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 - Date completed - 1997-07-21 N1 - Date created - 1997-07-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Methods Biochem Anal. 1966;14:113-76 [5328501] J Comp Neurol. 1994 Apr 8;342(2):186-205 [8201031] Teratology. 1981 Aug;24(1):65-78 [7302873] N Engl J Med. 1985 Jan 10;312(2):82-90 [3880598] Proc Natl Acad Sci U S A. 1986 Feb;83(4):1159-62 [3456568] Lancet. 1986 Aug 2;2(8501):288-9 [2874312] J Immunol. 1987 Apr 15;138(8):2640-4 [3031162] J Cell Biol. 1987 Jun;104(6):1603-10 [3584242] Nature. 1988 Oct 13;335(6191):639-42 [2845276] Proc Natl Acad Sci U S A. 1989 Jan;86(2):621-5 [2536171] J Immunol. 1989 May 1;142(9):3091-7 [2468713] J Immunol. 1989 May 15;142(10):3553-9 [2541200] N Engl J Med. 1989 Jun 22;320(25):1637-42 [2786145] Science. 1989 Sep 22;245(4924):1380-2 [2571187] Arch Dis Child. 1989 Aug;64(8):1140-5 [2782927] J Infect Dis. 1989 Oct;160(4):583-8 [2477467] AIDS. 1989 Oct;3(10):643-6 [2512957] Blood. 1990 Jan 1;75(1):152-9 [1967213] BMJ. 1989 Nov 18;299(6710):1250-2 [2513899] Proc Natl Acad Sci U S A. 1990 Mar;87(6):2379-83 [2315327] Science. 1990 Apr 20;248(4953):364-7 [2326646] JAMA. 1990 Oct 24-31;264(16):2088-92 [2214076] AIDS. 1990 Oct;4(10):1001-5 [2261113] Lancet. 1991 Feb 2;337(8736):253-60 [1671109] Science. 1990 Dec 14;250(4987):1593-6 [2148832] Ann Neurol. 1991 Feb;29(2):202-9 [1826418] Neuron. 1991 Jul;7(1):111-8 [1676893] Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11246-50 [1662389] J Acquir Immune Defic Syndr. 1992;5(3):251-6 [1740750] Brain Res. 1992 Jan 20;570(1-2):49-53 [1617429] Pediatrics. 1992 Sep;90(3):369-74 [1518690] AIDS. 1992 Aug;6(8):882-3 [1418789] Neuroreport. 1992 Oct;3(10):913-5 [1421098] Brain Res. 1992 Dec 11;598(1-2):10-8 [1486472] Nature. 1993 Mar 11;362(6416):155-8 [8383805] Brain Res. 1993 Feb 19;603(2):222-33 [8461978] Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2769-73 [8464887] Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3256-9 [8097316] AIDS Res Hum Retroviruses. 1993 May;9(5):439-44 [8318270] Biochem Biophys Res Commun. 1993 Jul 15;194(1):439-45 [7687436] J Pediatr. 1993 Oct;123(4):579-82 [8410511] Nature. 1994 Jan 13;367(6459):188-93 [8114918] Pediatr Infect Dis J. 1994 Feb;13(2):94-100 [8190558] J Leukoc Biol. 1994 Sep;56(3):389-98 [8083614] Ann N Y Acad Sci. 1994 Nov 17;738:76-85 [7832458] AJNR Am J Neuroradiol. 1994 Nov;15(10):1853-9 [7863935] Pediatr Res. 1995 Jan;37(1):56-63 [7700734] AIDS. 1995 Feb;9(2):137-43 [7536422] Int J Gynaecol Obstet. 1995 May;49(2):137-43 [7649317] J Infect Dis. 1995 Sep;172(3):638-47 [7658054] J Exp Med. 1995 Oct 1;182(4):941-51 [7561697] Int J Dev Neurosci. 1995 Jun-Jul;13(3-4):187-200 [7572275] Int J Epidemiol. 1995 Oct;24(5):1022-9 [8557435] J Clin Invest. 1996 Jan 1;97(1):202-8 [8550835] Biochem Biophys Res Commun. 1996 Apr 16;221(2):386-90 [8619865] Proc Natl Acad Sci U S A. 1996 May 14;93(10):4688-92 [8643465] J Clin Invest. 1996 May 15;97(10):2299-307 [8636410] J Neurobiol. 1996 Jun;30(2):255-66 [8738754] Biochem J. 1956 Feb;62(2):315-23 [13293190] Cell Mol Biol (Noisy-le-grand). 1994 May;40(3):319-23 [7522715] J Clin Invest. 1994 Nov;94(5):2020-7 [7962548] Mol Neurobiol. 1994 Apr-Jun;8(2-3):181-96 [7999315] Anal Biochem. 1976 May 7;72:248-54 [942051] N1 - 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] Carcinogenesis. 1993 May;14(5):969-73 [8504491] Mutat Res. 1993 Jul;288(1):103-12 [7686254] Mutat Res. 1993 Jul;288(1):113-21 [7686255] Mutat Res. 1993 Jul;288(1):163-72 [7686259] Mutat Res. 1993 Jul;288(1):65-77 [7686267] Proc Natl Acad Sci U S A. 1994 May 24;91(11):5022-6 [8197176] Am J Epidemiol. 1994 Jul 1;140(1):1-11 [8017398] FASEB J. 1994 Jul;8(10):766-70 [7914178] Mol Carcinog. 1994 Aug;10(4):181-8 [8068178] Pharmacogenetics. 1994 Apr;4(2):107-8 [8081412] Cancer Res. 1994 Nov 15;54(22):5801-3 [7954403] Cytogenet Cell Genet. 1995;68(1-2):11-6 [7956347] Carcinogenesis. 1994 Dec;15(12):2905-10 [8001254] Cancer Res. 1995 Feb 1;55(3):640-5 [7834635] N Engl J Med. 1995 Mar 16;332(11):712-7 [7854378] Fundam Appl Toxicol. 1994 Nov;23(4):553-61 [7867907] Cancer Genet Cytogenet. 1995 Feb;79(2):133-5 [7889505] Pharmacogenetics. 1994 Oct;4(5):242-6 [7894496] Clin Chem. 1974 Feb;20(2):222-9 [4813000] J Occup Med. 1974 Feb;16(2):119-20 [4815794] Phys Med Biol. 1975 Jan;20(1):88-95 [163479] Bull Environ Contam Toxicol. 1975 Apr;13(4):385-91 [805610] Int Arch Occup Environ Health. 1976 Mar 9;36(4):275-85 [1254345] Science. 1976 Nov 5;194(4265):627-30 [136041] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] Scand J Work Environ Health. 1979 Mar;5(1):59-69 [441710] Drug Metab Rev. 1979;10(1):35-58 [393482] Cancer Res. 1983 Jan;43(1):439-42 [6401170] Proc Natl Acad Sci U S A. 1983 Mar;80(6):1579-83 [6220406] Toxicol Appl Pharmacol. 1983 Mar 15;67(3):430-41 [6845369] Am J Med Genet. 1983 Jun;15(2):211-23 [6410915] J Occup Med. 1983 Nov;25(11):797-808 [6644390] Cancer Res. 1984 Mar;44(3):1235-7 [6581866] Am J Public Health. 1984 May;74(5):485-91 [6711724] Nucleic Acids Res. 1984 Dec 11;12(23):9155-63 [6595642] J Occup Med. 1985 Jan;27(1):19-28 [2982002] Mutat Res. 1985 Feb-Apr;147(1-2):29-36 [3974610] Proc Natl Acad Sci U S A. 1985 Mar;82(6):1795-9 [3885218] Science. 1985 Dec 13;230(4731):1242-6 [4071043] Mutat Res. 1991 Jan;262(1):63-71 [1702518] Mutat Res. 1991 May;248(1):17-26 [2030706] Mutat Res. 1991 May;248(1):27-33 [2030710] Eur J Clin Pharmacol. 1990;39(6):533-7 [2151318] Science. 1991 Jul 5;253(5015):49-53 [1905840] Cancer Res. 1991 Oct 1;51(19):5266-9 [1913649] Cancer Res. 1991 Nov 15;51(22):6185-9 [1933877] Environ Mol Mutagen. 1991;18(4):274-6 [1748090] Environ Mol Mutagen. 1991;18(4):277-91 [1748091] Science. 1991 Dec 20;254(5039):1745-50 [1845040] J Biochem. 1991 Sep;110(3):407-11 [1722803] Carcinogenesis. 1992 Jan;13(1):69-76 [1346372] J Biochem. 1991 Oct;110(4):559-65 [1778977] J Occup Environ Med. 1995 Aug;37(8):903-7 [8520951] J Occup Environ Med. 1995 Aug;37(8):922-30 [8520954] Pharmacogenetics. 1995 Aug;5(4):215-23 [8528268] Int Arch Occup Environ Health. 1995;67(4):253-6 [7591186] Cancer Epidemiol Biomarkers Prev. 1995 Jul-Aug;4(5):529-33 [7549810] Cancer Epidemiol Biomarkers Prev. 1995 Jul-Aug;4(5):535-42 [7549811] Environ Health Perspect. 1995 Sep;103(9):838-43 [7498096] Mutat Res. 1995 Dec;335(3):267-73 [8524342] Cancer Res. 1986 Mar;46(3):1530-4 [3002619] J Occup Med. 1986 Aug;28(8):563-8 [3746474] J Occup Med. 1986 Aug;28(8):572-7 [3746476] J Occup Med. 1986 Aug;28(8):628-36 [3746483] Toxicol Ind Health. 1985 Sep;1(1):75-80 [3842548] Science. 1987 Apr 24;236(4800):445-8 [3563520] J Natl Cancer Inst. 1987 May;78(5):887-98 [3471998] Am J Clin Pathol. 1987 Aug;88(2):216-20 [3039835] Nature. 1988 Feb 4;331(6155):442-6 [3123997] Poult Sci. 1988 Jan;67(1):52-7 [3131755] Proc Natl Acad Sci U S A. 1988 Oct;85(19):7293-7 [3174634] Am J Epidemiol. 1989 Jan;129(1):1-18 [2642648] Comp Biochem Physiol C. 1988;91(2):507-12 [2905963] Adv Cancer Res. 1988;51:147-82 [3066145] Cancer Res. 1989 Mar 1;49(5):1171-7 [2917348] Proc Natl Acad Sci U S A. 1989 Apr;86(8):2766-70 [2565038] Nature. 1989 May 18;339(6221):237-8 [2716852] Int J Radiat Biol. 1989 Jul;56(1):35-44 [2569008] Cancer Res. 1989 Sep 1;49(17):4682-9 [2547513] Nucleic Acids Res. 1989 Jul 11;17(13):4937-46 [2668874] Br J Ind Med. 1989 Sep;46(9):679-80 [2675958] Xenobiotica. 1989 Oct;19(10):1149-60 [2683414] Environ Mol Mutagen. 1989;14(4):229-37 [2583130] Pharmacol Biochem Behav. 1990 Jan;35(1):7-13 [2315373] Biochemistry. 1990 Feb 6;29(5):1322-9 [2322567] Cytometry. 1990;11(4):513-21 [2188817] Sci Total Environ. 1990 May 1;94(1-2):51-69 [2360039] Anticancer Res. 1990 May-Jun;10(3):597-603 [2164347] Science. 1990 Sep 21;249(4975):1376-8 [2169647] J Biol Chem. 1990 Oct 5;265(28):17209-14 [2211621] Environ Health Perspect. 1997 Jun;105 Suppl 4:807-16 [9255565] Environ Health Perspect. 1997 Jun;105 Suppl 4:817-22 [9255566] Environ Health Perspect. 1997 Jun;105 Suppl 4:823-7 [9255567] Environ Health Perspect. 1997 Jun;105 Suppl 4:829-35 [9255568] Environ Health Perspect. 1997 Jun;105 Suppl 4:837-41 [9255569] Environ Health Perspect. 1997 Jun;105 Suppl 4:855-60 [9255572] J Occup Med. 1986 Oct;28(10):958-65 [3772552] Mutat Res. 1992 Jul;280(1):1-7 [1377340] Crit Rev Toxicol. 1992;22(1):23-43 [1352103] Environ Health Perspect. 1991 Dec;96:91-5 [1820285] Epidemiology. 1995 Mar;6(2):190-4 [7742410] Carcinogenesis. 1995 Jun;16(6):1261-4 [7788840] Cancer Epidemiol Biomarkers Prev. 1995 Apr-May;4(3):253-9 [7606200] Methods Enzymol. 1991;206:3-11 [1784216] Carcinogenesis. 1992 Feb;13(2):303-5 [1740022] Int J Cancer. 1992 Mar 12;50(5):713-8 [1544704] Carcinogenesis. 1992 Jun;13(6):987-93 [1600621] Mutat Res. 1992 Jun;267(2):265-76 [1376429] Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5301-5 [1608939] Account Res. 1995;4(1):57-68 [11654230] Arch Environ Health. 1970 Dec;21(6):711-6 [5478556] Rev Epidemiol Sante Publique. 1992;40 Suppl 1:S63-9 [1626107] J Occup Med. 1992 Sep;34(9):940-5 [1447602] Toxicol Lett. 1992 Dec;64-65 Spec No:527-33 [1471205] Mutat Res. 1993 Jan;298(3):179-85 [7678152] J Expo Anal Environ Epidemiol. 1992 Oct-Dec;2(4):381-9 [1483027] Cancer Res. 1996 Jan 1;56(1):72-6 [8548778] Mutat Res. 1996 Mar 26;351(1):79-85 [8602177] Environ Health Perspect. 1995 Nov;103(11):1036-40 [8605853] Environ Mol Mutagen. 1996;27(1):39-45 [8625947] Sci Total Environ. 1996 May 17;184(1-2):37-43 [8693344] Mutagenesis. 1996 Mar;11(2):213-5 [8671741] Genome Res. 1995 Aug;5(1):91-4 [8717060] Pharmacogenetics. 1995 Dec;5(6):373-84 [8747409] Cancer Epidemiol Biomarkers Prev. 1996 Oct;5(10):801-10 [8896891] Toxicology. 1996 Oct 28;113(1-3):77-83 [8901885] Environ Health Perspect. 1997 Jun;105 Suppl 4:739-47 [9255555] Environ Health Perspect. 1997 Jun;105 Suppl 4:755-8 [9255557] Environ Health Perspect. 1997 Jun;105 Suppl 4:767-74 [9255560] Environ Health Perspect. 1997 Jun;105 Suppl 4:775-80 [9255561] Environ Health Perspect. 1997 Jun;105 Suppl 4:781-9 [9255562] Environ Health Perspect. 1997 Jun;105 Suppl 4:801-6 [9255564] Mutat Res. 1993 Jul;288(1):79-83 [7686268] Mutat Res. 1993 Jul;288(1):85-92 [7686269] J Natl Cancer Inst. 1993 Jul 21;85(14):1159-64 [8320745] Mutat Res. 1993 Sep;297(2):101-80 [7687323] Cancer Epidemiol Biomarkers Prev. 1993 Jul-Aug;2(4):299-303 [8348052] Pharmacol Ther. 1993 Feb-Mar;57(2-3):129-60 [8361990] Mutagenesis. 1993 Jul;8(4):275-83 [8377645] Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8586-90 [8397412] Fundam Appl Toxicol. 1993 Aug;21(2):187-95 [8405781] N Engl J Med. 1993 Oct 28;329(18):1318-27 [8413413] Carcinogenesis. 1993 Oct;14(10):2003-6 [8222045] Lancet. 1993 Dec 18-25;342(8886-8887):1520-1 [7902903] Cancer Res. 1994 Jan 1;54(1):62-8 [8261464] Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11825-9 [7903454] Mayo Clin Proc. 1994 Jan;69(1):59-68 [7505869] Mayo Clin Proc. 1994 Jan;69(1):69-79 [7505870] JAMA. 1994 Jan 19;271(3):197-203 [8277545] Mutat Res. 1994 Jan;304(1):33-105 [7506357] Mutat Res. 1994 Feb;316(1):1-7 [7507564] Comp Biochem Physiol B. 1993 Dec;106(4):1029-36 [7905372] Nucleic Acids Res. 1994 Feb 11;22(3):364-9 [8127674] Am J Public Health. 1994 Mar;84(3):446-51 [8129063] Mutagenesis. 1993 Nov;8(6):519-25 [8133781] Cancer Res. 1994 Mar 15;54(6):1551-5 [8137262] Cancer Res. 1994 Apr 1;54(7 Suppl):1934s-1938s [7907948] Environ Health Perspect. 1993 Oct;101 Suppl 3:139-43 [8143606] Environ Health Perspect. 1993 Oct;101 Suppl 3:335-8 [8143641] Biochim Biophys Acta. 1994 May 11;1191(2):384-8 [7909692] Cancer Res. 1994 Jun 1;54(11):2919-22 [8187078] Science. 1994 May 27;264(5163):1317-9 [8191284] J Natl Cancer Inst. 1995 Feb 1;87(3):223-4 [7707410] Environ Health Perspect. 1994 Dec;102 Suppl 12:9-12 [7713042] Mutat Res. 1995 Apr;342(3-4):113-23 [7715613] Carcinogenesis. 1995 Apr;16(4):947-50 [7728978] Occup Environ Med. 1995 Mar;52(3):196-203 [7735394] Proc Natl Acad Sci U S A. 1981 Apr;78(4):2110-4 [6941274] Annu Rev Pharmacol Toxicol. 1982;22:517-54 [6282188] J Occup Med. 1982 May;24(5):369-74 [7045298] Toxicol Lett. 1995 May;77(1-3):163-8 [7618131] J Occup Environ Med. 1995 Jan;37(1):12-3 [7620937] J Occup Environ Med. 1995 Jan;37(1):59-68 [7620944] J Occup Environ Med. 1995 Jan;37(1):69-76 [7620945] J Occup Environ Med. 1995 Jan;37(1):91-9 [7620948] Cancer Res. 1995 Aug 15;55(16):3483-5 [7627950] 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 -- biosyn