1 - Date created - 1997-02-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Migration of cells with immunoglobulin/c-myc recombinations in lymphoid tissues of mice. AN - 78784913; 8978304 AB - Recombinations between c-myc and immunoglobulin (Ig) sequences that typically occur in pristane-induced mouse plasmacytomas were detected in secondary lymphoid tissues from normal mice, chiefly in the gut-associated lymphoid tissue. Based on the analysis of recombination sequences as clonotypic markers, migration of c-myc recombination-positive cells was observed between Peyer's patches and into the intestine. Treatment of plasmacytoma-susceptible BALB/cAn mice with pristane induced proliferation and migration of these cells into mesenteric lymph node, spleen, and oil granuloma within 7 days. Plasmacytoma-resistant strains of mice (DBA/2N, C3H/HeJ, C57BL/6) differed in that (1) they harbored fewer clones (Ig/c-myc recombinations were detected in 33% of resistant mice versus 91% of BALB/cAn mice after pristane treatment); (2) Ig/c-myc-positive cells were rarely detected in the oil granuloma, and (3) c-myc recombined predominantly with the Ig alpha locus in BALB/cAn mice (72%), but with the Ig mu locus in DBA/2N and in C57BL/6 (67%). The results demonstrate that normal mice generate a large number of lymphocytes with aberrant c-myc in intestinal tissues without developing tumors. JF - Blood AU - Müller, J R AU - Jones, G M AU - Janz, S AU - Potter, M AD - Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1997/01/01/ PY - 1997 DA - 1997 Jan 01 SP - 291 EP - 296 VL - 89 IS - 1 SN - 0006-4971, 0006-4971 KW - DNA, Neoplasm KW - 0 KW - Immunoglobulin Heavy Chains KW - Terpenes KW - pristane KW - 26HZV48DT1 KW - Abridged Index Medicus KW - Index Medicus KW - Cell Movement KW - Animals KW - Disease Susceptibility KW - Plasmacytoma -- chemically induced KW - Plasmacytoma -- pathology KW - Cell Differentiation KW - Immunity, Innate KW - Mice KW - Organ Specificity KW - Polymerase Chain Reaction KW - Mice, Inbred Strains KW - Base Sequence KW - Recombination, Genetic KW - DNA, Neoplasm -- genetics KW - Time Factors KW - Lymphoid Tissue -- pathology KW - Genes, myc KW - Genes, Immunoglobulin KW - Immunoglobulin Heavy Chains -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78784913?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Migration+of+cells+with+immunoglobulin%2Fc-myc+recombinations+in+lymphoid+tissues+of+mice.&rft.au=M%C3%BCller%2C+J+R%3BJones%2C+G+M%3BJanz%2C+S%3BPotter%2C+M&rft.aulast=M%C3%BCller&rft.aufirst=J&rft.date=1997-01-01&rft.volume=89&rft.issue=1&rft.spage=291&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-27 N1 - Date created - 1997-01-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Quantification of local de novo synthesis versus blood contributions to quinolinic acid concentrations in brain and systemic tissues. AN - 78784254; 8978736 AB - The source of the neurotoxin quinolinic acid (QUIN) in brain and systemic tissues under normal and pathologic circumstances reflects either de novo synthesis from L-tryptophan and other precursors, or entry of QUIN itself from the blood. To quantify the relative contributions of blood- versus tissue-derived QUIN, [13C7]-QUIN was infused subcutaneously via osmotic pumps (0.55 microliter/h, 30 mM) in gerbils, and the fraction of QUIN in tissue (Tl; measured in tissue homogenates) derived from blood (Bl; measured in serum) was calculated by the formula ([13C7]QUINTi/QUINTi)/([13C7]QUINBl/ QUINBl). In controls, blood QUIN contributed 38-49% of QUIN in brain, 70% in CSF, between 40 and 70% in kidney, heart, and skeletal muscle, but < 5% in spleen, lung, liver, and intestine. Systemic endotoxin (450 micrograms/kg) increased blood, brain, CSF, and systemic tissue QUIN levels. Notably, the relative proportion of QUIN derived from blood in brain, spleen, lung, and intestine was unchanged by endotoxin, but increased in kidney, heart, and skeletal muscle. In contrast, cerebral ischemic injury (10 min of bilateral carotid artery occlusion) increased regional brain QUIN concentrations at 4 days post ischemia, with a proportional increase in the amount of QUIN derived from de novo synthesis by brain tissue. In the blood and systemic tissues of postischemic gerbils, there were no changes in systemic tissue or blood QUIN levels, or changes in the relative proportions of blood- versus systemic tissue-derived QUIN. These results establish that the brain normally synthesizes QUIN, that the blood is a significant source of QUIN in controls and during acute systemic immune activation, and that the rate of QUIN formation by brain tissue increases in conditions of brain and systemic immune activation. JF - Journal of neurochemistry AU - Heyes, M P AU - Morrison, P F AD - Laboratory of Neurotoxicology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1262, USA. Y1 - 1997/01// PY - 1997 DA - January 1997 SP - 280 EP - 288 VL - 68 IS - 1 SN - 0022-3042, 0022-3042 KW - Lipopolysaccharides KW - 0 KW - Quinolinic Acid KW - F6F0HK1URN KW - Index Medicus KW - Osmolar Concentration KW - Gerbillinae KW - Animals KW - Ischemic Attack, Transient -- metabolism KW - Ischemic Attack, Transient -- blood KW - Lipopolysaccharides -- pharmacology KW - Tissue Distribution KW - Time Factors KW - Models, Biological KW - Quinolinic Acid -- metabolism KW - Quinolinic Acid -- blood KW - Brain -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78784254?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=Quantification+of+local+de+novo+synthesis+versus+blood+contributions+to+quinolinic+acid+concentrations+in+brain+and+systemic+tissues.&rft.au=Heyes%2C+M+P%3BMorrison%2C+P+F&rft.aulast=Heyes&rft.aufirst=M&rft.date=1997-01-01&rft.volume=68&rft.issue=1&rft.spage=280&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-27 N1 - Date created - 1997-01-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of strychnine-insensitive glycine receptor ligands in rats discriminating dizocilpine or phencyclidine from saline. AN - 78781747; 8996180 AB - Several pharmacologically distinct sites are known to modulate the N-methyl-D-aspartate (NMDA) receptor/ion complex, including a site within the ion channel which binds uncompetitive antagonists like phencyclidine (PCP) or dizocilpine. Glycine acts as a co-agonist for activation of the NMDA receptor complex through a strychnine-insensitive receptor, which is a potential target for novel therapeutic agents (e.g., anticonvulsants, antidepressants). We evaluated the behavioral effects of glycine receptor ligands in rats trained to discriminate either dizocilpine or PCP from saline, to predict whether glycine receptor ligands might induce undesirable PCP-like subjective effects in humans. Dizocilpine ([+]-MK-801), (-)-MK-801 and PCP produced dose-dependent substitution in these rats with potencies in accord with NMDA receptor affinity. Pentobarbital and drugs acting at other sites of the NMDA receptor, including competitive antagonists (NPC 12626 and LY 274614) and the polyamine antagonist, ifenprodil, did not substitute for either dizocilpine or PCP. In contrast to the uncompetitive antagonists like PCP, none of the strychnine-insensitive glycine receptor ligands substituted. Neither the full agonist, glycine; the partial agonists, 1-amino-1-cyclopropanecarboxylic acid, D-cycloserine or (+)-3-amino-1-hydroxypyrrolid-2-one; nor the antagonists, 7-chloro and 5,7-dichlorokynurenic acid, mimicked the discriminative stimulus effects of dizocilpine or PCP. Further, co-administration of 1-amino-1-cyclopropanecarboxylic acid did not significantly enhance the discriminative stimulus effects of dizocilpine. Intracerebroventricular administration of D-serine, a selective agonist of the strychnine-insensitive glycine receptor, neither mimicked nor blocked the discriminative stimulus effects of PCP. These data suggest that functional antagonists of the strychnine-insensitive glycine receptor may be devoid of the subjective side effects characteristic of NMDA channel ligands. JF - The Journal of pharmacology and experimental therapeutics AU - Witkin, J M AU - Steele, T D AU - Sharpe, L G AD - Preclinical Pharmacology Laboratory, National Institute on Drug Abuse, Baltimore, Maryland, USA. Y1 - 1997/01// PY - 1997 DA - January 1997 SP - 46 EP - 52 VL - 280 IS - 1 SN - 0022-3565, 0022-3565 KW - Excitatory Amino Acid Antagonists KW - 0 KW - Receptors, Glycine KW - Receptors, N-Methyl-D-Aspartate KW - Serine KW - 452VLY9402 KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - Strychnine KW - H9Y79VD43J KW - Phencyclidine KW - J1DOI7UV76 KW - Index Medicus KW - Rats KW - Serine -- pharmacology KW - Animals KW - Rats, Sprague-Dawley KW - Dose-Response Relationship, Drug KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Male KW - Discrimination Learning -- drug effects KW - Phencyclidine -- pharmacology KW - Strychnine -- pharmacology KW - Receptors, Glycine -- drug effects KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Dizocilpine Maleate -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78781747?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Effects+of+strychnine-insensitive+glycine+receptor+ligands+in+rats+discriminating+dizocilpine+or+phencyclidine+from+saline.&rft.au=Witkin%2C+J+M%3BSteele%2C+T+D%3BSharpe%2C+L+G&rft.aulast=Witkin&rft.aufirst=J&rft.date=1997-01-01&rft.volume=280&rft.issue=1&rft.spage=46&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-10 N1 - Date created - 1997-02-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Type I transmembrane receptor with inhibitory function in mouse mast cells and NK cells. AN - 78775140; 8977169 AB - The MHC class I-specific inhibitory receptors on human and mouse NK cells have surprisingly different structures. The mouse receptors (Ly-49) are type II transmembrane glycoproteins of the C-type lectin family, whereas the human receptors (killer cell inhibitory receptors (KIR)) belong to the Ig superfamily. This difference prompted a search for Ig-like inhibitory receptors in mice. Here we show that gp49, a mouse mast cell protein of unknown function but with sequence similarity to KIR, is expressed in NK cells. The gp49 cytoplasmic tail, containing a sequence related to an inhibitory motif shared by KIR and Ly-49, delivered a strong inhibitory signal in both human and mouse NK cells when substituted for a KIR cytoplasmic tail. These data show that Ig-like receptors with inhibitory properties exist in both species and that mouse mast and NK cells may recognize common inhibitory ligands. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Rojo, S AU - Burshtyn, D N AU - Long, E O AU - Wagtmann, N AD - Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA. Y1 - 1997/01/01/ PY - 1997 DA - 1997 Jan 01 SP - 9 EP - 12 VL - 158 IS - 1 SN - 0022-1767, 0022-1767 KW - Gp49a protein, mouse KW - 0 KW - Immunoglobulins KW - Lilrb4 protein, mouse KW - Membrane Glycoproteins KW - Receptors, Immunologic KW - Abridged Index Medicus KW - Index Medicus KW - Immunoglobulins -- toxicity KW - Immunoglobulins -- analysis KW - Animals KW - Mice, Mutant Strains KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Mice KW - Mast Cells -- immunology KW - Membrane Glycoproteins -- toxicity KW - Membrane Glycoproteins -- analysis KW - Receptors, Immunologic -- analysis KW - Down-Regulation -- immunology KW - Killer Cells, Natural -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78775140?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Type+I+transmembrane+receptor+with+inhibitory+function+in+mouse+mast+cells+and+NK+cells.&rft.au=Rojo%2C+S%3BBurshtyn%2C+D+N%3BLong%2C+E+O%3BWagtmann%2C+N&rft.aulast=Rojo&rft.aufirst=S&rft.date=1997-01-01&rft.volume=158&rft.issue=1&rft.spage=9&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-30 N1 - Date created - 1997-01-30 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U70665; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Examination of potential mechanisms in the enhancement of cerebral blood flow by hypoglycemia and pharmacological doses of deoxyglucose. AN - 78773653; 8978387 AB - Cerebral blood flow (CBF) rises when the glucose supply to the brain is limited by hypoglycemia or glucose metabolism is inhibited by pharmacological doses of 2-deoxyglucose (DG). The present studies in unanesthetized rats with insulin-induced hypoglycemia show that the increases in CBF, measured with the [14C]iodoantipyrine method, are relatively small until arterial plasma glucose levels fall to 2.5 to 3.0 mM, at which point CBF rises sharply. A direct effect of insulin on CBF was excluded; insulin administered under euglycemic conditions maintained by glucose injections had no effects on CBF. Insulin administration raised plasma lactate levels and decreased plasma K+ and HCO3- concentrations and arterial pH. These could not, however, be related to the increased CBF because insulin under euglycemic conditions had similar effects without affecting CBF; furthermore, the inhibition of brain glucose metabolism with pharmacological doses (200 mg/kg intravenously) of DG increased CBF, just like insulin hypoglycemia, without altering plasma lactate and K+ levels and arterial blood gas tensions and pH. Nitric oxide also does not appear to mediate the increases in CBF. Chronic blockade of nitric oxide synthase activity by twice daily i.p. injections of NG-nitro-L-arginine methyl ester for 4 days or acutely by a single i.v. injection raised arterial blood pressure and lowered CBF in normoglycemic, hypoglycemic, and DG-treated rats but did not significantly reduce the increases in CBF due to insulin-induced hypoglycemia (arterial plasma glucose levels, 2.5-3 mM) or pharmacological doses of deoxyglucose. JF - Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism AU - Horinaka, N AU - Artz, N AU - Jehle, J AU - Takahashi, S AU - Kennedy, C AU - Sokoloff, L AD - Laboratory of Cerebral Metabolism, National Institute of Mental Health, Bethesda, Maryland 20892, USA. Y1 - 1997/01// PY - 1997 DA - January 1997 SP - 54 EP - 63 VL - 17 IS - 1 SN - 0271-678X, 0271-678X KW - Insulin KW - 0 KW - Vasodilator Agents KW - Deoxyglucose KW - 9G2MP84A8W KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - NG-Nitroarginine Methyl Ester KW - V55S2QJN2X KW - Index Medicus KW - Rats KW - Brain -- enzymology KW - Animals KW - Rats, Sprague-Dawley KW - NG-Nitroarginine Methyl Ester -- pharmacology KW - Regional Blood Flow -- drug effects KW - Electroencephalography -- drug effects KW - Insulin -- pharmacology KW - Nitric Oxide Synthase -- metabolism KW - Male KW - Vasodilator Agents -- pharmacology KW - Hypoglycemia -- physiopathology KW - Cerebrovascular Circulation -- physiology KW - Deoxyglucose -- pharmacology KW - Hypoglycemia -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78773653?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cerebral+blood+flow+and+metabolism+%3A+official+journal+of+the+International+Society+of+Cerebral+Blood+Flow+and+Metabolism&rft.atitle=Examination+of+potential+mechanisms+in+the+enhancement+of+cerebral+blood+flow+by+hypoglycemia+and+pharmacological+doses+of+deoxyglucose.&rft.au=Horinaka%2C+N%3BArtz%2C+N%3BJehle%2C+J%3BTakahashi%2C+S%3BKennedy%2C+C%3BSokoloff%2C+L&rft.aulast=Horinaka&rft.aufirst=N&rft.date=1997-01-01&rft.volume=17&rft.issue=1&rft.spage=54&rft.isbn=&rft.btitle=&rft.title=Journal+of+cerebral+blood+flow+and+metabolism+%3A+official+journal+of+the+International+Society+of+Cerebral+Blood+Flow+and+Metabolism&rft.issn=0271678X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-21 N1 - Date created - 1997-01-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Behavioral and neuroendocrine responses to m-chlorophenylpiperazine in subtypes of alcoholics and in healthy comparison subjects. AN - 78772784; 8988963 AB - The purpose of this study was to explore central serotonergic functions in subgroups of alcoholics and in healthy comparison subjects. The mixed serotonin (5-HT) agonist/antagonist m-chlorophenylpiperazine (m-CPP) was administered to male alcoholic patients who were classified according to the criteria of von Knorring et al. as type I alcoholics (late onset) (N = 16) or type II alcoholics (early onset with antisocial traits) (N = 24) and to 22 healthy comparison subjects. Psychological, physiological, and neuroendocrine measures were obtained before and after the m-CPP infusion. m-CPP elicited subtype-related differential effects among the alcoholics; the type I alcoholics reported more anger and anxiety, and the type II alcoholics reported increased euphoria and a greater likelihood of drinking. The healthy comparison subjects exhibited a greater increase in plasma ACTH response to the m-CPP infusion than the alcoholics regardless of subtype. Differences in certain 5-HT receptor functions may explain some of the clinical characteristics that differentiate the type II and type I subgroups of alcoholic patients. Furthermore, alcoholics may have reduced sensitivity of 5-HT2C receptors in comparison with healthy subjects. JF - The American journal of psychiatry AU - George, D T AU - Benkelfat, C AU - Rawlings, R R AU - Eckardt, M J AU - Phillips, M J AU - Nutt, D J AU - Wynne, D AU - Murphy, D L AU - Linnoila, M AD - Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892-1250, USA. Y1 - 1997/01// PY - 1997 DA - January 1997 SP - 81 EP - 87 VL - 154 IS - 1 SN - 0002-953X, 0002-953X KW - Piperazines KW - 0 KW - Receptors, Serotonin KW - Serotonin Receptor Agonists KW - Adrenocorticotropic Hormone KW - 9002-60-2 KW - 1-(3-chlorophenyl)piperazine KW - REY0CNO998 KW - Abridged Index Medicus KW - Index Medicus KW - Receptors, Serotonin -- physiology KW - Receptors, Serotonin -- drug effects KW - Euphoria -- drug effects KW - Anxiety -- psychology KW - Age of Onset KW - Humans KW - Antisocial Personality Disorder -- classification KW - Anger -- drug effects KW - Adult KW - Alcohol Drinking -- psychology KW - Antisocial Personality Disorder -- diagnosis KW - Middle Aged KW - Male KW - Adrenocorticotropic Hormone -- blood KW - Serotonin Receptor Agonists -- pharmacology KW - Alcoholism -- diagnosis KW - Alcoholism -- physiopathology KW - Piperazines -- pharmacology KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78772784?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+psychiatry&rft.atitle=Behavioral+and+neuroendocrine+responses+to+m-chlorophenylpiperazine+in+subtypes+of+alcoholics+and+in+healthy+comparison+subjects.&rft.au=George%2C+D+T%3BBenkelfat%2C+C%3BRawlings%2C+R+R%3BEckardt%2C+M+J%3BPhillips%2C+M+J%3BNutt%2C+D+J%3BWynne%2C+D%3BMurphy%2C+D+L%3BLinnoila%2C+M&rft.aulast=George&rft.aufirst=D&rft.date=1997-01-01&rft.volume=154&rft.issue=1&rft.spage=81&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+psychiatry&rft.issn=0002953X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-23 N1 - Date created - 1997-01-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanisms leading to the expression of recessive alleles: the use of polymorphic microsatellites and whole-chromosome painting probes to analyze mouse tumors, mutants, and micronuclei. AN - 78770581; 8912418 JF - Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer AU - Caspary, W J AU - Stopper, H AU - Hozier, J C AU - Liechty, M C AU - Davis, L M AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 161 EP - 182 VL - 143 SN - 0080-0015, 0080-0015 KW - DNA Probes KW - 0 KW - Index Medicus KW - Polymerase Chain Reaction KW - Animals KW - Chromosome Deletion KW - Alleles KW - Micronucleus Tests KW - Polymorphism, Restriction Fragment Length KW - Genetic Techniques KW - Humans KW - Mice KW - Male KW - Female KW - Microsatellite Repeats KW - Polymorphism, Genetic KW - Neoplasms, Experimental -- genetics KW - Gene Expression KW - Micronuclei, Chromosome-Defective -- ultrastructure KW - Mutation KW - Chromosome Mapping KW - Neoplasms -- genetics KW - Genes, Recessive UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78770581?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Recent+results+in+cancer+research.+Fortschritte+der+Krebsforschung.+Progres+dans+les+recherches+sur+le+cancer&rft.atitle=Mechanisms+leading+to+the+expression+of+recessive+alleles%3A+the+use+of+polymorphic+microsatellites+and+whole-chromosome+painting+probes+to+analyze+mouse+tumors%2C+mutants%2C+and+micronuclei.&rft.au=Caspary%2C+W+J%3BStopper%2C+H%3BHozier%2C+J+C%3BLiechty%2C+M+C%3BDavis%2C+L+M&rft.aulast=Caspary&rft.aufirst=W&rft.date=1997-01-01&rft.volume=143&rft.issue=&rft.spage=161&rft.isbn=&rft.btitle=&rft.title=Recent+results+in+cancer+research.+Fortschritte+der+Krebsforschung.+Progres+dans+les+recherches+sur+le+cancer&rft.issn=00800015&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-18 N1 - Date created - 1997-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Preferential use of less toxic detoxification pathways by long-lived species. AN - 78769177; 15374139 AB - This study was undertaken to determine whether the detoxification pathways producing the least oxidative stress appear to be favored in longer-lived mammalian species. Firstly, we focused on the cytochrome P-450 monooxygenase system. Although this system is an important component of the defenses that protect living organisms against toxic chemicals, some reactions catalyzed by the cytochrome P-450 system result in the formation of products that are highly reactive as well as active oxygen species. Our results suggest that the lower amount of hepatic cytochrome P-450 content found in longer-lived species may have evolved to reduce the toxic side-effect of this detoxification system. Support of the idea that the cytochrome P-450 system is an important source of oxidative stress is the positive correlation between cytochrome P-450 content and the amount of oxidized proteins found in liver of different human individuals. Secondly, we have measured the specific activity of other detoxification enzymes as a function of life span. Instead of a direct comparison of detoxification capabilities of the species, the approach used in this study was: (1) to select those detoxification enzymes which utilize the same substrate but differ in toxicity of the intermediate compounds formed in the reaction, and (2) to measure the levels of these enzymes in the two pathways to determine which pathway is dominant for each species. Our results suggest that the detoxification pathways producing the least oxidative stress do appear to be favored in longer-lived species. JF - Archives of gerontology and geriatrics AU - Ayala, A AU - Cutler, R G AD - Gerontology Research Center, National Institute on Aging, 4940 Eastern Avenue, Baltimore, MD 21224, USA. rayala@cica.es PY - 1997 SP - 87 EP - 102 VL - 24 IS - 1 SN - 0167-4943, 0167-4943 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78769177?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+gerontology+and+geriatrics&rft.atitle=Preferential+use+of+less+toxic+detoxification+pathways+by+long-lived+species.&rft.au=Ayala%2C+A%3BCutler%2C+R+G&rft.aulast=Ayala&rft.aufirst=A&rft.date=1997-01-01&rft.volume=24&rft.issue=1&rft.spage=87&rft.isbn=&rft.btitle=&rft.title=Archives+of+gerontology+and+geriatrics&rft.issn=01674943&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-14 N1 - Date created - 2004-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cognitive and behavioral effects of cholinergic, dopaminergic, and serotonergic blockade in humans. AN - 78766776; 8981385 AB - The purpose of this study was to investigate the cognitive and behavioral effects of anticholinergic, antidopaminergic, and antiserotonergic agents given alone and in combination to normal volunteers. Twelve young male volunteers took part in this double-blind, randomized, placebo-controlled, crossover study of six drug conditions, each administered on separate days [haloperidol (2 mg p.o.) +/-scopolamine (0.5 mg i.v.), metergoline (4 mg p.o.) +/-scopolamine (0.5 mg i.v.), placebo, and scopolamine alone (0.5 mg i.v.)]. Scopolamine-induced sedation (p < .01), slowed information processing (p < .01) and impaired new learning and memory (p < .01), but did not affect attention or retrieval from semantic memory. Given alone, haloperidol selectively impaired the ability to rapidly switch cognitive sets (p < .05), and metergoline decreased pupil size (p < .01) but did not induce cognitive deficits. In combination with scopolamine, neither haloperidol nor metergoline produced a worsening of the subjects' cognitive performance above and beyond that seen with scopolamine alone. On the contrary, a trend (p < .10) for haloperidol to reverse some of the scopolamine-induced exacerbation of verbal short-term forgetting was observed. The data indicate that scopolamine and haloperidol can independently and selectively affect cognition and that at the doses tested in this study no synergistic exacerbation of cognitive functioning was found when cholinergic blockage was coupled with dopaminergic or serotonergic blockade. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Vitiello, B AU - Martin, A AU - Hill, J AU - Mack, C AU - Molchan, S AU - Martinez, R AU - Murphy, D L AU - Sunderland, T AD - Section on Geriatric Psychiatry, National Institute of Mental Health, Bethesda, MD 20892-1264, USA. Y1 - 1997/01// PY - 1997 DA - January 1997 SP - 15 EP - 24 VL - 16 IS - 1 SN - 0893-133X, 0893-133X KW - Cholinergic Antagonists KW - 0 KW - Dopamine Antagonists KW - Serotonin Antagonists KW - Index Medicus KW - Hemodynamics -- drug effects KW - Reaction Time -- drug effects KW - Drug Interactions KW - Psychomotor Performance -- drug effects KW - Double-Blind Method KW - Humans KW - Adult KW - Verbal Learning -- drug effects KW - Cross-Over Studies KW - Male KW - Behavior -- drug effects KW - Serotonin Antagonists -- pharmacology KW - Cognition -- drug effects KW - Dopamine Antagonists -- pharmacology KW - Cholinergic Antagonists -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78766776?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cognitive+and+behavioral+effects+of+cholinergic%2C+dopaminergic%2C+and+serotonergic+blockade+in+humans.&rft.au=Vitiello%2C+B%3BMartin%2C+A%3BHill%2C+J%3BMack%2C+C%3BMolchan%2C+S%3BMartinez%2C+R%3BMurphy%2C+D+L%3BSunderland%2C+T&rft.aulast=Vitiello&rft.aufirst=B&rft.date=1997-01-01&rft.volume=16&rft.issue=1&rft.spage=15&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 - 1997-03-28 N1 - Date created - 1997-03-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Effects of Infant Child Care on Infant-Mother Attachment Security: Results of the NICHD [National Institute of Child Health and Human Development] Study of Early Child Care. AN - 62510664; EJ552805 AB - Examined validity of Strange Situation attachment classifications for infants with and without extensive child-care experience and the association of early child-care experience with attachment security. Found that infants were less likely to be secure when low maternal sensitivity was combined with poor quality child care, more than minimal amounts of child care, or more than one care arrangement. (Author) JF - Child Development AU - NICHD Early Child Care Research Network AD - NICHD Early Child Care Research Network Y1 - 1997 PY - 1997 DA - 1997 SP - 860 EP - 879 VL - 68 IS - 5 SN - 0009-3920, 0009-3920 KW - Maternal Sensitivity KW - Security Classifications KW - Security of Attachment KW - ERIC, Current Index to Journals in Education (CIJE) KW - Day Care Effects KW - Comparative Analysis KW - Parent Child Relationship KW - Infant Care KW - Infant Behavior KW - Test Validity KW - Attachment Behavior KW - Infants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/62510664?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aeric&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Child+Development&rft.atitle=The+Effects+of+Infant+Child+Care+on+Infant-Mother+Attachment+Security%3A+Results+of+the+NICHD+%5BNational+Institute+of+Child+Health+and+Human+Development%5D+Study+of+Early+Child+Care.&rft.au=NICHD+Early+Child+Care+Research+Network&rft.aulast=NICHD+Early+Child+Care+Research+Network&rft.aufirst=&rft.date=1997-01-01&rft.volume=68&rft.issue=5&rft.spage=860&rft.isbn=&rft.btitle=&rft.title=Child+Development&rft.issn=00093920&rft_id=info:doi/ LA - English DB - ERIC N1 - Last updated - 2014-03-21 N1 - SubjectsTermNotLitGenreText - Attachment Behavior 714 909; 1955 3629 6582; 2604; 5112 1432 909; 5113; Infants 5118 11655 1474 316 8016 4542; Parent Child Relationship 7537 3851 5449 8768; 10781 11210 3627 2416 10031 ER - TY - JOUR T1 - Alcohol, Drugs, Fighting and Suicide Attempt/Ideation AN - 61609521; 9907758 AB - In a representative US sample of 18,352 current drinkers age 18+, past-year alcohol- or other drug-related fighting & suicide attempt/ideation both showed strong positive bivariate associations with volume of alcohol intake, proportion of drinking days resulting in intoxication (the intoxication index), & past-year drug use, especially multiple drug use. After adjusting for potential confounders in a series of multiple logistic regression models, average daily ethanol intake retained a significant positive association with the odds of alcohol- & other drug-related fighting as did the intoxication index, except among drinkers who used only marijuana. Suicide attempt/ideation was positively associated with use of marijuana only or multiple other drugs. Because drug use was positively associated with alcohol use, models restricted to only alcohol or only drug use measures overestimated some of their associations with the two outcome measures, but the data do suggest a positive effect of simultaneous use on alcohol- & drug-related fighting. 5 Tables, 45 References. Adapted from the source document. JF - Addiction Research AU - Dawson, Deborah A AD - NIAAA/DBE Wilco Bldg Ste 514, 6000 Executive Blvd MSC 7003 Bethesda MD 20892-7003 tel/fax: 301-435-2255/443-8614 Y1 - 1997///0, PY - 1997 DA - 0, 1997 SP - 451 EP - 472 VL - 5 IS - 6 SN - 1606-6359, 1606-6359 KW - Alcohol Abuse KW - Drinking Behavior KW - United States of America KW - Suicide KW - Marijuana KW - Cocaine KW - Violence KW - Drug Abuse KW - article KW - 2079: sociology of health and medicine; substance use/abuse & compulsive behaviors (drug abuse, addiction, alcoholism, gambling, eating disorders, etc.) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61609521?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocabs&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Addiction+Research&rft.atitle=Alcohol%2C+Drugs%2C+Fighting+and+Suicide+Attempt%2FIdeation&rft.au=Dawson%2C+Deborah+A&rft.aulast=Dawson&rft.aufirst=Deborah&rft.date=1997-01-01&rft.volume=5&rft.issue=6&rft.spage=451&rft.isbn=&rft.btitle=&rft.title=Addiction+Research&rft.issn=16066359&rft_id=info:doi/ LA - English DB - Sociological Abstracts N1 - Date revised - 2007-04-01 N1 - Last updated - 2016-09-28 N1 - CODEN - AREREQ N1 - SubjectsTermNotLitGenreText - Suicide; Alcohol Abuse; Drug Abuse; Drinking Behavior; Violence; Cocaine; Marijuana; United States of America ER - TY - JOUR T1 - Savage Thought and Thoughtful Savages: On the Context of the Evaluation of Logical Thought by Levy-Bruhl and Evans-Pritchard AN - 61478570; 9715831 AB - The interaction of attitudes & expectations on the production of anthropological discourse is studied by examining theories in the prestructure of Edward E. Evans-Pritchard's "Witchcraft, Oracles, and Magic among the Azande" (1976 [1937]). Evans-Pritchard's new paradigm of primitive thought was not an intentional empirical test of Lucien Levy-Buhl's (1985 [1920]) notion of prelogical, primitive thought, but it is argued that Evans-Pritchard implicitly refuted Levy-Bruhl, claiming that Azande magical beliefs were coherent & consistent despite their mystical & nonscientific foundationa. In Evans-Pritchard's direct & friendly observations of the Azande, he brought a liberal & humane pole to studying the Other; however, it is suggested that the basis for it rests on the neglected interaction of the colonial presence, Azande witchcraft, & the produced anthropological discourse. 24 References. Adapted from the source document. JF - ANTHROPOS AU - Heinz, Andreas AD - NIMH Neuroscience Center Saint Elizabeths, Washington DC 20032 Y1 - 1997///0, PY - 1997 DA - 0, 1997 SP - 165 EP - 173 VL - 92 IS - 1-3 SN - 0257-9774, 0257-9774 KW - primitive thought, Edward E. Evans-Pritchard's paradigm, Lucien Levy-Bruhl's prelogic concept refuted, anthropological discourse production-attitudes/expectations interaction KW - Social Theories KW - Colonialism KW - Levy-Bruhl, Lucien KW - Witchcraft KW - Magic KW - Traditional Societies KW - Theoretical Problems KW - Beliefs KW - Evans-Pritchard, Sir Edward Evan KW - Divination KW - article KW - 0514: culture and social structure; social anthropology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61478570?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocabs&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=ANTHROPOS&rft.atitle=Savage+Thought+and+Thoughtful+Savages%3A+On+the+Context+of+the+Evaluation+of+Logical+Thought+by+Levy-Bruhl+and+Evans-Pritchard&rft.au=Heinz%2C+Andreas&rft.aulast=Heinz&rft.aufirst=Andreas&rft.date=1997-01-01&rft.volume=92&rft.issue=1-3&rft.spage=165&rft.isbn=&rft.btitle=&rft.title=ANTHROPOS&rft.issn=02579774&rft_id=info:doi/ LA - English DB - Sociological Abstracts N1 - Date revised - 2007-04-01 N1 - Last updated - 2016-09-28 N1 - CODEN - ANTHB6 N1 - SubjectsTermNotLitGenreText - Levy-Bruhl, Lucien; Evans-Pritchard, Sir Edward Evan; Traditional Societies; Beliefs; Social Theories; Theoretical Problems; Colonialism; Witchcraft; Magic; Divination ER - TY - JOUR T1 - L'Abandon du systeme d'irrigation qatabanite dans la vallee du wadi Bayhan (Yemen); analyse geo-archeologique TT - Abandonment of the Qatabanian irrigation system in the Wadi Bayhan Valley, Yemen; a geoarchaeological analysis AN - 52687290; 1997-065314 AB - New geoarchaeological investigations of the Qatabanian irrigation system of the Wadi Bayhan Valley were carried out by means of remote sensing and ground survey. Previous studies had suggested that, from a pure speculative viewpoint, the abandonment of the regional canal system around the end of the second century A.D. was due to the political, economic and social changes linked to the collapse of the Qatabanian kingdom and to the decrease in imports of oriental goods in the Mediterranean. Our research however shows that a severe neotectonic activity, which with cyclic earthquakes affected the whole valley, caused the folding and tilting of the ancient field plots thus compromising the functionality of the whole irrigation system. JF - Comptes Rendus de l'Academie des Sciences, Serie II. Sciences de la Terre et des Planetes AU - Marcolongo, B AU - Morandi Bonacossi, D Y1 - 1997 PY - 1997 DA - 1997 SP - 79 EP - 86 PB - Gauthier-Villars, Montrouge VL - 325 IS - 1 SN - 1251-8050, 1251-8050 KW - archaeology KW - anthropology KW - tilt KW - Wadi Bayhan Valley KW - satellite methods KW - irrigation KW - Arabian Peninsula KW - neotectonics KW - Yemen KW - folds KW - tectonics KW - geomorphology KW - Asia KW - Qataban Kingdom KW - earthquakes KW - remote sensing KW - 24:Quaternary geology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/52687290?accountid=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=Comptes+Rendus+de+l%27Academie+des+Sciences%2C+Serie+II.+Sciences+de+la+Terre+et+des+Planetes&rft.atitle=L%27Abandon+du+systeme+d%27irrigation+qatabanite+dans+la+vallee+du+wadi+Bayhan+%28Yemen%29%3B+analyse+geo-archeologique&rft.au=Marcolongo%2C+B%3BMorandi+Bonacossi%2C+D&rft.aulast=Marcolongo&rft.aufirst=B&rft.date=1997-01-01&rft.volume=325&rft.issue=1&rft.spage=79&rft.isbn=&rft.btitle=&rft.title=Comptes+Rendus+de+l%27Academie+des+Sciences%2C+Serie+II.+Sciences+de+la+Terre+et+des+Planetes&rft.issn=12518050&rft_id=info:doi/ LA - French DB - GeoRef N1 - Copyright - GeoRef, Copyright 2012, American Geosciences Institute. Reference includes data from PASCAL, Institute de l'Information Scientifique et Technique, Vandoeuvre-les-Nancy, France N1 - Date revised - 1997-01-01 N1 - Number of references - 13 N1 - Last updated - 2012-06-07 N1 - SubjectsTermNotLitGenreText - anthropology; Arabian Peninsula; archaeology; Asia; earthquakes; folds; geomorphology; irrigation; neotectonics; Qataban Kingdom; remote sensing; satellite methods; tectonics; tilt; Wadi Bayhan Valley; Yemen ER - TY - JOUR T1 - La zona a scaglie di Matrei in alta valle Isarco; revisione critica del limite Austroalpino-Pennidico TT - The "Zona a Scaglie di Matrei" in the Upper Isarco Valley; critical review of the Penninic-Austroalpine boundary AN - 52568853; 1998-053865 AB - The collisional contact between the Austroalpine and Penninic nappes in the westernmost Tauern Window is marked by a wide shear zone, i.e. the "Zona a scaglie di Matrei Auctorum", which is generally characterized by an irregular sequence of tectonic imbrications and slices of calcschists with ophiolites, marbles, quartzites and paragneisses, whose affinity is either Pennine or Austroalpine. This work deals with this tectonic contact in the Vipiteno-Brennero zone (upper Isarco valley) discusses previous studies and suggests a new interpretation based on the recognition of a shear zone running between the austroalpine Monte Cavallo Complex and its northern extension (Steinach nappe), the Breonie Complex and the Penninic nappes. Three main structural units can be recognized along the western slope of the upper Isarco valley i.e. along the "Zona a scaglie di Matrei". They are: (i) the Breonie Complex, (ii) the Penninic nappe of calcschist with ophiolites and (iii) the austro-alpine Merano-Mules Complex. The "Zona a scaglie di Matrei" clearly predates the extensional tectonics, which allowed the tectonic denudation of the Tauern Window during the Tertiary Age (41-15 My). JF - Atti Ticinensi di Scienze della Terra AU - Villi, V AU - Gatto, G O AU - Friz, C Y1 - 1997 PY - 1997 DA - 1997 SP - 31 EP - 39 PB - Universita Degli Studi di Pavia, Pavia VL - 5, Serie speciale SN - 0394-0691, 0394-0691 KW - Tauern Window KW - Alps KW - Europe KW - extension tectonics KW - nappes KW - Italy KW - Southern Europe KW - Cenozoic KW - Central Europe KW - Breonie Complex KW - Penninic Zone KW - Matrei Zone KW - tectonics KW - Trentino-Alto Adige Italy KW - faults KW - ophiolite complexes KW - shear zones KW - Isarco Valley KW - Austria KW - Paleogene KW - Miocene KW - Monte Cavallo Complex KW - Tertiary KW - South Austrian Alps KW - Neogene KW - Vitipeno Italy KW - 16:Structural geology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/52568853?accountid=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=Atti+Ticinensi+di+Scienze+della+Terra&rft.atitle=La+zona+a+scaglie+di+Matrei+in+alta+valle+Isarco%3B+revisione+critica+del+limite+Austroalpino-Pennidico&rft.au=Villi%2C+V%3BGatto%2C+G+O%3BFriz%2C+C&rft.aulast=Villi&rft.aufirst=V&rft.date=1997-01-01&rft.volume=5%2C+Serie+speciale&rft.issue=&rft.spage=31&rft.isbn=&rft.btitle=&rft.title=Atti+Ticinensi+di+Scienze+della+Terra&rft.issn=03940691&rft_id=info:doi/ L2 - http://manhattan.unipv.it/Atti_tic/volumi.html LA - Italian DB - GeoRef N1 - Copyright - GeoRef, Copyright 2012, American Geosciences Institute. N1 - Date revised - 1998-01-01 N1 - Number of references - 21 N1 - Document feature - illus. incl. sects., sketch map N1 - Last updated - 2012-06-07 N1 - CODEN - AIGPAV N1 - SubjectsTermNotLitGenreText - Alps; Austria; Breonie Complex; Cenozoic; Central Europe; Europe; extension tectonics; faults; Isarco Valley; Italy; Matrei Zone; Miocene; Monte Cavallo Complex; nappes; Neogene; ophiolite complexes; Paleogene; Penninic Zone; shear zones; South Austrian Alps; Southern Europe; Tauern Window; tectonics; Tertiary; Trentino-Alto Adige Italy; Vitipeno Italy ER - TY - JOUR T1 - Mobilization of lead from material skeleton during pregnancy AN - 52553287; 1998-068773 JF - Open-File Report - U. S. Geological Survey AU - Gulson, Brian L AU - Jameson, C W AU - Mahaffey, Kathryn R AU - Mizon, Karen J AU - Korsch, James J Y1 - 1997 PY - 1997 DA - 1997 SP - 31 EP - 32 PB - U. S. Geological Survey, Reston, VA SN - 0196-1497, 0196-1497 KW - concentration KW - toxic materials KW - toxicity KW - medical geology KW - metals KW - bones KW - pollution KW - lead KW - USGS KW - urban environment KW - human ecology KW - 22:Environmental geology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/52553287?accountid=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=Open-File+Report+-+U.+S.+Geological+Survey&rft.atitle=Mobilization+of+lead+from+material+skeleton+during+pregnancy&rft.au=Gulson%2C+Brian+L%3BJameson%2C+C+W%3BMahaffey%2C+Kathryn+R%3BMizon%2C+Karen+J%3BKorsch%2C+James+J&rft.aulast=Gulson&rft.aufirst=Brian&rft.date=1997-01-01&rft.volume=&rft.issue=&rft.spage=31&rft.isbn=&rft.btitle=&rft.title=Open-File+Report+-+U.+S.+Geological+Survey&rft.issn=01961497&rft_id=info:doi/ LA - English DB - GeoRef N1 - Conference title - 4th International symposium on Environmental geochemistry N1 - Copyright - GeoRef, Copyright 2014, American Geosciences Institute. N1 - Date revised - 1998-01-01 N1 - Availability - U. S. Geol. Surv., Denver, CO, United States N1 - PubXState - VA N1 - Last updated - 2014-03-14 N1 - CODEN - XGROAG N1 - SubjectsTermNotLitGenreText - bones; concentration; human ecology; lead; medical geology; metals; pollution; toxic materials; toxicity; urban environment; USGS ER - TY - JOUR T1 - Deformazioni gravitative profonde di versante e frane; casi di studio nella valle del Boite (Dolomiti, Italia) TT - Deep-seated gravitational slope deformation and landslides; case studies in the Boite Valley, Dolomites, Italy AN - 50921328; 1999-037180 JF - Geografia Fisica e Dinamica Quaternaria (Testo Stampato) AU - Pasuto, Alessandro AU - Silvano, Sandro AU - Soldati, Mauro AU - Anonymous Y1 - 1997 PY - 1997 DA - 1997 SP - 107 EP - 111 PB - Comitato Glaciologico Italiano, Turin VL - 20 IS - 1 SN - 0391-9838, 0391-9838 KW - Alps KW - Europe KW - deformation KW - Italy KW - Southern Europe KW - deep-seated structures KW - landslides KW - gravity sliding KW - Boite Valley KW - Veneto Italy KW - mass movements KW - Dolomites KW - tectonics KW - Eastern Alps KW - 23:Geomorphology KW - 16:Structural geology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/50921328?accountid=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=Geografia+Fisica+e+Dinamica+Quaternaria+%28Testo+Stampato%29&rft.atitle=Deformazioni+gravitative+profonde+di+versante+e+frane%3B+casi+di+studio+nella+valle+del+Boite+%28Dolomiti%2C+Italia%29&rft.au=Pasuto%2C+Alessandro%3BSilvano%2C+Sandro%3BSoldati%2C+Mauro%3BAnonymous&rft.aulast=Pasuto&rft.aufirst=Alessandro&rft.date=1997-01-01&rft.volume=20&rft.issue=1&rft.spage=107&rft.isbn=&rft.btitle=&rft.title=Geografia+Fisica+e+Dinamica+Quaternaria+%28Testo+Stampato%29&rft.issn=03919838&rft_id=info:doi/ LA - Italian DB - GeoRef N1 - Conference title - Meeting on Large and slow gravitational phenomena in inhabited centres of Alpine and Apenninic regions N1 - Copyright - GeoRef, Copyright 2012, American Geosciences Institute. Reference includes data supplied by CNR, Comitato Scienze Geologiche e Minerarie, Rome, Italy N1 - Date revised - 1999-01-01 N1 - Number of references - 32 N1 - Document feature - illus. N1 - Last updated - 2012-06-07 N1 - SubjectsTermNotLitGenreText - Alps; Boite Valley; deep-seated structures; deformation; Dolomites; Eastern Alps; Europe; gravity sliding; Italy; landslides; mass movements; Southern Europe; tectonics; Veneto Italy ER - TY - JOUR T1 - New anti-angiogenesis agents: review of the clinical experience with carboxyamido-triazole (CAI), thalidomide, TNP-470 and interleukin-12. AN - 1859446759; 14517390 AB - Angiogenesis was postulated to be a critical prognostic factor and therapeutic focus for malignancy more than two decades ago. Recent studies indicate quantitative assessments of microvessel count to be an independent prognostic variable for disease-free and overall survival in a wide variety of tumors, and that angiogenesis may be a feasible target against which to intervene pharmacologically. Several new and old agents have been found to have anti-angiogenic activity and have reached clinical trial. This review will focus on four agents under investigation in the US: carboxyamido-triazole (CAI), thalidomide, TNP-470 and interleukin (IL)-12. CAI, originally identified for its anti-invasive capacity, has been shown to inhibit tumor and endothelial cell proliferation by inhibition of calcium uptake. It is administered orally, is generally well tolerated, and has been shown to induce disease stabilization and occasional reductions in tumor mass. Thalidomide was shown to inhibit growth factor-induced neovessel formation, a process that can also explain its earlier devastating clinical toxicity. It is administered orally, and is currently in phase II clinical trials for prostate cancer, glioblastoma multiforme and breast cancer. TNP-470 is a fumagillin analog that has been shown in in vivo models to be a potent inhibitor of angiogenesis at concentrations that are cytostatic to endothelial cells and tumor cells. Lastly, IL-12 may exert its anti-angiogenic effects through activation of interferon-gamma to up-regulate interferon-inducible protein-10, an anti-angiogenic cytokine. Phase I clinical trials of IL-12 have shown disease stabilization in several tumor types in response to s.c. administration or using genetically engineered IL-12-expressing patient fibroblasts. These promising new agents join the matrix metalloproteinase inhibitors as important new drugs in the anti-cancer armamentarium. JF - Angiogenesis AU - Masiero, L AU - Figg, W D AU - Kohn, E C AD - Laboratory of Pathology, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 23 EP - 35 VL - 1 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859446759?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Angiogenesis&rft.atitle=New+anti-angiogenesis+agents%3A+review+of+the+clinical+experience+with+carboxyamido-triazole+%28CAI%29%2C+thalidomide%2C+TNP-470+and+interleukin-12.&rft.au=Masiero%2C+L%3BFigg%2C+W+D%3BKohn%2C+E+C&rft.aulast=Masiero&rft.aufirst=L&rft.date=1997-01-01&rft.volume=1&rft.issue=1&rft.spage=23&rft.isbn=&rft.btitle=&rft.title=Angiogenesis&rft.issn=1573-7209&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2003-09-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Challenge of Developing New Therapies for Childhood Cancers. AN - 1859305940; 10388032 AB - The current standard treatments for childhood cancers are highly successful. The five-year survival rates for all children diagnosed with cancer in the late 1980s approaches 70%, and the outlook continues to improve. For some types of localized embryonal tumors, such as retinoblastoma and Wilms' tumor, the cure rates approach or exceed 90%. Our success in treating childhood cancers can be attributed to the development and use of an integrated, multimodality treatment approach which includes surgery, radiaton, and combination chemotherapy. This approach has become standard treatment for most childhood solid tumors. However, for every two children who survive, one child still succumbs to cancer, and for some childhood cancers, such as neuroblastoma and certain types of brain tumors, the prognosis remains poor. Therefore, despite our successes, there remains a need to develop new chemotherapeutic agents as well as new treatment approaches for childhood cancers. In a previous volume of The Oncologist (1996;1:169-172), Dr. Charles Pratt discussed the need for developing new drugs to treat childhood cancers and the mechanisms by which the clinical trials can be efficiently conducted. However, the clinical development of new drugs and new treatment approaches becomes more difficult as our standard treatments improve. Clearly, as more patients are cured, fewer patients are available for treatment on conventional phase I and phase II trials, which are typically performed in patients who have relapsed after standard front-line and salvage therapy. The condition of patients at the time of entry onto investigational drug studies is also affected by the nature of their prior therapy. As a result of the increasing intensity of standard treatment regimens and the use of myeloablative therapy followed by bone marrow transplantation as salvage therapy, patients entering investigational drug trials are more intolerant of further treatment and they are more likely to have tumors that are refractory to any form of therapy. In essence, the children with refractory cancers who are entered on phase I and phase II trials are becoming less and less representative of children with newly diagnosed cancers. The tolerance of children and adults to anticancer drugs was reviewed by Marsoni et al. (Cancer Treat Rep 1985;69:1263-1269). Seventeen agents that entered into clinical testing prior to 1980 were studied on similar schedules in children and adults, and the pediatric maximum tolerated dose (MTD) exceeded the adult MTD for 16 of the 17 agents. For half the drugs the pediatric MTD was 30% higher than the adult MTD, suggesting that children had a significantly greater tolerance to the toxicity of cancer chemotherapy than adults. In the 1990s we have performed a number of phase I trials in children who were more heavily pretreated than those children treated on phase I trials in the 1970s, and the pediatric MTD has been equivalent to or below the adult MTD in several of our trials. Similarly, childhood cancers have been considered to be more chemosensitive than adult forms of cancer, but several recently approved agents that have significant antitumor activity in adult cancers appear to be inactive in conventional phase II trials performed in children with recurrent cancers. Careful meta-analysis of the results of phase I and II trials performed in children and adults in the 1990s will be needed to determine if the changes in the intensity of front-line and salvage treatment regimens for childhood cancers are having a significant impact on the results of conventional phase I and II trials. The clinical development of investigational drugs and the design of phase I and II may need to be adjusted to account for the apparent greater intolerance of the heavily pretreated children entering onto these trials and the greater refractoriness of their tumors. Phase I trials may need to be performed in both heavily pretreated and less heavily pretreated children, as is currently done in adults. Limited intrapatient dose escalations can also be incorporated into phase II trials, because the patient population entering phase II trials tends to be less heavily pretreated than patients entered onto phase I trials. For new agents that appear to be inactive in conventional phase II trials, additional testing can be performed in newly diagnosed patients by administering a limited number of doses of the new agent and assessing response prior to initiation of standard therapy. This phase II window has been incorporated into the design of several front-line treatment protocols. The design of future pediatric phase I and II trials must account for the changing characteristics of the patient population that will be treated on those trials. As our knowledge about the underlying molecular defects in cancer cells expands, new biologically based treatment approaches (e.g., tumor vaccines, differentiating agents, immunotherapy, growth factor inhibitors, gene therapy), which promise to provide more rational and selective therapy for childhood cancers, are being discovered. The clinical development of these exciting new approaches will also be challenging for clinical investigators. For cancers that are successfully treated with standard multimodality treatment regimens, the impact of adding one of these new treatment approaches to the standard regimen may be difficult to detect and quantify, because of the already high survival rates; and substituting a new unproven treatment approach for a highly successful standard treatment is difficult to justify. Evaluating these new treatment approaches in heavily pretreated patients with recurrent disease may also underestimate their antitumor activity. For example, tumor vaccines depend on the patient's immue response, which may be substantially suppressed by prior dose-intensive chemotherapy and radiation. It may be more feasible to initially test these new treatment approaches in those cancers in which current standard therapy is less successful. Once they have been demonstrated to have antitumor activity in poor prognosis tumors, they can be applied to the treatment of cancers that respond well to current standard multimodality treatments. With these changes in the patient population entering investigational drug studies and the development of new non-cytotoxic treatment approaches, the design and end-points of conventional phase I and II trials must be adapted to ensure that new therapies are efficiently developed in the pediatric population. JF - The oncologist AU - Balis AD - Pharmacology and Experimental Therapeutics Division, Pediatric Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20892-0001, USA. balisf@pbmac.nci.nih.gov Y1 - 1997 PY - 1997 DA - 1997 SP - I EP - II VL - 2 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859305940?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+oncologist&rft.atitle=The+Challenge+of+Developing+New+Therapies+for+Childhood+Cancers.&rft.au=Balis&rft.aulast=Balis&rft.aufirst=&rft.date=1997-01-01&rft.volume=2&rft.issue=1&rft.spage=I&rft.isbn=&rft.btitle=&rft.title=The+oncologist&rft.issn=1549-490X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 1999-06-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic Testing for Cancer Risk Assessment: A Review. AN - 1859305519; 10388052 AB - Both environmental factors and an inherited predisposition influence carcinogenesis. The direct role of inheritance in the development of cancer is evident in familial cancer syndromes. These syndromes predispose to cancer through the inheritance of a mutation in a single gene in affected carriers. While many inherited cancer syndromes are rare, an inherited predisposition is directly responsible for 5%-10% of all colon and breast cancers. Complex multigenic inheritance plays an important role in cancer predisposition for the population at large. The identification of genes responsible for an inherited predisposition to colon and breast cancer syndromes has directed public attention to genetic testing for susceptibility to cancer. Assays are currently available to determine individual susceptibility to specific cancers. Cancer genetic testing is currently a time-consuming and complex procedure which requires expertise in its application, interpretation, and follow-up strategic planning. This review discusses cancer genetics and its application to individual and family cancer risk assessment with particular emphasis on breast and colon cancer. JF - The oncologist AU - Grogan AU - Kirsch AD - Genetics Department, Medicine Branch, National Cancer Institute, Bethesda, Maryland, 20889-5105, USA. Y1 - 1997 PY - 1997 DA - 1997 SP - 208 EP - 222 VL - 2 IS - 4 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859305519?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+oncologist&rft.atitle=Genetic+Testing+for+Cancer+Risk+Assessment%3A+A+Review.&rft.au=Grogan%3BKirsch&rft.aulast=Grogan&rft.aufirst=&rft.date=1997-01-01&rft.volume=2&rft.issue=4&rft.spage=208&rft.isbn=&rft.btitle=&rft.title=The+oncologist&rft.issn=1549-490X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 1999-06-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of Fluorescence In Situ Hybridization (FISH) To Assess Effects of Smoking, Caffeine, and Alcohol on Aneuploidy Load in Sperm of Healthy Men AN - 17255986; 4549011 AB - Aneuploidy is a common cause of poor reproductive outcomes in humans and is associated with severe medical problems in liveborn offspring, yet little is known about its underlying cause. A substantial amount of aneuploidy is known to be contributed by the father through cytogenetically abnormal sperm. The purpose of this cross-sectional, observational study was to investigate the potential contribution of common lifestyle exposures (smoking, caffeine, and alcohol) to the aneuploidy load in sperm from 45 healthy male volunteers 19-35 years of age. Sperm FISH (fluorescence in situ hybridization) was used to determine aneuploidy and diploidy frequencies for chromosomes X, Y and 18 across varying exposure levels of smoking, caffeine, and alcohol. Caffeine was significantly associated with increased frequencies of sperm aneuploidy XX18 and XY18, diploidy XY18-18 and the duplication phenotype YY18-18 controlling for alcohol, smoking and donor age. Alcohol was significantly associated with increased frequencies of sperm aneuploidy XX18, diploidy XY18-18 and the duplication phenotype XX18-18 controlling for caffeine, smoking and donor age. There was a suggestive, but unstable, association between smoking and XX18. Even within our truncated age range, we were able to confirm an increased risk for XX18 aneuploidy with increasing donor age. Sperm FISH proved to be a useful biomarker to detect and compare numerical cytogenetic abnormalities in human sperm cells across differing levels of exposure to smoking, caffeine, and alcohol. JF - Environmental and Molecular Mutagenesis AU - Robbins, WA AU - Vine, M F AU - Truong, KY AU - Everson, R B AD - Room 266 Rosenau Hall, CB#7400, School of Public Health, Univ. of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7400, USA, robbins2@niehs.nih.gov Y1 - 1997 PY - 1997 DA - 1997 SP - 175 EP - 183 VL - 30 IS - 2 SN - 8093-6692, 8093-6692 KW - X chromosome KW - Y chromosome KW - man KW - Toxicology Abstracts; Genetics Abstracts KW - Aneuploidy KW - Sperm KW - Smoking KW - Caffeine KW - Reproduction KW - Ethanol KW - X 24190:Polycyclic hydrocarbons KW - G 07221:Specific chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17255986?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+and+Molecular+Mutagenesis&rft.atitle=Use+of+Fluorescence+In+Situ+Hybridization+%28FISH%29+To+Assess+Effects+of+Smoking%2C+Caffeine%2C+and+Alcohol+on+Aneuploidy+Load+in+Sperm+of+Healthy+Men&rft.au=Robbins%2C+WA%3BVine%2C+M+F%3BTruong%2C+KY%3BEverson%2C+R+B&rft.aulast=Robbins&rft.aufirst=WA&rft.date=1997-01-01&rft.volume=30&rft.issue=2&rft.spage=175&rft.isbn=&rft.btitle=&rft.title=Environmental+and+Molecular+Mutagenesis&rft.issn=80936692&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 - Reproduction; Smoking; Caffeine; Aneuploidy; Sperm; Ethanol ER - TY - JOUR T1 - The human health effects of DDT and PCBs (polychlorinated biphenyls) and an overview of organochlorines in public health AN - 17208576; 4488347 AB - Organochlorines are a diverse group of persistent synthetic compounds, some of which are detectable in nearly everyone. Many organochlorines are endocrine disruptors or carcinogens in experimental assays. p,p'-DDE (dichlorodiphenyl- dichloroethene) and PCBs (polychlorinated biphenyls) comprise the bulk of orga- nochlorine residues in human tissues. We reviewed relevant human data cited in the 1991-1995 Medline database and elsewhere. High-level exposure to selected organochlorines appears to cause abnormalities of liver function, skin (chloracne), and the nervous system. Of more general interest, however, is evidence suggesting insidious effects of background exposure. Of particular concern is the finding of neonatal hypotonia or hyporeflexia in relation to PCB exposure. The epidemiologic data reviewed, considered in isolation, provide no convincing evidence that organochlorines cause a large excess number of cancers. A recent risk assessment that considered animal data, however, gives a cancer risk estimate for background exposure to dioxin and dioxin-like compounds (e.g. some PCBs) with an upper bound in the range of 10 super(-4) per year. JF - Annual Review of Public Health AU - Longnecker, M P AU - Rogan, W J AU - Lucier, G AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA, longnecker@niehs.nih.gov Y1 - 1997 PY - 1997 DA - 1997 SP - 211 EP - 244 VL - 18 SN - 0163-7525, 0163-7525 KW - Health & Safety Science Abstracts KW - Risk assessment KW - DDT KW - Environmental health KW - PCB compounds KW - H 12000:Epidemiology and Public Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17208576?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annual+Review+of+Public+Health&rft.atitle=The+human+health+effects+of+DDT+and+PCBs+%28polychlorinated+biphenyls%29+and+an+overview+of+organochlorines+in+public+health&rft.au=Longnecker%2C+M+P%3BRogan%2C+W+J%3BLucier%2C+G&rft.aulast=Longnecker&rft.aufirst=M&rft.date=1997-01-01&rft.volume=18&rft.issue=&rft.spage=211&rft.isbn=&rft.btitle=&rft.title=Annual+Review+of+Public+Health&rft.issn=01637525&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - DDT; PCB compounds; Risk assessment; Environmental health ER - TY - JOUR T1 - Dry deposition and particle size distributions of nitrate and sulfate in ambient air AN - 17126523; 4434522 AB - This study reports the dry deposition pollutants of anion species (NO super(-) sub(3) and SO super(-) sub(4) super(2)) in the Ping Tung City of Southern Taiwan. Several deposition properties are discussed in this paper. It included dry deposition flux, anion species size distribution and deposition velocities. Noll Rotary Impactor (NRI) and Microorifice Uniform Deposit Impactor (MOUDI) were used to collect ambient air coarse and fine particulate. Dry deposition plate was applied to collect particle deposition flux. Dionex 2000i/SP Ion Chromatography equipped with 4 mm AG4A-SC and AS4A-SC column was employed to analyze the anion species. The eluent solution is 1.8 mM sodium carbonate/1.7 mM sodium bicarbonate. The measured dry deposition flux of nitrate ranged from 0.63 to 3.96 mg/m super(2)-day and averaged 2.12 mg/m super(2)-day, while the measured dry deposition of sulfate ranged from 1.17 to 9.53 mg/m super(2)-day and averaged 3.92 mg/m super(2)-day. The particle size distribution of nitrate has bimodal particle size distributions. However, the sulfate displayed uniform particle size distribution for all four sampling sites. Mean cumulative fraction (F%) of nitrate in the particle size range below 1, 2.5, 10 and 25 mu m, in sequence, were 34.6%, 60.9%, 91.0% and 97.6%, respectively. However, the mean F% of sulfate in the particle size range below 1, 2.5, 10 and 25 mu m, in sequence, were 57.3%, 82.6%, 90.3% and 98.0%, respectively. The sulfate has more F% in the submicron particles. The mean MMD sub(o) of nitrate and sulfate are 2.35 and 0.87 mu m, respectively. The mean dry deposition velocities of nitrate and sulfate are 0.45 and 0.38 cm/sec, respectively. JF - Toxicological and Environmental Chemistry AU - Chen, S-J AU - Fang, G-C AU - Lin, C-C AU - Hsieh, L-T AD - Department of Environmental Protection Technology, National Ping Tung Polytechnic Institute, Nei Pu 91207, Ping Tung, Taiwan Y1 - 1997 PY - 1997 DA - 1997 SP - 49 EP - 64 VL - 62 IS - 1-4 SN - 0277-2248, 0277-2248 KW - Taiwan, Ping Tung KW - Pollution Abstracts KW - Particle size KW - Sulfates KW - Anions KW - Nitrates KW - Velocity KW - Air sampling KW - Dry deposition KW - P 0000:AIR POLLUTION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17126523?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Apollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+and+Environmental+Chemistry&rft.atitle=Dry+deposition+and+particle+size+distributions+of+nitrate+and+sulfate+in+ambient+air&rft.au=Chen%2C+S-J%3BFang%2C+G-C%3BLin%2C+C-C%3BHsieh%2C+L-T&rft.aulast=Chen&rft.aufirst=S-J&rft.date=1997-01-01&rft.volume=62&rft.issue=1-4&rft.spage=49&rft.isbn=&rft.btitle=&rft.title=Toxicological+and+Environmental+Chemistry&rft.issn=02772248&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 - Sulfates; Nitrates; Dry deposition; Velocity; Particle size; Anions; Air sampling ER - TY - JOUR T1 - The height variation and particle size distribution of polycyclic aromatic hydrocarbons in the ambient air AN - 17125138; 4431508 AB - Polycyclic aromatic hydrocarbon (PAH) samples in the ambient air of rural, urban and traffic-intersection sites have been collected by PS-1 samplers, NRI (Noll Rotary Impactor) and MOUDIs (Micro-orifice Uniform Deposit Impactors) from July, 1993 to January, 1995 in southern Taiwan. Twenty one individual PAHs were analyzed primarily by a gas chromatograph/mass spectrometer (GC/MS). The mean total-PAH concentrations (gas+particle phases) in the ambient air of traffic-intersection was approximately 5.6 and 14.1 times higher than those mean values for the urban and rural atmosphere, respectively. It is reveals that the high density of vehicle exhaust raises the PAH concentrations in the urban ambient air. In the ambient air of the traffic-intersection, most of the G/R (ground/roof) ratios for individual PAHs concentration in gas phase were higher than 1.0, except BaA, BeP, PER and BghiP. This result shows that PAHs concentration in gas phase was related to the automobile exhaust. Upon entering the ambient air of the traffic-intersection, these PAHs was condensed, cooled and dispersed at higher elevation. In the traffic intersection, the PAHs are predominantly absorbed on particles with aerodynamic diameters less than 2.5 mu m (the fine particles), a fact which strongly relates to the risk potential. The results also show that the total PAHs in the ambient air of a traffic intersection originated mainly from mobile exhaust and the phenomena of condensation process for the young aerosols. However, in the traffic-intersection, higher fraction of total-particle mass in the coarse particle mode is primarily the road dust which is due to traveling vehicles. JF - Toxicological and Environmental Chemistry AU - Chen, Shui-Jen AU - Hwang, Ping-Shium AU - Hsieh, Lien-Te AD - Department of Environmental Protection Technology, National Ping Tung Polytechnic Institute, Nei Pui 91207, Ping Tung, Taiwan Y1 - 1997 PY - 1997 DA - 1997 SP - 111 EP - 128 VL - 60 IS - 1-4 SN - 0277-2248, 0277-2248 KW - Taiwan KW - Pollution Abstracts KW - Particle size KW - Polycyclic aromatic hydrocarbons KW - Motor vehicles KW - Mass spectrometry KW - Dust KW - Gas chromatography KW - Air sampling KW - Automotive exhaust emissions KW - Sampling methods KW - P 0000:AIR POLLUTION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17125138?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Apollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+and+Environmental+Chemistry&rft.atitle=The+height+variation+and+particle+size+distribution+of+polycyclic+aromatic+hydrocarbons+in+the+ambient+air&rft.au=Chen%2C+Shui-Jen%3BHwang%2C+Ping-Shium%3BHsieh%2C+Lien-Te&rft.aulast=Chen&rft.aufirst=Shui-Jen&rft.date=1997-01-01&rft.volume=60&rft.issue=1-4&rft.spage=111&rft.isbn=&rft.btitle=&rft.title=Toxicological+and+Environmental+Chemistry&rft.issn=02772248&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 - Dust; Gas chromatography; Mass spectrometry; Automotive exhaust emissions; Particle size; Motor vehicles; Sampling methods; Air sampling; Polycyclic aromatic hydrocarbons ER - TY - JOUR T1 - The importance of enzymatic biotransformation in immunotoxicology AN - 16540293; 4350889 AB - Many immunotoxic compounds, such as benzene and other organic solvents, pesticides, mycotoxins and polycyclic aromatic hydrocarbons, can alter immune function only after undergoing enzyme-mediated reactions within various tissues. In the review that follows the role of enzymatic transformation in immunotoxicity is examined. We begin with a brief overview of the immune system and a summary of the evidence which suggests that xenobiotics can alter the function of the cells and signaling molecules required for normal immune responses. We then examine the principal Phase I and Phase II enzymes involved in the bioactivation process, particularly the cytochrome P450s, the reactions by which these enzymes detoxify or bioactivate foreign compounds, and the factors which influence their expression and regulation. Finally, we present a number of immunotoxicants and discuss the role that metabolic activation plays in their toxicity. JF - Reviews in Toxicology AU - Germolec AU - Adams, N H AU - Luster, MI AD - NIEHS (MD C1-04), P.O. Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1997 PY - 1997 DA - 1997 SP - 33 EP - 51 VL - 1 IS - 7-8 SN - 1382-6980, 1382-6980 KW - biotransformation KW - cytochrome P450 KW - polycyclic aromatic hydrocarbons KW - Toxicology Abstracts KW - Mycotoxins KW - Reviews KW - Immune system KW - Pesticides KW - Enzymes KW - Organic compounds KW - Xenobiotics KW - Benzene KW - X 24250:Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16540293?accountid=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=Reviews+in+Toxicology&rft.atitle=The+importance+of+enzymatic+biotransformation+in+immunotoxicology&rft.au=Germolec%3BAdams%2C+N+H%3BLuster%2C+MI&rft.aulast=Germolec&rft.aufirst=&rft.date=1997-01-01&rft.volume=1&rft.issue=7-8&rft.spage=33&rft.isbn=&rft.btitle=&rft.title=Reviews+in+Toxicology&rft.issn=13826980&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 - Benzene; Pesticides; Xenobiotics; Enzymes; Organic compounds; Immune system; Mycotoxins; Reviews ER - TY - JOUR T1 - CYP2J subfamily P450s: Physiologically relevant hemoproteins active in the metabolism of arachidonic acid in hepatic and extrahepatic tissues AN - 16538276; 4350888 AB - Cytochromes P450 of the CYP2J subfamily are constitutively expressed heme-thiolate proteins that are active in the epoxidation and hydroxylation of arachidonic acid in hepatic and extrahepatic tissues. These hemoproteins also metabolize selected xenobiotics including benzphetamine and related compounds. This manuscript will focus on the first six members of the CYP2J subfamily and will review recent data on their structure, spectral characteristics, enzymatic properties, organ distribution, cellular localization, regulation, and the functional significance of their bioactive eicosanoid products. JF - Reviews in Toxicology AU - Zeldin, D C AU - Wu, Shu AU - Ma, Jixiang AD - Laboratory of Pulmonary Pathobiology, National Institutes of Health, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, USA, ZELDIN@NIEHS.NIH.GOV Y1 - 1997 PY - 1997 DA - 1997 SP - 1 EP - 32 VL - 1 IS - 7-8 SN - 1382-6980, 1382-6980 KW - benzphetamine KW - cytochrome P450 KW - hemoproteins KW - Toxicology Abstracts KW - Liver KW - Arachidonic acid KW - Xenobiotics KW - Hydroxylation KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16538276?accountid=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=Reviews+in+Toxicology&rft.atitle=CYP2J+subfamily+P450s%3A+Physiologically+relevant+hemoproteins+active+in+the+metabolism+of+arachidonic+acid+in+hepatic+and+extrahepatic+tissues&rft.au=Zeldin%2C+D+C%3BWu%2C+Shu%3BMa%2C+Jixiang&rft.aulast=Zeldin&rft.aufirst=D&rft.date=1997-01-01&rft.volume=1&rft.issue=7-8&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Reviews+in+Toxicology&rft.issn=13826980&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 - Xenobiotics; Liver; Arachidonic acid; Hydroxylation ER - TY - JOUR T1 - Complex behavior of marine animal tissue extracts in the competitive binding assay of brevetoxins with rat brain synaptosomes AN - 16519488; 4332618 AB - Brevetoxins are produced by the marine dinoflagellate Ptychodiscus brevis, an organism linked to red tide outbreaks, and the accompanying toxicity to marine animals and to neurotoxic shellfish poisoning in humans. Brevetoxins bind with high affinity to voltage-sensitive sodium channels and cause increased sodium ion conductance and nerve cell depolarization. The brevetoxin competitive binding assay with tritium-labeled brevetoxin 3 ( super(3)H-PbTx-3) and rat brain synaptosomes is a sensitive and specific assay for pure brevetoxins. Here we report that extracts of manatee, turtle, fish, and clam tissues contain components that interfere with the assay by cooperative, noncompetitive inhibition of super(3)H-PbTx-3 specific binding and increased nonspecific binding to synaptosomes. By determining the "apparent" toxin concentration ("[Toxin]") in the extract at several assay concentrations, a reasonable correction for the complex inhibition could be made using a semilog plot to extrapolate [Toxin] to zero extract concentration to obtain [Toxin] sub(0). Spiking 4 extracts with 60 nM PbTx-3 caused [Toxin] sub(0) to increase by 41 plus or minus 8 nM, indicating that the noncompetitive components did not prevent the assay of toxin but did reduce the accuracy of the result. Fourfold repetition of the assay of 4 samples gave standard deviations of 25 to 60% of the value of [Toxin] sub(0), so the error can be fairly large, especially for samples with little toxin. Purification of an extract with a 1 g sample prep column of C-18 decreased the complex inhibition by about 3-fold but did not eliminate interference in the assay. JF - Natural Toxins AU - Whitney, P L AU - Delgado, JA AU - Baden, D G AD - NIEHS Mar. and Freshwater Biomed. Sci. Cent., Univ. Miami RSMAS, 4600 Rickenbacker Causeway, Miami, FL 33149, USA Y1 - 1997 PY - 1997 DA - 1997 SP - 193 EP - 200 PB - JOHN WILEY & SONS, INC. VL - 5 IS - 5 SN - 1056-9014, 1056-9014 KW - Ptychodiscus brevis KW - brain KW - brevetoxin 3 KW - brevetoxin-3 KW - marine dinoflagellates KW - neurotoxins KW - rats KW - red tides KW - shellfish poisoning KW - synaptosomes KW - toxins KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; CSA Neurosciences Abstracts; Toxicology Abstracts KW - Marine KW - N3 11104:Mammals (except primates) KW - X 24172:Plants KW - K 03039:Algae UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16519488?accountid=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=Natural+Toxins&rft.atitle=Complex+behavior+of+marine+animal+tissue+extracts+in+the+competitive+binding+assay+of+brevetoxins+with+rat+brain+synaptosomes&rft.au=Whitney%2C+P+L%3BDelgado%2C+JA%3BBaden%2C+D+G&rft.aulast=Whitney&rft.aufirst=P&rft.date=1997-01-01&rft.volume=5&rft.issue=5&rft.spage=193&rft.isbn=&rft.btitle=&rft.title=Natural+Toxins&rft.issn=10569014&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 - Marine ER - TY - JOUR T1 - Tuberculosis vaccines: how close to human testing? AN - 16471415; 4329407 AB - On 24 July 1997, in Cleveland, Ohio, the National Institute for Allergy and Infectious Diseases (NIAID) convened a workshop entitled 'Tuberculosis vaccines: how close to human testing?' to disseminate information on the extensive progress made in the last 2-3 years in developing potential tuberculosis (TB) vaccine candidates and to explore the issues involved in successfully bringing such candidates from the research laboratory through the clinical evaluation process. Multiple factors render the development of improved TB vaccines a high priority in the effort to control and ultimately eliminate TB worldwide. Mycobacterium tuberculosis, the bacterium that causes TB, is the leading global infectious cause of morbidity and mortality due to a single pathogen. Effective control has been compromised by a variety of factors, including economic, societal and practical obstacles of implementing Directly Observed Treatment Short-course (DOTS) and the emergence of multidrug resistant TB. The currently available TB vaccine, bacille Calmette-Guerin (BCG), has variable efficacy against pulmonary tuberculosis and is unacceptable in countries with low TB case rates because it interferes with DTH skin response to skin test reagents. The imminent availability of the M. tuberculosis whole genome sequence coupled with other significant advances in mycobacterial research, such as improved genetic tools, are providing the foundation for new optimism regarding the possibility of developing improved TB vaccine candidates. The workshop was designed to initiate and provide a forum for an exchange of ideas and perspectives among the members of the disparate fields involved in TB vaccine development. JF - Tubercle and Lung Disease AU - Jacobs, G G AU - Johnson, J L AU - Boom, W H AU - Wallis, R S AU - Whalen, C C AU - Ginsberg, A M AD - NIH/NIAID/DMID, Respiratory Diseases Branch, Solor Bldg, Rm. 3A41, 6003 Executive Blvd MSC 7630, Bethesda, MD 20892-7630, USA, gg6z@nih.gov Y1 - 1997 PY - 1997 DA - 1997 SP - 159 EP - 169 VL - 78 IS - 3-4 SN - 0962-8479, 0962-8479 KW - man KW - Microbiology Abstracts B: Bacteriology KW - J 02834:Vaccination and immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16471415?accountid=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=Tubercle+and+Lung+Disease&rft.atitle=Tuberculosis+vaccines%3A+how+close+to+human+testing%3F&rft.au=Jacobs%2C+G+G%3BJohnson%2C+J+L%3BBoom%2C+W+H%3BWallis%2C+R+S%3BWhalen%2C+C+C%3BGinsberg%2C+A+M&rft.aulast=Jacobs&rft.aufirst=G&rft.date=1997-01-01&rft.volume=78&rft.issue=3-4&rft.spage=159&rft.isbn=&rft.btitle=&rft.title=Tubercle+and+Lung+Disease&rft.issn=09628479&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - The effect of lead exposure and serum deprivation on mesencephalic primary cultures AN - 16455259; 4345276 AB - The effect of Pb super(2+) was studied in embryonic mesencephalic primary cultures that contain neurons and glia. Pb super(2+) exposure in absence of serum, damaged more efficaciously the cultured cells than Pb super(2+) exposure in presence of serum. In serum-free medium, Pb super(2+) elicited mainly necrosis and apoptosis in maximally 13% of the cells in culture. The glial fibrillary acidic protein (GFAP) content was decreased by Pb super(2+) exposure in serum-containing medium. The abundance of GFAP was also decreased by serum deprivation that was augmented by the addition of 12.5 mu M Pb super(2+) in serum-free medium. A 6h exposure to 6 mu M Pb super(2+) in serum-free medium also lowered the low affinity super(3)H-D-aspartate uptake. A 6h exposure of mesencephalic cells to 3-25 mu M Pb super(2+) in serum-free medium failed to alter the number of tyrosine hydroxylase- and calretinin-immunoreactive cells, whereas, 50 mu M Pb super(2+) obliterated both cell types. A 6h exposure of cells to 3 mu M Pb super(2+) in serum-free medium decreased super(3)H-dopamine uptake by 50% and 12.5 mu M Pb super(2+) obliterated it. Addition of albumin to serum-free medium failed to prevent the Pb super(2+)-elicited inhibition of [ super(3)H]-dopamine uptake suggesting that the serum-afforded delay of cell death may not be due to a removal of reactive Pb super(2+) by protein/chelate formation but rather to the Pb super(2+)-scavenging function of glial cells. Serum deprivation may exacerbate the Pb super(2+)-induced neurotoxicity presumably by impairing the metal scavenging function of astrocytes. JF - Neurotoxicology AU - Scortegagna, M AU - Hanbauer, I AD - Lab. Mol. Immun., NHLBI, Bldg. 10 Rm. 7N-312, Bethesda, MD 20892-1674, USA Y1 - 1997 PY - 1997 DA - 1997 SP - 331 EP - 340 VL - 18 IS - 2 SN - 0161-813X, 0161-813X KW - cell culture KW - glia KW - lead KW - mesencephalon KW - neurons KW - neurotoxicity KW - rats KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - N3 11104:Mammals (except primates) KW - X 24164:Pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16455259?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicology&rft.atitle=The+effect+of+lead+exposure+and+serum+deprivation+on+mesencephalic+primary+cultures&rft.au=Scortegagna%2C+M%3BHanbauer%2C+I&rft.aulast=Scortegagna&rft.aufirst=M&rft.date=1997-01-01&rft.volume=18&rft.issue=2&rft.spage=331&rft.isbn=&rft.btitle=&rft.title=Neurotoxicology&rft.issn=0161813X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - A non-radioactive and two radioactive assays for selenophosphate synthetase activity AN - 16366842; 4228476 AB - In one assay frequently used, [8- super(14)C]AMP formation from [8- super(14)C]ATP is estimated after separation of the nucleotides by thin-layer chromatography. An alternative non-radioactive assay in which the AMP product is estimated using AMP deaminase is described. The highly oxygen-labile selenophosphate product can be estimated in an assay employing [ gamma - super(32)P]ATP. The super(32)P-labeled selenophosphate is converted to [ super(32)P]orthophosphate by treatment with iodine and estimated after removal of residual [ super(32)P]ATP on charcoal. JF - BioFactors AU - Liu, Song-Yuan AU - Stadtman, T C AD - NHLBI/IR/LB, Bldg. 3, Rm. 108, 3 Cent. Dr. MSC 0320, Bethesda, MD 20892-0320, USA Y1 - 1997 PY - 1997 DA - 1997 SP - 305 EP - 309 VL - 6 IS - 3 SN - 0951-6433, 0951-6433 KW - assays KW - radioactivity KW - selenophosphate synthase KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - N 14351:Enzymatic KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16366842?accountid=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=BioFactors&rft.atitle=A+non-radioactive+and+two+radioactive+assays+for+selenophosphate+synthetase+activity&rft.au=Liu%2C+Song-Yuan%3BStadtman%2C+T+C&rft.aulast=Liu&rft.aufirst=Song-Yuan&rft.date=1997-01-01&rft.volume=6&rft.issue=3&rft.spage=305&rft.isbn=&rft.btitle=&rft.title=BioFactors&rft.issn=09516433&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 - RecA protein assisted selection reveals a low fidelity of recognition of homology in a duplex DNA by an oligonucleotide AN - 16329879; 4265299 AB - We have developed an in vitro selection procedure to elucidate the specificity of RecA assisted oligonucleotide recognition of double stranded DNA. The procedure was based on formation of a synaptic complex between an oligonucleotide-RecA filament and a supercoiled plasmid bearing a homologous partially degenerate region. The specificity of the selection depended on the reaction conditions: starting with a population that had, on average, 2.8 randomly distributed mismatches out of 27 bp, a population selected in the presence of 100 mM KCl had on average 1.0 mismatches, while a population selected at low ionic strength was less specific and had, on average, 2.0 mismatches. From the distributions of mismatches observed we calculated that the average destabilization free energy for one mismatch is 1.7( plus or minus 0.5) kcal/mol. This is substantially less than the free energy for the incorporation of one mismatch in naked DNA duplex or a Py-Pu-Py triplex. Thus, RecA has an ability to decrease the fidelity of the homologous pairing reaction and minimize the cost of pairing between similar but not identical sequences. This "antiproofreading" activity of RecA protein does not require ATP hydrolysis. JF - Journal of Molecular Biology AU - Malkov, V A AU - Sastry, L AU - Camerini-Otero, R D AD - Genet. and Biochem. Branch, Natl. Institutes Health (NIDDK), Bldg. 10 Rm. 9D15, 10 Center Dr., MSC 1810, Bethesda, MD 20892-1810, USA Y1 - 1997 PY - 1997 DA - 1997 SP - 168 EP - 177 VL - 271 IS - 2 SN - 0022-2836, 0022-2836 KW - DNA KW - RecA protein KW - oligonucleotides KW - recombination KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - J 02740:Genetics and evolution KW - N 14940:Nucleic acid-binding proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16329879?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Biology&rft.atitle=RecA+protein+assisted+selection+reveals+a+low+fidelity+of+recognition+of+homology+in+a+duplex+DNA+by+an+oligonucleotide&rft.au=Malkov%2C+V+A%3BSastry%2C+L%3BCamerini-Otero%2C+R+D&rft.aulast=Malkov&rft.aufirst=V&rft.date=1997-01-01&rft.volume=271&rft.issue=2&rft.spage=168&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Arsenic carcinogenesis in animals and in humans: Mechanistic, experimental, and epidemiological evidence AN - 16321388; 4251612 AB - Purpose. In this paper we present a brief overview of the history of arsenic; some data on occurrence, production, and use of arsenic; metabolism and disposition of arsenic; and mainly we review and evaluate the published information on arsenic carcinogenesis in humans and in animals, including current mechanistic concepts, and offer the opinion that further consideration should be given to doing an NTP-type long-term carcinogenesis study. Because arsenic has long been known to cause cancer in humans, this would allow definitive answers to the question of whether arsenic is or is not carcinogenic to animals. The rationale for doing an NTP style study centers on two issues: 1] experimental studies conducted to date on arsenic are inadequate to fully evaluate the carcinogenicity to animals; and 2] the views expressed by some that the bioassay is not relevant or extrapolatable to humans because arsenic is a human carcinogen that has not been shown to convincingly cause cancer in experimental animals. Thus opponents of the use of chronic rodent testing in predicting human carcinogenic potential state that without positive experimental carcinogenesis findings it is difficult to accept that animal models [typically rodents] used by the NTP and others are truly useful for predicting carcinogenicity of chemicals to humans. Obversely, we believe that arsenic will be shown to cause cancer in laboratory animals under appropriately designed and adequate long-term exposure experiments. JF - Journal of Environmental Science and Health, Part C: Environmental Carcinogenesis and Ecotoxicology Reviews AU - Chan, Po C AU - Huff, J AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA Y1 - 1997 PY - 1997 DA - 1997 SP - 83 EP - 122 VL - C15 IS - 2 SN - 1059-0501, 1059-0501 KW - Health & Safety Science Abstracts; Pollution Abstracts; Toxicology Abstracts KW - H 14000:Toxicology KW - X 24162:Chronic exposure KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16321388?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Environmental+Science+and+Health%2C+Part+C%3A+Environmental+Carcinogenesis+and+Ecotoxicology+Reviews&rft.atitle=Arsenic+carcinogenesis+in+animals+and+in+humans%3A+Mechanistic%2C+experimental%2C+and+epidemiological+evidence&rft.au=Chan%2C+Po+C%3BHuff%2C+J&rft.aulast=Chan&rft.aufirst=Po&rft.date=1997-01-01&rft.volume=C15&rft.issue=2&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=Journal+of+Environmental+Science+and+Health%2C+Part+C%3A+Environmental+Carcinogenesis+and+Ecotoxicology+Reviews&rft.issn=10590501&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 - Double-blind placebo-controlled treatment trial of Chlamydia trachomatis endocervical infections in pregnant women AN - 16320981; 4248348 AB - Objective: The purpose of this study was to determine if treatment of pregnant women with Chlamydia trachomatis infection would lower the incidence of preterm delivery and/or low birth weight. Methods: Pregnant women between the 23rd and 29th weeks of gestation were randomized in double-blind fashion to receive either erythromycin 333 mg three times daily or an identical placebo. The trial continued until the end of the 35th week of gestation. Results: When the results were examined without regard to study site, erythromycin had little impact on reducing low birth weight (8% vs. 11%, P = 0.4) or preterm delivery (13% vs. 15%, P = 0.7). At the sites with high persistence of C. trachomatis in the placebo-treated women, low birth weight infants occurred in 9 (8%) of 114 erythromycin-treated and 18 (17%) of 105 placebo-treated women (P = 0.04) and delivery <37 weeks occurred in 15 (13%) of 115 erythromycin-treated and 18 (17%) of 105 placebo-treated women (P = 0.4). Conclusions: The results of this trial suggest that the risk of low birth weight can be decreased by giving erythromycin to some women with C. trachomatis. Due to the high clearance rate of C. trachomatis JF - Infectious Diseases in Obstetrics and Gynecology AU - Martin, D H AU - Eschenbach, DA AU - Cotch, M F AU - Nugent, R P AU - Rao, A V AU - Klebanoff, MA AU - Lou, Y AU - Rettig, P J AU - Gibbs, R S AU - Pastorek, JG II AU - Regan, JA AU - Kaslow, R A AD - NIH, NICHD, PAMA Branch, 6100 Executive Blvd., Rm. 4B11C, Bethesda, MD 20892, USA Y1 - 1997 PY - 1997 DA - 1997 SP - 10 EP - 17 PB - JOHN WILEY & SONS, INC. VL - 5 IS - 1 SN - 1064-7449, 1064-7449 KW - cervix KW - erythromycin KW - infection KW - pregnancy KW - treatment KW - Microbiology Abstracts B: Bacteriology; Microbiology Abstracts A: Industrial & Applied Microbiology KW - J 02847:Genitourinary tract KW - A 01066:Antibacterial & bactericidal KW - J 02849:Sexually-transmitted diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16320981?accountid=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=Infectious+Diseases+in+Obstetrics+and+Gynecology&rft.atitle=Double-blind+placebo-controlled+treatment+trial+of+Chlamydia+trachomatis+endocervical+infections+in+pregnant+women&rft.au=Martin%2C+D+H%3BEschenbach%2C+DA%3BCotch%2C+M+F%3BNugent%2C+R+P%3BRao%2C+A+V%3BKlebanoff%2C+MA%3BLou%2C+Y%3BRettig%2C+P+J%3BGibbs%2C+R+S%3BPastorek%2C+JG+II%3BRegan%2C+JA%3BKaslow%2C+R+A&rft.aulast=Martin&rft.aufirst=D&rft.date=1997-01-01&rft.volume=5&rft.issue=1&rft.spage=10&rft.isbn=&rft.btitle=&rft.title=Infectious+Diseases+in+Obstetrics+and+Gynecology&rft.issn=10647449&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 - Effects of glutathione depletion on cadmium-induced metallothionein synthesis, cytotoxicity, and proto-oncogene expression in cultured rat myoblasts AN - 16239985; 4230137 AB - Cadmium (Cd) is a highly toxic metal and a known carcinogen. Although the carcinogenic mechanism of action is unknown, Cd will induce transcriptional activation of c-myc and c-jun. We have previously found that the extent of Cd-induced oncogene expression is limited by the presence of cellular metallothionein (MT) in rat L6 myoblasts. Glutathione (GSH) is thought to play an important role in protection against Cd before the onset of MT synthesis. Thus, this study examined the effects of GSH depletion on Cd-induced MT synthesis, cytotoxicity, and proto-oncogene expression in rat L6 myoblasts after pretreatment with L-buthionine sulfoximine (BSO), a potent inhibitor of gamma -glutamylcysteine synthetase, which effectively depletes GSH. Exposure of L6 cells to BSO (5 or 25 mu M) resulted in a dose-dependent decrease in cellular GSH levels. GSH depletion had no effect on Cd- or zinc-induced MT synthesis. Although the depletion of GSH was not itself cytotoxic in L6 cells, BSO pretreatment, particularly at the higher dose (25 mu M), resulted in a dose-dependent increase in the sensitivity to Cd cytotoxicity, as assessed by a tetrazolium-based dye (MTT) assay. Low levels of Cd (1 mu M) slightly increased the expression of both c-myc and c-jun as assessed by increases in gene-specific mRNA levels, in accordance with previous studies. GSH depletion (5 mu M BSO) likewise caused an increase in expression of c-myc and c-jun. However, combined GSH depletion and Cd exposure decreased levels of c-myc and c-jun transcription well below control levels. These results suggest that increased cytotoxicity resulting from exposure to Cd after BSO depletion of cellular GSH abrogates the oncogene activation observed after either treatment alone. Thus proto-oncogene expression induced by Cd appears to be dependent on the absence of overt Cd-induced cytotoxicity. JF - Journal of Toxicology and Environmental Health AU - Shimizu, M AU - Hochadel, J F AU - Waalkes, M P AD - Inorganic Carcinogenesis Section, NCI at NIEHS, 111 Alexander Drive, PO Box 12233, MD F0-09, Research Triangle Park, NC 27709, USA Y1 - 1997 PY - 1997 DA - 1997 SP - 609 EP - 621 VL - 51 IS - 6 SN - 0093-4108, 0093-4108 KW - buthionine sulfoximine KW - c-jun gene KW - c-myc gene KW - cadmium KW - gene expression KW - glutathione KW - metallothionein KW - myoblasts KW - rats KW - Toxicology Abstracts KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16239985?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Toxicology+and+Environmental+Health&rft.atitle=Effects+of+glutathione+depletion+on+cadmium-induced+metallothionein+synthesis%2C+cytotoxicity%2C+and+proto-oncogene+expression+in+cultured+rat+myoblasts&rft.au=Shimizu%2C+M%3BHochadel%2C+J+F%3BWaalkes%2C+M+P&rft.aulast=Shimizu&rft.aufirst=M&rft.date=1997-01-01&rft.volume=51&rft.issue=6&rft.spage=609&rft.isbn=&rft.btitle=&rft.title=Journal+of+Toxicology+and+Environmental+Health&rft.issn=00934108&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Natural products in drug discovery and development AN - 16228770; 4218537 AB - Analysis of the number and sources of anticancer and antiinfective agents, reported mainly in Annual Reports of Medicinal Chemistry from 1984 to 1995, indicates that over 60% of the approved drugs and pre-NDA candidates (for the period 1989-1995), excluding biologics, developed in these disease areas are of natural origin. Drugs of natural origin have been classified as original natural products, products derived semisynthetically from natural products, or synthetic products based on natural product models. This review highlights the invaluable role that natural products have played, and continue to play, in the drug discovery process, particularly in the areas of cancer and infectious diseases. JF - Journal of Natural Products AU - Cragg, G M AU - Newman, D J AU - Snader, K M AD - Natural Products Branch, Developmental Therapeutics Program, Division of Cancer Treatment, Diagnosis and Centers, National Cancer Institute, Frederick Cancer Research and Development Center, P.O. Box B, Frederick, Maryland 21702-1201, USA Y1 - 1997/01// PY - 1997 DA - Jan 1997 SP - 52 EP - 60 VL - 60 IS - 1 SN - 0163-3864, 0163-3864 KW - drug discovery KW - natural products KW - reviews KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W 30965:Miscellaneous, Reviews KW - W3 33000:General topics and reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16228770?accountid=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+Natural+Products&rft.atitle=Natural+products+in+drug+discovery+and+development&rft.au=Cragg%2C+G+M%3BNewman%2C+D+J%3BSnader%2C+K+M&rft.aulast=Cragg&rft.aufirst=G&rft.date=1997-01-01&rft.volume=60&rft.issue=1&rft.spage=52&rft.isbn=&rft.btitle=&rft.title=Journal+of+Natural+Products&rft.issn=01633864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Stabilization of a recombinant Fv fragment by base-loop interconnection and V sub(H)-V sub(L) permutation AN - 16202258; 4277443 AB - We have developed a novel method to stabilize a recombinant antibody Fv fragment. The V sub(H) and V sub(L) domains of this Fv fragment, called pFv (permutated Fv), are covalently interconnected to each other at the two "base-loops" that normally connect V sub(H) beta strand 3 to 3b and V sub(L) beta strand 3 to 3b. To produce the base-loop stabilized Fv fragment, we connected the N-terminal half of the V sub(L) domain (V sub(L) 1-40) of murine antibody anti-Tac to the C-terminal half of V sub(H) (V sub(H) 42-115). We also fused the C terminus of V sub(H) by a (Gly sub(4)Ser) sub(3) linker to the N-terminal half of V sub(H) (V sub(H) 1-40, thereby generating a permutated V sub(H) domain). Finally we connected the base loop of V sub(H) (N-terminal half) to the C-terminal half of V sub(L) (V sub(H) 42-115). The anti-Tac pFv fragment was fused to a truncated form of Pseudomonas exotoxin to generate a pFv-immunotoxin. Fvs with the correct structure were produced by refolding of recombinant inclusion body protein using a renaturation protocol that was originally developed for Fab and scFv fragments. Due to the artificially connected and permutated primary sequence, the folding pathway for the pFv structure may possibly be different from the conventional folding of antibody domains. Analysis of antigen binding of anti-Tac pFv, and of the specific cytotoxicity of pFv-immunotoxin towards antigen expressing cancer cells demonstrated that the anti-Tac pFv retained most of its affinity and full specificity when compared to anti-Tac scFv. Also anti-Tac pFv was relatively stable, retaining 25% of its binding activity after a 24 hour incubation in human serum at 37 degree C. This indicates that connection of base loops can be a useful alternative to linker or disulfide stabilization of Fv fragments. JF - Journal of Molecular Biology AU - Brinkmann, U AU - Carlo, ADi AU - Vasmatzis, G AU - Kurochkina, N AU - Beers, R AU - Lee, Byungkook AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Building 37, Room 4E16 37, Convent Dr Msc 4255, Bethesda, MD 20892-4255, USA Y1 - 1997 PY - 1997 DA - 1997 SP - 107 EP - 117 VL - 268 IS - 1 SN - 0022-2836, 0022-2836 KW - Fv KW - antibodies KW - carcinoma KW - immunotherapy KW - protein engineering KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - W3 33365:Vaccines (other) KW - F 06818:Cancer immunotherapy KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16202258?accountid=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+Molecular+Biology&rft.atitle=Stabilization+of+a+recombinant+Fv+fragment+by+base-loop+interconnection+and+V+sub%28H%29-V+sub%28L%29+permutation&rft.au=Brinkmann%2C+U%3BCarlo%2C+ADi%3BVasmatzis%2C+G%3BKurochkina%2C+N%3BBeers%2C+R%3BLee%2C+Byungkook%3BPastan%2C+I&rft.aulast=Brinkmann&rft.aufirst=U&rft.date=1997-01-01&rft.volume=268&rft.issue=1&rft.spage=107&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Particle-bound composition of polycyclic aromatic hydrocarbons and aerosol carbons in the ambient air AN - 16100106; 4203802 AB - Particle-bound composition and size distributions of organic carbon (OC), elemental carbon (EC) and polycyclic aromatic hydrocarbons (PAHs) were measured by the PS-1 sampler, NRI (Noll Rotary Impactor) and MOUDIs (Micro-orifice Uniform Deposit Impactor) in the ambient air of the traffic intersection and rural site in Ping Tung area of Southern Taiwan from September 1994 to December 1995. Elemental analyzer was used to analyze the carbon composition of aerosol samples. Twenty one individual PAHs were analyzed primarily by a gas chromatography/mass spectrometer (GC/MS). In the ambient air of Ping Tung area, the aerosol carbons accounted for 18.7% similar to 25.5% of the total suspended particulate (TSP) mass loading. EC and OC comprised about 12% and 10% of the TSP mass, respectively. The concentration ratios for TC/EC ranged between 1.4 and 2.6 and averaged 2.0 during the sampling periods. More than 80% of particle-bound composition of 12 potential carcinogenic-PAHs, namely CYC, BaA, CHR, BbF, BkF, BeP, BaP, PER, IND, DBA, BbC, and BghiP, were existed in the particle size less than 2.5 mu m. The size distribution for particle-bound composition of OC, and EC are all bimodal. The bi-peaks were all localized at 0.18 similar to 0.32 and 1.8 similar to 3.2 mu m ranges, respectively. JF - Journal of Environmental Science and Health, Part A: Environmental Science and Engineering & Toxic and Hazardous Substance Control AU - Chen, Shui-Jen AU - Liao, Shi-Hu AU - Jian, Wei-Jain AU - Chiu, Shui-Chi AU - Fang, Guor-Cheng AD - Department of Environmental Protection Technology, National Ping Tung Polytechnic Institute, Nei Pu 91207, Ping Tung, Taiwan Y1 - 1997 PY - 1997 DA - 1997 SP - 585 EP - 604 VL - A32 IS - 3 SN - 0360-1226, 0360-1226 KW - Taiwan, Ping Tung KW - Pollution Abstracts KW - particle size KW - motor vehicles KW - exhaust emissions KW - gas chromatography KW - carbon KW - aerosols KW - polycyclic aromatic hydrocarbons KW - air sampling KW - organic carbon KW - P 0000:AIR POLLUTION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16100106?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Apollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Environmental+Science+and+Health%2C+Part+A%3A+Environmental+Science+and+Engineering+%26+Toxic+and+Hazardous+Substance+Control&rft.atitle=Particle-bound+composition+of+polycyclic+aromatic+hydrocarbons+and+aerosol+carbons+in+the+ambient+air&rft.au=Chen%2C+Shui-Jen%3BLiao%2C+Shi-Hu%3BJian%2C+Wei-Jain%3BChiu%2C+Shui-Chi%3BFang%2C+Guor-Cheng&rft.aulast=Chen&rft.aufirst=Shui-Jen&rft.date=1997-01-01&rft.volume=A32&rft.issue=3&rft.spage=585&rft.isbn=&rft.btitle=&rft.title=Journal+of+Environmental+Science+and+Health%2C+Part+A%3A+Environmental+Science+and+Engineering+%26+Toxic+and+Hazardous+Substance+Control&rft.issn=03601226&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - polycyclic aromatic hydrocarbons; organic carbon; carbon; air sampling; particle size; aerosols; gas chromatography; motor vehicles; exhaust emissions ER - TY - JOUR T1 - Size distribution of particle-bound PAH composition in the ambient air of bus station AN - 16097408; 4203798 AB - The particle-bound composition of polycyclic aromatic hydrocarbons (PAHs) associated with size distribution were measured for the ambient air of a bus station, an urban and a rural site with two MOUDIs and a NRI from April to September 1996 in Ping Tung area of Southern Taiwan. Twenty one individual PAH were analyzed primarily by using a gas chromatograph/ mass spectrometer (GC/MS). In the ambient air of bus station, the particle size distribution of particle-bound total-PAH composition was dominant in the submicron particles. In general, a smaller size particle has a higher total-PAH composition. This is due to the fact that a smaller size of particle has a higher specific area and may therefore contain a greater amount of organic carbon which allows more PAH adsorption. These results showed that the values of total-PAH composition in the fine particle mode (Dp < 1.0 mu m) for bus-station atmosphere averaged 2.2 and 9.0 times of magnitude higher than those measured in the urban and rural atmospheres. In the particle size range between 0.056 similar to 3.2 mu m, both the U/B and R/B ratios of particle-bound total-PAH composition have the lowest values, with the U/B ratio ranging from 0.31 to 0.47 and averaging 0.42 and the R/B ratio ranging from 0.13 to 0.26 and averaging 0.19, respectively. This reveals that the PAH mass, from the vehicular sources to the urban or rural site, is shifted from the particle phase to the gas phase, or react and decay in the atmosphere during the transport process, which results in the depletion of particlebound PAH composition. JF - Journal of Environmental Science and Health, Part A: Environmental Science and Engineering & Toxic and Hazardous Substance Control AU - Chen, Shui-Jen AU - Hwang, Wen-Ing AU - Chiu, Shui-Chi AU - Hung, Ming-Cheng AU - Lin, Chih-Chung AD - Department of Environmental Protection Technology, National Ping Tung Polytechnic Institute, Nei Pu 91207, Ping Tung, Taiwan Y1 - 1997 PY - 1997 DA - 1997 SP - 1781 EP - 1805 VL - A32 IS - 6 SN - 0360-1226, 0360-1226 KW - Taiwan, Ping Tung KW - Pollution Abstracts KW - particle size KW - atmosphere KW - polycyclic aromatic hydrocarbons KW - organic carbon KW - air sampling KW - P 0000:AIR POLLUTION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16097408?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Apollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Environmental+Science+and+Health%2C+Part+A%3A+Environmental+Science+and+Engineering+%26+Toxic+and+Hazardous+Substance+Control&rft.atitle=Size+distribution+of+particle-bound+PAH+composition+in+the+ambient+air+of+bus+station&rft.au=Chen%2C+Shui-Jen%3BHwang%2C+Wen-Ing%3BChiu%2C+Shui-Chi%3BHung%2C+Ming-Cheng%3BLin%2C+Chih-Chung&rft.aulast=Chen&rft.aufirst=Shui-Jen&rft.date=1997-01-01&rft.volume=A32&rft.issue=6&rft.spage=1781&rft.isbn=&rft.btitle=&rft.title=Journal+of+Environmental+Science+and+Health%2C+Part+A%3A+Environmental+Science+and+Engineering+%26+Toxic+and+Hazardous+Substance+Control&rft.issn=03601226&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 - air sampling; particle size; polycyclic aromatic hydrocarbons; organic carbon; atmosphere ER - TY - JOUR T1 - Biliary elimination of oral 2,4-dichlorophenoxyacetic acid and its metabolites in male and female Sprague-Dawley rats, B6C3F1 mice, and Syrian hamsters AN - 16054939; 4103083 AB - The role of biliary elimination in the metabolic disposition of 2,4-D was evaluated in male and female Sprague-Dawley rats, B6C3F1 mice, and Syrian hamsters. Following cannulation of the bile duct, an intragastric (ig) dose of 2,4-D (200 mg/kg) was administered and bile was collected at 30- or 60-min intervals for up to 6 h. Bile flow rates were constant in rats, increased in mice, and decreased in hamsters throughout the collection periods. Total recovery of radioactivity was greatest in male mice (about 7% of administered dose over 4 h). Female mice and rats of both sexes excreted about 3% over the same interval and male and female hamsters about 1%. About 71-88% of the activity in bile was parent compound. The glycine conjugate of 2,4-D was found in bile from mice, rats, and hamsters and the taurine conjugate in bile from mice. The only sex-dependent difference in the metabolite profile was in mice. Male mice excreted twice as much glycine conjugate as female mice. An additional minor metabolite (4-7%) was present in rat and mouse bile. This was tentatively identified as 2,4-D-glucuronide based on its hydrolysis by beta -glucuronidase. One more very minor metabolite (3%) was detected in rat bile but was not characterized due to its lability. The results of this study indicate that there are species-dependent differences in the biliary elimination of 2,4-D but not sex-dependent differences. JF - Journal of Toxicology and Environmental Health AU - Griffin, R J AU - Salemme, J AU - Clark, J AU - Myers, P AU - Burka, L T AD - NIEHS, P.O. Box 12233, B3-10, Research Triangle Park, NC 27709, USA Y1 - 1997 PY - 1997 DA - 1997 SP - 401 EP - 413 VL - 51 IS - 4 SN - 0093-4108, 0093-4108 KW - rats KW - mice KW - hamsters KW - 2,4-D KW - Toxicology Abstracts KW - bile KW - herbicides KW - sex differences KW - X 24133:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16054939?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Toxicology+and+Environmental+Health&rft.atitle=Biliary+elimination+of+oral+2%2C4-dichlorophenoxyacetic+acid+and+its+metabolites+in+male+and+female+Sprague-Dawley+rats%2C+B6C3F1+mice%2C+and+Syrian+hamsters&rft.au=Griffin%2C+R+J%3BSalemme%2C+J%3BClark%2C+J%3BMyers%2C+P%3BBurka%2C+L+T&rft.aulast=Griffin&rft.aufirst=R&rft.date=1997-01-01&rft.volume=51&rft.issue=4&rft.spage=401&rft.isbn=&rft.btitle=&rft.title=Journal+of+Toxicology+and+Environmental+Health&rft.issn=00934108&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 - bile; herbicides; sex differences ER - TY - JOUR T1 - Particle size distribution of aerosol carbons in ambient air AN - 16054410; 4104089 AB - The concentrations and size distributions of organic carbon (OC), elemental carbon (EC), and polycyclic aromatic hydrocarbons (PAHs) were measured with a PS-1 sampler, NRI (Noll Rotary Impactor), and MOUDIs (Micro-orifice Uniform Deposit Impactor) in the ambient air of the traffic intersection and rural site in the Ping Tung area of Southern Taiwan, from September 1994 to December 1995. An elemental analyzer was used to analyze the carbon composition of the aerosol samples. Twenty-one individual PAHs were analyzed primarily by a gas chromatography/mass spectrometer (GC/MS). In the ambient air of the traffic intersection (1.5 m height), the concentrations of EC were between 31.3 and 42.8 mu g/m super(3), averaging 39.8 mu g/m super(3); the concentration ratios for OC/EC ranged between 1.1 and 1.6 and averaged 1.4. Both TC/EC and OC/EC decreased as the height increased. The particle size distribution of OC, EC, and total-PAHs are all bimodal. The particle size distribution in the fine particle mode for OC, EC, and PAHs ranged from 0.18 to 0.32 mu m. However, the particle size distribution in the coarse mode for EC and total-PAHs ranged from 5.6 to 10 mu m. The major peaks of OC, EC, and total-PAHs particles size distribution located at the fine particle indicate not only the gas-to-particle condensation in the fine particle mode after those are emitted to the atmosphere, but also reveal some important information related to health hazards in the ambient air of the traffic intersection. The cumulative fraction of OC, EC, and total-PAHs in the particle size less than 1 mu m was 70.3%, 75.1%, and 64.1%, respectively, while the values in the particle size less than 2.5 mu m were 81.9%, 84.9%, and 73.9%, respectively. More than 93% of TC, OC, EC, and PAHs existed in the particle size less than 10 mu m. JF - Environment International AU - Chen, Shui-Jen AU - Liao, Shi-Hu AU - Jian, Wei-Jain AU - Lin, Chih-Chung AD - Dep. Environ. Prot. Technol., Natl. Ping Tung Polytech. Inst., Nei Pu 91207, Ping Tung, Taiwan Y1 - 1997 PY - 1997 DA - 1997 SP - 475 EP - 488 VL - 23 IS - 4 SN - 0160-4120, 0160-4120 KW - Pollution Abstracts; Health & Safety Science Abstracts KW - particle size KW - Taiwan KW - polycyclic aromatic hydrocarbons KW - aerosols KW - air sampling KW - organic carbon KW - H SE3.20:AIR POLLUTION/AIR QUALITY KW - P 0000:AIR POLLUTION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16054410?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Apollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environment+International&rft.atitle=Particle+size+distribution+of+aerosol+carbons+in+ambient+air&rft.au=Chen%2C+Shui-Jen%3BLiao%2C+Shi-Hu%3BJian%2C+Wei-Jain%3BLin%2C+Chih-Chung&rft.aulast=Chen&rft.aufirst=Shui-Jen&rft.date=1997-01-01&rft.volume=23&rft.issue=4&rft.spage=475&rft.isbn=&rft.btitle=&rft.title=Environment+International&rft.issn=01604120&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 - Taiwan; aerosols; particle size; organic carbon; polycyclic aromatic hydrocarbons; air sampling ER - TY - JOUR T1 - Statistical modeling, phylogenetic analysis and structure prediction of a protein splicing domain common to inteins and hedgehog proteins AN - 16028317; 4095441 AB - Inteins, introns spliced at the protein level, and the hedgehog family of proteins involved in eucaryotic development both undergo autocatalytic proteolysis. Here, a specific and sensitive hidden Markov model (HMM) of a protein splicing domain shared by inteins and the hedgehog proteins has been trained and employed for further analysis. The HMM characterizes the common features of this domain including the position where a site-specific DNA endonuclease domain is inserted in the majority of the inteins. The HMM was used to identify several new putative inteins, such as that in the Methanococcus jannaschii klbA protein, and to generate a multiple sequence alignment of sequences possessing this domain. Phylogenetic analysis suggests that hedgehog proteins evolved from inteins. Secondary and tertiary structure predictions suggest that the domain has a structure similar to a beta -sandwich. Similarities between the serine protease cleavage mechanism and the protein splicing reaction mechanism are discussed. Examination of the locations of inteins indicates that they are not inserted randomly in an extein, but are often inserted at functionally important positions in the host proteins. A specific and sensitive HMM for a domain present in klbA proteins identified several additional bacterial and archaeal family members, and analysis of the site of insertion of the intein suggests residues that may be functionally important. This domain may play a role in formation of surface-associated protein complexes. JF - Journal of Computational Biology AU - Dalgaard, J Z AU - Moser, MJ AU - Hughey, R AU - Mian, I S AD - NCI - Frederick Cancer Res. and Dev. Cent., P.O. Box B, Bldg. 539, Rm. 154, Frederick, MD 21702-1201, USA Y1 - 1997 PY - 1997 DA - 1997 SP - 193 EP - 214 VL - 4 IS - 2 SN - 1066-5277, 1066-5277 KW - inteins KW - Methanococcus jannaschii KW - Microbiology Abstracts B: Bacteriology KW - phylogeny KW - mathematical models KW - proteins KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16028317?accountid=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+Computational+Biology&rft.atitle=Statistical+modeling%2C+phylogenetic+analysis+and+structure+prediction+of+a+protein+splicing+domain+common+to+inteins+and+hedgehog+proteins&rft.au=Dalgaard%2C+J+Z%3BMoser%2C+MJ%3BHughey%2C+R%3BMian%2C+I+S&rft.aulast=Dalgaard&rft.aufirst=J&rft.date=1997-01-01&rft.volume=4&rft.issue=2&rft.spage=193&rft.isbn=&rft.btitle=&rft.title=Journal+of+Computational+Biology&rft.issn=10665277&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 - phylogeny; mathematical models; proteins ER - TY - CONF T1 - The role of carcinogen-metabolizing enzyme polymorphisms in cancer susceptibility AN - 15972678; 4070439 AB - Humans are exposed to over 70,000 man-made chemicals including drugs, food additives, herbicides, pesticides, industrial agents, and environmental contaminants. It is well established that chemicals are the cause of many human diseases including cancers. In most cases, cancer-causing chemicals, or chemical carcinogens require metabolic activation to derivatives that are capable of reacting with cellular macromolecules, the most important of which is DNA. Mutations in genes encoding enzymes or proteins involved in cellular control, such as oncogenes and tumor suppresser genes, result in uncontrolled cell growth and cancer. The steps required for the carcinogenesis process include 1) metabolic activation of a carcinogen by cellular "xenobiotic-metabolizing" enzymes, 2) binding of the active metabolite to DNA to produce a DNA adduct, 3) faulty repair of the adduct to produce a gene mutation, 4) cell replication to fix the mutation in the genome, and 5) progression of the replicating cell containing the mutated genes to a full neoplasm. This progression is usually accompanied by further genetic alterations in other cell cycle control genes that occur through gene mutations, gene rearrangement, and gene/chromosome deletion. The paradigm for mechanism of action of chemical carcinogens has been well established in model cell culture and animal systems and studies in humans appear to support the possibility that most cancers are initiated by chemical/dietary exposures and proceed through various stages of preneoplastic lesions consisting of partially transformed cells to full metastatic cancers. In rodent models, the progression stage can be enhanced by treatment with tumor promoters, which themselves do not necessarily exhibit the properties of carcinogens. These chemicals are thought to mediate cell proliferation that fix the mutations in the genome. Another class of chemicals called nongenotoxic carcinogens have been described in rodent model systems. These agents are not metabolically activated to genotoxic derivatives but presumably alter cell cycle control. Many nongenotoxic carcinogens are also tumor promoters, however, their mechanisms of action are not presently known. It is a widely held view that humans differ in their susceptibility to cancer. Certain individuals may be more susceptible while others are resistant to cancer. This may be due to a number of factors including health, nutritional status, and even gender. Genetics are also thought to play a significant role in cancer susceptibility. From the known mechanism of action of carcinogens, genetic background could play a significant role. The obvious candidate genes are those encoding the xenobiotic-metabolizing enzymes that activate or inactivate carcinogens. Variable levels of expression of these enzymes could result in increased or decreased carcinogen activation. In fact, it is well established that genetic differences occur in the expression of xenobiotic-metabolizing enzymes. Genetically based differences in sensitivity to therapeutically used drugs have been known for more than 30 years and has resulted in the field known as "pharmacogenetics". Historically, the term pharmacogenetics has been used to describe genetic differences in drug metabolism. However, this field has expanded into the area of cancer susceptibility. Recent developments in the cloning and identification of mutant and variant genes encoding xenobiotic-metabolizing enzymes has resulted in the availability of genotyping tools that can be used to investigate the role of genetic differences in human cancer susceptibility. JF - Reproductive Toxicology AU - Gonzalez, F J Y1 - 1997 PY - 1997 DA - 1997 SP - 397 EP - 412 VL - 11 IS - 2-3 KW - susceptibility KW - Toxicology Abstracts KW - genetics KW - carcinogens KW - enzymes KW - cancer KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15972678?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Reproductive+Toxicology&rft.atitle=The+role+of+carcinogen-metabolizing+enzyme+polymorphisms+in+cancer+susceptibility&rft.au=Gonzalez%2C+F+J&rft.aulast=Gonzalez&rft.aufirst=F&rft.date=1997-01-01&rft.volume=11&rft.issue=2-3&rft.spage=397&rft.isbn=&rft.btitle=&rft.title=Reproductive+Toxicology&rft.issn=08906238&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - CONF T1 - Molecular and cellular mechanisms of early mammalian development: An overview of NIEHS/EPA developmental toxicity workshops AN - 15971562; 4070451 AB - The goal of the workshops was to facilitate information exchange and integration of knowledge between the fields of molecular embryology and developmental toxicology. A primary objective was the identification of new scientific approaches for understanding the genetic, molecular, and cellular mechanisms associated with early mammalian development, especially those that might be perturbed and result in abnormal development. In the course of examining what was known about the molecular processes in early development and the approaches and methods used in their study, another objective was to identify and prioritize unmet research needs. The ultimate purpose of these efforts is to provide improved strategies for reducing the incidence of reproductive and developmental anomalies in the human population. JF - Reproductive Toxicology AU - Bishop, J B AU - Kimmel, CA Y1 - 1997 PY - 1997 DA - 1997 SP - 285 EP - 291 VL - 11 IS - 2-3 KW - Toxicology Abstracts KW - genetics KW - teratogens KW - risk assessment KW - teratogenicity KW - xenobiotics KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15971562?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Reproductive+Toxicology&rft.atitle=Molecular+and+cellular+mechanisms+of+early+mammalian+development%3A+An+overview+of+NIEHS%2FEPA+developmental+toxicity+workshops&rft.au=Bishop%2C+J+B%3BKimmel%2C+CA&rft.aulast=Bishop&rft.aufirst=J&rft.date=1997-01-01&rft.volume=11&rft.issue=2-3&rft.spage=285&rft.isbn=&rft.btitle=&rft.title=Reproductive+Toxicology&rft.issn=08906238&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - CONF T1 - Genomic imprinting AN - 15971420; 4070446 AB - In this workshop on Genomic Imprinting, there were nine scientific presentations covering five general topic areas: 1. A description of the abnormalities associated with the development of embryos containing either an entirely maternally derived genome (parthenotes) or paternally derived genome (androgenotes), both in mice and humans. Included in these presentations was a description of which cell types/tissues were particularly affected, because this might offer insights into the likely areas in which imprinted genes function (Pedersen and Mutter). 2. Two presentations focused on examples of abnormal human development: in particular, Prader-Willi, and Beckwith-Wiedemann syndrome in which the cause is thought to be associated with a gene(s) that is/are imprinted (Nicholls and Hastie). 3. Whether embryonic stem (ES) cells derived from parthenogenetic or androgenetic mouse embryos would be of use in analyzing imprinting, both in terms of its mechanisms and in furthering the identity of other as yet unknown imprinted genes (Stewart). 4. Subsequent presentations focused on the biology of three of the known imprinted genes: the insulin-like growth factor II (IGF II), the cation independent mannose-6-phosphate receptor or type 2 IGF II receptor, and Xist, a gene that maps to the X-inactivation center and is involved in regulating (inactivating) one X-chromosome; in mice the paternal X-chromosome is preferentially inactivated in the extraembryonic membrane (Rotwein and Rastan). 5. One of the final two presentations described the role of DNA methyl transferase in cytosine methylation and its relevance to controlling gene expression and mutagenesis. The other described how embryos appear to be particularly susceptible to producing developmental abnormalities in later postimplantation stages following exposure to mutagenising agents shortly after fertilization (Bestor and Generoso). The workshop was concluded with a general discussion of genomic imprinting and the subtopics covered, with an agreement being reached on where the principal gaps lie in the study of genomic imprinting and what areas of research could be pursued to fill those gaps. JF - Reproductive Toxicology AU - Stewart, CL AU - Pedersen, R AU - Rotwein, P AU - Bestor, T AU - Rastan, S AU - Hastie, N AU - Nichols, R AU - Mutter, G Y1 - 1997 PY - 1997 DA - 1997 SP - 309 EP - 316 VL - 11 IS - 2-3 KW - Toxicology Abstracts KW - teratogens KW - embryos KW - genes KW - genomes KW - gene expression KW - xenobiotics KW - imprinting KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15971420?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Reproductive+Toxicology&rft.atitle=Genomic+imprinting&rft.au=Stewart%2C+CL%3BPedersen%2C+R%3BRotwein%2C+P%3BBestor%2C+T%3BRastan%2C+S%3BHastie%2C+N%3BNichols%2C+R%3BMutter%2C+G&rft.aulast=Stewart&rft.aufirst=CL&rft.date=1997-01-01&rft.volume=11&rft.issue=2-3&rft.spage=309&rft.isbn=&rft.btitle=&rft.title=Reproductive+Toxicology&rft.issn=08906238&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Extended lifespan and immortalization of human fibroblasts induced by X-ray irradiation AN - 15934481; 4046658 AB - The induction of immortalization of human fibroblasts by carcinogens is a very rare process. Hybrids between immortal cells and normal fibroblasts senesce, indicating that immortal cells must lose one or more senescence genes for immortalization. To examine the possible involvement of multiple gene alterations in extended lifespan or immortalization of normal human fibroblasts, normal human fibroblasts (WHE-7 cells) and skin fibroblasts (MDAH 087 cells) derived from a Li-Fraumeni syndrome patient with a mutated p53 allele were periodically irradiated with x rays. All six unirradiated control MDAH 087 cell cultures ceased growing by 37 population doublings (PD) and senesced. In contrast, one of six MDAH 087 cultures irradiated one to three times with x rays (2 or 4 Gy at 2 Gy/min) grew continuously for over 450 PD, indicating that the cells were immortal. All 12 WHE-7 cell cultures that were irradiated under the same conditions and all 20 unirradiated control WHE-7 cultures did not become immortal. Single-stranded DNA conformation analysis and DNA sequencing revealed that no additional mutations were induced by x-ray irradiation in exons 2-10 of the p53 gene of the immortal cells (LCS-4X2 cells) and that loss of the wild-type p53 gene was necessary but not sufficient for immortalization. Karyotypic analysis and chromosome painting analysis demonstrated that a high percentage (more than 98%) of LCS-4X2 cells had lost chromosome 6. Irradiation of WHE-7 cells nine times with x rays (2 Gy at 2 Gy/min) extended the cells' lifespans but did not immortalize them. These cells (X9 cells) exhibited a nonrandom karyotypic alteration, monosomy 6, that was confirmed by loss of heterozygosity for a polymorphic dinucleotide repeat sequence on chromosome 6. DNA analysis showed that X9 cells had no mutations in exons 2-10 of the p53 gene. DNA fingerprint analysis with a multi-locus probe detected DNA rearrangements in LCS-4X2 cells and X9 cells, indicating that both cells could have mutations at a gene or genes other than the p53 gene. The results are consistent with our previous findings that cells with a mutation in one gene involved in cellular senescence (i.e., the p53 gene in Li-Fraumeni fibroblasts) are prone to immortalization. Furthermore, we conclude that immortalization of normal human fibroblasts is a multistep process involving loss or inactivation of multiple genes, such as p53 and a gene on chromosome 6. Loss of a gene on chromosome 6 without p53 alterations extends cellular lifespan without immortalizing the cells. JF - Molecular Carcinogenesis AU - Tsutsui, T AU - Tanaka, Y AU - Matsudo, Y AU - Hasegawa, K AU - Fujino, T AU - Kodama, S AU - Barrett, J C AD - National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1997/01// PY - 1997 DA - Jan 1997 SP - 7 EP - 18 PB - JOHN WILEY & SONS VL - 18 IS - 1 SN - 0899-1987, 0899-1987 KW - man KW - Toxicology Abstracts KW - X radiation KW - immortalization KW - fibroblasts KW - X 24210:Radiation & radioactive materials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15934481?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Carcinogenesis&rft.atitle=Extended+lifespan+and+immortalization+of+human+fibroblasts+induced+by+X-ray+irradiation&rft.au=Tsutsui%2C+T%3BTanaka%2C+Y%3BMatsudo%2C+Y%3BHasegawa%2C+K%3BFujino%2C+T%3BKodama%2C+S%3BBarrett%2C+J+C&rft.aulast=Tsutsui&rft.aufirst=T&rft.date=1997-01-01&rft.volume=18&rft.issue=1&rft.spage=7&rft.isbn=&rft.btitle=&rft.title=Molecular+Carcinogenesis&rft.issn=08991987&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 - X radiation; fibroblasts; immortalization ER - TY - JOUR T1 - Chronic toxicity studies of 5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione, a potential chemopreventive agent AN - 15922110; 4044690 AB - The synthetic compound Oltipraz, 5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione, is related to the 1,2-dithiolthiones naturally found in cruciferous vegetables, the consumption of which has been epidemiologically associated with reduced frequency of colorectal cancers. Oltipraz has shown chemopreventive efficacy in numerous laboratory epithelial cancer models and is a potential chemopreventive, antimutagenic compound that specifically induces Phase II enzymes. Thirteen-week and 1-year toxicity studies in rats and dogs were performed to characterize the toxicities of the compound at high dosages and to support potential further development as a chemopreventive agent in clinical trials. Administration to rats by gavage for 13 weeks at dosages of 5 and 50 mg/kg/day and for 52 weeks at dosages of 10, 30, and 60 mg/kg/day produced effects on the liver and on clinical chemistry and hematology parameters. Absolute and relative liver weight increases correlated with diffuse hypertrophy in the mid- and high-dose males and centrilobular hypertrophy in the high-dose females. Granularity of hepatocyte cytoplasm was also observed. These anatomical findings were associated with dose-associated slight increases in albumin, total protein, and cholesterol in the males and a moderate increase in cholesterol only in the females. In addition, slight decreases in erythrocyte count, hemoglobin, and hematocrit and reticulocyte elevations occurred. The no effect dose was considered 10 mg/kg/day. Administration by capsule to dogs at dosages of 10 and 100 mg/kg/day for 13 weeks and of 5, 15, and 60 mg/kg/day for 52 weeks also produced effects on the same endpoints noted in the rodent studies. In the 13-week study, precipitate was observed in the bile canaliculi, and gonadal atrophy and increased pituitary weights occurred in the males. Cholesterol and alkaline phosphatase activity were slightly elevated in both studies. Decreased hematology parameters in the 13-week study also occurred. The no effect dose was considered to be 5 mg/kg/day. Oltipraz is being carefully evaluated in clinical trials as a potential antimutagenic compound. JF - Fundamental and Applied Toxicology AU - Crowell, JA AU - Page, J G AU - Rodman, LE AU - Heath, JE AU - Goldenthal, E I AU - Hall, L B AU - Kelloff, G J AD - NIH/NCI/DCPC, Bldg. EPN, Suite 201, 9000 Rockville Pike, Bethesda, MD 20892-7322, USA Y1 - 1997/01// PY - 1997 DA - Jan 1997 SP - 9 EP - 21 VL - 35 IS - 1 SN - 0272-0590, 0272-0590 KW - rats KW - dogs KW - oltipraz KW - cholesterol KW - alkaline phosphatase KW - Toxicology Abstracts KW - hematological diseases KW - liver KW - X 24116:Hematology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15922110?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+Applied+Toxicology&rft.atitle=Chronic+toxicity+studies+of+5-%282-pyrazinyl%29-4-methyl-1%2C2-dithiole-3-thione%2C+a+potential+chemopreventive+agent&rft.au=Crowell%2C+JA%3BPage%2C+J+G%3BRodman%2C+LE%3BHeath%2C+JE%3BGoldenthal%2C+E+I%3BHall%2C+L+B%3BKelloff%2C+G+J&rft.aulast=Crowell&rft.aufirst=JA&rft.date=1997-01-01&rft.volume=35&rft.issue=1&rft.spage=9&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+Applied+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - liver; hematological diseases ER - TY - JOUR T1 - Sequence of exposure to cadmium and arsenic determines the extent of toxic effects in male Fischer rats AN - 15915948; 4043224 AB - Arsenic and cadmium are both priority hazardous substances and human carcinogens. Although there is the potential for simultaneous exposure to both metals, the interactions of cadmium and arsenic are not well defined. We examined the toxicity of these metals when given alone or in alternating sequence to adult male Fischer rats. In the first study, a non-toxic dose of arsenic (22.5 mu mol NaAsO sub(2)/kg, s.c.) was given 24 h before cadmium (10, 20, or 30 mu mol CdCl sub(2)/kg, s.c.) and toxicity was assessed 24 h later. Arsenic pretreatment markedly reduced mortality in rats given the high dose of cadmium (9 survivors/10 treated) compared to rats given cadmium alone (2/10). Arsenic pretreatment also reduced cadmium-induced hepatotoxicity, as indicated by serum glutamic oxalacetic transaminase (SGOT) activity, and markedly reduced cadmium-induced testicular hemorrhagic necrosis. Arsenic pretreatment produced an 8-fold increase in hepatic levels of metallothionein (MT), a metal-binding protein often associated with cadmium tolerance. In the second study, a non-toxic dose of cadmium (3 mu mol CdCl sub(2)/kg, s.c.) was given 24 h before arsenic (68, 79, 84, or 90 mu mol NaAsO sub(2)/kg, s.c.) and toxicity was assessed 24 h later. Cadmium pretreatment did not alter the lethality of the high dose of arsenic and had no effect on arsenic-induced hepatotoxicity. Although cadmium pretreatment had no effect on arsenic toxicity, it produced large increases in hepatic MT (26-fold) before the arsenic challenge and greatly enhanced MT induction after the challenge. Thus, even though both arsenic and cadmium induce MT synthesis, only arsenic pretreatment protects against cadmium intoxication, and cadmium pretreatment does not effect arsenic toxicity. Thus, toxic interactions of arsenic and cadmium appear to depend on the sequence of exposure. JF - Toxicology AU - Hochadel, J F AU - Waalkes, M P AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702-1201, USA Y1 - 1997/01// PY - 1997 DA - Jan 1997 SP - 89 EP - 98 VL - 116 IS - 1-3 SN - 0300-483X, 0300-483X KW - rats KW - cadmium KW - arsenic KW - heavy metals KW - Toxicology Abstracts KW - X 24161:Acute exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15915948?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=Sequence+of+exposure+to+cadmium+and+arsenic+determines+the+extent+of+toxic+effects+in+male+Fischer+rats&rft.au=Hochadel%2C+J+F%3BWaalkes%2C+M+P&rft.aulast=Hochadel&rft.aufirst=J&rft.date=1997-01-01&rft.volume=116&rft.issue=1-3&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - The effects of continuous testosterone exposure on spontaneous and cadmium-induced tumors in the male Fischer (F344/NCr) rat: Loss of testicular response AN - 15913379; 4043294 AB - In the rodent testes, cadmium induces severe necrosis followed by chronic degeneration. Cadmium is also an effective testicular tumorigen, and a single dose produces a high incidence of Leydig cell tumors. The mechanism of tumor formation is unknown, but pituitary feedback, i.e., increased luteinizing hormone (LH) production due to low circulating androgen, has been implicated in causation of proliferative lesions within degenerate, hypofunctioning testes. Thus, the effects of androgen replacement on the testicular toxicity of cadmium in Fischer (F344/NCr) rats was studied. Groups (n = 50) of 10-week-old rats either received testosterone implants that approximate normal circulating levels in castrated rats or were left untreated. After 2 weeks of stabilization, rats were given either 20 mu mol CdCl sub(2)/kg, sc, weekly for the next 5 weeks (total dose 100 mu mol/kg) or saline for a total of four treatment groups (control, testosterone alone, testosterone + cadmium, or cadmium alone). Portions of each group were killed either 10 weeks after initiation of cadmium exposure (n = 10), for assessment of endocrine function, or over the next 2 years (n = 40), for assessment of testicular neoplastic lesions. At 10 weeks, cadmium reduced circulating testosterone in nonimplanted rats by nearly 80% and induced a marked weight loss of the testes (>70%) and sex accessory glands (reflected in a 50% reduction in prostate mass). Testosterone implantation restored circulating testosterone levels in cadmium-treated rats and prevented Cd-induced weight loss of the sex accessory glands but not of the testes. Over 2 years, cadmium alone induced a >84% incidence of Leydig cell neoplasia and a >97% incidence of chronic degeneration, both significant increases over control rates (60 and 0%, respectively). Testosterone implantation abolished both cadmium-induced and spontaneously occurring Leydig cell tumors but had no effect on cadmium-induced chronic testicular degeneration. Thus cadmium-induced hypofunction of the testes, and subsequent loss of circulating testosterone, appears to be a critical aspect in cadmium induction of tumors in the rat testes. JF - Toxicology and Applied Pharmacology AU - Waalkes, M P AU - Rehm, S AU - Devor, DE AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, Building 538, Room 205E, NCI-Frederick Cancer Research and Development Center, Frederick, MD 21702, USA Y1 - 1997/01// PY - 1997 DA - Jan 1997 SP - 40 EP - 46 VL - 142 IS - 1 SN - 0041-008X, 0041-008X KW - rats KW - testosterone KW - cadmium KW - heavy metals KW - Toxicology Abstracts KW - testes KW - tumors KW - X 24162:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15913379?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+Applied+Pharmacology&rft.atitle=The+effects+of+continuous+testosterone+exposure+on+spontaneous+and+cadmium-induced+tumors+in+the+male+Fischer+%28F344%2FNCr%29+rat%3A+Loss+of+testicular+response&rft.au=Waalkes%2C+M+P%3BRehm%2C+S%3BDevor%2C+DE&rft.aulast=Waalkes&rft.aufirst=M&rft.date=1997-01-01&rft.volume=142&rft.issue=1&rft.spage=40&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 - tumors; testes ER - TY - JOUR T1 - Testosterone pretreatment mitigates cadmium toxicity in male C57 mice but not in C3H mice AN - 15911894; 4043231 AB - Previous work has indicated that testosterone pretreatment protects against cadmium-induced toxicity in male rats while other data indicate that pretreatment of mice with testosterone offers no such protection against cadmium. Since cadmium toxicity may vary widely with species and strain, we examined the effect of testosterone pretreatment on cadmium toxicity in two strains of mice, one that is sensitive (C3H) and one that is resistant (C57) to cadmium toxicity. A single sc injection of 20 mu mol CdCl sub(2)/kg to C3H mice or 45 mu mol CdCl sub(2)/kg to C57 mice proved very toxic, causing 50% and 44% mortalities, respectively. However, when C57 mice were pretreated with testosterone (5 mg/kg, s.c., at -48, -24, and 0 h) prior to cadmium (45 mu mol/kg), complete resistance to cadmium-induced lethality developed. Testosterone had no effect on cadmium-induced lethality in C3H mice. Testosterone prevented extensive hepatocellular damage caused by cadmium in C57 mice and also significantly reduced cadmium-induced elevations in serum lactate dehydrogenase (LDH) activity and blood urea nitrogen (BUN), which are indicators of hepatic and renal function, respectively. The toxicokinetics of cadmium were apparently not affected by testosterone pretreatment, as the distribution of cadmium to liver in either strain was unchanged by the steroid. Cadmium-induced metallothionein (MT) levels in liver and kidney of C57 mice were increased in testosterone-pretreated mice given the higher doses of metal but no such enhancement of MT synthesis occurred in C3H mice. This increase in MT may provide some level of protection against cadmium toxicity in the C57 mice. These results indicate that testosterone pretreatment prevents toxicity of cadmium in male C57 mice, possibly through enhancement of MT synthesis, but has no effect in male C3H mice. JF - Toxicology AU - Shimada, H AU - Bare, R M AU - Hochadel, J F AU - Waalkes, M P AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, MD 21702-1201, USA Y1 - 1997/01// PY - 1997 DA - Jan 1997 SP - 183 EP - 191 VL - 116 IS - 1-3 SN - 0300-483X, 0300-483X KW - mice KW - strain differences KW - cadmium KW - heavy metals KW - testosterone KW - Toxicology Abstracts KW - X 24161:Acute exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15911894?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=Testosterone+pretreatment+mitigates+cadmium+toxicity+in+male+C57+mice+but+not+in+C3H+mice&rft.au=Shimada%2C+H%3BBare%2C+R+M%3BHochadel%2C+J+F%3BWaalkes%2C+M+P&rft.aulast=Shimada&rft.aufirst=H&rft.date=1997-01-01&rft.volume=116&rft.issue=1-3&rft.spage=183&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Mouse models of human disease. Part I: Techniques and resources for genetic analysis in mice AN - 15875380; 4028081 AB - The mouse is an ideal model organism for human disease. Not only are mice physiologically similar to humans, but a large genetic reservoir of potential models of human disease has been generated through the identification of >1000 spontaneous, radiation- or chemically induced mutant loci. In addition, a number of recent technological advances have dramatically increased our ability to create mouse models of human disease. These technological advances include the development of high-resolution genetic and physical linkage maps of the mouse genome, which in turn are facilitating the identification and cloning of mouse disease loci. Furthermore, transgenic technologies that allow one to ectopically express or make germ-line mutations in virtually any gene in the mouse genome have been developed, as well as methods for analyzing complex genetic diseases. In Part I of this review, we summarize some of the classical and modern approaches that have fueled the recent dramatic explosion in mouse disease model development. In Part II of this review, we list >100 mouse models of human disease where the homologous gene has been shown to be mutated in both human and mouse (Bedell et al., this issue). In the vast majority of these models, the mouse mutant phenotype very closely resembles the human disease phenotype and these models therefore provide valuable resources to understand how the diseases develop and to test ways to prevent or treat these diseases. Additionally, we highlight a number of areas of this research where significant progress has been made in the past few years. JF - Genes & Development AU - Bedell, MA AU - Jenkins, NA AU - Copeland, NG AD - Mammalian Genet. Lab., ABL-Basic Res. Prog., NCI-Frederick Cancer Res. and Dev. Cent., Frederick, MD 21702-1201, USA Y1 - 1997/01// PY - 1997 DA - Jan 1997 SP - 1 EP - 10 VL - 11 IS - 1 SN - 0890-9369, 0890-9369 KW - diseases KW - genetic analysis KW - man KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Genetics Abstracts KW - germ cells KW - reviews KW - genetic resources KW - gene mapping KW - mutation KW - animal models KW - genetic markers KW - G 07439:General - reviews/ethics, etc. KW - W 30965:Miscellaneous, Reviews KW - W3 33055:Genetic engineering (general) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15875380?accountid=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=Genes+%26+Development&rft.atitle=Mouse+models+of+human+disease.+Part+I%3A+Techniques+and+resources+for+genetic+analysis+in+mice&rft.au=Bedell%2C+MA%3BJenkins%2C+NA%3BCopeland%2C+NG&rft.aulast=Bedell&rft.aufirst=MA&rft.date=1997-01-01&rft.volume=11&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Genes+%26+Development&rft.issn=08909369&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - germ cells; reviews; genetic resources; gene mapping; mutation; animal models; genetic markers ER - TY - JOUR T1 - Mouse models of human disease. Part II: Recent progress and future directions AN - 15875179; 4028080 AB - The development of new methods for manipulating the mouse genome, including transgenic and embryonic stem (ES) cell knockout technology, combined with greatly improved genetic and physical maps for mouse has revolutionized our ability to generate new mouse models of human disease. In Part I of this review, we described in detail the various techniques and genetic resources that have facilitated mouse model development. In Part II of this review we highlight some of the recent progress that has been made in mouse model development and discuss areas where these mouse models are likely to contribute in the future. We have focused in part II only on those models where the homologous gene is mutated in both the human and mouse disease. A total of similar to 100 such genes are listed in seven tables according to the primary tissue or organ system they affect. The chromosomal location of each mapped disease gene in the mouse can be found in Figure 1. Detailed information about each mouse model can be obtained by entering the corresponding gene symbol into the Mouse Genome Database (MGD), maintained by the Jackson Laboratory at http://www.informatics.jax.org/mgd.html. Detailed information about each human disease can be obtained using the Mendelian Inheritance in Man (MIM) accession nos. that are provided (McKusick et al. 1994). Each MIM entry may be accessed over the Internet at http://www3.ncbi.mlm.nih.gov/omim/, a site maintained by the National Center for Biotechnology Information. MIM accession nos. from 100050-195002 are for dominant traits; 200100-280000 are for recessive traits; and 300010-315000 are for X-linked traits. Although we have tried to be as inclusive as possible, our list of mouse models is unlikely to be complete. In addition, space limitations have precluded a complete description of all mouse models we have listed; instead, we discuss only a few models in each section where significant progress in either identifying or utilizing a mouse model has been made recently. Much of the success in developing mouse models has been with monogenic traits; however, great potential lies in modeling polygenic diseases. In the last section, we review some of the recent progress in this area. Throughout the text and tables, we have cited only the most recent papers and refer to reviews whenever possible. Interested readers are encouraged to read the primary papers on each model and associated disease. JF - Genes & Development AU - Bedell, MA AU - Largaespada, DA AU - Jenkins, NA AU - Copeland, NG AD - Mammalian Genet. Lab., ABL-Basic Res. Prog., NCI-Frederick Cancer Res. and Dev. Cent., Frederick, MD 21702-1201, USA Y1 - 1997/01// PY - 1997 DA - Jan 1997 SP - 11 EP - 43 VL - 11 IS - 1 SN - 0890-9369, 0890-9369 KW - Hirschsprung's disease KW - Krt1-10 gene KW - Krt1-14 gene KW - Krt1-16 gene KW - Rag1 gene KW - Waardenburg's syndrome KW - data banks KW - diseases KW - keratin KW - man KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Genetics Abstracts KW - reviews KW - genetic resources KW - gene mapping KW - X chromosome KW - computer applications KW - transgenic mice KW - animal models KW - G 07439:General - reviews/ethics, etc. KW - W 30965:Miscellaneous, Reviews KW - W3 33055:Genetic engineering (general) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15875179?accountid=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=Genes+%26+Development&rft.atitle=Mouse+models+of+human+disease.+Part+II%3A+Recent+progress+and+future+directions&rft.au=Bedell%2C+MA%3BLargaespada%2C+DA%3BJenkins%2C+NA%3BCopeland%2C+NG&rft.aulast=Bedell&rft.aufirst=MA&rft.date=1997-01-01&rft.volume=11&rft.issue=1&rft.spage=11&rft.isbn=&rft.btitle=&rft.title=Genes+%26+Development&rft.issn=08909369&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - reviews; genetic resources; X chromosome; gene mapping; computer applications; animal models; transgenic mice ER - TY - JOUR T1 - Regulation of cell surface GLUT4 in skeletal muscle of transgenic mice AN - 15870211; 4026352 AB - Marked overexpression of the glucose transporter GLUT4 in skeletal muscle membrane fractions of GLUT4 transgenic (TG) mice is accompanied by disproportionately small increases in basal and insulin-stimulated glucose transport activity. Thus we have assessed cell surface GLUT4 by photolabelling with the membrane-impermeant reagent 2-N-[4-(1-azi-2,2,2-trifluoroethyl)benzoyl]-1,3-bis(D-mannos-4-ylo x y)-2-propylamine (ATB-BMPA) and measured the corresponding glucose transport activity using 2-deoxyglucose in isolated extensor digitorum longus (EDL) muscles from non-transgenic (NTG) and GLUT4 TG mice in the absence and presence of 13.3 nM (2000 mu -units/ml) insulin, without or with hypoxia as a model of muscle contraction. TG mice displayed elevated rates of glucose transport activity under basal and insulin-stimulated conditions, and in the presence of insulin plus hypoxia, compared with NTG mice. Photoaffinity labelling of cell surface GLUT4 indicated corresponding elevations in plasma membrane GLUT4 in the basal and insulin-stimulated states, and with insulin plus hypoxia, but no difference in cell surface GLUT4 during hypoxia stimulation. Subcellular fractionation of hindlimb muscles confirmed the previously observed 3-fold overexpression of GLUT4 in the TG compared with the NTG mice. These results suggest that: (1) alterations in glucose transport activity which occur with GLUT4 overexpression in EDL muscles are directly related to cell surface GLUT4 content, regardless of the levels observed in the corresponding subcellular membrane fractions, (2) while overexpression of GLUT4 influences both basal and insulin-stimulated glucose transport activity, the response to hypoxia/contraction-stimulated glucose transport is unchanged, and (3) subcellular fractionation provides little insight into the subcellular trafficking of GLUT4, and whatever relationship is demonstrated in EDL muscles from NTG mice is disrupted on GLUT4 overexpression. JF - Biochemical Journal AU - Brozinick, JT Jr AU - McCoid, S C AU - Reynolds, TH AU - Wilson, C M AU - Stevenson, R W AU - Cushman, S W AU - Gibbs, E M AD - NIH/NIDDK/EDMNS, Bldg. 10, Rm. 5N102, 10 Center Dr. MSC 1420, Bethesda, MD 20892-1420, USA Y1 - 1997/01// PY - 1997 DA - Jan 1997 SP - 75 EP - 81 VL - 321 IS - 1 SN - 0264-6021, 0264-6021 KW - GLUT4 protein KW - glucose KW - insulin KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - transgenic mice KW - hypoxia KW - skeletal muscle KW - W 30965:Miscellaneous, Reviews KW - W3 33055:Genetic engineering (general) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15870211?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+Journal&rft.atitle=Regulation+of+cell+surface+GLUT4+in+skeletal+muscle+of+transgenic+mice&rft.au=Brozinick%2C+JT+Jr%3BMcCoid%2C+S+C%3BReynolds%2C+TH%3BWilson%2C+C+M%3BStevenson%2C+R+W%3BCushman%2C+S+W%3BGibbs%2C+E+M&rft.aulast=Brozinick&rft.aufirst=JT&rft.date=1997-01-01&rft.volume=321&rft.issue=1&rft.spage=75&rft.isbn=&rft.btitle=&rft.title=Biochemical+Journal&rft.issn=02646021&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - transgenic mice; hypoxia; skeletal muscle ER - TY - JOUR T1 - Inhibition of Plasmodium falciparum protein synthesis. Targeting the plastid-like organelle with thiostrepton AN - 15867941; 4021987 AB - The human malaria parasite Plasmodium falciparum has two extrachromosomal DNAs associated with organelles whose function is unclear. Both genomes encode ribosomal RNAs (rRNAs) that are distinct from the nuclear-encoded rRNAs. Secondary structure analysis of all the P. falciparum rRNAs indicates that only the large subunit (LSU) rRNA encoded by the plastid-like genome is the target for thiostrepton. Indeed we find that thiostrepton inhibits growth of the parasite in the micromolar range which is 10-fold below concentrations with observable effects on total protein synthesis. We have further examined selective effects of thiostrepton on the plastid function by comparing differential effects of the drug on cytoplasmic and organellar encoded transcripts. Treatment with either thiostrepton or rifampin, an inhibitor of organellar and eubacterial RNA polymerase, both showed disappearance of organellar-encoded RNA transcripts within 6 h of treatment while transcripts of a nuclear-encoded mRNA remained constant for at least 8 h of treatment. Hence, we show a selective effect on organelle function that is suggestive of interference in the protein synthesis apparatus of the plastid. Sensitivity of P. falciparum to thiostrepton confirms that the plastid-like genome is essential for the erythrocytic cycle and presents a novel therapeutic site for this class of antibiotics. JF - Journal of Biological Chemistry AU - McConkey, G A AU - Rogers, MJ AU - McCutchan, T F AD - Growth and Dev. Sect., Lab. Parasitic Dis., Bldg. 4, Rm. B1-28, NIAID, Natl. Institutes Health, Bethesda, MD 20892-0425, USA Y1 - 1997/01// PY - 1997 DA - Jan 1997 SP - 2046 EP - 2049 VL - 272 IS - 4 SN - 0021-9258, 0021-9258 KW - rRNA KW - thiostrepton KW - rifampin KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts C: Algology, Mycology & Protozoology; Biochemistry Abstracts 2: Nucleic Acids KW - protein biosynthesis KW - plastids KW - Plasmodium falciparum KW - A 01069:Antimicrobial & microbiocidal KW - N 14400:General KW - K 03017:Protozoa UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15867941?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Inhibition+of+Plasmodium+falciparum+protein+synthesis.+Targeting+the+plastid-like+organelle+with+thiostrepton&rft.au=McConkey%2C+G+A%3BRogers%2C+MJ%3BMcCutchan%2C+T+F&rft.aulast=McConkey&rft.aufirst=G&rft.date=1997-01-01&rft.volume=272&rft.issue=4&rft.spage=2046&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Plasmodium falciparum; protein biosynthesis; plastids ER - TY - JOUR T1 - Sunlight and skin cancer: Another link revealed AN - 15832673; 4007977 AB - Skin cancer is the most common neoplasm in Caucasians in the United States with a lifetime risk nearly equal to that of all other cancers combined. More than 800,000 people are expected to develop nonmelanoma skin cancer [basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) this year in the United States. Sun exposure is the major environmental agent implicated in induction of nonmelanoma skin cancer. While sun exposure begins early in life, the average patient with nonmelanoma skin cancer is about 60 years old. The article by Jonason et al. in a previous issue of the Proceedings provides a new insight into the link between sun exposure and nonmelanoma skin cancer and furnishes information about events occurring between the time of initial sun exposure and subsequent skin cancer years later. The multistage theory of carcinogenesis is based on experimental studies in rodents and has been proposed as a general model for environmental carcinogenesis. In the first stage--initiation--a carcinogen mutates a target gene. Initiation is followed by promotion, a process in visibly normal skin in which the single damaged cell expands to form a clone of damaged cells. These changes progress, leading to precancerous clinically abnormal skin and then to cancer. Many experimental studies have been designed to dissect the cellular and molecular mechanisms involved in this process. These studies involve investigations of DNA repair, eicosanoid and proteinase production, cytokine activation and immune suppression, and specific tumor-suppressor genes including patched and p53. JF - Proceedings of the National Academy of Sciences, USA AU - Kraemer, KH AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Building 37, Room 3E24, Bethesda, MD 20892, USA Y1 - 1997/01// PY - 1997 DA - Jan 1997 SP - 11 EP - 14 VL - 94 IS - 1 SN - 0027-8424, 0027-8424 KW - man KW - skin carcinoma KW - p53 gene KW - Toxicology Abstracts; Genetics Abstracts; Oncogenes & Growth Factors Abstracts KW - skin KW - U.V. radiation KW - carcinogenesis KW - reviews KW - sunlight KW - DNA repair KW - solar radiation KW - risk assessment KW - X 24210:Radiation & radioactive materials KW - B 26400:HUMAN-RELATED ONCOGENES AND GROWTH FACTORS: CROSS REFERENCES KW - G 07233:Radiation (U.V.) KW - B 26000:ONCOGENES AND GROWTH FACTORS: GENERAL UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15832673?accountid=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=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Sunlight+and+skin+cancer%3A+Another+link+revealed&rft.au=Kraemer%2C+KH&rft.aulast=Kraemer&rft.aufirst=KH&rft.date=1997-01-01&rft.volume=94&rft.issue=1&rft.spage=11&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 N1 - SubjectsTermNotLitGenreText - carcinogenesis; reviews; DNA repair; risk assessment; sunlight; solar radiation; U.V. radiation; skin ER - TY - JOUR T1 - An information-intensive approach to the molecular pharmacology of cancer AN - 15789313; 3989449 AB - Since 1990, the National Cancer Institute (NCI) has screened more than 60,000 compounds against a panel of 60 human cancer cell lines. The 50-percent growth-inhibitory concentration (GI sub(50)) for any single cell line is simply an index of cytotoxicity or cytostasis, but the patterns of 60 such GI sub(50) values encode unexpectedly rich, detailed information on mechanisms of drug action and drug resistance. Each compound's pattern is like a fingerprint, essentially unique among the many billions of distinguishable possibilities. These activity patterns are being used in conjunction with molecular structural features of the tested agents to explore the NCI's database of more than 460,000 compounds, and they are providing insight into potential target molecules and modulators of activity in the 60 cell lines. For example, the information is being used to search for candidate anticancer drugs that are not dependent on intact p53 suppressor gene function for their activity. It remains to be seen how effective this information-intensive strategy will be at generating new clinically active agents. JF - Science (Washington) AU - Weinstein, J N AU - Myers, T G AU - O'Connor, P M AU - Friend, SH AU - Fornace A.J.,Jr AU - Kohn, K W AU - Fojo, T AU - Bates, SE AU - Rubinstein, LV AU - Anderson, N L AU - Buolamwini, J K AU - van Osdol, WW AU - Monks AU - Scudiero, DA AU - Paull, K D AD - Lab. Mol. Pharmacol. (LMP), Div. Basic Sci., Natl. Cancer Inst. (NCI), NIH, Build., 37, Rm 5C-25, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1997/01// PY - 1997 DA - Jan 1997 SP - 343 EP - 349 VL - 275 IS - 5298 SN - 0036-8075, 0036-8075 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Oncogenes & Growth Factors Abstracts KW - reviews KW - data bases KW - computer applications KW - drug discovery KW - bioinformatics KW - cancer KW - W 30965:Miscellaneous, Reviews KW - W3 33000:General topics and reviews KW - B 26000:ONCOGENES AND GROWTH FACTORS: GENERAL UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15789313?accountid=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=Science+%28Washington%29&rft.atitle=An+information-intensive+approach+to+the+molecular+pharmacology+of+cancer&rft.au=Weinstein%2C+J+N%3BMyers%2C+T+G%3BO%27Connor%2C+P+M%3BFriend%2C+SH%3BFornace+A.J.%2CJr%3BKohn%2C+K+W%3BFojo%2C+T%3BBates%2C+SE%3BRubinstein%2C+LV%3BAnderson%2C+N+L%3BBuolamwini%2C+J+K%3Bvan+Osdol%2C+WW%3BMonks%3BScudiero%2C+DA%3BPaull%2C+K+D&rft.aulast=Weinstein&rft.aufirst=J&rft.date=1997-01-01&rft.volume=275&rft.issue=5298&rft.spage=343&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 - 2011-12-14 N1 - SubjectsTermNotLitGenreText - reviews; computer applications; data bases; drug discovery; bioinformatics; cancer ER - TY - JOUR T1 - Removal of copper(II) chelates of EDTA and NTA from dilute aqueous solutions by membrane filtration AN - 13634322; 199704454 AB - A batch stirred cell was used for investigating the ultrafiltration removal of copper(II) chelates of ethylenediaminetetraacetic acid (EDTA) and nitriloacetic acid (NTA) using ultrafiltration membranes formed from Amicon hydrophilic YM10 and YM30 regenerated cellulose, with the aid of polyethylene(imine) (PEI). The investigation examined the influence of the aqueous pH, the concentration ratios of the chelating agents and PEI to the copper(II) ions and also the applied pressure. In general, the removal efficiency of copper-EDTA chelates was more efficient compared with that for copper-NTA chelates. Membrane fouling was relatively serious for copper-NTA chelates, although the fouled cellulosic ultrafiltration membranes could be easily cleaned. The effect of the presence of inorganic salts (calcium chloride, sodium chloride and sodium sulphate) was also investigated. There are 32 references. JF - Industrial & Engineering Chemistry Research AU - Juang, R S AU - Chen, M N AD - Yuan-Ze Institute of Technology, Nei-Li, Taoyuan Y1 - 1997 PY - 1997 DA - 1997 SP - 179 EP - 186 VL - 36 IS - 1 SN - 0888-5885, 0888-5885 KW - Imine KW - Inorganic -- (see also without this prefix) KW - Nitriloacetic acid KW - Pei KW - Aqualine Abstracts KW - AQ 00007:Industrial Effluents UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/13634322?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aaqualine&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Industrial+%26+Engineering+Chemistry+Research&rft.atitle=Removal+of+copper%28II%29+chelates+of+EDTA+and+NTA+from+dilute+aqueous+solutions+by+membrane+filtration&rft.au=Juang%2C+R+S%3BChen%2C+M+N&rft.aulast=Juang&rft.aufirst=R&rft.date=1997-01-01&rft.volume=36&rft.issue=1&rft.spage=179&rft.isbn=&rft.btitle=&rft.title=Industrial+%26+Engineering+Chemistry+Research&rft.issn=08885885&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2000-09-01 N1 - SuppNotes - Publication focus: Experimental. N1 - Last updated - 2011-12-12 ER - TY - JOUR T1 - Evaluation of health risks for contaminated aquifers AN - 13623895; 199801090 AB - Progress in aspects of aquifer remediation technology is reviewed. The development of models for contaminant transport in the subsurface under conditions of uncertainty, cancer risk assessment models for heterogeneous human populations and approaches for evaluating aquifer remediation technology performance is considered. Limitations and areas for continuing research are identified. There are 156 references. JF - Environmental Health Perspectives AU - Piver, W T AU - Jacobs, T L AU - Medina, MA AD - National Institute of Environmental Health Sciences, Triangle Park, N.C. Y1 - 1997 PY - 1997 DA - 1997 SP - 127 EP - 143 VL - 105 SN - 0091-6765, 0091-6765 KW - Hazard KW - Modelling (-general-) KW - Aqualine Abstracts KW - AQ 00001:Water Resources and Supplies UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/13623895?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aaqualine&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=Evaluation+of+health+risks+for+contaminated+aquifers&rft.au=Piver%2C+W+T%3BJacobs%2C+T+L%3BMedina%2C+MA&rft.aulast=Piver&rft.aufirst=W&rft.date=1997-01-01&rft.volume=105&rft.issue=&rft.spage=127&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 - 2000-09-01 N1 - Last updated - 2011-12-12 ER - TY - JOUR T1 - Effects of BCL-2 overexpression on the sensitivity of MCF-7 breast cancer cells to ricin, diphtheria and Pseudomonas toxin and immunotoxins AN - 1285097512; 17027941 AB - Immunotoxins are presently being evaluated as novel agents for cancer therapy. The direct mechanism by which immunotoxins kill cancer cells is inhibition of protein synthesis, but cytotoxicity due to induction of apoptosis has also been observed with these agents. Some cancers that express high levels of BCL-2 are relatively resistant to apoptosis inducing agents. It is therefore important to determine to what degree the toxicity of ricin, diphtheria toxin, Pseudomonas exotoxin and Pseudomonas exotoxin derived immunotoxins towards cancer cells can be attributed to inhibition of protein synthesis, and to what degree to subsequent induction of apoptosis. We compared the sensitivity of MCF-7 breast cancer cells that were stably transfected with a BCL-2 expression plasmid and thus protected against apoptosis and of MCF-7 cells transfected with a control plasmid towards ricin, diphtheria and Pseudomonas toxin, a Pseudomonas toxin-derived immunotoxin (LMB-7) and tumour necrosis factor alpha (TNF). We found that BCL-2 mediated inhibition of apoptosis renders the cells almost completely resistant (1000-fold) to tumour necrosis factor, but the same cells were only 3-10 fold more resistant to cytotoxicity induced by immunotoxin LMB-7 as well as Pseudo-monas exotoxin, diphtheria toxin and ricin. We next studied several leukaemia cell lines with variable levels of BCL-2 expression and found them quite sensitive to a Pseudomonas exotoxin containing immunotoxin independent of the level of BCL-2. Our data indicate that although BCL-2 overexpression can have a modest effect on sensitivity to an immunotoxin, cell lines derived from patients are still very sensitive to immunotoxins. JF - Apoptosis AU - Brinkmann, U AU - Mansfield, E AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, USA Y1 - 1997/01// PY - 1997 DA - Jan 1997 SP - 192 EP - 198 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 2 IS - 2 SN - 1360-8185, 1360-8185 KW - Toxicology Abstracts; Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - Apoptosis KW - Pseudomonas KW - Immunotoxins KW - X 24370:Natural Toxins KW - F 06915:Cancer Immunology KW - J 02400:Human Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1285097512?accountid=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=Apoptosis&rft.atitle=Effects+of+BCL-2+overexpression+on+the+sensitivity+of+MCF-7+breast+cancer+cells+to+ricin%2C+diphtheria+and+Pseudomonas+toxin+and+immunotoxins&rft.au=Brinkmann%2C+U%3BMansfield%2C+E%3BPastan%2C+I&rft.aulast=Brinkmann&rft.aufirst=U&rft.date=1997-01-01&rft.volume=2&rft.issue=2&rft.spage=192&rft.isbn=&rft.btitle=&rft.title=Apoptosis&rft.issn=13608185&rft_id=info:doi/10.1023%2FA%3A1026468532413 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2013-02-01 N1 - Last updated - 2014-02-11 N1 - SubjectsTermNotLitGenreText - Immunotoxins; Pseudomonas DO - http://dx.doi.org/10.1023/A:1026468532413 ER - TY - JOUR T1 - Targeted disruption of the peroxisome proliferator-activated receptor alpha gene, PPAR alpha. AN - 78653411; 8993570 JF - Annals of the New York Academy of Sciences AU - Lee, S S AU - Gonzalez, F J AD - Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/12/27/ PY - 1996 DA - 1996 Dec 27 SP - 524 EP - 529 VL - 804 SN - 0077-8923, 0077-8923 KW - Carcinogens KW - 0 KW - Fatty Acids KW - Hypolipidemic Agents KW - Pyrimidines KW - Receptors, Cytoplasmic and Nuclear KW - Transcription Factors KW - pirinixic acid KW - 86C4MRT55A KW - Clofibrate KW - HPN91K7FU3 KW - Index Medicus KW - Animals KW - Hypolipidemic Agents -- pharmacology KW - Pyrimidines -- pharmacology KW - Mice KW - Mutagenesis, Insertional KW - Mice, Knockout KW - Fatty Acids -- metabolism KW - Clofibrate -- pharmacology KW - Microbodies -- enzymology KW - Receptors, Cytoplasmic and Nuclear -- genetics KW - Transcription Factors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78653411?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Targeted+disruption+of+the+peroxisome+proliferator-activated+receptor+alpha+gene%2C+PPAR+alpha.&rft.au=Lee%2C+S+S%3BGonzalez%2C+F+J&rft.aulast=Lee&rft.aufirst=S&rft.date=1996-12-27&rft.volume=804&rft.issue=&rft.spage=524&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-10 N1 - Date created - 1997-02-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional characterization of a mutant thyroid hormone receptor in Xenopus laevis. AN - 78636240; 8969201 AB - Thyroid hormone plays a causative role during frog metamorphosis, and its effect is mediated by thyroid hormone receptors (TRs). To investigate the function of Xenopus TRs, we have recently developed a thyroid hormone dependent in vivo transcription system by introducing TRs and RXRs (9-cis-retinoic acid receptors) into Xenopus oocytes. Interestingly, using this system, we have found that the TRalphaB cloned previously is defective in transcriptional activation compared with TRalphaA. In vitro DNA binding experiments show that TRalphaB.RXR heterodimers have drastically reduced affinity for a thyroid hormone response element. Site-directed mutagenesis shows that two of the seven amino acid residues that differ between TRalphaA and TRalphaB are responsible for the defect in TRalphaB function. These two residues affect the DNA binding by both TR.RXR heterodimers and TR homodimers. In contrast, heterodimer formation with RXRs is not affected as demonstrated by coimmunoprecipitation and dominant-transcriptional inhibition experiments. By cDNA and genomic DNA sequence analysis, we have demonstrated that the residues, which affect TRalphaB function when mutated, are identical between the wild type TRalphaB and TRalphaA. Thus, our experiments have discovered the first amphibian TR mutant. The DNA binding and transcription activation functions of the mutant are discussed in relation to the recently published TR crystal structure. JF - The Journal of biological chemistry AU - Puzianowska-Kuznicka, M AU - Wong, J AU - Kanamori, A AU - Shi, Y B AD - Laboratory of Molecular Embryology, NICHHD, National Institutes of Health, Bethesda, Maryland 20892-5430, USA. shi@helix.nih.gov Y1 - 1996/12/27/ PY - 1996 DA - 1996 Dec 27 SP - 33394 EP - 33403 VL - 271 IS - 52 SN - 0021-9258, 0021-9258 KW - RNA, Messenger KW - 0 KW - Receptors, Retinoic Acid KW - Receptors, Thyroid Hormone KW - Retinoid X Receptors KW - Transcription Factors KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Receptors, Retinoic Acid -- metabolism KW - Animals KW - Transcription Factors -- metabolism KW - Electrophoresis, Polyacrylamide Gel KW - DNA -- metabolism KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Xenopus laevis KW - Base Sequence KW - Blotting, Western KW - Oocytes -- metabolism KW - RNA, Messenger -- metabolism KW - Receptors, Retinoic Acid -- chemistry KW - Transcription Factors -- chemistry KW - Molecular Sequence Data KW - Female KW - Receptors, Thyroid Hormone -- genetics KW - Receptors, Thyroid Hormone -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78636240?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+mutant+thyroid+hormone+receptor+in+Xenopus+laevis.&rft.au=Puzianowska-Kuznicka%2C+M%3BWong%2C+J%3BKanamori%2C+A%3BShi%2C+Y+B&rft.aulast=Puzianowska-Kuznicka&rft.aufirst=M&rft.date=1996-12-27&rft.volume=271&rft.issue=52&rft.spage=33394&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-28 N1 - Date created - 1997-01-28 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - L76285; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structures of active site histidine mutants of IIIGlc, a major signal-transducing protein in Escherichia coli. Effects on the mechanisms of regulation and phosphoryl transfer. AN - 78635099; 8969208 AB - IIIGlc (also called IIAGlc), a major signal-transducing protein in Escherichia coli, is also a phosphorylcarrier in glucose uptake. The crystal and NMR structures of IIIGlc show that His90, the phosphoryl acceptor, adjoins His75 in the active site. Glutamine was substituted for His-, giving H75QIIIGlc and H90QIIIGlc, respectively (Presper, K. A., Wong, C.-Y., Liu, L., Meadow, N. D., and Roseman, S. (1989) Proc. Natl. Acad. Sci. U. S. A. 86, 4052-4055), but the mutants showed unexpected properties. H90QIIIGlc loses regulatory functions of IIIGlc, and the phosphoryltransfer rates between HPr/H75QIIIGlc are 200-fold less than HPr/IIIGlc (Meadow, N. D., and Roseman, S. (1996) J. Biol. Chem. 271, 33440-33445). X-ray crystallography, differential scanning calorimetry, and NMR have now been used to determine the structures of the mutants (phospho-H75QIIIGlc was studied by NMR). The three methods gave completely consistent results. Except for the His to Gln substitutions, the only significant structural changes were in a few hydrogen bonds. H90QIIIGlc contains two structured water molecules (to Gln90), which could explain its inability to regulate glycerol kinase. Phospho-IIIGlc contains a chymotrypsin-like, hydrogen bond network (Thr73-His75-O--phosphoryl), whereas phospho-H75QIIIGlc contains only one bond (Gln75-O--phosphoryl). Hydrogen bonds play an essential role in a proposed mechanism for the phosphoryltransfer reaction. JF - The Journal of biological chemistry AU - Pelton, J G AU - Torchia, D A AU - Remington, S J AU - Murphy, K P AU - Meadow, N D AU - Roseman, S AD - Bone Research Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/12/27/ PY - 1996 DA - 1996 Dec 27 SP - 33446 EP - 33456 VL - 271 IS - 52 SN - 0021-9258, 0021-9258 KW - Escherichia coli Proteins KW - 0 KW - crr protein, E coli KW - Histidine KW - 4QD397987E KW - Phosphoenolpyruvate Sugar Phosphotransferase System KW - EC 2.7.1.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Phosphorylation KW - Hydrogen-Ion Concentration KW - Escherichia coli -- chemistry KW - Calorimetry KW - Crystallography, X-Ray KW - Hydrogen Bonding KW - Magnetic Resonance Spectroscopy KW - Binding Sites KW - Phosphoenolpyruvate Sugar Phosphotransferase System -- chemistry KW - Models, Molecular UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78635099?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Structures+of+active+site+histidine+mutants+of+IIIGlc%2C+a+major+signal-transducing+protein+in+Escherichia+coli.+Effects+on+the+mechanisms+of+regulation+and+phosphoryl+transfer.&rft.au=Pelton%2C+J+G%3BTorchia%2C+D+A%3BRemington%2C+S+J%3BMurphy%2C+K+P%3BMeadow%2C+N+D%3BRoseman%2C+S&rft.aulast=Pelton&rft.aufirst=J&rft.date=1996-12-27&rft.volume=271&rft.issue=52&rft.spage=33446&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-28 N1 - Date created - 1997-01-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxaliplatin, tetraplatin, cisplatin, and carboplatin: spectrum of activity in drug-resistant cell lines and in the cell lines of the National Cancer Institute's Anticancer Drug Screen panel. AN - 78590992; 8951344 AB - The present study was designed to explore the activity of platinum compounds in cisplatin-resistant cell lines, the unselected cell lines of the National Cancer Institute's Anticancer Drug Screen, and the potential for use in combination. The activities of four platinum compounds in cisplatin-resistant KB and A2780 cells were investigated. The cells were highly resistant to cisplatin and cross-resistant to carboplatin, but less than one-tenth as resistant to oxaliplatin and tetraplatin. Cellular accumulation of all platinum compounds was decreased in both resistant cell lines. When the activities of cisplatin and oxaliplatin were evaluated in the National Cancer Institute's Anticancer Drug Screen, marked differences were observed. Evaluation of the activity profile using the COMPARE program revealed a different pattern for both agents: the cisplatin activity profile was similar to those of other diamine-platinum compounds, alkylating agents including melphalan, and camptothecin analogs, whereas the activity profile of oxaliplatin resembled those of other "dach" (diaminocyclohexane) platinum compounds and of acridine derivatives. The sensitivity profiles are influenced by the target(s)/mechanism(s) of action and the mechanism(s) of resistance of a drug. The dissimilarity in profiles suggests that these two platinum compounds have a different target(s)/mechanism(s) of action, a different mechanism(s) of resistance, or most likely both. Studies evaluating combinations of cisplatin/oxaliplatin suggest that the activities of these two agents are at least additive and possibly synergistic. Oxaliplatin has a different spectrum of activity and low cross-resistance to cisplatin and should be valuable in cisplatin refractory patients or in combination with cisplatin. JF - Biochemical pharmacology AU - Rixe, O AU - Ortuzar, W AU - Alvarez, M AU - Parker, R AU - Reed, E AU - Paull, K AU - Fojo, T AD - Division of Clinical Sciences, NCI, NIH, Bethesda, MD 20892, USA. Y1 - 1996/12/24/ PY - 1996 DA - 1996 Dec 24 SP - 1855 EP - 1865 VL - 52 IS - 12 SN - 0006-2952, 0006-2952 KW - Antineoplastic Agents KW - 0 KW - Organoplatinum Compounds KW - oxaliplatin KW - 04ZR38536J KW - Carboplatin KW - BG3F62OND5 KW - Cisplatin KW - Q20Q21Q62J KW - ormaplatin KW - SFK1SGY8V1 KW - Index Medicus KW - Drug Interactions KW - Cell Survival -- drug effects KW - Humans KW - Drug Resistance KW - Drug Synergism KW - Cell Line KW - Carboplatin -- pharmacology KW - Organoplatinum Compounds -- pharmacology KW - Tumor Cells, Cultured -- drug effects KW - Cisplatin -- pharmacology KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78590992?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Oxaliplatin%2C+tetraplatin%2C+cisplatin%2C+and+carboplatin%3A+spectrum+of+activity+in+drug-resistant+cell+lines+and+in+the+cell+lines+of+the+National+Cancer+Institute%27s+Anticancer+Drug+Screen+panel.&rft.au=Rixe%2C+O%3BOrtuzar%2C+W%3BAlvarez%2C+M%3BParker%2C+R%3BReed%2C+E%3BPaull%2C+K%3BFojo%2C+T&rft.aulast=Rixe&rft.aufirst=O&rft.date=1996-12-24&rft.volume=52&rft.issue=12&rft.spage=1855&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 - 1997-01-03 N1 - Date created - 1997-01-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Woodchuck p-glycoprotein found in virus-induced hepatocellular carcinomas binds anticancer drugs. AN - 78693530; 9018098 AB - Virally-induced hepatocellular carcinomas (HCC) are intrinsically resistant to cancer chemotherapy partly due to increased expression of p-glycoprotein (pgp). In this study, we determined that pgp expressed in woodchuck HCC had binding properties were similar to the drug resistant human pgp. Pgp drug binding properties were characterized by photoaffinity labeling with the calcium channel blocker [3H]azidopine (AZD). AZD bound pgp in HCC but not in non-tumor liver samples, and binding was confirmed by competition with Adriamycin (IC50 = 10 microM) and actinomycin D (IC50 = 1 microM). In summary, WHV-induced HCC overexpress a pgp which binds anticancer drugs suggesting a common pathway for drug resistance. JF - Cancer letters AU - Dunn, S E AU - Cullen, J M AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. dunn1@niehs.nih.gov Y1 - 1996/12/20/ PY - 1996 DA - 1996 Dec 20 SP - 177 EP - 180 VL - 110 IS - 1-2 SN - 0304-3835, 0304-3835 KW - Affinity Labels KW - 0 KW - Antineoplastic Agents KW - Azides KW - Dihydropyridines KW - P-Glycoprotein KW - azidopine KW - 63XR70204A KW - Doxorubicin KW - 80168379AG KW - Index Medicus KW - Animals KW - Marmota KW - Binding, Competitive KW - Azides -- metabolism KW - Liver Neoplasms -- metabolism KW - Carcinoma, Hepatocellular -- metabolism KW - Liver Neoplasms -- veterinary KW - Doxorubicin -- metabolism KW - Carcinoma, Hepatocellular -- veterinary KW - P-Glycoprotein -- metabolism KW - Antineoplastic Agents -- metabolism KW - Dihydropyridines -- metabolism KW - Affinity Labels -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78693530?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=Woodchuck+p-glycoprotein+found+in+virus-induced+hepatocellular+carcinomas+binds+anticancer+drugs.&rft.au=Dunn%2C+S+E%3BCullen%2C+J+M&rft.aulast=Dunn&rft.aufirst=S&rft.date=1996-12-20&rft.volume=110&rft.issue=1-2&rft.spage=177&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-21 N1 - Date created - 1997-02-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutational specificity of the syn 1,2-dihydrodiol 3,4-epoxide of 5-methylchrysene. AN - 78692973; 9018109 AB - The mutational specificity of the syn dihydrodiol epoxide of 5-methylchrysene in the supF gene of the pSP189 vector was examined. Transversion mutations at GC pairs predominated with G --> T and G --> C changes accounting for 42 and 21% of total base change mutations. The types of mutations found reflect the previously determined chemical preference of this reactive species for reaction with deoxyguanosine residues in DNA. JF - Cancer letters AU - Page, J E AU - Pataki, J AU - Harvey, R G AU - Dipple, A AD - Chemistry of Carcinogenesis Laboratory, NCI Frederick Cancer Research and Development Center, MD 21702-1201, USA. Y1 - 1996/12/20/ PY - 1996 DA - 1996 Dec 20 SP - 249 EP - 252 VL - 110 IS - 1-2 SN - 0304-3835, 0304-3835 KW - Carcinogens KW - 0 KW - Chrysenes KW - 1,2-dihydroxy-epoxy-1,2,3,4-tetrahydro-5-methylchrysene KW - 81851-68-5 KW - Index Medicus KW - Base Sequence KW - Transfection KW - Molecular Sequence Data KW - Genetic Vectors -- drug effects KW - Chrysenes -- toxicity KW - Mutagenesis, Site-Directed -- genetics KW - Carcinogens -- toxicity KW - Genetic Vectors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78692973?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=Mutational+specificity+of+the+syn+1%2C2-dihydrodiol+3%2C4-epoxide+of+5-methylchrysene.&rft.au=Page%2C+J+E%3BPataki%2C+J%3BHarvey%2C+R+G%3BDipple%2C+A&rft.aulast=Page&rft.aufirst=J&rft.date=1996-12-20&rft.volume=110&rft.issue=1-2&rft.spage=249&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-21 N1 - Date created - 1997-02-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lack of gender differences in neuroleptic response in patients with schizophrenia. AN - 78682935; 9000318 AB - The authors sought to determine if there were gender differences in neuroleptic response in male and female patients with schizophrenia who were matched for clinical and demographic variables and participated in a double-blind trial of traditional antipsychotic drugs. 24 males (m) and 20 females (f) with schizophrenia or schizoaffective disorder who did not differ in clinical characteristics (age of onset, course of illness, prior hospitalizations, premorbid functioning) participated in an extended drug-free period followed by a neuroleptic trial under double-blind, placebo-controlled conditions. Males and females showed significant improvement in total, positive and negative BPRS symptoms during neuroleptic treatment. However, there were no significant differences in treatment response between sexes. No sex differences were found in baseline drug-free symptomatology, neuroleptic dose or dosage by weight. There were no significant sex differences in neuroleptic treatment response in male and female patients well-matched for clinical, treatment and demographic characteristics. Methodological issues which distinguish this study from prior studies reporting gender differences in neuroleptic response are examined. JF - Schizophrenia research AU - Pinals, D A AU - Malhotra, A K AU - Missar, C D AU - Pickar, D AU - Breier, A AD - Experimental Therapeutics Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/12/15/ PY - 1996 DA - 1996 Dec 15 SP - 215 EP - 222 VL - 22 IS - 3 SN - 0920-9964, 0920-9964 KW - Antipsychotic Agents KW - 0 KW - Index Medicus KW - Psychiatric Status Rating Scales KW - Double-Blind Method KW - Sex Characteristics KW - Humans KW - Adult KW - Male KW - Female KW - Psychotic Disorders -- psychology KW - Antipsychotic Agents -- therapeutic use KW - Schizophrenic Psychology KW - Schizophrenia -- drug therapy KW - Antipsychotic Agents -- adverse effects KW - Psychotic Disorders -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78682935?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Lack+of+gender+differences+in+neuroleptic+response+in+patients+with+schizophrenia.&rft.au=Pinals%2C+D+A%3BMalhotra%2C+A+K%3BMissar%2C+C+D%3BPickar%2C+D%3BBreier%2C+A&rft.aulast=Pinals&rft.aufirst=D&rft.date=1996-12-15&rft.volume=22&rft.issue=3&rft.spage=215&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 - 1997-05-19 N1 - Date created - 1997-05-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The glycosylated gag protein of MuLV is a determinant of neuroinvasiveness: analysis of second site revertants of a mutant MuLV lacking expression of this protein. AN - 78623417; 8955058 AB - Neuroinvasiveness is a property of all neurovirulent murine retroviruses, although the factors which facilitate infection of the CNS are not understood. We previously showed that mutant MuLV which lack expression of an accessory protein, glycosylated gag, had lost neurovirulence, indicating that this protein may be involved in promoting CNS infection. The mutations were located in the "Kozak" consensus sequence of the initiation codon for this protein. Here it is shown that shortly after inoculation of mice with one of these mutant viruses, revertants emerged which had regained expression of glycosylated gag and had also regained the neuroinvasiveness and neurovirulence exhibited by the wild-type virus. The phenotypic revertants retained the mutations in the "Kozak" consensus sequence but exhibited a G-->A mutation 12 codons downstream from the mutated start site, creating a new initiation codon and a glycosylated gag protein, which was truncated at its N-terminus. Using antibodies specific for glycosylated gag it is shown that the frequency of splenic infectious centers expressing revertant virus increased progressively during the 2 months following inoculation of mutant virus until > or = 50% of the virus-producing cells in the spleen expressed revertant virus. In contrast, although phenotypic revertants were detectable at low frequency after cell-free passage in vitro in M. dunni fibroblasts, there was no evidence for selection. These results indicate that glycosylated gag facilitates virus spread within the spleen and to extra-splenic sites, such as the CNS, and suggest that the protein may function through its interaction with the host. JF - Virology AU - Portis, J L AU - Fujisawa, R AU - Mcatee, F J AD - Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840, USA. john_portis@nih.gov Y1 - 1996/12/15/ PY - 1996 DA - 1996 Dec 15 SP - 384 EP - 392 VL - 226 IS - 2 SN - 0042-6822, 0042-6822 KW - DNA, Viral KW - 0 KW - Gene Products, gag KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Immunoblotting KW - Amino Acid Sequence KW - Mice KW - Glycosylation KW - Mutagenesis KW - Phenotype KW - Animals, Newborn KW - Virulence -- genetics KW - Recombination, Genetic KW - Molecular Sequence Data KW - Spleen -- virology KW - Retroviridae Infections -- virology KW - Gene Products, gag -- genetics KW - Leukemia Virus, Murine -- genetics KW - Tumor Virus Infections -- virology KW - Gene Products, gag -- physiology KW - Nervous System Diseases -- virology KW - Leukemia Virus, Murine -- pathogenicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78623417?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Virology&rft.atitle=The+glycosylated+gag+protein+of+MuLV+is+a+determinant+of+neuroinvasiveness%3A+analysis+of+second+site+revertants+of+a+mutant+MuLV+lacking+expression+of+this+protein.&rft.au=Portis%2C+J+L%3BFujisawa%2C+R%3BMcatee%2C+F+J&rft.aulast=Portis&rft.aufirst=J&rft.date=1996-12-15&rft.volume=226&rft.issue=2&rft.spage=384&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-08 N1 - Date created - 1997-01-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of linear and branched peptide forms (MAPs) in the induction of T helper responses to point-mutated ras immunogens. AN - 78616325; 8954620 AB - The utility of multiple antigenic peptides (MAPs) for the induction of antibody and cellular immune responses in animal models has been demonstrated for a variety of peptide epitopes involved in human disease. However, little is known about immune responses to MAPs constructed with antigenic tumor epitopes, nor has peptide specificity in branched forms been addressed. A potentially important advantage of the MAP system over linear peptide immunogens for clinical applications is elimination of the need for a protein carrier with its associated toxicity and immunogenicity. Here, we examined cellular immune responses following in vivo administration of MAPs incorporating a 13-mer T helper epitope from point-mutated ras p21 (ras V12) and compared the potency of the responses to that of the linear peptide. The Gly --> Val mutation in position 12, which is associated with a range of human carcinomas, represents a useful system for evaluating the specificity of the immune response. In initial studies with the point-mutated linear peptide epitope, optimal in vitro proliferation responses were obtained following sc administration of the peptide in a squalane-containing adjuvant formulation. Comparative immunization studies using point-mutated MAPs bearing two, four, or eight branches were administered either in saline or in adjuvant. These studies showed that adjuvant was required for the induction of cellular immune responses using both linear and all three forms of branched peptides. Moreover, there was no apparent advantage of using any of the MAPs vs linear peptide when equivalent mass amounts were administered, i.e., the intensity of the immune response was no greater using any of the branched structures compared to the linear form. Specificity of the in vivo responses for both the linear and the MAP immunogens was demonstrated by the higher stimulation indices observed in vitro in the presence of the mutant ras V12 vs the normal ras G12 linear peptide. No apparent cellular immune response to the MAP core structure itself was observed. However, a nonspecific response to the two-branched MAP2G12 structure was observed in some assays, the nature of which is unknown at this time. This work represents the first reported investigation of a cellular immune response using MAP immunogens incorporating a tumor-specific peptide epitope and demonstrates that linear peptides are as efficient as three different MAP structures in the generation of specific T cell responses. JF - Cellular immunology AU - Schott, M E AU - Wells, D T AU - Schlom, J AU - Abrams, S I AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/12/15/ PY - 1996 DA - 1996 Dec 15 SP - 199 EP - 209 VL - 174 IS - 2 SN - 0008-8749, 0008-8749 KW - Adjuvants, Immunologic KW - 0 KW - Epitopes, T-Lymphocyte KW - Peptides KW - Oncogene Protein p21(ras) KW - EC 3.6.5.2 KW - ras Proteins KW - Index Medicus KW - Peptides -- chemical synthesis KW - Animals KW - Humans KW - Peptides -- immunology KW - Mice KW - Epitopes, T-Lymphocyte -- immunology KW - Cell Line KW - Structure-Activity Relationship KW - Protein Conformation KW - Oncogene Protein p21(ras) -- immunology KW - Oncogene Protein p21(ras) -- genetics KW - Oncogene Protein p21(ras) -- chemistry KW - ras Proteins -- immunology KW - Point Mutation KW - T-Lymphocytes, Helper-Inducer -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78616325?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+immunology&rft.atitle=Comparison+of+linear+and+branched+peptide+forms+%28MAPs%29+in+the+induction+of+T+helper+responses+to+point-mutated+ras+immunogens.&rft.au=Schott%2C+M+E%3BWells%2C+D+T%3BSchlom%2C+J%3BAbrams%2C+S+I&rft.aulast=Schott&rft.aufirst=M&rft.date=1996-12-15&rft.volume=174&rft.issue=2&rft.spage=199&rft.isbn=&rft.btitle=&rft.title=Cellular+immunology&rft.issn=00088749&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-15 N1 - Date created - 1997-01-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interaction of polycyclic aromatic hydrocarbons with human cytochrome P450 1A1: a CO flash photolysis study. AN - 78613792; 8954573 AB - The kinetics of CO binding to human cytochrome P450 1A1 was used to probe the interaction of polycyclic aromatic hydrocarbons (PAHs) with the membrane-bound P450 expressed in baculovirus-infected SF9 insect cells. Biexponential kinetics was observed, indicating that P450 1A1 is composed of at least two kinetically distinguishable species. To define the substrate specificity of the individual species, we evaluated the effect of a series of PAHs of varying sizes and shapes on the CO binding kinetics of P450 1A1. The overall rate of CO binding was increased in the presence of the tricyclic PAHs phenanthrene and anthracene and the tetracyclic PAHs pyrene and 1,2-benzanthracene, but was decreased by the pentacyclic PAHs benzo[a]pyrene and 1,2:3,4-dibenzanthracene. A kinetic difference method was applied to kinetically define the individual P450 1A1 species. Two species differing in their PAH specificities were identified: a slowly reacting species sensitive to the smaller PAHs, and a rapidly reacting species responsive to larger PAHs. Upon PAH binding, CO binding to these species was accelerated and decelerated, respectively. The results furthermore suggest that the two species are interconvertable. In addition to PAHs, the interactions of P450 1A1 with 7-ethoxy- and 7-pentoxyresorufin were likewise examined for their effect on the CO binding kinetics. These compounds interacted with and decreased the rate of the rapidly and slowly reacting P450 1A1 species, respectively. The markedly variable effects of these PAHs and resorufins on the CO binding kinetics indicate differential modes of interaction with the two target P450 1A1 species, resulting in differential modulation of their conformations. These results demonstrate that multiple P450 1A1 species with distinct conformations and substrate recognition profiles coexist in a biological membrane and are resolvable using a rapid kinetic technique. JF - Archives of biochemistry and biophysics AU - Koley, A P AU - Buters, J T AU - Robinson, R C AU - Markowitz, A AU - Friedman, F K AD - Laboratory of Molecular Carcinogenesis, National Institutes of Health, Bethesda, Maryland, 20892, USA. fkried@helix.nih.gov Y1 - 1996/12/15/ PY - 1996 DA - 1996 Dec 15 SP - 261 EP - 267 VL - 336 IS - 2 SN - 0003-9861, 0003-9861 KW - Polycyclic Aromatic Hydrocarbons KW - 0 KW - Recombinant Proteins KW - Carbon Monoxide KW - 7U1EE4V452 KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - Index Medicus KW - Animals KW - Photolysis KW - Spodoptera KW - Cell Membrane -- enzymology KW - Humans KW - Particle Size KW - Recombinant Proteins -- genetics KW - Protein Binding KW - Baculoviridae KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Carbon Monoxide -- metabolism KW - Cell Line KW - Cytochrome P-450 CYP1A1 -- genetics KW - Cytochrome P-450 CYP1A1 -- metabolism KW - Polycyclic Aromatic Hydrocarbons -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78613792?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+biochemistry+and+biophysics&rft.atitle=Interaction+of+polycyclic+aromatic+hydrocarbons+with+human+cytochrome+P450+1A1%3A+a+CO+flash+photolysis+study.&rft.au=Koley%2C+A+P%3BButers%2C+J+T%3BRobinson%2C+R+C%3BMarkowitz%2C+A%3BFriedman%2C+F+K&rft.aulast=Koley&rft.aufirst=A&rft.date=1996-12-15&rft.volume=336&rft.issue=2&rft.spage=261&rft.isbn=&rft.btitle=&rft.title=Archives+of+biochemistry+and+biophysics&rft.issn=00039861&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-07 N1 - Date created - 1997-01-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant immunotoxins specific for a mutant epidermal growth factor receptor: targeting with a single chain antibody variable domain isolated by phage display. AN - 78622092; 8962138 AB - EGFRvIII is a mutant epidermal growth factor receptor found in glioblastoma, and in carcinoma of the breast, ovary, and lung. The mutant receptor has a deletion in its extracellular domain that results in the formation of a new, tumor-specific extracellular sequence. Mice were immunized with a synthetic peptide corresponding to this sequence and purified EGFRvIII. A single chain antibody variable domain (scFv) phage display library of 8 x 10(6) members was made from the spleen of one immunized mouse. A scFv specific for EGFRvIII was isolated from this library by panning with successively decreasing amounts of synthetic peptide. This was used to make an immunotoxin by fusing the scFv DNA sequence to sequences coding for domains II and III of Pseudomonas exotoxin A. Purified immunotoxin had a Kd of 22 nM for peptide and a Kd of 11 nM for cell-surface EGFRvIII. The immunotoxin was very cytotoxic to cells expressing EGFRvIII, with an IC50 of 1 ng/ml (16 pM) on mouse fibroblasts transfected with EGFRvIII and an IC50 of 7-10 ng/ml (110-160 pM) on transfected glioblastoma cells. There was no cytotoxic activity at 1000 ng/ml on the untransfected parent glioblastoma cell line. The immunotoxin was completely stable upon incubation at 37 degrees C for 24 h in human serum. The combination of good affinity, cytotoxicity and stability make this immunotoxin a candidate for further preclinical evaluation. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Lorimer, I A AU - Keppler-Hafkemeyer, A AU - Beers, R A AU - Pegram, C N AU - Bigner, D D AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1996/12/10/ PY - 1996 DA - 1996 Dec 10 SP - 14815 EP - 14820 VL - 93 IS - 25 SN - 0027-8424, 0027-8424 KW - Immunoglobulin Variable Region KW - 0 KW - Immunotoxins KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured KW - Humans KW - Molecular Sequence Data KW - Mice KW - Mutation KW - Gene Library KW - Immunoglobulin Variable Region -- pharmacology KW - Receptor, Epidermal Growth Factor -- genetics KW - Immunotoxins -- immunology KW - Receptor, Epidermal Growth Factor -- immunology KW - Immunoglobulin Variable Region -- immunology KW - Glioblastoma -- metabolism KW - Immunotoxins -- genetics KW - Immunotoxins -- pharmacology KW - Glioblastoma -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78622092?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Recombinant+immunotoxins+specific+for+a+mutant+epidermal+growth+factor+receptor%3A+targeting+with+a+single+chain+antibody+variable+domain+isolated+by+phage+display.&rft.au=Lorimer%2C+I+A%3BKeppler-Hafkemeyer%2C+A%3BBeers%2C+R+A%3BPegram%2C+C+N%3BBigner%2C+D+D%3BPastan%2C+I&rft.aulast=Lorimer&rft.aufirst=I&rft.date=1996-12-10&rft.volume=93&rft.issue=25&rft.spage=14815&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-15 N1 - Date created - 1997-01-15 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U76382; GENBANK N1 - SuppNotes - Cited By: Nature. 1985 Jan 10-18;313(5998):144-7 [2981413] Nat Biotechnol. 1996 Mar;14(3):309-14 [9630891] Proc Natl Acad Sci U S A. 1988 Aug;85(16):5879-83 [3045807] Science. 1988 Oct 21;242(4877):423-6 [3140379] Nature. 1989 Jun 1;339(6223):394-7 [2498664] Proc Natl Acad Sci U S A. 1990 Jun;87(11):4207-11 [1693434] Jpn J Cancer Res. 1990 Aug;81(8):773-9 [2168866] Proc Natl Acad Sci U S A. 1990 Nov;87(21):8602-6 [2236070] J Biol Chem. 1991 Sep 15;266(26):17376-81 [1910044] Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8616-20 [1924323] J Immunol Methods. 1991 Dec 15;145(1-2):229-40 [1765656] Cancer Res. 1992 Jun 15;52(12):3402-8 [1596900] J Biol Chem. 1992 Jun 25;267(18):12420-3 [1618748] Annu Rev Biochem. 1992;61:331-54 [1497314] Clin Cancer Res. 1995 Aug;1(8):859-64 [9816055] Clin Cancer Res. 1996 Feb;2(2):245-52 [9816166] Proteins. 1993 May;16(1):1-7 [8497480] Cancer Res. 1993 Jul 15;53(14):3217-20 [8391918] Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7727-31 [8052651] Structure. 1993 Oct 15;1(2):83-93 [8069628] Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2765-9 [7708720] Cancer Res. 1995 Jul 15;55(14):3140-8 [7606735] Nucleic Acids Res. 1995 Aug 11;23(15):3067-8 [7659531] Int J Cancer. 1995 Nov 15;63(4):537-43 [7591264] Anal Biochem. 1992 Sep;205(2):263-70 [1332541] Cancer Res. 1995 Dec 1;55(23):5536-9 [7585629] Curr Opin Struct Biol. 1995 Aug;5(4):443-9 [8528759] J Mol Biol. 1996 Jan 12;255(1):28-43 [8568873] Nat Med. 1996 Mar;2(3):350-3 [8612238] Proc Natl Acad Sci U S A. 1986 Mar;83(5):1320-4 [3006045] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Stereoselective epoxidation and hydration at the K-region of polycyclic aromatic hydrocarbons by cDNA-expressed cytochromes P450 1A1, 1A2, and epoxide hydrolase. AN - 78618213; 8961944 AB - Stereoselective epoxidation by cytochrome P450s (P450s) and regioselective hydration by epoxide hydrolase determine the carcinogenic potency of some polycyclic aromatic hydrocarbons (PAHs). In this report, cDNA-expressed human and mouse P450s 1A1 and 1A2 and epoxide hydrolase were used to characterize the stereoselective epoxidation and regioselective hydration at the K-region of benz[a]-anthracene (BA), 7,12-dimethylbenz[a]anthracene (DMBA), chrysene (CR), benzo[a]pyrene (B[a]P), dibenz[a,h]anthracene (DB[a,h]A), and benzo[c]phenanthrene (B[c]Ph) by direct chiral stationary-phase HPLC (CSP-HPLC) analyses. Our results indicated that all P450 isoforms preferentially produced major K-region, S,R-epoxides of BA (95-98%), DMBA (94-97%), B[a]P (91-96%), DB[a,h]A (94-98%), and B[c]Ph (87-92%), and major R,S-epoxide of CR (74-85%) in the presence of 3,3,3-trichloropropylene 1,2-oxide (TCPO), an inhibitor of epoxide hydrolase, suggesting that P450 enzymes exhibited the high stereoselectivity toward one of two stereoheterotopic faces of K-region double bond of the PAHs. Epoxide hydrolase either expressed from recombinant vaccinia virus or contained in human hepatoma G2 cells (HepG2) hydrated the C-O bond of epoxy-ring at the S-carbon of major metabolically-formed K-region epoxide enantiomers of BA, CR, DMBA, B[a]P, and DB[a,h]A to yield 80-98% dihydrodiols enriched in R,R-form and that at the R-carbon of B[c]Ph epoxide to yield 77-92% dihydrodiol enriched in S,S-form, suggesting that epoxide hydrolase was highly regioselective. The various enantiomeric components of dihydrodiol products in the metabolism of PAHs were apparently due to the combined effect of stereoselectivity of the P450s and regioselectivity of epoxide hydrolase. Our results provide a clear understanding of how these enzymes catalyze overall stereoselective metabolism at the K-region of the PAHs. JF - Biochemistry AU - Shou, M AU - Gonzalez, F J AU - Gelboin, H V AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/12/10/ PY - 1996 DA - 1996 Dec 10 SP - 15807 EP - 15813 VL - 35 IS - 49 SN - 0006-2960, 0006-2960 KW - Anthracenes KW - 0 KW - Chrysenes KW - Dihydroxydihydrobenzopyrenes KW - Enzyme Inhibitors KW - Epoxy Compounds KW - Polycyclic Aromatic Hydrocarbons KW - Recombinant Proteins KW - chrysene KW - 084HCM49PT KW - Trichloroepoxypropane KW - 3083-23-6 KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - Cytochrome P-450 CYP1A2 KW - Epoxide Hydrolases KW - EC 3.3.2.- KW - Index Medicus KW - Molecular Structure KW - Vaccinia virus -- genetics KW - Animals KW - Anthracenes -- metabolism KW - Humans KW - Mice KW - Recombinant Proteins -- genetics KW - Chrysenes -- metabolism KW - Trichloroepoxypropane -- pharmacology KW - Dihydroxydihydrobenzopyrenes -- metabolism KW - Baculoviridae -- genetics KW - Gene Expression -- genetics KW - Recombinant Proteins -- metabolism KW - Enzyme Inhibitors -- pharmacology KW - Models, Chemical KW - Molecular Conformation KW - Epoxide Hydrolases -- metabolism KW - Cytochrome P-450 CYP1A1 -- genetics KW - Cytochrome P-450 CYP1A2 -- genetics KW - Epoxy Compounds -- metabolism KW - Cytochrome P-450 CYP1A2 -- metabolism KW - Cytochrome P-450 CYP1A1 -- metabolism KW - Polycyclic Aromatic Hydrocarbons -- metabolism KW - Epoxide Hydrolases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78618213?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Stereoselective+epoxidation+and+hydration+at+the+K-region+of+polycyclic+aromatic+hydrocarbons+by+cDNA-expressed+cytochromes+P450+1A1%2C+1A2%2C+and+epoxide+hydrolase.&rft.au=Shou%2C+M%3BGonzalez%2C+F+J%3BGelboin%2C+H+V&rft.aulast=Shou&rft.aufirst=M&rft.date=1996-12-10&rft.volume=35&rft.issue=49&rft.spage=15807&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-16 N1 - Date created - 1997-01-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intramembrane bis-heme motif for transmembrane electron transport conserved in a yeast iron reductase and the human NADPH oxidase. AN - 78566510; 8940093 AB - A plasma membrane iron reductase, required for cellular iron acquisition by Saccharomyces cerevisiae, and the human phagocytic NADPH oxidase, implicated in cellular defense, contain low potential plasma membrane b cytochromes that share elements of structure and function. Four critical histidine residues in the FRE1 protein of the iron reductase were identified by site-directed mutagenesis. Individual mutation of each histidine to alanine eliminated the entire heme spectrum without affecting expression of the apoprotein, documenting the specificity of the requirement for the histidine residues. These critical residues are predicted to coordinate a bis-heme structure between transmembrane domains of the FRE1 protein. The histidine residues are conserved in the related gp91(phox) protein of the NADPH oxidase of human granulocytes, predicting the sites of heme coordination in that protein complex. Similarly spaced histidine residues have also been implicated in heme binding by organelle b cytochromes with little overall sequence similarity to the plasma membrane b cytochromes. This bis-heme motif may play a role in transmembrane electron transport by distinct families of polytopic b cytochromes. JF - The Journal of biological chemistry AU - Finegold, A A AU - Shatwell, K P AU - Segal, A W AU - Klausner, R D AU - Dancis, A AD - Cell Biology and Metabolism Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/12/06/ PY - 1996 DA - 1996 Dec 06 SP - 31021 EP - 31024 VL - 271 IS - 49 SN - 0021-9258, 0021-9258 KW - Cytochrome b Group KW - 0 KW - Heme KW - 42VZT0U6YR KW - FMN Reductase KW - EC 1.5.1.38 KW - NADH, NADPH Oxidoreductases KW - EC 1.6.- KW - NADPH Oxidase KW - EC 1.6.3.1 KW - ferric citrate iron reductase KW - EC 1.6.99.- KW - Index Medicus KW - Cytochrome b Group -- metabolism KW - Alleles KW - Sequence Alignment KW - Electron Transport KW - Humans KW - Molecular Sequence Data KW - Models, Chemical KW - Amino Acid Sequence KW - Saccharomyces cerevisiae KW - NADPH Oxidase -- metabolism KW - NADH, NADPH Oxidoreductases -- metabolism KW - Heme -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78566510?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Intramembrane+bis-heme+motif+for+transmembrane+electron+transport+conserved+in+a+yeast+iron+reductase+and+the+human+NADPH+oxidase.&rft.au=Finegold%2C+A+A%3BShatwell%2C+K+P%3BSegal%2C+A+W%3BKlausner%2C+R+D%3BDancis%2C+A&rft.aulast=Finegold&rft.aufirst=A&rft.date=1996-12-06&rft.volume=271&rft.issue=49&rft.spage=31021&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-09 N1 - Date created - 1997-01-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of aflatoxin B1-8,9-epoxide-DNA adducts on transcription of a supF gene fragment. AN - 78681399; 9020905 AB - A linearized template, obtained from the vector pGEM-3Zf(+) containing a supF gene fragment, was treated with aflatoxin B1-8,9-epoxide (AFB1 epoxide) and transcription in vitro was then studied. The template functions of both strands of the supF gene were similarly inhibited as shown by transcription with both T7 and SP6 RNA polymerases. This inhibition was dose-dependent and affected the elongation step more extensively than the initiation step. Gel electrophoretic analysis of RNA formed by T7 RNA polymerase indicated that template treated with different AFB1 epoxide doses yielded the same three major truncated RNA fragments. Sequence analysis showed that these major sites of RNA truncation occurred in the vicinity of adjacent guanine residues in the template. JF - Cancer letters AU - Yu, F L AU - Cahill, J M AU - Lipinski, L J AU - Dipple, A AD - Chemistry of Carcinogenesis Laboratory, NCI-Frederick Cancer Research and Development Center, MD 21702, USA. Y1 - 1996/12/03/ PY - 1996 DA - 1996 Dec 03 SP - 77 EP - 83 VL - 109 IS - 1-2 SN - 0304-3835, 0304-3835 KW - DNA Adducts KW - 0 KW - Viral Proteins KW - supF tRNA KW - aflatoxin B1-2,3-oxide KW - 42583-46-0 KW - RNA KW - 63231-63-0 KW - RNA, Transfer KW - 9014-25-9 KW - Aflatoxin B1 KW - 9N2N2Y55MH KW - RNA polymerase SP6 KW - EC 2.7.7.- KW - bacteriophage T7 RNA polymerase KW - DNA-Directed RNA Polymerases KW - EC 2.7.7.6 KW - Dimethyl Sulfoxide KW - YOW8V9698H KW - Index Medicus KW - Dimethyl Sulfoxide -- pharmacology KW - Base Sequence KW - DNA-Directed RNA Polymerases -- metabolism KW - Molecular Sequence Data KW - Genetic Vectors -- genetics KW - DNA-Directed RNA Polymerases -- drug effects KW - Genes, Suppressor KW - Aflatoxin B1 -- pharmacology KW - Aflatoxin B1 -- chemical synthesis KW - Transcription, Genetic -- drug effects KW - Aflatoxin B1 -- metabolism KW - Aflatoxin B1 -- analogs & derivatives KW - RNA, Transfer -- genetics KW - DNA Adducts -- metabolism KW - RNA -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78681399?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=Effect+of+aflatoxin+B1-8%2C9-epoxide-DNA+adducts+on+transcription+of+a+supF+gene+fragment.&rft.au=Yu%2C+F+L%3BCahill%2C+J+M%3BLipinski%2C+L+J%3BDipple%2C+A&rft.aulast=Yu&rft.aufirst=F&rft.date=1996-12-03&rft.volume=109&rft.issue=1-2&rft.spage=77&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-27 N1 - Date created - 1997-02-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tiazofurin enhances the anabolism and toxicity of 5-fluorouracil. AN - 78676560; 9020902 AB - Tiazofurin, a clinically active anticancer agent, is undergoing additional clinical testing in combination with other agents. We found that tiazofurin is an effective biochemical modulator of 5-fluorouracil anabolism. Pretreatment of cultured L1210 cells with tiazofurin at concentrations of 1-100 microM results in an increase in the rate of conversion of 5-fluorouracil to phosphorylated metabolites. Concentrations of tiazofurin effective in increasing 5-fluorouracil anabolism cause a corresponding increase in the 5-phosphoribosyl-1-pyrophosphate pool. Studies in mice show that tiazofurin increases the lethal toxicity of 5-fluorouracil and increases the antitumor effectiveness of low doses of 5-fluorouracil: however, the combination is not more effective than an optimal dose of 5-fluorouracil given alone. These results indicate that caution should be exercised in the concurrent use of tiazofurin with other drugs, particularly 5-fluorouracil, that require 5-phosphoribosyl-1-pyrophosphate for activation or that are affected by a decrease in pyrimidine nucleotide synthesis. JF - Cancer letters AU - Cysyk, R L AU - Chisena, C A AU - Hyman, R AU - Monks, A AD - Laboratory of Medicinal Chemistry, National Cancer Institute, Bethesda, MD, USA. Y1 - 1996/12/03/ PY - 1996 DA - 1996 Dec 03 SP - 49 EP - 55 VL - 109 IS - 1-2 SN - 0304-3835, 0304-3835 KW - Antimetabolites, Antineoplastic KW - 0 KW - Ribavirin KW - 49717AWG6K KW - Phosphoribosyl Pyrophosphate KW - 7540-64-9 KW - Fluorouracil KW - U3P01618RT KW - tiazofurin KW - ULJ82834RE KW - Index Medicus KW - Animals KW - Enzyme Induction -- drug effects KW - Dose-Response Relationship, Drug KW - Leukemia L1210 -- metabolism KW - Mice KW - Mice, Inbred BALB C KW - Drug Synergism KW - Mice, Inbred DBA KW - Ribavirin -- pharmacology KW - Ribavirin -- analogs & derivatives KW - Fluorouracil -- pharmacology KW - Fluorouracil -- metabolism KW - Antimetabolites, Antineoplastic -- metabolism KW - Phosphoribosyl Pyrophosphate -- metabolism KW - Antimetabolites, Antineoplastic -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78676560?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=Tiazofurin+enhances+the+anabolism+and+toxicity+of+5-fluorouracil.&rft.au=Cysyk%2C+R+L%3BChisena%2C+C+A%3BHyman%2C+R%3BMonks%2C+A&rft.aulast=Cysyk&rft.aufirst=R&rft.date=1996-12-03&rft.volume=109&rft.issue=1-2&rft.spage=49&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-27 N1 - Date created - 1997-02-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gliosis in the LP-BM5 murine leukemia virus-infected mouse: an animal model of retrovirus-induced dementia. AN - 78665406; 9117405 AB - Mice infected with the LP-BM5 murine leukemia virus (MuLV) mixture develop severe immunosuppression, neurotransmitter abnormalities and cognitive impairments in the absence of significant viral or macrophage invasion of the CNS. The time-course of the changes in glial activation have been characterized in an effort to understand the cellular basis of the neurobehavioral abnormalities observed in these mice. Glial activation was determined by measuring the relative changes in F4/80 protein and GFAP immunoreactivity using immunoblots. Augmented F4/80 expression preceded that of GFAP, with global elevations of 4-6-fold at 3 weeks, sustained for up to 12 weeks after inoculation. GFAP immunoreactivity increased 2-fold only in the cerebral cortex and striatum 5 weeks postinfection, declining to control levels by 12 weeks. Immunohistochemistry revealed significant increases in microglial size and staining intensity in the cortex, corpus callosum and striatum, with the development of a unique population of highly ramified, intensely stained microglia and microglial nodules in the corpus callosum and striatum. No evidence of ameboid microglia was found. Astrocyte size and degree of ramification was increased in the hippocampus, cortex, striatum and corpus callosum. Thus, microgliosis is an early event in LP-BM5 infection, preceding astrocytosis, neurotransmitter loss, and development of cognitive deficits. Activated microglia may secrete neurotoxins leading to the neurochemical alterations and cognitive deficits observed in these mice. Because gliosis and microglial nodule formation are hallmarks of HIV-1 encephalopathy, LP-BM5 MuLV-infected C57/B16 mice may afford insights into the mechanisms contributing to the early stages of this syndrome. JF - Brain research AU - Kustova, Y AU - Sei, Y AU - Goping, G AU - Basile, A S AD - Laboratory of Neuroscience, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/12/02/ PY - 1996 DA - 1996 Dec 02 SP - 271 EP - 282 VL - 742 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Acquired Immunodeficiency Syndrome -- virology KW - Mice, Inbred C57BL KW - Mice KW - Immunohistochemistry KW - Leukemia Virus, Murine -- metabolism KW - Gliosis -- metabolism KW - Dementia -- virology KW - Disease Models, Animal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78665406?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Gliosis+in+the+LP-BM5+murine+leukemia+virus-infected+mouse%3A+an+animal+model+of+retrovirus-induced+dementia.&rft.au=Kustova%2C+Y%3BSei%2C+Y%3BGoping%2C+G%3BBasile%2C+A+S&rft.aulast=Kustova&rft.aufirst=Y&rft.date=1996-12-02&rft.volume=742&rft.issue=1-2&rft.spage=271&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 - 1997-04-22 N1 - Date created - 1997-04-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Core mutants of the immunoglobulin binding domain of streptococcal protein G: stability and structural integrity. AN - 78635817; 8977129 AB - A library of core mutants of the GB1 domain of streptococcal protein G was created, and the structure and stability of selected members was assessed by 1H-15N heteronuclear correlation NMR spectroscopy and fluorescence. All mutants comprised changes in beta-sheet residues, with sidechains at positions 5 (Leu), 7 (Leu), 52 (Phe) and 54 (Val) forming the beta-sheet side of the sheet-helix core interface. A solvent exposed position Ile-6 was chosen as a control. Randomization of bases at codon positions 1 and 3 with thymine at position 2 introduces five possible hydrophobic amino acids, namely Leu, Val, Ile, Phe, and Met. The distribution of encoded amino acids at all five positions is approximately as expected theoretically and indicates that no major bias was introduced towards particular residues. The overall structural integrity of several mutants, as assessed by NMR, ranges from very close to wild type to fully unfolded. Interestingly, the stability of the mutants is not strictly correlated with the number of changes or residue volume. JF - FEBS letters AU - Gronenborn, A M AU - Frank, M K AU - Clore, G M AD - Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520, USA. gronenborn@vger.niddk.nih.gov Y1 - 1996/12/02/ PY - 1996 DA - 1996 Dec 02 SP - 312 EP - 316 VL - 398 IS - 2-3 SN - 0014-5793, 0014-5793 KW - Bacterial Proteins KW - 0 KW - IgG Fc-binding protein, Streptococcus KW - Immunoglobulin G KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Protein Structure, Secondary KW - Thermodynamics KW - Models, Molecular KW - Protein Folding KW - Protein Denaturation KW - Protein Structure, Tertiary KW - Immunoglobulin G -- metabolism KW - Magnetic Resonance Spectroscopy KW - Binding Sites KW - Bacterial Proteins -- genetics KW - Bacterial Proteins -- chemistry KW - Protein Conformation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78635817?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEBS+letters&rft.atitle=Core+mutants+of+the+immunoglobulin+binding+domain+of+streptococcal+protein+G%3A+stability+and+structural+integrity.&rft.au=Gronenborn%2C+A+M%3BFrank%2C+M+K%3BClore%2C+G+M&rft.aulast=Gronenborn&rft.aufirst=A&rft.date=1996-12-02&rft.volume=398&rft.issue=2-3&rft.spage=312&rft.isbn=&rft.btitle=&rft.title=FEBS+letters&rft.issn=00145793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-31 N1 - Date created - 1997-01-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toward a quantitative assessment of diffusion anisotropy. AN - 85268358; pmid-8946355 AB - Indices of diffusion anisotropy calculated from diffusion coefficients acquired in two or three perpendicular directions are rotationally variant. In living monkey brain, these indices severely underestimate the degree of diffusion anisotropy. New indices calculated from the entire diffusion tensor are rotationally invariant (RI). They show that anisotropy is highly variable in different white matter regions depending on the degree of coherence of fiber tract directions. In structures with a regular, parallel fiber arrangement, water diffusivity in the direction parallel to the fibers (Dparallel approximately 1400-1800 x 10(-6) mm2/s) is almost 10 times higher than the average diffusivity in directions perpendicular to them (D + D)/2 [corrected] approximately 150-300 x 10(-6) mm2/s), and is almost three times higher than previously reported. In structures where the fiber pattern is less coherent (e.g., where fiber bundles merge), diffusion anisotropy is significantly reduced. However, RI anisotropy indices are still susceptible to noise contamination. Monte Carlo simulations show that these indices are statistically biased, particularly those requiring sorting of the eigenvalues of the diffusion tensor based on their magnitude. A new intervoxel anisotropy index is proposed that locally averages inner products between diffusion tensors in neighboring voxels. This "lattice" RI index has an acceptably low error variance and is less susceptible to bias than any other RI anisotropy index proposed to date. JF - Magnetic Resonance in Medicine AU - Pierpaoli, C AU - Basser, P J AD - Neuroimaging Branch, National Institute of Neurological Diseases and Stroke (NINDS), Bethesda, Maryland 20892, USA. PY - 1996 SP - 893 EP - 906 VL - 36 IS - 6 SN - 0740-3194, 0740-3194 KW - Magnetic Resonance Imaging KW - Anisotropy KW - Animal KW - Brain KW - Diffusion KW - Monte Carlo Method KW - Haplorhini KW - Water UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85268358?accountid=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=Toward+a+quantitative+assessment+of+diffusion+anisotropy.&rft.au=Pierpaoli%2C+C%3BBasser%2C+P+J&rft.aulast=Pierpaoli&rft.aufirst=C&rft.date=1996-12-01&rft.volume=36&rft.issue=6&rft.spage=893&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 - Solitary and collaborative pretense play in early childhood: sources of individual variation in the development of representational competence. AN - 85233971; pmid-9071765 AB - This study evaluates sources of individual variation in child pretense play as an expression of emerging mental representation. Family sociodemographic characteristics, maternal personological characteristics, and maternal affective and cognitive play behaviors, as well as children's gender, language competence, and play, were examined simultaneously. Naturalistic child solitary play and child collaborative play with mother were videorecorded in 141 20-month-olds. Child solitary play, child-initiated and mother-initiated collaborative play with mother, and maternal demonstrations and solicitations of play were then coded into nonsymbolic and symbolic acts. Zero-order relations obtained between child play and, respectively, child gender and language, family SES, and maternal verbal intelligence, personality, physical affection, and play demonstrations and solicitations. Structural equation modeling supported the following unique predictive relations: Child language and mothers' symbolic play positively influenced child collaborative play, and child gender and mothers' verbal intelligence predicted child solitary play. Child gender and mothers' verbal intelligence and physical affection influenced mothers' play and so influenced child collaborative play indirectly. The cognitive advantages of child play and maternal influences on child play are placed in an adaptive parenting framework. JF - Child Development AU - Bornstein, M H AU - Haynes, O M AU - O'Reilly, A W AU - Painter, K M AD - National Institute of Child Health and Human Development, Bethesda, MD 20892-2030, USA. BR2CU.NIH.GOV PY - 1996 SP - 2910 EP - 2929 VL - 67 IS - 6 SN - 0009-3920, 0009-3920 KW - Infant KW - Maternal Behavior KW - Videotape Recording KW - Child Behavior KW - Mothers KW - Mother-Child Relations KW - Human KW - Child Language KW - Male KW - Female KW - Cognition KW - Child, Preschool KW - Child Development KW - Play and Playthings UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85233971?accountid=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=Child+Development&rft.atitle=Solitary+and+collaborative+pretense+play+in+early+childhood%3A+sources+of+individual+variation+in+the+development+of+representational+competence.&rft.au=Bornstein%2C+M+H%3BHaynes%2C+O+M%3BO%27Reilly%2C+A+W%3BPainter%2C+K+M&rft.aulast=Bornstein&rft.aufirst=M&rft.date=1996-12-01&rft.volume=67&rft.issue=6&rft.spage=2910&rft.isbn=&rft.btitle=&rft.title=Child+Development&rft.issn=00093920&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Carbohydrate and lipid metabolism in endogenous hypercortisolism: shared features with metabolic syndrome X and NIDDM. AN - 78705023; 9075604 AB - Carbohydrate and lipid metabolism was cross-sectionally assessed in 16 patients with endogenous hypercortisolism (endogenous Cushing syndrome). Five patients (31%) had fasting glucose levels over 6.6 mmol/l and a HbA1C over 7.5%. Six patients (38%) had diabetes mellitus based on an abnormal 75 g oral glucose tolerance test (OGTT) and two additional patients (13%) had impaired glucose tolerance based on an OGTT. Compared to obese individuals, patients with Cushing syndrome had an elevated glucose but no elevated insulin response to the OGTT. Regression analysis showed positive correlations between 24-h urinary free cortisol (UFC) and fasting blood glucose (P < 0.0005), UFC and OGTT glucose area under the curve (AUC) (P < 0.01), and UFC and HbA1C (P < 0.005). UFC levels were negatively correlated (P < 0.05) with OGTT insulin AUC and insulin/glucose ratios. Eleven (69%) patients required anti-hypertensive therapy for blood pressure control. Total cholesterol and triglycerides were elevated in patients with Cushing syndrome compared to obese controls, while LDL and HDL cholesterol, and Lp(a) were similar in the two groups. We conclude that impaired glucose tolerance and/or diabetes in patients with endogenous Cushing syndrome is due to the hyperglycemic effects of cortisol with relative insulinopenia. Thus, Cushing syndrome shares features with both the Metabolic Syndrome X and NIDDM, including impaired glucose uptake, hyperlipidemia and hypertension. However, in Cushing syndrome, a relative insulinopenia occurs, while in Metabolic Syndrome X and NIDDM, insulin excess is observed. In Cushing syndrome, as the hypercortisolemia exacerbates, insulinopenia becomes more paramount, suggesting that cortisol exerts a direct or indirect "toxic" effect on the beta-cell. JF - Endocrine journal AU - Friedman, T C AU - Mastorakos, G AU - Newman, T D AU - Mullen, N M AU - Horton, E G AU - Costello, R AU - Papadopoulos, N M AU - Chrousos, G P AD - Laboratory of Developmental Neurobiology, NICHD, NIH, Bethesda, MD 20892, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 645 EP - 655 VL - 43 IS - 6 SN - 0918-8959, 0918-8959 KW - Blood Glucose KW - 0 KW - Carbohydrates KW - Hemoglobin A, Glycosylated KW - Insulin KW - Lipids KW - Lipoproteins KW - Triglycerides KW - Cholesterol KW - 97C5T2UQ7J KW - Hydrocortisone KW - WI4X0X7BPJ KW - Index Medicus KW - Triglycerides -- blood KW - Glucose Tolerance Test KW - Blood Glucose -- metabolism KW - Humans KW - Insulin -- blood KW - Aged KW - Lipoproteins -- blood KW - Hydrocortisone -- blood KW - Cholesterol -- blood KW - Hemoglobin A, Glycosylated -- metabolism KW - Adult KW - Middle Aged KW - Hydrocortisone -- urine KW - Male KW - Female KW - Lipids -- blood KW - Cushing Syndrome -- blood KW - Carbohydrates -- blood KW - Insulin Resistance KW - Diabetes Mellitus, Type 2 -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78705023?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Endocrine+journal&rft.atitle=Carbohydrate+and+lipid+metabolism+in+endogenous+hypercortisolism%3A+shared+features+with+metabolic+syndrome+X+and+NIDDM.&rft.au=Friedman%2C+T+C%3BMastorakos%2C+G%3BNewman%2C+T+D%3BMullen%2C+N+M%3BHorton%2C+E+G%3BCostello%2C+R%3BPapadopoulos%2C+N+M%3BChrousos%2C+G+P&rft.aulast=Friedman&rft.aufirst=T&rft.date=1996-12-01&rft.volume=43&rft.issue=6&rft.spage=645&rft.isbn=&rft.btitle=&rft.title=Endocrine+journal&rft.issn=09188959&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-29 N1 - Date created - 1997-05-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - LOH at the APC/MCC gene (5Q21) in gastric cancer and preneoplastic lesions. Prognostic implications. AN - 78705000; 9182290 AB - The APC/MCC gene (Familial Adenomatous Polyposis) at 5q21 plays a role in colon cancer carcinogenesis. LOH at this locus has also been described in gastric cancer and preneoplastic lesions. The APC locus has been recently related to a cell surface adhesion molecule and its alteration may favour metastatic dissemination. LOH at 5q21 has been associated with poor prognosis in other tumors such as lung cancer. Thirty-six gastric cancers were evaluated for LOH at 5q21 with 2 polymorphic markers from microdissected paraffin-embedded material. All tumors were classified by stage, histologic type, degree of differentiation and survival rates. In 4 cases, intestinal metaplasia cells in the adjacent mucosae were also microdissected. Six cases of moderate-severe gastric dysplasia were also added to the study. LOH was determined in 84% of the informative cases of GC, affecting both early and advanced stages of disease. Genomic instability was assessed in 5 cases, 3 of them associated with LOH. The only case of gastric cancer that did not show LOH or instability at 5q21 was a stage II, poorly differentiated intestinal carcinoma without evidence of recurrence after a 36 month follow-up period (the mean survival rate in our series was 28.3% at 36 months). We also found LOH in 2/6 dysplastic lesions and 1/4 intestinal metaplasias. Our data show that LOH at 5q21 is frequent in gastric cancer and is also present in intestinal metaplasia and dysplastic lesions. LOH at this locus is not a prognostic factor in GC in our study, due to the high incidence of LOH that we found. JF - Pathology, research and practice AU - Sanz-Ortega, J AU - Sanz-Esponera, J AU - Caldes, T AU - Gomez de la Concha, E AU - Sobel, M E AU - Merino, M J AD - Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 1206 EP - 1210 VL - 192 IS - 12 SN - 0344-0338, 0344-0338 KW - Index Medicus KW - Neoplasm Staging KW - Humans KW - Prognosis KW - Aged KW - Cell Differentiation KW - Polymerase Chain Reaction KW - Survival Rate KW - Aged, 80 and over KW - Heterozygote KW - Adult KW - Middle Aged KW - Female KW - Male KW - Precancerous Conditions -- genetics KW - Chromosome Deletion KW - Stomach Neoplasms -- genetics KW - Precancerous Conditions -- diagnosis KW - Stomach Neoplasms -- diagnosis KW - Genes, APC KW - Chromosomes, Human, Pair 5 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78705000?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pathology%2C+research+and+practice&rft.atitle=LOH+at+the+APC%2FMCC+gene+%285Q21%29+in+gastric+cancer+and+preneoplastic+lesions.+Prognostic+implications.&rft.au=Sanz-Ortega%2C+J%3BSanz-Esponera%2C+J%3BCaldes%2C+T%3BGomez+de+la+Concha%2C+E%3BSobel%2C+M+E%3BMerino%2C+M+J&rft.aulast=Sanz-Ortega&rft.aufirst=J&rft.date=1996-12-01&rft.volume=192&rft.issue=12&rft.spage=1206&rft.isbn=&rft.btitle=&rft.title=Pathology%2C+research+and+practice&rft.issn=03440338&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-11 N1 - Date created - 1997-06-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Psychobiology of suicide]. TT - Psychobiologie du suicide. AN - 78700749; 9138929 JF - L'Encephale AU - Linnoïla, M AD - NIMH (Bethesda, USA). Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 10 EP - 14 VL - 22 Spec No 4 SN - 0013-7006, 0013-7006 KW - Serotonin KW - 333DO1RDJY KW - Index Medicus KW - Psychophysiology KW - Humans KW - Alcoholism -- physiopathology KW - Alcoholism -- psychology KW - Male KW - Female KW - Aggression -- physiology KW - Serotonin -- physiology KW - Suicide, Attempted -- psychology KW - Depressive Disorder -- psychology KW - Depressive Disorder -- physiopathology KW - Suicide, Attempted -- prevention & control KW - Suicide -- psychology KW - Suicide -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78700749?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=L%27Encephale&rft.atitle=%5BPsychobiology+of+suicide%5D.&rft.au=Linno%C3%AFla%2C+M&rft.aulast=Linno%C3%AFla&rft.aufirst=M&rft.date=1996-12-01&rft.volume=22+Spec+No+4&rft.issue=&rft.spage=10&rft.isbn=&rft.btitle=&rft.title=L%27Encephale&rft.issn=00137006&rft_id=info:doi/ LA - fre DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-07 N1 - Date created - 1997-05-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of the aryl hydrocarbon receptor in animal development, physiological homeostasis and toxicity of TCDD. AN - 78690438; 9035034 JF - The Journal of toxicological sciences AU - Gonzalez, F J AU - Fernandez-Salguero, P AU - Ward, J M AD - Division of Basic Sciences, National Cancer Institute, Bethesda Maryland 20892, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 273 EP - 277 VL - 21 IS - 5 SN - 0388-1350, 0388-1350 KW - Polychlorinated Dibenzodioxins KW - 0 KW - Receptors, Aryl Hydrocarbon KW - Index Medicus KW - Animals KW - Receptors, Aryl Hydrocarbon -- drug effects KW - Receptors, Aryl Hydrocarbon -- physiology KW - Polychlorinated Dibenzodioxins -- toxicity KW - Animals, Newborn -- growth & development KW - Homeostasis -- drug effects KW - Animals, Newborn -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78690438?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+toxicological+sciences&rft.atitle=The+role+of+the+aryl+hydrocarbon+receptor+in+animal+development%2C+physiological+homeostasis+and+toxicity+of+TCDD.&rft.au=Gonzalez%2C+F+J%3BFernandez-Salguero%2C+P%3BWard%2C+J+M&rft.aulast=Gonzalez&rft.aufirst=F&rft.date=1996-12-01&rft.volume=21&rft.issue=5&rft.spage=273&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+toxicological+sciences&rft.issn=03881350&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-11 N1 - Date created - 1997-04-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Statistical methods in the Fourier domain to enhance and classify images. AN - 78686845; 9012568 AB - A mathematical model, for which rigorous methods of statistical inference are available, is described and techniques for image enhancement and linear discriminant analysis of groups are developed. Since the gray values of neighboring pixels in tomographically produced medical images are spatially correlated, the calculations are carried out in the Fourier domain to insure statistical independence of the variables. Furthermore, to increase the power of statistical tests the known spatial covariance was used to specify constraints in the spectral domain. These methods were compared to statistical procedures carried out in the spatial domain. Positron emission tomography (PET) images of alcoholics with organic brain disorders were compared by these techniques to age-matched normal volunteers. Although these techniques are employed to analyze group characteristics of functional images, they provide a comprehensive set of mathematical and statistical procedures in the spectral domain that can also be applied to images of other modalities, such as computed tomography (CT) or magnetic resonance imaging (MRI). JF - Computers and biomedical research, an international journal AU - Rio, D E AU - Rawlings, R R AU - Kerich, M J AU - Momenan, R AU - Eckardt, M J AD - Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 438 EP - 465 VL - 29 IS - 6 SN - 0010-4809, 0010-4809 KW - Index Medicus KW - Discriminant Analysis KW - Humans KW - Mathematical Computing KW - Case-Control Studies KW - Tomography, Emission-Computed KW - Aged KW - Middle Aged KW - Fourier Analysis KW - Alcoholism -- complications KW - Male KW - Brain Diseases -- complications KW - Brain Diseases -- diagnostic imaging KW - Models, Statistical KW - Image Enhancement -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78686845?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Computers+and+biomedical+research%2C+an+international+journal&rft.atitle=Statistical+methods+in+the+Fourier+domain+to+enhance+and+classify+images.&rft.au=Rio%2C+D+E%3BRawlings%2C+R+R%3BKerich%2C+M+J%3BMomenan%2C+R%3BEckardt%2C+M+J&rft.aulast=Rio&rft.aufirst=D&rft.date=1996-12-01&rft.volume=29&rft.issue=6&rft.spage=438&rft.isbn=&rft.btitle=&rft.title=Computers+and+biomedical+research%2C+an+international+journal&rft.issn=00104809&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-19 N1 - Date created - 1997-03-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Quantification of historical exposures in occupational cohort studies. AN - 78684816; 9000307 AB - Relatively few investigators have estimated quantitative exposure levels in epidemiologic studies, and, for those that have, few have discussed the strengths and weakness of their estimation method with respect to other methods. This paper reviews the steps for developing quantitative exposure estimates that have been used in published studies. First, the qualitative considerations to be evaluated in the selection of the agent to be estimated (i.e., the disease mechanism, the effects of exposure mixtures and interactions, the physical state of the agent, and the routes of exposures) are discussed. Considerations for developing exposure groups are then presented, including work history and exposure information characteristics, the homogeneity of exposures within exposure groups, the exposure estimation method, and the disease risk analyses to be performed. The various exposure estimation approaches are reviewed for their strengths and weaknesses, including the calculation of the mean exposures from existing exposure measurements, statistical models, measurement data from surrogate exposures, and professional judgment. Recommendations for future studies are provided. JF - Scandinavian journal of work, environment & health AU - Stewart, P A AU - Lees, P S AU - Francis, M AD - Occupational Epidemiology Branch, National Cancer Institute, Rockville, MD 20892, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 405 EP - 414 VL - 22 IS - 6 SN - 0355-3140, 0355-3140 KW - Index Medicus KW - Reproducibility of Results KW - Humans KW - Data Interpretation, Statistical KW - Predictive Value of Tests KW - Models, Statistical KW - Epidemiological Monitoring KW - Cohort Studies KW - Occupational Diseases -- etiology KW - Occupational Diseases -- epidemiology KW - Occupational Exposure -- analysis KW - Environmental Monitoring -- methods KW - Risk Assessment UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78684816?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scandinavian+journal+of+work%2C+environment+%26+health&rft.atitle=Quantification+of+historical+exposures+in+occupational+cohort+studies.&rft.au=Stewart%2C+P+A%3BLees%2C+P+S%3BFrancis%2C+M&rft.aulast=Stewart&rft.aufirst=P&rft.date=1996-12-01&rft.volume=22&rft.issue=6&rft.spage=405&rft.isbn=&rft.btitle=&rft.title=Scandinavian+journal+of+work%2C+environment+%26+health&rft.issn=03553140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-20 N1 - Date created - 1997-03-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Scand J Work Environ Health. 1996 Dec;22(6):401-3 [9000306] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of cyclosporin A on the replication cycle of human immunodeficiency virus type 1 derived from H9 and Molt-4 producer cells. AN - 78683518; 9000086 AB - The effect of cyclosporin A (CsA) on the replication of human immunodeficiency virus type 1 (HIV-1) was studied. CsA treatment inhibited virus production in chronically infected H9 and Molt-4 cells. CsA treatment of HeLaCD4-LTR/beta-gal cells or extracellular viruses also inhibited infection (IC50 1 microg/ml). The intracellular CsA-binding molecule cyclophilin A was detected in HIV-1 derived from chronically infected H9 cells, but it was present at a substantially lower level in HIV-1 derived from chronically infected Molt-4 cells. The low level of cyclophilin A in viral particles derived from Molt-4 cells correlated well with their substantially lower infectivity as assayed on HeLaCD4-LTR beta-gal cells. CsA treatment of infected cells showed a dose-dependent reduction of cyclophilin A incorporation into virions; the amount of cyclophilin A incorporation was found to be dependent on the producer cell type. JF - The Journal of general virology AU - Briggs, C J AU - Tözsér, J AU - Oroszlan, S AD - Laboratory of Molecular Virology and Carcinogenesis, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, MD 21702-1201, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 2963 EP - 2967 VL - 77 ( Pt 12) SN - 0022-1317, 0022-1317 KW - Carrier Proteins KW - 0 KW - HIV Core Protein p24 KW - Cyclosporine KW - 83HN0GTJ6D KW - Amino Acid Isomerases KW - EC 5.1.1.- KW - Peptidylprolyl Isomerase KW - EC 5.2.1.8 KW - Index Medicus KW - AIDS/HIV KW - Amino Acid Isomerases -- metabolism KW - Carrier Proteins -- metabolism KW - Tumor Cells, Cultured KW - Virus Replication -- drug effects KW - Humans KW - HIV Core Protein p24 -- metabolism KW - HIV-1 -- metabolism KW - Cyclosporine -- pharmacology KW - HIV-1 -- physiology KW - HIV-1 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78683518?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+general+virology&rft.atitle=Effect+of+cyclosporin+A+on+the+replication+cycle+of+human+immunodeficiency+virus+type+1+derived+from+H9+and+Molt-4+producer+cells.&rft.au=Briggs%2C+C+J%3BT%C3%B6zs%C3%A9r%2C+J%3BOroszlan%2C+S&rft.aulast=Briggs&rft.aufirst=C&rft.date=1996-12-01&rft.volume=77+%28+Pt+12%29&rft.issue=&rft.spage=2963&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+general+virology&rft.issn=00221317&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-18 N1 - Date created - 1997-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Conditioned medium from a rat ureteric bud cell line in combination with bFGF induces complete differentiation of isolated metanephric mesenchyme. AN - 78681431; 9012535 AB - Differentiation of metanephric mesenchyme is triggered by an inductive signal(s) from the epithelial ureteric bud. As a result of this induction, most of the metanephric mesenchyme converts into epithelium of a nephron. We have developed and characterized an explant culture system, in which metanephric mesenchyme can grow and completely differentiate in vitro in the absence of an inductive tissue. When separated 13 dpc rat metanephric mesenchymes were cultured in serum-free conditioned medium from a rat ureteric bud cell line (RUB1) in the presence of bFGF and TGFalpha, they were induced to differentiate into nephron epithelia and glomeruli-like structures. The nephric type of differentiation was confirmed by both morphological and molecular criteria and paralleled the developmental changes of nephron differentiation in vivo. Expression patterns of brush-border antigen as well as molecular markers of kidney differentiation Wt1, Lim1, Hgf and c-met, c-ret, Shh, Wnt4, Wnt7b, and Wnt11 were analyzed in explants by whole mount and tissue section in situ hybridization following 1-9 days in culture. The expression of secreted patterning molecules Bmp7 and Wnt7b, but not Shh or Wnt11, were demonstrated by RT-PCR and northern blot hybridization with RNA from the RUB1 cells. Our culture system lends itself to examining the relevance of these and other signaling molecules required for nephron differentiation. JF - Development (Cambridge, England) AU - Karavanova, I D AU - Dove, L F AU - Resau, J H AU - Perantoni, A O AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute--Frederick Cancer Research and Development Center, MD 21702, USA. karavano@fcrfv1.ncifcrf.gov Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 4159 EP - 4167 VL - 122 IS - 12 SN - 0950-1991, 0950-1991 KW - Antigens, Differentiation KW - 0 KW - Culture Media, Conditioned KW - Transforming Growth Factor alpha KW - Fibroblast Growth Factor 2 KW - 103107-01-3 KW - Index Medicus KW - Rats KW - Fibroblast Growth Factor 2 -- pharmacology KW - Culture Media, Conditioned -- pharmacology KW - Animals KW - Organ Culture Techniques -- methods KW - Immunohistochemistry KW - Signal Transduction KW - Kidney Tubules, Collecting -- embryology KW - Epithelium -- embryology KW - Embryonic Induction KW - Kidney -- embryology KW - Mesoderm -- physiology KW - Ureter -- embryology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78681431?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Conditioned+medium+from+a+rat+ureteric+bud+cell+line+in+combination+with+bFGF+induces+complete+differentiation+of+isolated+metanephric+mesenchyme.&rft.au=Karavanova%2C+I+D%3BDove%2C+L+F%3BResau%2C+J+H%3BPerantoni%2C+A+O&rft.aulast=Karavanova&rft.aufirst=I&rft.date=1996-12-01&rft.volume=122&rft.issue=12&rft.spage=4159&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 - 1997-02-24 N1 - Date created - 1997-02-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Maltol (3-hydroxy-2-methyl-4-pyrone) toxicity in neuroblastoma cell lines and primary murine fetal hippocampal neuronal cultures. AN - 78681039; 9117544 AB - Maltol (3-hydroxy-2-methyl-4-pyrone), a product of carbohydrate degradation, is known to enhance aluminium-induced neurofibrillary degeneration in neuronal systems, but few toxicological studies have been conducted. We report maltol toxicity in neuroblastoma cell lines of mouse (Neuro 2a) and human (IMR 32) origin, and in primary murine fetal hippocampal neuronal cultures. As determined by MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2 -(4-sulfophenyl)-2H-tetrazolium, inner salt] conversion, maltol exhibited a dose-dependent toxicity on the viability of both neuroblastoma cell lines, but the toxicity was more pronounced in Neuro 2a cells. Maltol was also toxic in a dose-dependent manner in primary murine fetal hippocampal neurons at micromolar concentrations. Electrophoresis of DNA extracted from maltol-intoxicated cells showed a laddering pattern, suggestive of apoptotic cell death. In the maltol-exposed hippocampal neuronal cultures, fragmented DNA ends were visualized in situ in morphologically condensed nuclei by terminal deoxynucleotidyl transferase with digoxigenin-labelled UTP and subsequent immunohistochemistry. Collectively, our findings suggest that the toxic effect of maltol is mediated through apoptosis. Further toxicological investigations are warranted, since maltol is found in the daily diet of humans. JF - Neurodegeneration : a journal for neurodegenerative disorders, neuroprotection, and neuroregeneration AU - Hironishi, M AU - Kordek, R AU - Yanagihara, R AU - Garruto, R M AD - Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 325 EP - 329 VL - 5 IS - 4 SN - 1055-8330, 1055-8330 KW - Pyrones KW - 0 KW - maltol KW - 3A9RD92BS4 KW - Index Medicus KW - Osmolar Concentration KW - Animals KW - Mice -- embryology KW - Apoptosis KW - Tumor Cells, Cultured -- drug effects KW - Cells, Cultured KW - Humans KW - DNA Fragmentation KW - Cell Survival KW - Neuroblastoma -- pathology KW - Neurons -- drug effects KW - Hippocampus -- cytology KW - Pyrones -- poisoning KW - Neurons -- ultrastructure KW - Hippocampus -- embryology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78681039?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurodegeneration+%3A+a+journal+for+neurodegenerative+disorders%2C+neuroprotection%2C+and+neuroregeneration&rft.atitle=Maltol+%283-hydroxy-2-methyl-4-pyrone%29+toxicity+in+neuroblastoma+cell+lines+and+primary+murine+fetal+hippocampal+neuronal+cultures.&rft.au=Hironishi%2C+M%3BKordek%2C+R%3BYanagihara%2C+R%3BGarruto%2C+R+M&rft.aulast=Hironishi&rft.aufirst=M&rft.date=1996-12-01&rft.volume=5&rft.issue=4&rft.spage=325&rft.isbn=&rft.btitle=&rft.title=Neurodegeneration+%3A+a+journal+for+neurodegenerative+disorders%2C+neuroprotection%2C+and+neuroregeneration&rft.issn=10558330&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-24 N1 - Date created - 1997-04-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Assessing environmental chemicals for estrogenicity using a combination of in vitro and in vivo assays. AN - 78673814; 9118870 AB - Because of rampant concern that estrogenic chemicals in the environment may be adversely affecting the health of humans and wildlife, reliable methods for detecting and characterizing estrogenic chemicals are needed. It is important that general agreement be reached on which tests to use and that these tests then be applied to the testing of both man-made and naturally occurring chemicals. As a step toward developing a comprehensive approach to screening chemicals for estrogenic activity, three assays for detecting estrogenicity were conducted on 10 chemicals with known or suspected estrogenic activity. The assays were 1) competitive binding with the mouse uterine estrogen receptor, 2) transcriptional activation in HeLa cells transfected with plasmids containing an estrogen receptor and a response element, and 3) the uterotropic assay in mice. The chemicals studied were 17 beta-estradiol, diethylstilbestrol, tamoxifen, 4-hydroxytamoxifen, methoxychlor, the methoxychlor metabolite 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE), endosulfan, nonylphenol, o,p'-DDT, and kepone. These studies were conducted to assess the utility of this three-assay combination in the routine screening of chemicals, or combinations of chemicals, for estrogenic activity. Results were consistent among the three assays with respect to what is known about the estrogenic activities of the chemicals tested and their requirements for metabolic activation. By providing information on three levels of hormonal activity (receptor binding, transcriptional activation, and an in vivo effect in an estrogen-responsive tissue), an informative profile of estrogenic activity is obtained with a reasonable investment of resources. JF - Environmental health perspectives AU - Shelby, M D AU - Newbold, R R AU - Tully, D B AU - Chae, K AU - Davis, V L AD - Reproductive Toxicology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 1296 EP - 1300 VL - 104 IS - 12 SN - 0091-6765, 0091-6765 KW - Environmental Pollutants KW - 0 KW - Estrogens KW - Hazardous Substances KW - Phenols KW - Receptors, Estrogen KW - Tamoxifen KW - 094ZI81Y45 KW - nonylphenol KW - 79F6A2ILP5 KW - DDT KW - CIW5S16655 KW - Endosulfan KW - OKA6A6ZD4K KW - Chlordecone KW - RG5XJ88UDF KW - Methoxychlor KW - RIA79UD69L KW - Index Medicus KW - Tamoxifen -- pharmacology KW - Animals KW - Environmental Pollutants -- pharmacology KW - Methoxychlor -- metabolism KW - Receptors, Estrogen -- drug effects KW - HeLa Cells -- drug effects KW - Phenols -- pharmacology KW - Dose-Response Relationship, Drug KW - Humans KW - Transcriptional Activation -- drug effects KW - Mice KW - Receptors, Estrogen -- physiology KW - Receptors, Estrogen -- genetics KW - Chlordecone -- pharmacology KW - Binding, Competitive KW - In Vitro Techniques KW - Tamoxifen -- metabolism KW - Endosulfan -- pharmacology KW - DDT -- pharmacology KW - Methoxychlor -- pharmacology KW - Female KW - Uterus -- metabolism KW - Uterus -- growth & development KW - Biological Assay -- methods KW - Estrogens -- pharmacology KW - Hazardous Substances -- pharmacology KW - Uterus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78673814?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Assessing+environmental+chemicals+for+estrogenicity+using+a+combination+of+in+vitro+and+in+vivo+assays.&rft.au=Shelby%2C+M+D%3BNewbold%2C+R+R%3BTully%2C+D+B%3BChae%2C+K%3BDavis%2C+V+L&rft.aulast=Shelby&rft.aufirst=M&rft.date=1996-12-01&rft.volume=104&rft.issue=12&rft.spage=1296&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 - 1997-04-22 N1 - Date created - 1997-04-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Environ Health Perspect. 1994 Apr;102(4):380-3 [7925178] Environ Health Perspect. 1993 Oct;101(5):386-7 [8119246] Science. 1996 Jun 7;272(5267):1489-92 [8633243] Annu Rev Pharmacol Toxicol. 1995;35:195-211 [7598491] Endocrinology. 1994 Jul;135(1):175-82 [8013351] Endocrinology. 1992 May;130(5):2617-24 [1572285] Mol Cell Endocrinol. 1984 Jun;36(1-2):11-5 [6378689] Biol Res Pregnancy Perinatol. 1986;7(1):6-10 [3955129] Environ Health Perspect. 1991 May;92:167-73 [1935846] Endocrinology. 1979 May;104(5):1324-32 [436778] Biochem Pharmacol. 1978;27(20):2417-23 [728194] CRC Crit Rev Toxicol. 1975 Oct;4(1):83-124 [172280] Toxicol Appl Pharmacol. 1969 Sep;15(2):441-50 [5804755] Science. 1968 Oct 18;162(3851):371-2 [5677532] Fundam Appl Toxicol. 1996 Apr;30(2):229-32 [8812270] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of calcium in endothelin-induced contractions and prostacyclin release. AN - 78672095; 9014219 AB - Endothelin-1 (ET-1) is a potent vasoconstrictor peptide that induces characteristically long-lasting contractions. We used rat aortic rings to investigate the role of protein kinase C (PKC) in ET-1-induced contractions and prostacyclin (PGI2) release. ET-1 (10(-9) M) produced a gradual and sustained contraction in rat aortic rings. Pretreatment of aortic rings with different doses (10(-9) M and 10(-6) M) of diltiazem (voltage-sensitive L-type calcium channel blocker) produced significant inhibition of ET-1- and PDBu-induced contractions and PGI2 release. Inhibition was first noted at 10(-9) M and was complete at 10(-6) M. Conversely, pretreatment of aortic rings with different doses (10(-9) M and 10(-6) M) of calcium channel blockers (thapsigargin, an intracellular calcium channel blocker, or conotoxin, a voltage-sensitive N-type calcium channel blocker) produced no changes on ET-1-or PDBu-induced contraction or PGI2 release. These results provide further support for the concept that PKC mediates ET-induced contractions and PGI2 release in rat aortic rings via an increase in intracellular calcium and this increase is due to the influx of extracellular calcium and not to the release of calcium from the sarcoplasmic reticulum. JF - Prostaglandins, leukotrienes, and essential fatty acids AU - Oriji, G K AU - Keiser, H R AD - Hypertension-Endocrine Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 413 EP - 417 VL - 55 IS - 6 SN - 0952-3278, 0952-3278 KW - Calcium Channel Blockers KW - 0 KW - Endothelin-1 KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - Thapsigargin KW - 67526-95-8 KW - Epoprostenol KW - DCR9Z582X0 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Diltiazem KW - EE92BBP03H KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Thapsigargin -- pharmacology KW - Rats KW - Protein Kinase C -- metabolism KW - Protein Kinase C -- drug effects KW - Animals KW - Diltiazem -- pharmacology KW - Aorta -- physiology KW - Calcium Channel Blockers -- pharmacology KW - Aorta -- drug effects KW - Dose-Response Relationship, Drug KW - Male KW - Phorbol 12,13-Dibutyrate -- pharmacology KW - Calcium -- metabolism KW - Muscle Contraction -- drug effects KW - Epoprostenol -- metabolism KW - Calcium -- physiology KW - Endothelin-1 -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78672095?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Prostaglandins%2C+leukotrienes%2C+and+essential+fatty+acids&rft.atitle=Role+of+calcium+in+endothelin-induced+contractions+and+prostacyclin+release.&rft.au=Oriji%2C+G+K%3BKeiser%2C+H+R&rft.aulast=Oriji&rft.aufirst=G&rft.date=1996-12-01&rft.volume=55&rft.issue=6&rft.spage=413&rft.isbn=&rft.btitle=&rft.title=Prostaglandins%2C+leukotrienes%2C+and+essential+fatty+acids&rft.issn=09523278&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-15 N1 - Date created - 1997-04-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Variant mutational activation of the K-ras oncogene in renal mesenchymal tumors induced in newborn F344 rats by methyl(methoxymethyl)nitrosamine. AN - 78669732; 9006098 AB - Renal mesenchymal tumors were induced at high incidence in F344 rats by a single intraperitoneal injection of methyl(methoxymethyl)nitrosamine (DMN-OMe) within 48 h after birth. DNAs from 18 of 35 mesenchymal tumors contained transforming ras sequences in NIH3T3 transfection assays: K-ras (17/18) or N-ras (1/18). Single-stranded conformational polymorphism analysis or dideoxy sequencing of polymerase chain reaction-amplified K-ras gene fragments revealed that these neoplasms contained a variety of activating mutations in the K-ras oncogene. Alterations in codon 12 predominated and included GGT --> GAT transitions, GGT --> GTT or TGT transversions, and previously reported insertion mutations, although some tumors expressed more than one mutation and the pattern of mutations even varied within tumors. Mutations were also found in exons 2 and 3. In addition, tumor transplantability into syngeneic hosts correlated positively and significantly with K-ras activation. Renal mesenchymal tumors with transforming mutations in exon 1 were often successfully passaged (10/12) while tumors which lacked mutations in exon 1 were infrequently transplantable (2/14). While the observed base substitutions in K-ras are consistent with adduct formation, the presence of insertion mutations and intratumor heterogeneity of alterations suggest that ras activation in DMN-OMe-induced tumors is not necessarily an early event in tumorigenesis. JF - Carcinogenesis AU - Higinbotham, K G AU - Rice, J M AU - Reed, C D AU - Watatani, M AU - Enomoto, T AU - Anderson, L M AU - Perantoni, A O AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702-1201, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 2625 EP - 2630 VL - 17 IS - 12 SN - 0143-3334, 0143-3334 KW - Nitrosamines KW - 0 KW - Index Medicus KW - Rats KW - Gene Expression Regulation, Neoplastic KW - Animals KW - Rats, Inbred F344 KW - Polymorphism, Single-Stranded Conformational KW - Male KW - Female KW - Kidney Neoplasms -- genetics KW - Genes, ras KW - Kidney Neoplasms -- chemically induced KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78669732?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Variant+mutational+activation+of+the+K-ras+oncogene+in+renal+mesenchymal+tumors+induced+in+newborn+F344+rats+by+methyl%28methoxymethyl%29nitrosamine.&rft.au=Higinbotham%2C+K+G%3BRice%2C+J+M%3BReed%2C+C+D%3BWatatani%2C+M%3BEnomoto%2C+T%3BAnderson%2C+L+M%3BPerantoni%2C+A+O&rft.aulast=Higinbotham&rft.aufirst=K&rft.date=1996-12-01&rft.volume=17&rft.issue=12&rft.spage=2625&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-13 N1 - Date created - 1997-02-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isolation and characterization of a novel gene induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in rat liver. AN - 78665605; 9006096 AB - The differential display technique was used to identify genes whose expression was regulated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Expression of a novel sequence was up-regulated in a dose-dependent fashion in liver of Sprague-Dawley male rats exposed to both chronic and acute treatment with TCDD, as measured by densitometry of Northern blot analyses (P < 0.01). A rapid amplification of cDNA ends (RACE) procedure was used to isolate a 1.8 kb cDNA from a rat liver cDNA preparation. This cloned cDNA, called 25-Dx, was sequenced and found to encode a peptide of 223 amino acids. In control rats, the 25-Dx gene was expressed at high levels in lung and liver. A hydrophobic domain of 14 residues followed by a proline-rich domain, both located in the N-terminal region, showed 71% homology with the transmembrane domain of the precursor for the interleukin-6 receptor and a conserved consensus sequence found in the cytokine/growth factor/prolactin receptor superfamily respectively. JF - Carcinogenesis AU - Selmin, O AU - Lucier, G W AU - Clark, G C AU - Tritscher, A M AU - Vanden Heuvel, J P AU - Gastel, J A AU - Walker, N J AU - Sutter, T R AU - Bell, D A AD - Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 2609 EP - 2615 VL - 17 IS - 12 SN - 0143-3334, 0143-3334 KW - DNA, Complementary KW - 0 KW - Polychlorinated Dibenzodioxins KW - Index Medicus KW - Rats KW - Protein Biosynthesis KW - Polymerase Chain Reaction KW - Animals KW - Rats, Sprague-Dawley KW - Base Sequence KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Male KW - Liver -- drug effects KW - Polychlorinated Dibenzodioxins -- toxicity KW - Liver -- metabolism KW - DNA, Complementary -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78665605?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Isolation+and+characterization+of+a+novel+gene+induced+by+2%2C3%2C7%2C8-tetrachlorodibenzo-p-dioxin+in+rat+liver.&rft.au=Selmin%2C+O%3BLucier%2C+G+W%3BClark%2C+G+C%3BTritscher%2C+A+M%3BVanden+Heuvel%2C+J+P%3BGastel%2C+J+A%3BWalker%2C+N+J%3BSutter%2C+T+R%3BBell%2C+D+A&rft.aulast=Selmin&rft.aufirst=O&rft.date=1996-12-01&rft.volume=17&rft.issue=12&rft.spage=2609&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-13 N1 - Date created - 1997-02-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased gene specific repair of cisplatin induced interstrand crosslinks in cisplatin resistant cell lines, and studies on carrier ligand specificity. AN - 78665549; 9006094 AB - Development of resistance to cisplatin in previously treatment-responsive malignancies is a major obstacle to successful treatment. Enhanced DNA repair as well as enhanced replicative bypass of DNA adducts have been suggested to play a role in the development of resistance to cisplatin. However, the relative contribution of these mechanisms is unknown. Second generation platinum compounds containing the 1,2-diaminocyclohexane (dach) carrier ligand have been of particular interest in the studies of resistance mechanisms since they have been effective in treatment of cells resistant to cisplatin. We have investigated the formation and repair of interstrand crosslinks (ICL) in the mouse leukemia cell line L1210/0 and its carrier ligand specific resistant derivatives L1210/DDP and L1210/DACH after treatment with ethylenediamine (en)-Pt and diaminocyclohexane (dach)-Pt compounds. ICL in the overall genome were examined using a modification of the alkaline elution assay. A Southern blot technique was employed for the study of ICL in specific regions of the genome. In the overall genome we found decreased formation of ICL with either -en or -dach carrier ligands in the two resistant cell lines without carrier ligand specificity. Some carrier ligand specificity of ICL formation was observed in the dihydrofolate reductase (DHFR) gene, but it did not correlate with the carrier ligand specificity of resistance. At the level of the overall genome there was no difference in repair of ICL between the sensitive and the two resistant cell lines. When measured in the DHFR gene, however, there was enhanced repair of ICL in the two resistant cell lines compared with the sensitive cell line. The enhanced repair at the level of the gene did not display any carrier ligand specificity. JF - Carcinogenesis AU - Petersen, L N AU - Mamenta, E L AU - Stevnsner, T AU - Chaney, S G AU - Bohr, V A AD - Laboratory of Molecular Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 2597 EP - 2602 VL - 17 IS - 12 SN - 0143-3334, 0143-3334 KW - Antineoplastic Agents KW - 0 KW - Cyclohexylamines KW - Drug Carriers KW - Ligands KW - 1,2-cyclohexanediamine KW - 694-83-7 KW - DNA KW - 9007-49-2 KW - Tetrahydrofolate Dehydrogenase KW - EC 1.5.1.3 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured KW - DNA -- metabolism KW - Drug Resistance KW - Mice KW - Tetrahydrofolate Dehydrogenase -- genetics KW - DNA Repair KW - Cyclohexylamines -- metabolism KW - Cisplatin -- pharmacology KW - Cisplatin -- metabolism KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78665549?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Increased+gene+specific+repair+of+cisplatin+induced+interstrand+crosslinks+in+cisplatin+resistant+cell+lines%2C+and+studies+on+carrier+ligand+specificity.&rft.au=Petersen%2C+L+N%3BMamenta%2C+E+L%3BStevnsner%2C+T%3BChaney%2C+S+G%3BBohr%2C+V+A&rft.aulast=Petersen&rft.aufirst=L&rft.date=1996-12-01&rft.volume=17&rft.issue=12&rft.spage=2597&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-13 N1 - Date created - 1997-02-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transplacental mutagenicity of cisplatin: H-ras codon 12 and 13 mutations in skin tumors of SENCAR mice. AN - 78664840; 9006114 AB - Cisplatin is an anticancer agent sometimes used in pregnant women. It is also a potent initiator of skin tumors in mice when administered transplacentally. For characterization of the transplacental mutagenicity of cisplatin, tumors initiated in fetal skin by cisplatin or 7,12-dimethylbenz[a]anthracene (DMBA) and promoted by postnatal 12-O-tetradecanoyl-phorbol-13-acetate (TPA) were analyzed for H-ras mutations by 'cold' single-strand conformation polymorphism analysis and direct sequencing. The expected high incidence of exon II codon 61 mutations (20/20) was found in transplacental DMBA-initiated tumors, with no exon I change. By contrast, 6/10 cisplatin tumors had seven mutations in codons 12 or 13 of exon I, all at GpG dinucleotides. Four of these were unique codon 13 GGC --> GTC changes, significantly different from the DMBA group and from historical TPA-only controls. The activation of codons 12 and 13 by cisplatin is in accord with the known in vitro preference of cisplatin for GpG sites for intrastrand cross-linking adduct formation. These results provide the first evidence that cisplatin can act transplacentally to cause specific mutations in fetal skin that are not seen in skin tumors caused by treatment of adult skin with this agent. This is evidence for unique molecular fetal carcinogenic pathways and underscores concern about human fetal risk due to maternal cisplatin treatment. JF - Carcinogenesis AU - Munoz, E F AU - Diwan, B A AU - Calvert, R J AU - Weghorst, C M AU - Anderson, J AU - Rice, J M AU - Buzard, G S AD - Intramural Research Support Program, SAIC Frederick, National Cancer Institute--Frederick Cancer Research and Development Center, MD 21702-1201, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 2741 EP - 2745 VL - 17 IS - 12 SN - 0143-3334, 0143-3334 KW - Antineoplastic Agents KW - 0 KW - Codon KW - Mutagens KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Animals KW - Mice KW - Female KW - Pregnancy KW - Skin Neoplasms -- genetics KW - Genes, ras KW - Fetus -- drug effects KW - Skin Neoplasms -- chemically induced KW - Cisplatin -- toxicity KW - Antineoplastic Agents -- toxicity KW - Mutagens -- toxicity KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78664840?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Transplacental+mutagenicity+of+cisplatin%3A+H-ras+codon+12+and+13+mutations+in+skin+tumors+of+SENCAR+mice.&rft.au=Munoz%2C+E+F%3BDiwan%2C+B+A%3BCalvert%2C+R+J%3BWeghorst%2C+C+M%3BAnderson%2C+J%3BRice%2C+J+M%3BBuzard%2C+G+S&rft.aulast=Munoz&rft.aufirst=E&rft.date=1996-12-01&rft.volume=17&rft.issue=12&rft.spage=2741&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-13 N1 - Date created - 1997-02-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Replication and extension of Marlatt's taxonomy of relapse precipitants: overview of procedures and results. The Relapse Research Group. AN - 78659919; 8997781 AB - The Relapse Replication and Extension Project (RREP) was a multisite study to replicate and extend Marlatt's taxonomy of relapse precipitants. In addition to replicating Marlatt's original taxonomic system, three independent research teams utilized prospective designs to identify additional predictors of relapse and developed and evaluated two alternative systems for assessing high risk relapse situations. This overview describes the replication methodology, summarizes seven RREP studies completed by the three research groups, and discusses five cross-cutting conclusions emerging from the studies. These conclusions are: (1) reliability of Marlatt's taxonomic system was variable both within and across the three research sites; (2) Marlatt's taxonomic system showed little predictive validity in analyses that used pretreatment relapse data to predict post-treatment relapse, but there are important unresolved issues; (3) an alternative taxonomy provided little more predictive validity than the original taxonomy even though it measured more dimensions of relapse situations and provided greater analytic flexibility; (4) the Reasons for Drinking Questionnaire appeared to be a successful psychometric transformation of Marlatt's taxonomy, one which did demonstrate predictive validity; and (5) Marlatt's taxonomy was based on a time-intensive model of relapse prediction whereas RREP prospective analyses represented time-extensive models of relapse prediction. Coping responses are noted to be effective predictors of relapse under both models. JF - Addiction (Abingdon, England) AU - Lowman, C AU - Allen, J AU - Stout, R L AD - National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-7003, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - S51 EP - S71 VL - 91 Suppl SN - 0965-2140, 0965-2140 KW - Index Medicus KW - Reproducibility of Results KW - Risk Factors KW - Humans KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Personality Assessment KW - Recurrence KW - Male KW - Female KW - Alcoholism -- rehabilitation KW - Cognitive Therapy KW - Substance-Related Disorders -- classification KW - Alcoholism -- classification KW - Social Facilitation KW - Substance-Related Disorders -- rehabilitation KW - Substance-Related Disorders -- psychology KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78659919?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Addiction+%28Abingdon%2C+England%29&rft.atitle=Replication+and+extension+of+Marlatt%27s+taxonomy+of+relapse+precipitants%3A+overview+of+procedures+and+results.+The+Relapse+Research+Group.&rft.au=Lowman%2C+C%3BAllen%2C+J%3BStout%2C+R+L&rft.aulast=Lowman&rft.aufirst=C&rft.date=1996-12-01&rft.volume=91+Suppl&rft.issue=&rft.spage=S51&rft.isbn=&rft.btitle=&rft.title=Addiction+%28Abingdon%2C+England%29&rft.issn=09652140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-21 N1 - Date created - 1997-02-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gender differences in the risk of alcohol dependence: United States, 1992. AN - 78659739; 8997764 AB - Data from a representative sample of US adults revealed that 24% of male life-time drinkers and 15% of female life-time drinkers met the DSM-IV criteria for life-time alcohol dependence, i.e. dependence during the year preceding interview or in any 12-month period prior to that year. The median interval from first drink to onset of dependence was 3.6 years for men and 3.0 years for women. After using survival techniques to adjust for potential gender differences in the exposure to risk of developing alcohol dependence, the cumulative conditional probability of having experienced onset of dependence was 35.1% for men and 24.6% for women. The conditional probability of onset of dependence was equal for men and women in the first year after initiation of drinking, about 30% higher for men in the period 1-4 years after the first drink, and about 45% higher for men thereafter. After using proportional hazards models to adjust for the effects of age cohort, race and ethnicity, family history of alcoholism and age at first drink, these period-specific risk ratios remained virtually unchanged. Including a measure of average daily ethanol intake during periods of heaviest consumption rendered most of the gender differences statistically insignificant, revealing a slight excess risk of female dependence within the first year after initiation of drinking among the heaviest drinkers and leaving an excess male risk of dependence mostly among individuals with average daily intakes of less than one ounce of ethanol. The results suggest that different frequencies of binge drinking might help to account for these remaining gender differences and that men's and women's relative risks of developing alcohol dependence may vary as a function of life cycle stage, with men's excess risk greatest in the college/young adult years. JF - Addiction (Abingdon, England) AU - Dawson, D AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 1831 EP - 1842 VL - 91 IS - 12 SN - 0965-2140, 0965-2140 KW - Index Medicus KW - Risk KW - Age Factors KW - Psychiatric Status Rating Scales KW - Sex Factors KW - Humans KW - Adult KW - Middle Aged KW - Longitudinal Studies KW - Adolescent KW - United States -- epidemiology KW - Male KW - Female KW - Alcoholism -- epidemiology KW - Alcoholism -- diagnosis KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78659739?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Addiction+%28Abingdon%2C+England%29&rft.atitle=Gender+differences+in+the+risk+of+alcohol+dependence%3A+United+States%2C+1992.&rft.au=Dawson%2C+D&rft.aulast=Dawson&rft.aufirst=D&rft.date=1996-12-01&rft.volume=91&rft.issue=12&rft.spage=1831&rft.isbn=&rft.btitle=&rft.title=Addiction+%28Abingdon%2C+England%29&rft.issn=09652140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-27 N1 - Date created - 1997-02-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Specificity of cDNA-expressed human and rodent cytochrome P450s in the oxidative metabolism of the potent carcinogen 7,12-dimethylbenz[a]anthracene. AN - 78652713; 8989918 AB - 7,12-Dimethylbenz[a]anthracene (DMBA), a potent carcinogen, requires metabolic activation by cytochrome P450s (P450s) to electrophilic metabolites that result in DNA modification, mutagenicity, and carcinogenicity. In this study, we used eight human forms, four rodent forms, and one rabbit form of P450 expressed from recombinant vaccinia or baculovirus vectors to define their specificity for metabolizing DMBA. Of the eight human P450s, 1A1 was the most active (specific activity = 14.7 nmol/min/nmol of P450) in total metabolism of DMBA and showed approximately 6- to 33-fold more activity than other P450s, 2B6, 2C9, and 1A2 were also capable of metabolizing DMBA (2.0-2.5 nmol/min/nmol of P450), whereas 2C8, 2E1, 3A4, and 3A5 exhibited relatively low activities. Among animal P450s, mouse 1A1 exhibited activity similar to that of human 1A1 and had 5.0- to 37-fold more activity than other rodent and rabbit P450s. In regard to enzyme regioselectivity, most human and rodent P450s predominantly formed the 8,9-diol, but human 2B6 and rat 2B1 preferentially formed the 5,6-diol. In the production of monohydroxymethyl metabolites, all the enzymes yielded more 7-hydroxymethyl-12-methylbenz[a]anthracene (7HOM12MBA) than 12-hydroxymethyl-7-methylbenz[a]anthracene (7M12HOMBA), except for human 1A1, which presented the reverse selectivity. Human liver microsomes from 10 organ donors were shown to metabolize DMBA and in most circumstances generated the metabolic profile DMBA trans-8,9-dihydrodiol > 7HOM12MBA > or = DMBA trans-5,6-dihydrodiol > or = 7,12-dihydroxymethylbenz[a]anthracene > 7M12HOMBA > DMBA trans-3,4-dihydrodiol. Thus, the combined activity of hepatic microsomal 2C9, 1A2, and 2B6 may contribute to the metabolic activation and the metabolism of DMBA in normal human liver. JF - Molecular carcinogenesis AU - Shou, M AU - Korzekwa, K R AU - Krausz, K W AU - Buters, J T AU - Grogan, J AU - Goldfarb, I AU - Hardwick, J P AU - Gonzalez, F J AU - Gelboin, H V AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 241 EP - 249 VL - 17 IS - 4 SN - 0899-1987, 0899-1987 KW - Carcinogens KW - 0 KW - DNA, Complementary KW - Isoenzymes KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Sensitivity and Specificity KW - Animals KW - Humans KW - Microsomes, Liver -- metabolism KW - Mice KW - Rabbits KW - Binding Sites KW - Oxidation-Reduction KW - Rats KW - Rats, Sprague-Dawley KW - Biotransformation KW - Microsomes, Liver -- enzymology KW - Substrate Specificity KW - Species Specificity KW - Male KW - 9,10-Dimethyl-1,2-benzanthracene -- pharmacokinetics KW - DNA, Complementary -- genetics KW - Carcinogens -- metabolism KW - Cytochrome P-450 Enzyme System -- genetics KW - Isoenzymes -- biosynthesis KW - DNA, Complementary -- metabolism KW - Carcinogens -- pharmacokinetics KW - Cytochrome P-450 Enzyme System -- metabolism KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - 9,10-Dimethyl-1,2-benzanthracene -- metabolism KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78652713?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Specificity+of+cDNA-expressed+human+and+rodent+cytochrome+P450s+in+the+oxidative+metabolism+of+the+potent+carcinogen+7%2C12-dimethylbenz%5Ba%5Danthracene.&rft.au=Shou%2C+M%3BKorzekwa%2C+K+R%3BKrausz%2C+K+W%3BButers%2C+J+T%3BGrogan%2C+J%3BGoldfarb%2C+I%3BHardwick%2C+J+P%3BGonzalez%2C+F+J%3BGelboin%2C+H+V&rft.aulast=Shou&rft.aufirst=M&rft.date=1996-12-01&rft.volume=17&rft.issue=4&rft.spage=241&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 - 1997-01-31 N1 - Date created - 1997-01-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An epidemiologic study of early biologic effects of benzene in Chinese workers. AN - 78649791; 9118921 AB - Benzene is a recognized hematotoxin and leukemogen, but its mechanisms of action in humans are still uncertain. To provide insight into these processes, we carried out a cross-sectional study of 44 healthy workers currently exposed to benzene (median 8-hr time-weighted average; 31 ppm), and unexposed controls in Shanghai, China. Here we provide an overview of the study results on peripheral blood cells levels and somatic cell mutation frequency measured by the glycophorin A (GPA) gene loss assay and report on peripheral cytokine levels. All peripheral blood cells levels (i.e., total white blood cells, absolute lymphocyte count, platelets, red blood cells, and hemoglobin) were decreased among exposed workers compared to controls, with the exception of the red blood cell mean corpuscular volume, which was higher among exposed subjects. In contrast, peripheral cytokine levels (interleukin-3, interleukin-6, erythropoietin, granulocyte colony-stimulating factor, tissue necrosis factor-alpha) in a subset of the most highly exposed workers (n = 11) were similar to values in controls (n = 11), suggesting that benzene does not affect these growth factor levels in peripheral blood. The GPA assay measures stem cell or precursor erythroid cell mutations expressed in peripheral red blood cells of MN heterozygous subjects, identifying NN variants, which result from loss of the GPA M allele and duplication of the N allele, and N phi variants, which arise from gene inactivation. The NN (but not N phi) GPA variant cell frequency was elevated in the exposed workers compared with controls (mean +/- SD, 13.9 +/- 8.4 mutants per million cells versus 7.4 +/- 5.2 per million cells, (respectively; p = 0.0002), suggesting that benzene produces gene-duplicating but not gene-inactivating mutations at the GPA locus in bone marrow cells of exposed humans. These findings, combined with ongoing analyses of benzene macromolecular adducts and chromosomal aberrations, will provide an opportunity to comprehensively evaluate a wide range of early biologic effects associated with benzene exposure in humans. JF - Environmental health perspectives AU - Rothman, N AU - Smith, M T AU - Hayes, R B AU - Li, G L AU - Irons, R D AU - Dosemeci, M AU - Haas, R AU - Stillman, W S AU - Linet, M AU - Xi, L Q AU - Bechtold, W E AU - Wiemels, J AU - Campleman, S AU - Zhang, L AU - Quintana, P J AU - Titenko-Holland, N AU - Wang, Y Z AU - Lu, W AU - Kolachana, P AU - Meyer, K B AU - Yin, S AD - Division of Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA. rothmann@epndce.nci.nih.gov Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 1365 EP - 1370 VL - 104 Suppl 6 SN - 0091-6765, 0091-6765 KW - Cytokines KW - 0 KW - DNA Adducts KW - Glycophorin KW - Benzene KW - J64922108F KW - Index Medicus KW - Cytokines -- blood KW - Glycophorin -- genetics KW - Humans KW - Occupational Diseases -- chemically induced KW - Blood Cell Count KW - DNA Adducts -- blood KW - Cross-Sectional Studies KW - China -- epidemiology KW - Adult KW - Chromosome Aberrations KW - Occupational Diseases -- epidemiology KW - Mutation KW - Female KW - Male KW - Occupational Exposure KW - Benzene -- metabolism KW - Benzene -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78649791?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=An+epidemiologic+study+of+early+biologic+effects+of+benzene+in+Chinese+workers.&rft.au=Rothman%2C+N%3BSmith%2C+M+T%3BHayes%2C+R+B%3BLi%2C+G+L%3BIrons%2C+R+D%3BDosemeci%2C+M%3BHaas%2C+R%3BStillman%2C+W+S%3BLinet%2C+M%3BXi%2C+L+Q%3BBechtold%2C+W+E%3BWiemels%2C+J%3BCampleman%2C+S%3BZhang%2C+L%3BQuintana%2C+P+J%3BTitenko-Holland%2C+N%3BWang%2C+Y+Z%3BLu%2C+W%3BKolachana%2C+P%3BMeyer%2C+K+B%3BYin%2C+S&rft.aulast=Rothman&rft.aufirst=N&rft.date=1996-12-01&rft.volume=104+Suppl+6&rft.issue=&rft.spage=1365&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 - 1997-04-18 N1 - Date created - 1997-04-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Toxicol Environ Health Suppl. 1977;2:69-105 [342717] Environ Health Perspect. 1996 Dec;104 Suppl 6:1349-52 [9118919] Arch Toxicol. 1980 Oct;45(4):297-305 [7447702] Toxicol Lett. 1984 Mar;20(3):337-42 [6701920] Chem Biol Interact. 1984 Apr;49(1-2):133-54 [6202430] Chem Biol Interact. 1985 May;53(3):327-50 [4006011] Cell. 1985 Dec;43(2 Pt 1):531-42 [3878229] Br J Ind Med. 1987 Feb;44(2):124-8 [3814544] Toxicol Appl Pharmacol. 1987 Oct;91(1):85-95 [2823417] Proc Natl Acad Sci U S A. 1988 May;85(9):3189-92 [3258992] Cell. 1988 Jun 17;53(6):869-79 [2838175] Occup Med. 1988 Jul-Sep;3(3):541-54 [3043738] Blood. 1989 May 1;73(6):1487-97 [2653457] Toxicol Appl Pharmacol. 1989 Jul;99(3):421-44 [2749731] Environ Health Perspect. 1989 Jul;82:31-5 [2792049] Environ Health Perspect. 1989 Jul;82:81-9 [2676505] Environ Health Perspect. 1989 Jul;82:97-108 [2792054] Eur J Biochem. 1989 Oct 20;185(1):1-17 [2680485] Cytometry. 1990;11(4):513-21 [2188817] Arch Toxicol. 1990;64(7):539-44 [2073127] Chem Res Toxicol. 1990 Nov-Dec;3(6):566-73 [2103328] Am Ind Hyg Assoc J. 1991 Nov;52(11):473-8 [1746409] Proc Natl Acad Sci U S A. 1992 May 1;89(9):3691-5 [1570288] Biotherapy. 1992;4(2):147-53 [1377927] Leuk Res. 1992 Jun-Jul;16(6-7):585-8 [1635376] Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10464-8 [1438235] Leukemia. 1992 Dec;6(12):1268-72 [1280751] Fundam Appl Toxicol. 1993 May;20(4):503-7 [8314465] Stem Cells. 1993 May;11(3):235-42 [8318910] Am J Ind Med. 1994 Sep;26(3):401-11 [7977413] Biopharm Drug Dispos. 1994 Oct;15(7):587-97 [7849234] Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):4069-73 [7732033] Am J Ind Med. 1996 Mar;29(3):227-35 [8833775] Am J Ind Med. 1996 Mar;29(3):236-46 [8833776] Environ Health Perspect. 1996 Dec;104 Suppl 6:1247-50 [9118900] Environ Health Perspect. 1996 Dec;104 Suppl 6:1325-9 [9118914] Blood. 1978 Aug;52(2):285-92 [667356] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mortality among benzene-exposed workers in China. AN - 78649717; 9118919 AB - A large cohort of 74,828 benzene-exposed and 35,805 nonexposed workers employed between 1972 and 1987 in 12 cities in China was followed to determine mortality from all causes. Benzene-exposed study subjects were employed in a variety of occupations including coating applications, and rubber, chemical, and shoe production. Mortality was slightly increased among workers with greater cumulative exposure to benzene (ptrend < 0.05), but this excess was largely due to cancer deaths (ptrend < 0.01). Deaths due to lymphatic and hematopoietic malignancies (ptrend = 0.01) and lung cancer (ptrend = 0.01) increased with increasing cumulative exposure to benzene. Investigations continue to relate benzene exposure to specific lymphatic and hematopoietic malignancies and other causes of death. JF - Environmental health perspectives AU - Hayes, R B AU - Yin, S N AU - Dosemeci, M AU - Li, G L AU - Wacholder, S AU - Chow, W H AU - Rothman, N AU - Wang, Y Z AU - Dai, T R AU - Chao, X J AU - Jiang, Z L AU - Ye, P Z AU - Zhao, H B AU - Kou, Q R AU - Zhang, W Y AU - Meng, J F AU - Zho, J S AU - Lin, X F AU - Ding, C Y AU - Li, C Y AU - Zhang, Z N AU - Li, D G AU - Travis, L B AU - Blot, W J AU - Linet, M S AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-7368, USA. hayesr@epndce.nci.nih.gov Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 1349 EP - 1352 VL - 104 Suppl 6 SN - 0091-6765, 0091-6765 KW - Benzene KW - J64922108F KW - Index Medicus KW - Leukemia -- chemically induced KW - Neoplasms -- mortality KW - Humans KW - Lymphoma -- chemically induced KW - Lymphoma -- mortality KW - Leukemia -- mortality KW - Risk Factors KW - China -- epidemiology KW - Cohort Studies KW - Neoplasms -- chemically induced KW - Lung Neoplasms -- mortality KW - Lung Neoplasms -- chemically induced KW - Female KW - Male KW - Occupational Exposure KW - Benzene -- toxicity KW - Occupational Diseases -- chemically induced KW - Occupational Diseases -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78649717?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mortality+among+benzene-exposed+workers+in+China.&rft.au=Hayes%2C+R+B%3BYin%2C+S+N%3BDosemeci%2C+M%3BLi%2C+G+L%3BWacholder%2C+S%3BChow%2C+W+H%3BRothman%2C+N%3BWang%2C+Y+Z%3BDai%2C+T+R%3BChao%2C+X+J%3BJiang%2C+Z+L%3BYe%2C+P+Z%3BZhao%2C+H+B%3BKou%2C+Q+R%3BZhang%2C+W+Y%3BMeng%2C+J+F%3BZho%2C+J+S%3BLin%2C+X+F%3BDing%2C+C+Y%3BLi%2C+C+Y%3BZhang%2C+Z+N%3BLi%2C+D+G%3BTravis%2C+L+B%3BBlot%2C+W+J%3BLinet%2C+M+S&rft.aulast=Hayes&rft.aufirst=R&rft.date=1996-12-01&rft.volume=104+Suppl+6&rft.issue=&rft.spage=1349&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 - 1997-04-18 N1 - Date created - 1997-04-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Arch Environ Health. 1978 Jan-Feb;33(1):3-10 [629594] Environ Health Perspect. 1996 Dec;104 Suppl 6:1365-70 [9118921] Br J Ind Med. 1987 Mar;44(3):192-5 [3828244] N Engl J Med. 1987 Apr 23;316(17):1044-50 [3561457] Br J Ind Med. 1987 Jun;44(6):382-95 [3606967] Am J Ind Med. 1989;15(5):495-8 [2741955] Environ Health Perspect. 1989 Jul;82:109-24 [2792037] Environ Health Perspect. 1989 Jul;82:165-9 [2477239] Environ Health Perspect. 1989 Jul;82:207-13 [2792042] Ann N Y Acad Sci. 1990;609:225-30; discussion 230-4 [2264646] Am J Ind Med. 1991;20(5):707-11 [1793112] Leuk Lymphoma. 1994 Jun;14(1-2):91-102 [7920231] Am J Ind Med. 1994 Sep;26(3):383-400 [7977412] Am J Ind Med. 1994 Sep;26(3):401-11 [7977413] Am J Ind Med. 1996 Mar;29(3):227-35 [8833775] Environ Health Perspect. 1996 Dec;104 Suppl 6:1343-7 [9118918] Environ Health Perspect. 1996 Dec;104 Suppl 6:1353-64 [9118920] Br J Ind Med. 1987 Feb;44(2):124-8 [3814544] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Indirect validation of benzene exposure assessment by association with benzene poisoning. AN - 78648963; 9118918 AB - We present a validation study of a quantitative retrospective exposure assessment method used in a follow-up study of workers exposed to benzene. Assessment of exposure to benzene was carried out in 672 factories in 12 cities in China. Historical exposure data were collected for 3179 unique job titles. The basic unit for exposure assessment was a factory/work unit/job title combination over seven periods between 1949 and 1987. A total of 18,435 exposure estimates was developed, using all available historical information, including 8477 monitoring data. Overall, 38% of the estimates were based on benzene monitoring data. The highest time-weighted average exposures were observed for the rubber industry (30.7 ppm) and for rubber glue applicators (52.6 ppm). Because of its recognized link with benzene exposure, the association between a clinical diagnosis of benzene poisoning and benzene exposure was evaluated to validate the assessment method that we used in the cohort study. Our confidence in the assessment method is supported by the observation of a strong positive trend between benzene poisoning and various measures, especially recent intensity of exposure to benzene. JF - Environmental health perspectives AU - Dosemeci, M AU - Yin, S N AU - Linet, M AU - Wacholder, S AU - Rothman, N AU - Li, G L AU - Chow, W H AU - Wang, Y Z AU - Jiang, Z L AU - Dai, T R AU - Zhang, W U AU - Chao, X J AU - Ye, P Z AU - Kou, Q R AU - Fan, Y H AU - Zhang, X C AU - Lin, X F AU - Meng, J F AU - Zho, J S AU - Blot, W J AU - Hayes, R B AD - Division of Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA. dosemecm@epndce.nci.nih.gov Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 1343 EP - 1347 VL - 104 Suppl 6 SN - 0091-6765, 0091-6765 KW - Benzene KW - J64922108F KW - Index Medicus KW - Reproducibility of Results KW - Risk Factors KW - Humans KW - Cohort Studies KW - Retrospective Studies KW - Male KW - Female KW - China KW - Occupational Exposure KW - Benzene -- administration & dosage KW - Benzene -- poisoning UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78648963?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Indirect+validation+of+benzene+exposure+assessment+by+association+with+benzene+poisoning.&rft.au=Dosemeci%2C+M%3BYin%2C+S+N%3BLinet%2C+M%3BWacholder%2C+S%3BRothman%2C+N%3BLi%2C+G+L%3BChow%2C+W+H%3BWang%2C+Y+Z%3BJiang%2C+Z+L%3BDai%2C+T+R%3BZhang%2C+W+U%3BChao%2C+X+J%3BYe%2C+P+Z%3BKou%2C+Q+R%3BFan%2C+Y+H%3BZhang%2C+X+C%3BLin%2C+X+F%3BMeng%2C+J+F%3BZho%2C+J+S%3BBlot%2C+W+J%3BHayes%2C+R+B&rft.aulast=Dosemeci&rft.aufirst=M&rft.date=1996-12-01&rft.volume=104+Suppl+6&rft.issue=&rft.spage=1343&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 - 1997-04-18 N1 - Date created - 1997-04-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Br J Ind Med. 1985 Aug;42(8):563-4 [4016009] Am J Ind Med. 1994 Sep;26(3):401-11 [7977413] Br J Ind Med. 1987 Mar;44(3):192-5 [3828244] Br J Ind Med. 1987 Oct;44(10):702-10 [3118933] Am J Ind Med. 1987;12(5):551-62 [3687951] Am J Ind Med. 1988;14(6):703-13 [3232688] Environ Health Perspect. 1989 Jul;82:199-206 [2792041] Am J Epidemiol. 1989 Dec;130(6):1236-46 [2589314] Scand J Work Environ Health. 1989 Dec;15(6):424-9 [2617258] Am J Ind Med. 1992;21(1):125-32 [1553981] Am J Ind Med. 1992;21(1):53-63 [1553986] Am J Epidemiol. 1992 Mar 1;135(5):564-70 [1570822] Occup Environ Med. 1994 Feb;51(2):136-8 [8111462] Epidemiology. 1994 Jan;5(1):124-7 [8117771] Am J Ind Med. 1994 Sep;26(3):383-400 [7977412] Br J Ind Med. 1986 Oct;43(10):667-76 [3778837] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Topical cyclosporine inhibits mast cell-mediated conjunctivitis. AN - 78634143; 8977483 AB - Allergic conjunctivitis is a common condition caused by a mast cell-mediated hypersensitivity reaction to immunoglobulin E-bound allergens. The purpose of this study was to investigate the effect of topical cyclosporine A on the development of mast cell-mediated conjunctivitis in mice. Allergic conjunctivitis was induced in C57BL/6 mice by topical applications of compound 48/80, a mast cell degranulating agent. In two separate experiments, mice were treated with topical cyclosporine A (0.05%, 0.2%, or 0.4%), prednisolone acetate 1%, or phosphate-buffered saline. Twenty-four hours after compound 48/80 instillation, the number of neutrophils, eosinophils, lymphocytes, macrophages, and the number of preserved goblet cells and undegranulated mast cells in the conjunctiva were counted by a masked observer. In both experiments, treatment with all three doses of cyclosporine A resulted in a statistically significant reduction in the number of infiltrating neutrophils and eosinophils compared to saline-treated controls. There was no significant difference in the treatment effect of cyclosporine and prednisolone acetate. In addition, there was increased preservation of goblet cells in the cyclosporine A-treated animals. Immunohistochemical staining showed a reduction in infiltrating lymphocytes and a smaller reduction in infiltrating macrophages in animals treated with cyclosporine compared to saline-treated controls. Topical cyclosporine A was effective in inhibiting the development of mast cell-mediated allergic conjunctivitis in mice. This study suggests that topical cyclosporine A may be effective in treating allergic conjunctivitis in humans. JF - Investigative ophthalmology & visual science AU - Whitcup, S M AU - Chan, C C AU - Luyo, D A AU - Bo, P AU - Li, Q AD - National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-1858, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 2686 EP - 2693 VL - 37 IS - 13 SN - 0146-0404, 0146-0404 KW - Anti-Inflammatory Agents KW - 0 KW - Immunosuppressive Agents KW - Ophthalmic Solutions KW - p-Methoxy-N-methylphenethylamine KW - 4091-50-3 KW - Cyclosporine KW - 83HN0GTJ6D KW - prednisolone acetate KW - 8B2807733D KW - Prednisolone KW - 9PHQ9Y1OLM KW - Index Medicus KW - Animals KW - p-Methoxy-N-methylphenethylamine -- toxicity KW - Neutrophils -- pathology KW - Mice KW - Macrophages -- drug effects KW - Leukocyte Count KW - Lymphocytes -- pathology KW - Neutrophils -- drug effects KW - Macrophages -- pathology KW - Prednisolone -- analogs & derivatives KW - Prednisolone -- pharmacology KW - Mice, Inbred C57BL KW - Lymphocytes -- drug effects KW - Administration, Topical KW - Female KW - Anti-Inflammatory Agents -- pharmacology KW - Cyclosporine -- administration & dosage KW - Conjunctivitis, Allergic -- pathology KW - Conjunctivitis, Allergic -- chemically induced KW - Cyclosporine -- pharmacology KW - Conjunctivitis, Allergic -- prevention & control KW - Mast Cells -- drug effects KW - Immunosuppressive Agents -- pharmacology KW - Immunosuppressive Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78634143?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Topical+cyclosporine+inhibits+mast+cell-mediated+conjunctivitis.&rft.au=Whitcup%2C+S+M%3BChan%2C+C+C%3BLuyo%2C+D+A%3BBo%2C+P%3BLi%2C+Q&rft.aulast=Whitcup&rft.aufirst=S&rft.date=1996-12-01&rft.volume=37&rft.issue=13&rft.spage=2686&rft.isbn=&rft.btitle=&rft.title=Investigative+ophthalmology+%26+visual+science&rft.issn=01460404&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-08 N1 - Date created - 1997-01-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Subjective and cardiovascular effects of intravenous nicotine in smokers and non-smokers. AN - 78631570; 8972541 AB - The present study assessed the subjective and cardiovascular effects of intravenous nicotine in smokers and nonsmokers. Nonsmokers (n = 5) and smokers (n = 5) were administered a single dose of nicotine (0.75 or 1.5 mg) or saline on each of 3 days. The nicotine doses were given in ascending order in a double-blind fashion. Although smokers and nonsmokers manifested significant increases in systolic and diastolic blood pressure and heart rate 1 min after administration of all active test doses, the difference between peak heart rate and that measured at later times was greater in nonsmokers than in smokers. Nonsmokers and smokers also differed in subjective self-reports. In response to items on visual analogue scales indicative of positive effects (e.g., "good effects," "like drug," "use again," and "feel energetic"), smokers but not nonsmokers reported high scores (> 40) after nicotine injection. In addition, responses on the MBG and LSD subscales of the Addiction Research Center Inventory indicated that smokers experienced positive subjective effects after the test doses, whereas nonsmokers experienced disorientation. The fact that intravenous nicotine was not associated with positive subjective effects in nonsmokers indicates that repeated exposure is required to establish positive reinforcing effects of nicotine. JF - Psychopharmacology AU - Soria, R AU - Stapleton, J M AU - Gilson, S F AU - Sampson-Cone, A AU - Henningfield, J E AU - London, E D AD - Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 221 EP - 226 VL - 128 IS - 3 SN - 0033-3158, 0033-3158 KW - Nicotinic Agonists KW - 0 KW - Tobacco Smoke Pollution KW - Nicotine KW - 6M3C89ZY6R KW - Index Medicus KW - Analysis of Variance KW - Injections, Intravenous KW - Double-Blind Method KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Male KW - Female KW - Heart Rate -- drug effects KW - Nicotine -- pharmacology KW - Tobacco Smoke Pollution -- adverse effects KW - Smoking -- adverse effects KW - Nicotinic Agonists -- pharmacology KW - Blood Pressure -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78631570?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology&rft.atitle=Subjective+and+cardiovascular+effects+of+intravenous+nicotine+in+smokers+and+non-smokers.&rft.au=Soria%2C+R%3BStapleton%2C+J+M%3BGilson%2C+S+F%3BSampson-Cone%2C+A%3BHenningfield%2C+J+E%3BLondon%2C+E+D&rft.aulast=Soria&rft.aufirst=R&rft.date=1996-12-01&rft.volume=128&rft.issue=3&rft.spage=221&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-24 N1 - Date created - 1997-03-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of false positive and false negative outcomes in NTP long-term rodent carcinogenicity studies. AN - 78628417; 8972110 AB - The decision-making process used by the National Toxicology Program (NTP) in its evaluation of long-term rodent carcinogenicity studies was investigated to determine whether or not this procedure resulted in an excessive number of false positive or false negative outcomes. All site-specific tumor incidences that were found to be significantly (p 90%) for this target site. JF - Risk analysis : an official publication of the Society for Risk Analysis AU - Haseman, J K AU - Elwell, M R AD - Statistics and Biomathematics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 813 EP - 820 VL - 16 IS - 6 SN - 0272-4332, 0272-4332 KW - Carcinogens KW - 0 KW - Index Medicus KW - United States KW - Sensitivity and Specificity KW - Animals KW - Dose-Response Relationship, Drug KW - Disease Models, Animal KW - Mice KW - Testicular Neoplasms -- chemically induced KW - Decision Making KW - Longitudinal Studies KW - Rats KW - Body Weight KW - Evaluation Studies as Topic KW - Mice, Inbred Strains KW - Rats, Inbred F344 KW - Incidence KW - Leydig Cell Tumor -- chemically induced KW - Toxicology KW - Female KW - Male KW - False Negative Reactions KW - Carcinogens -- administration & dosage KW - Neoplasms, Experimental -- chemically induced KW - Outcome Assessment (Health Care) KW - False Positive Reactions KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78628417?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Risk+analysis+%3A+an+official+publication+of+the+Society+for+Risk+Analysis&rft.atitle=Evaluation+of+false+positive+and+false+negative+outcomes+in+NTP+long-term+rodent+carcinogenicity+studies.&rft.au=Haseman%2C+J+K%3BElwell%2C+M+R&rft.aulast=Haseman&rft.aufirst=J&rft.date=1996-12-01&rft.volume=16&rft.issue=6&rft.spage=813&rft.isbn=&rft.btitle=&rft.title=Risk+analysis+%3A+an+official+publication+of+the+Society+for+Risk+Analysis&rft.issn=02724332&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-21 N1 - Date created - 1997-01-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evolving concepts of prevention and treatment of invasive fungal infections in pediatric bone marrow transplant recipients. AN - 78626214; 8971401 AB - Fungal infections have emerged as a major complication of marrow transplantation in children. Most episodes occur within the first 100 days and are often difficult to diagnose. Until recently, a limited number of therapeutic options were available but with new antifungal agents, including azole compounds and less toxic preparations of amphotericin, there is promise for improvements in the prevention of fungal infections as well as the treatment of established infections. This review will summarize the current approach towards therapeutic options available for the supportive care of children undergoing marrow transplantation. JF - Bone marrow transplantation AU - Chanock, S J AU - Walsh, T J AD - Pediatric Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - S15 EP - S20 VL - 18 Suppl 3 SN - 0268-3369, 0268-3369 KW - Antifungal Agents KW - 0 KW - Imidazoles KW - Triazoles KW - Itraconazole KW - 304NUG5GF4 KW - Amphotericin B KW - 7XU7A7DROE KW - Fluconazole KW - 8VZV102JFY KW - Flucytosine KW - D83282DT06 KW - Index Medicus KW - Fluconazole -- therapeutic use KW - Fluconazole -- administration & dosage KW - Humans KW - Imidazoles -- administration & dosage KW - Neutropenia -- complications KW - Clinical Trials as Topic KW - Amphotericin B -- administration & dosage KW - Child KW - Antifungal Agents -- therapeutic use KW - Flucytosine -- therapeutic use KW - Transplantation Conditioning -- adverse effects KW - Itraconazole -- therapeutic use KW - Imidazoles -- therapeutic use KW - Immunocompromised Host KW - Antifungal Agents -- administration & dosage KW - Triazoles -- therapeutic use KW - Flucytosine -- administration & dosage KW - Itraconazole -- administration & dosage KW - Amphotericin B -- therapeutic use KW - Triazoles -- administration & dosage KW - Mycoses -- prevention & control KW - Mycoses -- drug therapy KW - Bone Marrow Transplantation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78626214?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bone+marrow+transplantation&rft.atitle=Evolving+concepts+of+prevention+and+treatment+of+invasive+fungal+infections+in+pediatric+bone+marrow+transplant+recipients.&rft.au=Chanock%2C+S+J%3BWalsh%2C+T+J&rft.aulast=Chanock&rft.aufirst=S&rft.date=1996-12-01&rft.volume=18+Suppl+3&rft.issue=&rft.spage=S15&rft.isbn=&rft.btitle=&rft.title=Bone+marrow+transplantation&rft.issn=02683369&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-06-09 N1 - Date created - 1997-06-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Arterial and venous cocaine plasma concentrations in humans: relationship to route of administration, cardiovascular effects and subjective effects. AN - 78623616; 8968359 AB - Arterial plasma drug concentrations should be a strong predictor of resultant physiological and behavioral effects of smoked drugs. Nine healthy male volunteers, who were current users of smoked and i.v. cocaine, participated in a study directly comparing arterial and venous cocaine plasma concentrations after smoked and i.v. cocaine. Each volunteer was first tested under all dosing conditions without an arterial catheter (phase I), to determine whether subjects could tolerate each cocaine dose, before testing with an arterial catheter (phase II). Phase II consisted of two test days, each consisting of either four smoked-cocaine sessions (sham, 12.5, 25 and 50 mg) or four i.v. cocaine sessions (0, 8, 16 and 32 mg) in ascending order, spaced 90 min apart. For the two highest doses for each route, arterial and venous blood samples were taken simultaneously before drug administration, during drug administration and frequently after drug administration. At the same time, cardiovascular effects and subjective effects were measured. Arterial cocaine concentrations were substantially higher than venous cocaine concentrations after both routes of cocaine administration. After either smoked or i.v. cocaine, maximal arterial cocaine concentrations occurred within 15 sec, whereas maximal venous cocaine concentrations occurred within 4 min. The onset of cardiovascular and subjective effects was also rapid, and arterial cocaine concentrations tended to account for these effects to a greater extent than did venous cocaine concentrations. Even though arterial and venous cocaine concentrations were lower after smoked cocaine, compared with i.v. cocaine, the magnitudes of cardiovascular and subjective effects were similar, suggesting that smoked cocaine may produce a greater effect at similar concentrations. These findings do not support the hypothesis that the greater effects observed after smoking are a result of smoked cocaine reaching the brain faster than i.v. cocaine as measured by peripheral arterial plasma concentrations. JF - The Journal of pharmacology and experimental therapeutics AU - Evans, S M AU - Cone, E J AU - Henningfield, J E AD - Addiction Research Center, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 1345 EP - 1356 VL - 279 IS - 3 SN - 0022-3565, 0022-3565 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Smoking KW - Reference Values KW - Veins KW - Humans KW - Arteries KW - Adult KW - Substance Abuse, Intravenous -- blood KW - Blood Pressure -- drug effects KW - Male KW - Cocaine -- pharmacology KW - Cocaine -- blood KW - Cocaine -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78623616?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Arterial+and+venous+cocaine+plasma+concentrations+in+humans%3A+relationship+to+route+of+administration%2C+cardiovascular+effects+and+subjective+effects.&rft.au=Evans%2C+S+M%3BCone%2C+E+J%3BHenningfield%2C+J+E&rft.aulast=Evans&rft.aufirst=S&rft.date=1996-12-01&rft.volume=279&rft.issue=3&rft.spage=1345&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-23 N1 - Date created - 1997-01-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Acquired camptothecin resistance of human breast cancer MCF-7/C4 cells with normal topoisomerase I and elevated DNA repair. AN - 78622115; 8967967 AB - A camptothecin (CPT)-resistant cell line (MCF-7/C4) was established from MCF-7 cells by mutagenic treatment with methylmethanesulfonate and selection with CPT. MCF-7/C4 is 30-fold resistant to CPT and is cross-resistant to UV and cis-dichlorodiammineplatinum(II) but not to VP-16 or ionizing radiation. Topoisomerase I (top1)-mediated cleavable complexes in the presence of CPT, measured by oligonucleotide assay and by alkaline elution, were similar in both cell lines. Other top1 parameters such as top1 protein, RNA levels, and DNA relaxation were also similar in both cell lines. Thus, CPT resistance is not due to alterations in top1 activity but is caused by changes in the downstream pathways from the top1-induced damage. Both cell lines had similar doubling time (22 hr), but MCF-7/C4 cells showed reduced S-phase fraction in the absence of CPT and reduced G2 delay after CPT treatment. p53, GADD45, and p21WAF1/CIP1 were induced similarly by CPT in both cell lines. The overall repair capacity estimated by the ability of cells to reactivate UV-damaged pSV-CAT plasmid was increased in MCF-7/C4 cells. These observations suggest that enhanced DNA repair is one of the factors involved in CPT resistance. JF - Molecular pharmacology AU - Fujimori, A AU - Gupta, M AU - Hoki, Y 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 - 1996/12// PY - 1996 DA - December 1996 SP - 1472 EP - 1478 VL - 50 IS - 6 SN - 0026-895X, 0026-895X KW - Tumor Suppressor Protein p53 KW - 0 KW - Methyl Methanesulfonate KW - AT5C31J09G KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Methyl Methanesulfonate -- toxicity KW - Tumor Cells, Cultured KW - DNA Damage KW - Humans KW - Tumor Suppressor Protein p53 -- metabolism KW - Cell Cycle KW - Mutagenesis KW - Breast Neoplasms -- genetics KW - DNA Repair KW - Camptothecin -- pharmacology KW - Breast Neoplasms -- pathology KW - Drug Resistance, Neoplasm -- genetics KW - Breast Neoplasms -- enzymology KW - DNA Topoisomerases, Type I -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78622115?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Acquired+camptothecin+resistance+of+human+breast+cancer+MCF-7%2FC4+cells+with+normal+topoisomerase+I+and+elevated+DNA+repair.&rft.au=Fujimori%2C+A%3BGupta%2C+M%3BHoki%2C+Y%3BPommier%2C+Y&rft.aulast=Fujimori&rft.aufirst=A&rft.date=1996-12-01&rft.volume=50&rft.issue=6&rft.spage=1472&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 - 1997-01-23 N1 - Date created - 1997-01-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transgenic mice with high levels of superoxide dismutase activity are protected from the neurotoxic effects of 2'-NH2-MPTP on serotonergic and noradrenergic nerve terminals. AN - 78621578; 8967972 AB - Administration of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) analog 1-methyl-4-(2'-aminophenyl)-1,2,3,6-tetrahydropyridine (2'-NH2-MPTP; 4 x 15 mg/kg) to CD-1 mice was found to cause substantial decreases in cortical and hippocampal 5-hydroxytryptamine (5-HT) and norepinephrine (NE) to 20-30% of control 3 weeks after treatment. The magnitude of these depletions was similar to those reported previously in Swiss Webster and C57BL/6 mice given 4 x 20 mg/kg 2'-NH2-MPTP, and in keeping with these prior studies, striatal dopamine levels were unchanged by 2'-NH2-MPTP treatment in CD-1 mice. Subsequently, transgenic CD-1 mice producing high levels of human cytosolic Cu-Zn superoxide dismutase (SOD) were studied to assess the role of oxygen radicals in the mechanism of action of 2'-NH2-MPTP. In contrast to the results described above, 5-HT and NE levels were almost completely unaffected by 2'-NH2-MPTP treatment in homozygous SOD mice bearing 5-fold increases in brain SOD activity. In 2'-NH2-MPTP-treated heterozygous SOD mice, which showed an average 3-fold increase in brain SOD activity, only moderate depletions in cortical and hippocampal 5-HT (50-60% of control) and NE (30-40% of control) were observed. Additionally, the density of [125I]RTI-55-labeled 5-HT uptake sites was studied to further assess possible 5-HT terminal loss. In various cortical and hippocampal subregions of nontransgenic mice, 5-HT uptake sites were reduced to 20-35% of control after 2'-NH2-MPTP treatment, in comparison with homozygous SOD mice, which were affected only minimally by 2'-NH2-MPTP administration, and heterozygous SOD mice, which showed intermediate reductions in 5-HT uptake site density on the order of 55-80% of control. Together, these data indicate that mice genetically endowed with increased SOD activity are protected from 2'-NH2-MPTP-induced toxicity, thereby implicating superoxide radicals in the mechanism of action of a neurotoxin that selectively depletes 5-HT and NE without affecting dopamine. JF - Molecular pharmacology AU - Andrews, A M AU - Ladenheim, B AU - Epstein, C J AU - Cadet, J L AU - Murphy, D L AD - Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland 20892, USA. ama@helix.nih.gov Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 1511 EP - 1519 VL - 50 IS - 6 SN - 0026-895X, 0026-895X KW - 1-methyl-4-(2'-aminophenyl)-1,2,3,6-tetrahydropyridine KW - 108114-93-8 KW - Serotonin KW - 333DO1RDJY KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - 9P21XSP91P KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Monoamine Oxidase KW - EC 1.4.3.4 KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Brain -- enzymology KW - Animals KW - MPTP Poisoning KW - Humans KW - Brain -- drug effects KW - In Vitro Techniques KW - Mice, Inbred C57BL KW - Mice KW - Brain -- metabolism KW - Monoamine Oxidase -- metabolism KW - Mice, Transgenic KW - Male KW - Nerve Endings -- metabolism KW - Nerve Endings -- enzymology KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine -- analogs & derivatives KW - Norepinephrine -- metabolism KW - Superoxide Dismutase -- metabolism KW - Serotonin -- metabolism KW - Nerve Endings -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78621578?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Transgenic+mice+with+high+levels+of+superoxide+dismutase+activity+are+protected+from+the+neurotoxic+effects+of+2%27-NH2-MPTP+on+serotonergic+and+noradrenergic+nerve+terminals.&rft.au=Andrews%2C+A+M%3BLadenheim%2C+B%3BEpstein%2C+C+J%3BCadet%2C+J+L%3BMurphy%2C+D+L&rft.aulast=Andrews&rft.aufirst=A&rft.date=1996-12-01&rft.volume=50&rft.issue=6&rft.spage=1511&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 - 1997-01-23 N1 - Date created - 1997-01-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Asbestos induction of nuclear transcription factors and interleukin 8 gene regulation. AN - 78618962; 8969274 AB - Proinflammatory cytokines and chemotactic peptides are strongly implicated as mediators of the pathophysiologic responses of asbestosis and other chronic inflammatory lung diseases. Recent studies in our laboratory have demonstrated that asbestos fibers stimulate lung epithelial cells to produce interleukin-8 (IL-8), the major neutrophil chemoattractant in the lung. The mechanisms by which asbestos regulates IL-8 expression were studied using the pulmonary type II-like epithelial cell line A549. Membrane permeable hydroxyl scavengers inhibited asbestos induced IL-8 expression. Using A549 cells transfected with the -546 IL-8 construct linked to a chloramphenicol acetyl transferase reporter gene, we have shown that these antioxidants directly inhibited asbestos-stimulated IL-8 promoter-dependent transcription. Asbestos fibers as well as reactive oxygen species generating systems hypoxanthine-xanthine oxidase and hydrogen peroxide stimulated DNA binding activity to the regulatory elements in the IL-8 promoter, binding sites of nuclear factor (NF)-kappaB- and NF-IL-6-like transcription factors. Asbestos-inducible DNA binding activity was partially inhibited by tetramethylthiourea, a hydroxyl radical scavenger. IL-8 secretion was also suppressed by staurosporine, an inhibitor of protein kinase C, and by inhibitors of tyrosine kinase such as herbimycin A and genistein. The suppression paralleled the effect of these inhibitors on asbestos-induced DNA binding to the NF-kappaB- and NF-IL-6-like binding sites of the IL-8 promoter. Taken together, the results suggest that asbestos-induced redox changes and phosphorylation events, mediated by staurosporine-sensitive and tyrosine kinase(s), activate nuclear proteins which recognize the NF-kappaB/NF-IL-6 binding sites of the IL-8 promoter and contribute to the regulation of IL-8 gene expression. JF - American journal of respiratory cell and molecular biology AU - Simeonova, P P AU - Luster, M I AD - Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 787 EP - 795 VL - 15 IS - 6 SN - 1044-1549, 1044-1549 KW - Antioxidants KW - 0 KW - Free Radical Scavengers KW - Interleukin-6 KW - Interleukin-8 KW - NF-kappa B KW - RNA, Messenger KW - Reactive Oxygen Species KW - Recombinant Fusion Proteins KW - Transcription Factors KW - Asbestos KW - 1332-21-4 KW - DNA KW - 9007-49-2 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Index Medicus KW - Reactive Oxygen Species -- metabolism KW - DNA -- metabolism KW - Humans KW - Hydrogen Peroxide -- pharmacology KW - Interleukin-6 -- metabolism KW - Epithelium -- drug effects KW - Chloramphenicol O-Acetyltransferase -- genetics KW - Antioxidants -- pharmacology KW - RNA, Messenger -- metabolism KW - Transfection KW - Epithelium -- metabolism KW - Cell Line KW - Free Radical Scavengers -- pharmacology KW - NF-kappa B -- metabolism KW - Cell Nucleus -- metabolism KW - Lung -- drug effects KW - Asbestos -- pharmacology KW - Interleukin-8 -- genetics KW - Gene Expression Regulation -- drug effects KW - Lung -- metabolism KW - Transcription Factors -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78618962?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+respiratory+cell+and+molecular+biology&rft.atitle=Asbestos+induction+of+nuclear+transcription+factors+and+interleukin+8+gene+regulation.&rft.au=Simeonova%2C+P+P%3BLuster%2C+M+I&rft.aulast=Simeonova&rft.aufirst=P&rft.date=1996-12-01&rft.volume=15&rft.issue=6&rft.spage=787&rft.isbn=&rft.btitle=&rft.title=American+journal+of+respiratory+cell+and+molecular+biology&rft.issn=10441549&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-23 N1 - Date created - 1997-01-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cell cycle-independent regulation of p21Waf1/Cip1 and retinoblastoma protein during okadaic acid-induced apoptosis is coupled with induction of Bax protein in human breast carcinoma cells. AN - 78617639; 8959327 AB - Okadaic acid (OA) is a serine/threonine protein phosphatase inhibitor and has been shown to induce apoptosis in a number of different tumor cell lines, including human breast carcinoma (HBC) cells. The molecular basis of OA-induced apoptosis remains to be investigated. Here, we demonstrate that the OA concentration that inhibits only protein phosphatase 1 and 2A was sufficient to induce apoptosis in HBC cells. In MCF-7 cells, the OA-induced apoptosis was coupled with the overexpression of endogenous p53, p21Waf1/Cip1, and Bax proteins, whereas the Rb protein levels were decreased. OA also induced apoptosis and concomitantly enhanced the p21Waf1/Cip1 and Bex levels in human papilloma virus protein E6-transfected variants of MCF-7 cells, in which p53 function had been disrupted. OA, by contrast, had no effect on the levels or the subcellular localization of Gadd45 and Bcl2 proteins in either wild-type of E6-transfected MCF-7 cells. Bcl-xL, Bcl-xS, and Bak levels were also unchanged after OA treatment in both cell types. OA-induced apoptosis and its effect on the expression of the above molecular markers occurred in the absence of any detectable changes in the cell cycle phase distribution. On the basis of our findings, we conclude the following: (a) OA-induced apoptosis in HBC cells occurs independently of cell cycle arrest; (b) the wild-type p53 function is not an absolute prerequisite for OA-induced cell death; and (c) OA-induced apoptosis is associated with up-regulation of endogenous p21Waf1/Cip1 and Bax protein levels. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Sheikh, M S AU - Garcia, M AU - Zhan, Q AU - Liu, Y AU - Fornace, A J AD - Laboratory of Molecular Pharmacology, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. mssheikh@box-m.nih.gov Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 1599 EP - 1607 VL - 7 IS - 12 SN - 1044-9523, 1044-9523 KW - BAX protein, human KW - 0 KW - Biomarkers KW - CDKN1A protein, human KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - Enzyme Inhibitors KW - GADD45 protein KW - Intracellular Signaling Peptides and Proteins KW - Proteins KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - Retinoblastoma Protein KW - Tumor Suppressor Protein p53 KW - bcl-2-Associated X Protein KW - Okadaic Acid KW - 1W21G5Q4N2 KW - Phosphoric Monoester Hydrolases KW - EC 3.1.3.2 KW - Index Medicus KW - Tumor Cells, Cultured -- cytology KW - DNA Damage -- physiology KW - Tumor Cells, Cultured -- drug effects KW - Cell Cycle -- physiology KW - Humans KW - Gene Expression Regulation, Neoplastic -- physiology KW - Breast Neoplasms KW - Tumor Suppressor Protein p53 -- metabolism KW - Proteins -- metabolism KW - Tumor Cells, Cultured -- enzymology KW - Phosphoric Monoester Hydrolases -- antagonists & inhibitors KW - Tumor Suppressor Protein p53 -- analysis KW - Blotting, Western KW - Tumor Suppressor Protein p53 -- drug effects KW - Proto-Oncogene Proteins c-bcl-2 -- metabolism KW - Proteins -- analysis KW - Down-Regulation -- drug effects KW - Immunohistochemistry KW - Female KW - Cyclins -- analysis KW - Proto-Oncogene Proteins -- analysis KW - Apoptosis -- physiology KW - Apoptosis -- drug effects KW - Retinoblastoma Protein -- metabolism KW - Okadaic Acid -- pharmacology KW - Cyclins -- metabolism KW - Enzyme Inhibitors -- metabolism KW - Enzyme Inhibitors -- analysis KW - Proto-Oncogene Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78617639?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cell+cycle-independent+regulation+of+p21Waf1%2FCip1+and+retinoblastoma+protein+during+okadaic+acid-induced+apoptosis+is+coupled+with+induction+of+Bax+protein+in+human+breast+carcinoma+cells.&rft.au=Sheikh%2C+M+S%3BGarcia%2C+M%3BZhan%2C+Q%3BLiu%2C+Y%3BFornace%2C+A+J&rft.aulast=Sheikh&rft.aufirst=M&rft.date=1996-12-01&rft.volume=7&rft.issue=12&rft.spage=1599&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 - 1997-03-07 N1 - Date created - 1997-03-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 mutations and occupational exposures in a surgical series of lung cancers. AN - 78617107; 8959323 AB - p53 mutations are frequent in malignant lung tumors. Of 88 surgically treated lung cancers from cigarette smokers previously evaluated for p53 mutations, 45 tumors (51.1%) had mutations in exons 5-8 (D. G. Guinee, Jr. et al., Carcinogenesis (Lond.), 16: 993-1002, 1995). We report here the examination of 13 occupational exposures and 13 high-risk occupations in relation to these p53 mutations. Two molecular abnormalities were associated with occupational exposures: (a) G:C-->T:A transversions on the coding (nontranscribed) strand (n = 13) were associated with chromate exposure and employment in the metal industry (P A:T transitions at non-CpG sites (n = 9) were associated with work in the petrochemical industry (P = 0.05). No association was found between p53 mutations and gender, cigarette pack-years, tumor histology, age at diagnosis, or family history of lung cancer. Because all three chromate-exposed subjects had large cell carcinomas exhibiting G: C-->T:A coding-strand transversions, follow-up of a cohort with this exposure should clarify the association with the p53 gene. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Harty, L C AU - Guinee, D G AU - Travis, W D AU - Bennett, W P AU - Jett, J AU - Colby, T V AU - Tazelaar, H AU - Trastek, V AU - Pairolero, P AU - Liotta, L A AU - Harris, C C AU - Caporaso, N E AD - Genetic Epidemiology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 997 EP - 1003 VL - 5 IS - 12 SN - 1055-9965, 1055-9965 KW - DNA Probes KW - 0 KW - DNA, Neoplasm KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - DNA Probes -- chemistry KW - DNA Mutational Analysis KW - Humans KW - Retrospective Studies KW - Smoking -- adverse effects KW - Aged KW - DNA, Neoplasm -- analysis KW - Polymerase Chain Reaction KW - Aged, 80 and over KW - Adult KW - Surveys and Questionnaires KW - Middle Aged KW - Female KW - Male KW - Carcinoma -- surgery KW - Carcinoma -- etiology KW - Genes, p53 -- drug effects KW - Occupational Diseases -- etiology KW - Lung Neoplasms -- surgery KW - Lung Neoplasms -- etiology KW - Occupational Diseases -- genetics KW - Genes, p53 -- genetics KW - Point Mutation KW - Lung Neoplasms -- genetics KW - Occupational Exposure -- adverse effects KW - Tumor Suppressor Protein p53 -- genetics KW - Occupational Diseases -- surgery KW - Carcinoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78617107?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+and+occupational+exposures+in+a+surgical+series+of+lung+cancers.&rft.au=Harty%2C+L+C%3BGuinee%2C+D+G%3BTravis%2C+W+D%3BBennett%2C+W+P%3BJett%2C+J%3BColby%2C+T+V%3BTazelaar%2C+H%3BTrastek%2C+V%3BPairolero%2C+P%3BLiotta%2C+L+A%3BHarris%2C+C+C%3BCaporaso%2C+N+E&rft.aulast=Harty&rft.aufirst=L&rft.date=1996-12-01&rft.volume=5&rft.issue=12&rft.spage=997&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-12 N1 - Date created - 1997-03-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hepatocyte growth factor/scatter factor-Met signaling induces proliferation, migration, and morphogenesis of pancreatic oval cells. AN - 78616041; 8959349 AB - Hepatocyte growth factor/scatter factor (HGF/SF) is a pleiotropic effector for cells expressing the Met tyrosine kinase receptor. In this investigation, we show that pancreatic oval cells express Met and exhibit a proliferative response to HGF/SF. Additionally, we found that oval cells treated transiently with this factor become "scattered," whereas those exposed to HGF/ SF for extended periods of time form branching tubular structures. These structures possess true lumens, which are lined by cells with ductal features, including apical microvilli, well-developed intercellular junctions, interdigitation of plasma membranes, and abundant cytoplasmic organelles. Interestingly, these ductal structures are formed by HGF/SF-treated cells cultured on plastic dishes in the absence of exogenous extracellular matrix components. Consistent with their ability to form ductal structures in vitro, we found that pancreatic oval cells form ductal adenocarcinomas in nude mice. This study supports the involvement of HGF/SF-Met signaling in the growth, migration, and morphogenesis of pancreatic oval cells and may have important implications for the expansion and morphogenic differentiation of these cells during developmental, regenerative, and neoplastic growth. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Jeffers, M AU - Rao, M S AU - Rulong, S AU - Reddy, J K AU - Subbarao, V AU - Hudson, E AU - Vande Woude, G F AU - Resau, J H AD - Advanced BioScience Laboratories, Inc.-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 1805 EP - 1813 VL - 7 IS - 12 SN - 1044-9523, 1044-9523 KW - Hepatocyte Growth Factor KW - 67256-21-7 KW - Copper KW - 789U1901C5 KW - DNA KW - 9007-49-2 KW - Receptor Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Index Medicus KW - Animals KW - Cells, Cultured -- chemistry KW - Humans KW - Cell Division -- drug effects KW - Mice, Nude KW - Mice KW - Cells, Cultured -- cytology KW - Copper -- deficiency KW - DNA -- biosynthesis KW - Rats KW - Antibody Specificity KW - Blotting, Western KW - Carcinogenicity Tests KW - Morphogenesis -- drug effects KW - Microscopy, Electron KW - Cells, Cultured -- enzymology KW - Adenocarcinoma KW - Cell Transplantation KW - Fluorescent Antibody Technique KW - Signal Transduction -- physiology KW - Receptor Protein-Tyrosine Kinases -- immunology KW - Pancreas -- cytology KW - Hepatocyte Growth Factor -- pharmacology KW - Signal Transduction -- drug effects KW - Cell Movement -- drug effects KW - Receptor Protein-Tyrosine Kinases -- physiology KW - Pancreas -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78616041?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hepatocyte+growth+factor%2Fscatter+factor-Met+signaling+induces+proliferation%2C+migration%2C+and+morphogenesis+of+pancreatic+oval+cells.&rft.au=Jeffers%2C+M%3BRao%2C+M+S%3BRulong%2C+S%3BReddy%2C+J+K%3BSubbarao%2C+V%3BHudson%2C+E%3BVande+Woude%2C+G+F%3BResau%2C+J+H&rft.aulast=Jeffers&rft.aufirst=M&rft.date=1996-12-01&rft.volume=7&rft.issue=12&rft.spage=1805&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 - 1997-03-07 N1 - Date created - 1997-03-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Up-regulation and functional role of p21Waf1/Cip1 during growth arrest of human breast carcinoma MCF-7 cells by phenylacetate. AN - 78615957; 8959328 AB - Phenylacetate (PA) and related aromatic fatty acids constitute a novel class of relatively nontoxic antineoplastic agents. These compounds induce tumor cytostasis and growth inhibition and differentiation of cancer cells, but little is known regarding the molecular events mediating these biological effects. Using human breast carcinoma MCF-7 cells as a model, we show here that PA-induced growth arrest is associated with enhanced expression of the cyclin-dependent kinase inhibitor p21Waf1/Cip1 and dephosphorylation of the retinoblastoma protein (pRB). The induction of p21WAF1/CIP1 mRNA by PA was independent of the cellular p53 status. To directly assess the contribution of p21Waf1/Cip1 to PA-mediated cytostasis, we compared the effects of PA in parental MCF-7 cells and cells expressing reduced levels of p21Waf1/Cip1 protein (clones AS.3 and AS.4), accomplished through constitutive expression of antisense p21Waf1/Cip1 transcripts. In contrast to parental cells, AS.3 and AS.4 cells did not show reduced pRB phosphorylation following PA treatment, indicating that p21Waf1/Cip1 induction by PA is required for dephosphorylation (inactivation) of pRB, a known mediator of cell cycle control. A prominent role for p21Waf1/Cip1 in mediating PA-induced growth arrest was further supported by the demonstration that embryonal fibroblasts derived from a p21WAF1/CIP1 knockout mouse (p21-/- mouse embryonal fibroblasts) did not growth arrest following PA treatment, whereas PA effectively induced p21WAF1/CIP1 mRNA and growth inhibition of the wild-type mouse embryonal fibroblasts. Taken together, our findings strongly support a role for p21Waf1/Cip1 in the PA-mediated inhibition of cell growth. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Gorospe, M AU - Shack, S AU - Guyton, K Z AU - Samid, D AU - Holbrook, N J AD - Laboratory of Cellular and Molecular Biology, Gerontology Research Center, National Institute on Aging, NIH, Baltimore, Maryland 21224, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 1609 EP - 1615 VL - 7 IS - 12 SN - 1044-9523, 1044-9523 KW - Antimetabolites, Antineoplastic KW - 0 KW - Antisense Elements (Genetics) KW - CDKN1A protein, human KW - Cdkn1a protein, mouse KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - Enzyme Inhibitors KW - Phenylacetates KW - RNA, Messenger KW - Retinoblastoma Protein KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - CDC2-CDC28 Kinases KW - EC 2.7.11.22 KW - CDK2 protein, human KW - Cdk2 protein, mouse KW - Cyclin-Dependent Kinase 2 KW - Cyclin-Dependent Kinases KW - phenylacetic acid KW - ER5I1W795A KW - Index Medicus KW - Cyclin-Dependent Kinases -- genetics KW - Cyclin-Dependent Kinases -- metabolism KW - Animals KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Fibroblasts -- drug effects KW - Tumor Cells, Cultured -- cytology KW - Fibroblasts -- enzymology KW - Protein-Serine-Threonine Kinases -- metabolism KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Gene Expression Regulation, Neoplastic -- physiology KW - Cell Division -- drug effects KW - Breast Neoplasms KW - Protein-Serine-Threonine Kinases -- genetics KW - Mice KW - Fibroblasts -- cytology KW - Tumor Cells, Cultured -- enzymology KW - Mice, Knockout KW - Signal Transduction -- physiology KW - RNA, Messenger -- metabolism KW - Phosphorylation KW - Up-Regulation -- drug effects KW - Retinoblastoma Protein -- metabolism KW - Female KW - Phenylacetates -- pharmacology KW - Cyclins -- metabolism KW - Enzyme Inhibitors -- metabolism KW - Cyclins -- genetics KW - Antimetabolites, Antineoplastic -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78615957?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Up-regulation+and+functional+role+of+p21Waf1%2FCip1+during+growth+arrest+of+human+breast+carcinoma+MCF-7+cells+by+phenylacetate.&rft.au=Gorospe%2C+M%3BShack%2C+S%3BGuyton%2C+K+Z%3BSamid%2C+D%3BHolbrook%2C+N+J&rft.aulast=Gorospe&rft.aufirst=M&rft.date=1996-12-01&rft.volume=7&rft.issue=12&rft.spage=1609&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 - 1997-03-07 N1 - Date created - 1997-03-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Childhood-onset schizophrenia. A double-blind clozapine-haloperidol comparison. AN - 78615674; 8956674 AB - Childhood-onset schizophrenia is a rare but severe form of the disorder that is often treatment-refractory. In this study, the efficacy and adverse effects of clozapine and haloperidol were compared for children and adolescents with early-onset schizophrenia. Twenty-one patients (mean [+/-SD] age, 14.0 +/- 2.3 years) with onset of Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition-defined schizophrenia that began by age 12 years and who had been nonresponsive to typical neuroleptics participated in the study. Patients were randomized to a 6-week double-blind parallel comparison of clozapine (mean [+/-SD] final dose, 176 +/- 149 mg/d), or haloperidol, (16 +/- 8 mg/d). Clozapine was superior to haloperidol on all measures of psychosis (P = .04-.002). Positive and negative symptoms of schizophrenia improved. However, neutropenia and seizures were major concerns. To date, one third of the group has discontinued using clozapine. Clozapine has striking superiority for positive and negative symptoms in treatment-refractory childhood-onset schizophrenia. However, due to possibly increased toxic effects in this pediatric population, close monitoring for adverse events is essential. JF - Archives of general psychiatry AU - Kumra, S AU - Frazier, J A AU - Jacobsen, L K AU - McKenna, K AU - Gordon, C T AU - Lenane, M C AU - Hamburger, S D AU - Smith, A K AU - Albus, K E AU - Alaghband-Rad, J AU - Rapoport, J L AD - Child Psychiatry Branch, National Institute of Mental Health, Bethesda, Md, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 1090 EP - 1097 VL - 53 IS - 12 SN - 0003-990X, 0003-990X KW - Clozapine KW - J60AR2IKIC KW - Haloperidol KW - J6292F8L3D KW - Abridged Index Medicus KW - Index Medicus KW - Severity of Illness Index KW - Seizures -- chemically induced KW - Drug Administration Schedule KW - Age Factors KW - Psychiatric Status Rating Scales KW - Double-Blind Method KW - Age of Onset KW - Humans KW - Treatment Outcome KW - Neutropenia -- chemically induced KW - Child KW - Adolescent KW - Child, Preschool KW - Haloperidol -- adverse effects KW - Haloperidol -- therapeutic use KW - Clozapine -- therapeutic use KW - Schizophrenia, Childhood -- psychology KW - Schizophrenia, Childhood -- drug therapy KW - Clozapine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78615674?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+general+psychiatry&rft.atitle=Childhood-onset+schizophrenia.+A+double-blind+clozapine-haloperidol+comparison.&rft.au=Kumra%2C+S%3BFrazier%2C+J+A%3BJacobsen%2C+L+K%3BMcKenna%2C+K%3BGordon%2C+C+T%3BLenane%2C+M+C%3BHamburger%2C+S+D%3BSmith%2C+A+K%3BAlbus%2C+K+E%3BAlaghband-Rad%2C+J%3BRapoport%2C+J+L&rft.aulast=Kumra&rft.aufirst=S&rft.date=1996-12-01&rft.volume=53&rft.issue=12&rft.spage=1090&rft.isbn=&rft.btitle=&rft.title=Archives+of+general+psychiatry&rft.issn=0003990X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-10 N1 - Date created - 1997-01-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Arch Gen Psychiatry. 1998 Jan;55(1):90-2 [9435769] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The glutathione S-transferase M1 (GSTM1) null genotype and benzidine-associated bladder cancer, urine mutagenicity, and exfoliated urothelial cell DNA adducts. AN - 78612680; 8959320 AB - Multiple studies in the general population have suggested that subjects with the glutathione S-transferase M1 (GSTM1)-null genotype, who lack functional GSTM1, are at higher risk for bladder cancer. To evaluate the impact of the GSTM1-null genotype on bladder cancer caused by occupational exposure to benzidine and to determine its influence on benzidine metabolism, we carried out three complementary investigations: a case-control study of bladder cancer among workers previously exposed to benzidine in China, a cross-sectional study of urothelial cell DNA adducts and urinary mutagenicity in workers currently exposed to benzidine in India, and a laboratory study of the ability of human GSTM1 to conjugate benzidine and its known metabolites in vitro. There was no overall increase in bladder cancer risk for the GSTM1-null genotype among 38 bladder cancer cases and 43 controls (odds ratio, 1.0; 95% confidence interval, 0.4-2.7), although there was some indication that highly exposed workers with the GSTM1-null genotype were at greater risk of bladder cancer compared to similarly exposed workers without this allele. However, the GSTM1 genotype had no impact on urothelial cell DNA adduct and urinary mutagenicity levels in workers currently exposed to benzidine. Furthermore, human GSTM1 did not conjugate benzidine or its metabolites. These results led us to conclude that the GSTM1-null genotype does not have an impact on bladder cancer caused by benzidine, providing a contrast to its association with elevated bladder cancer risk in the general population. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Rothman, N AU - Hayes, R B AU - Zenser, T V AU - DeMarini, D M AU - Bi, W AU - Hirvonen, A AU - Talaska, G AU - Bhatnagar, V K AU - Caporaso, N E AU - Brooks, L R AU - Lakshmi, V M AU - Feng, P AU - Kashyap, S K AU - You, X AU - Eischen, B T AU - Kashyap, R AU - Shelton, M L AU - Hsu, F F AU - Jaeger, M AU - Parikh, D J AU - Davis, B B AU - Yin, S AU - Bell, D A AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 979 EP - 983 VL - 5 IS - 12 SN - 1055-9965, 1055-9965 KW - Benzidines KW - 0 KW - DNA Adducts KW - DNA, Neoplasm KW - benzidine KW - 2X02101HVF KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Humans KW - Retrospective Studies KW - DNA, Neoplasm -- analysis KW - Genotype KW - Cross-Sectional Studies KW - Mutagenicity Tests KW - Risk Factors KW - China -- epidemiology KW - Case-Control Studies KW - Occupational Exposure -- adverse effects KW - Middle Aged KW - Male KW - Prevalence KW - Urothelium -- metabolism KW - Urinary Bladder Neoplasms -- epidemiology KW - Glutathione Transferase -- metabolism KW - Urothelium -- chemistry KW - Glutathione Transferase -- genetics KW - Occupational Diseases -- chemically induced KW - Occupational Diseases -- urine KW - Benzidines -- adverse effects KW - Occupational Diseases -- enzymology KW - Benzidines -- metabolism KW - Urothelium -- pathology KW - DNA Adducts -- analysis KW - Urinary Bladder Neoplasms -- urine KW - Urinary Bladder Neoplasms -- enzymology KW - Occupational Diseases -- epidemiology KW - Urinary Bladder Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78612680?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+glutathione+S-transferase+M1+%28GSTM1%29+null+genotype+and+benzidine-associated+bladder+cancer%2C+urine+mutagenicity%2C+and+exfoliated+urothelial+cell+DNA+adducts.&rft.au=Rothman%2C+N%3BHayes%2C+R+B%3BZenser%2C+T+V%3BDeMarini%2C+D+M%3BBi%2C+W%3BHirvonen%2C+A%3BTalaska%2C+G%3BBhatnagar%2C+V+K%3BCaporaso%2C+N+E%3BBrooks%2C+L+R%3BLakshmi%2C+V+M%3BFeng%2C+P%3BKashyap%2C+S+K%3BYou%2C+X%3BEischen%2C+B+T%3BKashyap%2C+R%3BShelton%2C+M+L%3BHsu%2C+F+F%3BJaeger%2C+M%3BParikh%2C+D+J%3BDavis%2C+B+B%3BYin%2C+S%3BBell%2C+D+A&rft.aulast=Rothman&rft.aufirst=N&rft.date=1996-12-01&rft.volume=5&rft.issue=12&rft.spage=979&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-12 N1 - Date created - 1997-03-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risk factors for in situ breast cancer. AN - 78612293; 8959317 AB - Few data exist on risk factors for in situ breast carcinoma. We examined risk factors for in situ breast carcinoma in data from two population-based case-control studies of breast cancer conducted among female residents of Los Angeles County. Cases with in situ or invasive disease were identified through the cancer registry for Los Angeles Country in the 1980s. We included all cases ages 40 years or younger diagnosed over a 5.5-year period and all cases ages 55-64 years diagnosed over a 3-year period. Control subjects were individually matched to cases by age (+/-3 years), neighborhood of residence, and, for younger controls, parity (nulliparous versus parous). The analysis included 233 cases with in situ cancer, 2057 cases with invasive cancer, and 2203 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted for screening mammography and established risk factors. In general, risk factors for in situ breast cancer were similar to those for invasive disease in this population. In premenopausal women, however, the risk of in situ breast cancer decreased with increasing body mass index, whereas for invasive disease, body mass index was unrelated to risk. In addition, in postmenopausal women with known age at menopause, use of unopposed estrogen replacement therapy was associated with increased risk of in situ disease [OR for ever use of estrogen alone was 1.60 (95% CI, 1.00-2.58)], whereas for invasive disease the OR was 1.23 (95% CI, 1.00-1.50). A similar difference was seen for combined hormone replacement therapy. Unmeasured increased screening among estrogen or combined replacement hormone users compared with nonusers could account for some of the association of in situ breast cancer risk with hormone replacement use. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Longnecker, M P AU - Bernstein, L AU - Paganini-Hill, A AU - Enger, S M AU - Ross, R K AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 961 EP - 965 VL - 5 IS - 12 SN - 1055-9965, 1055-9965 KW - Index Medicus KW - Mammography KW - Humans KW - Retrospective Studies KW - Body Mass Index KW - Mass Screening -- methods KW - Estrogen Replacement Therapy -- adverse effects KW - Risk Factors KW - Adult KW - Case-Control Studies KW - Incidence KW - Interviews as Topic KW - Middle Aged KW - California -- epidemiology KW - Female KW - Carcinoma in Situ -- chemically induced KW - Breast Neoplasms -- prevention & control KW - Carcinoma in Situ -- epidemiology KW - Breast Neoplasms -- epidemiology KW - Breast Neoplasms -- chemically induced KW - Carcinoma in Situ -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78612293?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Risk+factors+for+in+situ+breast+cancer.&rft.au=Longnecker%2C+M+P%3BBernstein%2C+L%3BPaganini-Hill%2C+A%3BEnger%2C+S+M%3BRoss%2C+R+K&rft.aulast=Longnecker&rft.aufirst=M&rft.date=1996-12-01&rft.volume=5&rft.issue=12&rft.spage=961&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-12 N1 - Date created - 1997-03-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanistic studies of the inhibition of MutT dGTPase by the carcinogenic metal Ni(II). AN - 78599308; 8951243 AB - Promutagenic 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) levels are increased in DNA of animals exposed to carcinogenic metals, such as Ni(II). Besides being generated directly in genomic DNA, 8-oxo-dG may be incorporated there from 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate (8-oxo-dGTP), a product of oxidative damage to the nucleotide pool. The Escherichia coli dGTPase MutT, and analogous dGTPases in rats and humans, have been suggested as a defense against such incorporation because they hydrolyze 8-oxo-dGTP to 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-monophosphate (8-oxo-dGMP). MutT and its mammalian counterparts are Mg(II)-dependent enzymes. Ni(II), in turn, is known to interact antagonistically with Mg(II) in biological systems. Thus, we hypothesized that Ni(II) might inhibit the activity of MutT. As an initial examination of this hypothesis, we conducted enzyme kinetic studies of MutT to determine the effect of Ni(II) on MutT activity and the mechanisms involved. As found, Ni(II) inhibited MutT in a concentration-dependent manner when either dGTP or 8-oxo-dGTP was the nucleotide substrate. Ni(II) was determined to be an uncompetitive inhibitor of MutT with respect to Mg(II) when dGTP was the substrate, with apparent Ki of 1.2 mM Ni(II), and a noncompetitive inhibitor with respect to Mg(II) when 8-oxo-dGTP was the substrate, with apparent Ki of 0.9 mM Ni(II). Hence, the two metal cations did not compete with each other for binding at the MutT active site. This makes it difficult to predict Ni(II) effects on 8-oxo-dGTPases of other species. However, based upon the amino acid sequences of human and rat MutT-like dGTPases, their capacity for Ni(II) binding should be greater than that of MutT. Whether this could lead to stronger inhibition of those enzymes by Ni(II), or not, remains to be investigated. JF - Chemical research in toxicology AU - Porter, D W AU - Nelson, V C AU - Fivash, M J AU - Kasprzak, K S AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute-FCRDC, Frederick, Maryland 21702, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 1375 EP - 1381 VL - 9 IS - 8 SN - 0893-228X, 0893-228X KW - Carcinogens KW - 0 KW - Nickel KW - 7OV03QG267 KW - Phosphoric Monoester Hydrolases KW - EC 3.1.3.2 KW - Index Medicus KW - Rats KW - Animals KW - Kinetics KW - Humans KW - Models, Chemical KW - Escherichia coli -- enzymology KW - Chromatography, High Pressure Liquid KW - Carcinogens -- pharmacology KW - Nickel -- pharmacology KW - Phosphoric Monoester Hydrolases -- genetics KW - Phosphoric Monoester Hydrolases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78599308?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mechanistic+studies+of+the+inhibition+of+MutT+dGTPase+by+the+carcinogenic+metal+Ni%28II%29.&rft.au=Porter%2C+D+W%3BNelson%2C+V+C%3BFivash%2C+M+J%3BKasprzak%2C+K+S&rft.aulast=Porter&rft.aufirst=D&rft.date=1996-12-01&rft.volume=9&rft.issue=8&rft.spage=1375&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-17 N1 - Date created - 1997-03-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Plasma protein binding of phenylacetate and phenylbutyrate, two novel antineoplastic agents. AN - 78592251; 8946671 AB - Phenylacetate and phenylbutyrate, two novel inducers of tumor cytostasis and differentiation, are currently in clinical trials for the treatment of cancer in adults. The purpose of our study was to evaluate the plasma protein-binding characteristics of phenylacetate and phenylbutyrate in the plasma of normal volunteers and that of patients with cancer. Drug plasma protein-binding analysis was examined using three separate devices: a micropartition system and two equilibrium dialysis systems, all of which exhibited similar results. Phenylacetate and phenylbutyrate concentrations were determined by high-performance liquid chromatography. Both drugs exhibited concentration-dependent binding. Our results showed sodium phenylacetate to have a higher free fraction than sodium phenylbutyrate at corresponding concentrations (> 0.442 +/- 0.008 and > 0.188 +/- 0.001, respectively). Plasma pH did not greatly affect protein binding of either drug. As albumin concentration decreased, an increase in free fraction of both drugs was observed, however alpha 1-acid glyco-protein showed no change in free fraction as its concentration increased. Patients with cancer with lower levels of albumin showed an increase in free fraction with both phenylacetate and phenylbutyrate. When phenylacetate and phenylbutyrate were added together in plasma, the free fraction of phenylacetate increased, whereas the phenylbutyrate free fraction slightly decreased. We conclude that phenylacetate and phenylbutyrate have high free fractions that change with varying albumin levels and when both phenylacetate and phenylbutyrate are present together in plasma. JF - Therapeutic drug monitoring AU - Boudoulas, S AU - Lush, R M AU - McCall, N A AU - Samid, D AU - Reed, E AU - Figg, W D AD - Clinical Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 714 EP - 720 VL - 18 IS - 6 SN - 0163-4356, 0163-4356 KW - Antimetabolites, Antineoplastic KW - 0 KW - Phenylacetates KW - Phenylbutyrates KW - Serum Albumin KW - phenylacetic acid KW - ER5I1W795A KW - Index Medicus KW - Serum Albumin -- metabolism KW - Neoplasms -- drug therapy KW - Hydrogen-Ion Concentration KW - Humans KW - Neoplasms -- blood KW - Adult KW - Protein Binding KW - Phenylbutyrates -- therapeutic use KW - Phenylbutyrates -- blood KW - Phenylacetates -- blood KW - Antimetabolites, Antineoplastic -- blood KW - Antimetabolites, Antineoplastic -- therapeutic use KW - Phenylacetates -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78592251?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Therapeutic+drug+monitoring&rft.atitle=Plasma+protein+binding+of+phenylacetate+and+phenylbutyrate%2C+two+novel+antineoplastic+agents.&rft.au=Boudoulas%2C+S%3BLush%2C+R+M%3BMcCall%2C+N+A%3BSamid%2C+D%3BReed%2C+E%3BFigg%2C+W+D&rft.aulast=Boudoulas&rft.aufirst=S&rft.date=1996-12-01&rft.volume=18&rft.issue=6&rft.spage=714&rft.isbn=&rft.btitle=&rft.title=Therapeutic+drug+monitoring&rft.issn=01634356&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-16 N1 - Date created - 1997-04-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - N-methyl-D-aspartate antagonists limit aminoglycoside antibiotic-induced hearing loss. AN - 78581333; 8946832 AB - The use of aminoglycoside antibiotics is limited by ototoxicity that can produce permanent hearing loss. We report that concurrent administration of N-methyl-D-aspartate (NMDA) antagonists markedly attenuates both the hearing loss and destruction of cochlear hair cells in guinea pigs treated with aminoglycoside antibiotics. These findings indicate that aminoglycoside-induced hearing loss is mediated, in part, through an excitotoxic process. The high correlation (Spearman correlation coefficient: 0.928; P < 0.01) obtained between the relative cochleotoxicities of a series of aminoglycosides in humans and the potencies of these compounds to produce a polyamine-like enhancement of [3H]dizocilpine binding to NMDA receptors is consistent with this hypothesis, and provides a simple in vitro assay that can predict this aspect of aminoglycoside-induced ototoxicity. JF - Nature medicine AU - Basile, A S AU - Huang, J M AU - Xie, C AU - Webster, D AU - Berlin, C AU - Skolnick, P AD - Laboratory of Neuroscience, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 1338 EP - 1343 VL - 2 IS - 12 SN - 1078-8956, 1078-8956 KW - Anti-Bacterial Agents KW - 0 KW - Excitatory Amino Acid Antagonists KW - Piperidines KW - Receptors, N-Methyl-D-Aspartate KW - Neomycin KW - 1404-04-2 KW - Kanamycin KW - 59-01-8 KW - N-Methylaspartate KW - 6384-92-5 KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - ifenprodil KW - R8OE3P6O5S KW - Index Medicus KW - Animals KW - Neomycin -- adverse effects KW - Dizocilpine Maleate -- metabolism KW - Guinea Pigs KW - Kanamycin -- adverse effects KW - Receptors, N-Methyl-D-Aspartate -- metabolism KW - Radioligand Assay KW - Hair Cells, Auditory KW - Piperidines -- metabolism KW - Dizocilpine Maleate -- pharmacology KW - Rats KW - Piperidines -- pharmacology KW - Rats, Sprague-Dawley KW - Hearing Tests KW - Cochlea -- pathology KW - Prosencephalon KW - Male KW - Excitatory Amino Acid Antagonists -- metabolism KW - Anti-Bacterial Agents -- adverse effects KW - N-Methylaspartate -- antagonists & inhibitors KW - Hearing Loss -- pathology KW - Hearing Loss -- chemically induced KW - Hearing Loss -- prevention & control KW - Excitatory Amino Acid Antagonists -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78581333?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=N-methyl-D-aspartate+antagonists+limit+aminoglycoside+antibiotic-induced+hearing+loss.&rft.au=Basile%2C+A+S%3BHuang%2C+J+M%3BXie%2C+C%3BWebster%2C+D%3BBerlin%2C+C%3BSkolnick%2C+P&rft.aulast=Basile&rft.aufirst=A&rft.date=1996-12-01&rft.volume=2&rft.issue=12&rft.spage=1338&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 - 1997-01-07 N1 - Date created - 1997-01-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Nat Med. 1996 Dec;2(12):1313-4 [8946827] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Estrogens for prevention of coronary heart disease. Putting the brakes on the bandwagon. AN - 78577277; 8941130 JF - Circulation AU - Rossouw, J E AD - Office of Disease Prevention, National Institutes of Health, Bethesda, Md, USA. JacquesvRossouw@NIH.GOV Y1 - 1996/12/01/ PY - 1996 DA - 1996 Dec 01 SP - 2982 EP - 2985 VL - 94 IS - 11 SN - 0009-7322, 0009-7322 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Breast Neoplasms -- chemically induced KW - Female KW - Coronary Disease -- prevention & control KW - Estrogen Replacement Therapy -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78577277?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Circulation&rft.atitle=Estrogens+for+prevention+of+coronary+heart+disease.+Putting+the+brakes+on+the+bandwagon.&rft.au=Rossouw%2C+J+E&rft.aulast=Rossouw&rft.aufirst=J&rft.date=1996-12-01&rft.volume=94&rft.issue=11&rft.spage=2982&rft.isbn=&rft.btitle=&rft.title=Circulation&rft.issn=00097322&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-02 N1 - Date created - 1997-01-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Circulation. 1996 Dec 1;94(11):2699-702 [8941091] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation of LH receptors expressed in GnRH neurons stimulates cyclic AMP production and inhibits pulsatile neuropeptide release. AN - 78571983; 8940408 AB - The GT1-7 cell line of immortalized GnRH neurons has been shown to express receptors for GnRH, LH, and prolactin, as well as a variety of other hormones and transmitters. Treatment of GT1-7 cells with hCG caused a dose-dependent increase in cAMP production, with a rapid increase during the first 15 min and a subsequent decrease that was prevented by pre-treatment with pertussis toxin. Furthermore, the stimulatory effect of cholera toxin on cAMP production was inhibited by hCG in a dose-dependent manner. These data indicate that the LH receptors expressed in GT1-7 cells are coupled to adenylyl cyclase both stimulatory (Gs) and inhibitory (Gi) proteins. In perifused cell cultures, treatment with forskolin and 8-bromo cAMP increased the amplitude of spontaneous GnRH release. However, treatment with nanomolar concentrations of hCG abolished pulsatile GnRH release from both GT1-7 cells and rat hypothalamic cells. The similarity of hCG action on pulsatile GnRH release to that of extracellular Ca2+ depletion and calcium channel antagonists, and its partial resistance to potassium-induced depolarization, suggest that it results from inhibition of plasma-membrane ion channel activity. It is probable that the inhibitory action of hCG on pulsatile GnRH release is responsible for initiation of the suppression of pituitary LH secretion during pregnancy. JF - Endocrinology AU - Mores, N AU - Krsmanovic, L Z AU - Catt, K J AD - Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 5731 EP - 5734 VL - 137 IS - 12 SN - 0013-7227, 0013-7227 KW - Adenylate Cyclase Toxin KW - 0 KW - Chorionic Gonadotropin KW - Neuropeptides KW - Receptors, LH KW - Virulence Factors, Bordetella KW - Colforsin KW - 1F7A44V6OU KW - Gonadotropin-Releasing Hormone KW - 33515-09-2 KW - Cholera Toxin KW - 9012-63-9 KW - Cyclic AMP KW - E0399OZS9N KW - Pertussis Toxin KW - EC 2.4.2.31 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Hypothalamus -- cytology KW - Hypothalamus -- embryology KW - Cholera Toxin -- pharmacology KW - Binding Sites KW - Rats KW - Virulence Factors, Bordetella -- pharmacology KW - Colforsin -- pharmacology KW - Chorionic Gonadotropin -- pharmacology KW - Hypothalamus -- metabolism KW - Binding, Competitive KW - Pulsatile Flow KW - Cell Line KW - Neuropeptides -- metabolism KW - Gonadotropin-Releasing Hormone -- metabolism KW - Cyclic AMP -- biosynthesis KW - Neurons -- metabolism KW - Receptors, LH -- drug effects KW - Neurons -- drug effects KW - Gonadotropin-Releasing Hormone -- antagonists & inhibitors KW - Receptors, LH -- metabolism KW - Neuropeptides -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78571983?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Activation+of+LH+receptors+expressed+in+GnRH+neurons+stimulates+cyclic+AMP+production+and+inhibits+pulsatile+neuropeptide+release.&rft.au=Mores%2C+N%3BKrsmanovic%2C+L+Z%3BCatt%2C+K+J&rft.aulast=Mores&rft.aufirst=N&rft.date=1996-12-01&rft.volume=137&rft.issue=12&rft.spage=5731&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-23 N1 - Date created - 1997-01-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Copper(II) interactions with an experimental antiviral agent, I-deoxynojirimycin, and oxygen activation by resulting complexes. AN - 78531217; 8916412 AB - 1-deoxynojirimycin (DNJ), a 5-imino analog of 1-deoxyglucose, is a potent inhibitor of alpha-glucosidase 1. DNJ and its derivatives have been considered as experimental drugs against human HIV-1 and hepatitis B viruses. Since amino and imino ligands have a high affinity for copper, it seems possible that biological activity of DNJ may be, at least in part, modulated by tissue copper. To test this possibility, potentiometric and spectroscopic studies of the complexation of DNJ by cupric ions were performed in order to obtain thermodynamic and structural background for further pharmacologic investigations. The effect of histidine, a major tissue copper carrier, on coordination equilibria was also studied. Results indicate that DNJ and Cu(II) form two stable complexes at physiological pH, CuH-1(DNJ)2+ and CuH-2(DNJ)2, involving Cu(II) chelation by the N-5 and O-6 donor atoms. In the presence of histidine, ternary complexes are also formed, of which the CuDNJHis+ species is stable in the physiological pH range. Binary Cu(II)-DNJ complexes are extremely effective mediators of in vitro oxidation of the guanine moiety in both 2'-deoxyguanosine (dG) and DNA to 8-oxoguanine (8-oxo-dG) and of DNA double strand scission by ambient O2 or H2O2. This mediation is suppressed by histidine in dG, but not in DNA. The results suggest that tissue Cu(II) may greatly enhance nonspecific cytotoxic effects of systemically administered DNJ through oxidative damage mechanisms, and therefore the prospective use of DNJ for therapeutic purposes must be developed with caution. On the other hand, however, the expected high genotoxic potential of synthetic Cu(II)-DNJ complexes may be used against viruses by means of targeted delivery of these complexes to the infected cells. JF - Journal of inorganic biochemistry AU - Jezowska-Bojczuk, M AU - Bal, W AU - Kasprzak, K S AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland, USA. Y1 - 1996/12// PY - 1996 DA - December 1996 SP - 231 EP - 246 VL - 64 IS - 4 SN - 0162-0134, 0162-0134 KW - Antiviral Agents KW - 0 KW - Phosphates KW - 1-Deoxynojirimycin KW - 19130-96-2 KW - Histidine KW - 4QD397987E KW - Copper KW - 789U1901C5 KW - Index Medicus KW - AIDS/HIV KW - Oxidation-Reduction KW - Molecular Structure KW - Histidine -- chemistry KW - Drug Stability KW - Drug Interactions KW - DNA Damage KW - Phosphates -- chemistry KW - Spectrum Analysis -- methods KW - Potentiometry KW - Antiviral Agents -- chemistry KW - 1-Deoxynojirimycin -- chemistry KW - Copper -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78531217?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+inorganic+biochemistry&rft.atitle=Copper%28II%29+interactions+with+an+experimental+antiviral+agent%2C+I-deoxynojirimycin%2C+and+oxygen+activation+by+resulting+complexes.&rft.au=Jezowska-Bojczuk%2C+M%3BBal%2C+W%3BKasprzak%2C+K+S&rft.aulast=Jezowska-Bojczuk&rft.aufirst=M&rft.date=1996-12-01&rft.volume=64&rft.issue=4&rft.spage=231&rft.isbn=&rft.btitle=&rft.title=Journal+of+inorganic+biochemistry&rft.issn=01620134&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-30 N1 - Date created - 1997-01-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical features of hematopoietic malignancies and related disorders among benzene-exposed workers in China. Benzene Study Group. AN - 21260148; 11701770 AB - Previous occupational cohort studies of benzene-exposed workers have for the most part used only death certificates to validate diagnoses of workers developing leukemia and other hematopoietic and lymphoproliferative malignancies and related disorders (HLD). In a follow-up study of 74,828 benzene-exposed workers and a comparison group of 35,805 nonexposed workers from 12 cities in China, we sought to characterized clinicopathologically and to confirm diagnoses of all cases of HLD. Using medical records, laboratory hematology results, and histopathology, U.S. and Chinese expert hematopathologists, blinded to exposure status, carried out a detailed review using standardized evaluation forms. Key among the findings were a notable diversity of malignant and nonneoplastic hematopoietic and lymphoproliferative disorders, documentation of excess myelodysplastic syndromes among benzene workers, and widespread dyspoiesis involving all hematopoietic cell lines. As sophisticated clinicopathologic characterization and corresponding classification schemes for HLD become increasingly widespread, it is recommended that future epidemiologic investigations of benzene workers incorporate similarly detailed morphologic evaluation. In extending follow-up of this cohort of young workers, we will continue to use all available clinical, laboratory hematology, and pathology data as well as cytogenetic and biochemical markers to characterized various HLD outcomes. These careful surveillance mechanisms should also provide additional insight into carcinogenic mechanisms of benzene and allow comparison of the molecular pathogenesis of HLD induced by benzene versus chemotherapy, radiation, or other exposure. JF - Environmental Health Perspectives AU - Linet, M S AU - Yin, S N AU - Travis, L B AU - Li, C Y AU - Zhang, Z N AU - Li, D G AU - Rothman, N AU - Li, G L AU - Chow, W H AU - Donaldson, J AU - Dosemeci, M AU - Wacholder, S AU - Blot, W J AU - Hayes, R B AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892-7368, USA., linetm@epndce.nci.nih.gov Y1 - 1996/12// PY - 1996 DA - Dec 1996 SP - 1353 EP - 1364 PB - US Government Printing Office, Superintendent of Documents, P.O. Box 371954 Pittsburgh PA 15250-7954 USA VL - 104 IS - Suppl 6 SN - 0091-6765, 0091-6765 KW - Environment Abstracts KW - Mortality KW - USA KW - Biochemistry KW - Pathology KW - Carcinogenicity KW - Hematology KW - Standards KW - China, People's Rep. KW - Occupational exposure KW - Benzene KW - chemotherapy KW - ENA 02:Toxicology & Environmental Safety UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21260148?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aenvabstractsmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=Clinical+features+of+hematopoietic+malignancies+and+related+disorders+among+benzene-exposed+workers+in+China.+Benzene+Study+Group.&rft.au=Linet%2C+M+S%3BYin%2C+S+N%3BTravis%2C+L+B%3BLi%2C+C+Y%3BZhang%2C+Z+N%3BLi%2C+D+G%3BRothman%2C+N%3BLi%2C+G+L%3BChow%2C+W+H%3BDonaldson%2C+J%3BDosemeci%2C+M%3BWacholder%2C+S%3BBlot%2C+W+J%3BHayes%2C+R+B&rft.aulast=Linet&rft.aufirst=M&rft.date=1996-12-01&rft.volume=104&rft.issue=Suppl+6&rft.spage=1353&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-01-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Mortality; Pathology; Biochemistry; Carcinogenicity; Standards; Hematology; chemotherapy; Benzene; Occupational exposure; USA; China, People's Rep. ER - TY - JOUR T1 - The Dawn of a New Era AN - 21128593; 11162277 AB - This paper reviews the scientific events culminating in the fluoridation of communal water supplies. Dental and medical studies completed by 1942 had established the safety and benefits of exposure to drinking water naturally containing fluoride. Researchers and public health workers concluded that it was possible to test the hypothesis that the dental benefits attained where fluoride levels around 1 ppm occurred naturally in drinking water could be safely replicated in low-fluoride areas by raising the level to this optimal concentration. Grand Rapids became the first test site and by the time the demonstration ended in 1959, around 40 million people in about 2,000 communities already were drinking water with fluoride levels that had been adjusted to optimal. The success of fluoridation brought the dawn of the era of caries control and created great opportunities for research and public health. JF - Journal of Public Health Dentistry AU - Scott, David B AD - Dr. Scott, formerly director, National Institute of Dental Research, National Institutes of Health, Bethesda, MD, currently resides at 9100 Belvoir Woods Parkway, Apt. 209, Fort Belvoir, VA 22060-2713. Y1 - 1996/12// PY - 1996 DA - Dec 1996 SP - 235 EP - 238 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 USA VL - 56 IS - 5 SN - 0022-4006, 0022-4006 KW - Health & Safety Science Abstracts KW - Water supplies KW - Public health KW - dentistry KW - Fluoride KW - Reviews KW - Drinking water KW - Occupational exposure KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21128593?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Public+Health+Dentistry&rft.atitle=The+Dawn+of+a+New+Era&rft.au=Scott%2C+David+B&rft.aulast=Scott&rft.aufirst=David&rft.date=1996-12-01&rft.volume=56&rft.issue=5&rft.spage=235&rft.isbn=&rft.btitle=&rft.title=Journal+of+Public+Health+Dentistry&rft.issn=00224006&rft_id=info:doi/10.1111%2Fj.1752-7325.1996.tb02444.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Fluoride; Drinking water; Public health; Reviews; Occupational exposure; Water supplies; dentistry DO - http://dx.doi.org/10.1111/j.1752-7325.1996.tb02444.x ER - TY - JOUR T1 - Human microglia convert L-tryptophan into the neurotoxin quinolinic acid AN - 16025151; 4094169 AB - Immune activation leads to accumulations of the neurotoxin and kynurenine pathway metabolite quinolinic acid within the central nervous system of human patients. Whereas macrophages can convert L-tryptophan to quinolinic acid, it is not known whether human brain microglia can synthesize quinolinic acid. Human microglia, peripheral blood macrophages and cultures of human fetal brain cells (astrocytes and neurons) were incubated with [ super(13)C sub(6)]L-tryptophan in the absence or presence of interferon gamma . [ super(13)C sub(6)]Quinolinic acid was identified and quantified by gas chromatography and electron-capture negative-chemical ionization mass spectrometry. Both L-kynurenine and [ super(13)C sub(6)]quinolinic acid were produced by unstimulated cultures of microglia and macrophages. Interferon gamma , an inducer of indoleamine 2,3-dioxygenase, increased the accumulation of L-kynurenine by all three cell types (to more than 40 mu M). Whereas large quantities of [ super(13)C sub(6)]quinolinic acid were produced by microglia and macrophages (to 438 and 1410 nM respectively), minute quantities of [ super(13)C sub(6)]quinolinic acid were produced in human fetal brain cultures (not more than 2 nM). Activated microglia and macrophage infiltrates into the brain might be an important source of accelerated conversion of L-tryptophan into quinolinic acid within the central nervous system in inflammatory diseases. JF - Biochemical Journal AU - Heyes, M P AU - Achim, CL AU - Wiley, CA AU - Major, E O AU - Saito, K AU - Markey, S P AD - Section on Analytical Biochemistry, Laboratory of Clinical Science, Building 10,9000 Rockville Pike, National Institute of Mental Health, Bethesda, MD 20892, USA Y1 - 1996/12// PY - 1996 DA - Dec 1996 VL - 320 IS - 2 SN - 0264-6021, 0264-6021 KW - cell culture KW - man KW - brain KW - microglial cells KW - Tryptophan KW - quinolinic acid KW - L-tryptophan KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - X 24120:Food, additives & contaminants KW - N3 11073:Glial cell biology and metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16025151?accountid=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=Biochemical+Journal&rft.atitle=Human+microglia+convert+L-tryptophan+into+the+neurotoxin+quinolinic+acid&rft.au=Heyes%2C+M+P%3BAchim%2C+CL%3BWiley%2C+CA%3BMajor%2C+E+O%3BSaito%2C+K%3BMarkey%2C+S+P&rft.aulast=Heyes&rft.aufirst=M&rft.date=1996-12-01&rft.volume=320&rft.issue=2&rft.spage=microglial+cells&rft.isbn=&rft.btitle=&rft.title=Biochemical+Journal&rft.issn=02646021&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 - brain ER - TY - JOUR T1 - Structural analysis of the native and drug-resistant HIV-1 proteinases complexed with an aminodiol inhibitor AN - 15786799; 3991747 AB - Crystal structures of the native HIV-1 proteinase and an A71T/V82A mutant have been solved in complexes with a symmetric aminodiol inhibitor, BMS-182193. Some of the conformational differences between these two complexes can be traced to their non-isomorphous crystal forms, but numerous rearrangements due to mutations are clearly visible. The V82A mutation creates more space at the periphery of the active site cleft, allowing distal parts of the inhibitor to move more freely, whereas the non-active-site mutation A71T stabilizes the enzyme backbone. The role of mutations in eliciting drug resistance is discussed. JF - Protein & Peptide Letters AU - Kervinen, J AU - Thanki, N AU - Zdanov, A AU - Tino, J AU - Barrish, J AU - Lin, P F AU - Calonno, R AU - Riccardi, K AU - Samanta, H AU - Wlodawer, A AD - Macromol. Struct. Lab., NCI-Frederick Cancer Res. and Dev. Cent., ABL-Basic Res. Prog., Frederick, MD 21702, USA Y1 - 1996/12// PY - 1996 DA - Dec 1996 SP - 399 EP - 406 VL - 3 IS - 6 SN - 0929-8665, 0929-8665 KW - proteinase KW - aminodiol KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - stabilization KW - human immunodeficiency virus 1 KW - inhibitors KW - mutation KW - drug resistance KW - crystallography KW - V 22002:AIDS: Molecular and in vitro aspects KW - A 01064:Microbial resistance UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15786799?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+%26+Peptide+Letters&rft.atitle=Structural+analysis+of+the+native+and+drug-resistant+HIV-1+proteinases+complexed+with+an+aminodiol+inhibitor&rft.au=Kervinen%2C+J%3BThanki%2C+N%3BZdanov%2C+A%3BTino%2C+J%3BBarrish%2C+J%3BLin%2C+P+F%3BCalonno%2C+R%3BRiccardi%2C+K%3BSamanta%2C+H%3BWlodawer%2C+A&rft.aulast=Kervinen&rft.aufirst=J&rft.date=1996-12-01&rft.volume=3&rft.issue=6&rft.spage=399&rft.isbn=&rft.btitle=&rft.title=Protein+%26+Peptide+Letters&rft.issn=09298665&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; drug resistance; crystallography; mutation; stabilization; inhibitors ER - TY - JOUR T1 - Detection of heterozygous mutations in BRCA1 using high density oligonucleotide arrays and two-colour fluorescence analysis AN - 15774880; 3989317 AB - The ability to scan a large gene rapidly and accurately for all possible heterozygous mutations in large numbers of patient samples will be critical for the future of medicine. We have designed high-density arrays consisting of over 96,600 oligonucleotides 20-nucleotides (nt) in length to screen for a wide range of heterozygous mutations in the 3.45-kilobases (kb) exon 11 of the hereditary breast and ovarian cancer gene BRCA1. Reference and test samples were co-hybridized to these arrays and differences in hybridization patterns quantitated by two-colour analysis. Fourteen of fifteen patient samples with known mutations were accurately diagnosed, and no false positive mutations were identified in 20 control samples. Eight single nucleotide polymorphisms were also readily detected. DNA chip-based assays may provide a valuable new technology for high-throughput cost-efficient detection of genetic alterations. JF - Nature Genetics AU - Hacia, J G AU - Brody, L C AU - Chee AU - Fodor, SPA AU - Collins, F S AD - National Center for Human Genome Research, Building 49/3A14, National Institutes of Health, Bethesda, Maryland 20892, USA Y1 - 1996/12// PY - 1996 DA - Dec 1996 SP - 441 EP - 447 VL - 14 IS - 4 SN - 1061-4036, 1061-4036 KW - BRCA1 gene KW - DNA KW - man KW - oligonucleotides KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Genetics Abstracts; Oncogenes & Growth Factors Abstracts KW - breast carcinoma KW - fluorescence KW - ovarian carcinoma KW - mutation KW - G 07470:Cytogenetics & general KW - B 26400:HUMAN-RELATED ONCOGENES AND GROWTH FACTORS: CROSS REFERENCES KW - B 26416:Other tumor suppressor genes/antioncogenes KW - W 30965:Miscellaneous, Reviews KW - W3 33130:Genetic based (PCR, etc.) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15774880?accountid=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+Genetics&rft.atitle=Detection+of+heterozygous+mutations+in+BRCA1+using+high+density+oligonucleotide+arrays+and+two-colour+fluorescence+analysis&rft.au=Hacia%2C+J+G%3BBrody%2C+L+C%3BChee%3BFodor%2C+SPA%3BCollins%2C+F+S&rft.aulast=Hacia&rft.aufirst=J&rft.date=1996-12-01&rft.volume=14&rft.issue=4&rft.spage=441&rft.isbn=&rft.btitle=&rft.title=Nature+Genetics&rft.issn=10614036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - breast carcinoma; fluorescence; ovarian carcinoma; DNA; mutation ER - TY - JOUR T1 - Effect of Magnesium and Calcium Complexation on the Photochemical Properties of Norfloxacin AN - 1315605183; 17424640 AB - Abstract- The fluoroquinolone antibiotics can induce skin photosensitivity in some patients and this has been ascribed to the generation of reactive oxygen species, such as singlet oxygen (O2[1 Delta g]). We have studied the photochemical properties of the different ionized forms of the fluoroquinolone norfloxacin upon complexation with Mg2+ and Ca2+ ions, as it is proposed that the antibiotic exists mainly as a complex in the blood plasma. We found that the norfloxacin cation (pH 8.5) and anionic (pH > 9) forms of norfloxacin are able to complex calcium and magnesium, and their generation of O2 (1 Delta g) is decreased by complexation. The neutral zwitterionic form and the anionic form also quench singlet oxygen by both chemical and physical pathways regardless of complex formation, while physical quenching is observed for the cation. At pH > 7.4, norfloxacin photobleaches and complexation to Ca2+ and Mg2+ increases the rate at which photobleaching occurs. Thus, both the pH of the medium and complexation with metal cations may affect the phototoxic potential of this antibiotic. JF - Photochemistry and Photobiology AU - Martinez, Lydia AU - Bilski, Piotr AU - Chignell, Colin F AD - Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA Y1 - 1996/12// PY - 1996 DA - Dec 1996 SP - 911 EP - 917 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 64 IS - 6 SN - 0031-8655, 0031-8655 KW - Calcium & Calcified Tissue Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology KW - Metals KW - Ions KW - Norfloxacin KW - Fluorescence KW - Skin KW - Calcium KW - Fluoroquinolones KW - Photobleaching KW - Antibiotics KW - Blood KW - U.V. radiation KW - Reactive oxygen species KW - Photodegradation KW - Photosensitivity KW - Magnesium KW - pH effects KW - A 01340:Antibiotics & Antimicrobials KW - T 2000:Cellular Calcium UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1315605183?accountid=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=Photochemistry+and+Photobiology&rft.atitle=Effect+of+Magnesium+and+Calcium+Complexation+on+the+Photochemical+Properties+of+Norfloxacin&rft.au=Martinez%2C+Lydia%3BBilski%2C+Piotr%3BChignell%2C+Colin+F&rft.aulast=Martinez&rft.aufirst=Lydia&rft.date=1996-12-01&rft.volume=64&rft.issue=6&rft.spage=911&rft.isbn=&rft.btitle=&rft.title=Photochemistry+and+Photobiology&rft.issn=00318655&rft_id=info:doi/10.1111%2Fj.1751-1097.1996.tb01855.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2013-03-01 N1 - Last updated - 2013-07-26 N1 - SubjectsTermNotLitGenreText - Ions; Metals; Norfloxacin; Calcium; Skin; Fluorescence; Fluoroquinolones; Photobleaching; Antibiotics; Blood; U.V. radiation; Photodegradation; Reactive oxygen species; Photosensitivity; Magnesium; pH effects DO - http://dx.doi.org/10.1111/j.1751-1097.1996.tb01855.x ER - TY - JOUR T1 - Cloning of a cDNA encoding the murine orphan receptor RZR/ROR gamma and characterization of its response element. AN - 78637736; 8973331 AB - In this study, we describe the cloning of the mouse homologue of the orphan receptor, RZR/ROR gamma, a member of the nuclear receptor superfamily, from a mouse muscle cDNA library. The amino acid sequence of mouse ROR gamma (mROR gamma) is highly homologous to that of human ROR gamma, with an overall identity of 88%. Northern blot analysis using RNA from different tissues showed that mROR gamma was found to be highly expressed in skeletal muscle, liver and kidney. Analysis of the ROR gamma-response element using in vitro synthesized ROR gamma revealed that it binds as a monomer to response elements composed of a single core motif GGTCA preceded by a 6 bp AT-rich sequence. The ROR gamma-binding specificity was further defined by mutational analysis of the consensus RORE. ROR gamma was able to activate RORE-dependent transcription of the CAT reporter gene in mouse fibroblast D1 cells. ROR alpha 1 and ROR gamma inhibit the transactivation induced by GAL4(DBD)-ROR gamma in fibroblast D1 cells suggesting that these receptors compete for binding to the same coactivators. JF - Gene AU - Medvedev, A AU - Yan, Z H AU - Hirose, T AU - Giguère, V AU - Jetten, A M AD - Cell Biology Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 1996/11/28/ PY - 1996 DA - 1996 Nov 28 SP - 199 EP - 206 VL - 181 IS - 1-2 SN - 0378-1119, 0378-1119 KW - DNA, Complementary KW - 0 KW - Nuclear Receptor Subfamily 1, Group F, Member 3 KW - RORC protein, human KW - Receptors, Cytoplasmic and Nuclear KW - Receptors, Retinoic Acid KW - Receptors, Thyroid Hormone KW - Rorc protein, mouse KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Index Medicus KW - Animals KW - Humans KW - Amino Acid Sequence KW - Mice KW - Tissue Distribution KW - Transcriptional Activation KW - Mutagenesis KW - Binding Sites KW - Cloning, Molecular KW - Chloramphenicol O-Acetyltransferase -- genetics KW - Base Sequence KW - Genes, Reporter KW - Molecular Sequence Data KW - Consensus Sequence KW - Sequence Homology, Amino Acid KW - Receptors, Cytoplasmic and Nuclear -- metabolism KW - Receptors, Cytoplasmic and Nuclear -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78637736?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gene&rft.atitle=Cloning+of+a+cDNA+encoding+the+murine+orphan+receptor+RZR%2FROR+gamma+and+characterization+of+its+response+element.&rft.au=Medvedev%2C+A%3BYan%2C+Z+H%3BHirose%2C+T%3BGigu%C3%A8re%2C+V%3BJetten%2C+A+M&rft.aulast=Medvedev&rft.aufirst=A&rft.date=1996-11-28&rft.volume=181&rft.issue=1-2&rft.spage=199&rft.isbn=&rft.btitle=&rft.title=Gene&rft.issn=03781119&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-16 N1 - Date created - 1997-01-16 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF019660; GENBANK; U43508; AF019658; AF019659; AF019656; AF019657; AF019655 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular analysis of the cyclin-dependent kinase inhibitor genes p15INK4b/MTS2, p16INK4/MTS1, p18 and p19 in human cancer cell lines. AN - 78569122; 8938142 AB - Cyclin-dependent kinase-4 inhibitor genes (INK4) regulate the cell cycle and are candidate tumor-suppressor genes. To determine if alterations in the coding regions of the p18 and p19 genes, which are novel members of the INK4 family and if they correlate with the development of human cancer, 100 human cancer cell lines were analyzed. Two other INK4 gene family members, p15INK4b/MTS2 and p16INK4/MTS1 genes were also analyzed. Homozygous deletions of the p15INK4b/MTS2 gene were detected in 29 cancer cell lines. Thirty-five homozygous deletions and 7 intragenic mutations of the pl6INK4/MTS1 gene were also detected in these cell lines. Neither homozygous deletions nor intragenic mutations of the p18 and p19 genes were found except in an ovarian cancer cell line, SKOV3, harboring a single base pair deletion in exon 1 of p19. In p16INK4/MTS1 expression analysis, 5 cell lines with both authentic and alternative spliced p16INK4/MTS1 mRNA had no detectable p16INK4/MTS1 protein. These results suggest the hypotheses that either post-translational modification or enhanced degradation may be responsible for the lack of detection of the p16INK4/MTS1 protein. Using Western blot analysis, subsets of 26 human cancer cell lines were examined for p18 expression and 39 cell lines for p19 expression. All of these cell lines expressed the p18 or p19 protein, with the exception of SKOV3, which did not express p19. Therefore, the INK4 gene family may be divided into 2 groups. One group includes p15INK4b/MTS2 and p16INK4/MTS1, in which genetic and epigenetic alterations might contribute to the development of human cancers. The other group includes p18 and p19, in which somatic mutations are uncommon in many types of human cancer, and their role in human carcinogenesis and cancer progression is uncertain. JF - International journal of cancer AU - Gemma, A AU - Takenoshita, S AU - Hagiwara, K AU - Okamoto, A AU - Spillare, E A AU - McMemamin, M G AU - Hussain, S P AU - Forrester, K AU - Zariwala, M AU - Xiong, Y AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD 20892-4255, USA. Y1 - 1996/11/27/ PY - 1996 DA - 1996 Nov 27 SP - 605 EP - 611 VL - 68 IS - 5 SN - 0020-7136, 0020-7136 KW - CDKN2D protein, human KW - 0 KW - Carrier Proteins KW - Cell Cycle Proteins KW - Cyclin-Dependent Kinase Inhibitor p16 KW - Cyclin-Dependent Kinase Inhibitor p19 KW - Enzyme Inhibitors KW - Cyclin-Dependent Kinases KW - EC 2.7.11.22 KW - Index Medicus KW - Tumor Cells, Cultured KW - Humans KW - Gene Expression Regulation, Neoplastic KW - Carrier Proteins -- genetics KW - Cyclin-Dependent Kinases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78569122?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Molecular+analysis+of+the+cyclin-dependent+kinase+inhibitor+genes+p15INK4b%2FMTS2%2C+p16INK4%2FMTS1%2C+p18+and+p19+in+human+cancer+cell+lines.&rft.au=Gemma%2C+A%3BTakenoshita%2C+S%3BHagiwara%2C+K%3BOkamoto%2C+A%3BSpillare%2C+E+A%3BMcMemamin%2C+M+G%3BHussain%2C+S+P%3BForrester%2C+K%3BZariwala%2C+M%3BXiong%2C+Y%3BHarris%2C+C+C&rft.aulast=Gemma&rft.aufirst=A&rft.date=1996-11-27&rft.volume=68&rft.issue=5&rft.spage=605&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-02 N1 - Date created - 1997-01-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sensitization by interleukin-1alpha of carboplatinum anti-tumor activity against human ovarian (NIH:OVCAR-3) carcinoma cells in vitro and in vivo. AN - 78568369; 8938138 AB - Cytokines are directly cytotoxic to tumor cells in vitro and in vivo, and interleukin-1alpha (IL-1alpha) potentiates the cytotoxicity of a number of clinically active drugs in several human tumor cells, including carcinomas of the breast and ovary. In this study, we found that IL-1alpha potentiated the cytotoxicity of carboplatin in human ovarian NIH:OVCAR-3 cancer cells during simultaneous drug exposure in vitro. Human ovarian carcinoma NIH:OVCAR-3 cells are resistant to clinically relevant concentrations of chemotherapeutic agents, including cisplatin. Both carboplatin and IL-1alpha as single agents inhibited the growth of NIH:OVCAR-3 cells grown as xenograft in nude mice; however, carboplatin was more effective in delaying tumor growth, and this inhibition was dose-dependent. Treatment with IL-1alpha followed by carboplatin caused a significant delay in tumor growth, resulting in a significant enhancement (4-fold) of the anti-tumor effect of carboplatin. In vitro potentiation of carboplatin cytotoxicity by IL-1alpha did not involve formation of nitric oxide as IL-1 or combinations of IL-1 with carboplatin failed to modulate basal nitric oxide production in OVCAR-3 cells. Potentiation of the anti-tumor activity of carboplatin by IL-1alpha was due to a significant (3- to 4-fold) increase in the accumulation of total Pt in IL-1-treated tumor xenograft, resulting in a 2-fold increase in DNA-Pt adduct formation in these tumors. In contrast, IL-1alpha had no significant effect on DNA-Pt adduct formation in the kidney. The potent synergy of IL-1alpha and carboplatin in vitro and in vivo against ovarian carcinoma cells suggests that combinations of carboplatinum and interleukin-1alpha may be effective against this disease in the clinic. JF - International journal of cancer AU - Wang, Z AU - Lee, K B AU - Reed, E AU - Sinha, B K AD - Clinical Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/11/27/ PY - 1996 DA - 1996 Nov 27 SP - 583 EP - 587 VL - 68 IS - 5 SN - 0020-7136, 0020-7136 KW - Interleukin-1 KW - 0 KW - Recombinant Proteins KW - Carboplatin KW - BG3F62OND5 KW - Index Medicus KW - Neoplasm Transplantation KW - Animals KW - Tumor Cells, Cultured KW - Interleukin-1 -- administration & dosage KW - Humans KW - Mice, Nude KW - Mice KW - Drug Resistance, Neoplasm KW - Drug Synergism KW - Carboplatin -- administration & dosage KW - Recombinant Proteins -- administration & dosage KW - Female KW - Carcinoma -- drug therapy KW - Neoplasms, Experimental -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Ovarian Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78568369?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Sensitization+by+interleukin-1alpha+of+carboplatinum+anti-tumor+activity+against+human+ovarian+%28NIH%3AOVCAR-3%29+carcinoma+cells+in+vitro+and+in+vivo.&rft.au=Wang%2C+Z%3BLee%2C+K+B%3BReed%2C+E%3BSinha%2C+B+K&rft.aulast=Wang&rft.aufirst=Z&rft.date=1996-11-27&rft.volume=68&rft.issue=5&rft.spage=583&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-02 N1 - Date created - 1997-01-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts. AN - 78575908; 8943005 AB - Human diploid fibroblasts (HDFs) can be grown in culture for a finite number of population doublings before they cease proliferation and enter a growth-arrest state termed replicative senescence. The retinoblastoma gene product, Rb, expressed in these cells is hypophosphorylated. To determine a possible mechanism by which senescent human fibroblasts maintain a hypophosphorylated Rb, we examined the expression levels and interaction of the Rb kinases, CDK4 and CDK6, and the cyclin-dependent kinase inhibitors p21 and p16 in senescent HDFs. Cellular p21 protein expression increased dramatically during the final two to three passages when the majority of cells lost their growth potential and neared senescence but p21 levels declined in senescent HDFs. During this period, p16 mRNA and cellular protein levels gradually rose with the protein levels in senescent HDFs reaching nearly 40-fold higher than early passage cells. In senescent HDFs, p16 was shown to be complexed to both CDK4 and CDK6. Immunodepletion analysis of p21 and p16 from the senescent cell extracts revealed that p16 is the major CDK inhibitor for both CDK4 and CDK6 kinases. Immunoprecipitation of CDK4 and CDK6 and their associated proteins from radiolabeled extracts from senescent HDFs showed no other CDK inhibitors. Based upon these results, we propose that senescence is a multistep process requiring the expression of both p21 and p16. p16 up-regulation is a key event in the terminal stages of growth arrest in senescence, which may explain why p16 but not p21 is commonly mutated in immortal cells and human tumors. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Alcorta, D A AU - Xiong, Y AU - Phelps, D AU - Hannon, G AU - Beach, D AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1996/11/26/ PY - 1996 DA - 1996 Nov 26 SP - 13742 EP - 13747 VL - 93 IS - 24 SN - 0027-8424, 0027-8424 KW - CDKN1C protein, human KW - 0 KW - Carrier Proteins KW - Cell Cycle Proteins KW - Cyclin-Dependent Kinase Inhibitor p16 KW - Cyclin-Dependent Kinase Inhibitor p57 KW - Enzyme Inhibitors KW - Microtubule-Associated Proteins KW - Nuclear Proteins KW - Proto-Oncogene Proteins KW - Recombinant Fusion Proteins KW - Tumor Suppressor Proteins KW - Cyclin-Dependent Kinase Inhibitor p27 KW - 147604-94-2 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - CDK4 protein, human KW - EC 2.7.11.22 KW - CDK6 protein, human KW - Cyclin-Dependent Kinase 4 KW - Cyclin-Dependent Kinase 6 KW - Cyclin-Dependent Kinases KW - Index Medicus KW - Nuclear Proteins -- isolation & purification KW - Microtubule-Associated Proteins -- metabolism KW - Protein-Serine-Threonine Kinases -- metabolism KW - Humans KW - Recombinant Fusion Proteins -- isolation & purification KW - Fibroblasts -- cytology KW - Recombinant Fusion Proteins -- metabolism KW - Microtubule-Associated Proteins -- isolation & purification KW - Nuclear Proteins -- metabolism KW - Male KW - Cyclin-Dependent Kinases -- isolation & purification KW - Cell Division KW - Cyclin-Dependent Kinases -- metabolism KW - Protein-Serine-Threonine Kinases -- isolation & purification KW - Infant, Newborn KW - Fibroblasts -- metabolism KW - Protein Binding KW - Cells, Cultured KW - Enzyme Inhibitors -- metabolism KW - Cell Line KW - Carrier Proteins -- metabolism KW - Cell Aging KW - Skin -- metabolism KW - Skin -- cytology KW - Carrier Proteins -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78575908?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Involvement+of+the+cyclin-dependent+kinase+inhibitor+p16+%28INK4a%29+in+replicative+senescence+of+normal+human+fibroblasts.&rft.au=Alcorta%2C+D+A%3BXiong%2C+Y%3BPhelps%2C+D%3BHannon%2C+G%3BBeach%2C+D%3BBarrett%2C+J+C&rft.aulast=Alcorta&rft.aufirst=D&rft.date=1996-11-26&rft.volume=93&rft.issue=24&rft.spage=13742&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-16 N1 - Date created - 1997-01-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1990 Aug 10;249(4969):666-9 [2166342] Cancer Res. 1995 Jul 15;55(14):2988-94 [7606716] Biochem Biophys Res Commun. 1991 Aug 30;179(1):528-34 [1909121] Exp Gerontol. 1992 Jul-Aug;27(4):429-32 [1281114] Physiol Rev. 1993 Jul;73(3):617-38 [8332640] Blood. 1995 Aug 1;86(3):841-54 [7620180] Nature. 1995 Oct 12;377(6549):552-7 [7566157] FEBS Lett. 1995 Oct 9;373(2):164-9 [7589458] Cell. 1995 Dec 15;83(6):993-1000 [8521522] Cell. 1996 Apr 5;85(1):27-37 [8620534] Mol Cell Biol. 1996 Mar;16(3):859-67 [8622687] Cell. 1996 May 31;85(5):707-20 [8646779] Cell. 1996 May 31;85(5):721-32 [8646780] Cell. 1996 May 31;85(5):733-44 [8646781] Exp Gerontol. 1996 Jan-Apr;31(1-2):311-25 [8706801] Mol Carcinog. 1996 Aug;16(4):221-8 [8784465] Cell Growth Differ. 1996 Aug;7(8):979-88 [8853893] Exp Cell Res. 1965 Mar;37:614-36 [14315085] J Cell Sci. 1993 May;105 ( Pt 1):123-33 [8360268] Cell. 1993 Nov 19;75(4):805-16 [8242751] Cell. 1993 Nov 19;75(4):817-25 [8242752] Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11034-8 [8248208] Nature. 1993 Dec 16;366(6456):701-4 [8259214] Nature. 1993 Dec 16;366(6456):704-7 [8259215] Exp Cell Res. 1994 Mar;211(1):90-8 [8125163] Nature. 1994 Apr 21;368(6473):753-6 [8152487] Science. 1994 Apr 15;264(5157):436-40 [8153634] J Biol Chem. 1994 Jun 10;269(23):16180-6 [8206919] Cancer Res. 1994 Nov 15;54(22):5816-20 [7954407] Cancer Res. 1994 Dec 1;54(23):6078-82 [7954450] Cell. 1995 May 5;81(3):323-30 [7736585] Cancer Res. 1995 Jun 1;55(11):2404-9 [7538902] Genes Dev. 1995 May 15;9(10):1149-63 [7758941] Nature. 1995 Jun 8;375(6531):503-6 [7777060] Exp Cell Res. 1991 Sep;196(1):33-9 [1652450] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Zinc folds the N-terminal domain of HIV-1 integrase, promotes multimerization, and enhances catalytic activity. AN - 78575740; 8942990 AB - The N-terminal domain of HIV-1 integrase contains a pair of His and Cys residues (the HHCC motif) that are conserved among retroviral integrases. Although His and Cys residues are often involved in binding zinc, the HHCC motif does not correspond to any recognized class of zinc binding domain. We have investigated the binding of zinc to HIV-1 integrase protein and find that it binds zinc with a stoichiometry of one zinc per integrase monomer. Analysis of zinc binding to deletion derivatives of integrase locates the binding site to the N-terminal domain. Integrase with a mutation in the HHCC motif does not bind zinc, consistent with coordination of zinc by these residues. The isolated N-terminal domain is disordered in the absence of zinc but, in the presence of zinc, it adopts a secondary structure with a high alpha helical content. Integrase bound by zinc tetramerizes more readily than the apoenzyme and is also more active than the apoenzyme in in vitro integration assays. We conclude that binding of zinc to the HHCC motif stabilizes the folded state of the N-terminal domain of integrase and bound zinc is required for optimal enzymatic activity. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Zheng, R AU - Jenkins, T M AU - Craigie, R AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0560, USA. Y1 - 1996/11/26/ PY - 1996 DA - 1996 Nov 26 SP - 13659 EP - 13664 VL - 93 IS - 24 SN - 0027-8424, 0027-8424 KW - Apoenzymes KW - 0 KW - DNA, Viral KW - Macromolecular Substances KW - Oligodeoxyribonucleotides KW - Recombinant Proteins KW - Cystine KW - 48TCX9A1VT KW - HIV Integrase KW - EC 2.7.7.- KW - Zinc KW - J41CSQ7QDS KW - Index Medicus KW - AIDS/HIV KW - Circular Dichroism KW - Spectrophotometry, Atomic KW - Amino Acid Sequence KW - Mutagenesis, Site-Directed KW - DNA, Viral -- chemistry KW - Conserved Sequence KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Oligodeoxyribonucleotides -- chemistry KW - Apoenzymes -- chemistry KW - Point Mutation KW - Substrate Specificity KW - Recombinant Proteins -- chemistry KW - Oligodeoxyribonucleotides -- metabolism KW - Protein Conformation KW - Catalysis KW - DNA, Viral -- metabolism KW - Zinc -- analysis KW - Zinc -- metabolism KW - Protein Folding KW - HIV-1 -- enzymology KW - HIV Integrase -- chemistry KW - HIV Integrase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78575740?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Zinc+folds+the+N-terminal+domain+of+HIV-1+integrase%2C+promotes+multimerization%2C+and+enhances+catalytic+activity.&rft.au=Zheng%2C+R%3BJenkins%2C+T+M%3BCraigie%2C+R&rft.aulast=Zheng&rft.aufirst=R&rft.date=1996-11-26&rft.volume=93&rft.issue=24&rft.spage=13659&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-16 N1 - Date created - 1997-01-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: CRC Crit Rev Biochem. 1974 Jan;2(1):113-75 [4591332] J Biol Chem. 1996 Mar 29;271(13):7712-8 [8631811] J Virol. 1986 Aug;59(2):284-91 [3016298] Cell. 1988 Aug 12;54(4):497-504 [3401925] Proc Natl Acad Sci U S A. 1989 Apr;86(8):2525-9 [2539592] Proc Natl Acad Sci U S A. 1990 Jul;87(13):5119-23 [2164223] Mol Microbiol. 1990 Jun;4(6):961-75 [2170815] Mol Microbiol. 1990 Oct;4(10):1771-7 [1963920] Science. 1992 Feb 7;255(5045):723-6 [1738845] Mol Cell Biol. 1992 May;12(5):2331-8 [1314954] J Biol Chem. 1992 May 15;267(14):9639-44 [1577801] Virology. 1992 Jun;188(2):459-68 [1585629] Biochem Biophys Res Commun. 1992 Jun 30;185(3):874-80 [1627142] J Biol Chem. 1992 Aug 15;267(23):16037-40 [1322888] J Virol. 1992 Nov;66(11):6361-9 [1404595] Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9598-602 [1409671] J Virol. 1993 Jan;67(1):425-37 [8416376] Annu Rev Cell Biol. 1992;8:275-306 [1282352] Annu Rev Genet. 1992;26:527-44 [1482125] J Biol Chem. 1993 Jan 25;268(3):2113-9 [8420982] Nucleic Acids Res. 1993 Mar 25;21(6):1419-25 [8464733] Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3428-32 [8386373] EMBO J. 1993 Aug;12(8):3261-7 [8344263] EMBO J. 1993 Aug;12(8):3269-75 [8344264] J Mol Biol. 1993 Jul 20;232(2):584-99 [8345525] Nucleic Acids Res. 1993 Jul 25;21(15):3507-11 [8346030] Trends Genet. 1993 Dec;9(12):433-8 [8122311] J Virol. 1994 Sep;68(9):5911-7 [8057470] Science. 1994 Dec 23;266(5193):1981-6 [7801124] J Biol Chem. 1995 Feb 17;270(7):3320-6 [7852418] Proc Natl Acad Sci U S A. 1995 Jun 20;92(13):6057-61 [7597080] Biochemistry. 1995 Aug 8;34(31):9826-33 [7632683] J Virol. 1995 Sep;69(9):5908-11 [7637039] Nat Struct Biol. 1995 Sep;2(9):807-10 [7552753] J Mol Biol. 1995 Oct 20;253(2):333-46 [7563093] Biochem Biophys Res Commun. 1995 Dec 26;217(3):802-10 [8554601] J Biol Chem. 1996 Jan 19;271(3):1498-506 [8576144] Science. 1996 Feb 23;271(5252):1081-5 [8599083] Biochemistry. 1996 Mar 26;35(12):3837-44 [8620007] J Virol. 1996 Mar;70(3):1424-32 [8627659] Virology. 1978 Aug;89(1):119-32 [210568] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Development of novel, potent, and selective dopamine reuptake inhibitors through alteration of the piperazine ring of 1-[2-(diphenylmethoxy)ethyl]-and 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazines (GBR 12935 and GBR 12909). AN - 78569110; 8941383 AB - The design, synthesis, and biological evaluation of compounds related to the dopamine (DA) uptake inhibitors: 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine (1) and 1-[2-[bis-(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine (2) (GBR 12395 and GBR 12909, respectively), directed toward the development and identification of new ligands interacting with high potency and selectivity at the dopamine transporter (DAT) is reported. The substitution of the piperazine ring in the GBR structure with other diamine moieties resulted in the retention of the high affinity of new ligands for the DAT. Some of the modified GBR analogs (e.g. 8, 10, (-)-49, or (-)-50) displayed substantially higher selectivity (4736- to 693-fold) for the dopamine (DA) versus the serotonin (5HT) reuptake site than the parent compounds. The bis(p-fluoro) substitution in the (diphenylmethoxy)ethyl fragment slightly increased the affinity of the ligands at the DA reuptake site but reduced their selectivity at this site (e.g. 9 and 8, 11 and 10, or 17 and 16, respectively). Congeners, such as the series of monosubstituted and symmetrically disubstituted piperazines and trans-2,5-dimethylpiperazines, which lack the (diphenylmethoxy)ethyl substituent lost the affinity for the DAT yet exhibited very high potency for binding to the sigma receptors (e.g.28). The chiral pyrrolidine derivatives of 1, (-)-49, and (+)-49, exhibited an enantioselectivity ratio of 181 and 146 for the inhibition of DA reuptake and binding to the DAT, respectively. JF - Journal of medicinal chemistry AU - Matecka, D AU - Rothman, R B AU - Radesca, L AU - de Costa, B R AU - Dersch, C M AU - Partilla, J S AU - Pert, A AU - Glowa, J R AU - Wojnicki, F H AU - Rice, K C AD - Laboratory of Medicinal Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/11/22/ PY - 1996 DA - 1996 Nov 22 SP - 4704 EP - 4716 VL - 39 IS - 24 SN - 0022-2623, 0022-2623 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 - Receptors, Drug KW - Slc6a3 protein, rat KW - cocaine receptor KW - Serotonin KW - 333DO1RDJY KW - vanoxerine KW - 90X28IKH43 KW - 1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine KW - 9J9974WIBA KW - Cocaine KW - I5Y540LHVR KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Molecular Structure KW - Animals KW - Mass Spectrometry KW - Carrier Proteins -- metabolism KW - Dopamine -- metabolism KW - Drug Design KW - Magnetic Resonance Spectroscopy KW - Rats KW - Substance-Related Disorders -- therapy KW - Receptors, Drug -- metabolism KW - Carrier Proteins -- drug effects KW - Molecular Conformation KW - Serotonin -- metabolism KW - Cocaine -- pharmacology KW - Piperazines -- chemical synthesis KW - Dopamine Uptake Inhibitors -- chemical synthesis KW - Piperazines -- pharmacology KW - Piperazines -- metabolism KW - Dopamine Uptake Inhibitors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78569110?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Development+of+novel%2C+potent%2C+and+selective+dopamine+reuptake+inhibitors+through+alteration+of+the+piperazine+ring+of+1-%5B2-%28diphenylmethoxy%29ethyl%5D-and+1-%5B2-%5Bbis%284-fluorophenyl%29methoxy%5Dethyl%5D-4-%283-phenylpropyl%29piperazines+%28GBR+12935+and+GBR+12909%29.&rft.au=Matecka%2C+D%3BRothman%2C+R+B%3BRadesca%2C+L%3Bde+Costa%2C+B+R%3BDersch%2C+C+M%3BPartilla%2C+J+S%3BPert%2C+A%3BGlowa%2C+J+R%3BWojnicki%2C+F+H%3BRice%2C+K+C&rft.aulast=Matecka&rft.aufirst=D&rft.date=1996-11-22&rft.volume=39&rft.issue=24&rft.spage=4704&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 - 1997-01-06 N1 - Date created - 1997-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulation of JunD.AP-1 DNA binding activity by AP-1-associated factor 1 (AF-1). AN - 78566967; 8939957 AB - AP-1-associated factor 1 (AF-1), is a novel protein complex that dramatically enhances the assembly of JunD-containing dimers onto AP-1 consensus sites. We describe the partial purification of AF-1 from nuclear extracts of the T-cell line MLA 144 by ionic, hydrophobic and gel filtration chromatography. AF-1 is a DNA-binding protein composed of low molecular mass polypeptides of 7-17 kDa that exists in solution as a 34-kDa complex. JunD interactions with DNA are accelerated in the presence of AF-1 through the formation of a true tri-molecular complex with JunD dimers and DNA that assembles much more rapidly on DNA than JunD alone. DNA binding analysis of AF-1 interaction with JunD.AP-1 and DNA shows that AF-1 increases the DNA binding affinity of JunD for AP-1 sites over 100-fold. DNA cleavage footprint analysis of isolated AF-1.JunD DNA complexes shows that the ternary complex makes nearly twice as many contacts with DNA than JunD dimers alone. AF-1 interacts readily, but differentially with Jun homodimers and Jun.Fos heterodimers. These findings distinguish AF-1 as a significant protein-specific modulator of AP-1.JunD in T-cells. JF - The Journal of biological chemistry AU - Powers, C AU - Krutzsch, H AU - Gardner, K AD - Laboratory of Pathology, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/11/22/ PY - 1996 DA - 1996 Nov 22 SP - 30089 EP - 30095 VL - 271 IS - 47 SN - 0021-9258, 0021-9258 KW - Biopolymers KW - 0 KW - DNA-Binding Proteins KW - Nuclear Proteins KW - Proto-Oncogene Proteins c-fos KW - Transcription Factor AP-1 KW - DNA KW - 9007-49-2 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Chromatography, Affinity KW - T-Lymphocytes -- metabolism KW - Proto-Oncogene Proteins c-fos -- metabolism KW - Cell Nucleus -- metabolism KW - Humans KW - DNA -- metabolism KW - Jurkat Cells KW - Tetradecanoylphorbol Acetate -- pharmacology KW - T-Lymphocytes -- drug effects KW - Protein Binding KW - Transcription Factor AP-1 -- metabolism KW - DNA-Binding Proteins -- isolation & purification KW - Transcription Factor AP-1 -- isolation & purification KW - Nuclear Proteins -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78566967?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Modulation+of+JunD.AP-1+DNA+binding+activity+by+AP-1-associated+factor+1+%28AF-1%29.&rft.au=Powers%2C+C%3BKrutzsch%2C+H%3BGardner%2C+K&rft.aulast=Powers&rft.aufirst=C&rft.date=1996-11-22&rft.volume=271&rft.issue=47&rft.spage=30089&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-13 N1 - Date created - 1997-01-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanism-based inhibition of mouse P4502b-10 by selected arylalkynes. AN - 78564686; 8937464 AB - Suicide inhibitors of cytochrome P450 families are excellent tools to predict which isoforms mediate the metabolism/activation of a variety of chemical agents. We compared the inhibitory effects of several arylalkynes on mouse cytochromes P450 with published data for the rat model. The inhibition of P4502b specific dealkylation of benzyloxyresorufin by 2-ethynylnaphthalene (2-EN), 5-phenyl-1-pentyne (PPY), 4-phenyl-1-butyne (PBY), and 9-ethynylphenanthrene (9-EPh) was measured in hepatic microsomes from male mice treated with 1,4-bis[2-(3,5-dichloropyridyloxy)]-benzene (TCPOBOP) to induce cytochrome P4502b. Pulmonary microsomes were prepared from untreated mice. 9-EPh, 2-EN, and PPY caused a time-, concentration-, and NADPH-dependent loss in P4502b activity in both tissues. PBY, however, demonstrated this type of inhibition only in liver microsomes. The IC50 was calculated for both liver and lung microsomes and compared with published Ki (concentration required for half-maximal inhibition) or KI (concentration required for half-maximal inactivation) values for the rat. PPY, PBY, and 9-EPh were equally effective inhibitors of mouse P4502b and rat P4502B1. 2-EN was a 5- to 10-fold less potent inhibitor of mouse P4502b, as compared with the rat, even though it was shown to bind to the active site of the mouse isoform as demonstrated by its metabolism to 2-naphthylacetic acid. These data suggest that the active site of the mouse P4502b enzyme is functionally similar to the rat P4502B isoform, with the exception of the disparity in its susceptibility to inactivation by 2-EN as measured by the Ki values. JF - Biochemical pharmacology AU - Beebe, L E AU - Roberts, E S AU - Fornwald, L W AU - Hollenberg, P F AU - Alworth, W L AD - Laboratory of Comparative Carcinogenesis, NCI-FCRDC, Frederick, MD 21702, USA. Y1 - 1996/11/22/ PY - 1996 DA - 1996 Nov 22 SP - 1507 EP - 1513 VL - 52 IS - 10 SN - 0006-2952, 0006-2952 KW - 9-ethynylphenanthrene KW - 0 KW - Alkynes KW - Cytochrome P-450 Enzyme Inhibitors KW - Enzyme Inhibitors KW - Naphthalenes KW - Oxazines KW - Phenanthrenes KW - 2-ethynylnaphthalene KW - 2949-26-0 KW - benzyloxyresorufin KW - 87687-02-3 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Steroid Hydroxylases KW - EC 1.14.- KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - Cyp2b10 protein, mouse KW - Cytochrome P450 Family 2 KW - Index Medicus KW - Naphthalenes -- pharmacology KW - Animals KW - Cytochrome P-450 Enzyme System -- metabolism KW - Mice KW - Microsomes -- enzymology KW - Rats KW - Kinetics KW - In Vitro Techniques KW - Microsomes, Liver -- enzymology KW - Lung -- enzymology KW - Phenanthrenes -- pharmacology KW - Male KW - Oxazines -- metabolism KW - Enzyme Inhibitors -- pharmacology KW - Alkynes -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78564686?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mechanism-based+inhibition+of+mouse+P4502b-10+by+selected+arylalkynes.&rft.au=Beebe%2C+L+E%3BRoberts%2C+E+S%3BFornwald%2C+L+W%3BHollenberg%2C+P+F%3BAlworth%2C+W+L&rft.aulast=Beebe&rft.aufirst=L&rft.date=1996-11-22&rft.volume=52&rft.issue=10&rft.spage=1507&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 - 1996-12-31 N1 - Date created - 1996-12-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Avian exposure and risk of lung cancer in women in Missouri: population based case-control study. AN - 78561154; 8939111 AB - To investigate the association, previously reported in three European studies, between ownership of pet birds and the risk of lung cancer. A population based case-control study with a structured questionnaire administered by telephone. Missouri, a midwestern state in the United States with a population of about 5 million. All newly diagnosed cases of primary lung cancer in women aged 30-84 years in Missouri from 1 January 1993 to 31 January 1994 reported to the state cancer registry were invited to participate (n = 652); and 629 population based controls. Odds ratios were computed in relation to whether or not the study subject ever kept pet birds, the type of bird kept, and several measures of intensity or duration of exposure. Odds ratios were adjusted for smoking. The odds ratio (95% confidence interval) for the development of lung cancer associated with keeping pet birds was 0.84 (0.65 to 1.09). The results were similar for the type of pet bird kept, the number of birds kept, the location of the bird in the house, and the duration of ownership. The keeping of pet birds carries no excess risk for the development of lung cancer. JF - BMJ (Clinical research ed.) AU - Alavanja, M C AU - Brownson, R C AU - Berger, E AU - Lubin, J AU - Modigh, C AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockvilie, MD 20852, USA. Y1 - 1996/11/16/ PY - 1996 DA - 1996 Nov 16 SP - 1233 EP - 1235 VL - 313 IS - 7067 SN - 0959-8138, 0959-8138 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Missouri -- epidemiology KW - Odds Ratio KW - Age Factors KW - Humans KW - Aged KW - Aged, 80 and over KW - Logistic Models KW - Risk Factors KW - Adult KW - Case-Control Studies KW - Incidence KW - Middle Aged KW - Female KW - Animals, Domestic KW - Lung Neoplasms -- etiology KW - Lung Neoplasms -- epidemiology KW - Environmental Exposure KW - Birds UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78561154?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BMJ+%28Clinical+research+ed.%29&rft.atitle=Avian+exposure+and+risk+of+lung+cancer+in+women+in+Missouri%3A+population+based+case-control+study.&rft.au=Alavanja%2C+M+C%3BBrownson%2C+R+C%3BBerger%2C+E%3BLubin%2C+J%3BModigh%2C+C&rft.aulast=Alavanja&rft.aufirst=M&rft.date=1996-11-16&rft.volume=313&rft.issue=7067&rft.spage=1233&rft.isbn=&rft.btitle=&rft.title=BMJ+%28Clinical+research+ed.%29&rft.issn=09598138&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-03 N1 - Date created - 1997-07-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Practitioner. 1975 Aug;215(1286):165-71 [1101246] BMJ. 1988 Nov 19;297(6659):1319-21 [3144376] Biometrics. 1990 Dec;46(4):963-75 [2085641] Am J Epidemiol. 1991 Aug 15;134(4):421-32 [1877602] J Natl Cancer Inst. 1994 Dec 21;86(24):1829-37 [7990157] Cancer Causes Control. 1995 May;6(3):209-16 [7612800] BMJ. 1996 Jul 6;313(7048):1-2 [8664757] Occup Med. 1991 Jul-Sep;6(3):335-54 [1835166] Am J Epidemiol. 1992 Sep 15;136(6):623-32 [1442729] Am J Public Health. 1992 Nov;82(11):1525-30 [1443304] BMJ. 1992 Oct 24;305(6860):986-9 [1458145] BMJ. 1992 Oct 24;305(6860):989-92 [1458146] Cancer Causes Control. 1993 Sep;4(5):449-54 [8218877] J Natl Cancer Inst. 1993 Dec 1;85(23):1906-16 [8230280] Comment In: BMJ. 1996 Nov 16;313(7067):1218-9 [8939094] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The sympathetic nervous system contributes to capsaicin-evoked mechanical allodynia but not pinprick hyperalgesia in humans. AN - 78556036; 8929439 AB - The contribution of the sympathetic nervous system (SNS) to pain, mechanical allodynia (MA), and hyperalgesia in humans is controversial. A clearer understanding is crucial to guide therapeutic use of sympatholytic surgery, blocks, and drug treatments. In rats, capsaicin-evoked MA, and to some extent, pinprick hyperalgesia (PPH), can be blocked with alpha-adrenoreceptor antagonists. In this study, we examined the contribution of the SNS to MA and PPH in normal human subjects by blocking alpha-adrenoreceptors with intravenous phentolamine. In a double-blinded, placebo-controlled, crossover study, subjects were given IV saline or phentolamine, 1 mg/kg over 20 min. Ten minutes after the start of the infusion, subjects received 100 micrograms of intradermal capsaicin on the foot dorsum with the temperature of the injected site clamped at 36 degrees C. The temperature of the uninjected foot was used to monitor the degree of alpha-adrenoreceptor blockade produced by phentolamine. Ongoing pain and MA and PPH areas were measured every 5 min for 60 min. A significantly greater increase in temperature on the uninjected foot was seen during the phentolamine infusion compared with the saline infusion, indicating alpha-adrenergic blockade. Significantly less MA was observed with the phentolamine infusion 10-25 min after capsaicin injection than with the saline infusion. No significant differences in ongoing pain or PPH areas were seen between the two infusions at any time. Our results suggest that capsaicin-evoked MA and PPH have different mechanisms, with the SNS having a role in MA but not in PPH or ongoing pain. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Liu, M AU - Max, M B AU - Parada, S AU - Rowan, J S AU - Bennett, G J AD - Neurobiology and Anesthesiology Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/11/15/ PY - 1996 DA - 1996 Nov 15 SP - 7331 EP - 7335 VL - 16 IS - 22 SN - 0270-6474, 0270-6474 KW - Placebos KW - 0 KW - Sympatholytics KW - Capsaicin KW - S07O44R1ZM KW - Phentolamine KW - Z468598HBV KW - Index Medicus KW - Sympatholytics -- pharmacology KW - Injections, Intradermal KW - Touch -- physiology KW - Pain -- drug therapy KW - Pain -- physiopathology KW - Double-Blind Method KW - Phentolamine -- pharmacology KW - Pain -- chemically induced KW - Humans KW - Cross-Over Studies KW - Hyperalgesia -- physiopathology KW - Sympathetic Nervous System -- physiology KW - Sympathetic Nervous System -- drug effects KW - Hyperalgesia -- chemically induced KW - Hyperalgesia -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78556036?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=The+sympathetic+nervous+system+contributes+to+capsaicin-evoked+mechanical+allodynia+but+not+pinprick+hyperalgesia+in+humans.&rft.au=Liu%2C+M%3BMax%2C+M+B%3BParada%2C+S%3BRowan%2C+J+S%3BBennett%2C+G+J&rft.aulast=Liu&rft.aufirst=M&rft.date=1996-11-15&rft.volume=16&rft.issue=22&rft.spage=7331&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 - 1996-12-19 N1 - Date created - 1996-12-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Single amino acid changes in the murine leukemia virus capsid protein gene define the target of Fv1 resistance. AN - 78547128; 8918916 AB - The mouse Fv1 genetic locus controls resistance to subgroups of ecotropic, MCF, and amphotropic murine leukemia viruses (MuLVs). In addition to the four previously defined alleles of Fv1 (Fv1(n), Fv1(b), Fv1(nr), Fv1(0)), we present evidence that the novel restriction pattern characteristic of DBA/2J mice maps to the Fv1 locus and therefore represents a novel allele, here designated Fv1(d). Previous studies had demonstrated that the Fv1-mediated viral tropism is determined within the capsid protein gene, and that N- and B-tropic virus capsids differ only in two adjacent amino acids. We introduced various amino acid substitutions at these two sites in the N-tropic AKV MLV capsid gene, and typed resulting viruses for host range on cells carrying all five Fv1 alleles as well as on cells from additional wild mouse species with Fv1-like differences in virus susceptibility. Results indicate that alteration of the first of the two amino acids does not alter tropism, but alteration of the second alone is sufficient to convert the N-tropic AKV MLV to a B-tropic virus. Substitution of leucine for arginine at this site produced a virus with an unusual tropism not characteristic of any of the naturally occurring or laboratory strains of MuLV. JF - Virology AU - Kozak, C A AU - Chakraborti, A AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0460, USA. ckozak@nih.gov. Y1 - 1996/11/15/ PY - 1996 DA - 1996 Nov 15 SP - 300 EP - 305 VL - 225 IS - 2 SN - 0042-6822, 0042-6822 KW - Viral Envelope Proteins KW - 0 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Drug Resistance -- genetics KW - Alleles KW - Point Mutation KW - Mice KW - Gene Targeting KW - Leukemia Virus, Murine -- metabolism KW - Leukemia Virus, Murine -- genetics KW - Capsid -- genetics KW - Genes, Viral KW - Viral Envelope Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78547128?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Single+amino+acid+changes+in+the+murine+leukemia+virus+capsid+protein+gene+define+the+target+of+Fv1+resistance.&rft.au=Kozak%2C+C+A%3BChakraborti%2C+A&rft.aulast=Kozak&rft.aufirst=C&rft.date=1996-11-15&rft.volume=225&rft.issue=2&rft.spage=300&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-31 N1 - Date created - 1996-12-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nucleotide sequence analysis of the respiratory syncytial virus subgroup A cold-passaged (cp) temperature sensitive (ts) cpts-248/404 live attenuated virus vaccine candidate. AN - 78547042; 8918930 AB - The complete nucleotide sequence of the RSV cpts-248/404 live attenuated vaccine candidate was determined from cloned cDNA and was compared to that of the RSV A2/HEK7 wild-type, cold-passaged cp-RSV, and cpts-248 virus, which constitute the series of progenitor viruses. RSV cpts-248/404 is more attenuated and more temperature sensitive (ts) (shut-off temperature 36 degrees) than its cpts-248 parent virus (shut-off temperature 38 degrees) and is currently being evaluated in phase I clinical trials in humans. Our ultimate goal is to identify the genetic basis for the host range attenuation phenotype exhibited by cp-RSV (i.e., efficient replication in tissue culture but decreased replication in chimpanzees and humans) and for the ts and attenuation phenotypes of its chemically mutagenized derivatives, cpts-248 and cpts-248/404. Compared with its cpts-248 parent, the cpts-248/404 virus possesses an amino acid change in the polymerase (L) protein and a single nucleotide substitution in the M2 gene start sequence. In total, the cpts-248/404 mutant differs from its wild-type RSV A2/HEK7 progenitor in seven amino acids [four in the polymerase (L) protein, two in the fusion (F) glycoprotein, and one in the (N) nucleoprotein] and one nucleotide difference in the M2 gene start sequence. Heterogeneity at nucleotide position 4 (G or C, negative sense, compared to G in the RSV A2/HEK7 progenitor) in the leader region of vRNA developed during passage of the cpts-248/404 in tissue culture. Biologically cloned derivatives of RSV cpts-248/404 virus that differed at position 4 possessed the same level of temperature sensitivity and exhibited the same level of replication in the upper and lower respiratory tract of mice, suggesting that heterogeneity at this position is not clinically relevant. The determination of the nucleotide sequence of the cpts-248/404 virus will allow evaluation of the stability of the eight mutations that are associated with the attenuation phenotype during vaccine production and following replication in humans. JF - Virology AU - Firestone, C Y AU - Whitehead, S S AU - Collins, P L AU - Murphy, B R AU - Crowe, J E AD - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0720, USA. Y1 - 1996/11/15/ PY - 1996 DA - 1996 Nov 15 SP - 419 EP - 422 VL - 225 IS - 2 SN - 0042-6822, 0042-6822 KW - RNA, Viral KW - 0 KW - Viral Vaccines KW - Index Medicus KW - Animals KW - Sequence Analysis KW - Humans KW - Temperature KW - Molecular Sequence Data KW - Mice KW - Cold Temperature KW - Mutation KW - Respiratory Syncytial Viruses -- genetics KW - RNA, Viral -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78547042?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Nucleotide+sequence+analysis+of+the+respiratory+syncytial+virus+subgroup+A+cold-passaged+%28cp%29+temperature+sensitive+%28ts%29+cpts-248%2F404+live+attenuated+virus+vaccine+candidate.&rft.au=Firestone%2C+C+Y%3BWhitehead%2C+S+S%3BCollins%2C+P+L%3BMurphy%2C+B+R%3BCrowe%2C+J+E&rft.aulast=Firestone&rft.aufirst=C&rft.date=1996-11-15&rft.volume=225&rft.issue=2&rft.spage=419&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-31 N1 - Date created - 1996-12-31 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U63644; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhanced sensitivity to 1-beta-D-arabinofuranosylcytosine and topoisomerase II inhibitors in tumor cell lines harboring activated ras oncogenes. AN - 78524503; 8912859 AB - We used human tumor cell lines from the National Cancer Institute's In Vitro Antineoplastic Drug Screen to assess whether sensitivity to any of the approximately 45,000 compounds tested previously correlated with the presence of a ras oncogene. Among these cell lines, the mutations in Ki-ras2 clustered in non-small cell lung and colon carcinoma subpanels, and five of the six leukemia lines contained mutations in either N-ras or Ki-ras2. These analyses revealed a striking correlation with 1-beta-D-arabinofuranosylcytosine (Ara-C) and 2,2'-O-cyclocytidine sensitivity in the cell lines harboring ras mutations compared to the tumor lines with wild-type ras alleles. Strong correlations were also found with topoisomerase (topo) II inhibitors, especially 3'-hydroxydaunorubicin and an olivacine derivative. These differential sensitivities persisted in an additional 22 non-small cell lung carcinoma lines (ras mutations, n = 12 and wild-type ras, n = 10). Thus, the association with Ara-C sensitivity was greatest while topo II inhibitors showed a lower, but significant, correlation. These results suggest that the ras oncogene may play a determinant role in rendering tumor cells sensitive to deoxycytidine analogues and topo II inhibitors. JF - Cancer research AU - Koo, H M AU - Monks, A AU - Mikheev, A AU - Rubinstein, L V AU - Gray-Goodrich, M AU - McWilliams, M J AU - Alvord, W G AU - Oie, H K AU - Gazdar, A F AU - Paull, K D AU - Zarbl, H AU - Vande Woude, G F AD - ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201, USA. Y1 - 1996/11/15/ PY - 1996 DA - 1996 Nov 15 SP - 5211 EP - 5216 VL - 56 IS - 22 SN - 0008-5472, 0008-5472 KW - Antibiotics, Antineoplastic KW - 0 KW - Antimetabolites, Antineoplastic KW - Topoisomerase II Inhibitors KW - Cytarabine KW - 04079A1RDZ KW - Deoxycytidine KW - 0W860991D6 KW - gemcitabine KW - B76N6SBZ8R KW - Daunorubicin KW - ZS7284E0ZP KW - Index Medicus KW - Software KW - Daunorubicin -- administration & dosage KW - Antibiotics, Antineoplastic -- administration & dosage KW - Colonic Neoplasms -- genetics KW - Humans KW - Carcinoma, Non-Small-Cell Lung -- genetics KW - DNA Mutational Analysis KW - Deoxycytidine -- analogs & derivatives KW - Lung Neoplasms -- drug therapy KW - Drug Resistance, Neoplasm KW - Daunorubicin -- pharmacology KW - Tumor Cells, Cultured KW - Antibiotics, Antineoplastic -- pharmacology KW - Colonic Neoplasms -- drug therapy KW - Lung Neoplasms -- genetics KW - Deoxycytidine -- administration & dosage KW - Drug Screening Assays, Antitumor -- methods KW - Carcinoma, Non-Small-Cell Lung -- drug therapy KW - Deoxycytidine -- pharmacology KW - Gene Expression Regulation, Neoplastic -- genetics KW - Cytarabine -- pharmacology KW - Antimetabolites, Antineoplastic -- administration & dosage KW - Genes, ras -- genetics KW - Cytarabine -- administration & dosage KW - Antimetabolites, Antineoplastic -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78524503?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Enhanced+sensitivity+to+1-beta-D-arabinofuranosylcytosine+and+topoisomerase+II+inhibitors+in+tumor+cell+lines+harboring+activated+ras+oncogenes.&rft.au=Koo%2C+H+M%3BMonks%2C+A%3BMikheev%2C+A%3BRubinstein%2C+L+V%3BGray-Goodrich%2C+M%3BMcWilliams%2C+M+J%3BAlvord%2C+W+G%3BOie%2C+H+K%3BGazdar%2C+A+F%3BPaull%2C+K+D%3BZarbl%2C+H%3BVande+Woude%2C+G+F&rft.aulast=Koo&rft.aufirst=H&rft.date=1996-11-15&rft.volume=56&rft.issue=22&rft.spage=5211&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-07 N1 - Date created - 1997-01-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - CD44 is a cytotoxic triggering molecule on human polymorphonuclear cells. AN - 78523320; 8906846 AB - In this study, we present evidence that CD44 is a cytotoxic triggering molecule on freshly isolated polymorphonuclear cells (PMN). PMN constitutively express high levels of CD44 as determined by FACS analysis, and immunoprecipitation studies using PMN lysates and an anti-CD44 mAb show a band of 80 to 90 kDa that migrates slightly faster than CD44 from PBL. A bispecific Ab consisting of anti-CD44 Fab cross-linked to anti-DNP Fab (anti-CD44(Fab) x anti-DNP(Fab)) induces PMN to lyse DNP-coated tumor cells in an 18-h assay, and this lysis is specifically inhibited by a polyclonal anti-CD44 F(ab')2. A second bispecific Ab, anti-CD16(Fab) x anti-DNP(Fab), that binds to Fc(gamma)RIIIb on PMN does not induce lysis, indicating that the bridging of target cells to PMN per se is not sufficient for killing. Moreover, CD44-directed killing by PMN results in the lysis of bystander cells, suggesting that the mechanisms of tumor cytolysis by CD44-targeted PMN does not require cell-cell contact. Lastly, PMN lyse target cells coated with hyaluronic acid (HA), the principal ligand for CD44, and this cytolytic activity is specifically blocked by the polyclonal anti-CD44 F(ab')2 and by an anti-CD44 mAb. We suggest that the interaction of HA with CD44 on neutrophils might initiate cytotoxic or inflammatory responses in vivo when neutrophils encounter high amounts of HA, for example on tumor cells, or in the extracellular matrix. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Pericle, F AU - Sconocchia, G AU - Titus, J A AU - Segal, D M AD - Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1996/11/15/ PY - 1996 DA - 1996 Nov 15 SP - 4657 EP - 4663 VL - 157 IS - 10 SN - 0022-1767, 0022-1767 KW - Antigens, CD44 KW - 0 KW - Hyaluronic Acid KW - 9004-61-9 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured KW - Humans KW - Cytotoxicity Tests, Immunologic KW - Mice KW - Hyaluronic Acid -- pharmacology KW - Neutrophils -- drug effects KW - Antigens, CD44 -- biosynthesis KW - Neutrophils -- immunology KW - Antigens, CD44 -- immunology KW - Antigens, CD44 -- pharmacology KW - Cytotoxicity, Immunologic -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78523320?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=CD44+is+a+cytotoxic+triggering+molecule+on+human+polymorphonuclear+cells.&rft.au=Pericle%2C+F%3BSconocchia%2C+G%3BTitus%2C+J+A%3BSegal%2C+D+M&rft.aulast=Pericle&rft.aufirst=F&rft.date=1996-11-15&rft.volume=157&rft.issue=10&rft.spage=4657&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 - 1996-12-31 N1 - Date created - 1996-12-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nitric oxide modification of rat brain neurogranin. Identification of the cysteine residues involved in intramolecular disulfide bridge formation using site-directed mutagenesis. AN - 78514913; 8910523 AB - Neurogranin (Ng) is a neuron-specific protein kinase C-selective substrate, which binds calmodulin (CaM) in the dephosphorylated form at low levels of Ca2+. This protein contains redox active Cys residues that are readily oxidized by several nitric oxide (NO) donors and other oxidants to form intramolecular disulfide. Identification of the Cys residues of rat brain Ng, Cys3, Cys4, Cys9, and Cys51, involved in NO-mediated intramolecular disulfide bridge formation was examined by site-directed mutagenesis. Mutation of all four Cys residues or single mutation of Cys51 blocked the oxidant-mediated intramolecular disulfide formation as monitored by the downward mobility shift under nonreducing SDS-polyacrylamide gel electrophoresis. Single mutation of Cys3, Cys4, or Cys9 or double mutation of any pair of these three Cys residues did not block such intramolecular disulfide formation, although the rates of oxidation of these mutant proteins were different. Thus, Cys51 is an essential pairing partner in NO-mediated intramolecular disulfide formation in Ng. Cys3, Cys4, and Cys9 individually could pair with Cys51, and the order of reactivity was Cys9 > Cys4 > Cys3, suggesting that Cys9 and Cys51 form the preferential disulfide bridge. In all cases tested, the intramolecularly disulfide bridged Ng proteins displayed dramatically attenuated CaM-binding affinity and approximately 2-3-fold weaker protein kinase C substrate phosphorylation activity. The data indicate that the N-terminal Cys3, Cys4, and Cys9 are in close proximity to the C-terminal Cys51 in solution. The disulfide bridge between the N- and C-terminal domains of Ng renders the central CaM-binding and phosphorylation site domain in a fixed conformation unfavorable for binding to CaM and as a substrate of protein kinase C. JF - The Journal of biological chemistry AU - Mahoney, C W AU - Pak, J H AU - Huang, K P AD - Section on Metabolic Regulation, Endocrinology and Reproduction Research Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892-4510, USA. Y1 - 1996/11/15/ PY - 1996 DA - 1996 Nov 15 SP - 28798 EP - 28804 VL - 271 IS - 46 SN - 0021-9258, 0021-9258 KW - Calmodulin-Binding Proteins KW - 0 KW - Disulfides KW - Nerve Tissue Proteins KW - Nrgn protein, rat KW - Neurogranin KW - 132654-77-4 KW - Nitric Oxide KW - 31C4KY9ESH KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Rats KW - Mutagenesis, Site-Directed KW - Animals KW - Cell Line KW - Disulfides -- chemistry KW - Cysteine -- analysis KW - Calmodulin-Binding Proteins -- genetics KW - Nitric Oxide -- chemistry KW - Nerve Tissue Proteins -- genetics KW - Nerve Tissue Proteins -- chemistry KW - Calmodulin-Binding Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78514913?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Nitric+oxide+modification+of+rat+brain+neurogranin.+Identification+of+the+cysteine+residues+involved+in+intramolecular+disulfide+bridge+formation+using+site-directed+mutagenesis.&rft.au=Mahoney%2C+C+W%3BPak%2C+J+H%3BHuang%2C+K+P&rft.aulast=Mahoney&rft.aufirst=C&rft.date=1996-11-15&rft.volume=271&rft.issue=46&rft.spage=28798&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-07 N1 - Date created - 1997-01-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional domains for assembly of histones H3 and H4 into the chromatin of Xenopus embryos. AN - 78537566; 8917496 AB - Histones H3 and H4 have a well defined structural role in the nucleosome and an established role in the regulation of transcription. We have made use of a microinjection strategy using Xenopus embryos to define the minimal structural components of H3 and H4 necessary for nucleosome assembly into metazoan chromosomes in vivo. We find that both the N-terminal tail of H4, including all sites of acetylation, and the C-terminal alpha-helix of the H4 histone fold domain are dispensable for chromatin assembly. The N-terminal tail and an N-terminal alpha-helix of H3 are also dispensable for chromatin assembly. However, the remainder of the H3 and H4 histone folds are essential for incorporation of these proteins into chromatin. We suggest that elements of the histone fold domain maintain both nucleosomal integrity and have distinct functions essential for cell viability. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Freeman, L AU - Kurumizaka, H AU - Wolffe, A P AD - Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2710, USA. Y1 - 1996/11/12/ PY - 1996 DA - 1996 Nov 12 SP - 12780 EP - 12785 VL - 93 IS - 23 SN - 0027-8424, 0027-8424 KW - Chromatin KW - 0 KW - Histones KW - Nucleosomes KW - Recombinant Proteins KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Models, Structural KW - Recombinant Proteins -- biosynthesis KW - DNA -- metabolism KW - Nucleosomes -- metabolism KW - Embryo, Nonmammalian KW - Cell Survival KW - Mutagenesis, Site-Directed KW - Acetylation KW - Nucleosomes -- ultrastructure KW - Point Mutation KW - Xenopus KW - DNA -- chemistry KW - Recombinant Proteins -- chemistry KW - Protein Structure, Secondary KW - Chromatin -- metabolism KW - Histones -- chemistry KW - Histones -- biosynthesis KW - Protein Folding KW - Chromatin -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78537566?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Functional+domains+for+assembly+of+histones+H3+and+H4+into+the+chromatin+of+Xenopus+embryos.&rft.au=Freeman%2C+L%3BKurumizaka%2C+H%3BWolffe%2C+A+P&rft.aulast=Freeman&rft.aufirst=L&rft.date=1996-11-12&rft.volume=93&rft.issue=23&rft.spage=12780&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 - 1996-12-30 N1 - Date created - 1996-12-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6829-33 [1650485] Cell. 1991 Jun 14;65(6):1023-31 [2044150] Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1229-33 [1741376] EMBO J. 1992 Jun;11(6):2201-9 [1600945] Cell. 1993 Oct 8;75(1):5-8 [8402900] Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10489-93 [8248135] J Mol Biol. 1994 Feb 25;236(3):685-90 [8114086] Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2339-43 [8134397] EMBO J. 1994 Apr 15;13(8):1823-30 [8168481] J Cell Biol. 1994 Aug;126(3):591-601 [8045925] Genes Dev. 1994 May 15;8(10):1147-59 [7926720] Cold Spring Harb Symp Quant Biol. 1993;58:265-72 [7956038] Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1237-41 [7862667] Cell. 1995 Feb 24;80(4):583-92 [7867066] Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1624-8 [7878029] Bioessays. 1995 Feb;17(2):161-70 [7748166] Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5664-8 [7777566] Nucleic Acids Res. 1995 Jul 25;23(14):2685-91 [7651829] Nature. 1996 Mar 28;380(6572):316-22 [8598927] Nature. 1996 Mar 28;380(6572):356-9 [8598932] Genes Dev. 1996 Mar 15;10(6):686-99 [8598296] J Biol Chem. 1969 Oct 25;244(20):5669-79 [5388597] Science. 1974 May 24;184(4139):865-8 [4825888] Science. 1974 May 24;184(4139):868-71 [4825889] Cell. 1976 Jul;8(3):333-47 [986252] Dev Biol. 1977 May;57(1):118-35 [558925] Biochemistry. 1978 Nov 14;17(23):4955-64 [718868] J Mol Biol. 1985 Oct 5;185(3):479-99 [3863963] Proc Natl Acad Sci U S A. 1985 Dec;82(23):8048-52 [3865215] Nature. 1988 Jan 28;331(6154):365-7 [3340182] EMBO J. 1988 May;7(5):1395-402 [3409869] Cell. 1988 Oct 7;55(1):27-39 [3048701] Cell. 1989 Jul 14;58(1):15-25 [2546672] Science. 1990 Feb 16;247(4944):841-5 [2106160] Proc Natl Acad Sci U S A. 1990 Aug;87(16):6286-90 [2201024] Mol Cell Biol. 1990 Sep;10(9):4932-4 [2117703] EMBO J. 1991 Apr;10(4):971-80 [1849080] Nucleic Acids Res. 1991 Apr 25;19 Suppl:2173-88 [2041803] Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10148-52 [1946434] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Complete restoration of glucocerebrosidase deficiency in Gaucher fibroblasts using a bicistronic MDR retrovirus and a new selection strategy. AN - 78550746; 8934230 AB - Retrovirus-mediated gene transfer is currently the most common method for the application of genetic therapy to cancer and many inherited and acquired disorders. Here we report the generation of an amphotropic producer cell line (CA2) that synthesizes viral particles carrying a bicistronic cassette in which the selectable MDR1 cDNA encoding P-glycoprotein (P-gp) a multidrug efflux pump, and the human glucocerebrosidase (GC) gene are transcriptionally fused. Transduction of human Gaucher fibroblasts with this recombinant virus allowed coordinate expression of P-gp and GC. Treatment of the transduced fibroblasts with various cytotoxic substrates of P-gp selected for cells with increased expression of GC, which paralleled the stringency of drug selection. Thus, selection of the genetically modified Gaucher fibroblasts in 1 microgram/ml colchicine raised their GC activity levels from nearly undetectable to those present in WI-38 normal human fibroblasts, correcting the enzyme deficiency present in Gaucher cells. Moreover, by simultaneously inhibiting the P-gp pump, it was possible to use much lower concentrations of colchicine to select for high-level expression of MDR1 and GC. Thus, selection with colchicine at 5 ng/ml in combination with the P-gp inhibitors verapamil or PSC 833 produced a complete correction of the GC deficiency in the CA2-transduced fibroblasts. These combination regimens, already in clinical use for the treatment of multidrug-resistant malignancies, may prove useful in gene therapy trials when utilized for high level selection of a nonselectable gene such as glucocerebrosidase when transcriptionally fused to the MDR1 gene. JF - Human gene therapy AU - Aran, J M AU - Licht, T AU - Gottesman, M M AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Md 20892, USA. Y1 - 1996/11/10/ PY - 1996 DA - 1996 Nov 10 SP - 2165 EP - 2175 VL - 7 IS - 17 SN - 1043-0342, 1043-0342 KW - Anthracenes KW - 0 KW - Cyclosporins KW - DNA, Complementary KW - P-Glycoprotein KW - bisantrene KW - 39C34M111K KW - Etoposide KW - 6PLQ3CP4P3 KW - Doxorubicin KW - 80168379AG KW - Verapamil KW - CJ0O37KU29 KW - Glucosylceramidase KW - EC 3.2.1.45 KW - valspodar KW - Q7ZP55KF3X KW - Colchicine KW - SML2Y3J35T KW - Index Medicus KW - Etoposide -- pharmacology KW - Animals KW - Anthracenes -- pharmacology KW - Blotting, Northern KW - DNA, Complementary -- genetics KW - Humans KW - Mice KW - Cyclosporins -- pharmacology KW - Verapamil -- pharmacology KW - Drug Resistance, Multiple KW - Fibroblasts KW - Blotting, Western KW - Colchicine -- pharmacology KW - Doxorubicin -- pharmacology KW - Transfection KW - Cells, Cultured KW - Gene Expression Regulation KW - Retroviridae -- genetics KW - Mutagenesis, Insertional KW - P-Glycoprotein -- genetics KW - Glucosylceramidase -- drug effects KW - Gaucher Disease -- genetics KW - Glucosylceramidase -- metabolism KW - Genetic Therapy -- methods KW - Glucosylceramidase -- genetics KW - Genetic Vectors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78550746?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+gene+therapy&rft.atitle=Complete+restoration+of+glucocerebrosidase+deficiency+in+Gaucher+fibroblasts+using+a+bicistronic+MDR+retrovirus+and+a+new+selection+strategy.&rft.au=Aran%2C+J+M%3BLicht%2C+T%3BGottesman%2C+M+M%3BPastan%2C+I&rft.aulast=Aran&rft.aufirst=J&rft.date=1996-11-10&rft.volume=7&rft.issue=17&rft.spage=2165&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 completed - 1997-03-03 N1 - Date created - 1997-03-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The inhibitory effect of staurosporine on insulin action is prevented by okadaic acid. Evidence for an important role of serine/threonine phosphorylation in eliciting insulin-like effects. AN - 78630243; 8972717 AB - The serine/threonine phosphatase inhibitor, okadaic acid (OA), exerted several insulin-like effects in rat adipose cells and was, in part, synergistic with insulin. OA stimulated glucose transport activity, altered the electrophoretic mobility of IRS-1, increased the phosphorylation of the MAP-kinases ERK 1 and 2 on tyrosine sites, markedly increased MAP kinase activity and also acted synergistically with insulin in activating these enzymes. However, OA did not increase PI 3-kinase activity or the tyrosine phosphorylation of key upstream proteins in insulin's signaling cascade. Staurosporine virtually completely inhibited the insulin-stimulated glucose transport and MAP kinase activation in spite of a maintained high PI 3-kinase activity. In contrast, the effects of OA alone or in the presence of insulin were less, or not at all, affected. These data suggest that OA exerts an insulin-like effect through a serine/threonine-related pathway which is distinct from, but converges with, that of insulin downstream PI 3-kinase and upon which staurosporine exerts an inhibitory effect. JF - Biochimica et biophysica acta AU - Rondinone, C M AU - Zarnowski, M J AU - Londos, C AU - Smith, U P AD - Laboratory of Cellular and Developmental Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/11/08/ PY - 1996 DA - 1996 Nov 08 SP - 49 EP - 56 VL - 1314 IS - 1-2 SN - 0006-3002, 0006-3002 KW - Enzyme Inhibitors KW - 0 KW - Insulin KW - Insulin Antagonists KW - Okadaic Acid KW - 1W21G5Q4N2 KW - Threonine KW - 2ZD004190S KW - Tyrosine KW - 42HK56048U KW - Serine KW - 452VLY9402 KW - Protein Kinases KW - EC 2.7.- KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Phosphotransferases (Alcohol Group Acceptor) KW - Receptor, Insulin KW - EC 2.7.10.1 KW - Phosphoprotein Phosphatases KW - EC 3.1.3.16 KW - Protein Phosphatase 1 KW - Staurosporine KW - H88EPA0A3N KW - Glucose KW - IY9XDZ35W2 KW - Index Medicus KW - Phosphoprotein Phosphatases -- antagonists & inhibitors KW - Animals KW - Enzyme Activation KW - Glucose -- metabolism KW - Biological Transport KW - Insulin -- pharmacology KW - Rats KW - Protein Kinases -- metabolism KW - Phosphorylation KW - Enzyme Inhibitors -- pharmacology KW - Tyrosine -- metabolism KW - Phosphotransferases (Alcohol Group Acceptor) -- metabolism KW - Male KW - Receptor, Insulin -- metabolism KW - Staurosporine -- pharmacology KW - Threonine -- metabolism KW - Okadaic Acid -- pharmacology KW - Staurosporine -- antagonists & inhibitors KW - Serine -- metabolism KW - Insulin Antagonists -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78630243?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochimica+et+biophysica+acta&rft.atitle=The+inhibitory+effect+of+staurosporine+on+insulin+action+is+prevented+by+okadaic+acid.+Evidence+for+an+important+role+of+serine%2Fthreonine+phosphorylation+in+eliciting+insulin-like+effects.&rft.au=Rondinone%2C+C+M%3BZarnowski%2C+M+J%3BLondos%2C+C%3BSmith%2C+U+P&rft.aulast=Rondinone&rft.aufirst=C&rft.date=1996-11-08&rft.volume=1314&rft.issue=1-2&rft.spage=49&rft.isbn=&rft.btitle=&rft.title=Biochimica+et+biophysica+acta&rft.issn=00063002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-22 N1 - Date created - 1997-01-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alpha-Tocopherol and beta-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: effects of base-line characteristics and study compliance. AN - 78496256; 8901854 AB - Experimental and epidemiologic investigations suggest that alpha-tocopherol (the most prevalent chemical form of vitamin E found in vegetable oils, seeds, grains, nuts, and other foods) and beta-carotene (a plant pigment and major precursor of vitamin A found in many yellow, orange, and dark-green, leafy vegetables and some fruit) might reduce the risk of cancer, particularly lung cancer. The initial findings of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study) indicated, however, that lung cancer incidence was increased among participants who received beta-carotene as a supplement. Similar results were recently reported by the Beta-Carotene and Retinol Efficacy Trial (CARET), which tested a combination of beta-carotene and vitamin A. We examined the effects of alpha-tocopherol and beta-carotene supplementation on the incidence of lung cancer across subgroups of participants in the ATBC Study defined by base-line characteristics (e.g., age, number of cigarettes smoked, dietary or serum vitamin status, and alcohol consumption), by study compliance, and in relation to clinical factors, such as disease stage and histologic type. Our primary purpose was to determine whether the pattern of intervention effects across subgroups could facilitate further interpretation of the main ATBC Study results and shed light on potential mechanisms of action and relevance to other populations. A total of 29,133 men aged 50-69 years who smoked five or more cigarettes daily were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), alpha-tocopherol and beta-carotene, or a placebo daily for 5-8 years (median, 6.1 years). Data regarding smoking and other risk factors for lung cancer and dietary factors were obtained at study entry, along with measurements of serum levels of alpha-tocopherol and beta-carotene. Incident cases of lung cancer (n = 894) were identified through the Finnish Cancer Registry and death certificates. Each lung cancer diagnosis was independently confirmed, and histology or cytology was available for 94% of the cases. Intervention effects were evaluated by use of survival analysis and proportional hazards models. All P values were derived from two-sided statistical tests. No overall effect was observed for lung cancer from alpha-tocopherol supplementation (relative risk [RR] = 0.99; 95% confidence interval [CI] = 0.87-1.13; P = .86, logrank test). beta-Carotene supplementation was associated with increased lung cancer risk (RR = 1.16; 95% CI = 1.02-1.33; P = .02, logrank test). The beta-carotene effect appeared stronger, but not substantially different, in participants who smoked at least 20 cigarettes daily (RR = 1.25; 95% CI = 1.07-1.46) compared with those who smoked five to 19 cigarettes daily (RR = 0.97; 95% CI = 0.76-1.23) and in those with a higher alcohol intake (> or = 11 g of ethanol/day [just under one drink per day]; RR = 1.35; 95% CI = 1.01-1.81) compared with those with a lower intake (RR = 1.03; 95% CI = 0.85-1.24). Supplementation with alpha-tocopherol or beta-carotene does not prevent lung cancer in older men who smoke. beta-Carotene supplementation at pharmacologic levels may modestly increase lung cancer incidence in cigarette smokers, and this effect may be associated with heavier smoking and higher alcohol intake. While the most direct way to reduce lung cancer risk is not to smoke tobacco, smokers should avoid high-dose beta-carotene supplementation. JF - Journal of the National Cancer Institute AU - Albanes, D AU - Heinonen, O P AU - Taylor, P R AU - Virtamo, J AU - Edwards, B K AU - Rautalahti, M AU - Hartman, A M AU - Palmgren, J AU - Freedman, L S AU - Haapakoski, J AU - Barrett, M J AU - Pietinen, P AU - Malila, N AU - Tala, E AU - Liippo, K AU - Salomaa, E R AU - Tangrea, J A AU - Teppo, L AU - Askin, F B AU - Taskinen, E AU - Erozan, Y AU - Greenwald, P AU - Huttunen, J K AD - Division of Cancer Prevention and Control, National Cancer Institute, Bethesda, MD 20892-7326, USA. Y1 - 1996/11/06/ PY - 1996 DA - 1996 Nov 06 SP - 1560 EP - 1570 VL - 88 IS - 21 SN - 0027-8874, 0027-8874 KW - Anticarcinogenic Agents KW - 0 KW - Antioxidants KW - Carcinogens KW - beta Carotene KW - 01YAE03M7J KW - Vitamin E KW - 1406-18-4 KW - Index Medicus KW - Age Factors KW - Anticarcinogenic Agents -- therapeutic use KW - Humans KW - Alcohol Drinking -- adverse effects KW - Smoking -- adverse effects KW - Aged KW - Multivariate Analysis KW - Risk KW - Patient Compliance KW - Risk Factors KW - Food, Fortified KW - Incidence KW - Middle Aged KW - Male KW - Proportional Hazards Models KW - Carcinogens -- adverse effects KW - Lung Neoplasms -- prevention & control KW - Lung Neoplasms -- etiology KW - beta Carotene -- therapeutic use KW - beta Carotene -- blood KW - Lung Neoplasms -- blood KW - Antioxidants -- therapeutic use KW - Vitamin E -- therapeutic use KW - Lung Neoplasms -- mortality KW - Vitamin E -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78496256?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Alpha-Tocopherol+and+beta-carotene+supplements+and+lung+cancer+incidence+in+the+alpha-tocopherol%2C+beta-carotene+cancer+prevention+study%3A+effects+of+base-line+characteristics+and+study+compliance.&rft.au=Albanes%2C+D%3BHeinonen%2C+O+P%3BTaylor%2C+P+R%3BVirtamo%2C+J%3BEdwards%2C+B+K%3BRautalahti%2C+M%3BHartman%2C+A+M%3BPalmgren%2C+J%3BFreedman%2C+L+S%3BHaapakoski%2C+J%3BBarrett%2C+M+J%3BPietinen%2C+P%3BMalila%2C+N%3BTala%2C+E%3BLiippo%2C+K%3BSalomaa%2C+E+R%3BTangrea%2C+J+A%3BTeppo%2C+L%3BAskin%2C+F+B%3BTaskinen%2C+E%3BErozan%2C+Y%3BGreenwald%2C+P%3BHuttunen%2C+J+K&rft.aulast=Albanes&rft.aufirst=D&rft.date=1996-11-06&rft.volume=88&rft.issue=21&rft.spage=1560&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-04 N1 - Date created - 1996-12-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Natl Cancer Inst. 1996 Nov 6;88(21):1513-5 [8901847] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A Symposium Summary and Perspective on Comparative Molecular Biology of Cancer AN - 856756565; 13645795 JF - Toxicologic Pathology AU - Maronpot, R R AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709 Y1 - 1996/11// PY - 1996 DA - Nov 1996 SP - 801 EP - 804 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU UK VL - 24 IS - 6 SN - 0192-6233, 0192-6233 KW - Toxicology Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/856756565?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+Pathology&rft.atitle=A+Symposium+Summary+and+Perspective+on+Comparative+Molecular+Biology+of+Cancer&rft.au=Maronpot%2C+R+R&rft.aulast=Maronpot&rft.aufirst=R&rft.date=1996-11-01&rft.volume=24&rft.issue=6&rft.spage=801&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1177%2F019262339602400628 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-10-01 N1 - Last updated - 2012-03-29 DO - http://dx.doi.org/10.1177/019262339602400628 ER - TY - JOUR T1 - Effects of diminished and conflicting sensory information on balance in patients with cerebellar deficits. AN - 85273633; pmid-8914091 AB - We studied the effects of altered sensory information on standing balance in 25 patients with cortical cerebellar atrophy (CCA), nine patients with olivoponto-cerebellar atrophy (OPCA), and 10 normal subjects. The total sway path and its components, the anteroposterior (AP) sway path and the lateral sway path, were measured under six conditions: (1) standing on a fixed platform with the eyes open and visual surroundings fixed, (2) standing on a fixed platform with the eyes closed, (3) standing on a fixed platform with the eyes open and visual surroundings AP sway referenced, (4) standing on an AP sway-referenced platform with the eyes open and visual surroundings fixed, (5) standing on an AP sway-referenced platform with the eyes closed, and (6) standing on an AP sway-referenced platform with the eyes open and visual surroundings AP sway referenced. Patients swayed more than normal subjects during normal stance (condition 1), when the visual information was absent (condition 2) or distorted (condition 3), and when the proprioceptive information from the ankles was distorted (condition 4). Patients swayed much more than normal, and most fell, when two sensory modalities were affected under condition 5 (proprioceptive information distorted and visual information absent) and condition 6 (both proprioceptive information and visual information distorted). When the patients' sway was normalized to that of the first condition, however, only their lateral sway was greater than the sway in normal subjects. Unlike in normal subjects, the patients' lateral sway varied with the AP sway to approximately the same degree in each condition for conditions 1-5. Clinical ratings of gait and balance were highly correlated with the sway measures. Quantitative testing of standing balance with altered sensory information has better sensitivity than normal stance testing. JF - Movement Disorders AU - Gatev, P AU - Thomas, S AU - Lou, J S AU - Lim, M AU - Hallett, M AD - Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1428, USA. PY - 1996 SP - 654 EP - 664 VL - 11 IS - 6 SN - 0885-3185, 0885-3185 KW - Support, U.S. Gov't, P.H.S. KW - Sensory Deprivation KW - Human KW - Perceptual Distortion KW - Aged KW - Cerebellar Cortex KW - Kinesthesis KW - Cerebellar Ataxia KW - Equilibrium KW - Proprioception KW - Adult KW - Middle Age KW - Olivopontocerebellar Atrophies KW - Atrophy KW - Posture KW - Male KW - Female UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85273633?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Movement+Disorders&rft.atitle=Effects+of+diminished+and+conflicting+sensory+information+on+balance+in+patients+with+cerebellar+deficits.&rft.au=Gatev%2C+P%3BThomas%2C+S%3BLou%2C+J+S%3BLim%2C+M%3BHallett%2C+M&rft.aulast=Gatev&rft.aufirst=P&rft.date=1996-11-01&rft.volume=11&rft.issue=6&rft.spage=654&rft.isbn=&rft.btitle=&rft.title=Movement+Disorders&rft.issn=08853185&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Use of quantitative assays for hepatitis B e antigen and IgM antibody to hepatitis B core antigen to monitor therapy in chronic hepatitis B. AN - 85233062; pmid-8931411 AB - OBJECTIVES: We evaluated the clinical utility of IgM antibody to the hepatitis B (HB) core antigen (anti-HBc) and HB e antigen (HBeAg) serum levels in patients with chronic HB receiving interferon alfa. METHODS: Stored serum from 47 patients with chronic HB participating in a controlled trial of interferon alfa therapy (10 million U three times a week for 16 wk) were analyzed. All were seropositive for HB surface Ag, HBeAg, and HB virus (HBV) DNA before entry. IgM anti-HBc index values and HBeAg standard values were determined by automated microparticle enzyme immunoassay on samples drawn just before therapy and 6 months later. Ten normal subjects were tested as controls. IgM anti-HBc and HBeAg levels were compared to initial serum HBV DNA, DNA polymerase, serum aminotransferase levels, and demographic features. Serial IgM anti-HBc levels were also obtained during and after therapy in 10 responders and five nonresponders, and serial HBeAg levels were also obtained during and after therapy in four responders and four nonresponders. RESULTS: Neither IgM anti-HBc nor HBeAg levels correlated significantly with values for serum HBV DNA, DNA polymerase, aminotransferases, or demographic features. The initial mean IgM anti-HBc level among the 15 responders to therapy (loss of HBeAg and HBV DNA from serum) was no different from that in nonresponders (mean 1.15 vs 1.27, p = not significant). However, the initial mean HBeAg level was significantly lower in responders than in nonresponders (749.4 vs 1356.4, p = 0.019). Among 10 responders, IgM anti-HBc levels decreased progressively over time, so that at latest follow-up (1.5-4 yr later, mean 2.6 yr), the mean had decreased from 1.325 to 0.312 (p = < 0.001). Among five nonresponders, the mean did not change significantly over 1.5-3 yr (mean 2.2 yr) (1.26 vs 1.08, p = not significant). HBeAg values fell in parallel with HBV DNA and DNA polymerase values in four responders tested but remained elevated in four nonresponders. CONCLUSIONS: HBeAg levels, but not IgM anti-HBc levels, are useful in predicting response to interferon alfa, with responders tending to have lower pretreatment HBeAg levels than nonresponders. HBeAg levels may be used to monitor response to interferon alfa in patients with chronic HB. JF - The American Journal of Gastroenterology AU - Hayashi, P H AU - Beames, M P AU - Kuhns, M C AU - Hoofnagle, J H AU - Di Bisceglie A M AD - Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA. PY - 1996 SP - 2323 EP - 2328 VL - 91 IS - 11 SN - 0002-9270, 0002-9270 KW - Hepatitis, Chronic KW - Human KW - Hepatitis B Core Antigens KW - Predictive Value of Tests KW - Hepatitis B e Antigens KW - Antiviral Agents KW - Comparative Study KW - Hepatitis B Antibodies KW - Cohort Studies KW - Case-Control Studies KW - Hepatitis B KW - Follow-Up Studies KW - Interferon Alfa-2b KW - Time Factors KW - Immunoglobulin M KW - Immunoenzyme Techniques UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85233062?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+Journal+of+Gastroenterology&rft.atitle=Use+of+quantitative+assays+for+hepatitis+B+e+antigen+and+IgM+antibody+to+hepatitis+B+core+antigen+to+monitor+therapy+in+chronic+hepatitis+B.&rft.au=Hayashi%2C+P+H%3BBeames%2C+M+P%3BKuhns%2C+M+C%3BHoofnagle%2C+J+H%3BDi+Bisceglie+A+M&rft.aulast=Hayashi&rft.aufirst=P&rft.date=1996-11-01&rft.volume=91&rft.issue=11&rft.spage=2323&rft.isbn=&rft.btitle=&rft.title=The+American+Journal+of+Gastroenterology&rft.issn=00029270&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Nasopharyngeal radium irradiation: the Washington County, Maryland, study. AN - 85205019; pmid-8903438 AB - Although there have been many studies of cancer risk associated with a variety of x-ray treatments for benign conditions of the head and neck, little is known about the possible long-term health consequences of nasopharyngeal radium irradiation. This treatment results in minimal radiation exposure to the thyroid gland, which is the focus of much of the research regarding other head and neck irradiation. With nasopharyngeal radiation, on the other hand, exposure to the pituitary gland and the nasopharynx in the area immediately adjacent to the application site may have been substantial. In 1975 a follow-up study was undertaken in Washington County, Maryland, of 2925 persons who were treated at the Health Department's Clinic for the Prevention of Deafness in Children between 1943 and 1960. Of these, 904 persons had been treated with nasopharyngeal radium. After an average of 24 years of follow-up, an excess risk from brain cancer was suggested on the basis of three cases of cancer occurring in the treated group and none occurring in those who were not treated. This finding could have resulted by chance. Other results were consistent with a potential pituitary effect of radiation, but interpretation is limited by the absence of clinical and laboratory data. The history of the study is reported along with an overview of study methods and results. JF - Otolaryngology--Head and Neck Surgery AU - Sandler, D P AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. PY - 1996 SP - 409 EP - 414 VL - 115 IS - 5 SN - 0194-5998, 0194-5998 KW - United States KW - Brain Neoplasms KW - Radiation Dosage KW - Human KW - Adult KW - Radiotherapy KW - Follow-Up Studies KW - Nasopharynx KW - Maryland KW - Pituitary Neoplasms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85205019?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Otolaryngology--Head+and+Neck+Surgery&rft.atitle=Nasopharyngeal+radium+irradiation%3A+the+Washington+County%2C+Maryland%2C+study.&rft.au=Sandler%2C+D+P&rft.aulast=Sandler&rft.aufirst=D&rft.date=1996-11-01&rft.volume=115&rft.issue=5&rft.spage=409&rft.isbn=&rft.btitle=&rft.title=Otolaryngology--Head+and+Neck+Surgery&rft.issn=01945998&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Head and neck radiation carcinogenesis: epidemiologic evidence. AN - 85204887; pmid-8903437 AB - This article provides an overview of the long-term carcinogenic effects of medical radiation exposure to the head and neck and focuses on studies that allow risk quantification. The thyroid gland in children is extremely sensitive to the tumorigenic effects of external radiation for many years after exposure. Risk of thyroid cancer decreases with increasing age at exposure, with little risk, if any, apparent among persons exposed as adults. Large risks of neural tumors have been reported after moderate- and high-dose radiotherapy in childhood; however, the magnitude of the risk at low doses and for adult exposures is unclear. Data on salivary gland tumors are limited but tend to support an association with radiation exposure. In contrast, the pituitary gland appears to be relatively resistant to the tumorigenic effects of radiation. Several cohort studies have reported an increased risk of hyperparathyroidism among irradiated populations. In summary, radiation exposure to the head and neck can result in tumors of the thyroid, salivary, and parathyroid glands, as well as the brain and central nervous system. JF - Otolaryngology--Head and Neck Surgery AU - Ron, E AU - Saftlas, A F AD - Division of Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. PY - 1996 SP - 403 EP - 408 VL - 115 IS - 5 SN - 0194-5998, 0194-5998 KW - Brain Neoplasms KW - Parathyroid Neoplasms KW - Radiation Dosage KW - Age Factors KW - Thyroid Neoplasms KW - Human KW - Incidence KW - Radiotherapy KW - Child KW - Pituitary Neoplasms KW - Adolescent KW - Salivary Gland Neoplasms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85204887?accountid=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=Computers+in+Human+Behavior&rft.atitle=Examining+effective+technology+project+leadership+traits+and+behaviors&rft.au=Strang%2C+Kenneth+David&rft.aulast=Strang&rft.aufirst=Kenneth&rft.date=2007-01-01&rft.volume=23&rft.issue=1&rft.spage=424&rft.isbn=&rft.btitle=&rft.title=Computers+in+Human+Behavior&rft.issn=07475632&rft_id=info:doi/10.1016%2Fj.chb.2004.10.041 LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Prevention and treatment of alcohol-related problems: an international medical education model. AN - 78748795; 9217509 AB - Alcohol abuse and alcoholism are among the world's most pressing public health concerns. Research has shown that while primary care physicians are in a good position to screen for alcohol-use disorders and to aid in treating these problems, they tend to identify only a small percentage of patients with such disorders and they rarely intervene with these persons. This situation is probably attributable to the fact that medical students worldwide are taught very little about alcohol-related problems. Clearly there is an urgent need to educate the world's doctors about preventing, diagnosing, and treating alcohol abuse and addiction. In this paper, the authors describe a model international program for educating physicians about alcohol-related problems that was developed by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) in cooperation with the Center for Addiction Research and Education (CARE) at the University of Wisconsin-Madison. They describe the components of the initiative's "trainer-development" approach and critical issues in implementing the program in other countries. Finally, they discuss how the program was successfully implemented in Poland and describe the NIAAA's plans for introducing the model in several other countries. JF - Academic medicine : journal of the Association of American Medical Colleges AU - Murray, M AU - Fleming, M AD - International Research and Training Program, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892-7033, USA. pmurray@willco.niaaa.nih.gov Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 1204 EP - 1210 VL - 71 IS - 11 SN - 1040-2446, 1040-2446 KW - Abridged Index Medicus KW - Index Medicus KW - United States KW - Poland KW - Humans KW - Curriculum KW - National Institutes of Health (U.S.) KW - Models, Educational KW - Education, Medical KW - International Cooperation KW - Alcoholism -- therapy KW - Alcoholism -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78748795?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Academic+medicine+%3A+journal+of+the+Association+of+American+Medical+Colleges&rft.atitle=Prevention+and+treatment+of+alcohol-related+problems%3A+an+international+medical+education+model.&rft.au=Murray%2C+M%3BFleming%2C+M&rft.aulast=Murray&rft.aufirst=M&rft.date=1996-11-01&rft.volume=71&rft.issue=11&rft.spage=1204&rft.isbn=&rft.btitle=&rft.title=Academic+medicine+%3A+journal+of+the+Association+of+American+Medical+Colleges&rft.issn=10402446&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-07 N1 - Date created - 1997-08-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pretreatment with phorbol ester and an LHRH agonist reduces testosterone production and protein kinase C activity in rat Leydig cells challenged with PDBu and LHRH. AN - 78739069; 9196561 AB - We have investigated the role of protein kinase C (PK-C) in luteinizing hormone-releasing hormone (LHRH)-induced testosterone secretion from purified rat Leydig cells (70-80-day old Sprague-Dawley rats) by pretreating the cells in vitro with 200 mM phorbol 12,13-dibutyrate (PDBu) (a known procedure to down-modulate this enzyme in most cell types) and 1 muM [D-Ala6,Des-Gly10]-LHRH ethylamide, an LHRH agonist (LHRH-A). Following pretreatment we measured PK-C activity and secretion of testosterone in response to subsequent challenges with the PK-C activator PDBu (20-2000 nM) and with LHRH (0.001-1.0 muM) and the Ca(2+)-mobilizing secretagogue A23187 (0.1-100 microM) in the same cell preparation. PDBu and LHRH-A pretreatments caused a reduction in testosterone secretion in response to subsequent exposure to PDBu or LHRH. Both pretreatments decreased PK-C activity in crude and purified extracts of the same cells. The magnitude of reduction of the secretory response was greater than that of enzyme activity for both PDBu and LHRH-A pretreatment (68.9% reduction of testosterone secretion vs 54.7% reduction of PK-C activity in PDBu-pretreated cells and 78.6% reduction of testosterone production vs 36.6% reduction of PK-C activity in LHRH-A-pretreated cells). The effect of phorbol ester pretreatment on PDBu- or LHRH-stimulated testosterone secretion and PK-C activity was specific (no measurable effect with 4 alpha-PDBu, an inactive phorbol ester). While PDBu and LHRH-A pretreatment reduced Leydig cell responsiveness to PDBu or LHRH, the secretion of testosterone in response to the Ca2+ -mobilizing secretagogue A23187 was similar in PDBu- and LHRH-A-pretreated and in control (non-pretreated) cells. We conclude that down-modulation of protein kinase C by prolonged exposure of Leydig cells to phorbol esters or LHRH-A results in decreased PK-C activity and testosterone secretion. These results provide the first evidence that pretreatment with LHRH-A, which does not enter the cell, can affect the steroidogenesis and PK-C activity responses to PDBu (the intracellular ligand of PK-C). JF - Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas AU - Wanderley, M I AU - Negro-Vilar, A AD - Laboratory of Molecular and Integrative Neuroscience, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. miw@npd.ufe.br Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 1557 EP - 1565 VL - 29 IS - 11 SN - 0100-879X, 0100-879X KW - Phorbol Esters KW - 0 KW - Gonadotropin-Releasing Hormone KW - 33515-09-2 KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - Testosterone KW - 3XMK78S47O KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - In Vitro Techniques KW - Male KW - Phorbol 12,13-Dibutyrate -- pharmacology KW - Protein Kinase C -- metabolism KW - Protein Kinase C -- drug effects KW - Phorbol Esters -- pharmacology KW - Gonadotropin-Releasing Hormone -- agonists KW - Leydig Cells -- metabolism KW - Phorbol Esters -- administration & dosage KW - Testosterone -- biosynthesis KW - Gonadotropin-Releasing Hormone -- administration & dosage KW - Leydig Cells -- drug effects KW - Gonadotropin-Releasing Hormone -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78739069?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brazilian+journal+of+medical+and+biological+research+%3D+Revista+brasileira+de+pesquisas+medicas+e+biologicas&rft.atitle=Pretreatment+with+phorbol+ester+and+an+LHRH+agonist+reduces+testosterone+production+and+protein+kinase+C+activity+in+rat+Leydig+cells+challenged+with+PDBu+and+LHRH.&rft.au=Wanderley%2C+M+I%3BNegro-Vilar%2C+A&rft.aulast=Wanderley&rft.aufirst=M&rft.date=1996-11-01&rft.volume=71&rft.issue=3&rft.spage=402&rft.isbn=&rft.btitle=&rft.title=Journal+of+Applied+Psychology&rft.issn=00219010&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-09-11 N1 - Date created - 1997-09-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of lupus nephritis. AN - 78732715; 9125797 AB - Lupus nephritis is a prototype of immune complex-mediated glomerulonephritis. A broad range of clinical presentations and histological changes (proliferative, membranous, or both) are observed. Patients are at risk for progressive renal function deterioration as a result of the interaction of various active immunologic and chronic sclerosing mechanisms of kidney injury. Hypertension and hyperlipidemia contribute to morbidity and mortality. Monitoring serological parameters, urinary protein excretion rate and, especially, the urinary sediment facilitate the prompt recognition and treatment of this disorder. Kidney biopsy evaluation often clarifies the type, severity, and potential reversibility of the underlying renal lesions. Although contemporary immunosuppressive regimens for proliferative lupus nephritis have reduced the risk of end-stage renal failure, they are potentially toxic and not universally effective. Decisions regarding the intensity and duration of these treatments are difficult and are based on the severity of the disease, the initial response to therapy, and the risk for drug-induced toxicities. Studies are in progress to evaluate alternative regimens for proliferative lupus nephritis and membranous lupus nephropathy. JF - Seminars in nephrology AU - Austin, H A AU - Boumpas, D T AD - Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892-1268, USA. Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 527 EP - 535 VL - 16 IS - 6 SN - 0270-9295, 0270-9295 KW - Glucocorticoids KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Prognosis KW - Clinical Trials as Topic KW - Immunosuppression -- methods KW - Lupus Nephritis -- physiopathology KW - Lupus Nephritis -- drug therapy KW - Lupus Nephritis -- diagnosis KW - Glucocorticoids -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78732715?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+nephrology&rft.atitle=Treatment+of+lupus+nephritis.&rft.au=Austin%2C+H+A%3BBoumpas%2C+D+T&rft.aulast=Austin&rft.aufirst=H&rft.date=1996-11-01&rft.volume=16&rft.issue=6&rft.spage=527&rft.isbn=&rft.btitle=&rft.title=Seminars+in+nephrology&rft.issn=02709295&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-20 N1 - Date created - 1997-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Repetitive movements of the upper limbs: results of exposure evaluation and clinical investigation in the manual sanding of wood in the Valdichiana region]. TT - Movimenti ripetitivi degli arti superiori: risultati della valutazione dell'esposizione e dell'indagine clinica nella carteggiatura manuale del legno in Valdichiana. AN - 78730859; 9148119 AB - The aim of this study was to evaluate the level of risk exposure deriving from repetitive movements of the upper limbs, among a population of female workers manually sand papering timber products. The study also included an anamnestic and clinical assessment for the purpose of detecting and diagnosing WMSDs in the study population. The authors report a distinct prevalence of such disorders among the female workers exposed to a high level of risk, also in view of the total absence of recovery periods. JF - La Medicina del lavoro AU - Biondi, M C AU - Nanni, C AU - Sallese, D AD - Sezione Aggregata Igiene e Salute nei Luoghi di Lavoro, Torrita di Siena. PY - 1996 SP - 625 EP - 633 VL - 87 IS - 6 SN - 0025-7818, 0025-7818 KW - Index Medicus KW - Humans KW - Biomechanical Phenomena KW - Adult KW - Italy -- epidemiology KW - Adolescent KW - Male KW - Female KW - Risk Assessment KW - Prevalence KW - Wood KW - Occupational Exposure -- adverse effects KW - Occupational Diseases -- epidemiology KW - Arm KW - Cumulative Trauma Disorders -- epidemiology KW - Musculoskeletal Diseases -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78730859?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=La+Medicina+del+lavoro&rft.atitle=%5BRepetitive+movements+of+the+upper+limbs%3A+results+of+exposure+evaluation+and+clinical+investigation+in+the+manual+sanding+of+wood+in+the+Valdichiana+region%5D.&rft.au=Biondi%2C+M+C%3BNanni%2C+C%3BSallese%2C+D&rft.aulast=Biondi&rft.aufirst=M&rft.date=1996-11-01&rft.volume=87&rft.issue=6&rft.spage=625&rft.isbn=&rft.btitle=&rft.title=La+Medicina+del+lavoro&rft.issn=00257818&rft_id=info:doi/ LA - Italian DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-12 N1 - Date created - 1997-05-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A new metabolite of retinol: all-trans-4-oxo-retinol as a receptor activator and differentiation agent. AN - 78730732; 9110564 AB - All-trans-4-oxo-retinol, a metabolite of retinol synthesized in mouse embryonal carcinoma F9 cells, is active in inducing differentiation of these cells. It also functions as a ligand of retinoic acid receptors and a transcriptional activator of reporter genes. These findings may dispel the notion that retinoic acids are the only transactivators of retinoid receptor-dependent pathways. However, there are weaknesses that need to be addressed in order to confirm the relevance of this retinol-mediated signaling pathway. JF - Nutrition reviews AU - Ross, S A AU - De Luca, L M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 355 EP - 356 VL - 54 IS - 11 Pt 1 SN - 0029-6643, 0029-6643 KW - Receptors, Retinoic Acid KW - 0 KW - Vitamin A KW - 11103-57-4 KW - 4-oxoretinol KW - 62702-55-0 KW - Index Medicus KW - Molecular Structure KW - Animals KW - Binding Sites KW - Receptors, Retinoic Acid -- metabolism KW - Vitamin A -- analogs & derivatives KW - Vitamin A -- chemistry KW - Vitamin A -- pharmacology KW - Receptors, Retinoic Acid -- chemistry KW - Vitamin A -- metabolism KW - Receptors, Retinoic Acid -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78730732?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nutrition+reviews&rft.atitle=A+new+metabolite+of+retinol%3A+all-trans-4-oxo-retinol+as+a+receptor+activator+and+differentiation+agent.&rft.au=Ross%2C+S+A%3BDe+Luca%2C+L+M&rft.aulast=Ross&rft.aufirst=S&rft.date=1996-11-01&rft.volume=54&rft.issue=11+Pt+1&rft.spage=355&rft.isbn=&rft.btitle=&rft.title=Nutrition+reviews&rft.issn=00296643&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-09 N1 - Date created - 1997-05-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Carpal tunnel syndrome in workers engaged in the assembly of manufactured products in various industries in the province of Brescia]. TT - Sindrome del tunnel carpale in addetti all'assemblaggio di manufatti vari nell'industria del bresciano. AN - 78715808; 9148125 AB - Tests were carried out on five manual assembly departments in a variety of different factories, in order to assess the risks associated with the onset of Carpal Tunnel Syndrome and to describe the prevalence of this disorder among exposed workers. The application of the risk analysis method proposed by the EPM Research Unit in Milan (Italy) demonstrated the presence of numerous jobs featuring both a high frequency of actions per minute and a total lack of recovery times, in addition to a variety of incongrous upper limb postures. The clinical and instrumental investigation diagnosed 76 cases of Carpal Tunnel Syndrome among the 170 exposed workers. 62% of the cases was bilateral and 24% was associated with Guyon Channel Syndrome. In two of the five departments reviewed, the carpal tunnel disorders detected were endemic, and featured unusually high prevalence. The situation had been seriously underestimated by the company technical and medical staff, resulting in a failure to call for the urgent adoption of individual protection and collective prevention measures. The authors recommend that an extensive and adequate occupational risk assessment analysis be performed: the local occupational health services could play a critical role in identifying the highest risk industries and the diseases diagnosed in a hospital environment. JF - La Medicina del lavoro AU - Barbieri, P G AD - U.O. Tutela della Salute nei Luoghi di Lavoro, Azienda USSL 14, Chiari, Brescia. PY - 1996 SP - 686 EP - 692 VL - 87 IS - 6 SN - 0025-7818, 0025-7818 KW - Index Medicus KW - Risk Factors KW - Humans KW - Adult KW - Italy -- epidemiology KW - Risk Assessment KW - Prevalence KW - Carpal Tunnel Syndrome -- epidemiology KW - Occupational Diseases -- epidemiology KW - Industry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78715808?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=La+Medicina+del+lavoro&rft.atitle=%5BCarpal+tunnel+syndrome+in+workers+engaged+in+the+assembly+of+manufactured+products+in+various+industries+in+the+province+of+Brescia%5D.&rft.au=Barbieri%2C+P+G&rft.aulast=Barbieri&rft.aufirst=P&rft.date=1996-11-01&rft.volume=87&rft.issue=6&rft.spage=686&rft.isbn=&rft.btitle=&rft.title=La+Medicina+del+lavoro&rft.issn=00257818&rft_id=info:doi/ LA - Italian DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-12 N1 - Date created - 1997-05-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The cellular interaction of 5-fluorouracil and cisplatin in a human colon carcinoma cell line. AN - 78689882; 9014759 AB - The combination of 5-fluorouracil (5-FU) and cisplatin (CDDP) has been shown to have synergistic cytotoxicity in human tumours, but the biochemical mechanism for this interaction remains unclear. Therefore, the aim of this study was to investigate the interaction of 5-FU and CDDP in a human colon carcinoma cell line, NCI H548. A 24 h exposure to 5-FU resulted in a 5-FU IC50 value of 24.2 +/- 4.5 microM, Dm 22.6 microM; exposure to CDDP for 2 h resulted in a IC50 value of 20.8 +/- 8.0 microM, Dm 21.9 microM. When cells were exposed simultaneously to 5-FU for 24 h and CDDP for the initial 2 h, or when cells were treated with CDDP for 2 h followed by various concentrations of 5-FU for 24 h, no greater than additive cytotoxicity was observed. In contrast, when cells were treated with 5-FU for 24 h prior to CDDP for 2 h, a greater than additive interaction was noted (5-FU IC50 1.2 +/- 0.6 microM, Dm 1.3 microM, CI 0.45). Thymidine 10 microM partially reversed the growth inhibitory effects of the 5-FU/ CDDP combination. Using both immunological and biochemical assays, no notable differences in the total amount of TS enzyme or the fraction of bound TS enzyme could be detected in the absence or presence of CDDP. No notable differences could be detected in intracellular reduced folate pools, FdUMP or FUTP pools, or 5-FU incorporation into RNA or DNA with the addition of CDDP to 5-FU. DNA fragmentation studies revealed that the combination of 5-FU followed by CDDP demonstrated a greater degree of single-stranded DNA fragments in parental (P = 0.024) and newly synthesised DNA (P = 0.025) compared with the administration of CDDP prior to 5-FU or either drug alone. The increase in smaller DNA fragment size was reversed with the addition of thymidine (10 microM). These findings suggest that the interaction of 5-FU and CDDP is associated with a greater degree of fragmentation of both nascent and parental DNA. JF - European journal of cancer (Oxford, England : 1990) AU - Johnston, P G AU - Geoffrey, F AU - Drake, J AU - Voeller, D AU - Grem, J L AU - Allegra, C J AD - NCI-Navy Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 2148 EP - 2154 VL - 32A IS - 12 SN - 0959-8049, 0959-8049 KW - DNA, Neoplasm KW - 0 KW - Folic Acid KW - 935E97BOY8 KW - Thymidylate Synthase KW - EC 2.1.1.45 KW - Cisplatin KW - Q20Q21Q62J KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Drug Administration Schedule KW - Tumor Cells, Cultured -- drug effects KW - Thymidylate Synthase -- drug effects KW - DNA Damage KW - Humans KW - Cell Division -- drug effects KW - Cisplatin -- administration & dosage KW - DNA, Neoplasm -- drug effects KW - Fluorouracil -- administration & dosage KW - Blotting, Western KW - Folic Acid -- metabolism KW - Cisplatin -- pharmacology KW - Fluorouracil -- pharmacology KW - Drug Synergism KW - Colonic Neoplasms -- genetics KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacology KW - Colonic Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78689882?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+cancer+%28Oxford%2C+England+%3A+1990%29&rft.atitle=The+cellular+interaction+of+5-fluorouracil+and+cisplatin+in+a+human+colon+carcinoma+cell+line.&rft.au=Johnston%2C+P+G%3BGeoffrey%2C+F%3BDrake%2C+J%3BVoeller%2C+D%3BGrem%2C+J+L%3BAllegra%2C+C+J&rft.aulast=Johnston&rft.aufirst=P&rft.date=1996-11-01&rft.volume=32A&rft.issue=12&rft.spage=2148&rft.isbn=&rft.btitle=&rft.title=European+journal+of+cancer+%28Oxford%2C+England+%3A+1990%29&rft.issn=09598049&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-18 N1 - Date created - 1997-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Update on therapy for refractory dermatomyositis and polymyositis. AN - 78673874; 9018458 AB - Evaluation of new therapies for the inflammatory myopathies is complicated by the heterogeneity of these syndromes as well as by the lack of internationally accepted definitions of disease categories and assessments of disease activity and chronicity. This review covers our opinion of therapies and emphasizes the need for an early rehabilitation evaluation for these patients. Oral corticosteroids are the first line of therapy for the inflammatory myopathies, but because of their side effects and the existence of a subset of patients in whom disease is controlled only with high-dose corticosteroids, we recommend considering the early use of a second-line immunomodulating agents or pulse intravenous methylprednisolone. A stepwise progression of therapies is suggested for patients who have increasing muscle weakness resulting from active disease. JF - Current opinion in rheumatology AU - Villalba, L AU - Adams, E M AD - National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Arthritis and Rheumatism Branch, Bethesda, MD 20892-1820, USA. Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 544 EP - 551 VL - 8 IS - 6 SN - 1040-8711, 1040-8711 KW - Glucocorticoids KW - 0 KW - Immunoglobulins, Intravenous KW - Immunosuppressive Agents KW - Chlorambucil KW - 18D0SL7309 KW - Cyclosporine KW - 83HN0GTJ6D KW - Cyclophosphamide KW - 8N3DW7272P KW - Azathioprine KW - MRK240IY2L KW - Tacrolimus KW - WM0HAQ4WNM KW - Methylprednisolone KW - X4W7ZR7023 KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Immunoglobulins, Intravenous -- therapeutic use KW - Drug Therapy, Combination KW - Methylprednisolone -- therapeutic use KW - Cyclophosphamide -- therapeutic use KW - Tacrolimus -- therapeutic use KW - Humans KW - Cyclosporine -- therapeutic use KW - Azathioprine -- therapeutic use KW - Methotrexate -- therapeutic use KW - Chlorambucil -- therapeutic use KW - Dermatomyositis -- drug therapy KW - Polymyositis -- drug therapy KW - Glucocorticoids -- therapeutic use KW - Immunosuppressive Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78673874?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+rheumatology&rft.atitle=Update+on+therapy+for+refractory+dermatomyositis+and+polymyositis.&rft.au=Villalba%2C+L%3BAdams%2C+E+M&rft.aulast=Villalba&rft.aufirst=L&rft.date=1996-11-01&rft.volume=8&rft.issue=6&rft.spage=544&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+rheumatology&rft.issn=10408711&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-20 N1 - Date created - 1997-03-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I study of pentosan polysulfate sodium in patients with advanced malignancies. AN - 78672189; 9006745 AB - Pentosan polysulfate (xylanopolyhydrogensulfate) is a semi-synthetic sulfated heparinoid polysaccharide which has been used as an anticoagulant for nearly thirty years in Europe. It antagonizes the binding of bFGF to cell surface receptors and has thus been evaluated for antitumor activity in several animal models and human tumor cell lines. In two angiogenic models pentosan has been shown to inhibit bFGF stimulation of angiogenesis. Previous clinical studies have determined the coagulation effects of pentosan to be the dose-limiting toxicity. We conducted a phase I study designed to define the duration-limiting toxicity associated with progressive prolongation of a continuous intravenous infusion (three, five, and eight weeks). This study was not designed to escalate the dose of pentosan beyond that required to maintain the activated partial thromboplastin time (aPTT) between 1.8 and 2.2 times the baseline value. Thirteen patients with advanced stage metastatic cancer were enrolled (median age 50 years, range 34 to 61 years). Four patients were treated in cohort #1 (three weeks of infusional therapy), five patients were treated in cohort #2 (five weeks of therapy), and four patients in cohort #3 (eight weeks of therapy). All patients experienced a progressive prolongation of their aPTT and PT. Furthermore, all patients experienced at least grade I thrombocytopenia. Other complications were, in general, mild. One patient developed grade III liver abnormalities while receiving the eight-week infusion and another patient developed grade IV thrombocytopenia while receiving the same regimen. One patient with colon cancer had stable disease for 24 weeks, while the remaining 12 patients had no objective evidence of response. Pentosan was well tolerated when doses were adjusted for aPTT prolongations and a five-week cycle appeared to be the maximum tolerated duration of infusion (initially 4 mg/kg/day). One patient had stable disease, but there was no objective tumor response noted in the remaining 12 patients. JF - Annals of oncology : official journal of the European Society for Medical Oncology AU - Lush, R M AU - Figg, W D AU - Pluda, J M AU - Bitton, R AU - Headlee, D AU - Kohler, D AU - Reed, E AU - Sartor, O AU - Cooper, M R AD - Clinical Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 939 EP - 944 VL - 7 IS - 9 SN - 0923-7534, 0923-7534 KW - Antineoplastic Agents KW - 0 KW - Pentosan Sulfuric Polyester KW - 37300-21-3 KW - Index Medicus KW - Drug Administration Schedule KW - Infusions, Intravenous KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Middle Aged KW - Male KW - Female KW - Neoplasms -- drug therapy KW - Pentosan Sulfuric Polyester -- therapeutic use KW - Antineoplastic Agents -- therapeutic use KW - Pentosan Sulfuric Polyester -- adverse effects KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78672189?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+oncology+%3A+official+journal+of+the+European+Society+for+Medical+Oncology&rft.atitle=A+phase+I+study+of+pentosan+polysulfate+sodium+in+patients+with+advanced+malignancies.&rft.au=Lush%2C+R+M%3BFigg%2C+W+D%3BPluda%2C+J+M%3BBitton%2C+R%3BHeadlee%2C+D%3BKohler%2C+D%3BReed%2C+E%3BSartor%2C+O%3BCooper%2C+M+R&rft.aulast=Lush&rft.aufirst=R&rft.date=1996-11-01&rft.volume=7&rft.issue=9&rft.spage=939&rft.isbn=&rft.btitle=&rft.title=Annals+of+oncology+%3A+official+journal+of+the+European+Society+for+Medical+Oncology&rft.issn=09237534&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-02 N1 - Date created - 1997-04-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The contribution of the mouse in hazard identification studies. AN - 78652519; 8994301 AB - Because three is usually more extensive toxicity, metabolism, and pharmacokinetic information for pharmaceuticals as opposed to environmental agents, including pesticides, the argument has been made that carcinogenicity testing in two rodent species may not have been necessary for carcinogenicity testing of pharmaceuticals. On the basis of numerical data only, it may be argued that carcinogenicity testing of pharmaceuticals in one species, typically the rat, is sufficient to identify potential human carcinogens. The argument that testing in a second species, typically the mouse, is redundant overlooks the value added by the second species carcinogenicity study. Bioassay data from the second species allows balance and perspective in evaluating the observed effects, and this is especially critical when there is a marginal, questionable, or inconclusive response in one species. Utilization of two species for carcinogen identification is the principal means for identifying trans-species carcinogens-those mostly likely to be carcinogenic in humans. Given that neither rat nor mouse are ideal surrogates for humans, concordant data from both species strengthens the ability to extrapolate findings to humans. We believe that testing in two species should continue to be the default approach used for carcinogen hazard identification whenever scientifically indicated until such time that acceptable and suitable alternatives are available. To utilize only one species for this important means of protecting human health is premature at this time. JF - Toxicologic pathology AU - Maronpot, R R AU - Boorman, G A AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. PY - 1996 SP - 726 EP - 731 VL - 24 IS - 6 SN - 0192-6233, 0192-6233 KW - Carcinogens KW - 0 KW - Hazardous Substances KW - Index Medicus KW - Animals KW - Mice KW - Models, Biological KW - Hazardous Substances -- adverse effects KW - Carcinogenicity Tests KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78652519?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+contribution+of+the+mouse+in+hazard+identification+studies.&rft.au=Maronpot%2C+R+R%3BBoorman%2C+G+A&rft.aulast=Maronpot&rft.aufirst=R&rft.date=1996-11-01&rft.volume=24&rft.issue=6&rft.spage=726&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 - 1997-03-31 N1 - Date created - 1997-03-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tumor suppressor p53 gene forms multiple isoforms: evidence for single locus origin and cytoplasmic complex formation with heat shock proteins. AN - 78648501; 8982609 AB - The tumor suppressor protein p53 is a major cell cycle control factor, and mutations in p53 are the most common genetic lesion found in human tumors, resulting in loss of function and contributing to malignant transformation. This report reviews several studies which show that p53 protein appears as at least eleven isoforms having the same amino acid backbone but varying in charge by level of phosphorylation. All isoforms are derived from a single locus, which indicates that p53 activity is modulated by post-translational modification. In addition, mutant p53 forms hetero-oligomers with two families of proteins: HSP70 and a 90 kDa group similar to HSP90. Cytoplasmic complexes are most likely formed to protect p53 from proteolysis and are probably involved in translocation of activated p53 from the cytoplasm to the nucleus for transactivation of other cell cycle control genes. JF - Electrophoresis AU - Selkirk, J K AU - He, C AU - Patterson, R M AU - Merrick, B A AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 1764 EP - 1771 VL - 17 IS - 11 SN - 0173-0835, 0173-0835 KW - HSP90 Heat-Shock Proteins KW - 0 KW - Macromolecular Substances KW - Neoplasm Proteins KW - Phosphoproteins KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Animals KW - Pleural Effusion -- pathology KW - Carcinoma, Ductal, Breast -- pathology KW - Cell Cycle -- physiology KW - Humans KW - Protein Processing, Post-Translational KW - Biological Transport KW - Mice KW - Mice, Knockout KW - Tumor Cells, Cultured KW - Phosphorylation KW - Breast Neoplasms -- pathology KW - Cytoplasm -- metabolism KW - Electrophoresis, Gel, Two-Dimensional KW - Point Mutation KW - Female KW - HSP90 Heat-Shock Proteins -- isolation & purification KW - Phosphoproteins -- genetics KW - Genes, p53 KW - Tumor Suppressor Protein p53 -- isolation & purification KW - Neoplasm Proteins -- isolation & purification KW - Neoplasm Proteins -- genetics KW - HSP90 Heat-Shock Proteins -- metabolism KW - Phosphoproteins -- isolation & purification KW - Tumor Suppressor Protein p53 -- metabolism KW - Neoplasm Proteins -- metabolism KW - Phosphoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78648501?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Electrophoresis&rft.atitle=Tumor+suppressor+p53+gene+forms+multiple+isoforms%3A+evidence+for+single+locus+origin+and+cytoplasmic+complex+formation+with+heat+shock+proteins.&rft.au=Selkirk%2C+J+K%3BHe%2C+C%3BPatterson%2C+R+M%3BMerrick%2C+B+A&rft.aulast=Selkirk&rft.aufirst=J&rft.date=1996-11-01&rft.volume=17&rft.issue=11&rft.spage=1764&rft.isbn=&rft.btitle=&rft.title=Electrophoresis&rft.issn=01730835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-29 N1 - Date created - 1997-05-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Endothelin-induced prostacyclin production in rat aortic rings is mediated by protein kinase C. AN - 78639358; 8981627 AB - Endothelin (ET) is a vasoconstrictor peptide released from endothelial cells that is known to cause prostaglandin release. The mechanism remains unclear. To determine whether the protein kinase C (PKC) signaling pathway is stimulated by endothelin, we pretreated rat aortic rings with either PKC activator or inhibitors and measured the release of prostacyclin (PGI2) by radioimmunoassay. ET (10(-9) M) produced a 10-fold increase in PGI2 release. Pretreatment with 10(-9) M of three different PKC inhibitors, 1-(5-isoquinolinesulfonyl)piperazine(CL), staurosporine, and 1-(5-isoquinolinesulfonyltmethyl)piperazine (H7), blocked ET-induced PGI2 release. ET-induced PGI2 release was also blocked by pretreatment with inhibitors of either phospholipase A2 7,7-dimethyleicosadienoic acid or trifluoromethyl ketone analogue) (10(-9) M) or cyclooxygenase (indomethacin) (10(-9) M). We conclude that ET activates PKC, which activates phospholipase A2, which liberates arachidonic acid, which increases PGI2 production and release. JF - Prostaglandins, leukotrienes, and essential fatty acids AU - Oriji, G K AU - Tate, J E AU - Keiser, H R AD - Hypertension-Endocrine Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 309 EP - 313 VL - 55 IS - 5 SN - 0952-3278, 0952-3278 KW - Arachidonic Acids KW - 0 KW - Cyclooxygenase Inhibitors KW - Endothelins KW - Enzyme Inhibitors KW - Fatty Acids, Unsaturated KW - Phosphodiesterase Inhibitors KW - arachidonyltrifluoromethane KW - 00XIW1CR0F KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - 7,7-dimethyl-5,8-eicosadienoic acid KW - 89560-01-0 KW - Epoprostenol KW - DCR9Z582X0 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Indomethacin KW - XXE1CET956 KW - Index Medicus KW - Rats KW - Phosphodiesterase Inhibitors -- pharmacology KW - Animals KW - Dose-Response Relationship, Drug KW - Enzyme Inhibitors -- pharmacology KW - Fatty Acids, Unsaturated -- pharmacology KW - Signal Transduction KW - Male KW - Phorbol 12,13-Dibutyrate -- pharmacology KW - Indomethacin -- pharmacology KW - Cyclooxygenase Inhibitors -- pharmacology KW - Arachidonic Acids -- pharmacology KW - Protein Kinase C -- metabolism KW - Aorta -- metabolism KW - Protein Kinase C -- drug effects KW - Endothelins -- pharmacology KW - Protein Kinase C -- antagonists & inhibitors KW - Aorta -- drug effects KW - Epoprostenol -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78639358?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Prostaglandins%2C+leukotrienes%2C+and+essential+fatty+acids&rft.atitle=Endothelin-induced+prostacyclin+production+in+rat+aortic+rings+is+mediated+by+protein+kinase+C.&rft.au=Oriji%2C+G+K%3BTate%2C+J+E%3BKeiser%2C+H+R&rft.aulast=Oriji&rft.aufirst=G&rft.date=1996-11-01&rft.volume=55&rft.issue=5&rft.spage=309&rft.isbn=&rft.btitle=&rft.title=Prostaglandins%2C+leukotrienes%2C+and+essential+fatty+acids&rft.issn=09523278&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-21 N1 - Date created - 1997-03-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Temporal drinking patterns and variation in social consequences. AN - 78634253; 8972921 AB - Temporal drinking patterns and their associated social consequences are described for a sample of US adults aged 18 years and over who drank at least 12 drinks in the preceding year and did not restrict their drinking to special occasions (n = 16086). The earliest time of day when these current regular drinkers reported usually drinking was between 6 a.m. and 11 a.m. for 1.2%, between 11 a.m. and 3 p.m. for 7.3%, between 3 p.m. and 6 p.m. for 31.2%, and after 6 p.m. for 60.3%. Less than one-tenth (7.7%) reported any drinking (not necessarily their earliest drinking) between midnight and 6 a. m. Characteristics associated with above-average rates of both early (6 a.m.-3 p.m.) and late-night (midnight-6 a.m.) drinking included male gender, black race, low education and income and heavy quantity of ethanol intake per drinking day. Early drinking was also characteristic of the elderly and daily drinkers. Prior to adjusting for background variables and quantity and frequency of intake, early drinking was associated with a two- to nine-fold increase in the risk of alcohol-related interpersonal problems, hazardous use, job/school problems and legal problems, and late-night drinking was associated with a three- to eight-fold increase in their prevalence. After adjusting for these factors in multiple logistic regression models, early drinking was associated with a 54% increase in the odds of interpersonal problems, a 39% increase in the odds of hazardous use and a 52% increase in the odds of legal problems. The association between early drinking and job/school problems fell just short of statistical significance. After adjusting for other factors, late-night drinking retained a significant association with all of the outcomes except legal problems. The magnitude of its association was greater than that of early drinking but varied substantially (i.e. interacted) with quantity of intake, race, ethnicity and gender. JF - Addiction (Abingdon, England) AU - Dawson, D A AD - National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892-7003, USA. Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 1623 EP - 1635 VL - 91 IS - 11 SN - 0965-2140, 0965-2140 KW - Index Medicus KW - Cross-Sectional Studies KW - Social Adjustment KW - Risk Factors KW - Humans KW - Adult KW - Incidence KW - Aged KW - Middle Aged KW - Adolescent KW - United States -- epidemiology KW - Male KW - Female KW - Alcoholism -- epidemiology KW - Social Problems -- statistics & numerical data KW - Alcohol Drinking -- adverse effects KW - Social Problems -- psychology KW - Alcohol Drinking -- epidemiology KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78634253?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Addiction+%28Abingdon%2C+England%29&rft.atitle=Temporal+drinking+patterns+and+variation+in+social+consequences.&rft.au=Dawson%2C+D+A&rft.aulast=Dawson&rft.aufirst=D&rft.date=1996-11-01&rft.volume=91&rft.issue=11&rft.spage=1623&rft.isbn=&rft.btitle=&rft.title=Addiction+%28Abingdon%2C+England%29&rft.issn=09652140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-29 N1 - Date created - 1997-01-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metabolic activation of the potent carcinogen dibenzo[a,l]pyrene by human recombinant cytochromes P450, lung and liver microsomes. AN - 78619813; 8968059 AB - The metabolic activation of dibenzo[a,l]pyrene (DB[a,l]P), recently considered the most potent carcinogen among all polycyclic aromatic hydrocarbons, to the 11,12-dihydrodiol, a precursor of the ultimate carcinogens, the 11,12-diol-13,14-epoxides, was investigated using eleven human recombinant cytochrome P450s, as well as human lung and liver microsomes. Of all human P450s, 1A1 was the most active in the metabolism of DB[a,l]P (310 pmol/min, nmol P450) and had 5-23-fold higher catalytic activity than other P450s examined. The order of activity in the formation of the 11,12-dihydrodiol was as follows: 1A1 (116 pmol/min, nmol P450) > 2C9 (29) > 1A2 (22) > 2B6 (18) > 3A4 (16) > others (< or = 5). The Km of 1A1 for DB[a,l]P and Vmax for the formation of 11,12-dihydrodiol were 3.9 microM and 0.13/min, respectively. Liver microsomes from 14 individuals were shown to metabolize DB[a,l]P and the rates for production of 11,12-dihydrodiol ranged from 4 to 71 pmol/min, nmol P450. Lung microsomes from six organ donors formed the 11,12-dihydrodiol at a rate from 0.1 to 1.3 pmol/min, mg of microsomal protein. These findings describe the potential of individual P450s present in liver and lung to contribute to the metabolic activation and the carcinogenicity of DB[a,l]P. JF - Carcinogenesis AU - Shou, M AU - Krausz, K W 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 - 1996/11// PY - 1996 DA - November 1996 SP - 2429 EP - 2433 VL - 17 IS - 11 SN - 0143-3334, 0143-3334 KW - Benzopyrenes KW - 0 KW - Carcinogens KW - Recombinant Proteins KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - dibenzo(a,l)pyrene KW - G3X629VE4A KW - Index Medicus KW - Recombinant Proteins -- metabolism KW - Biotransformation KW - Microsomes -- metabolism KW - Kinetics KW - Humans KW - Adult KW - Middle Aged KW - Microsomes -- enzymology KW - Substrate Specificity KW - Adolescent KW - Carcinogens -- metabolism KW - Microsomes, Liver -- metabolism KW - Carcinogens -- pharmacokinetics KW - Microsomes, Liver -- enzymology KW - Benzopyrenes -- pharmacokinetics KW - Cytochrome P-450 Enzyme System -- metabolism KW - Lung -- enzymology KW - Lung -- metabolism KW - Benzopyrenes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78619813?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Metabolic+activation+of+the+potent+carcinogen+dibenzo%5Ba%2Cl%5Dpyrene+by+human+recombinant+cytochromes+P450%2C+lung+and+liver+microsomes.&rft.au=Shou%2C+M%3BKrausz%2C+K+W%3BGonzalez%2C+F+J%3BGelboin%2C+H+V&rft.aulast=Shou&rft.aufirst=M&rft.date=1996-11-01&rft.volume=17&rft.issue=11&rft.spage=2429&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-27 N1 - Date created - 1997-01-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Type D retrovirus markers in healthy Africans from Guinea. AN - 78617656; 8958587 AB - Sixteen matching sera and DNA samples from healthy African blood donors living in rural areas of Guinea were analysed for the presence of type D retrovirus markers. Screening for the antibodies against structural proteins of Mason-Pfizer monkey virus (M-PMV) was carried out by Western blot with a purified M-PMV as an antigen. Eight out of 16 sera samples were found to contain antibodies against at least two gag gene-coded proteins, and three of these were weakly positive against env gene-coded protein. Using PCR amplification and Southern hybridization, we detected M-PMV-like gag sequences in 11 out of 16 samples and env-related sequences in 8 out of 16 samples. Six DNAs were found to contain both M-PMV gag- and env-related sequences. Restriction endonuclease analysis of the PCR-amplified gag sequences from two individuals and direct DNA sequencing analysis of the amplimers confirmed their M-PMV-like origin. Detection of antibodies and M-PMV-related sequences in blood donors from Guinea, but not in French or Algerian blood donors, indicated exogenous SRV infection in humans from certain geographic areas of Western Africa. JF - Research in virology AU - Morozov, V A AU - Lagaye, S AU - Lyakh, L AU - ter Meulen, J AD - Laboratory of Molecular Virology and Carcinogenesis, NCI-Frederick Cancer Research and Development Center, MD 21702, USA. PY - 1996 SP - 341 EP - 351 VL - 147 IS - 6 SN - 0923-2516, 0923-2516 KW - Antibodies, Viral KW - 0 KW - Biomarkers KW - DNA, Viral KW - Viral Structural Proteins KW - DNA Restriction Enzymes KW - EC 3.1.21.- KW - Index Medicus KW - AIDS/HIV KW - Tumor Virus Infections -- virology KW - Humans KW - Pilot Projects KW - Child KW - Viral Structural Proteins -- analysis KW - Antibodies, Viral -- analysis KW - Retroviridae Infections -- virology KW - Polymerase Chain Reaction KW - Blotting, Western KW - Blotting, Southern KW - DNA, Viral -- analysis KW - Guinea KW - Adult KW - Adolescent KW - Male KW - Cell Line KW - Female KW - Mason-Pfizer monkey virus -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78617656?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Research+in+virology&rft.atitle=Type+D+retrovirus+markers+in+healthy+Africans+from+Guinea.&rft.au=Morozov%2C+V+A%3BLagaye%2C+S%3BLyakh%2C+L%3Bter+Meulen%2C+J&rft.aulast=Morozov&rft.aufirst=V&rft.date=1996-11-01&rft.volume=147&rft.issue=6&rft.spage=341&rft.isbn=&rft.btitle=&rft.title=Research+in+virology&rft.issn=09232516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-25 N1 - Date created - 1997-02-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pseudomonas exotoxin exhibits increased sensitivity to furin when sequences at the cleavage site are mutated to resemble the arginine-rich loop of diphtheria toxin. AN - 78596257; 8951823 AB - To be toxic for mammalian cells, Pseudomonas exotoxin (PE) requires proteolytic cleavage between Arg-279 and Gly-280. Cleavage, which is mediated by the cellular protease furin, generates an active C-terminal fragment which translocates to the cytosol and inhibits protein synthesis. In vitro, furin-mediated cleavage is optimal at pH 5.5 with a relatively slow turnover rate. Within cells, only 5-10% of cell-associated PE is cleaved. To investigate the reasons for this inefficient cleavage, the amino acid composition near the cleavage site was altered to resemble more closely the arginine-rich sequence from the functionally similar region of diphtheria toxin (DT). Four PE-DT mutants were generated, whereby 1, 5, 6 or 8 amino acids at the PE-cleavage site were changed to amino acids found at the DT-cleavage site. Mutant proteins were expressed in Escherichia coli, purified and then analysed for their susceptibility to cleavage by furin and trypsin, susceptibility to cell-mediated cleavage, and cytotoxic activity relative to wild-type PE. At pH 5.5, the rate of both furin-mediated cleavage and trypsin-mediated cleavage increased dramatically when amino acids in PE were altered to resemble the DT sequence. This increase did not alter the pH optimum for furin-mediated cleavage of PE toxins, which remained at pH 5.0-5.5. When radioactive versions of selected PE-DT proteins were added to intact cells, an increase in the percentage of molecules that were cleaved relative to wild-type PE was also seen. However, changes that favoured increased proteolysis apparently interfered with other important toxin functions because none of the PE-DT proteins exhibited enhanced toxicity for cells when compared with the activity of wild-type PE. JF - Molecular microbiology AU - Chiron, M F AU - Ogata, M AU - FitzGerald, D J AD - Biotherapy Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 769 EP - 778 VL - 22 IS - 4 SN - 0950-382X, 0950-382X KW - Bacterial Toxins KW - 0 KW - Cytotoxins KW - Diphtheria Toxin KW - Exotoxins KW - Recombinant Fusion Proteins KW - Arginine KW - 94ZLA3W45F KW - Subtilisins KW - EC 3.4.21.- KW - Trypsin KW - EC 3.4.21.4 KW - Furin KW - EC 3.4.21.75 KW - Index Medicus KW - Animals KW - Diphtheria Toxin -- chemistry KW - Humans KW - Diphtheria Toxin -- metabolism KW - Protein Processing, Post-Translational KW - Mice KW - Diphtheria Toxin -- genetics KW - Binding Sites KW - Mutagenesis KW - Recombinant Fusion Proteins -- metabolism KW - Tumor Cells, Cultured KW - Kinetics KW - Recombinant Fusion Proteins -- genetics KW - Trypsin -- metabolism KW - Cell Line KW - Bacterial Toxins -- genetics KW - Pseudomonas aeruginosa -- metabolism KW - Exotoxins -- genetics KW - Pseudomonas aeruginosa -- genetics KW - Cytotoxins -- metabolism KW - Bacterial Toxins -- metabolism KW - Subtilisins -- genetics KW - Exotoxins -- metabolism KW - Cytotoxins -- genetics KW - Subtilisins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78596257?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+microbiology&rft.atitle=Pseudomonas+exotoxin+exhibits+increased+sensitivity+to+furin+when+sequences+at+the+cleavage+site+are+mutated+to+resemble+the+arginine-rich+loop+of+diphtheria+toxin.&rft.au=Chiron%2C+M+F%3BOgata%2C+M%3BFitzGerald%2C+D+J&rft.aulast=Chiron&rft.aufirst=M&rft.date=1996-11-01&rft.volume=22&rft.issue=4&rft.spage=769&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 - 1997-03-31 N1 - Date created - 1997-03-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Subtypes of alcohol-dependent men: a typology based on relative genetic and environmental loading. AN - 78588428; 8947327 AB - Using scales that distinguish between relative genetic and environmental loading, cluster analysis was used to identify three subtypes of alcohol dependence in Caucasian men from the Epidemiologic Catchment Area study (n = 911). Although all subjects met DSM-III criteria for alcohol dependence, only the severe subtype showed evidence of substantial genetic influence. When compared on a range of clinical characteristics, the mild subtype (53% of the sample) was typically least adversely affected and the severe subtype (17%) most affected, with the dyssocial subtype (30%) falling between. Severe subtype subjects had significantly greater comorbid drug dependence and were at least four times more likely than mild subjects to have sought treatment for alcohol problems. Ratio of genetic scale score to total symptom count (genetic ratio) was highest for the severe subtype (mean = 0.37), and negatively correlated with age of first alcohol problem (rs = -0.16) and years between first intoxication and first problem (rs = 0.19). No significant correlations were found between these clinical features and genetic ratio for the mild or dyssocial subtypes. Use of these scales and subtypes may improve our ability to detect specific gene effects in genetic linkage studies and to identify environmental influences in behavioral and epidemiological studies. JF - Alcoholism, clinical and experimental research AU - Johnson, E O AU - van den Bree, M B AU - Pickens, R W AD - Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 1472 EP - 1480 VL - 20 IS - 8 SN - 0145-6008, 0145-6008 KW - Index Medicus KW - Factor Analysis, Statistical KW - Psychiatric Status Rating Scales KW - Risk Factors KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Comorbidity KW - Genotype KW - Alcoholism -- rehabilitation KW - Alcoholism -- classification KW - Alcoholism -- genetics KW - Alcoholism -- psychology KW - Social Environment UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78588428?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Subtypes+of+alcohol-dependent+men%3A+a+typology+based+on+relative+genetic+and+environmental+loading.&rft.au=Johnson%2C+E+O%3Bvan+den+Bree%2C+M+B%3BPickens%2C+R+W&rft.aulast=Johnson&rft.aufirst=E&rft.date=1996-11-01&rft.volume=20&rft.issue=8&rft.spage=1472&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 - 1997-03-18 N1 - Date created - 1997-03-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DSM-IV, DSM-III-R, and ICD-10 alcohol and drug abuse/harmful use and dependence, United States, 1992: a nosological comparison. AN - 78584490; 8947328 AB - This study assessed agreement between DSM-IV, DSM-III-R, and ICD-10 diagnoses of alcohol and drug use disorders using data from a large representative sample of the United States population. Agreement between the three diagnostic systems for dependence was good to excellent for past year, prior to the past year, and life-time diagnoses, for both genders, each ethnic group, and younger and older respondents. Cross-system comparisons between DSM-IV and DSM-III-R abuse were good to excellent, but concordance was consistently poor when ICD-10 harmful use diagnoses were compared with DSM-IV and DSM-III-R abuse diagnoses. Implications of these results are discussed in terms of the degree to which future research findings could be integrated with one another and the results from earlier studies using older versions of the DSM, to advance scientific knowledge in the drug and alcohol fields. JF - Alcoholism, clinical and experimental research AU - Grant, B F AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892, USA. Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 1481 EP - 1488 VL - 20 IS - 8 SN - 0145-6008, 0145-6008 KW - Psychotropic Drugs KW - 0 KW - Street Drugs KW - Index Medicus KW - Reproducibility of Results KW - Substance-Related Disorders -- classification KW - Humans KW - Aged KW - Substance-Related Disorders -- psychology KW - Longitudinal Studies KW - Psychometrics KW - Comorbidity KW - Substance-Related Disorders -- diagnosis KW - Adult KW - Middle Aged KW - Adolescent KW - United States -- epidemiology KW - Female KW - Male KW - Alcoholism -- diagnosis KW - Alcoholism -- classification KW - Psychiatric Status Rating Scales -- statistics & numerical data KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78584490?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=DSM-IV%2C+DSM-III-R%2C+and+ICD-10+alcohol+and+drug+abuse%2Fharmful+use+and+dependence%2C+United+States%2C+1992%3A+a+nosological+comparison.&rft.au=Grant%2C+B+F&rft.aulast=Grant&rft.aufirst=B&rft.date=1996-11-01&rft.volume=20&rft.issue=8&rft.spage=1481&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 - 1997-03-18 N1 - Date created - 1997-03-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Craving for alcohol and cocaine: from inside the brain to the clinic. AN - 78584032; 8947232 JF - Alcoholism, clinical and experimental research AU - Newlin, D B Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 45A EP - 47A VL - 20 IS - 8 Suppl KW - Neurotransmitter Agents KW - 0 KW - Receptors, Dopamine KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Receptors, Dopamine -- drug effects KW - Receptors, Dopamine -- physiology KW - Neurotransmitter Agents -- physiology KW - Humans KW - Cues KW - Tomography, Emission-Computed KW - Recurrence KW - Brain -- physiopathology KW - Alcoholism -- rehabilitation KW - Opioid-Related Disorders -- physiopathology KW - Motivation KW - Brain -- drug effects KW - Opioid-Related Disorders -- rehabilitation KW - Alcoholism -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78584032?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Craving+for+alcohol+and+cocaine%3A+from+inside+the+brain+to+the+clinic.&rft.au=Newlin%2C+D+B&rft.aulast=Newlin&rft.aufirst=D&rft.date=1996-11-01&rft.volume=20&rft.issue=8+Suppl&rft.spage=45A&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 - 1997-03-19 N1 - Date created - 1997-03-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Potentiation of diethylstilbestrol-induced alterations in the female mouse reproductive tract by transforming growth factor-alpha transgene expression. AN - 78582223; 8944077 AB - Neonatal estrogen exposure causes numerous abnormalities in the female reproductive tract, including carcinogenesis. One mechanism by which neonatal estrogen elicits teratogenic and carcinogenic effects is epigenetic and involves the modulation of a number of estrogen-regulated genes including epidermal growth factor (EGF). Because of the evidence that there is an integral relationship between the EGF family, estrogen action, and the regulation of the growth and differentiation of the reproductive tract, we used transforming growth factor-alpha (TGF alpha) transgenic mice to investigate the interaction of constitutive TGF alpha expression with the potent estrogen diethylstilbestrol (DES) in the induction of reproductive-tract alterations. Our study was designed to determine whether TGF alpha expression could modulate DES-induced carcinogenesis of the female mouse reproductive tract. The animals were homozygous TGF alpha transgenic female mice from the MT42 line and the parental CD-1 outbred mice. The presence of the TGF alpha transgene significantly increased the incidence of DES-induced vaginal adenosis, uterine endometrial hyperplasia, uterine polyps, hypospadia, benign ovarian cysts, and pituitary adenomas. However, constitutive TGF alpha expression did not promote reproductive-tract neoplasia. This study demonstrates that TGF alpha participates in the regulation of developmental and morphogenic events in the Müllerian duct and urogenital sinus, suggesting a role for TGF alpha in the pathogenesis of reproductive-tract diseases. Furthermore, we showed that although constitutive expression of the TGF alpha transgene did have an effect on the reproductive tract, TGF alpha overexpression alone could not substitute for DES as a reproductive-tract carcinogen or as a promoter of uterine neoplasia, indicating that DES-induced carcinogenesis requires events in addition to the overexpression of this single peptide growth factor. JF - Molecular carcinogenesis AU - Gray, K AU - Bullock, B AU - Dickson, R AU - Raszmann, K AU - Walmer, D AU - McLachlan, J AU - Merlino, G AD - Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 163 EP - 173 VL - 17 IS - 3 SN - 0899-1987, 0899-1987 KW - Carcinogens KW - 0 KW - Transforming Growth Factor alpha KW - Diethylstilbestrol KW - 731DCA35BT KW - Index Medicus KW - Vagina -- drug effects KW - Animals KW - Fallopian Tubes -- drug effects KW - Humans KW - Ovary -- drug effects KW - Gene Expression KW - Mice KW - Mice, Transgenic KW - Uterus -- drug effects KW - Uterus -- metabolism KW - Mice, Inbred Strains KW - Ovary -- metabolism KW - Fallopian Tubes -- metabolism KW - Vagina -- metabolism KW - Female KW - Genitalia, Female -- drug effects KW - Cocarcinogenesis KW - Transforming Growth Factor alpha -- genetics KW - Transforming Growth Factor alpha -- physiology KW - Genitalia, Female -- metabolism KW - Diethylstilbestrol -- toxicity KW - Transgenes KW - Transforming Growth Factor alpha -- biosynthesis KW - Carcinogens -- toxicity KW - Genitalia, Female -- physiology KW - Genital Neoplasms, Female -- genetics KW - Genital Neoplasms, Female -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78582223?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Potentiation+of+diethylstilbestrol-induced+alterations+in+the+female+mouse+reproductive+tract+by+transforming+growth+factor-alpha+transgene+expression.&rft.au=Gray%2C+K%3BBullock%2C+B%3BDickson%2C+R%3BRaszmann%2C+K%3BWalmer%2C+D%3BMcLachlan%2C+J%3BMerlino%2C+G&rft.aulast=Gray&rft.aufirst=K&rft.date=1996-11-01&rft.volume=17&rft.issue=3&rft.spage=163&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 - 1996-12-27 N1 - Date created - 1996-12-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular genetics of renal cell carcinoma. AN - 78581849; 8946625 AB - Renal cell carcinoma can be divided into sporadic and inheritable forms. One of the most common inheritable forms occurs in von Hippel-Lindau disease (VHL). VHL is a multisystem neoplastic disorder in which individuals develop tumors and cysts in multiple organs including the kidneys. Careful linkage analysis and cloning identified the VHL gene on chromosome 3p. In accordance with Knudson's hypothesis and tumor suppression theory, the VHL gene has been shown to have an important role in sporadic renal carcinoma as well. Further understanding of the VHL protein is likely to enhance our understanding of renal carcinogenesis, and clinical implications are beginning to evolve. JF - Seminars in urologic oncology AU - Wagner, J R AU - Linehan, W M AD - Section of Urologic Oncology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 244 EP - 249 VL - 14 IS - 4 SN - 1081-0943, 1081-0943 KW - Index Medicus KW - Risk Factors KW - Humans KW - von Hippel-Lindau Disease -- genetics KW - Kidney Neoplasms -- genetics KW - Molecular Biology KW - Carcinoma, Renal Cell -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78581849?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+urologic+oncology&rft.atitle=Molecular+genetics+of+renal+cell+carcinoma.&rft.au=Wagner%2C+J+R%3BLinehan%2C+W+M&rft.aulast=Wagner&rft.aufirst=J&rft.date=1996-11-01&rft.volume=14&rft.issue=4&rft.spage=244&rft.isbn=&rft.btitle=&rft.title=Seminars+in+urologic+oncology&rft.issn=10810943&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-06 N1 - Date created - 1997-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - NF-kappa B, a prototypical cytokine-regulated transcription factor: implications for alcohol-mediated responses. AN - 78581593; 8947272 JF - Alcoholism, clinical and experimental research AU - Zakhari, S Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 236A EP - 242A VL - 20 IS - 8 Suppl KW - Cytokines KW - 0 KW - NF-kappa B KW - Transcription Factors KW - Index Medicus KW - Animals KW - Liver -- immunology KW - Humans KW - Cytokines -- physiology KW - Genes, MHC Class II -- physiology KW - Gene Expression -- physiology KW - Alcoholism -- immunology KW - Alcoholism -- genetics KW - Transcription Factors -- genetics KW - NF-kappa B -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78581593?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=NF-kappa+B%2C+a+prototypical+cytokine-regulated+transcription+factor%3A+implications+for+alcohol-mediated+responses.&rft.au=Zakhari%2C+S&rft.aulast=Zakhari&rft.aufirst=S&rft.date=1996-11-01&rft.volume=20&rft.issue=8+Suppl&rft.spage=236A&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 - 1997-03-19 N1 - Date created - 1997-03-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - International update: new findings on promising medications. AN - 78581213; 8947268 JF - Alcoholism, clinical and experimental research AU - Litten, R Z Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 216A EP - 218A VL - 20 IS - 8 Suppl KW - Alcohol Deterrents KW - 0 KW - Narcotic Antagonists KW - Taurine KW - 1EQV5MLY3D KW - Naltrexone KW - 5S6W795CQM KW - Cocaine KW - I5Y540LHVR KW - acamprosate KW - N4K14YGM3J KW - nalmefene KW - TOV02TDP9I KW - Index Medicus KW - United States KW - Animals KW - Taurine -- adverse effects KW - Humans KW - Naltrexone -- adverse effects KW - Naltrexone -- analogs & derivatives KW - Clinical Trials as Topic KW - Opioid-Related Disorders -- rehabilitation KW - Taurine -- therapeutic use KW - Europe KW - Comorbidity KW - Naltrexone -- therapeutic use KW - Taurine -- analogs & derivatives KW - Alcoholism -- rehabilitation KW - Alcohol Deterrents -- adverse effects KW - Narcotic Antagonists -- therapeutic use KW - Narcotic Antagonists -- adverse effects KW - Alcoholism -- psychology KW - Alcohol Deterrents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78581213?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=International+update%3A+new+findings+on+promising+medications.&rft.au=Litten%2C+R+Z&rft.aulast=Litten&rft.aufirst=R&rft.date=1996-11-01&rft.volume=20&rft.issue=8+Suppl&rft.spage=216A&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 - 1997-03-19 N1 - Date created - 1997-03-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ethanol-inducible cytochrome P450 (CYP2E1): biochemistry, molecular biology and clinical relevance: 1996 update. AN - 78580791; 8947253 JF - Alcoholism, clinical and experimental research AU - Song, B J AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD, USA. Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 138A EP - 146A VL - 20 IS - 8 Suppl SN - 0145-6008, 0145-6008 KW - Reactive Oxygen Species KW - 0 KW - Ethanol KW - 3K9958V90M KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Index Medicus KW - Liver Diseases, Alcoholic -- enzymology KW - Animals KW - Liver Diseases, Alcoholic -- genetics KW - Enzyme Induction -- drug effects KW - Polymorphism, Genetic KW - Gene Expression Regulation, Enzymologic -- drug effects KW - Humans KW - Microsomes, Liver -- enzymology KW - Enzyme Induction -- genetics KW - Alcoholism -- enzymology KW - Ethanol -- toxicity KW - Alcoholism -- genetics KW - Cytochrome P-450 CYP2E1 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78580791?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Ethanol-inducible+cytochrome+P450+%28CYP2E1%29%3A+biochemistry%2C+molecular+biology+and+clinical+relevance%3A+1996+update.&rft.au=Song%2C+B+J&rft.aulast=Song&rft.aufirst=B&rft.date=1996-11-01&rft.volume=20&rft.issue=8+Suppl&rft.spage=138A&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 - 1997-03-19 N1 - Date created - 1997-03-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Zero tolerance laws: effective public policy? AN - 78580556; 8947254 JF - Alcoholism, clinical and experimental research AU - Martin, S Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 147A EP - 150A VL - 20 IS - 8 Suppl KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - California KW - Ethanol -- pharmacokinetics KW - Humans KW - Adult KW - Health Knowledge, Attitudes, Practice KW - Adolescent KW - Male KW - Female KW - Alcoholism -- rehabilitation KW - Automobile Driving -- legislation & jurisprudence KW - Public Policy KW - Alcoholism -- prevention & control KW - Alcohol Drinking -- legislation & jurisprudence UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78580556?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Zero+tolerance+laws%3A+effective+public+policy%3F&rft.au=Martin%2C+S&rft.aulast=Martin&rft.aufirst=S&rft.date=1996-11-01&rft.volume=20&rft.issue=8+Suppl&rft.spage=147A&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 - 1997-03-19 N1 - Date created - 1997-03-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - NIAAA 25th anniversary: advances in the neuroscience of alcohol. AN - 78580545; 8947231 JF - Alcoholism, clinical and experimental research AU - Gordis, E Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 38A EP - 44A VL - 20 IS - 8 Suppl KW - Index Medicus KW - United States KW - Humans KW - Infant, Newborn KW - Research KW - Female KW - Pregnancy KW - Brain -- physiopathology KW - Alcoholism -- rehabilitation KW - Fetal Alcohol Spectrum Disorders -- physiopathology KW - Anniversaries and Special Events KW - Alcoholism -- physiopathology KW - Alcoholism -- genetics KW - United States Substance Abuse and Mental Health Services Administration UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78580545?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=NIAAA+25th+anniversary%3A+advances+in+the+neuroscience+of+alcohol.&rft.au=Gordis%2C+E&rft.aulast=Gordis&rft.aufirst=E&rft.date=1996-11-01&rft.volume=20&rft.issue=8+Suppl&rft.spage=38A&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 - 1997-03-19 N1 - Date created - 1997-03-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Community organizing, public policy and the prevention of alcohol problems. AN - 78579924; 8947278 JF - Alcoholism, clinical and experimental research AU - Howard, J Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 265A EP - 269A VL - 20 IS - 8 Suppl KW - Index Medicus KW - United States KW - Randomized Controlled Trials as Topic KW - Humans KW - Social Problems -- prevention & control KW - Wounds and Injuries -- prevention & control KW - Alcoholism -- rehabilitation KW - Consumer Organizations KW - Public Policy KW - Alcoholism -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78579924?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Community+organizing%2C+public+policy+and+the+prevention+of+alcohol+problems.&rft.au=Howard%2C+J&rft.aulast=Howard&rft.aufirst=J&rft.date=1996-11-01&rft.volume=20&rft.issue=8+Suppl&rft.spage=265A&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 - 1997-03-19 N1 - Date created - 1997-03-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Medical consequences of alcohol consumption--United States, 1992. AN - 78578376; 8947320 AB - There is plenty of evidence in the alcohol literature that chronic excessive use of alcohol poses a threat to every organ system in the body. At the same time, there is a growing consensus that drinking in moderation protects against cardiovascular disease. This study was based on the most recent national household survey of the United States general population on drinking practices, alcohol use disorders, and their associated disabilities. The prevalence of major alcohol-related diseases were examined across different categories of drinking status. Excess morbidity caused by heavy intake of alcohol was also studied. Results were generally in agreement with the popular belief that light or moderate drinking is beneficial relative to abstention, particularly that moderate alcohol consumption confers a beneficial cardiovascular effect. Our findings also pointed toward the injurious effect of heavy alcohol use. However, results on benefits of drinking must be interpreted with caution. JF - Alcoholism, clinical and experimental research AU - Chou, S P AU - Grant, B F AU - Dawson, D A AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892-7003, USA. Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 1423 EP - 1429 VL - 20 IS - 8 SN - 0145-6008, 0145-6008 KW - Index Medicus KW - Causality KW - Dose-Response Relationship, Drug KW - Humans KW - Aged KW - Longitudinal Studies KW - Cross-Sectional Studies KW - Risk Factors KW - Adult KW - Sampling Studies KW - Incidence KW - Middle Aged KW - Adolescent KW - United States -- epidemiology KW - Female KW - Male KW - Alcoholism -- epidemiology KW - Alcoholic Beverages -- adverse effects KW - Alcoholism -- prevention & control KW - Alcoholism -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78578376?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Medical+consequences+of+alcohol+consumption--United+States%2C+1992.&rft.au=Chou%2C+S+P%3BGrant%2C+B+F%3BDawson%2C+D+A&rft.aulast=Chou&rft.aufirst=S&rft.date=1996-11-01&rft.volume=20&rft.issue=8&rft.spage=1423&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 - 1997-03-18 N1 - Date created - 1997-03-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Microsomal epoxide hydrolase polymorphism as a risk factor for ovarian cancer. AN - 78578318; 8944076 AB - Microsomal epoxide hydrolase (EPHX) is one of many enzymes involved in the metabolism of endogenous and exogenous toxicants. Polymorphic forms of the human EPHX gene have been described that vary in enzymatic activity, and one, Tyr113His, has been associated with hepatocellular carcinoma susceptibility. We demonstrated that EPHX was highly expressed in the human ovary, and investigated whether specific EPHX genotypes are associated with ovarian cancer susceptibility. Seventy-three Caucasian patients with ovarian cancer and 75 Caucasian-female controls without cancer were genotyped for the Tyr113His polymorphism by a polymerase chain reaction-restriction fragment length polymorphism assay. The frequency of the homozygous high-activity genotype was 41% in the control population and 64% in the ovarian cancer patients. The odds ratio for ovarian cancer with this genotype was 2.6 (95% confidence interval 1.3, 5.0; P < 0.01). The increased ovarian cancer risk associated with the high-activity genotype could reflect differences in metabolic activation of endogenous or exogenous carcinogens. JF - Molecular carcinogenesis AU - Lancaster, J M AU - Brownlee, H A AU - Bell, D A AU - Futreal, P A AU - Marks, J R AU - Berchuck, A AU - Wiseman, R W AU - Taylor, J A AD - National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 160 EP - 162 VL - 17 IS - 3 SN - 0899-1987, 0899-1987 KW - Epoxide Hydrolases KW - EC 3.3.2.- KW - Index Medicus KW - Genotype KW - Blotting, Northern KW - Risk Factors KW - Humans KW - Case-Control Studies KW - Female KW - Epoxide Hydrolases -- genetics KW - Polymorphism, Genetic KW - Ovarian Neoplasms -- genetics KW - Ovarian Neoplasms -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78578318?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Microsomal+epoxide+hydrolase+polymorphism+as+a+risk+factor+for+ovarian+cancer.&rft.au=Lancaster%2C+J+M%3BBrownlee%2C+H+A%3BBell%2C+D+A%3BFutreal%2C+P+A%3BMarks%2C+J+R%3BBerchuck%2C+A%3BWiseman%2C+R+W%3BTaylor%2C+J+A&rft.aulast=Lancaster&rft.aufirst=J&rft.date=1996-11-01&rft.volume=17&rft.issue=3&rft.spage=160&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 - 1996-12-27 N1 - Date created - 1996-12-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A cytochrome P4502E1 genetic polymorphism and tobacco smoking in breast cancer. AN - 78577606; 8944074 AB - Known breast-cancer risk factors account for only part of the variability in breast-cancer incidence. Tobacco smoke is not commonly considered a breast carcinogen, but many of its constituents, such as N-nitrosamines, are carcinogenic in laboratory animal studies. Herein, we assessed a cytochrome P4502E1 (CYP2E1) genetic polymorphism (a Dral restriction enzyme site in intron 6) as a risk factor for breast cancer in both premenopausal and postmenopausal women. Because N-nitrosamines are metabolically activated by CYP2E1, the risk among women smokers was investigated. Caucasian women were enrolled in a case-control study of breast cancer between 1986 and 1991. A subset of the women (219 premenopausal and 387 postmenopausal women) consented to phlebotomy. The allelic frequencies for the premenopausal women (D allele = 0.91 and C allele = 0.09) and postmenopausal women (D allele = 0.93 and C allele = 0.07) were similar to those previously reported. There was no statistically significant association between the CYP2E1 polymorphism and breast-cancer risk for premenopausal or postmenopausal women (adjusted odds ratio (OR) = 1.04, 95% confidence interval (CI) = 0.48, 2.24, and OR = 1.01, 95% CI = 0.55, 1.84, respectively). When the women were categorized as nonsmokers versus smokers (those who smoked more than one cigarette per week for more than 1 yr), premenopausal women with one or two C alleles who had a history of smoking were found to be at increased risk (unadjusted OR = 7.00, 95% CI = 0.75, 14.53, and adjusted OR = 11.09, 95% CI = 1.51, 81.41), although the number of study subjects with those genotypes was small. The small number of study subjects with a C allele precluded meaningful classification by level of smoking, but categorizing the smokers into two groups (above and below the median) also suggested an increased risk. Premenopausal women with the DD genotype and postmenopausal women with any genotype were not at increased risk. Breast-cancer risk was not related to the CYP2E1 genotype in either premenopausal nonsmokers or smokers (adjusted OR = 0.66, 95% CI = 0.20, 2.17, and OR = 2.13, 95% CI = 0.60, 7.59, respectively) or postmenopausal nonsmokers or smokers (OR = 0.90, 95% CI = 0.34, 2.35, and OR = 1.02, 95% CI = 0.46, 2.23, respectively), although the difference in the ORs for premenopausal nonsmokers and smokers suggests an increased risk for smokers. While there are limitations to this study, particularly related to the small number of subjects with the DC and CC genotypes, the study suggests that some women may be susceptible to tobacco smoke because of a CYP2E1 polymorphism. However, these results are preliminary and must be replicated. JF - Molecular carcinogenesis AU - Shields, P G AU - Ambrosone, C B AU - Graham, S AU - Bowman, E D AU - Harrington, A M AU - Gillenwater, K A AU - Marshall, J R AU - Vena, J E AU - Laughlin, R AU - Nemoto, T AU - Freudenheim, J L AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 144 EP - 150 VL - 17 IS - 3 SN - 0899-1987, 0899-1987 KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Index Medicus KW - Alleles KW - Risk Factors KW - Humans KW - Adult KW - Case-Control Studies KW - Premenopause -- physiology KW - Middle Aged KW - Postmenopause -- physiology KW - Female KW - Breast Neoplasms -- genetics KW - Polymorphism, Genetic KW - Breast Neoplasms -- etiology KW - Smoking -- adverse effects KW - Breast Neoplasms -- enzymology KW - Cytochrome P-450 CYP2E1 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78577606?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+cytochrome+P4502E1+genetic+polymorphism+and+tobacco+smoking+in+breast+cancer.&rft.au=Shields%2C+P+G%3BAmbrosone%2C+C+B%3BGraham%2C+S%3BBowman%2C+E+D%3BHarrington%2C+A+M%3BGillenwater%2C+K+A%3BMarshall%2C+J+R%3BVena%2C+J+E%3BLaughlin%2C+R%3BNemoto%2C+T%3BFreudenheim%2C+J+L&rft.aulast=Shields&rft.aufirst=P&rft.date=1996-11-01&rft.volume=17&rft.issue=3&rft.spage=144&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 - 1996-12-27 N1 - Date created - 1996-12-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High levels of MDM2 are not correlated with the presence of wild-type p53 in human malignant mesothelioma cell lines. AN - 78553707; 8932331 AB - Prior analysis of 20 human mesothelioma cell lines for p53 status revealed only two mutations and one p53 null cell line, although p53 expression was detected in most cell lines. In addition, mRNA and protein expression of the retinoblastoma gene product in human mesothelioma cell lines is similar to normal controls. We have tested for p53 induction after exposure to ionising radiation and demonstrate this induction and, to a lesser extent, p21(WAF1) induction, in both normal mesothelial cells and p53-positive mesothelioma cell lines. We postulated that high levels of MDM2 might alter p53 and retinoblastoma tumour-suppressor function in mesothelioma. However, Southern blot analysis for mdm2 indicated that no amplification had occurred in 18 mesothelioma cell lines tested. Steady-state mRNA and protein levels also did not indicate overexpression. These results indicate that high levels of MDM2 are not responsible for inactivating the functions of wild-type p53 or the retinoblastoma gene product during the pathogenesis of malignant mesothelioma. JF - British journal of cancer AU - Ungar, S AU - Van de Meeren, A AU - Tammilehto, L AU - Linnainmaa, K AU - Mattson, K AU - Gerwin, B I AD - Laboratory of Human Carcinogenesis, Division of Basic Sciences, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 1534 EP - 1540 VL - 74 IS - 10 SN - 0007-0920, 0007-0920 KW - DNA, Neoplasm KW - 0 KW - Neoplasm Proteins KW - Nuclear Proteins KW - Proto-Oncogene Proteins KW - RNA, Messenger KW - Tumor Suppressor Protein p53 KW - MDM2 protein, human KW - EC 2.3.2.27 KW - Proto-Oncogene Proteins c-mdm2 KW - Index Medicus KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - Genes, p53 KW - Humans KW - Gene Expression KW - DNA, Neoplasm -- genetics KW - DNA, Neoplasm -- analysis KW - Mutation KW - Gene Amplification KW - Tumor Suppressor Protein p53 -- biosynthesis KW - Proto-Oncogene Proteins -- biosynthesis KW - Neoplasm Proteins -- biosynthesis KW - Mesothelioma -- metabolism KW - Neoplasm Proteins -- genetics KW - Proto-Oncogene Proteins -- metabolism KW - Mesothelioma -- genetics KW - Tumor Suppressor Protein p53 -- genetics KW - Proto-Oncogene Proteins -- genetics KW - Tumor Suppressor Protein p53 -- metabolism KW - Neoplasm Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78553707?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=High+levels+of+MDM2+are+not+correlated+with+the+presence+of+wild-type+p53+in+human+malignant+mesothelioma+cell+lines.&rft.au=Ungar%2C+S%3BVan+de+Meeren%2C+A%3BTammilehto%2C+L%3BLinnainmaa%2C+K%3BMattson%2C+K%3BGerwin%2C+B+I&rft.aulast=Ungar&rft.aufirst=S&rft.date=1996-11-01&rft.volume=74&rft.issue=10&rft.spage=1534&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 - 1996-12-27 N1 - Date created - 1996-12-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Oncogene. 1994 Sep;9(9):2745-50 [8058341] Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7491-5 [1323840] Cancer Res. 1994 Nov 1;54(21):5547-51 [7923195] Genes Dev. 1994 Aug 1;8(15):1739-49 [7958853] Br J Cancer. 1969 Sep;23(3):567-81 [5360333] N Engl J Med. 1982 Jun 17;306(24):1446-55 [7043267] Nucleic Acids Res. 1985 Mar 11;13(5):1431-42 [2987824] Proc Natl Acad Sci U S A. 1985 Jun;82(11):3884-8 [2987952] Lab Invest. 1986 Feb;54(2):204-12 [3945053] Somat Cell Mol Genet. 1987 May;13(3):235-44 [3474784] Anal Biochem. 1987 Apr;162(1):156-9 [2440339] Nature. 1988 Jul 14;334(6178):124-9 [2968522] Cell. 1988 Jul 15;54(2):275-83 [2839300] In Vitro Cell Dev Biol. 1988 Nov;24(11):1077-84 [2461356] Science. 1989 Feb 17;243(4893):934-7 [2537532] J Cell Physiol. 1989 May;139(2):295-300 [2497107] J Clin Invest. 1990 Apr;85(4):988-93 [2180983] EMBO J. 1991 Jun;10(6):1565-9 [2026149] Nature. 1991 Jun 6;351(6326):453-6 [2046748] Science. 1991 Jul 5;253(5015):49-53 [1905840] Cancer Res. 1992 May 1;52(9):2610-5 [1568228] Cell. 1992 Aug 21;70(4):523-6 [1505019] Cancer Res. 1992 Nov 15;52(22):6305-9 [1330290] EMBO J. 1992 Dec;11(13):5013-20 [1464323] Cancer Res. 1993 Jan 1;53(1):16-8 [8416741] Mol Cell Biol. 1993 Jan;13(1):301-6 [8417333] EMBO J. 1993 Feb;12(2):461-8 [8440237] Cancer Res. 1993 May 15;53(10 Suppl):2231-4 [8387391] Cell. 1993 May 7;73(3):487-97 [8343202] Biochim Biophys Acta. 1993 May 25;1155(1):43-61 [8504130] Cancer Res. 1993 Jun 15;53(12):2736-9 [8504413] Genes Dev. 1993 Jul;7(7A):1126-32 [8319905] Mol Cell Biol. 1993 Jul;13(7):4107-14 [7686617] EMBO J. 1993 Jul;12(7):2799-808 [8334996] Cell. 1981 Dec;27(3 Pt 2):583-91 [6101209] Nature. 1993 Sep 2;365(6441):17-8 [8361531] Oncogene. 1993 Sep;8(9):2353-60 [7689721] Oncogene. 1993 Oct;8(10):2805-12 [8378089] Blood. 1993 Nov 1;82(9):2617-23 [8219216] Cell. 1993 Nov 19;75(4):765-78 [8242748] Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11623-7 [8265599] Bioessays. 1993 Oct;15(10):689-90 [7506024] Mol Cell Biol. 1994 Feb;14(2):1171-8 [8289798] Cancer Res. 1994 Feb 1;54(3):794-9 [8306343] Oncogene. 1994 Jun;9(6):1781-90 [8183577] Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11045-9 [7972006] Br J Haematol. 1994 Oct;88(2):415-8 [7803295] Blood. 1995 Mar 15;85(6):1608-14 [7888679] Nature. 1995 Jun 22;375(6533):691-4 [7791903] Nature. 1995 Jun 22;375(6533):694-8 [7791904] Cancer Res. 1995 Jul 15;55(14):2968-71 [7606711] Nucleic Acids Res. 1995 Jul 25;23(14):2584-92 [7651818] Diagn Mol Pathol. 1995 Jun;4(2):93-7 [7551299] Virchows Arch. 1995;427(4):431-6 [8548129] Genes Dev. 1996 May 15;10(10):1219-32 [8675009] Clin Cancer Res. 1995 Jan;1(1):71-80 [9815889] Nature. 1992 May 7;357(6373):82-5 [1533443] EMBO J. 1992 Jun;11(6):2115-21 [1600943] Nature. 1992 Jul 2;358(6381):80-3 [1614537] Nature. 1992 Jul 2;358(6381):83-6 [1614538] Cell. 1992 Jun 26;69(7):1237-45 [1535557] Pathol Res Pract. 1994 Feb;190(2):138-41 [7520164] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased expression of the ETS-related transcription factor FLI-1/ERGB correlates with and can induce the megakaryocytic phenotype. AN - 78552605; 8930402 AB - The human leukemia cell line K562 can be induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) to differentiate along the megakaryocytic pathway, generating morphological changes and increased expression of lineage-specific surface markers. We report that TPA-treated K562 cells also express higher levels of FLI-1/ERGB, a member of the ETS family of transcription factors. Furthermore, introduction of a retroviral construct expressing human FLI-1/ERGB into K562 cells induces changes similar to those seen following TPA treatment, including increased adherence to the surface of the culture vessel and altered size and morphology. Infected cells exhibit higher levels of the megakaryocyte marker CD41a and, to a lesser extent, CD49b. These markers, as well as virally encoded FLI-1/ERGB-specific RNA and protein, are expressed at the highest levels in the attached cell population, while the growth rate of adherent cells is reduced, and the fraction of cells in G0-G1 is increased. FLI-1/ERGB virus-infected cells also exhibit increased expression of hemoglobin, a marker of erythroid differentiation. Our results suggest FLI-1/ERGB plays a role in controlling differentiation and gene expression along the megakaryocyte/platelet pathway, and further implicate ETS-related genes in the control of multiple developmentally regulated hematopoietic genes. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Athanasiou, M AU - Clausen, P A AU - Mavrothalassitis, G J AU - Zhang, X K AU - Watson, D K AU - Blair, D G AD - SAIC-Frederick, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702-1201, USA. Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 1525 EP - 1534 VL - 7 IS - 11 SN - 1044-9523, 1044-9523 KW - Antigens, CD KW - 0 KW - DNA-Binding Proteins KW - FLI1 protein, human KW - Fli1 protein, mouse KW - Hemoglobins KW - Integrin alpha2 KW - Platelet Glycoprotein GPIIb-IIIa Complex KW - Proto-Oncogene Protein c-fli-1 KW - Proto-Oncogene Proteins KW - RNA, Messenger KW - Trans-Activators KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Antigens, CD -- analysis KW - Humans KW - Resting Phase, Cell Cycle KW - RNA, Messenger -- analysis KW - Cell Differentiation KW - Mice KW - Hemoglobins -- analysis KW - Leukemia, Erythroblastic, Acute KW - Tumor Cells, Cultured KW - Platelet Glycoprotein GPIIb-IIIa Complex -- analysis KW - Tetradecanoylphorbol Acetate -- pharmacology KW - G1 Phase KW - Genetic Vectors -- genetics KW - Retroviridae -- genetics KW - Cell Adhesion KW - Cell Division KW - Gene Expression Regulation, Developmental -- physiology KW - DNA-Binding Proteins -- analysis KW - Trans-Activators -- genetics KW - DNA-Binding Proteins -- genetics KW - Trans-Activators -- analysis KW - Megakaryocytes -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78552605?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Increased+expression+of+the+ETS-related+transcription+factor+FLI-1%2FERGB+correlates+with+and+can+induce+the+megakaryocytic+phenotype.&rft.au=Athanasiou%2C+M%3BClausen%2C+P+A%3BMavrothalassitis%2C+G+J%3BZhang%2C+X+K%3BWatson%2C+D+K%3BBlair%2C+D+G&rft.aulast=Athanasiou&rft.aufirst=M&rft.date=1996-11-01&rft.volume=7&rft.issue=11&rft.spage=1525&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 - 1997-02-27 N1 - Date created - 1997-02-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of transdermal nicotine delivery on measures of acute nicotine withdrawal. AN - 78550495; 8930145 AB - The effects of transedermal nicotine on acute physiologic, performance and subjective measures of tobacco withdrawal were evaluated in a residential, double-blind, placebo-controlled, crossover study. Ten subjects smoked ad libitum for 4 days and underwent monitored tobacco abstinence for 3 days. On no-smoking days, three transdermal nicotine delivery systems (patches) that delivered a total of 0, 10, 20 or 30 mg of nicotine were applied for 16 hr. Experimental measures were collected 6 hr after the application of the patches. Plasma levels of nicotine and cotinine indicated that the 20- and 30-mg treatment condition fully replaced the nicotine ordinarily obtained from smoking. During nicotine abstinence (0 mg condition) typical signs of tobacco withdrawal were evident including: decreases in pulse rate, increases in electroencephalographic theta power, increases in subjective measures of tobacco abstinence and slowed performance on computer-delivered cognitive tests. Nicotine patch treatment diminished the physiologic and performance changes, but subjective measures of tobacco abstinence (cigarette craving, increases in withdrawal scores) were not significantly reduced. These data indicate that the nicotine patch may be used to diminish aspects of tobacco abstinence that could affect performance even though withdrawal discomfort may persist. JF - The Journal of pharmacology and experimental therapeutics AU - Pickworth, W B AU - Fant, R V AU - Butschky, M F AU - Henningfield, J E AD - National Institute on Drug Abuse, Division of Intramural Research, Baltimore, Maryland, USA. Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 450 EP - 456 VL - 279 IS - 2 SN - 0022-3565, 0022-3565 KW - Nicotine KW - 6M3C89ZY6R KW - Cotinine KW - K5161X06LL KW - Index Medicus KW - Administration, Cutaneous KW - Psychomotor Performance -- drug effects KW - Double-Blind Method KW - Cognition -- drug effects KW - Humans KW - Adult KW - Cross-Over Studies KW - Cotinine -- blood KW - Electroencephalography -- drug effects KW - Blood Pressure -- drug effects KW - Male KW - Female KW - Plants, Toxic KW - Tobacco KW - Substance Withdrawal Syndrome -- drug therapy KW - Nicotine -- administration & dosage KW - Nicotine -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78550495?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Effects+of+transdermal+nicotine+delivery+on+measures+of+acute+nicotine+withdrawal.&rft.au=Pickworth%2C+W+B%3BFant%2C+R+V%3BButschky%2C+M+F%3BHenningfield%2C+J+E&rft.aulast=Pickworth&rft.aufirst=W&rft.date=1996-11-01&rft.volume=279&rft.issue=2&rft.spage=450&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 - 1996-12-24 N1 - Date created - 1996-12-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Papillomaviruses and potential copathogens. AN - 78538707; 8920709 AB - An in vitro multistage genital epithelial cell model for cervical cancer that parallels the in vivo neoplastic process has been developed using recombinant human papillomavirus (HPV) DNA and genital cells. HPV-16-immortalized genital cells are responsive to the genotoxic action of known chemical carcinogens (polycyclic hydrocarbons, alkylating agents or cigarette smoke condensate), but are not converted to malignancy. Ras oncogene and human herpes virus-2 did convert HPV immortalized cells to malignancy, whereas human herpes virus-6 infection only increased HPV expression. Human immunodeficiency virus did not infect genital cells. JF - Toxicology letters AU - DiPaolo, J A AU - Popescu, N C AU - Woodworth, C D AU - Zimonjic, D B AD - Laboratory of Biology, National Cancer Institute, Bethesda MD 20892, USA. Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 1 EP - 7 VL - 88 IS - 1-3 SN - 0378-4274, 0378-4274 KW - Carcinogens KW - 0 KW - Index Medicus KW - AIDS/HIV KW - HIV-1 -- isolation & purification KW - Humans KW - Cervix Uteri -- drug effects KW - Skin -- virology KW - Skin -- drug effects KW - Cells, Cultured KW - HIV-1 -- pathogenicity KW - Genes, ras -- physiology KW - Herpesviridae -- pathogenicity KW - Cervix Uteri -- cytology KW - Cervix Uteri -- virology KW - Skin -- cytology KW - Female KW - Male KW - Papillomavirus Infections -- pathology KW - Carcinogens -- pharmacology KW - Papillomaviridae -- pathogenicity KW - Cocarcinogenesis KW - Tumor Virus Infections -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78538707?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+letters&rft.atitle=Papillomaviruses+and+potential+copathogens.&rft.au=DiPaolo%2C+J+A%3BPopescu%2C+N+C%3BWoodworth%2C+C+D%3BZimonjic%2C+D+B&rft.aulast=DiPaolo&rft.aufirst=J&rft.date=1996-11-01&rft.volume=88&rft.issue=1-3&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Toxicology+letters&rft.issn=03784274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-18 N1 - Date created - 1996-12-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Arsenic induces overexpression of growth factors in human keratinocytes. AN - 78533234; 8917704 AB - Although epidemiological studies have shown that inorganic arsenicals are human skin carcinogens and induce hyperproliferation and hyperkeratosis, there is currently no known mechanism for their action or an established animal model for its study. We observed increased mRNA transcripts and secretion of keratinocyte growth factors, including granulocyte macrophage-colony stimulating factor (GM-CSF) and transforming growth factor-alpha (TGF alpha) and the proinflammatory cytokine tumor necrosis factor-alpha in primary human epidermal keratinocytes cultured in the presence of low micromolar concentrations of sodium arsenite. Treatment with sodium arsenite resulted in a significant increase in cell proliferation, as indicated by increases in cell numbers, c-myc gene expression, and incorporation of [3H]thymidine into cellular DNA. Studies of transcriptional regulation indicate that the rate of GM-CSF mRNA transcription is increased, while the elevated TGF alpha is likely the results of message stabilization. While a number of cytokine regulatory networks exist in the skin, studies utilizing neutralizing antibodies against the growth factors of interest indicate that inhibition of the arsenic-induced increase in TGF alpha results in a corresponding decrease in the gene expression and secretion of GM-CSF. The present studies demonstrate that growth-promoting cytokines and growth factors are induced in keratinocytes following treatment with arsenic and could play a significant role in arsenic-induced skin cancer. JF - Toxicology and applied pharmacology AU - Germolec, D R AU - Yoshida, T AU - Gaido, K AU - Wilmer, J L AU - Simeonova, P P AU - Kayama, F AU - Burleson, F AU - Dong, W AU - Lange, R W AU - Luster, M I AD - Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. GERMOLEC@NIEHS.NIH.GOV Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 308 EP - 318 VL - 141 IS - 1 SN - 0041-008X, 0041-008X KW - Arsenites KW - 0 KW - Sodium Compounds KW - Transforming Growth Factor alpha KW - Tumor Necrosis Factor-alpha KW - sodium arsenite KW - 48OVY2OC72 KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Index Medicus KW - Cells, Cultured KW - Humans KW - Cell Division -- drug effects KW - Enzyme-Linked Immunosorbent Assay KW - Genes, myc -- drug effects KW - Gene Expression Regulation -- drug effects KW - Female KW - Granulocyte-Macrophage Colony-Stimulating Factor -- secretion KW - Keratinocytes -- drug effects KW - Arsenites -- toxicity KW - Sodium Compounds -- toxicity KW - Tumor Necrosis Factor-alpha -- secretion KW - Transforming Growth Factor alpha -- secretion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78533234?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Arsenic+induces+overexpression+of+growth+factors+in+human+keratinocytes.&rft.au=Germolec%2C+D+R%3BYoshida%2C+T%3BGaido%2C+K%3BWilmer%2C+J+L%3BSimeonova%2C+P+P%3BKayama%2C+F%3BBurleson%2C+F%3BDong%2C+W%3BLange%2C+R+W%3BLuster%2C+M+I&rft.aulast=Germolec&rft.aufirst=D&rft.date=1996-11-01&rft.volume=141&rft.issue=1&rft.spage=308&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 - 1996-12-23 N1 - Date created - 1996-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Physiologically based pharmacodynamic modeling of an interaction threshold between trichloroethylene and 1,1-dichloroethylene in Fischer 344 rats. AN - 78532525; 8917684 AB - Physiologically based pharmacokinetic modeling (PBPK) and gas uptake experiments have been used by researchers to demonstrate the competitive inhibition mechanism between trichloroethylene (TCE) and 1,1-dichloroethylene (DCE). Expanding on their work, we showed that this pharmacokinetic interaction was absent at levels of 100 ppm or less of either chemical in gas uptake systems. In this study, we further illustrate the presence of such an interaction threshold at the pharmacodynamic level by examining the interaction effect of either chemical on the other's ability to bind and deplete hepatic glutathione (GSH) in Fischer 344 rats. However, at this end point, the pharmacodynamic interaction is complicated by the ability of the liver to resynthesize GSH in response to its depletion. To quantitatively resolve the interaction effects on GSH content from the resynthesis effects, physiologically based pharmacodynamic (PBPD) modeling is applied. Initially, the PBPD model description of hepatic GSH kinetics was calibrated against previously published data and by gas uptake experiments conducted in our laboratory. Then, the model was used to determine the duration of the gas uptake exposure experiments by identifying the critical time point at which hepatic GSH is at a minimum in response to both chemicals. Subsequently, gas uptake experiments were designed following the PBPK/PD model predictions. In these model-directed experiments, DCE was the only chemical capable of significantly depleting hepatic GSH. The application of TCE to the rats at concentrations higher than 100 ppm obstructed the ability of DCE to deplete hepatic GSH. Since the metabolites of DCE bind to hepatic GSH, this obstruction signaled the presence of metabolic inhibition by TCE. However, TCE, at concentrations less than 100 ppm, was not effective in inhibiting DCE from significantly depleting hepatic GSH. The same observations were made when the ability of DCE to cause hepatic injury, as measured by aspartate aminotransferase serum activity, was assessed. Both conclusions validated the previous findings of the presence of the interaction threshold at the pharmacokinetic level. JF - Toxicology and applied pharmacology AU - el-Masri, H A AU - Constan, A A AU - Ramsdell, H S AU - Yang, R S AD - Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 124 EP - 132 VL - 141 IS - 1 SN - 0041-008X, 0041-008X KW - Dichloroethylenes KW - 0 KW - Solvents KW - vinylidene chloride KW - 21SK105J9D KW - Trichloroethylene KW - 290YE8AR51 KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Drug Interactions KW - Models, Biological KW - Chromatography, High Pressure Liquid KW - Binding Sites KW - Dichloroethylenes -- pharmacology KW - Trichloroethylene -- metabolism KW - Dichloroethylenes -- metabolism KW - Liver -- drug effects KW - Solvents -- metabolism KW - Glutathione -- metabolism KW - Trichloroethylene -- pharmacology KW - Liver -- metabolism KW - Solvents -- pharmacology KW - Liver -- physiology KW - Glutathione -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78532525?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Physiologically+based+pharmacodynamic+modeling+of+an+interaction+threshold+between+trichloroethylene+and+1%2C1-dichloroethylene+in+Fischer+344+rats.&rft.au=el-Masri%2C+H+A%3BConstan%2C+A+A%3BRamsdell%2C+H+S%3BYang%2C+R+S&rft.aulast=el-Masri&rft.aufirst=H&rft.date=1996-11-01&rft.volume=141&rft.issue=1&rft.spage=124&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 - 1996-12-23 N1 - Date created - 1996-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isolated limb perfusion for malignant melanoma. AN - 78531110; 8914206 AB - The technique of isolated limb perfusion for treatment of extremity melanoma has been used in the United States for almost 40 years. The treatment is based upon the ability to isolate the circulation of the afflicted extremity from the systemic circulation, thereby allowing dose-intensive delivery of anti-cancer agents to the limb while eliminating systemic exposure and toxicity. A number of agents have been used in ILP, however, the bulk of clinical experience has been with the alkylating agent melphalan, typically used under conditions of mild hyperthermia. Despite considerable clinical experience, there has been a lack of agreement about the role of ILP in the prophylaxis against or the treatment of recurrent extremity melanoma. Recently there has been renewed interest in the use of ILP based upon the very promising results using a combination of tumor necrosis factor, melphalan, and interferon-gamma which have produced complete response (CR) rates of almost 90%. The utility of this regimen in extremity melanoma is actively being evaluated by clinical trials in the United States and Europe. JF - Seminars in surgical oncology AU - Alexander, H R AU - Fraker, D L AU - Bartlett, D L AD - Surgery Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892-1502, USA. PY - 1996 SP - 416 EP - 428 VL - 12 IS - 6 SN - 8756-0437, 8756-0437 KW - Antineoplastic Agents, Alkylating KW - 0 KW - Tumor Necrosis Factor-alpha KW - Interferon-gamma KW - 82115-62-6 KW - Melphalan KW - Q41OR9510P KW - Index Medicus KW - Drug Therapy, Combination KW - Humans KW - Hyperthermia, Induced KW - Clinical Trials as Topic KW - Time Factors KW - Leg KW - Tumor Necrosis Factor-alpha -- administration & dosage KW - Melanoma -- mortality KW - Melphalan -- administration & dosage KW - Chemotherapy, Cancer, Regional Perfusion KW - Melanoma -- drug therapy KW - Interferon-gamma -- administration & dosage KW - Antineoplastic Agents, Alkylating -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78531110?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+surgical+oncology&rft.atitle=Isolated+limb+perfusion+for+malignant+melanoma.&rft.au=Alexander%2C+H+R%3BFraker%2C+D+L%3BBartlett%2C+D+L&rft.aulast=Alexander&rft.aufirst=H&rft.date=1996-11-01&rft.volume=12&rft.issue=6&rft.spage=416&rft.isbn=&rft.btitle=&rft.title=Seminars+in+surgical+oncology&rft.issn=87560437&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-18 N1 - Date created - 1997-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemical induction of fenestrae in vessels of the blood-brain barrier. AN - 78529320; 8912894 AB - The endothelium responsible for the blood-brain barrier to hydrophilic solutes has been converted here, by chemical means, to the fenestrated, permeable type of vessel (FV). During development, some brain vessels are reported to be transiently fenestrated. Endothelial fenestrae of adrenal glands are known to be reinduced in vitro by retinoic acid (RA) or phorbol myristate acetate (PMA). Could fenestrae be likewise reinduced in brain barrier vessels? When RA or PMA were infused continuously by an osmotic pump for 28 days into the cerebral cortex of rats, some brain vessels in the lesion cavity created by the reagents were FV. There were no FV in adjacent brain. When 100 microM RA was infused, about 20% of vessels in the cyst were FV, as were about 29% after infusion of 150 ng/ml PMA. Fenestra development depended on concentration and time. Reversibility of fenestra formation was complete at 1-2 months after delivery of RA or PMA had ceased. It is proposed that the RA and PMA effect is mediated by the plasminogen activator urokinase, in as much as both RA and PMA stimulate its production. This notion is supported by preliminary experiments in which urokinase infusion into brain also produced fenestrae. It is further suggested that the reversible induction of fenestrae in the mature brain by RA, PMA, and, perhaps, a variety of other conversion factors may be confined to a subset of brain barrier vessels that must be regenerating and of the kind that were temporarily fenestrated during fetal life. JF - Experimental neurology AU - Kaya, M AU - Chang, L AU - Truong, A AU - Brightman, M W AD - Laboratory of Neurobiology, NINDS, National Institutes of Health, Bethesda, Maryland 20892-4062, USA. Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 6 EP - 13 VL - 142 IS - 1 SN - 0014-4886, 0014-4886 KW - Carcinogens KW - 0 KW - Keratolytic Agents KW - Evans Blue KW - 45PG892GO1 KW - Tretinoin KW - 5688UTC01R KW - Horseradish Peroxidase KW - EC 1.11.1.- KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Tretinoin -- pharmacology KW - Animals KW - Carcinogens -- pharmacology KW - Endothelium, Vascular -- metabolism KW - Dose-Response Relationship, Drug KW - Rats KW - Rats, Sprague-Dawley KW - Endothelium, Vascular -- drug effects KW - Capillaries -- pathology KW - Endothelium, Vascular -- pathology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Keratolytic Agents -- pharmacology KW - Time Factors KW - Capillaries -- metabolism KW - Male KW - Blood-Brain Barrier -- drug effects KW - Horseradish Peroxidase -- pharmacokinetics KW - Evans Blue -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78529320?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+neurology&rft.atitle=Chemical+induction+of+fenestrae+in+vessels+of+the+blood-brain+barrier.&rft.au=Kaya%2C+M%3BChang%2C+L%3BTruong%2C+A%3BBrightman%2C+M+W&rft.aulast=Kaya&rft.aufirst=M&rft.date=1996-11-01&rft.volume=142&rft.issue=1&rft.spage=6&rft.isbn=&rft.btitle=&rft.title=Experimental+neurology&rft.issn=00144886&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-08 N1 - Date created - 1997-01-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A characteristic eruption associated with ifosfamide, carboplatin, and etoposide chemotherapy after pretreatment with recombinant interleukin-1 alpha. AN - 78526808; 8912565 AB - Patients who received recombinant interleukin-1 alpha (IL-1 alpha) before chemotherapy followed by autologous bone marrow transplantation had a characteristic intertriginous cutaneous eruption that has not previously been described. Our aim was to document these skin changes and to determine whether IL-1 alpha as a sole agent caused recognizable changes in the skin. A prospective study of the skin changes in eight patients was performed. We characterized the clinical, histologic, and immunohistochemical features of the patient's skin after IL-1 alpha infusions and after chemotherapy. No specific clinical or histologic changes were seen immediately after IL-1 alpha infusions. Immunohistochemical studies showed significant upregulation of endothelial leukocyte adhesion molecule-1 (ELAM-1) expression. Within 1 day of the initiation of chemotherapy (ifosfamide, carboplatin, and etoposide), a cutaneous eruption consisting of mucositis and varying degrees of erythema progressing to painful erosions in body folds and under adhesive tape developed in all patients. Histologic features were consistent with a chemotherapeutic effect on the epidermis as well as eccrine and apocrine glands. Expression of keratinocyte intercellular adhesion molecule-1 and HLA-DR as well as of ELAM-1 on dermal endothelial cells was increased. The perivascular lymphocytic infiltrate consisted mainly of CD4+ T cells. High-dose chemotherapy with ifosfamide, carboplatin, and etoposide resulted in a characteristic cutaneous eruption that is consistent with a toxic reaction to chemotherapeutic agents. Its accentuation in skin folds and under taped areas suggests that eccrine excretion of the drugs or a toxic metabolite is an important contributing factor. IL-1 alpha may induce the expression of ELAM-1 but does not cause a cutaneous eruption. JF - Journal of the American Academy of Dermatology AU - Prussick, R AU - Horn, T D AU - Wilson, W H AU - Turner, M C AD - Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 705 EP - 709 VL - 35 IS - 5 Pt 1 SN - 0190-9622, 0190-9622 KW - Antineoplastic Agents KW - 0 KW - Interleukin-1 KW - Etoposide KW - 6PLQ3CP4P3 KW - Carboplatin KW - BG3F62OND5 KW - Ifosfamide KW - UM20QQM95Y KW - Index Medicus KW - Prospective Studies KW - Humans KW - Bone Marrow Transplantation -- adverse effects KW - Adult KW - Ifosfamide -- adverse effects KW - Etoposide -- adverse effects KW - Middle Aged KW - Carboplatin -- adverse effects KW - Male KW - Female KW - Antineoplastic Agents -- adverse effects KW - Drug Eruptions -- etiology KW - Premedication KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Interleukin-1 -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78526808?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Academy+of+Dermatology&rft.atitle=A+characteristic+eruption+associated+with+ifosfamide%2C+carboplatin%2C+and+etoposide+chemotherapy+after+pretreatment+with+recombinant+interleukin-1+alpha.&rft.au=Prussick%2C+R%3BHorn%2C+T+D%3BWilson%2C+W+H%3BTurner%2C+M+C&rft.aulast=Prussick&rft.aufirst=R&rft.date=1996-11-01&rft.volume=35&rft.issue=5+Pt+1&rft.spage=705&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Academy+of+Dermatology&rft.issn=01909622&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-23 N1 - Date created - 1996-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The MPTP-induced parkinsonian syndrome in the goldfish is associated with major cell destruction in the forebrain and subtle changes in the optic tectum. AN - 78526278; 8912908 AB - The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can induce a parkinsonian syndrome in humans and nonhuman primates, which is susceptible to treatment and prevention by drugs such as L-DOPA and L-deprenyl. Recently, we have reported that MPTP can also cause a parkinsonian syndrome in the common goldfish, which appears to faithfully mirror the neurochemical and behavioral aspects of the action of MPTP in the higher vertebrates. In addition, we recently identified the likely teleost equivalent of the substantia nigra in the goldfish forebrain, the "nucleus pars medialis," on the basis of its destruction by MPTP and selective protection by the MAO-B blocker L-deprenyl. In the present work we substantiate this conclusion by examining tissue destruction the goldfish forebrain at increasing MPTP concentrations, up to the the LD50 of 200 mg/kg. In addition, we show that at the highest MPTP dose subtle changes also occur with low frequency in nondopaminergic cells in the optic tectum, and in ependymal cells lining the midbrain ventricle. The effects on ependymal cells are similar to those previously noted in the forebrain. We conclude that the goldfish model continues to faithfully mimic the histologic pattern of parkinsonian tissue destruction engendered by MPTP in primate models. JF - Experimental neurology AU - Pollard, H B AU - Kuijpers, G A AU - Adeyemo, O M AU - Youdim, M B AU - Goping, G AD - Laboratory of Cell Biology and Genetics, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 170 EP - 178 VL - 142 IS - 1 SN - 0014-4886, 0014-4886 KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - 9P21XSP91P KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Behavior, Animal -- drug effects KW - Animals KW - Dose-Response Relationship, Drug KW - Cell Compartmentation -- drug effects KW - Dopamine -- physiology KW - Neurons, Afferent -- ultrastructure KW - Neurons, Afferent -- drug effects KW - Microscopy, Electron KW - Cell Nucleus -- drug effects KW - Visual Pathways -- drug effects KW - Neurons, Afferent -- pathology KW - Cell Size -- drug effects KW - Superior Colliculi -- ultrastructure KW - Superior Colliculi -- pathology KW - Prosencephalon -- ultrastructure KW - Parkinson Disease, Secondary -- chemically induced KW - Parkinson Disease, Secondary -- pathology KW - Goldfish -- physiology KW - Prosencephalon -- drug effects KW - Prosencephalon -- pathology KW - Superior Colliculi -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78526278?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+neurology&rft.atitle=The+MPTP-induced+parkinsonian+syndrome+in+the+goldfish+is+associated+with+major+cell+destruction+in+the+forebrain+and+subtle+changes+in+the+optic+tectum.&rft.au=Pollard%2C+H+B%3BKuijpers%2C+G+A%3BAdeyemo%2C+O+M%3BYoudim%2C+M+B%3BGoping%2C+G&rft.aulast=Pollard&rft.aufirst=H&rft.date=1996-11-01&rft.volume=142&rft.issue=1&rft.spage=170&rft.isbn=&rft.btitle=&rft.title=Experimental+neurology&rft.issn=00144886&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-08 N1 - Date created - 1997-01-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pulmonary fibrogenesis after three consecutive inhalation exposures to chrysotile asbestos. AN - 78525237; 8912773 AB - Previously, this laboratory developed a model of asbestos-induced pulmonary fibrogenesis in rats and mice after a brief (1 to 3-h) inhalation exposure. However, typical human environmental exposures would be repeated, although at lower concentrations than those used in our animal model. Here we have extended this model to encompass repeated exposures and consequent long-term effects. Groups of rats were exposed to chrysotile aerosol (10 mg/m3) for 3- to 5-h periods over 3 consecutive days. Lung fiber burden and pathologic features were studied for as long as 6 mo after exposure. We found that many of the longest (> or = 8 microm) fibers were retained in the lung for at least 6 mo, whereas shorter fibers were cleared more rapidly. The three exposures to chrysotile caused a large increase in DNA synthesis in the epithelium of terminal bronchioles and more proximal airways. When compared with a single exposure, the triple exposure caused an enhanced inflammatory response as well as a prolonged period of increased DNA synthesis in the proximal alveolar region. Hyperplastic, fibrotic lesions subsequently developed in the same region and persisted for at least 6 mo after exposure. These findings will be valuable in directing future studies of the mechanisms of pulmonary fibrosis in this model. JF - American journal of respiratory and critical care medicine AU - Coin, P G AU - Osornio-Vargas, A R AU - Roggli, V L AU - Brody, A R AD - Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 1511 EP - 1519 VL - 154 IS - 5 SN - 1073-449X, 1073-449X KW - Asbestos, Serpentine KW - 0 KW - DNA KW - 9007-49-2 KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Macrophages, Alveolar -- metabolism KW - Animals KW - Rats, Sprague-Dawley KW - Dose-Response Relationship, Drug KW - Administration, Inhalation KW - Macrophages, Alveolar -- pathology KW - DNA -- biosynthesis KW - Male KW - Pulmonary Fibrosis -- pathology KW - Pulmonary Fibrosis -- etiology KW - Asbestos, Serpentine -- administration & dosage KW - Pulmonary Fibrosis -- metabolism KW - Asbestos, Serpentine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78525237?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pulmonary+fibrogenesis+after+three+consecutive+inhalation+exposures+to+chrysotile+asbestos.&rft.au=Coin%2C+P+G%3BOsornio-Vargas%2C+A+R%3BRoggli%2C+V+L%3BBrody%2C+A+R&rft.aulast=Coin&rft.aufirst=P&rft.date=1996-11-01&rft.volume=154&rft.issue=5&rft.spage=1511&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 - 1997-01-03 N1 - Date created - 1997-01-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dopamine induces apoptotic cell death of a catecholaminergic cell line derived from the central nervous system. AN - 78521751; 8913362 AB - Dopamine produces a time- and dose-dependent increase in cell death in a clonal catecholaminergic cell line (CATH.a) derived from the central nervous system. Cell death also occurred after treatment with the catecholamines L-dihydroxyphenylalanine, norepinephrine, epinephrine, and isoproterenol, as well as the neurotoxic compound 6-hydroxydopamine. Cell death is not receptor mediated because selective noradrenergic and dopaminergic receptor agonists had no effect on CATH.a cell viability. Dopamine induces apoptotic cell death as indicated by DNA fragmentation measured by gel electrophoresis and by flow cytometric analysis. Apoptosis seems to be produced by dopamine autoxidation, because intracellular peroxides increase after dopamine treatment and cell death can be inhibited by catalase and N-acetylcysteine. N-acetylcysteine produced a dose-dependent decrease in dopamine-induced cell death; this correlated with a decrease in peroxide formation. In addition, antisense to the antioxidant protein bcl-2 increases the sensitivity of CATH.a cells to dopamine-induced cell death. These findings indicate that the oxidative products of dopamine cause neurotoxicity through apoptosis. JF - Molecular pharmacology AU - Masserano, J M AU - Gong, L AU - Kulaga, H AU - Baker, I AU - Wyatt, R J AD - National Institute of Mental Health Neuroscience Center at Saint Elizabeths, Neuropsychiatry Branch, Washington, D.C. 20032, USA. masseraj@dirpc.nimh.nih.gov Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 1309 EP - 1315 VL - 50 IS - 5 SN - 0026-895X, 0026-895X KW - Catecholamines KW - 0 KW - Oligonucleotides, Antisense KW - Peroxides KW - Proto-Oncogene Proteins c-bcl-2 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Sensitivity and Specificity KW - Brain Neoplasms KW - Animals KW - Peroxides -- metabolism KW - Tumor Cells, Cultured KW - Oligonucleotides, Antisense -- pharmacology KW - Mice KW - Proto-Oncogene Proteins c-bcl-2 -- genetics KW - Mice, Transgenic KW - Cell Death -- drug effects KW - Central Nervous System -- metabolism KW - Catecholamines -- pharmacology KW - Catecholamines -- physiology KW - Apoptosis -- drug effects KW - Central Nervous System -- drug effects KW - Central Nervous System -- cytology KW - Dopamine -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78521751?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dopamine+induces+apoptotic+cell+death+of+a+catecholaminergic+cell+line+derived+from+the+central+nervous+system.&rft.au=Masserano%2C+J+M%3BGong%2C+L%3BKulaga%2C+H%3BBaker%2C+I%3BWyatt%2C+R+J&rft.aulast=Masserano&rft.aufirst=J&rft.date=1996-11-01&rft.volume=50&rft.issue=5&rft.spage=1309&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 - 1996-12-26 N1 - Date created - 1996-12-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Requirements for RNA polymerase II carboxyl-terminal domain for activated transcription of human retroviruses human T-cell lymphotropic virus I and HIV-1. AN - 78519725; 8910388 AB - The carboxyl-terminal domain (CTD) of RNA polymerase (RNAP) II contains multiple repeats with a heptapeptide consensus: Tyr-Ser-Pro-Thr-Ser-Pro-Ser. It has been proposed that phosphorylation of this CTD facilitates clearance and elongation of transcription complexes initiated at the promoters. However, not all transcribed promoters require RNAP II with full-length CTD. Furthermore, different activators can promote capably the transcriptional activity of polymerase II mutants deleted in the CTD. Thus, the role of the RNAP II CTD in transcription and in response to activators remains incompletely understood. To study the role of CTD in the regulated transcription of human retroviruses human-T cell lymphotropic virus I and human immunodeficiency virus 1, we used an alpha-amanitin-resistant system developed previously (Gerber, H. P., Hagmann, M., Seipel, K., Georgiev, O., West, M. A., Litingtung, Y., Schaffner, W., and Corden, J. L. (1995) Nature 374, 660-662). We found that transcription directed by the human T-cell lymphotropic virus I activator protein Tax was strongly promoted by CTD-deficient RNA polymerase II. By contrast, the human immunodeficiency virus 1 activator Tat, which is recruited to the promoter by tethering to a nascent leader RNA, requires CTD-containing polymerase II for transcriptional activity. Biochemically, we characterized that Tat associated with a cellular CTD kinase activity, whereas Tax did not. Concordantly, we found that cellular transcription factor Sp1, which can activate CTD-deficient polymerase II with an efficiency similar to Tax, also failed to bind a CTD kinase. Taken together, these observations address mechanistic corollaries between activators with(out) a linked CTD kinase and regulated transcription by RNA polymerase II moieties with(out) a CTD. JF - The Journal of biological chemistry AU - Chun, R F AU - Jeang, K T AD - Molecular Virology Section, Laboratory of Molecular Microbiology, NIAID, National Institutes of Health, Bethesda, Maryland 20892-0460, USA. kjeang@atlas.niaid.nih.gov Y1 - 1996/11/01/ PY - 1996 DA - 1996 Nov 01 SP - 27888 EP - 27894 VL - 271 IS - 44 SN - 0021-9258, 0021-9258 KW - Amanitins KW - 0 KW - Gene Products, tat KW - Gene Products, tax KW - Recombinant Proteins KW - tat Gene Products, Human Immunodeficiency Virus KW - RNA Polymerase II KW - EC 2.7.7.- KW - Index Medicus KW - AIDS/HIV KW - Gene Products, tax -- metabolism KW - HeLa Cells KW - Humans KW - Amino Acid Sequence KW - Plasmids KW - Transcriptional Activation KW - HIV Long Terminal Repeat KW - Promoter Regions, Genetic KW - Phosphorylation KW - Transfection KW - Amanitins -- pharmacology KW - Recombinant Proteins -- metabolism KW - Consensus Sequence KW - Gene Products, tat -- metabolism KW - RNA Polymerase II -- metabolism KW - Human T-lymphotropic virus 1 -- genetics KW - HIV-1 -- metabolism KW - HIV-1 -- genetics KW - RNA Polymerase II -- chemistry KW - Transcription, Genetic KW - Human T-lymphotropic virus 1 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78519725?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Requirements+for+RNA+polymerase+II+carboxyl-terminal+domain+for+activated+transcription+of+human+retroviruses+human+T-cell+lymphotropic+virus+I+and+HIV-1.&rft.au=Chun%2C+R+F%3BJeang%2C+K+T&rft.aulast=Chun&rft.aufirst=R&rft.date=1996-11-01&rft.volume=271&rft.issue=44&rft.spage=27888&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 - 1996-12-26 N1 - Date created - 1996-12-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transient elevation of serum thyroid hormone levels following lithium discontinuation. AN - 78519309; 8911893 AB - Lithium therapy has been associated with altered thyroid function and even goiter in as many as half of chronically treated patients. We describe the case of a 16-year-old boy who developed transient hyperthyroxinemia after discontinuation of chronic lithium therapy. The lack of clinical hyperthyroidism and the gradual resolution of the biochemical abnormalities in this patient pointed to the benign character of his condition known as "euthyroid hyperthyroxinemia". Euthyroid hyperthyroxinemia may be a benign, transient complication of lithium-therapy discontinuation and should be considered in the diagnostic evaluation of lithium-related thyroid abnormalities. JF - European journal of pediatrics AU - Stratakis, C A AU - Chrousos, G P AD - NIH/Georgetown University, NIH (NICHD, DEB), Bethesda, MD 20892, USA. Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 939 EP - 941 VL - 155 IS - 11 SN - 0340-6199, 0340-6199 KW - Thyroid Hormones KW - 0 KW - Lithium KW - 9FN79X2M3F KW - Index Medicus KW - Humans KW - Adolescent KW - Thyroid Hormones -- blood KW - Male KW - Substance Withdrawal Syndrome KW - Hyperthyroxinemia -- chemically induced KW - Lithium -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78519309?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pediatrics&rft.atitle=Transient+elevation+of+serum+thyroid+hormone+levels+following+lithium+discontinuation.&rft.au=Stratakis%2C+C+A%3BChrousos%2C+G+P&rft.aulast=Stratakis&rft.aufirst=C&rft.date=1996-11-01&rft.volume=155&rft.issue=11&rft.spage=939&rft.isbn=&rft.btitle=&rft.title=European+journal+of+pediatrics&rft.issn=03406199&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-04 N1 - Date created - 1997-02-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemical trapping of ternary complexes of human immunodeficiency virus type 1 integrase, divalent metal, and DNA substrates containing an abasic site. Implications for the role of lysine 136 in DNA binding. AN - 78514874; 8910309 AB - We report a novel assay for monitoring the DNA binding of human immunodeficiency virus type 1 (HIV-1) integrase and the effect of cofactors and inhibitors. The assay uses depurinated oligonucleotides that can form a Schiff base between the aldehydic abasic site and a nearby enzyme lysine epsilon-amino group which can subsequently be trapped by reduction with sodium borohydride. Chemically depurinated duplex substrates representing the U5 end of the HIV-1 DNA were initially used. We next substituted an enzymatically generated abasic site for each of 10 nucleotides normally present in a 21-mer duplex oligonucleotide representing the U5 end of the HIV-1 DNA. Using HIV-1, HIV-2, or simian immunodeficiency virus integrases, the amount of covalent enzyme-DNA complex trapped decreased as the abasic site was moved away from the conserved CA dinucleotide. The enzyme-DNA complexes formed in the presence of manganese were not reversed by subsequent addition of EDTA, indicating that the divalent metal required for integrase catalysis is tightly bound in a ternary enzyme-metal-DNA complex. Both the N- and C-terminal domains of integrase contributed to efficient DNA binding, and mutation of Lys-136 significantly reduced Schiff base formation, implicating this residue in viral DNA binding. JF - The Journal of biological chemistry AU - Mazumder, A AU - Neamati, N AU - Pilon, A A AU - Sunder, S AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, Division of Basic Sciences, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. pommiery@box-P.nci.nih.gov Y1 - 1996/11/01/ PY - 1996 DA - 1996 Nov 01 SP - 27330 EP - 27338 VL - 271 IS - 44 SN - 0021-9258, 0021-9258 KW - Cations, Divalent KW - 0 KW - Oligodeoxyribonucleotides KW - Recombinant Proteins KW - Schiff Bases KW - DNA KW - 9007-49-2 KW - HIV Integrase KW - EC 2.7.7.- KW - Lysine KW - K3Z4F929H6 KW - Index Medicus KW - AIDS/HIV KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Recombinant Proteins -- metabolism KW - Humans KW - Molecular Sequence Data KW - Substrate Specificity KW - Sequence Deletion KW - Binding Sites KW - Cations, Divalent -- metabolism KW - Oligodeoxyribonucleotides -- chemistry KW - DNA -- metabolism KW - HIV Integrase -- isolation & purification KW - HIV-1 -- enzymology KW - Oligodeoxyribonucleotides -- metabolism KW - Oligodeoxyribonucleotides -- isolation & purification KW - HIV Integrase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78514874?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Chemical+trapping+of+ternary+complexes+of+human+immunodeficiency+virus+type+1+integrase%2C+divalent+metal%2C+and+DNA+substrates+containing+an+abasic+site.+Implications+for+the+role+of+lysine+136+in+DNA+binding.&rft.au=Mazumder%2C+A%3BNeamati%2C+N%3BPilon%2C+A+A%3BSunder%2C+S%3BPommier%2C+Y&rft.aulast=Mazumder&rft.aufirst=A&rft.date=1996-11-01&rft.volume=271&rft.issue=44&rft.spage=27330&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 - 1996-12-26 N1 - Date created - 1996-12-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tissue-specific growth suppression and chemosensitivity promotion in human hepatocellular carcinoma cells by retroviral-mediated transfer of the wild-type p53 gene. AN - 78514562; 8903408 AB - Selective expression of cytotoxic gene products in tumor cells is one of the goals of gene therapy for treating cancer. We are developing such a strategy for the treatment of human hepatocellular carcinoma (HCC) by linking the wild-type p53 (WT-p53) gene with HCC-associated transcriptional control elements (TCE) to achieve selective growth inhibition of retrovirally transduced HCC cells. Replication-defective, amphotrophic retroviruses were constructed containing a WT-p53 complementary DNA (cDNA) that is transcriptionally regulated by the HCC-associated alpha-fetoprotein (AFP) gene TCE. Expression of exogenous WT-p53 from this retroviral vector was limited to AFP-producing cells. Introduction of WT-p53 into AFP-positive HCC cells by retroviral infection markedly inhibited their clonal growth in monolayer and soft agar cultures, and increased the sensitivity of these cells to the chemotherapeutic drug, cisplatin. Therefore, restoration of WT-p53 expression in HCC cells, in combination with chemotherapeutic drugs, can be considered as a strategy for the therapy of human liver cancer. JF - Hepatology (Baltimore, Md.) AU - Xu, G W AU - Sun, Z T AU - Forrester, K AU - Wang, X W AU - Coursen, J AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD, USA. Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 1264 EP - 1268 VL - 24 IS - 5 SN - 0270-9139, 0270-9139 KW - Antineoplastic Agents KW - 0 KW - alpha-Fetoproteins KW - Index Medicus KW - Apoptosis KW - Tumor Cells, Cultured KW - Humans KW - Gene Expression KW - Organ Specificity KW - Retroviridae -- genetics KW - Antineoplastic Agents -- therapeutic use KW - Liver Neoplasms -- therapy KW - Genes, p53 KW - Carcinoma, Hepatocellular -- therapy KW - Genetic Therapy KW - alpha-Fetoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78514562?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Tissue-specific+growth+suppression+and+chemosensitivity+promotion+in+human+hepatocellular+carcinoma+cells+by+retroviral-mediated+transfer+of+the+wild-type+p53+gene.&rft.au=Xu%2C+G+W%3BSun%2C+Z+T%3BForrester%2C+K%3BWang%2C+X+W%3BCoursen%2C+J%3BHarris%2C+C+C&rft.aulast=Xu&rft.aufirst=G&rft.date=1996-11-01&rft.volume=24&rft.issue=5&rft.spage=1264&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 - 1996-12-12 N1 - Date created - 1996-12-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phenolphthalein exposure causes multiple carcinogenic effects in experimental model systems. AN - 78495861; 8895745 AB - Phenolphthalein (a triphenylmethane derivative) has been commonly used as a laxative for most of the twentieth century, but little is known about its long-term carcinogenic potential in experimental studies. In our studies, phenolphthalein administered continuously in the feed for 2 years to F344 rats at doses of 0, 12,500, 25,000, and 50,000 ppm and to C57BL/6 x CH3 F1 (hereafter called B6C3F1) mice at doses of 0, 3,000, 6,000, and 12,000 ppm caused multiple carcinogenic effects. Treatment-related neoplasms occurred in the kidney and adrenal medulla in male rats, adrenal medulla in female rats, hematopoietic system in male and female mice (histiocytic sarcomas and malignant lymphomas), and ovary of female mice. Phenolphthalein has been shown to have estrogenic and clastogenic properties. Previous studies of other estrogenic chemicals (e.g., zearalenone) in the F344 rat and B6C3F1 mouse have not shown the same spectrum of carcinogenic activity as that found with phenolphthalein, suggesting that phenolphthalein estrogenic activity alone is not responsible for the spectrum of tumors observed. It is more likely that the multiple biological properties of phenolphthalein, including its ability to form free radicals, its clastogenic activity, and its estrogenic activity, contributed to the carcinogenic effects observed. These studies show that phenolphthalein is a multisite/multispecies carcinogen. One of the sites for neoplasm that is of particular concern is the ovary, and epidemiology studies are under way to identify any potential effects of phenolphthalein exposure at this site in humans. JF - Cancer research AU - Dunnick, J K AU - Hailey, J R AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996/11/01/ PY - 1996 DA - 1996 Nov 01 SP - 4922 EP - 4926 VL - 56 IS - 21 SN - 0008-5472, 0008-5472 KW - Cathartics KW - 0 KW - Phenolphthaleins KW - Phenolphthalein KW - 6QK969R2IF KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Primary Myelofibrosis -- chemically induced KW - Kidney Neoplasms -- chemically induced KW - Body Weight -- drug effects KW - Ovarian Neoplasms -- chemically induced KW - Mice KW - Hematopoietic System -- drug effects KW - Male KW - Female KW - Phenolphthaleins -- toxicity KW - Cathartics -- toxicity KW - Neoplasms, Experimental -- chemically induced KW - Phenolphthaleins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78495861?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phenolphthalein+exposure+causes+multiple+carcinogenic+effects+in+experimental+model+systems.&rft.au=Dunnick%2C+J+K%3BHailey%2C+J+R&rft.aulast=Dunnick&rft.aufirst=J&rft.date=1996-11-01&rft.volume=56&rft.issue=21&rft.spage=4922&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-06 N1 - Date created - 1997-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Loss of retinoic acid receptors in mouse skin and skin tumors is associated with activation of the ras(Ha) oncogene and high risk for premalignant progression. AN - 78493387; 8895748 AB - Retinoic acid receptor transcripts (RARalpha and RARgamma) are decreased in benign mouse epidermal tumors relative to normal skin and are almost absent in carcinomas. In this report, the expression of RARalpha and RARgamma proteins was analyzed by immunoblotting in benign skin tumors induced by two different promotion protocols designed to yield tumors at low or high risk for malignant conversion. RARalpha was slightly reduced in papillomas promoted with 12-O-tetradecanoylphorbol-13-acetate (low risk) and markedly decreased or absent in papillomas promoted by mezerein (high risk). However, mezerein also caused substantial reduction of RARalpha in nontumorous skin. RARgamma was not detected in tumors from either protocol and was greatly reduced in skin treated by either promoter. Both RARalpha and RARgamma proteins were decreased in keratinocytes overexpressing an oncogenic v-ras(Ha) gene, and RARalpha was underexpressed in a benign keratinocyte cell line carrying a mutated c-ras(Ha) gene. Introduction of a recombinant RARalpha expression vector into benign keratinocyte tumor cells reduced the S-phase population and inhibited [3H]thymidine incorporation in response to retinoic acid. Furthermore, transactivation of B-RARE-tk-LUC by retinoic acid was markedly decreased in keratinocytes transduced with the v-ras(Ha) oncogene (v-ras(Ha)-keratinocytes). Blocking protein kinase C function in v-ras(Ha)-keratinocytes with bryostatin restored RARalpha protein to near normal levels, reflecting the involvement of protein kinase C in RARalpha regulation. Both RARalpha and RARgamma are down-regulated in cultured keratinocytes by 12-O-tetradecanoylphorbol-13-acetate, further implicating PKC in the regulation of retinoid receptors. Our data suggest that modulation of RARs could contribute to the neoplastic phenotype in mouse skin carcinogenesis and may be involved in the differential promoting activity of mezerein and 12-O-tetradecanoylphorbol-13-acetate, particularly for selecting tumors at high risk for malignant conversion. JF - Cancer research AU - Darwiche, N AU - Scita, G AU - Jones, C AU - Rutberg, S AU - Greenwald, E AU - Tennenbaum, T AU - Collins, S J AU - De Luca, L M AU - Yuspa, S H AD - Division of Basic Science, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1996/11/01/ PY - 1996 DA - 1996 Nov 01 SP - 4942 EP - 4949 VL - 56 IS - 21 SN - 0008-5472, 0008-5472 KW - Receptors, Retinoic Acid KW - 0 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Keratinocytes -- chemistry KW - Mice KW - Gene Expression Regulation KW - Protein Kinase C -- physiology KW - Mice, Inbred BALB C KW - Cell Cycle KW - Transcriptional Activation KW - Female KW - Cell Division KW - Skin Neoplasms -- genetics KW - Genes, ras KW - Skin -- chemistry KW - Precancerous Conditions -- genetics KW - Skin Neoplasms -- etiology KW - Precancerous Conditions -- etiology KW - Receptors, Retinoic Acid -- analysis KW - Precancerous Conditions -- metabolism KW - Skin Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78493387?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Loss+of+retinoic+acid+receptors+in+mouse+skin+and+skin+tumors+is+associated+with+activation+of+the+ras%28Ha%29+oncogene+and+high+risk+for+premalignant+progression.&rft.au=Darwiche%2C+N%3BScita%2C+G%3BJones%2C+C%3BRutberg%2C+S%3BGreenwald%2C+E%3BTennenbaum%2C+T%3BCollins%2C+S+J%3BDe+Luca%2C+L+M%3BYuspa%2C+S+H&rft.aulast=Darwiche&rft.aufirst=N&rft.date=1996-11-01&rft.volume=56&rft.issue=21&rft.spage=4942&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-06 N1 - Date created - 1997-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Epidemiologic determinants of seroreactivity to human papillomavirus (HPV) type 16 virus-like particles in cervical HPV-16 DNA-positive and-negative women. AN - 78491429; 8896493 AB - The epidemiologic determinants of seroreactivity to human papillomavirus (HPV) type 16 L1/L2 virus-like particles (VLPs) were assessed separately in HPV-16 DNA-positive and -negative women participating in a nested case-control study of incident cervical neoplasia. Seventy-four women with cervical HPV-16 DNA and 656 cytologically normal HPV-16 DNA-negative subjects were interviewed and tested at two time points for viral DNA and once (at the later time) for VLP seroreactivity. Among subjects who were currently HPV-16 DNA-negative, seroreactivity odds ratios increased from 2.9 for 2-5 male sex partners (vs. 0 or 1) to 5.4 for 6-9 partners and 14.0 for > or = 10. Thus, prior cervical infection may be a major determinant of seroreactivity in HPV-16 DNA-negative women. This trend was not observed in HPV-16 DNA-positive subjects. Seroreactivity was independently associated with oral contraceptive use, particularly in HPV-16 DNA-negative subjects with use for > or = 10 years. Consequently, a possible role for virus-steroid hormone interactions in seroconversion is suggested. JF - The Journal of infectious diseases AU - Wideroff, L AU - Schiffman, M H AU - Hoover, R AU - Tarone, R E AU - Nonnenmacher, B AU - Hubbert, N AU - Kirnbauer, R AU - Greer, C E AU - Lorincz, A T AU - Manos, M M AU - Glass, A G AU - Scott, D R AU - Sherman, M E AU - Buckland, J AU - Lowy, D AU - Schiller, J AD - Epidemiology and Biostatistics Program, National Cancer Institute, Bethesda, MD 20892-7374, USA. Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 937 EP - 943 VL - 174 IS - 5 SN - 0022-1899, 0022-1899 KW - Antibodies, Viral KW - 0 KW - Contraceptives, Oral KW - DNA, Viral KW - Abridged Index Medicus KW - Index Medicus KW - Contraceptives, Oral -- adverse effects KW - Sexual Behavior KW - Humans KW - Case-Control Studies KW - Male KW - Female KW - Antibodies, Viral -- blood KW - DNA, Viral -- analysis KW - Cervix Uteri -- virology KW - Papillomaviridae -- genetics KW - Virion -- immunology KW - Papillomaviridae -- immunology KW - Uterine Cervical Neoplasms -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78491429?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Epidemiologic+determinants+of+seroreactivity+to+human+papillomavirus+%28HPV%29+type+16+virus-like+particles+in+cervical+HPV-16+DNA-positive+and-negative+women.&rft.au=Wideroff%2C+L%3BSchiffman%2C+M+H%3BHoover%2C+R%3BTarone%2C+R+E%3BNonnenmacher%2C+B%3BHubbert%2C+N%3BKirnbauer%2C+R%3BGreer%2C+C+E%3BLorincz%2C+A+T%3BManos%2C+M+M%3BGlass%2C+A+G%3BScott%2C+D+R%3BSherman%2C+M+E%3BBuckland%2C+J%3BLowy%2C+D%3BSchiller%2C+J&rft.aulast=Wideroff&rft.aufirst=L&rft.date=1996-11-01&rft.volume=174&rft.issue=5&rft.spage=937&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 - 1996-11-27 N1 - Date created - 1996-11-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Apoptosis signaling pathways in normal T cells: differential activity of Bcl-2 and IL-1beta-converting enzyme family protease inhibitors on glucocorticoid- and Fas-mediated cytotoxicity. AN - 78487504; 8892614 AB - Fas-mediated apoptosis plays an important role in regulating the immune response in peripheral T cells. Restimulation of T cell blasts up-regulates Fas and Fas ligand expression, with subsequent interaction leading to cell death. Overexpression of Bcl-2 in tumor cells blocks apoptosis induced by many stimuli, but inhibition of Fas-mediated killing has not been consistently observed. To examine the behavior of Bcl-2 in normal cells, T cell blasts were transiently transfected with Bcl-2 and related gene products to determine the effect on apoptotic signaling. Transient overexpression of Bcl-2 in mouse and human T cell blasts did not block Fas-mediated apoptosis, whereas etoposide- and glucocorticoid-induced cytotoxicity was potently inhibited. Expression of Bcl-xL and adenovirus E1B 19K did not interfere with anti-Fas killing. In contrast, interleukin-1beta-converting enzyme family protease inhibitors Ac-DEVD-CHO and CrmA blocked Fas-mediated apoptosis. These results suggest that peripheral T cells use distinct apoptosis signaling pathways with differential sensitivity to Bcl-2 and interleukin-1beta-converting enzyme family protease inhibitors. Since T cells normally express Bcl-2 and Bcl-xL following activation, their inability to block Fas-mediated apoptosis may allow for the elimination of self-reactive cells and the appropriate regulation of immune responses. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Moreno, M B AU - Memon, S A AU - Zacharchuk, C M AD - Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/11/01/ PY - 1996 DA - 1996 Nov 01 SP - 3845 EP - 3849 VL - 157 IS - 9 SN - 0022-1767, 0022-1767 KW - Adenovirus E1B Proteins KW - 0 KW - Antigens, CD95 KW - BCL2L1 protein, human KW - Bcl2l1 protein, mouse KW - FASLG protein, human KW - Fas Ligand Protein KW - Fasl protein, mouse KW - Ionophores KW - Membrane Glycoproteins KW - Oligopeptides KW - Protease Inhibitors KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - Recombinant Fusion Proteins KW - acetyl-aspartyl-glutamyl-valyl-aspartal KW - bcl-X Protein KW - L 709049 KW - 143313-51-3 KW - Ionomycin KW - 56092-81-0 KW - Etoposide KW - 6PLQ3CP4P3 KW - Dexamethasone KW - 7S5I7G3JQL KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Caspase 1 KW - EC 3.4.22.36 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Abridged Index Medicus KW - Index Medicus KW - Etoposide -- pharmacology KW - Recombinant Fusion Proteins -- biosynthesis KW - Animals KW - Adenovirus E1B Proteins -- biosynthesis KW - Humans KW - Mice KW - Ionomycin -- pharmacology KW - Hybridomas -- drug effects KW - Mice, Inbred BALB C KW - Lymphocyte Activation KW - Proto-Oncogene Proteins -- biosynthesis KW - Hybridomas -- metabolism KW - Ionophores -- pharmacology KW - Adenovirus E1B Proteins -- genetics KW - Transfection KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Gene Expression Regulation KW - Cytotoxicity, Immunologic -- drug effects KW - Proto-Oncogene Proteins -- genetics KW - Hybridomas -- cytology KW - Protease Inhibitors -- pharmacology KW - Antigens, CD95 -- genetics KW - Membrane Glycoproteins -- physiology KW - Cysteine Endopeptidases -- physiology KW - Apoptosis -- physiology KW - Dexamethasone -- pharmacology KW - T-Lymphocytes, Cytotoxic -- cytology KW - Proto-Oncogene Proteins c-bcl-2 -- physiology KW - T-Lymphocytes, Cytotoxic -- metabolism KW - Signal Transduction -- physiology KW - Antigens, CD95 -- physiology KW - Signal Transduction -- drug effects KW - Apoptosis -- drug effects KW - Oligopeptides -- pharmacology KW - Proto-Oncogene Proteins c-bcl-2 -- genetics KW - T-Lymphocytes, Cytotoxic -- drug effects KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78487504?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Apoptosis+signaling+pathways+in+normal+T+cells%3A+differential+activity+of+Bcl-2+and+IL-1beta-converting+enzyme+family+protease+inhibitors+on+glucocorticoid-+and+Fas-mediated+cytotoxicity.&rft.au=Moreno%2C+M+B%3BMemon%2C+S+A%3BZacharchuk%2C+C+M&rft.aulast=Moreno&rft.aufirst=M&rft.date=1996-11-01&rft.volume=157&rft.issue=9&rft.spage=3845&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 - 1996-12-13 N1 - Date created - 1996-12-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Multicolour spectral karyotyping of mouse chromosomes. AN - 78487387; 8896561 AB - Murine models of human carcinogenesis are exceedingly valuable tools to understand genetic mechanisms of neoplastic growth. The identification of recurrent chromosomal rearrangements by cytogenetic techniques serves as an initial screening test for tumour specific aberrations. In murine models of human carcinogenesis, however, karyotype analysis is technically demanding because mouse chromosomes are acrocentric and of similar size. Fluorescence in situ hybridization (FISH) with mouse chromosome specific painting probes can complement conventional banding analysis. Although sensitive and specific, FISH analyses are restricted to the visualization of only a few mouse chromosomes at a time. Here we apply a novel imaging technique that we developed recently for the visualization of human chromosomes to the simultaneous discernment of all mouse chromosomes. The approach is based on spectral imaging to measure chromosome-specific spectra after FISH with differentially labelled mouse chromosome painting probes. Utilizing a combination of Fourier spectroscopy, CCD-imaging and conventional optical microscopy, spectral imaging allows simultaneous measurement of the fluorescence emission spectrum at all sample points. A spectrum-based classification algorithm has been adapted to karyotype mouse chromosomes. We have applied spectral karyotyping (SKY) to chemically induced plasmocytomas, mammary gland tumours from transgenic mice overexpressing the c-myc oncogene and thymomas from mice deficient for the ataxia telangiectasia (Atm) gene. Results from these analyses demonstrate the potential of SKY to identify complex chromosomal aberrations in mouse models of human carcinogenesis. JF - Nature genetics AU - Liyanage, M AU - Coleman, A AU - du Manoir, S AU - Veldman, T AU - McCormack, S AU - Dickson, R B AU - Barlow, C AU - Wynshaw-Boris, A AU - Janz, S AU - Wienberg, J AU - Ferguson-Smith, M A AU - Schröck, E AU - Ried, T AD - Diagnostic Development Branch, National Center for Human Genome Research, National Institutes of Health, Bethesda, Maryland 20892-4470, USA. Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 312 EP - 315 VL - 14 IS - 3 SN - 1061-4036, 1061-4036 KW - Cell Cycle Proteins KW - 0 KW - DNA-Binding Proteins KW - Proteins KW - Tumor Suppressor Proteins KW - ATM protein, human KW - EC 2.7.11.1 KW - Ataxia Telangiectasia Mutated Proteins KW - Atm protein, mouse KW - Protein-Serine-Threonine Kinases KW - Index Medicus KW - Animals KW - Genes, myc KW - Humans KW - Disease Models, Animal KW - Mice KW - Mice, Inbred BALB C KW - Mice, Transgenic KW - Proteins -- genetics KW - Neoplasms -- genetics KW - Mice, Inbred Strains KW - Plasmacytoma -- genetics KW - In Situ Hybridization, Fluorescence -- methods KW - Chromosomes KW - Karyotyping -- methods KW - Chromosome Aberrations UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78487387?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Multicolour+spectral+karyotyping+of+mouse+chromosomes.&rft.au=Liyanage%2C+M%3BColeman%2C+A%3Bdu+Manoir%2C+S%3BVeldman%2C+T%3BMcCormack%2C+S%3BDickson%2C+R+B%3BBarlow%2C+C%3BWynshaw-Boris%2C+A%3BJanz%2C+S%3BWienberg%2C+J%3BFerguson-Smith%2C+M+A%3BSchr%C3%B6ck%2C+E%3BRied%2C+T&rft.aulast=Liyanage&rft.aufirst=M&rft.date=1996-11-01&rft.volume=14&rft.issue=3&rft.spage=312&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 - 1996-12-16 N1 - Date created - 1996-12-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of a regulatory subcomplex in the guanine nucleotide exchange factor eIF2B that mediates inhibition by phosphorylated eIF2. AN - 78475461; 8887689 AB - Eukaryotic translation initiation factor 2B (eIF2B) is a five-subunit complex that catalyzes guanine nucleotide exchange on eIF2. Phosphorylation of the alpha subunit of eIF2 [creating eIF2(alphaP]) converts eIF2 x GDP from a substrate to an inhibitor of eIF2B. We showed previously that the inhibitory effect of eIF2(alphaP) can be decreased by deletion of the eIF2B alpha subunit (encoded by GCN3) and by point mutations in the beta and delta subunits of eIF2B (encoded by GCD7 and GCD2, respectively). These findings, plus sequence similarities among GCD2, GCD7, and GCN3, led us to propose that these proteins comprise a regulatory domain that interacts with eIF2(alphaP) and mediates the inhibition of eIF2B activity. Supporting this hypothesis, we report here that overexpression of GCD2, GCD7, and GCN3 specifically reduced the inhibitory effect of eIF2(alphaP) on translation initiation in vivo. The excess GCD2, GCD7, and GCN3 were coimmunoprecipitated from cell extracts, providing physical evidence that these three proteins can form a stable subcomplex. Formation of this subcomplex did not compensate for a loss of eIF2B function by mutation and in fact lowered eIF2B activity in strains lacking eIF2(alphaP). These findings indicate that the trimeric subcomplex does not possess guanine nucleotide exchange activity; we propose, instead, that it interacts with eIF2(alphaP) and prevents the latter from inhibiting native eIF2B. Overexpressing only GCD2 and GCD7 also reduced eIF2(alphaP) toxicity, presumably by titrating GCN3 from eIF2B and producing the four-subunit form of eIF2B that is less sensitive to eIF2(alphaP). This interpretation is supported by the fact that overexpressing GCD2 and GCD7 did not reduce eIF2(alphaP) toxicity in a strain lacking GCN3; however, it did suppress the impairment of eIF2B caused by the gcn3c-R104K mutation. An N-terminally truncated GCD2 protein interacted with other eIF2B subunits only when GCD7 and GCN3 were overexpressed, in accordance with the idea that the portion of GCD2 homologous to GCD7 and GCN3 is sufficient for complex formation by these three proteins. Together, our results provide strong evidence that GCN3, GCD7, and the C-terminal half of GCD2 comprise the regulatory domain in eIF2B. JF - Molecular and cellular biology AU - Yang, W AU - Hinnebusch, A G AD - Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, Bethesda, Maryland 20892-2785, USA. Y1 - 1996/11// PY - 1996 DA - November 1996 SP - 6603 EP - 6616 VL - 16 IS - 11 SN - 0270-7306, 0270-7306 KW - DNA Primers KW - 0 KW - DNA-Binding Proteins KW - Epitopes KW - Eukaryotic Initiation Factor-2 KW - Eukaryotic Initiation Factor-2B KW - Fungal Proteins KW - GCD2 protein, S cerevisiae KW - GCD7 protein, S cerevisiae KW - GCN3 protein, S cerevisiae KW - Guanine Nucleotide Exchange Factors KW - Macromolecular Substances KW - Proteins KW - Recombinant Proteins KW - Repressor Proteins KW - Saccharomyces cerevisiae Proteins KW - Guanosine Diphosphate KW - 146-91-8 KW - Protein Kinases KW - EC 2.7.- KW - Index Medicus KW - Models, Structural KW - DNA-Binding Proteins -- chemistry KW - Guanosine Diphosphate -- metabolism KW - Repressor Proteins -- metabolism KW - Amino Acid Sequence KW - Repressor Proteins -- chemistry KW - Mutagenesis, Site-Directed KW - Fungal Proteins -- chemistry KW - Protein Kinases -- metabolism KW - Polymerase Chain Reaction KW - Base Sequence KW - Fungal Proteins -- metabolism KW - Phosphorylation KW - Recombinant Proteins -- metabolism KW - Point Mutation KW - Epitopes -- chemistry KW - Recombinant Proteins -- chemistry KW - Protein Kinases -- chemistry KW - DNA-Binding Proteins -- metabolism KW - Saccharomyces cerevisiae -- genetics KW - Saccharomyces cerevisiae -- metabolism KW - Proteins -- chemistry KW - Saccharomyces cerevisiae -- growth & development KW - Eukaryotic Initiation Factor-2 -- metabolism KW - Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78475461?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Identification+of+a+regulatory+subcomplex+in+the+guanine+nucleotide+exchange+factor+eIF2B+that+mediates+inhibition+by+phosphorylated+eIF2.&rft.au=Yang%2C+W%3BHinnebusch%2C+A+G&rft.aulast=Yang&rft.aufirst=W&rft.date=1996-11-01&rft.volume=16&rft.issue=11&rft.spage=6603&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 - 1996-12-16 N1 - Date created - 1996-12-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Anal Biochem. 1976 May 7;72:248-54 [942051] Mol Cell Biol. 1995 Nov;15(11):6351-63 [7565788] Anal Biochem. 1981 Apr;112(2):195-203 [6266278] Cell. 1982 Mar;28(3):477-87 [6176330] J Bacteriol. 1983 Jan;153(1):163-8 [6336730] J Biol Chem. 1988 Apr 25;263(12):5526-33 [3356695] Nucleic Acids Res. 1988 Oct 11;16(19):9253-65 [3050897] J Biol Chem. 1989 May 25;264(15):8443-6 [2656679] Genetics. 1989 May;122(1):19-27 [2659436] Genetics. 1989 Jul;122(3):551-9 [2668117] Genetics. 1990 Nov;126(3):549-62 [2249755] Methods Enzymol. 1991;194:428-53 [2005802] Methods Enzymol. 1991;194:477-90 [2005804] Mol Cell Biol. 1991 Jun;11(6):3217-28 [2038327] Cell. 1992 Feb 7;68(3):585-96 [1739968] Gene. 1992 Jan 2;110(1):119-22 [1544568] EMBO J. 1992 Apr;11(4):1553-62 [1348691] Mol Cell Biol. 1992 Dec;12(12):5801-15 [1448107] Mol Cell Biol. 1993 Jan;13(1):506-20 [8417348] Mol Cell Biol. 1993 Mar;13(3):1920-32 [8441423] Proc Natl Acad Sci U S A. 1993 May 15;90(10):4616-20 [8099443] Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5350-4 [8506384] Mol Cell Biol. 1993 Aug;13(8):4618-31 [8336705] Mol Cell Biol. 1994 May;14(5):3208-22 [8164676] Mol Microbiol. 1993 Oct;10(2):215-23 [7934812] Trends Biochem Sci. 1994 Oct;19(10):409-14 [7817398] Semin Cell Biol. 1994 Dec;5(6):417-26 [7711290] Genes Dev. 1995 Jul 15;9(14):1781-96 [7542616] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - AMPA receptor flip/flop mutants affecting deactivation, desensitization, and modulation by cyclothiazide, aniracetam, and thiocyanate. AN - 78363456; 8824304 AB - AMPA receptor GluRA subunits with mutations at position 750, a residue shown previously to control allosteric regulation by cyclothiazide, were analyzed for modulation of deactivation and desensitization by cyclothiazide, aniracetam, and thiocyanate. Point mutations from Ser to Asn, Ala, Asp, Gly, Gln, Met, Cys, Thr, Leu, Val, and Tyr were constructed in GluRAflip. The last four of these mutants were not functional; S750D was active only in the presence of cyclothiazide, and the remaining mutants exhibited altered rates of deactivation and desensitization for control responses to glutamate, and showed differential modulation by cyclothiazide and aniracetam. Results from kinetic analysis are consistent with aniracetam and cyclothiazide acting via distinct mechanisms. Our experiments demonstrate for the first time the functional importance of residue 750 in regulating intrinsic channel-gating kinetics and emphasize the biological significance of alternative splicing in the M3-M4 extracellular loop. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Partin, K M AU - Fleck, M W AU - Mayer, M L AD - Laboratory of Cellular and Molecular Neurophysiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-4495, USA. Y1 - 1996/11/01/ PY - 1996 DA - 1996 Nov 01 SP - 6634 EP - 6647 VL - 16 IS - 21 SN - 0270-6474, 0270-6474 KW - Antihypertensive Agents KW - 0 KW - Benzothiadiazines KW - Pyrrolidinones KW - Receptors, AMPA KW - Thiocyanates KW - thiocyanate KW - 302-04-5 KW - aniracetam KW - 5L16LKN964 KW - cyclothiazide KW - P71U09G5BW KW - Index Medicus KW - Sensitivity and Specificity KW - Humans KW - Fetus -- cytology KW - Amino Acid Sequence KW - Cell Line -- physiology KW - Fibroblasts -- physiology KW - Patch-Clamp Techniques KW - Alternative Splicing -- physiology KW - Cell Line -- chemistry KW - Kinetics KW - Fibroblasts -- chemistry KW - Kidney -- cytology KW - Molecular Sequence Data KW - Mutagenesis, Site-Directed -- physiology KW - Thiocyanates -- pharmacology KW - Receptors, AMPA -- antagonists & inhibitors KW - Benzothiadiazines -- pharmacology KW - Receptors, AMPA -- genetics KW - Receptors, AMPA -- agonists KW - Antihypertensive Agents -- pharmacology KW - Pyrrolidinones -- pharmacology KW - Ion Channel Gating -- genetics KW - Ion Channel Gating -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78363456?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=AMPA+receptor+flip%2Fflop+mutants+affecting+deactivation%2C+desensitization%2C+and+modulation+by+cyclothiazide%2C+aniracetam%2C+and+thiocyanate.&rft.au=Partin%2C+K+M%3BFleck%2C+M+W%3BMayer%2C+M+L&rft.aulast=Partin&rft.aufirst=K&rft.date=1996-11-01&rft.volume=16&rft.issue=21&rft.spage=6634&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 - 1996-11-27 N1 - Date created - 1996-11-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Spontaneous Lesions in Aging FVB/N Mice AN - 755139354; 13645777 AB - The FVB/N mouse strain was created in the early 1970s and has since been used extensively in transgenic research because of its well-defined inbred background, superior reproductive performance, and prominent pronuclei of fertilized zygotes, which facilitate microinjection of DNA. Little is known, however, about the survivability and spontaneous disease of nontransgenic FVB/N mice. Therefore, the purpose of this study was to determine survival to 24 mo of age and the incidence of neoplastic and nonneoplastic disease at 14 and 24 mo of age. At 14 mo of age, the incidence of tumor-bearing mice was 13% in males (n = 45) and 26% in females (n = 98). All tumors in males and most in females at this time were alveolar-bronchiolar (AB) neoplasms of the lung. Survival to 24 mo of age was approximately 60% in both sexes (29/50 males, 71/116 females), and the incidence of mice with tumors at this time was 55% in males and 66% in females. In decreasing order of frequency, the following neoplasms were observed in >5% of subjects: in males, lung AB tumors, liver hepatocellular tumors, subcutis neural crest tumors, and Harderian gland adenomas; in females, lung AB tumors, pituitary gland adenomas, ovarian tumors (combined types), lymphomas, histiocytic sarcomas, Harderian gland adenomas, and pheochromocytomas. Compared with other mouse strains, the observed incidences of tumors in FVB/N mice suggest a higher than usual rate of lung tumors and a lower than usual incidence of liver tumors and lymphomas. This tumor profile should be considered in the interpretation of neoplastic phenotypes in FVB/N-derived transgenic lines. JF - Toxicologic Pathology AU - Mahler, Joel F AU - Stokes, William AU - Mann, Peter C AU - Takaoka, Masaya AU - Maronpot, Robert R AD - Laboratory of Experimental Pathology, Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709 Y1 - 1996/11// PY - 1996 DA - Nov 1996 SP - 710 EP - 716 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU UK VL - 24 IS - 6 SN - 0192-6233, 0192-6233 KW - Toxicology Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/755139354?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+Pathology&rft.atitle=Spontaneous+Lesions+in+Aging+FVB%2FN+Mice&rft.au=Mahler%2C+Joel+F%3BStokes%2C+William%3BMann%2C+Peter+C%3BTakaoka%2C+Masaya%3BMaronpot%2C+Robert+R&rft.aulast=Mahler&rft.aufirst=Joel&rft.date=1996-11-01&rft.volume=24&rft.issue=6&rft.spage=710&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1177%2F019262339602400606 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-09-01 N1 - Last updated - 2011-12-14 DO - http://dx.doi.org/10.1177/019262339602400606 ER - TY - JOUR T1 - Disruption of Cyclooxygenase Genes in Mice AN - 755137816; 13645778 JF - Toxicologic Pathology AU - Mahler, Joel F AU - Davis, Barbara J AU - Morham, Scott G AU - Langenbach, Robert AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709 Y1 - 1996/11// PY - 1996 DA - Nov 1996 SP - 717 EP - 719 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU UK VL - 24 IS - 6 SN - 0192-6233, 0192-6233 KW - Toxicology Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/755137816?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+Pathology&rft.atitle=Disruption+of+Cyclooxygenase+Genes+in+Mice&rft.au=Mahler%2C+Joel+F%3BDavis%2C+Barbara+J%3BMorham%2C+Scott+G%3BLangenbach%2C+Robert&rft.aulast=Mahler&rft.aufirst=Joel&rft.date=1996-11-01&rft.volume=24&rft.issue=6&rft.spage=717&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1177%2F019262339602400607 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-09-01 N1 - Last updated - 2012-03-29 DO - http://dx.doi.org/10.1177/019262339602400607 ER - TY - JOUR T1 - Endocrine responses during acute nicotine withdrawal AN - 16421933; 4328111 AB - Acute administration of nicotine increases cortisol and prolactin but the endocrine effects of tobacco withdrawal are unknown. In a residential, double-blind, placebo-controlled, crossover study, volunteers smoked ad lib for 4 days and underwent monitored tobacco abstinence for 3 days. On no-smoking days, patches delivering 0, 10, 20, or 30 mg nicotine were applied for 16 h. Daily plasma samples were analyzed for ACTH, cortisol, and prolactin. During nicotine abstinence (0 mg patch), circulating levels of ACTH, cortisol, and prolactin did not significantly change from ad lib smoking levels. Over all the patch conditions there was a significant effect of day, with modest but significant elevations of cortisol and ACTH levels on the second no-smoking day (Wed, 37 h abstinent). Prolactin levels increased during nicotine abstinence, but this effect was not significant. The observed endocrine changes did not correlate with physiologic, performance, or subjective measures of tobacco withdrawal. Our data indicate endocrine changes during acute tobacco withdrawal are transient and small. Thus, the present results do not support the use of ACTH as a treatment for tobacco cessation. JF - Pharmacology Biochemistry and Behavior AU - Pickworth, W B AU - Baumann, M H AU - Fant, R V AU - Rothman, R B AU - Henningfield, JE AD - National Institute on Drug Abuse, Addiction Research Center, Intramural Research Program, P.O. Box 5180, Baltimore, MD 21224, USA Y1 - 1996/11// PY - 1996 DA - Nov 1996 SP - 433 EP - 437 VL - 55 IS - 3 SN - 0091-3057, 0091-3057 KW - endocrine system KW - man KW - nicotine KW - smoking KW - tobacco KW - withdrawal KW - Toxicology Abstracts KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16421933?accountid=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=Pharmacology+Biochemistry+and+Behavior&rft.atitle=Endocrine+responses+during+acute+nicotine+withdrawal&rft.au=Pickworth%2C+W+B%3BBaumann%2C+M+H%3BFant%2C+R+V%3BRothman%2C+R+B%3BHenningfield%2C+JE&rft.aulast=Pickworth&rft.aufirst=W&rft.date=1996-11-01&rft.volume=55&rft.issue=3&rft.spage=433&rft.isbn=&rft.btitle=&rft.title=Pharmacology+Biochemistry+and+Behavior&rft.issn=00913057&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 - Histogenesis and the role of p53 and K-ras mutations in hepatocarcinogenesis by glyceryl trinitrate (nitroglycerin) in male F344 rats AN - 15957780; 4064880 AB - Glyceryl trinitrate (GTN) was previously reported to induce hepatocellular carcinoma (HCC) in rats after prolonged feeding. The present experiments were undertaken to evaluate the histogenesis and molecular biology of these tumors and the possible role of nitric oxide (NO), a GTN metabolite, in their development. Male F344 rats received a single i.g. intubation of GTN (1.2 g/kg) at 6 weeks of age and/or a diet containing 1% GTN from 8 weeks of age until necropsy, i.e. for up to 78 weeks. Some animals were subjected to 2/3 partial hepatectomy (PH) at 9 weeks of age. Five sequential sacrifices (14, 32, 52, 78 and 84 weeks of age) were performed. No liver tumors developed in control rats or in rats that received GTN only by a single i.g. intubation, even when intubation was followed by PH. Preneoplastic foci, mainly of clear cell and mixed cell type (identified as positive for glutathione S-transferase placental form) were found from 14 weeks of age in rats receiving GTN in the diet. Focal eosinophilic areas (atypical foci) composed of atypical hepatocytes that often extended into the veins were observed beginning at 52 weeks of age. Some mixed hepatocholangiocellular adenomas and carcinomas arose in eosinophilic lesions. HCCs were seen beginning at 78 weeks of age, but only in rats receiving dietary GTN. Incidence of HCC in the latter animals was 50-75%. Most HCCs were well differentiated. The carcinogenic effect of GTN given in the diet was not affected by prior intubation of a large single dose followed by PH. No p53 mutations were found in 18 tumors but K-ras point mutations, all within codon 12, were found in 8/18 tumors, mostly those with cholangiocellular elements. These were first or second position G arrow right T transversions or second position G arrow right A transitions. While these mutation types have also been commonly seen in bacteria after NO-related DNA damage, the fact that tumors arose only on prolonged feeding of this potently bioactive agent at massive doses seems consistent with a more complex mechanism involving multiple (i.e. genetic and/or epigenetic) factors in carcinogenesis by GTN. JF - Carcinogenesis AU - Tamano, S AU - Ward, J M AU - Diwan, BA AU - Keefer, L K AU - Weghorst, C M AU - Calvert, R J AU - Henneman, J R AU - Ramljak, D AU - Rice, J M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, MD 21702, USA Y1 - 1996/11// PY - 1996 DA - Nov 1996 SP - 2477 EP - 2486 VL - 17 IS - 11 SN - 0143-3334, 0143-3334 KW - rats KW - males KW - histopathology KW - p53 gene KW - K-ras gene KW - glyceryl trinitrate KW - nitroglycerin KW - Toxicology Abstracts; Oncogenes & Growth Factors Abstracts KW - carcinogenesis KW - mutation KW - liver KW - B 26130:Ras and Ras related oncogenes (Rho/Rac/Ral) KW - X 24154:Pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15957780?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Histogenesis+and+the+role+of+p53+and+K-ras+mutations+in+hepatocarcinogenesis+by+glyceryl+trinitrate+%28nitroglycerin%29+in+male+F344+rats&rft.au=Tamano%2C+S%3BWard%2C+J+M%3BDiwan%2C+BA%3BKeefer%2C+L+K%3BWeghorst%2C+C+M%3BCalvert%2C+R+J%3BHenneman%2C+J+R%3BRamljak%2C+D%3BRice%2C+J+M&rft.aulast=Tamano&rft.aufirst=S&rft.date=1996-11-01&rft.volume=17&rft.issue=11&rft.spage=2477&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - mutation; liver; carcinogenesis ER - TY - JOUR T1 - Pathogenicity of the Aedes albopictus parvovirus (AaPV), a denso-like virus, for Aedes aegypti mosquitoes AN - 15923723; 4044782 AB - AaPV, a denso-like virus isolated from a C6/36 clone of the Aedes albopictus cell line, proved to be very pathogenic for Aedes aegypti first and third instar larvae following per os infection. The mortality reached 90% in 10 days for larvae infected at the first instar. Several factors, such as temperature, larval density and stage, and duration of contact with infectious particles, influenced infection. The virus titer in females surviving infection at the third larval instar reached 10 super(8) TCID sub(50). Adult mosquitoes were sensitive to virus inoculation and to cytotransfection by viral DNA. Histological and ultrastructural studies revealed the presence of dense nuclei in almost all of the larval tissues with the exception of the midgut. JF - Journal of Invertebrate Pathology AU - Barreau, C AU - Jousset, F-X AU - Bergoin, M AD - Lab. Parasitic Dis., NIAID, NIH, Bldg. 4, Rm. 128, 9000 Rockville Pike, Bethesda, MD 20892-0424, USA Y1 - 1996/11// PY - 1996 DA - Nov 1996 SP - 299 EP - 309 VL - 68 IS - 3 SN - 0022-2011, 0022-2011 KW - Diptera KW - aquatic insects KW - cell lines KW - insect larvae KW - larvae KW - viral diseases KW - ASFA 3: Aquatic Pollution & Environmental Quality; Virology & AIDS Abstracts; Entomology Abstracts KW - Aedes aegypti KW - Culicidae KW - Freshwater KW - Aedes albopictus KW - pest control KW - mortality KW - viruses KW - parvovirus KW - V 22160:Viral infections of invertebrates KW - Z 05182:Pathology KW - Q5 08524:Public health, medicines, dangerous organisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15923723?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Invertebrate+Pathology&rft.atitle=Pathogenicity+of+the+Aedes+albopictus+parvovirus+%28AaPV%29%2C+a+denso-like+virus%2C+for+Aedes+aegypti+mosquitoes&rft.au=Barreau%2C+C%3BJousset%2C+F-X%3BBergoin%2C+M&rft.aulast=Barreau&rft.aufirst=C&rft.date=1996-11-01&rft.volume=68&rft.issue=3&rft.spage=299&rft.isbn=&rft.btitle=&rft.title=Journal+of+Invertebrate+Pathology&rft.issn=00222011&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2014-05-06 N1 - SubjectsTermNotLitGenreText - pest control; larvae; mortality; viruses; viral diseases; insect larvae; aquatic insects; cell lines; Aedes aegypti; Culicidae; Diptera; Aedes albopictus; parvovirus; Freshwater ER - TY - JOUR T1 - Altered physical state of p210 super(bcr-abl) in tyrphostin AG957-treated K562 cells AN - 15825657; 4007633 AB - AG957 is a tyrosine kinase antagonist which prior studies had shown inhibits p210 super(bcr-abl) tyrosine kinase activity and K562 chronic myelogenous leukemia cell growth. We report here the effects of AG957 on the physical state of p210 super(bcr-abl) and its signaling adapter molecules Shc and Grb2 in K562 cells. After exposure to AG957, the amount of tyrosine-phosphorylated native p210 super(bcr-abl) decreases, with the appearance of a high molecular weight (>210 kDa) p210 super(bcr-abl). This effect is seen after [ super(32)P]orthophosphate and [ super(35)S]methionine labeling. Material suggesting the involvement of p210 super(bcr-abl) in high molecular weight complexes also appears using anti-Shc, anti-Grb2 and antiphosphotyrosine antibodies. AG957 also acts in vitro to shift native p210 super(bcr-abl) in anti-p210 super(bcr-abl) or anti-Grb2 immunoprecipitates to higher molecular weight forms under conditions where the drug can also act as an antagonist of p210 super(bcr-abl) autokinase activity. Incubation with dithiothreitol inhibits the appearance of > 210 kDa forms of p210 super(bcr-abl) in the in vitro reaction. These results lead to the hypothesis that AG957 does not act simply as a reversible tyrosine kinase antagonist, but can alter the normal amounts and physical associations of molecules important in tyrosine kinase signaling. These effects likely reflect covalent cross-links induced by the drug. JF - Anti-Cancer Drugs AU - Kaur, G AU - Sausville, E A AD - Lab. Biol. Chem., Div. Cancer Treatment, Diagnosis and Centers, National Cancer Institute, NIH, Executive Plaza North, Room 843, Bethesda, MD 20892, USA Y1 - 1996/11// PY - 1996 DA - Nov 1996 SP - 815 EP - 824 VL - 7 IS - 8 SN - 0959-4973, 0959-4973 KW - AG957 KW - Abl protein KW - Bcr protein KW - Grb2 protein KW - K562 cells KW - Shc protein KW - p210 protein KW - tyrosine kinase KW - tyrphostin KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - chronic myeloid leukemia KW - W3 33370:Antibiotics KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15825657?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anti-Cancer+Drugs&rft.atitle=Altered+physical+state+of+p210+super%28bcr-abl%29+in+tyrphostin+AG957-treated+K562+cells&rft.au=Kaur%2C+G%3BSausville%2C+E+A&rft.aulast=Kaur&rft.aufirst=G&rft.date=1996-11-01&rft.volume=7&rft.issue=8&rft.spage=815&rft.isbn=&rft.btitle=&rft.title=Anti-Cancer+Drugs&rft.issn=09594973&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - chronic myeloid leukemia ER - TY - JOUR T1 - Antiviral activity and mechanism of action of calanolide A against the human immunodeficiency virus type-1 AN - 15801195; 3992160 AB - Calanolide A, recently discovered in extracts from the tropical rainforest tree, Calophyllum lanigerum, is a novel inhibitor of the human immunodeficiency virus (HIV) type 1. The compound is essentially inactive against strains of the less common HIV type 2. The present study focused on the further characterization of the selective antiviral activity and mechanism of action of calanolide A. The compound inhibited a wide variety of laboratory strains of HIV type 1, with EC sub(50) values ranging from 0.10 to 0.17 mu M. The compound similarly inhibited promonocytotropic and lymphocytotropic isolates from patients in various stages of HIV disease, as well as drug-resistant strains. Viral life-cycle studies indicated that calanolide A acted early in the infection process, similar to the known HIV reverse transcriptase (RT) inhibitor 2', 3'-dideoxycytidine. In enzyme inhibition assays, calanolide A potently and selectively inhibited recombinant HIV type 1 RT but not cellular DNA polymerases or HIV type 2 RT within the concentration range tested. Serial passage of the virus in host cells exposed to increasing concentrations of calanolide A yielded a calanolide A resistant virus strain. RT from the resistant virus was not inhibited by calanolide A but retained sensitivity to other nonnucleoside as well as nucleoside RT inhibitors, including 3'-azido-2',3'-dideoxythymidine triphosphate and nevirapine. The study substantially supports the conclusion that calanolide A represents a novel subclass of nonnucleoside RT inhibitor which merits consideration for anti-HIV drug development. JF - Journal of Pharmacology and Experimental Therapeutics AU - Currens, MJ AU - Gulakowski, R J AU - Mariner, J M AU - Moran, R A AU - Buckheit, RW Jr AU - Gustafson, K R AU - McMahon, J B AU - Boyd, M R AD - NCI-FCRDC, Bldg. 1052, Rm. 121, Frederick, MD 21702-1201, USA Y1 - 1996/11// PY - 1996 DA - Nov 1996 SP - 645 EP - 651 VL - 279 IS - 2 SN - 0022-3565, 0022-3565 KW - calanolide A KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - plant extracts KW - replication KW - antiviral agents KW - human immunodeficiency virus 1 KW - inhibitors KW - V 22002:AIDS: Molecular and in vitro aspects KW - A 01068:Antiviral & viricidal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15801195?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Pharmacology+and+Experimental+Therapeutics&rft.atitle=Antiviral+activity+and+mechanism+of+action+of+calanolide+A+against+the+human+immunodeficiency+virus+type-1&rft.au=Currens%2C+MJ%3BGulakowski%2C+R+J%3BMariner%2C+J+M%3BMoran%2C+R+A%3BBuckheit%2C+RW+Jr%3BGustafson%2C+K+R%3BMcMahon%2C+J+B%3BBoyd%2C+M+R&rft.aulast=Currens&rft.aufirst=MJ&rft.date=1996-11-01&rft.volume=279&rft.issue=2&rft.spage=645&rft.isbn=&rft.btitle=&rft.title=Journal+of+Pharmacology+and+Experimental+Therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - human immunodeficiency virus 1; antiviral agents; plant extracts; inhibitors; replication ER - TY - JOUR T1 - Antireplicative and anticytopathic activities of prostratin, a non-tumor-promoting phorbol ester, against human immunodeficiency virus (HIV) AN - 15794243; 3996365 AB - Prostratin, a non-tumor-promoting phorbol ester, inhibited human immunodeficiency virus (HIV)-induced cell killing and viral replication in a variety of acutely-infected cell systems. The potency and degree of cytoprotection was dependent on both viral strain and host cell type. Prostratin activated viral expression in two latently-infected cell lines, but had little or no effect on chronically-infected cell lines. Prostratin caused a dose-dependent, but reversible, decrease in CD4 expression in the CEM-SS and MT-2 cell lines. This down-regulation of CD4 was inhibited in a dose-dependent manner by the protein kinase C (PKC) antagonist, staurosporine. In addition, the cytoprotective and cytostatic effects of prostratin in CEM-SS cells acutely infected with HIV-1RF were reversed by bryostatin-1, a PKC agonist. Prostratin had no effect on reverse transcriptase or HIV-1 protease, nor did it inhibit the binding of gp120 to CD4. We conclude that prostratin inhibits HIV cytopathicity and replication through mechanism(s) involving PKC enzyme(s). JF - Antiviral Research AU - Gulakowski, R J AU - McMahon, J B AU - Buckheit Jr, RW AU - Gustafson, K R AU - Boyd, M R AD - Laboratory of Drug Discovery Research and Development, Developmental Therapeutics Program, Division of Cancer Treatment, Diagnosis and Centers, National Cancer Institute, NCI-Frederick Cancer Research and Development Center Freder Y1 - 1996/11// PY - 1996 DA - Nov 1996 SP - 87 EP - 97 PB - ELSEVIER SCIENCE IRELAND LTD. VL - 33 IS - 2 SN - 0166-3542, 0166-3542 KW - prostratin KW - staurosporine KW - CD4 antigen KW - bryostatin-1 KW - protein kinase C KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - lymphocytes T KW - antiviral agents KW - human immunodeficiency virus KW - V 22002:AIDS: Molecular and in vitro aspects KW - A 01068:Antiviral & viricidal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15794243?accountid=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=Antiviral+Research&rft.atitle=Antireplicative+and+anticytopathic+activities+of+prostratin%2C+a+non-tumor-promoting+phorbol+ester%2C+against+human+immunodeficiency+virus+%28HIV%29&rft.au=Gulakowski%2C+R+J%3BMcMahon%2C+J+B%3BBuckheit+Jr%2C+RW%3BGustafson%2C+K+R%3BBoyd%2C+M+R&rft.aulast=Gulakowski&rft.aufirst=R&rft.date=1996-11-01&rft.volume=33&rft.issue=2&rft.spage=87&rft.isbn=&rft.btitle=&rft.title=Antiviral+Research&rft.issn=01663542&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - human immunodeficiency virus; antiviral agents; lymphocytes T ER - TY - JOUR T1 - Comparison of the enhancing effects of dehydroepiandrosterone with the structural analog 16 alpha -fluoro-5-androsten-17-one on aflatoxin B sub(1) hepatocarcinogenesis in rainbow trout AN - 15791124; 3993485 AB - Dehydroepiandrosterone (DHEA) is an adrenal steroid with chemoprotective effects against a wide variety of conditions including cancer, obesity, diabetes, and cardiovascular disease. However, DHEA is also a carcinogen in laboratory animals, possibly through its function as a precursor of sex steroids or peroxisome proliferation. The structural analog 16 alpha -fluoro-5-androsten-17-one (8354) has been reported to have enhanced chemopreventive activity without the steroid precursor and peroxisome proliferating effects of DHEA. This study compares DHEA and 8354 in rainbow (Oncorhynchus mykiss) trout, a species that is resistant to peroxisome proliferation but is highly susceptible to the carcinogenic and tumor enhancing effects of DHEA. Trout were exposed as fry to aflatoxin B sub(1) (AFB sub(1)) or given a sham exposure, then were fed diets containing 444 ppm DHEA or 8354 for 6 months. Postinitiation treatment with DHEA significantly increased liver tumor incidence, multiplicity, and size compared to initiated controls. The analog 8354 slightly increased tumor incidence (p = 0.06) but had no effect on multiplicity or size. Six percent of trout treated with DHEA alone developed tumors, whereas no tumors occurred in noninitiated trout fed control or 8354-containing diets. Serum levels of androstenedione were elevated by DHEA (48-fold) or 8354 (6-fold) treatment. Serum beta -estradiol titers were increased in DHEA- but not 8354-treated trout. Vitellogenin was induced significantly by either DHEA (434-fold) or 8354 (21-fold). Peroxisomal beta -oxidation was not increased by either compound and catalase activity was decreased in DHEA-treated animals. Both steroids were potent inhibitors in vitro of trout liver glucose-6-phosphate dehydrogenase with IC50s of 24 and 0.5 mu M for DHEA and 8354, respectively. This research suggests that in trout the tumor enhancing effects of DHEA may be due to its function as a sex steroid precursor and are unrelated to peroxisome proliferation. These carcinogenic properties are reduced in the analog 8354 which has been advocated as an alternative to DHEA for chemoprevention. JF - Fundamental and Applied Toxicology AU - Orner, G A AU - Donohoe, R M AU - Hendricks, J D AU - Curtis, L R AU - Williams, DE AD - Toxicol. Prog., NIEHS Mar./Freshwater Biomed. Sci. Cent., Dep. Food Sci. and Technol., and Oregon State Univ., Corvallis, OR 97331-6602, USA Y1 - 1996/11// PY - 1996 DA - Nov 1996 SP - 132 EP - 140 VL - 34 IS - 1 SN - 0272-0590, 0272-0590 KW - 16 alpha -fluoro-5-androsten-17-one KW - aflatoxin B1 KW - dehydroepiandrosterone KW - mycotoxins KW - steroid hormones KW - ASFA 1: Biological Sciences & Living Resources; Toxicology Abstracts KW - Oncorhynchus mykiss KW - Freshwater KW - pharmacology KW - carcinogenesis KW - sex hormones KW - liver KW - Q1 08346:Physiology, biochemistry, biophysics KW - X 24171:Microbial UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15791124?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+Applied+Toxicology&rft.atitle=Comparison+of+the+enhancing+effects+of+dehydroepiandrosterone+with+the+structural+analog+16+alpha+-fluoro-5-androsten-17-one+on+aflatoxin+B+sub%281%29+hepatocarcinogenesis+in+rainbow+trout&rft.au=Orner%2C+G+A%3BDonohoe%2C+R+M%3BHendricks%2C+J+D%3BCurtis%2C+L+R%3BWilliams%2C+DE&rft.aulast=Orner&rft.aufirst=G&rft.date=1996-11-01&rft.volume=34&rft.issue=1&rft.spage=132&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+Applied+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2014-05-06 N1 - SubjectsTermNotLitGenreText - carcinogenesis; sex hormones; liver; pharmacology; steroid hormones; mycotoxins; Oncorhynchus mykiss; Freshwater ER - TY - JOUR T1 - The apoptosis-associated gamma -ray response of BCL-X sub(L) depends on normal p53 function AN - 15775105; 3989303 AB - We have investigated the effect of DNA damage on the expression of BCL-X, a member of the BCL-2 family. BCL-X mRNA levels were found to increase upon exposure human cells to ionizing radiation (IR). The Bcl-X sub(L) protein, but not Bcl-X sub(S), was identified to be induced by IR. Like BAX, another member of the BCL-2 family and a p53-regulated gene, the induction of BCL-X sub(L) was dependent on normal p53 function and required that cells have an apoptosis-susceptible phenotype. The induction of BCL-X sub(L) was rapid, transient and dose-dependent. The mRNA level peaked at 4 h and returned to baseline by 24 h post-irradiation. In agreement with the increased transcript level, Bcl-X sub(L) protein level was also observed to increase in cells with wild-type p53 where IR triggered apoptosis. In addition, a survey of the BCL-X sub(L) mRNA basal levels in human cells with known apoptotic responses showed that low basal levels of BCL-X sub(L) mRNA in cells were highly correlated with a strong ability of cells to undergo IR-induced apoptosis. On the other hand, high levels of basal BCL-X sub(L) were correlated with the resistance of cells to IR-induced apoptosis regardless of p53 status. These results indicate that BCL-2 and BCL-X sub(L) behave differently in response to DNA damage treatment even though they both are able to protect cells from p53-mediated apoptosis; along with down-regulation of BCL-2, BCL-X sub(L) was up-regulated by IR in human cells with wild-type p53 and susceptibility to IR-induced apoptosis. We speculate that the physiological function of increased BCL-X sub(L) protein would be expected to probably limit the severity and length of BAX effect in order to maintain a proper threshold for apoptosis and to complete cell cycle arrest activated by p53. JF - Oncogene AU - Zhan, Qimin AU - Alamo, I AU - Yu, K AU - Boise, L H AU - Cherney, B AU - Tosato, G AU - O'Connor, P M AU - Fornace, AJ Jr AD - Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, Room 5C09, Building 37, Bethesda, MD 20892-4255; USA Y1 - 1996/11// PY - 1996 DA - Nov 1996 SP - 2287 EP - 2293 VL - 13 IS - 10 SN - 0950-9232, 0950-9232 KW - man KW - cell culture KW - Bcl-xL gene KW - p53 gene KW - Toxicology Abstracts; Oncogenes & Growth Factors Abstracts KW - ionizing radiation KW - DNA damage KW - radiation KW - apoptosis KW - X 24210:Radiation & radioactive materials KW - B 26405:p53 gene, anti-suppressor genes (K-rev/rap/rab/RSU-1) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15775105?accountid=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=Oncogene&rft.atitle=The+apoptosis-associated+gamma+-ray+response+of+BCL-X+sub%28L%29+depends+on+normal+p53+function&rft.au=Zhan%2C+Qimin%3BAlamo%2C+I%3BYu%2C+K%3BBoise%2C+L+H%3BCherney%2C+B%3BTosato%2C+G%3BO%27Connor%2C+P+M%3BFornace%2C+AJ+Jr&rft.aulast=Zhan&rft.aufirst=Qimin&rft.date=1996-11-01&rft.volume=13&rft.issue=10&rft.spage=2287&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&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 - apoptosis; radiation; ionizing radiation; DNA damage ER - TY - JOUR T1 - Controlled trial of interleukin-2 infusions in patients infected with the human immunodeficiency virus. AN - 78419475; 8857018 AB - Interleukin-2 is a cytokine that regulates the proliferation and differentiation of lymphocytes. In preliminary studies, intermittent infusions of interleukin-2 led to increases in CD4 counts in patients with human immunodeficiency virus (HIV) infection and more than 200 CD4 cells per cubic millimeter. We conducted a controlled study to evaluate the long-term effects of such therapy on both CD4 counts and the viral burden. Sixty HIV-infected patients with base-line CD4 counts above 200 cells per cubic millimeter were randomly assigned to receive either interleukin-2 plus antiretroviral therapy (31 patients, 1 of whom was lost to follow-up) or antiretroviral therapy alone (29 patients). Interleukin-2 was administered every two months for six cycles of five days each, starting at a dosage of 18 million i.u. per day. Safety and immunologic and virologic measures were monitored monthly until four months after the last treatment cycle. In patients treated with interleukin-2, the mean (+/-SE) CD4 count increased from 428 +/- 25 cells per cubic millimeter at base line to 916 +/- 128 at month 12, whereas in the control group, the mean CD4 count decreased from 406 +/- 29 cells per cubic millimeter to 349 +/- 41 (P < 0.001). There were no significant differences between the groups in serial measurements of the plasma HIV RNA or p24 antigen concentration during the 12 months of treatment. Constitutional symptoms (fever, malaise, and fatigue) and asymptomatic hyperbilirubinemia were the chief dose-limiting toxic effects of interleukin-2 therapy. In patients with HIV infection and base-line CD4 counts above 200 cells per cubic millimeter, intermittent infusions of interleukin-2 produced substantial and sustained increases in CD4 counts with no associated increase in plasma HIV RNA levels. JF - The New England journal of medicine AU - Kovacs, J A AU - Vogel, S AU - Albert, J M AU - Falloon, J AU - Davey, R T AU - Walker, R E AU - Polis, M A AU - Spooner, K AU - Metcalf, J A AU - Baseler, M AU - Fyfe, G AU - Lane, H C AD - Critical Care Medicine Department, National Institute of Allergy and Infectious Diseases, Bethesda, Md. 20892-1662, USA. Y1 - 1996/10/31/ PY - 1996 DA - 1996 Oct 31 SP - 1350 EP - 1356 VL - 335 IS - 18 SN - 0028-4793, 0028-4793 KW - Anti-HIV Agents KW - 0 KW - HIV Core Protein p24 KW - Interleukin-2 KW - RNA, Viral KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - HIV Core Protein p24 -- blood KW - Humans KW - CD4 Lymphocyte Count KW - HIV -- genetics KW - Viral Load KW - Drug Therapy, Combination KW - Anti-HIV Agents -- therapeutic use KW - Adult KW - Treatment Outcome KW - HIV -- isolation & purification KW - Middle Aged KW - Follow-Up Studies KW - AIDS-Related Opportunistic Infections -- mortality KW - Female KW - Male KW - RNA, Viral -- blood KW - Interleukin-2 -- therapeutic use KW - HIV Infections -- therapy KW - HIV Infections -- immunology KW - HIV Infections -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78419475?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+journal+of+medicine&rft.atitle=Controlled+trial+of+interleukin-2+infusions+in+patients+infected+with+the+human+immunodeficiency+virus.&rft.au=Kovacs%2C+J+A%3BVogel%2C+S%3BAlbert%2C+J+M%3BFalloon%2C+J%3BDavey%2C+R+T%3BWalker%2C+R+E%3BPolis%2C+M+A%3BSpooner%2C+K%3BMetcalf%2C+J+A%3BBaseler%2C+M%3BFyfe%2C+G%3BLane%2C+H+C&rft.aulast=Kovacs&rft.aufirst=J&rft.date=1996-10-31&rft.volume=335&rft.issue=18&rft.spage=1350&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=00284793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-07 N1 - Date created - 1996-11-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: N Engl J Med. 1997 Apr 24;336(17):1260-1 [9121530] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of the human immunodeficiency virus type 1 integrase by guanosine quartet structures. AN - 78499917; 8901518 AB - An oligonucleotide (T30177) composed entirely of deoxyguanosine and thymidine has previously been shown to fold upon itself in the presence of potassium into a highly stable four-stranded DNA structure containing two stacked deoxyguanosine quartets (G4s). T30177 also protects host cells from the cytopathic effects of human immunodeficiency virus type 1 (HIV-1). We report that this G4 oligonucleotide is the most potent inhibitor of HIV-1 integrase identified to date, with IC50 values in the nanomolar range. Both the number of quartets formed and the sequence of the loops between the quartets are important for optimal activity. T30177 binds to HIV-1 integrase without being processed and blocks the binding of the normal viral DNA substrate to the enzyme. The normal DNA substrate was not able to compete off T30177 binding to HIV-1 integrase, indicating a tight binding of G4s to the enzyme. Experiments with truncated HIV-1 integrases indicate that the N-terminal region containing a putative zinc finger is required for inhibition by T30177 and that T30177 binds better to full-length or deletion mutant integrases containing the zinc finger region than to a deletion mutant consisting of only the central catalytic domain. The N-terminal region of integrase alone is able to bind efficiently to T30177, but not the linear viral DNA substrate, in the presence of zinc. Hence, G4s represent the first class of compounds that inhibit HIV-1 integrase by interacting with the enzyme N-terminal domain. The greater inhibitory potency of T30177 in buffer containing magnesium versus manganese suggests that divalent metal ion coordination along the phosphodiester backbone may play a role in the inhibitory activity. T30177 inhibited HIV-2 integrase with similar potency as HIV-1 but inhibited feline and simian immunodeficiency virus integrases at higher concentrations, suggesting selectivity can be achieved. We propose that novel AIDS therapies could be based upon guanosine quarters as inhibitors of HIV-1 integrase. JF - Biochemistry AU - Mazumder, A AU - Neamati, N AU - Ojwang, J O AU - Sunder, S AU - Rando, R F AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1996/10/29/ PY - 1996 DA - 1996 Oct 29 SP - 13762 EP - 13771 VL - 35 IS - 43 SN - 0006-2960, 0006-2960 KW - Cross-Linking Reagents KW - 0 KW - DNA-Binding Proteins KW - Deoxyadenosines KW - Enzyme Inhibitors KW - HIV Integrase Inhibitors KW - Oligodeoxyribonucleotides KW - Oligonucleotides KW - T 30177 KW - Manganese KW - 42Z2K6ZL8P KW - DNA KW - 9007-49-2 KW - Deoxyguanosine KW - G9481N71RO KW - cordycepin KW - GZ8VF4M2J8 KW - Magnesium KW - I38ZP9992A KW - Index Medicus KW - AIDS/HIV KW - Ultraviolet Rays KW - Manganese -- pharmacology KW - Oligonucleotides -- pharmacology KW - Electrophoresis, Polyacrylamide Gel KW - DNA -- metabolism KW - Enzyme Inhibitors -- chemistry KW - Cross-Linking Reagents -- metabolism KW - Deoxyadenosines -- metabolism KW - Immunodeficiency Virus, Feline -- enzymology KW - Zinc Fingers -- genetics KW - Sequence Deletion -- genetics KW - Binding, Competitive KW - Magnesium -- pharmacology KW - Mutation -- genetics KW - Enzyme Inhibitors -- pharmacology KW - HIV-2 -- enzymology KW - HIV Integrase Inhibitors -- chemistry KW - Oligodeoxyribonucleotides -- chemistry KW - Oligodeoxyribonucleotides -- pharmacology KW - HIV Integrase Inhibitors -- pharmacology KW - HIV-1 -- enzymology KW - Oligodeoxyribonucleotides -- metabolism KW - Deoxyguanosine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78499917?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inhibition+of+the+human+immunodeficiency+virus+type+1+integrase+by+guanosine+quartet+structures.&rft.au=Mazumder%2C+A%3BNeamati%2C+N%3BOjwang%2C+J+O%3BSunder%2C+S%3BRando%2C+R+F%3BPommier%2C+Y&rft.aulast=Mazumder&rft.aufirst=A&rft.date=1996-10-29&rft.volume=35&rft.issue=43&rft.spage=13762&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-03 N1 - Date created - 1996-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhalation toxicity and carcinogenicity of isoprene in rats and mice: comparisons with 1,3-butadiene. AN - 78505157; 8901905 AB - As with 1,3-butadiene (BD), inhalation exposure of B6C3F1 mice to isoprene (2-methyl-1,3-butadiene) caused a macrocytic anemia; induced increases in sister chromatid exchanges in bone marrow cells and in levels of micronucleated erythrocytes in peripheral blood; and produced degeneration of the olfactory epithelium, forestomach epithelial hyperplasia, and testicular atrophy. Most notable was the finding that like BD, isoprene induced neoplasms in the liver, lung, Harderian gland, and forestomach of mice. The carcinogenic effects of isoprene were observed after a 26-week exposure (6 h/day, 5 days/week) of male mice to 700 ppm or higher concentrations of isoprene followed by a 26-week recovery period. Unlike BD, isoprene did not induce lymphomas or hemangiosarcomas of the heart in mice under these conditions nor did it induce chromosomal aberrations in mouse bone marrow cells. No toxicological effects were evident in rats exposed for 13 weeks to either isoprene or BD at concentrations up to 7000 ppm or 8000 ppm, respectively. Interstitial cell hyperplasia of the testis was observed in male F344 rats exposed to 7000 ppm isoprene for 26 weeks, and following a 26-week recovery period, there was a marginal increase in benign testicular interstitial cell tumors. JF - Toxicology AU - Melnick, R L AU - Sills, R C AU - Roycroft, J H AU - Chou, B J AU - Ragan, H A AU - Miller, R A AD - Laboratory of Quantitative and Computational Biology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1996/10/28/ PY - 1996 DA - 1996 Oct 28 SP - 247 EP - 252 VL - 113 IS - 1-3 SN - 0300-483X, 0300-483X KW - Butadienes KW - 0 KW - Carcinogens KW - Hemiterpenes KW - Mutagens KW - Pentanes KW - isoprene KW - 0A62964IBU KW - 1,3-butadiene KW - JSD5FGP5VD KW - Index Medicus KW - Rats KW - Animals KW - Neoplasms, Experimental -- chemically induced KW - Chromosome Aberrations KW - Mice KW - Administration, Inhalation KW - Male KW - Butadienes -- toxicity KW - Carcinogens -- toxicity KW - Mutagens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78505157?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=Inhalation+toxicity+and+carcinogenicity+of+isoprene+in+rats+and+mice%3A+comparisons+with+1%2C3-butadiene.&rft.au=Melnick%2C+R+L%3BSills%2C+R+C%3BRoycroft%2C+J+H%3BChou%2C+B+J%3BRagan%2C+H+A%3BMiller%2C+R+A&rft.aulast=Melnick&rft.aufirst=R&rft.date=1996-10-28&rft.volume=113&rft.issue=1-3&rft.spage=247&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-06 N1 - Date created - 1996-12-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of the structure of a toxicokinetic model of butadiene inhalation exposure on computed production of carcinogenic intermediates. AN - 78501295; 8901880 AB - A flow-limited physiologically based toxicokinetic model was constructed for uptake, metabolism, and clearance of butadiene (BD) and its principal metabolite 1,2-epoxy-3-butene (EB), using physiological and biochemical parameters from the literature where available. The model includes compartments for blood, liver, lung, fat, GI tract, other rapidly perfused tissues, and slowly perfused tissues. The blood was distributed among compartments for arterial plus venous blood and subcompartments for vascular spaces associated with each of the tissue compartments. The lung contained a subcompartment for the alveolar space. Metabolic activation of BD by cytochrome P450-catalyzed epoxidation was modeled as occurring in liver, lung, and the rapidly perfused tissue compartments. The detoxication of EB catalyzed by epoxide hydrolase and glutathione S-transferase (GST) was modeled as occurring in liver, lung, and the rapidly perfused tissues compartments and by blood GST activity. The model also includes depletion of glutathione (GSH) by GST-catalyzed conjugation of EB and 3-butene-1,2-diol and resynthesis of GSH from cysteine. Values of biochemical parameters that were unavailable in the literature were estimated by iteratively reweighted least squares optimization to reproduce data for uptake of BD and EB by rats and mice in closed chambers. The resulting model also reproduced the depletion of GSH in liver and lung in flow-through systems. It reproduced the concentrations of expired EB produced from BD in closed chambers but overpredicted separately measured blood EB concentrations in flow-through systems, indicating an inconsistency between these two experiments that cannot be resolved by this model or an inadequacy in the model. Equilibration of chamber gases with the alveolar space and alveolar gas with lung capillary blood results in much less dilution of the inhaled gas in the blood compared with the predictions of models in which chamber gas equilibrates directly with the total circulation. The production of EB predicted by the present model was found to be sensitive to a number of physiological and biochemical parameters. A valid and useful toxicokinetic model must have reliable physiological and enzymological data for BD biotransformation before it can be credibly used for human risk assessment. JF - Toxicology AU - Kohn, M C AU - Melnick, R L AD - Laboratory of Quantitative and Computational Biology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709-2233, USA. Y1 - 1996/10/28/ PY - 1996 DA - 1996 Oct 28 SP - 31 EP - 39 VL - 113 IS - 1-3 SN - 0300-483X, 0300-483X KW - Butadienes KW - 0 KW - Carcinogens KW - Glutathione KW - GAN16C9B8O KW - 1,3-butadiene KW - JSD5FGP5VD KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Humans KW - Glutathione -- metabolism KW - Mice KW - Administration, Inhalation KW - Models, Biological KW - Butadienes -- toxicity KW - Carcinogens -- pharmacokinetics KW - Butadienes -- administration & dosage KW - Butadienes -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78501295?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=Effects+of+the+structure+of+a+toxicokinetic+model+of+butadiene+inhalation+exposure+on+computed+production+of+carcinogenic+intermediates.&rft.au=Kohn%2C+M+C%3BMelnick%2C+R+L&rft.aulast=Kohn&rft.aufirst=M&rft.date=1996-10-28&rft.volume=113&rft.issue=1-3&rft.spage=31&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-06 N1 - Date created - 1996-12-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - hprt mutation frequency among workers exposed to 1,3-butadiene in China. AN - 78501028; 8901888 AB - Hypoxanthine-guanine phosphoribosyl transferase (hprt) mutation frequency (M(f)) was studied in workers at a polybutadiene rubber production facility in Yanshan, China. Exposed workers included for study were active either as process analysts, who sampled butadiene production process lines and analyzed product by gas chromatography, or as process operators, who did routine process control, minor maintenance and, as needed, major repair operations. For process analysts at the polymer and dimethyl formamide (DMF) facilities, the median air levels of BD were 1.0 and 3.5 ppm, respectively. Among process operators, air levels of 1.1 ppm were found during routine activities, while the median air level during pump repair and related operations was 45 ppm (6-h time-weighted average). Overall, M(f) was similar in unexposed (mean M(f) = 20.2 x 10(-6)) and butadiene-exposed (mean M(f) = 21.6 x 10(-6)) workers (P = 0.68). M(f) decreased with cloning efficiency, increased with age, and was moderately greater in women than in men. After adjustment by multiple regression analysis for mean age, sex, and cloning efficiency, the adjusted mean M(f)(Xadj) was 13.6 x 10(-6) in unexposed and 18.0 x 10(-6) in butadiene-exposed. This 32% difference was, however, not statistically significant (P = 0.13). Butadiene exposure was associated with a modest, if any, increase in hprt M(f) in this population of Chinese workers. JF - Toxicology AU - Hayes, R B AU - Xi, L AU - Bechtold, W E AU - Rothman, N AU - Yao, M AU - Henderson, R AU - Zhang, L AU - Smith, M T AU - Zhang, D AU - Wiemels, J AU - Dosemeci, M AU - Yin, S AU - O'Neill, J P AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. hayesr/epndce.nih.nci.gov Y1 - 1996/10/28/ PY - 1996 DA - 1996 Oct 28 SP - 100 EP - 105 VL - 113 IS - 1-3 SN - 0300-483X, 0300-483X KW - Butadienes KW - 0 KW - Mutagens KW - Hypoxanthine Phosphoribosyltransferase KW - EC 2.4.2.8 KW - 1,3-butadiene KW - JSD5FGP5VD KW - Index Medicus KW - Humans KW - Adult KW - Mutation KW - Male KW - Female KW - China KW - Hypoxanthine Phosphoribosyltransferase -- genetics KW - Butadienes -- toxicity KW - Occupational Exposure -- adverse effects KW - Mutagens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78501028?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=hprt+mutation+frequency+among+workers+exposed+to+1%2C3-butadiene+in+China.&rft.au=Hayes%2C+R+B%3BXi%2C+L%3BBechtold%2C+W+E%3BRothman%2C+N%3BYao%2C+M%3BHenderson%2C+R%3BZhang%2C+L%3BSmith%2C+M+T%3BZhang%2C+D%3BWiemels%2C+J%3BDosemeci%2C+M%3BYin%2C+S%3BO%27Neill%2C+J+P&rft.aulast=Hayes&rft.aufirst=R&rft.date=1996-10-28&rft.volume=113&rft.issue=1-3&rft.spage=100&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-06 N1 - Date created - 1996-12-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glucocorticoids modulate CD28 mediated pathways for interleukin 2 production in human T cells: evidence for posttranscriptional regulation. AN - 78491043; 8900312 AB - In T cells stimulated through the T cell receptor (TCR), both cyclosporine (CsA) and glucocorticoids (GC) inhibit the transcription of the IL-2 gene. In these cells costimulation via the CD28 cell surface molecule further increases the transcription of IL-2 and stabilizes its mRNA, resulting in a 20-30 fold induction in IL-2 production. This pathway is relatively resistant to the inhibitory effect of CsA. In this study, we asked whether GC interfere with CD28-mediated costimulatory signals for T cell activation. Primary human T cells or Jurkat T cells were stimulated with anti-CD28 and phorbol myristate acetate (PMA) in the presence of dexamethasone (Dex, 10(-10)-10(-5) M). Dex inhibited both the mRNA for IL-2 and IL-2 production in a dose-dependent fashion (minimum effective dose 10(-9) M). In similar experiments employing anti-CD3 mAb and PMA, a 7-20 fold higher concentration of Dex was required to obtain comparable inhibition. To determine if transcriptional modulation is occurring, Jurkat T cells were transfected with a plasmid containing the IL-2 promoter linked to the chloramphenicol acetyl transferase reporter gene. Following stimulation with ionomycin and PMA, high doses (10(-6) M) of Dex inhibited the activity of the IL-2 promoter (approximately 50% inhibition). However, in the presence of anti-CD28 mAb, this promoter became resistant to Dex (< or = 10% inhibition). These results suggest that GC inhibit accessory pathways for IL-2 production via CD28 by predominantly posttranscriptional mechanisms. Inhibition of the CD28 pathway may be an important mechanism for the T cell directed immunosuppressive effects of low-to-moderate doses of GC. JF - Transplantation AU - Fessler, B J AU - Paliogianni, F AU - Hama, N AU - Balow, J E AU - Boumpas, D T AD - Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/10/27/ PY - 1996 DA - 1996 Oct 27 SP - 1113 EP - 1118 VL - 62 IS - 8 SN - 0041-1337, 0041-1337 KW - Antibodies KW - 0 KW - Antigens, CD28 KW - Antigens, CD3 KW - Glucocorticoids KW - Interleukin-2 KW - Phorbol Esters KW - RNA, Messenger KW - Dexamethasone KW - 7S5I7G3JQL KW - Index Medicus KW - Antigens, CD3 -- immunology KW - Phorbol Esters -- pharmacology KW - Transcription, Genetic -- drug effects KW - Humans KW - Dexamethasone -- pharmacology KW - RNA, Messenger -- physiology KW - Antibodies -- drug effects KW - RNA Processing, Post-Transcriptional -- physiology KW - T-Lymphocytes -- metabolism KW - Antigens, CD28 -- physiology KW - Interleukin-2 -- biosynthesis KW - Interleukin-2 -- genetics KW - Glucocorticoids -- pharmacology KW - Antigens, CD28 -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78491043?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Transplantation&rft.atitle=Glucocorticoids+modulate+CD28+mediated+pathways+for+interleukin+2+production+in+human+T+cells%3A+evidence+for+posttranscriptional+regulation.&rft.au=Fessler%2C+B+J%3BPaliogianni%2C+F%3BHama%2C+N%3BBalow%2C+J+E%3BBoumpas%2C+D+T&rft.aulast=Fessler&rft.aufirst=B&rft.date=1996-10-27&rft.volume=62&rft.issue=8&rft.spage=1113&rft.isbn=&rft.btitle=&rft.title=Transplantation&rft.issn=00411337&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-04 N1 - Date created - 1996-12-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of a DinB/UmuC homolog in the archeon Sulfolobus solfataricus. AN - 78449921; 8876701 AB - To date, eight closely related homologs of the Escherichia coli UmuC protein have been identified. All of these homologs appear to play critical roles in damage-inducible mutagenesis in enterobacteriaceae. Recently, a distantly related UmuC-homolog, DinB, has also been identified in E. coli. Using the polymerase chain reaction together with degenerate primers designed against conserved regions found in UmuC-like proteins, we have identified a new member of the UmuC-superfamily in the archeon Sulfolobus solfataricus. This new homolog shows high sequence similarity to DinB and a lower level of similarity to UmuC. As a consequence, we have called this new gene dbh (dinB homolog). Analysis of approximately 2.7 kb DNA encompassing the dbh region revealed several open reading frames (orfs). One, encoding a putative ribokinase, was located immediately upstream of dbh. This orf overlaps the dbh gene by 4 bp suggesting that both proteins might be coordinately expressed. Further upstream of the ribokinase-dbh locus was another orf encoding a potential ATPase homologous to two uncharacterized S. cerevisiae proteins (YD9346.02c and SC38KCXVI_20) and another E. coli DNA repair protein, RuvB. While this is the first report of a UmuC-like homolog in an archeon, we detected additional homologs using protein sequence comparisons in Gram-positive bacteria, cyanobacteria, and among potential human EST products, indicating that UmuC-related proteins comprise a ubiquitous superfamily of proteins probably involved in DNA repair and mutagenesis. JF - Mutation research AU - Kulaeva, O I AU - Koonin, E V AU - McDonald, J P AU - Randall, S K AU - Rabinovich, N AU - Connaughton, J F AU - Levine, A S AU - Woodgate, R AD - Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2725, USA. Y1 - 1996/10/25/ PY - 1996 DA - 1996 Oct 25 SP - 245 EP - 253 VL - 357 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Archaeal Proteins KW - 0 KW - Bacterial Proteins KW - DinB protein, E coli KW - Escherichia coli Proteins KW - UmuC protein, E coli KW - 98059-80-4 KW - Phosphotransferases (Alcohol Group Acceptor) KW - EC 2.7.1.- KW - ribokinase KW - EC 2.7.1.15 KW - Dbh protein, Sulfolobus solfataricus KW - EC 2.7.7.- KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - Index Medicus KW - Phylogeny KW - Base Sequence KW - Sequence Alignment KW - DNA Damage KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Consensus Sequence KW - Sequence Homology, Amino Acid KW - Adenosine Triphosphatases -- genetics KW - Phosphotransferases (Alcohol Group Acceptor) -- genetics KW - Genes, Bacterial KW - Bacterial Proteins -- genetics KW - Sulfolobus -- genetics KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78449921?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Identification+of+a+DinB%2FUmuC+homolog+in+the+archeon+Sulfolobus+solfataricus.&rft.au=Kulaeva%2C+O+I%3BKoonin%2C+E+V%3BMcDonald%2C+J+P%3BRandall%2C+S+K%3BRabinovich%2C+N%3BConnaughton%2C+J+F%3BLevine%2C+A+S%3BWoodgate%2C+R&rft.aulast=Kulaeva&rft.aufirst=O&rft.date=1996-10-25&rft.volume=357&rft.issue=1-2&rft.spage=245&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 - 1996-11-25 N1 - Date created - 1996-11-25 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U52110; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effect of donor age on the processing of UV-damaged DNA by cultured human cells: reduced DNA repair capacity and increased DNA mutability. AN - 78450015; 8879277 AB - Aging in humans carries an increased risk of skin cancer, a disorder linked to somatic mutations in sun damaged skin. DNA repair plays a major role in protection against sun damage. We found an age-related decline in post-UV DNA repair capacity (measured by the ability to repair a UV-treated plasmid (pCMVcat)) of-0.6% per year (p = 0.0001) in cultured primary skin fibroblasts from normal donors from the first to the tenth decade of life. There was a corresponding age-related increase in post-UV mutability (measured as mutations introduced into a transfected, UV-treated plasmid (pSP189)) of +0.6% per year (p = 0.001) in lymphoblastoid cell lines from normal donors of the same age range. This study indicates that aging in humans is associated with decreasing ability to process new UV-induced DNA damage and this age-related reduction in DNA repair capacity and increase in DNA mutability is reflected in cultured skin and blood cells. JF - Mutation research AU - Moriwaki, S AU - Ray, S AU - Tarone, R E AU - Kraemer, K H AU - Grossman, L AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1996/10/18/ PY - 1996 DA - 1996 Oct 18 SP - 117 EP - 123 VL - 364 IS - 2 SN - 0027-5107, 0027-5107 KW - DNA-Binding Proteins KW - 0 KW - DNA Ligases KW - EC 6.5.1.- KW - Index Medicus KW - Cells, Cultured KW - Aged, 80 and over KW - Skin -- metabolism KW - Humans KW - Adult KW - Skin -- cytology KW - Aged KW - Middle Aged KW - Fibroblasts -- cytology KW - Child KW - Adolescent KW - Child, Preschool KW - Aging -- physiology KW - DNA Repair KW - DNA Damage KW - Ultraviolet Rays -- adverse effects KW - DNA-Binding Proteins -- isolation & purification KW - DNA Ligases -- metabolism KW - DNA Ligases -- isolation & purification KW - Mutagenesis KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78450015?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=The+effect+of+donor+age+on+the+processing+of+UV-damaged+DNA+by+cultured+human+cells%3A+reduced+DNA+repair+capacity+and+increased+DNA+mutability.&rft.au=Moriwaki%2C+S%3BRay%2C+S%3BTarone%2C+R+E%3BKraemer%2C+K+H%3BGrossman%2C+L&rft.aulast=Moriwaki&rft.aufirst=S&rft.date=1996-10-18&rft.volume=364&rft.issue=2&rft.spage=117&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 - 1996-11-29 N1 - Date created - 1996-11-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of tyrosine 187 as a protein kinase C-delta phosphorylation site. AN - 78358573; 8824297 AB - Protein kinase C-delta (PKC-delta) has been demonstrated to be phosphorylated on tyrosine residue(s) in many different biological systems (Li, W., Yu, J.-C., Michieli, P., Beeler, J. F., Ellmore, N., Heidaran, M. A., and Pierce, J. H. (1994) Mol. Cell. Biol. 14, 6727-6735; Li, W., Mischak, H., Yu, J.-C., Wang, L.-M., Mushinski, J. F., Heidaran, M. A., and Pierce, J. H. (1994) J. Biol. Chem. 269, 2349-2352; Denning, M. F., Dlugosz, A. A., Howett, M. A., and Yuspa, S. H. (1993) J. Biol. Chem. 268, 26079-26081). Tyrosine phosphorylation of PKC-delta has also been shown to occur in vitro when purified PKC-delta is coincubated with different tyrosine kinase sources. However, the tyrosine phosphorylation site(s) is currently unknown and the exact effect of this phosphorylation on its serine/threonine kinase activity and biological functions is still controversial. To directly investigate the potential role of PKC-delta tyrosine phosphorylation, tyrosine 187 was converted to phenylalanine (PKC-deltaY187F) by site-directed mutagenesis, and expression vectors containing PKC-deltaY187F cDNAs were transfected into both 32D myeloid progenitor cells and NIH 3T3 fibroblasts. The results showed that tyrosine 187 of PKC-delta became phosphorylated in vivo in response to 12-O-tetradecanoylphorbol-13-acetate stimulation or platelet-derived growth factor receptor activation. In vivo labeling and subsequent two-dimensional phosphopeptide analysis demonstrated that one phosphopeptide was absent in PKC-deltaY187F when compared to wild type PKC-delta, further substantiating that tyrosine 187 of PKC-delta is phosphorylated in vivo. Although the phosphotyrosine content of PKC-deltaY187F was reduced compared with PKC-deltaWT, the kinase activity of PKC-deltaY187F toward a PKC-delta substrate was not altered. Moreover, 12-O-tetradecanoylphorbol-13-acetate-mediated monocytic differentiation of 32D cells was not affected by expression of the PKC-deltaY187F mutant. Taken together, these results suggest that tyrosine phosphorylation of PKC-delta on 187 may not influence PKC-delta activation and known functions. JF - The Journal of biological chemistry AU - Li, W AU - Chen, X H AU - Kelley, C A AU - Alimandi, M AU - Zhang, J AU - Chen, Q AU - Bottaro, D P AU - Pierce, J H AD - Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1996/10/18/ PY - 1996 DA - 1996 Oct 18 SP - 26404 EP - 26409 VL - 271 IS - 42 SN - 0021-9258, 0021-9258 KW - DNA, Complementary KW - 0 KW - Isoenzymes KW - Platelet-Derived Growth Factor KW - Tyrosine KW - 42HK56048U KW - Phenylalanine KW - 47E5O17Y3R KW - Prkcd protein, mouse KW - EC 2.7.1.- KW - Protein Kinase C KW - EC 2.7.11.13 KW - Protein Kinase C-delta KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - 3T3 Cells KW - Phenylalanine -- metabolism KW - Phosphorylation KW - Transfection KW - Platelet-Derived Growth Factor -- pharmacology KW - Electrophoresis, Gel, Two-Dimensional KW - DNA, Complementary -- chemistry KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Mice KW - Substrate Specificity KW - Protein Kinase C -- metabolism KW - Protein Kinase C -- genetics KW - Tyrosine -- metabolism KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78358573?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Identification+of+tyrosine+187+as+a+protein+kinase+C-delta+phosphorylation+site.&rft.au=Li%2C+W%3BChen%2C+X+H%3BKelley%2C+C+A%3BAlimandi%2C+M%3BZhang%2C+J%3BChen%2C+Q%3BBottaro%2C+D+P%3BPierce%2C+J+H&rft.aulast=Li&rft.aufirst=W&rft.date=1996-10-18&rft.volume=271&rft.issue=42&rft.spage=26404&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 - 1996-11-26 N1 - Date created - 1996-11-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of the association of p120cbl with Grb2 in Jurkat T cells. AN - 78351289; 8824292 AB - The c-cbl protooncogene product (p120(cbl)) is a known substrate of multiple tyrosine kinases. It is found in complexes with critical signal transduction molecules, including the linker protein Grb2. Here, we demonstrate using an immobilized Grb2-binding peptide that the Grb2-p120(cbl) complex dissociates in vivo following engagement of the T-cell antigen receptor in Jurkat T-cells. The early kinetics of this dissociation correlate with the known time course of tyrosine phosphorylation of p120(cbl) and other substrates. This dissociation persists in vivo even when p120(cbl) becomes dephosphorylated to basal levels. However, this decreased association is not observed in protein overlay assays on nitrocellulose membranes in which a Grb2 fusion protein is used to detect p120(cbl) from stimulated or unstimulated cells. These data suggest that the tyrosine phosphorylation of p120(cbl) does not completely account for the regulation of its association with Grb2. Additionally, we used truncation mutations of p120(cbl) to map the p120(cbl)-Grb2 interaction to amino acids 481-528 of p120(cbl); this interaction is stronger in longer constructs that include additional proline-rich motifs. The in vivo regulation of the Grb2-p120(cbl) complex further supports the idea of a significant role for p120(cbl) in receptor-mediated signaling pathways. JF - The Journal of biological chemistry AU - Donovan, J A AU - Ota, Y AU - Langdon, W Y AU - Samelson, L E AD - CBMB/NICHD, National Institutes of Health, Bethesda, Maryland, 20892, USA. Y1 - 1996/10/18/ PY - 1996 DA - 1996 Oct 18 SP - 26369 EP - 26374 VL - 271 IS - 42 SN - 0021-9258, 0021-9258 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - GRB2 Adaptor Protein KW - GRB2 protein, human KW - Muromonab-CD3 KW - Proteins KW - Proto-Oncogene Proteins KW - Receptors, Antigen, T-Cell KW - Recombinant Fusion Proteins KW - pervanadate KW - Vanadates KW - 3WHH0066W5 KW - Proto-Oncogene Proteins c-cbl KW - EC 2.3.2.27 KW - Ubiquitin-Protein Ligases KW - CBL protein, human KW - EC 6.3.2.- KW - Index Medicus KW - Electrophoresis, Polyacrylamide Gel KW - Vanadates -- pharmacology KW - Humans KW - Jurkat Cells KW - Receptors, Antigen, T-Cell -- metabolism KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Recombinant Fusion Proteins -- metabolism KW - Kinetics KW - Molecular Sequence Data KW - Muromonab-CD3 -- pharmacology KW - T-Lymphocytes -- metabolism KW - Proto-Oncogene Proteins -- chemistry KW - Proto-Oncogene Proteins -- metabolism KW - Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78351289?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Regulation+of+the+association+of+p120cbl+with+Grb2+in+Jurkat+T+cells.&rft.au=Donovan%2C+J+A%3BOta%2C+Y%3BLangdon%2C+W+Y%3BSamelson%2C+L+E&rft.aulast=Donovan&rft.aufirst=J&rft.date=1996-10-18&rft.volume=271&rft.issue=42&rft.spage=26369&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 - 1996-11-26 N1 - Date created - 1996-11-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structure and function of the p53 tumor suppressor gene: clues for rational cancer therapeutic strategies. AN - 78385126; 8841019 AB - The p53 tumor suppressor protein is involved in multiple central cellular processes, including transcription, DNA repair, genomic stability, senescence, cell cycle control, and apoptosis. p53 is functionally inactivated by structural mutations, interaction with viral products, and endogenous cellular mechanisms in the majority of human cancers. This functional inactivation can, in some circumstances, produce resistance to DNA-damaging agents commonly used in cancer chemotherapy and radiotherapeutic approaches. Current research is defining the biochemical pathways through which p53 induces cell cycle arrest and apoptosis. Knowledge of these fundamental processes is leading to the identification of molecular targets toward which multimodality cancer therapies, using chemotherapeutic, immunotherapeutic, and gene-therapeutic strategies, can be based. JF - Journal of the National Cancer Institute AU - Harris, C C AD - Laboratory of Human Carcinogenesis, Division of Basic Science, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 1996/10/16/ PY - 1996 DA - 1996 Oct 16 SP - 1442 EP - 1455 VL - 88 IS - 20 SN - 0027-8874, 0027-8874 KW - DNA, Neoplasm KW - 0 KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Animals KW - Apoptosis KW - Phosphorylation KW - DNA Damage KW - Combined Modality Therapy KW - Immunotherapy KW - Humans KW - Tumor Suppressor Protein p53 -- genetics KW - Tumor Suppressor Protein p53 -- metabolism KW - Mutation KW - Structure-Activity Relationship KW - Genes, p53 -- physiology KW - Genetic Therapy KW - Neoplasms -- therapy KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78385126?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=PR+Newswire&rft.atitle=Rural%2FMetro+Wins+Exclusive+Contract+as+Emergency+Ambulance+Provider+for+Tacoma%2C+Washington&rft.au=&rft.aulast=&rft.aufirst=&rft.date=2004-07-21&rft.volume=&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=PR+Newswire&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-06 N1 - Date created - 1996-11-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - D2 dopamine receptor gene TaqI A1 and B1 restriction fragment length polymorphisms: enhanced frequencies in psychostimulant-preferring polysubstance abusers. AN - 78484683; 8894071 AB - Several lines of evidence suggest that presence of a D2 dopamine receptor (DRD2) gene variant marked by TaqI restriction fragment length polymorphisms (RFLPs) might contribute to vulnerability to substance abuse. Psychostimulants display the most robust enhancement of dopamine activity in mesolimbic/mesocortical circuits important for behavioral reward. The present study tests the hypothesis that a DRD2 gene variant might be more prominent in polysubstance users who preferentially use psychostimulants than in addicts with preferential opiate use or in those with no drug preference. Polysubstance users with histories of heavy daily preferential psychostimulant use more often displayed one or two copies of the TaqI A1 (27/62 = 43.5% vs 33/119 = 27.7% for controls), and B1 (20/62 = 32.3% vs 23/119 = 19.8% for controls) markers at the DRD2 locus. DRD2 gene marker distributions in abusers with more prominent opiate use, or those with no history of drug preference, were similar to control genotypes. Psychostimulant-preferring drug users also reported earlier onset of psychostimulant use. Our data are consistent with the hypothesis that DRD2 gene variants marked by these polymorphisms may work, probably in concert with other genetic and environmental factors, to enhance vulnerability to psychostimulant abuse. JF - Biological psychiatry AU - Persico, A M AU - Bird, G AU - Gabbay, F H AU - Uhl, G R AD - Molecular Neurobiology Branch, National Institute on Drug Abuse/National Institutes of Health, Bethesda, MD, USA. Y1 - 1996/10/15/ PY - 1996 DA - 1996 Oct 15 SP - 776 EP - 784 VL - 40 IS - 8 SN - 0006-3223, 0006-3223 KW - Genetic Markers KW - 0 KW - Receptors, Dopamine D2 KW - Amphetamine KW - CK833KGX7E KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Limbic System -- physiopathology KW - Humans KW - Polymerase Chain Reaction -- methods KW - Mesencephalon -- physiopathology KW - Adult KW - Male KW - Female KW - Genetic Markers -- genetics KW - Opioid-Related Disorders -- psychology KW - Polymorphism, Restriction Fragment Length KW - Receptors, Dopamine D2 -- genetics KW - Opioid-Related Disorders -- genetics KW - Substance-Related Disorders -- psychology KW - Substance-Related Disorders -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78484683?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biological+psychiatry&rft.atitle=D2+dopamine+receptor+gene+TaqI+A1+and+B1+restriction+fragment+length+polymorphisms%3A+enhanced+frequencies+in+psychostimulant-preferring+polysubstance+abusers.&rft.au=Persico%2C+A+M%3BBird%2C+G%3BGabbay%2C+F+H%3BUhl%2C+G+R&rft.aulast=Persico&rft.aufirst=A&rft.date=1996-10-15&rft.volume=40&rft.issue=8&rft.spage=776&rft.isbn=&rft.btitle=&rft.title=Biological+psychiatry&rft.issn=00063223&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-21 N1 - Date created - 1997-02-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation of memory circuits during cue-elicited cocaine craving. AN - 78454050; 8876259 AB - Evidence accumulated over more than 45 years has indicated that environmental stimuli can induce craving for drugs of abuse in individuals who have addictive disorders. However, the brain mechanisms that subserve such craving have not been elucidated. Here a positron emission tomographic study shows increased glucose metabolism in cortical and limbic regions implicated in several forms of memory when human volunteers who abuse cocaine are exposed to drug-related stimuli. Correlations of metabolic increases in the dorsolateral prefrontal cortex, medial temporal lobe (amygdala), and cerebellum with self-reports of craving suggest that a distributed neural network, which integrates emotional and cognitive aspects of memory, links environmental cues with cocaine craving. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Grant, S AU - London, E D AU - Newlin, D B AU - Villemagne, V L AU - Liu, X AU - Contoreggi, C AU - Phillips, R L AU - Kimes, A S AU - Margolin, A AD - Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224, USA. Y1 - 1996/10/15/ PY - 1996 DA - 1996 Oct 15 SP - 12040 EP - 12045 VL - 93 IS - 21 SN - 0027-8424, 0027-8424 KW - Fluorine Radioisotopes KW - 0 KW - Fluorodeoxyglucose F18 KW - 0Z5B2CJX4D KW - Deoxyglucose KW - 9G2MP84A8W KW - Cocaine KW - I5Y540LHVR KW - Glucose KW - IY9XDZ35W2 KW - Index Medicus KW - Analysis of Variance KW - Fluorine Radioisotopes -- pharmacokinetics KW - Humans KW - Adult KW - Deoxyglucose -- analogs & derivatives KW - Tomography, Emission-Computed KW - Deoxyglucose -- pharmacokinetics KW - Male KW - Functional Laterality KW - Female KW - Substance-Related Disorders -- physiopathology KW - Opioid-Related Disorders -- diagnostic imaging KW - Brain -- physiopathology KW - Opioid-Related Disorders -- physiopathology KW - Opioid-Related Disorders -- psychology KW - Glucose -- metabolism KW - Memory -- physiology KW - Substance-Related Disorders -- diagnostic imaging KW - Substance-Related Disorders -- psychology KW - Brain -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78454050?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Activation+of+memory+circuits+during+cue-elicited+cocaine+craving.&rft.au=Grant%2C+S%3BLondon%2C+E+D%3BNewlin%2C+D+B%3BVillemagne%2C+V+L%3BLiu%2C+X%3BContoreggi%2C+C%3BPhillips%2C+R+L%3BKimes%2C+A+S%3BMargolin%2C+A&rft.aulast=Grant&rft.aufirst=S&rft.date=1996-10-15&rft.volume=93&rft.issue=21&rft.spage=12040&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 - 1996-12-04 N1 - Date created - 1996-12-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Br J Psychol. 1970 Aug;61(3):303-21 [5457503] Nature. 1996 Apr 25;380(6576):715-7 [8614466] Circ Res. 1979 Jan;44(1):127-37 [363301] Ann Neurol. 1979 Nov;6(5):371-88 [117743] Psychol Rev. 1984 Apr;91(2):251-68 [6571424] Pharmacol Ther. 1987;35(1-2):227-63 [3321101] J Abnorm Psychol. 1988 May;97(2):118-32 [3290303] Neurosci Biobehav Rev. 1989 Summer-Fall;13(2-3):155-62 [2682402] J Pharmacol Exp Ther. 1990 May;253(2):760-70 [2338656] Arch Gen Psychiatry. 1990 Jun;47(6):567-74 [2350209] Am J Psychiatry. 1991 May;148(5):621-6 [2018164] J Neurosci. 1991 Jul;11(7):2107-16 [2066777] Psychopharmacology (Berl). 1992;107(4):523-9 [1603895] J Neurosci. 1992 Oct;12(10):4112-21 [1403102] Biol Psychiatry. 1993 Apr 1;33(7):554-6 [8513042] Can J Neurol Sci. 1993 May;20 Suppl 3:S75-7 [8334596] Behav Brain Res. 1993 Jun 30;55(2):167-83 [8357526] Brain Res Brain Res Rev. 1993 Sep-Dec;18(3):247-91 [8401595] J Subst Abuse Treat. 1993 Nov-Dec;10(6):577-83 [8308943] Behav Brain Res. 1993 Dec 20;58(1-2):69-79 [8136051] Nature. 1994 Oct 20;371(6499):702-4 [7935815] Science. 1994 Oct 21;266(5184):458-61 [7939688] Biol Psychiatry. 1994 Aug 1;36(3):189-97 [7948456] Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):11771-6 [7991534] Psychopharmacology (Berl). 1993;113(1):123-30 [7862818] Addict Behav. 1994 Nov-Dec;19(6):599-607 [7701971] Nature. 1995 Sep 28;377(6547):295-6 [7566084] Am J Psychiatry. 1995 Nov;152(11):1576-85 [7485619] Science. 1995 Nov 3;270(5237):769-75 [7481764] Science. 1996 Jan 26;271(5248):512-5 [8560267] Neurosci Lett. 1995 Oct 27;199(3):175-8 [8577391] Neuron. 1996 Jan;16(1):13-5 [8562076] Science. 1996 Apr 26;272(5261):545-7 [8614803] J Clin Psychol. 1971 Oct;27(4):455-6 [5115648] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutational analysis of a neutralization epitope on the dengue type 2 virus (DEN2) envelope protein: monoclonal antibody resistant DEN2/DEN4 chimeras exhibit reduced mouse neurovirulence. AN - 78450991; 8874504 AB - The antigenic site of dengue type 2 virus (DEN2)-neutralizing monoclonal antibody (mab) 3H5 was investigated by mutational analysis. Sequence comparisons indicated that much of the 12-amino-acid sequence extending from position 386 to 397 of the DEN2 envelope glycoprotein (E) previously thought to represent the DEN2-specific mab 3H5 binding site was also present in some dengue type 1, 3, or 4 virus strains. However, the region occupied by the Glu-Pro-Gly sequence at upstream positions 383 to 385 was completely conserved among DEN2 strains, but divergent in other serotype viruses, suggesting that this sequence might be part of the antigenic site of mab 3H5. We investigated this possibility by employing the previously constructed chimeric DEN2(PreM-E)/DEN4 cDNA clone to produce viable mutants bearing DEN2 PreM and E sequences that could be analyzed for binding to and neutralization by mab 3H5. We constructed 13 such DEN2 mutants that contained a single amino acid substitution in the region between positions 383 and 393 of DEN2 E. Each single substitution in the region spanning positions 386 through 393 of DEN2 yielded a virus that was as reactive with mab 3H5 as the parental chimeric virus. These results are consistent with the extent of sequence conservation in the region. In contrast, 5 of 6 mutants that sustained an amino acid substitution at position 383, 384, or 385 failed to react with mab 3H5 as detected by immunofluorescence assay and failed to be neutralized by the mab. Interestingly, each of the 5 mab-resistant DEN2 mutants also exhibited reduced mouse neurovirulence compared to parental chimeric DEN2 when inoculated intracerebrally. These observations suggest that the Glu-Pro-Gly sequence at positions 383-386 of the DEN2 E is a component of the site against which mab 3H5 is directed. In the recently determined three-dimensional structure of the related tick-borne encephalitis virus E, the Glu-Pro-Gly sequence would be located on the lateral surface of the immunoglobulin-like domain that is proposed to bind to the host cell receptor. JF - Virology AU - Hiramatsu, K AU - Tadano, M AU - Men, R AU - Lai, C J AD - Molecular Viral Biology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/10/15/ PY - 1996 DA - 1996 Oct 15 SP - 437 EP - 445 VL - 224 IS - 2 SN - 0042-6822, 0042-6822 KW - Antibodies, Monoclonal KW - 0 KW - Antibodies, Viral KW - E-glycoprotein, Dengue virus type 2 KW - Epitopes, B-Lymphocyte KW - Oligopeptides KW - Recombinant Fusion Proteins KW - Viral Envelope Proteins KW - Index Medicus KW - Virulence KW - Animals KW - Recombinant Fusion Proteins -- immunology KW - Humans KW - Recombinant Fusion Proteins -- genetics KW - Oligopeptides -- immunology KW - Neutralization Tests KW - Molecular Sequence Data KW - Serotyping KW - Mice KW - Amino Acid Sequence KW - Cell Line KW - Aedes -- cytology KW - Mutagenesis KW - Antibodies, Monoclonal -- immunology KW - Viral Envelope Proteins -- immunology KW - Dengue Virus -- immunology KW - Dengue Virus -- pathogenicity KW - Epitopes, B-Lymphocyte -- immunology KW - Antibodies, Viral -- immunology KW - Viral Envelope Proteins -- genetics KW - Dengue Virus -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78450991?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutational+analysis+of+a+neutralization+epitope+on+the+dengue+type+2+virus+%28DEN2%29+envelope+protein%3A+monoclonal+antibody+resistant+DEN2%2FDEN4+chimeras+exhibit+reduced+mouse+neurovirulence.&rft.au=Hiramatsu%2C+K%3BTadano%2C+M%3BMen%2C+R%3BLai%2C+C+J&rft.aulast=Hiramatsu&rft.aufirst=K&rft.date=1996-10-15&rft.volume=224&rft.issue=2&rft.spage=437&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-03 N1 - Date created - 1996-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA sequence- and structure-selective alkylation of guanine N2 in the DNA minor groove by ecteinascidin 743, a potent antitumor compound from the Caribbean tunicate Ecteinascidia turbinata. AN - 78445313; 8873596 AB - Ecteinascidin 743 is one of several related marine alkaloids isolated from the Caribbean tunicate Ecteinascidia turbinata. It is remarkably active and potent in a variety of in vitro and in vivo systems and has been selected for development as an anticancer agent. The present study investigates the interactions of ecteinascidin 743 with DNA. Ecteinascidin 743 retarded the electrophoretic migration of both supercoiled and relaxed simian virus 40 DNA even in the presence of sodium dodecyl sulfate and after ethanol precipitation, consistent with covalent DNA modifications. Similar results were obtained in a DNA oligonucleotide derived from ribosomal DNA. However, DNA denaturation reversed the DNA modifications. The homopolymeric oligonucleotide dG/dC was modified while neither the dI/dC nor the dA/dT oligonucleotides were, consistent with covalent attachment of ecteinascidin 743 to the exocyclic amino group at position 2 of guanine. Ecteinascidin 743 was then compared to another known DNA minor groove alkylating agent, anthramycin, which has also been shown to alkylate guanine N2. Footprinting analyses with DNase I and 1,10-phenanthroline-copper and exonuclease III digestions showed that ecteinascidin 743 covers three to five bases of DNA and exhibits a different sequence specificity than anthramycin in the Escherichia coli tyrosine tRNA promoter (tyrT DNA). The binding of ecteinascidin to DNA was abolished when guanines were substituted with inosines in this promoter. A band shift assay was designed to evaluate the influence of the bases flanking a centrally located guanine in an oligonucleotide containing inosines in place of guanines elsewhere. Ecteinascidin 743 and anthramycin showed similarities as well as differences in sequence selectivity. Ecteinascidin 743-guanine adducts appeared to require at least one flanking guanine and were strongest when the flanking guanine was 3' to the targeted guanine. These data indicate that ecteinascidin 743 is a novel DNA minor groove, guanine-specific alkylating agent. JF - Biochemistry AU - Pommier, Y AU - Kohlhagen, G AU - Bailly, C AU - Waring, M AU - Mazumder, A AU - Kohn, K W AD - Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1996/10/15/ PY - 1996 DA - 1996 Oct 15 SP - 13303 EP - 13309 VL - 35 IS - 41 SN - 0006-2960, 0006-2960 KW - Antineoplastic Agents, Alkylating KW - 0 KW - Dioxoles KW - Isoquinolines KW - Tetrahydroisoquinolines KW - Anthramycin KW - 0WZD9Y66WN KW - Guanine KW - 5Z93L87A1R KW - DNA KW - 9007-49-2 KW - trabectedin KW - ID0YZQ2TCP KW - Index Medicus KW - Molecular Structure KW - Animals KW - Base Sequence KW - Guanine -- chemistry KW - DNA Footprinting KW - Anthramycin -- pharmacology KW - Molecular Sequence Data KW - Urochordata KW - Anthramycin -- chemistry KW - Binding Sites KW - Alkylation KW - Isoquinolines -- pharmacology KW - Isoquinolines -- chemistry KW - Antineoplastic Agents, Alkylating -- pharmacology KW - DNA -- genetics KW - DNA -- chemistry KW - Dioxoles -- chemistry KW - Dioxoles -- pharmacology KW - Antineoplastic Agents, Alkylating -- chemistry KW - DNA -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78445313?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=DNA+sequence-+and+structure-selective+alkylation+of+guanine+N2+in+the+DNA+minor+groove+by+ecteinascidin+743%2C+a+potent+antitumor+compound+from+the+Caribbean+tunicate+Ecteinascidia+turbinata.&rft.au=Pommier%2C+Y%3BKohlhagen%2C+G%3BBailly%2C+C%3BWaring%2C+M%3BMazumder%2C+A%3BKohn%2C+K+W&rft.aulast=Pommier&rft.aufirst=Y&rft.date=1996-10-15&rft.volume=35&rft.issue=41&rft.spage=13303&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-27 N1 - Date created - 1996-11-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Benign thyroid tumors: general risk factors and their effects on radiation risk estimation. AN - 78415412; 8857821 AB - The authors examined risk factors for benign thyroid nodules and their influence on radiation effects among 544 subjects who were exposed to childhood radiation treatment for benign head and neck conditions at a Chicago, Illinois hospital during 1939-1962. In follow-up through 1991, benign thyroid nodules were diagnosed in 131 patients. The risk of benign nodules was elevated in women (relative risk (RR) = 2.2, 95% confidence interval (CI) 1.6-3.2), Jews (RR = 1.7, 95% CI 1.2-2.5), college graduates (RR = 1.8, 95% CI 1.2-2.8), and subjects whose mother had cancer (RR = 1.7, 95% CI 1.2-2.5). There were increasing trends for risk with increasing body mass index in women and decreasing height in men. Risk was increased for women who never married (RR = 3.7, 95% CI 1.6-7.3) or who never had a full-term pregnancy (RR = 2.0, 95% CI 1.1-3.3). A significant radiation dose-response relationship was observed that was not modified by sex, education, Jewish religion, or reproductive factors. The data suggest that there are genetic, life-style (including ascertainment), and hormonal factors associated with the development of benign thyroid nodules. JF - American journal of epidemiology AU - Wong, F L AU - Ron, E AU - Gierlowski, T AU - Schneider, A B AD - Radiation Epidemiology Branch, National Cancer Institute, Bethesda, MD, USA. Y1 - 1996/10/15/ PY - 1996 DA - 1996 Oct 15 SP - 728 EP - 733 VL - 144 IS - 8 SN - 0002-9262, 0002-9262 KW - Index Medicus KW - Socioeconomic Factors KW - Reproductive History KW - Risk Factors KW - Humans KW - Cohort Studies KW - Incidence KW - Middle Aged KW - Poisson Distribution KW - Dose-Response Relationship, Radiation KW - Male KW - Female KW - Thyroid Nodule -- genetics KW - Thyroid Gland -- radiation effects KW - Thyroid Nodule -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78415412?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+epidemiology&rft.atitle=Benign+thyroid+tumors%3A+general+risk+factors+and+their+effects+on+radiation+risk+estimation.&rft.au=Wong%2C+F+L%3BRon%2C+E%3BGierlowski%2C+T%3BSchneider%2C+A+B&rft.aulast=Wong&rft.aufirst=F&rft.date=1996-10-15&rft.volume=144&rft.issue=8&rft.spage=728&rft.isbn=&rft.btitle=&rft.title=American+journal+of+epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-19 N1 - Date created - 1996-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Understanding drug addiction: implications for treatment. AN - 78412863; 8859207 AB - The addicted brain is qualitatively different from the nonaddicted brain, in ways that include glucose use, gene expression, and responsiveness to environmental cues. Such discoveries place researchers in the early but hopeful stages of translating fundamental findings into new treatments that address the neurobiologic basis of drug craving--even for cocaine, against which there are currently no pharmacologic interventions. JF - Hospital practice (1995) AU - Leshner, A I AD - National Institute on Drug Abuse, National Institutes of Health, Rockville, Md., USA. Y1 - 1996/10/15/ PY - 1996 DA - 1996 Oct 15 SP - 47 EP - 54, 57-9 VL - 31 IS - 10 SN - 2154-8331, 2154-8331 KW - Cocaine KW - I5Y540LHVR KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Animals KW - Humans KW - Opioid-Related Disorders -- metabolism KW - Brain -- drug effects KW - Opioid-Related Disorders -- therapy KW - Brain -- metabolism KW - Cocaine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78412863?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hospital+practice+%281995%29&rft.atitle=Understanding+drug+addiction%3A+implications+for+treatment.&rft.au=Leshner%2C+A+I&rft.aulast=Leshner&rft.aufirst=A&rft.date=1996-10-15&rft.volume=31&rft.issue=10&rft.spage=47&rft.isbn=&rft.btitle=&rft.title=Hospital+practice+%281995%29&rft.issn=21548331&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-19 N1 - Date created - 1996-11-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Hosp Pract (1995). 1997 Mar 15;32(3):41 [9078970] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of cornifin alpha expression in the vaginal and uterine epithelium by estrogen and retinoic acid. AN - 78523316; 8912806 AB - In this study, we analyze the regulation of the squamous-specific gene, cornifin alpha, by estrogen and retinoic acid in vaginal and uterine epithelial cells. In ovariectomized animals, the vaginal epithelium consists of a stratified, nonkeratinizing epithelium which changes into a highly-stratified, keratinizing epithelium upon treatment with estradiol. This transition is accompanied by a dramatic induction of the crosslinked envelope precursor, cornifin alpha. An increase in cornifin mRNA can be detected as early as 3 h after treatment. A similar effect is observed for the synthetic estrogenic agent diethylstilbestrol while other steroid hormones, including testosterone, progesterone or dexamethasone have little effect on cornifin expression. In contrast to the vagina, estradiol induces neither squamous differentiation nor expression of cornifin alpha in the uterine epithelium. Similar to the action of estradiol, vitamin A-deficiency greatly enhances squamous differentiation and keratinization in the vaginal epithelium. But unlike estradiol, it induces squamous metaplasia in the normally columnar, uterine epithelium, which eventually is replaced by a keratinizing epithelium in severe deficiency. This transition is associated with an induction of cornifin alpha expression. Immunohistochemical and in situ hybridization analysis localizes cornifin protein and mRNA in the suprabasal layers of the squamous epithelium. Our results demonstrate that estrogen and retinoids play key roles in the regulation of differentiation and cornifin alpha expression in the uterine and vaginal epithelium. JF - Molecular and cellular endocrinology AU - Jetten, A M AU - De Luca, L M AU - Nelson, K AU - Schroeder, W AU - Burlingame, S AU - Fujimoto, W AD - Laboratory of Pulmonary Pathobiology, NIEHS, NIH, Research Triangle Park, NC 27709, USA. jetten@niehs.nih.gov Y1 - 1996/10/14/ PY - 1996 DA - 1996 Oct 14 SP - 7 EP - 15 VL - 123 IS - 1 SN - 0303-7207, 0303-7207 KW - Membrane Proteins KW - 0 KW - RNA, Messenger KW - Dihydrotestosterone KW - 08J2K08A3Y KW - Progesterone KW - 4G7DS2Q64Y KW - Estradiol KW - 4TI98Z838E KW - Tretinoin KW - 5688UTC01R KW - Diethylstilbestrol KW - 731DCA35BT KW - Dexamethasone KW - 7S5I7G3JQL KW - Index Medicus KW - Vitamin A Deficiency -- metabolism KW - Animals KW - Dexamethasone -- pharmacology KW - Progesterone -- pharmacology KW - Epithelium -- drug effects KW - RNA, Messenger -- biosynthesis KW - Rats KW - Rats, Sprague-Dawley KW - Epithelial Cells KW - Dihydrotestosterone -- pharmacology KW - Diethylstilbestrol -- pharmacology KW - Epithelium -- metabolism KW - Ovariectomy KW - Female KW - Uterus -- metabolism KW - Tretinoin -- pharmacology KW - Transcription, Genetic -- drug effects KW - Membrane Proteins -- biosynthesis KW - Estradiol -- pharmacology KW - Vagina -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78523316?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+endocrinology&rft.atitle=Regulation+of+cornifin+alpha+expression+in+the+vaginal+and+uterine+epithelium+by+estrogen+and+retinoic+acid.&rft.au=Jetten%2C+A+M%3BDe+Luca%2C+L+M%3BNelson%2C+K%3BSchroeder%2C+W%3BBurlingame%2C+S%3BFujimoto%2C+W&rft.aulast=Jetten&rft.aufirst=A&rft.date=1996-10-14&rft.volume=123&rft.issue=1&rft.spage=7&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+endocrinology&rft.issn=03037207&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-20 N1 - Date created - 1996-12-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Site-directed mutagenesis of nm23-H1. Mutation of proline 96 or serine 120 abrogates its motility inhibitory activity upon transfection into human breast carcinoma cells. AN - 78342360; 8810265 AB - We report the first correlation of Nm23 sequence and its tumor metastasis-suppressive capacity using site-directed mutagenesis and an in vitro tumor cell motility assay. MDA-MB-435 human breast carcinoma cells were transfected with a control expression vector (pCMVBamneo), the vector containing the wild type nm23-H1, or the nm23-H1 vector encoding mutations at the following amino acids: serine 44, a phosphorylation site; proline 96, the k-pn mutation in the Drosophila nm23 homolog that causes developmental defects; histidine 118, involved in Nm23's nucleoside diphosphate kinase activity; and serine 120, a site of mutation in human neuroblastomas and phosphorylation. The wild type nm23-H1 transfectants were 44-98% less motile to serum and 86-99% less motile to autotaxin than control vector transfectants. The proline 96 k-pn, serine 120 to glycine, and to a lesser extent serine 120 to alanine mutant nm23-H1-transfected cell lines exhibited motility levels at or above the control transfectants, indicating that these mutations can abrogate the motility-suppressive phenotype of nm23-H1. No effect was observed on cellular proliferation, nor were the serine 44 to alanine nm23-H1 mutant transfectants motile, demonstrating the specificity of the data. The data identify the first structural motifs of nm23-H1 that influence its metastasis suppressive effect and suggest complex biochemical associations or activities in the Nm23 suppressive pathway. JF - The Journal of biological chemistry AU - MacDonald, N J AU - Freije, J M AU - Stracke, M L AU - Manrow, R E AU - Steeg, P S AD - Women's Cancers Section, Laboratory of Pathology, Division of Clinical Sciences, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/10/11/ PY - 1996 DA - 1996 Oct 11 SP - 25107 EP - 25116 VL - 271 IS - 41 SN - 0021-9258, 0021-9258 KW - NM23 Nucleoside Diphosphate Kinases KW - 0 KW - Recombinant Proteins KW - Transcription Factors KW - Serine KW - 452VLY9402 KW - Histidine KW - 4QD397987E KW - Proline KW - 9DLQ4CIU6V KW - NME1 protein, human KW - EC 2.7.4.6 KW - Nucleoside-Diphosphate Kinase KW - Monomeric GTP-Binding Proteins KW - EC 3.6.5.2 KW - Alanine KW - OF5P57N2ZX KW - Glycine KW - TE7660XO1C KW - Index Medicus KW - Animals KW - Humans KW - Breast Neoplasms KW - Amino Acid Sequence KW - Chemotaxis KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Neuroblastoma -- genetics KW - Tumor Cells, Cultured KW - Phosphorylation KW - Transfection KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Drosophila KW - Female KW - Cell Division KW - Transcription Factors -- physiology KW - Nucleoside-Diphosphate Kinase -- biosynthesis KW - Transcription Factors -- biosynthesis KW - Nucleoside-Diphosphate Kinase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78342360?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Site-directed+mutagenesis+of+nm23-H1.+Mutation+of+proline+96+or+serine+120+abrogates+its+motility+inhibitory+activity+upon+transfection+into+human+breast+carcinoma+cells.&rft.au=MacDonald%2C+N+J%3BFreije%2C+J+M%3BStracke%2C+M+L%3BManrow%2C+R+E%3BSteeg%2C+P+S&rft.aulast=MacDonald&rft.aufirst=N&rft.date=1996-10-11&rft.volume=271&rft.issue=41&rft.spage=25107&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 - 1996-11-19 N1 - Date created - 1996-11-19 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - X17620; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of functional elements of the chicken epsilon-globin promoter involved in stage-specific interaction with the beta/epsilon enhancer. AN - 78333524; 8810316 AB - Expression of the chicken globin genes is regulated in part by competition between the betaA-globin and epsilon-globin promoters for the enhancer found between the genes. To understand the determinants of the enhancer-promoter interaction in stage-specific regulation, the functional elements of the embryonic chicken epsilon-globin promoter were characterized. In vitro assays demonstrated that: (a) the TATA motif at -30 bound GATA-1, (b) Sp1 bound to an element centered at -54, and (c) both Sp1 and another factor, designated CACCC (which appears related to erythroid Krüppel-like factor, EKLF) bound in the -120 to -128 region. The functions of these motifs were tested using transient expression in embryonic erythroid cells. In the absence of the enhancer, promoter point mutants showed that the TATA, Sp1, and CCAAT motifs (but not the CACCC motif) contributed to promoter activity. In contrast, in the presence of the enhancer, all four motifs (including the CACCC motif) contributed to transcription. Developmental regulation of the enhancer activity was observed, with enhancement decreasing sharply from 185-fold at 4 days (cells expressing epsilon-globin) to 16-fold at 10 days (when epsilon-globin is no longer expressed). Taken together, the data suggest that multiple transcription factors contribute to promoter-enhancer interaction and the developmental regulation of epsilon-globin expression, with EKLF-like factors having an especially important role. Regulation of stage specificity occurs at the level of enhancer/epsilon-promoter interaction, even in the absence of competition, and is not simply a property of the enhancer or promoter in isolation. JF - The Journal of biological chemistry AU - Mason, M M AU - Grasso, J A AU - Gavrilova, O AU - Reitman, M AD - Diabetes Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/10/11/ PY - 1996 DA - 1996 Oct 11 SP - 25459 EP - 25467 VL - 271 IS - 41 SN - 0021-9258, 0021-9258 KW - DNA-Binding Proteins KW - 0 KW - Kruppel-Like Transcription Factors KW - Sp1 Transcription Factor KW - Transcription Factors KW - erythroid Kruppel-like factor KW - Globins KW - 9004-22-2 KW - Deoxyribonuclease I KW - EC 3.1.21.1 KW - Index Medicus KW - Animals KW - Transcription Factors -- metabolism KW - Chick Embryo KW - Mice KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Chickens KW - DNA Footprinting KW - Sp1 Transcription Factor -- metabolism KW - Point Mutation KW - Molecular Sequence Data KW - Zinc Fingers KW - TATA Box KW - DNA-Binding Proteins -- metabolism KW - Promoter Regions, Genetic KW - Enhancer Elements, Genetic KW - Globins -- genetics KW - Globins -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78333524?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Identification+of+functional+elements+of+the+chicken+epsilon-globin+promoter+involved+in+stage-specific+interaction+with+the+beta%2Fepsilon+enhancer.&rft.au=Mason%2C+M+M%3BGrasso%2C+J+A%3BGavrilova%2C+O%3BReitman%2C+M&rft.aulast=Mason&rft.aufirst=M&rft.date=1996-10-11&rft.volume=271&rft.issue=41&rft.spage=25459&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 - 1996-11-19 N1 - Date created - 1996-11-19 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - L17432; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pain responses, anxiety and aggression in mice deficient in pre-proenkephalin. AN - 78395911; 8849726 AB - Enkephalins are endogenous opioid peptides that are derived from a pre-proenkephalin precursor protein. They are thought to be vital in regulating many physiological functions, including pain perception and analgesia, responses to stress, aggression and dominance. Here we have used a genetic approach to study the role of the mammalian opioid system. We disrupted the pre-proenkephalin gene using homologous recombination in embryonic stem cells to generate enkephalin-deficient mice. Mutant enk-/- animals are healthy, fertile, and care for their offspring, but display significant behavioural abnormalities. Mice with the enk-/- genotype are more anxious and males display increased offensive aggressiveness. Mutant animals show marked differences from controls in supraspinal, but not in spinal, responses to painful stimuli. Unexpectedly, enk-/- mice exhibit normal stress-induced analgesia. Our results show that enkephalins modulate responses to painful stimuli. Thus, genetic factors may contribute significantly to the experience of pain. JF - Nature AU - König, M AU - Zimmer, A M AU - Steiner, H AU - Holmes, P V AU - Crawley, J N AU - Brownstein, M J AU - Zimmer, A AD - Unit on Developmental Biology, Laboratory of Cell Biology, Section on Neuroanatomy, Laboratory of Neurophysiology, National Institute of Mental Health, Bethesda, Maryland 20892, USA. Y1 - 1996/10/10/ PY - 1996 DA - 1996 Oct 10 SP - 535 EP - 538 VL - 383 IS - 6600 SN - 0028-0836, 0028-0836 KW - Enkephalins KW - 0 KW - Protein Precursors KW - preproenkephalin KW - 93443-35-7 KW - Index Medicus KW - Animals KW - Analgesia KW - Homozygote KW - Restriction Mapping KW - Mice KW - Gene Targeting KW - Male KW - Female KW - Cell Line KW - Mutagenesis KW - Enkephalins -- deficiency KW - Protein Precursors -- physiology KW - Enkephalins -- physiology KW - Anxiety -- genetics KW - Pain KW - Protein Precursors -- deficiency KW - Aggression UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78395911?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=Pain+responses%2C+anxiety+and+aggression+in+mice+deficient+in+pre-proenkephalin.&rft.au=K%C3%B6nig%2C+M%3BZimmer%2C+A+M%3BSteiner%2C+H%3BHolmes%2C+P+V%3BCrawley%2C+J+N%3BBrownstein%2C+M+J%3BZimmer%2C+A&rft.aulast=K%C3%B6nig&rft.aufirst=M&rft.date=1996-10-10&rft.volume=383&rft.issue=6600&rft.spage=535&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-12 N1 - Date created - 1996-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Requirement for PCNA in DNA mismatch repair at a step preceding DNA resynthesis. AN - 78418307; 8858149 AB - A two-hybrid system was used to screen yeast and human expression libraries for proteins that interact with mismatch repair proteins. PCNA was recovered from both libraries and shown in the case of yeast to interact with both MLH1 and MSH2. A yeast strain containing a mutation in the PCNA gene had a strongly elevated mutation rate in a dinucleotide repeat, and the rate was not further elevated in a strain also containing a mutation in MLH1. Mismatch repair activity was examined in human cell extracts using an assay that does not require DNA repair synthesis. Activity was inhibited by p21WAF1 or a p21 peptide, both of which bind to PCNA, and activity was restored to inhibited reactions by addition of PCNA. The data suggest a PCNA requirement in mismatch repair at a step preceding DNA resynthesis. The ability of PCNA to bind to MLH1 and MSH2 may reflect linkage between mismatch repair and replication and may be relevant to the roles of mismatch repair proteins in other DNA transactions. JF - Cell AU - Umar, A AU - Buermeyer, A B AU - Simon, J A AU - Thomas, D C AU - Clark, A B AU - Liskay, R M AU - Kunkel, T A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996/10/04/ PY - 1996 DA - 1996 Oct 04 SP - 65 EP - 73 VL - 87 IS - 1 SN - 0092-8674, 0092-8674 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - CDKN1A protein, human KW - Carrier Proteins KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - DNA-Binding Proteins KW - Fungal Proteins KW - MLH1 protein, S cerevisiae KW - Neoplasm Proteins KW - Nucleic Acid Heteroduplexes KW - PMS1 protein, human KW - Peptides KW - Proliferating Cell Nuclear Antigen KW - Saccharomyces cerevisiae Proteins KW - DNA KW - 9007-49-2 KW - MutL Protein Homolog 1 KW - EC 3.6.1.3 KW - MutL Proteins KW - MutS Homolog 2 Protein KW - Index Medicus KW - Humans KW - Yeasts -- genetics KW - Amino Acid Sequence KW - Peptides -- pharmacology KW - Protein Binding KW - Mutagenesis KW - Cloning, Molecular KW - Fungal Proteins -- metabolism KW - Cyclins -- pharmacology KW - Molecular Sequence Data KW - Cell Line KW - DNA-Binding Proteins -- metabolism KW - DNA Repair -- physiology KW - Proliferating Cell Nuclear Antigen -- physiology KW - Proliferating Cell Nuclear Antigen -- pharmacology KW - DNA -- biosynthesis KW - Proliferating Cell Nuclear Antigen -- metabolism KW - DNA Repair -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78418307?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell&rft.atitle=Requirement+for+PCNA+in+DNA+mismatch+repair+at+a+step+preceding+DNA+resynthesis.&rft.au=Umar%2C+A%3BBuermeyer%2C+A+B%3BSimon%2C+J+A%3BThomas%2C+D+C%3BClark%2C+A+B%3BLiskay%2C+R+M%3BKunkel%2C+T+A&rft.aulast=Umar&rft.aufirst=A&rft.date=1996-10-04&rft.volume=87&rft.issue=1&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Cell&rft.issn=00928674&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-25 N1 - Date created - 1996-11-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Stimulation of tumor cell motility linked to phosphodiesterase catalytic site of autotaxin. AN - 78322733; 8798697 AB - A family of extracellular type I phosphodiesterases has recently been isolated by cDNA cloning, but a physiological function linked to the phosphodiesterase active site has remained unknown. We now present evidence that the phosphodiesterase catalytic site, 201YMRPVYPTKTFPN213, is essential for the motility stimulating activity of autotaxin (ATX), one member of the exophosphodiesterase family. Native ATX possesses phosphodiesterase activity at neutral and alkaline pH, binds ATP noncovalently, and undergoes threonine phosphorylation. Homogeneously purified recombinant ATX, based on the teratocarcinoma sequence, retains these same activities. A single amino acid in the phosphodiesterase catalytic site, Thr210, is found to be necessary for motility stimulation, phosphodiesterase activity, and phosphorylation. Two mutant recombinant proteins, Ala210- and Asp210-ATX, lack motility stimulation and lack both enzymatic activities; Ser210-ATX possesses intermediate activities. Another mutation, with the adjacent lysine (Lys209) changed to Leu209-ATX, possesses normal motility stimulation with sustained phosphodiesterase activity but exhibits no detectable phosphorylation. This mutation eliminates the phosphorylation reaction and indicates that the dephosphorylated state is an active motility-stimulating form of the ATX molecule. By demonstrating that the phosphodiesterase enzymatic site is linked to motility stimulation, these data reveal a novel role for this family of exo/ecto-enzymes and open up the possibility of extracellular enzymatic cascades as a regulatory mechanism for cellular motility. JF - The Journal of biological chemistry AU - Lee, H Y AU - Clair, T AU - Mulvaney, P T AU - Woodhouse, E C AU - Aznavoorian, S AU - Liotta, L A AU - Stracke, M L AD - Laboratory of Pathology, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/10/04/ PY - 1996 DA - 1996 Oct 04 SP - 24408 EP - 24412 VL - 271 IS - 40 SN - 0021-9258, 0021-9258 KW - Glycoproteins KW - 0 KW - Multienzyme Complexes KW - Recombinant Proteins KW - Phosphoric Diester Hydrolases KW - EC 3.1.4.- KW - Phosphodiesterase I KW - EC 3.1.4.1 KW - alkylglycerophosphoethanolamine phosphodiesterase KW - EC 3.1.4.39 KW - Pyrophosphatases KW - EC 3.6.1.- KW - Glucose-6-Phosphate Isomerase KW - EC 5.3.1.9 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Tumor Cells, Cultured KW - Recombinant Proteins -- metabolism KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Catalysis KW - Binding Sites KW - Phosphoric Diester Hydrolases -- genetics KW - Cell Movement KW - Glucose-6-Phosphate Isomerase -- metabolism KW - Melanoma -- pathology KW - Glycoproteins -- metabolism KW - Phosphoric Diester Hydrolases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78322733?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Stimulation+of+tumor+cell+motility+linked+to+phosphodiesterase+catalytic+site+of+autotaxin.&rft.au=Lee%2C+H+Y%3BClair%2C+T%3BMulvaney%2C+P+T%3BWoodhouse%2C+E+C%3BAznavoorian%2C+S%3BLiotta%2C+L+A%3BStracke%2C+M+L&rft.aulast=Lee&rft.aufirst=H&rft.date=1996-10-04&rft.volume=271&rft.issue=40&rft.spage=24408&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 - 1996-11-25 N1 - Date created - 1996-11-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tumor growth and tumor radiosensitivity in mice given myeloprotective doses of fibroblast growth factors. AN - 78365513; 8827018 AB - Radiation at doses high enough to cure cancer also frequently destroys normal tissue. Development of agents that protect normal tissue without also protecting diseased tissue has been difficult. In vivo radioprotection of bone marrow by acidic and basic fibroblast growth factors (FGF1 and FGF2, respectively) has recently been demonstrated after whole-body irradiation of C3H/HeN mice. Our purpose was to determine whether myeloprotective doses of those growth factors also protect malignant tumors. First, we investigated the effects of exogenous FGF1 or FGF2 (FGF1/2) administration (treatment group receiving two intravenous injections of 3 micrograms FGF1/2 per mouse 24 hours and 4 hours before local irradiation of right hind leg and control group receiving two intravenous injections of 0.1 mL of saline) on growth and radiosensitivity of three transplantable murine tumors (one squamous cell carcinoma [SCC-VII] and two sarcomas [KHT and Rif-1]), all of which were grown in C3H/HeN mice. We then evaluated the effect of FGF1/2 on tumor cell proliferation, cell cycle distribution, and pulmonary metastatic frequency in the mice. Specifically, survival studies were performed in mice treated with 0, 6, 6.5, 7.5, 8.5, 9, or 10 Gy whole-body irradiation with or without FGF2 (n = 250). Rif-1 (n = 40), KHT (n = 40), and SCC-VII (n = 40) tumors were implanted in the hind leg of mice, and mice were treated with FGF2 or saline when their tumor-bearing thighs were 9 mm in diameter. In separate experiments (treatment group receiving two injections of 3 micrograms each of FGF2 [6 micrograms total] either intravenously or intratumorally 24 hours and 4 hours before local tumor irradiation and control group receiving 0.1 mL saline), tumor growth was followed, and mice were killed to count lung metastases and measure tumor proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine labeling at various times thereafter (three to eight mice per group). Tumor growth curves of untreated and irradiated tumors were determined with and without intravenous or intratumoral FGF1/2 in SCC-VII tumors (n = 120). Radiation doses to the tumor-bearing leg were 15 and 30 Gy for SCC-VII, 30 Gy for Rif-1, and 15 Gy for KHT. From each experiment, the mean (+/- 1 standard error) was calculated from data obtained from three to 20 mice. Statistical tests used included two-tailed Student's t test, the chi-squared test, and Fisher's exact test. All P values represent two-tailed tests of statistical significance. There was no statistically significant difference in tumor growth rate between FGF2-treated and saline-treated mice when FGF2 was administered intravenously at doses and schedules found to be optimally myeloprotective in whole-body irradiation experiments. Intravenous administration of FGF2 did not induce lung metastases, and it did not augment the S-phase fraction of tumor cells. Likewise, there was no evidence of enhanced cell proliferation as measured by PCNA-labeling index. Intratumoral injection of FGF1/2 did increase the size of SCC-VII tumors (P < .05 [Student's t test] at 3 days after treatment); however, the radiation response after intratumoral injection of growth factor was not compromised. Low intravenous doses of FGF1 or FGF2 appear to protect bone marrow from the toxic effects of radiation without increasing the rates of tumor growth or metastases or decreasing the radiosensitivity of tumors. JF - Journal of the National Cancer Institute AU - Ding, I AU - Huang, K AU - Snyder, M L AU - Cook, J AU - Zhang, L AU - Wersto, N AU - Okunieff, P AD - Radiation Oncology Branch, National Cancer Institute, Bethesda, MD, USA. Y1 - 1996/10/02/ PY - 1996 DA - 1996 Oct 02 SP - 1399 EP - 1404 VL - 88 IS - 19 SN - 0027-8874, 0027-8874 KW - Proliferating Cell Nuclear Antigen KW - 0 KW - Radiation-Protective Agents KW - Receptors, Fibroblast Growth Factor KW - Recombinant Proteins KW - Fibroblast Growth Factor 2 KW - 103107-01-3 KW - Index Medicus KW - Neoplasm Transplantation KW - Animals KW - Lung Neoplasms -- prevention & control KW - Recombinant Proteins -- pharmacology KW - Injections, Intravenous KW - Lung Neoplasms -- secondary KW - Mice, Inbred C3H KW - Cell Division -- drug effects KW - Proliferating Cell Nuclear Antigen -- analysis KW - Mice KW - Immunohistochemistry -- methods KW - Time Factors KW - Receptors, Fibroblast Growth Factor -- analysis KW - Cell Division -- radiation effects KW - Sarcoma, Experimental -- secondary KW - Fibroblast Growth Factor 2 -- pharmacology KW - Sarcoma, Experimental -- radiotherapy KW - Carcinoma, Squamous Cell -- secondary KW - Radiation-Protective Agents -- pharmacology KW - Carcinoma, Squamous Cell -- radiotherapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78365513?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Tumor+growth+and+tumor+radiosensitivity+in+mice+given+myeloprotective+doses+of+fibroblast+growth+factors.&rft.au=Ding%2C+I%3BHuang%2C+K%3BSnyder%2C+M+L%3BCook%2C+J%3BZhang%2C+L%3BWersto%2C+N%3BOkunieff%2C+P&rft.aulast=Ding&rft.aufirst=I&rft.date=1996-10-02&rft.volume=88&rft.issue=19&rft.spage=1399&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-24 N1 - Date created - 1996-10-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulation of calcium currents by electrical activity. AN - 85243101; pmid-8899630 AB - Electrical activation of mouse dorsal root ganglion (DRG) neurons in cultures for 1-2 days produced a downregulation of voltage sensitive calcium currents, which persisted for > or = 24 h after stimulation was terminated. This regulation varied with different patterns of activation. Both the magnitude and time course of regulation of the low-threshold voltage-activated (LVA) and high-threshold voltage-activated (HVA) currents were differentially sensitive to neural impulse activity. Tonic stimulation at 0.5 Hz did not affect the HVA currents, but 2.5 Hz did produce a significant decrease. Phasic stimulation (10 Hz for 0.5 s every 2 s) with an average frequency of 2.5 Hz produced significantly more downregulation of HVA currents than did the tonic 2.5-Hz stimulation. The efficacy of phasic stimulation varied inversely with the interval between bursts. Thus phasic stimulation of 10 Hz for 0.5 s but delivered every 4 s produced no effects on HVA currents. Stimulation optimal for downregulation of Ca2+ currents also produced a decreased binding by the DRG neurons of an L-type Ca2+ channel antagonist. This suggests a downregulation by electrical activity of the number of Ca2+ channels, rather than an alteration in a constant number of channels. Depression of LVA currents was produced by all stimulus patterns tested, including 0.5-Hz tonic stimulation. Chronic stimulation with a stimulation pattern that downregulated Ca2+ currents also produced a slowing of the increase in intracellular Ca2+ (as measured by Fura-2/AM) that is produced acutely by repetitive stimulation. This is consonant with earlier studies of intracellular Ca2+ concentration kinetics in growth cones. JF - Journal of Neurophysiology AU - Li M AU - Jia, M AU - Fields, R D AU - Nelson, P G AD - Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-4480, USA. PY - 1996 SP - 2595 EP - 2607 VL - 76 IS - 4 SN - 0022-3077, 0022-3077 KW - Calcium Channels KW - Patch-Clamp Techniques KW - Down-Regulation KW - Cells, Cultured KW - Evoked Potentials KW - Neurons KW - Animal KW - Ganglia, Spinal KW - Membrane Potentials KW - Mice KW - Electric Stimulation KW - Statistics, Nonparametric UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85243101?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Neurophysiology&rft.atitle=Modulation+of+calcium+currents+by+electrical+activity.&rft.au=Li+M%3BJia%2C+M%3BFields%2C+R+D%3BNelson%2C+P+G&rft.aulast=Li+M&rft.aufirst=&rft.date=1996-10-01&rft.volume=76&rft.issue=4&rft.spage=2595&rft.isbn=&rft.btitle=&rft.title=Journal+of+Neurophysiology&rft.issn=00223077&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Differential expression of bone morphogenetic proteins in the developing vestibular and auditory sensory organs. AN - 85221106; pmid-8815925 AB - The genes responsible for the formation of various sensory organs in the inner ear are not known. There are eight sensory organs in the chick inner ear, and our previous study showed that all presumptive sensory organs initially express bone morphogenetic protein 4 (BMP4), a member of the transforming growth factor (TGF)-beta gene family. To address the potential role of BMPs in the patterning of different sensory organ structures, we investigated the expression of BMP4, BMP5, and BMP7 during sensory organ differentiation in the chick inner ear. The gene expression pattern of BMP5, although similar to that of BMP4, was transient and disappeared by embryonic day 3.5 (E3.5). In contrast, BMP7 gene expression was quite extensive, starting in the otic placode. By E5, gene expression patterns of BMP4 and BMP7 differed among vestibular and auditory sensory organs. In the vestibular sensory organs, BMP7 gene expression segregated from the main sensory tissue areas at the onset of differentiation, whereas BMP4 expression concentrated in supporting cells. In the cochlea, however, BMP7 gene expression became restricted to sensory tissue over time and eventually concentrated in supporting cells, whereas BMP4 gene expression was localized to hair cells. The different BMP expression patterns in developing auditory and vestibular sensory organs may help to shape each respective sensory structure. Furthermore, the expression of BMP4 in the cochlea also revealed an interesting pattern of sensory cell differentiation: the distal portion of the cochlea differentiates first, and the tall hair cells develop before the short hair cells. JF - The Journal of Neuroscience AU - Oh, S H AU - Johnson, R AU - Wu, D K AD - National Institute on Deafness and Other Communication Disorders, Rockville, Maryland 20850, USA. PY - 1996 SP - 6463 EP - 6475 VL - 16 IS - 20 SN - 0270-6474, 0270-6474 KW - Cochlea KW - Labyrinth KW - Bone and Bones KW - In Situ Hybridization KW - Chick Embryo KW - Animal KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Receptors, Cell Surface KW - Vestibular Nuclei UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85221106?accountid=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=Differential+expression+of+bone+morphogenetic+proteins+in+the+developing+vestibular+and+auditory+sensory+organs.&rft.au=Oh%2C+S+H%3BJohnson%2C+R%3BWu%2C+D+K&rft.aulast=Oh&rft.aufirst=S&rft.date=1996-10-01&rft.volume=16&rft.issue=20&rft.spage=6463&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 - The novel UGT1 gene complex links bilirubin, xenobiotics, and therapeutic drug metabolism by encoding UDP-glucuronosyltransferase isozymes with a common carboxyl terminus. AN - 78729097; 9131487 AB - The UDP-glucuronosyltransferase system (transferase) plays an important role in the pharmacokinetics of clearance of endogenous metabolites, therapeutic drugs, and xenobiotics. The human bilirubin and phenol transferases are encoded by the same gene complex which we designate UGT1. The gene arrangement indicates there are 6 exon 1s each with a promoter and each of which can predictably undergo differential splicing to the 4 common exons (2 through 5) to generate possibly 6 different mRNAs. The entire unique amino acid terminus of each isoform is encoded by an exon 1, and the common carboxyl terminus is encoded by the 4 common exons. Evidence supports the existence of other exon 1s upstream of the currently described locus. The 13-bp deletion in exon 2 represents the most common defect, to date, in the Crigler-Najjar, Type I individuals. Different point mutations in the 4 common exons and in exon 1 of UGT1A, however, also account for defective bilirubin transferase activity. The gene arrangement, in conjunction with the toxicity data from the Gunn rat, leads to the prediction that detoxification of bilirubin, xenobiotics, and therapeutic drugs is linked to the UGT1 locus. The Crigler-Najjar syndromes are uncommon, but the Gilbert individuals are commonly represented in 6% of the population. It is expected that, similar to the deleterious mutations in the common region of the UGT1 locus in Crigler-Najjar, Type I individuals, there is a range of moderate to intermediate deleterious mutations in this region of the gene of at least some Gilbert's individuals. Linkages, therefore, at this locus could signal that these individuals are at risk for certain drug toxicities and/or idiosyncratic drug reactions. JF - Journal of pharmacokinetics and biopharmaceutics AU - Owens, I S AU - Ritter, J K AU - Yeatman, M T AU - Chen, F AD - Heritable Disorders Branch, National Institute of Child and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 491 EP - 508 VL - 24 IS - 5 SN - 0090-466X, 0090-466X KW - Pharmaceutical Preparations KW - 0 KW - Xenobiotics KW - RNA KW - 63231-63-0 KW - DNA KW - 9007-49-2 KW - Glucuronosyltransferase KW - EC 2.4.1.17 KW - Index Medicus KW - Animals KW - Xenobiotics -- metabolism KW - Humans KW - Rats, Gunn KW - Gilbert Disease -- enzymology KW - Gilbert Disease -- genetics KW - Cloning, Molecular KW - Rats KW - Phenotype KW - Genotype KW - Crigler-Najjar Syndrome -- enzymology KW - Pharmaceutical Preparations -- metabolism KW - DNA -- genetics KW - Molecular Sequence Data KW - Crigler-Najjar Syndrome -- genetics KW - Female KW - Male KW - RNA -- genetics KW - Glucuronosyltransferase -- genetics KW - Hyperbilirubinemia, Hereditary -- genetics KW - Hyperbilirubinemia, Hereditary -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78729097?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+pharmacokinetics+and+biopharmaceutics&rft.atitle=The+novel+UGT1+gene+complex+links+bilirubin%2C+xenobiotics%2C+and+therapeutic+drug+metabolism+by+encoding+UDP-glucuronosyltransferase+isozymes+with+a+common+carboxyl+terminus.&rft.au=Owens%2C+I+S%3BRitter%2C+J+K%3BYeatman%2C+M+T%3BChen%2C+F&rft.aulast=Owens&rft.aufirst=I&rft.date=1996-10-01&rft.volume=24&rft.issue=5&rft.spage=491&rft.isbn=&rft.btitle=&rft.title=Journal+of+pharmacokinetics+and+biopharmaceutics&rft.issn=0090466X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-07-15 N1 - Date created - 1997-07-15 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - M84130; GENBANK; M84128; M84129; M84126; M84127; M84124; M84125; M84122; M84123 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Development of a replication-deficient recombinant vaccinia virus vaccine effective against parainfluenza virus 3 infection in an animal model. AN - 78654981; 8994321 AB - The highly attenuated, replication-deficient, modified vaccinia virus Ankara (MVA) was used to express the fusion (F) and/or hemagglutinin-neuraminidase (HN) glycoproteins of parainfluenza virus 3 (PIV3). Initial recombinant viruses in which the HN gene was regulated by a very strong synthetic earlyllate promoter replicated poorly in permissive chick embryo cells evidently due to toxic levels of the gene product. This result led us to construct and evaluate a modified earlyllate promoter derived from the H5 gene of vaccinia virus. Reporter gene experiments indicated that the enhanced H5 promoter was about five times stronger than the 7.5 promoter used in previous recombinant vaccinia/ PIV3 viruses. Although the overall expression from the modified H5 promoter was less than that of the strong synthetic promoter, early expression, determined in the presence of an inhibitor of DNA replication, was higher. Importantly, recombinant MVA employing the modified H5 promoter to regulate the F or HN gene of PIV3 replicated to high titers in chick cells and expressed functional F or HN proteins as measured by syncytial formation upon dual infection of mammalian cells. Cotton rats inoculated with recombinant MVA expressing F or HN by intramuscular or intranasal routes produced high levels of antibody. The virus expressing HN, however, was the more effective of the two in inducing immunity to PIV3 challenge, reducing PIV3 viral titers in the nasal turbinates by at least 4.7 logs and in the lungs by 3.4 logs, similar to that achieved by immunization with PIV3. These studies support further testing of recombinant MVA/PIV3 viruses as safe and effective candidate vaccines. JF - Vaccine AU - Wyatt, L S AU - Shors, S T AU - Murphy, B R AU - Moss, B AD - Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0445, USA. Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 1451 EP - 1458 VL - 14 IS - 15 SN - 0264-410X, 0264-410X KW - Antibodies, Viral KW - 0 KW - Vaccines, Synthetic KW - Viral Vaccines KW - Index Medicus KW - Animals KW - Virus Replication -- genetics KW - HeLa Cells KW - Humans KW - Sigmodontinae KW - Antibodies, Viral -- blood KW - Viral Vaccines -- administration & dosage KW - Vaccinia virus -- genetics KW - Vaccinia virus -- immunology KW - Vaccines, Synthetic -- immunology KW - Vaccines, Synthetic -- administration & dosage KW - Respirovirus Infections -- prevention & control KW - Viral Vaccines -- immunology KW - Parainfluenza Virus 3, Human -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78654981?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vaccine&rft.atitle=Development+of+a+replication-deficient+recombinant+vaccinia+virus+vaccine+effective+against+parainfluenza+virus+3+infection+in+an+animal+model.&rft.au=Wyatt%2C+L+S%3BShors%2C+S+T%3BMurphy%2C+B+R%3BMoss%2C+B&rft.aulast=Wyatt&rft.aufirst=L&rft.date=1996-10-01&rft.volume=14&rft.issue=15&rft.spage=1451&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-17 N1 - Date created - 1997-04-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Recent research trends in diagnosis, treatment, and prevention of drug-induced extrapyramidal symptoms seen in psychiatric patients]. AN - 78622273; 8962437 AB - Extrapyramidal symptoms (EPS) induced by neuroleptics (NLP) are still one of the major clinical problems in treating psychiatric patients. The reliability of the drug-induced extrapyramidal symptoms scale (DIEPSS) and the Japanese version of Barnes Akathisia Scale has recently been established, and these scales are used in the clinical psychopharmacological studies performed in Japan. One of the recent research trends of the epidemiological studies on tardive dyskinesia (TD) is characterized by the prospective longitudinal design with older subjects. Although no effective treatment for TD has yet been established, the efficacy of vitamin E for TD has been tested in the USA, while an open clinical trial of rolipram was recently performed in Japan. One of the preventive studies for TD, searching for genetic variations that could act as a marker to identify especially vulnerable patients to TD, is now being conducted by our research group. It is believed that the use of clozapine, an atypical antipsychotic drug, or a serotonin-dopamine antagonist such as risperidone will leave patients free of EPS, however, the real value of these drugs in terms of the effect of reducing EPS, including TD, in Japanese patients requires further evaluation. JF - Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology AU - Inada, T AD - National Institute of Mental Health, National Center of Neurology and Psychiatry, Ichikawa, Japan. Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 181 EP - 185 VL - 16 IS - 5 SN - 1340-2544, 1340-2544 KW - Antipsychotic Agents KW - 0 KW - Index Medicus KW - Humans KW - Aged KW - Male KW - Female KW - Dyskinesia, Drug-Induced -- drug therapy KW - Mental Disorders -- drug therapy KW - Dyskinesia, Drug-Induced -- prevention & control KW - Dyskinesia, Drug-Induced -- diagnosis KW - Antipsychotic Agents -- adverse effects KW - Mental Disorders -- complications KW - Basal Ganglia Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78622273?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+shinkei+seishin+yakurigaku+zasshi+%3D+Japanese+journal+of+psychopharmacology&rft.atitle=%5BRecent+research+trends+in+diagnosis%2C+treatment%2C+and+prevention+of+drug-induced+extrapyramidal+symptoms+seen+in+psychiatric+patients%5D.&rft.au=Inada%2C+T&rft.aulast=Inada&rft.aufirst=T&rft.date=1996-10-01&rft.volume=16&rft.issue=5&rft.spage=181&rft.isbn=&rft.btitle=&rft.title=Nihon+shinkei+seishin+yakurigaku+zasshi+%3D+Japanese+journal+of+psychopharmacology&rft.issn=13402544&rft_id=info:doi/ LA - Japanese DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-19 N1 - Date created - 1997-02-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reduced expression of voltage-gated sodium channels in neurons cultured from trisomy 16 mouse hippocampus. AN - 78618615; 8960982 AB - Voltage-gated sodium channels are responsible for the initial depolarizing phase of the action potential. In hippocampal neurons cultured from trisomy 16 (Ts16) mice (a model for Down's syndrome), the maximum inward conductance mediated by these channels was reduced 47% relative to control diploid neurons. This reduced conductance was reflected in a 35% decrease in binding of radiolabeled saxitoxin, a sodium channel-specific ligand, indicating expression of fewer channels in these neurons. The mRNAs encoding the alpha and beta 1 subunits were, however, present at the same levels in Ts16 neurons and control diploid neurons. Thus, the altered regulation of voltage-gated sodium channels in Ts16 neurons is apparently a post-transcriptional event and possible mechanisms are discussed. JF - International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience AU - Stoll, J AU - Galdzicki, Z AD - Laboratory of Neurosciences, National Institute on Aging, Bethesda, MD, USA. jim@cortex.ama.ttuhsc.edu Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 749 EP - 760 VL - 14 IS - 6 SN - 0736-5748, 0736-5748 KW - Culture Media, Serum-Free KW - 0 KW - RNA, Messenger KW - Sodium Channel Blockers KW - Sodium Channels KW - Tritium KW - 10028-17-8 KW - Saxitoxin KW - 35523-89-8 KW - Tetrodotoxin KW - 4368-28-9 KW - Index Medicus KW - Animals KW - Immunoblotting KW - Cells, Cultured -- chemistry KW - Humans KW - Mice KW - Saxitoxin -- pharmacology KW - Electrophysiology KW - Saxitoxin -- metabolism KW - Pregnancy KW - Ion Channel Gating -- physiology KW - Polymerase Chain Reaction KW - Mice, Mutant Strains KW - RNA, Messenger -- metabolism KW - Mice, Inbred C57BL KW - Cells, Cultured -- physiology KW - Tetrodotoxin -- pharmacology KW - Gene Expression -- physiology KW - Cell Survival -- physiology KW - Female KW - Male KW - Sodium Channels -- genetics KW - Neurons -- chemistry KW - Neurons -- cytology KW - Hippocampus -- cytology KW - Neurons -- physiology KW - Sodium Channels -- metabolism KW - Trisomy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78618615?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+developmental+neuroscience+%3A+the+official+journal+of+the+International+Society+for+Developmental+Neuroscience&rft.atitle=Reduced+expression+of+voltage-gated+sodium+channels+in+neurons+cultured+from+trisomy+16+mouse+hippocampus.&rft.au=Stoll%2C+J%3BGaldzicki%2C+Z&rft.aulast=Stoll&rft.aufirst=J&rft.date=1996-10-01&rft.volume=14&rft.issue=6&rft.spage=749&rft.isbn=&rft.btitle=&rft.title=International+journal+of+developmental+neuroscience+%3A+the+official+journal+of+the+International+Society+for+Developmental+Neuroscience&rft.issn=07365748&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-07 N1 - Date created - 1997-03-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Long-term maintenance of monkey lenses in organ culture: a potential model system for the study of human cataractogenesis. AN - 78572838; 8944549 AB - Lenses from Rhesus monkeys were maintained in protein-free medium and both their biochemical and histological changes were examined. Lenses were dissected under a dissecting microscope to ensure minimal contamination by other ocular tissue, which allowed successful observation of whole lens morphology during culture. Lenses in culture showed no acute leakage of protein into medium, indicating that they had not been physically damaged during dissection. Cultured lenses remained transparent for 21 days without any noticeable histological changes. Even at 21 days of culture, 35S-methionine incorporation into lens protein was approximately 60% of the level observed in fresh lenses. The amounts of most protein species were rather constant in the lens capsule/epithelium throughout culture, but the amount of crystallins gradually decreased during the first 14 days, of culture due to selective decrease in crystallin synthesis. After day 14, both the amount of crystallins and their synthesis became stable. When 30 mM fructose, present in the control medium, was replaced with 30 mM xylose, lens opacification with some histological abnormalities such as vacuole formation was observed. In the xylose-induced cataract, the protein synthetic activity decreased dramatically. This system would be a valuable tool in investigating the mechanisms of lens homeostasis as well as mechanisms of cataractogenesis in primate lens. JF - Experimental eye research AU - Kamiya, T AU - Zigler, J S AD - Laboratory of Mechanisms of Ocular Diseases, National Eye Institute, NIH, Bethesda, MD 20892-2735, USA. Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 425 EP - 431 VL - 63 IS - 4 SN - 0014-4835, 0014-4835 KW - Crystallins KW - 0 KW - Xylose KW - A1TA934AKO KW - Index Medicus KW - Animals KW - Electrophoresis, Polyacrylamide Gel KW - Humans KW - Macaca mulatta KW - Time Factors KW - Organ Culture Techniques KW - Models, Biological KW - Cataract -- pathology KW - Cataract -- metabolism KW - Lens, Crystalline -- metabolism KW - Cataract -- chemically induced KW - Crystallins -- biosynthesis KW - Crystallins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78572838?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+eye+research&rft.atitle=Long-term+maintenance+of+monkey+lenses+in+organ+culture%3A+a+potential+model+system+for+the+study+of+human+cataractogenesis.&rft.au=Kamiya%2C+T%3BZigler%2C+J+S&rft.aulast=Kamiya&rft.aufirst=T&rft.date=1996-10-01&rft.volume=63&rft.issue=4&rft.spage=425&rft.isbn=&rft.btitle=&rft.title=Experimental+eye+research&rft.issn=00144835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-19 N1 - Date created - 1996-12-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Na(+)-K(+)-Cl- cotransport system in brain capillary endothelial cells: response to endothelin and hypoxia. AN - 78558650; 8923488 AB - Effect of endothelin-1 and chemically induced hypoxia on Na(+)-K(+)-Cl- cotransport activity in cultured rat brain capillary endothelial cells was examined by using 86Rb+ as a tracer for K+; bumetanide-sensitive K+ uptake was defined as Na(+)-K(+)-Cl- cotransport activity. Endothelin-1, phorbol 12-myristate 13-acetate (PMA), or thapsigargin increased Na(+)-K(+)-Cl- cotransport activity. A protein kinase C inhibitor, bisindolylmaleimide, inhibited PMA- and endothelin-1- (but not thapsigargin-) induced Na(+)-K(+)-Cl- cotransport activity, indicating the presence of both protein kinase C-dependent regulatory mechanisms and protein kinase C-independent mechanisms which involve intracellular Ca2+. Oligomycin, sodium azide, or antimycin A increased Na(+)-K(+)-Cl- cotransport activity by 80-200%. Oligomycin-induced Na(+)-K(+)-Cl- cotransport activity was reduced by an intracellular Ca2+ chelator (BAPTA/AM) but not affected by bisindolylmaleimide, suggesting the involvement of intracellular Ca2+, and not protein kinase C, in hypoxia-induced Na(+)-K(+)-Cl- cotransport activity. JF - Neurochemical research AU - Kawai, N AU - McCarron, R M AU - Spatz, M AD - Stroke Branch, National Institute of Neurological Disease and Stroke, National Institutes of Health, Bethesda, Maryland 20892-4128, USA. Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 1259 EP - 1266 VL - 21 IS - 10 SN - 0364-3190, 0364-3190 KW - Carrier Proteins KW - 0 KW - Chlorides KW - Endothelin-1 KW - Enzyme Inhibitors KW - Indoles KW - Maleimides KW - Membrane Proteins KW - Sodium-Potassium-Chloride Symporters KW - Thapsigargin KW - 67526-95-8 KW - Sodium KW - 9NEZ333N27 KW - bisindolylmaleimide KW - MBK3OO5K8T KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Potassium KW - RWP5GA015D KW - Index Medicus KW - Animals KW - Endothelium, Vascular -- metabolism KW - Endothelium, Vascular -- cytology KW - Thapsigargin -- pharmacology KW - Rats KW - Cells, Cultured KW - Hypoxia, Brain -- metabolism KW - Enzyme Inhibitors -- pharmacology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Indoles -- pharmacology KW - Endothelin-1 -- pharmacology KW - Maleimides -- pharmacology KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- drug effects KW - Membrane Proteins -- metabolism KW - Brain -- blood supply KW - Chlorides -- metabolism KW - Brain -- metabolism KW - Membrane Proteins -- drug effects KW - Potassium -- metabolism KW - Sodium -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78558650?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurochemical+research&rft.atitle=Na%28%2B%29-K%28%2B%29-Cl-+cotransport+system+in+brain+capillary+endothelial+cells%3A+response+to+endothelin+and+hypoxia.&rft.au=Kawai%2C+N%3BMcCarron%2C+R+M%3BSpatz%2C+M&rft.aulast=Kawai&rft.aufirst=N&rft.date=1996-10-01&rft.volume=21&rft.issue=10&rft.spage=1259&rft.isbn=&rft.btitle=&rft.title=Neurochemical+research&rft.issn=03643190&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-14 N1 - Date created - 1997-05-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human DNA adduct measurements: state of the art. AN - 78558178; 8933030 AB - Human DNA adduct formation (covalent modification of DNA with chemical carcinogens) is a promising biomarker for elucidating the molecular epidemiology of cancer. Classes of compounds for which human DNA adducts have been observed include polycyclic aromatic hydrocarbons (PAHs), nitrosamines, mycotoxins, aromatic amines, heterocyclic amines, ultraviolet light, and alkylating cancer chemotherapeutic agents. Most human DNA adduct exposure monitoring has been performed with either 32P-postlabeling or immunoassays, neither of which is able to chemically characterize specific DNA adducts. Recently developed combinations of methods with chemical and physical end points have allowed identification of specific adducts in human tissues. Studies are presented that demonstrate that high ambient levels of benzo[a]pyrene are associated with high levels of DNA adducts in human blood cell DNA and that the same DNA adduct levels drop when the ambient PAH levels decrease significantly. DNA adduct dosimetry, which has been achieved with some dietary carcinogens and cancer chemotherapeutic agents, is described, as well as studies correlating DNA adducts with other biomarkers. It is likely that some toxic, noncarcinogenic compounds may have genotoxic effects, including oxidative damage, and that adverse health outcomes other than cancer may be correlated with DNA adduct formation. The studies presented here may serve as useful prototypes for exploration of other toxicological end points. JF - Environmental health perspectives AU - Poirier, M C AU - Weston, A AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892, USA. poirierm@dc37a.nci.nih.gov Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 883 EP - 893 VL - 104 Suppl 5 SN - 0091-6765, 0091-6765 KW - Biomarkers KW - 0 KW - DNA Adducts KW - Index Medicus KW - Luminescent Measurements KW - Humans KW - Gas Chromatography-Mass Spectrometry KW - Immunoassay KW - Environmental Monitoring KW - DNA Adducts -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78558178?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Human+DNA+adduct+measurements%3A+state+of+the+art.&rft.au=Poirier%2C+M+C%3BWeston%2C+A&rft.aulast=Poirier&rft.aufirst=M&rft.date=1996-10-01&rft.volume=104+Suppl+5&rft.issue=&rft.spage=883&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 - 1997-02-21 N1 - Date created - 1997-02-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mutat Res. 1993 Jul;288(1):19-29 [7686262] Mutat Res. 1993 Jul;288(1):5-18 [7686266] Cancer Epidemiol Biomarkers Prev. 1992 Mar-Apr;1(3):221-7 [1339082] Environ Health Perspect. 1993 Mar;99:143-7 [8319612] Environ Health Perspect. 1993 Mar;99:257-9 [8319638] Environ Health Perspect. 1993 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Oct;82(19):6492-6 [3931076] Proc Natl Acad Sci U S A. 1985 Oct;82(19):6672-6 [2413443] Int J Cancer. 1985 Dec 15;36(6):661-5 [4066072] Carcinogenesis. 1986 Jan;7(1):49-52 [3943144] Environ Health Perspect. 1985 Oct;62:89-94 [4085451] Environ Health Perspect. 1985 Oct;62:95-9 [4085452] J Clin Invest. 1986 Feb;77(2):545-50 [3944268] Cancer Res. 1986 Jul;46(7):3249-53 [3085918] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Introduction to the conference on beryllium-related diseases. AN - 78557589; 8933037 JF - Environmental health perspectives AU - Jameson, C W AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. jameson@niehs.nih.gov Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 935 EP - 936 VL - 104 Suppl 5 SN - 0091-6765, 0091-6765 KW - Biomarkers KW - 0 KW - Beryllium KW - OW5102UV6N KW - Index Medicus KW - Humans KW - Berylliosis -- prevention & control KW - Beryllium -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78557589?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Introduction+to+the+conference+on+beryllium-related+diseases.&rft.au=Jameson%2C+C+W&rft.aulast=Jameson&rft.aufirst=C&rft.date=1996-10-01&rft.volume=104+Suppl+5&rft.issue=&rft.spage=935&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 - 1997-02-21 N1 - Date created - 1997-02-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am Rev Respir Dis. 1989 Jun;139(6):1479-86 [2729754] Clin Diagn Lab Immunol. 1994 Mar;1(2):164-71 [7496939] Science. 1993 Oct 8;262(5131):242-4 [8105536] Lab Invest. 1992 Jul;67(1):138-46 [1625444] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Predictions for the outcome of rodent carcinogenicity bioassays: identification of trans-species carcinogens and noncarcinogens. AN - 78557506; 8933059 AB - Thirty chemicals or substances currently undergoing long-term carcinogenicity bioassays in rodents have been used in a project to further evaluate methods and information that may have the capability of predicting potential carcinogens. In our predictions the principal information used includes structural alerts and in vitro test results for Salmonella mutagenicity, relative subchronic toxicity, and the sites and types of pathology found in subchronic (90-day) studies. This group of chemicals differs significantly from those used previously to evaluate predictive methods in that 23 of 30 are defined as nonmutagenic by conventional criteria. The goal of this predictive effort is to identify categorically the chemicals that have the capacity to induce cancers in both rats and mice (trans-species carcinogens) and those that are not carcinogenic in either rats or mice. Chemicals that show properties that may be associated with tumor induction in either species, i.e., species-specific cancers, are categorized as being of "uncertain predictability." This category includes chemicals believed to have limited carcinogenic potential that is manifested principally as a consequence of the genetic background of the test strain of inbred rodent. JF - Environmental health perspectives AU - Tennant, R W AU - Spalding, J AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. tennant@niehs.nih.gov Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 1095 EP - 1100 VL - 104 Suppl 5 SN - 0091-6765, 0091-6765 KW - Carcinogens KW - 0 KW - Index Medicus KW - Rats KW - Animals KW - Mice KW - Species Specificity KW - Carcinogens -- toxicity KW - Carcinogenicity Tests UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78557506?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Predictions+for+the+outcome+of+rodent+carcinogenicity+bioassays%3A+identification+of+trans-species+carcinogens+and+noncarcinogens.&rft.au=Tennant%2C+R+W%3BSpalding%2C+J&rft.aulast=Tennant&rft.aufirst=R&rft.date=1996-10-01&rft.volume=104+Suppl+5&rft.issue=&rft.spage=1095&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 - 1997-02-21 N1 - Date created - 1997-02-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mutat Res. 1995 Dec;333(1-2):101-9 [8538617] Toxicol Lett. 1995 Dec;82-83:673-81 [8597126] Environ Mutagen. 1986;8(2):205-27 [3698943] Mutagenesis. 1990 Jan;5(1):3-14 [2184307] Annu Rev Pharmacol Toxicol. 1990;30:349-67 [1693054] Nature. 1990 Oct 18;347(6294):645-50 [2129546] Environ Health Perspect. 1995 Oct;103(10):942-50 [8529591] Mutat Res. 1993 Mar;286(1):111-8 [7678907] Environ Health Perspect. 1993 Mar;99:313-49 [7686485] Environ Health Perspect. 1993 Oct;101(5):444-5 [8119256] Mutagenesis. 1994 Jan;9(1):7-15 [8208133] Environ Health Perspect. 1995 Jan;103(1):44-52 [7628425] Mutat Res. 1991 May;257(3):229-306 [1707500] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Trial of Calcium for Preeclampsia Prevention (CPEP): rationale, design, and methods. AN - 78557395; 8932976 AB - The results of ten clinical trials suggest that supplemental calcium may prevent preeclampsia. However, methodologic problems and differences in study design limit the acceptance of the results and their relevance to other patient populations. Many of the trials were conducted in countries where, unlike the United States, the usual daily diet contained little calcium. Moreover, none of the trials has reported the outcome of systematic surveillance for urolithiasis, a potential complication of calcium supplementation. In response to the need for a thorough evaluation of the effects of calcium supplementation for the prevention of preeclampsia in the United States, the trial of Calcium for Preeclampsia Prevention (CPEP) was undertaken at five university medical centers. Healthy nulliparous patients were randomly assigned to receive either 2 g supplemental calcium daily (n = 2295) or placebo (n = 2294) in a double-blind study. Study tablets were administered beginning from 13 to 21 completed weeks of gestation and continued until the termination of pregnancy. CPEP employed detailed diagnostic criteria, standardized techniques of measurement, and systematic surveillance for the major study endpoints and for urolithiasis. The nutrient intake of each patient was assessed at randomization and at 32-33 weeks gestation. This report describes the study rationale, design, and methods. JF - Controlled clinical trials AU - Levine, R J AU - Esterlitz, J R AU - Raymond, E G AU - DerSimonian, R AU - Hauth, J C AU - Ben Curet, L AU - Sibai, B M AU - Catalano, P M AU - Morris, C D AU - Clemens, J D AU - Ewell, M G AU - Friedman, S A AU - Goldenberg, R L AU - Jacobson, S L AU - Joffe, G M AU - Klebanoff, M A AU - Petrulis, A S AU - Rigau-Perez, J G AD - National Institute of Child Health and Human Development, Division of Epidemiology, Statistics, and Prevention Research, Bethesda, MD 20892, USA. Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 442 EP - 469 VL - 17 IS - 5 SN - 0197-2456, 0197-2456 KW - Placebos KW - 0 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - United States KW - Severity of Illness Index KW - Urinary Calculi -- prevention & control KW - Management Information Systems KW - Double-Blind Method KW - Urinary Calculi -- etiology KW - Random Allocation KW - Nutrition Assessment KW - Humans KW - Urinary Calculi -- diagnosis KW - Patient Selection KW - Pregnancy KW - Hypertension -- diagnosis KW - Patient Compliance KW - Pregnancy Complications, Cardiovascular -- diagnosis KW - Statistics as Topic KW - Sample Size KW - Quality Control KW - Female KW - Calcium -- adverse effects KW - Pre-Eclampsia -- prevention & control KW - Multicenter Studies as Topic -- methods KW - Pre-Eclampsia -- diagnosis KW - Multicenter Studies as Topic -- statistics & numerical data KW - Calcium -- therapeutic use KW - Research Design KW - Randomized Controlled Trials as Topic -- methods KW - Randomized Controlled Trials as Topic -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78557395?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Controlled+clinical+trials&rft.atitle=Trial+of+Calcium+for+Preeclampsia+Prevention+%28CPEP%29%3A+rationale%2C+design%2C+and+methods.&rft.au=Levine%2C+R+J%3BEsterlitz%2C+J+R%3BRaymond%2C+E+G%3BDerSimonian%2C+R%3BHauth%2C+J+C%3BBen+Curet%2C+L%3BSibai%2C+B+M%3BCatalano%2C+P+M%3BMorris%2C+C+D%3BClemens%2C+J+D%3BEwell%2C+M+G%3BFriedman%2C+S+A%3BGoldenberg%2C+R+L%3BJacobson%2C+S+L%3BJoffe%2C+G+M%3BKlebanoff%2C+M+A%3BPetrulis%2C+A+S%3BRigau-Perez%2C+J+G&rft.aulast=Levine&rft.aufirst=R&rft.date=1996-10-01&rft.volume=17&rft.issue=5&rft.spage=442&rft.isbn=&rft.btitle=&rft.title=Controlled+clinical+trials&rft.issn=01972456&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-13 N1 - Date created - 1997-03-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Air toxics regulatory issues facing urban settings. AN - 78554097; 8933026 AB - Biomarker research does not exist in isolation. Its usefulness can only be realized when it is translated into prevention strategies to protect public health. In the context of air toxics, these prevention strategies begin with the development of regulatory standards derived from risk assessment schemes. The Clean Air Act Amendments of 1990 list 189 air toxics, including many volatile organics, metals, and pesticides. The National Institute of Environmental Health Sciences (NIEHS), through its affiliation with the National Toxicology Program, has generated toxicity and carcinogenicity data on more than 100 of these air toxics. The NIEHS extramural and intramural research portfolios support a variety of projects that develop and validate biomarkers for use in environmental health science and risk assessment. Biomarkers have a tremendous potential in the areas of regulating air toxics and protecting public health. Risk assessors need data provided by biomarkers of exposure, biomarkers of dose/pharmacokinetics, biomarkers of susceptibility or individual variability, and biomarkers of effects. The greatest benefit would be realized if biomarkers could be employed in four areas of primary and secondary prevention. The first is the use of biomarkers to enhance extrapolation of animal data to human exposure situations in establishing risk standards. The second is the use of biomarkers that assess noncancer, as well as cancer, end points. Important health end points include pulmonary dysfunction, immunotoxicity, and neurotoxicity. Third, biomarkers that serve as early waming signs to detect intermediate effects would enhance our ability to design timely and cost-effective intervention strategies. Finally, biomarkers used to evaluate the effectiveness of intervention strategies, both in clinical and regulatory settings, would enable us to ensure that programs designed to protect public health do, in fact, achieve the desired outcome. JF - Environmental health perspectives AU - Olden, K AU - Guthrie, J AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 857 EP - 860 VL - 104 Suppl 5 SN - 0091-6765, 0091-6765 KW - Air Pollutants KW - 0 KW - Biomarkers KW - Index Medicus KW - Information Systems KW - Urban Health KW - Humans KW - Risk Assessment KW - Air Pollutants -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78554097?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Air+toxics+regulatory+issues+facing+urban+settings.&rft.au=Olden%2C+K%3BGuthrie%2C+J&rft.aulast=Olden&rft.aufirst=K&rft.date=1996-10-01&rft.volume=104+Suppl+5&rft.issue=&rft.spage=857&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 - 1997-02-21 N1 - Date created - 1997-02-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer Res. 1993 Feb 1;53(3):460-3 [8425177] Nature. 1992 Nov 19;360(6401):256-8 [1436106] Annu Rev Pharmacol Toxicol. 1991;31:321-37 [2064378] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Results of lead research: prenatal exposure and neurological consequences. AN - 78547505; 8930545 AB - The history of advances in the understanding of the toxic effects of lead over the past 20 years is an outstanding example of how knowledge learned from research can impact public health. Measures that have had the greatest impact on reducing exposure to lead are reduction of lead from gasoline, elimination of lead solder from canned food, removal of lead from paint, and abatement of housing containing lead-based paint. Nevertheless, continuing factors that enhance risk to lead exposure, particularly during fetal life, are low socioeconomic status, old housing with lead-containing paint, and less than ideal nutrition, particularly low dietary intake of calcium, iron, and zinc. Prenatal exposure may result from endogenous sources such as lead in the maternal skeletal system or maternal exposures from diet and the environment. Experimental studies have shown that the developing nervous system is particularly sensitive to the toxic effects of lead and that a large number of the effects in the nervous system are due to interference of lead with biochemical functions dependent on calcium ions and impairment of neuronal connections dependent on dendritic pruning. There is need for more study to determine whether these effects are a continuum of prenatal lead exposure or whether prenatal exposure to lead produces unique effects. JF - Environmental health perspectives AU - Goyer, R A AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 1050 EP - 1054 VL - 104 IS - 10 SN - 0091-6765, 0091-6765 KW - Lead KW - 2P299V784P KW - Index Medicus KW - Animals KW - Humans KW - Female KW - Pregnancy KW - Fetus -- drug effects KW - Lead -- toxicity KW - Brain -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78547505?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Results+of+lead+research%3A+prenatal+exposure+and+neurological+consequences.&rft.au=Goyer%2C+R+A&rft.aulast=Goyer&rft.aufirst=R&rft.date=1996-10-01&rft.volume=104&rft.issue=10&rft.spage=1050&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 - 1997-02-20 N1 - Date created - 1997-02-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Lab Clin Med. 1972 Jan;79(1):128-36 [5007557] Environ Health Perspect. 1994 Oct;102(10):876-80 [9644197] Environ Health Perspect. 1978 Aug;25:141-5 [569050] Int Arch Occup Environ Health. 1979 Jan 15;42(3-4):341-8 [422275] Proc Soc Exp Biol Med. 1980 Feb;163(2):278-82 [7360758] Behav Neural Biol. 1981 Jul;32(3):319-33 [7283922] Neurotoxicology. 1983 Spring;4(1):1-17 [6308527] Experientia. 1983 Sep 15;39(9):1030-1 [6884491] Environ Res. 1986 Oct;41(1):327-38 [3489614] N Engl J Med. 1987 Apr 23;316(17):1037-43 [3561456] J Neurochem. 1987 Aug;49(2):399-403 [3598579] Br Med Bull. 1986 Oct;42(4):431-4 [3308000] Toxicol Appl Pharmacol. 1987 Oct;91(1):132-9 [2823415] Neurosci Lett. 1988 Mar 21;86(1):33-7 [2896324] N Engl J Med. 1988 Aug 25;319(8):468-75 [3405253] Toxicol Appl Pharmacol. 1988 Oct;96(1):14-23 [3188018] Am J Clin Nutr. 1989 Sep;50(3 Suppl):687-96; discussion 696-7 [2773846] Neurotoxicol Teratol. 1990 May-Jun;12(3):215-29 [2196421] Environ Health Perspect. 1990 Nov;89:101-5 [2088735] Environ Health Perspect. 1990 Nov;89:95-100 [2088762] Neurotoxicol Teratol. 1992 Jul-Aug;14(4):235-45 [1522828] FASEB J. 1992 Oct;6(13):3201-6 [1397842] Environ Health Perspect. 1993 Apr;100:177-87 [8354166] Eur J Pharmacol. 1993 Oct 1;248(3):273-5 [8293792] JAMA. 1994 Jul 27;272(4):284-91 [8028141] Am J Ind Med. 1994 Jul;26(1):13-32 [8074121] Neurotoxicol Teratol. 1994 May-Jun;16(3):233-40 [7523846] Am J Clin Nutr. 1995 Mar;61(3 Suppl):646S-650S [7879732] Epidemiology. 1995 Mar;6(2):104-9 [7742393] J Lab Clin Med. 1995 Jun;125(6):703-12 [7769364] Neurotoxicol Teratol. 1995 May-Jun;17(3):201-12 [7542726] Neurotoxicol Teratol. 1995 May-Jun;17(3):219-21; discussion 249-51 [7542729] Environ Health Perspect. 1995 Nov;103(11):1048-52 [8605855] Environ Health Perspect. 1996 Jan;104(1):60-6 [8834863] Brain Res. 1978 May 19;147(1):131-8 [656908] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacological and neurochemical differences between acute and tardive vacuous chewing movements induced by haloperidol. AN - 78544535; 8923569 AB - Late onset vacuous chewing movements (VCMs) from chronic neuroleptic treatment have been used as a rat model of tardive dyskinesia (TD). Early onset VCMs have also been observed, raising questions about the validity of this model. To assess the relationship between these two types of VCMs, pharmacological and neurochemical properties of early and late onset VCMs were compared. "Acute" VCMs were induced by daily intraperitoneal injections for 1-21 days. "Tardive" VCMs were induced by intramuscular injections of haloperidol decanoate every 3 weeks for 30 weeks followed by a 24-week withdrawal period. Suppression was attempted for both types of VCMs using several doses of intraperitoneal haloperidol. Striatonigral activation was assessed by measuring mRNA expression levels of the neuropeptides dynorphin and substance P using in situ hybridization histochemistry. Enkephalin mRNA was also measured as an index of striatopallidal activation. The results indicate that acute VCMs cannot be suppressed with increased doses of haloperidol and are associated with reduced dynorphin and substance P. This profile is similar to that seen with an animal model of parkinsonism. Tardive VCMs, in contrast, were markedly suppressed by haloperidol. They have previously been shown to be associated with increased striatonigral activation as indicated by increased dynorphin mRNA. Enkephalin mRNA was elevated following both short and long term treatment. Although superficially similar, acute and tardive VCMs appear to have different pharmacological and neurochemical profiles, suggesting they are related to acute extrapyramidal side effects and tardive dyskinesia, respectively. JF - Psychopharmacology AU - Egan, M F AU - Hurd, Y AU - Ferguson, J AU - Bachus, S E AU - Hamid, E H AU - Hyde, T M AD - Clinical Research Services, National Institute of Mental Health, NIMH Neuroscience Research Center at St. Elizabeths, Washington, DC 20032, USA. Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 337 EP - 345 VL - 127 IS - 4 SN - 0033-3158, 0033-3158 KW - Antipsychotic Agents KW - 0 KW - Enkephalins KW - RNA, Messenger KW - Substance P KW - 33507-63-0 KW - Dynorphins KW - 74913-18-1 KW - Haloperidol KW - J6292F8L3D KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - In Situ Hybridization KW - Nucleus Accumbens -- drug effects KW - RNA, Messenger -- analysis KW - Nucleus Accumbens -- metabolism KW - Enkephalins -- metabolism KW - Male KW - Behavior, Animal -- drug effects KW - Corpus Striatum -- metabolism KW - Mastication -- drug effects KW - Substance P -- metabolism KW - Corpus Striatum -- drug effects KW - Dyskinesia, Drug-Induced -- etiology KW - Dynorphins -- metabolism KW - Haloperidol -- toxicity KW - Antipsychotic Agents -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78544535?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology&rft.atitle=Pharmacological+and+neurochemical+differences+between+acute+and+tardive+vacuous+chewing+movements+induced+by+haloperidol.&rft.au=Egan%2C+M+F%3BHurd%2C+Y%3BFerguson%2C+J%3BBachus%2C+S+E%3BHamid%2C+E+H%3BHyde%2C+T+M&rft.aulast=Egan&rft.aufirst=M&rft.date=1996-10-01&rft.volume=127&rft.issue=4&rft.spage=337&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-03-25 N1 - Date created - 1997-03-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Strategies for identification and clinical evaluation of promising chemopreventive agents. AN - 78509637; 8905841 AB - Strategies for chemopreventative drug development are based on the use of well-characterized agents, intermediate biomarkers correlating to cancer incidence, and suitable cohorts for efficacy studies. Since chemoprevention is applied over the long-term, chemopreventive drugs must have low toxicity. Strategies for enhancing chemopreventive drug efficacy and minimizing toxicity include combinations of drugs with complementary mechanisms and/or synergistic activity; coadministration of drugs to counter the toxicity of the chemopreventive agents; and pursuit of related compounds that retain efficacy with reduced side effects. Because of its slow development, cancer is not a feasible end point for clinical evaluation of chemoprevention, and so intermediate biomarkers that can serve as surrogate end points are crucial. Particularly important biomarkers are the morphometric and cytometric changes defining intraepithelial neoplasia (IEN). Cohorts for chemoprevention trials should have high incidences of the cancer or intermediate biomarker(s) under study within the trial duration. JF - Oncology (Williston Park, N.Y.) AU - Kelloff, G J AU - Hawk, E T AU - Crowell, J A AU - Boone, C W AU - Nayfield, S G AU - Perloff, M AU - Steele, V E AU - Lubet, R A AD - Chemoprevention Branch, National Cancer Institute National Institutes of Health Bethesda, Maryland, USA. Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 1471 EP - 84; discussion 1484-8 VL - 10 IS - 10 SN - 0890-9091, 0890-9091 KW - Biomarkers, Tumor KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Clinical Trials as Topic KW - Chemoprevention -- methods KW - Neoplasms -- diagnosis KW - Neoplasms -- prevention & control KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78509637?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncology+%28Williston+Park%2C+N.Y.%29&rft.atitle=Strategies+for+identification+and+clinical+evaluation+of+promising+chemopreventive+agents.&rft.au=Kelloff%2C+G+J%3BHawk%2C+E+T%3BCrowell%2C+J+A%3BBoone%2C+C+W%3BNayfield%2C+S+G%3BPerloff%2C+M%3BSteele%2C+V+E%3BLubet%2C+R+A&rft.aulast=Kelloff&rft.aufirst=G&rft.date=1996-10-01&rft.volume=10&rft.issue=10&rft.spage=1471&rft.isbn=&rft.btitle=&rft.title=Oncology+%28Williston+Park%2C+N.Y.%29&rft.issn=08909091&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-14 N1 - Date created - 1997-02-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pathogenesis of the antiphospholipid antibody syndrome. AN - 78504141; 8902770 AB - Endothelial and/or platelet activation likely initiates thrombus formation. Whether antiphospholipid antibody (aPL) is an activator, a toxic response, or a protective response is not clear, nor is it certain whether aPL is germ-line encoded or antigen-driven. The pregnancy model is particularly informative. Alternative hypotheses about thrombogenicity which relegate aPL to the role of bystander have not yet been excluded. JF - Lupus AU - Lockshin, M D AD - Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 404 EP - 408 VL - 5 IS - 5 SN - 0961-2033, 0961-2033 KW - Index Medicus KW - Abortion, Spontaneous -- etiology KW - Endothelium, Vascular -- cytology KW - Humans KW - Blood Platelets -- physiology KW - Female KW - Pregnancy KW - Antiphospholipid Syndrome -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78504141?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lupus&rft.atitle=Pathogenesis+of+the+antiphospholipid+antibody+syndrome.&rft.au=Lockshin%2C+M+D&rft.aulast=Lockshin&rft.aufirst=M&rft.date=1996-10-01&rft.volume=5&rft.issue=5&rft.spage=404&rft.isbn=&rft.btitle=&rft.title=Lupus&rft.issn=09612033&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-12 N1 - Date created - 1997-02-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of perturbations of the hypothalamic-pituitary-adrenal axis on the acute phase response: altered C/EBP and acute phase response gene expression in lipopolysaccharide-treated rats. AN - 78500603; 8902947 AB - In this study, we investigated the influence of long term perturbations of the hypothalamicpituitary-adrenal axis on the acute phase response elicited following lipopolysaccharide (LPS) challenge in rats. Specifically, we examined the effects of either long term absence of glucocorticoids (adrenalectomized rats treated with placebo chronic release pellets) or extended exposure to pharmacologic levels of glucocorticoids (adrenalectomized rats treated with dexamethasone chronic release pellets) on the expression of selected acute phase proteins and various members of the CCAAT/enhancer-binding protein (C/EBP) family of transcription factors. Both hypothalamic-pituitary-adrenal axis manipulations resulted in a reduction of the acute phase response as assessed by the LPS-mediated induction of acute phase proteins and C/EBP gene expression, with dexamethasone treatment exhibiting a greater inhibitory effect than adrenalectomy. Induction of hemopexin, alpha 1-acid glycoprotein, alpha 2-macroglobulin, GADD153, C/EBP beta, and C/EBP delta mRNAs by LPS were all abolished in dexamethasone-treated rats. These findings have direct implications for patients undergoing chronic high dose glucocorticoid therapy. JF - Shock (Augusta, Ga.) AU - Eastman, H B AU - Fawcett, T W AU - Udelsman, R AU - Holbrook, N J AD - Gene Expression and Aging Section, National institute on Aging, Baltimore, Maryland 21224, USA. Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 286 EP - 292 VL - 6 IS - 4 SN - 1073-2322, 1073-2322 KW - Acute-Phase Proteins KW - 0 KW - CCAAT-Enhancer-Binding Proteins KW - DNA-Binding Proteins KW - Glucocorticoids KW - Lipopolysaccharides KW - Nuclear Proteins KW - Dexamethasone KW - 7S5I7G3JQL KW - Corticosterone KW - W980KJ009P KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Dexamethasone -- pharmacology KW - Dexamethasone -- administration & dosage KW - Liver -- metabolism KW - Lung -- metabolism KW - Adrenalectomy KW - Rats KW - Corticosterone -- blood KW - Liver -- drug effects KW - Acute-Phase Reaction -- metabolism KW - Rats, Wistar KW - Lung -- drug effects KW - Corticosterone -- pharmacology KW - Male KW - Hypothalamo-Hypophyseal System -- drug effects KW - Glucocorticoids -- metabolism KW - Nuclear Proteins -- genetics KW - Acute-Phase Proteins -- genetics KW - DNA-Binding Proteins -- genetics KW - Lipopolysaccharides -- toxicity KW - Hypothalamo-Hypophyseal System -- metabolism KW - Glucocorticoids -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78500603?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Shock+%28Augusta%2C+Ga.%29&rft.atitle=Effects+of+perturbations+of+the+hypothalamic-pituitary-adrenal+axis+on+the+acute+phase+response%3A+altered+C%2FEBP+and+acute+phase+response+gene+expression+in+lipopolysaccharide-treated+rats.&rft.au=Eastman%2C+H+B%3BFawcett%2C+T+W%3BUdelsman%2C+R%3BHolbrook%2C+N+J&rft.aulast=Eastman&rft.aufirst=H&rft.date=1996-10-01&rft.volume=6&rft.issue=4&rft.spage=286&rft.isbn=&rft.btitle=&rft.title=Shock+%28Augusta%2C+Ga.%29&rft.issn=10732322&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-24 N1 - Date created - 1997-02-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant immunotoxins: protein engineering for cancer therapy. AN - 78498896; 8897439 AB - Recombinant immunotoxins for cancer therapy are composed of the variable regions of 'cancer-specific' antibodies fused to truncated toxins that are usually derived from bacteria or plants. Protein engineering has been used to modify these molecules so that the toxin moiety by itself does not bind to normal human cells, but retains all other cytotoxic functions. The antibody moiety directs the toxin selectively to cancer cells, which are killed; cells that do not carry that particular cancer antigen are not recognized and are therefore spared. Many recombinant immunotoxins show a high degree of cytotoxic activity and specificity towards cancer cells cultured in vitro and have been shown to cause the regression of human tumor xenografts grown in mice. Clinical trials that are in progress will show whether these promising pre-clinical results can be translated into successful cancer therapy. JF - Molecular medicine today AU - Brinkmann, U AD - Laboratory of molecular biology, National Institutes of Health, National Cancer Institute, Bethesda, MD 20892-4255, USA. uli@helix.nih.gov Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 439 EP - 446 VL - 2 IS - 10 SN - 1357-4310, 1357-4310 KW - Antibodies, Monoclonal KW - 0 KW - Antigens KW - Bacterial Toxins KW - Exotoxins KW - Growth Substances KW - Immunoglobulin Fab Fragments KW - Immunoglobulin Variable Region KW - Immunotoxins KW - Recombinant Fusion Proteins KW - Virulence Factors KW - immunotoxin LMB-7 KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Animals KW - Growth Substances -- genetics KW - Exotoxins -- pharmacology KW - Leukemia -- therapy KW - Models, Molecular KW - Humans KW - Immunoglobulin Variable Region -- immunology KW - Mice KW - Growth Substances -- metabolism KW - Antibodies, Monoclonal -- immunology KW - Antibodies, Monoclonal -- therapeutic use KW - Lymphoma -- therapy KW - Protein Engineering KW - Immunoglobulin Fab Fragments -- immunology KW - Antigens -- immunology KW - Immunotoxins -- chemistry KW - Recombinant Fusion Proteins -- genetics KW - Immunotoxins -- therapeutic use KW - Immunotoxins -- genetics KW - Immunotoxins -- metabolism KW - Neoplasms -- therapy KW - Recombinant Fusion Proteins -- therapeutic use KW - Recombinant Fusion Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78498896?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+today&rft.atitle=Recombinant+immunotoxins%3A+protein+engineering+for+cancer+therapy.&rft.au=Brinkmann%2C+U&rft.aulast=Brinkmann&rft.aufirst=U&rft.date=1996-10-01&rft.volume=2&rft.issue=10&rft.spage=439&rft.isbn=&rft.btitle=&rft.title=Molecular+medicine+today&rft.issn=13574310&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-05 N1 - Date created - 1997-02-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Crystal structure of human interleukin-10 at 1.6 A resolution and a model of a complex with its soluble receptor. AN - 78497408; 8897595 AB - The crystal structure of human interleukin-10 (IL-10) was refined at 1.6 A resolution against X-ray diffraction data collected at 100 K with the use of synchrotron radiation. Although similar to the IL-10 structure determined previously at room temperature, this low-temperature IL-10 structure contains, in addition, four N-terminal residues, three sulfate anions, and 175 extra water molecules. Whereas the main-chain conformation is preserved, about 30% of the side chains, most of them on the protein surface, assume different conformations. A computer model of a complex of IL-10 with its two soluble receptors was generated based on the topological similarity of IL-10 to interferon-gamma. The contact region between the cytokine and each receptor shows excellent complementarity of polar and hydrophobic interactions, suggesting that the model is generally correct and should be useful in guiding mutagenesis experiments. JF - Protein science : a publication of the Protein Society AU - Zdanov, A AU - Schalk-Hihi, C AU - Wlodawer, A AD - Macromolecular Structure Laboratory, NCI-Frederick Cancer Research and Development Center, ABL-Basic Research Program, Frederick, Maryland 21702, USA. Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 1955 EP - 1962 VL - 5 IS - 10 SN - 0961-8368, 0961-8368 KW - Macromolecular Substances KW - 0 KW - Receptors, Interleukin KW - Receptors, Interleukin-10 KW - Interleukin-10 KW - 130068-27-8 KW - Interferon-gamma KW - 82115-62-6 KW - Index Medicus KW - Sequence Alignment KW - Models, Molecular KW - Humans KW - Temperature KW - Molecular Sequence Data KW - Interferon-gamma -- chemistry KW - Crystallography, X-Ray KW - Amino Acid Sequence KW - Protein Binding KW - Binding Sites KW - Interleukin-10 -- chemistry KW - Receptors, Interleukin -- metabolism KW - Interleukin-10 -- metabolism KW - Receptors, Interleukin -- chemistry KW - Protein Conformation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78497408?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+science+%3A+a+publication+of+the+Protein+Society&rft.atitle=Crystal+structure+of+human+interleukin-10+at+1.6+A+resolution+and+a+model+of+a+complex+with+its+soluble+receptor.&rft.au=Zdanov%2C+A%3BSchalk-Hihi%2C+C%3BWlodawer%2C+A&rft.aulast=Zdanov&rft.aufirst=A&rft.date=1996-10-01&rft.volume=5&rft.issue=10&rft.spage=1955&rft.isbn=&rft.btitle=&rft.title=Protein+science+%3A+a+publication+of+the+Protein+Society&rft.issn=09618368&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-05-19 N1 - Date created - 1997-05-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Exp Med. 1993 Sep 1;178(3):1041-8 [8102388] Annu Rev Immunol. 1993;11:165-90 [8386517] Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11267-71 [8248239] J Immunol. 1994 Feb 15;152(4):1821-9 [8120391] Trends Microbiol. 1994 Apr;2(4):125-30 [8012755] J Biol Chem. 1994 Sep 16;269(37):23286-9 [8083235] J Mol Biol. 1994 Sep 30;242(4):309-20 [7932691] Nature. 1994 Dec 1;372(6505):478-81 [7984244] Science. 1995 Jan 20;267(5196):383-6 [7529940] J Biol Chem. 1995 May 26;270(21):12906-11 [7759550] Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5401-5 [7777519] Blood. 1995 Jun 15;85(12):3577-85 [7540068] Nature. 1995 Jul 20;376(6537):230-5 [7617032] J Mol Biol. 1995 Dec 15;254(5):795-800 [7500350] Structure. 1995 Jun 15;3(6):591-601 [8590020] Methods Enzymol. 1985;115:157-71 [3841179] Proc Natl Acad Sci U S A. 1989 Sep;86(17):6592-6 [2771946] Cell Immunol. 1990 Aug;129(1):228-40 [2194678] Proc Natl Acad Sci U S A. 1990 Sep;87(18):6934-8 [2169613] J Immunol. 1990 Dec 15;145(12):4167-73 [2124236] J Exp Med. 1991 Feb 1;173(2):507-10 [1899106] Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1172-6 [1847510] Science. 1991 May 3;252(5006):698-702 [1902591] J Biol Chem. 1991 Nov 15;266(32):21791-7 [1939201] J Exp Med. 1991 Nov 1;174(5):1209-20 [1940799] J Exp Med. 1992 Mar 1;175(3):671-82 [1371300] Biochemistry. 1992 Mar 10;31(9):2469-81 [1547232] Science. 1992 Jan 17;255(5042):306-12 [1549776] J Biol Chem. 1993 Oct 5;268(28):21053-9 [8407942] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interleukin 10 inhibits inflammatory cells infiltration in endotoxin-induced uveitis. AN - 78491689; 8897056 AB - Endotoxin-induced uveitis (EIU) is a model for acute anterior uveitis associated with a variety of pro-inflammatory cytokines and nitric oxide production. Interleukin 10 (IL-10) down-regulates these inflammatory mediators. We report a study of the effect of systemic administration of IL-10 on the inflammatory parameters of EIU. Uveitis was induced in C3H/HeN mice by subcutaneous injection of 200 micrograms lipopolysaccharide (LPS) per mouse. Intraocular inflammation was assessed by leukocyte count and measurement of the protein concentration in the aqueous humor (AH). Mouse recombinant IL-10 at 1000 U or its vehicle alone were administered by three intravenous injections given 4.0 h and 0.5 h before and 8.0 h after LPS injection. The inflammatory cell infiltration in the eyes was significantly reduced in four of five experiments from 40% to 64% in the groups treated with IL-10 compared to the control groups (P < 0.05). In contrast, the level of protein exudation in the anterior chamber (AC) was not significantly affected by IL-10 treatment. IL-10 reduces the cellular infiltration in the ocular inflammation produced by endotoxin. This result suggests potential usefulness for IL-10 in the treatment of severe anterior uveitis with a strong cellular component. JF - Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie AU - Hayashi, S AU - Guex-Crosier, Y AU - Delvaux, A AU - Velu, T AU - Roberge, F G AD - National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1858, USA. Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 633 EP - 636 VL - 234 IS - 10 SN - 0721-832X, 0721-832X KW - Lipopolysaccharides KW - 0 KW - Interleukin-10 KW - 130068-27-8 KW - Index Medicus KW - Animals KW - Infusions, Intravenous KW - Mice, Inbred C3H KW - Mice KW - Female KW - Uveitis, Anterior -- physiopathology KW - Neutrophils -- drug effects KW - Uveitis, Anterior -- chemically induced KW - Chemotaxis, Leukocyte -- drug effects KW - Macrophages -- physiology KW - Interleukin-10 -- pharmacology KW - Neutrophils -- physiology KW - Uveitis, Anterior -- drug therapy KW - Salmonella typhimurium KW - Macrophages -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78491689?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Graefe%27s+archive+for+clinical+and+experimental+ophthalmology+%3D+Albrecht+von+Graefes+Archiv+fur+klinische+und+experimentelle+Ophthalmologie&rft.atitle=Interleukin+10+inhibits+inflammatory+cells+infiltration+in+endotoxin-induced+uveitis.&rft.au=Hayashi%2C+S%3BGuex-Crosier%2C+Y%3BDelvaux%2C+A%3BVelu%2C+T%3BRoberge%2C+F+G&rft.aulast=Hayashi&rft.aufirst=S&rft.date=1996-10-01&rft.volume=234&rft.issue=10&rft.spage=633&rft.isbn=&rft.btitle=&rft.title=Graefe%27s+archive+for+clinical+and+experimental+ophthalmology+%3D+Albrecht+von+Graefes+Archiv+fur+klinische+und+experimentelle+Ophthalmologie&rft.issn=0721832X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-31 N1 - Date created - 1997-01-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of the human ABC superfamily: isolation and mapping of 21 new genes using the expressed sequence tags database. AN - 78490995; 8894702 AB - As an approach to characterizing all human ATP-binding cassette (ABC) superfamily genes, a search of the human expressed sequence tag (EST) database was performed using sequences from known ABC genes. A total of 105 clones, containing sequences of potential ABC genes, were identified, representing 21 distinct genes. This brings the total number of characterized human ABC genes from 12 to 33. The new ABC genes were mapped by PCR on somatic cell and radiation hybrid panels and yeast artificial chromosomes (YACs). The genes are located on human chromosomes 1, 2, 3, 4, 6, 7, 10, 12, 13, 14, 16, 17 and X; at locations distinct from previously mapped members of the superfamily. The characterized genes display extensive diversity in sequence and expression pattern and this information was utilized to determine potential structural, functional and evolutionary relationships to previously characterized members of the ABC superfamily. JF - Human molecular genetics AU - Allikmets, R AU - Gerrard, B AU - Hutchinson, A AU - Dean, M AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702, USA. Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 1649 EP - 1655 VL - 5 IS - 10 SN - 0964-6906, 0964-6906 KW - Index Medicus KW - Phylogeny KW - Polymerase Chain Reaction KW - Sequence Analysis KW - Humans KW - Molecular Sequence Data KW - Databases, Factual KW - Amino Acid Sequence KW - Drug Resistance, Multiple -- genetics KW - ATP-Binding Cassette Transporters -- genetics KW - Chromosome Mapping UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78490995?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+molecular+genetics&rft.atitle=Characterization+of+the+human+ABC+superfamily%3A+isolation+and+mapping+of+21+new+genes+using+the+expressed+sequence+tags+database.&rft.au=Allikmets%2C+R%3BGerrard%2C+B%3BHutchinson%2C+A%3BDean%2C+M&rft.aulast=Allikmets&rft.aufirst=R&rft.date=1996-10-01&rft.volume=5&rft.issue=10&rft.spage=1649&rft.isbn=&rft.btitle=&rft.title=Human+molecular+genetics&rft.issn=09646906&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-04 N1 - Date created - 1997-02-04 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U66692; GENBANK; U66672 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Abrogation of p53 function affects gadd gene responses to DNA base-damaging agents and starvation. AN - 78486938; 8892753 AB - The tumor suppressor p53 is required for induction of its downstream effector genes such as GADD45 and CIP1/WAF1 by ionizing radiation (IR). This response is probably mediated through defined p53 binding sites located in the promoter of CIP1/WAF1 and in the third intron of GADD45. In contrast, the gadd gene stress response to base-damaging agents, such as methylmethane sulfonate (MMS) or UV radiation, or medium depletion (starvation) occurs in all mammalian cells examined to date regardless of p53 status for both GADD45 and also GADD153, which is not IR-responsive in many lines with functional p53. These agents strongly induce the p53 protein and raise the possibility that, although p53 is not required for the typical "gadd" response to these agents, p53 may contribute to these non-IR stress responses. This possibility was confirmed by the finding that disruption of p53 function by transfection with dominant-negative vectors expressing HPV E6, mutant p53, or SV40 T Ag reduced the induction of GADD45 and GADD153 as measured by increases in mRNA and protein levels in human lines with wild-type p53. Similarly, induction of these genes by MMS or UV radiation was consistently stronger in the parental mouse embryo fibroblasts compared to cells derived from mice where both p53 alleles had been deleted. Similar qualitative responses were also seen for CIP1/WAF1. In agreement with reduced induction of p53-regulated genes, the G1 checkpoint activated by MMS or UV radiation was markedly abrogated in p53-wt human MCF-7 breast carcinoma cells by E6 expression. Interestingly, induction of reporter constructs driven by the GADD45 or GADD153 promoters was substantially reduced in human cells transfected with mutant p53 or E6 expression vectors or in cells lacking p53 following treatment with MMS, UV radiation, or starvation. Because neither promoter is inducible by IR, and neither contains a strong p53 binding site, these results indicate that p53 has a synergistic or cooperative role in these non-IR stress responses for both GADD45 and GADD153, and that this role is not mediated through identifiable p53-binding sites. JF - DNA and cell biology AU - Zhan, Q AU - Fan, S AU - Smith, M L AU - Bae, I AU - Yu, K AU - Alamo, I AU - O'Connor, P M AU - Fornace, A J AD - Laboratory of Molecular Pharmacology, National Cancer Institute, NIH, Bethesda, MD 20892-4255, USA. Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 805 EP - 815 VL - 15 IS - 10 SN - 1044-5498, 1044-5498 KW - CCAAT-Enhancer-Binding Proteins KW - 0 KW - CDKN1A protein, human KW - Cdkn1a protein, mouse KW - Culture Media KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - DDIT3 protein, human KW - DNA-Binding Proteins KW - Ddit3 protein, mouse KW - GADD45 protein KW - Intracellular Signaling Peptides and Proteins KW - Proteins KW - Transcription Factors KW - Tumor Suppressor Protein p53 KW - Transcription Factor CHOP KW - 147336-12-7 KW - Methyl Methanesulfonate KW - AT5C31J09G KW - Index Medicus KW - Gene Expression -- drug effects KW - Animals KW - Ultraviolet Rays KW - Cyclins -- biosynthesis KW - Mammals KW - Humans KW - Fibroblasts KW - Methyl Methanesulfonate -- toxicity KW - Promoter Regions, Genetic KW - Tumor Cells, Cultured KW - Lung Neoplasms KW - Genes, Reporter KW - Gene Expression -- radiation effects KW - Protein Biosynthesis KW - Breast Neoplasms KW - Mice KW - Transfection KW - Carcinoma, Large Cell KW - Female KW - Colorectal Neoplasms KW - Cell Line KW - Radiation, Ionizing KW - Stress, Physiological KW - DNA Damage KW - DNA-Binding Proteins -- genetics KW - DNA-Binding Proteins -- biosynthesis KW - Cell Cycle -- radiation effects KW - Tumor Suppressor Protein p53 -- metabolism KW - Transcription Factors -- genetics KW - Transcription Factors -- biosynthesis KW - Proteins -- genetics KW - Cell Cycle -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78486938?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=DNA+and+cell+biology&rft.atitle=Abrogation+of+p53+function+affects+gadd+gene+responses+to+DNA+base-damaging+agents+and+starvation.&rft.au=Zhan%2C+Q%3BFan%2C+S%3BSmith%2C+M+L%3BBae%2C+I%3BYu%2C+K%3BAlamo%2C+I%3BO%27Connor%2C+P+M%3BFornace%2C+A+J&rft.aulast=Zhan&rft.aufirst=Q&rft.date=1996-10-01&rft.volume=15&rft.issue=10&rft.spage=805&rft.isbn=&rft.btitle=&rft.title=DNA+and+cell+biology&rft.issn=10445498&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-03 N1 - Date created - 1996-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dexamethasone stimulation of rat insulin-like growth factor binding protein-1 promoter activity involves multiple cis-elements. AN - 78485210; 9121490 AB - Insulin-like growth factor binding protein-1 (IGFBP-1) modulates the mitogenic actions of IGF-I and IGF-II. Dexamethasone increases IGFBP-1 mRNA abundance and gene transcription in rat liver and in H4-II-E rat hepatoma cells. A glucocorticoid response element (GRE) located at nucleotide (nt) -91/-77 is required for dexamethasone to stimulate rat IGFBP-1 promoter activity in transient transfection assays in H4-II-E cells. Mutagenesis of nt -108/-99 (the M4 region of the insulin response element), however, decreased dexamethasone-stimulated promoter activity despite the presence of an intact GRE, suggesting that regulatory sites in addition to the GRE were required for optimal dexamethasone stimulation. To identify these sites, we introduced 5'-deletion and substitution mutations into rat IGFBP-1 promoter fragments coupled to a luciferase reporter gene and transfected these constructs into H4-II-E cells. Three sites are required for optimal basal promoter activity: a site (nt -62/-50) that binds the liver-enriched transcription factor, hepatocyte nuclear factor-1 (HNF-1), the M4 site, and a putative binding site for transcription factor AP-2 (nt -293/-286). The HNF-1 and M4 sites and an upstream site (nt -252/-236) are also involved in dexamethasone stimulation under some, but not all, circumstances. Mutation of either the HNF-1 site or the M4 site decreased dexamethasone stimulation by more than 80% in constructs whose 5'-end was at nt -92, -135, or -235 but not if the 5' -end was at nt -278 or -327. These results suggest that the nt -278/-236 region can compensate for the loss of the HNF-1 site or the M4 site but that the HNF-1 and M4 sites do not compensate for each other in constructs whose 5'-end was at nt -135 or -235, which lack the nt -278/-236 region. The site within the nt -278/-236 region was localized to nt -252/-236 by deoxyribonuclease I protection and transfection assays. Thus, several cis-elements in the rat IGFBP-1 promoter cooperate, in varying combinations, with the low-affinity GRE to allow optimal dexamethasone-stimulated promoter activity. JF - Molecular endocrinology (Baltimore, Md.) AU - Suh, D S AU - Zhou, Y AU - Ooi, G T AU - Rechler, M M AD - Growth and Development Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 1227 EP - 1237 VL - 10 IS - 10 SN - 0888-8809, 0888-8809 KW - Glucocorticoids KW - 0 KW - Insulin-Like Growth Factor Binding Protein 1 KW - RNA, Messenger KW - Dexamethasone KW - 7S5I7G3JQL KW - Index Medicus KW - Rats KW - Animals KW - Transcription, Genetic KW - RNA, Messenger -- genetics KW - RNA, Messenger -- biosynthesis KW - Cell Line KW - Enhancer Elements, Genetic KW - Dexamethasone -- pharmacology KW - Signal Transduction -- drug effects KW - Insulin-Like Growth Factor Binding Protein 1 -- genetics KW - Promoter Regions, Genetic -- genetics KW - Insulin-Like Growth Factor Binding Protein 1 -- metabolism KW - Glucocorticoids -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78485210?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.atitle=Dexamethasone+stimulation+of+rat+insulin-like+growth+factor+binding+protein-1+promoter+activity+involves+multiple+cis-elements.&rft.au=Suh%2C+D+S%3BZhou%2C+Y%3BOoi%2C+G+T%3BRechler%2C+M+M&rft.aulast=Suh&rft.aufirst=D&rft.date=1996-10-01&rft.volume=10&rft.issue=10&rft.spage=1227&rft.isbn=&rft.btitle=&rft.title=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.issn=08888809&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-23 N1 - Date created - 1997-04-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vinorelbine neurotoxicity: clinical and neurophysiological findings in 23 patients. AN - 78482084; 8890782 AB - Vinorelbine (5'-noranhydrovinblastine) is a new semisynthetic antineoplastic vinca alkaloid which interfers with axonal transport, inducing spiralisation of axonal microtubules and resulting in peripheral neurotoxicity. A prospective detailed neurological and electrophysiological evaluation was performed in 23 patients treated with 25 mg vinorelbine a week. All patients developed a sensory-motor distal symmetric axonal neuropathy. The neurotoxicity increased with cumulative vinorelbine doses and peripheral neuropathy was mild or moderate in most patients. After discontinuation of vinorelbine treatment, neuropathic signs and symptoms were partially reversible. JF - Journal of neurology, neurosurgery, and psychiatry AU - Pace, A AU - Bove, L AU - Nisticò, C AU - Ranuzzi, M AU - Innocenti, P AU - Pietrangeli, A AU - Terzoli, E AU - Jandolo, B AD - Neurology Service, Regina Elena National Cancer Institute, Rome, Italy. Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 409 EP - 411 VL - 61 IS - 4 SN - 0022-3050, 0022-3050 KW - Antineoplastic Agents KW - 0 KW - Vinblastine KW - 5V9KLZ54CY KW - vinorelbine KW - Q6C979R91Y KW - Index Medicus KW - Axons -- drug effects KW - Dose-Response Relationship, Drug KW - Neural Conduction -- drug effects KW - Humans KW - Adult KW - Retrospective Studies KW - Breast -- pathology KW - Aged KW - Middle Aged KW - Female KW - Vinblastine -- therapeutic use KW - Vinblastine -- pharmacology KW - Breast Neoplasms -- drug therapy KW - Vinblastine -- analogs & derivatives KW - Carcinoma -- pathology KW - Breast Neoplasms -- pathology KW - Carcinoma -- drug therapy KW - Vinblastine -- adverse effects KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78482084?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurology%2C+neurosurgery%2C+and+psychiatry&rft.atitle=Vinorelbine+neurotoxicity%3A+clinical+and+neurophysiological+findings+in+23+patients.&rft.au=Pace%2C+A%3BBove%2C+L%3BNistic%C3%B2%2C+C%3BRanuzzi%2C+M%3BInnocenti%2C+P%3BPietrangeli%2C+A%3BTerzoli%2C+E%3BJandolo%2C+B&rft.aulast=Pace&rft.aufirst=A&rft.date=1996-10-01&rft.volume=61&rft.issue=4&rft.spage=409&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurology%2C+neurosurgery%2C+and+psychiatry&rft.issn=00223050&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-04 N1 - Date created - 1996-12-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Neurology. 1979 Apr;29(4):429-31 [220559] Ann Neurol. 1980 Dec;8(6):590-6 [7212646] Am J Clin Oncol. 1982 Dec;5(6):649-55 [7165009] J Neurol Neurosurg Psychiatry. 1984 May;47(5):536-42 [6330307] J Clin Oncol. 1994 Oct;12(10):2094-101 [7931479] Drugs. 1992;44 Suppl 4:36-45; discussion 66-9 [1283849] Ann Neurol. 1994 Mar;35(3):304-11 [7907208] Neurology. 1994 Mar;44(3 Pt 1):488-94 [8145920] Drugs. 1992;44 Suppl 4:1-16; discussion 66-9 [1283846] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selection of transplant donors based on MHC microsatellite data. AN - 78480236; 8891740 JF - Human immunology AU - Carrington, M AU - Wade, J AD - Biological Carcinogenesis and Development Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland, USA. carringt@fcrfv2.ncifcrf.gov Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 151 EP - 154 VL - 50 IS - 2 SN - 0198-8859, 0198-8859 KW - DNA, Satellite KW - 0 KW - Index Medicus KW - Humans KW - DNA, Satellite -- genetics KW - Microsatellite Repeats KW - Major Histocompatibility Complex -- genetics KW - Tissue Donors -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78480236?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+immunology&rft.atitle=Selection+of+transplant+donors+based+on+MHC+microsatellite+data.&rft.au=Carrington%2C+M%3BWade%2C+J&rft.aulast=Carrington&rft.aufirst=M&rft.date=1996-10-01&rft.volume=50&rft.issue=2&rft.spage=151&rft.isbn=&rft.btitle=&rft.title=Human+immunology&rft.issn=01988859&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-27 N1 - Date created - 1997-02-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Republished In: Hum Immunol. 1996 Dec;51(2):106-9 [8960914] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inducible nitric oxide synthase in tangle-bearing neurons of patients with Alzheimer's disease. AN - 78459482; 8879214 AB - In Alzheimer's disease (AD), affected neurons accumulate beta amyloid protein, components of which can induce mouse microglia to express the high-output isoform of nitric oxide synthase (NOS2) in vitro. Products of NOS2 can be neurotoxic. In mice, NOS2 is normally suppressed by transforming growth factor beta 1 (TGF-beta 1). Expression of TGF-beta 1 is decreased in brains from AD patients, a situation that might be permissive for accumulation of NOS2. Accordingly, we investigated the expression of NOS2 in patients with AD, using three monospecific antibodies: a previously described polyclonal and two new monoclonal antibodies. Neurofibrillary tangle-bearing neurons and neuropil threads contained NOS2 in brains from each of 11 AD patients ranging in age from 47 to 81 years. NOS2 was undetectable in brains from 6 control subjects aged 23-72 years, but was expressed in small amounts in 3 control subjects aged 77-87 years. Thus, human neurons can express NOS2 in vivo. The high-output pathway of NO production may contribute to pathogenesis in AD. JF - The Journal of experimental medicine AU - Vodovotz, Y AU - Lucia, M S AU - Flanders, K C AU - Chesler, L AU - Xie, Q W AU - Smith, T W AU - Weidner, J AU - Mumford, R AU - Webber, R AU - Nathan, C AU - Roberts, A B AU - Lippa, C F AU - Sporn, M B AD - Laboratory of Chemoprevention, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/10/01/ PY - 1996 DA - 1996 Oct 01 SP - 1425 EP - 1433 VL - 184 IS - 4 SN - 0022-1007, 0022-1007 KW - Antibodies, Monoclonal KW - 0 KW - Isoenzymes KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Index Medicus KW - Immunoblotting KW - Humans KW - Aged KW - Amino Acid Sequence KW - Antibody Specificity KW - Aged, 80 and over KW - Adult KW - Molecular Sequence Data KW - Enzyme Induction KW - Middle Aged KW - Immunohistochemistry KW - Female KW - Male KW - Brain -- enzymology KW - Isoenzymes -- isolation & purification KW - Brain -- pathology KW - Neurons -- enzymology KW - Nitric Oxide Synthase -- isolation & purification KW - Alzheimer Disease -- enzymology KW - Neurons -- pathology KW - Alzheimer Disease -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78459482?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Inducible+nitric+oxide+synthase+in+tangle-bearing+neurons+of+patients+with+Alzheimer%27s+disease.&rft.au=Vodovotz%2C+Y%3BLucia%2C+M+S%3BFlanders%2C+K+C%3BChesler%2C+L%3BXie%2C+Q+W%3BSmith%2C+T+W%3BWeidner%2C+J%3BMumford%2C+R%3BWebber%2C+R%3BNathan%2C+C%3BRoberts%2C+A+B%3BLippa%2C+C+F%3BSporn%2C+M+B&rft.aulast=Vodovotz&rft.aufirst=Y&rft.date=1996-10-01&rft.volume=184&rft.issue=4&rft.spage=1425&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 - 1996-12-13 N1 - Date created - 1996-12-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Neurology. 1984 Jul;34(7):939-44 [6610841] J Exp Med. 1996 May 1;183(5):2337-42 [8642342] J Immunol. 1990 Aug 1;145(3):940-4 [2115549] Neurology. 1991 Apr;41(4):479-86 [2011243] FEBS Lett. 1992 Aug 3;307(3):287-93 [1379542] Ann Neurol. 1992 Dec;32(6):818-20 [1281971] J Neurochem. 1993 May;60(5):1665-72 [8097233] Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3491-5 [7682706] J Immunol. 1993 Aug 15;151(4):2132-41 [8102159] Neuroreport. 1993 Jun;4(6):760-2 [7688591] Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):9813-7 [8234317] J Cell Biochem. 1993 Dec;53(4):314-22 [8300749] Neurosci Lett. 1994 Jan 17;166(1):31-4 [7514775] Prog Brain Res. 1994;101:383-90 [8029466] Neuron. 1994 Nov;13(5):1245-52 [7946360] Ann Neurol. 1994 Nov;36(5):778-86 [7526776] Biochem Biophys Res Commun. 1994 Nov 30;205(1):659-65 [7528015] J Biol Chem. 1994 Dec 30;269(52):33082-90 [7528745] Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12599-603 [7809085] J Exp Med. 1995 Feb 1;181(2):735-45 [7530762] Nature. 1995 Feb 9;373(6514):523-7 [7845465] Nature. 1995 Apr 13;374(6523):647-50 [7715705] Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5312-6 [7539914] Prog Growth Factor Res. 1994;5(4):341-51 [7540059] Mech Ageing Dev. 1995 Apr 14;79(2-3):115-26 [7616762] Neurology. 1995 Aug;45(8):1561-9 [7543987] J Neuropathol Exp Neurol. 1995 Nov;54(6):802-11 [7595653] J Exp Med. 1996 May 1;183(5):2293-302 [8642338] Ann Neurol. 1988 Feb;23(2):105-14 [2897822] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mml1, a new common integration site in murine leukemia virus-induced promonocytic leukemias maps to mouse chromosome 10. AN - 78431135; 8862417 AB - MuLV-induced myeloid leukemias (MML) having promonocytic characteristics are produced with high incidence in some strains of adult mice that are undergoing chronic peritoneal inflammation. Previously we showed that many leukemias have rearrangements of the c-myb locus due to insertional mutagenesis, however, we also identified a number of leukemias that had proviral integrations in the absence of c-myb rearrangement in the present study, a new locus, Mml1, was found to be a target of insertional mutagenesis in 10 of the promonocytic leukemias that lacked c-myb alterations. Chromosomal mapping studies, performed using progeny from interspecies backcross mice generated by mating (BALB/cAn x M. spretus)F1 females to BALB/cAN males, determined that Mml1 is located on the proximal end of mouse chromosome 10. Interestingly, there were no recombinants between c-myb and Mml1 in 101 backcross progeny and Mml1 was mapped approximately 20-25 kb upsteam of c-myb. Interestingly, c-myb mRNA and Myb protein are expressed at levels similar to the levels observed in myeloid progenitor cells, but are not overexpressed. It is anticipated that future experiments will determine whether Mml1 integration prevents down regulation of c-myb expression or activates another gene on chromosome 10. JF - Virology AU - Koller, R AU - Krall, M AU - Mock, B AU - Bies, J AU - Nazarov, V AU - Wolff, L AD - Laboratory of Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1996/10/01/ PY - 1996 DA - 1996 Oct 01 SP - 224 EP - 234 VL - 224 IS - 1 SN - 0042-6822, 0042-6822 KW - Proto-Oncogene Proteins KW - 0 KW - Proto-Oncogene Proteins c-myb KW - Trans-Activators KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Gene Expression KW - Gene Rearrangement KW - Mice KW - Mice, Inbred BALB C KW - Binding Sites KW - Cloning, Molecular KW - Mice, Inbred DBA KW - Tumor Cells, Cultured KW - Trans-Activators -- genetics KW - Proviruses -- genetics KW - Proto-Oncogene Proteins -- genetics KW - Female KW - Male KW - Mutagenesis, Insertional KW - Retroviridae Infections -- virology KW - Leukemia Virus, Murine -- genetics KW - Tumor Virus Infections -- virology KW - Tumor Virus Infections -- genetics KW - Leukemia, Experimental -- virology KW - Virus Integration KW - Chromosome Mapping KW - Retroviridae Infections -- genetics KW - Leukemia, Experimental -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78431135?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mml1%2C+a+new+common+integration+site+in+murine+leukemia+virus-induced+promonocytic+leukemias+maps+to+mouse+chromosome+10.&rft.au=Koller%2C+R%3BKrall%2C+M%3BMock%2C+B%3BBies%2C+J%3BNazarov%2C+V%3BWolff%2C+L&rft.aulast=Koller&rft.aufirst=R&rft.date=1996-10-01&rft.volume=224&rft.issue=1&rft.spage=224&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-26 N1 - Date created - 1996-11-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interleukin-6 induces expression of peripherin and cooperates with Trk receptor signaling to promote neuronal differentiation in PC12 cells. AN - 78416460; 8858917 AB - In contrast to the intensively studied nerve growth factor (NGF)-related family of cytokines, relatively little is known about the mechanisms of neurotrophic activity elicited by the cytokine interleukin-6 (IL-6). We have examined the mechanisms of IL-6-induced neuronal differentiation of the pheochromocytoma cell line PC12. IL-6 independently induced the expression of peripherin, identifying this gene as the first neuronal-specific target of IL-6. However, IL-6 alone failed to elicit neurite outgrowth in PC12 cells and instead required low levels of Trk/NGF receptor tyrosine kinase activity to induce neuronal differentiation. The cooperating Trk signal could be provided by either overexpression of Trk or exposure to low concentrations of NGF. IL-6 also functioned cooperatively with basic fibroblast growth factor to promote PC12 differentiation. IL-6 and Trk/NGF synergized in enhancing tyrosine phosphorylation of the Erk-1 mitogen-activated protein kinase and in activating expression of certain NGF target genes. NGF also induced expression of the gp80 subunit of the IL-6 receptor, providing another potential mechanism of cooperativity between NGF and IL-6 signaling. We propose that IL-6 functions as an enhancer of NGF signaling rather than as an autonomous neuronal differentiation signal. Moreover, our results demonstrate that a Trk receptor-specific cellular response can be achieved in the absence of NGF through amplification of its basal signaling activity by the IL-6 receptor system. JF - Journal of neurochemistry AU - Sterneck, E AU - Kaplan, D R AU - Johnson, P F AD - Eukaryotic Transcriptional Regulation Group, NCI-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA. Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 1365 EP - 1374 VL - 67 IS - 4 SN - 0022-3042, 0022-3042 KW - Antigens, CD KW - 0 KW - Endothelial Growth Factors KW - Eye Proteins KW - Interleukin-6 KW - Intermediate Filament Proteins KW - Lymphokines KW - Membrane Glycoproteins KW - Nerve Growth Factors KW - Nerve Tissue Proteins KW - Neuropeptides KW - Peripherins KW - Proto-Oncogene Proteins KW - RNA, Messenger KW - Receptors, Interleukin KW - Receptors, Interleukin-6 KW - Receptors, Nerve Growth Factor KW - Vascular Endothelial Growth Factor A KW - Vascular Endothelial Growth Factors KW - Phosphotyrosine KW - 21820-51-9 KW - Receptor Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Receptor, trkA KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Mitogen-Activated Protein Kinase 3 KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinases KW - Index Medicus KW - Antigens, CD -- biosynthesis KW - Animals KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Endothelial Growth Factors -- biosynthesis KW - Phosphotyrosine -- metabolism KW - Transcription, Genetic KW - Neuropeptides -- biosynthesis KW - Receptors, Interleukin -- biosynthesis KW - RNA, Messenger -- biosynthesis KW - Pheochromocytoma KW - Rats KW - Polymerase Chain Reaction KW - Lymphokines -- biosynthesis KW - Adrenal Gland Neoplasms KW - Phosphorylation KW - Cell Differentiation -- drug effects KW - Drug Synergism KW - PC12 Cells KW - Gene Expression -- drug effects KW - Receptors, Nerve Growth Factor -- physiology KW - Nerve Growth Factors -- pharmacology KW - Interleukin-6 -- pharmacology KW - Receptor Protein-Tyrosine Kinases -- physiology KW - Proto-Oncogene Proteins -- physiology KW - Intermediate Filament Proteins -- biosynthesis KW - Neurons -- cytology KW - Eye Proteins -- biosynthesis KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78416460?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=Interleukin-6+induces+expression+of+peripherin+and+cooperates+with+Trk+receptor+signaling+to+promote+neuronal+differentiation+in+PC12+cells.&rft.au=Sterneck%2C+E%3BKaplan%2C+D+R%3BJohnson%2C+P+F&rft.aulast=Sterneck&rft.aufirst=E&rft.date=1996-10-01&rft.volume=67&rft.issue=4&rft.spage=1365&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-02 N1 - Date created - 1996-12-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A preliminary study of flutamide, testolactone, and reduced hydrocortisone dose in the treatment of congenital adrenal hyperplasia. AN - 78412180; 8855797 AB - Treatment outcome in congenital adrenal hyperplasia is often suboptimal due to hyperandrogenism, treatment-induced hypercortisolism, or both. As a new approach, we hypothesized that the effects of androgen could be blocked by an antiandrogen (flutamide) and an inhibitor androgen to estrogen conversion (testolactone), thus allowing the hydrocortisone dose to be reduced. We conducted a short term pilot study in 12 children with congenital adrenal hyperplasia in a randomised cross-over open design to determine whether flutamide, testolactone, reduced hydrocortisone dose, and fludrocortisone are more effective than hydrocortisone and fludrocortisone treatment in normalizing linear growth, weight gain, and bone maturation. Each regimen was administered for 6 months, with a 3-month washout period, consisting of hydrocortisone and fludrocortisone treatment, between regimens. Compared to hydrocortisone and fludrocortisone treatment, the regimen of flutamide, testolactone, reduced hydrocortisone dose (from 12.9 to 7.9 mg/m2 day), and fludrocortisone produced an increase in plasma 17-hydroxyprogesterone levels (P < 0.05) and a decline in urinary cortisol (P < 0.01), linear growth rate (-0.9 +/- 0.5 vs. 1.4 +/- 0.6 SD U; P = 0.003), weight velocity (-0.80 +/- 4.0 vs 0.6 +/- 0.4 SD U; P = 0.01), and bone maturation (0.6 +/- 0.6 vs. 1.4 +/- 0.9 yr bone age/yr chronological age; P = 0.02). Although no important adverse effects were observed, the known potential for flutamide-induced hepatotoxicity made frequent monitoring essential. We conclude that the regimen of flutamide, testolactone, reduced hydrocortisone does, and fludrocortisone improve the short term control of growth and bone maturation in children with congenital adrenal hyperplasia. Long term studies are required to determine whether this approach can improve these children's growth and development. JF - The Journal of clinical endocrinology and metabolism AU - Laue, L AU - Merke, D P AU - Jones, J V AU - Barnes, K M AU - Hill, S AU - Cutler, G B AD - Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 3535 EP - 3539 VL - 81 IS - 10 SN - 0021-972X, 0021-972X KW - Dehydroepiandrosterone KW - 459AG36T1B KW - 17-alpha-Hydroxyprogesterone KW - 68-96-2 KW - Testolactone KW - 6J9BLA949Q KW - Flutamide KW - 76W6J0943E KW - Adrenocorticotropic Hormone KW - 9002-60-2 KW - Hydrocortisone KW - WI4X0X7BPJ KW - Abridged Index Medicus KW - Index Medicus KW - Infant KW - Bone Development KW - 17-alpha-Hydroxyprogesterone -- blood KW - Humans KW - Seasons KW - Dehydroepiandrosterone -- blood KW - Child KW - Weight Gain KW - Male KW - Female KW - Child, Preschool KW - Adrenocorticotropic Hormone -- blood KW - Testolactone -- adverse effects KW - Testolactone -- administration & dosage KW - Adrenal Hyperplasia, Congenital -- drug therapy KW - Hydrocortisone -- adverse effects KW - Flutamide -- therapeutic use KW - Hydrocortisone -- administration & dosage KW - Testolactone -- therapeutic use KW - Hydrocortisone -- urine KW - Flutamide -- adverse effects KW - Adrenal Hyperplasia, Congenital -- physiopathology KW - Hydrocortisone -- therapeutic use KW - Flutamide -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78412180?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+endocrinology+and+metabolism&rft.atitle=A+preliminary+study+of+flutamide%2C+testolactone%2C+and+reduced+hydrocortisone+dose+in+the+treatment+of+congenital+adrenal+hyperplasia.&rft.au=Laue%2C+L%3BMerke%2C+D+P%3BJones%2C+J+V%3BBarnes%2C+K+M%3BHill%2C+S%3BCutler%2C+G+B&rft.aulast=Laue&rft.aufirst=L&rft.date=1996-10-01&rft.volume=81&rft.issue=10&rft.spage=3535&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+endocrinology+and+metabolism&rft.issn=0021972X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-19 N1 - Date created - 1996-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Factitious Cushing syndrome. AN - 78408282; 8855803 AB - There have been few reports of factitious Cushing syndrome. To characterize the clinical and laboratory features leading to this unusual diagnosis, we describe 6 patients (5 women, 1 man), ages 31-44, identified retrospectively among 860 patients evaluated for hypercortisolism at the National Institutes of Health Clinical Center. All six patients had multiple surgeries unrelated to Cushing syndrome and a history of depression or anxiety. Four patients had close contact with the medical profession, three a history of drug abuse, and three had undergone previous treatment for Cushing syndrome. The physical features of Cushing syndrome were variable and not helpful in the differential diagnosis with endogenous Cushing syndrome. Four patients had striking variability in urine-free cortisol (UFC) and 17-hydroxysteroid (17-OHCS) values from low to high. Adrenal computed tomography, performed in two patients, showed small adrenal glands (n = 1) or a left-sided mass (n = 1), and adrenal magnetic resonance imaging, performed in one patient, showed atrophic glands. Pituitary magnetic resonance imaging, carried out in four patients, was either normal (n = 1) or exhibited questionable signs of microadenoma (n = 3). Determination of synthetic glucocorticoids by high pressure liquid chromatography (HPLC) was positive in the four patients in whom it was performed. Factitious Cushing syndrome is a difficult diagnosis. To conserve time and resources, high pressure liquid chromatography analysis of urine steroids, the most definitive test for the factitious disorder, should be performed whenever there is clinical suspicion of glucocorticoid abuse. JF - The Journal of clinical endocrinology and metabolism AU - Cizza, G AU - Nieman, L K AU - Doppman, J L AU - Passaro, M D AU - Czerwiec, F S AU - Chrousos, G P AU - Cutler, G B AD - Developmental Endocrinology Branch, National Institute of Child Health and Human Development, NIH, Bethesda, Maryland 20892-1262, USA. Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 3573 EP - 3577 VL - 81 IS - 10 SN - 0021-972X, 0021-972X KW - Glucocorticoids KW - 0 KW - Hydroxysteroids KW - Adrenocorticotropic Hormone KW - 9002-60-2 KW - Hydrocortisone KW - WI4X0X7BPJ KW - Abridged Index Medicus KW - Index Medicus KW - Magnetic Resonance Imaging KW - Diagnosis, Differential KW - Humans KW - Tomography, X-Ray Computed KW - Adrenal Glands -- pathology KW - Hydroxysteroids -- urine KW - Chromatography, High Pressure Liquid KW - Hydrocortisone -- blood KW - Pituitary Gland -- pathology KW - Adult KW - Hydrocortisone -- urine KW - Female KW - Male KW - Adrenocorticotropic Hormone -- blood KW - Munchausen Syndrome -- diagnosis KW - Glucocorticoids -- urine KW - Cushing Syndrome -- diagnosis KW - Glucocorticoids -- administration & dosage KW - Substance-Related Disorders UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78408282?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+endocrinology+and+metabolism&rft.atitle=Factitious+Cushing+syndrome.&rft.au=Cizza%2C+G%3BNieman%2C+L+K%3BDoppman%2C+J+L%3BPassaro%2C+M+D%3BCzerwiec%2C+F+S%3BChrousos%2C+G+P%3BCutler%2C+G+B&rft.aulast=Cizza&rft.aufirst=G&rft.date=1996-10-01&rft.volume=81&rft.issue=10&rft.spage=3573&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+endocrinology+and+metabolism&rft.issn=0021972X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-19 N1 - Date created - 1996-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Quantitation of galactosemic cataracts in dogs using magnetization transfer contrast-enhanced magnetic resonance imaging. AN - 78398850; 8843908 AB - Magnetic resonance imaging (MRI) is becoming increasingly important for the diagnosis and characterization of ocular pathologies. A drawback to this technique is that image contrast between different regions of tissue can be obscured because of the similarity of their nuclear magnetic resonance relaxation parameters. This problem is addressed by magnetization transfer contrast (MTC) enhancement, a MRI technique that generates high-contrast images based on characteristic tissue differences resulting from the interaction of water and macromolecules. The purpose of this study was to investigate the feasibility of using MTC-enhanced imaging to monitor quantitatively the lens changes associated with sugar cataract formation in galactose-fed dogs. Male beagles fed a diet containing 30% galactose were periodically examined by MRI for changes in tissue character. Each examination included a gradient recalled echo image (M0), an MTC-enhanced gradient recalled echo image (Ms), a T1 image determined from a one-shot T1 imaging sequence, and a T1-weighted image taken from the raw T1 data. Average values were obtained for several regions of interest and tabulated. These were correlated with cataractous stages visually observed by slit lamp biomicroscopy and retroillumination photography. Enhanced image details of the lens and anterior segment that documented osmotic changes from initial cortical vacuole formation to cortical and nuclear changes associated with advanced sugar cataracts were characterized from measurements of parameters obtained from M0, Ms, T1-weighted, and T1 images. Changes in the cross-sectional areas of lenses during sugar cataract formation also were documented. The magnetic resonance images showed visible changes from the onset of cortical vacuole formation. Region of interest (ROI) analysis of the images showed tissue changes occurring throughout the cataract progression. The MTC-enhanced MRI technique is well suited to detecting lens changes associated with cataractogenesis. All but the earliest changes were readily apparent from the images with no further analysis. Graphic ROI analysis was able to detect regional changes associated the cataract progression for all degrees of severity. Furthermore, the images demonstrated changes in size and shape that would not be detectable by visual inspection. JF - Investigative ophthalmology & visual science AU - Lizak, M J AU - Mori, K AU - Ceckler, T L AU - Balaban, R S AU - Kador, P F AD - Laboratory of Ocular Therapeutics, National Eye Institute, Bethesda, MD 20892-1850, USA. Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 2219 EP - 2227 VL - 37 IS - 11 SN - 0146-0404, 0146-0404 KW - Galactose KW - X2RN3Q8DNE KW - Index Medicus KW - Severity of Illness Index KW - Animals KW - Dogs KW - Disease Progression KW - Male KW - Cataract -- pathology KW - Magnetic Resonance Imaging -- methods KW - Lens, Crystalline -- pathology KW - Galactosemias -- chemically induced KW - Cataract -- chemically induced KW - Lens, Crystalline -- physiopathology KW - Galactosemias -- physiopathology KW - Cataract -- physiopathology KW - Galactosemias -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78398850?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Quantitation+of+galactosemic+cataracts+in+dogs+using+magnetization+transfer+contrast-enhanced+magnetic+resonance+imaging.&rft.au=Lizak%2C+M+J%3BMori%2C+K%3BCeckler%2C+T+L%3BBalaban%2C+R+S%3BKador%2C+P+F&rft.aulast=Lizak&rft.aufirst=M&rft.date=1996-10-01&rft.volume=37&rft.issue=11&rft.spage=2219&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 - 1996-11-06 N1 - Date created - 1996-11-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Invest Ophthalmol Vis Sci. 1997 May;38(6):1053 [9152222] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA repair and ultraviolet mutagenesis in cells from a new patient with xeroderma pigmentosum group G and cockayne syndrome resemble xeroderma pigmentosum cells. AN - 78355701; 8823375 AB - Xeroderma pigmentosum (XP)/Cockayne syndrome (CS) complex is a combination of clinical features of two rare genetic disorders in one individual. A sun-sensitive boy (XP20BE) who had severe symptoms of CS, with dwarfism, microcephaly, retinal degeneration, and mental impairment, had XP-type pigmentation and died at 6 y with marked cachexia (weight 14.5 lb) without skin cancers. We evaluated his cultured cells for characteristic CS or XP DNA-repair abnormalities. The level of ultraviolet (UV)-induced unscheduled DNA synthesis was less than 5% of normal, characteristic of the excision-repair defect of XP. Cell fusion studies indicated that his cells were in XP complementation group G. His cells were hypersensitive to killing by UV, and their post-UV recovery of RNA synthesis was abnormally low, features of both CS and XP. Post-UV survival of plasmid pSP189 in his cells was markedly reduced, and post-UV plasmid mutation frequency was higher than with normal cells, as in both CS and XP. Sequence analysis of the mutated plasmid marker gene showed normal frequency of plasmids with multiple base substitutions, as in CS, and an abnormally increased frequency of G:C-->A:T mutations, a feature of XP. Transfection of UV-treated pRSVcat with or without photoreactivation revealed that his cells, like XP cells, could not repair either cyclobutane pyrimidine dimers or non-dimer photoproducts. These results indicate that the DNA-repair features of the XP20BE (XP-G/CS) cells are phenotypically more like XP cells than CS cells, whereas clinically the CS phenotype is more prominent than XP. JF - The Journal of investigative dermatology AU - Moriwaki, S AU - Stefanini, M AU - Lehmann, A R AU - Hoeijmakers, J H AU - Robbins, J H AU - Rapin, I AU - Botta, E AU - Tanganelli, B AU - Vermeulen, W AU - Broughton, B C AU - Kraemer, K H AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 647 EP - 653 VL - 107 IS - 4 SN - 0022-202X, 0022-202X KW - RNA KW - 63231-63-0 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Plasmids -- genetics KW - Humans KW - Genetic Complementation Test KW - Fibroblasts -- radiation effects KW - Child KW - Cell Survival -- radiation effects KW - DNA -- radiation effects KW - Male KW - RNA -- biosynthesis KW - Xeroderma Pigmentosum -- pathology KW - DNA Repair KW - Cockayne Syndrome -- genetics KW - Ultraviolet Rays -- adverse effects KW - Xeroderma Pigmentosum -- genetics KW - Xeroderma Pigmentosum -- complications KW - Cockayne Syndrome -- complications KW - Cockayne Syndrome -- pathology KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78355701?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+investigative+dermatology&rft.atitle=DNA+repair+and+ultraviolet+mutagenesis+in+cells+from+a+new+patient+with+xeroderma+pigmentosum+group+G+and+cockayne+syndrome+resemble+xeroderma+pigmentosum+cells.&rft.au=Moriwaki%2C+S%3BStefanini%2C+M%3BLehmann%2C+A+R%3BHoeijmakers%2C+J+H%3BRobbins%2C+J+H%3BRapin%2C+I%3BBotta%2C+E%3BTanganelli%2C+B%3BVermeulen%2C+W%3BBroughton%2C+B+C%3BKraemer%2C+K+H&rft.aulast=Moriwaki&rft.aufirst=S&rft.date=1996-10-01&rft.volume=107&rft.issue=4&rft.spage=647&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+investigative+dermatology&rft.issn=0022202X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-12-10 N1 - Date created - 1996-12-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Destabilization of Raf-1 by geldanamycin leads to disruption of the Raf-1-MEK-mitogen-activated protein kinase signalling pathway. AN - 78344871; 8816498 AB - The serine/threonine kinase Raf-1 functions downstream of Rats in a signal transduction cascade which transmits mitogenic stimuli from the plasma membrane to the nucleus. Raf-1 integrates signals coming from extracellular factors and, in turn, activates its substrate, MEK kinase. MEK activates mitogen-activated protein kinase (MAPK), which phosphorylates other kinases as well as transcription factors. Raf-1 exists in a complex with HSP90 and other proteins. The benzoquinone ansamycin geldanamycin (GA) binds to HSP90 and disrupts the Raf-1-HSP90 multimolecular complex, leading to destabilization of Raf-1. In this study, we examined whether Raf-1 destabilization is sufficient to block the Raf-1-MEK-MAPK signalling pathway and whether GA specifically inactivates the Raf-1 component of this pathway. Using the model system of NIH 3T3 cells stimulated with phorbol 12-myristate 13-acetate (PMA), we show that GA does not affect the ability of protein kinase C alpha to be activated by phorbol esters, but it does block activation of MEK and MAPK. Further, GA does not decrease the activity of constitutively active MEK in transiently transfected cells. Finally, disruption of the Raf-1-MEK-MAPK signalling pathway by GA prevents both the PMA-induced proliferative response and PMA-induced activation of a MAPK-sensitive nuclear transcription factor. Thus, we demonstrate that interaction between HSP90 and Raf-1 is a sine qua non for Raf stability and function as a signal transducer and that the effects observed cannot be attributed to a general impairment of protein kinase function. JF - Molecular and cellular biology AU - Schulte, T W AU - Blagosklonny, M V AU - Romanova, L AU - Mushinski, J F AU - Monia, B P AU - Johnston, J F AU - Nguyen, P AU - Trepel, J AU - Neckers, L M AD - Clinical Pharmacology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. tschulte@helix.nih.gov Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 5839 EP - 5845 VL - 16 IS - 10 SN - 0270-7306, 0270-7306 KW - Benzoquinones KW - 0 KW - Enzyme Inhibitors KW - HSP90 Heat-Shock Proteins KW - Lactams, Macrocyclic KW - Oligonucleotides, Antisense KW - Proto-Oncogene Proteins KW - Quinones KW - Recombinant Proteins KW - DNA KW - 9007-49-2 KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Proto-Oncogene Proteins c-raf KW - Protein Kinase C KW - EC 2.7.11.13 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - MAP Kinase Kinase Kinase 1 KW - EC 2.7.11.25 KW - MAP3K1 protein, human KW - Map3k1 protein, mouse KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - geldanamycin KW - Z3K3VJ16KU KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Humans KW - Jurkat Cells KW - Cell Division -- drug effects KW - Oligonucleotides, Antisense -- pharmacology KW - HSP90 Heat-Shock Proteins -- drug effects KW - Mice KW - DNA -- biosynthesis KW - Rats KW - Protein-Tyrosine Kinases -- antagonists & inhibitors KW - Protein Kinase C -- metabolism KW - Transfection KW - Recombinant Proteins -- metabolism KW - Genes, Reporter KW - Tetradecanoylphorbol Acetate -- pharmacology KW - HSP90 Heat-Shock Proteins -- metabolism KW - Protein-Serine-Threonine Kinases -- biosynthesis KW - Signal Transduction -- physiology KW - Proto-Oncogene Proteins -- biosynthesis KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Protein-Serine-Threonine Kinases -- metabolism KW - Signal Transduction -- drug effects KW - Proto-Oncogene Proteins -- metabolism KW - Transcriptional Activation -- drug effects KW - Enzyme Inhibitors -- pharmacology KW - Quinones -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78344871?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Destabilization+of+Raf-1+by+geldanamycin+leads+to+disruption+of+the+Raf-1-MEK-mitogen-activated+protein+kinase+signalling+pathway.&rft.au=Schulte%2C+T+W%3BBlagosklonny%2C+M+V%3BRomanova%2C+L%3BMushinski%2C+J+F%3BMonia%2C+B+P%3BJohnston%2C+J+F%3BNguyen%2C+P%3BTrepel%2C+J%3BNeckers%2C+L+M&rft.aulast=Schulte&rft.aufirst=T&rft.date=1996-10-01&rft.volume=16&rft.issue=10&rft.spage=5839&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 - 1996-11-15 N1 - Date created - 1996-11-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1988 Oct 7;55(1):101-12 [3262423] Nature. 1988 Aug 25;334(6184):715-8 [2842685] Nature. 1991 Jan 31;349(6308):426-8 [1992343] J Biol Chem. 1991 Mar 15;266(8):4661-4 [2002013] Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4981-5 [2052581] J Biol Chem. 1991 Sep 25;266(27):18162-71 [1680858] Nature. 1991 Oct 17;353(6345):670-4 [1922387] J Biol Chem. 1991 Dec 15;266(35):23521-4 [1748630] Biochim Biophys Acta. 1991 Dec 10;1072(2-3):129-57 [1751545] J Exp Med. 1992 Mar 1;175(3):853-62 [1740667] Genes Dev. 1992 Apr;6(4):545-56 [1313769] Trends Biochem Sci. 1995 Mar;20(3):117-22 [7709430] J Biol Chem. 1995 Apr 28;270(17):9991-10001 [7730383] EMBO J. 1995 Jul 3;14(13):3136-45 [7542586] Mol Cell Biol. 1995 Aug;15(8):4125-35 [7623807] Mol Cell Biol. 1995 Oct;15(10):5214-25 [7565670] J Biol Chem. 1995 Oct 13;270(41):24585-8 [7592678] EMBO J. 1995 Oct 16;14(20):4905-13 [7588619] Nat Med. 1996 Jun;2(6):668-75 [8640558] Mol Pharmacol. 1992 Jun;41(6):1023-33 [1352033] Cell Signal. 1992 May;4(3):275-86 [1510878] Science. 1992 Sep 4;257(5075):1404-7 [1326789] EMBO J. 1992 Nov;11(11):3985-94 [1327754] J Biol Chem. 1992 Dec 5;267(34):24796-804 [1332967] Biochem J. 1992 Dec 1;288 ( Pt 2):351-5 [1334404] Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3216-20 [8386367] Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5016-20 [8389463] Curr Opin Cell Biol. 1993 Apr;5(2):254-60 [8389568] J Biol Chem. 1993 Jul 5;268(19):14514-22 [8390996] Nature. 1993 Jul 15;364(6434):249-52 [8321321] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):5889-92 [8392180] J Biol Chem. 1993 Aug 15;268(23):17309-16 [8349614] J Biol Chem. 1993 Oct 15;268(29):21455-8 [8407992] J Biol Chem. 1993 Oct 15;268(29):21711-6 [8408024] Mol Cell Biol. 1993 Nov;13(11):7170-9 [7692235] Oncogene. 1993 Nov;8(11):3175-81 [8414521] Nature. 1993 Dec 16;366(6456):643-54 [8259209] J Biol Chem. 1994 Mar 4;269(9):6695-701 [8120027] EMBO J. 1994 Apr 1;13(7):1610-9 [8157000] Curr Opin Genet Dev. 1994 Feb;4(1):82-9 [8193545] Science. 1994 Jun 3;264(5164):1463-7 [7811320] J Immunol. 1994 Sep 1;153(5):2046-51 [8051409] Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8324-8 [8078881] Cell. 1994 Sep 23;78(6):1027-37 [7923353] Mol Cell Biol. 1994 Oct;14(10):6696-703 [7935389] Semin Cancer Biol. 1994 Aug;5(4):247-53 [7803760] Cell. 1995 Jan 27;80(2):179-85 [7834738] EMBO J. 1995 Mar 1;14(5):951-62 [7889942] J Biol Chem. 1995 Mar 31;270(13):7644-55 [7706312] Biochem Biophys Res Commun. 1979 Jul 12;89(1):175-80 [314289] J Cell Biol. 1981 Jan;88(1):189-98 [6259177] Cell. 1987 Jun 19;49(6):729-39 [3034432] Cell. 1988 Aug 12;54(4):541-52 [3135940] Cell Immunol. 1990 Nov;131(1):242-52 [2121373] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of seven hydrophobic clusters in GCN4 making redundant contributions to transcriptional activation. AN - 78344853; 8816468 AB - GCN4 is a transcriptional activator in the bZIP family that regulates amino acid biosynthetic genes in the yeast Saccharomyces cerevisiae. The N-terminal 100 amino acids of GCN4 contains a potent activation function that confers high-level transcription in the absence of the centrally located acidic activation domain (CAAD) delineated in previous studies. To identify specific amino acids important for activation by the N-terminal domain, we mutagenized a GCN4 allele lacking the CAAD and screened alleles in vivo for reduced expression of the HIS3 gene. We found four pairs of closely spaced phenylalanines and a leucine residue distributed throughout the N-terminal 100 residues of GCN4 that are required for high-level activation in the absence of the CAAD. Trp, Leu, and Tyr were highly functional substitutions for the Phe residue at position 45. Combined with our previous findings, these results indicate that GCN4 contains seven clusters of aromatic or bulky hydrophobic residues which make important contributions to transcriptional activation at HIS3. None of the seven hydrophobic clusters is essential for activation by full-length GCN4, and the critical residues in two or three clusters must be mutated simultaneously to observe a substantial reduction in GCN4 function. Numerous combinations of four or five intact clusters conferred high-level transcription of HIS3. We propose that many of the hydrophobic clusters in GCN4 act independently of one another to provide redundant means of stimulating transcription and that the functional contributions of these different segments are cumulative at the HIS3 promoter. On the basis of the primacy of bulky hydrophobic residues throughout the activation domain, we suggest that GCN4 contains multiple sites that mediate hydrophobic contacts with one or more components of the transcription initiation machinery. JF - Molecular and cellular biology AU - Jackson, B M AU - Drysdale, C M AU - Natarajan, K AU - Hinnebusch, A G AD - Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA. Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 5557 EP - 5571 VL - 16 IS - 10 SN - 0270-7306, 0270-7306 KW - Amino Acids KW - 0 KW - DNA-Binding Proteins KW - Fungal Proteins KW - Recombinant Fusion Proteins KW - Saccharomyces cerevisiae Proteins KW - Trans-Activators KW - Protein Kinases KW - EC 2.7.- KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Hydro-Lyases KW - EC 4.2.1.- KW - imidazoleglycerolphosphate dehydratase KW - EC 4.2.1.19 KW - Index Medicus KW - Gene Expression Regulation, Fungal KW - Trans-Activators -- metabolism KW - Recombinant Fusion Proteins -- biosynthesis KW - Protein Structure, Secondary KW - Models, Structural KW - Genes, Fungal KW - Hydro-Lyases -- biosynthesis KW - Amino Acids -- biosynthesis KW - Transcription, Genetic KW - Amino Acid Sequence KW - Mutagenesis, Site-Directed KW - Alleles KW - Restriction Mapping KW - Hydro-Lyases -- genetics KW - Molecular Sequence Data KW - Point Mutation KW - beta-Galactosidase -- biosynthesis KW - Saccharomyces cerevisiae -- genetics KW - Fungal Proteins -- chemistry KW - Protein Kinases -- metabolism KW - Fungal Proteins -- metabolism KW - Saccharomyces cerevisiae -- metabolism KW - Saccharomyces cerevisiae -- growth & development KW - Transcriptional Activation KW - Protein Kinases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78344853?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Identification+of+seven+hydrophobic+clusters+in+GCN4+making+redundant+contributions+to+transcriptional+activation.&rft.au=Jackson%2C+B+M%3BDrysdale%2C+C+M%3BNatarajan%2C+K%3BHinnebusch%2C+A+G&rft.aulast=Jackson&rft.aufirst=B&rft.date=1996-10-01&rft.volume=16&rft.issue=10&rft.spage=5557&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 - 1996-11-15 N1 - Date created - 1996-11-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1991 Jan 4;251(4989):87-90 [1846049] Mol Cell Biol. 1991 Feb;11(2):935-44 [1824960] Cell. 1991 Mar 8;64(5):971-81 [2001592] Mol Cell Biol. 1991 May;11(5):2723-35 [2017175] Nature. 1991 Jun 13;351(6327):588-90 [1646402] Cell. 1991 Oct 18;67(2):365-76 [1833071] Nature. 1991 Oct 10;353(6344):569-71 [1922364] Cell. 1992 Jul 24;70(2):251-65 [1638630] J Virol. 1992 Sep;66(9):5500-8 [1323708] EMBO J. 1992 Nov;11(11):4145-52 [1396595] Cell. 1992 Dec 24;71(7):1223-37 [1473154] PCR Methods Appl. 1992 Aug;2(1):28-33 [1490172] Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):883-7 [8381535] Cell. 1993 Feb 26;72(4):575-85 [8440021] Mol Cell Biol. 1993 Oct;13(10):5981-9 [8413201] Mol Cell Biol. 1993 Nov;13(11):6733-41 [8413269] Nature. 1993 Sep 30;365(6445):412-9 [8413585] Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):8832-6 [8415616] Cell. 1993 Nov 5;75(3):519-30 [8221891] EMBO J. 1993 Nov;12(11):4269-78 [8223437] Nature. 1993 Dec 9;366(6455):531-6 [8255291] Nucleic Acids Res. 1993 Nov 11;21(22):4998-5004 [8255752] Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):192-6 [8278363] Nature. 1994 Jan 20;367(6460):295-9 [8121496] Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2488-92 [8146144] Cell. 1994 Apr 8;77(1):1-3 [8156586] J Biol Chem. 1994 Apr 29;269(17):12755-63 [8175688] Nature. 1994 May 19;369(6477):252-5 [8183347] Proc Natl Acad Sci U S A. 1994 May 10;91(10):4170-4 [8183887] Cell. 1994 Jun 3;77(5):749-59 [8205623] EMBO J. 1994 Jul 1;13(13):3039-49 [8039499] Cell. 1994 Aug 12;78(3):513-23 [8062391] Mol Cell Biol. 1994 Sep;14(9):6021-9 [8065335] Mol Cell Biol. 1994 Sep;14(9):6056-67 [8065339] EMBO J. 1994 Aug 15;13(16):3832-42 [8070410] Cell. 1994 Oct 7;79(1):107-17 [7923369] Cell. 1994 Oct 7;79(1):93-105 [7923382] Genes Dev. 1994 May 15;8(10):1235-46 [7926727] J Biol Chem. 1994 Oct 14;269(41):25613-20 [7929265] Mol Cell Biol. 1994 Oct;14(10):7013-24 [7935417] Mol Cell Biol. 1994 Nov;14(11):7226-34 [7935437] Mol Cell Biol. 1994 Nov;14(11):7507-16 [7935466] Biol Chem Hoppe Seyler. 1994 Jul;375(7):463-70 [7945996] Science. 1995 Jan 6;267(5194):100-4 [7809597] Mol Cell Biol. 1995 Mar;15(3):1220-33 [7862116] Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1699-703 [7878043] Mol Gen Genet. 1995 Mar 20;246(6):723-8 [7898440] Trends Biochem Sci. 1995 Mar;20(3):113-6 [7709429] Nature. 1995 Apr 27;374(6525):820-2 [7723828] Nature. 1995 Apr 27;374(6525):822-3 [7723829] Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3259-63 [7724549] EMBO J. 1995 Apr 3;14(7):1490-7 [7729424] Mol Cell Biol. 1995 May;15(5):2839-48 [7739564] Proc Natl Acad Sci U S A. 1995 May 23;92(11):5154-8 [7761466] Trends Biochem Sci. 1995 Apr;20(4):143-6 [7770913] Genes Dev. 1995 Apr 15;9(8):897-910 [7774808] Mol Gen Genet. 1995 Jun 10;247(5):571-8 [7603436] J Biol Chem. 1995 Aug 18;270(33):19337-44 [7642611] Mol Cell Biol. 1995 Oct;15(10):5461-9 [7565697] Mol Cell Biol. 1995 Oct;15(10):5757-61 [7565728] J Biol Chem. 1996 Mar 1;271(9):4819-26 [8617751] J Biol Chem. 1996 Mar 1;271(9):4827-37 [8617752] Mol Cell Biol. 1993 Sep;13(9):5233-44 [8395001] Anal Biochem. 1976 May 7;72:248-54 [942051] Proc Natl Acad Sci U S A. 1983 Sep;80(17):5374-8 [6351059] Proc Natl Acad Sci U S A. 1984 Oct;81(20):6442-6 [6387704] Cell. 1985 Nov;43(1):177-88 [3907851] Cell. 1986 Sep 12;46(6):885-94 [3530496] EMBO J. 1987 Sep;6(9):2781-4 [3678204] Nature. 1988 Jun 16;333(6174):635-40 [3287180] Yeast. 1985 Dec;1(2):83-138 [3916863] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An unusual mechanism of self-primed reverse transcription requires the RNase H domain of reverse transcriptase to cleave an RNA duplex. AN - 78337739; 8816477 AB - The reverse transcription of retroviruses and long terminal repeat-containing retrotransposons requires that tRNA species serve as primers. We recently reported that the long terminal repeat-containing retrotransposon Tf1 is a unique exception in that reverse transcription is independent of tRNA and is instead initiated by a self-priming mechanism. The first 11 bases of the Tf1 transcript fold back and anneal to the primer binding site in a process that results in the priming of minus-strand strong-stop DNA. Data presented here demonstrate that a cleavage occurs between the 11th and 12th bases of the transcript, resulting in the generation of the primer. Mutagenesis experiments presented here indicate that the RNase H domain of the Tf1 reverse transcriptase is required for the cleavage reaction, suggesting that this RNase H may have the novel ability to cleave double-stranded RNA at the end of a duplexed region. JF - Molecular and cellular biology AU - Levin, H L AD - Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA. Henry_Levin@nih.gov Y1 - 1996/10// PY - 1996 DA - October 1996 SP - 5645 EP - 5654 VL - 16 IS - 10 SN - 0270-7306, 0270-7306 KW - DNA Primers KW - 0 KW - RNA, Messenger KW - RNA, Viral KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - RNA-Directed DNA Polymerase KW - Ribonuclease H KW - EC 3.1.26.4 KW - Index Medicus KW - AIDS/HIV KW - RNA, Viral -- biosynthesis KW - RNA, Messenger -- chemistry KW - Transcription, Genetic KW - Schizosaccharomyces -- physiology KW - Amino Acid Sequence KW - HIV Reverse Transcriptase -- chemistry KW - RNA, Messenger -- biosynthesis KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Base Sequence KW - RNA, Viral -- chemistry KW - HIV Reverse Transcriptase -- metabolism KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Retroviridae -- enzymology KW - RNA-Directed DNA Polymerase -- chemistry KW - RNA-Directed DNA Polymerase -- metabolism KW - Ribonuclease H -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78337739?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=An+unusual+mechanism+of+self-primed+reverse+transcription+requires+the+RNase+H+domain+of+reverse+transcriptase+to+cleave+an+RNA+duplex.&rft.au=Levin%2C+H+L&rft.aulast=Levin&rft.aufirst=H&rft.date=1996-10-01&rft.volume=16&rft.issue=10&rft.spage=5645&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 - 1996-11-15 N1 - Date created - 1996-11-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell Biol. 1996 Jan;16(1):338-46 [8524313] Cell. 1995 Aug 25;82(4):545-54 [7664334] Cell. 1985 Sep;42(2):507-17 [2411424] Nature. 1986 Oct 30-Nov 5;323(6091):824-6 [2430190] Nature. 1987 Jun 25-Jul 1;327(6124):716-7 [2439916] Methods Enzymol. 1987;154:164-75 [3323810] Cell. 1988 Sep 23;54(7):955-66 [2843295] J Virol. 1989 Mar;63(3):1460-4 [2464706] Mol Biol Evol. 1988 Nov;5(6):675-90 [2464735] Cell. 1989 Feb 24;56(4):701-7 [2465091] Science. 1989 Feb 24;243(4894 Pt 1):1033-8 [2466332] Q Rev Biol. 1989 Mar;64(1):1-30 [2469098] Genes Dev. 1990 Mar;4(3):324-30 [2159935] Nature. 1990 Sep 20;347(6290):306-9 [1698262] Science. 1990 Sep 21;249(4975):1398-405 [2169648] EMBO J. 1990 Oct;9(10):3353-62 [1698615] Proc Natl Acad Sci U S A. 1990 Oct;87(20):8105-9 [1700426] Mol Cell Biol. 1990 Dec;10(12):6791-8 [2174117] Methods Enzymol. 1991;194:795-823 [2005825] Science. 1991 Apr 5;252(5002):88-95 [1707186] EMBO J. 1992 Mar;11(3):1145-53 [1312461] Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3236-40 [1314382] Science. 1992 May 15;256(5059):992-7 [1589782] J Biol Chem. 1992 Jun 15;267(17):11972-6 [1601867] J Biol Chem. 1992 Jul 15;267(20):13823-9 [1378431] Cell. 1992 Nov 13;71(4):663-70 [1384989] J Biol Chem. 1993 Feb 5;268(4):2674-83 [7679100] Cell. 1993 Feb 26;72(4):595-605 [7679954] Nucleic Acids Res. 1993 May 11;21(9):2117-23 [8389039] EMBO J. 1993 Dec;12(12):4885-95 [8223497] J Biol Chem. 1993 Nov 5;268(31):23585-92 [7693692] J Virol. 1994 Jan;68(1):6-13 [7504742] Cell. 1993 Dec 17;75(6):1071-81 [7505202] Mol Biol Evol. 1993 Nov;10(6):1370-9 [7506345] J Virol. 1994 Mar;68(3):1970-1 [7509004] J Biol Chem. 1994 Jul 29;269(30):19245-9 [7518454] EMBO J. 1995 Feb 15;14(4):833-41 [7533725] Mol Cell Biol. 1995 Jun;15(6):3310-7 [7760826] Cell. 1995 Nov 17;83(4):529-38 [7585955] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tumor necrosis factor-alpha modulates the expression of its p60 receptor and several cytokines in rat tracheal epithelial cells. AN - 78335614; 8816419 AB - The epithelium of the conducting airways is frequently the target of toxic chemical and microbial agents causing inflammation, hypersecretion, and epithelial necrosis. TNF-alpha is a prototypical inflammatory cytokine released by macrophages and other inflammatory cells. The purpose of this study was to characterize TNF-alpha receptors in fully differentiated rat tracheal epithelial (RTE) cells in culture and to examine the effects of TNF-alpha on this epithelium. We demonstrated the presence of approximately 250 TNF-alpha receptors per RTE cell. Both known receptor types, p60 (TNF-RI, CD 120a) and p80 (TNF-RII, CD 120b), were expressed. The level of p80 mRNA was unaffected by TNF-alpha treatment, whereas p60 mRNA was down-regulated, and soluble TNF-RI was shed from cells within 30 min. Treatment of RTE cultures with TNF-alpha (1000 U) caused no cytotoxicity (as determined by lactate dehydrogenase release). However, TNF-alpha exposure of the cultures induced the expression of several inflammatory mediators, as determined by reverse transcription-PCR and ELISA. Low levels of IFN-gamma mRNA became detectable after 4 h. Increased levels of TNF-alpha mRNA and protein were found, which peaked after 6 h of TNF-alpha treatment, but neither IL-1 alpha nor IL-1 beta was detectable. Calcium-independent nitric oxide synthase transcripts were elevated two- to threefold within 2 to 6 h of TNF-alpha treatment. These findings suggest that the airway epithelium may actively participate in the pathogenesis of airway inflammation through the production of mediators similar to those found in a Th1 response. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Bader, T AU - Nettesheim, P AD - National Institute of Environmental Health Sciences, Research Triangle Park NC 27709, USA. Y1 - 1996/10/01/ PY - 1996 DA - 1996 Oct 01 SP - 3089 EP - 3096 VL - 157 IS - 7 SN - 0022-1767, 0022-1767 KW - Antigens, CD KW - 0 KW - RNA, Messenger KW - Receptors, Tumor Necrosis Factor KW - Receptors, Tumor Necrosis Factor, Type I KW - Receptors, Tumor Necrosis Factor, Type II KW - Tumor Necrosis Factor-alpha KW - Interferon-gamma KW - 82115-62-6 KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Abridged Index Medicus KW - Index Medicus KW - Specific Pathogen-Free Organisms KW - Animals KW - Interferon-gamma -- genetics KW - Cell Differentiation KW - Interferon-gamma -- biosynthesis KW - RNA, Messenger -- genetics KW - RNA, Messenger -- biosynthesis KW - Epithelium -- drug effects KW - Nitric Oxide Synthase -- biosynthesis KW - Rats KW - Rats, Inbred F344 KW - Base Sequence KW - Enzyme Induction -- drug effects KW - Cells, Cultured KW - Nitric Oxide Synthase -- genetics KW - Molecular Sequence Data KW - Down-Regulation -- drug effects KW - Male KW - Antigens, CD -- biosynthesis KW - Receptors, Tumor Necrosis Factor -- biosynthesis KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Antigens, CD -- genetics KW - Antigens, CD -- drug effects KW - Gene Expression Regulation -- drug effects KW - Trachea -- drug effects KW - Receptors, Tumor Necrosis Factor -- drug effects KW - Receptors, Tumor Necrosis Factor -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78335614?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Tumor+necrosis+factor-alpha+modulates+the+expression+of+its+p60+receptor+and+several+cytokines+in+rat+tracheal+epithelial+cells.&rft.au=Bader%2C+T%3BNettesheim%2C+P&rft.aulast=Bader&rft.aufirst=T&rft.date=1996-10-01&rft.volume=157&rft.issue=7&rft.spage=3089&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 - 1996-11-25 N1 - Date created - 1996-11-25 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U55849; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The NIEHS Predictive-Toxicology Evaluation Project. AN - 36360041; 201002-31-0247417 (CE); 11701761 (EN) AB - The Predictive-Toxicology Evaluation (PTE) project conducts collaborative experiments that subject the performance of predictive-toxicology (PT) methods to rigorous, objective evaluation in a uniquely informative manner. Sponsored by the National Institute of Environmental Health Sciences, it takes advantage of the ongoing testing conducted by the U.S. National Toxicology Program (NTP) to estimate the true error of models that have been applied to make prospective predictions on previously untested, noncongeneric-chemical substances. The PTE project first identifies a group of standardized NTP chemical bioassays either scheduled to be conducted or are ongoing, but not yet complete. The project then announces and advertises the evaluation experiment, disseminates information about the chemical bioassays, and encourages researchers from a wide variety of disciplines to publish their predictions in peer-reviewed journals, using whatever approaches and methods they feel are best. A collection of such papers is published in this Environmental Health Perspectives Supplement, providing readers the opportunity to compare and contrast PT approaches and models, within the context of their prospective application to an actual-use situation. This introduction to this collection of papers on predictive toxicology summarizes the predictions made and the final results obtained for the 44 chemical carcinogenesis bioassays of the first PTE experiment (PTE-1) and presents information that identifies the 30 chemical carcinogenesis bioassays of PTE-2, along with a table of prediction sets that have been published to date. It also provides background about the origin and goals of the PTE project, outlines the special challenge associated with estimating the true error of models that aspire to predict open-system behavior, and summarizes what has been learned to date. JF - Environmental Health Perspectives AU - Bristol, D W AU - Wachsman, J T AU - Greenwell, A AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. bristol@niehs.nih.gov PY - 1996 SP - 1001 EP - 1010 PB - U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES, NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES VL - 104 SN - 0091-6765, 0091-6765 KW - Civil Engineering (CE); Environmental Engineering (EN) KW - Mathematical models KW - Bioassay KW - Health KW - Collection KW - Toxicology KW - Carcinogens KW - Errors KW - Tables (data) KW - Article KW - EE 10:General Environmental Engineering (EN) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/36360041?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aenvironmentalengabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=The+NIEHS+Predictive-Toxicology+Evaluation+Project.&rft.au=Bristol%2C+D+W%3BWachsman%2C+J+T%3BGreenwell%2C+A&rft.aulast=Bristol&rft.aufirst=D&rft.date=1996-10-01&rft.volume=104&rft.issue=&rft.spage=1001&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-02-01 N1 - Last updated - 2011-11-14 ER - TY - JOUR T1 - Multicomponent criteria for predicting carcinogenicity: dataset of 30 NTP chemicals. AN - 21257817; 11704936 AB - This article is in response to the challenge issued to the scientific community by the National Toxicology Program to predict the carcinogenicity potential of 30 chemicals previously selected for long-term carcinogenicity testing. Utilizing the available toxicologic, genetic, and structural information on 30 chemicals previously selected for long-term carcinogenicity testing, we predict that 16 chemicals (53%) would induce some indication of carcinogenic activity in rodents; we further predict that 10 chemicals (33%) would be associated with weak or equivocal carcinogenic responses, and another 4 (13%) would give no indication of carcinogenicity. Our level of certainty is indicated for many of these predictions. Nonetheless, we believe that most instances of guessing whether a chemical would eventually induce cancer in experimental animals and hence represent a carcinogenic hazard to humans are fraught with considerable uncertainty: uncertainty that can only be relieved by long-term testing for carcinogenicity in animals or by conducting an epidemiologic investigation of exposed individuals or groups. We further believe that the day may come when our predictive acumen will be upgraded to such an extent that we might eventually obviate cancer testing. Until then, and in the best interests of public health, however, we urge long term testing of chemicals in animals be continued, at increased pace. JF - Environmental Health Perspectives AU - Huff, J AU - Weisburger, E AU - Fung, V A AD - National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA, huff1@niehs.nih.gov Y1 - 1996/10// PY - 1996 DA - Oct 1996 SP - 1105 EP - 1112 PB - US Government Printing Office, Superintendent of Documents, P.O. Box 371954 Pittsburgh PA 15250-7954 USA VL - 104 IS - Suppl 5 SN - 0091-6765, 0091-6765 KW - Environment Abstracts KW - Chemicals KW - Carcinogenicity KW - Cancer KW - Toxicology KW - rodents KW - Public health KW - ENA 02:Toxicology & Environmental Safety UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21257817?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aenvabstractsmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=Multicomponent+criteria+for+predicting+carcinogenicity%3A+dataset+of+30+NTP+chemicals.&rft.au=Huff%2C+J%3BWeisburger%2C+E%3BFung%2C+V+A&rft.aulast=Huff&rft.aufirst=J&rft.date=1996-10-01&rft.volume=104&rft.issue=Suppl+5&rft.spage=1105&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-01-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Chemicals; Carcinogenicity; rodents; Toxicology; Cancer; Public health ER - TY - JOUR T1 - Forensic drug testing for opiates. VII. Urinary excretion profile of intranasal (snorted) heroin AN - 16021988; 4085073 AB - The urinary excretion profile of free and conjugated morphine and 6-acetylmorphine was determined by gas chromatography-mass spectrometry (GC-MS) and immunoassay for six healthy male subjects after intranasal administration of 6 and 12 mg of heroin HCl. Results were compared with heroin administration (6 mg) by the intramuscular route. Heroin metabolites were rapidly excreted with peak concentrations appearing in the first or second specimen collection after drug administration. Concentrations of total morphine and 6-acetylmorphine after intranasal heroin were similar to those after intramuscular administration, but free morphine concentrations after the lower intranasal dose were significantly lower than the same dose given intramuscularly. Detection times for total morphine by GC-MS and immunoassay (300-ng/mL cutoff concentration) were generally 24-36 h, but were reduced to less than 12 h at the higher cutoff concentration of 2000 ng/mL. 6-Acetylmorphine concentrations were highly variable and short-lived; detection times (10 ng/mL) were approximately 2-3 h for most subjects, but some failed to produce positive specimens. Of 14 specimens with 6-acetylmorphine concentrations of 10 ng/mL or more, ten were associated with total morphine concentrations greater than 2000 ng/mL, and four specimens had total morphine concentrations less than 2000 ng/mL. Overall, intranasal administration of heroin produced a similar profile of excretion of heroin metabolites to intramuscular administration. JF - Journal of Analytical Toxicology AU - Cone, E J AU - Jufer, R AU - Darwin, W D AU - Needleman, S B AD - Addiction Research Center, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA Y1 - 1996/10// PY - 1996 DA - Oct 1996 SP - 379 EP - 392 VL - 20 IS - 6 SN - 0146-4760, 0146-4760 KW - excretion KW - man KW - heroin KW - Toxicology Abstracts KW - opiates KW - urine KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16021988?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Analytical+Toxicology&rft.atitle=Forensic+drug+testing+for+opiates.+VII.+Urinary+excretion+profile+of+intranasal+%28snorted%29+heroin&rft.au=Cone%2C+E+J%3BJufer%2C+R%3BDarwin%2C+W+D%3BNeedleman%2C+S+B&rft.aulast=Cone&rft.aufirst=E&rft.date=1996-10-01&rft.volume=20&rft.issue=6&rft.spage=379&rft.isbn=&rft.btitle=&rft.title=Journal+of+Analytical+Toxicology&rft.issn=01464760&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - opiates; urine ER - TY - JOUR T1 - In vitro binding studies of drugs to hair: Influence of melanin and lipids on cocaine binding to Caucasoid and Africoid hair AN - 16019561; 4085068 AB - Although the mechanism(s) of drug deposition in hair are unknown, there is evidence that suggests that the amount and type of melanin present are major factors in determining how much drug enters hair after exposure. The role of other hair components, such as lipids, has received less attention. We used in vitro binding techniques to evaluate the binding of radiolabeled cocaine to different types of treated and untreated hair specimens. Divided male and female Caucasoid (black/brown and blond colored) and Africoid (black colored) hair specimens (N = 7) were exhaustively extracted to remove lipid components (lipid-extracted hair). Separate portions were bleached to denature or alter melanin content. Experiments with radiolabeled cocaine were performed on untreated, lipid-extracted, and bleached portions of hair from different groups. Cocaine binding was significantly higher (p < .01) to male Africoid hair compared with other groups. The amount of drug binding was similar among female Africoid and male and female, black/brown Caucasoid specimens. The lowest amount of binding was observed with blond, female Caucasoid specimens. Binding experiments also revealed that specific cocaine binding generally did not differ significantly between lipid-extracted hair and untreated hair, but bleaching of most hair specimens resulted in significant (p < .01) decreases in specific binding compared with untreated hair. In separate experiments with cocaine-treated hair specimens, digested samples were evaluated to determine if removal of the insoluble melanin fraction from soluble hair components provided a means of normalization of drug content and elimination of color bias. Removal of the insoluble melanin fraction was not effective in removal of significant amounts of cocaine, which indicated that the digestion process released bound cocaine into the digest solution. Overall, these experiments suggested that lipids in hair play a minor role in drug binding, whereas melanin functions as a major binding site for cocaine. Natural (ethnic) or artificial (bleaching) differences in melanin content may determine the extent of cocaine entrapment in hair after drug exposure. Further, digestion of hair samples and removal of insoluble melanin failed to be effective in removal of hair color bias. JF - Journal of Analytical Toxicology AU - Joseph, RE Jr AU - Su, Tsung-Ping AU - Cone, E J AD - P.O. Box 5180, Division of Intramural Research, Addiction Research Center, National Institute on Drug Abuse, Baltimore, MD 21224, USA Y1 - 1996/10// PY - 1996 DA - Oct 1996 SP - 338 EP - 344 VL - 20 IS - 6 SN - 0146-4760, 0146-4760 KW - melanins KW - cocaine KW - Toxicology Abstracts KW - drug abuse KW - lipids KW - hair KW - X 24222:Analytical procedures KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16019561?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Analytical+Toxicology&rft.atitle=In+vitro+binding+studies+of+drugs+to+hair%3A+Influence+of+melanin+and+lipids+on+cocaine+binding+to+Caucasoid+and+Africoid+hair&rft.au=Joseph%2C+RE+Jr%3BSu%2C+Tsung-Ping%3BCone%2C+E+J&rft.aulast=Joseph&rft.aufirst=RE&rft.date=1996-10-01&rft.volume=20&rft.issue=6&rft.spage=338&rft.isbn=&rft.btitle=&rft.title=Journal+of+Analytical+Toxicology&rft.issn=01464760&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - drug abuse; hair; lipids ER - TY - JOUR T1 - Probing the structure-function relationship of alpha -latrotoxin-formed channels with antibodies and pronase AN - 15888797; 4029419 AB - The major toxic component of black widow spider (Latrodectus mactans tredecimguttatus) venom, alpha -latrotoxin, is known to form ionic channels in different membranes. In order to probe the extramembrane domains of alpha -latrotoxin molecule, alpha -latrotoxin channels in planar lipid membrane were treated with antibodies to latrotoxin or with pronase added to different sides of the membrane. It was found that antibody addition to the same side as the toxin (cis) decreased channel conductance only at positive potentials across the membrane. In contrast, trans side addition of antibodies changed the channel conductance at both positive and negative potentials: at positive potential conductance first slightly increased then decreased by more then 50%; at negative potential it decreased much more quickly, to only about 20% of the initial value. No dependence on membrane potential was found for pronase treatment of incorporated channels. For both cis and trans application of pronase, channel selectivity for Ca super(2+), Mg super(2+), Ba super(2+) and K super(+), Na super(+), Li super(+) ions did not change significantly but Cd super(2+) block was decreased. Trans pronase treatment also resulted in some rectification of I/V curves and an increase in channel conductance. We interpret these findings as evidence that alpha -latrotoxin channel has protruding parts on both sides of the membrane and that its conformation in the membrane depends on membrane potential. JF - Toxicon AU - Chanturiya, AN AU - Nikolaenko, AN AU - Shatursky, OYa AU - Lishko, V K AD - LTPB/NICHD, NIH, Bd. 10, Rm. 10D04, 10 Cent. Dr., Bethesda, MD 20892, USA Y1 - 1996/10// PY - 1996 DA - Oct 1996 SP - 1157 EP - 1164 VL - 34 IS - 10 SN - 0041-0101, 0041-0101 KW - structure-activity relationships KW - channels KW - mycolysin KW - Latrodectus mactans tredecimguttatus KW - pronase KW - Entomology Abstracts; Toxicology Abstracts KW - venom KW - antibodies KW - membrane potential KW - Theridiidae KW - X 24173:Animals KW - Z 05183:Toxicology & resistance UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15888797?accountid=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=Toxicon&rft.atitle=Probing+the+structure-function+relationship+of+alpha+-latrotoxin-formed+channels+with+antibodies+and+pronase&rft.au=Chanturiya%2C+AN%3BNikolaenko%2C+AN%3BShatursky%2C+OYa%3BLishko%2C+V+K&rft.aulast=Chanturiya&rft.aufirst=AN&rft.date=1996-10-01&rft.volume=34&rft.issue=10&rft.spage=1157&rft.isbn=&rft.btitle=&rft.title=Toxicon&rft.issn=00410101&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 - Theridiidae; venom; membrane potential; antibodies ER - TY - JOUR T1 - Ethanol inhibition of nicotinic acetylcholine type alpha 7 receptors involves the amino-terminal domain of the receptor AN - 15886237; 4033501 AB - Recent studies have suggested that alcohols can affect the function of neurotransmitter-gated ion channels by a direct interaction with the receptor protein. However, the molecular region of the receptor protein that mediates the alcohol action is not known. To address this question, we studied the effect of ethanol on the function of recombinant nicotinic acetylcholine type alpha 7 (nACh sub( alpha 7)) receptors, 5-hydroxytryptamine (serotonin) type 3 (5-HT sub(3)) receptors, and a chimeric receptor constructed from these two receptors. The receptors were expressed in Xenopus oocytes and their function was studied using the two-electrode voltage-clamp technique. Ethanol inhibited the response of nACh sub( alpha 7) receptors in a concentration-dependent manner over the concentration range of 5-100 mM; the EC sub(50) for this inhibition was 33 mM ethanol. Ethanol decreased the maximal amplitude (E sub(max)) of the nACh sub( alpha 7) receptor agonist concentration-response curve, without significantly affecting the EC sub(50). In contrast, ethanol potentiated 5-HT sub(3) receptor-mediated responses at low agonist concentrations. The potentiation was concentration-dependent over the concentration range of 10-100 mM; the EC sub(50) for this potentiation was 57 mM ethanol. The magnitude of the ethanol potentiation of 5-HT sub(3) receptor-mediated responses decreased with increasing agonist concentration. The chimeric receptor had the amino-terminal domain from the nACh sub( alpha 7) receptor and the transmembrane and carboxyl-terminal domains from the 5-HT sub(3) receptor. Ethanol was found to inhibit the function of this chimeric receptor in a manner similar to that of nACh sub( alpha 7) receptors. Because the inhibition transfers with the amino-terminal domain of the receptor, the observations suggest that the amino-terminal domain of the receptor is involved in the inhibition. JF - Molecular Pharmacology AU - Yu, D AU - Zhang, L AU - Eisele, J-L AU - Bertrand, D AU - Changeux, J-P AU - Weight, F F AD - LMCN, NIAAA, NIH, 12501 Washington Ave., Rockville, MD 20852, USA Y1 - 1996/10// PY - 1996 DA - Oct 1996 SP - 1010 EP - 1016 VL - 50 IS - 4 SN - 0026-895X, 0026-895X KW - ethanol KW - acetylcholine receptors (nicotinic) KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - neurotoxicity KW - oocytes KW - Xenopus KW - N3 11101:General KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15886237?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Pharmacology&rft.atitle=Ethanol+inhibition+of+nicotinic+acetylcholine+type+alpha+7+receptors+involves+the+amino-terminal+domain+of+the+receptor&rft.au=Yu%2C+D%3BZhang%2C+L%3BEisele%2C+J-L%3BBertrand%2C+D%3BChangeux%2C+J-P%3BWeight%2C+F+F&rft.aulast=Yu&rft.aufirst=D&rft.date=1996-10-01&rft.volume=50&rft.issue=4&rft.spage=1010&rft.isbn=&rft.btitle=&rft.title=Molecular+Pharmacology&rft.issn=0026895X&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 - Xenopus; neurotoxicity; oocytes ER - TY - JOUR T1 - Crystal structure and amino acid sequence of Wolinella succinogenes L-asparaginase AN - 15815092; 4006409 AB - The amino acid sequence and tertiary structure of Wolinella succinogenes L-asparaginase were determined, and were compared with the structures of other type-II bacterial L-asparaginases. Each chain of this homotetrameric enzyme consists of 330 residues. The amino acid sequence is 40-50% identical to the sequences of related proteins from other bacterial sources, and all residues previously shown to be crucial for the catalytic action of these enzymes are identical. Differences between the amino acid sequence of W. succinogenes L-asparaginase and that of related enzymes are discussed in terms of the possible influence on the substrate specificity. The overall fold of the protein subunit is almost identical to that observed for other L-asparaginases. Two fragments in each subunit, a very highly flexible loop ( approximately 20 amino acids) that forms part of the active site, and the N-terminus (two amino acids), are not defined in the structure. The orientation of Thr14, a residue probably involved in the catalytic activity, indicates the absence of ligand in the active-site pocket. The rigid part of the active site, which includes the asparaginase triad Thr93-Lys166-Asp94, is structurally very highly conserved with equivalent regions found in other type-II bacterial L-asparaginases. JF - European Journal of Biochemistry AU - Lubkowski, J AU - Palm, G J AU - Gilliland, G L AU - Derst, C AU - Roehm, K-H AU - Wlodawer, A AD - Macromolecular Struct. Lab., NCI-Frederick Cancer Res. and Dev. Cent., ABL-Basic Res. Prog., Frederick, MD 21702-1201, USA Y1 - 1996/10// PY - 1996 DA - Oct 1996 SP - 201 EP - 207 VL - 241 IS - 1 SN - 0014-2956, 0014-2956 KW - asparaginase KW - Microbiology Abstracts B: Bacteriology KW - amino acid sequence KW - crystal structure KW - Wolinella succinogenes KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15815092?accountid=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+Biochemistry&rft.atitle=Crystal+structure+and+amino+acid+sequence+of+Wolinella+succinogenes+L-asparaginase&rft.au=Lubkowski%2C+J%3BPalm%2C+G+J%3BGilliland%2C+G+L%3BDerst%2C+C%3BRoehm%2C+K-H%3BWlodawer%2C+A&rft.aulast=Lubkowski&rft.aufirst=J&rft.date=1996-10-01&rft.volume=241&rft.issue=1&rft.spage=201&rft.isbn=&rft.btitle=&rft.title=European+Journal+of+Biochemistry&rft.issn=00142956&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 - Wolinella succinogenes; crystal structure; amino acid sequence ER - TY - JOUR T1 - Laboratory Validation Study of Drug Evaluation and Classification Program: Ethanol, Cocaine, and Marijuana AN - 1093467631; 17185717 AB - The Drug Evaluation and Classification (DEC) program is used by police agencies to determine if individuals are behaviorally impaired because of drug use, and, if impaired, to determine the class of drug(s) causing the impairment. Although widely used, the validity of the DEC evaluation has not been rigorously tested. The primary goal of this study was to determine the validity of the variables of the DEC evaluation in predicting whether research volunteers had been administered ethanol, cocaine, or marijuana; a secondary goal was to determine the accuracy of trained police officers (Drug Recognition Examiner, DRE) in detecting whether subjects had been dosed with ethanol, cocaine, or marijuana. Community volunteers (n = 18) with histories of drug use received ethanol (,0.2,0.52 g/kg), cocaine (4, 48, 96 mg/70 kg), and marijuana (0, 1.75, 3.55% THC) in a double-blind, randomized, within-subjects design. A single drug dose or placebo was administered during each of nine experimental sessions, and blood samples were obtained before and periodically after dosing. With the exception of marijuana, plasma drug concentration was at or near the observed maximum during the DEC evaluation. The ability of the DEC evaluation to predict the intake of ethanol, cocaine, or marijuana was optimal when using 17a-'28 variables from the evaluation. When DREs concluded impairment was due to drugs other than ethanol, their opinions were consistent with toxicology in 44% of cases. These findings suggest that the DEC evaluation can be used to predict accurately acute administration of ethanol, cocaine, or marijuana, and that predictions of drug use may be improved if DREs focused on a subset of variables. JF - Journal of Analytical Toxicology AU - Heishman, Stephen J AU - Singleton, Edward G AU - Crouch, Dennis J AD - Addiction Research Center, National Institute on Drug Abuse, Baltimore, Maryland Y1 - 1996/10// PY - 1996 DA - Oct 1996 SP - 468 EP - 483 PB - Preston Publications, Inc., 6600 W. Touhy Ave. Niles IL 60714 United States VL - 20 IS - 6 SN - 0146-4760, 0146-4760 KW - Toxicology Abstracts KW - Cannabis KW - Classification KW - Cocaine KW - Drug abuse KW - Drug development KW - Ethanol KW - Tetrahydrocannabinol KW - X 24380:Social Poisons & Drug Abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1093467631?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Analytical+Toxicology&rft.atitle=Laboratory+Validation+Study+of+Drug+Evaluation+and+Classification+Program%3A+Ethanol%2C+Cocaine%2C+and+Marijuana&rft.au=Heishman%2C+Stephen+J%3BSingleton%2C+Edward+G%3BCrouch%2C+Dennis+J&rft.aulast=Heishman&rft.aufirst=Stephen&rft.date=1996-10-01&rft.volume=20&rft.issue=6&rft.spage=468&rft.isbn=&rft.btitle=&rft.title=Journal+of+Analytical+Toxicology&rft.issn=01464760&rft_id=info:doi/ L2 - http://www.ingentaconnect.com/content/oup/jat/1996/00000020/00000006/art00018 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-10-01 N1 - Last updated - 2012-10-19 N1 - SubjectsTermNotLitGenreText - Tetrahydrocannabinol; Classification; Cannabis; Drug development; Cocaine; Drug abuse; Ethanol ER - TY - JOUR T1 - Cocaine Disposition in Meconium from Newborns of Cocaine-Abusing Mothers and Urine of Adult Drug Users AN - 1093467593; 17185715 AB - The analysis of meconium for cocaine and metabolites has proved to be a reliable method for the detection of fetal cocaine exposure. Better sensitivity and a larger gestational window of detection have been demonstrated for meconium testing as compared with neonatal urine testing. Cocaine and cocaine metabolites, including benzoylecgonine, ecgonine methyl ester, cocaethylene, norcocaine, benzoylnorecgonine, and m-hydroxybenzoylecgonine, have been identified in meconium. The origin of these metabolites, whether maternal or fetal, has not been established. This study was conducted to compare the disposition of cocaine and metabolites in meconium from fetuses exposed to cocaine with that of urine from cocaine abusers. Meconium specimens were obtained from six neonates of mothers positive for cocaine use by urinalysis or self-reporting or both during pregnancy. Urine specimens were obtained from 17 adult female and 17 adult male cocaine users enrolled in a treatment program. Specimens were analyzed by gas chromatographya-'mass spectrometry for cocaine and 12 related analytes. The following analytes were identified and measured in meconium and urine: anhydroecgonine methyl ester; ecgonine methyl ester; ecgonine ethyl ester; cocaine; cocaethylene; benzoylecgonine; norcocaine; norcocaethylene; benzoylnorecgonine; m- and p-hydroxycocaine; and m- and p-hydroxybenzoylecgonine. In addition, both m- and p-hydroxybenzoylecgonine were found to exhibit approximately equal cross-reactivity with benzoylecgonine in the EMIT and TDx assays. The presence of p-hydroxybenzoylecgonine in meconium suggested that this newly identified metabolite, like m-hydroxybenzoylecgonine, might serve as a valuable marker of fetal cocaine exposure during pregnancy. The presence of cocaine and anhydroecgonine methyl ester in meconium was attributed to transfer across the placenta from the mother. However, the origin of the hydrolytic and oxidative metabolites of cocaine could not be established because they were also identified in urine specimens of adult female cocaine users and could have arisen in meconium from either fetal or maternal metabolism. JF - Journal of Analytical Toxicology AU - Oyler, Jonathan AU - Darwin, William D AU - Preston, Kenzie L AU - Suess, Patricia AU - Cone, Edward J AD - Addiction Research Center, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224 Y1 - 1996/10// PY - 1996 DA - Oct 1996 SP - 453 EP - 462 PB - Preston Publications, Inc., 6600 W. Touhy Ave. Niles IL 60714 United States VL - 20 IS - 6 SN - 0146-4760, 0146-4760 KW - Toxicology Abstracts KW - Cocaethylene KW - Cocaine KW - Cross-reactivity KW - Disposition KW - Drug abuse KW - Fetuses KW - Meconium KW - Metabolites KW - Neonates KW - Placenta KW - Pregnancy KW - Spectrometry KW - Urinalysis KW - Urine KW - X 24380:Social Poisons & Drug Abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1093467593?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Analytical+Toxicology&rft.atitle=Cocaine+Disposition+in+Meconium+from+Newborns+of+Cocaine-Abusing+Mothers+and+Urine+of+Adult+Drug+Users&rft.au=Oyler%2C+Jonathan%3BDarwin%2C+William+D%3BPreston%2C+Kenzie+L%3BSuess%2C+Patricia%3BCone%2C+Edward+J&rft.aulast=Oyler&rft.aufirst=Jonathan&rft.date=1996-10-01&rft.volume=20&rft.issue=6&rft.spage=453&rft.isbn=&rft.btitle=&rft.title=Journal+of+Analytical+Toxicology&rft.issn=01464760&rft_id=info:doi/ L2 - http://www.ingentaconnect.com/content/oup/jat/1996/00000020/00000006/art00016 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-10-01 N1 - Last updated - 2012-10-19 N1 - SubjectsTermNotLitGenreText - Cross-reactivity; Meconium; Metabolites; Disposition; Drug abuse; Fetuses; Pregnancy; Spectrometry; Cocaethylene; Urine; Placenta; Neonates; Urinalysis; Cocaine ER - TY - JOUR T1 - Urinary Excretion Profiles of 11-Nor-9-Carboxy-I'9-Tetrahydrocannabinol in Humans after Single Smoked Doses of Marijuana AN - 1093467522; 17185714 AB - Interpretation of marijuana-positive urine tests requires an understanding of the excretion pattern of marijuana metabolites in humans. However, limited urinary excretion data from controlled clinical studies of marijuana use are available. In this study, six subjects smoked a single marijuana cigarette (placebo, 1.75% I'9-tetrahydrocannabinol [THC], or 3.55% THC) each week while residing on the clinical ward of the Addiction Research Center. Individual urine specimens were collected for 7 days after drug administration and analyzed for 11-nor-9-carboxy-I'9-tetrahydrocannabinol (THCCOOH) by gas chromatographya-'mass spectrometry (GCa-'MS) with a limit of detection of 0.5 ng/mL. Substantial intersubject variability in patterns of THCCOOH excretion was noted between subjects and between doses. Mean THCCOOH concentrations in the first urine collections were 47 A? 22.3 ng/mL and 75.3 A? 48.9 ng/mL after the 1.75 and 3.55% THC cigarettes, respectively. Mean peak urine THCCOOH concentrations averaged 89.8 A? 31.9 ng/mL and 153.4 A? 49.2 ng/mL after smoking of approximately 15.8 mg and 33.8 mg THC, respectively. The mean times of peak urine concentration were 7.7 A? 0.8 h after the 1.75% THC and 13.9 A? 3.5 h after the 3.55% THC dose. Mean GCa-'MS THCCOOH detection times for the last positive urine sample after the smoking of a single 1.75 or 3.55% THC cigarette were 33.7 A? 9.2 h and 88.6 A? 9.5 h, respectively, when a 15-ng/mL cutoff concentration was used. An average of 93.9 A? 24.5 A Delta *mg THCCOOH (range, 34.6a-'171.6 A Delta *mg) was excreted by each subject during the 7-day period after smoking of a single 1.75% THC cigarette. The average amount of THCCOOH excreted in the same time period after the high dose was 197.4 A? 33.6 A Delta *mg (range, 107.5a-'305.0 A Delta *mg). This represented an average of only 0.54 A? 0.14% and 0.53 A? 0.09% of the original amount of THC in the low- and high-dose cigarettes, respectively. These data provide a detailed compilation of THCCOOH concentrations in urine after administration of marijuana that may aid in the interpretation of urine cannabinoid results. JF - Journal of Analytical Toxicology AU - Huestis, Marilyn A AU - Mitchell, John M AU - Cone, Edward J AD - Addiction Research Center, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224 Y1 - 1996/10// PY - 1996 DA - Oct 1996 SP - 441 EP - 452 PB - Preston Publications, Inc., 6600 W. Touhy Ave. Niles IL 60714 United States VL - 20 IS - 6 SN - 0146-4760, 0146-4760 KW - Toxicology Abstracts KW - Addiction KW - Cannabinoids KW - Cannabis KW - Cigarettes KW - Data processing KW - Excretion KW - Metabolites KW - Smoking KW - Spectrometry KW - Tetrahydrocannabinol KW - Urine KW - X 24380:Social Poisons & Drug Abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1093467522?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Analytical+Toxicology&rft.atitle=Urinary+Excretion+Profiles+of+11-Nor-9-Carboxy-I%279-Tetrahydrocannabinol+in+Humans+after+Single+Smoked+Doses+of+Marijuana&rft.au=Huestis%2C+Marilyn+A%3BMitchell%2C+John+M%3BCone%2C+Edward+J&rft.aulast=Huestis&rft.aufirst=Marilyn&rft.date=1996-10-01&rft.volume=20&rft.issue=6&rft.spage=441&rft.isbn=&rft.btitle=&rft.title=Journal+of+Analytical+Toxicology&rft.issn=01464760&rft_id=info:doi/ L2 - http://www.ingentaconnect.com/content/oup/jat/1996/00000020/00000006/art00015 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-10-01 N1 - Last updated - 2012-10-19 N1 - SubjectsTermNotLitGenreText - Tetrahydrocannabinol; Smoking; Data processing; Cannabinoids; Cigarettes; Urine; Cannabis; Metabolites; Excretion; Addiction; Spectrometry ER -