TY - JOUR T1 - NIH-supported intervention trials in osteoporosis. AN - 80004646; 9666216 JF - Aging (Milan, Italy) AU - McGowan, J A AD - National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 160 VL - 10 IS - 2 SN - 0394-9532, 0394-9532 KW - Vitamin D KW - 1406-16-2 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - United States KW - Randomized Controlled Trials as Topic KW - Humans KW - Aged KW - Calcium -- administration & dosage KW - Vitamin D -- administration & dosage KW - Cardiovascular Diseases -- prevention & control KW - Estrogen Replacement Therapy -- adverse effects KW - Risk Factors KW - National Institutes of Health (U.S.) KW - Cohort Studies KW - Breast Neoplasms -- etiology KW - Breast Neoplasms -- prevention & control KW - Middle Aged KW - Diet KW - Colorectal Neoplasms -- prevention & control KW - Female KW - Research Support as Topic KW - Osteoporosis -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80004646?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Aging+%28Milan%2C+Italy%29&rft.atitle=NIH-supported+intervention+trials+in+osteoporosis.&rft.au=McGowan%2C+J+A&rft.aulast=McGowan&rft.aufirst=J&rft.date=1998-04-01&rft.volume=10&rft.issue=2&rft.spage=160&rft.isbn=&rft.btitle=&rft.title=Aging+%28Milan%2C+Italy%29&rft.issn=03949532&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-20 N1 - Date created - 1998-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Heterocyclic amine content in beef cooked by different methods to varying degrees of doneness and gravy made from meat drippings. AN - 79973462; 9651044 AB - Meats cooked at high temperatures sometimes contain heterocyclic amines (HCAs) that are known mutagens and animal carcinogens, but their carcinogenic potential in humans has not been established. To investigate the association between HCAs and cancer, sources of exposure to these compounds need to be determined. Beef is the most frequently consumed meat in the United States and for this study we determined HCA values in beef samples cooked in ways to represent US cooking practices, the results of which can be used in epidemiological studies to estimate HCA exposure from dietary questionnaires. We measured five HCAs [2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)] in different types of cooked beef using solid-phase extraction and HPLC. Steak and hamburger patties were pan-fried, oven-broiled, and grilled/barbecued to four levels of doneness (rare, medium, well done or very well done), while beef roasts were oven cooked to three levels of doneness (rare, medium or well done). The measured values of the specific HCAs varied with the cut of beef, cooking method, and doneness level. In general, MeIQx content increased with doneness under each cooking condition for steak and hamburger patties, up to 8.2 ng/g. PhIP was the predominant HCA produced in steak (1.9 to 30 ng/g), but was formed only in very well done fried or grilled hamburger. DiMeIQx was found in trace levels in pan-fried steaks only, while IQ and MeIQ were not detectable in any of the samples. Roast beef did not contain any of the HCAs, but the gravy made from the drippings from well done roasts had 2 ng/g of PhIP and 7 ng/g of MeIQx. Epidemiological studies need to consider the type of meat, cooking method and degree of doneness/surface browning in survey questions to adequately assess an individual's exposure to HCAs. JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association AU - Sinha, R AU - Rothman, N AU - Salmon, C P AU - Knize, M G AU - Brown, E D AU - Swanson, C A AU - Rhodes, D AU - Rossi, S AU - Felton, J S AU - Levander, O A AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20892, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 279 EP - 287 VL - 36 IS - 4 SN - 0278-6915, 0278-6915 KW - Heterocyclic Compounds KW - 0 KW - Index Medicus KW - Animals KW - Cattle KW - Temperature KW - Chromatography, High Pressure Liquid KW - Heterocyclic Compounds -- analysis KW - Cooking KW - Meat -- analysis KW - Meat Products -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79973462?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Food+and+chemical+toxicology+%3A+an+international+journal+published+for+the+British+Industrial+Biological+Research+Association&rft.atitle=Heterocyclic+amine+content+in+beef+cooked+by+different+methods+to+varying+degrees+of+doneness+and+gravy+made+from+meat+drippings.&rft.au=Sinha%2C+R%3BRothman%2C+N%3BSalmon%2C+C+P%3BKnize%2C+M+G%3BBrown%2C+E+D%3BSwanson%2C+C+A%3BRhodes%2C+D%3BRossi%2C+S%3BFelton%2C+J+S%3BLevander%2C+O+A&rft.aulast=Sinha&rft.aufirst=R&rft.date=1998-04-01&rft.volume=36&rft.issue=4&rft.spage=279&rft.isbn=&rft.btitle=&rft.title=Food+and+chemical+toxicology+%3A+an+international+journal+published+for+the+British+Industrial+Biological+Research+Association&rft.issn=02786915&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-10 N1 - Date created - 1998-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Heterocyclic amine content of pork products cooked by different methods and to varying degrees of doneness. AN - 79970326; 9651045 AB - Heterocyclic amines (HCAs) are known mutagens and animal carcinogens produced in meats cooked at high temperature. As pork is the second most frequently consumed meat in the United States, five predominant HCAs [2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4.5-f]quinoxaline (DiMeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)] were measured in various pork products, cooked by different techniques and to varying doneness levels. Pork chops and ham slices were pan-fried and oven-broiled; bacon was pan-fried, oven-broiled or microwaved; hot dogs were pan-fried, oven-broiled, grilled/barbecued or boiled; sausage links and patties were pan-fried. All the products were cooked to three levels of doneness: just until done, well done or very well done. HCA type and level varied substantially by pork product, cooking method and doneness level. The highest PhIP levels were found in well done and very well done oven-broiled bacon; for very well done 30.3 and 4.0 ng per gram of meat of PhIP and MeIQx, respectively. Pan-fried very well done sausage patties contained 5.4 ng of MeIQx per gram of meat, while sausage links contained 1.3 ng per gram of meat. MeIQx was formed in well done and very well done pan-fried but not broiled pork chops. Hot dogs or ham slices had low or undetectable levels of HCAs. These results demonstrate that epidemiological studies investigating the relationship between HCA intake and cancer risk need to incorporate type of meat, cooking method and degree of doneness/surface browning into questions to assess adequately an individual's HCA exposure. JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association AU - Sinha, R AU - Knize, M G AU - Salmon, C P AU - Brown, E D AU - Rhodes, D AU - Felton, J S AU - Levander, O A AU - Rothman, N AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20892, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 289 EP - 297 VL - 36 IS - 4 SN - 0278-6915, 0278-6915 KW - Heterocyclic Compounds KW - 0 KW - Index Medicus KW - Swine KW - Animals KW - Temperature KW - Chromatography, High Pressure Liquid KW - Heterocyclic Compounds -- analysis KW - Cooking KW - Meat -- analysis KW - Meat Products -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79970326?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Food+and+chemical+toxicology+%3A+an+international+journal+published+for+the+British+Industrial+Biological+Research+Association&rft.atitle=Heterocyclic+amine+content+of+pork+products+cooked+by+different+methods+and+to+varying+degrees+of+doneness.&rft.au=Sinha%2C+R%3BKnize%2C+M+G%3BSalmon%2C+C+P%3BBrown%2C+E+D%3BRhodes%2C+D%3BFelton%2C+J+S%3BLevander%2C+O+A%3BRothman%2C+N&rft.aulast=Sinha&rft.aufirst=R&rft.date=1998-04-01&rft.volume=36&rft.issue=4&rft.spage=289&rft.isbn=&rft.btitle=&rft.title=Food+and+chemical+toxicology+%3A+an+international+journal+published+for+the+British+Industrial+Biological+Research+Association&rft.issn=02786915&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-10 N1 - Date created - 1998-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Anthralin stimulates keratinocyte-derived proinflammatory cytokines via generation of reactive oxygen species. AN - 79932746; 9628260 AB - Topical application of anthralin, used in the treatment of psoriasis, is often accompanied by severe skin inflammation, presumably due to free radical products of the drug. The role of inflammatory cytokines and their induction by anthralin-derived reactive oxygen species were studied in cultures of normal human keratinocytes (NHKs). Anthralin was added to cultures of NHKs in the presence or absence of various antioxidants, including superoxide dismutase, tetramethylthiourea, N-acetylcysteine and vitamin E and relative changes in cytokine secretion and in the number of mRNA transcripts were examined. In addition, NHKs were either treated with neutralizing antibodies to tumor necrosis factor (TNF)-alpha or transfected with a CAT-linked IL-8 promoter to establish the direct effects of anthralin on chemokine synthesis. Anthralin, at concentrations between 5 microM and 25 microM, caused a marked increase in granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-6, IL-8 and TNFalpha synthesis that was selectively inhibited by specific antioxidants. Furthermore, anthralin induced chemokine secretion without the need of primary cytokines. Taken together, these studies suggest that oxygen radicals generated from anthralin are responsible for the induction of inflammatory cytokines which, in turn contributes to their dermal toxicity. JF - Inflammation research : official journal of the European Histamine Research Society ... [et al.] AU - Lange, R W AU - Hayden, P J AU - Chignell, C F AU - Luster, M I AD - Environmental Immunology Section, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA. lange+@pitt.edu Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 174 EP - 181 VL - 47 IS - 4 SN - 1023-3830, 1023-3830 KW - Anti-Inflammatory Agents KW - 0 KW - Antibodies KW - Antioxidants KW - Cytokines KW - Interleukin-6 KW - Interleukin-8 KW - RNA, Messenger KW - Reactive Oxygen Species KW - Tumor Necrosis Factor-alpha KW - Vitamin E KW - 1406-18-4 KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Thiourea KW - GYV9AM2QAG KW - tetramethylthiourea KW - J6T67A1P72 KW - Anthralin KW - U8CJK0JH5M KW - Acetylcysteine KW - WYQ7N0BPYC KW - Index Medicus KW - Transcription, Genetic -- drug effects KW - Dose-Response Relationship, Drug KW - Humans KW - Tumor Necrosis Factor-alpha -- biosynthesis KW - Acetylcysteine -- pharmacology KW - Thiourea -- analogs & derivatives KW - Granulocyte-Macrophage Colony-Stimulating Factor -- biosynthesis KW - Superoxide Dismutase -- pharmacology KW - Interleukin-8 -- biosynthesis KW - RNA, Messenger -- metabolism KW - Transfection KW - Cells, Cultured KW - Thiourea -- pharmacology KW - Antibodies -- pharmacology KW - Vitamin E -- pharmacology KW - Interleukin-6 -- biosynthesis KW - Administration, Topical KW - Reactive Oxygen Species -- metabolism KW - Antioxidants -- pharmacology KW - Keratinocytes -- drug effects KW - Cytokines -- biosynthesis KW - Keratinocytes -- metabolism KW - Anthralin -- pharmacology KW - Anti-Inflammatory Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79932746?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Inflammation+research+%3A+official+journal+of+the+European+Histamine+Research+Society+...+%5Bet+al.%5D&rft.atitle=Anthralin+stimulates+keratinocyte-derived+proinflammatory+cytokines+via+generation+of+reactive+oxygen+species.&rft.au=Lange%2C+R+W%3BHayden%2C+P+J%3BChignell%2C+C+F%3BLuster%2C+M+I&rft.aulast=Lange&rft.aufirst=R&rft.date=1998-04-01&rft.volume=47&rft.issue=4&rft.spage=174&rft.isbn=&rft.btitle=&rft.title=Inflammation+research+%3A+official+journal+of+the+European+Histamine+Research+Society+...+%5Bet+al.%5D&rft.issn=10233830&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-25 N1 - Date created - 1998-09-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Introduction and summary of the 13th meeting of the Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SGOMSEC): alternative testing methodologies. AN - 79898356; 9599686 AB - A workshop on alternative toxicological testing methodologies was convened by the Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SGOMSEC) 26-31 January 1997 in Ispra, Italy, at the European Centre for the Validation of Alternative Methods. The purpose of the workshop was to assess the current status of alternative testing methodologies available to evaluate adverse human health and environmental effects of chemicals. Another objective of the workshop was to identify and recommend research needed to fill knowledge gaps that would lead to new test methodologies. Four work groups were established to address conceptual issues, acute toxicity, organ toxicity, and ecotoxicology. A joint workshop report was prepared for each topic and included recommendations for the development and use of alternative methods. Participants concluded that alternative methods and approaches are available that can be incorporated into tiered strategies for toxicological assessments. Use of these methods will reduce the numbers of animals required, and in some instances reduce animal pain and distress. It was recommended that future efforts to develop test methods should emphasize mechanism-based methods that can provide improved predictions of toxicity. Continued international cooperation was encouraged to facilitate future progress in the development of alternative toxicological testing methods. These methods will provide for improvements in human health protection, environmental protection, and animal welfare. JF - Environmental health perspectives AU - Stokes, W S AU - Marafante, E Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 405 EP - 412 VL - 106 Suppl 2 KW - Environmental Pollutants KW - 0 KW - Index Medicus KW - Animals KW - Public Health KW - Humans KW - Animal Testing Alternatives KW - Animal Welfare KW - Toxicity Tests -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79898356?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=Environmental+health+perspectives&rft.atitle=Introduction+and+summary+of+the+13th+meeting+of+the+Scientific+Group+on+Methodologies+for+the+Safety+Evaluation+of+Chemicals+%28SGOMSEC%29%3A+alternative+testing+methodologies.&rft.au=Stokes%2C+W+S%3BMarafante%2C+E&rft.aulast=Stokes&rft.aufirst=W&rft.date=1998-04-01&rft.volume=106+Suppl+2&rft.issue=&rft.spage=405&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-16 N1 - Date created - 1998-07-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Environ Health Perspect. 1998 Apr;106 Suppl 2:441-51 [9599690] Fundam Appl Toxicol. 1992 Feb;18(2):200-10 [1534777] Environ Health Perspect. 1998 Apr;106 Suppl 2:413-8 [9599687] Environ Health Perspect. 1998 Apr;106 Suppl 2:419-25 [9599688] Environ Health Perspect. 1998 Apr;106 Suppl 2:427-39 [9599689] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A selective historical review of congener-specific human tissue measurements as sensitive and specific biomarkers of exposure to dioxins and related compounds. AN - 79897846; 9599725 AB - Estimating internal exposure or dose of dioxins and related chemicals such as dibenzofurans and dioxinlike polychlorinated biphenyls is relatively straightforward in laboratory animals because a known dose is given and the amount absorbed can be measured. In wildlife, direct tissue measurement and measurement of environmental samples have both recently been used to estimate exposure. Until recently, human studies used only indirect indicators such as skin lesions to qualitatively estimate exposure to these chlorinated organic compounds. Environmental measurements have also sometimes been used to estimate human exposure. Dioxins in human tissue were not measured until the 1970s, when 2,3,7,8-tetrachlorodibenzo-p-dioxin was measured in mothers' milk; congener-specific measurement of dioxins and dibenzofurans in tissues (blood, milk, and adipose tissue) of the general population and exposed workers was first performed in the United States in the 1980s. Measurement in a sensitive and specific fashion of the 17 toxic dioxin and dibenzofuran congeners currently found in human tissue from industrial countries began in the 1980s. The use of known chemical standards, capillary columns, high resolution gas chromatography and mass spectrometry (GC-MS) has now become relatively common. GC-MS analysis of blood is currently accepted as the gold standard for estimating human exposure to dioxins. However, analyses are still costly and time consuming, and worldwide there are few qualified laboratories. There is currently a lack of knowledge concerning kinetics at higher and lower exposure levels for most of the toxic dioxin congeners and of levels in target tissues of concern. JF - Environmental health perspectives AU - Schecter, A AD - Department of Preventive Medicine, State University of New York Health Science Center-Syracuse, Binghamton, USA. schecter@niehs.nih.gov Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 737 EP - 742 VL - 106 Suppl 2 SN - 0091-6765, 0091-6765 KW - Benzofurans KW - 0 KW - Biomarkers KW - Dioxins KW - Index Medicus KW - Sensitivity and Specificity KW - Mass Spectrometry KW - Chromatography, Gas KW - Dose-Response Relationship, Drug KW - Humans KW - Risk Assessment KW - Dioxins -- analysis KW - Environmental Exposure KW - Benzofurans -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79897846?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=A+selective+historical+review+of+congener-specific+human+tissue+measurements+as+sensitive+and+specific+biomarkers+of+exposure+to+dioxins+and+related+compounds.&rft.au=Schecter%2C+A&rft.aulast=Schecter&rft.aufirst=A&rft.date=1998-04-01&rft.volume=106+Suppl+2&rft.issue=&rft.spage=737&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-16 N1 - Date created - 1998-07-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Toxicol Appl Pharmacol. 1971 Nov;20(3):396-403 [5132781] Toxicol Appl Pharmacol. 1992 May;114(1):97-107 [1585378] Toxicol Appl Pharmacol. 1978 Nov;46(2):279-303 [734660] Br J Cancer. 1979 Jun;39(6):711-7 [444410] Anal Chem. 1980 Aug;52(9):1497-500 [6774628] Br J Cancer. 1981 Feb;43(2):169-76 [7470379] J Occup Med. 1992 Jul;34(7):702-7 [1494962] Arch Environ Contam Toxicol. 1993 May;24(4):504-12 [8507107] Anal Biochem. 1993 May 15;211(1):102-12 [8323021] Epidemiology. 1993 Sep;4(5):398-406 [8399687] J Toxicol Environ Health. 1994 Apr;41(4):481-8 [8145287] Environ Health Perspect. 1994 Jan;102 Suppl 1:135-47 [8187703] Environ Health Perspect. 1994 Jan;102 Suppl 1:149-58 [8187704] Environ Health Perspect. 1994 Jan;102 Suppl 1:159-71 [8187705] Pediatr Res. 1994 Oct;36(4):468-73 [7816522] Anal Biochem. 1994 Oct;222(1):217-23 [7856852] Am J Public Health. 1995 Apr;85(4):516-22 [7702115] Early Hum Dev. 1995 Apr 14;41(2):111-27 [7601016] Am J Epidemiol. 1995 Dec 1;142(11):1165-75 [7485063] J Toxicol Environ Health. 1996 Mar;47(4):363-78 [8600289] J Toxicol Environ Health. 1996 Feb 23;47(3):209-20 [8604146] Am J Ind Med. 1996 Dec;30(6):647-54 [8914711] Environ Res. 1984 Feb;33(1):261-8 [6692811] Rocz Panstw Zakl Hig. 1984;35(4):297-301 [6522993] Environ Health Perspect. 1985 May;60:241-54 [3928350] Am J Ind Med. 1986;9(4):305-21 [3706306] JAMA. 1988 Mar 18;259(11):1661-7 [3343772] Toxicol Appl Pharmacol. 1988 Mar 30;93(1):22-30 [3353999] Environ Res. 1988 Dec;47(2):112-28 [3263267] J Toxicol Environ Health. 1989;27(2):165-71 [2733058] Int Arch Occup Environ Health. 1990;62(2):139-57 [2139014] N Engl J Med. 1991 Jan 24;324(4):212-8 [1985242] Lancet. 1991 Oct 19;338(8773):959-64 [1681339] Lancet. 1991 Oct 26;338(8774):1027-32 [1681353] Toxicol Appl Pharmacol. 1992 May;114(1):108-17 [1585363] Toxicol Appl Pharmacol. 1992 May;114(1):118-26 [1585364] Environ Health Perspect. 1973 Sep;5:27-35 [4752911] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation and validation issues in the development of transgenic mouse carcinogenicity bioassays. AN - 79896872; 9599694 AB - Transgenic mouse models have emerged as plausible alternatives to long-term bioassays for carcinogenicity. Three transgenic lines evaluated to date have shown a clear capability to discriminate between carcinogens and noncarcinogens, using long-term bioassay results as the standard. The data also suggest that the transgenic lines will not fully duplicate long-term bioassay results. It is proposed that these models do not respond to chemicals that have induced highly restricted species or strain-specific tumor responses in mice or rats. Rather, the value of the transgenic models is predicated on a preferential response to transspecies carcinogens (i.e., those positive in both rats and mice, often including tumors in the same tissues). Thus, although results in transgenic models may not be completely concordant with long-term bioassays, the data can be used effectively in chemical and drug safety assessments. Further, it is proposed that validation of the models is readily achievable via ongoing studies. Validation of any alternative model is best achieved by sufficient mechanistic understanding of the model to reasonably predict the outcome of bioassays conducted in the models and use all available information on the drug or chemical. This goal can now be met with the transgenic mouse lines. JF - Environmental health perspectives AU - Tennant, R W AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. tennant@niehs.nih.gov Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 473 EP - 476 VL - 106 Suppl 2 SN - 0091-6765, 0091-6765 KW - Index Medicus KW - Animals KW - Reproducibility of Results KW - Animal Welfare KW - Mice KW - Models, Biological KW - Animal Testing Alternatives KW - Carcinogenicity Tests -- methods KW - Mice, Transgenic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79896872?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Evaluation+and+validation+issues+in+the+development+of+transgenic+mouse+carcinogenicity+bioassays.&rft.au=Tennant%2C+R+W&rft.aulast=Tennant&rft.aufirst=R&rft.date=1998-04-01&rft.volume=106+Suppl+2&rft.issue=&rft.spage=473&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-16 N1 - Date created - 1998-07-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1987 May 22;236(4804):933-41 [3554512] Prog Exp Tumor Res. 1964;4:207-50 [14150247] Mutagenesis. 1990 Mar;5(2):191-7 [2188074] Proc Natl Acad Sci U S A. 1990 Dec;87(23):9178-82 [2251261] Prog Exp Tumor Res. 1991;33:1-20 [2028021] Nature. 1992 Mar 19;356(6366):215-21 [1552940] Mutat Res. 1993 Mar;286(1):111-8 [7678907] Carcinogenesis. 1993 Jul;14(7):1335-41 [8330346] Environ Health Perspect. 1993 Apr;100:307-15 [8354178] Nat Genet. 1993 Nov;5(3):225-9 [8275085] Mol Carcinog. 1994 Mar;9(3):143-54 [7908201] Oncogene. 1994 Dec;9(12):3731-6 [7970733] Environ Mol Mutagen. 1995;25(4):302-13 [7607185] Toxicology. 1995 Aug 25;101(3):125-56 [7676462] Prog Clin Biol Res. 1995;391:223-35 [8532720] Environ Health Perspect. 1995 Oct;103(10):942-50 [8529591] Hum Exp Toxicol. 1996 Mar;15(3):183-202 [8839204] Carcinogenesis. 1996 Nov;17(11):2455-61 [8968063] Cell. 1990 May 4;61(3):407-17 [2185890] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Animal models of human response to dioxins. AN - 79895455; 9599728 AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent member of a class of chlorinated hydrocarbons that interact with the aryl hydrocarbon receptor (AhR). TCDD and dioxinlike compounds are environmentally and biologically stable and as a result, human exposure is chronic and widespread. Studies of highly exposed human populations show that dioxins produce developmental effects, chloracne, and an increase in all cancers and suggest that they may also alter immune and endocrine function. In contrast, the health effects of low-level environmental exposure have not been established. Experimental animal models can enhance the understanding of the effects of low-level dioxin exposure, particularly when there is evidence that humans respond similarly to the animal models. Although there are species differences in pharmacokinetics, experimental animal models demonstrate AhR-dependent health effects that are similar to those found in exposed human populations. Comparisons of biochemical changes show that humans and animal models have similar degrees of sensitivity to dioxin-induced effects. The information gained from animal models is important for developing mechanistic models of dioxin toxicity and critical for assessing the risks to human populations under different circumstances of exposure. JF - Environmental health perspectives AU - Grassman, J A AU - Masten, S A AU - Walker, N J AU - Lucier, G W AD - Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. grassman@niehs.nih.gov Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 761 EP - 775 VL - 106 Suppl 2 SN - 0091-6765, 0091-6765 KW - Dioxins KW - 0 KW - Polychlorinated Dibenzodioxins KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Humans KW - Gene Expression KW - Cytochrome P-450 Enzyme System -- drug effects KW - Risk Assessment KW - Dioxins -- adverse effects KW - Dioxins -- pharmacokinetics KW - Polychlorinated Dibenzodioxins -- pharmacokinetics KW - Polychlorinated Dibenzodioxins -- adverse effects KW - Disease Models, Animal KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79895455?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Animal+models+of+human+response+to+dioxins.&rft.au=Grassman%2C+J+A%3BMasten%2C+S+A%3BWalker%2C+N+J%3BLucier%2C+G+W&rft.aulast=Grassman&rft.aufirst=J&rft.date=1998-04-01&rft.volume=106+Suppl+2&rft.issue=&rft.spage=761&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-16 N1 - Date created - 1998-07-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Public Health. 1994 Mar;84(3):415-21 [8129058] Am J Public Health. 1994 Mar;84(3):439-45 [8129062] Environ Health Perspect. 1993 Nov;101(6):504-8 [8137779] Environ Health Perspect. 1993 Dec;101(7):634-42 [8143597] J Toxicol Environ Health. 1994 Apr;41(4):481-8 [8145287] Toxicol Appl Pharmacol. 1995 Jun;132(2):237-44 [7540335] Carcinogenesis. 1995 Jun;16(6):1319-27 [7788849] J Occup Environ Med. 1995 Jan;37(1):25-36 [7620940] N Engl J Med. 1973 Nov 1;289(18):934-7 [4126515] Endocrinology. 1977 Jul;101(1):292-6 [862558] Toxicol Appl Pharmacol. 1995 Aug;133(2):285-94 [7645025] Pharmacogenetics. 1995 Jun;5(3):151-8 [7550366] Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9220-4 [7568105] Environ Health Perspect. 1995 Jul-Aug;103(7-8):708-13 [7588483] Epidemiology. 1995 Jul;6(4):396-402 [7548348] Am J Epidemiol. 1995 Dec 1;142(11):1165-75 [7485063] Carcinogenesis. 1995 Nov;16(11):2807-11 [7586202] Pharmacol Ther. 1995;67(2):247-81 [7494865] Reprod Toxicol. 1995 May-Jun;9(3):233-8 [7579907] Environ Health Perspect. 1995 Sep;103(9):820-31 [7498094] Environ Health Perspect. 1994 May;102(5):476-7 [8593852] Cancer Lett. 1996 Jan 2;98(2):219-25 [8556712] Toxicol Appl Pharmacol. 1996 Jan;136(1):29-48 [8560478] Environ Health Perspect. 1995 Oct;103 Suppl 7:89-94 [8593882] J Toxicol Environ Health. 1996 Mar;47(4):363-78 [8600289] J Toxicol Environ Health. 1996 Feb 23;47(3):209-20 [8604146] Pediatrics. 1996 May;97(5):700-6 [8628610] Toxicol Appl Pharmacol. 1996 May;138(1):158-68 [8658505] Environ Health Perspect. 1995 Dec;103 Suppl 9:47-53 [8635439] Cancer Res. 1996 Jul 1;56(13):2979-84 [8674051] Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6731-6 [8692887] Annu Rev Pharmacol Toxicol. 1996;36:203-32 [8725388] Reprod Fertil Dev. 1995;7(6):1465-70 [8743148] Environ Health Perspect. 1996 Apr;104(4):422-6 [8732953] Am J Epidemiol. 1989 Jun;129(6):1187-200 [2729256] Fundam Appl Toxicol. 1989 May;12(4):629-97 [2663577] Immunopharmacology. 1988 Nov-Dec;16(3):167-80 [3267010] J Biochem Toxicol. 1989 Summer;4(2):105-9 [2593129] Pharmacol Ther. 1990;45(2):241-98 [2405437] Toxicol Lett. 1990 Feb;50(2-3):275-82 [2309246] Endocrinology. 1990 Jun;126(6):3101-6 [2161748] Occup Environ Med. 1996 Sep;53(9):606-12 [8882118] Arch Biochem Biophys. 1996 Nov 1;335(1):205-10 [8914852] Arch Biochem Biophys. 1996 Dec 15;336(2):297-308 [8954578] Annu Rev Cell Dev Biol. 1996;12:55-89 [8970722] Toxicol Ind Health. 1996 Sep-Oct;12(5):593-611 [8989841] Biochem Biophys Res Commun. 1997 Feb 3;231(1):227-30 [9070254] Hum Mol Genet. 1997 Apr;6(4):641-7 [9097971] Crit Rev Toxicol. 1997 Mar;27(2):109-34 [9099515] Biochem Biophys Res Commun. 1997 Apr 7;233(1):20-4 [9144388] Pharmacogenetics. 1997 Apr;7(2):95-101 [9170146] Am J Respir Cell Mol Biol. 1997 Jul;17(1):114-24 [9224217] Cancer Res. 1997 Jul 15;57(14):3026-31 [9230218] Biochem Biophys Res Commun. 1997 Jul 18;236(2):431-3 [9240455] Lancet. 1997 Jun 21;349(9068):1811 [9269218] Endocrinology. 1997 Sep;138(9):3727-34 [9275058] Environ Health Perspect. 1997 Jul;105(7):750-5 [9294722] Carcinogenesis. 1997 Sep;18(9):1793-8 [9328177] Epidemiology. 1997 Nov;8(6):646-52 [9345664] Cancer Res. 1992 Jun 15;52(12):3436-42 [1596902] Carcinogenesis. 1992 Aug;13(8):1389-95 [1354083] JAMA. 1992 Dec 9;268(22):3213-8 [1433761] Endocrinology. 1992 Dec;131(6):3067-76 [1332854] Environ Health Perspect. 1992 Nov;98:125-32 [1336723] Pharmacol Toxicol. 1993;72 Suppl 1:28-32 [8474985] Pharmacogenetics. 1991 Nov;1(2):68-78 [1844873] Toxicol Appl Pharmacol. 1993 May;120(1):138-54 [8511776] Environ Health Perspect. 1993 Apr 22;101(1):36-44 [8390353] Pharmacogenetics. 1992 Jun;2(3):116-27 [1306111] Cancer Res. 1993 Jul 1;53(13):3149-53 [8319224] Br J Dermatol. 1990 Jun;122(6):799-808 [2142435] Crit Rev Toxicol. 1990;21(1):51-88 [2124811] Biochem Pharmacol. 1991 Jan 1;41(1):85-92 [1846074] Toxicol Appl Pharmacol. 1991 Feb;107(2):203-14 [1847246] Cancer Res. 1991 Mar 1;51(5):1391-7 [1671757] Mol Pharmacol. 1991 Mar;39(3):307-13 [1848654] Toxicol Appl Pharmacol. 1991 Mar 15;108(1):129-39 [1672475] Fundam Appl Toxicol. 1990 Nov;15(4):722-31 [2128284] J Toxicol Environ Health. 1991 Apr;32(4):357-66 [1826746] Cell Biol Toxicol. 1991 Jan;7(1):67-94 [2054688] Cancer Res. 1991 Oct 1;51(19):5284-91 [1913651] Crit Rev Biochem Mol Biol. 1991;26(2):129-50 [1914494] Hum Reprod. 1991 Apr;6(4):544-9 [1918305] Lancet. 1991 Oct 19;338(8773):959-64 [1681339] Science. 1991 Oct 18;254(5030):415-8 [1925598] Hepatology. 1991 Nov;14(5):848-56 [1657755] Sci Total Environ. 1991 Jul 1;106(1-2):5-20 [1835132] Int Arch Occup Environ Health. 1991;63(5):325-7 [1837285] Mol Pharmacol. 1993 Nov;44(5):911-7 [8246913] Fundam Appl Toxicol. 1993 Nov;21(4):433-41 [8253297] Life Sci. 1993;53(26):1995-2006 [8255162] Cancer Res. 1994 Jan 1;54(1):62-8 [8261464] Ann Epidemiol. 1991 Aug;1(5):407-13 [1669521] Pharmacogenetics. 1993 Oct;3(5):239-49 [8287062] Toxicol Lett. 1994 Jan;70(1):1-22 [8310450] Am J Epidemiol. 1994 Feb 1;139(3):272-81 [8116602] Chem Res Toxicol. 1993 Nov-Dec;6(6):754-63 [8117913] Toxicol Appl Pharmacol. 1994 Mar;125(1):7-16 [8128497] Environ Health Perspect. 1996 Jul;104(7):756-64 [8841762] Int Arch Occup Environ Health. 1993;65(1):1-8 [8354568] Epidemiology. 1993 Sep;4(5):398-406 [8399687] Carcinogenesis. 1993 Sep;14(9):1885-93 [8403215] Carcinogenesis. 1993 Oct;14(10):2003-6 [8222045] Environ Res. 1994 Apr;65(1):1-11 [8162876] Crit Rev Toxicol. 1994;24(1):1-74 [8172651] J Biol Chem. 1994 May 6;269(18):13092-9 [8175734] Biochem Pharmacol. 1994 Apr 20;47(8):1445-8 [8185651] Environ Health Perspect. 1994 Jan;102 Suppl 1:195-204 [8187709] J Biol Chem. 1994 May 27;269(21):14905-11 [8195121] Carcinogenesis. 1994 May;15(5):801-6 [7515333] Crit Rev Toxicol. 1994;24(2):87-149 [8037844] Nucleic Acids Res. 1994 Aug 11;22(15):3038-44 [8065918] Toxicol Appl Pharmacol. 1994 Sep;128(1):138-50 [8079347] Dermatol Clin. 1994 Jul;12(3):569-76 [7923954] Cancer Res. 1994 Dec 1;54(23):6154-9 [7954461] J Biol Chem. 1994 Nov 4;269(44):27337-43 [7961644] Arch Biochem Biophys. 1994 Dec;315(2):279-84 [7986069] Pediatr Res. 1994 Oct;36(4):468-73 [7816522] J Steroid Biochem Mol Biol. 1994 Dec;51(5-6):251-8 [7826886] Fundam Appl Toxicol. 1994 Oct;23(3):465-9 [7835546] Chemosphere. 1994 Nov-Dec;29(9-11):2423-37 [7850391] Toxicol Appl Pharmacol. 1995 Feb;130(2):197-208 [7871533] Cancer Epidemiol Biomarkers Prev. 1994 Dec;3(8):675-82 [7881341] Crit Rev Oncol Hematol. 1995 Feb;18(2):111-27 [7695826] Environ Health Perspect. 1994 Nov;102 Suppl 9:157-67 [7698077] Fundam Appl Toxicol. 1995 Jan;24(1):145-8 [7713338] Teratology. 1994 Nov;50(5):361-6 [7716743] Arch Toxicol. 1994;69(2):79-86 [7717865] Science. 1995 May 5;268(5211):722-6 [7732381] Cancer Epidemiol Biomarkers Prev. 1995 Mar;4(2):147-53 [7742722] J Biol Chem. 1995 May 12;270(19):11595-602 [7744798] J Pharmacol Exp Ther. 1995 May;273(2):977-85 [7752103] Occup Environ Med. 1995 Feb;52(2):86-91 [7757172] DNA Cell Biol. 1994 Jul;13(7):763-9 [7772257] Lancet. 1996 Aug 10;348(9024):409 [8709758] Cancer Res. 1996 Sep 1;56(17):3926-33 [8752159] Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9776-81 [8790407] Fundam Appl Toxicol. 1996 Jan;29(1):40-7 [8838638] J Toxicol Environ Health. 1977 Oct;3(3):451-64 [926199] Toxicol Appl Pharmacol. 1978 Nov;46(2):279-303 [734660] Arch Toxicol Suppl. 1980;4:163-5 [6933896] Cancer Res. 1980 Oct;40(10):3616-20 [6108157] Annu Rev Pharmacol Toxicol. 1982;22:517-54 [6282188] Cancer Res. 1982 Dec;42(12):5030-7 [6291746] Am J Ind Med. 1984;5(1-2):81-115 [6230932] Mol Pharmacol. 1984 Jan;25(1):185-91 [6708934] Eur J Biochem. 1985 Mar 1;147(2):429-35 [2982617] Toxicol Appl Pharmacol. 1985 Feb;77(2):251-9 [2579474] Toxicol Appl Pharmacol. 1985 Mar 15;77(3):434-43 [2579475] Toxicol Appl Pharmacol. 1985 Jun 15;79(1):99-111 [4049410] Cancer Res. 1986 Feb;46(2):999-1004 [3079671] Cancer Res. 1986 Mar;46(3):1030-7 [3002608] Drug Metab Dispos. 1986 Jan-Feb;14(1):34-40 [2868862] J Steroid Biochem. 1986 Jan;24(1):353-6 [3009986] JAMA. 1986 Nov 21;256(19):2687-95 [2877102] Annu Rev Biochem. 1987;56:881-914 [3039909] Toxicol Appl Pharmacol. 1987 Sep 15;90(2):206-16 [3629596] Mol Pharmacol. 1987 Nov;32(5):572-8 [3119985] Toxicol Appl Pharmacol. 1988 Apr;93(2):231-46 [3358261] Environ Health Perspect. 1987 Dec;76:79-87 [2834196] Hepatology. 1989 Jan;9(1):126-38 [2642290] Neurotoxicol Teratol. 1989 Jan-Feb;11(1):13-9 [2725437] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A human vascular endothelial cell model to study angiogenesis and tumorigenesis. AN - 79888138; 9600354 AB - Endothelial cell biology has recently been the subject of considerable interest in thrombosis and cancer research. However, the successful establishment of immortalized human endothelial cells which retain differentiated cell characteristics has been rare. We have successfully established immortalized human umbilical vein endothelial cells (HUVECs) by human papilloma virus (HPV)-16 E6-E7. HPV-16 E6, E7 and E6-E7 were successfully introduced into HUVEC cells. Both E6 and E7 cultures had an extended lifespan but eventually underwent senescence. E6-E7 cultures 4-5-2G, however, acquired an indefinite lifespan in culture but did not undergo malignant conversion. Telomerase activity was not detected in either E6 or E7 cultures; however, telomerase was detected in E6-E7 4-5-2G cells. The cells exhibited a 'cobblestone' morphology and developed a capillary-like tube structure upon reaching confluence. The 4-5-2G line expressed Factor VIII related antigen and took up DiI-Ac-LDL as markers of endothelial origin. The line expressed integrin subunits (alpha(v)beta3, alph(v)beta5, beta1, alpha2, alpha3, beta4 and alpha6) consistent with an endothelial origin. The higher passage of 4-5-2G line showed a similar intensity of integrin immunostaining to that of primary HUVECS. Subsequent infection of these immortal cells with the Kirsten murine sarcoma virus which contains an activated K-ras oncogene induced morphological transformation that led to the acquisition of invasion capability and neoplastic properties. Telomerase was also detected in the tumorigenic v-Ki-ras transformed cell line. These cell lines should be useful for studies of the molecular mechanisms underlying normal and neoplastic endothelial cell proliferation and migration, and might also provide an in vitro model for development of pharmacologic and gene therapy for cardiovascular thrombosis and cancer. JF - Carcinogenesis AU - Rhim, J S AU - Tsai, W P AU - Chen, Z Q AU - Chen, Z AU - Van Waes, C AU - Burger, A M AU - Lautenberger, J A AD - Laboratory of Biochemical Physiology, National Cancer Institute, Frederick, MD 21702, USA. rhimi@fcrfv1.ncifcrf.gov Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 673 EP - 681 VL - 19 IS - 4 SN - 0143-3334, 0143-3334 KW - DNA, Viral KW - 0 KW - E6 protein, Human papillomavirus type 16 KW - Integrins KW - Oncogene Proteins, Viral KW - Papillomavirus E7 Proteins KW - Repressor Proteins KW - oncogene protein E7, Human papillomavirus type 16 KW - Index Medicus KW - Karyotyping KW - Papillomaviridae -- physiology KW - Humans KW - Oncogene Proteins, Viral -- physiology KW - Genes, ras KW - Cell Aging KW - Chromosome Aberrations KW - Oncogene Proteins, Viral -- genetics KW - Cell Line, Transformed KW - Integrins -- metabolism KW - DNA, Viral -- genetics KW - Cell Transformation, Neoplastic KW - Cell Transformation, Viral KW - Neoplasms -- pathology KW - Neoplasms -- blood supply KW - Endothelium, Vascular -- pathology KW - Models, Biological UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79888138?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=A+human+vascular+endothelial+cell+model+to+study+angiogenesis+and+tumorigenesis.&rft.au=Rhim%2C+J+S%3BTsai%2C+W+P%3BChen%2C+Z+Q%3BChen%2C+Z%3BVan+Waes%2C+C%3BBurger%2C+A+M%3BLautenberger%2C+J+A&rft.aulast=Rhim&rft.aufirst=J&rft.date=1998-04-01&rft.volume=19&rft.issue=4&rft.spage=673&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-04 N1 - Date created - 1998-06-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of retinoid analogues on mammary cancer in transgenic mice with c-neu breast cancer oncogene. AN - 79881069; 9598873 AB - Breast cancer is one of the most common cancers and is a leading cause of mortality in women. The TG.NK transgenic mouse line expresses the c-neu breast cancer oncogene under the control of an MMTV promoter and appears to be a useful animal model for evaluation of intervention strategies to delay/prevent breast cancer. Fiber-rich nonpurified diet (NTP-2000), as compared to a purified diet (AIN-76A), has previously been shown to significantly delay the development of mammary cancer in the TG.NK model. Four-week old hemizygous TG.NK female mice with MMTV/c-neu oncogene were fed NTP-2000 diet containing the retinoid analogue 4-hydroxyphenyl retinamide (4-HPR) at 5 mM/kg or an arotinoid Ro 40-8757 at 2 and 3 mmol/kg for 26 weeks. The 4-HPR at 5 mmol/kg diet delayed the development of palpable tumors up to 24 weeks, but by 26 weeks, the incidence was not significantly different from the NTP-2000 diet control group. However, the 4-HPR diet markedly decreased the average weight of the tumors at 26 weeks. The 4-HPR diet also caused a significant increase in body weight without an increase in food consumption. Arotinoid Ro-40-8757 at both doses inhibited the development of mammary tumors for the duration of the study. However, the Ro 40-8757 at 3 mmol/kg appeared to be toxic as indicated by a significant depression of the average body weight with alopecia and skin scaling in some mice. Our observations with TG.NK transgenic mouse and fiber-rich diet (NTP-2000) indicate that the arotinoid Ro 40-8757 has a markedly higher inhibitory effect on the development of mammary cancer than 4-HPR. Studies to evaluate genetic changes and expression of hormonal receptors and growth factors associated with the inhibition of mammary cancer development by the retinoid analogues are in progress. JF - Breast cancer research and treatment AU - Rao, G N AU - Ney, E AU - Herbert, R A AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 265 EP - 271 VL - 48 IS - 3 SN - 0167-6806, 0167-6806 KW - Anticarcinogenic Agents KW - 0 KW - Morpholines KW - Retinoids KW - Fenretinide KW - 187EJ7QEXL KW - mofarotene KW - 8K3CVY8F8V KW - Index Medicus KW - Animals KW - Retinoids -- therapeutic use KW - Morpholines -- therapeutic use KW - Genes, erbB-2 -- genetics KW - Mice KW - Mice, Transgenic KW - Female KW - Fenretinide -- therapeutic use KW - Anticarcinogenic Agents -- therapeutic use KW - Mammary Neoplasms, Animal -- genetics KW - Mammary Neoplasms, Animal -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79881069?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Breast+cancer+research+and+treatment&rft.atitle=Effect+of+retinoid+analogues+on+mammary+cancer+in+transgenic+mice+with+c-neu+breast+cancer+oncogene.&rft.au=Rao%2C+G+N%3BNey%2C+E%3BHerbert%2C+R+A&rft.aulast=Rao&rft.aufirst=G&rft.date=1998-04-01&rft.volume=48&rft.issue=3&rft.spage=265&rft.isbn=&rft.btitle=&rft.title=Breast+cancer+research+and+treatment&rft.issn=01676806&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-13 N1 - Date created - 1998-08-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular genetic dissection of mouse unconventional myosin-VA: tail region mutations. AN - 79845965; 9560409 AB - We used an RT-PCR-based sequencing approach to identify the mutations responsible for 17 viable dilute alleles, a mouse-coat-color locus encoding unconventional myosin-VA. Ten of the mutations mapped to the MyoVA tail and are reported here. These mutations represent the first extensive collection of tail mutations reported for any unconventional mammalian myosin. They identify sequences important for tail function and identify domains potentially involved in cargo binding and/or proper folding of the MyoVA tail. Our results also provide support for the notion that different myosin tail isoforms produced by alternative splicing encode important cell-type-specific functions. JF - Genetics AU - Huang, J D AU - Mermall, V AU - Strobel, M C AU - Russell, L B AU - Mooseker, M S AU - Copeland, N G AU - Jenkins, N A AD - ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 1963 EP - 1972 VL - 148 IS - 4 SN - 0016-6731, 0016-6731 KW - Intermediate Filament Proteins KW - 0 KW - Myo5a protein, mouse KW - RNA, Messenger KW - DNA KW - 9007-49-2 KW - Myosin Type V KW - EC 3.6.1.- KW - Myosin Heavy Chains KW - EC 3.6.4.1 KW - Index Medicus KW - Animals KW - Base Sequence KW - Molecular Sequence Data KW - Mice, Inbred C57BL KW - Mice, Inbred C3H KW - Gene Expression KW - Mice KW - Male KW - Female KW - Sequence Deletion KW - Intermediate Filament Proteins -- genetics KW - Intermediate Filament Proteins -- biosynthesis KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79845965?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genetics&rft.atitle=Molecular+genetic+dissection+of+mouse+unconventional+myosin-VA%3A+tail+region+mutations.&rft.au=Huang%2C+J+D%3BMermall%2C+V%3BStrobel%2C+M+C%3BRussell%2C+L+B%3BMooseker%2C+M+S%3BCopeland%2C+N+G%3BJenkins%2C+N+A&rft.aulast=Huang&rft.aufirst=J&rft.date=1998-04-01&rft.volume=148&rft.issue=4&rft.spage=1963&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-26 N1 - Date created - 1998-06-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1982 Jun;79(11):3589-91 [6954505] Brain Res. 1996 Apr 1;714(1-2):226-30 [8861629] Genes Dev. 1988 Dec;2(12A):1627-38 [3215513] Mol Cell Biol. 1989 Apr;9(4):1604-10 [2725519] Nucleic Acids Res. 1989 Oct 11;17(19):7905-21 [2798134] Nucleic Acids Res. 1992 Mar 25;20(6):1201-8 [1373235] FEBS Lett. 1992 Oct 26;311(3):295-8 [1383040] J Cell Biol. 1992 Dec;119(6):1541-57 [1469047] Genes Dev. 1993 Mar;7(3):407-18 [8449402] Eur J Pediatr. 1993 May;152(5):402-5 [8319705] Cell. 1993 Oct 8;75(1):13-23 [8402892] Genomics. 1996 Sep 15;36(3):431-9 [8884266] Nat Genet. 1996 Nov;14(3):307-11 [8896560] Neurosci Lett. 1996 Sep 13;215(3):169-72 [8899740] Am J Hum Genet. 1996 Nov;59(5):1074-83 [8900236] Genes Dev. 1997 Jan 1;11(1):11-43 [9000048] Genetics. 1997 Feb;145(2):435-43 [9071596] J Cell Sci. 1997 Apr;110 ( Pt 7):847-59 [9133672] Nat Genet. 1997 Jun;16(2):188-90 [9171832] Nat Genet. 1997 Jul;16(3):289-92 [9207796] Genetics. 1998 Apr;148(4):1951-61 [9560408] Nucleic Acids Res. 1987 Oct 12;15(19):7725-33 [3671064] Mol Cell Biol. 1990 Feb;10(2):696-704 [2153921] Genes Dev. 1991 Feb;5(2):211-20 [1847346] Nature. 1991 Feb 21;349(6311):709-13 [1996138] J Cell Biol. 1991 May;113(3):539-51 [2016335] Cell. 1991 May 31;65(5):837-47 [1710172] Eur J Pediatr. 1991 Apr;150(6):419-22 [1828234] J Biol Chem. 1992 Mar 15;267(8):5330-8 [1544914] J Theor Biol. 1991 Jun 7;150(3):385-420 [1798333] Cancer Res. 1993 Dec 1;53(23):5624-8 [8242616] Genomics. 1994 Feb;19(3):407-16 [8188282] J Cell Biol. 1994 May;125(4):825-42 [8188749] J Cell Sci. 1994 Apr;107 ( Pt 4):1055-64 [8056830] Cytogenet Cell Genet. 1995;69(1-2):53-8 [7835087] Nature. 1995 Mar 2;374(6517):60-1 [7870171] Nature. 1995 Mar 2;374(6517):62-4 [7870172] Genes Dev. 1995 Mar 1;9(5):612-25 [7698650] EMBO J. 1995 May 15;14(10):2326-32 [7774591] Cell. 1996 Mar 8;84(5):687-97 [8625407] J Biol Chem. 1996 Jul 12;271(28):16431-4 [8690736] Nature. 1996 Jul 18;382(6588):262-5 [8717042] Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10826-31 [8855265] Erratum In: Genetics 1998 Nov;150(3):1332 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Relationship of binge drinking to alcohol dependence, other psychiatric disorders, and behavioral problems in an American Indian tribe. AN - 79844565; 9581662 AB - The hypothesis that binge drinking is a benign behavior not associated with alcohol dependence, other psychiatric disorders, or problem areas, in American Indians, was tested in a sample of 582 adult Southwestern American Indian males and females in large multigenerational pedigrees. All information was obtained from semistructured psychiatric interviews that were independently blind-rated for DSM-III-R diagnoses. Three main outcome measures were used: the relationship between binge drinking and (1) alcohol dependence and other psychiatric disorders, (2) substance abuse treatment, and (3) four behavioral problem categories-violence/lawlessness, physical, social, and work. Binge drinking and alcohol dependence were strongly associated. Most binge drinkers were diagnosed as alcohol dependent. However, when controlling for alcohol dependence and other covariates, binge drinking was independently associated with an increase in odds for positive diagnoses for multiple psychiatric disorders, and for social, work, physical, and violence/lawlessness behavioral problems. In sum, binge drinking was found to be a common and severe problem with deleterious consequences in multiple domains of functioning. Assessment instruments should be designed to elicit information on binge patterns of drinking and strategies devised to provide appropriate treatment. JF - Alcoholism, clinical and experimental research AU - Robin, R W AU - Long, J C AU - Rasmussen, J K AU - Albaugh, B AU - Goldman, D AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 518 EP - 523 VL - 22 IS - 2 SN - 0145-6008, 0145-6008 KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Psychiatric Status Rating Scales KW - Ethanol -- poisoning KW - Social Problems -- statistics & numerical data KW - Humans KW - Adult KW - Social Problems -- psychology KW - Southwestern United States KW - Male KW - Female KW - Comorbidity KW - Social Behavior Disorders -- epidemiology KW - Alcoholic Intoxication -- psychology KW - Alcoholic Intoxication -- epidemiology KW - Social Behavior Disorders -- psychology KW - Alcoholism -- epidemiology KW - Mental Disorders -- epidemiology KW - Mental Disorders -- psychology KW - Indians, North American -- psychology KW - Indians, North American -- statistics & numerical data KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79844565?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Relationship+of+binge+drinking+to+alcohol+dependence%2C+other+psychiatric+disorders%2C+and+behavioral+problems+in+an+American+Indian+tribe.&rft.au=Robin%2C+R+W%3BLong%2C+J+C%3BRasmussen%2C+J+K%3BAlbaugh%2C+B%3BGoldman%2C+D&rft.aulast=Robin&rft.aufirst=R&rft.date=1998-04-01&rft.volume=22&rft.issue=2&rft.spage=518&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-20 N1 - Date created - 1998-07-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Posttranslational inhibition of Ty1 retrotransposition by nucleotide excision repair/transcription factor TFIIH subunits Ssl2p and Rad3p. AN - 79840811; 9560391 AB - rtt4-1 (regulator of Ty transposition) is a cellular mutation that permits a high level of spontaneous Ty1 retrotransposition in Saccharomyces cerevisiae. The RTT4 gene is allelic with SSL2 (RAD25), which encodes a DNA helicase present in basal transcription (TFIIH) and nucleotide excision repair (NER) complexes. The ssl2-rtt (rtt4-1) mutation stimulates Ty1 retrotransposition, but does not alter Ty1 target site preferences, or increase cDNA or mitotic recombination. In addition to ssl2-rtt, the ssl2-dead and SSL2-1 mutations stimulate Ty1 transposition without altering the level of Ty1 RNA or proteins. However, the level of Ty1 cDNA markedly increases in the ssl2 mutants. Like SSL2, certain mutations in another NER/TFIIH DNA helicase encoded by RAD3 stimulate Ty1 transposition. Although Ssl2p and Rad3p are required for NER, inhibition of Ty1 transposition is independent of Ssl2p and Rad3p NER functions. Our work suggests that NER/TFIIH subunits antagonize Ty1 transposition posttranslationally by inhibiting reverse transcription or destabilizing Ty1 cDNA. JF - Genetics AU - Lee, B S AU - Lichtenstein, C P AU - Faiola, B AU - Rinckel, L A AU - Wysock, W AU - Curcio, M J AU - Garfinkel, D J AD - Gene Regulation and Chromosome Biology Laboratory, Advanced BioScience Laboratories-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 1743 EP - 1761 VL - 148 IS - 4 SN - 0016-6731, 0016-6731 KW - DNA Transposable Elements KW - 0 KW - DNA, Complementary KW - Fungal Proteins KW - Retroelements KW - SSL2 protein, S cerevisiae KW - Saccharomyces cerevisiae Proteins KW - TAF6 protein, S cerevisiae KW - TATA-Binding Protein Associated Factors KW - Transcription Factor TFIID KW - Transcription Factors KW - Transcription Factors, TFII KW - Transcription Factor TFIIH KW - 148710-81-0 KW - Alcohol Oxidoreductases KW - EC 1.1.- KW - HIS4 protein, S cerevisiae KW - EC 1.1.1.23 KW - Aminohydrolases KW - EC 3.5.4.- KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - Pyrophosphatases KW - Rad3 protein, S cerevisiae KW - DNA Helicases KW - EC 3.6.4.- KW - Index Medicus KW - DNA Helicases -- metabolism KW - Adenosine Triphosphatases -- metabolism KW - Fungal Proteins -- genetics KW - Mutagenesis KW - Chromosomes, Fungal KW - Alleles KW - Fungal Proteins -- metabolism KW - Recombination, Genetic KW - DNA Helicases -- genetics KW - Adenosine Triphosphatases -- genetics KW - Protein Biosynthesis KW - DNA Repair KW - Transcription Factors -- metabolism KW - Transcription Factors -- chemistry KW - Gene Expression Regulation KW - Transcription Factors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79840811?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genetics&rft.atitle=Posttranslational+inhibition+of+Ty1+retrotransposition+by+nucleotide+excision+repair%2Ftranscription+factor+TFIIH+subunits+Ssl2p+and+Rad3p.&rft.au=Lee%2C+B+S%3BLichtenstein%2C+C+P%3BFaiola%2C+B%3BRinckel%2C+L+A%3BWysock%2C+W%3BCurcio%2C+M+J%3BGarfinkel%2C+D+J&rft.aulast=Lee&rft.aufirst=B&rft.date=1998-04-01&rft.volume=148&rft.issue=4&rft.spage=1743&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-26 N1 - Date created - 1998-06-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1990 Jul 27;62(2):339-52 [2164889] J Biol Chem. 1994 Jan 21;269(3):1852-7 [8294433] J Bacteriol. 1990 Dec;172(12):6620-30 [2174856] Nature. 1994 Jan 6;367(6458):91-4 [8107780] Nature. 1994 Mar 3;368(6466):74-6 [8107888] Nature. 1994 Jun 16;369(6481):578-81 [8202161] Genetics. 1994 Apr;136(4):1245-59 [8013902] Mol Cell Biol. 1994 Oct;14(10):6540-51 [7523854] Genes Dev. 1994 Dec 15;8(24):2974-85 [8001818] Science. 1994 Dec 23;266(5193):2002-6 [7801128] Cell. 1995 Jan 13;80(1):21-8 [7813015] Genetics. 1994 Nov;138(3):587-95 [7851757] Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6479-83 [7604017] Mol Cell Biol. 1995 Aug;15(8):3998-4008 [7623796] Mol Biol Cell. 1995 May;6(5):611-25 [7545033] Trends Biochem Sci. 1995 Oct;20(10):402-5 [8533152] Genes Dev. 1996 Mar 1;10(5):620-33 [8598291] J Biol Chem. 1996 May 3;271(18):10821-6 [8631896] J Biol Chem. 1996 Apr 12;271(15):8903-10 [8621533] Nature. 1996 Aug 29;382(6594):826-9 [8752279] Curr Biol. 1996 Aug 1;6(8):959-61 [8805314] Science. 1996 Oct 25;274(5287):546, 563-7 [8849441] Genetics. 1996 Mar;142(3):761-76 [8849886] Nature. 1996 Nov 28;384(6607):379-83 [8934527] Genes Dev. 1996 Nov 1;10(21):2657-83 [8946909] Trends Genet. 1996 Nov;12(11):436-8 [8973141] J Virol. 1997 Jul;71(7):5382-90 [9188609] Proc Natl Acad Sci U S A. 1979 Mar;76(3):1035-9 [375221] Gene. 1979 Dec;8(1):121-33 [395029] Cell. 1980 Nov;22(2 Pt 2):427-36 [6256080] Proc Natl Acad Sci U S A. 1981 Apr;78(4):2460-4 [6787605] EMBO J. 1982;1(8):945-51 [6329717] Cell. 1984 Dec;39(3 Pt 2):675-82 [6096019] Mol Gen Genet. 1984;197(2):345-6 [6394957] Cell. 1985 Mar;40(3):491-500 [2982495] Cell. 1985 Sep;42(2):507-17 [2411424] Mol Cell Biol. 1986 Nov;6(11):3575-81 [3025601] Genetics. 1987 Aug;116(4):541-5 [3305158] Proc Natl Acad Sci U S A. 1987 Sep;84(17):6045-9 [2957691] Gene. 1987;57(2-3):267-72 [3319781] Mol Biol Evol. 1985 Nov;2(6):455-68 [2835576] Mol Cell Biol. 1988 Apr;8(4):1432-42 [2837641] Genetics. 1989 May;122(1):19-27 [2659436] Mol Gen Genet. 1989 Sep;218(3):465-74 [2555668] Genetics. 1989 Dec;123(4):655-65 [2558956] Mol Gen Genet. 1990 Jan;220(2):213-21 [2157950] Genes Dev. 1990 Mar;4(3):324-30 [2159935] Genetics. 1988 Jun;119(2):289-301 [2840336] Mol Cell Biol. 1988 Jul;8(7):2964-75 [3043201] Cell. 1988 Sep 23;54(7):955-66 [2843295] Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):936-40 [1846969] Annu Rev Genet. 1990;24:491-518 [1965102] J Virol. 1991 Sep;65(9):4573-81 [1714514] Mol Cell Biol. 1992 Jun;12(6):2813-25 [1317008] Cell. 1992 Jun 12;69(6):1031-42 [1318786] Trends Genet. 1992 Jun;8(6):187-90 [1323152] J Virol. 1992 Oct;66(10):5959-66 [1326652] Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11416-20 [1333609] Cell. 1992 Dec 11;71(6):925-37 [1458540] Genetics. 1993 Mar;133(3):499-508 [8384143] Cell. 1993 Jun 4;73(5):1007-18 [8388781] Genes Dev. 1993 Nov;7(11):2161-71 [7693549] Cell. 1993 Dec 31;75(7):1379-87 [8269516] Cell. 1990 Aug 24;62(4):777-91 [2167179] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Aspects of the ultraviolet photobiology of some T-even bacteriophages. AN - 79840391; 9560380 AB - Bacteriophage T4 DNA metabolism is largely insulated from that of its host, although some host functions assist in the repair of T4 DNA damage. Environmental factors sometimes affect survival and mutagenesis after ultraviolet (UV) irradiation of T4, and can affect mutagenesis in many organisms. We therefore tested the effect of certain environmental factors and host genetic defects upon spontaneous and UV-induced mutagenesis and survival in T4 and some related T-even phages. Plating at pH 9 enhances UV resistance in T4 by about 14% compared to pH 7. The host cAMP regulatory system affects host survival after UV irradiation but does not affect T4 survival. Thermal rescue, the increasing survival of irradiated T4 with increasing plating temperature, occurs also in phage T6, but only weakly in phages T2 and RB69; this temperature effect is not altered by supplementing infected cells with additional Holliday resolvase (gp49) early in infection. Phage RB69 turns out to have almost 50% greater UV resistance than T4, but has a genome of about the same size; RB69 is UV-mutable but does not produce r mutants, which are easily seen in T2, T4, and T6. Spontaneous mutagenesis in T4 shows no dependence on medium and little dependence on temperature overall, but mutation rates can increase and probably decrease with temperature at specific sites. UV mutagenesis is not affected by incubating irradiated particles under various conditions before plating, in contrast to phage S13. JF - Genetics AU - Smith, L A AU - Drake, J W AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709-2233, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 1611 EP - 1618 VL - 148 IS - 4 SN - 0016-6731, 0016-6731 KW - Index Medicus KW - Genotype KW - Hydrogen-Ion Concentration KW - Escherichia coli -- genetics KW - Mutagenesis KW - Ultraviolet Rays KW - T-Phages -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79840391?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genetics&rft.atitle=Aspects+of+the+ultraviolet+photobiology+of+some+T-even+bacteriophages.&rft.au=Smith%2C+L+A%3BDrake%2C+J+W&rft.aulast=Smith&rft.aufirst=L&rft.date=1998-04-01&rft.volume=148&rft.issue=4&rft.spage=1611&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-26 N1 - Date created - 1998-06-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Genetics. 1987 Mar;115(3):405-17 [3552872] Genetics. 1984 Aug;107(4):505-23 [6745639] Mol Gen Genet. 1989 Feb;215(3):537-42 [2540417] Mol Gen Genet. 1991 May;227(1):144-8 [2046654] Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7160-4 [1831267] Genetics. 1984 Aug;107(4):525-36 [6745640] Mutat Res. 1984 Nov;129(2):149-52 [6504055] J Bacteriol. 1986 Nov;168(2):936-9 [3096964] Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1159-63 [1741372] New Biol. 1991 Dec;3(12):1195-205 [1812964] Mutat Res. 1992 Aug;282(4):247-52 [1379686] J Mol Biol. 1994 Jan 21;235(3):807-12 [8289321] Genetics. 1994 Nov;138(3):553-64 [7851754] Cell. 1997 Jun 27;89(7):1087-99 [9215631] Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8042-6 [9223311] Genetics. 1998 Apr;148(4):1539-50 [9560373] Proc Natl Acad Sci U S A. 1961 Jun 15;47:845-55 [13701658] Genetics. 1946 Nov;31(6):620-40 [17247224] J Bacteriol. 1966 May;91(5):1775-80 [5937237] Genetics. 1970 Jul;65(3):379-90 [4933467] Genetics. 1974 Dec;78(4):989-1014 [4455560] Genetics. 1988 Oct;120(2):329-43 [2974005] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Heart rate variability as an index of cue reactivity in alcoholics. AN - 79800151; 9547935 AB - Autonomic responses follow exposure to conditioned stimuli such as contextual factors associated with alcohol ingestion. Heart rate variability is under autonomic control and may be a measure of such response. Twenty alcoholics and 23 matched social drinkers (all male) were exposed to a neutral cue and then an alcohol cue in identical settings, during which the electrocardiogram of these subjects was recorded. Time and frequency domain parameters of heart rate variability (HRV) were computed by a blind rater. Coefficient of variation of R-R intervals and absolute powers of HRV spectrum (in frequency bands 0.05-0.15 Hz and 0.01-0.05 Hz) following alcohol cue were significantly higher in alcoholics than social drinkers. The mean heart rate (MHR) failed to reflect this difference. HRV paradigm appears more sensitive than MHR to measure cue reactivity. JF - Biological psychiatry AU - Rajan, I AU - Murthy, P J AU - Ramakrishnan, A G AU - Gangadhar, B N AU - Janakiramaiah, N AD - Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India. Y1 - 1998/04/01/ PY - 1998 DA - 1998 Apr 01 SP - 544 EP - 546 VL - 43 IS - 7 SN - 0006-3223, 0006-3223 KW - Index Medicus KW - Humans KW - Conditioning (Psychology) -- physiology KW - Adult KW - Cues KW - Alcohol Drinking -- physiopathology KW - Autonomic Nervous System -- physiopathology KW - Male KW - Heart Rate -- physiology KW - Alcoholism -- physiopathology KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79800151?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biological+psychiatry&rft.atitle=Heart+rate+variability+as+an+index+of+cue+reactivity+in+alcoholics.&rft.au=Rajan%2C+I%3BMurthy%2C+P+J%3BRamakrishnan%2C+A+G%3BGangadhar%2C+B+N%3BJanakiramaiah%2C+N&rft.aulast=Rajan&rft.aufirst=I&rft.date=1998-04-01&rft.volume=43&rft.issue=7&rft.spage=544&rft.isbn=&rft.btitle=&rft.title=Biological+psychiatry&rft.issn=00063223&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-08 N1 - Date created - 1998-06-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential selectivity of ligands for the C1a and C1b phorbol ester binding domains of protein kinase Cdelta: possible correlation with tumor-promoting activity. AN - 79776006; 9537243 AB - Protein kinase C (PKC) represents the major, high-affinity receptor for the phorbol esters as well as for a series of structurally diverse natural products. The phorbol esters function by binding to the tandem C1a and C1b domains in PKC, leading to enzyme activation. Although the typical phorbol esters represent the paradigm for tumor promoters in mouse skin, it is now clear that different high affinity ligands for PKC have distinct biological effects. Thus, the daphnane analogue mezerein is a second-stage promoter, the macrolide bryostatin 1 is a partial antagonist, and certain 12-deoxyphorbol 13-monoesters also function as partial antagonists but with a different pattern of activity. The biochemical basis for these differences is an area of active investigation. In this report, we have examined the relative interaction of ligands differing in structure and pattern of biological response with the C1a and C1b domains of PKCdelta. We mutated either or both of the C1 domains of PKCdelta, expressed the constructs in NIH 3T3 cells, and monitored the interaction of the ligands by their ability to induce translocation of the mutated PKCdelta from the cytosol to the particulate fraction. We found that different ligands showed different dependence on the C1a and C1b domains for translocation. Whereas phorbol 12-myristate 13-acetate and the indole alkaloids indolactam and octylindolactam were selectively dependent on the C1b domain, selectivity was not observed for mezerein, for the 12-deoxyphorbol 13-monoesters prostratin or 12-deoxyphorbol 13-phenylacetate, or for the macrocyclic lactone bryostatin 1. Provocatively, the pattern of response corresponds with the activity of the compounds as complete tumor promoters. JF - Cancer research AU - Bögi, K AU - Lorenzo, P S AU - Szállási, Z AU - Acs, P AU - Wagner, G S AU - Blumberg, P M AD - Molecular Mechanisms of Tumor Promotion Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1998/04/01/ PY - 1998 DA - 1998 Apr 01 SP - 1423 EP - 1428 VL - 58 IS - 7 SN - 0008-5472, 0008-5472 KW - Carcinogens KW - 0 KW - Diterpenes KW - Indoles KW - Isoenzymes KW - Lactams KW - Ligands KW - Phorbol Esters KW - Terpenes KW - 7-octylindolactam V KW - 109346-66-9 KW - mezerein KW - 34807-41-5 KW - 12-deoxyphorbolphenylacetate KW - 58821-98-0 KW - prostratin KW - 60857-08-1 KW - indolactam V KW - 8CIY9O1323 KW - Prkcd protein, mouse KW - EC 2.7.1.- KW - Protein Kinase C KW - EC 2.7.11.13 KW - Protein Kinase C-delta KW - Index Medicus KW - Terpenes -- toxicity KW - Animals KW - Mice KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Blotting, Western KW - Lactams -- metabolism KW - Lactams -- toxicity KW - Indoles -- toxicity KW - Terpenes -- metabolism KW - 3T3 Cells -- metabolism KW - Indoles -- metabolism KW - Protein Structure, Tertiary KW - Protein Kinase C -- metabolism KW - Isoenzymes -- chemistry KW - Phorbol Esters -- metabolism KW - Carcinogens -- metabolism KW - Protein Kinase C -- chemistry KW - Carcinogens -- toxicity KW - Phorbol Esters -- toxicity KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79776006?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Differential+selectivity+of+ligands+for+the+C1a+and+C1b+phorbol+ester+binding+domains+of+protein+kinase+Cdelta%3A+possible+correlation+with+tumor-promoting+activity.&rft.au=B%C3%B6gi%2C+K%3BLorenzo%2C+P+S%3BSz%C3%A1ll%C3%A1si%2C+Z%3BAcs%2C+P%3BWagner%2C+G+S%3BBlumberg%2C+P+M&rft.aulast=B%C3%B6gi&rft.aufirst=K&rft.date=1998-04-01&rft.volume=58&rft.issue=7&rft.spage=1423&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-16 N1 - Date created - 1998-04-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of the juxtamembrane dileucine motif in the insulin receptor. AN - 79759075; 9528942 AB - Dileucine-containing motifs are involved in trans-Golgi sorting, lysosomal targeting, and internalization. Previously, we have shown that the dileucine motif (EKITLL, residues 982-987) in the juxtamembrane region of the insulin receptor is involved in receptor internalization. Substitution of alanine residues for Leu986 and Leu987 led to a 3- to 5-fold decrease in the ability of the receptors to mediate insulin uptake. In the current study, we show that mutation of the same motif to Met986Ser987, the sequence found in the homologous position in the type I insulin-like growth factor receptor, did not affect insulin uptake. Therefore, we inquired whether the sequence EKITMS as an isolated motif could mediate the targeting of a reporter molecule to endosomes and then lysosomes, as was shown previously with the EKITLL motif of the normal receptor. Chimeric molecules containing Tac antigen fused to different hexapeptide sequences showed distinct patterns of subcellular localization by immunofluorescence microscopy. Tac-EKITLL and Tac-EKITAA were found predominantly in lysosomes and the plasma membrane, respectively. In contrast, Tac-EKITMS was found at the plasma membrane, in the trans-Golgi network, and in endosomes, but only small amounts were found in lysosomes. Thus, the dileucine motif (EKITLL) plays an important role in directing endocytosis of the intact insulin receptor and in mediating efficient endocytosis and lysosomal targeting as an isolated motif. Substitution of AA for LL inhibits endocytosis and lysosomal targeting in both systems. In contrast, substitution of MS for LL permits rapid endocytosis in the intact receptor, but mediates modest endocytosis and very little targeting to lysosomes as an isolated motif. Our observations support the idea that sorting signals are recognized at multiple steps in the cell, and that specific amino acid substitutions may differentially affect each of these sorting steps. JF - Endocrinology AU - Haft, C R AU - De La Luz Sierra, M AU - Hamer, I AU - Carpentier, J L AU - Taylor, S I AD - Diabetes Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1829, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 1618 EP - 1629 VL - 139 IS - 4 SN - 0013-7227, 0013-7227 KW - Antigens, CD3 KW - 0 KW - Insulin KW - Recombinant Fusion Proteins KW - Recombinant Proteins KW - Receptor, Insulin KW - EC 2.7.10.1 KW - Leucine KW - GMW67QNF9C KW - Abridged Index Medicus KW - Index Medicus KW - Antigens, CD3 -- genetics KW - 3T3 Cells KW - Animals KW - HeLa Cells KW - Humans KW - Insulin -- metabolism KW - Amino Acid Sequence KW - Mice KW - Structure-Activity Relationship KW - Mutagenesis KW - Recombinant Fusion Proteins -- metabolism KW - Base Sequence KW - Sequence Alignment KW - Phosphorylation KW - Transfection KW - Molecular Sequence Data KW - Receptor, Insulin -- chemistry KW - Receptor, Insulin -- genetics KW - Sequence Analysis KW - Leucine -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79759075?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Endocrinology&rft.atitle=Analysis+of+the+juxtamembrane+dileucine+motif+in+the+insulin+receptor.&rft.au=Haft%2C+C+R%3BDe+La+Luz+Sierra%2C+M%3BHamer%2C+I%3BCarpentier%2C+J+L%3BTaylor%2C+S+I&rft.aulast=Haft&rft.aufirst=C&rft.date=1998-04-01&rft.volume=139&rft.issue=4&rft.spage=1618&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-14 N1 - Date created - 1998-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Angiotensin II activates mitogen-activated protein kinase via protein kinase C and Ras/Raf-1 kinase in bovine adrenal glomerulosa cells. AN - 79755320; 9528965 AB - Angiotensin II (Ang II) stimulates growth and mitogenesis in bovine adrenal glomerulosa cells, but little is known about the signaling pathways that mediate these responses. An analysis of the growth-promoting pathways in cultured bovine adrenal glomerulosa cells revealed that Ang II, acting via the AT1 receptor, caused rapid but transient activation of mitogen-activated protein kinase (MAPK), with an ED50 of 10-50 pM. Although neither Ca2+ influx nor Ca2+ release from intracellular stores was sufficient to activate MAPK, Ca2+ appeared to play a permissive role in this response. A major component of Ang II-induced MAPK activation was insensitive to pertussis toxin (PTX), although a minor PTX-sensitive component could not be excluded. Ang II also induced the rapid activation of ras and raf-1 kinase with time-courses that correlated with that of MAPK. Activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetate was sufficient to activate both MAPK and raf-1 kinase. However, whereas PKC depletion had no effect on Ang II-induced raf-1 kinase activation, it attenuated Ang II-induced MAPK activation. Ang II also stimulated a mobility shift of raf-1, reflecting hyperphosphorylation of the kinase. However, unlike its activation, raf-1 hyperphosphorylation was dependent on PKC and its time-course correlated not with activation, but rather with deactivation of the kinase. Taken together, these findings indicate that Ang II stimulates multiple pathways to MAPK activation via PKC and ras/raf-1 kinase in bovine adrenal glomerulosa cells. JF - Endocrinology AU - Tian, Y AU - Smith, R D AU - Balla, T AU - Catt, K J AD - Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 1801 EP - 1809 VL - 139 IS - 4 SN - 0013-7227, 0013-7227 KW - Receptor, Angiotensin, Type 1 KW - 0 KW - Receptor, Angiotensin, Type 2 KW - Receptors, Angiotensin KW - Virulence Factors, Bordetella KW - Angiotensin II KW - 11128-99-7 KW - Egtazic Acid KW - 526U7A2651 KW - Pertussis Toxin KW - EC 2.4.2.31 KW - Proto-Oncogene Proteins c-raf KW - EC 2.7.11.1 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - ras Proteins KW - EC 3.6.5.2 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Calcium -- metabolism KW - Virulence Factors, Bordetella -- pharmacology KW - Cattle KW - Phosphorylation KW - Receptors, Angiotensin -- physiology KW - Kinetics KW - Enzyme Activation -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Egtazic Acid -- pharmacology KW - Protein Kinase C -- metabolism KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Proto-Oncogene Proteins c-raf -- metabolism KW - ras Proteins -- metabolism KW - Zona Glomerulosa -- enzymology KW - Angiotensin II -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79755320?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Endocrinology&rft.atitle=Angiotensin+II+activates+mitogen-activated+protein+kinase+via+protein+kinase+C+and+Ras%2FRaf-1+kinase+in+bovine+adrenal+glomerulosa+cells.&rft.au=Tian%2C+Y%3BSmith%2C+R+D%3BBalla%2C+T%3BCatt%2C+K+J&rft.aulast=Tian&rft.aufirst=Y&rft.date=1998-04-01&rft.volume=139&rft.issue=4&rft.spage=1801&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-14 N1 - Date created - 1998-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Long-term salivary effects of single-dose head and neck irradiation in the rat. AN - 70086553; 9839705 AB - The effect of a single dose of X-irradiation (either 2.5, 5, 7.5, 10 or 15 Gy) to the head and neck region on parotid and submandibular gland function in rats was evaluated for up to 1 year. No animal receiving 15 Gy survived the entire study. Animals receiving > or = 7.5 Gy showed significantly less increase in body weight over time. Average wet weights of both gland types were reduced with as little as 2.5 Gy. Pilocarpine-stimulated parotid salivary flow was diminished significantly at 12 months for each radiation-dose group. Significant salivary flow reductions from submandibular glands were seen at > or = 7.5 Gy at this same time-point. These results show that a single radiation exposure of as low as 2.5 Gy to the head and neck region of rats can cause significant long-term alterations in salivary gland function. JF - Archives of oral biology AU - Nagler, R M AU - Baum, B J AU - Miller, G AU - Fox, P C AD - Gene Therapy and Therapeutics Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892-1190, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 297 EP - 303 VL - 43 IS - 4 SN - 0003-9969, 0003-9969 KW - Parasympathomimetics KW - 0 KW - Pilocarpine KW - 01MI4Q9DI3 KW - Dentistry KW - Index Medicus KW - Animals KW - Analysis of Variance KW - Pilocarpine -- pharmacology KW - Dose-Response Relationship, Radiation KW - Stimulation, Chemical KW - Rats KW - Secretory Rate -- drug effects KW - Body Weight -- radiation effects KW - Parasympathomimetics -- pharmacology KW - Rats, Wistar KW - Organ Size -- radiation effects KW - Secretory Rate -- radiation effects KW - Time Factors KW - Male KW - Parotid Gland -- anatomy & histology KW - Neck -- radiation effects KW - Submandibular Gland -- anatomy & histology KW - Submandibular Gland -- radiation effects KW - Parotid Gland -- drug effects KW - Parotid Gland -- secretion KW - Submandibular Gland -- drug effects KW - Head -- radiation effects KW - Parotid Gland -- radiation effects KW - Submandibular Gland -- secretion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70086553?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+oral+biology&rft.atitle=Long-term+salivary+effects+of+single-dose+head+and+neck+irradiation+in+the+rat.&rft.au=Nagler%2C+R+M%3BBaum%2C+B+J%3BMiller%2C+G%3BFox%2C+P+C&rft.aulast=Nagler&rft.aufirst=R&rft.date=1998-04-01&rft.volume=43&rft.issue=4&rft.spage=297&rft.isbn=&rft.btitle=&rft.title=Archives+of+oral+biology&rft.issn=00039969&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-22 N1 - Date created - 1999-01-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Burkholderia pseudomallei infection in a Puerto Rican patient with chronic granulomatous disease: Case report and review of occurrences in the Americas AN - 16487443; 4367653 AB - Burkholderia species, notably Burkholderia cepacia and Burkholderia gladioli, are important pathogens in patients with chronic granulomatous disease (CGD). Burkholderia pseudomallei, the causative agent of melioidosis, is endemic in Southeast Asia and northern Australia but is a rare pathogen in other parts of the world. We describe the occurrence of B. pseudomallei infection in a Puerto Rican patient with CGD. This is one of only a small number of documented cases of melioidosis autochthonous to the Americas and is the first reported case of B. pseudomallei infection in a CGD patient from the Americas. We conclude that B. pseudomallei, like B. cepacia and B. gladioli, should be considered a potential pathogen in patients with CGD and that melioidosis should be considered in the differential diagnosis for ill residents of or travelers to Puerto Rico. JF - Clinical Infectious Diseases AU - Dorman, SE AU - Gill, V J AU - Gallin, JI AU - Holland, S M AD - National Institutes of Health, Building 10, Room 11N103, 10 Center Drive, MSC 1886, Bethesda, MD 20892-1886, USA Y1 - 1998/04// PY - 1998 DA - Apr 1998 SP - 889 EP - 894 VL - 26 IS - 4 SN - 1058-4838, 1058-4838 KW - Puerto Rico KW - chronic granulomatous disease KW - man KW - Microbiology Abstracts B: Bacteriology KW - J 02855:Human Bacteriology: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16487443?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Infectious+Diseases&rft.atitle=Burkholderia+pseudomallei+infection+in+a+Puerto+Rican+patient+with+chronic+granulomatous+disease%3A+Case+report+and+review+of+occurrences+in+the+Americas&rft.au=Dorman%2C+SE%3BGill%2C+V+J%3BGallin%2C+JI%3BHolland%2C+S+M&rft.aulast=Dorman&rft.aufirst=SE&rft.date=1998-04-01&rft.volume=26&rft.issue=4&rft.spage=889&rft.isbn=&rft.btitle=&rft.title=Clinical+Infectious+Diseases&rft.issn=10584838&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Genomics: Re-evaluation of translation machinery evolution AN - 16455894; 4370512 AB - Experiments based on genome sequence analysis have revealed unexpected complexity in the evolution of the translation apparatus, including concerted evolution of Gln-tRNA synthetase and Glu-tRNA super(Gln) amidotransferase, and a novel, class I Lys-tRNA synthetase shared by archaea and spirochaetes. JF - Current Biology AU - Koonin, E V AU - Aravind, L AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA Y1 - 1998/04// PY - 1998 DA - Apr 1998 SP - R266 EP - R269 VL - 8 IS - 8 SN - 0960-9822, 0960-9822 KW - Spirochaetes KW - Spirochetes KW - evolutionary genetics KW - glutamine-tRNA ligase KW - reviews KW - tRNA Lys KW - translation KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution KW - G 07260:Taxonomy, systematics and evolutionary genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16455894?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Biology&rft.atitle=Genomics%3A+Re-evaluation+of+translation+machinery+evolution&rft.au=Koonin%2C+E+V%3BAravind%2C+L&rft.aulast=Koonin&rft.aufirst=E&rft.date=1998-04-01&rft.volume=8&rft.issue=8&rft.spage=R266&rft.isbn=&rft.btitle=&rft.title=Current+Biology&rft.issn=09609822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Antimutator mutants in bacteriophage T4 and Escherichia coli AN - 16419042; 4320339 AB - Antimutators are mutant strains that have reduced mutation rates compared to the corresponding wild-type strain. Their existence, along with mutator mutants that have higher mutation rates compared to the wild-type strain, are powerful evidence that mutation rates are genetically controlled. Compared to mutator mutants, antimutators have a very distinguishing property. Because they prevent normally occurring mutations, they, uniquely, are capable of providing insight into the mechanisms of spontaneous mutations. In this review, antimutator mutants are discussed in bacteriophage T4 and the bacterium Escherichia coli, with regard to their properties, possible mechanisms, and implications for the sources of spontaneous mutations in these two organisms. JF - Genetics AU - Schaaper, R M AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, 111 TW Alexander Dr., Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1998/04// PY - 1998 DA - Apr 1998 SP - 1579 EP - 1585 VL - 148 IS - 4 SN - 0016-6731, 0016-6731 KW - antimutators KW - mutants KW - spontaneous mutation KW - Microbiology Abstracts B: Bacteriology; Virology & AIDS Abstracts; Genetics Abstracts KW - V 22050:Viral genetics including virus reactivation KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16419042?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genetics&rft.atitle=Antimutator+mutants+in+bacteriophage+T4+and+Escherichia+coli&rft.au=Schaaper%2C+R+M&rft.aulast=Schaaper&rft.aufirst=R&rft.date=1998-04-01&rft.volume=148&rft.issue=4&rft.spage=1579&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - CRE-Palindrome Oligonucleotide as a Transcription Factor Decoy and an Inhibitor of Tumor Growth AN - 16416829; 4310398 AB - A major focus of cellular and molecular research has been to develop means to regulate gene expression in an effort to treat and cure a variety of diseases and abnormal physiologic conditions. The importance of such research has dramatically increased as the Human Genomic Project continues to identify genes at an accelerated pace. Currently, several general methods have been developed to regulate and control gene expression at either the transcriptional or translational steps. This article describes oligonucleotides with high affinity for a target transcription factor that can be introduced into cells as decoy cis-elements to bind the factor and alter gene expression. Specifically, nucleic acid molecules that compete with cAMP response element (CRE) enhancers for binding transcription factors are described. These nucleic acid molecules were shown to function in vitro and in vivo as inhibitors of cancer cell growth, without adversely affecting the growth of noncancerous cells. The CRE-decoy oligonucleotides provide powerful new means of combating cancers by regulating the expression of cAMP-responsive genes. JF - Antisense and Nucleic Acid Drug Development AU - Cho-Chung, Yoon S AD - National Cancer Institute, Building 10, Room 5B05, Bethesda, MD 20892-1750, USA Y1 - 1998/04// PY - 1998 DA - Apr 1998 SP - 167 EP - 170 VL - 8 IS - 2 SN - 1087-2906, 1087-2906 KW - Human Genome Project KW - cAMP response elements KW - cancer KW - cyclic AMP response element KW - gene regulation KW - man KW - oligonucleotides KW - transcription factors KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33385:DNA/RNA KW - N 14250:Biological properties KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16416829?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antisense+and+Nucleic+Acid+Drug+Development&rft.atitle=CRE-Palindrome+Oligonucleotide+as+a+Transcription+Factor+Decoy+and+an+Inhibitor+of+Tumor+Growth&rft.au=Cho-Chung%2C+Yoon+S&rft.aulast=Cho-Chung&rft.aufirst=Yoon&rft.date=1998-04-01&rft.volume=8&rft.issue=2&rft.spage=167&rft.isbn=&rft.btitle=&rft.title=Antisense+and+Nucleic+Acid+Drug+Development&rft.issn=10872906&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Non-Antisense Oligonucleotide Approaches for Experimental Treatment of Glioblastoma AN - 16410087; 4310400 AB - Malignant gliomas constitute 40%-50% of all brain tumors, which in themselves cause approximately 2% of all cancer deaths. Astrocytomas, the most common form of brain tumor, are classified by degree of malignancy into three groups: astrocytoma, anaplastic astrocytoma, and glioblastoma multiforme. Glioblastoma multiforme is the most malignant and has an extremely poor prognosis given current available treatments. Cells from such tumors aggressively infiltrate normal tissue, making total surgical removal of tumor impossible, and median survival time from diagnosis is less than 2 years. Thus, development of experimental therapy for glioblastoma, perhaps in combination with more standard chemotherapy, irradiation, or surgery, is warranted. We are taking two approaches to the use of synthetic oligonucleotides in experimental therapy of these tumors. The first approach makes use of synthetic ribozymes delivered to the tumor by continuous infusion with microosmotic minipumps. These studies are being carried out in collaboration with Nigel Davis and Brian Sproat of Innovir Ltd. The experimental model consists of U87MG human glioblastoma cells directly implanted into the striatum of adult athymic rats. Concurrent with tumor inoculation, an indwelling cannula is set in place that allows access to the striatum at or near the site of tumor implantation. Following a period of recovery (usually 24 hours), oligonucleotides are infused continuously for 2 weeks. Animal survival is monitored thereafter. JF - Antisense and Nucleic Acid Drug Development AU - Neckers, L M AU - Kanekal, M AU - Connell, Y AD - Medicine Branch, NCI, NIH, Key West Facility, 9610 Center Drive, Suite 300, Rockville, MD 20850, USA Y1 - 1998/04// PY - 1998 DA - Apr 1998 SP - 177 EP - 179 VL - 8 IS - 2 SN - 1087-2906, 1087-2906 KW - brain carcinoma KW - gioblastoma KW - oigonucleotides KW - oligonucleotides KW - rats KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33385:DNA/RNA KW - N 14250:Biological properties KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16410087?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antisense+and+Nucleic+Acid+Drug+Development&rft.atitle=Non-Antisense+Oligonucleotide+Approaches+for+Experimental+Treatment+of+Glioblastoma&rft.au=Neckers%2C+L+M%3BKanekal%2C+M%3BConnell%2C+Y&rft.aulast=Neckers&rft.aufirst=L&rft.date=1998-04-01&rft.volume=8&rft.issue=2&rft.spage=177&rft.isbn=&rft.btitle=&rft.title=Antisense+and+Nucleic+Acid+Drug+Development&rft.issn=10872906&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Locus coeruleus neurons from morphine-treated rats do not show opiate-withdrawal hyperactivity in vitro. AN - 79815154; 9555033 AB - In vitro studies have not consistently demonstrated naloxone-precipitated opiate-withdrawal hyperactivity of locus coeruleus neurons. The reason for this inconsistency may be because partial or complete withdrawal occurred during preparation of the locus coeruleus slice. The aim of the present study was to assay opiate withdrawal-related hyperactivity in neurons recorded from locus coeruleus slices while ensuring the maintenance of dependence until naloxone-precipitated withdrawal. Extracellular recordings were obtained from individual locus coeruleus neurons in slices from morphine-treated and drug-naive rats. Morphine 1 microM was present in all solutions during preparation and recording in slices from morphine-treated rats. The average firing rate of the drug-naive controls was 0.93 Hz (+/-0.04 Hz). Bath application of morphine (1 microM) almost completely suppressed firing in drug-naive controls (0.058 Hz, +/-0.04 Hz, n=12), whereas in solutions containing 1 microM morphine, the firing rate of cells from morphine-treated rats averaged 0.71 Hz (+/-0.05 Hz), indicating considerable, but incomplete tolerance. In the same slices, naloxone increased the average spontaneous firing of locus coeruleus cells to 0.96 Hz (+/-0. 04 Hz). Thus, naloxone did not produce withdrawal hyperactivity, but returned the cells from morphine-treated rats to control rates. We conclude that locus coeruleus cells in locus coeruleus slice preparations from morphine-treated rats did not demonstrate withdrawal-related hyperactivity even when dependence was maintained until naloxone-precipitated withdrawal. Thus, our results do not support a role for adaptations intrinsic to locus coeruleus neurons in withdrawal hyperexcitability, but instead imply the necessity of functional afferent activity. Copyright 1998 Elsevier Science B.V. JF - Brain research AU - Bell, J A AU - Grant, S J AD - Brain Imaging Section, Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 1998/03/30/ PY - 1998 DA - 1998 Mar 30 SP - 237 EP - 244 VL - 788 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Naloxone KW - 36B82AMQ7N KW - Morphine KW - 76I7G6D29C KW - Index Medicus KW - Rats KW - Naloxone -- pharmacology KW - Evoked Potentials -- drug effects KW - Animals KW - Rats, Sprague-Dawley KW - Basal Metabolism KW - Analysis of Variance KW - In Vitro Techniques KW - Locus Coeruleus -- drug effects KW - Substance Withdrawal Syndrome KW - Morphine -- adverse effects KW - Neurons -- drug effects KW - Locus Coeruleus -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79815154?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research&rft.atitle=Locus+coeruleus+neurons+from+morphine-treated+rats+do+not+show+opiate-withdrawal+hyperactivity+in+vitro.&rft.au=Bell%2C+J+A%3BGrant%2C+S+J&rft.aulast=Bell&rft.aufirst=J&rft.date=1998-03-30&rft.volume=788&rft.issue=1-2&rft.spage=237&rft.isbn=&rft.btitle=&rft.title=Brain+research&rft.issn=00068993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-23 N1 - Date created - 1998-07-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparative pharmacodynamics of CYP2B induction by DDT, DDE, and DDD in male rat liver and cultured rat hepatocytes. AN - 79781567; 9537282 AB - In this study the pharmacodynamics were characterized of rat hepatic cytochrome P-450 2B (CYP2B) induction by the pesticide DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] and its metabolites DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene], which is bioretained, and DDD [1,1-dichloro-2,2-bis(p-chlorophenyl)ethane], which is metabolized further and therefore less prone to bioaccumulate. DDT, DDE, and DDD were each found to be pure phenobarbital-type cytochrome P-450 inducers in the male F344/NCr rat, causing induction of hepatic CYP2B and CYP3A, but not CYP1A. The ED50 values for CYP2B induction (benzyloxyresorufin O-dealkylation) by DDT, DDE, and DDD were, respectively, 103, 88, and > or = 620 ppm in diet (14 d of exposure). The efficacies (Emax values) for induction of benzyloxyresorufin O-dealkylation by DDT, DDE, and DDD were 24-, 22-, and > or = 1-fold, respectively, compared to control values. The potencies of the three congeners for CYP2B induction appeared also to be similar, with EC50 values (based on total serum DDT equivalents) of 1.5, 1.8, and > or = 0.51 microM, respectively. The EC50 values based on DDT equivalents in hepatic tissue were 15, 16, and > or = 5.9 micromol/kg liver tissue, respectively. In primary cultures of adult rat hepatocytes, DDT, DDE, and DDD each displayed ability to induce total cellular RNA coding for CYP2B (ED50 values of 0.98, 0.83, and > or = 2.7 microM, respectively). These results suggest that DDT, DDE, and DDD each possess a high degree of intrinsic CYP2B-inducing ability for rat liver, despite marked differences in bioretention among the congeners. JF - Journal of toxicology and environmental health. Part A AU - Nims, R W AU - Lubet, R A AU - Fox, S D AU - Jones, C R AU - Thomas, P E AU - Reddy, A B AU - Kocarek, T A AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland, USA. rnims@mabioservices.com Y1 - 1998/03/27/ PY - 1998 DA - 1998 Mar 27 SP - 455 EP - 477 VL - 53 IS - 6 SN - 1528-7394, 1528-7394 KW - Insecticides KW - 0 KW - Dichlorodiphenyl Dichloroethylene KW - 4M7FS82U08 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - DDT KW - CIW5S16655 KW - Mixed Function Oxygenases KW - EC 1.- KW - CYP3A protein, human KW - EC 1.14.14.1 KW - Cytochrome P-450 CYP1A1 KW - Cytochrome P-450 CYP2B1 KW - Cytochrome P-450 CYP3A KW - Dichlorodiphenyldichloroethane KW - V14159DF29 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Mixed Function Oxygenases -- biosynthesis KW - Cells, Cultured KW - Enzyme Induction KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Male KW - Cytochrome P-450 CYP1A1 -- biosynthesis KW - Organ Size -- drug effects KW - Dichlorodiphenyldichloroethane -- pharmacology KW - Liver -- anatomy & histology KW - Cytochrome P-450 CYP2B1 -- biosynthesis KW - Liver -- enzymology KW - Liver -- drug effects KW - DDT -- pharmacology KW - Dichlorodiphenyl Dichloroethylene -- pharmacology KW - Insecticides -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79781567?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+toxicology+and+environmental+health.+Part+A&rft.atitle=Comparative+pharmacodynamics+of+CYP2B+induction+by+DDT%2C+DDE%2C+and+DDD+in+male+rat+liver+and+cultured+rat+hepatocytes.&rft.au=Nims%2C+R+W%3BLubet%2C+R+A%3BFox%2C+S+D%3BJones%2C+C+R%3BThomas%2C+P+E%3BReddy%2C+A+B%3BKocarek%2C+T+A&rft.aulast=Nims&rft.aufirst=R&rft.date=1998-03-27&rft.volume=53&rft.issue=6&rft.spage=455&rft.isbn=&rft.btitle=&rft.title=Journal+of+toxicology+and+environmental+health.+Part+A&rft.issn=15287394&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-30 N1 - Date created - 1998-04-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Breastfeeding, genetic, obstetric and other risk factors associated with mother-to-child transmission of HIV-1 in Sao Paulo State, Brazil AN - 16511347; 4326230 AB - Objectives: To evaluate the effect of maternal, obstetric, neonatal and post-natal factors on the risk of vertical transmission of HIV-1. Design: Multicentre retrospective cohort study. Setting: Obstetric and paediatric clinics in four cities in Sao Paulo State, Brazil. Main outcome: Child's HIV-1 infection status. Methods: Data were collected by standardized record abstraction and interview on 553 children born to women identified as HIV-1-infected before or at delivery. Paediatric infection was determined by immunoglobulin G anti-HIV-1 tests at age 18 months or by AIDS diagnosis at any age. Multivariate logistic regression was used to assess the effect of potential risk factors on vertical transmission of HIV-1. Results: HIV-1 infection status was determined for 434 children (follow-up rate of 78%); 69 were classified as HIV-1-infected [transmission risk, 16%; 95% confidence interval (CI), 13-20%]. In multivariate analysis, advanced maternal HIV-1 disease [odds ratio (OR), 4.5; 95% CI, 2.1-9.5], ever breastfed (OR, 2.2; 95% CI, 1.2-4.2), child's negative Rhesus blood group (OR, 2.5; 95% CI, 1.2-5.5), third trimester amniocentesis (OR, 4.1; 95% CI, 1.2-13.5) and black racial group (OR, 0.3; 95% CI, 0.1-0.9) were independently and significantly associated with mother-to-child transmission of HIV-1. Transmission was increased marginally with prematurity, more than 10 lifetime sexual partners and prolonged duration of membrane rupture. No association was found between child's HIV-1 infection and mode of delivery or serological evidence of syphilis during pregnancy. Conclusion: These findings support the importance of severity of maternal HIV-1 disease in the risk of vertical transmission of HIV-1, indicate measures to reduce transmission by avoiding amniocentesis and breastfeeding and suggest that race and Rhesus blood type may be markers for genetic susceptibility to infection. JF - AIDS AU - Tess, B H AU - Rodrigues, L C AU - Newell, M-L AU - Dunn, D T AU - Lago, TDG AD - Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 6130 Executive Blvd., EPN/434, Rockville, MD 20852, USA Y1 - 1998/03/26/ PY - 1998 DA - 1998 Mar 26 SP - 513 EP - 520 VL - 12 IS - 5 SN - 0269-9370, 0269-9370 KW - Brazil KW - Brazil, Sao Paulo KW - HIV-1 KW - breast feeding KW - disease transmission KW - man KW - parent-offspring interactions KW - Risk Abstracts; Virology & AIDS Abstracts KW - V 22006:AIDS: Other aspects KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16511347?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS&rft.atitle=Breastfeeding%2C+genetic%2C+obstetric+and+other+risk+factors+associated+with+mother-to-child+transmission+of+HIV-1+in+Sao+Paulo+State%2C+Brazil&rft.au=Tess%2C+B+H%3BRodrigues%2C+L+C%3BNewell%2C+M-L%3BDunn%2C+D+T%3BLago%2C+TDG&rft.aulast=Tess&rft.aufirst=B&rft.date=1998-03-26&rft.volume=12&rft.issue=5&rft.spage=513&rft.isbn=&rft.btitle=&rft.title=AIDS&rft.issn=02699370&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - In cortical cultures of trisomy 16 mouse brain the upregulated metallothionein-I/II fails to respond to H2O2 exposure or glutamate receptor stimulation. AN - 79764036; 9518655 AB - To assess whether a defective oxidative defense may contribute to Down's syndrome, we studied the regulation of the metallothionein(MT)-I/II isoforms in primary cultures of cerebral cortex from fetal trisomy 16 mice and their euploid littermates. Western blot analysis showed that MT-I/II was upregulated and the protein carbonyl content was higher in trisomy 16 compared with euploid cultures. Addition of N-acetyl-l-cysteine to the culture medium reduced the increment of MT-I/II in trisomy 16 cortical cells. In euploid, but not trisomic cortical cultures, kainic acid, trans-(+/-)-ACPD, or H2O2 exposure elicited a dose-dependent increase of the MT-I/II immunoblots. In trisomic cells, the MT-I/II immunoblot densities were not increased beyond their elevated basal levels. In contrast, 25 microM Pb induced MT-I/II, to a similar extent, in cortical cultures from euploid and trisomy 16 mice. This suggests that the antioxidant-but not the metal-response element of the MT-I/II promoter was altered by increased oxidative stress. Our data suggest that, in the trisomy 16 mouse, the effects of increased production of reactive oxygen species, due to the increased SOD-1, GluR5, or amyloid precursor protein gene dosage, is exacerbated by an insufficient or missing antioxidant response. Copyright 1998 Elsevier Science B.V. JF - Brain research AU - Scortegagna, M AU - Galdzicki, Z AU - Rapoport, S I AU - Hanbauer, I AD - Laboratory of Molecular Immunology, NHLBI, Bethesda, MD 20892, USA. Y1 - 1998/03/23/ PY - 1998 DA - 1998 Mar 23 SP - 292 EP - 298 VL - 787 IS - 2 SN - 0006-8993, 0006-8993 KW - Excitatory Amino Acid Agonists KW - 0 KW - Free Radical Scavengers KW - Oxidants KW - Receptors, Glutamate KW - Lead KW - 2P299V784P KW - Metallothionein KW - 9038-94-2 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Acetylcysteine KW - WYQ7N0BPYC KW - Index Medicus KW - Animals KW - Astrocytes -- drug effects KW - Acetylcysteine -- pharmacology KW - Mice KW - Stimulation, Chemical KW - Oxidation-Reduction KW - Blotting, Western KW - Mice, Inbred C57BL KW - Lead -- pharmacology KW - Female KW - Free Radical Scavengers -- pharmacology KW - Male KW - Astrocytes -- metabolism KW - Up-Regulation -- physiology KW - Cerebral Cortex -- cytology KW - Metallothionein -- biosynthesis KW - Oxidants -- pharmacology KW - Receptors, Glutamate -- drug effects KW - Cerebral Cortex -- pathology KW - Hydrogen Peroxide -- pharmacology KW - Metallothionein -- drug effects KW - Trisomy -- pathology KW - Excitatory Amino Acid Agonists -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79764036?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research&rft.atitle=In+cortical+cultures+of+trisomy+16+mouse+brain+the+upregulated+metallothionein-I%2FII+fails+to+respond+to+H2O2+exposure+or+glutamate+receptor+stimulation.&rft.au=Scortegagna%2C+M%3BGaldzicki%2C+Z%3BRapoport%2C+S+I%3BHanbauer%2C+I&rft.aulast=Scortegagna&rft.aufirst=M&rft.date=1998-03-23&rft.volume=787&rft.issue=2&rft.spage=292&rft.isbn=&rft.btitle=&rft.title=Brain+research&rft.issn=00068993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-10 N1 - Date created - 1998-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Visceral abdominal-fat accumulation associated with use of indinavir AN - 17152366; 4451152 AB - After the addition of the protease inhibitor indinavir to combination drug regimens for HIV-1 infection, some patients have experienced an increase in abdominal girth with symptoms of abdominal fullness, distension, or bloating. We aimed to find out whether this collection of symptoms was associated with changes in abdominal fat and whether such changes were associated with indinavir use. Abdominal computed tomography was used in ten HIV-1-positive patients who had such abdominal symptoms to measure total adipose tissue (TAT) and visceral adipose tissue (VAT) at the umbilicus (L4 vertebral level). The VAT:TAT ratio in the ten cases was compared with that in ten HIV-1-infected patients who had been using indinavir without abdominal symptoms for at least 6 months and ten HIV-1-infected patients who were not using indinavir. The mean VAT:TAT ratios for the three groups - non-users, symptom-free indinavir users, and symptomatic indinavir users - were 0.40 (SD 0.15), 0.59 (0.18), and 0.70 (0.20), respectively (p=0.004). The VAT:TAT ratio correlated with duration of indinavir use (r=0.47, p=0.01). The mean areas of VAT for the three groups were 106 cm super(2) (SD 72), 141 cm super(2) (65) and 202 cm super(2) (93), respectively (p=0.03). The mean body-mass index of the groups was similar, and patients in the two indinavir groups did not gain a significant amount of weight after starting the drug. Serum triglyceride values increased after starting indinavir and correlated with VAT:TAT ratios. Our data suggest that some HIV-1-infected patients on indinavir treatment accumulate intra-abdominal fat that may cause abdominal symptoms. Recent evidence suggests that other HIV-1 protease inhibitors may be associated with changes in body-fat distribution. Larger studies of protease-inhibitor treatment are needed to investigate this association further and to investigate metabolic or endocrine mechanisms that may underlie this phenomenon. JF - Lancet AU - Miller, K D AU - Jones, E AU - Yanovski, JA AU - Shankar, R AU - Feuerstein, I AU - Falloon, J AD - National Institutes of Health (Bldg 10, Room 8C410), Bethesda, MD 20892, USA, kmiller@atlas.niaid.nih.gov Y1 - 1998/03/21/ PY - 1998 DA - 1998 Mar 21 SP - 871 EP - 875 VL - 351 IS - 9106 SN - 0099-5355, 0099-5355 KW - HIV-1 KW - indinavir KW - man KW - proteinase inhibitors KW - Virology & AIDS Abstracts; Toxicology Abstracts KW - Symptoms KW - Acquired immune deficiency syndrome KW - Metabolic disorders KW - Therapy KW - Antiviral agents KW - Computed tomography KW - Human immunodeficiency virus 1 KW - Body fat KW - Endocrine system KW - Side effects KW - Fat metabolism KW - X 24114:Metabolism KW - V 22004:AIDS: Clinical aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17152366?accountid=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=Lancet&rft.atitle=Visceral+abdominal-fat+accumulation+associated+with+use+of+indinavir&rft.au=Miller%2C+K+D%3BJones%2C+E%3BYanovski%2C+JA%3BShankar%2C+R%3BFeuerstein%2C+I%3BFalloon%2C+J&rft.aulast=Miller&rft.aufirst=K&rft.date=1998-03-21&rft.volume=351&rft.issue=9106&rft.spage=871&rft.isbn=&rft.btitle=&rft.title=Lancet&rft.issn=00995355&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus 1; Computed tomography; Fat metabolism; Body fat; Side effects; Acquired immune deficiency syndrome; Symptoms; Therapy; Endocrine system; Antiviral agents; Metabolic disorders ER - TY - JOUR T1 - Immunologic cross-reaction between HIV type 1 p17 and Mycoplasma hyorhinis variable lipoprotein. AN - 79786499; 9546801 AB - Monoclonal antibodies directed against the HIV-1 matrix protein p17 that react with a component present on the surface of HIV-1-infected cells have previously been described. In this study we show that one of these monoclonal antibodies binds to persistently HIV-1-infected cell lines that are coinfected with Mycoplasma hyorhinis, but not to cell lines that are uninfected with mycoplasma. Mycoplasma-infected cells secrete HIV-1 at a higher rate, have a slight increase in cell surface expression of gp120 and gp41, and are less sensitive to immunotoxins than uninfected cells. The anti-p17 antibody binds to a protein of M. hyorhinis grown in cell-free culture. The variable expression and size of the protein among strains is typical of the variable lipoprotein (Vlp) system of M. hyorhinis. Confirmation of the reactivity of the antibody with a Vlp was provided by demonstrating its specific binding to recombinant VlpF expressed in E. coli, and to a synthetic peptide representing the carboxy-terminal region of VlpF, but not to other recombinant Vlp products or peptides. This is a true cross-reaction because the antibody also binds to recombinant p17 expressed in E. coli and the binding is inhibited by the VlpF peptide. These analyses highlight the potential of mycoplasma contamination of tissue culture cell lines to cause anomalous results. With regard to HIV-1, mycoplasma infection of cells results in increased rates of virus secretion, and introduces a potential confounding immunologic cross-reaction as well. The existence of a cell surface form of p17 is unlikely. JF - AIDS research and human retroviruses AU - Pincus, S H AU - Cole, R L AU - Watson-McKown, R AU - Pinter, A AU - Honnen, W AU - Cole, B AU - Wise, K S AD - Laboratory of Microbial Structure and Function, NIAID Rocky Mountain Laboratories, Hamilton, Montana 59840, USA. Y1 - 1998/03/20/ PY - 1998 DA - 1998 Mar 20 SP - 419 EP - 425 VL - 14 IS - 5 SN - 0889-2229, 0889-2229 KW - Antibodies, Monoclonal KW - 0 KW - Bacterial Outer Membrane Proteins KW - Bacterial Proteins KW - Gene Products, gag KW - HIV Antigens KW - Lipoproteins KW - Viral Proteins KW - VlpF protein, Mycoplasma hyorhinis KW - gag Gene Products, Human Immunodeficiency Virus KW - p17 protein, Human Immunodeficiency Virus Type 1 KW - Index Medicus KW - AIDS/HIV KW - Immunoblotting KW - Cells, Cultured KW - Enzyme-Linked Immunosorbent Assay KW - Flow Cytometry KW - Cross Reactions -- immunology KW - HIV-1 -- immunology KW - Lipoproteins -- immunology KW - HIV-1 -- isolation & purification KW - Bacterial Outer Membrane Proteins -- immunology KW - Bacterial Proteins -- immunology KW - Mycoplasma -- growth & development KW - HIV-1 -- growth & development KW - Gene Products, gag -- immunology KW - HIV Antigens -- immunology KW - Mycoplasma -- isolation & purification KW - Mycoplasma -- immunology KW - Antibodies, Monoclonal -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79786499?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+research+and+human+retroviruses&rft.atitle=Immunologic+cross-reaction+between+HIV+type+1+p17+and+Mycoplasma+hyorhinis+variable+lipoprotein.&rft.au=Pincus%2C+S+H%3BCole%2C+R+L%3BWatson-McKown%2C+R%3BPinter%2C+A%3BHonnen%2C+W%3BCole%2C+B%3BWise%2C+K+S&rft.aulast=Pincus&rft.aufirst=S&rft.date=1998-03-20&rft.volume=14&rft.issue=5&rft.spage=419&rft.isbn=&rft.btitle=&rft.title=AIDS+research+and+human+retroviruses&rft.issn=08892229&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-14 N1 - Date created - 1998-05-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mammalian DNA topoisomerase I activity and poisoning by camptothecin are inhibited by simian virus 40 large T antigen. AN - 79764431; 9521701 AB - DNA topoisomerase I (top1) is a ubiquitous enzyme that forms reversible DNA single-strand breaks (cleavage complexes) and plays a role in transcription, DNA replication, and repair. Top1 is the target of camptothecins which selectively trap top1 cleavage complexes and represent a novel class of anticancer drugs active against human solid tumors. The present study demonstrates that recombinant large T antigen (T-Ag), a virus encoded helicase with strong affinity for tumor suppressors and cell cycle- and replication-related proteins, suppresses top1 cleavage complexes and top1 catalytic activity. This top1 suppressive activity is probably not due to T-Ag binding to DNA, as a T-Ag truncation mutant containing only the first 246 amino acids and deficient in DNA binding also inhibited top1, and the inhibition was independent of ATP. T-Ag also antagonized and reversed the trapping of top1 cleavage complexes by camptothecin. These results demonstrate a functional interaction between T-Ag and top1: they also suggest the importance of top1-protein interactions for the regulation of DNA replication and modulation of camptothecin activity. JF - Biochemistry AU - Pommier, Y AU - Kohlhagen, G AU - Wu, C AU - Simmons, D T AD - Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. pommier@nih.gov Y1 - 1998/03/17/ PY - 1998 DA - 1998 Mar 17 SP - 3818 EP - 3823 VL - 37 IS - 11 SN - 0006-2960, 0006-2960 KW - Antigens, Polyomavirus Transforming KW - 0 KW - DNA-Binding Proteins KW - Topoisomerase I Inhibitors KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - DNA Topoisomerases, Type II KW - EC 5.99.1.3 KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Base Sequence KW - Humans KW - DNA Topoisomerases, Type II -- metabolism KW - Molecular Sequence Data KW - Enzyme Activation -- drug effects KW - Electrophoresis, Agar Gel KW - DNA-Binding Proteins -- genetics KW - Sequence Deletion KW - Camptothecin -- antagonists & inhibitors KW - Simian virus 40 -- genetics KW - Camptothecin -- toxicity KW - Antigens, Polyomavirus Transforming -- physiology KW - Antigens, Polyomavirus Transforming -- genetics KW - DNA Topoisomerases, Type I -- genetics KW - Simian virus 40 -- immunology KW - DNA Topoisomerases, Type I -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79764431?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=Mammalian+DNA+topoisomerase+I+activity+and+poisoning+by+camptothecin+are+inhibited+by+simian+virus+40+large+T+antigen.&rft.au=Pommier%2C+Y%3BKohlhagen%2C+G%3BWu%2C+C%3BSimmons%2C+D+T&rft.aulast=Pommier&rft.aufirst=Y&rft.date=1998-03-17&rft.volume=37&rft.issue=11&rft.spage=3818&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-14 N1 - Date created - 1998-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of monocyte chemoattractant protein-1 in HIV-1 Tat-stimulated astrocytes and elevation in AIDS dementia. AN - 79735450; 9501225 AB - Activated monocytes release a number of substances, including inflammatory cytokines and eicosanoids, that are highly toxic to cells of the central nervous system. Because monocytic infiltration of the central nervous system closely correlates with HIV-1-associated dementia, it has been suggested that monocyte-derived toxins mediate nervous system damage. In the present study, we show that the HIV-1 transactivator protein Tat significantly increases astrocytic expression and release of monocyte chemoattractant protein-1 (MCP-1). Astrocytic release of beta-chemokines, which are relatively less selective for monocytes, including RANTES, macrophage inflammatory protein-1alpha, and macrophage inflammatory protein-1beta, was not observed. We also show that MCP-1 is expressed in the brains of patients with HIV-1-associated dementia and that, of the beta-chemokines tested, only MCP-1 could be detected in the cerebrospinal fluid of patients with this condition. Together, these data provide a potential link between the presence of HIV-1 in the brain and the monocytic infiltration that may substantially contribute to dementia. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Conant, K AU - Garzino-Demo, A AU - Nath, A AU - McArthur, J C AU - Halliday, W AU - Power, C AU - Gallo, R C AU - Major, E O AD - Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, Building 36, Room 5W21, National Institutes of Health, Bethesda, MD 20892, USA. conant@codon.nih.gov Y1 - 1998/03/17/ PY - 1998 DA - 1998 Mar 17 SP - 3117 EP - 3121 VL - 95 IS - 6 SN - 0027-8424, 0027-8424 KW - Chemokine CCL2 KW - 0 KW - Chemokine CCL4 KW - Chemokine CCL5 KW - Gene Products, tat KW - Macrophage Inflammatory Proteins KW - tat Gene Products, Human Immunodeficiency Virus KW - Index Medicus KW - AIDS/HIV KW - Prospective Studies KW - Macrophage Inflammatory Proteins -- analysis KW - Cells, Cultured KW - Humans KW - Adult KW - Middle Aged KW - Brain -- metabolism KW - Monocytes KW - Chemokine CCL5 -- analysis KW - Chemokine CCL2 -- blood KW - AIDS Dementia Complex -- metabolism KW - AIDS Dementia Complex -- cerebrospinal fluid KW - Astrocytes -- drug effects KW - AIDS Dementia Complex -- etiology KW - AIDS Dementia Complex -- blood KW - Chemokine CCL2 -- biosynthesis KW - Gene Products, tat -- pharmacology KW - HIV-1 KW - Chemokine CCL2 -- cerebrospinal fluid UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79735450?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Induction+of+monocyte+chemoattractant+protein-1+in+HIV-1+Tat-stimulated+astrocytes+and+elevation+in+AIDS+dementia.&rft.au=Conant%2C+K%3BGarzino-Demo%2C+A%3BNath%2C+A%3BMcArthur%2C+J+C%3BHalliday%2C+W%3BPower%2C+C%3BGallo%2C+R+C%3BMajor%2C+E+O&rft.aulast=Conant&rft.aufirst=K&rft.date=1998-03-17&rft.volume=95&rft.issue=6&rft.spage=3117&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-10 N1 - Date created - 1998-04-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Immunol. 1994 Sep 1;153(5):2052-63 [8051410] J Virol. 1996 Mar;70(3):1384-9 [8627654] Eur J Immunol. 1995 Jan;25(1):64-8 [7531149] Ann Neurol. 1995 Mar;37(3):373-80 [7695237] Hum Gene Ther. 1995 Feb;6(2):177-84 [7734518] Nature. 1997 Feb 13;385(6617):645-9 [9024664] J Immunol. 1997 Mar 1;158(5):2449-55 [9036996] J Exp Med. 1997 Jul 7;186(1):131-7 [9207007] J Leukoc Biol. 1997 Jul;62(1):34-40 [9225990] J Clin Invest. 1997 Aug 1;100(3):497-502 [9239395] J Biol Chem. 1997 Sep 5;272(36):22385-8 [9278385] Eur J Immunol. 1997 Oct;27(10):2484-9 [9368600] Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):494-8 [8290553] Nature. 1994 Jan 13;367(6459):188-93 [8114918] Ann Neurol. 1983 Mar;13(3):227-31 [6847134] Science. 1986 Jul 11;233(4760):215-9 [3014648] Science. 1986 Sep 5;233(4768):1089-93 [3016903] Proc Natl Acad Sci U S A. 1986 Sep;83(18):7089-93 [3018755] Science. 1988 Feb 5;239(4840):586-92 [3277272] Science. 1990 Apr 20;248(4953):364-7 [2326646] Neurology. 1991 Jun;41(6):778-85 [2046917] Blood. 1991 Aug 15;78(4):1112-6 [1868242] Am J Pathol. 1992 Nov;141(5):1209-16 [1279980] J Virol. 1993 Jan;67(1):277-87 [8416373] FASEB J. 1993 Apr 1;7(6):592-600 [8472896] Ann Neurol. 1993 May;33(5):429-36 [8498818] Ann Neurol. 1993 Jun;33(6):576-82 [8498837] Nature. 1993 Sep 9;365(6442):182-5 [8371761] Exp Hematol. 1996 Feb;24(2):169-75 [8641338] Curr Opin Pediatr. 1995 Dec;7(6):655-62 [8776015] AIDS. 1996 Jul;10(8):843-7 [8828741] Neuroscience. 1996 Sep;74(1):283-92 [8843093] J Infect Dis. 1996 Nov;174(5):1098-101 [8896515] Nat Med. 1996 Nov;2(11):1174-8 [8898734] Science. 1996 Dec 13;274(5294):1917-21 [8943206] Biochem Biophys Res Commun. 1994 Mar 15;199(2):761-6 [7510961] Crit Rev Oral Biol Med. 1995;6(2):109-18 [7548618] Neuropathol Appl Neurobiol. 1995 Jun;21(3):208-17 [7477729] Ann Neurol. 1995 Nov;38(5):755-62 [7486867] J Immunol. 1995 Dec 15;155(12):5769-76 [7499865] Science. 1995 Dec 15;270(5243):1811-5 [8525373] Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):700-4 [8570619] J Immunol. 1996 Apr 15;156(8):3017-23 [8609424] AIDS. 1994 Oct;8(10):1504-6 [7818827] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carbon dioxide stimulates peroxynitrite-mediated nitration of tyrosine residues and inhibits oxidation of methionine residues of glutamine synthetase: Both modifications mimic effects of adenylylation AN - 16373152; 4257269 AB - The activity of glutamine synthetase (EC 6.3.1.2) from Escherichia coli is regulated by the cyclic adenylylation and deadenylylation of Tyr-397 in each of the enzyme's 12 identical subunits. The nitration of Tyr-397 or of the nearby Tyr-326 by peroxynitrite can convert the unadenylylated enzyme to a form exhibiting regulatory characteristics similar to the form obtained by adenylylation. The adenylylated conformation can also be elicited by the oxidation of surface-exposed methionine residues to methionine sulfoxide. However, the nitration of tyrosine residues and the oxidation of methionine residues are oppositely directed by the presence and absence of CO sub(2.) At physiological concentrations of CO sub(2), pH 7.4, nitration occurs but oxidation of methionine residues is inhibited. Conversely, in the absence of CO sub(2) methionine oxidation is stimulated and nitration of tyrosine is prevented. It was further established that adenylylation of Tyr-397 precludes its nitration by peroxynitrite. Furthermore, nitration of Tyr-326 together with either nitration or adenylylation of Tyr-397 leads to inactivation of the enzyme. These results demonstrate that CO sub(2) can alter the course of peroxynitrite-dependent reactions and serve notice that (i) the reactions have physiological significance only if they are shown to occur at physiological concentrations of CO sub(2) and physiological pH; and (ii) the peroxynitrite-dependent nitration of tyrosine residues or the oxidation of methionine residues of metabolically regulated proteins can seriously compromise their biological function. JF - Proceedings of the National Academy of Sciences, USA AU - Berlett, B AU - Levine, R AU - Stadtman, E AD - Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-0342, erstadtman@nih.gov Y1 - 1998/03/17/ PY - 1998 DA - 1998 Mar 17 SP - 2784 EP - 2789 VL - 95 IS - 6 SN - 0027-8424, 0027-8424 KW - glutamate-ammonia ligase KW - methionine sulfoxide KW - oxidation KW - peroxynitrate KW - Microbiology Abstracts B: Bacteriology KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16373152?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Carbon+dioxide+stimulates+peroxynitrite-mediated+nitration+of+tyrosine+residues+and+inhibits+oxidation+of+methionine+residues+of+glutamine+synthetase%3A+Both+modifications+mimic+effects+of+adenylylation&rft.au=Berlett%2C+B%3BLevine%2C+R%3BStadtman%2C+E&rft.aulast=Berlett&rft.aufirst=B&rft.date=1998-03-17&rft.volume=95&rft.issue=6&rft.spage=2784&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - The rpoB mutants destabilizing initiation complexes at stringently controlled promoters behave like 'stringent' RNA polymerases in Escherichia coli AN - 16314522; 4257291 AB - In Escherichia coli, stringently controlled genes are highly transcribed during rapid growth, but 'turned off' under nutrient limiting conditions, a process called the stringent response. To understand how transcriptional initiation at these promoters is coordinately regulated, we analyzed the interactions between RNA polymerase (RNAP) (both wild type and mutants) and four stringently controlled promoters. Our results show that the interactions between RNAP and stringently controlled promoters are intrinsically unstable and can alternate between relatively stable and metastable states. The mutant RNAPs appear to specifically further weaken interactions with these promoters in vitro and behave like 'stringent' RNAPs in the absence of the stringent response in vivo, constituting a novel class of mutant RNAPs. Consistently, these mutant RNAPs also activate the expression of other genes that normally require the response. We propose that the stability of initiation complexes is coupled to the transcription of stringently controlled promoters, and this unique feature coordinates the expression of genes positively and negatively regulated by the stringent response. JF - Proceedings of the National Academy of Sciences, USA AU - Zhou, Y AU - Jin, D AD - Laboratory of Molecular Biology, Building 37, Room 2E14, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, djjin@helix.nih.gov Y1 - 1998/03/17/ PY - 1998 DA - 1998 Mar 17 SP - 2908 EP - 2913 VL - 95 IS - 6 SN - 0027-8424, 0027-8424 KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - N 14721:RNA polymerases KW - J 02726:RNA and ribosomes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16314522?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=The+rpoB+mutants+destabilizing+initiation+complexes+at+stringently+controlled+promoters+behave+like+%27stringent%27+RNA+polymerases+in+Escherichia+coli&rft.au=Zhou%2C+Y%3BJin%2C+D&rft.aulast=Zhou&rft.aufirst=Y&rft.date=1998-03-17&rft.volume=95&rft.issue=6&rft.spage=2908&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Role of individual N-linked glycosylation sites in the function and intracellular transport of the human alpha folate receptor. AN - 79809737; 9515058 AB - Glycosylation is a structural feature of all three isoforms of the human folate receptor. We have used site-directed mutagenesis to study the role of individual glycosylation sites in the assembly and function of the a isoform of the human folate receptor (alpha(h)FR). Three potential N-linked glycosylation sites in the alpha(h)FR sequence were disrupted by conservative mutation of the S or T residues in the consensus sequence (N-X-S/T) to A or V, respectively. Constructs with the single mutations S(71)-->A (alpha(h)FR(-1)), T(163)-->V (alpha(h)FR(-2)), and S(203)-->A (alpha(h)FR(-3)); the double mutation S(71)--> A/S(203)-->A (alpha(h)FR(-1-3)); and the triple mutation S(71)--> A/S(203)--> A/T(163)--> V (alpha(h)FR(-1-2-3)) were stably transfected into Chinese hamster ovary (CHO) cells. The proteins produced in CHO cells by the mutated cDNAs have apparent molecular weights that are reduced relative to the wild type and are consistent with the loss of carbohydrate residues. The triple mutant, which lacks all three consensus glycosylation sites, yields protein that comigrates with the enzymatically deglycosylated native protein. Determinations of the K(D) for folic acid by Scatchard analyses of the glycosylation mutants indicate that folic acid binding affinity is not significantly affected in the single mutants alpha(h)FR(-1) and alpha(h)FR(-2). However, in the single mutant, alpha(h)FR(-3), and the double mutant, alpha(h)FR(-1-3), folic acid binding affinity is respectively 2.7- and 3.5-fold lower than that in wild type. Deglycosylation by mutation of all three consensus sites (alpha(h)FR(-1-2-3) eliminates both folic acid binding and cell surface expression. In contrast, enzymatic deglycosylation of purified wild-type alpha(h)FR with endoglycosidase F does not significantly affect folate binding affinity. Thus, while carbohydrate residues are not essential for the folate binding activity of the mature folate receptor, at least one of the three core glycosylated residues is necessary for the synthesis of alpha(h)FR in its active conformation. Copyright 1998 Academic Press. JF - Archives of biochemistry and biophysics AU - Roberts, S J AU - Petropavlovskaja, M AU - Chung, K N AU - Knight, C B AU - Elwood, P C AD - Section of Experimental Hematology, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/03/15/ PY - 1998 DA - 1998 Mar 15 SP - 227 EP - 235 VL - 351 IS - 2 SN - 0003-9861, 0003-9861 KW - Carrier Proteins KW - 0 KW - Folate Receptors, GPI-Anchored KW - RNA, Messenger KW - Receptors, Cell Surface KW - Recombinant Proteins KW - Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase KW - EC 3.2.1.96 KW - Index Medicus KW - Animals KW - Humans KW - RNA, Messenger -- analysis KW - Protein Denaturation KW - Glycosylation KW - Recombinant Proteins -- genetics KW - Precipitin Tests KW - Protein Binding -- physiology KW - Consensus Sequence -- genetics KW - Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase -- metabolism KW - Transfection KW - Kinetics KW - CHO Cells KW - Cricetinae KW - Protein Conformation KW - Carrier Proteins -- genetics KW - Carrier Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79809737?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+biochemistry+and+biophysics&rft.atitle=Role+of+individual+N-linked+glycosylation+sites+in+the+function+and+intracellular+transport+of+the+human+alpha+folate+receptor.&rft.au=Roberts%2C+S+J%3BPetropavlovskaja%2C+M%3BChung%2C+K+N%3BKnight%2C+C+B%3BElwood%2C+P+C&rft.aulast=Roberts&rft.aufirst=S&rft.date=1998-03-15&rft.volume=351&rft.issue=2&rft.spage=227&rft.isbn=&rft.btitle=&rft.title=Archives+of+biochemistry+and+biophysics&rft.issn=00039861&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-20 N1 - Date created - 1998-04-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adenovirus-mediated human immunodeficiency virus-1 Nef expression in human monocytes/macrophages and effect of Nef on downmodulation of Fcgamma receptors and expression of monokines. AN - 79717683; 9490697 AB - To characterize the effect of human immunodeficiency virus-1 (HIV-1) nef expression in human monocytes/macrophage (HMO) and U937 on the levels of FcgammaRs, HLA antigens, and monokines, elutriated HMOs and U937 cells were transfected with an adenovirus-mediated Nef expression system. Nef-expressing cells downmodulated FcgammaRI, FcgammaRII, and upregulated HLA class I molecules. Nef-expressing HMOs, treated with lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA), overexpressed tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-10. However, IL-6 was induced by LPS and inhibited by PMA. Additionally, a subpopulation of Nef-expressing HMOs underwent apoptosis. Our data suggest that HIV-1 nef downmodulated FcgammaRs in myeloid cells in a manner similar to that previously reported for its effect on CD4+ in T cells. JF - Blood AU - De, S K AU - Venkateshan, C N AU - Seth, P AU - Gajdusek, D C AU - Gibbs, C J AD - Oral Infection and Immunity Branch, National Institute of Dental Research, the Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA. Y1 - 1998/03/15/ PY - 1998 DA - 1998 Mar 15 SP - 2108 EP - 2117 VL - 91 IS - 6 SN - 0006-4971, 0006-4971 KW - Antigens, CD4 KW - 0 KW - Cation Exchange Resins KW - DNA, Antisense KW - Gene Products, nef KW - HLA Antigens KW - Interleukin-1 KW - Interleukin-6 KW - Lipids KW - Lipofectamine KW - Lipopolysaccharides KW - Monokines KW - Receptors, IgG KW - Receptors, Interleukin-2 KW - Tumor Necrosis Factor-alpha KW - nef Gene Products, Human Immunodeficiency Virus KW - Interleukin-10 KW - 130068-27-8 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Apoptosis KW - Lymphoma, Large B-Cell, Diffuse -- pathology KW - Humans KW - Lipopolysaccharides -- pharmacology KW - Tumor Necrosis Factor-alpha -- genetics KW - Receptors, Interleukin-2 -- genetics KW - HLA Antigens -- biosynthesis KW - Tumor Cells, Cultured KW - Down-Regulation KW - Antigens, CD4 -- genetics KW - Interleukin-6 -- genetics KW - Antigens, CD4 -- biosynthesis KW - Interleukin-1 -- genetics KW - Interleukin-10 -- genetics KW - HLA Antigens -- genetics KW - 3T3 Cells KW - Interleukin-1 -- biosynthesis KW - Receptors, Interleukin-2 -- biosynthesis KW - Tumor Necrosis Factor-alpha -- biosynthesis KW - DNA, Antisense -- genetics KW - Mice KW - Transfection KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Interleukin-10 -- biosynthesis KW - Interleukin-6 -- biosynthesis KW - Receptors, IgG -- biosynthesis KW - HIV-1 -- genetics KW - Gene Products, nef -- physiology KW - Gene Expression Regulation, Viral KW - Monocytes -- metabolism KW - Monokines -- genetics KW - Genetic Vectors -- genetics KW - Monokines -- biosynthesis KW - Genes, nef KW - Receptors, IgG -- genetics KW - Macrophages -- metabolism KW - Adenoviridae -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79717683?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Adenovirus-mediated+human+immunodeficiency+virus-1+Nef+expression+in+human+monocytes%2Fmacrophages+and+effect+of+Nef+on+downmodulation+of+Fcgamma+receptors+and+expression+of+monokines.&rft.au=De%2C+S+K%3BVenkateshan%2C+C+N%3BSeth%2C+P%3BGajdusek%2C+D+C%3BGibbs%2C+C+J&rft.aulast=De&rft.aufirst=S&rft.date=1998-03-15&rft.volume=91&rft.issue=6&rft.spage=2108&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-09 N1 - Date created - 1998-04-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Incidence and risk factors for self-reported peptic ulcer disease in the United States AN - 16374302; 4297636 AB - Incidence and risk factors for peptic ulcer disease in the United States have not been well defined. During the 1989 National Health Interview Survey, a population-based sample of 42,392 individuals responded to questions regarding doctor-diagnosed ulcers with confirmation by either an upper gastrointestinal series or endoscopy. Ulcers present during the previous 12 months were considered either incident ulcers if diagnosed during this period or chronic active ulcers if diagnosed more than 12 months before the interview. The incidence of ulcers over the year prior to the interview was 5.27 per 1,000 adults. Whereas incident duodenal ulcer cases represented only 2.4 percent of all persons with a history of duodenal ulcer, the corresponding value for gastric ulcer was 8.7 percent. Risk factors for incident ulcers included increasing age, lower income and educational attainment, and musculoskeletal pain or headache. These were similar to risk factors for chronic active ulcers, except smoking was an additional important risk factor for chronic active ulcers. Thus, incident peptic ulcers are common in the United States but represent a small proportion of persons with a history of ulcer disease. Smoking may be a stronger risk factor for chronic ulcers than for new ulcers. JF - American Journal of Epidemiology AU - Everhart, JE AU - Byrd-Holt, D AU - Sonnenberg, A AD - Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA Y1 - 1998/03/15/ PY - 1998 DA - 1998 Mar 15 SP - 529 EP - 536 VL - 147 IS - 6 SN - 0002-9262, 0002-9262 KW - USA KW - man KW - Toxicology Abstracts KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16374302?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Epidemiology&rft.atitle=Incidence+and+risk+factors+for+self-reported+peptic+ulcer+disease+in+the+United+States&rft.au=Everhart%2C+JE%3BByrd-Holt%2C+D%3BSonnenberg%2C+A&rft.aulast=Everhart&rft.aufirst=JE&rft.date=1998-03-15&rft.volume=147&rft.issue=6&rft.spage=529&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Transmembrane topology of glucose-6-phosphatase. AN - 79732042; 9497333 AB - Deficiency of microsomal glucose-6-phosphatase (G6Pase), the key enzyme in glucose homeostasis, causes glycogen storage disease type 1a, an autosomal recessive disorder. Characterization of the transmembrane topology of G6Pase should facilitate the identification of amino acid residues contributing to the active site and broaden our understanding of the effects of mutations that cause glycogen storage disease type 1a. Using N- and C-terminal tagged G6Pase, we show that in intact microsomes, the N terminus is resistant to protease digestion, whereas the C terminus is sensitive to such treatment. Our results demonstrate that G6Pase possesses an odd number of transmembrane helices, with its N and C termini facing the endoplasmic reticulum lumen and the cytoplasm, respectively. During catalysis, a phosphoryl-enzyme intermediate is formed, and the phosphoryl acceptor in G6Pase is a His residue. Sequence alignment suggests that mammalian G6Pases, lipid phosphatases, acid phosphatases, and a vanadium-containing chloroperoxidase (whose tertiary structure is known) share a conserved phosphatase motif. Active-site alignment of the vanadium-containing chloroperoxidase and G6Pases predicts that Arg-83, His-119, and His-176 in G6Pase contribute to the active site and that His-176 is the residue that covalently binds the phosphoryl moiety during catalysis. This alignment also predicts that Arg-83, His-119, and His-176 reside on the same side of the endoplasmic reticulum membrane, which is supported by the recently predicted nine-transmembrane helical model for G6Pase. We have previously shown that Arg-83 is involved in positioning the phosphate during catalysis and that His-119 is essential for G6Pase activity. Here we demonstrate that substitution of His-176 with structurally similar or dissimilar amino acids inactivates the enzyme, suggesting that His-176 could be the phosphoryl acceptor in G6Pase during catalysis. JF - The Journal of biological chemistry AU - Pan, C J AU - Lei, K J AU - Annabi, B AU - Hemrika, W AU - Chou, J Y AD - Heritable Disorders Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/03/13/ PY - 1998 DA - 1998 Mar 13 SP - 6144 EP - 6148 VL - 273 IS - 11 SN - 0021-9258, 0021-9258 KW - Membrane Proteins KW - 0 KW - Histidine KW - 4QD397987E KW - Glucose-6-Phosphatase KW - EC 3.1.3.9 KW - Trypsin KW - EC 3.4.21.4 KW - Endopeptidase K KW - EC 3.4.21.64 KW - Index Medicus KW - Endopeptidase K -- pharmacology KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Glycogen Storage Disease Type I -- enzymology KW - Trypsin -- pharmacology KW - Sequence Deletion KW - Protein Conformation KW - Mutagenesis KW - Binding Sites KW - Membrane Proteins -- chemistry KW - Glucose-6-Phosphatase -- metabolism KW - Membrane Proteins -- metabolism KW - Glucose-6-Phosphatase -- chemistry KW - Glucose-6-Phosphatase -- drug effects KW - Microsomes -- enzymology KW - Membrane Proteins -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79732042?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Transmembrane+topology+of+glucose-6-phosphatase.&rft.au=Pan%2C+C+J%3BLei%2C+K+J%3BAnnabi%2C+B%3BHemrika%2C+W%3BChou%2C+J+Y&rft.aulast=Pan&rft.aufirst=C&rft.date=1998-03-13&rft.volume=273&rft.issue=11&rft.spage=6144&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-07 N1 - Date created - 1998-04-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of the direct genotoxic potential of cadmium in four different rodent cell lines AN - 16489162; 4366720 AB - Cadmium is a toxic environmental contaminant that is carcinogenic in humans and laboratory animals. Although the mechanism underlying cadmium carcinogenesis has not yet been determined experimental evidence suggests that the stress-inducible, metal-binding proteins, metallothioneins, may mediate organ specificity. In the present study, four different rodent cell lines (Chinese hamster ovary cells, rat L6 myoblast cells, rat Clone 9 liver cells, and rat TRL 1215 liver cells) were exposed to 0, 1, 5, 10, 50, or 100 mu M CdCl sub(2) and monitored for evidence of direct DNA damage. A microfiltration assay was used to measure DNA strand breaks and a filter-binding assay was used to measure DNA-protein crosslinks, two lesions that have been associated with cadmium exposure and may mediate genotoxicity of the metal. Although variability in sensitivity to DNA damage was evident between the different cell lines, in all of the cell lines tested, increases in DNA damage were observed only at cadmium doses that completely arrested cell growth. In addition, in three of the four cell lines tested, induction of metallothionein had no substantial protective effect against cadmium-induced cytotoxicity or genotoxicity. While protection against cadmium-induced DNA strand breakage with metallothionein preinduction was observed in the TRL 1215 rat liver cells, metallothionein preinduction did not protect against cadmium-induced DNA-protein crosslinking in that cell line. Taken together, our results support the hypothesis that cadmium is not directly genotoxic. JF - Toxicology AU - Misra, R R AU - Smith, G T AU - Waalkes, M P AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, Division of Basic Sciences, Bldg. 538, Room 205E, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702-1201, USA Y1 - 1998/03/13/ PY - 1998 DA - 1998 Mar 13 SP - 103 EP - 114 VL - 126 IS - 2 SN - 0300-483X, 0300-483X KW - cell lines KW - Toxicology Abstracts KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16489162?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=Evaluation+of+the+direct+genotoxic+potential+of+cadmium+in+four+different+rodent+cell+lines&rft.au=Misra%2C+R+R%3BSmith%2C+G+T%3BWaalkes%2C+M+P&rft.aulast=Misra&rft.aufirst=R&rft.date=1998-03-13&rft.volume=126&rft.issue=2&rft.spage=103&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Catalytic mechanism of aldose reductase studied by the combined potentials of quantum mechanics and molecular mechanics. AN - 79788404; 9546197 AB - The catalytic reduction of D-glyceraldehyde to glycerol by aldose reductase has been investigated with the combined potentials of quantum mechanics (QM) and molecular mechanics (MM) to resolve the question of whether Tyr48 or His110 serves as the proton donor during catalysis. Site directed mutagenesis studies favor Tyr48 as the proton donor while the presence of a water channel linking the N delta 1 of His110 to the bulk solvent suggests that His110 is the proton donor. Utilizing the combined potentials of QM and MM, the binding mode of substrate D-glyceraldehyde was investigated by optimizing the local geometry of Asp43, Lys77, Tyr48, His110 and NADPH at the active site of aldose reductase. Reaction pathways for the reduction of D-glyceraldehyde to glycerol were then constructed by treating both Tyr48 and His110 as proton donors. Comparison of energetics obtained from the reaction pathways suggests His110 to be the proton donor. Based on these findings, a reduction mechanism of D-glyceraldehyde to glycerol is described. JF - Biophysical chemistry AU - Lee, Y S AU - Hodoscek, M AU - Brooks, B R AU - Kador, P F AD - National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA. yongslee@helix.nih.gov Y1 - 1998/03/09/ PY - 1998 DA - 1998 Mar 09 SP - 203 EP - 216 VL - 70 IS - 3 SN - 0301-4622, 0301-4622 KW - Protons KW - 0 KW - Aldehyde Reductase KW - EC 1.1.1.21 KW - Index Medicus KW - Quantum Theory KW - Models, Molecular KW - Chemistry, Physical KW - Humans KW - Chemical Phenomena KW - Molecular Conformation KW - Energy Metabolism KW - Catalysis KW - Binding Sites KW - Aldehyde Reductase -- chemistry KW - Aldehyde Reductase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79788404?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biophysical+chemistry&rft.atitle=Catalytic+mechanism+of+aldose+reductase+studied+by+the+combined+potentials+of+quantum+mechanics+and+molecular+mechanics.&rft.au=Lee%2C+Y+S%3BHodoscek%2C+M%3BBrooks%2C+B+R%3BKador%2C+P+F&rft.aulast=Lee&rft.aufirst=Y&rft.date=1998-03-09&rft.volume=70&rft.issue=3&rft.spage=203&rft.isbn=&rft.btitle=&rft.title=Biophysical+chemistry&rft.issn=03014622&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-05 N1 - Date created - 1998-05-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Conditioned release of corticosterone by contextual stimuli associated with cocaine is mediated by corticotropin-releasing factor AN - 16291135; 4276865 AB - Elevated blood concentrations of corticosterone (CORT), an adrenal steroid associated with stress responses, is one of the endocrine correlates of cocaine treatment. Experiment 1 confirmed and extended previous findings that chronic cocaine treatment does not alter corticosteroid responses to cocaine. In Experiment 2, conditioned endocrine effects of cocaine were examined in three groups of rats after 7 consecutive days of treatment. Cocaine-induced conditioning was achieved using a simple contextual design. In group 1 (paired), rats were injected with cocaine (30 mg/kg), then immediately placed into a locomotor activity chamber for 30 min. One hour after the rats were returned to their home cages, they received an injection of saline. In group 2 (unpaired), rats were injected with saline, then immediately placed into a locomotor activity chamber for 30 min. One hour after the rats were returned to their home cages, they received an injection of cocaine (30 mg/kg). Rats in group 3 (control) received only saline injections, but otherwise were treated as animals in the other treatment groups. On the test day (Day 8), all rats were placed immediately into the locomotor apparatus for 30 min prior to collection of a blood sample. Blood CORT concentrations and locomotor activity in the paired group were significantly higher than in the unpaired and control groups. However, pretreatment of the rats in Experiment 3 with the corticotropin-releasing factor (CRF) antagonist, alpha -helical CRF 9-41 (1 mu g, i.c.v.), on the test day, prior to exposure to cocaine-associated contextual cues, attenuated the subsequent conditioned increase in blood CORT concentrations. These data represent the first demonstration of classical conditioning of a steroid hormone response to stimuli associated with a psychoactive drug in rats and suggest that the effect is mediated by endogenous CRF. Because the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in modulating the actions of cocaine, it is plausible that such conditioned increases in CORT release by cocaine-associated cues may further predispose an organism to the reinforcing effects of the drug or enhance the susceptibility to drug-taking behavior. Alternatively, such conditioned effects may be related to the anxiogenic properties of cocaine. Further understanding of the conditioned effects of hormones in the development and expression of addictive behaviors may provide new insights into treatment of drug addiction. JF - Brain Research AU - DeVries, A C AU - Taymans, SE AU - Sundstrom, J M AU - Pert, A AD - Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892, USA Y1 - 1998/03/09/ PY - 1998 DA - 1998 Mar 09 SP - 39 EP - 46 PB - Elsevier Science B.V. VL - 786 IS - 1-2 SN - 0006-8993, 0006-8993 KW - hypothalamic-pituitary-adrenal axis KW - rats KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - N3 11106:Neurobiology of drug abuse KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16291135?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+Research&rft.atitle=Conditioned+release+of+corticosterone+by+contextual+stimuli+associated+with+cocaine+is+mediated+by+corticotropin-releasing+factor&rft.au=DeVries%2C+A+C%3BTaymans%2C+SE%3BSundstrom%2C+J+M%3BPert%2C+A&rft.aulast=DeVries&rft.aufirst=A&rft.date=1998-03-09&rft.volume=786&rft.issue=1-2&rft.spage=39&rft.isbn=&rft.btitle=&rft.title=Brain+Research&rft.issn=00068993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Mutations in the contact region between the alpha and beta subunits of tryptophan synthase alter subunit interaction and intersubunit communication. AN - 79716121; 9485448 AB - Interaction between the alpha and beta subunits of tryptophan synthase leads to mutual stabilization of the active conformations and to coordinated control of the activities of the two subunits. To elucidate the roles of specific residues in the interaction site between the alpha and beta subunits, mutant alpha and beta subunits were constructed, and the effects of mutation on subunit interaction and intersubunit communication were determined. Mutation of either alpha subunit Asp56 (alphaD56A) or beta subunit Lys167 (betaK167T), residues that interact in some crystal structures of the tryptophan synthase alpha2beta2 complex, decreases the ability of the alpha subunit to activate the beta subunit and alters the reaction and substrate specificity of the beta subunit. Partial conformational repair is provided by alpha-glycerol 3-phosphate, a ligand that binds to the alpha subunit, or by Cs+ or NH4+, ligands that bind to the beta subunit. Mutation of beta subunit Arg175 (betaR175A), a residue that interacts with alpha subunit Pro57 in some structures, has much smaller effects on activity but results in a 15-fold increase in the apparent Kd for dissociation of the alpha and beta subunits. Replacement of the single tryptophan in the beta subunit by phenylalanine (W177F) has only small effects on activity but increases the apparent subunit dissociation constant approximately 10-fold. The most important conclusions of this investigation are that interaction between alphaAsp56 and betaLys167 is important for intersubunit communication and that mutual stabilization of the active conformations of the two subunits is impaired by mutation of either residue. JF - Biochemistry AU - Rowlett, R AU - Yang, L H AU - Ahmed, S A AU - McPhie, P AU - Jhee, K H AU - Miles, E W AD - Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/03/03/ PY - 1998 DA - 1998 Mar 03 SP - 2961 EP - 2968 VL - 37 IS - 9 SN - 0006-2960, 0006-2960 KW - Ligands KW - 0 KW - Tryptophan Synthase KW - EC 4.2.1.20 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Kinetics KW - Molecular Sequence Data KW - Circular Dichroism KW - Models, Chemical KW - Crystallography, X-Ray KW - Substrate Specificity KW - Amino Acid Substitution KW - Structure-Activity Relationship KW - Protein Conformation KW - Tryptophan Synthase -- chemistry KW - Tryptophan Synthase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79716121?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=Mutations+in+the+contact+region+between+the+alpha+and+beta+subunits+of+tryptophan+synthase+alter+subunit+interaction+and+intersubunit+communication.&rft.au=Rowlett%2C+R%3BYang%2C+L+H%3BAhmed%2C+S+A%3BMcPhie%2C+P%3BJhee%2C+K+H%3BMiles%2C+E+W&rft.aulast=Rowlett&rft.aufirst=R&rft.date=1998-03-03&rft.volume=37&rft.issue=9&rft.spage=2961&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-03 N1 - Date created - 1998-04-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Galpha12 requires acylation for its transforming activity. AN - 79713959; 9485474 AB - The alpha subunit of the heterotrimeric G protein G12, harboring a mutation in the GTP binding domain (Q229L), behaves as a potent oncogene in NIH 3T3 cells. This alpha subunit, like most other G protein alpha subunits, undergoes palmitoylation, the reversible posttranslational addition of palmitate to cysteine residues. We investigated the role of palmitoylation of alpha12 in membrane localization and transformation efficiency and whether another lipid modification, myristoylation, could substitute for palmitoylation. NIH 3T3 cells were stably transfected with plasmids that expressed the wild-type alpha12, the constitutively active Q229L (QL) mutant, and mutants in which C11 was changed to S (C11S) and S2 and R6 were changed to G and S, respectively (S2G). Incorporation of [3H]palmitate was found in the endogenous and expressed alpha12 but not in the C11S mutants. Incorporation of [3H]myristate was found only in the S2G mutants. The wild type, QL mutant, and all the acylation mutants were found in the particulate fraction. Cells expressing the nonpalmitoylated C11S,QL mutant did not undergo transformation. The S2G mutation in the nonpalmitoylated C11S,QL mutant restored the transformation efficiency to a greater level than that of the palmitoylated QL mutant as measured by foci formation, growth in soft agar, and growth rate. Palmitoylation was critical for the transformation efficiency of alpha12 but not specifically required because myristoylation could substitute for these functions. JF - Biochemistry AU - Jones, T L AU - Gutkind, J S AD - Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. tlzj@helix.nih.gov Y1 - 1998/03/03/ PY - 1998 DA - 1998 Mar 03 SP - 3196 EP - 3202 VL - 37 IS - 9 SN - 0006-2960, 0006-2960 KW - Proto-Oncogene Proteins KW - 0 KW - Palmitic Acid KW - 2V16EO95H1 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - GTP-Binding Protein alpha Subunit, Gi2 KW - EC 3.6.5.1 KW - GTP-Binding Protein alpha Subunits, Gi-Go KW - Gnai2 protein, mouse KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - 3T3 Cells KW - Transfection KW - Molecular Sequence Data KW - Mice KW - Amino Acid Sequence KW - Cell Membrane -- metabolism KW - Acylation KW - Palmitic Acid -- metabolism KW - GTP-Binding Proteins -- metabolism KW - Proto-Oncogene Proteins -- metabolism KW - Proto-Oncogene Proteins -- genetics KW - GTP-Binding Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79713959?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=Galpha12+requires+acylation+for+its+transforming+activity.&rft.au=Jones%2C+T+L%3BGutkind%2C+J+S&rft.aulast=Jones&rft.aufirst=T&rft.date=1998-03-03&rft.volume=37&rft.issue=9&rft.spage=3196&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-03 N1 - Date created - 1998-04-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronic lithium treatment robustly protects neurons in the central nervous system against excitotoxicity by inhibiting N-methyl-D-aspartate receptor-mediated calcium influx. AN - 79710340; 9482940 AB - Lithium is the most commonly used drug for the treatment of manic depressive illness. The precise mechanisms underlying its clinical efficacy remain unknown. We found that long-term exposure to lithium chloride dramatically protects cultured rat cerebellar, cerebral cortical, and hippocampal neurons against glutamate-induced excitotoxicity, which involves apoptosis mediated by N-methyl-D-aspartate (NMDA) receptors. This neuroprotection is long-lasting, occurs at therapeutically relevant concentrations of lithium with an EC50 of approximately 1.3 mM, and requires treatment for 6-7 days for complete protection to occur. In contrast, a 24-h treatment with lithium is ineffective. The protection in cerebellar neurons is specific for glutamate-induced excitotoxicity and can be attributed to inhibition of NMDA receptor-mediated calcium influx measured by 45Ca2+ uptake studies and fura-2 fluorescence microphotometry. The long-term effects of lithium are not caused by down-regulation of NMDA receptor subunit proteins and are unlikely related to its known ability to block inositol monophosphatase activity. Our results suggest that modulation of glutamate receptor hyperactivity represents at least part of the molecular mechanisms by which lithium alters brain function and exerts its clinical efficacy in the treatment for manic depressive illness. These actions of lithium also suggest that abnormality of glutamatergic neurotransmission as a pathogenic mechanism underlying bipolar illness warrants future investigation. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Nonaka, S AU - Hough, C J AU - Chuang, D M AD - Section on Molecular Neurobiology, Biological Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, MSC 1272, Bethesda, MD 20892-1272, USA. Y1 - 1998/03/03/ PY - 1998 DA - 1998 Mar 03 SP - 2642 EP - 2647 VL - 95 IS - 5 SN - 0027-8424, 0027-8424 KW - Chromatin KW - 0 KW - Neurotoxins KW - Receptors, N-Methyl-D-Aspartate KW - Glutamic Acid KW - 3KX376GY7L KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - 6-Cyano-7-nitroquinoxaline-2,3-dione KW - 6OTE87SCCW KW - Lithium Chloride KW - G4962QA067 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Cerebral Cortex -- cytology KW - Hippocampus -- physiology KW - 6-Cyano-7-nitroquinoxaline-2,3-dione -- pharmacology KW - Chromatin -- physiology KW - Cerebellum -- physiology KW - Cell Survival KW - Dizocilpine Maleate -- pharmacology KW - Rats KW - Rats, Sprague-Dawley KW - Cerebellum -- cytology KW - Cerebral Cortex -- physiology KW - Hippocampus -- cytology KW - Apoptosis -- drug effects KW - Chromatin -- drug effects KW - Embryo, Mammalian KW - DNA Fragmentation KW - Calcium -- metabolism KW - Receptors, N-Methyl-D-Aspartate -- physiology KW - Glutamic Acid -- toxicity KW - Brain -- cytology KW - Receptors, N-Methyl-D-Aspartate -- drug effects KW - Neurons -- drug effects KW - Neurons -- cytology KW - Neurons -- physiology KW - Lithium Chloride -- pharmacology KW - Neurotoxins -- toxicity KW - Brain -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79710340?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Chronic+lithium+treatment+robustly+protects+neurons+in+the+central+nervous+system+against+excitotoxicity+by+inhibiting+N-methyl-D-aspartate+receptor-mediated+calcium+influx.&rft.au=Nonaka%2C+S%3BHough%2C+C+J%3BChuang%2C+D+M&rft.aulast=Nonaka&rft.aufirst=S&rft.date=1998-03-03&rft.volume=95&rft.issue=5&rft.spage=2642&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-09 N1 - Date created - 1998-04-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Trends Pharmacol Sci. 1990 Jun;11(6):254-60 [2166370] Science. 1997 Mar 28;275(5308):1899 [9122692] Br J Psychiatry. 1990 Sep;157:327-30 [1978786] Neuroscience. 1990;39(1):25-32 [1982465] Trends Biochem Sci. 1991 May;16(5):177-81 [1652801] J Clin Psychopharmacol. 1992 Feb;12(1 Suppl):23S-35S [1541715] Mol Pharmacol. 1992 Aug;42(2):210-6 [1355259] Biochim Biophys Acta. 1992 Dec 16;1114(2-3):147-62 [1333807] J Neurobiol. 1992 Nov;23(9):1261-76 [1361523] J Neurochem. 1993 Feb;60(2):652-8 [8380439] Synapse. 1993 Apr;13(4):315-21 [8097597] Life Sci. 1994;55(22):1683-99 [7968248] Trends Neurosci. 1995 Feb;18(2):54-6 [7537406] Neurochem Int. 1995 Jan;26(1):53-8 [7787763] Alcohol Clin Exp Res. 1995 Jun;19(3):721-6 [7573799] Neuron. 1995 Oct;15(4):961-73 [7576644] Nature. 1995 Nov 9;378(6553):182-6 [7477320] J Pharmacol Exp Ther. 1996 Jan;276(1):143-9 [8558424] J Neuropathol Exp Neurol. 1996 Jan;55(1):1-13 [8558164] J Neurosci Res. 1995 Dec;42(5):674-83 [8600300] Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8455-9 [8710892] Brain Res. 1995 Dec 12;703(1-2):63-71 [8719616] Prog Neurobiol. 1996 Apr;48(6):613-34 [8809910] Funct Neurol. 1996 Jan-Feb;11(1):3-15 [8936453] Proc Natl Acad Sci U S A. 1982 Dec;79(24):7919-23 [6130529] J Immunol Methods. 1983 Dec 16;65(1-2):55-63 [6606682] J Biol Chem. 1985 Mar 25;260(6):3440-50 [3838314] Nature. 1990 Jun 28;345(6278):825-9 [2113617] J Neurochem. 1997 Feb;68(2):469-78 [9003031] Trends Pharmacol Sci. 1990 Sep;11(9):379-87 [2238094] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mice with type 2 and 3 Gaucher disease point mutations generated by a single insertion mutagenesis procedure. AN - 79709194; 9482915 AB - Gaucher disease is caused by mutations in the gene encoding the lysosomal enzyme glucocerebrosidase (GC). Three clinical types of Gaucher disease have been defined according to the presence (type 2 and 3) or absence (type 1) of central nervous system disease and severity of clinical manifestations. The clinical course of the disease correlates with the mutation carried by the GC gene. To produce mice with point mutations that correspond to the clinical types of Gaucher disease, we have devised a highly efficient one-step mutagenesis method-the single insertion mutagenesis procedure (SIMP)-to introduce human disease mutations into the mouse GC gene. By using SIMP, mice were generated carrying either the very severe RecNciI mutation that can cause type 2 disease or the less severe L444P mutation associated with type 3 disease. Mice homozygous for the RecNciI mutation had little GC enzyme activity and accumulated glucosylceramide in brain and liver. In contrast, the mice homozygous for the L444P mutation had higher levels of GC activity and no detectable accumulation of glucosylceramide in brain and liver. Surprisingly, both point mutation mice died within 48 hr of birth, apparently of a compromised epidermal permeability barrier caused by defective glucosylceramide metabolism in the epidermis. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Liu, Y AU - Suzuki, K AU - Reed, J D AU - Grinberg, A AU - Westphal, H AU - Hoffmann, A AU - Döring, T AU - Sandhoff, K AU - Proia, R L AD - Section on Biochemical Genetics, Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/03/03/ PY - 1998 DA - 1998 Mar 03 SP - 2503 EP - 2508 VL - 95 IS - 5 SN - 0027-8424, 0027-8424 KW - Recombinant Proteins KW - 0 KW - Sphingolipids KW - Glucosylceramidase KW - EC 3.2.1.45 KW - Index Medicus KW - Animals KW - Liver -- pathology KW - Recombinant Proteins -- biosynthesis KW - Humans KW - Skin -- pathology KW - Liver -- metabolism KW - Amino Acid Sequence KW - Brain -- metabolism KW - Mice KW - Mice, Inbred Strains KW - Base Sequence KW - Brain -- pathology KW - Restriction Mapping KW - Recombinant Proteins -- chemistry KW - Sphingolipids -- metabolism KW - Glucosylceramidase -- biosynthesis KW - Gaucher Disease -- genetics KW - Gaucher Disease -- classification KW - Point Mutation KW - Glucosylceramidase -- genetics KW - Glucosylceramidase -- chemistry KW - Gaucher Disease -- pathology KW - Mutagenesis, Insertional UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79709194?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Mice+with+type+2+and+3+Gaucher+disease+point+mutations+generated+by+a+single+insertion+mutagenesis+procedure.&rft.au=Liu%2C+Y%3BSuzuki%2C+K%3BReed%2C+J+D%3BGrinberg%2C+A%3BWestphal%2C+H%3BHoffmann%2C+A%3BD%C3%B6ring%2C+T%3BSandhoff%2C+K%3BProia%2C+R+L&rft.aulast=Liu&rft.aufirst=Y&rft.date=1998-03-03&rft.volume=95&rft.issue=5&rft.spage=2503&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-09 N1 - Date created - 1998-04-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1983 May;33(1):25-35 [6380756] Proc Natl Acad Sci U S A. 1995 May 9;92(10):4547-51 [7753840] Nature. 1988 Nov 24;336(6197):348-52 [3194019] Nat Genet. 1995 Oct;11(2):170-6 [7550345] Medicine (Baltimore). 1995 Nov;74(6):305-23 [7500895] Am J Med Genet. 1995 Nov 20;59(3):356-8 [8599361] J Med Genet. 1996 Feb;33(2):132-6 [8929950] J Lipid Res. 1997 Mar;38(3):576-84 [9101438] Hum Mol Genet. 1997 Jun;6(6):887-95 [9175735] Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8138-43 [9223328] Genome Res. 1997 Oct;7(10):1020-6 [9331372] Pediatr Res. 1997 Nov;42(5):610-4 [9357932] Am J Med Genet. 1997 Nov 28;73(1):41-7 [9375921] Science. 1989 Jun 16;244(4910):1288-92 [2660260] Mol Cell Biol. 1991 Mar;11(3):1402-8 [1996101] Cell. 1991 Mar 22;64(6):1155-61 [2004421] Nature. 1991 Mar 21;350(6315):243-6 [1672446] Mol Cell Biol. 1991 Sep;11(9):4389-97 [1875928] Mol Cell Biol. 1991 Sep;11(9):4509-17 [1875936] Science. 1991 Dec 6;254(5037):1494-7 [1962209] Nature. 1992 Jun 4;357(6377):407-10 [1594045] Semin Dermatol. 1992 Jun;11(2):106-13 [1498013] Pediatr Res. 1992 Oct;32(4):494-8 [1437405] Mol Cell Biol. 1993 Apr;13(4):2134-40 [8455602] Mol Cell Biol. 1993 Jul;13(7):4115-24 [8391633] Mol Cell Biol. 1994 Feb;14(2):1009-16 [8289781] J Biol Chem. 1994 Jan 21;269(3):2283-91 [8294487] Hum Mutat. 1994;3(1):1-11 [8118460] Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2819-23 [8146196] J Clin Invest. 1994 Apr;93(4):1756-64 [8163674] Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9975-9 [7937929] J Biol Chem. 1994 Nov 4;269(44):27155-8 [7961620] Biochem Med Metab Biol. 1994 Oct;53(1):16-21 [7857677] Biol Neonate. 1986;49(2):74-80 [3697429] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isotope exchange studies on the Escherichia coli selenophosphate synthetase mechanism AN - 16362480; 4252767 AB - Selenophosphate synthetase, the Escherichia coli selD gene product, is a 37-kDa protein that catalyzes the synthesis of selenophosphate from ATP and selenide. In the absence of selenide, ATP is converted quantitatively to AMP and two orthophosphates in a very slow partial reaction. A monophosphorylated enzyme derivative containing the gamma -phosphoryl group of ATP has been implicated as an intermediate from the results of positional isotope exchange studies. Conservation of the phosphate bond energy in the final selenophosphate product is indicated by its ability to phosphorylate alcohols and amines to form O- phosphoryl- and N-phosphoryl-derivatives. To further probe the mechanism of action of selenophosphate synthetase, isotope exchange studies with [8- super(14)C]ADP or [8- super(14)C]AMP and unlabeled ATP were carried out, and super(31)P NMR analysis of reaction mixtures enriched in H sub(2) super(18)O was performed. A slow enzyme-catalyzed exchange of ADP with ATP observed in the absence of selenide implies the existence of a phosphorylated enzyme and further supports an intermediary role of ADP in the reaction. Under these conditions ADP is slowly converted to AMP. Incorporation of super(18)O from H sub(2) super(18)O exclusively into orthophosphate in the overall selenide-dependent reaction indicates that the beta -phosphoryl group of the enzyme-bound ADP is attacked by water with liberation of orthophosphate and formation of AMP. Based on these results and the failure of the enzyme to catalyze an exchange of labeled AMP with ATP, the existence of a pyrophosphorylated enzyme intermediate that was postulated earlier can be excluded. JF - Proceedings of the National Academy of Sciences, USA AU - Walker, H AU - Ferretti, J AU - Stadtman, T AD - Laboratory of Biochemistry and Laboratory of Biophysical Chemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, tcstadtman@nih.gov Y1 - 1998/03/03/ PY - 1998 DA - 1998 Mar 03 SP - 2180 EP - 2185 VL - 95 IS - 5 SN - 0027-8424, 0027-8424 KW - ATP KW - N-phosphoryl derivatives KW - O-phosphoryl derivatives KW - alcohols KW - amines KW - isotopes KW - orthophosphate KW - se1D gene KW - selenide KW - selenophosphate KW - selenophosphate synthetase KW - Microbiology Abstracts B: Bacteriology KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16362480?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Isotope+exchange+studies+on+the+Escherichia+coli+selenophosphate+synthetase+mechanism&rft.au=Walker%2C+H%3BFerretti%2C+J%3BStadtman%2C+T&rft.aulast=Walker&rft.aufirst=H&rft.date=1998-03-03&rft.volume=95&rft.issue=5&rft.spage=2180&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Sequence-specific ligation of DNA using RecA protein AN - 16305573; 4252772 AB - A method is described that allows the sequence-specific ligation of DNA. The method is based on the ability of RecA protein from Escherichia coli to selectively pair oligonucleotides to their homologous sequences at the ends of fragments of duplex DNA. These three-stranded complexes were protected from the action of DNA polymerase. When treated with DNA polymerase, unprotected duplex fragments were converted to fragments with blunt ends, whereas protected fragments retained their cohesive ends. By using conditions that greatly favored ligation of cohesive ends, a second DNA fragment could be selectively ligated to a previously protected fragment of DNA. When this second DNA was a vector, selected fragments were preferentially cloned. The method had sufficient power to be used for the isolation of single-copy genes directly from yeast or human genomic DNA, and potentially could allow the isolation of much longer fragments with greater fidelity than obtainable by using PCR. JF - Proceedings of the National Academy of Sciences, USA AU - Ferrin, L AU - Camerini-Otero, R AD - Genetics and Biochemistry Branch, National Institute of Diabetes, Digestive, and Kidney Disorders, Building 10, Room 9D20, 10 Center Drive, MSC 1810, Bethesda, MD 20892-1810, lancef@bdg10.niddk.nih.gov Y1 - 1998/03/03/ PY - 1998 DA - 1998 Mar 03 SP - 2152 EP - 2157 VL - 95 IS - 5 SN - 0027-8424, 0027-8424 KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - J 02725:DNA KW - J 02727:Amino acids, peptides and proteins KW - N 14940:Nucleic acid-binding proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16305573?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Sequence-specific+ligation+of+DNA+using+RecA+protein&rft.au=Ferrin%2C+L%3BCamerini-Otero%2C+R&rft.aulast=Ferrin&rft.aufirst=L&rft.date=1998-03-03&rft.volume=95&rft.issue=5&rft.spage=2152&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Transition phase in the production of recombinant proteins in yeast under the ADH2 promoter: an important step for reproducible manufacturing of a malaria transmission blocking vaccine candidate AN - 856785294; 14295528 AB - TBV25H, a malaria transmission blocking vaccine candidate, has been cloned in Saccharomyces cerevisiae under the control of the glucose repressed ADH2 promoter. Available fermentation procedures for production of this protein have been unsatisfactory, mainly because of irreproducibility. This work presents an efficient and reproducible method for the production of this vaccine candidate by implementing a three-stage fermentation process. During the first (glucose fed-batch) phase, the promoter is repressed and the culture is allowed to grow exponentially. In the second stage, the glucose supply is provided at a slower constant rate. In the third (ethanol consumption) stage, accumulated ethanol is first allowed to be consumed and an external ethanol supplement is then added as required. The promoter is fully derepressed in this phase, and TBV25H is synthesized. The period of glucose limitation was concluded to be essential for reproducibility. It is presumed that during this period, the culture moves gradually from glucose to ethanol utilization, derepressing the promoter, activating recombinant protein biosynthesis and consequently resuming metabolism without the typical diauxic phase of batch cultures. JF - Journal of Industrial Microbiology & Biotechnology AU - Noronha, S B AU - Kaslow, D C AU - Shiloach, J AD - Biotechnology Unit, LCDB, NIDDK, NIH, Bethesda, MD 20892, USA, US Y1 - 1998/03// PY - 1998 DA - Mar 1998 SP - 192 EP - 199 PB - Springer-Verlag, Tiergartenstrasse 17 Heidelberg 69121 Germany VL - 20 IS - 3-4 SN - 1367-5435, 1367-5435 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; ASFA 1: Biological Sciences & Living Resources; ASFA 3: Aquatic Pollution & Environmental Quality; Microbiology Abstracts C: Algology, Mycology & Protozoology; Biotechnology and Bioengineering Abstracts KW - Yeasts KW - Human diseases KW - Protein biosynthesis KW - Fermentation KW - Glucose KW - Disease control KW - Malaria KW - Saccharomyces cerevisiae KW - Batch culture KW - Recombinants KW - Promoters KW - Protein turnover KW - Vaccines KW - Ethanol KW - A 01490:Miscellaneous KW - Q1 08484:Species interactions: parasites and diseases KW - W 30915:Pharmaceuticals & Vaccines KW - Q5 08524:Public health, medicines, dangerous organisms KW - K 03310:Genetics & Taxonomy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/856785294?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Industrial+Microbiology+%26+Biotechnology&rft.atitle=Transition+phase+in+the+production+of+recombinant+proteins+in+yeast+under+the+ADH2+promoter%3A+an+important+step+for+reproducible+manufacturing+of+a+malaria+transmission+blocking+vaccine+candidate&rft.au=Noronha%2C+S+B%3BKaslow%2C+D+C%3BShiloach%2C+J&rft.aulast=Noronha&rft.aufirst=S&rft.date=1998-03-01&rft.volume=20&rft.issue=3-4&rft.spage=192&rft.isbn=&rft.btitle=&rft.title=Journal+of+Industrial+Microbiology+%26+Biotechnology&rft.issn=13675435&rft_id=info:doi/10.1038%2Fsj.jim.2900507 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-03-01 N1 - Last updated - 2015-10-28 N1 - SubjectsTermNotLitGenreText - Yeasts; Recombinants; Promoters; Human diseases; Fermentation; Disease control; Glucose; Malaria; Vaccines; Protein biosynthesis; Protein turnover; Batch culture; Ethanol; Saccharomyces cerevisiae DO - http://dx.doi.org/10.1038/sj.jim.2900507 ER - TY - JOUR T1 - Square-wave action dystonia in Parkinson's disease. AN - 85420469; pmid-9539355 JF - Movement disorders : official journal of the Movement Disorder Society AU - van den Munckhof, P AU - Lenz, F A AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1406, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 354 EP - 356 VL - 13 IS - 2 SN - 0885-3185, 0885-3185 KW - Index Medicus KW - National Library of Medicine KW - Carbidopa -- administration & dosage KW - Antiparkinson Agents -- adverse effects KW - Dominance, Cerebral -- physiology KW - Antiparkinson Agents -- administration & dosage KW - Humans KW - Carbidopa -- adverse effects KW - Globus Pallidus -- physiopathology KW - Globus Pallidus -- surgery KW - Drug Combinations KW - Dominance, Cerebral -- drug effects KW - Levodopa -- administration & dosage KW - Neurologic Examination -- drug effects KW - Globus Pallidus -- drug effects KW - Middle Aged KW - Levodopa -- adverse effects KW - Male KW - Dystonia -- surgery KW - Dystonia -- chemically induced KW - Dystonia -- diagnosis KW - Parkinson Disease -- physiopathology KW - Dystonia -- physiopathology KW - Parkinson Disease -- surgery KW - Parkinson Disease -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85420469?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.atitle=Square-wave+action+dystonia+in+Parkinson%27s+disease.&rft.au=van+den+Munckhof%2C+P%3BLenz%2C+F+A%3BChase%2C+T+N&rft.aulast=van+den+Munckhof&rft.aufirst=P&rft.date=1998-03-01&rft.volume=13&rft.issue=2&rft.spage=354&rft.isbn=&rft.btitle=&rft.title=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.issn=08853185&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2008-01-14 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Quantitative and qualitative differences in the verbal learning performance of elderly depressives and healthy controls. AN - 85420208; pmid-9529821 AB - We compared the verbal learning and memory performance of 57 inpatients with unipolar major depression and 30 nondepressed control participants using the California Verbal Learning Test. The effect of age within this elderly sample was also examined, controlling for sex, educational attainment, and estimated level of intelligence. Except for verbal retention, the depressive had deficits in most aspects of performance, including cued and uncued recall and delayed recognition memory. As well, there were interactions between depression effects and age effects on some measures such that depressives' performance declined more rapidly with age than did the performance of controls. The results are discussed in the context of recent contradictory reports about the integrity of learning and memory functions in late-life depression. We conclude that there is consistent evidence, from this and other studies, that elderly depressed inpatients have significant deficits in a range of explicit verbal learning functions. JF - Journal of the International Neuropsychological Society : JINS AU - King, D A AU - Cox, C AU - Lyness, J M AU - Conwell, Y AU - Caine, E D AD - Department of Psychiatry, University of Rochester School of Medicine and Dentistry, UR-NIMH Center for the Study of Psychopathology of the Elderly, NY 14642-8408, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 115 EP - 126 VL - 4 IS - 2 SN - 1355-6177, 1355-6177 KW - Index Medicus KW - National Library of Medicine KW - Aged, 80 and over KW - Humans KW - Adult KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - Depressive Disorder -- psychology KW - Aged -- psychology KW - Verbal Learning -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85420208?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+International+Neuropsychological+Society+%3A+JINS&rft.atitle=Quantitative+and+qualitative+differences+in+the+verbal+learning+performance+of+elderly+depressives+and+healthy+controls.&rft.au=King%2C+D+A%3BCox%2C+C%3BLyness%2C+J+M%3BConwell%2C+Y%3BCaine%2C+E+D&rft.aulast=King&rft.aufirst=D&rft.date=1998-03-01&rft.volume=4&rft.issue=2&rft.spage=115&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+International+Neuropsychological+Society+%3A+JINS&rft.issn=13556177&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2008-01-14 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Behavioral phenotype of Smith-Magenis syndrome (del 17p11.2). AN - 85278215; pmid-9613859 AB - Smith-Magenis syndrome (SMS) is a distinct and clinically recognizable multiple congenital anomaly (MCA) and mental retardation syndrome caused by an interstitial deletion of chromosome 17 p11.2. The phenotype of SMS has been well described and includes: a characteristic pattern of physical features; a hoarse, deep voice; speech delay with or without associated hearing loss; signs of peripheral neuropathy; variable levels of mental retardation; and neurobehavioral problems. Although self-injury and sleep disturbance are major problems in SMS, studies are limited on the behavioral phenotype of SMS. This report reviews the current state of knowledge about SMS and presents new data based on syndrome-specific observations by the authors' longitudinal experience working with SMS, specifically related to the behavioral aspects of SMS. This information should have relevance for parents, clinicians, geneticists, and educators involved in the care of individuals with SMS. JF - American Journal of Medical Genetics AU - Smith, A C AU - Dykens, E AU - Greenberg, F AD - Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892-1267, USA. PY - 1998 SP - 179 EP - 185 VL - 81 IS - 2 SN - 0148-7299, 0148-7299 KW - Mental Retardation KW - Phenotype KW - Behavior Therapy KW - Human KW - Syndrome KW - Abnormalities, Multiple KW - Sleep Disorders KW - Child KW - Self-Injurious Behavior KW - Chromosomes, Human, Pair 17 KW - Behavioral Symptoms KW - Gene Deletion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85278215?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Medical+Genetics&rft.atitle=Behavioral+phenotype+of+Smith-Magenis+syndrome+%28del+17p11.2%29.&rft.au=Smith%2C+A+C%3BDykens%2C+E%3BGreenberg%2C+F&rft.aulast=Smith&rft.aufirst=A&rft.date=1998-03-01&rft.volume=81&rft.issue=2&rft.spage=179&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Medical+Genetics&rft.issn=01487299&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Coding strategies in monkey V1 and inferior temporal cortices. AN - 85242721; pmid-9497396 AB - We would like to know whether the statistics of neuronal responses vary across cortical areas. We examined stimulus-elicited spike count response distributions in V1 and inferior temporal (IT) cortices of awake monkeys. In both areas, the distribution of spike counts for each stimulus was well described by a Gaussian distribution, with the log of the variance in the spike count linearly related to the log of the mean spike count. Two significant differences in response characteristics were found: both the range of spike counts and the slope of the log(variance) versus log(mean) regression were larger in V1 than in IT. However, neurons in the two areas transmitted approximately the same amount of information about the stimuli and had about the same channel capacity (the maximum possible transmitted information given noise in the responses). These results suggest that neurons in V1 use more variable signals over a larger dynamic range than IT neurons, which use less variable signals over a smaller dynamic range. The two coding strategies are approximately as effective in transmitting information. JF - Journal of Neurophysiology AU - Gershon, E D AU - Wiener, M C AU - Latham, P E AU - Richmond, B J AD - Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1998 SP - 1135 EP - 1144 VL - 79 IS - 3 SN - 0022-3077, 0022-3077 KW - Probability KW - Regression Analysis KW - Neurons KW - Pattern Recognition, Visual KW - Temporal Lobe KW - Animal KW - Normal Distribution KW - Macaca mulatta KW - Electrophysiology KW - Poisson Distribution KW - Wakefulness KW - Brain Mapping UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85242721?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Neurophysiology&rft.atitle=Coding+strategies+in+monkey+V1+and+inferior+temporal+cortices.&rft.au=Gershon%2C+E+D%3BWiener%2C+M+C%3BLatham%2C+P+E%3BRichmond%2C+B+J&rft.aulast=Gershon&rft.aufirst=E&rft.date=1998-03-01&rft.volume=79&rft.issue=3&rft.spage=1135&rft.isbn=&rft.btitle=&rft.title=Journal+of+Neurophysiology&rft.issn=00223077&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Contribution of human prefrontal cortex to delay performance. AN - 85236176; pmid-9555105 AB - Neurological patients with focal lesions in the dorsolateral prefrontal cortex and age-matched control subjects were tested on an auditory version of the delayed-match-to-sample task employing environmental sounds. Subjects had to indicate whether a cue (s/S1) and a subsequent target sound (S2) were identical. On some trials, S1 and S2 were separated by a silent period of 5 sec. On other trials, the 5-sec delay between S1 and S2 was filled with irrelevant tone pips that served as distractors. Behaviorally, frontal patients were impaired by the presence of distractors. Electrophysiologically, patients generated enhanced primary auditory cortex-evoked responses to the tone pips, supporting a failure in inhibitory control of sensory processing after prefrontal damage. Intrahemispheric reductions of neural activity generated in the auditory association cortex and additional intrahemispheric reductions of attention-related frontal activity were also observed in the prefrontal patients. Together, these findings suggest that the dorsolateral prefrontal cortex is crucial for gating distracting information as well as maintaining distributed intrahemispheric neural activity during auditory working memory. JF - Journal of Cognitive Neuroscience AU - Chao, L L AU - Knight, R T AD - National Institute of Mental Health, Laboratory of Brain and Cognition, Bethesda, MD 20892, USA. PY - 1998 SP - 167 EP - 177 VL - 10 IS - 2 SN - 0898-929X, 0898-929X KW - Human KW - Electroencephalography KW - Cues KW - Evoked Potentials, Auditory KW - Aged KW - Acoustic Stimulation KW - Psychomotor Performance KW - Prefrontal Cortex KW - Cerebrovascular Disorders KW - Female KW - Male KW - Reaction Time UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85236176?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Cognitive+Neuroscience&rft.atitle=Contribution+of+human+prefrontal+cortex+to+delay+performance.&rft.au=Chao%2C+L+L%3BKnight%2C+R+T&rft.aulast=Chao&rft.aufirst=L&rft.date=1998-03-01&rft.volume=10&rft.issue=2&rft.spage=167&rft.isbn=&rft.btitle=&rft.title=Journal+of+Cognitive+Neuroscience&rft.issn=0898929X&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Biological evaluation of compounds for their physical dependence potential and abuse liability. XXI. Drug evaluation committee of the college on problems of drug dependence (1997). AN - 80034834; 9686403 JF - NIDA research monograph AU - Jacobson, A E AD - Laboratory of Medicinal Chemistry, National Institutes of Health, Bethesda, MD, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 346 EP - 362 VL - 178 SN - 1046-9516, 1046-9516 KW - Analgesics KW - 0 KW - Analgesics, Opioid KW - Index Medicus KW - Animals KW - Organizations KW - Analgesics, Opioid -- pharmacology KW - Analgesics -- pharmacology KW - Haplorhini KW - Structure-Activity Relationship KW - Substance-Related Disorders -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80034834?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NIDA+research+monograph&rft.atitle=Biological+evaluation+of+compounds+for+their+physical+dependence+potential+and+abuse+liability.+XXI.+Drug+evaluation+committee+of+the+college+on+problems+of+drug+dependence+%281997%29.&rft.au=Jacobson%2C+A+E&rft.aulast=Jacobson&rft.aufirst=A&rft.date=1998-03-01&rft.volume=178&rft.issue=&rft.spage=346&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-06 N1 - Date created - 1998-10-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - IBC Conference on Engineered Animal Models: Advances and Applications, Washington, DC, USA, 22-23 September 1997. AN - 79959378; 9643963 JF - Transgenic research AU - Wawrousek, E Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 141 EP - 145 VL - 7 IS - 2 KW - Antibodies, Monoclonal KW - 0 KW - Index Medicus KW - Antibodies, Monoclonal -- biosynthesis KW - Animals KW - Humans KW - Carcinogenicity Tests KW - Biological Specimen Banks KW - Mice KW - Mice, Transgenic KW - Genetic Engineering KW - Transgenes KW - Disease Models, Animal KW - Cloning, Organism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79959378?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=Transgenic+research&rft.atitle=IBC+Conference+on+Engineered+Animal+Models%3A+Advances+and+Applications%2C+Washington%2C+DC%2C+USA%2C+22-23+September+1997.&rft.au=Wawrousek%2C+E&rft.aulast=Wawrousek&rft.aufirst=E&rft.date=1998-03-01&rft.volume=7&rft.issue=2&rft.spage=141&rft.isbn=&rft.btitle=&rft.title=Transgenic+research&rft.issn=09628819&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-24 N1 - Date created - 1998-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mortality and cancer incidence of aircraft maintenance workers exposed to trichloroethylene and other organic solvents and chemicals: extended follow up. AN - 79934766; 9624267 AB - To extend the follow up of a cohort of 14,457 aircraft maintenance workers to the end of 1990 to evaluate cancer risks from potential exposure to trichloroethylene and other chemicals. The cohort comprised civilians employed for at least one year between 1952 and 1956, of whom 5727 had died by 31 December 1990. Analyses compared the mortality of the cohort with the general population of Utah and the mortality and cancer incidence of exposed workers with those unexposed to chemicals, while adjusting for age, sex and calendar time. In the combined follow up period (1952-90), mortality from all causes and all cancer was close to expected (standardised mortality ratios (SMRs) 97 and 96, respectively). Significant excesses occurred for ischaemic heart disease (SMR 108), asthma (SMR 160), and cancer of the bone (SMR 227), whereas significant deficits occurred for cerebrovascular disease (SMR 88), accidents (SMR 70), and cancer of the central nervous system (SMR 64). Workers exposed to trichloroethylene showed non-significant excesses for non-Hodgkin's lymphoma (relative risk (RR) 2.0), and cancers of the oesophagus (RR 5.6), colon (RR 1.4), primary liver (RR 1.7), breast (RR 1.8), cervix (RR 1.8), kidney (RR 1.6), and bone (RR 2.1). None of these cancers showed an exposure-response gradient and RRs among workers exposed to other chemicals but not trichloroethylene often had RRs as large as workers exposed to trichloroethylene. Workers exposed to solvents other than trichloroethylene had slightly increased mortality from asthma, non-Hodgkin's lymphoma, multiple myeloma, and breast cancer. These findings do not strongly support a causal link with trichloroethylene because the associations were not significant, not clearly dose-related, and inconsistent between men and women. Because findings from experimental investigations and other epidemiological studies on solvents other than trichloroethylene provide some biological plausibility, the suggested links between these chemicals and non-Hodgkin's lymphoma, multiple myeloma, and breast cancer found here deserve further attention. Although this extended follow up cannot rule out a connection between exposures to solvents and some diseases, it seems clear that these workers have not experienced a major increase in cancer mortality or cancer incidence. JF - Occupational and environmental medicine AU - Blair, A AU - Hartge, P AU - Stewart, P A AU - McAdams, M AU - Lubin, J AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7364, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 161 EP - 171 VL - 55 IS - 3 SN - 1351-0711, 1351-0711 KW - Solvents KW - 0 KW - Trichloroethylene KW - 290YE8AR51 KW - Index Medicus KW - Asthma -- mortality KW - Humans KW - Utah -- epidemiology KW - Cohort Studies KW - Retrospective Studies KW - Incidence KW - Myocardial Ischemia -- mortality KW - Time Factors KW - Male KW - Female KW - Aviation KW - Neoplasms -- mortality KW - Trichloroethylene -- adverse effects KW - Solvents -- adverse effects KW - Occupational Exposure -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79934766?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+environmental+medicine&rft.atitle=Mortality+and+cancer+incidence+of+aircraft+maintenance+workers+exposed+to+trichloroethylene+and+other+organic+solvents+and+chemicals%3A+extended+follow+up.&rft.au=Blair%2C+A%3BHartge%2C+P%3BStewart%2C+P+A%3BMcAdams%2C+M%3BLubin%2C+J&rft.aulast=Blair&rft.aufirst=A&rft.date=1998-03-01&rft.volume=55&rft.issue=3&rft.spage=161&rft.isbn=&rft.btitle=&rft.title=Occupational+and+environmental+medicine&rft.issn=13510711&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-22 N1 - Date created - 1998-06-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Occup Med. 1990 Mar;32(3):234-40 [2319356] J Occup Med. 1985 Dec;27(12):881-4 [4087053] Am Rev Respir Dis. 1991 Apr;143(4 Pt 1):751-4 [2008987] Am J Ind Med. 1991;19(5):569-86 [2053576] Br J Ind Med. 1991 Aug;48(8):515-30 [1878308] Br J Ind Med. 1991 Aug;48(8):531-7 [1878309] Scand J Work Environ Health. 1992 Apr;18(2):90-6 [1604278] Scand J Work Environ Health. 1992 Jun;18(3):145-54 [1615288] Cancer Causes Control. 1992 Sep;3(5):427-32 [1525323] Int Arch Occup Environ Health. 1992;64(3):195-200 [1399033] Cancer Causes Control. 1992 Nov;3(6):555-68 [1420859] Am J Ind Med. 1993 Feb;23(2):301-12 [8427258] Am J Ind Med. 1993 Apr;23(4):629-39 [8338527] Epidemiol Rev. 1993;15(1):133-44 [8405196] Epidemiol Rev. 1993;15(1):36-47 [8405211] Chest. 1993 Nov;104(5):1364-70 [8222789] Am J Ind Med. 1993 Oct;24(4):355-64 [8250056] J Occup Med. 1994 May;36(5):556-62 [8027881] Scand J Work Environ Health. 1994 Aug;20(4):251-61 [7801070] J Occup Med. 1994 Aug;36(8):855-9 [7807265] Int Arch Occup Environ Health. 1994;66(4):261-7 [7843837] J Occup Environ Med. 1995 Mar;37(3):336-48 [7796202] J Occup Environ Med. 1995 Mar;37(3):349-56 [7796203] Cancer Causes Control. 1995 May;6(3):257-66 [7612805] Arch Toxicol. 1995;69(5):291-9 [7654132] J Occup Environ Med. 1995 Jul;37(7):797-806 [7552463] Occup Environ Med. 1996 Jan;53(1):1-5 [8563851] J Occup Med. 1987 Jun;29(6):535-41 [3612328] Occup Environ Med. 1996 Mar;53(3):145-56 [8704854] Am J Ind Med. 1996 Mar;29(3):227-35 [8833775] Br J Ind Med. 1975 Feb;32(1):1-10 [1125123] J Occup Med. 1976 Mar;18(3):165-8 [1255276] Scand J Work Environ Health. 1986 Dec;12(6):545-51 [3823803] Br J Ind Med. 1987 Apr;44(4):220-7 [3567096] J Occup Med. 1987 Apr;29(4):340-4 [3585565] Am J Ind Med. 1988;13(1):105-18 [3344750] Am J Ind Med. 1988;13(1):59-69 [3344756] Am J Ind Med. 1988;13(6):683-93 [3389363] Cancer. 1989 May 1;63(9):1838-42 [2702592] Br J Ind Med. 1989 Aug;46(8):516-20 [2775671] Br J Cancer. 1989 Sep;60(3):385-8 [2789947] Br J Prev Soc Med. 1976 Dec;30(4):225-30 [1009272] J Occup Med. 1978 Mar;20(3):194-6 [627938] Am J Public Health. 1981 Mar;71(3):242-50 [7468855] Br J Cancer. 1981 Feb;43(2):169-76 [7470379] Acta Med Scand. 1981;210(5):415-8 [7336998] Am J Ind Med. 1984;5(3):239-49 [6702828] Br J Ind Med. 1990 Mar;47(3):162-8 [2328223] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Diversity of DNA topoisomerases I and inhibitors. AN - 79920915; 9615865 AB - The present review first describes the different type I topoisomerases found in eukaryotic cells: nuclear topoisomerase I (top1), topoisomerase 3 (top3), mitochondrial topoisomerase I and viral topoisomerases I. The second part of the review provides extensive information on the topoisomerase I inhibitors identified to date. These drugs can be grouped in two categories: top1 poisons and top1 suppressors. Both inhibit enzyme catalytic activity but top1 poisons trap the top1 catalytic intermediates ('cleavage complexes') while top1 suppressors prevent or reverse top1 cleavage complexes. The molecular interactions of camptothecin with the top1 cleavage complexes are discussed as well as the mechanisms of selective killing of cancer cells. JF - Biochimie AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 255 EP - 270 VL - 80 IS - 3 SN - 0300-9084, 0300-9084 KW - Antineoplastic Agents KW - 0 KW - Enzyme Inhibitors KW - Topoisomerase I Inhibitors KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Index Medicus KW - Animals KW - Humans KW - Enzyme Inhibitors -- pharmacology KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79920915?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochimie&rft.atitle=Diversity+of+DNA+topoisomerases+I+and+inhibitors.&rft.au=Pommier%2C+Y&rft.aulast=Pommier&rft.aufirst=Y&rft.date=1998-03-01&rft.volume=80&rft.issue=3&rft.spage=255&rft.isbn=&rft.btitle=&rft.title=Biochimie&rft.issn=03009084&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-07 N1 - Date created - 1998-08-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Delayed auditory feedback during smoking cessation. AN - 79900909; 9604857 AB - Delays between speech production and hearing, delayed auditory feedback (DAF), reduce speech and reading rates. Smoking cessation in heavy smokers causes subjective reports of difficulty in concentration, decrements in cognitive performance, and EEG changes. The purpose of the present study was to determine if tobacco cessation disrupts linguistic processing as modeled by the DAF paradigm. Smokers (n = 14) were tested on 3 d of ad libitum smoking and 3 d no smoking. At each session, they read a word list (24 words) and a story (about 57 words) with and without delay (220 msec). The delay significantly decreased reading speed of the story from 3.4 to 2.9 words per second (wps) and of list from 2.1 to 1.7 wps. However, tobacco cessation had no significant effect on reading speed and no interaction with DAF. Although tobacco withdrawal slows performance on cognitive tasks, linguistic processing modeled by DAF is preserved. DAF may prove useful for the study of other drug classes and drug withdrawal states. JF - Methods and findings in experimental and clinical pharmacology AU - Friedman, A AU - Stanton, J P AU - Gnjidic, M AU - Fant, R V AU - Pickworth, W B AD - National Institute on Drug Abuse, Addiction Research Center, Baltimore, Maryland, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 147 EP - 153 VL - 20 IS - 2 SN - 0379-0355, 0379-0355 KW - Nicotine KW - 6M3C89ZY6R KW - Index Medicus KW - Humans KW - Nicotine -- adverse effects KW - Adult KW - Substance Withdrawal Syndrome -- physiopathology KW - Auditory Perception -- physiology KW - Smoking Cessation KW - Feedback UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79900909?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+and+findings+in+experimental+and+clinical+pharmacology&rft.atitle=Delayed+auditory+feedback+during+smoking+cessation.&rft.au=Friedman%2C+A%3BStanton%2C+J+P%3BGnjidic%2C+M%3BFant%2C+R+V%3BPickworth%2C+W+B&rft.aulast=Friedman&rft.aufirst=A&rft.date=1998-03-01&rft.volume=20&rft.issue=2&rft.spage=147&rft.isbn=&rft.btitle=&rft.title=Methods+and+findings+in+experimental+and+clinical+pharmacology&rft.issn=03790355&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-30 N1 - Date created - 1998-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The cloning and characterization of a novel cytochrome P450 family, CYP26, with specificity toward retinoic acid. AN - 79821590; 9564181 AB - A new family of cytochrome P450 enzymes, CYP26, has been cloned and characterized in zebra fish, human, and mouse tissues. CYP26 displays specificity toward retinoic acid and it may function as an important regulator or differentiation and a possible modulator of disease states by controlling retinoid concentration and homeostasis. JF - Nutrition reviews AU - Haque, M AU - Anreola, F AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 84 EP - 85 VL - 56 IS - 3 SN - 0029-6643, 0029-6643 KW - Tretinoin KW - 5688UTC01R KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - Retinoic Acid 4-Hydroxylase KW - EC 1.14.14.1 KW - Index Medicus KW - Animals KW - Humans KW - Cloning, Molecular KW - Mixed Function Oxygenases -- metabolism KW - Cytochrome P-450 Enzyme System -- genetics KW - Tretinoin -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Tretinoin -- therapeutic use KW - Mixed Function Oxygenases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79821590?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nutrition+reviews&rft.atitle=The+cloning+and+characterization+of+a+novel+cytochrome+P450+family%2C+CYP26%2C+with+specificity+toward+retinoic+acid.&rft.au=Haque%2C+M%3BAnreola%2C+F&rft.aulast=Haque&rft.aufirst=M&rft.date=1998-03-01&rft.volume=56&rft.issue=3&rft.spage=84&rft.isbn=&rft.btitle=&rft.title=Nutrition+reviews&rft.issn=00296643&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-28 N1 - Date created - 1998-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Current management of infectious complications in the injecting drug user. AN - 79818418; 9561947 AB - The diagnosis and management of infectious complications associated with injection drug use (IDU) are among some of the more challenging aspects of working with substance abusing populations. As the population of injection drug users age, we expect the number and severity of these complications to increase. Commonly seen infections, such as bacterial endocarditis and bacterial infections of bones, joints, and soft tissue, are now frequently complicated by concurrent immunodeficiency. Parenterally and sexually transmitted viral hepatitis is responsible for significant IDU morbidity and mortality. The human leukemia/lymphoma virus types I and II are increasing in prevalence in the IDU with uncertain long-term clinical effects. Immune dysfunction has been described in the IDU for decades, but the impact of host immune compromise on the transmission and the course of HIV-1 has yet to be fully appreciated. The integration of the treatment of substance abuse and its concurrent psychiatric disorders with the management of infectious complications, including immunodeficiency, promises to improve patient compliance with possible savings of overall medical costs. JF - Journal of substance abuse treatment AU - Contoreggi, C AU - Rexroad, V E AU - Lange, W R AD - Division of Intramural Research, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. ccontore@irp.nida.nih.gov PY - 1998 SP - 95 EP - 106 VL - 15 IS - 2 SN - 0740-5472, 0740-5472 KW - Index Medicus KW - AIDS/HIV KW - Humans KW - Infection -- etiology KW - Infection -- therapy KW - Substance Abuse, Intravenous -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79818418?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+substance+abuse+treatment&rft.atitle=Current+management+of+infectious+complications+in+the+injecting+drug+user.&rft.au=Contoreggi%2C+C%3BRexroad%2C+V+E%3BLange%2C+W+R&rft.aulast=Contoreggi&rft.aufirst=C&rft.date=1998-03-01&rft.volume=15&rft.issue=2&rft.spage=95&rft.isbn=&rft.btitle=&rft.title=Journal+of+substance+abuse+treatment&rft.issn=07405472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-16 N1 - Date created - 1998-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Estrogen-dependent gene regulation by an oxidative metabolite of diethylstilbestrol, diethylstilbestrol-4',4"-quinone. AN - 79816846; 9558716 AB - Diethylstilbestrol (DES) is a well-characterized carcinogen in humans and animals although its mechanisms of carcinogenicity are not yet known. While the estrogenic activity of DES is important, there is evidence that oxidative metabolism also plays an important role for its toxicity. DES is oxidatively metabolized in vivo and in vitro to a number of compounds including diethylstilbestrol-4',4"-quinone (DQ), an unstable and reactive intermediate, and Z,Z-dienestrol (ZZ-DIEN). Estrogen receptor (ER) binding assays with mouse uterine cytosol indicate that DES, DQ and ZZ-DIEN have relative binding affinities of 286, 3.6 and 0.3, respectively, relative to estradiol as 100. In addition, DQ binds irreversibly and specifically to ER suggesting that DQ may be biologically active despite its rapid metabolism and lower binding affinity compared to DES. To test this, COS-1 cells were transfected with an estrogen responsive reporter construct containing of VitA2 estrogen response element (ERE) with or without an ER expression vector. In the presence of ER, treatments with DES, DQ and ZZ-DIEN resulted in 11, 10, and 2-fold induction of chloramphenicol acetyltransferase (CAT) activity, respectively. This induction was mediated by estrogen receptor since it was suppressed by pretreatment with a 10-fold excess of the pure antiestrogen ICI 182,780. These data indicate that DQ is a biologically active intermediate that is capable of transactivation of estrogen responsive genes through the ER. Furthermore, the data suggest that the ability of DQ to irreversibly bind ER may result in persistent stimulation of ER. This persistent stimulation may be related to the carcinogenicity of DES. JF - Steroids AU - Chae, K AU - Lindzey, J AU - McLachlan, J A AU - Korach, K S AD - Receptor Biology Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 149 EP - 157 VL - 63 IS - 3 SN - 0039-128X, 0039-128X KW - Receptors, Estrogen KW - 0 KW - diethylstilbestrol quinone KW - 5664-37-9 KW - Diethylstilbestrol KW - 731DCA35BT KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Index Medicus KW - Oxidation-Reduction KW - Chloramphenicol O-Acetyltransferase -- genetics KW - Animals KW - COS Cells KW - Transfection KW - Mice KW - Female KW - Chromatography, High Pressure Liquid KW - Diethylstilbestrol -- metabolism KW - Receptors, Estrogen -- genetics KW - Diethylstilbestrol -- pharmacology KW - Gene Expression Regulation -- drug effects KW - Diethylstilbestrol -- analogs & derivatives KW - Receptors, Estrogen -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79816846?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Steroids&rft.atitle=Estrogen-dependent+gene+regulation+by+an+oxidative+metabolite+of+diethylstilbestrol%2C+diethylstilbestrol-4%27%2C4%22-quinone.&rft.au=Chae%2C+K%3BLindzey%2C+J%3BMcLachlan%2C+J+A%3BKorach%2C+K+S&rft.aulast=Chae&rft.aufirst=K&rft.date=1998-03-01&rft.volume=63&rft.issue=3&rft.spage=149&rft.isbn=&rft.btitle=&rft.title=Steroids&rft.issn=0039128X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-27 N1 - Date created - 1998-05-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Perchlorate and the thyroid gland. AN - 79807953; 9549759 AB - Perchlorate competitively blocks iodide from entering the thyroid by an effect on the Na+/I- symporter thus preventing the further synthesis of thyroid hormone but has no effect on the iodination process itself. It is concentrated by thyroid tissue in a manner similar to iodide but is not significantly metabolized in the gland or peripherally. What is not settled is whether there are additional perchlorate effects on iodide transport. Perchlorate has a fast turnover in the body and requires frequent daily doses for therapy of thyrotoxicosis. Perchlorate appears to be substantially more effective against large iodide loads than the thionamides, and, with long-term iodide contamination, combined therapy of perchlorate (with < or = 1 g/day) and thionamides is recommended for the more severe cases of thyrotoxicosis that may result from excess iodide or iodide-generating organic compounds, as for example with amiodarone. After approximately 30 days, the perchlorate dosage can be tapered or stopped, continuing with thionamides alone. This markedly increases its safe use. Despite serious side effects during its early use, lower dosages and shorter treatment periods appear to have prevented such reactions in its recent reintroduction, mostly for amiodarone-induced thyroid dysfunction. Perchlorate can also protect against inhibition of thyroid function and the resulting hypothyroidism caused by excess iodide, presumably by reducing the formation of an iodinated inhibitor. The reduction of the iodide pool by perchlorate thus has dual effects--reduction of excess hormone synthesis and hyperthyroidism, on the one hand, and reduction of thyroid inhibitor synthesis and hypothyroidism on the other. Perchlorate remains very useful also as a single dose application in tests measuring the discharge of radioiodide accumulated in the thyroid as a result of many different disruptions in the further metabolism of iodide in the thyroid gland. JF - Pharmacological reviews AU - Wolff, J AD - Laboratory of Biochemical Pharmacology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 89 EP - 105 VL - 50 IS - 1 SN - 0031-6997, 0031-6997 KW - Enzyme Inhibitors KW - 0 KW - Iodides KW - Perchlorates KW - Sodium Compounds KW - sodium perchlorate KW - 97F4MTY3VA KW - Iodide Peroxidase KW - EC 1.11.1.8 KW - Amiodarone KW - N3RQ532IUT KW - Index Medicus KW - Iodide Peroxidase -- metabolism KW - Animals KW - Enzyme Inhibitors -- therapeutic use KW - Iodides -- pharmacology KW - Humans KW - Hypothyroidism -- drug therapy KW - Amiodarone -- therapeutic use KW - Enzyme Inhibitors -- chemistry KW - Thyrotoxicosis -- drug therapy KW - Amiodarone -- adverse effects KW - Amiodarone -- chemistry KW - Iodide Peroxidase -- drug effects KW - Amiodarone -- pharmacology KW - Iodides -- metabolism KW - Kinetics KW - Thyrotoxicosis -- chemically induced KW - Sodium Compounds -- therapeutic use KW - Sodium Compounds -- pharmacology KW - Thyroid Gland -- physiology KW - Sodium Compounds -- chemistry KW - Thyroid Gland -- drug effects KW - Sodium Compounds -- metabolism KW - Perchlorates -- adverse effects KW - Perchlorates -- therapeutic use KW - Perchlorates -- chemistry KW - Sodium Compounds -- adverse effects KW - Perchlorates -- pharmacology KW - Perchlorates -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79807953?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacological+reviews&rft.atitle=Perchlorate+and+the+thyroid+gland.&rft.au=Wolff%2C+J&rft.aulast=Wolff&rft.aufirst=J&rft.date=1998-03-01&rft.volume=50&rft.issue=1&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=Pharmacological+reviews&rft.issn=00316997&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-11 N1 - Date created - 1998-05-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicity and carcinogenicity studies of oxazepam in the Fischer 344 rat. AN - 79791841; 9538042 AB - Oxazepam and related benzodiazepines are used in the treatment of anxiety. Carcinogenicity studies of oxazepam were performed with the F344 rat because of marked differences in tumor responses observed in NTP studies with B6C3F1 and Swiss-Webster mice compared to the results of Sprague-Dawley rat studies submitted to the FDA by a manufacturer to support registration of the drug. Groups of 50 male and 50 female F344/N rats were fed diets containing 0, 625, 2500, or 5000 ppm oxazepam for up to 105 weeks. A stop-exposure group of 50 males and 50 females received 10,000 ppm oxazepam in diet for 26 weeks, after which animals received control diet. All 5000- and 10, 000-ppm stop-exposure males died before the end of the study. Survival of 2500-ppm males and females was lower than that of controls. Body weight gains of 2500- and 5000-ppm males and females were less than those of controls. Male rats exposed to 2500 ppm had an increased incidence of renal tubule adenoma and hyperplasia. In addition, the incidences of renal tubule adenoma and hyperplasia were increased in the 10,000-ppm stop-exposure group. The incidences of nephropathy in exposed females were greater than those in controls, and the severity of nephropathy increased in exposed males. Epithelial hyperplasia and chronic inflammation of the nonglandular stomach were increased in males given 2500 and 5000 ppm and the incidence of ulcers of the nonglandular stomach in 2500-ppm males was also greater than that in controls. In males exposed to 5000 ppm, mineralization of the glandular stomach and erosion of the duodenum were observed. In females exposed to 2500 ppm, the incidences of epithelial hyperplasia, chronic inflammation, and ulcers of the nonglandular stomach and the incidence of erosion in the glandular stomach were increased. The incidences of centrilobular hepatocyte hypertrophy in males and females given 2500 and 5000 ppm were greater than those in controls. In summary, there was equivocal evidence of carcinogenicity in males based on increased renal tubule adenomas in groups which also had significantly enhanced nephropathy. There was no evidence of carcinogenicity of oxazepam in females given a diet containing 625, 2500, or 5000 ppm for 2 years or 10,000 ppm for 6 months. Copyright 1998 Academic Press. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Bucher, J R AU - Haseman, J K AU - Herbert, R A AU - Hejtmancik, M AU - Ryan, M J AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 1 EP - 12 VL - 42 IS - 1 SN - 1096-6080, 1096-6080 KW - Anti-Anxiety Agents KW - 0 KW - Oxazepam KW - 6GOW6DWN2A KW - Index Medicus KW - Animals KW - Liver -- pathology KW - Kidney -- pathology KW - Kidney -- drug effects KW - Rats KW - Rats, Inbred F344 KW - Digestive System -- drug effects KW - Liver -- drug effects KW - Body Weight -- drug effects KW - Toxicity Tests KW - Carcinogenicity Tests KW - Digestive System -- pathology KW - Female KW - Male KW - Survival Analysis KW - Oxazepam -- toxicity KW - Kidney Neoplasms -- chemically induced KW - Adenoma -- chemically induced KW - Anti-Anxiety Agents -- toxicity KW - Oxazepam -- blood KW - Anti-Anxiety Agents -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79791841?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Toxicity+and+carcinogenicity+studies+of+oxazepam+in+the+Fischer+344+rat.&rft.au=Bucher%2C+J+R%3BHaseman%2C+J+K%3BHerbert%2C+R+A%3BHejtmancik%2C+M%3BRyan%2C+M+J&rft.aulast=Bucher&rft.aufirst=J&rft.date=1998-03-01&rft.volume=42&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-22 N1 - Date created - 1998-05-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Power and sample size for stratified prospective studies using the score method for testing relative risk. AN - 79790120; 9544526 AB - We derive the asymptotic power function of the score test for detecting a common relative risk greater than unity from multiple 2 x 2 tables and formulate methods of sample size determination for use when designing stratified prospective studies. The stratified score test is more efficient than the unstratified test when the latter is unbiased. JF - Biometrics AU - Nam, J M AD - Biostatistics Branch, National Cancer Institute, Rockville, Maryland 20892-7368, USA. jn26r@nih.gov Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 331 EP - 336 VL - 54 IS - 1 SN - 0006-341X, 0006-341X KW - Fungicides, Industrial KW - 0 KW - Thiocarbamates KW - di-allate KW - 77003KI5VJ KW - Index Medicus KW - Animals KW - Biometry KW - Humans KW - Cohort Studies KW - Mice KW - Thiocarbamates -- toxicity KW - Sample Size KW - Lung Neoplasms -- chemically induced KW - Fungicides, Industrial -- toxicity KW - Male KW - Female KW - Carcinogenicity Tests -- statistics & numerical data KW - Risk KW - Prospective Studies UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79790120?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biometrics&rft.atitle=Power+and+sample+size+for+stratified+prospective+studies+using+the+score+method+for+testing+relative+risk.&rft.au=Nam%2C+J+M&rft.aulast=Nam&rft.aufirst=J&rft.date=1998-03-01&rft.volume=54&rft.issue=1&rft.spage=331&rft.isbn=&rft.btitle=&rft.title=Biometrics&rft.issn=0006341X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-01 N1 - Date created - 1998-05-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Low genetic variation among killer whales (Orcinus orca) in the eastern north Pacific and genetic differentiation between foraging specialists. AN - 79789340; 9542159 AB - Killer whales from the coastal waters off California through Alaska were compared for genetic variation at three nuclear DNA markers and sequenced for a total of 520 bp from the mitochondrial control region. Two putative sympatric populations that range throughout this region were compared. They can be distinguished by social and foraging behavior and are known as "residents" and "transients". We found low levels of variation within populations compared to other cetacean species. Comparisons between fish (resident) versus marine mammal (transient) foraging specialists indicated highly significant genetic differentiation at both nuclear and mitochondrial loci. This differentiation is at a level consistent with intraspecific variation. A comparison between two parapatric resident populations showed a small but fixed mtDNA haplotype difference. Together these data suggest low levels of genetic dispersal between foraging specialists and a pattern of genetic differentiation consistent with matrifocal population structure and small effective population size. JF - The Journal of heredity AU - Hoelzel, A R AU - Dahlheim, M AU - Stern, S J AD - National Cancer Institute, Laboratory of Viral Carcinogenesis, Frederick, Maryland, USA. PY - 1998 SP - 121 EP - 128 VL - 89 IS - 2 SN - 0022-1503, 0022-1503 KW - DNA Primers KW - 0 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Phylogeny KW - Animals KW - Tooth -- chemistry KW - Feeding Behavior KW - Polymorphism, Single-Stranded Conformational KW - Skin -- chemistry KW - DNA -- isolation & purification KW - Microsatellite Repeats KW - Alleles KW - Base Sequence KW - DNA -- blood KW - Pacific Ocean KW - Molecular Sequence Data KW - DNA -- chemistry KW - Gene Library KW - Genetic Variation KW - Polymorphism, Genetic KW - Whales -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79789340?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+heredity&rft.atitle=Low+genetic+variation+among+killer+whales+%28Orcinus+orca%29+in+the+eastern+north+Pacific+and+genetic+differentiation+between+foraging+specialists.&rft.au=Hoelzel%2C+A+R%3BDahlheim%2C+M%3BStern%2C+S+J&rft.aulast=Hoelzel&rft.aufirst=A&rft.date=1998-03-01&rft.volume=89&rft.issue=2&rft.spage=121&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+heredity&rft.issn=00221503&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-12 N1 - Date created - 1998-05-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunochemical detection and identification of protein adducts of diclofenac in the small intestine of rats: possible role in allergic reactions. AN - 79786431; 9544613 AB - Idiosyncratic adverse drug reactions are unpredictable, target multiple organ systems, and often become life-threatening events. Although the causes of idiosyncratic adverse drug reactions are not known in most cases, evidence suggests that they may be mediated through immunological mechanisms. It is generally thought that for a drug to lead to an immune response, it must first become covalently bound to a carrier protein. Since most drugs are unreactive, it is usually a reactive metabolite that is expected to form covalent adducts. However, it is not clear why more people do not develop immune reactions against drug-protein adducts. One possible explanation is that orally administered drugs may lead to oral tolerance in most individuals through mechanisms similar to that found with orally administered antigens. However, very little is known regarding the interaction of drugs with gut-associated lymphoid tissue of the small intestine, where oral tolerance can develop. As an initial step to test this hypothesis, we have investigated whether diclofenac, a commonly used nonsteroidal antiinflammatory drug, can lead to protein adducts in rat small intestine. Diclofenac was administered to rats by gastric gavage. Immunoblot analysis of small intestine homogenates and isolated enterocyte subcellular fractions with drug-specific antiserum revealed 142-, 130-, 110-, and 55-kDa protein adducts of diclofenac. The 142- and 130-kDa adducts of diclofenac were identified as aminopeptidase N (CD13) and sucrase-isomaltase, respectively, by amino acid sequence analyses and by their reactions with protein-specific antibodies. The adducts were localized by immunohistochemistry and found primarily in the mid-villus and villus-tip enterocytes and also in the dome overlying Peyer's patches. Similar adducts were detected immunochemically in villus-tip enterocytes of animals treated with halothane or acetaminophen. These results show that intestinal protein adducts of drugs can be formed in gut-associated lymphoid tissue where they may lead to the down-regulation of drug-induced allergic reactions in many individuals. JF - Chemical research in toxicology AU - Ware, J A AU - Graf, M L AU - Martin, B M AU - Lustberg, L R AU - Pohl, L R AD - Molecular and Cellular Toxicology Section, Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland 20892, USA. warej@gwgate.nhlbi.nih.gov Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 164 EP - 171 VL - 11 IS - 3 SN - 0893-228X, 0893-228X KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Carrier Proteins KW - Diclofenac KW - 144O8QL0L1 KW - Acetaminophen KW - 362O9ITL9D KW - Halothane KW - UQT9G45D1P KW - Index Medicus KW - Administration, Oral KW - Animals KW - Drug Hypersensitivity -- immunology KW - Halothane -- metabolism KW - Carrier Proteins -- metabolism KW - Liver -- metabolism KW - Mice KW - Rats KW - Down-Regulation KW - Liver -- drug effects KW - Peyer's Patches -- metabolism KW - Peyer's Patches -- drug effects KW - Acetaminophen -- metabolism KW - Female KW - Male KW - Diclofenac -- chemistry KW - Anti-Inflammatory Agents, Non-Steroidal -- immunology KW - Diclofenac -- toxicity KW - Diclofenac -- immunology KW - Intestine, Small -- metabolism KW - Intestine, Small -- drug effects KW - Intestine, Small -- pathology KW - Anti-Inflammatory Agents, Non-Steroidal -- toxicity KW - Lymphoid Tissue -- drug effects KW - Lymphoid Tissue -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79786431?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Immunochemical+detection+and+identification+of+protein+adducts+of+diclofenac+in+the+small+intestine+of+rats%3A+possible+role+in+allergic+reactions.&rft.au=Ware%2C+J+A%3BGraf%2C+M+L%3BMartin%2C+B+M%3BLustberg%2C+L+R%3BPohl%2C+L+R&rft.aulast=Ware&rft.aufirst=J&rft.date=1998-03-01&rft.volume=11&rft.issue=3&rft.spage=164&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-28 N1 - Date created - 1998-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Patterns of Y and X chromosome DNA sequence divergence during the Felidae radiation. AN - 79783664; 9539439 AB - The 37 species of modern cats have evolved from approximately eight phylogenetic lineages within the past 10 to 15 million years. The Felidae family has been described with multiple measures of morphologic and molecular evolutionary methods that serve as a framework for tracking gene divergence during brief evolutionary periods. In this report, we compare the mode and tempo of evolution of noncoding sequences of a large intron within Zfy (783 bp) and Zfx (854 bp), homologous genes located on the felid Y and X chromosomes, respectively. Zfy sequence variation evolves at about twice the rate of Zfx, and both gene intron sequences track feline hierarchical topologies accurately. As homoplasies are infrequent in patterns of nucleotide substitution, the Y chromosome sequence displays a remarkable degree of phylogenetic consistency among cat species and provides a highly informative glimpse of divergence of sex chromosome sequences in Felidae. JF - Genetics AU - Pecon Slattery, J AU - O'Brien, S J AD - Laboratory of Genomic Diversity, Frederick Cancer and Research and Development Center, National Cancer Institute, Maryland 21702, USA. slattery@fcrfv2.ncifcrf.gov Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 1245 EP - 1255 VL - 148 IS - 3 SN - 0016-6731, 0016-6731 KW - DNA-Binding Proteins KW - 0 KW - Kruppel-Like Transcription Factors KW - Transcription Factors KW - zinc finger protein, X-linked KW - Index Medicus KW - Phylogeny KW - Animals KW - Cats -- genetics KW - Introns KW - DNA-Binding Proteins -- genetics KW - Sequence Analysis, DNA KW - Mutagenesis KW - Genetic Variation KW - X Chromosome KW - Carnivora -- genetics KW - Y Chromosome KW - Carnivora -- classification KW - Evolution, Molecular UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79783664?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genetics&rft.atitle=Patterns+of+Y+and+X+chromosome+DNA+sequence+divergence+during+the+Felidae+radiation.&rft.au=Pecon+Slattery%2C+J%3BO%27Brien%2C+S+J&rft.aulast=Pecon+Slattery&rft.aufirst=J&rft.date=1998-03-01&rft.volume=148&rft.issue=3&rft.spage=1245&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-01 N1 - Date created - 1998-06-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Mol Biol. 1970 Mar;48(3):443-53 [5420325] J Mol Evol. 1997 Apr;44(4):463-5 [9089087] Cell. 1987 Dec 24;51(6):1091-104 [3690661] Cold Spring Harb Symp Quant Biol. 1987;52:863-7 [3454295] Science. 1989 Jan 6;243(4887):78-80 [2563173] Cell. 1989 Mar 10;56(5):765-70 [2493989] Cell. 1989 Jun 30;57(7):1247-58 [2500252] Nature. 1989 Dec 7;342(6250):708-11 [2512506] Proc Natl Acad Sci U S A. 1990 Mar;87(5):1681-5 [2308929] Science. 1991 Mar 1;251(4997):1030-3 [1998119] J Mol Evol. 1991 Apr;32(4):310-5 [1907665] J Mol Evol. 1992 Jan;34(1):54-61 [1556744] Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7591-5 [1323846] Genomics. 1993 Feb;15(2):317-22 [8449497] Nature. 1993 Apr 22;362(6422):745-7 [8469284] J Mol Evol. 1993 Aug;37(2):160-6 [8411204] Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):827-31 [8290607] J Mol Evol. 1993 Oct;37(4):441-56 [8308912] J Mol Evol. 1994 Sep;39(3):296-305 [7932791] J Mol Evol. 1994 Dec;39(6):569-78 [7807546] J Mol Evol. 1995 Jan;40(1):70-7 [7714913] Bioessays. 1995 Apr;17(4):311-20 [7741724] Mol Biol Evol. 1995 Jul;12(4):690-707 [7544865] Mol Phylogenet Evol. 1996 Dec;6(3):351-65 [8975691] Mol Biol Evol. 1997 Mar;14(3):277-86 [9066795] Nature. 1997 Mar 27;386(6623):388-92 [9121553] Proc Natl Acad Sci U S A. 1978 Nov;75(11):5618-22 [281711] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - T cell-depleted bone marrow transplantation and delayed T cell add-back to control acute GVHD and conserve a graft-versus-leukemia effect. AN - 79782507; 9543057 AB - Thirty-eight patients with hematological malignancies, received T cell-depleted marrow transplants (BMT) and cyclosporine to prevent acute graft-versus-host disease (aGVHD), followed by delayed add-back of donor lymphocytes to prevent leukemia relapse. In 26 patients scheduled for donor T cell add-back of 2 x 10(6) cells/kg on day 30 and 5 x 10(7) cells/kg on day 45 (schedule 1), the overall probability of grade > or = II aGVHD developing was 31.5%, with a 15.5% probability of aGVHD occurring after T cell add-back. In 12 patients receiving 10(7) donor T cells/kg on day 30 (schedule 2), the probability of grade > or = II aGVHD was 100%. The incidence of grade III-IV aGVHD was higher in schedule 2 than in schedule 1 (P=0.02). Of 24 evaluable patients, 10 (46%) developed chronic GVHD which was limited in eight and extensive in two. Current disease-free survival for 18 patients at standard risk for relapse (chronic myeloid leukemia (CML) in chronic or accelerated phase, acute myeloid leukemia in remission) vs 20 patients with more advanced leukemia or multiple myeloma were respectively 72% vs 12% (P < 0.01) with a 29% vs 69% probability of relapse (P=0.08). In 12 CML patients surviving more than 3 months, PCR analysis of the BCR/ABL transcript showed that minimal residual disease after T cell add-back was transient except in two patients who developed hematological relapse. Results indicate that the risk of acute GVHD is low following substantial T cell doses, transfused 45 days after transplant, using cyclosporine prophylaxis. Furthermore a graft-versus-leukemia effect was conserved. JF - Bone marrow transplantation AU - Barrett, A J AU - Mavroudis, D AU - Tisdale, J AU - Molldrem, J AU - Clave, E AU - Dunbar, C AU - Cottler-Fox, M AU - Phang, S AU - Carter, C AU - Okunnieff, P AU - Young, N S AU - Read, E J AD - Bone Marrow Transplant Unit, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 543 EP - 551 VL - 21 IS - 6 SN - 0268-3369, 0268-3369 KW - Immunosuppressive Agents KW - 0 KW - Cyclophosphamide KW - 8N3DW7272P KW - Index Medicus KW - Transplantation Conditioning KW - Humans KW - Whole-Body Irradiation KW - Cyclophosphamide -- therapeutic use KW - Cytomegalovirus Infections -- complications KW - Adult KW - Treatment Outcome KW - Incidence KW - Middle Aged KW - Immunosuppressive Agents -- therapeutic use KW - Female KW - Male KW - Secondary Prevention KW - Bone Marrow Transplantation -- methods KW - Leukemia -- therapy KW - Lymphocyte Transfusion KW - T-Lymphocytes -- transplantation KW - Graft vs Host Disease -- epidemiology KW - Leukemia -- complications KW - Graft vs Host Disease -- prevention & control KW - Graft vs Host Reaction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79782507?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bone+marrow+transplantation&rft.atitle=T+cell-depleted+bone+marrow+transplantation+and+delayed+T+cell+add-back+to+control+acute+GVHD+and+conserve+a+graft-versus-leukemia+effect.&rft.au=Barrett%2C+A+J%3BMavroudis%2C+D%3BTisdale%2C+J%3BMolldrem%2C+J%3BClave%2C+E%3BDunbar%2C+C%3BCottler-Fox%2C+M%3BPhang%2C+S%3BCarter%2C+C%3BOkunnieff%2C+P%3BYoung%2C+N+S%3BRead%2C+E+J&rft.aulast=Barrett&rft.aufirst=A&rft.date=1998-03-01&rft.volume=21&rft.issue=6&rft.spage=543&rft.isbn=&rft.btitle=&rft.title=Bone+marrow+transplantation&rft.issn=02683369&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-27 N1 - Date created - 1998-05-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Melatonin: receptor-mediated events that may affect breast and other steroid hormone-dependent cancers. AN - 79775570; 9537645 AB - Epidemiological studies have suggested a possible link between extremely low frequency electromagnetic fields (EMFs) and increased rates of certain cancers. One cancer that has been postulated to be associated with EMF exposure is breast cancer, for which increased rates have been reported among electricians. These cancer associations are weak, and the link to EMF exposures remains tenuous. Understanding the mechanisms by which EMFs could have biological effects will help in elucidating the risk, if any, from EMFs. One hypothesis that has received considerable attention involves reduction of melatonin levels by EMFs. This hypothesis suggests that loss of melatonin affects a variety of hormonal processes such as estrogen homeostasis and thereby may increase breast cancer rates. Since this theory was first presented, putative melatonin receptors have been cloned, providing new tools with which to examine melatonin's mechanism of action and the melatonin hypothesis. These receptors are found in nuclear and membrane fractions of cells. The nuclear receptors (retinoid Z receptors) are found both in the brain and in non-neural tissues, whereas the membrane-bound receptors are found primarily in neural tissue and have a higher affinity for melatonin. These receptors may control a variety of hormonal and immunological functions, including the release of gonadotropins from the hypothalamus and pituitary and 5-lipoxygenase activity in B lymphocytes. This Working Hypothesis briefly reviews our current knowledge of melatonin receptors and then provides theories on how the inactivation of melatonin receptors may cause cancer and suggests areas of research for addressing this question. JF - Molecular carcinogenesis AU - Baldwin, W S AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 149 EP - 155 VL - 21 IS - 3 SN - 0899-1987, 0899-1987 KW - Receptors, Cell Surface KW - 0 KW - Receptors, Cytoplasmic and Nuclear KW - Receptors, Melatonin KW - Melatonin KW - JL5DK93RCL KW - Index Medicus KW - Humans KW - Receptors, Cytoplasmic and Nuclear -- physiology KW - Melatonin -- physiology KW - Electromagnetic Fields -- adverse effects KW - Breast Neoplasms -- etiology KW - Neoplasms, Hormone-Dependent -- etiology KW - Receptors, Cell Surface -- physiology KW - Breast Neoplasms -- ultrastructure KW - Neoplasms, Hormone-Dependent -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79775570?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+carcinogenesis&rft.atitle=Melatonin%3A+receptor-mediated+events+that+may+affect+breast+and+other+steroid+hormone-dependent+cancers.&rft.au=Baldwin%2C+W+S%3BBarrett%2C+J+C&rft.aulast=Baldwin&rft.aufirst=W&rft.date=1998-03-01&rft.volume=21&rft.issue=3&rft.spage=149&rft.isbn=&rft.btitle=&rft.title=Molecular+carcinogenesis&rft.issn=08991987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-16 N1 - Date created - 1998-04-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synergistic effects of 8-chlorocyclic-AMP and retinoic acid on induction of apoptosis in Ewing's sarcoma CHP-100 cells. AN - 79773777; 9533545 AB - The enhanced expression of the regulatory subunit of cyclic AMP (cAMP)-dependent protein kinase type I, RIalpha, has been correlated with cancer cell growth. Retinoic acid (RA) has been shown to play an important role in the regulation of proliferation and differentiation in neoplastic cells. In the present study, the effects of cAMP analogue 8-chlorocyclic-AMP (8-Cl-cAMP) and RA (both singly and combined) on growth inhibition and apoptosis in Ewing's sarcoma CHP-100 cells were evaluated. The inhibitory effects of 8-Cl-cAMP and RA (9-cis-RA, 13-cis-RA, and all-trans-RA) on cell viability were time and dose related. The degree of growth inhibition induced by 9-cis-RA was the greatest among all of the RA analogues (13-cis-RA and all-trans-RA) examined. The combined effects of 8-Cl-cAMP and RA on the induction of growth arrest at the G0-G1 stage of the cell cycle, apoptosis, down-regulation of RIalpha, and cleavage of poly(ADP-ribose) polymerase were synergistic. In conclusion, it is clear that RA and 8-Cl-cAMP act in a synergistic fashion and have potential for combination chemotherapy for the treatment of malignant disease. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Srivastava, R K AU - Srivastava, A R AU - Cho-Chung, Y S AD - Cellular Biochemistry Section, Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 755 EP - 761 VL - 4 IS - 3 SN - 1078-0432, 1078-0432 KW - Antineoplastic Agents KW - 0 KW - Nucleosomes KW - 8-Bromo Cyclic Adenosine Monophosphate KW - 23583-48-4 KW - 8-chloro-cyclic adenosine monophosphate KW - 41941-56-4 KW - Tretinoin KW - 5688UTC01R KW - Index Medicus KW - Nucleosomes -- pathology KW - Tumor Cells, Cultured KW - Nucleosomes -- drug effects KW - Cell Survival -- drug effects KW - Bone Neoplasms KW - Humans KW - Cell Division -- drug effects KW - Enzyme-Linked Immunosorbent Assay KW - Sarcoma, Ewing KW - Drug Synergism KW - 8-Bromo Cyclic Adenosine Monophosphate -- analogs & derivatives KW - Apoptosis -- drug effects KW - 8-Bromo Cyclic Adenosine Monophosphate -- toxicity KW - Tretinoin -- toxicity KW - Antineoplastic Agents -- toxicity KW - Cell Cycle -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79773777?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=unknown&rft.jtitle=Mental+Health+and+Social+Inclusion&rft.atitle=Mind+your+language%21&rft.au=Gilfoyle%2C+Sharon+Ann&rft.aulast=Gilfoyle&rft.aufirst=Sharon&rft.date=2017-02-01&rft.volume=21&rft.issue=1&rft.spage=47&rft.isbn=&rft.btitle=&rft.title=Mental+Health+and+Social+Inclusion&rft.issn=20428308&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-28 N1 - Date created - 1998-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Distinct localization of GLUT-1, -3, and -5 in human monocyte-derived macrophages: effects of cell activation. AN - 79764866; 9530136 AB - We determined subcellular localization of GLUT-1, GLUT-3, and GLUT-5 as human monocytes differentiate into macrophages in culture, and effects of the activating agents N-formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol myristate acetate (PMA). Western blot analysis demonstrated progressively increased GLUT-1, rapidly decreased GLUT-3, and a delayed increase of GLUT-5 expression during differentiation. Confocal microscopy revealed that each isoform displayed a unique subcellular distribution and cell-activation response. GLUT-1 was localized primarily to the cell surface but was also detected in the perinuclear region in a pattern characteristic of recycling endosomes. GLUT-3 exhibited predominantly a distinct vesicle-like staining but was present only in monocytes. GLUT-5 was found primarily at the cell surface but was detectable intracellularly. Activation with fMLP induced similar GLUT-1 and GLUT-5 redistributions from intracellular compartments toward the cell surface. PMA elicited a similar translocation of GLUT-1, but GLUT-5 was redistributed from the plasma membrane to a distinct intracellular compartment that appeared connected to the cell surface. These results suggest specific subcellular targeting of each transporter isoform and differential regulation of their trafficking pathways in cultured macrophages. JF - The American journal of physiology AU - Malide, D AU - Davies-Hill, T M AU - Levine, M AU - Simpson, I A AD - Experimental Diabetes, Metabolism, and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - E516 EP - E526 VL - 274 IS - 3 Pt 1 SN - 0002-9513, 0002-9513 KW - Glucose Transporter Type 1 KW - 0 KW - Glucose Transporter Type 3 KW - Glucose Transporter Type 5 KW - Monosaccharide Transport Proteins KW - Nerve Tissue Proteins KW - SLC2A1 protein, human KW - SLC2A3 protein, human KW - N-Formylmethionine Leucyl-Phenylalanine KW - 59880-97-6 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - N-Formylmethionine Leucyl-Phenylalanine -- pharmacology KW - Microscopy, Confocal KW - Cells, Cultured KW - Humans KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Differentiation KW - Molecular Weight KW - Macrophage Activation -- drug effects KW - Monosaccharide Transport Proteins -- metabolism KW - Monocytes -- cytology KW - Monocytes -- metabolism KW - Monocytes -- drug effects KW - Macrophages -- drug effects KW - Macrophages -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79764866?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+physiology&rft.atitle=Distinct+localization+of+GLUT-1%2C+-3%2C+and+-5+in+human+monocyte-derived+macrophages%3A+effects+of+cell+activation.&rft.au=Malide%2C+D%3BDavies-Hill%2C+T+M%3BLevine%2C+M%3BSimpson%2C+I+A&rft.aulast=Malide&rft.aufirst=D&rft.date=1998-03-01&rft.volume=274&rft.issue=3+Pt+1&rft.spage=E516&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+physiology&rft.issn=00029513&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-24 N1 - Date created - 1998-04-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of mutagenesis by O6-methyl- and O6-ethylguanine and O4-methylthymine in Escherichia coli using double-stranded and gapped plasmids. AN - 79757060; 9525280 AB - To compare mutagenesis by O6-methylguanine (m6G), O4-methylthymine (m4T) and O6-ethylguanine (e6G), and assess their genotoxicity in Escherichia coli, double-stranded and gapped plasmids were constructed containing a single m6G, e6G or m4T in the initiation codon (ATG) of a lacZ' gene. Modified base induced mutations were scored by the loss of lacZ' activity on X-gal-containing media resulting in formation of white or sectored (mutant) rather than blue (non-mutant) colonies. Genotoxicity experiments with gapped plasmids containing the modified bases indicated that m4T produced a greater number of bacterial colonies than m6G or e6G. m4T was more mutagenic (45% mutant colonies) than m6G (6%) or e6G (11%) in repair competent (w.t.) E. coli when incorporated in double-stranded plasmids. In gapped plasmids, m4T produced 99% mutant colonies (as was observed previously for e6G) in both w.t. E. coli or E. coli deficient in both O6-alkylguanine-DNA alkyltransferases as well as methylation-directed mismatch repair (ada(-)-ogt(-)-mutS[-]). m6G in gapped plasmids produced 62% mutant colonies in w.t. E. coli, but this percentage increased to 94% in the ada(-)-ogt(-)-mutS(-) strain. In double-stranded plasmids both m4T and m6G produced very similar distributions of mutant and non-mutant colonies in the ada(-)-ogt(-)-mutS(-) strain. These observations led to the conclusion that differences in the mutagenicity of m6G and m4T in w.t. E. coli were a result of preferential repair of m6G compared to m4T by alkyltransferase and mismatch repair mechanisms, and did not reflect differences in their respective coding efficiency or their inherent obstructiveness to DNA synthesis as was observed with e6G. The combination of alkyltransferase and mismatch repair was concluded to be primarily responsible for the apparent genotoxicity of m6G compared to m4T in double-stranded plasmids. JF - Carcinogenesis AU - Pauly, G T AU - Hughes, S H AU - Moschel, R C AD - Chemistry of Carcinogenesis Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, MD 21702, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 457 EP - 461 VL - 19 IS - 3 SN - 0143-3334, 0143-3334 KW - Mutagens KW - 0 KW - O-4-methylthymine KW - 25902-89-0 KW - Guanine KW - 5Z93L87A1R KW - O-(6)-methylguanine KW - 9B710FV2AE KW - O(6)-Methylguanine-DNA Methyltransferase KW - EC 2.1.1.63 KW - Thymine KW - QR26YLT7LT KW - Index Medicus KW - DNA Repair KW - DNA Methylation KW - O(6)-Methylguanine-DNA Methyltransferase -- metabolism KW - Mutagenesis KW - Guanine -- toxicity KW - Thymine -- analogs & derivatives KW - Mutagens -- toxicity KW - Escherichia coli -- genetics KW - Guanine -- analogs & derivatives KW - Thymine -- toxicity KW - Plasmids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79757060?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Comparison+of+mutagenesis+by+O6-methyl-+and+O6-ethylguanine+and+O4-methylthymine+in+Escherichia+coli+using+double-stranded+and+gapped+plasmids.&rft.au=Pauly%2C+G+T%3BHughes%2C+S+H%3BMoschel%2C+R+C&rft.aulast=Pauly&rft.aufirst=G&rft.date=1998-03-01&rft.volume=19&rft.issue=3&rft.spage=457&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-08 N1 - Date created - 1998-04-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adolescent substance abuse: a review of the past 10 years. AN - 79753717; 9519629 AB - To review and synthesize the recent scientific literature on adolescent substance abuse, covering natural history, epidemiology, etiology, comorbidity, assessment, treatment, and prevention, and to highlight areas for future research. Studies of adolescent substance abuse were reviewed with the focus on substance abuse and dependence rather than substance use. There has been a sharp recent resurgence in adolescent drug use. Biological factors, including genetic and temperament characteristics, as well as family environment factors, are emerging as important etiological variables. Comorbidity with other psychiatric disorders, particularly with conduct disorder, is frequent and complicates treatment. New assessment instruments are available for clinical and research use. Among treatment modalities, family-based interventions have received the most study. The past decade has seen growth in the volume and sophistication of research on adolescent substance abuse and in the conceptualization of this problem. Further research is needed, particularly on the significance of comorbid conditions and on individualized and effective treatment approaches. JF - Journal of the American Academy of Child and Adolescent Psychiatry AU - Weinberg, N Z AU - Rahdert, E AU - Colliver, J D AU - Glantz, M D AD - National Institute on Drug Abuse, National Institutes of Health, Rockville, MD, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 252 EP - 261 VL - 37 IS - 3 SN - 0890-8567, 0890-8567 KW - Index Medicus KW - Substance Abuse Detection KW - Risk Factors KW - Humans KW - Child KW - Adolescent KW - United States -- epidemiology KW - Male KW - Female KW - Comorbidity KW - Substance-Related Disorders -- rehabilitation KW - Substance-Related Disorders -- prevention & control KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79753717?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Academy+of+Child+and+Adolescent+Psychiatry&rft.atitle=Adolescent+substance+abuse%3A+a+review+of+the+past+10+years.&rft.au=Weinberg%2C+N+Z%3BRahdert%2C+E%3BColliver%2C+J+D%3BGlantz%2C+M+D&rft.aulast=Weinberg&rft.aufirst=N&rft.date=1998-03-01&rft.volume=37&rft.issue=3&rft.spage=252&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Academy+of+Child+and+Adolescent+Psychiatry&rft.issn=08908567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-20 N1 - Date created - 1998-04-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Levels and membrane localization of the c-K-ras p21 protein in lungs of mice of different genetic strains and effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and Aroclor 1254. AN - 79752616; 9525281 AB - Mutational activation of the K-ras oncogene often occurs in human and mouse lung adenocarcinomas. Since K-ras p21 functions in trans-membrane signaling, we have investigated whether the amount of this protein in lung cell membranes is a variable that could influence lung tumorigenesis, either due to genetic differences or in response to tumor promoters. The six mouse strains assessed showed little difference in the total lung K-ras p21 after immunoprecipitation and immunoblotting. However, amount of ras p21 in the membrane fraction showed significant differences, with C57BL/6 and BALB/c having 3-5-fold more than NIH Swiss, AKR and DBA mice. Interestingly, a congenic AKR strain having the Ahr(b-1) Ah receptor allele from C57BL/6 mice (designated AKR.B6Ah) had high lung membrane K-ras p21 similar to that of C57BL/6. To test for possible changes related to lung tumor promotion, mice were treated with a promotional dose of TCDD (5 nmol/kg). After 48 h C57BL/6 lungs showed an increase in p21 in both total and membrane fractions. BALB/c, DBA and Swiss mice showed an increase only in membranes. There was no change in the AKR and AKR.B6Ah. Aroclor 1254 (250 mg/kg) caused an increase in membrane/cytosol ratio in Swiss mice. Thus the membrane:cytosol K-ras p21 ratio may be influenced by the Ahr phenotype, and TCDD and PCBs can induce p21 or increase its membrane level in certain strains, but these properties are not fully dependent on Ahr receptor type. In confirmation of the relevance of these findings for the tumor target cell type, the immortalized alveolar type 2 E10 cell line presented K-ras p21 in membrane, and this was increased 4-fold by treatment with 10 nM TCDD. JF - Carcinogenesis AU - Ramakrishna, G AU - Anderson, L M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 463 EP - 470 VL - 19 IS - 3 SN - 0143-3334, 0143-3334 KW - Aroclors KW - 0 KW - Carcinogens KW - Polychlorinated Dibenzodioxins KW - Chlorodiphenyl (54% Chlorine) KW - 11097-69-1 KW - Proto-Oncogene Proteins p21(ras) KW - EC 3.6.5.2 KW - Index Medicus KW - Animals KW - Cytosol -- metabolism KW - Adenocarcinoma -- chemically induced KW - Cell Membrane -- drug effects KW - Adenocarcinoma -- genetics KW - Mice KW - Mice, Inbred Strains KW - Cells, Cultured KW - Lung Neoplasms -- genetics KW - Cell Membrane -- metabolism KW - Lung Neoplasms -- chemically induced KW - Species Specificity KW - Male KW - Proto-Oncogene Proteins p21(ras) -- metabolism KW - Lung -- cytology KW - Polychlorinated Dibenzodioxins -- toxicity KW - Lung -- drug effects KW - Carcinogens -- toxicity KW - Aroclors -- toxicity KW - Lung -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79752616?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Levels+and+membrane+localization+of+the+c-K-ras+p21+protein+in+lungs+of+mice+of+different+genetic+strains+and+effects+of+2%2C3%2C7%2C8-tetrachlorodibenzo-p-dioxin+%28TCDD%29+and+Aroclor+1254.&rft.au=Ramakrishna%2C+G%3BAnderson%2C+L+M&rft.aulast=Ramakrishna&rft.aufirst=G&rft.date=1998-03-01&rft.volume=19&rft.issue=3&rft.spage=463&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-08 N1 - Date created - 1998-04-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacokinetics of fentanyl during hyperthermic, isolated lung perfusion. AN - 79752012; 9521366 AB - Hyperthermic, isolated pulmonary perfusion with tumor necrosis factor is a surgical procedure that isolates the pulmonary vasculature from the systemic circulation in patients with unresectable primary or metastatic disease confined to the chest. High drug levels are delivered to the perfused organ, avoiding systemic toxicity, and preventing loss of active drug through metabolism. The pharmacokinetics of fentanyl are evaluated in three patients while the operative lung is hyperthermic, ventilated, and perfused with an asanguineous solution during nonpulsatile bypass. A loading dose of fentanyl, 1.5 microg/kg to 2.5 microg/kg, was given during the induction of anesthesia followed by a continuous infusion of 150 microg/hr. Results showed no difference in mean plasma fentanyl concentrations before, during, or after bypass and was consistent with clearance values previously reported in healthy adult surgical patients in the absence of an extracorporeal circuit. Adjustments in fentanyl dosing are not required before, during, or after hyperthermic, isolated pulmonary perfusion is established and a steady state of fentanyl is achieved. JF - Southern medical journal AU - Williams, K S AU - Susla, G AU - Temeck, B K AU - Piscitelli, S C AU - Pass, H I AD - Anesthesia Section, Clinical Center Pharmacy, and National Cancer Institute/Surgery Branch, National Institutes of Health, Bethesda, MD 20892-1512, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 261 EP - 265 VL - 91 IS - 3 SN - 0038-4348, 0038-4348 KW - Anesthetics, Intravenous KW - 0 KW - Fentanyl KW - UF599785JZ KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Adult KW - Hemodynamics KW - Middle Aged KW - Fentanyl -- blood KW - Anesthetics, Intravenous -- blood KW - Fentanyl -- pharmacokinetics KW - Hyperthermia, Induced KW - Anesthetics, Intravenous -- pharmacokinetics KW - Lung -- metabolism KW - Chemotherapy, Cancer, Regional Perfusion -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79752012?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Southern+medical+journal&rft.atitle=Pharmacokinetics+of+fentanyl+during+hyperthermic%2C+isolated+lung+perfusion.&rft.au=Williams%2C+K+S%3BSusla%2C+G%3BTemeck%2C+B+K%3BPiscitelli%2C+S+C%3BPass%2C+H+I&rft.aulast=Williams&rft.aufirst=K&rft.date=1998-03-01&rft.volume=91&rft.issue=3&rft.spage=261&rft.isbn=&rft.btitle=&rft.title=Southern+medical+journal&rft.issn=00384348&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-02 N1 - Date created - 1998-04-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tolerance and pharmacokinetic interactions of rifabutin and clarithromycin in human immunodeficiency virus-infected volunteers. AN - 79746017; 9517944 AB - This study evaluated the tolerance and potential pharmacokinetic interactions between clarithromycin (500 mg every 12 h) and rifabutin (300 mg daily) in clinically stable human immunodeficiency virus-infected volunteers with CD4 counts of <200 cells/mm3. Thirty-four subjects were randomized equally to either regimen A or regimen B. On days 1 to 14, subjects assigned to regimen A received clarithromycin and subjects assigned to regimen B received rifabutin, and then both groups received both drugs on days 15 to 42. Of the 14 regimen A and the 15 regimen B subjects who started combination therapy, 1 subject in each group prematurely discontinued therapy due to toxicity, but 19 of 29 subjects reported nausea, vomiting, and/or diarrhea. Pharmacokinetic analysis included data for 11 regimen A and 14 regimen B subjects. Steady-state pharmacokinetic parameters for single-agent therapy (day 14) and combination therapy (day 42) were compared. Regimen A resulted in a mean decrease of 44% (P = 0.003) in the clarithromycin area under the plasma concentration-time curve (AUC), while there was a mean increase of 57% (P = 0.004) in the AUC of the clarithromycin metabolite 14-OH-clarithromycin. Regimen B resulted in a mean increase of 99% (P = 0.001) in the rifabutin AUC and a mean increase of 375% (P < 0.001) in the AUC of the rifabutin metabolite 25-O-desacetyl-rifabutin. The usefulness of this combination for prophylaxis of Mycobacterium avium infections is limited by frequent gastrointestinal adverse events. Coadministration of clarithromycin and rifabutin results in significant bidirectional pharmacokinetic interactions. The resulting increase in rifabutin levels may explain the increased frequency of uveitis observed with concomitant use of these drugs. JF - Antimicrobial agents and chemotherapy AU - Hafner, R AU - Bethel, J AU - Power, M AU - Landry, B AU - Banach, M AU - Mole, L AU - Standiford, H C AU - Follansbee, S AU - Kumar, P AU - Raasch, R AU - Cohn, D AU - Mushatt, D AU - Drusano, G AD - Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852-7620, USA. rh23v@nih.gov Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 631 EP - 639 VL - 42 IS - 3 SN - 0066-4804, 0066-4804 KW - Rifabutin KW - 1W306TDA6S KW - Clarithromycin KW - H1250JIK0A KW - Index Medicus KW - AIDS/HIV KW - Drug Interactions KW - Area Under Curve KW - Humans KW - Adult KW - CD4 Lymphocyte Count KW - Male KW - Female KW - Drug Therapy, Combination -- adverse effects KW - Rifabutin -- adverse effects KW - Drug Therapy, Combination -- pharmacokinetics KW - Clarithromycin -- pharmacokinetics KW - Rifabutin -- pharmacokinetics KW - Clarithromycin -- adverse effects KW - Acquired Immunodeficiency Syndrome -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79746017?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+agents+and+chemotherapy&rft.atitle=Tolerance+and+pharmacokinetic+interactions+of+rifabutin+and+clarithromycin+in+human+immunodeficiency+virus-infected+volunteers.&rft.au=Hafner%2C+R%3BBethel%2C+J%3BPower%2C+M%3BLandry%2C+B%3BBanach%2C+M%3BMole%2C+L%3BStandiford%2C+H+C%3BFollansbee%2C+S%3BKumar%2C+P%3BRaasch%2C+R%3BCohn%2C+D%3BMushatt%2C+D%3BDrusano%2C+G&rft.aulast=Hafner&rft.aufirst=R&rft.date=1998-03-01&rft.volume=42&rft.issue=3&rft.spage=631&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+agents+and+chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-12 N1 - Date created - 1998-05-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Antimicrob Agents Chemother. 1995 Jun;39(6):1355-60 [7574530] Clin Pharmacokinet. 1995 Feb;28(2):115-25 [7736687] Ann Intern Med. 1996 Mar 15;124(6):573-6 [8597321] Clin Infect Dis. 1996 Apr;22 Suppl 1:S43-7; discussion S47-9 [8785256] N Engl J Med. 1996 Aug 8;335(6):392-8 [8676932] Tuber Lung Dis. 1996 Feb;77(1):19-26 [8733409] J Antimicrob Chemother. 1996 Jun;37 Suppl C:133-42 [8818854] Antimicrob Agents Chemother. 1997 May;41(5):924-6 [9145845] Clin Pharmacol Ther. 1997 May;61(5):554-62 [9164417] Comput Programs Biomed. 1983 Jun;16(3):203-16 [6688572] Antimicrob Agents Chemother. 1985 Oct;28(4):570-5 [4073881] Eur J Clin Pharmacol. 1988;34(6):595-9 [2901960] Xenobiotica. 1989 Jul;19(7):769-80 [2549734] Antimicrob Agents Chemother. 1989 Aug;33(8):1237-41 [2552902] AIDS. 1990 May;4(5):433-41 [2164820] Pharm Res. 1991 Nov;8(11):1434-40 [1665904] Am Rev Respir Dis. 1992 Apr;145(4 Pt 1):856-8 [1532486] J Chromatogr. 1991 Nov 15;571(1-2):199-208 [1839793] J Chemother. 1991 Dec;3(6):357-62 [1840274] Antimicrob Agents Chemother. 1992 Nov;36(11):2413-7 [1336945] J Antimicrob Chemother. 1992 Nov;30(5):643-50 [1493981] Clin Infect Dis. 1993 Jul;17(1):7-20 [8353249] N Engl J Med. 1993 Sep 16;329(12):828-33 [8179648] Drugs. 1993 Aug;46(2):289-312 [7691518] J Clin Pharmacol. 1993 Aug;33(8):719-26 [8408732] N Engl J Med. 1994 Feb 10;330(6):438-9 [8284019] N Engl J Med. 1994 Mar 24;330(12):868 [8114854] Drugs. 1994 Jun;47(6):983-1009 [7521834] Ann Intern Med. 1994 Dec 15;121(12):905-11 [7978715] AIDS Res Hum Retroviruses. 1994 Aug;10(8):913-6 [7811542] J Infect Dis. 1995 Mar;171(3):747-50 [7876634] Drug Metab Dispos. 1994 Nov-Dec;22(6):849-57 [7895601] Antimicrob Agents Chemother. 1994 Dec;38(12):2738-42 [7695255] Ann Pharmacother. 1995 Sep;29(9):906-17 [8547740] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacodynamic responses of F344 rats to the mouse hepatocarcinogen oxazepam in a 90-day feed study. AN - 79741907; 9512725 AB - Oxazepam (Serax) is a widely used benzodiazepine anxiolytic agent and a metabolite of other benzodiazepines such as Valium and Librium. Chronic feeding studies indicated that oxazepam is an hepatocarcinogen in B6C3F1 mice but did not increase hepatic tumors in F344 rats. The present study was performed to compare the hepatic responses of rats with our previous findings in mice to explore the reason(s) for the dramatic differences in tumor response between the two species. Male F344 rats (10 per dose-time group) received diets containing oxazepam at 0, 25, 125, 2500, and 5000 ppm. Hepatocyte labeling indices were measured immunohistochemically by PCNA and BrDU during the last 7 days before sacrifices after 15, 30, 45, and 90 days of dosing. Serum oxazepam was determined by reverse phase HPLC. Results indicated that oxazepam induced significant liver weight increases in a dose-related fashion by 15 days, which remained elevated for the entire study. No important clinical chemistry or pathology changes were noted except those related to hypertrophy. Cell proliferation was significantly increased in a dose-related manner by the 15- and 30-day timepoint in the 2500 and 5000 ppm groups. The most significant finding in the present study of oxazepam was plasma levels of the parent compound. Plasma levels in rats were dramatically lower than in B6C3F1 mice exposed to oxazepam in studies conducted earlier at the same dose levels. These results suggest that the early responses of rats and mice to oxazepam, such as cell proliferation and clinical chemistry parameters, are similar. Our previous studies demonstrated that oxazepam metabolites are excreted in the urine of rats, similar to humans, whereas mice excrete oxazepam metabolites in bile allowing enterohepatic recirculation, which results in high plasma levels of oxazepam. These data indicate that the rat excretes oxazepam kinetically (rate and route) similar to humans, but the mouse produces metabolites similar to humans. JF - Toxicology and applied pharmacology AU - Cunningham, M L AU - Bucher, J R AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. cunning1@niehs.nih.gov Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 41 EP - 48 VL - 149 IS - 1 SN - 0041-008X, 0041-008X KW - Carcinogens KW - 0 KW - Oxazepam KW - 6GOW6DWN2A KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Dose-Response Relationship, Drug KW - Body Weight -- drug effects KW - Cell Division -- drug effects KW - Species Specificity KW - Male KW - Organ Size -- drug effects KW - Liver -- cytology KW - Oxazepam -- toxicity KW - Oxazepam -- pharmacokinetics KW - Liver -- drug effects KW - Carcinogens -- toxicity KW - Liver -- metabolism KW - Oxazepam -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79741907?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Pharmacodynamic+responses+of+F344+rats+to+the+mouse+hepatocarcinogen+oxazepam+in+a+90-day+feed+study.&rft.au=Cunningham%2C+M+L%3BBucher%2C+J+R&rft.aulast=Cunningham&rft.aufirst=M&rft.date=1998-03-01&rft.volume=149&rft.issue=1&rft.spage=41&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=0041008X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-16 N1 - Date created - 1998-04-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - K-ras point mutation occurs in the early stage of carcinogenesis in lung cancer. AN - 79741433; 9514049 AB - In order to determine the topographical distribution of the K-ras codon 12 mutations in carcinoma and preneoplastic lesions of the lung, selective ultraviolet radiation fractionation, as well as microdissection followed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RELP), was performed. Fourteen of 61 samples amplified (23.0%) had a mutation in the K-ras codon 12. Of 41 adenocarcinoma, 12 samples (29.3%) had a mutation, whereas none of the squamous cell carcinomas had a mutation. One of six large-cell carcinomas, one of three carcinoid tumours and none of three other carcinomas had a mutation. Direct sequencing revealed that K-ras codon 12 of six samples were TGT (Cys), five samples were GTT (Val), two samples were GCT (Ala) and one sample was TTT (Phe). A total of 113 lesions of 13 cases covered by dot were amplified after UV radiation. All of 74 carcinoma lesions had the mutation, and intratumour heterogeneity was not observed. Of 39 non-malignant lesions, one type II cell hyperplasia had the mutation, which suggests that the K-ras mutation occurs in the early stage of carcinogenesis. The lack of intratumour heterogeneity supports the hypothesis. JF - British journal of cancer AU - Sagawa, M AU - Saito, Y AU - Fujimura, S AU - Linnoila, R I AD - Biomarkers and Prevention Research Branch, National Cancer Institute, Rockville, Maryland 20850, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 720 EP - 723 VL - 77 IS - 5 SN - 0007-0920, 0007-0920 KW - DNA, Neoplasm KW - 0 KW - Index Medicus KW - Polymerase Chain Reaction KW - Hyperplasia KW - Polymorphism, Restriction Fragment Length KW - Humans KW - DNA Mutational Analysis KW - DNA, Neoplasm -- genetics KW - Lung -- pathology KW - Genes, ras KW - Precancerous Conditions -- genetics KW - Lung Diseases -- genetics KW - Point Mutation KW - Carcinoma, Squamous Cell -- genetics KW - Carcinoma, Large Cell -- genetics KW - Lung Neoplasms -- genetics KW - Carcinoid Tumor -- genetics KW - Adenocarcinoma -- genetics KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79741433?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+cancer&rft.atitle=K-ras+point+mutation+occurs+in+the+early+stage+of+carcinogenesis+in+lung+cancer.&rft.au=Sagawa%2C+M%3BSaito%2C+Y%3BFujimura%2C+S%3BLinnoila%2C+R+I&rft.aulast=Sagawa&rft.aufirst=M&rft.date=1998-03-01&rft.volume=77&rft.issue=5&rft.spage=720&rft.isbn=&rft.btitle=&rft.title=British+journal+of+cancer&rft.issn=00070920&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-02 N1 - Date created - 1998-04-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Pathol. 1995 Jul;147(1):92-101 [7604888] JAMA. 1995 Feb 15;273(7):558-63 [7837389] Cancer Res. 1995 Nov 15;55(22):5133-9 [7585560] Cancer Res. 1996 May 1;56(9):2224-8 [8616876] N Engl J Med. 1988 Sep 1;319(9):525-32 [2841597] Oncogene. 1991 Aug;6(8):1353-62 [1679529] West J Med. 1991 Nov;155(5):505-14 [1815390] Am J Pathol. 1992 Sep;141(3):539-43 [1325739] Oncogene. 1992 Oct;7(10):1989-97 [1408139] J Natl Cancer Inst. 1993 Jul 7;85(13):1058-63 [8515492] Cancer. 1993 Jul 15;72(2):432-8 [8319174] Am J Pathol. 1994 Feb;144(2):303-9 [8311114] Virchows Arch. 1994;424(2):129-34 [7910096] Cancer Res. 1994 Nov 15;54(22):5811-5 [7954406] J Natl Cancer Inst. 1995 Jul 19;87(14):1056-60 [7616596] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human immunodeficiency virus disease: changing patterns of intraocular inflammation. AN - 79737794; 9512156 AB - To evaluate and put into perspective five articles in this issue of the AMERICAN JOURNAL OF OPHTHALMOLOGY that discuss ocular inflammatory disorders in patients with human immunodeficiency virus (HIV) disease. We drew upon recent observations concerning the effect of HIV disease on the immune system in an attempt to understand the current reports describing intraocular inflammation. Intraocular inflammation appears to be dependent on several factors, including specific antigenic stimuli and the state of the host immune system. During dynamic changes in these factors, conditions may arise that favor inflammatory reactions. Use of antiretroviral therapies is one mechanism that can effect these dynamics. As the immune system equilibrates at one extreme or the other (depletion or reconstitution), conditions favoring inflammation appear to dissipate. Restoration of immune function by the use of combination antiretroviral therapy, including protease inhibitors, may lead to additional cases of transient intraocular inflammation in the future. JF - American journal of ophthalmology AU - Nussenblatt, R B AU - Lane, H C AD - National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. rnq@helix.nih.gov Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 374 EP - 382 VL - 125 IS - 3 SN - 0002-9394, 0002-9394 KW - Anti-HIV Agents KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Drug Therapy, Combination KW - Immune System -- drug effects KW - Eye Infections, Bacterial -- complications KW - Syphilis -- complications KW - Humans KW - Eye Diseases -- etiology KW - Anti-HIV Agents -- adverse effects KW - Eye Diseases -- immunology KW - Uveitis, Posterior -- immunology KW - HIV Infections -- complications KW - Eye Infections, Viral KW - Vitreous Body -- pathology KW - Uveitis, Posterior -- etiology KW - HIV Infections -- immunology KW - Vitreous Body -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79737794?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+ophthalmology&rft.atitle=Human+immunodeficiency+virus+disease%3A+changing+patterns+of+intraocular+inflammation.&rft.au=Nussenblatt%2C+R+B%3BLane%2C+H+C&rft.aulast=Nussenblatt&rft.aufirst=R&rft.date=1998-03-01&rft.volume=125&rft.issue=3&rft.spage=374&rft.isbn=&rft.btitle=&rft.title=American+journal+of+ophthalmology&rft.issn=00029394&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-24 N1 - Date created - 1998-03-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Am J Ophthalmol. 1998 Mar;125(3):411-5 [9512171] Am J Ophthalmol. 1998 Mar;125(3):383-5 [9512157] Comment On: Am J Ophthalmol. 1998 Mar;125(3):411-5 [9512171] Am J Ophthalmol. 1998 Mar;125(3):292-300 [9512145] Am J Ophthalmol. 1998 Mar;125(3):312-24 [9512148] Am J Ophthalmol. 1998 Mar;125(3):301-5 [9512146] Am J Ophthalmol. 1998 Mar;125(3):306-11 [9512147] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of refractory myositis: a randomized crossover study of two new cytotoxic regimens. AN - 79732352; 9506565 AB - To assess the clinical usefulness of 2 novel therapies for treatment-resistant myositis. Thirty patients with refractory myositis, of whom 25 had an inadequate or no response to previous cytotoxic therapy, were randomized to begin either a combination of weekly oral methotrexate and daily azathioprine (MTX/AZA) or intravenous methotrexate with leucovorin rescue (I.V. MTX) every 2 weeks for 6 months. Crossover to the alternate therapy occurred according to defined rules; evaluations of muscle strength and functional abilities were performed at the beginning, and after 3 and 6 months, of each treatment. Of the 15 patients initially randomized to oral MTX/AZA, 8 improved with oral therapy and 1 improved with I.V. MTX during the crossover period. Of the 15 patients initially randomized to I.V. MTX therapy, 3 improved with the I.V. therapy and 4 with the oral combination during the crossover period. Although the study lacked the power to directly compare both treatments, intention-to-treat analysis showed a trend in favor of those patients who first received oral combination therapy (P = 0.025). There were 0.09 adverse events per patient-month with oral combination therapy and 0.16 per patient-month with I.V. therapy (P = 0.09). Combination oral MTX/AZA may benefit patients with treatment-resistant myositis, including those who previously had inadequate responses to either MTX or AZA alone. I.V. MTX with leucovorin rescue may also benefit some patients with refractory myositis. JF - Arthritis and rheumatism AU - Villalba, L AU - Hicks, J E AU - Adams, E M AU - Sherman, J B AU - Gourley, M F AU - Leff, R L AU - Thornton, B C AU - Burgess, S H AU - Plotz, P H AU - Miller, F W AD - National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 392 EP - 399 VL - 41 IS - 3 SN - 0004-3591, 0004-3591 KW - Antimetabolites, Antineoplastic KW - 0 KW - Antirheumatic Agents KW - Azathioprine KW - MRK240IY2L KW - Leucovorin KW - Q573I9DVLP KW - Methotrexate KW - YL5FZ2Y5U1 KW - Abridged Index Medicus KW - Index Medicus KW - Drug Therapy, Combination KW - Administration, Oral KW - Injections, Intravenous KW - Humans KW - Salvage Therapy KW - Adult KW - Cross-Over Studies KW - Aged KW - Middle Aged KW - Male KW - Female KW - Antimetabolites, Antineoplastic -- administration & dosage KW - Azathioprine -- adverse effects KW - Antimetabolites, Antineoplastic -- adverse effects KW - Azathioprine -- therapeutic use KW - Myositis -- drug therapy KW - Methotrexate -- adverse effects KW - Antirheumatic Agents -- administration & dosage KW - Antirheumatic Agents -- adverse effects KW - Methotrexate -- therapeutic use KW - Antimetabolites, Antineoplastic -- therapeutic use KW - Methotrexate -- administration & dosage KW - Antirheumatic Agents -- therapeutic use KW - Leucovorin -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79732352?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Arthritis+and+rheumatism&rft.atitle=Treatment+of+refractory+myositis%3A+a+randomized+crossover+study+of+two+new+cytotoxic+regimens.&rft.au=Villalba%2C+L%3BHicks%2C+J+E%3BAdams%2C+E+M%3BSherman%2C+J+B%3BGourley%2C+M+F%3BLeff%2C+R+L%3BThornton%2C+B+C%3BBurgess%2C+S+H%3BPlotz%2C+P+H%3BMiller%2C+F+W&rft.aulast=Villalba&rft.aufirst=L&rft.date=1998-03-01&rft.volume=41&rft.issue=3&rft.spage=392&rft.isbn=&rft.btitle=&rft.title=Arthritis+and+rheumatism&rft.issn=00043591&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-14 N1 - Date created - 1998-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Conduct of phase I trials in children with cancer. AN - 79729984; 9508179 AB - Future progress in the care of children with cancer requires appropriate evaluations of promising new agents for pediatric indications, beginning with well-conducted phase I trials. This report summarizes current guidelines for the conduct of pediatric phase I trials and represents a consensus between American and European investigators. The primary objective of pediatric phase I trials is to define safe and appropriate doses and schedules of new agents that can subsequently be used in phase II trials to test for activity against specific childhood malignancies. Prioritization of agents for evaluation in children is critical, since many more investigational agents are evaluated in adult patients than can be systematically evaluated in children. Considerations used in prioritizing agents include activity in xenograft models, novel mechanism of action, favorable drug-resistance profile, and activity observed in adult trials of the agent. Distinctive characteristics of pediatric phase I trials, in comparison to adult phase I trials, include the necessity for multiinstitutional participation and their higher starting dose (typically 80% of the adult maximum-tolerated dose [MTD]), both of which reflect the relative unavailability of appropriate patients. The application of uniform eligibility criteria and standard definitions for MTD and dose-limiting toxicity (DLT) help to assure that pediatric phase I trials are safely conducted and reliably identify appropriate doses and schedules of agents for phase II evaluation. Where possible, pediatric phase I trials also define the pharmacokinetic behavior of new agents in children. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Smith, M AU - Bernstein, M AU - Bleyer, W A AU - Borsi, J D AU - Ho, P AU - Lewis, I J AU - Pearson, A AU - Pein, F AU - Pratt, C AU - Reaman, G AU - Riccardi, R AU - Seibel, N AU - Trueworthy, R AU - Ungerleider, R AU - Vassal, G AU - Vietti, T AD - Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD 20892, USA. smithm@ctep.nci.nih.gov Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 966 EP - 978 VL - 16 IS - 3 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Infant KW - Humans KW - Guidelines as Topic KW - Child KW - Child, Preschool KW - Antineoplastic Agents -- administration & dosage KW - Clinical Trials, Phase I as Topic -- standards KW - Antineoplastic Agents -- pharmacokinetics KW - Neoplasms -- therapy KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79729984?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Conduct+of+phase+I+trials+in+children+with+cancer.&rft.au=Smith%2C+M%3BBernstein%2C+M%3BBleyer%2C+W+A%3BBorsi%2C+J+D%3BHo%2C+P%3BLewis%2C+I+J%3BPearson%2C+A%3BPein%2C+F%3BPratt%2C+C%3BReaman%2C+G%3BRiccardi%2C+R%3BSeibel%2C+N%3BTrueworthy%2C+R%3BUngerleider%2C+R%3BVassal%2C+G%3BVietti%2C+T&rft.aulast=Smith&rft.aufirst=M&rft.date=1998-03-01&rft.volume=16&rft.issue=3&rft.spage=966&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-24 N1 - Date created - 1998-03-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The cytotoxicity of nitroxyl: possible implications for the pathophysiological role of NO. AN - 79729300; 9501920 AB - In addition to the broad repertoire of regulatory functions nitric oxide (NO) serves in mammalian physiology, the L-arginine:NO pathway is also involved in numerous pathophysiological mechanisms. While NO itself may actually protect cells from the toxicity of reactive oxygen radicals in some cases, it has been suggested that reactive nitrogen oxide species formed from nitric oxide synthase (NOS) can be cytotoxic. In addition to NO, the one electron reduction product NO- has been proposed to be formed from NOS. We investigated the potential cytotoxic role of nitroxyl (NO-), using the nitroxyl donor Angelis's salt, (AS; sodium trioxodinitrate, Na2N2O3) as the source of NO-. As was found to be cytotoxic to Chinese hamster V79 lung fibroblast cells over a concentration range of 2-4 mM. The presence of equimolar ferricyanide (Fe(III)-(CN6)3-), which converts NO- to NO, afforded dramatic protection against AS-mediated cytotoxicity. Treatment of V79 cells with L-buthionine sulfoximine to reduce intracellular glutathione markedly enhanced AS cytotoxicity, which suggests that GSH is critical for cellular protection against the toxicity of NO-. Further experiments showed that low molecular weight transition metal complexes associated with the formation of reactive oxygen species are not involved in AS-mediated cytotoxicity since metal chelators had no effect. However, under aerobic conditions, AS was more toxic than under hypoxic conditions, suggesting that oxygen dramatically enhanced AS-mediated cytotoxicity. At a molecular level, AS exposure resulted in DNA double strand breaks in whole cells, and this effect was completely prevented by coincubation of cells with ferricyanide or Tempol. The data in this study suggest that nitroxyl may contribute to the cytotoxicity associated with an enhanced expression of the L-arginine:NO pathway under different biological conditions. JF - Archives of biochemistry and biophysics AU - Wink, D A AU - Feelisch, M AU - Fukuto, J AU - Chistodoulou, D AU - Jourd'heuil, D AU - Grisham, M B AU - Vodovotz, Y AU - Cook, J A AU - Krishna, M AU - DeGraff, W G AU - Kim, S AU - Gamson, J AU - Mitchell, J B AD - Tumor Biology Section, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1998/03/01/ PY - 1998 DA - 1998 Mar 01 SP - 66 EP - 74 VL - 351 IS - 1 SN - 0003-9861, 0003-9861 KW - Cyclic N-Oxides KW - 0 KW - Ferricyanides KW - Free Radical Scavengers KW - Free Radicals KW - Nitrites KW - Nitrogen Oxides KW - Spin Labels KW - hexacyanoferrate III KW - 13408-62-3 KW - oxyhyponitrite KW - 18550-55-5 KW - Nitric Oxide KW - 31C4KY9ESH KW - Buthionine Sulfoximine KW - 5072-26-4 KW - Arginine KW - 94ZLA3W45F KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Glutathione KW - GAN16C9B8O KW - nitroxyl KW - GFQ4MMS07W KW - tempol KW - U78ZX2F65X KW - Index Medicus KW - Animals KW - Nitrites -- pharmacology KW - Arginine -- metabolism KW - Cricetulus KW - DNA Damage KW - Glutathione -- metabolism KW - Fibroblasts KW - Ferricyanides -- pharmacology KW - Lung KW - Cyclic N-Oxides -- pharmacology KW - Buthionine Sulfoximine -- pharmacology KW - Nitric Oxide Synthase -- metabolism KW - Cell Line KW - Cricetinae KW - Cell Death KW - Nitric Oxide -- metabolism KW - Nitrogen Oxides -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79729300?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+biochemistry+and+biophysics&rft.atitle=The+cytotoxicity+of+nitroxyl%3A+possible+implications+for+the+pathophysiological+role+of+NO.&rft.au=Wink%2C+D+A%3BFeelisch%2C+M%3BFukuto%2C+J%3BChistodoulou%2C+D%3BJourd%27heuil%2C+D%3BGrisham%2C+M+B%3BVodovotz%2C+Y%3BCook%2C+J+A%3BKrishna%2C+M%3BDeGraff%2C+W+G%3BKim%2C+S%3BGamson%2C+J%3BMitchell%2C+J+B&rft.aulast=Wink&rft.aufirst=D&rft.date=1998-03-01&rft.volume=351&rft.issue=1&rft.spage=66&rft.isbn=&rft.btitle=&rft.title=Archives+of+biochemistry+and+biophysics&rft.issn=00039861&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-26 N1 - Date created - 1998-03-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase II trial with dose titration of paclitaxel for the therapy of human immunodeficiency virus-associated Kaposi's sarcoma. AN - 79728804; 9508198 AB - To investigate the antitumor activity and safety of paclitaxel in patients with advanced human immunodeficiency virus (HIV)-associated Kaposi's sarcoma (KS). Twenty-nine patients with advanced HIV-associated KS were enrolled. The patients were overall quite immunosuppressed (median CD4 count, 15 cells/microL). Paclitaxel was initially administered at 135 mg/m2 over 3 hours every 3 weeks without filgrastim support; the dose was increased as tolerated to a maximum of 175 mg/m2. Patients who failed to respond or progressed could then receive filgrastim support or paclitaxel administered over 96 hours. Of 28 assessable patients, 20 had major responses (18 partial responses [PRs], one clinical complete response [CR], and one CR), for a major response rate of 71.4% (95% confidence interval [CI], 51.3% to 86.8%). Each of the five patients with pulmonary KS responded, as did all four assessable patients who had previously received anthracycline therapy for KS. Of six patients who went on to receive a 96-hour infusion of paclitaxel, five had major responses. Neutropenia was the most frequent dose-limiting toxicity; possible novel toxicities included late fevers, late rash, and eosinophilia. Two patients developed an elevated creatinine concentration and one cardiomyopathy. Paclitaxel has substantial activity against advanced HIV-associated KS as a single agent, even in patients with pulmonary involvement or who had previously received anthracyclines. Further research is needed to define the optimal treatment schedule and its role vis-a-vis the other available therapies for this disease. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Welles, L AU - Saville, M W AU - Lietzau, J AU - Pluda, J M AU - Wyvill, K M AU - Feuerstein, I AU - Figg, W D AU - Lush, R AU - Odom, J AU - Wilson, W H AU - Fajardo, M T AU - Humphrey, R W AU - Feigal, E AU - Tuck, D AU - Steinberg, S M AU - Broder, S AU - Yarchoan, R AD - HIV and AIDS Malignancy Branch, National Cancer Institute; the Warren G. Magnuson Clinical Center, Bethesda, MD 20892-1906, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 1112 EP - 1121 VL - 16 IS - 3 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Recombinant Proteins KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Paclitaxel KW - P88XT4IS4D KW - Filgrastim KW - PVI5M0M1GW KW - Index Medicus KW - AIDS/HIV KW - Probability KW - Acquired Immunodeficiency Syndrome -- complications KW - Drug Administration Schedule KW - Granulocyte Colony-Stimulating Factor -- therapeutic use KW - Humans KW - Adult KW - Middle Aged KW - Male KW - Survival Analysis KW - Remission Induction KW - Paclitaxel -- administration & dosage KW - Antineoplastic Agents, Phytogenic -- pharmacokinetics KW - Sarcoma, Kaposi -- drug therapy KW - Paclitaxel -- pharmacokinetics KW - Antineoplastic Agents, Phytogenic -- therapeutic use KW - Paclitaxel -- therapeutic use KW - Antineoplastic Agents, Phytogenic -- administration & dosage KW - Sarcoma, Kaposi -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79728804?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Phase+II+trial+with+dose+titration+of+paclitaxel+for+the+therapy+of+human+immunodeficiency+virus-associated+Kaposi%27s+sarcoma.&rft.au=Welles%2C+L%3BSaville%2C+M+W%3BLietzau%2C+J%3BPluda%2C+J+M%3BWyvill%2C+K+M%3BFeuerstein%2C+I%3BFigg%2C+W+D%3BLush%2C+R%3BOdom%2C+J%3BWilson%2C+W+H%3BFajardo%2C+M+T%3BHumphrey%2C+R+W%3BFeigal%2C+E%3BTuck%2C+D%3BSteinberg%2C+S+M%3BBroder%2C+S%3BYarchoan%2C+R&rft.aulast=Welles&rft.aufirst=L&rft.date=1998-03-01&rft.volume=16&rft.issue=3&rft.spage=1112&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-24 N1 - Date created - 1998-03-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Accumulation of a recombinant immunotoxin in a tumor in vivo: fewer than 1000 molecules per cell are sufficient for complete responses. AN - 79728776; 9500458 AB - Recombinant immunotoxins have been shown to cure human tumor xenografts in mice, but their biodistribution to both tumors and normal organs has not been reported. Anti-Tac(Fv)-PE38 is a single-chain recombinant immunotoxin composed of the variable heavy and light domains of the anti-Tac monoclonal antibody that reacts with the primate interleukin 2 (IL2) receptor alpha subunit (IL2R alpha or CD25) fused to a truncated form of Pseudomonas exotoxin (PE). 125I-labeled anti-Tac(Fv)-PE38 was given i.v. to immunodeficient mice each bearing two A431 tumors, one that expresses IL2R alpha (ATAC-4) and one that does not (A431, parental). A single i.v. dose of 4 microg/mouse caused complete regression of the IL2R alpha + tumor. At 6 h, over 6% of the injected dose/g was found in the ATAC-4 tumor, and 2% was in the A431 tumor. Uptake in the ATAC-4 tumor was higher than in any other tissue. Sections of tumor examined by autoradiography indicated that anti-Tac(Fv)-PE38 was distributed throughout the entire tumor, with some portions having higher uptake than others. By subtracting uptake in tumors without receptor (A431) from uptake in receptor-containing tumors (ATAC-4), we calculated that at least 400 molecules/cell specifically bound to IL2R alpha-positive tumor cells at 90 min and 750 molecules/cell bound at 360 min. This is similar to the 400-870 molecules/cell required for >99.9% killing of ATAC-4 cells growing as a monolayer. The results show that solid tumors in mice can be eradicated like cells in tissue culture, and that delivery of less than 1000 molecules/cell is sufficient to cause complete tumor regressions. JF - Cancer research AU - Kreitman, R J AU - Pastan, I AD - Laboratory of Molecular Biology, Division of Cancer Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/03/01/ PY - 1998 DA - 1998 Mar 01 SP - 968 EP - 975 VL - 58 IS - 5 SN - 0008-5472, 0008-5472 KW - Antibodies, Monoclonal KW - 0 KW - Bacterial Toxins KW - Exotoxins KW - Immunotoxins KW - Receptors, Interleukin-2 KW - Recombinant Fusion Proteins KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Animals KW - Recombinant Fusion Proteins -- pharmacokinetics KW - Antibodies, Monoclonal -- pharmacokinetics KW - Humans KW - Mice, Nude KW - Mice KW - Recombinant Fusion Proteins -- therapeutic use KW - Antibodies, Monoclonal -- therapeutic use KW - Immunotoxins -- pharmacokinetics KW - Neoplasms, Experimental -- immunology KW - Immunotoxins -- therapeutic use KW - Neoplasms, Experimental -- drug therapy KW - Neoplasms, Experimental -- pathology KW - Exotoxins -- therapeutic use KW - Receptors, Interleukin-2 -- immunology KW - Exotoxins -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79728776?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Accumulation+of+a+recombinant+immunotoxin+in+a+tumor+in+vivo%3A+fewer+than+1000+molecules+per+cell+are+sufficient+for+complete+responses.&rft.au=Kreitman%2C+R+J%3BPastan%2C+I&rft.aulast=Kreitman&rft.aufirst=R&rft.date=1998-03-01&rft.volume=58&rft.issue=5&rft.spage=968&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-25 N1 - Date created - 1998-03-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Volume of ethanol consumption: effects of different approaches to measurement. AN - 79726968; 9500306 AB - Eight different approaches to measuring alcohol consumption were compared in terms of average daily volume of ethanol intake, selected percentiles of the volume distribution, the proportion of drinkers exceeding a volume-based cutpoint for moderate drinking and the estimated association between volume of intake and alcohol use disorders. Data were drawn from the 1988 National Health Interview Survey and the 1992 National Longitudinal Alcohol Epidemiologic Survey. The eight approaches compared overall and beverage-specific questions, reference periods of varying lengths, and measures based solely on usual intake with those that incorporated different aspects of atypical heavy drinking. Average daily ethanol intake ranged from 0.43 oz based on two questions on current usual frequency and quantity of drinking (assuming 0.5 oz of ethanol per drink) to 0.72 oz based on 21 questions that included usual and heaviest consumption of beer, wine and distilled spirits in the year preceding interview. Estimated volume was highly sensitive to the number and types of questions upon which it was based, and changes in formulation that resulted in relatively small increases in mean volume often were associated with much larger increases in the proportion of drinkers exceeding some specified level of intake and in the estimated association between consumption and alcohol use disorders. These issues should be considered when deciding on the consumption items to be included in alcohol surveys. JF - Journal of studies on alcohol AU - Dawson, D A AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-7003, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 191 EP - 197 VL - 59 IS - 2 SN - 0096-882X, 0096-882X KW - Index Medicus KW - Sex Factors KW - Humans KW - Reference Standards KW - Aged KW - Longitudinal Studies KW - Cross-Sectional Studies KW - Psychiatric Status Rating Scales KW - Adult KW - Incidence KW - Middle Aged KW - Alcoholic Beverages -- classification KW - Adolescent KW - United States -- epidemiology KW - Female KW - Male KW - Alcoholism -- epidemiology KW - Alcoholism -- diagnosis KW - Alcohol Drinking -- adverse effects KW - Alcohol Drinking -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79726968?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+studies+on+alcohol&rft.atitle=Volume+of+ethanol+consumption%3A+effects+of+different+approaches+to+measurement.&rft.au=Dawson%2C+D+A&rft.aulast=Dawson&rft.aufirst=D&rft.date=1998-03-01&rft.volume=59&rft.issue=2&rft.spage=191&rft.isbn=&rft.btitle=&rft.title=Journal+of+studies+on+alcohol&rft.issn=0096882X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-06 N1 - Date created - 1998-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulation of methylnitrosourea-induced breast cancer in Sprague Dawley rats by dehydroepiandrosterone: dose-dependent inhibition, effects of limited exposure, effects on peroxisomal enzymes, and lack of effects on levels of Ha-Ras mutations. AN - 79726740; 9500451 AB - Dehydroepiandrosterone (DHEA), the major steroid precursor of androgens and estrogens produced in peripheral tissues in primates, is an effective chemopreventive agent in the N-methyl-N-nitrosourea (MNU)-induced rat mammary tumor model. Dietary DHEA (5-600 ppm; 600 mg/kg diet) was administered beginning 1 week before MNU and administered continually throughout the duration of the experiment. The highest dose of DHEA (600 ppm) significantly decreased tumor incidence from 95 to 45% and increased tumor latency and decreased tumor multiplicity from 4.1 to 0.5 tumors/rat. Lower doses of DHEA (5, 24, and 120 ppm) were also effective, decreasing tumor multiplicity by 28, 40, and 55%, respectively, increasing tumor latency in a dose-dependent manner but only minimally affecting final tumor incidence. DHEA in the diet caused a dose-dependent increase in serum levels of DHEA. The 120-ppm dietary dose of DHEA resulted in serum levels of DHEA of approximately 42 pmol/ml levels, similar to those seen in young humans. When we examined whole mounts of mammary glands derived from rats exposed to higher levels of DHEA (600 ppm), we observed a striking increase in lobular development. The doses of DHEA used in these studies (< or =600 ppm) had minimal effects on the induction of fatty acid CoA synthetase, a peroxisome-associated enzyme. In contrast, a dose of 2000 ppm substantially increased levels of peroxisome-associated fatty acid CoA synthetase. The varied and striking efficacy of DHEA was achieved in the absence of any significant effect on body weight gain in the treated rats. Furthermore, tumors from rats treated with MNU alone or rats treated with MNU plus DHEA were examined for the presence of mutations in the Ha-Ras oncogene. There was a slight decrease in the percentage of tumors bearing Ha-Ras mutations in tumors derived from MNU-control rats as contrasted with tumors from MNU-DHEA (120 and 600 ppm)-treated rats. Based on the striking chemopreventive efficacy of continual exposure to DHEA, we examined the effects of more limited exposure to DHEA. Rats were treated with DHEA for a period of 7 weeks immediately before and after MNU injection. Rats were then placed on the control diet for the ensuing 15 weeks. Even this limited exposure to DHEA for a period of 7 weeks profoundly decreased final tumor incidence and multiplicity. Additionally, we examined the effects of intermittent dosing with DHEA. Rats were treated alternatively at 3-week intervals either with diet containing DHEA or with control diet. It was found that this intermittent dosing with DHEA also substantially inhibited the formation of mammary tumors. JF - Cancer research AU - Lubet, R A AU - Gordon, G B AU - Prough, R A AU - Lei, X D AU - You, M AU - Wang, Y AU - Grubbs, C J AU - Steele, V E AU - Kelloff, G J AU - Thomas, C F AU - Moon, R D AD - National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1998/03/01/ PY - 1998 DA - 1998 Mar 01 SP - 921 EP - 926 VL - 58 IS - 5 SN - 0008-5472, 0008-5472 KW - Dehydroepiandrosterone KW - 459AG36T1B KW - Methylnitrosourea KW - 684-93-5 KW - Coenzyme A Ligases KW - EC 6.2.1.- KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Dose-Response Relationship, Drug KW - Cell Division -- drug effects KW - Coenzyme A Ligases -- drug effects KW - Diet KW - Mutation KW - Female KW - Genes, ras KW - Mammary Neoplasms, Animal -- pathology KW - Neoplasms, Experimental -- chemically induced KW - Mammary Neoplasms, Animal -- genetics KW - Dehydroepiandrosterone -- therapeutic use KW - Neoplasms, Experimental -- drug therapy KW - Microbodies -- drug effects KW - Mammary Neoplasms, Animal -- chemically induced KW - Neoplasms, Experimental -- pathology KW - Mammary Neoplasms, Animal -- drug therapy KW - Dehydroepiandrosterone -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79726740?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Modulation+of+methylnitrosourea-induced+breast+cancer+in+Sprague+Dawley+rats+by+dehydroepiandrosterone%3A+dose-dependent+inhibition%2C+effects+of+limited+exposure%2C+effects+on+peroxisomal+enzymes%2C+and+lack+of+effects+on+levels+of+Ha-Ras+mutations.&rft.au=Lubet%2C+R+A%3BGordon%2C+G+B%3BPrough%2C+R+A%3BLei%2C+X+D%3BYou%2C+M%3BWang%2C+Y%3BGrubbs%2C+C+J%3BSteele%2C+V+E%3BKelloff%2C+G+J%3BThomas%2C+C+F%3BMoon%2C+R+D&rft.aulast=Lubet&rft.aufirst=R&rft.date=1998-03-01&rft.volume=58&rft.issue=5&rft.spage=921&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-25 N1 - Date created - 1998-03-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Open-label trial of oral nalmefene therapy for the pruritus of cholestasis. AN - 79726388; 9500694 AB - The aims of this study were to determine whether long-term oral administration of the opiate antagonist nalmefene is associated with any beneficial effects in patients with pruritus secondary to cholestatic liver disease and to assess the safety of long-term administration of this drug to these patients. Fourteen patients with unrelieved chronic pruritus of cholestasis were studied. Scratching activity, independent of limb movements, was recorded continuously for 24-hour periods before and during treatment with an initial ameliorating dose of nalmefene. Simultaneously, during these periods, visual analogue scores (VASs) of pruritus were recorded every 4 hours while patients were awake. The dose of nalmefene, which initially was 2 mg orally twice daily, was increased during the study, usually until a satisfactory clinical response was achieved. Five patients experienced a transient opioid withdrawal-like reaction that did not preclude continuing with nalmefene therapy. Serum biochemical indices of cholestasis did not change appreciably during treatment. Thirteen patients reported amelioration of the perception of pruritus on nalmefene. In 5 patients, exacerbations of pruritus occurred approximately 4 weeks after an initial ameliorating dose had been reached; these exacerbations were managed by increasing the dose. Baseline mean values for VAS and scratching activity were higher than corresponding means during nalmefene therapy in 13 (P = .002) and 12 (P = .013) patients, respectively. Possible tolerance to nalmefene occurred in 3 patients. Three patients experienced marked exacerbation of pruritus after nalmefene therapy was suddenly discontinued. Blood levels of nalmefene were consistent with normal pharmacokinetics of the drug. These results suggest that nalmefene may have a favorable risk-to-benefit ratio when it is administered orally long-term to patients with the pruritus of cholestasis. JF - Hepatology (Baltimore, Md.) AU - Bergasa, N V AU - Schmitt, J M AU - Talbot, T L AU - Alling, D W AU - Swain, M G AU - Turner, M L AU - Jenkins, J B AU - Jones, E A AD - Liver Diseases Section, Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 679 EP - 684 VL - 27 IS - 3 SN - 0270-9139, 0270-9139 KW - Narcotic Antagonists KW - 0 KW - Naltrexone KW - 5S6W795CQM KW - nalmefene KW - TOV02TDP9I KW - Index Medicus KW - Administration, Oral KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Child KW - Adolescent KW - Pruritus -- drug therapy KW - Narcotic Antagonists -- therapeutic use KW - Naltrexone -- adverse effects KW - Naltrexone -- analogs & derivatives KW - Cholestasis -- drug therapy KW - Naltrexone -- pharmacokinetics KW - Naltrexone -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79726388?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepatology+%28Baltimore%2C+Md.%29&rft.atitle=Open-label+trial+of+oral+nalmefene+therapy+for+the+pruritus+of+cholestasis.&rft.au=Bergasa%2C+N+V%3BSchmitt%2C+J+M%3BTalbot%2C+T+L%3BAlling%2C+D+W%3BSwain%2C+M+G%3BTurner%2C+M+L%3BJenkins%2C+J+B%3BJones%2C+E+A&rft.aulast=Bergasa&rft.aufirst=N&rft.date=1998-03-01&rft.volume=27&rft.issue=3&rft.spage=679&rft.isbn=&rft.btitle=&rft.title=Hepatology+%28Baltimore%2C+Md.%29&rft.issn=02709139&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-19 N1 - Date created - 1998-03-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Development of a murine mutant Ras CD8+ CTL peptide epitope variant that possesses enhanced MHC class I binding and immunogenic properties. AN - 79721420; 9498787 AB - We recently identified a murine mutant Ras p21 CD8+ CTL epitope reflecting residues 4 to 12, containing the mutation of Gly to Val at codon 12, that bound weakly to H-2Kd in vitro and generated a weak primary CTL response in immunized BALB/c mice. Here, we explored the hypothesis that specific modifications to the Ras4-12 peptide sequence can improve MHC binding, leading to enhanced immunogenicity without altering immune specificity. We synthesized Ras4-12 peptides in which Val at residue 12 was replaced with the more dominant H-2Kd C-terminus anchor residue Leu or Ile. In functional H-2Kd binding assays, Ras4-12(L12 or I12) peptide variants competed more effectively than the Ras4-12(V12) peptide. Ras4-12(L12 or I12) peptide variants enhanced both in vitro cytotoxicity and proliferation responses of anti-Ras4-12 CTL compared with the mutant Ras4-12(V12) peptide. Additionally, the Ras4-12(L12) peptide variant induced a quantitatively greater T cell response in vivo compared with that produced by Ras4-12(V12) as determined by IFN-gamma production. Mice immunized with Ras4-12(L12) peptide elicited CD8+ CTL activity specific for target cells presenting the Ras4-12(V12) epitope exogenously and endogenously. Moreover, both anti-Ras4-12(V12)-derived and anti-Ras4-12(L12)-derived CTL lines were similar insofar as their TCR usage and amino acid contact residues in the Ras4-12(V12) peptide. These experiments demonstrate that modifications can be introduced in tumor-specific peptide epitopes to enhance both in vitro and in vivo immunogenicity. The design of oncogene-specific peptide epitope variants as immunogens may accelerate the generation of anti-tumor T cell responses for cancer immunotherapy. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Bristol, J A AU - Schlom, J AU - Abrams, S I AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1998/03/01/ PY - 1998 DA - 1998 Mar 01 SP - 2433 EP - 2441 VL - 160 IS - 5 SN - 0022-1767, 0022-1767 KW - Antigens, CD8 KW - 0 KW - Epitopes KW - H-2 Antigens KW - Peptide Fragments KW - Receptors, Antigen, T-Cell, alpha-beta KW - ras Proteins KW - EC 3.6.5.2 KW - Abridged Index Medicus KW - Index Medicus KW - Amino Acid Substitution -- immunology KW - Animals KW - Receptors, Antigen, T-Cell, alpha-beta -- metabolism KW - Antigens, CD8 -- physiology KW - Genes, ras -- immunology KW - Mice KW - Mice, Inbred BALB C KW - Receptors, Antigen, T-Cell, alpha-beta -- biosynthesis KW - Lymphocyte Activation -- drug effects KW - Amino Acid Substitution -- genetics KW - Injections, Subcutaneous KW - Cytotoxicity, Immunologic -- drug effects KW - Epitope Mapping KW - Cell Line KW - Female KW - ras Proteins -- genetics KW - Epitopes -- genetics KW - Peptide Fragments -- genetics KW - H-2 Antigens -- physiology KW - T-Lymphocytes, Cytotoxic -- immunology KW - T-Lymphocytes, Cytotoxic -- metabolism KW - Peptide Fragments -- immunology KW - Mutagenesis KW - H-2 Antigens -- genetics KW - ras Proteins -- administration & dosage KW - ras Proteins -- immunology KW - Peptide Fragments -- pharmacology KW - ras Proteins -- metabolism KW - Epitopes -- immunology KW - Peptide Fragments -- administration & dosage KW - Epitopes -- metabolism KW - H-2 Antigens -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79721420?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=Development+of+a+murine+mutant+Ras+CD8%2B+CTL+peptide+epitope+variant+that+possesses+enhanced+MHC+class+I+binding+and+immunogenic+properties.&rft.au=Bristol%2C+J+A%3BSchlom%2C+J%3BAbrams%2C+S+I&rft.aulast=Bristol&rft.aufirst=J&rft.date=1998-03-01&rft.volume=160&rft.issue=5&rft.spage=2433&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-18 N1 - Date created - 1998-03-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of cell proliferation and induction of apoptosis by the retinoid AHPN in human lung carcinoma cells. AN - 79717757; 9490650 AB - In this study, we investigated the effect of the novel retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (AHPN/CD437) on the growth of human lung carcinoma cell lines. AHPN inhibits the proliferation of all cell lines tested, irrespective of the lung tumor type, in a concentration- and time-dependent manner. A dramatic reduction in cell number was observed in adenocarcinoma H460 cells, and was shown to be related to an induction of apoptosis. Bromodeoxyuridine (BrdU) incorporation and flow-cytometric analyses indicated that treatment of H460 cells with AHPN induces cell-cycle arrest at the G1 phase. We therefore investigated the effect of AHPN on several regulatory proteins of the G1 phase of the cell-cycle. The cell-cycle arrest induced by AHPN was accompanied by an inhibition of the hyperphosphorylation of the retinoblastoma (Rb) protein, an indication of G1 arrest. Furthermore, two cyclin-dependent kinases, cdk2 and cdk4, which are normally involved in the phosphorylation of Rb, were shown to have decreased activity. In some cell lines, the decrease in cdk activity may be partly related to an increase in p21(WAF1/Cip1) (p21), an inhibitor of cyclin-dependent kinases. No changes were observed in the cyclin-dependent kinase inhibitor p27(Kip1). The observed increase in p53 in response to AHPN could at least to some extent be responsible for the increased levels of p21. The increase in p53 expression was found to be regulated at a post-transcriptional level. Our results suggest that the growth inhibition of certain lung carcinoma cell lines by AHPN is at least partly related to an increase in p21. However, in other cell lines, different mechanisms appear to be involved. The specificity with which AHPN and other retinoids induce growth arrest and p21 expression indicates that the action of AHPN is not mediated by RAR or RXR receptors, but involves a novel signaling pathway. JF - American journal of respiratory cell and molecular biology AU - Adachi, H AU - Preston, G AU - Harvat, B AU - Dawson, M I AU - Jetten, A M AD - Laboratories of Pulmonary Pathobiology and Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, 27709, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 323 EP - 333 VL - 18 IS - 3 SN - 1044-1549, 1044-1549 KW - CD 437 KW - 0 KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - Retinoblastoma Protein KW - Retinoids KW - bcl-2-Associated X Protein KW - Index Medicus KW - Proto-Oncogene Proteins c-bcl-2 -- biosynthesis KW - Proto-Oncogene Proteins -- biosynthesis KW - Carcinoma, Non-Small-Cell Lung -- metabolism KW - Tumor Cells, Cultured KW - Carcinoma, Small Cell -- metabolism KW - Humans KW - Retinoblastoma Protein -- metabolism KW - Cell Division -- drug effects KW - Phosphorylation -- drug effects KW - Apoptosis KW - Lung -- drug effects KW - Retinoids -- pharmacology KW - Lung -- pathology KW - Carcinoma -- metabolism KW - Lung Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79717757?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+respiratory+cell+and+molecular+biology&rft.atitle=Inhibition+of+cell+proliferation+and+induction+of+apoptosis+by+the+retinoid+AHPN+in+human+lung+carcinoma+cells.&rft.au=Adachi%2C+H%3BPreston%2C+G%3BHarvat%2C+B%3BDawson%2C+M+I%3BJetten%2C+A+M&rft.aulast=Adachi&rft.aufirst=H&rft.date=1998-03-01&rft.volume=18&rft.issue=3&rft.spage=323&rft.isbn=&rft.btitle=&rft.title=American+journal+of+respiratory+cell+and+molecular+biology&rft.issn=10441549&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-31 N1 - Date created - 1998-03-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activated T lymphocytes induce degranulation and cytokine production by human mast cells following cell-to-cell contact. AN - 79717040; 9500521 AB - Activated mast cells reside in close apposition to T cells in some inflammatory processes. In this study, we analyzed whether this close physical proximity affects human mast cell degranulation and cytokine release. Thus HMC-1 human mast cells or primary bone marrow-derived human mast cells were cocultured with activated and with resting T cells. Mast cells cocultured with activated T cells released histamine and beta-hexosaminidase and produced tumor necrosis factor alpha (TNF-alpha), an effect that peaked at 20 h. Kinetics of histamine release paralleled the formation of heterotypic aggregates. Separation of the two cell populations with a porous membrane prevented mediator release and TNF-alpha production. Addition of the PI3-kinase inhibitor, wortmannin, inhibited the heterotypic adhesion-associated degranulation but not TNF-alpha production. These data thus indicate a novel pathway through which human mast cells are activated to both release granule-associated mediators and to produce cytokines in association with heterotypic adhesion to activated human T cells. JF - Journal of leukocyte biology AU - Bhattacharyya, S P AU - Drucker, I AU - Reshef, T AU - Kirshenbaum, A S AU - Metcalfe, D D AU - Mekori, Y A AD - The Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1881, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 337 EP - 341 VL - 63 IS - 3 SN - 0741-5400, 0741-5400 KW - Androstadienes KW - 0 KW - Antibodies, Monoclonal KW - Antigens, CD3 KW - Cytokines KW - Tumor Necrosis Factor-alpha KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - beta-N-Acetylhexosaminidases KW - EC 3.2.1.52 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - wortmannin KW - XVA4O219QW KW - Index Medicus KW - Coculture Techniques KW - Humans KW - Androstadienes -- pharmacology KW - Antibodies, Monoclonal -- pharmacology KW - Antigens, CD3 -- immunology KW - Bone Marrow Cells KW - beta-N-Acetylhexosaminidases -- metabolism KW - Kinetics KW - Histamine Release KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Adhesion -- drug effects KW - Time Factors KW - Phosphatidylinositol 3-Kinases -- antagonists & inhibitors KW - Antigens, CD3 -- physiology KW - Lymphocyte Activation KW - Mast Cells -- immunology KW - Cytokines -- biosynthesis KW - Cytoplasmic Granules -- immunology KW - Tumor Necrosis Factor-alpha -- biosynthesis KW - T-Lymphocytes -- immunology KW - Mast Cells -- drug effects KW - Cell Communication -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79717040?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+leukocyte+biology&rft.atitle=Activated+T+lymphocytes+induce+degranulation+and+cytokine+production+by+human+mast+cells+following+cell-to-cell+contact.&rft.au=Bhattacharyya%2C+S+P%3BDrucker%2C+I%3BReshef%2C+T%3BKirshenbaum%2C+A+S%3BMetcalfe%2C+D+D%3BMekori%2C+Y+A&rft.aulast=Bhattacharyya&rft.aufirst=S&rft.date=1998-03-01&rft.volume=63&rft.issue=3&rft.spage=337&rft.isbn=&rft.btitle=&rft.title=Journal+of+leukocyte+biology&rft.issn=07415400&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-24 N1 - Date created - 1998-03-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I/II study of the protease inhibitor ritonavir in children with human immunodeficiency virus infection. AN - 79707793; 9480994 AB - Ritonavir, a potent antiretroviral protease inhibitor, has been approved for the treatment of adults and children with human immunodeficiency virus (HIV) infection. In a phase I/II study, we assessed the safety, tolerability, and pharmacokinetic profile of the oral solution of ritonavir in HIV-infected children and studied the preliminary antiviral and clinical effects. HIV-infected children between 6 months and 18 years of age were eligible. Four dose levels of ritonavir oral solution (250, 300, 350, and 400 mg/m given every 12 hours) were evaluated in two age groups (2 years). Ritonavir was administered alone for the first 12 weeks and then in combination with zidovudine and/or didanosine. Clinical and laboratory parameters were monitored every 2 to 4 weeks. A total of 48 children (median age, 7.7 years; range, 0.5 to 14.4 years) were included in this analysis. Dose-related nausea, diarrhea, and abdominal pain were the most common toxicities and resulted in discontinuation of ritonavir in 7 children. Ritonavir was well absorbed at all dose levels, and plasma concentrations reached a peak 2 to 4 hours after a dose. CD4 cells counts increased by a median of 79 cells/mm3 after 4 weeks of monotherapy and were maintained throughout the study. Plasma HIV RNA decreased by 1 to 2 log10 copies/mL within 4 to 8 weeks of ritonavir monotherapy, and this level was sustained in patients enrolled at the highest dose level of 400 mg/m for the 24-week period. The oral solution of ritonavir has potent antiretroviral activity as a single agent and is relatively well tolerated by children when administered alone or in combination with zidovudine or didanosine. JF - Pediatrics AU - Mueller, B U AU - Nelson, R P AU - Sleasman, J AU - Zuckerman, J AU - Heath-Chiozzi, M AU - Steinberg, S M AU - Balis, F M AU - Brouwers, P AU - Hsu, A AU - Saulis, R AU - Sei, S AU - Wood, L V AU - Zeichner, S AU - Katz, T T AU - Higham, C AU - Aker, D AU - Edgerly, M AU - Jarosinski, P AU - Serchuck, L AU - Whitcup, S M AU - Pizzuti, D AU - Pizzo, P A AD - HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 335 EP - 343 VL - 101 IS - 3 Pt 1 SN - 0031-4005, 0031-4005 KW - Anti-HIV Agents KW - 0 KW - HIV Protease Inhibitors KW - Zidovudine KW - 4B9XT59T7S KW - Didanosine KW - K3GDH6OH08 KW - Ritonavir KW - O3J8G9O825 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Zidovudine -- therapeutic use KW - Administration, Oral KW - Humans KW - Child KW - CD4 Lymphocyte Count KW - Child, Preschool KW - Viral Load KW - Drug Therapy, Combination KW - Infant KW - Didanosine -- therapeutic use KW - Anti-HIV Agents -- therapeutic use KW - Adolescent KW - Female KW - Male KW - Ritonavir -- therapeutic use KW - Ritonavir -- pharmacokinetics KW - HIV Infections -- drug therapy KW - HIV Protease Inhibitors -- pharmacokinetics KW - HIV Protease Inhibitors -- therapeutic use KW - HIV Protease Inhibitors -- adverse effects KW - Ritonavir -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79707793?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatrics&rft.atitle=A+phase+I%2FII+study+of+the+protease+inhibitor+ritonavir+in+children+with+human+immunodeficiency+virus+infection.&rft.au=Mueller%2C+B+U%3BNelson%2C+R+P%3BSleasman%2C+J%3BZuckerman%2C+J%3BHeath-Chiozzi%2C+M%3BSteinberg%2C+S+M%3BBalis%2C+F+M%3BBrouwers%2C+P%3BHsu%2C+A%3BSaulis%2C+R%3BSei%2C+S%3BWood%2C+L+V%3BZeichner%2C+S%3BKatz%2C+T+T%3BHigham%2C+C%3BAker%2C+D%3BEdgerly%2C+M%3BJarosinski%2C+P%3BSerchuck%2C+L%3BWhitcup%2C+S+M%3BPizzuti%2C+D%3BPizzo%2C+P+A&rft.aulast=Mueller&rft.aufirst=B&rft.date=1998-03-01&rft.volume=101&rft.issue=3+Pt+1&rft.spage=335&rft.isbn=&rft.btitle=&rft.title=Pediatrics&rft.issn=00314005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-10 N1 - Date created - 1998-03-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Construction and characterization of a temperature-sensitive human immunodeficiency virus type 1 reverse transcriptase mutant. AN - 79697840; 9499059 AB - A temperature-sensitive (ts) human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) mutant was generated by charged-cluster-to-alanine mutagenesis. The mutant virus, containing three charged residues within the RT finger domain changed to alanine (K64A, K66A, and D67A), replicated normally at 34.5 but not 39.5 degrees C. Quantitating virus particle production by p24 antigen capture or virion-associated RT activity and virus infectivity by the MAGI cell assay, we found that (i) mutant virions produced at the permissive temperature were indistinguishable from wild-type virus in assays performed at the nonpermissive temperature, suggesting that the ts mutation did not impair early steps in the virus replication cycle and that the mutant RT enzyme was not ts; and (ii) virus particle production in cells transfected with the ts mutant at the nonpermissive temperature was comparable to that of wild-type virus. However, the particle-associated RT activity and infectivity of mutant virions produced at the nonpermissive temperature were greatly reduced when assays were conducted at the permissive temperature. These results are consistent with an irreversible ts event affecting RT that occurs during virus particle production. Radioimmunoprecipitation analyses revealed that both p66 and p51 RT subunits were absent from mutant virions generated at 39.5 degrees C. The presence of normal levels of HIV-1 integrase in mutant particles produced at the nonpermissive temperature was inconsistent with defective Gag-Pol synthesis or Gag-Pol incorporation into progeny virions. Furthermore, wild-type levels of the mutant Pr160(gag-pol) were detected in virions produced at the nonpermissive temperature when the HIV-1 protease was inactivated by site-specific mutagenesis. Taken together, these results are most consistent with a ts defect affecting the degradation or aberrant processing of the mutated RT during its processing/maturation within nascent particles. JF - Journal of virology AU - Huang, M AU - Zensen, R AU - Cho, M AU - Martin, M A AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 2047 EP - 2054 VL - 72 IS - 3 SN - 0022-538X, 0022-538X KW - Gene Products, gag KW - 0 KW - Protein Precursors KW - gag Gene Products, Human Immunodeficiency Virus KW - pol Gene Products, Human Immunodeficiency Virus KW - pr160 gag-pol precursor protein, Human immunodeficiency virus 1 KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - AIDS/HIV KW - Protein Precursors -- metabolism KW - HeLa Cells KW - Protein Precursors -- biosynthesis KW - Humans KW - Temperature KW - Gene Products, gag -- biosynthesis KW - Virion -- metabolism KW - Gene Products, gag -- metabolism KW - Cloning, Molecular KW - HIV Reverse Transcriptase -- genetics KW - HIV-1 -- genetics KW - Alanine -- metabolism KW - HIV Reverse Transcriptase -- metabolism KW - Alanine -- genetics KW - HIV-1 -- enzymology KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79697840?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Construction+and+characterization+of+a+temperature-sensitive+human+immunodeficiency+virus+type+1+reverse+transcriptase+mutant.&rft.au=Huang%2C+M%3BZensen%2C+R%3BCho%2C+M%3BMartin%2C+M+A&rft.aulast=Huang&rft.aufirst=M&rft.date=1998-03-01&rft.volume=72&rft.issue=3&rft.spage=2047&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-12 N1 - Date created - 1998-03-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Antimicrob Agents Chemother. 1993 Jun;37(6):1390-2 [8392313] Antimicrob Agents Chemother. 1993 Jun;37(6):1207-13 [8328771] Biochem Pharmacol. 1994 Jan 20;47(2):155-69 [7508227] J Virol. 1994 Apr;68(4):2503-12 [8139032] Proc Natl Acad Sci U S A. 1994 May 10;91(10):4554-8 [8183946] Antimicrob Agents Chemother. 1994 Feb;38(2):275-81 [7514855] Antimicrob Agents Chemother. 1994 Feb;38(2):282-7 [7514856] Proc Natl Acad Sci U S A. 1994 May 24;91(11):4882-6 [7515182] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7242-6 [7518928] Curr Opin Biotechnol. 1994 Aug;5(4):414-21 [7520785] J Virol. 1994 Oct;68(10):6782-6 [8084015] J Biol Chem. 1994 Oct 21;269(42):26472-8 [7523408] J Biol Chem. 1994 Nov 11;269(45):28091-7 [7525566] J Biol Chem. 1994 Nov 11;269(45):28118-22 [7525567] J Mol Biol. 1994 Oct 28;243(3):472-83 [7525967] J Virol. 1995 Jan;69(1):597-601 [7983762] Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1222-6 [7532306] Nucleic Acids Res. 1995 Mar 11;23(5):803-10 [7535923] J Virol. 1995 Nov;69(11):6810-8 [7474093] J Acquir Immune Defic Syndr Hum Retrovirol. 1995;10 Suppl 1:S28-33 [8595505] J Virol. 1996 Jun;70(6):3698-705 [8648704] J Biol Chem. 1996 Mar 1;271(9):4872-8 [8617758] J Biol Chem. 1996 May 24;271(21):12213-20 [8647817] Biochemistry. 1996 Jul 2;35(26):8553-62 [8679616] Science. 1986 Mar 14;231(4743):1289-91 [2418504] Nature. 1987 Jun 25-Jul 1;327(6124):716-7 [2439916] J Virol. 1988 Jan;62(1):139-47 [3257102] EMBO J. 1987 Oct;6(10):3133-7 [2446866] Methods Enzymol. 1987;154:367-82 [3323813] Proc Natl Acad Sci U S A. 1988 Feb;85(4):1218-22 [2448794] Proc Natl Acad Sci U S A. 1988 Dec;85(24):9580-4 [2849111] DNA. 1988 Jul-Aug;7(6):407-16 [2462482] Biochemistry. 1988 Dec 13;27(25):8884-9 [2466481] Proc Natl Acad Sci U S A. 1989 Jul;86(13):4803-7 [2472634] Nature. 1989 Aug 3;340(6232):397-400 [2666861] J Biol Chem. 1989 Aug 25;264(24):13975-8 [2474539] Biochem Biophys Res Commun. 1990 Mar 16;167(2):673-9 [1690991] J Biol Chem. 1990 Jun 5;265(16):8986-8 [1693146] AIDS Res Hum Retroviruses. 1990 Jun;6(6):753-64 [1694680] Proc Natl Acad Sci U S A. 1991 May 15;88(10):4498-502 [2034689] FEBS Lett. 1991 May 6;282(2):231-4 [1709876] Biochemistry. 1991 Jul 2;30(26):6351-6 [1711368] J Virol. 1991 Aug;65(8):4350-8 [2072454] Virology. 1991 Sep;184(1):319-29 [1871974] AIDS. 1991 Jun;5(6):639-54 [1883539] EMBO J. 1991 Dec;10(12):3905-11 [1718745] Virology. 1991 Dec;185(2):661-72 [1683726] J Virol. 1992 Feb;66(2):1031-9 [1370546] J Virol. 1992 Apr;66(4):2232-9 [1548759] Science. 1992 Jun 26;256(5065):1783-90 [1377403] J Virol. 1992 Nov;66(11):6304-13 [1383561] Genetics. 1992 Oct;132(2):337-50 [1427032] J Virol. 1992 Dec;66(12):7533-7 [1279205] J Virol. 1993 Apr;67(4):2266-75 [8445731] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6320-4 [7687065] J Virol. 1994 Feb;68(2):863-76 [8289389] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - CD4 glycoprotein degradation induced by human immunodeficiency virus type 1 Vpu protein requires the function of proteasomes and the ubiquitin-conjugating pathway. AN - 79696543; 9499087 AB - The human immunodeficiency virus type 1 (HIV-1) vpu gene encodes a type I anchored integral membrane phosphoprotein with two independent functions. First, it regulates virus release from a post-endoplasmic reticulum (ER) compartment by an ion channel activity mediated by its transmembrane anchor. Second, it induces the selective down regulation of host cell receptor proteins (CD4 and major histocompatibility complex class I molecules) in a process involving its phosphorylated cytoplasmic tail. In the present work, we show that the Vpu-induced proteolysis of nascent CD4 can be completely blocked by peptide aldehydes that act as competitive inhibitors of proteasome function and also by lactacystin, which blocks proteasome activity by covalently binding to the catalytic beta subunits of proteasomes. The sensitivity of Vpu-induced CD4 degradation to proteasome inhibitors paralleled the inhibition of proteasome degradation of a model ubiquitinated substrate. Characterization of CD4-associated oligosaccharides indicated that CD4 rescued from Vpu-induced degradation by proteasome inhibitors is exported from the ER to the Golgi complex. This finding suggests that retranslocation of CD4 from the ER to the cytosol may be coupled to its proteasomal degradation. CD4 degradation mediated by Vpu does not require the ER chaperone calnexin and is dependent on an intact ubiquitin-conjugating system. This was demonstrated by inhibition of CD4 degradation (i) in cells expressing a thermally inactivated form of the ubiquitin-activating enzyme E1 or (ii) following expression of a mutant form of ubiquitin (Lys48 mutated to Arg48) known to compromise ubiquitin targeting by interfering with the formation of polyubiquitin complexes. CD4 degradation was also prevented by altering the four Lys residues in its cytosolic domain to Arg, suggesting a role for ubiquitination of one or more of these residues in the process of degradation. The results clearly demonstrate a role for the cytosolic ubiquitin-proteasome pathway in the process of Vpu-induced CD4 degradation. In contrast to other viral proteins (human cytomegalovirus US2 and US11), however, whose translocation of host ER molecules into the cytosol occurs in the presence of proteasome inhibitors, Vpu-targeted CD4 remains in the ER in a transport-competent form when proteasome activity is blocked. JF - Journal of virology AU - Schubert, U AU - Antón, L C AU - Bacík, I AU - Cox, J H AU - Bour, S AU - Bennink, J R AU - Orlowski, M AU - Strebel, K AU - Yewdell, J W AD - Laboratories of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-0440, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 2280 EP - 2288 VL - 72 IS - 3 SN - 0022-538X, 0022-538X KW - Antigens, CD4 KW - 0 KW - Calcium-Binding Proteins KW - Cysteine Proteinase Inhibitors KW - Glycoproteins KW - Human Immunodeficiency Virus Proteins KW - Leupeptins KW - Multienzyme Complexes KW - Ubiquitins KW - Viral Regulatory and Accessory Proteins KW - vpu protein, Human immunodeficiency virus 1 KW - lactacystin KW - 133343-34-7 KW - Calnexin KW - 139873-08-8 KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - benzyloxycarbonylleucyl-leucyl-leucine aldehyde KW - RF1P63GW3K KW - Acetylcysteine KW - WYQ7N0BPYC KW - Index Medicus KW - AIDS/HIV KW - Cytosol -- metabolism KW - Acetylcysteine -- analogs & derivatives KW - Enzyme Activation KW - HeLa Cells KW - Humans KW - Acetylcysteine -- pharmacology KW - Mutagenesis KW - Cysteine Proteinase Inhibitors -- pharmacology KW - Leupeptins -- pharmacology KW - Cytoplasm KW - Calcium-Binding Proteins -- genetics KW - Calcium-Binding Proteins -- metabolism KW - Cell Line KW - Multienzyme Complexes -- metabolism KW - HIV-1 -- metabolism KW - Ubiquitins -- metabolism KW - Glycoproteins -- metabolism KW - Cysteine Endopeptidases -- metabolism KW - Antigens, CD4 -- genetics KW - Viral Regulatory and Accessory Proteins -- metabolism KW - Glycoproteins -- genetics KW - Viral Regulatory and Accessory Proteins -- genetics KW - Antigens, CD4 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79696543?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=CD4+glycoprotein+degradation+induced+by+human+immunodeficiency+virus+type+1+Vpu+protein+requires+the+function+of+proteasomes+and+the+ubiquitin-conjugating+pathway.&rft.au=Schubert%2C+U%3BAnt%C3%B3n%2C+L+C%3BBac%C3%ADk%2C+I%3BCox%2C+J+H%3BBour%2C+S%3BBennink%2C+J+R%3BOrlowski%2C+M%3BStrebel%2C+K%3BYewdell%2C+J+W&rft.aulast=Schubert&rft.aufirst=U&rft.date=1998-03-01&rft.volume=72&rft.issue=3&rft.spage=2280&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-12 N1 - Date created - 1998-03-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Immunol. 1997 Jul 15;159(2):554-64 [9218569] J Immunol. 1985 Feb;134(2):971-6 [3871222] Proc Natl Acad Sci U S A. 1985 Jul;82(13):4539-43 [2989831] Mol Cell Biol. 1985 Dec;5(12):3403-9 [3939316] J Biol Chem. 1987 Mar 15;262(8):3524-7 [3029116] Nature. 1988 Jan 7;331(6151):82-4 [3257544] Nature. 1988 Aug 11;334(6182):532-4 [3043230] Science. 1988 Sep 2;241(4870):1221-3 [3261888] J Virol. 1989 Sep;63(9):3784-91 [2788224] J Virol. 1996 Feb;70(2):809-19 [8551619] Curr Top Microbiol Immunol. 1996;205:19-46 [8575196] Cell. 1996 Mar 8;84(5):769-79 [8625414] J Cell Biol. 1996 Feb;132(3):291-8 [8636208] Biochem J. 1996 Jun 1;316 ( Pt 2):401-7 [8687380] J Biochem. 1996 Mar;119(3):572-6 [8830056] Int J Pept Protein Res. 1996 Apr;47(4):297-310 [8738656] Immunity. 1996 Aug;5(2):103-14 [8769474] Science. 1996 Sep 20;273(5282):1725-8 [8781238] J Virol. 1996 Oct;70(10):7108-15 [8794357] J Biol Chem. 1996 Sep 13;271(37):22791-5 [8798455] Annu Rev Genet. 1995;29:729-54 [8825492] J Biol Chem. 1996 Nov 1;271(44):27280-4 [8910302] J Exp Med. 1988 Oct 1;168(4):1211-24 [2459295] J Virol. 1990 Feb;64(2):621-9 [2404139] Nature. 1990 Jun 14;345(6276):625-8 [2190096] EMBO J. 1990 Sep;9(9):2923-9 [2390975] J Virol. 1990 Nov;64(11):5585-93 [2214026] J Virol. 1991 Dec;65(12):6387-96 [1942241] J Virol. 1992 Jan;66(1):226-34 [1727486] Virology. 1992 Jan;186(1):261-73 [1370128] J Biol Chem. 1992 Feb 15;267(5):3268-73 [1737783] Eur J Biochem. 1992 Mar 1;204(2):875-83 [1541298] Cell. 1992 May 29;69(5):725-35 [1317266] Biochemistry. 1992 Oct 6;31(39):9421-8 [1356435] J Virol. 1992 Dec;66(12):7193-200 [1433512] Cell. 1992 Dec 11;71(6):963-72 [1333889] Biochemistry. 1993 Feb 16;32(6):1563-72 [8431436] Virology. 1993 Mar;193(1):483-91 [8438583] J Virol. 1993 Jul;67(7):3877-84 [8510209] J Virol. 1993 Aug;67(8):5056-61 [8331740] J Virol. 1993 Dec;67(12):7238-45 [8230446] J Mol Biol. 1994 Feb 11;236(1):16-25 [8107101] Cell. 1994 Mar 11;76(5):853-64 [8124721] J Biol Chem. 1994 Mar 11;269(10):7514-9 [8125971] J Virol. 1994 Apr;68(4):2260-71 [8139011] J Virol. 1994 May;68(5):3092-101 [8151774] J Biol Chem. 1994 Apr 29;269(17):12784-8 [7513695] Trends Biochem Sci. 1994 Mar;19(3):124-8 [8203019] Mol Cell Biol. 1994 Aug;14(8):5501-9 [8035826] Virology. 1994 Oct;204(1):482-6 [8091684] J Immunol. 1995 Jan 15;154(2):511-9 [7814864] J Virol. 1995 Mar;69(3):1510-20 [7853484] Science. 1995 May 5;268(5211):726-31 [7732382] Int J Pept Protein Res. 1995 Jan;45(1):35-43 [7775007] Cell. 1995 Jul 28;82(2):189-92 [7628010] Cell. 1995 Oct 6;83(1):121-7 [7553863] Cell. 1995 Oct 6;83(1):129-35 [7553864] J Virol. 1995 Dec;69(12):7699-711 [7494279] J Biol Chem. 1982 Sep 25;257(18):10766-9 [6955305] Nature. 1996 Dec 5;384(6608):432-8 [8945469] FEBS Lett. 1996 Nov 25;398(1):12-8 [8946945] J Gen Virol. 1997 Mar;78 ( Pt 3):619-25 [9049413] Virology. 1997 Mar 3;229(1):1-11 [9123850] J Exp Med. 1997 Apr 7;185(7):1295-305 [9104816] J Biol Chem. 1997 May 2;272(18):11824-31 [9115240] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Three amino acid substitutions in the L protein of the human parainfluenza virus type 3 cp45 live attenuated vaccine candidate contribute to its temperature-sensitive and attenuation phenotypes. AN - 79694258; 9499025 AB - Studies were initiated to define the genetic basis of the temperature-sensitive (ts), cold adaptation (ca), and attenuation (att) phenotypes of the human parainfluenza virus type 3 (PIV3) cp45 live attenuated vaccine candidate. Genetic data had previously suggested that the L polymerase protein of cp45, which contains three amino acid substitutions at positions 942, 992, and 1558, contributed to its temperature sensitivity (R. Ray, M. S. Galinski, B. R. Heminway, K. Meyer, F. K. Newman, and R. B. Belshe, J. Virol. 70:580-584, 1996; A. Stokes, E. L. Tierney, C. M. Sarris, B. R. Murphy, and S. L. Hall, Virus Res. 30:43-52, 1993). To study the individual and aggregate contributions that these amino acid substitutions make to the ts, att, and ca phenotypes of cp45, seven PIV3 recombinant viruses (three single, three double, and one triple mutant) representing all possible combinations of the three amino acid substitutions were recovered from full-length antigenomic cDNA and analyzed for their ts, att, and ca phenotypes. None of the seven mutant recombinant PIVs was cold adapted. The substitutions at L protein amino acid positions 992 and 1558 each specified a 105-fold reduction in plaque formation in cell culture at 40 degrees C, whereas the substitution at position 942 specified a 300-fold reduction. Thus, each of the three mutations contributes individually to the ts phenotype. The triple recombinant which possesses an L protein with all three mutations was almost as temperature sensitive as cp45, indicating that these mutations are the major contributors to the ts phenotype of cp45. The three individual mutations in the L protein each contributed to restricted replication in the upper or lower respiratory tract of hamsters, and this likely contributes to the observed stability of the ts and att phenotypes of cp45 during replication in vivo. Importantly, the recombinant virus possessing L protein with all three mutations was as restricted in replication as was the cp45 mutant in both the upper and lower respiratory tracts of hamsters, indicating that the L gene of the cp45 virus is a major attenuating component of this candidate vaccine. JF - Journal of virology AU - Skiadopoulos, M H AU - Durbin, A P AU - Tatem, J M AU - Wu, S L AU - Paschalis, M AU - Tao, T AU - Collins, P L AU - Murphy, B R AD - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland 20892, USA. mskiadopoulos@atlas.niaid.nih.gov Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 1762 EP - 1768 VL - 72 IS - 3 SN - 0022-538X, 0022-538X KW - Vaccines, Attenuated KW - 0 KW - Viral Proteins KW - Viral Vaccines KW - parainfluenza 3 virus, L Protein KW - DNA-Directed RNA Polymerases KW - EC 2.7.7.6 KW - Index Medicus KW - Phenotype KW - Mutagenesis, Site-Directed KW - Animals KW - Viral Plaque Assay KW - Tumor Cells, Cultured KW - Humans KW - Temperature KW - Mesocricetus KW - Macaca mulatta KW - Cell Line KW - Cricetinae KW - Viral Proteins -- genetics KW - Parainfluenza Virus 3, Human -- growth & development KW - Parainfluenza Virus 3, Human -- genetics KW - DNA-Directed RNA Polymerases -- metabolism KW - Viral Proteins -- metabolism KW - Parainfluenza Virus 3, Human -- enzymology KW - DNA-Directed RNA Polymerases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79694258?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Three+amino+acid+substitutions+in+the+L+protein+of+the+human+parainfluenza+virus+type+3+cp45+live+attenuated+vaccine+candidate+contribute+to+its+temperature-sensitive+and+attenuation+phenotypes.&rft.au=Skiadopoulos%2C+M+H%3BDurbin%2C+A+P%3BTatem%2C+J+M%3BWu%2C+S+L%3BPaschalis%2C+M%3BTao%2C+T%3BCollins%2C+P+L%3BMurphy%2C+B+R&rft.aulast=Skiadopoulos&rft.aufirst=M&rft.date=1998-03-01&rft.volume=72&rft.issue=3&rft.spage=1762&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-12 N1 - Date created - 1998-03-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1998 Apr;72(4):2955-61 [9525616] J Virol. 1997 Dec;71(12):8973-82 [9371553] J Med Virol. 1984;13(3):243-9 [6327899] Proc Natl Acad Sci U S A. 1986 Nov;83(21):8122-6 [3095828] J Virol. 1988 Feb;62(2):488-95 [3336068] Virology. 1988 Jun;164(2):487-97 [2835864] Virology. 1988 Aug;165(2):499-510 [2841798] Vaccine. 1990 Oct;8(5):497-502 [2251875] J Virol Methods. 1991 Feb-Mar;31(2-3):161-70 [1650782] Virus Res. 1992 Mar;22(3):173-84 [1320790] Virology. 1992 Nov;191(1):506-10 [1413525] Virus Res. 1992 Sep 1;25(1-2):91-103 [1329377] J Infect Dis. 1993 Apr;167(4):958-62 [8383726] Virology. 1993 Apr;193(2):786-93 [8384756] Virus Res. 1993 Oct;30(1):43-52 [8266719] EMBO J. 1994 Sep 15;13(18):4195-203 [7925265] J Infect Dis. 1995 May;171(5):1107-14 [7751684] Proc Natl Acad Sci U S A. 1995 May 9;92(10):4477-81 [7753828] Virology. 1995 Jun 20;210(1):202-5 [7793072] Virology. 1995 Aug 20;211(2):577-82 [7645261] J Virol. 1995 Oct;69(10):5969-77 [7666501] J Infect Dis. 1995 Dec;172(6):1445-50 [7594701] J Virol. 1996 Jan;70(1):580-4 [8523574] Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11563-7 [8524804] EMBO J. 1995 Dec 1;14(23):5773-84 [8846771] EMBO J. 1995 Dec 15;14(24):6087-94 [8557028] Virology. 1996 Nov 15;225(2):419-22 [8918930] Virus Genes. 1996;13(3):269-73 [9035372] Genes Cells. 1996 Jun;1(6):569-79 [9078386] J Virol. 1997 Jun;71(6):4272-7 [9151814] J Virol. 1997 Aug;71(8):5814-9 [9223470] Virology. 1997 Jul 21;234(1):74-83 [9234948] Virology. 1997 Sep 1;235(2):323-32 [9281512] J Med Virol. 1982;10(4):235-42 [6298358] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacological therapy. AN - 79619242; 10872480 AB - Collectively sickle cell disease and beta-thalassaemia are the most commonly inherited single-gene defects world-wide and were the first group of diseases for which DNA-based detection strategies were utilized. Although genotypically distinct, these two groups of diseases exhibit several common clinical features: moderate-to-severe haemolytic anaemia, acute and progressive tissue damage, disease- or treatment-related organ failure and premature death. Within the last two decades, a striking improvement in life expectancy in the two patient populations has been observed, by dint of primary and secondary prevention strategies. However, apart from bone marrow transplantation, a generally applicable, specific and non-toxic form of treatment remains unavailable for these disorders. Nonetheless, a greater appreciation of the developmental control of human globin gene expression coupled with observations of the effects of certain classes of agents to 'reverse' erythroid cellular phenotype in in vitro and animal models have led to pharmacological trials to obtain meaningful increases in haemoglobin F production in patients affected by these two severe beta-globin disorders. Contemporary understanding of the quantitative relationship between the abnormal molecules in the red cells (aggregates of sickle haemoglobin) in the sickle cell syndromes and aggregated alpha-globin polypeptides in the beta-thalassemia syndromes, and the extent of the red cell and/or organ involvement, has now enabled investigators to predict how much inhibition of these intracellular pathogenic processes might be necessary to achieve partial or total abrogation of disease manifestations. The results of the Multicenter Study of Hydroxyurea and other controlled trials now bear out these predictions. JF - Bailliere's clinical haematology AU - Rodgers, G P AD - Molecular and Clinical Hematology Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1822, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 239 EP - 255 VL - 11 IS - 1 SN - 0950-3536, 0950-3536 KW - Antisickling Agents KW - 0 KW - Fatty Acids KW - Fetal Hemoglobin KW - 9034-63-3 KW - Hydroxyurea KW - X6Q56QN5QC KW - Index Medicus KW - Multicenter Studies as Topic KW - Animals KW - Randomized Controlled Trials as Topic KW - Antisickling Agents -- therapeutic use KW - Fetal Hemoglobin -- physiology KW - Humans KW - Hydroxyurea -- therapeutic use KW - Fetal Hemoglobin -- biosynthesis KW - Child KW - Fatty Acids -- therapeutic use KW - Anemia, Sickle Cell -- drug therapy KW - beta-Thalassemia -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79619242?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bailliere%27s+clinical+haematology&rft.atitle=Pharmacological+therapy.&rft.au=Rodgers%2C+G+P&rft.aulast=Rodgers&rft.aufirst=G&rft.date=1998-03-01&rft.volume=11&rft.issue=1&rft.spage=239&rft.isbn=&rft.btitle=&rft.title=Bailliere%27s+clinical+haematology&rft.issn=09503536&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-14 N1 - Date created - 2000-07-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The incidence of Listeria spp., Salmonella spp., and Clostridium botulinum in smoked fish and shellfish. AN - 73834347; 9708303 AB - The frequency of occurrence of Listeria spp., Salmonella spp., and Clostridium botulinum is samples of smoked finfish and smoked shellfish was analyzed over a 5-year period. Listeria monocytogenes were isolated from 14% of 1,080 samples. For those samples where the smoke process was known, the incidence of L. monocytogenes was higher in cold-smoked than hot-smoked products (51 of 240 cold-smoked compared to 19 of 215 hot-smoked products). Listeria species other than L. monocytogenes were also detected (in 7.2% of cold-smoked and 3.8% of hot-smoked products). The time and temperature smoke processing guidelines are reviewed for a few state authorities. L. monocytogenes was isolated from 15.2% of the 559 samples of foreign origin. There were four countries for which more than 70 samples were analyzed: Canada, Norway, the Philippines, and the United Kingdom. The occurrence of L. monocytogenes in samples from these four countries was 14.3%, 23.7%, 0%, and 16.1%, respectively. The 521 samples originating in the United States were processed by 194 plants. Thirty-seven plants in 13 states produced contaminated product. Salmonella species were isolated from 5 (3.2%) of 156 samples tested for this organism. All positive samples were of foreign origin (4 from the Philippines and 1 from the United Kingdom). No C. botulinum spores were detected in any of the 201 vacuum-packed samples tested for this organism. JF - Journal of food protection AU - Heinitz, M L AU - Johnson, J M AD - U.S. Food and Drug Administration, Minneapolis, Minnesota 55401-1999, USA. gvl@cu.nih.gov Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 318 EP - 323 VL - 61 IS - 3 SN - 0362-028X, 0362-028X KW - Index Medicus KW - Fishes -- microbiology KW - Animals KW - Food Microbiology KW - Cooking -- methods KW - Food Preservation KW - Shellfish -- microbiology KW - Fish Products -- microbiology KW - Salmonella -- isolation & purification KW - Clostridium botulinum -- isolation & purification KW - Listeria -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73834347?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+food+protection&rft.atitle=The+incidence+of+Listeria+spp.%2C+Salmonella+spp.%2C+and+Clostridium+botulinum+in+smoked+fish+and+shellfish.&rft.au=Heinitz%2C+M+L%3BJohnson%2C+J+M&rft.aulast=Heinitz&rft.aufirst=M&rft.date=1998-03-01&rft.volume=61&rft.issue=3&rft.spage=318&rft.isbn=&rft.btitle=&rft.title=Journal+of+food+protection&rft.issn=0362028X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-10 N1 - Date created - 1998-09-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Topical liposome-encapsulated FK506 for the treatment of endotoxin-induced uveitis. AN - 70029206; 9798194 AB - Liposome preparations of FK506 improve the penetration of topically administered drug into the aqueous humor. The purpose of the experiment was to compare topically administered highdose oil-dissolved FK506 (OD-FK506) and low-dose liposome-bound FK506 (LB-506) for the treatment of endotoxin-induced uveitis (EIU). Endotoxin-induced uveitis was produced in female Lewis rats with Salmonella typhimurium endotoxin. Four hours prior to endotoxin injection, one eye received 20 mul eyedrops every four hours containing either high-dose OD-FK506 at 3 mg/ml (N = 20), low-dose LB-FK506 at 0.16 mg/ml (N = 19), prednisolone acetate 1% (N = 20), or empty liposomes (N = 20). Eyes were enucleated 24 hours after endotoxin injection and inflammatory cells were counted on histologic sections by two masked observers. The mean number of infiltrating inflammatory cells per section +/- S.E.M. was 127.8 +/- 20.1, 76.8 +/- 16.7, 75.0 +/- 19.1, and 3.6 +/- 0.4 for animals treated with empty liposomes, LB-FK506, OD-FK506, and prednisolone acetate, respectively. The difference in inflammation between the empty liposome controls and the LB-FK506- and OD-FK506-treated animals was statistically significant (p = 0.03 and p = 0.02, respectively). The difference in inflammation between the high-dose OD-FK506- and low-dose LB-FK506-treated animals was not statistically significant (0 = 0.94). In this study, low-dose LB-FK506 and high-dose (OD-FK506) were both effective in inhibiting EIU. Higher concentrations of LB-FK506 are being developed and should augment the therapeutic effect of topical FK506. JF - Ocular immunology and inflammation AU - Whitcup, S M AU - Pleyer, U AU - Lai, J C AU - Lutz, S AU - Mochizuki, M AU - Chan, C C AD - National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1863, USA. Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 51 EP - 56 VL - 6 IS - 1 SN - 0927-3948, 0927-3948 KW - Drug Carriers KW - 0 KW - Endotoxins KW - Immunosuppressive Agents KW - Liposomes KW - Tacrolimus KW - WM0HAQ4WNM KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred Lew KW - Dose-Response Relationship, Drug KW - Female KW - Administration, Topical KW - Uveitis -- pathology KW - Tacrolimus -- therapeutic use KW - Tacrolimus -- administration & dosage KW - Immunosuppressive Agents -- therapeutic use KW - Uveitis -- drug therapy KW - Uveitis -- chemically induced KW - Immunosuppressive Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70029206?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ocular+immunology+and+inflammation&rft.atitle=Topical+liposome-encapsulated+FK506+for+the+treatment+of+endotoxin-induced+uveitis.&rft.au=Whitcup%2C+S+M%3BPleyer%2C+U%3BLai%2C+J+C%3BLutz%2C+S%3BMochizuki%2C+M%3BChan%2C+C+C&rft.aulast=Whitcup&rft.aufirst=S&rft.date=1998-03-01&rft.volume=6&rft.issue=1&rft.spage=51&rft.isbn=&rft.btitle=&rft.title=Ocular+immunology+and+inflammation&rft.issn=09273948&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-29 N1 - Date created - 1999-01-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Crystallization and preliminary X-ray analysis of tetanus neurotoxin C fragment. AN - 69953381; 9761892 AB - Two crystal forms of recombinant tetanus neurotoxin C fragment have been obtained. The C fragment corresponds to the C-terminal 451 amino-acid residues of tetanus neurotoxin and is the subunit responsible for receptor binding by the toxin. Both forms belong to space group P212121. Form I has unit-cell dimensions of a = 71.3, b = 79.7, c = 94.0 A and produces thin plate crystals. Form II has unit-cell dimensions of a = 67.4, b = 79.7, c = 91.1 A and produces thick rod-shaped crystals. Diffraction data to 2.6 A have been collected from form II crystals. JF - Acta crystallographica. Section D, Biological crystallography AU - Umland, T C AU - Wingert, L AU - Swaminathan, S AU - Schmidt, J J AU - Sax, M AD - Biocrystallography Laboratory, PO Box 12055, VA Medical Center, Pittsburgh, PA 15240, USA. umland@vger.niddk.nih.gov Y1 - 1998/03/01/ PY - 1998 DA - 1998 Mar 01 SP - 273 EP - 275 VL - 54 SN - 0907-4449, 0907-4449 KW - Peptide Fragments KW - 0 KW - Recombinant Proteins KW - Tetanus Toxin KW - tetanospasmin KW - 11032-48-7 KW - Metalloendopeptidases KW - EC 3.4.24.- KW - Index Medicus KW - Crystallization KW - Recombinant Proteins -- isolation & purification KW - Crystallography, X-Ray KW - Recombinant Proteins -- chemistry KW - Tetanus Toxin -- isolation & purification KW - Peptide Fragments -- chemistry KW - Peptide Fragments -- isolation & purification KW - Tetanus Toxin -- chemistry KW - Metalloendopeptidases -- isolation & purification KW - Metalloendopeptidases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69953381?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Acta+crystallographica.+Section+D%2C+Biological+crystallography&rft.atitle=Crystallization+and+preliminary+X-ray+analysis+of+tetanus+neurotoxin+C+fragment.&rft.au=Umland%2C+T+C%3BWingert%2C+L%3BSwaminathan%2C+S%3BSchmidt%2C+J+J%3BSax%2C+M&rft.aulast=Umland&rft.aufirst=T&rft.date=1998-03-01&rft.volume=54&rft.issue=&rft.spage=273&rft.isbn=&rft.btitle=&rft.title=Acta+crystallographica.+Section+D%2C+Biological+crystallography&rft.issn=09074449&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-11-18 N1 - Date created - 1998-11-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - JC virus type 2B is found more frequently in brain tissue of progressive multifocal leukoencephalopathy patients than in urine from controls. AN - 69194123; 10195243 AB - Previous studies have shown that strains of human polyomavirus JC (JCV) of Asian origin (type 2) are much more highly represented in progressive multifocal leukoencephalopathy (PML) brain than would be expected from their frequency of excretion in urine samples of a comparable control group. The present studies were designed to test whether one subtype of type 2 was preferentially elevated. The statistical relation between JCV subtypes represented in PML brain tissue from 51 probands and those in urine samples from 115 control individuals was examined. The proportion of the JCV subtype 2B in PML brain (36%) was highly significantly increased relative to its occurrence in control urine samples (5.9%; P < .001). Type 1 and its subtypes were not different in the PML brain and control urine cohorts. The number of type 4 strains in PML brains was reduced, although the difference did not reach statistical significance (P = .08). The results predict that the human immunodeficiency virus (HIV)-positive individuals at highest risk of PML infection are those carrying the JCV genotype known as type 2B. Prospective studies will be required to confirm this finding. JF - Journal of human virology AU - Agostini, H T AU - Ryschkewitsch, C F AU - Singer, E J AU - Baumhefner, R W AU - Stoner, G L AD - Neurotoxicology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1998 SP - 200 EP - 206 VL - 1 IS - 3 SN - 1090-9508, 1090-9508 KW - Index Medicus KW - AIDS/HIV KW - Genotype KW - California KW - HIV Seropositivity KW - Humans KW - Cohort Studies KW - Adult KW - Maryland KW - Pennsylvania KW - HIV Seronegativity KW - Male KW - Female KW - Leukoencephalopathy, Progressive Multifocal -- virology KW - JC Virus -- genetics KW - Urine -- virology KW - Brain -- virology KW - JC Virus -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69194123?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+human+virology&rft.atitle=JC+virus+type+2B+is+found+more+frequently+in+brain+tissue+of+progressive+multifocal+leukoencephalopathy+patients+than+in+urine+from+controls.&rft.au=Agostini%2C+H+T%3BRyschkewitsch%2C+C+F%3BSinger%2C+E+J%3BBaumhefner%2C+R+W%3BStoner%2C+G+L&rft.aulast=Agostini&rft.aufirst=H&rft.date=1998-03-01&rft.volume=1&rft.issue=3&rft.spage=200&rft.isbn=&rft.btitle=&rft.title=Journal+of+human+virology&rft.issn=10909508&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-06 N1 - Date created - 1999-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Why Reading Is Not a Natural Process AN - 58369765; 9900668 AB - The National Institute of Child Health & Human Development's research program on reading development; the roles of phonemic awareness, automaticity, & understanding in developing reading skills; & current refutations to the assertion that reading is a natural process are examined. Although phonemic awareness is necessary for children's development of reading skills, it is contended that acquisition of automaticity in decoding & word recognition is essential for reading comprehension. The findings of contemporary studies that challenge traditional interpretations of instruction in phonemic awareness & reading strategies as unnecessary are reported. In addition to findings that indicate that underdeveloped phonemic & grammatical skills obstruct children's development of reading skills, research has also shown that deficient development of phonemic awareness negatively affects reading acquisition. It is concluded that teachers' confidence in contemporary research is integral to the improvement of reading skills instruction. 13 References. J. W. Parker JF - Educational Leadership AU - Lyon, G Reid AD - National Instit Child Health & Human Development National Instits Health US Dept Health & Human Services, Bldg 6100 Room 4B05 9000 Rockville Pike Bethesda MD 20892 lyonr@exchange.NIH.gov Y1 - 1998/03// PY - 1998 DA - March 1998 SP - 14 EP - 18 VL - 55 IS - 6 SN - 0013-1784, 0013-1784 KW - Phonological Awareness (64970) KW - Reading Instruction (70950) KW - Reading Acquisition (70650) KW - Decoding (Reading) (17600) KW - Word Recognition (98200) KW - article KW - 4116: applied linguistics; reading readiness/acquisition UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/58369765?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Allba&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Educational+Leadership&rft.atitle=Why+Reading+Is+Not+a+Natural+Process&rft.au=Lyon%2C+G+Reid&rft.aulast=Lyon&rft.aufirst=G&rft.date=1998-03-01&rft.volume=55&rft.issue=6&rft.spage=14&rft.isbn=&rft.btitle=&rft.title=Educational+Leadership&rft.issn=00131784&rft_id=info:doi/ LA - English DB - Linguistics and Language Behavior Abstracts (LLBA) N1 - Date revised - 2003-10-01 N1 - Last updated - 2016-09-27 N1 - CODEN - EDLEAW N1 - SubjectsTermNotLitGenreText - Reading Acquisition (70650); Decoding (Reading) (17600); Word Recognition (98200); Phonological Awareness (64970); Reading Instruction (70950) ER - TY - JOUR T1 - Emerging targets for the development of novel antifungal therapeutics AN - 17568495; 4323309 AB - Invasive mycoses have become important causes of morbidity and mortality in immunocompromised patients. New approaches for antifungal therapy are required to meet the challenges imposed by these life-threatening infections. Such approaches are being developed through identification of novel biochemical and molecular targets of pathogenic fungi. JF - Trends in Microbiology AU - Groll, AH AU - De Lucca, AJ AU - Walsh, T J AD - Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, NIH, Bethesda, MD, USA, twalsh@pbmac.nci.nih.gov Y1 - 1998/03// PY - 1998 DA - Mar 1998 SP - 117 EP - 124 VL - 6 IS - 3 SN - 0966-842X, 0966-842X KW - drug targets KW - Microbiology Abstracts A: Industrial & Applied Microbiology KW - Antifungal agents KW - Reviews KW - A 01067:Antifungal & fungicidal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17568495?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+Microbiology&rft.atitle=Emerging+targets+for+the+development+of+novel+antifungal+therapeutics&rft.au=Groll%2C+AH%3BDe+Lucca%2C+AJ%3BWalsh%2C+T+J&rft.aulast=Groll&rft.aufirst=AH&rft.date=1998-03-01&rft.volume=6&rft.issue=3&rft.spage=117&rft.isbn=&rft.btitle=&rft.title=Trends+in+Microbiology&rft.issn=0966842X&rft_id=info:doi/10.1016%2FS0966-842X%2897%2901206-7 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Antifungal agents; Reviews DO - http://dx.doi.org/10.1016/S0966-842X(97)01206-7 ER - TY - JOUR T1 - Occupational infection with hepatitis B virus--waging war against an insidious, intractable, intolerable foe AN - 16528160; 4367595 AB - The potential for occupational transmission of bloodborne hepatitis was first identified in the 1940s. The discovery of hepatitis B surface antigen (HBsAg) led to the development of sensitive, specific serological tests for hepatitis B virus infection and immunity and ultimately permitted the characterization of hepatitis B as an important cause of bloodborne hepatitis. Elucidation of the seroepidemiology of hepatitis B virus infection also facilitated quantitation of the magnitude of occupational risk for health care workers contributed by this bloodborne pathogen, and it clearly associated the occupational risk with exposure to blood. JF - Clinical Infectious Diseases AU - Hendersn, D K AD - Warren G. Magnuson Clinical Center, Building 10, Room 2C146, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 1998/03// PY - 1998 DA - Mar 1998 SP - 572 EP - 574 VL - 26 IS - 3 SN - 1058-4838, 1058-4838 KW - disease transmission KW - hepatitis B KW - man KW - Health & Safety Science Abstracts; Virology & AIDS Abstracts KW - H 1000:Occupational Safety and Health KW - V 22122:Symptomatology, pathology & etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16528160?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Infectious+Diseases&rft.atitle=Occupational+infection+with+hepatitis+B+virus--waging+war+against+an+insidious%2C+intractable%2C+intolerable+foe&rft.au=Hendersn%2C+D+K&rft.aulast=Hendersn&rft.aufirst=D&rft.date=1998-03-01&rft.volume=26&rft.issue=3&rft.spage=572&rft.isbn=&rft.btitle=&rft.title=Clinical+Infectious+Diseases&rft.issn=10584838&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Mechanisms involved in the intrinsic isoniazid resistance of Mycobacterium avium AN - 16512098; 4298668 AB - Isoniazid (INH), which acts by inhibiting mycolic acid biosynthesis, is very potent against the tuberculous mycobacteria. It is about 100-fold less effective against Mycobacterium avium. This difference has often been attributed to a decreased permeability of the cell wall. We measured the rate of conversion of radiolabelled INH to 4-pyridylmethanol by whole cells and cell-free extracts and estimated the permeability barrier imposed by the cell wall to INH influx in Mycobacterium tuberculosis and M. avium. There was no significant difference in the relative permeability to INH between these two species. However, the total conversion rate in M. tuberculosis was found to be four times greater. Examination of in vitro-generated mutants revealed that the major resistance mechanism for both species is loss of the catalase-peroxidase KatG. Analysis of lipid and protein biosynthetic profiles demonstrated that the molecular target of activated INH was identical for both species. M. avium, however, formed colonies at INH concentrations inhibitory for mycolic acid biosynthesis. These mycolate-deficient M. avium exhibited altered colony morphologies, modified cell wall ultrastructure and were 10-fold more sensitive to treatment with hydrophobic antibiotics, such as rifampin. These findings may significantly impact the design of new therapeutic regimens for the treatment of infections with atypical mycobacteria. JF - Molecular Microbiology AU - Mdluli, K AU - Swanson, J AU - Fischer, E AU - Lee, R E AU - Barry, CE III AD - Tuberculosis Research Unit, National Institutes of Health, National Institutes for Allergy and Infectious Diseases, 903 S. Fourth St., Hamilton, MT 59840, USA, e.clifton_barry@nih.gov Y1 - 1998/03// PY - 1998 DA - Mar 1998 SP - 1223 EP - 1233 VL - 27 IS - 6 SN - 0950-382X, 0950-382X KW - isoniazid KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts B: Bacteriology KW - A 01064:Microbial resistance KW - J 02814:Drug resistance UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16512098?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Microbiology&rft.atitle=Mechanisms+involved+in+the+intrinsic+isoniazid+resistance+of+Mycobacterium+avium&rft.au=Mdluli%2C+K%3BSwanson%2C+J%3BFischer%2C+E%3BLee%2C+R+E%3BBarry%2C+CE+III&rft.aulast=Mdluli&rft.aufirst=K&rft.date=1998-03-01&rft.volume=27&rft.issue=6&rft.spage=1223&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Effect of cadmium exposure on background and anti-5-methylchrysene-1,2-dihydrodiol 3,4-epoxide-induced mutagenesis in the supF gene of pS189 in human Ad293 cells AN - 16511605; 4413782 AB - Cadmium is a toxic environmental contaminant that is carcinogenic in humans and rodents. Although cadmium has proven to be mutagenic in a variety of assay systems, exactly how cadmium achieves gentoxicity is poorly understood. To define the mechanism(s) underlying the mutagenicity and comutagenicity of cadmium, human Ad293 cells were exposed to subtoxic doses of the metal and transfected with untreated or anti-5-methylchrysene-3,4-dihydrodiol 1,2-epoxide (5-MCDE)-treated pS189 shuttle vector. Alterations in the frequency, types, and distribution of mutations were subsequently assessed in the supF gene of pS189 that was replicated in Ad293 cells and screened in indicator bacteria. Doses of 0.5 and 1 mu M CdCl sub(2) increased the mutation frequency of untreated pS189 by approximately 4- and 8-fold, respectively, with no apparent effect on the types of mutations generated. In contrast, host-cell exposure to cadmium had little or no effect on the frequency, types, or distribution of mutations generated with 5-MCDE-treated pS189. These results indicate that cadmium increases mutagenesis of untreated pS189 by affecting a process that is not involved in mutagenesis of the 5-MCDE-treated vector. Although it is not clear exactly how host-cell exposure to cadmium increases background mutagenesis, presumably, the mutagenic effect does not involve cadmium interaction with the cellular machinery used to replicate past bulky DNA lesions. JF - Chemical Research in Toxicology AU - Misra, R R AU - Page, JE AU - Smith, G T AU - Waalkes, M P AU - Dipple, A AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, Division of Basic Sciences, National Cancer Institute, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA Y1 - 1998/03// PY - 1998 DA - Mar 1998 SP - 211 EP - 216 VL - 11 IS - 3 SN - 0893-228X, 0893-228X KW - 5-methylchrysene-3,4-dihydrodiol 1,2-epoxide KW - Ad293 cells KW - cadmium KW - cell culture KW - man KW - mutagenicity KW - supF gene KW - transfection KW - Toxicology Abstracts KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16511605?accountid=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=Effect+of+cadmium+exposure+on+background+and+anti-5-methylchrysene-1%2C2-dihydrodiol+3%2C4-epoxide-induced+mutagenesis+in+the+supF+gene+of+pS189+in+human+Ad293+cells&rft.au=Misra%2C+R+R%3BPage%2C+JE%3BSmith%2C+G+T%3BWaalkes%2C+M+P%3BDipple%2C+A&rft.aulast=Misra&rft.aufirst=R&rft.date=1998-03-01&rft.volume=11&rft.issue=3&rft.spage=211&rft.isbn=&rft.btitle=&rft.title=Chemical+Research+in+Toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Serum hormone levels in relation to reproductive and lifestyle factors in postmenopausal women (United States) AN - 16488263; 4374946 AB - Objectives: Endogenous sex hormones are thought to be involved in breast and endometrial cancers, but few studies have evaluated the relationships between hormones and risk factors for these diseases. Methods: We related serum hormone and sex-hormone binding globulin (SHBG) levels to reproductive and lifestyle risk factors in a cross-sectional study of 125 postmenopausal women in five geographic regions of the United States. Results: The estrogens were associated positively, while SHBG was associated negatively with body mass index (wt/ht super(2)). Estrone, (E1), estrone sulfate, and bioavailable estradiol (BioE2) were inversely associated with height. Androstenedione was positively associated with age at menopause, while androstenedione, E1, estradiol, and BioE2 were inversely associated with age at menarche. Weekly alcohol drinkers had higher hormone levels, and lower SHBG levels than those who abstained. Androstenedione and E1 decreased with increasing levels of nonrecreational activity. Conclusions: Several of these findings support the hypothesis that breast and endometrial cancer risk factors are mediated, in part, through increased endogenous hormone levels. The androstenedione findings are of interest in light of studies relating androstenedione to endometrial and possibly breast cancer. An association of age at menarche with E2, independent of androstenedione, may reflect increased aromatase activity in women with earlier menarche. JF - Cancer Causes & Control AU - Madigan, M P AU - Troisi, R AU - Potischman, N AU - Dorgan, J F AU - Brinton, LA AU - Hoover, R N AD - US National Cancer Institute, Division of Cancer Epidemiology & Genetics, Environmental Epidemiology Branch, EPN 443, Bethesda, MD 20892, USA Y1 - 1998/03// PY - 1998 DA - Mar 1998 SP - 199 EP - 207 VL - 9 IS - 2 SN - 0957-5243, 0957-5243 KW - endometrium KW - estrogens KW - hormones KW - physical activity KW - post-menopause KW - Risk Abstracts KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16488263?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Causes+%26+Control&rft.atitle=Serum+hormone+levels+in+relation+to+reproductive+and+lifestyle+factors+in+postmenopausal+women+%28United+States%29&rft.au=Madigan%2C+M+P%3BTroisi%2C+R%3BPotischman%2C+N%3BDorgan%2C+J+F%3BBrinton%2C+LA%3BHoover%2C+R+N&rft.aulast=Madigan&rft.aufirst=M&rft.date=1998-03-01&rft.volume=9&rft.issue=2&rft.spage=199&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Neisseria meningitidis producing the Opc adhesin binds epithelial cell proteoglycan receptors AN - 16482038; 4298666 AB - Neisseria meningitidis possesses a repertoire of surface adhesins that promote bacterial adherence to and entry into mammalian cells. Here, we have identified heparan sulphate proteoglycans as epithelial cell receptors for the meningococcal Opc invasin. Binding studies with radiolabelled heparin and heparin affinity chromatography demonstrated that Opc is a heparin binding protein. Subsequent binding experiments with purified super(35)SO sub(4)-labelled epithelial cell proteoglycan receptors and infection assays with epithelial cells that had been treated with heparitinase to remove glycosaminoglycans confirmed that Opc-expressing meningococci exploit host cell-surface proteoglycans to gain access to the epithelial cell interior. Unexpectedly, Opa28-producing meningococci lacking Opc also bound proteoglycans. These bacteria also bound CEA receptors in contrast to the Opc-expressing phenotype, suggesting that Opa28 may possess domains with specificity for different receptors. Opa/Opc-negative meningococci did not bind either proteoglycan or CEA receptors. Using a set of genetically defined mutants with different lipopolysaccharide (LPS) and capsular phenotype, we were able to demonstrate that surface sialic acids interfere with the Opc-proteoglycan receptor interaction. This effect may provide the molecular basis for the reported modulatory effect of capsule and LPS on meningococcal adherence to and entry into various cell types. JF - Molecular Microbiology AU - De Vries, FP AU - Cole, R AU - Dankert, J AU - Frosch, M AU - Van Putten, JPM AD - Rocky Mountain Laboratories, National Institutes for Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840, USA, jos_van_putten@nih.gov Y1 - 1998/03// PY - 1998 DA - Mar 1998 SP - 1203 EP - 1212 VL - 27 IS - 6 SN - 0950-382X, 0950-382X KW - Opc protein KW - adhesins KW - proteoglycans KW - Microbiology Abstracts B: Bacteriology KW - J 02848:Nervous system UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16482038?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Microbiology&rft.atitle=Neisseria+meningitidis+producing+the+Opc+adhesin+binds+epithelial+cell+proteoglycan+receptors&rft.au=De+Vries%2C+FP%3BCole%2C+R%3BDankert%2C+J%3BFrosch%2C+M%3BVan+Putten%2C+JPM&rft.aulast=De+Vries&rft.aufirst=FP&rft.date=1998-03-01&rft.volume=27&rft.issue=6&rft.spage=1203&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Inhibition of acute-, latent-, and chronic-phase human immunodeficiency virus type 1 (HIV-1) replication by a bistriazoloacridone analog that selectively inhibits HIV-1 transcription AN - 16439109; 4343517 AB - Nanomolar concentrations of temacrazine (1,4-bis[3-(6-oxo-6H-v-triazolo[4,5,1-de]acridin-5-yl)amino-propyl ] piperazine) were discovered to inhibit acute human immunodeficiency virus type 1 (HIV-1) infections and suppress the production of virus from chronically and latently infected cells containing integrated proviral DNA. This bistriazoloacridone derivative exerted its mechanism of antiviral action through selective inhibition of HIV-1 transcription during the postintegrative phase of virus replication. Mechanistic studies revealed that temacrazine blocked HIV-1 RNA formation without interference with the transcription of cellular genes or with events associated with the HIV-1 Tat and Rev regulatory proteins. Although temacrazine inhibited the in vitro 3' processing and strand transfer activities of HIV-1 integrase, with a 50% inhibitory concentration of approximately 50 nM, no evidence of an inhibitory effect on the intracellular integration of proviral DNA into the cellular genome during the early phase of infection could be detected. Furthermore, temacrazine did not interfere with virus attachment or fusion to host cells or the enzymatic activities of HIV-1 reverse transcriptase or protease, and the compound was not directly virucidal. Demonstration of in vivo anti-HIV-1 activity by temacrazine identifies bistriazoloacridones as a new class of pharmaceuticals that selectively blocks HIV-1 transcription. JF - Antimicrobial Agents & Chemotherapy AU - Turpin, JA AU - Buckheit, RW Jr AU - Derse, D AU - Hollingshead, M AU - Williamson, K AU - Palamone, C AU - Osterling, M C AU - Hill, SA AU - Graham, L AU - Schaeffer, CA AU - Bu, M AU - Huang, M AU - Cholody, WM AU - Michejda, C J AU - Rice, W G AD - Laboratory of Antiviral Drug Mechanisms, Developmental Therapeutics Program, National Cancer Institute-Frederick Cancer Research and Development Center, SAIC Frederick, Building 431T-B, P.O. Box B, Frederick, MD 21702-1201, USA Y1 - 1998/03// PY - 1998 DA - Mar 1998 SP - 487 EP - 494 VL - 42 IS - 3 SN - 0066-4804, 0066-4804 KW - HIV-1 KW - RNA KW - acquired immune deficiency syndrome KW - antiviral agents KW - human immunodeficiency virus 1 KW - temacrazine KW - transcription KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - V 22002:AIDS: Molecular and in vitro aspects KW - W3 33372:Antiviral agents KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16439109?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+Agents+%26+Chemotherapy&rft.atitle=Inhibition+of+acute-%2C+latent-%2C+and+chronic-phase+human+immunodeficiency+virus+type+1+%28HIV-1%29+replication+by+a+bistriazoloacridone+analog+that+selectively+inhibits+HIV-1+transcription&rft.au=Turpin%2C+JA%3BBuckheit%2C+RW+Jr%3BDerse%2C+D%3BHollingshead%2C+M%3BWilliamson%2C+K%3BPalamone%2C+C%3BOsterling%2C+M+C%3BHill%2C+SA%3BGraham%2C+L%3BSchaeffer%2C+CA%3BBu%2C+M%3BHuang%2C+M%3BCholody%2C+WM%3BMichejda%2C+C+J%3BRice%2C+W+G&rft.aulast=Turpin&rft.aufirst=JA&rft.date=1998-03-01&rft.volume=42&rft.issue=3&rft.spage=487&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+Agents+%26+Chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Induction of melanoma antigen-specific cytotoxic T lymphocytes in vitro by stimulation with B7-expressing human melanoma cell lines AN - 16414217; 4315583 AB - Crosslinking of CD28 receptors on resting T lymphocytes by B7 costimulatory molecules expressed by antigen-presenting cells (APCs) plays a critical role in T-cell activation. Human melanomas express major histocompatibility complex (MHC)-restricted tumor-associated antigens that can be recognized by cytotoxic T lymphocytes (CTL), yet they remain poorly immunogenic. One mechanism for the failure of T-cell response is the lack of expression of costimulatory molecules by human melanoma cells. We have transfected the B7-1 gene into three HLA-A2-expressing human melanoma cell lines, and studied their capacity to stimulate primary human T cells. B7-expressing melanoma cells were excellent inducers of T-cell proliferation, cytokine production, and cytolytic activity in allogeneic mixed lymphocyte cultures through a process dependent on the function of the T-cell receptor as well as interactions between B7:CD28, CD2:LFA-3, and LFA-1:ICAM-1. Subset analysis demonstrated that CD4 super(+) T cells or addition of exogenous interleukin-2 was required for the induction of CD8 super(+) CTL. Untransfected parental melanoma cells were inert as APCs in these cultures. Rotating stimulation of T cells with the three B7-expressing cell lines led to the generation of T-cell lines that were cytolytic for HLA-A2 super(+) melanoma cells and other HLA-A2 super(+) targets that were pulsed with HLA-A2-restricted MART-1 peptides. These data demonstrate that expression of B7-1 by human melanoma cells converts them into effective APCs for the in vitro induction of MHC-restricted, melanoma-specific CTL. JF - Journal of Immunotherapy with Emphasis on Tumor Biology AU - Fenton, R G AU - Turcovski-Corrales, S M AU - Taub, D D AD - National Cancer Institute-FCRDC, P.O. Box B, Building 567, Room 207 Frederick, MD 21702, USA Y1 - 1998/03// PY - 1998 DA - Mar 1998 SP - 95 EP - 108 VL - 21 IS - 2 SN - 1053-8550, 1053-8550 KW - A2 determinant KW - double prime B7 antigen KW - histocompatibility antigen HLA KW - man KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - F 06816:Antitumor immune response KW - W3 33350:Cancer vaccines KW - F 06756:Function KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16414217?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunotherapy+with+Emphasis+on+Tumor+Biology&rft.atitle=Induction+of+melanoma+antigen-specific+cytotoxic+T+lymphocytes+in+vitro+by+stimulation+with+B7-expressing+human+melanoma+cell+lines&rft.au=Fenton%2C+R+G%3BTurcovski-Corrales%2C+S+M%3BTaub%2C+D+D&rft.aulast=Fenton&rft.aufirst=R&rft.date=1998-03-01&rft.volume=21&rft.issue=2&rft.spage=95&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunotherapy+with+Emphasis+on+Tumor+Biology&rft.issn=10538550&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - RapA, a novel RNA polymerase-associated protein, is a bacterial homolog of SWI2/SNF2 AN - 16289150; 4295161 AB - We have identified a novel Escherichia coli RNA polymerase (RNAP)-associated protein, an ATPase named RapA. Almost all of this 110-kDa protein in the cell copurifies with RNAP holoenzyme as a 1:1 complex. Purified to homogeneity, RapA also forms a stable complex with RNAP, as if it were a subunit of RNAP. The ATPase activity of RapA is stimulated by binding to RNAP, and thus, RapA and RNAP interact physically as well as functionally. Interestingly, RapA is a homolog of the SWI/SNF family of eukaryotic proteins whose members are involved in transcription activation, nucleosome remodeling, and DNA repair. JF - Journal of Biological Chemistry AU - Sukhodolets, M V AU - Jin, Ding Jun AD - LMB, NCI, Natl. Institutes Health, Bldg. 37, Rm. 2E14, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1998/03// PY - 1998 DA - Mar 1998 SP - 7018 EP - 7023 VL - 273 IS - 12 SN - 0021-9258, 0021-9258 KW - DNA-directed RNA polymerase-associated protein KW - RapA protein KW - SWI2/SNF2 protein KW - adenosinetriphosphatase KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - N 14721:RNA polymerases KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16289150?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=RapA%2C+a+novel+RNA+polymerase-associated+protein%2C+is+a+bacterial+homolog+of+SWI2%2FSNF2&rft.au=Sukhodolets%2C+M+V%3BJin%2C+Ding+Jun&rft.aulast=Sukhodolets&rft.aufirst=M&rft.date=1998-03-01&rft.volume=273&rft.issue=12&rft.spage=7018&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Control of ftsZ expression, cell division, and glutamine metabolism in Luria-Bertani medium by the alarmone ppGpp in Escherichia coli AN - 16282992; 4282245 AB - Inactivation of transcription factor sigma super(54), encoded by rpoN (glnF), restores high-temperature growth in Luria-Bertani (LB) medium to strains containing the heat-sensitive cell division mutation ftsZ84. Mutational defects in three other genes involved in general nitrogen control (glnD, glnG, and glnL) also suppress lethal filamentation. Since addition of glutamine to LB medium fully blocks suppression by each mutation, the underlying cause of suppression likely derives from a stringent response to the limitation of glutamine. This model is supported by several observations. The glnL mutation requires RelA-directed synthesis of the nutrient alarmone ppGpp to suppress filamentation. Artificially elevated levels of ppGpp suppress ftsZ84, as do RNA polymerase mutations that reproduce global effects of the ppGpp-induced state. Both the glnF null mutation and an elevated copy number of the relA gene similarly affect transcription from the upstream (pQ) promoters of the ftsQAZ operon, and both of these genetic conditions increase the steady-state level of the FtsZ84 protein. Physiological suppression of ftsZ84 by a high salt concentration was also shown to involve RelA. Additionally, we found that the growth of a glnF or glnD strain on LB medium depends on RelA or supplemental glutamine in the absence of RelA function. These data expand the roles for ppGpp in the regulation of glutamine metabolism and the expression of FtsZ during cell division. JF - Journal of Bacteriology AU - Powell, B S AU - Court, D L AD - Mol. Control and Genet., ABL-Basic Res. Prog., NCI-Frederick Cancer Res. and Dev. Cent., Frederick, MD 21702, USA Y1 - 1998/03// PY - 1998 DA - Mar 1998 SP - 1053 EP - 1062 VL - 180 IS - 5 SN - 0021-9193, 0021-9193 KW - FtsZ protein KW - cell division KW - ftsZ gene KW - gene expression KW - gln gene KW - glutamine KW - Microbiology Abstracts B: Bacteriology KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16282992?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=Control+of+ftsZ+expression%2C+cell+division%2C+and+glutamine+metabolism+in+Luria-Bertani+medium+by+the+alarmone+ppGpp+in+Escherichia+coli&rft.au=Powell%2C+B+S%3BCourt%2C+D+L&rft.aulast=Powell&rft.aufirst=B&rft.date=1998-03-01&rft.volume=180&rft.issue=5&rft.spage=1053&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Cellular resistance and hypermutability in mismatch repair-deficient human cancer cell lines following treatment with methyl methanesulfonate. AN - 79934579; 9626980 AB - Resistance to the cytotoxic effects of S(N)1 alkylating agents such as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and N-methyl-N-nitrosourea (MNU) is well established in mismatch repair-defective cells, however, little is known about the cellular response to S(N)2 alkylating agents in these cells. Here we describe the cytotoxic response and the mutagenic response at the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus to the S(N)2 alkylating agent methyl methanesultfonate (MMS) in human cancer cell lines defective in mismatch repair (MMR). Our findings suggest that cytotoxicity to MMS is mediated through MMR, as indicated by an increased resistance to MMS in MMR-deficient cells. Cells in which specific MMR-gene defects were complemented by chromosome transfer were generally more sensitive to the cytotoxic effects of MMS. Additionally, the induced mutant frequency at HPRT following exposure to MMS is significantly increased in MMR-deficient lines. These findings suggest that resistance to S(N)2 alkylation damage is mediated by MMR genes, and that resistance to such damage in MMR-defective cells correlates with an increase in genomic mutations. The results are consistent with the hypothesis that abasic sites may be substrates for repair involving MMR-gene products in human cells. JF - Mutation research AU - Glaab, W E AU - Risinger, J I AU - Umar, A AU - Barrett, J C AU - Kunkel, T A AU - Tindall, K R AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1998/02/26/ PY - 1998 DA - 1998 Feb 26 SP - 197 EP - 207 VL - 398 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Mutagens KW - 0 KW - Nucleic Acid Heteroduplexes KW - Methyl Methanesulfonate KW - AT5C31J09G KW - Index Medicus KW - Tumor Cells, Cultured KW - Humans KW - Mutation KW - Cell Line KW - Methyl Methanesulfonate -- toxicity KW - DNA Repair KW - Mutagens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79934579?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Cellular+resistance+and+hypermutability+in+mismatch+repair-deficient+human+cancer+cell+lines+following+treatment+with+methyl+methanesulfonate.&rft.au=Glaab%2C+W+E%3BRisinger%2C+J+I%3BUmar%2C+A%3BBarrett%2C+J+C%3BKunkel%2C+T+A%3BTindall%2C+K+R&rft.aulast=Glaab&rft.aufirst=W&rft.date=1998-02-26&rft.volume=398&rft.issue=1-2&rft.spage=197&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-24 N1 - Date created - 1998-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Further studies on anti- and proconvulsant effects of inhibitors of nitric oxide synthase in rodents. AN - 79829893; 9570442 AB - We confirmed that the effects of inhibitors of nitric oxide (NO) synthase, such as Nomega-nitro-L-arginine methyl ester and Nomega-nitro-L-arginine, differ depending on several experimental factors. Both compounds but not their less active enantiomers delayed picrotoxin-induced clonus in mice yet increased the incidence of clonus following low-dose picrotoxin. Nomega-nitro-L-arginine methyl ester significantly reduced the latencies of both myoclonus and clonus in older but not younger Sprague-Dawley rats receiving pentylenetetrazol s.c. By contrast, there was no significant change in the latencies for myoclonus and clonus in Wistar rats (older and younger). However, when pentylenetetrazol was administered i.p. rather than s.c., Nomega-nitro-L-arginine methyl ester dramatically increased latencies of convulsive indicators, including tonus, in both Sprague-Dawley and Wistar rats. Nomega-nitro-L-arginine methyl ester also delayed tonus but not myoclonus or clonus in mice, regardless of the systemic route of administration of pentylenetetrazol. Both Nomega-nitro-L-arginine methyl ester and NG-nitro-L-arginine increased the tonic CD50 of pentylenetetrazol in mice and Nomega-nitro-L-arginine methyl ester delayed 4-aminopyridine-induced tonus. However, Nomega-nitro-L-arginine methyl ester reduced the tonic CD50 of both picrotoxin and 4-aminopyridine in mice and failed to suppress tonus following maximal electroshock. Evidently, inhibitors of NO synthase are not universally effective antitonic drugs. JF - European journal of pharmacology AU - Alexander, C B AU - Ellmore, T M AU - Kokate, T G AU - Kirkby, R D AD - Neuronal Excitability Section, Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1408, USA. Y1 - 1998/02/26/ PY - 1998 DA - 1998 Feb 26 SP - 15 EP - 25 VL - 344 IS - 1 SN - 0014-2999, 0014-2999 KW - Anticonvulsants KW - 0 KW - Convulsants KW - Enzyme Inhibitors KW - Picrotoxin KW - 124-87-8 KW - Nitroarginine KW - 2149-70-4 KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - NG-Nitroarginine Methyl Ester KW - V55S2QJN2X KW - Pentylenetetrazole KW - WM5Z385K7T KW - Index Medicus KW - Seizures -- chemically induced KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Pentylenetetrazole -- pharmacology KW - Picrotoxin -- pharmacology KW - Rats, Wistar KW - Mice KW - Male KW - Anticonvulsants -- pharmacology KW - NG-Nitroarginine Methyl Ester -- pharmacology KW - Nitric Oxide Synthase -- antagonists & inhibitors KW - Convulsants -- pharmacology KW - Nitroarginine -- pharmacology KW - Enzyme Inhibitors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79829893?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+pharmacology&rft.atitle=Further+studies+on+anti-+and+proconvulsant+effects+of+inhibitors+of+nitric+oxide+synthase+in+rodents.&rft.au=Alexander%2C+C+B%3BEllmore%2C+T+M%3BKokate%2C+T+G%3BKirkby%2C+R+D&rft.aulast=Alexander&rft.aufirst=C&rft.date=1998-02-26&rft.volume=344&rft.issue=1&rft.spage=15&rft.isbn=&rft.btitle=&rft.title=European+journal+of+pharmacology&rft.issn=00142999&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-09 N1 - Date created - 1998-06-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Apolipoprotein E allelic frequency in elderly smokers. AN - 79734337; 9508061 AB - Susceptibility genes for human diseases (e.g., cancer and atherosclerosis) increase disease risk by altering the metabolic activation of exogenous (e.g., carcinogens) and endogenous (e.g., cholesterol) compounds. The function of these genes, and subsequent risk, can be adversely affected by polymorphisms. This study tests the hypothesis that if specific genetic polymorphisms are related to mortality, then in elderly heavy smokers, there should be a decreased frequency of "at risk" alleles and an increased frequency of "protective" alleles, i.e., a survival effect. One such potential polymorphism is in the apolipoprotein E (apoE) gene, which is involved in cholesterol metabolism, where the epsilon4 allele is associated with an increased risk of coronary artery disease and is under represented in elderly populations. In this study, ApoE variant alleles were determined in 81 living, elderly current smokers (mean age: 72.5; range: 65-94; mean pack-years: 78; range: 13-192) and in 82 younger autopsy donors (mean age: 33; range: 1-58). There was a borderline difference in the apoE 4 allelic frequencies among the groups (11% in the elderly and 18% in the comparable younger group [df = 1; chi(2) = 4.02; P = 0.05]). A significant difference was found for age when stratified as a continuous variable by genotype in the elderly smokers (P = 0.03; mean age for persons with and without epsilon4 was 69.9 and 73.2, respectively). Pack-years of cigarette smokers did not differ by genotype, indicating no selective effect. These results confirm earlier associations for differences in the apoE allelic frequencies in the elderly and extend it to smokers, who generally have increased mortality at younger ages. JF - American journal of medical genetics AU - Bowman, E D AU - Brömeke, B AU - Lensing, W AU - Shields, P G AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1998/02/26/ PY - 1998 DA - 1998 Feb 26 SP - 32 EP - 36 VL - 76 IS - 1 SN - 0148-7299, 0148-7299 KW - Apolipoproteins E KW - 0 KW - DNA Primers KW - Index Medicus KW - Coronary Disease -- etiology KW - Gene Frequency KW - Polymorphism, Genetic KW - DNA Primers -- genetics KW - Humans KW - Aged KW - Child KW - Child, Preschool KW - Infant KW - Polymerase Chain Reaction KW - Base Sequence KW - Longevity -- genetics KW - Aged, 80 and over KW - Risk Factors KW - Adult KW - Coronary Disease -- genetics KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Smoking -- mortality KW - Alleles KW - Smoking -- adverse effects KW - Smoking -- genetics KW - Apolipoproteins E -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79734337?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+medical+genetics&rft.atitle=Apolipoprotein+E+allelic+frequency+in+elderly+smokers.&rft.au=Bowman%2C+E+D%3BBr%C3%B6meke%2C+B%3BLensing%2C+W%3BShields%2C+P+G&rft.aulast=Bowman&rft.aufirst=E&rft.date=1998-02-26&rft.volume=76&rft.issue=1&rft.spage=32&rft.isbn=&rft.btitle=&rft.title=American+journal+of+medical+genetics&rft.issn=01487299&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-21 N1 - Date created - 1998-04-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - hSmad5 gene, a human hSmad family member: its full length cDNA, genomic structure, promoter region and mutation analysis in human tumors. AN - 79702574; 9484787 AB - hSmad (mothers against decapentaplegic)-related proteins are important messengers within the Transforming Growth Factor-beta1 (TGF-beta1) superfamily signal transduction pathways. To further characterize a member of this family, we obtained a full length cDNA of the human hSmad5 (hSmad5) gene by rapid amplification of cDNA ends (RACE) and then determined the genomic structure of the gene. There are eight exons and two alternative transcripts; the shorter transcript lacks exon 2. We identified the hSmad5 promoter region from a human genomic YAC clone by obtaining the nucleotide sequence extending 1235 base pairs upstream of the 5' end of the cDNA. We found a CpG island consistent with a promoter region, and we demonstrated promoter activity in a 1232 bp fragment located upstream of the transcription initiation site. To investigate the frequency of somatic hSmad5 mutations in human cancers, we designed intron-based primers to examine coding regions by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. Neither homozygous deletions or point mutations were found in 40 primary gastric tumors and 51 cell lines derived from diverse types of human cancer including 20 cell lines resistant to the growth inhibitory effects of TGF-beta1. These results suggest that the hSmad5 gene is not commonly mutated and that other genetic alterations mediate the loss of TGF-beta1 responsiveness in human cancers. JF - Oncogene AU - Gemma, A AU - Hagiwara, K AU - Vincent, F AU - Ke, Y AU - Hancock, A R AU - Nagashima, M AU - Bennett, W P AU - Harris, C C AD - Laboratory of Human Carcinogenesis, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 1998/02/19/ PY - 1998 DA - 1998 Feb 19 SP - 951 EP - 956 VL - 16 IS - 7 SN - 0950-9232, 0950-9232 KW - DNA, Complementary KW - 0 KW - DNA, Neoplasm KW - DNA-Binding Proteins KW - Phosphoproteins KW - RNA, Messenger KW - SMAD5 protein, human KW - Smad5 Protein KW - Trans-Activators KW - Index Medicus KW - DNA, Complementary -- genetics KW - Humans KW - Amino Acid Sequence KW - RNA, Messenger -- genetics KW - Base Sequence KW - Promoter Regions, Genetic KW - Genes KW - Tumor Cells, Cultured KW - Sequence Alignment KW - Alternative Splicing KW - Molecular Sequence Data KW - DNA, Neoplasm -- genetics KW - Phosphoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79702574?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=hSmad5+gene%2C+a+human+hSmad+family+member%3A+its+full+length+cDNA%2C+genomic+structure%2C+promoter+region+and+mutation+analysis+in+human+tumors.&rft.au=Gemma%2C+A%3BHagiwara%2C+K%3BVincent%2C+F%3BKe%2C+Y%3BHancock%2C+A+R%3BNagashima%2C+M%3BBennett%2C+W+P%3BHarris%2C+C+C&rft.aulast=Gemma&rft.aufirst=A&rft.date=1998-02-19&rft.volume=16&rft.issue=7&rft.spage=951&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-13 N1 - Date created - 1998-03-13 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U73825; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Case-control study of childhood acute lymphoblastic leukemia and residential radon exposure. AN - 79705276; 9486815 AB - Several ecologic analyses have shown significant positive associations between mean indoor radon concentrations and risk of leukemia at all ages (acute myeloid leukemia and chronic lymphocytic leukemia) and for children (all leukemia, acute myeloid leukemia, and acute lymphoblastic leukemia [ALL]). As part of an age-matched, case-control study of childhood ALL in the United States, we investigated the association between the incidence of ALL in children under age 15 years and indoor radon exposure. Radon detectors were placed in current and previous homes of subjects where they resided for 6 months or longer. Children were included in analyses if radon measurements covered 70% or more of the 5-year period prior to diagnosis for case subjects (or from birth for case subjects under age 5 years) and the corresponding reference dates for control subjects. Radon levels could be estimated for 97% of the exposure period for the eligible 505 case subjects and 443 control subjects. Mean radon concentration was lower for case subjects (65.4 becquerels per cubic meter [Bqm(-3)]) than for control subjects (79.1 Bqm(-3)). For categories less than 37, 37-73, 74-147, and 148 or more Bqm(-3) of radon exposure, relative risks based on matched case-control pairs were 1.00, 1.22, 0.82, and 1.02, respectively, and were similar to results from an unmatched analysis. There was no association between ALL and radon exposure within subgroups defined by categories of age, income, birth order, birth weight, sex, type of residence, magnetic field exposure, parental age at the subject's birth, parental occupation, or parental smoking habits. In contrast to prior ecologic studies, the results from this analytic study provide no evidence for an association between indoor radon exposure and childhood ALL. JF - Journal of the National Cancer Institute AU - Lubin, J H AU - Linet, M S AU - Boice, J D AU - Buckley, J AU - Conrath, S M AU - Hatch, E E AU - Kleinerman, R A AU - Tarone, R E AU - Wacholder, S AU - Robison, L L AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. Y1 - 1998/02/18/ PY - 1998 DA - 1998 Feb 18 SP - 294 EP - 300 VL - 90 IS - 4 SN - 0027-8874, 0027-8874 KW - Carcinogens, Environmental KW - 0 KW - Radon KW - Q74S4N8N1G KW - Index Medicus KW - Infant KW - Risk KW - Humans KW - Case-Control Studies KW - Child KW - Male KW - Female KW - Matched-Pair Analysis KW - Child, Preschool KW - Carcinogens, Environmental -- adverse effects KW - Radon -- 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/79705276?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Case-control+study+of+childhood+acute+lymphoblastic+leukemia+and+residential+radon+exposure.&rft.au=Lubin%2C+J+H%3BLinet%2C+M+S%3BBoice%2C+J+D%3BBuckley%2C+J%3BConrath%2C+S+M%3BHatch%2C+E+E%3BKleinerman%2C+R+A%3BTarone%2C+R+E%3BWacholder%2C+S%3BRobison%2C+L+L&rft.aulast=Lubin&rft.aufirst=J&rft.date=1998-02-18&rft.volume=90&rft.issue=4&rft.spage=294&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-06 N1 - Date created - 1998-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chimeric papillomavirus virus-like particles elicit antitumor immunity against the E7 oncoprotein in an HPV16 tumor model AN - 16263958; 4242105 AB - Papillomavirus-like particles (VLPs) are a promising prophylactic vaccine candidate to prevent human papillomavirus (HPV) infections and associated epithelial neoplasia. However, they are unlikely to have therapeutic effects because the virion capsid proteins are not detected in the proliferating cells of the infected epithelia or in cervical carcinomas. To increase the number of viral antigen targets for cell-mediated immune responses in a VLP-based vaccine, we have generated stable chimeric VLPs consisting of the L1 major capsid protein plus the entire E7 (11 kDa) or E2 (43 kDa) nonstructural papillomavirus protein fused to the L2 minor capsid protein. The chimeric VLPs are indistinguishable from the parental VLPs in their morphology and in their ability to agglutinate erythrocytes and elicit high titers of neutralizing antibodies. Protection from tumor challenge was tested in C57BL/6 mice by using the tumor cell line TC-1, which expresses HPV16 E7, but not the virion structural proteins. Injection of HPV16 L1/L2-HPV16 E7 chimeric VLPs, but not HPV16 L1/L2 VLPs, protected the mice from tumor challenge, even in the absence of adjuvant. The chimeric VLPs also induced protection against tumor challenge in major histocompatibility class II-deficient mice, but not in beta sub(2)-microglobulin or perforin knockout mice implying that protection was mediated by class I-restricted cytotoxic lymphocytes. These findings raise the possibility that VLPs may generally be efficient vehicles for generating cell-mediated immune responses and that, specifically, chimeric VLPs containing papillomavirus nonstructural proteins may increase the therapeutic potential of VLP-based prophylactic vaccines in humans. JF - Proceedings of the National Academy of Sciences, USA AU - Greenstone, H AU - Nieland, J AU - de Visser, K AU - De Bruijn, M AU - Kirnbauer, R AU - Roden, R AU - Lowy, D AU - Kast, W AU - Schiller, J AD - Laboratory of Cellular Oncology, National Institutes of Health, 36 Convent Drive, MSC 4040, Bethesda, MD 20892-4040 Y1 - 1998/02/17/ PY - 1998 DA - 1998 Feb 17 SP - 1800 EP - 1805 VL - 95 IS - 4 SN - 0027-8424, 0027-8424 KW - double prime E7 protein KW - human papillomavirus 16 KW - mice KW - papillomavirus-like particles KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - F 06818:Cancer immunotherapy KW - W3 33350:Cancer vaccines KW - V 22114:Human oncogenic viruses KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16263958?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Chimeric+papillomavirus+virus-like+particles+elicit+antitumor+immunity+against+the+E7+oncoprotein+in+an+HPV16+tumor+model&rft.au=Greenstone%2C+H%3BNieland%2C+J%3Bde+Visser%2C+K%3BDe+Bruijn%2C+M%3BKirnbauer%2C+R%3BRoden%2C+R%3BLowy%2C+D%3BKast%2C+W%3BSchiller%2C+J&rft.aulast=Greenstone&rft.aufirst=H&rft.date=1998-02-17&rft.volume=95&rft.issue=4&rft.spage=1800&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - ISSN for electronic version: 1091-6490. ISSN for print version: 0027-8424. N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Mucosal immunization with HIV-1 peptide vaccine induces mucosal and systemic cytotoxic T lymphocytes and protective immunity in mice against intrarectal recombinant HIV-vaccinia challenge AN - 16262747; 4242089 AB - Mucosal tissues are major sites of HIV entry and initial infection. Thus, the induction of a mucosal cytotoxic T lymphocyte (CTL) response is an important feature for an effective HIV vaccine. However, little is known about approaches to induce such a protective CTL response in the mucosa. Here for the first time we show that intrarectal immunization with a synthetic, multideterminant HIV peptide plus cholera toxin adjuvant induced long-lasting, antigen-specific CTL memory in both the inductive (Peyer's patch) and effector (lamina propria) mucosal sites, as well as in systemic sites (spleen), whereas systemic immunization induced specific CTL only in the spleen. Cholera toxin adjuvant, while enhancing the response, was not essential. The CTL recognized target cells either pulsed with HIV peptide or expressing endogenous whole envelope glycoprotein of M sub(r) 160,000 (gp160). Exploring the requirements for CTL induction, we show that mucosal CTL responses are both interleukin 12 and interferon- gamma dependent by using antibody-treated and knock-out mice. Finally, to determine whether a mucosal response is actually protective against local mucosal challenge with virus, we show that intrarectal immunization with the synthetic HIV peptide vaccine protected mice against infection via mucosal challenge with a recombinant vaccinia virus expressing HIV-1IIIB gp160. These studies provide an approach to development of an HIV vaccine that induces CTL immunity in the mucosal and systemic immune systems and protects against mucosal infection with a virus expressing HIV-1 gp160. JF - Proceedings of the National Academy of Sciences, USA AU - Belyakov, I AU - Derby, M AU - Ahlers, J AU - Kelsall, B AU - Earl, P AU - Moss, B AU - Strober, W AU - Berzofsky, J AD - Metabolism Branch, National Cancer Institute, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, and Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 Y1 - 1998/02/17/ PY - 1998 DA - 1998 Feb 17 SP - 1709 EP - 1714 VL - 95 IS - 4 SN - 0027-8424, 0027-8424 KW - HIV-1 KW - glycoprotein gp160 KW - human immunodeficiency virus 1 KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts; Immunology Abstracts KW - W3 33365:Vaccines (other) KW - F 06807:Active immunization KW - V 22003:AIDS: Immunological aspects KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16262747?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Mucosal+immunization+with+HIV-1+peptide+vaccine+induces+mucosal+and+systemic+cytotoxic+T+lymphocytes+and+protective+immunity+in+mice+against+intrarectal+recombinant+HIV-vaccinia+challenge&rft.au=Belyakov%2C+I%3BDerby%2C+M%3BAhlers%2C+J%3BKelsall%2C+B%3BEarl%2C+P%3BMoss%2C+B%3BStrober%2C+W%3BBerzofsky%2C+J&rft.aulast=Belyakov&rft.aufirst=I&rft.date=1998-02-17&rft.volume=95&rft.issue=4&rft.spage=1709&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - ISSN for electronic version: 1091-6490. ISSN for print version: 0027-8424. N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Intermolecular cleavage by UmuD-like mutagenesis proteins AN - 16259803; 4242048 AB - The activity of a number of proteins is regulated by self-processing reactions. Elegant examples are the cleavage of the prokaryotic LexA and lambda CI transcriptional repressors and the UmuD- like mutagenesis proteins. Various studies support the hypothesis that LexA and lambda CI cleavage reactions are predominantly intramolecular in nature. The recently described crystal structure of the Escherichia coli UmuD' protein (the posttranslational cleavage product of the UmuD protein) suggests, however, that the region of the protein corresponding to the cleavage site is at least 50 Aa away from the catalytic active site. We considered the possibility, therefore, that the UmuD-like proteins might undergo self-processing that, in contrast to LexA and lambda CI, occurs via an intermolecular rather than intramolecular reaction. To test this hypothesis, we introduced into E. coli compatible plasmids with mutations at either the cleavage or the catalytic site of three UmuD-like proteins. Cleavage of these proteins only occurs in the presence of both plasmids, indicating that the reaction is indeed intermolecular in nature. Furthermore, this intermolecular reaction is completely dependent upon the multifunctional RecA protein and leads to the restoration of cellular mutagenesis in nonmutable E. coli strains. Intermolecular cleavage of a biotinylated UmuD active site mutant was also observed in super( ) vitro in the presence of the wild-type UmuD' protein, indicating that in addition to the intact UmuD protein, the normal cleavage product (UmuD') can also act as a classical enzyme. JF - Proceedings of the National Academy of Sciences, USA AU - McDonald, J AU - Frank, E AU - Levine, A AU - Woodgate, R AD - Section on DNA Replication, Repair, and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2725 Y1 - 1998/02/17/ PY - 1998 DA - 1998 Feb 17 SP - 1478 EP - 1483 VL - 95 IS - 4 SN - 0027-8424, 0027-8424 KW - UmuD protein KW - UmuD' protein KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - N 14681:Mutagenesis techniques KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16259803?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Intermolecular+cleavage+by+UmuD-like+mutagenesis+proteins&rft.au=McDonald%2C+J%3BFrank%2C+E%3BLevine%2C+A%3BWoodgate%2C+R&rft.aulast=McDonald&rft.aufirst=J&rft.date=1998-02-17&rft.volume=95&rft.issue=4&rft.spage=1478&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - ISSN for electronic version: 1091-6490. ISSN for print version: 0027-8424. N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Characterization of functional vanilloid receptors expressed by mast cells. AN - 79678265; 9454764 AB - Capsaicin and its ultrapotent analog resiniferatoxin (RTX) act through specific vanilloid receptors on sensory neurons. The C-type receptor is coupled to 45Ca uptake, whereas the R-type is detectable by [3H]RTX binding. We describe here specific vanilloid responses in murine mast cells (MCs). In the MC lines and in bone marrow-derived mast cells, capsaicin and RTX induced 45Ca uptake similarly to that observed for cultured rat dorsal root ganglion neurons (DRGs). This response was antagonized by the antagonists capsazepine and ruthenium red. As in DRGs, pretreatment of MCs with capsaicin or RTX induced desensitization to subsequent stimulation of 45Ca uptake. The potency for desensitization by RTX in the MCs corresponded to that for 45Ca uptake, whereas in DRGs it occurred at significantly lower concentrations corresponding to that for the high-affinity [3H]RTX binding site. Consistent with this difference, in MCs we were unable to detect [3H]RTX binding. Vanilloids were noncytotoxic to the MCs, in contrast to the DRGs. Although vanilloids did not cause degranulation in MCs, in the P815 clone capsaicin evoked selective interleukin-4 release. We conclude that certain MCs possess vanilloid receptors, but only the C-type that functions as a channel. Our finding that MCs can respond directly to capsaicin necessitates a reevaluation of the in vivo pathway of inflammation in response to vanilloids. JF - Blood AU - Bíró, T AU - Maurer, M AU - Modarres, S AU - Lewin, N E AU - Brodie, C AU - Acs, G AU - Acs, P AU - Paus, R AU - Blumberg, P M AD - Molecular Mechanisms of Tumor Promotion Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1998/02/15/ PY - 1998 DA - 1998 Feb 15 SP - 1332 EP - 1340 VL - 91 IS - 4 SN - 0006-4971, 0006-4971 KW - Receptors, Drug KW - 0 KW - Capsaicin KW - S07O44R1ZM KW - Calcium KW - SY7Q814VUP KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Calcium -- metabolism KW - Animals KW - Mice KW - Signal Transduction KW - Cell Line KW - Bone Marrow Cells -- metabolism KW - Receptors, Drug -- metabolism KW - Mast Cells -- metabolism KW - Capsaicin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79678265?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Characterization+of+functional+vanilloid+receptors+expressed+by+mast+cells.&rft.au=B%C3%ADr%C3%B3%2C+T%3BMaurer%2C+M%3BModarres%2C+S%3BLewin%2C+N+E%3BBrodie%2C+C%3BAcs%2C+G%3BAcs%2C+P%3BPaus%2C+R%3BBlumberg%2C+P+M&rft.aulast=B%C3%ADr%C3%B3&rft.aufirst=T&rft.date=1998-02-15&rft.volume=91&rft.issue=4&rft.spage=1332&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-03 N1 - Date created - 1998-03-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutagenesis of a single AT basepair in mice transgenic for PhiX174 am3 cs70. I. Spleen and testis AN - 16206800; 4277316 AB - Mutations induced in a single AT base pair were studied in spleen and testis by using mice transgenic for PhiX174 am3, cs70 and ethylnitrosourea (ENU) as the mutagen. The transgenic mice were produced on the C57BL6/J background. The line (am54), which carries 50 copies of PhiX per haploid genome integrated in a tandem array, was selected for experimental use and was maintained by random breeding. The animals for mutagenesis studies were produced by mating homozygous am54 males to wildtype C57BL6/J females. Hemizygous male offspring (8 to 10 weeks old) from this cross were injected i.p. with 150 mg ENU per kg and were euthanized 3, 10 or 110 days after treatment. The spontaneous revertant frequency in the spleen was 1.42 x 10 -6 per plaque forming unit (pfu) and in the testis it was 1.41 x 10 -6 per pfu. There was no significant difference between the two tissues. In spleen, it was not until 110 days after ENU treatment that the average revertant frequency among treated animals was significantly higher than the revertant frequency among the control animals. In spleen, the induced frequency of basepair substitutions in the center AT basepair in the am3 nonsense codon was 2 x 10 -6 . Also at this post-injection interval the variance of revertant frequencies in the spleen was not different from control variance. In testis, the average revertant frequency 110 days post ENU injection was not significantly different from the control. However, two important observations were made regarding the testis data. First, one animal had a significantly increased revertant frequency 110 days after ENU treatment in comparison to the other four animals in the group that had revertant frequencies equal to or lower than the average control frequency. Second, the variance of revertant frequencies in the testis among the treated animals increased as the post injection period increased. Taken together, these observations may indicate that the revertants formed large clusters in one testis sample. JF - Mutation Research-Genetic Toxicology and Environmental Mutagenesis AU - Malling, H V AU - Weaver, R P AD - Mammalian Genetics Group, Laboratory of Toxicology, Environmental Toxicology Program, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709-2233, USA Y1 - 1998/02/13/ PY - 1998 DA - 1998 Feb 13 SP - 271 EP - 281 PB - Elsevier Science B.V. VL - 412 IS - 3 SN - 1383-5718, 1383-5718 KW - mutagenesis KW - transgenic mice KW - Genetics Abstracts; Toxicology Abstracts KW - X 24200:Nitrosamines & related compounds KW - G 07221:Specific chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16206800?accountid=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=Mutagenesis+of+a+single+AT+basepair+in+mice+transgenic+for+PhiX174+am3+cs70.+I.+Spleen+and+testis&rft.au=Malling%2C+H+V%3BWeaver%2C+R+P&rft.aulast=Malling&rft.aufirst=H&rft.date=1998-02-13&rft.volume=412&rft.issue=3&rft.spage=271&rft.isbn=&rft.btitle=&rft.title=Mutation+Research-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 ER - TY - JOUR T1 - Identification of cdk2 binding sites on the p27Kip1 cyclin-dependent kinase inhibitor. AN - 79709335; 9488039 AB - A cdk2 binding domain on p27Kip1 located within the sequence of amino acids 53-85 was further characterized by generating a series of point mutations within amino acid residues 62-75. Two regions, FDF (residues 62-64) and GXY (residues 72 and 74), were identified within the beta hairpin region of p27Kip1. Mutations within these regions essentially completely inhibited the binding to in vitro translated cdk2 and cdk2/cyclin E complexes formed in vitro or in vivo. The p27Kip1 GST-fusion protein of the point mutation that replaces phenylalanine at residue 64 to alanine (F64A) showed approximately twofold less inhibition of cdk2 kinase activity. The cellular response to the introduction of the F64A mutant form of p27Kip1 was compared to that of p27Kip1 wild type by transfecting HeLa cells with constructs of full length sense and antisense coding sequences. Overexpression of the F64A mutant form of p27Kip1 bound significantly lower levels of cdk2 as compared to wild type and did not affect the cdk2 related kinase activity of the transfected HeLa cells. Overexpression of wild type p27Kip1 resulted in a reduction of the level of cdk2 kinase activity and effectively suppressed the growth of the transfected HeLa cells. JF - Oncogene AU - Kwon, T K AU - Nordin, A A AD - Laboratory of Immunology, Gerontology Research Center, National Institute on Aging, NIH, Baltimore, Maryland 21224, USA. Y1 - 1998/02/12/ PY - 1998 DA - 1998 Feb 12 SP - 755 EP - 762 VL - 16 IS - 6 SN - 0950-9232, 0950-9232 KW - Cdkn1b protein, mouse KW - 0 KW - Cell Cycle Proteins KW - Cyclin E KW - Enzyme Inhibitors KW - Microtubule-Associated Proteins KW - Recombinant Fusion Proteins KW - Tumor Suppressor Proteins KW - Cyclin-Dependent Kinase Inhibitor p27 KW - 147604-94-2 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - CDC2-CDC28 Kinases KW - EC 2.7.11.22 KW - CDK2 protein, human KW - Cdk2 protein, mouse KW - Cyclin-Dependent Kinase 2 KW - Cyclin-Dependent Kinases KW - Index Medicus KW - Animals KW - HeLa Cells KW - Humans KW - Mice KW - Binding Sites KW - Cyclin E -- metabolism KW - Mutagenesis, Site-Directed KW - Recombinant Fusion Proteins -- metabolism KW - Tumor Cells, Cultured KW - Transfection KW - Recombinant Fusion Proteins -- genetics KW - Cell Division KW - Cyclin-Dependent Kinases -- metabolism KW - Microtubule-Associated Proteins -- metabolism KW - Microtubule-Associated Proteins -- genetics KW - Protein-Serine-Threonine Kinases -- metabolism KW - Cyclin-Dependent Kinases -- antagonists & inhibitors KW - Enzyme Inhibitors -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79709335?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Identification+of+cdk2+binding+sites+on+the+p27Kip1+cyclin-dependent+kinase+inhibitor.&rft.au=Kwon%2C+T+K%3BNordin%2C+A+A&rft.aulast=Kwon&rft.aufirst=T&rft.date=1998-02-12&rft.volume=16&rft.issue=6&rft.spage=755&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-13 N1 - Date created - 1998-03-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Involvement of p85 in p53-dependent apoptotic response to oxidative stress. AN - 79700053; 9490416 AB - Reactive oxygen species have damaging effects on cellular components and so trigger defensive responses by the cell and even programmed cell death, although the mechanisms by which mammalian cells transmit signals in response to oxidative damage are unknown. We report here that the protein p85, a regulator of the signalling protein phosphatidyl-3-OH kinase (PI(3)K), participates in the cell death process that is induced in response to oxidative stress and that this role of p85 in apoptosis does not involve PI(3)K. We show that disruption of p85 by homologous recombination impairs the cellular apoptotic response to oxidative stress. Because the protein p53 is required for cell death induced by oxidative damage, we examined the relation between p85 and p53. Using a chimaeric p53 fusion protein with the oestrogen receptor (p53ER) to supply p53 (p53 is induced upon binding of p53ER to oestradiol) in a p53-deficient cell line, we found that p85 is upregulated by p53 and that its involvement in p53-mediated apoptosis is independent of PI(3)K. We propose that p85 acts as a signal transducer in the cellular response to oxidative stress, mediating cell death regulated by p53. JF - Nature AU - Yin, Y AU - Terauchi, Y AU - Solomon, G G AU - Aizawa, S AU - Rangarajan, P N AU - Yazaki, Y AU - Kadowaki, T AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/02/12/ PY - 1998 DA - 1998 Feb 12 SP - 707 EP - 710 VL - 391 IS - 6668 SN - 0028-0836, 0028-0836 KW - Androstadienes KW - 0 KW - Antisense Elements (Genetics) KW - Enzyme Inhibitors KW - Recombinant Fusion Proteins KW - Tumor Suppressor Protein p53 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - wortmannin KW - XVA4O219QW KW - Index Medicus KW - Animals KW - Fibroblasts -- drug effects KW - Fibroblasts -- enzymology KW - Humans KW - Hydrogen Peroxide -- pharmacology KW - Androstadienes -- pharmacology KW - Fibroblasts -- cytology KW - Mice KW - Recombinant Fusion Proteins -- metabolism KW - Tumor Cells, Cultured KW - Enzyme Inhibitors -- pharmacology KW - Signal Transduction KW - Cell Line KW - Phosphatidylinositol 3-Kinases -- genetics KW - Tumor Suppressor Protein p53 -- physiology KW - Apoptosis KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Oxidative Stress KW - Tumor Suppressor Protein p53 -- genetics KW - Phosphatidylinositol 3-Kinases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79700053?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=Involvement+of+p85+in+p53-dependent+apoptotic+response+to+oxidative+stress.&rft.au=Yin%2C+Y%3BTerauchi%2C+Y%3BSolomon%2C+G+G%3BAizawa%2C+S%3BRangarajan%2C+P+N%3BYazaki%2C+Y%3BKadowaki%2C+T%3BBarrett%2C+J+C&rft.aulast=Yin&rft.aufirst=Y&rft.date=1998-02-12&rft.volume=391&rft.issue=6668&rft.spage=707&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-02 N1 - Date created - 1998-03-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dopamine induces apoptosis through an oxidation-involved SAPK/JNK activation pathway. AN - 79680204; 9452508 AB - Dopamine (DA) is a neurotransmitter, but it also exerts a neurotoxic effect under certain pathological conditions, including age-related neurodegeneration such as Parkinson's disease. By using both the 293 cell line and primary neonatal rat postmitotic striatal neuron cultures, we show here that DA induces apoptosis in a time- and concentration-dependent manner. Concomitant with the apoptosis, DA activates the JNK pathway, including increases in JNK activity, phosphorylation of c-Jun, and subsequent increase in c-Jun protein. This DA-induced JNK activation precedes apoptosis and is persistently sustained during the process of apoptosis. Transient expression of a dominant negative mutant SEK1(Lys --> Arg), an upstream kinase of JNK, prevents both DA-induced JNK activation and apoptosis. A dominant negative c-Jun mutant FLAGDelta169 also reduces DA-induced apoptotic cell death. Anti-oxidants N-acetylcysteine and catalase, which serve as scavengers of reactive oxygen species generated by metabolic DA oxidation, effectively block DA-induced JNK activation and subsequent apoptosis. Thus, our data suggest that DA triggers an apoptotic death program through an oxidative stress-involved JNK activation signaling pathway. Given the fact that the anti-oxidative defense system declines during aging, this molecular event may be implicated in the age-related striatal neuronal cell loss and age-related dopaminergic neurodegenerative disorders, such as Parkinson's and Huntington's diseases. JF - The Journal of biological chemistry AU - Luo, Y AU - Umegaki, H AU - Wang, X AU - Abe, R AU - Roth, G S AD - Molecular Physiology and Genetics Section, Gerontology Research Center, NIA, National Institutes of Health, Baltimore, Maryland 21224, USA. luoyq@helix.nih.gov Y1 - 1998/02/06/ PY - 1998 DA - 1998 Feb 06 SP - 3756 EP - 3764 VL - 273 IS - 6 SN - 0021-9258, 0021-9258 KW - Antioxidants KW - 0 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - JNK Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinases KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Oxidation-Reduction KW - Animals KW - Antioxidants -- pharmacology KW - Enzyme Activation KW - Humans KW - Neurons -- cytology KW - Kidney -- cytology KW - Signal Transduction KW - Cell Line KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Apoptosis -- physiology KW - Apoptosis -- drug effects KW - Dopamine -- physiology KW - Dopamine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79680204?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Dopamine+induces+apoptosis+through+an+oxidation-involved+SAPK%2FJNK+activation+pathway.&rft.au=Luo%2C+Y%3BUmegaki%2C+H%3BWang%2C+X%3BAbe%2C+R%3BRoth%2C+G+S&rft.aulast=Luo&rft.aufirst=Y&rft.date=1998-02-06&rft.volume=273&rft.issue=6&rft.spage=3756&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-05 N1 - Date created - 1998-03-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transformation suppressor activity of C3G is independent of its CDC25-homology domain. AN - 79700398; 9482107 AB - The guanine nucleotide releasing protein C3G was initially identified as a Crk SH3-binding protein and recently shown to exhibit exchange activity on Rap1 proteins. Overexpression in NIH3T3 cells of a full-length C3G cDNA isolated from human placenta markedly reduced the focus forming activity of cotransfected, malignantly activated, ras oncogenes (5-7-fold). C3G also had a reverting effect on sis-mediated transformation, decreasing the number of c-sis-induced foci by a factor of 5-10-fold. The observed inhibitory effect of C3G on focus-forming activity of Ras and Sis was always higher than that observed with Rap1A, a known target of C3G. The inhibition of focus formation observed in the presence of C3G was not due to toxic effects on cell viability, since transfected C3G cells exhibited the same survival and growth rates as untransfected NIH3T3 cells or cells transfected with plasmid vector alone. Surprisingly, as opposed to Rap1A, which has no effect on Raf-1 oncogene-mediated transformation, C3G also reduced dramatically (6-8-fold) the number of v-raf-induced foci in transfected NIH3T3 cells. The inhibitory effect on Raf-induced transformation suggests that C3G has other functional targets in addition to Rap1. A C3G mutant (C3G deltaCat) lacking the catalytic domain (CDC25-H) but retaining the rest of the N-terminal sequences, including the Crk-binding domain, exhibited similar ability than full length C3G to inhibit focus formation. In contrast, a C3G mutant (C3G Cat), containing the catalytic domain only but lacking the rest of the N-terminal sequences, did not have any inhibitory effect on transformation mediated by the oncogenes tested. The C3G-derived gene products overexpressed in our transfected cell lines localized to the cytoplasm and did not change the basal MAPK or JNK activity of those cell lines nor their ability to activate the kinases in response to agonists. Our results suggest that the N-terminal region of C3G, and not its catalytic domain, may be responsible for the inhibitory effects observed. JF - Oncogene AU - Guerrero, C AU - Fernandez-Medarde, A AU - Rojas, J M AU - Font de Mora, J AU - Esteban, L M AU - Santos, E AD - Laboratory of Cellular and Molecular Biology, NCI, DBS, NIH, Bethesda, Maryland 20892, USA. Y1 - 1998/02/05/ PY - 1998 DA - 1998 Feb 05 SP - 613 EP - 624 VL - 16 IS - 5 SN - 0950-9232, 0950-9232 KW - Cell Cycle Proteins KW - 0 KW - DNA, Complementary KW - Guanine Nucleotide Exchange Factors KW - Platelet-Derived Growth Factor KW - Proteins KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-sis KW - Retroviridae Proteins, Oncogenic KW - ras Guanine Nucleotide Exchange Factors KW - ras-GRF1 KW - Oncogene Proteins v-raf KW - EC 2.7.11.1 KW - Phosphoprotein Phosphatases KW - EC 3.1.3.16 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - rap GTP-Binding Proteins KW - EC 3.6.5.2 KW - Index Medicus KW - Animals KW - Peptide Mapping KW - Retroviridae Proteins, Oncogenic -- physiology KW - Humans KW - Proto-Oncogene Proteins -- genetics KW - Platelet-Derived Growth Factor -- physiology KW - Placenta -- chemistry KW - Protein Biosynthesis KW - DNA, Complementary -- genetics KW - Mice KW - GTP-Binding Proteins -- physiology KW - Platelet-Derived Growth Factor -- genetics KW - GTP-Binding Proteins -- genetics KW - Proto-Oncogene Proteins -- physiology KW - Cloning, Molecular KW - Binding Sites KW - Retroviridae Proteins, Oncogenic -- genetics KW - Transfection KW - DNA, Complementary -- metabolism KW - 3T3 Cells -- metabolism KW - Placenta -- metabolism KW - Genes, ras KW - Cell Cycle Proteins -- physiology KW - Phosphoprotein Phosphatases -- physiology KW - Gene Expression Regulation -- physiology KW - Cell Cycle Proteins -- genetics KW - Phosphoprotein Phosphatases -- genetics KW - Proteins -- genetics KW - Proteins -- physiology KW - src Homology Domains KW - Transformation, Genetic -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79700398?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Transformation+suppressor+activity+of+C3G+is+independent+of+its+CDC25-homology+domain.&rft.au=Guerrero%2C+C%3BFernandez-Medarde%2C+A%3BRojas%2C+J+M%3BFont+de+Mora%2C+J%3BEsteban%2C+L+M%3BSantos%2C+E&rft.aulast=Guerrero&rft.aufirst=C&rft.date=1998-02-05&rft.volume=16&rft.issue=5&rft.spage=613&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-09 N1 - Date created - 1998-03-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Plasmodium malariae infection in an asymptomatic 74-year-old Greek woman with splenomegaly. AN - 79672836; 9449730 JF - The New England journal of medicine AU - Vinetz, J M AU - Li, J AU - McCutchan, T F AU - Kaslow, D C AD - Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md 20892, USA. Y1 - 1998/02/05/ PY - 1998 DA - 1998 Feb 05 SP - 367 EP - 371 VL - 338 IS - 6 SN - 0028-4793, 0028-4793 KW - Antibodies, Protozoan KW - 0 KW - Methotrexate KW - YL5FZ2Y5U1 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Lymphoma -- diagnosis KW - Base Sequence KW - Diagnosis, Differential KW - Greece KW - Humans KW - Antibodies, Protozoan -- blood KW - Molecular Sequence Data KW - Lymphoma -- drug therapy KW - Aged KW - Female KW - Splenomegaly -- etiology KW - Methotrexate -- adverse effects KW - Plasmodium malariae -- immunology KW - Plasmodium malariae -- genetics KW - Malaria -- diagnosis KW - Malaria -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79672836?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+journal+of+medicine&rft.atitle=Plasmodium+malariae+infection+in+an+asymptomatic+74-year-old+Greek+woman+with+splenomegaly.&rft.au=Vinetz%2C+J+M%3BLi%2C+J%3BMcCutchan%2C+T+F%3BKaslow%2C+D+C&rft.aulast=Vinetz&rft.aufirst=J&rft.date=1998-02-05&rft.volume=338&rft.issue=6&rft.spage=367&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=00284793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-05 N1 - Date created - 1998-02-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: N Engl J Med. 2000 Jun 22;342(25):1924 [10877649] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Much ado about not...enough data: high-dose chemotherapy with autologous stem cell rescue for breast cancer. AN - 79683132; 9462677 AB - High-dose chemotherapy with autologous bone marrow or stem cell rescue (HDC/ASCR) has been proposed as a promising treatment strategy for breast cancer. Despite the frequency with which this procedure is performed, the role of HDC/ASCR in the treatment of breast cancer remains undefined. The purpose of this review is to examine the rationale for the procedure, the research progress to date, and the limitations of available data. A literature search of Medline from January 1966 through May 1997, CancerLit from January 1983 through May 1997, and Current Contents through May 1997 identified more than 600 English language papers or abstracts on this topic. Our review focuses on the preclinical and clinical data that explore the concept of chemotherapy dose intensity and the role of dose intensity in treating breast cancer. HDC/ASCR is based on the hypothesis that high-dose chemotherapy will overcome drug resistance, eradicate metastatic disease, and increase the proportion of women with breast cancer who are "cured." To date, results from only one phase 3 trial of HDC/ASCR compared with more conventional therapy have been published. Phase 2 and some phase 3 data on HDC/ASCR in the treatment of high-risk primary breast cancer and metastatic breast cancer are discussed. However, the results are inconclusive. The completion of national and international randomized trials is urgently needed to establish definitively the role of HDC/ASCR in the treatment of breast cancer. JF - Journal of the National Cancer Institute AU - Zujewski, J AU - Nelson, A AU - Abrams, J AD - National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1998/02/04/ PY - 1998 DA - 1998 Feb 04 SP - 200 EP - 209 VL - 90 IS - 3 SN - 0027-8874, 0027-8874 KW - Index Medicus KW - Randomized Controlled Trials as Topic KW - Humans KW - Clinical Trials as Topic KW - Transplantation, Autologous KW - Female KW - Breast Neoplasms -- drug therapy KW - Hematopoietic Stem Cell Transplantation KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Breast Neoplasms -- surgery UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79683132?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Much+ado+about+not...enough+data%3A+high-dose+chemotherapy+with+autologous+stem+cell+rescue+for+breast+cancer.&rft.au=Zujewski%2C+J%3BNelson%2C+A%3BAbrams%2C+J&rft.aulast=Zujewski&rft.aufirst=J&rft.date=1998-02-04&rft.volume=90&rft.issue=3&rft.spage=200&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-17 N1 - Date created - 1998-02-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Unusual insertion element polymorphisms in the promoter and terminator regions of the mucAB-like genes of R471a and R446b. AN - 79790298; 9541650 AB - We have previously identified umu-complementing genes on two incL/M plasmids, R471a and R446b (C. Ho et al., J. Bacteriol., 175 (1993) 5411-5419). Molecular analysis of these genes revealed that they are more structurally and functionally related to mucAB from the incN plasmid pKM101 than to other members of the previously identified Umu-like family. As a consequence, we have termed these new homologs mucAB(R471a) and mucAB(R446b) respectively. Interestingly, while the location of the mucAB-like genes is essentially the same in both R471a and R446b, the regions immediately flanking the mucAB-like genes are highly polymorphic. For example, 5' to mucAB(R471a) we found an insert that appears to be a novel retroelement encoding a putative reverse transcriptase (RT). This RT is related to the reverse transcriptases encoded by group II introns but is embedded in a retron-like context. Immediately 3' to the mucAB(R471a) locus is a putative insertion element of a sparsely-dispersed class not previously reported from enteric bacteria. Both the RT and insertion element are absent in R446b. These observations suggest that the mucAB-like genes from R471a and R446b are located within regions of the R-plasmids that perhaps were once (or still are) mobile genetic elements. Such observations might help explain the distribution of umu-like genes on R-plasmids and bacterial chromosomes. JF - Mutation research AU - Kulaeva, O I AU - Koonin, E V AU - Wootton, J C AU - Levine, A S AU - Woodgate, R AD - Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2725, USA. Y1 - 1998/02/02/ PY - 1998 DA - 1998 Feb 02 SP - 247 EP - 262 VL - 397 IS - 2 SN - 0027-5107, 0027-5107 KW - Bacterial Proteins KW - 0 KW - DNA Transposable Elements KW - DNA, Bacterial KW - Escherichia coli Proteins KW - mucAB protein, E coli KW - 138186-81-9 KW - RNA-Directed DNA Polymerase KW - EC 2.7.7.49 KW - Aspartic Acid Endopeptidases KW - EC 3.4.23.- KW - signal peptidase II KW - EC 3.4.23.36 KW - Index Medicus KW - Phenotype KW - Base Sequence KW - Aspartic Acid Endopeptidases -- genetics KW - Operon KW - Molecular Sequence Data KW - Escherichia coli -- genetics KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - RNA-Directed DNA Polymerase -- genetics KW - Terminator Regions, Genetic KW - Promoter Regions, Genetic KW - Bacterial Proteins -- genetics KW - Polymorphism, Genetic KW - DNA Transposable Elements -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79790298?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Unusual+insertion+element+polymorphisms+in+the+promoter+and+terminator+regions+of+the+mucAB-like+genes+of+R471a+and+R446b.&rft.au=Kulaeva%2C+O+I%3BKoonin%2C+E+V%3BWootton%2C+J+C%3BLevine%2C+A+S%3BWoodgate%2C+R&rft.aulast=Kulaeva&rft.aufirst=O&rft.date=1998-02-02&rft.volume=397&rft.issue=2&rft.spage=247&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-22 N1 - Date created - 1998-04-22 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF027768; GENBANK; AF027767 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effortful echolalia. AN - 85420418; pmid-9533994 AB - We report three cases of effortful echolalia in patients with cerebral infarction. The clinical picture of speech disturbance is associated with Type 1 Transcortical Motor Aphasia (TCMA, Goldstein, 1915). The patients always spoke nonfluently with loss of speech initiative, dysarthria, dysprosody, agrammatism, and increased effort and were unable to repeat sentences longer than those containing four or six words. In conversation, they first repeated a few words spoken to them, and then produced self initiated speech. The initial repetition as well as the subsequent self initiated speech, which were realized equally laboriously, can be regarded as mitigated echolalia (Pick, 1924). They were always aware of their own echolalia and tried to control it without effect. These cases demonstrate that neither the ability to repeat nor fluent speech are always necessary for echolalia. The possibility that a lesion in the left medial frontal lobe, including the supplementary motor area, plays an important role in effortful echolalia is discussed. JF - Cortex; a journal devoted to the study of the nervous system and behavior AU - Hadano, K AU - Nakamura, H AU - Hamanaka, T AD - Department of Psychogeriatrics, National Institute of Mental Health (NCNP), Nagoya. hadano@ncnp-k.go.jp Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 67 EP - 82 VL - 34 IS - 1 SN - 0010-9452, 0010-9452 KW - Index Medicus KW - National Library of Medicine KW - Magnetic Resonance Imaging KW - Humans KW - Cerebral Infarction -- pathology KW - Echolalia -- psychology KW - Tomography, X-Ray Computed KW - Memory -- physiology KW - Echolalia -- etiology KW - Aged KW - Echolalia -- pathology KW - Music KW - Middle Aged KW - Neuropsychological Tests KW - Female KW - Male KW - Cerebral Infarction -- complications KW - Cerebral Infarction -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85420418?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cortex%3B+a+journal+devoted+to+the+study+of+the+nervous+system+and+behavior&rft.atitle=Effortful+echolalia.&rft.au=Hadano%2C+K%3BNakamura%2C+H%3BHamanaka%2C+T&rft.aulast=Hadano&rft.aufirst=K&rft.date=1998-02-01&rft.volume=34&rft.issue=1&rft.spage=67&rft.isbn=&rft.btitle=&rft.title=Cortex%3B+a+journal+devoted+to+the+study+of+the+nervous+system+and+behavior&rft.issn=00109452&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2008-01-14 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Presynaptic localization of G protein isoforms in the efferent nerve terminals of the mammalian cochlea. AN - 85417643; pmid-9508023 AB - Heterotrimeric guanine nucleotide binding proteins (G proteins) are known to be involved in receptor-mediated synaptic activity. In order to determine which G protein isoforms, if any, are involved in synaptic regulation in the organ of Corti, we performed an extensive immunocytochemical screening. We localized a Galpha(q/11) isoform to the efferent nerve terminals using antibodies specific against the alpha subunit of these proteins. The label was observed in the efferent boutons contacting either the outer hair cells or the afferent fibers at the inner spiral bundle. We compared the localization of this isoform to that of the presynaptic protein SNAP-25 in double labeling experiments. Galpha(q/11) immunoreactivity was present predominantly in the cytoplasm of the presynaptic boutons in a region of high density of synaptic vesicles, while SNAP-25 was localized predominantly in the plasma membrane of the boutons. No label for these proteins was found at the afferent synapses, including the presynaptic terminals on hair cells. These results suggest that an isoform of the Gq subfamily of the G proteins might be involved in presynaptic modulation of neurotransmitter release at the cochlear efferents. JF - Hearing research AU - Kurc, M AU - Dodane, V AU - Pinto, D S AU - Kachar, B AD - Section on Structural Cell Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 1 EP - 9 VL - 116 IS - 1-2 SN - 0378-5955, 0378-5955 KW - Index Medicus KW - National Library of Medicine KW - Animals KW - Efferent Pathways -- metabolism KW - Guinea Pigs KW - GTP-Binding Proteins -- chemistry KW - Organ of Corti -- metabolism KW - Hair Cells, Auditory -- metabolism KW - Synaptosomal-Associated Protein 25 KW - GTP-Binding Proteins -- metabolism KW - Nerve Tissue Proteins -- metabolism KW - GTP-Binding Proteins -- immunology KW - Immunohistochemistry KW - Male KW - Female KW - Signal Transduction KW - Cochlea -- metabolism KW - Cochlea -- innervation KW - Membrane Proteins KW - Presynaptic Terminals -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85417643?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hearing+research&rft.atitle=Presynaptic+localization+of+G+protein+isoforms+in+the+efferent+nerve+terminals+of+the+mammalian+cochlea.&rft.au=Kurc%2C+M%3BDodane%2C+V%3BPinto%2C+D+S%3BKachar%2C+B&rft.aulast=Kurc&rft.aufirst=M&rft.date=1998-02-01&rft.volume=116&rft.issue=1-2&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Hearing+research&rft.issn=03785955&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2008-01-14 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Using joint geometry to determine the motion of the cricoarytenoid joint. AN - 85416803; pmid-9479765 AB - Facet surfaces of the cricoarytenoid joints from two cadaver larynges were digitized. The data were used to compute the optimal axis of rotation for each of the joints in the sense that the computed axis minimized the variance of the joint gap over the full range of joint motion. The optimal axis corresponded to a rocking motion of the arytenoid on the corresponding cricoid. This motion was consistent with experimental data from digitized recordings of vocal fold movement. Using the rigid laryngoscopic view, a similarity in vocal process movement, over the range in motion, between the rocking axis and the vertical axis described in the literature was found, resolving the controversy between two conflicting views of motion of the vocal processes. JF - The Journal of the Acoustical Society of America AU - Selbie, W S AU - Zhang, L AU - Levine, W S AU - Ludlow, C L AD - Voice and Speech Section, National Institute on Deafness and Other Communication Disorders, Bethesda, Maryland 20892-1416, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 1115 EP - 1127 VL - 103 IS - 2 SN - 0001-4966, 0001-4966 KW - Index Medicus KW - National Library of Medicine KW - Humans KW - Aged KW - Female KW - Male KW - Models, Anatomic KW - Cricoid Cartilage -- physiology KW - Arytenoid Cartilage -- physiology KW - Movement -- physiology KW - Joints -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85416803?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+the+Acoustical+Society+of+America&rft.atitle=Using+joint+geometry+to+determine+the+motion+of+the+cricoarytenoid+joint.&rft.au=Selbie%2C+W+S%3BZhang%2C+L%3BLevine%2C+W+S%3BLudlow%2C+C+L&rft.aulast=Selbie&rft.aufirst=W&rft.date=1998-02-01&rft.volume=103&rft.issue=2&rft.spage=1115&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+the+Acoustical+Society+of+America&rft.issn=00014966&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2008-01-14 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Endbulb synapses in the anteroventral cochlear nucleus express a specific subset of AMPA-type glutamate receptor subunits. AN - 85220569; pmid-9437035 AB - The anteroventral cochlear nucleus (AVCN) acts as the first relay center in the conduction of auditory information from the ear to the brain, and it probably performs a crucial role in sound localization. Auditory nerve input to the principal neurons of the AVCN, the spherical bushy cells, appears to be mediated by an excitatory amino acid such as glutamate, which acts at a specialized, large synaptic ending called an endbulb of Held. Presumably, endbulb synapses contain some specific combination of glutamate receptors to facilitate rapid neurotransmission of auditory signals. AMPA glutamate receptor composition at the endbulb synapses was examined with both light and electron microscope immunocytochemistry. Electron microscope localization of AMPA receptors was examined with two techniques, preembedding immunoperoxidase and postembedding immunogold, which provide maximum sensitivity and greatest accuracy, respectively. Dense and frequent labeling was seen with the AMPA receptor subunit antibodies GluR2/3 and GluR4, which were colocalized at the endbulb synapses. In contrast, immunolabeling with antibody to GluR2 was low. These data indicate that the major glutamate receptor at this synapse is an AMPA receptor made up mainly of GluR3 and GluR4 subunits. Receptors composed of these subunits display properties, such as calcium permeability and rapid desensitization, that facilitate their specialized functions in auditory information processing. JF - The Journal of Neuroscience AU - Wang, Y X AU - Wenthold, R J AU - Ottersen, O P AU - Petralia, R S AD - National Institute on Deafness and Other Communication Disorders/National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1998 SP - 1148 EP - 1160 VL - 18 IS - 3 SN - 0270-6474, 0270-6474 KW - Sound Localization KW - Synapses KW - Calcium KW - Support, U.S. Gov't, P.H.S. KW - Animal KW - Cochlear Nucleus KW - Rats KW - Rats, Sprague-Dawley KW - Neurons KW - Receptors, AMPA KW - Microscopy, Immunoelectron KW - Immunohistochemistry KW - Male KW - Immunoenzyme Techniques UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85220569?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+Neuroscience&rft.atitle=Endbulb+synapses+in+the+anteroventral+cochlear+nucleus+express+a+specific+subset+of+AMPA-type+glutamate+receptor+subunits.&rft.au=Wang%2C+Y+X%3BWenthold%2C+R+J%3BOttersen%2C+O+P%3BPetralia%2C+R+S&rft.aulast=Wang&rft.aufirst=Y&rft.date=1998-02-01&rft.volume=18&rft.issue=3&rft.spage=1148&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+Neuroscience&rft.issn=02706474&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Dose-dependent prevention of sugar cataracts in galactose-fed dogs by the aldose reductase inhibitor M79175. AN - 79933482; 9533847 AB - Sugar cataracts rapidly develop in dogs fed a diet containing 30% galactose. While studies on the formation and progression of these sugar cataracts suggest that they are osmotic in nature and are linked to aldose reductase, sugar cataract formation in the dog to date has not been completely prevented by the administration of aldose reductase inhibitors sorbinil and M79175. To demonstrate that the formation and progression of sugar cataracts in galactose-fed dogs can be dose-dependently inhibited by the administration of aldose reductase inhibitors, 9-month old male beagles were placed on diet containing 30% galactose with/without 10 or 16 mg kg-1 day-1 of M79175 for up to 39 months. Cataract progression in all dogs was followed by periodic slit lamp examination and documented by retroillumination photography. Although large variations in cataract formation and progression were observed, all dogs fed a 30% galactose diet for 39 months developed cataracts. Lens changes were significantly less in galactose-fed dogs treated with either 10 or 16 mg kg-1 M79175 and no cataract formation was observed in 3 of 6 galactose-fed dogs treated with 16 mg kg-1 M79175. These observations confirm that aldose reductase plays a key role in initiating cataract formation in galactose-fed dogs and that cataract formation can be prevented by adequate inhibition of aldose reductase. Copyright 1998 Academic Press Limited. JF - Experimental eye research AU - Sato, S AU - Mori, K AU - Wyman, M AU - Kador, P F AD - Laboratory of Ocular Therapeutics, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-1850, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 217 EP - 222 VL - 66 IS - 2 SN - 0014-4835, 0014-4835 KW - Dietary Carbohydrates KW - 0 KW - Enzyme Inhibitors KW - Imidazoles KW - Imidazolidines KW - M 79175 KW - 82319-87-7 KW - Aldehyde Reductase KW - EC 1.1.1.21 KW - Galactose KW - X2RN3Q8DNE KW - Index Medicus KW - Animals KW - Dietary Carbohydrates -- toxicity KW - Dose-Response Relationship, Drug KW - Dogs KW - Male KW - Imidazoles -- pharmacology KW - Galactose -- administration & dosage KW - Cataract -- chemically induced KW - Enzyme Inhibitors -- pharmacology KW - Galactose -- toxicity KW - Aldehyde Reductase -- antagonists & inhibitors KW - Aldehyde Reductase -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79933482?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Traumatic+Stress&rft.atitle=International+tourists%E2%80%99+reactions+to+a+natural+disaster%3A+Experiences+of+the+2015+earthquake+in+Nepal+among+Israeli+travelers&rft.au=Itzhaky%2C+Haya%3BKissil%2C+Karni%3BWeiss%E2%80%90Dagan%2C+Shlomit&rft.aulast=Itzhaky&rft.aufirst=Haya&rft.date=2016-12-01&rft.volume=29&rft.issue=6&rft.spage=522&rft.isbn=&rft.btitle=&rft.title=Journal+of+Traumatic+Stress&rft.issn=08949867&rft_id=info:doi/10.1002%2Fjts.22136 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-24 N1 - Date created - 1998-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Endocrine effects of nicotine administration, tobacco and other drug withdrawal in humans. AN - 79927354; 9621394 AB - The focus of this manuscript is on the effects of smoking and tobacco withdrawal on the hypothalamic-pituitary axis (HPA). A variety of studies have shown that nicotine administered intravenously or through intense cigarette smoking can induce changes in hormones associated with the HPA. Administration of, and abrupt cessation from, other drugs of abuse has also been shown to affect levels of these hormones. Additionally, many of the symptoms of stress and tobacco withdrawal overlap suggesting that the hormonal changes seen during periods of stress may be observed during tobacco abstinence. These findings led to a study of the effects of tobacco withdrawal on plasma ACTH, cortisol, and prolactin levels. The results indicated tobacco cessation caused small and transient effects on plasma hormone levels which were not significantly influenced by nicotine replacement and were not related to other signs of withdrawal. JF - Psychoneuroendocrinology AU - Pickworth, W B AU - Fant, R V AD - National Institute on Drug Abuse, Addiction Research Center, Baltimore, MD 21224, USA. wpickwo@irp.nida.nih.gov Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 131 EP - 141 VL - 23 IS - 2 SN - 0306-4530, 0306-4530 KW - Nicotinic Agonists KW - 0 KW - Nicotine KW - 6M3C89ZY6R KW - Index Medicus KW - Hypothalamo-Hypophyseal System -- drug effects KW - Animals KW - Humans KW - Smoking -- physiopathology KW - Substance Withdrawal Syndrome -- physiopathology KW - Nicotine -- pharmacology KW - Endocrine Glands -- drug effects KW - Smoking Cessation KW - Nicotinic Agonists -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79927354?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychoneuroendocrinology&rft.atitle=Endocrine+effects+of+nicotine+administration%2C+tobacco+and+other+drug+withdrawal+in+humans.&rft.au=Pickworth%2C+W+B%3BFant%2C+R+V&rft.aulast=Pickworth&rft.aufirst=W&rft.date=1998-02-01&rft.volume=23&rft.issue=2&rft.spage=131&rft.isbn=&rft.btitle=&rft.title=Psychoneuroendocrinology&rft.issn=03064530&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-26 N1 - Date created - 1998-08-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ifenprodil blocks the excitatory effects of the opioid peptide dynorphin 1-17 on NMDA receptor-mediated currents in the CA3 region of the guinea pig hippocampus. AN - 79831943; 9571650 AB - This study found that dynorphin had a biphasic concentration response relationship on N-methyl-D-aspartate (NMDA) receptor-mediated currents in the CA3 region of the guinea pig hippocampal slice. A previous study demonstrated that the inhibitory effect was mediated by a kappa 2 opioid receptor. In the present study, the polyamine site antagonist ifenprodil converted dynorphin's biphasic concentration response relationship to a monophasic inhibitory curve. The polyamine diethylenetriamine also blocked dynorphin's excitatory actions. The combination of dynorphin 1-17 and naloxone produced neurotoxicity, presumably as a result of dynorphin's excitatory actions on NMDA receptors. In addition, the release of endogenous dynorphin from mossy fibers in the presence of naloxone injured the cells. Ifenprodil prevented the neurotoxicity of both applied and released dynorphin. These findings suggest that dynorphin acts at a polyamine site to produce its excitatory effects and, further, suggest that dynorphin may mediate some neuropathologies through its interaction at this site. JF - Neuropeptides AU - Caudle, R M AU - Dubner, R AD - Pain and Neurosensory Mechanisms Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892, USA. Robert Caudle@NIH.GOV Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 87 EP - 95 VL - 32 IS - 1 SN - 0143-4179, 0143-4179 KW - Excitatory Amino Acid Antagonists KW - 0 KW - Narcotic Antagonists KW - Piperidines KW - Polyamines KW - Receptors, N-Methyl-D-Aspartate KW - diethylenetriamine KW - 03K6SX4V2J KW - Naloxone KW - 36B82AMQ7N KW - Dynorphins KW - 74913-18-1 KW - ifenprodil KW - R8OE3P6O5S KW - Index Medicus KW - Naloxone -- pharmacology KW - Animals KW - Polyamines -- pharmacology KW - Electric Conductivity KW - Guinea Pigs KW - Electric Stimulation KW - Narcotic Antagonists -- pharmacology KW - Male KW - Binding Sites KW - Piperidines -- pharmacology KW - Receptors, N-Methyl-D-Aspartate -- physiology KW - Hippocampus -- physiology KW - Receptors, N-Methyl-D-Aspartate -- drug effects KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Dynorphins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79831943?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropeptides&rft.atitle=Ifenprodil+blocks+the+excitatory+effects+of+the+opioid+peptide+dynorphin+1-17+on+NMDA+receptor-mediated+currents+in+the+CA3+region+of+the+guinea+pig+hippocampus.&rft.au=Caudle%2C+R+M%3BDubner%2C+R&rft.aulast=Caudle&rft.aufirst=R&rft.date=1998-02-01&rft.volume=32&rft.issue=1&rft.spage=87&rft.isbn=&rft.btitle=&rft.title=Neuropeptides&rft.issn=01434179&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-11 N1 - Date created - 1998-06-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic influences in antisocial personality and drug use disorders. AN - 79831494; 9571383 AB - While an association between antisocial personality disorder (APD) and substance use disorder (SUD) has been frequently observed, the causes of the comorbidity remain unclear. Adoption and twin studies have found evidence of both genetic and environmental influences in APD and SUD. Therefore, comorbidity between APD and SUD may be the result of shared genetic influences, shared environmental influences, or a combination of the two. However, only a limited number of adoption and twin studies have addressed this issue and the results have not been conclusive. In future studies, a distinction should be made between alcohol and drug abuse and between juvenile and adult APD symptoms. Twin samples of adequate size would allow use of structural equation analytical methods for estimation of the relative magnitude of genetic and environmental influences shared between the two conditions, as well as influences contributing to each specifically. Results would be highly relevant for the clinical setting as well as for efforts to identify the genes involved in either trait. JF - Drug and alcohol dependence AU - van den Bree, M B AU - Svikis, D S AU - Pickens, R W AD - Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. mvandenb@irp.nida.nih.gov Y1 - 1998/02/01/ PY - 1998 DA - 1998 Feb 01 SP - 177 EP - 187 VL - 49 IS - 3 SN - 0376-8716, 0376-8716 KW - Index Medicus KW - Environment KW - Humans KW - Adult KW - Twin Studies as Topic KW - Adoption KW - Research Design KW - Family Health KW - Comorbidity KW - Antisocial Personality Disorder -- epidemiology KW - Antisocial Personality Disorder -- genetics KW - Substance-Related Disorders -- genetics KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79831494?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+and+alcohol+dependence&rft.atitle=Genetic+influences+in+antisocial+personality+and+drug+use+disorders.&rft.au=van+den+Bree%2C+M+B%3BSvikis%2C+D+S%3BPickens%2C+R+W&rft.aulast=van+den+Bree&rft.aufirst=M&rft.date=1998-02-01&rft.volume=49&rft.issue=3&rft.spage=177&rft.isbn=&rft.btitle=&rft.title=Drug+and+alcohol+dependence&rft.issn=03768716&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-06 N1 - Date created - 1998-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - New delta-opioid antagonists as pharmacological probes. AN - 79808768; 9550939 JF - Trends in pharmacological sciences AU - Bryant, S D AU - Salvadori, S AU - Cooper, P S AU - Lazarus, L H AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 22709, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 42 EP - 46 VL - 19 IS - 2 SN - 0165-6147, 0165-6147 KW - Ligands KW - 0 KW - Narcotic Antagonists KW - Oligopeptides KW - Receptors, Opioid, delta KW - Receptors, Opioid, kappa KW - Receptors, Opioid, mu KW - Tetrahydroisoquinolines KW - tyrosyl-1,2,3,4-tetrahydro-3-isoquinolinecarbonyl-phenylalanyl-phenylalanine KW - 146369-65-5 KW - Index Medicus KW - Receptors, Opioid, mu -- antagonists & inhibitors KW - Receptors, Opioid, kappa -- antagonists & inhibitors KW - Oligopeptides -- pharmacology KW - Opioid-Related Disorders -- genetics KW - Molecular Conformation KW - Drug Design KW - Cloning, Molecular KW - Receptors, Opioid, delta -- antagonists & inhibitors KW - Receptors, Opioid, delta -- genetics KW - Narcotic Antagonists -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79808768?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+pharmacological+sciences&rft.atitle=New+delta-opioid+antagonists+as+pharmacological+probes.&rft.au=Bryant%2C+S+D%3BSalvadori%2C+S%3BCooper%2C+P+S%3BLazarus%2C+L+H&rft.aulast=Bryant&rft.aufirst=S&rft.date=1998-02-01&rft.volume=19&rft.issue=2&rft.spage=42&rft.isbn=&rft.btitle=&rft.title=Trends+in+pharmacological+sciences&rft.issn=01656147&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-07 N1 - Date created - 1998-05-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular modeling of cytochrome P450 2B1: mode of membrane insertion and substrate specificity. AN - 79779255; 9535274 AB - A molecular model of a mammalian membrane-bound cytochrome P450, rat P450 2B1, was constructed in order to elucidate its mode of attachment to the endoplasmic reticulum and the structural basis of substrate specificity. The model was primarily derived from the structure of P450BM-3, which as a class II P450 is the most functionally similar P450 of known structure. However, model development was also guided by the conserved core regions of P450cam and P450terp. To optimally align the P450 2B1 and P450BM-3 sequences, multiple alignment was performed using sequences of five P450s in the II family, followed by minor adjustments on the basis of secondary structure predictions. The resulting P450 2B1 homology model structure was refined by molecular dynamics heating, equilibration, simulation, and energy minimization. The model suggests that the F-G loop serves as both a hydrophobic membrane anchor and entrance channel for hydrophobic substrates from the membrane to the P450 active site. To assess the mode of substrate binding, benzphetamine, testosterone, and benzo[a]pyrene were docked into the active site. The hydrophobic substrate-binding pocket is consistent with the preferences of this P450 toward hydrophobic substrates, while the presence of an acidic Glu-105 in this pocket is consistent with the preference of this P450 for the cationic substrate benzphetamine. This model is thus consistent with several known experimental properties of this P450, such as membrane attachment and substrate selectivity. JF - Journal of protein chemistry AU - Dai, R AU - Pincus, M R AU - Friedman, F K AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 121 EP - 129 VL - 17 IS - 2 SN - 0277-8033, 0277-8033 KW - Membrane Proteins KW - 0 KW - Benzphetamine KW - 0M3S43XK27 KW - Benzo(a)pyrene KW - 3417WMA06D KW - Testosterone KW - 3XMK78S47O KW - Cytochrome P-450 CYP2B1 KW - EC 1.14.14.1 KW - Index Medicus KW - Rats KW - Animals KW - Protein Structure, Secondary KW - Testosterone -- metabolism KW - Models, Molecular KW - Molecular Sequence Data KW - Benzphetamine -- metabolism KW - Amino Acid Sequence KW - Substrate Specificity KW - Sequence Homology, Amino Acid KW - Binding Sites KW - Benzo(a)pyrene -- metabolism KW - Membrane Proteins -- chemistry KW - Membrane Proteins -- metabolism KW - Cytochrome P-450 CYP2B1 -- metabolism KW - Cytochrome P-450 CYP2B1 -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79779255?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+protein+chemistry&rft.atitle=Molecular+modeling+of+cytochrome+P450+2B1%3A+mode+of+membrane+insertion+and+substrate+specificity.&rft.au=Dai%2C+R%3BPincus%2C+M+R%3BFriedman%2C+F+K&rft.aulast=Dai&rft.aufirst=R&rft.date=1998-02-01&rft.volume=17&rft.issue=2&rft.spage=121&rft.isbn=&rft.btitle=&rft.title=Journal+of+protein+chemistry&rft.issn=02778033&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-18 N1 - Date created - 1998-05-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The U.S. National Toxicology Program evaluation of transgenic mice as predictive models for identifying carcinogens. AN - 79778494; 9539007 AB - National Institute of Environmental Health Sciences researchers have invested considerable effort in exploring the utility of transgenic mice to detect carcinogens and study mechanisms of carcinogenesis. Work has assessed several mouse models genetically altered to enhance their expression of chemically induced tumors. Results with the p53def (hemizygous for the tumor-suppressor gene) and the Tg.AC (carrier of an activated H-ras oncogene) mice have been used as a basis for a proposed new strategy for identifying chemical carcinogens and assessing risk. The U.S. National Toxicology Program is conducting a series of studies with these two transgenic strains to further examine their strengths and weaknesses for identification of documented rodent and human carcinogens and to explore their ability to provide information concerning the effective dosimetry for target organ mutation. JF - Environmental health perspectives AU - Eastin, W C AD - Experimental Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. eastin@niehs.nih.gov Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 81 EP - 84 VL - 106 Suppl 1 SN - 0091-6765, 0091-6765 KW - Index Medicus KW - Animals KW - Genes, p53 -- physiology KW - Humans KW - Genes, ras -- physiology KW - Mice KW - Carcinogenicity Tests KW - Mice, Transgenic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79778494?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=The+U.S.+National+Toxicology+Program+evaluation+of+transgenic+mice+as+predictive+models+for+identifying+carcinogens.&rft.au=Eastin%2C+W+C&rft.aulast=Eastin&rft.aufirst=W&rft.date=1998-02-01&rft.volume=106+Suppl+1&rft.issue=&rft.spage=81&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-23 N1 - Date created - 1998-04-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1990 Dec;87(23):9178-82 [2251261] Nature. 1992 Mar 19;356(6366):215-21 [1552940] Environ Health Perspect. 1993 Apr;100:307-15 [8354178] Mutat Res. 1996 Sep;365(1-3):119-27 [8898993] Carcinogenesis. 1996 Feb;17(2):177-84 [8625435] Environ Health Perspect. 1996 Jan;104(1):84-8 [8834866] Environ Health Perspect. 1995 Oct;103(10):942-50 [8529591] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carcinogenesis studies of tetrahydrofuran vapors in rats and mice. AN - 79761024; 9520354 AB - Tetrahydrofuran (THF) is a widely used industrial solvent and was selected for carcinogenesis studies by the National Toxicology Program (NTP) because of its potential for widespread occupational exposure in humans and a lack of information on animal toxicity and carcinogenicity. Groups of 50 male and 50 female F344/N rats and B6C3F1 mice were exposed to 0, 200, 600, or 1800 ppm THF by inhalation, 6 h per day, 5 days per week, for 105 weeks. Survival and mean body weights of male and female rats exposed to THF were comparable to that of the controls. No clinical findings or nonneoplastic lesions related to THF exposure were observed in male or female rats. The incidences of renal tubule epithelial adenoma or carcinoma (combined) in exposed male rats occurred with a positive trend, and in males exposed to 600 and 1800 ppm exceeded the historical range for controls in 2-year NTP inhalation studies. There were no other neoplastic lesions related to THF exposure observed in male or female rats. After week 36, the survival of male mice exposed to 1800 ppm was significantly lower than that of the controls. Mean body weights of male and female mice exposed to THF were similar to those of the controls throughout the study. Male mice exposed to 1800 ppm were observed in a state of narcosis during and up to 1 h after the exposure periods. Nonneoplastic lesions related to THF exposure were not observed in male or female mice. The neoplastic lesions related to THF exposure were seen in female mice only. In female mice exposed to 1800 ppm, the incidences of hepatocellular neoplasms were significantly greater than those in the controls. In conclusion, there was some evidence of carcinogenic activity of THF in male F344/N rats due to increased incidences of adenoma or carcinoma (combined) of the kidney at the 600 and 1800 ppm exposure levels. There was clear evidence of carcinogenic activity in female B6C3F1 mice based on increased incidences of hepatocellular neoplasms at the 1800 ppm exposure level. THF was not carcinogenic in female rats or male mice exposed at 200, 600, or 1800 ppm. Copyright 1998 Academic Press. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Chhabra, R S AU - Herbert, R A AU - Roycroft, J H AU - Chou, B AU - Miller, R A AU - Renne, R A AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 183 EP - 188 VL - 41 IS - 2 SN - 1096-6080, 1096-6080 KW - Furans KW - 0 KW - Solvents KW - tetrahydrofuran KW - 3N8FZZ6PY4 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Kidney Neoplasms -- chemically induced KW - Liver Neoplasms -- chemically induced KW - Carcinogenicity Tests KW - Volatilization KW - Mice KW - Male KW - Female KW - Solvents -- toxicity KW - Furans -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79761024?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Carcinogenesis+studies+of+tetrahydrofuran+vapors+in+rats+and+mice.&rft.au=Chhabra%2C+R+S%3BHerbert%2C+R+A%3BRoycroft%2C+J+H%3BChou%2C+B%3BMiller%2C+R+A%3BRenne%2C+R+A&rft.aulast=Chhabra&rft.aufirst=R&rft.date=1998-02-01&rft.volume=41&rft.issue=2&rft.spage=183&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-28 N1 - Date created - 1998-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - CD40 ligand and IFN-gamma synergistically restore IL-12 production in HIV-infected patients. AN - 79750265; 9521075 AB - IL-12 production in HIV-infected (HIV+) individuals is severely impaired after stimulation by bacterial products or T cell-dependent stimuli. Because CD40-CD40 ligand (CD40L) interactions are the major mechanism involved in the T cell-dependent activation of antigen-presenting cells, we investigated whether this pathway was functional in HIV+ donors. CD40 expression was increased on freshly isolated monocytes from HIV+ individuals compared to HIV donors. However, equivalent CD40 expression was obtained in the two groups after cytokine stimulation. Since CD40 expression was intact in HIV+ donors' cells, we determined whether IL-12 production could be restored by providing exogenous T cell-dependent stimuli, CD40L and IFN-gamma, at the time of bacterial stimulation. IL-12 production was not altered by CD40L alone, was increased by IFN-gamma, and was synergistically restored to normal values by IFN-gamma + CD40L. This combination was more efficient for enhancing IL-12 production than granulocyte-macrophage colony-stimulating factor + CD40L or neutralizing anti-IL-10 antibody + CD40L. CD40L did not affect IL-10 production, whereas IFN-gamma significantly decreased it. This study demonstrates that the defect in IL-12 production by leukocytes from HIV+ donors can be overcome in vitro if the interacting cells are provided with the right T cell-dependent co-stimuli. JF - European journal of immunology AU - Chougnet, C AU - Thomas, E AU - Landay, A L AU - Kessler, H A AU - Buchbinder, S AU - Scheer, S AU - Shearer, G M AD - Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 646 EP - 656 VL - 28 IS - 2 SN - 0014-2980, 0014-2980 KW - Antibodies KW - 0 KW - Antigens, CD40 KW - Interleukin-1 KW - Ligands KW - Membrane Glycoproteins KW - Recombinant Proteins KW - CD40 Ligand KW - 147205-72-9 KW - Interleukin-12 KW - 187348-17-0 KW - Interferon-gamma KW - 82115-62-6 KW - Index Medicus KW - AIDS/HIV KW - Recombinant Proteins -- pharmacology KW - Interleukin-1 -- immunology KW - Humans KW - HIV Seronegativity -- immunology KW - Blood Donors KW - HIV Seropositivity -- immunology KW - Lymphocyte Activation KW - Interleukin-1 -- metabolism KW - Antibodies -- pharmacology KW - Monocytes -- metabolism KW - Adult KW - Leukocytes, Mononuclear -- metabolism KW - Drug Synergism KW - T-Lymphocytes -- immunology KW - Antigens, CD40 -- biosynthesis KW - Membrane Glycoproteins -- physiology KW - Interleukin-12 -- biosynthesis KW - HIV Infections -- immunology KW - Interferon-gamma -- pharmacology KW - Antigens, CD40 -- metabolism KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79750265?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Social+Work&rft.atitle=The+challenges+of+realising+social+justice+in+21+%26lt%3Bsup%26gt%3Bst%26lt%3B%2Fsup%26gt%3B+century+social+work&rft.au=Dominelli%2C+Lena%3BIoakimidis%2C+Vasilios&rft.aulast=Dominelli&rft.aufirst=Lena&rft.date=2016-11-01&rft.volume=59&rft.issue=6&rft.spage=693&rft.isbn=&rft.btitle=&rft.title=International+Social+Work&rft.issn=00208728&rft_id=info:doi/10.1177%2F0020872816665981 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-31 N1 - Date created - 1998-03-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase II trial of topotecan administered as 72-hour continuous infusion in children with refractory solid tumors: a collaborative Pediatric Branch, National Cancer Institute, and Children's Cancer Group Study. AN - 79746244; 9516923 AB - The antitumor activity of topotecan administered as a 72-h continuous i.v. infusion was evaluated in children with refractory neuroblastoma and sarcomas of soft tissue and bone. We also attempted to increase the dose intensity of topotecan by including an intrapatient dose escalation in the trial design. Ninety-three children (85 eligible and evaluable for response) with recurrent or refractory neuroblastoma, osteosarcoma, Ewing's sarcoma/peripheral neuroectodermal tumor, rhabdomyosarcoma, or other soft-tissue sarcomas received topotecan administered as a 72-h i.v. infusion every 21 days. The initial dose was 1.0 mg/m2/day, with subsequent intrapatient dose escalation to 1.3 mg/m2/day for those patients who did not experience dose-limiting toxicity after their first cycle of topotecan. There was one complete response in a patient with neuroblastoma (n = 26) and one partial response in a patient with Ewing's sarcoma/peripheral neuroectodermal tumor (n = 25). No complete or partial responses were observed in 17 patients with osteosarcoma, 15 patients with rhabdomyosarcoma, or 2 patients with other soft-tissue sarcomas; however, 8 patients had prolonged (15-48 weeks) stable disease while receiving topotecan. Topotecan was well tolerated. The most commonly observed toxicities were myelosuppression (dose-limiting) and nausea and vomiting. Intrapatient dose escalations were performed in 68% of the patients who received more than one cycle of topotecan, and 1.3 mg/m2/day was tolerated by 79% of the patients who received the higher dose and were evaluable for hematological toxicity. In conclusion, topotecan administered as a 72-h continuous infusion every 21 days is inactive (objective response rate, < 20%) in children with refractory or recurrent neuroblastoma and sarcomas of soft tissue or bone. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Blaney, S M AU - Needle, M N AU - Gillespie, A AU - Sato, J K AU - Reaman, G H AU - Berg, S L AU - Adamson, P C AU - Krailo, M D AU - Bleyer, W A AU - Poplack, D G AU - Balis, F M AD - Pediatric Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 357 EP - 360 VL - 4 IS - 2 SN - 1078-0432, 1078-0432 KW - Antineoplastic Agents KW - 0 KW - Topotecan KW - 7M7YKX2N15 KW - Index Medicus KW - Osteosarcoma -- drug therapy KW - Drug Administration Schedule KW - Infusions, Intravenous KW - Dose-Response Relationship, Drug KW - Humans KW - Soft Tissue Neoplasms -- drug therapy KW - Child KW - Sarcoma, Ewing -- drug therapy KW - Child, Preschool KW - Infant KW - Neuroblastoma -- drug therapy KW - Adult KW - Bone Neoplasms -- drug therapy KW - Rhabdomyosarcoma -- drug therapy KW - Adolescent KW - Neuroectodermal Tumors, Primitive, Peripheral -- drug therapy KW - Female KW - Male KW - Topotecan -- adverse effects KW - Neoplasms -- drug therapy KW - Antineoplastic Agents -- therapeutic use KW - Topotecan -- therapeutic use KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79746244?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Phase+II+trial+of+topotecan+administered+as+72-hour+continuous+infusion+in+children+with+refractory+solid+tumors%3A+a+collaborative+Pediatric+Branch%2C+National+Cancer+Institute%2C+and+Children%27s+Cancer+Group+Study.&rft.au=Blaney%2C+S+M%3BNeedle%2C+M+N%3BGillespie%2C+A%3BSato%2C+J+K%3BReaman%2C+G+H%3BBerg%2C+S+L%3BAdamson%2C+P+C%3BKrailo%2C+M+D%3BBleyer%2C+W+A%3BPoplack%2C+D+G%3BBalis%2C+F+M&rft.aulast=Blaney&rft.aufirst=S&rft.date=1998-02-01&rft.volume=4&rft.issue=2&rft.spage=357&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-09 N1 - Date created - 1998-04-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carbon disulfide neurotoxicity in rats: II. Toxicokinetics. AN - 79727155; 9498225 AB - Carbon disulfide (CS2) is an important industrial chemical widely used in the production of rayon, cellophane, fungicides and biocides. The uptake and elimination kinetics of CS2 was characterized for a single i.v. dose and for a single inhalation exposure. The uptake of CS2 into the blood was rapid with half times of 6 to 9 minutes. Elimination was relatively quick with terminal elimination half times of 41 to 77 minutes. The plateau CS2 blood concentration was lower in females than in males and lower in the male 50 ppm treatment group than would be predicted by linear dose proportionality compared to the 500 ppm and 800 ppm treatments. The CS2 blood concentration for the female 50 ppm group was below the limit of detection. The total and central compartment apparent volumes of distribution, 4.2 l/kg and .9 l/kg, were estimated from a single 50 mg/kg i.v. dose. The concentration of CS2 in blood resulting from repeated exposure, was investigated in a 13 week inhalation study. Blood samples were taken in rats previously exposed to 0, 50, 500, and 800 ppm CS2 for 2, 4, 8, or 13 weeks. The concentration of CS2 in the blood of male rats remained relatively constant throughout study. However the female 500 and 800 ppm groups showed a marked decrease over the course of the 13 week study. The concentration of CS2 in the blood from the 500 and 800 ppm groups of both sexes at all time points was higher compared to the 50 ppm group, than would be predicted by linear dose proportionality. The concentration of 2-thiothiazolidine-4-carboxylic acid in urine collected from the same animals lacked dose proportionality between the treatment groups at all time points. CS2 exposure caused dose-related decreases in body weight gain in both male and female rats. JF - Neurotoxicology AU - Moorman, M P AU - Sills, R C AU - Collins, B J AU - Morgan, D L AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 89 EP - 97 VL - 19 IS - 1 SN - 0161-813X, 0161-813X KW - Thiazoles KW - 0 KW - Thiazolidines KW - 2-thioxo-4-thiazolidinecarboxylic acid KW - 20933-67-9 KW - Carbon Disulfide KW - S54S8B99E8 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Drug Administration Schedule KW - Injections, Intravenous KW - Dose-Response Relationship, Drug KW - Thiazoles -- urine KW - Administration, Inhalation KW - Male KW - Female KW - Carbon Disulfide -- blood KW - Carbon Disulfide -- toxicity KW - Carbon Disulfide -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79727155?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicology&rft.atitle=Carbon+disulfide+neurotoxicity+in+rats%3A+II.+Toxicokinetics.&rft.au=Moorman%2C+M+P%3BSills%2C+R+C%3BCollins%2C+B+J%3BMorgan%2C+D+L&rft.aulast=Moorman&rft.aufirst=M&rft.date=1998-02-01&rft.volume=19&rft.issue=1&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=Neurotoxicology&rft.issn=0161813X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-21 N1 - Date created - 1998-04-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human glutathione S-transferase P1 polymorphisms: relationship to lung tissue enzyme activity and population frequency distribution. AN - 79721271; 9498276 AB - The association between glutathione S-transferase (GST) activity as measured by 1-chloro-2,4-dinitrobenzene (CDNB) conjugation and genotype at exon 5 and exon 6 of the human GSTP1 gene was investigated in normal lung tissue obtained from 34 surgical patients. These samples were genotyped for previously identified polymorphisms in exon 5 (Ile105Val) and exon 6 (Ala114Val) by PCR-RFLP and direct sequencing. GST enzyme activity was significantly lower among individuals with the 105 Val allele. Homozygous Ile/Ile samples (n = 18) had a mean cytosolic CDNB conjugating activity of 74.9 +/- 3.8 nmol/mg per min; heterozygotes (n = 13) had a mean specific activity of 62.1 +/- 4.2 nmol/mg per min and homozygous Val/Val (n = 3) had a mean specific activity of 52.5 +/- 4.5 nmol/mg per min. The CDNB conjugating activity measured for the Ile/Ile genotype group was significantly different from that observed in the Ile/Val group (P = 0.03), and from Ile/Val and Val/Val genotypes combined (P = 0.009). Mean GST activity values were consistently lower in individuals with genotypes containing the 105 valine allele, regardless of smoking exposure. Genotypes at codon 114 were also assessed but the mean GST activity was not significantly lower in individuals with the 114 valine allele. A new haplotype, present in two samples who were homozygous 105Ile and had a 114Val, was identified and proposed as GSTP1*D. Frequencies of the exon 5 and exon 6 polymorphisms were determined in samples obtained from European-Americans, African-Americans and Taiwanese. The differences observed were highly significant suggesting the possibility of GSTP1 genotype-associated, ethnic differences in cancer susceptibility and chemotherapeutic response. JF - Carcinogenesis AU - Watson, M A AU - Stewart, R K AU - Smith, G B AU - Massey, T E AU - Bell, D A AD - Laboratory of Computational Biology and Risk Assessment, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 275 EP - 280 VL - 19 IS - 2 SN - 0143-3334, 0143-3334 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Genotype KW - Polymerase Chain Reaction KW - African Continental Ancestry Group -- genetics KW - Polymorphism, Restriction Fragment Length KW - Polymorphism, Genetic KW - Humans KW - Taiwan -- epidemiology KW - United States -- epidemiology KW - European Continental Ancestry Group -- genetics KW - Asian Continental Ancestry Group -- genetics KW - Polymorphism, Single-Stranded Conformational KW - Continental Population Groups -- genetics KW - Gene Frequency KW - Glutathione Transferase -- metabolism KW - Lung -- enzymology KW - Glutathione Transferase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79721271?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Human+glutathione+S-transferase+P1+polymorphisms%3A+relationship+to+lung+tissue+enzyme+activity+and+population+frequency+distribution.&rft.au=Watson%2C+M+A%3BStewart%2C+R+K%3BSmith%2C+G+B%3BMassey%2C+T+E%3BBell%2C+D+A&rft.aulast=Watson&rft.aufirst=M&rft.date=1998-02-01&rft.volume=19&rft.issue=2&rft.spage=275&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-24 N1 - Date created - 1998-03-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isolation of recombinant secretory proteins by limited induction and quantitative harvest. AN - 79715123; 9494711 JF - BioTechniques AU - Rosenberg, H F AD - Laboratory of Host Defenses, NIAID/NIH, Bethesda, MD 20892, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 188 EP - 90, 192 VL - 24 IS - 2 SN - 0736-6205, 0736-6205 KW - Bacterial Proteins KW - 0 KW - Neurotoxins KW - Oligopeptides KW - Peptides KW - Protein Sorting Signals KW - Recombinant Proteins KW - Isopropyl Thiogalactoside KW - 367-93-1 KW - FLAG peptide KW - 98849-88-8 KW - Eosinophil-Derived Neurotoxin KW - EC 3.1.- KW - Ribonucleases KW - Index Medicus KW - Periplasm -- chemistry KW - Bacterial Proteins -- genetics KW - Protein Sorting Signals -- genetics KW - Plasmids -- genetics KW - Neurotoxins -- genetics KW - Peptides -- immunology KW - Bacterial Proteins -- isolation & purification KW - Peptides -- genetics KW - Isopropyl Thiogalactoside -- pharmacology KW - Ribonucleases -- metabolism KW - Recombinant Proteins -- isolation & purification KW - Recombinant Proteins -- secretion KW - Escherichia coli -- genetics KW - Gene Expression Regulation -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79715123?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BioTechniques&rft.atitle=Isolation+of+recombinant+secretory+proteins+by+limited+induction+and+quantitative+harvest.&rft.au=Rosenberg%2C+H+F&rft.aulast=Rosenberg&rft.aufirst=H&rft.date=1998-02-01&rft.volume=24&rft.issue=2&rft.spage=188&rft.isbn=&rft.btitle=&rft.title=BioTechniques&rft.issn=07366205&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-10 N1 - Date created - 1998-04-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Skeletal muscle-specific immunotoxin for the treatment of focal muscle spasm. AN - 79707660; 9484377 AB - Intramuscular injection of botulinum toxin type A (BTX) is used to treat many disorders characterized by muscular spasms. The utility of BTX, however, is limited by its short duration of action, the development of resistance after repeated injections, and cross-reactivity with autonomic neurons. To overcome these limitations, we engineered an immunotoxin (ITX) to damage skeletal muscle fibers selectively by chemically linking a monoclonal antibody against the nicotinic acetylcholine receptor to the toxin ricin. In vitro, the ITX was 20,000-fold more toxic to myotubes than myoblasts, consistent with the degree of acetylcholine receptor expression. The gastrocnemius muscles of 30 rats were unilaterally injected with a series of protein toxins at various concentrations and examined histopathologically 7 and 30 days later. ITX produced destructive myopathic changes at a dose 300-fold less than the maximum tolerated dose. Assessment of rat muscle strength after unilateral gastrocnemius injections showed that ITX was more effective and had a longer duration of action than BTX. ITXs may have potential for the treatment of involuntary muscle spasms. JF - Neurology AU - Hott, J S AU - Dalakas, M C AU - Sung, C AU - Hallett, M AU - Youle, R J AD - Biochemistry Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 485 EP - 491 VL - 50 IS - 2 SN - 0028-3878, 0028-3878 KW - Antibodies, Monoclonal KW - 0 KW - Immunotoxins KW - Muscle Proteins KW - Receptors, Nicotinic KW - Ricin KW - 9009-86-3 KW - Botulinum Toxins, Type A KW - EC 3.4.24.69 KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Protein Engineering KW - Cell Survival -- drug effects KW - Botulinum Toxins, Type A -- toxicity KW - Mice KW - Receptors, Nicotinic -- immunology KW - Mice, Inbred BALB C KW - Muscle Proteins -- biosynthesis KW - Female KW - Muscular Diseases -- drug therapy KW - Muscle, Skeletal -- pathology KW - Ricin -- toxicity KW - Muscle, Skeletal -- cytology KW - Immunotoxins -- toxicity KW - Ricin -- therapeutic use KW - Immunotoxins -- therapeutic use KW - Spasm -- drug therapy KW - Muscle, Skeletal -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79707660?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=Skeletal+muscle-specific+immunotoxin+for+the+treatment+of+focal+muscle+spasm.&rft.au=Hott%2C+J+S%3BDalakas%2C+M+C%3BSung%2C+C%3BHallett%2C+M%3BYoule%2C+R+J&rft.aulast=Hott&rft.aufirst=J&rft.date=1998-02-01&rft.volume=50&rft.issue=2&rft.spage=485&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-16 N1 - Date created - 1998-03-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Multiple regions of ligand discrimination revealed by analysis of chimeric parathyroid hormone 2 (PTH2) and PTH/PTH-related peptide (PTHrP) receptors. AN - 79701425; 9482662 AB - PTH and PTH-related peptide (PTHrP) bind to the PTH/PTHrP receptor and stimulate cAMP accumulation with similar efficacy. Only PTH activates the PTH2 receptor. To examine the structural basis for this selectivity, we analyzed receptor chimeras in which the amino terminus and third extracellular domains of the two receptors were interchanged. All chimeric receptors bound radiolabeled PTH with high affinity. Transfer of the PTH2 receptor amino terminus to the PTH/PTHrP receptor eliminated high-affinity PTHrP binding and significantly decreased activation by PTHrP. A PTH/PTHrP receptor N terminus modified by deletion of the nonhomologous E2 domain transferred weak PTHrP interaction to the PTH2 receptor. Introduction of the PTH2 receptor third extracellular loop into the PTH/PTHrP receptor increased the EC50 for PTH and PTHrP, while preserving high-affinity PTH binding and eliminating high-affinity PTHrP binding. Similarly, transfer of the PTH/PTHrP receptor third extracellular loop preserved high-affinity PTH binding by the PTH2 receptor but decreased its activation. Return of Gln440 and Arg394, corresponding residues in the PTH/PTHrP and PTH2 receptor third extracellular loops, to the parent residue restored function of these receptors. Simultaneous interchange of wild-type amino termini and third extracellular loops eliminated agonist activation but not binding for both receptors. Function was restored by elimination of the E2 domain in the receptor with a PTH/PTHrP receptor N terminus and return of Gln440/Arg394 to the parent sequence in both receptors. These data suggest that the amino terminus and third extracellular loop of the PTH2 and PTH/PTHrP receptors interact similarly with PTH, and that both domains contribute to differential interaction with PTHrP. JF - Molecular endocrinology (Baltimore, Md.) AU - Clark, J A AU - Bonner, T I AU - Kim, A S AU - Usdin, T B AD - Section on Genetics, National Institute of Mental Health, Bethesda, Maryland 20892-4090, USA. janet@codon.nih.gov Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 193 EP - 206 VL - 12 IS - 2 SN - 0888-8809, 0888-8809 KW - Ligands KW - 0 KW - Receptor, Parathyroid Hormone, Type 1 KW - Receptor, Parathyroid Hormone, Type 2 KW - Receptors, Parathyroid Hormone KW - Recombinant Fusion Proteins KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - COS Cells KW - Amino Acid Substitution -- genetics KW - Humans KW - Protein Binding -- genetics KW - Binding Sites -- genetics KW - Protein Structure, Tertiary KW - Recombinant Fusion Proteins -- metabolism KW - Receptors, Parathyroid Hormone -- genetics KW - Receptors, Parathyroid Hormone -- analysis KW - Receptors, Parathyroid Hormone -- chemistry KW - Recombinant Fusion Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79701425?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.atitle=Multiple+regions+of+ligand+discrimination+revealed+by+analysis+of+chimeric+parathyroid+hormone+2+%28PTH2%29+and+PTH%2FPTH-related+peptide+%28PTHrP%29+receptors.&rft.au=Clark%2C+J+A%3BBonner%2C+T+I%3BKim%2C+A+S%3BUsdin%2C+T+B&rft.aulast=Clark&rft.aufirst=J&rft.date=1998-02-01&rft.volume=12&rft.issue=2&rft.spage=193&rft.isbn=&rft.btitle=&rft.title=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.issn=08888809&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-30 N1 - Date created - 1998-03-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A pilot study of 2-chloro-2'-deoxyadenosine in the treatment of systemic lupus erythematosus-associated glomerulonephritis. AN - 79700393; 9485092 AB - To determine the safety and tolerability, as well as the clinical and immunologic effects, of 2-chloro-2'-deoxyadenosine (2-CdA) in patients with systemic lupus erythematosus-associated glomerulonephritis. In a phase I study, 12 patients with proliferative lupus nephritis received 2-CdA either in weekly escalating intravenous treatments (0.15 mg/kg/week x 4, 0.1875 mg/kg/week x 4, 0.225 mg/kg/week x 4; n = 5) or in a continuous 7-day infusion (0.05 mg/kg/day; n = 7). Safety, renal improvement, and immunologic effects were evaluated for 12 months. Patients treated with 2-CdA showed peripheral lymphocyte depletion without a significant reduction in neutrophil, monocyte, or platelet numbers or hematocrit levels. Naive and memory T cells were decreased, as were lymphocytes with markers of early and late activation. Peripheral B cell depletion was not associated with significant decreases in serum immunoglobulin levels. Continuous infusion induced better clinical responses than weekly infusions, as evidenced by 1) the percentage of patients showing complete response (43% versus 0%), 2) the percentage with at least 50% reduction in proteinuria (43% versus 20%), 3) the percentage with at least a 50% reduction in urinary dysmorphic red cells (57% versus 0%), and 4) the percentage in whom cellular casts disappeared (43% versus 0%). Several infections occurred; these responded to standard antibiotic therapy. In this pilot study, 2-CdA was safely administered to 12 patients with lupus nephritis. It induced prolonged reductions in lymphocyte populations and may be efficacious in selected patients with lupus nephritis when administered as a continuous infusion. JF - Arthritis and rheumatism AU - Davis, J C AU - Austin, H AU - Boumpas, D AU - Fleisher, T A AU - Yarboro, C AU - Larson, A AU - Balow, J AU - Klippel, J H AU - Scott, D AD - National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 335 EP - 343 VL - 41 IS - 2 SN - 0004-3591, 0004-3591 KW - Cytokines KW - 0 KW - Immunosuppressive Agents KW - Cladribine KW - 47M74X9YT5 KW - Abridged Index Medicus KW - Index Medicus KW - Gene Expression -- drug effects KW - Cytokines -- genetics KW - Humans KW - Adult KW - Kidney -- drug effects KW - Pilot Projects KW - Middle Aged KW - Cytokines -- antagonists & inhibitors KW - Male KW - Female KW - Lupus Nephritis -- physiopathology KW - Cladribine -- adverse effects KW - Lupus Nephritis -- drug therapy KW - Cladribine -- therapeutic use KW - Lupus Nephritis -- immunology KW - Immunosuppressive Agents -- therapeutic use KW - Immunosuppressive Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79700393?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Arthritis+and+rheumatism&rft.atitle=A+pilot+study+of+2-chloro-2%27-deoxyadenosine+in+the+treatment+of+systemic+lupus+erythematosus-associated+glomerulonephritis.&rft.au=Davis%2C+J+C%3BAustin%2C+H%3BBoumpas%2C+D%3BFleisher%2C+T+A%3BYarboro%2C+C%3BLarson%2C+A%3BBalow%2C+J%3BKlippel%2C+J+H%3BScott%2C+D&rft.aulast=Davis&rft.aufirst=J&rft.date=1998-02-01&rft.volume=41&rft.issue=2&rft.spage=335&rft.isbn=&rft.btitle=&rft.title=Arthritis+and+rheumatism&rft.issn=00043591&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-19 N1 - Date created - 1998-03-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Arthritis Rheum. 1998 Sep;41(9):1704-5 [9751108] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human endometrial stromal cells generate uncombined alpha-subunit from human chorionic gonadotropin, which can synergize with progesterone to induce decidualization. AN - 79695745; 9467577 AB - During the secretory phase of the menstrual cycle, endometrial stromal cells differentiate into decidual cells, which play a crucial role in implantation and maintenance of pregnancy. In this and our previous study, we demonstrate that glycoprotein hormone free alpha-subunit potentiates progesterone-mediated decidualization of human endometrial stromal cells in vitro. Although addition of intact hCG to cultures resulted in stimulatory activity, its potency was 20-fold less than that of alpha-subunit. However, in the present study we show that decidualizing endometrial cells actively generate uncombined alpha-subunit by dissociating hCG. The amount of dissociated alpha-subunit could fully account for the stimulatory activity observed with hCG. Active dissociation of hCG was dependent on the presence of endometrial cells and did not occur in conditioned medium, excluding involvement of a stable secreted factor such as a protease. In addition to dissociated alpha- and beta-subunits, minor amounts of beta-core and alpha-fragments were detected as degradation products during active dissociation. We also observed an increase in beta-immunoreactivity that coeluted with hCG on size-exclusion gel chromatography, indicating that a portion of the still dimeric hCG may have been nicked in the dissociation process. However, using an assay with specificity for nicked hCG, we showed that dissociation of hCG was not produced from a pool of preexisting nicked hCG. These findings more firmly establish the concept that gonadotropin hormone free alpha-subunit plays a role in the regulation of human endometrial cell differentiation. In addition, identification of the various products formed by incubation of hCG with decidualizing cells yielded insight into the mechanism of hCG degradation, and may explain some activity previously ascribed to hCG. JF - The Journal of clinical endocrinology and metabolism AU - Nemansky, M AU - Moy, E AU - Lyons, C D AU - Yu, I AU - Blithe, D L AD - Unit of Glycobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 575 EP - 581 VL - 83 IS - 2 SN - 0021-972X, 0021-972X KW - Chorionic Gonadotropin KW - 0 KW - Culture Media, Conditioned KW - Glycoprotein Hormones, alpha Subunit KW - Progesterone KW - 4G7DS2Q64Y KW - Prolactin KW - 9002-62-4 KW - Abridged Index Medicus KW - Index Medicus KW - Prolactin -- biosynthesis KW - Ovulation KW - Chorionic Gonadotropin -- pharmacology KW - Cells, Cultured KW - Kinetics KW - Humans KW - Adult KW - Middle Aged KW - Drug Synergism KW - Female KW - Glycoprotein Hormones, alpha Subunit -- metabolism KW - Progesterone -- pharmacology KW - Decidua -- physiology KW - Glycoprotein Hormones, alpha Subunit -- pharmacology KW - Stromal Cells -- metabolism KW - Decidua -- drug effects KW - Endometrium -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79695745?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+endocrinology+and+metabolism&rft.atitle=Human+endometrial+stromal+cells+generate+uncombined+alpha-subunit+from+human+chorionic+gonadotropin%2C+which+can+synergize+with+progesterone+to+induce+decidualization.&rft.au=Nemansky%2C+M%3BMoy%2C+E%3BLyons%2C+C+D%3BYu%2C+I%3BBlithe%2C+D+L&rft.aulast=Nemansky&rft.aufirst=M&rft.date=1998-02-01&rft.volume=83&rft.issue=2&rft.spage=575&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+endocrinology+and+metabolism&rft.issn=0021972X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-27 N1 - Date created - 1998-02-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Case series: spectrum of neuroleptic-induced movement disorders and extrapyramidal side effects in childhood-onset schizophrenia. AN - 79695446; 9473920 AB - Neuroleptic-treated pediatric patients with childhood-onset schizophrenia (COS) are at risk for developing extrapyramidal side effects and involuntary movement disorders. A preliminary examination of the incidence of withdrawal dyskinesias (WD), tardive dyskinesia (TD), and extrapyramidal side effects in these patients is presented. Thirty-four COS patients (mean age +/- SD, 14.2 +/- 2.1 years) were examined for TD using the Abnormal Involuntary Movements Scale and for extrapyramidal side effects using the Simpson-Angus Neurologic Rating Scale, after a 14- to 28-day drug-free period (n = 33), at week 6 of treatment and 2 to 4 years after completion of the study (n = 14). The mean (+/-SD) number of months of prior neuroleptic exposure for the group was 22.4 (15.0) months. Seventeen (50%) of 34 patients were noted to have either WD or TD at some point during their participation in the studies. The majority of patients experienced WD that were mainly in the orofacial region, transient in nature, and diminished with haloperidol and clozapine. Patients with TD/WD had greater levels of premorbid impairment (p = .02), increased severity of positive symptoms of schizophrenia (p < .01), and a trend toward more months of neuroleptic exposure (p = .10, one-tailed). A high proportion of COS patients were found to have TD/WD. The majority of these abnormal movements were not severe and generally improved over time. TD/WD in COS appears to be associated with greater premorbid impairment, severity of illness, and duration of neuroleptic exposure. J. Am. Acad. JF - Journal of the American Academy of Child and Adolescent Psychiatry AU - Kumra, S AU - Jacobsen, L K AU - Lenane, M AU - Smith, A AU - Lee, P AU - Malanga, C J AU - Karp, B I AU - Hamburger, S AU - Rapoport, J L AD - Child Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892-1600, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 221 EP - 227 VL - 37 IS - 2 SN - 0890-8567, 0890-8567 KW - Antipsychotic Agents KW - 0 KW - Index Medicus KW - Cross-Sectional Studies KW - Substance Withdrawal Syndrome KW - Prospective Studies KW - Humans KW - Chi-Square Distribution KW - Child KW - Adolescent KW - Male KW - Female KW - Dyskinesia, Drug-Induced KW - Schizophrenia, Childhood -- drug therapy KW - Antipsychotic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79695446?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Academy+of+Child+and+Adolescent+Psychiatry&rft.atitle=Case+series%3A+spectrum+of+neuroleptic-induced+movement+disorders+and+extrapyramidal+side+effects+in+childhood-onset+schizophrenia.&rft.au=Kumra%2C+S%3BJacobsen%2C+L+K%3BLenane%2C+M%3BSmith%2C+A%3BLee%2C+P%3BMalanga%2C+C+J%3BKarp%2C+B+I%3BHamburger%2C+S%3BRapoport%2C+J+L&rft.aulast=Kumra&rft.aufirst=S&rft.date=1998-02-01&rft.volume=37&rft.issue=2&rft.spage=221&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Academy+of+Child+and+Adolescent+Psychiatry&rft.issn=08908567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-05 N1 - Date created - 1998-05-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neuroprotection by S-nitrosoglutathione of brain dopamine neurons from oxidative stress. AN - 79692884; 9472981 AB - The proposed anti- and pro-oxidant effects of nitric oxide (NO) derivatives, such as S-nitrosoglutathione (GSNO) and peroxynitrite, were investigated in the rat nigrostriatal dopaminergic system. Intranigral infusion of freshly prepared GSNO (0-16.8 nmol, i.n.) prevented iron-induced (4.2 nmol, i.n.) oxidative stress and nigral injury, reflected by a decrease in striatal dopamine levels. This neuroprotective effect of GSNO was verified by ex vivo imaging of brain dopamine uptake sites using 125I-labeled RTI-55. In addition, in vitro data indicate that GSNO concentration-dependently inhibited iron-evoked hydroxyl radical generation and brain lipid peroxidation. In this iron-induced oxidant stress model, GSNO was approximately 100-fold more potent than the antioxidant glutathione (GSH). Light-exposed, NO-exhausted GSNO produced neither antioxidative nor neuroprotective effects, which indicates that NO may mediate at least part of GSNO's effects. Moreover, GSNO completely (and GSH only partially) inhibited the weak pro-oxidant effect of peroxynitrite, which produced little injury to nigral neurons in vivo. This study provides relevant in vivo evidence suggesting that nanomol GSNO can protect brain dopamine neurons from iron-induced oxidative stress and degeneration. In conclusion, S-nitrosylation of GSH by NO and oxygen may be part of the antioxidative cellular defense system. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Rauhala, P AU - Lin, A M AU - Chiueh, C C AD - Unit on Neurodegeneration and Neuroprotection, Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland 20892-1264, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 165 EP - 173 VL - 12 IS - 2 SN - 0892-6638, 0892-6638 KW - Ferrous Compounds KW - 0 KW - Iodine Radioisotopes KW - Neuroprotective Agents KW - Nitrates KW - Nitroso Compounds KW - Oxidants KW - peroxynitric acid KW - 26404-66-0 KW - monoferrous acid citrate KW - 33KM3X4QQW KW - 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane KW - 4H1Z7121WS KW - S-Nitrosoglutathione KW - 57564-91-7 KW - Glutathione KW - GAN16C9B8O KW - Cocaine KW - I5Y540LHVR KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Ferrous Compounds -- toxicity KW - Cocaine -- analogs & derivatives KW - Nitrates -- toxicity KW - Oxidants -- toxicity KW - Cocaine -- pharmacokinetics KW - Autoradiography KW - Infusions, Parenteral KW - Male KW - Nitroso Compounds -- administration & dosage KW - Neurons -- drug effects KW - Neuroprotective Agents -- administration & dosage KW - Lipid Peroxidation -- drug effects KW - Substantia Nigra -- drug effects KW - Dopamine -- metabolism KW - Glutathione -- administration & dosage KW - Glutathione -- pharmacology KW - Neurons -- pathology KW - Neuroprotective Agents -- pharmacology KW - Substantia Nigra -- pathology KW - Oxidative Stress -- drug effects KW - Neurons -- physiology KW - Nitroso Compounds -- pharmacology KW - Substantia Nigra -- physiology KW - Glutathione -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79692884?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.atitle=Neuroprotection+by+S-nitrosoglutathione+of+brain+dopamine+neurons+from+oxidative+stress.&rft.au=Rauhala%2C+P%3BLin%2C+A+M%3BChiueh%2C+C+C&rft.aulast=Rauhala&rft.aufirst=P&rft.date=1998-02-01&rft.volume=12&rft.issue=2&rft.spage=165&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=08926638&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-27 N1 - Date created - 1998-02-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulation of fluorouracil cytotoxicity by interferon-alpha and -gamma. AN - 79690252; 9463483 AB - Because interferons (IFN)-alpha and -gamma individually have increased fluorouracil (FUra) cytotoxicity in several in vitro models, we studied the effects of FUra combined with IFN-alpha + gamma in HT29 colon cancer cells. A 96-hr exposure to IFN-alpha (500 units/ml) plus IFN-gamma (10 units/ml) and a 72-hr exposure to 0. 25-1 microM FUra (hr 24-96) inhibited cell growth and colony formation in an additive or more-than-additive fashion. When cells were exposed to IFN-alpha + gamma and FUra, free FdUMP levels became detectable, whereas [3H]FUra-RNA incorporation decreased. Exposure to IFN-alpha + gamma, FUra, or the combination decreased dTTP pools to 58%, 43%, and 17% of control, respectively. A marked increase in the dATP to dTTP ratio was seen with FUra with or without IFN-alpha + gamma. Thymidylate synthase catalytic activity was reduced to 28% and 24% of control with FUra with or without IFN-alpha + gamma, suggesting that the enhanced dTTP depletion must be due to another mechanism. FUra-mediated thymidylate synthase inhibition was accompanied by a 124-fold increase in total deoxyuridylate immunoreactivity and a 31-fold increase in dUTP pools, but the addition of IFN-alpha + gamma attenuated the accumulation. Treatment with IFN-alpha + gamma and FUra individually interfered with nascent DNA chain elongation, whereas the three-drug combination produced the most striking effects. IFN-alpha + gamma plus FUra produced the greatest amount of single-strand breaks in nascent DNA and dramatically decreased net DNA synthesis. IFN-alpha + gamma with or without FUra produced double-strand breaks in parental DNA. These results suggest that dTTP depletion, dATP/dTTP imbalance, pronounced inhibition of DNA synthesis, and damage to nascent and parental DNA contribute to the enhanced cytotoxicity with the triple combination. JF - Molecular pharmacology AU - Ismail, A AU - Van Groeningen, C J AU - Hardcastle, A AU - Ren, Q AU - Aherne, G W AU - Geoffroy, F AU - Allegra, C J AU - Grem, J L AD - National Cancer Institute-Navy Medical Oncology Branch, National Naval Medical Center, Bethesda, Maryland 20889, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 252 EP - 261 VL - 53 IS - 2 SN - 0026-895X, 0026-895X KW - DNA, Neoplasm KW - 0 KW - Interferon-alpha KW - RNA, Neoplasm KW - Thymine Nucleotides KW - Interferon-gamma KW - 82115-62-6 KW - thymidine 5'-triphosphate KW - QOP4K539MU KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - RNA, Neoplasm -- biosynthesis KW - Drug Interactions KW - Drug Administration Schedule KW - Thymine Nucleotides -- metabolism KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - DNA, Neoplasm -- biosynthesis KW - DNA Fragmentation KW - DNA Repair -- drug effects KW - Fluorouracil -- administration & dosage KW - Interferon-alpha -- administration & dosage KW - Interferon-gamma -- administration & dosage KW - Fluorouracil -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79690252?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=Modulation+of+fluorouracil+cytotoxicity+by+interferon-alpha+and+-gamma.&rft.au=Ismail%2C+A%3BVan+Groeningen%2C+C+J%3BHardcastle%2C+A%3BRen%2C+Q%3BAherne%2C+G+W%3BGeoffroy%2C+F%3BAllegra%2C+C+J%3BGrem%2C+J+L&rft.aulast=Ismail&rft.aufirst=A&rft.date=1998-02-01&rft.volume=53&rft.issue=2&rft.spage=252&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-10 N1 - Date created - 1998-03-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vinblastine for recurrent Hodgkin's disease following autologous bone marrow transplant. AN - 79685327; 9469345 AB - Bone marrow transplant (BMT) can cure recurrent Hodgkin's disease, but more than half of patients will progress and require additional treatment. When this occurs, there are no curative options and palliative therapy is usually indicated. In such patients, we have routinely used long-term vinblastine therapy because of its relatively low toxicity and high activity. We retrospectively reviewed the charts of all patients with Hodgkin's disease who relapsed after autologous BMT since 1991. Of 23 patients, 16 received vinblastine; we also include our index case, who began vinblastine following relapse in 1987. Patients received vinblastine 4 to 6 mg/m2 every 1 to 2 weeks, and continued until evidence of disease progression. The 17 patients in this report had a median age of 31 years, performance status of 2, had received a median of three prior regimens, and 12 (71%) patients were advanced stage. Ten (59%) patients had objective responses, of which two (12%) were complete (CR) and eight (47%) were partial (PR). Two additional patients without measurable disease clinically improved for more than 6 months, and 1 patient had stable disease for more than 18 months. With a median follow-up of 20.4 months, the median event-free (EFS) and overall survival were 8.3 and 38.8 months, respectively. The two complete responders remain in remission at 4.6+ and 9+ years. Vinblastine was well tolerated with 3% of cycles associated with fever and neutropenia, and no cumulative or chronic toxicity. Vinblastine provides effective palliation with low toxicity in recurrent Hodgkin's disease following transplant. These results suggest that long-term vinblastine therapy may be potentially curative and should be considered as initial therapy for such patients. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Little, R AU - Wittes, R E AU - Longo, D L AU - Wilson, W H AD - Medicine Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 584 EP - 588 VL - 16 IS - 2 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Vinblastine KW - 5V9KLZ54CY KW - Index Medicus KW - Disease-Free Survival KW - Survival Rate KW - Combined Modality Therapy KW - Humans KW - Adult KW - Retrospective Studies KW - Middle Aged KW - Transplantation, Autologous KW - Recurrence KW - Male KW - Female KW - Vinblastine -- therapeutic use KW - Antineoplastic Agents, Phytogenic -- adverse effects KW - Antineoplastic Agents, Phytogenic -- therapeutic use KW - Vinblastine -- adverse effects KW - Hodgkin Disease -- therapy KW - Hodgkin Disease -- mortality KW - Bone Marrow Transplantation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79685327?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Vinblastine+for+recurrent+Hodgkin%27s+disease+following+autologous+bone+marrow+transplant.&rft.au=Little%2C+R%3BWittes%2C+R+E%3BLongo%2C+D+L%3BWilson%2C+W+H&rft.aulast=Little&rft.aufirst=R&rft.date=1998-02-01&rft.volume=16&rft.issue=2&rft.spage=584&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-02 N1 - Date created - 1998-03-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A T cell-independent antitumor response in mice with bone marrow cells retrovirally transduced with an antibody/Fc-gamma chain chimeric receptor gene recognizing a human ovarian cancer antigen. AN - 79683783; 9461189 AB - In order to treat common cancers with immunotherapy, chimeric receptors have been developed that combine the tumor specificity of antibodies with T-cell effector functions. Previously, we demonstrated that T cells transduced with a chimeric receptor gene against human ovarian cancer were able to recognize ovarian cancer cells in vitro and in vivo. We now report that recipients of bone marrow cells transduced with these genes exhibited significant antitumor activity in vivo. Moreover, in vivo depletion of T cells in reconstituted mice did not affect antitumor activity, suggesting that other immune cells expressing the chimeric receptor gene may play an important role in tumor rejection. JF - Nature medicine AU - Wang, G AU - Chopra, R K AU - Royal, R E AU - Yang, J C AU - Rosenberg, S A AU - Hwu, P AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 168 EP - 172 VL - 4 IS - 2 SN - 1078-8956, 1078-8956 KW - Antibodies, Monoclonal KW - 0 KW - Cytokines KW - Immunoglobulin Variable Region KW - Receptors, Antigen, T-Cell KW - Recombinant Fusion Proteins KW - Index Medicus KW - Radiation Dosage KW - Animals KW - Antibodies, Monoclonal -- genetics KW - Ovarian Neoplasms -- genetics KW - Humans KW - Neoplasms, Experimental -- genetics KW - Cytokines -- metabolism KW - Mice KW - Immunotherapy -- methods KW - Neoplasms, Experimental -- immunology KW - Mice, Inbred C57BL KW - Retroviridae -- genetics KW - T-Lymphocytes -- immunology KW - Female KW - Recombinant Fusion Proteins -- genetics KW - Recombinant Fusion Proteins -- pharmacology KW - Hematopoietic Stem Cells -- virology KW - Receptors, Antigen, T-Cell -- genetics KW - Hematopoietic Stem Cell Transplantation -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79683783?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+medicine&rft.atitle=A+T+cell-independent+antitumor+response+in+mice+with+bone+marrow+cells+retrovirally+transduced+with+an+antibody%2FFc-gamma+chain+chimeric+receptor+gene+recognizing+a+human+ovarian+cancer+antigen.&rft.au=Wang%2C+G%3BChopra%2C+R+K%3BRoyal%2C+R+E%3BYang%2C+J+C%3BRosenberg%2C+S+A%3BHwu%2C+P&rft.aulast=Wang&rft.aufirst=G&rft.date=1998-02-01&rft.volume=4&rft.issue=2&rft.spage=168&rft.isbn=&rft.btitle=&rft.title=Nature+medicine&rft.issn=10788956&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-23 N1 - Date created - 1998-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I study of paclitaxel as a radiation sensitizer in the treatment of mesothelioma and non-small-cell lung cancer. AN - 79683647; 9469352 AB - To determine the maximum-tolerated dose (MTD) and dose-limiting toxicities of paclitaxel with concurrent thoracic irradiation in patients with malignant pleural mesothelioma and locally advanced non-small-cell lung cancer (NSCLC) using a 120-hour continuous infusion regimen. A secondary objective was to assess the effect of paclitaxel on the cell cycle through serial tumor biopsies. Paclitaxel was administered as a 120-hour (5-day) continuous infusion repeated every 3 weeks during the course of radiation therapy. The starting dose of paclitaxel was 90 mg/m2. Doses were escalated at 15-mg/m2 increments in successive cohorts of three patients. In NSCLC patients, radiation was delivered to the primary tumor and regional lymph nodes for a total tumor dose of 6,120 cGy. In mesothelioma patients, hemithoracic irradiation was delivered as the initial treatment field with a conedown to the tumor volume for a total dose of 5,760 to 6,300 cGy. Tumor biopsies were obtained, if possible, before and during paclitaxel treatment. Thirty patients were entered onto this study through three dose levels (from 90 mg/m2 to 120 mg/m2). The MTD was determined to be 105 mg/m2. The dose-limiting toxicity was grade 4 neutropenia (two patients). Grade 2 gastrointestinal (GI) toxicity (nausea and vomiting) was also observed at 120 mg/m2. Three of 30 patients developed a hypersensitivity reaction. Six patients had grade 2 lung injury manifested by a persistent cough that required antitussives. Five patients underwent tumor biopsies. None of the patients showed a significant block of cells in mitosis (G2/M) after paclitaxel infusion. The MTD of paclitaxel, when administered as a 120-hour continuous infusion with concurrent radiotherapy, was determined to be 105 mg/m2. The dose-limiting toxicity was neutropenia. Continuous infusion paclitaxel administered with large field irradiation of the lung is well tolerated and deserves continued evaluation. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Herscher, L L AU - Hahn, S M AU - Kroog, G AU - Pass, H AU - Temeck, B AU - Goldspiel, B AU - Cook, J AU - Mitchell, J B AU - Liebmann, J AD - Radiation Oncology Branch, Division of Cancer Treatment, National Cancer Institute, Bethesda, MD 20892, USA. herscher@box-h.nih.gov Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 635 EP - 641 VL - 16 IS - 2 SN - 0732-183X, 0732-183X KW - Radiation-Sensitizing Agents KW - 0 KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Infusions, Intravenous KW - Radiotherapy Dosage KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Female KW - Paclitaxel -- administration & dosage KW - Paclitaxel -- adverse effects KW - Lung Neoplasms -- radiotherapy KW - Mesothelioma -- radiotherapy KW - Pleural Neoplasms -- radiotherapy KW - Radiation-Sensitizing Agents -- adverse effects KW - Radiation-Sensitizing Agents -- administration & dosage KW - Carcinoma, Non-Small-Cell Lung -- radiotherapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79683647?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Phase+I+study+of+paclitaxel+as+a+radiation+sensitizer+in+the+treatment+of+mesothelioma+and+non-small-cell+lung+cancer.&rft.au=Herscher%2C+L+L%3BHahn%2C+S+M%3BKroog%2C+G%3BPass%2C+H%3BTemeck%2C+B%3BGoldspiel%2C+B%3BCook%2C+J%3BMitchell%2C+J+B%3BLiebmann%2C+J&rft.aulast=Herscher&rft.aufirst=L&rft.date=1998-02-01&rft.volume=16&rft.issue=2&rft.spage=635&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-02 N1 - Date created - 1998-03-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of p53 and apoptosis in sensitization of cis-diamminedichloroplatinum antitumor activity by interleukin-1 in ovarian carcinoma cells. AN - 79682871; 9458352 AB - We have previously reported that interleukin-1 (IL-1 ) sensitized cisplatin cytotoxicity against human ovarian NIH:OVCAR-3 tumor cells. We have further examined inter-actions of IL-1 with cisplatin in these ovarian cells. Treatment of cells with either IL-1 or CDDP or combinations resulted in a significant accumulation of cells in G1 phase and a concomitant decrease in the S phase of the cell cycle. IL-1 and CDDP treatment induced p53 protein in NIH:OVCAR-3 tumor cells. CDDP and IL-1 treatment decreased the steady-state expression of c-myc RNA and induced significant degradation of the genomic DNA into internucleosomal sized DNA fragments which was further increased in the presence of both agents in these cells. Taken together, these studies suggest that IL-1 may kill ovarian NIH:OVCAR-3 tumor cells by inducing a blockade at G1/S of the cell cycle, down-regulating c-myc gene and inducing p53-dependent apoptosis. The synergistic interactions of IL-1 with CDDP may involve the enhancement of p53-dependent apoptosis. JF - International journal of oncology AU - Song, K AU - Fukushima, P AU - Seth, P AU - Sinha, B K AD - Developmental Therapeutics Department, Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 299 EP - 304 VL - 12 IS - 2 SN - 1019-6439, 1019-6439 KW - Interleukin-1 KW - 0 KW - Tumor Suppressor Protein p53 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Gene Expression -- drug effects KW - DNA Fragmentation -- genetics KW - Down-Regulation KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - In Vitro Techniques KW - Enzyme-Linked Immunosorbent Assay KW - Genes, myc -- drug effects KW - Drug Synergism KW - Genes, myc -- genetics KW - Female KW - Cell Cycle -- drug effects KW - Cisplatin -- therapeutic use KW - Interleukin-1 -- pharmacology KW - Ovarian Neoplasms -- genetics KW - Ovarian Neoplasms -- pathology KW - Apoptosis -- physiology KW - Tumor Suppressor Protein p53 -- drug effects KW - Apoptosis -- drug effects KW - Interleukin-1 -- therapeutic use KW - Cisplatin -- pharmacology KW - Tumor Suppressor Protein p53 -- metabolism KW - Ovarian Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79682871?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+oncology&rft.atitle=Role+of+p53+and+apoptosis+in+sensitization+of+cis-diamminedichloroplatinum+antitumor+activity+by+interleukin-1+in+ovarian+carcinoma+cells.&rft.au=Song%2C+K%3BFukushima%2C+P%3BSeth%2C+P%3BSinha%2C+B+K&rft.aulast=Song&rft.aufirst=K&rft.date=1998-02-01&rft.volume=12&rft.issue=2&rft.spage=299&rft.isbn=&rft.btitle=&rft.title=International+journal+of+oncology&rft.issn=10196439&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-01 N1 - Date created - 2001-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic alterations in the development of mammary and prostate cancer in the C3(1)/Tag transgenic mouse model. AN - 79682040; 9458374 AB - We have generated a transgenic mouse model in which female mice develop ductal mammary adenocarcinomas and male mice develop prostatic adenocarcinomas by using a transgene containing the hormone-responsive rat prostatic steroid binding protein 5' flanking region C3(1) fused to the simian virus 40 (SV40) large T antigen. We have identified some genetic alterations during mammary and prostate tumor progression: (i) p53 is functionally inactivated during mammary cancer development without p53 mutations; (ii) Alterations in apoptosis during mammary tumor progression are p53 and bcl-2 independent; (iii) Ha-ras mutations occur early in the development of prostate cancer. This unique animal model offers the opportunity to study multistep tumorigenesis in these organs. JF - International journal of oncology AU - Yoshidome, K AU - Shibata, M A AU - Maroulakou, I G AU - Liu, M L AU - Jorcyk, C L AU - Gold, L G AU - Welch, V N AU - Green, J E AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Building 41, Room C629, 9000 Rockville Pike, Bethesda, MD 20892, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 449 EP - 453 VL - 12 IS - 2 SN - 1019-6439, 1019-6439 KW - Index Medicus KW - Animals KW - Disease Models, Animal KW - Mice KW - Mice, Transgenic KW - Rats KW - Phenotype KW - Apoptosis -- genetics KW - Genes, ras -- genetics KW - Genes, bcl-2 -- genetics KW - Genes, p53 -- genetics KW - Mutation KW - Female KW - Male KW - Breast Neoplasms -- genetics KW - Mammary Neoplasms, Animal -- genetics KW - Prostatic Neoplasms -- genetics KW - Adenocarcinoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79682040?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Nervous+and+Mental+Disease&rft.atitle=Risk+factors+for+posttraumatic+stress+symptoms+among+avalanche+survivors%3A+A+16-year+follow-up&rft.au=Thordardottir%2C+Edda+Bjork%3BHansdottir%2C+Ingunn%3BShipherd%2C+Jillian+C.%3BValdimarsdottir%2C+Unnur+Anna%3BResnick%2C+Heidi%3BElklit%2C+Ask%3BGudmundsdottir%2C+Ragnhildur%3BGudmundsdottir%2C+Berglind&rft.aulast=Thordardottir&rft.aufirst=Edda&rft.date=2016-04-01&rft.volume=204&rft.issue=4&rft.spage=298&rft.isbn=&rft.btitle=&rft.title=Journal+of+Nervous+and+Mental+Disease&rft.issn=00223018&rft_id=info:doi/10.1097%2FNMD.0000000000000475 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-01 N1 - Date created - 2001-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutation of polyadenylation signals generates murine retroviruses that produce fused virus-cell RNA transcripts at high frequency. AN - 79678775; 9454719 AB - Retroviruses act as insertional mutagens and can also capture cellular sequences through a mechanism which initially requires the generation of RNA transcripts which fail to cleave and polyadenylate correctly. The correct termination of retroviral transcripts at the 3' LTR R/U5 junction is primarily dependent on the canonical AAUAAA polyadenylation signal, so we have analyzed the effect of mutating the polyadenylation signal sequences on the properties of a selectable murine retroviral vector. Mutation of consensus polyadenylation signal sequences in the 5' and/or 3' proviral LTRs demonstrated that a UA to GG change generated larger sized virus-specific RNA, consistent with loss of normal polyadenylation. Cell clones infected with viruses generated by proviral constructs containing this mutation in the 5' LTR express either normal-length or elongated viral RNA. Fused transcripts contained the mutant polyadenylation signal, while sequence analysis was consistent with the hypothesis that premature 5' to 3' primer strand transfer was responsible for the high frequency (80%) of wild-type polyadenylation. Cells infected by viruses from constructs mutated in both 5' and 3' proviral LTRs expressed poly(A)+ viral RNA between 0.3 and 3 kb larger than normal virus in 100% of infected clones, and sequence analysis of clones derived from either infected rodent or human cells confirmed that these transcripts contained both viral and adjacent cellular sequences. While mutant virus exhibits no increased ability to alter cell phenotypes, the read-through transcripts contain both unique and repetitive cell-derived sequences and can easily be recovered using PCR techniques, suggesting that these viruses may serve as effective tools for rapidly cloning cellular sequences and generating random genomic markers for gene mapping. Copyright 1998 Academic Press. JF - Virology AU - Zhang, Q Y AU - Clausen, P A AU - Yatsula, B A AU - Calothy, G AU - Blair, D G AD - Division of Basic Sciences, NCI-FCRDC, Frederick, Maryland, 21702-1201, USA. Y1 - 1998/02/01/ PY - 1998 DA - 1998 Feb 01 SP - 80 EP - 93 VL - 241 IS - 1 SN - 0042-6822, 0042-6822 KW - RNA, Viral KW - 0 KW - Poly A KW - 24937-83-5 KW - RNA KW - 63231-63-0 KW - Ribonucleases KW - EC 3.1.- KW - Index Medicus KW - 3T3 Cells KW - Animals KW - HeLa Cells KW - Humans KW - Mice KW - Ribonucleases -- metabolism KW - Binding Sites KW - Mutagenesis KW - Rats KW - Base Sequence KW - RNA -- metabolism KW - Molecular Sequence Data KW - Proviruses -- genetics KW - Repetitive Sequences, Nucleic Acid KW - RNA, Viral -- metabolism KW - Cell Line KW - Poly A -- genetics KW - Moloney murine leukemia virus -- genetics KW - Virus Integration KW - Poly A -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79678775?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Virology&rft.atitle=Mutation+of+polyadenylation+signals+generates+murine+retroviruses+that+produce+fused+virus-cell+RNA+transcripts+at+high+frequency.&rft.au=Zhang%2C+Q+Y%3BClausen%2C+P+A%3BYatsula%2C+B+A%3BCalothy%2C+G%3BBlair%2C+D+G&rft.aulast=Zhang&rft.aufirst=Q&rft.date=1998-02-01&rft.volume=241&rft.issue=1&rft.spage=80&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-26 N1 - Date created - 1998-02-26 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF014457; GENBANK; AF014450; AF014452; AF014451; AF014454; AF014453; AF014456; AF014455 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of ferrous iron chelator 2,2'-dipyridyl in preventing delayed vasospasm in a primate model of subarachnoid hemorrhage. AN - 79671933; 9452239 AB - Oxyhemoglobin (HbO2) causes vasospasm after subarachnoid hemorrhage (SAH). The most likely spasmogenic component of HbO2 is iron. Various iron chelators, such as deferoxamine, have prevented vasospasm in vivo with limited success. However, only chelators of iron in the ferric state have been studied in animal models of vasospasm after SAH. Because free radical formation requires the ferrous (Fe++) moiety and Fe++ is a potent binder of the vasodilator nitric oxide, the authors hypothesized that iron in the ferrous state causes vasospasm and that chelators of Fe++, such as 2,2'-dipyridyl, may prevent vasospasm. This study was undertaken to investigate the influence of 2,2'-dipyridyl on vasospasm after induction of SAH in a primate model. Twelve cynomolgus monkeys were randomly divided into two groups and then both groups underwent placement of an arterial autologous blood clot in the subarachnoid space around the right middle cerebral artery (MCA). The five animals in the control group received intravenously administered saline and the seven treated animals received intravenously administered chelator (2,2'-dipyridyl) for 14 days. Sequential arteriography for assessment of MCA diameter was performed before and on the 7th day after SAH. Prevention of cerebral vasospasm by means of treatment with continuous intravenous administration of 2,2'-dipyridyl is reported in a primate model of SAH. This result provides insight into the possible mechanism of delayed vasospasm after aneurysmal SAH and provides a potential preventive therapy for it. JF - Journal of neurosurgery AU - Horky, L L AU - Pluta, R M AU - Boock, R J AU - Oldfield, E H AD - Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 298 EP - 303 VL - 88 IS - 2 SN - 0022-3085, 0022-3085 KW - Ferrous Compounds KW - 0 KW - Iron Chelating Agents KW - Transferrin KW - 2,2'-Dipyridyl KW - 551W113ZEP KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Liver -- pathology KW - Cerebral Angiography KW - Macaca fascicularis KW - Injections, Intravenous KW - Liver -- drug effects KW - Transferrin -- analysis KW - Time Factors KW - Male KW - Female KW - Ischemic Attack, Transient -- prevention & control KW - Iron Chelating Agents -- therapeutic use KW - Iron Chelating Agents -- adverse effects KW - 2,2'-Dipyridyl -- adverse effects KW - Ferrous Compounds -- antagonists & inhibitors KW - Ischemic Attack, Transient -- diagnostic imaging KW - 2,2'-Dipyridyl -- therapeutic use KW - Subarachnoid Hemorrhage -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79671933?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurosurgery&rft.atitle=Role+of+ferrous+iron+chelator+2%2C2%27-dipyridyl+in+preventing+delayed+vasospasm+in+a+primate+model+of+subarachnoid+hemorrhage.&rft.au=Horky%2C+L+L%3BPluta%2C+R+M%3BBoock%2C+R+J%3BOldfield%2C+E+H&rft.aulast=Horky&rft.aufirst=L&rft.date=1998-02-01&rft.volume=88&rft.issue=2&rft.spage=298&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurosurgery&rft.issn=00223085&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-12 N1 - Date created - 1998-02-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - N18-RE-105 cells: differentiation and activation of p53 in response to glutamate and adriamycin is blocked by SV40 large T antigen tsA58. AN - 79662864; 9426307 AB - Process extension was induced in cells of the N18-RE-105 neuroblastoma-retinal hybrid line by toxic agents, including glutamate and the p53-inducing anticancer agents adriamycin and etoposide. Both adriamycin and glutamate activated p53 as measured by a plasmid transfection assay. It was therefore hypothesized that SV40 large T antigen, which binds p53, would interfere with cellular differentiation. To test this hypothesis, the temperature-sensitive form of SV40 large T was transduced into N18-RE-105 cells by retroviral infection. SV40 large T-infected cells became de-differentiated, grew in tightly-packed colonies, lost expression of neurofilament, and lost the ability to differentiate in response to glutamate and adriamycin. The de-differentiating effect of SV40 large T antigen may be due to binding and inactivation of cellular proteins, such as p53, p107, p130, p300, and retinoblastoma protein, which are important in cellular growth and differentiation. It is suggested that p53 may play a role in cellular differentiation, perhaps under unusual circumstances involving stress or cytotoxicity. JF - Cell and tissue research AU - Dillon-Carter, O AU - Conejero, C AU - Tornatore, C AU - Poltorak, M AU - Freed, W J AD - Section on Preclinical Neuroscience Neuropsychiatry Branch, NIMH Neuroscience Center at St. Elizabeths, 2700 Martin Luther King Ave., Washington, D.C., 20032, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 191 EP - 205 VL - 291 IS - 2 SN - 0302-766X, 0302-766X KW - Antigens, Polyomavirus Transforming KW - 0 KW - Antiporters KW - Excitatory Amino Acid Agonists KW - Neurotoxins KW - Tumor Suppressor Protein p53 KW - Homocysteine KW - 0LVT1QZ0BA KW - homocysteic acid KW - 1001-13-4 KW - Glutamic Acid KW - 3KX376GY7L KW - Cystine KW - 48TCX9A1VT KW - Etoposide KW - 6PLQ3CP4P3 KW - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid KW - 77521-29-0 KW - Doxorubicin KW - 80168379AG KW - Index Medicus KW - Etoposide -- pharmacology KW - Neuroblastoma -- pathology KW - Animals KW - Temperature KW - Neurotoxins -- pharmacology KW - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid -- pharmacology KW - Mice KW - Retina -- cytology KW - Rats KW - Cystine -- metabolism KW - Rats, Inbred F344 KW - Tumor Cells, Cultured KW - Neurites -- drug effects KW - Apoptosis -- drug effects KW - Hybrid Cells KW - Excitatory Amino Acid Agonists -- pharmacology KW - Homocysteine -- pharmacology KW - Cell Differentiation -- drug effects KW - Homocysteine -- analogs & derivatives KW - Antigens, Polyomavirus Transforming -- pharmacology KW - Neurons -- metabolism KW - Doxorubicin -- pharmacology KW - Neurons -- drug effects KW - Tumor Suppressor Protein p53 -- metabolism KW - Neurons -- ultrastructure KW - Glutamic Acid -- pharmacology KW - Antiporters -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79662864?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell+and+tissue+research&rft.atitle=N18-RE-105+cells%3A+differentiation+and+activation+of+p53+in+response+to+glutamate+and+adriamycin+is+blocked+by+SV40+large+T+antigen+tsA58.&rft.au=Dillon-Carter%2C+O%3BConejero%2C+C%3BTornatore%2C+C%3BPoltorak%2C+M%3BFreed%2C+W+J&rft.aulast=Dillon-Carter&rft.aufirst=O&rft.date=1998-02-01&rft.volume=291&rft.issue=2&rft.spage=191&rft.isbn=&rft.btitle=&rft.title=Cell+and+tissue+research&rft.issn=0302766X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-23 N1 - Date created - 1998-03-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - N terminus of Sos1 Ras exchange factor: critical roles for the Dbl and pleckstrin homology domains. AN - 79662103; 9447973 AB - We have studied the functional importance of the N terminus of mouse Sos1 (mSos1), a ubiquitously expressed Ras-specific guanine nucleotide exchange factor whose C-terminal sequences bind Grb-2. Consistent with previous reports, addition of a myristoylation signal to mSos1 (MyrSos1) rendered it transforming for NIH 3T3 cells and deletion of the mSos C terminus (MyrSos1-deltaC) did not interfere with this activity. However, an N-terminally deleted myristoylated mSos1 protein (MyrSos1-deltaN) was transformation defective, although the protein was stable and localized to the membrane. Site-directed mutagenesis was used to examine the role of the Dbl and pleckstrin homology (PH) domains located in the N terminus. When mutations in the PH domain were introduced into two conserved amino acids either singly or together in MyrSos1 or MyrSos1-deltaC, the transforming activity was severely impaired. An analogous reduction in biological activity was seen when a cluster of point mutations was engineered into the Dbl domain. The mitogen-activation protein (MAP) kinase activities induced by the various Dbl and PH mutants of MyrSos1 correlated with their biological activities. When NIH 3T3 cells were transfected with a myristoylated Sos N terminus, their growth response to epidermal growth factor (EGF), platelet-derived growth factor, lysophosphatidic acid or serum was greatly impaired. The dominant inhibitory biological activity of the N terminus correlated with its ability to impair EGF-dependent activation of GTP-Ras and of MAP kinase, as well with the ability of endogenous Sos to form a stable complex with activated EGF receptors. The N terminus with mutations in the Dbl and PH domains was much less inhibitory in these biological and biochemical assays. In contrast to wild-type Sos1, nonmyristoylated versions of Sos1-deltaN and Sos1-deltaC did not form a stable complex with activated EGF receptors. We conclude that the Dbl and PH domains are critical for Sos function and that stable association of Sos with activated EGF receptors requires both the Sos N and C termini. JF - Molecular and cellular biology AU - Qian, X AU - Vass, W C AU - Papageorge, A G AU - Anborgh, P H AU - Lowy, D R AD - Laboratory of Cellular Oncology, Division of Basic Sciences, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 771 EP - 778 VL - 18 IS - 2 SN - 0270-7306, 0270-7306 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Blood Proteins KW - GRB2 Adaptor Protein KW - Grb2 protein, mouse KW - Guanine Nucleotide Exchange Factors KW - Mcf2 protein, mouse KW - Phosphoproteins KW - Proteins KW - Retroviridae Proteins, Oncogenic KW - platelet protein P47 KW - ras Guanine Nucleotide Exchange Factors KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Animals KW - 3T3 Cells KW - Receptor, Epidermal Growth Factor -- metabolism KW - Mice KW - Protein Binding KW - Amino Acid Substitution KW - Structure-Activity Relationship KW - Binding Sites KW - Proteins -- chemistry KW - Blood Proteins -- chemistry KW - Retroviridae Proteins, Oncogenic -- chemistry KW - Blood Proteins -- metabolism KW - Retroviridae Proteins, Oncogenic -- metabolism KW - Proteins -- metabolism KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79662103?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=N+terminus+of+Sos1+Ras+exchange+factor%3A+critical+roles+for+the+Dbl+and+pleckstrin+homology+domains.&rft.au=Qian%2C+X%3BVass%2C+W+C%3BPapageorge%2C+A+G%3BAnborgh%2C+P+H%3BLowy%2C+D+R&rft.aulast=Qian&rft.aufirst=X&rft.date=1998-02-01&rft.volume=18&rft.issue=2&rft.spage=771&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-24 N1 - Date created - 1998-02-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1993 May 7;73(3):611-20 [8490966] Mol Cell Biol. 1997 Dec;17(12):7132-8 [9372945] Annu Rev Biochem. 1993;62:851-91 [8352603] Mol Cell Biol. 1993 Dec;13(12):7718-24 [8246988] J Biol Chem. 1994 Jan 7;269(1):62-5 [8276860] Mol Cell Biol. 1994 Aug;14(8):5192-201 [7518560] Trends Biochem Sci. 1994 Jul;19(7):279-83 [8048167] J Biol Chem. 1994 Aug 19;269(33):21103-9 [8063729] Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8512-6 [8078913] Cell. 1994 Sep 23;78(6):949-61 [7923364] Biochemistry. 1995 Feb 7;34(5):1475-81 [7849006] Science. 1995 Apr 28;268(5210):576-9 [7725106] Proc Natl Acad Sci U S A. 1983 Aug;80(16):4949-53 [6192445] J Biol Chem. 1989 Apr 5;264(10):5791-8 [2564392] Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6511-5 [1631150] Science. 1992 Jul 31;257(5070):671-4 [1496380] Nature. 1993 May 6;363(6424):45-51 [8479536] Nature. 1993 May 6;363(6424):85-8 [8479541] Nature. 1993 May 6;363(6424):88-92 [8386805] Cancer Res. 1991 Jan 15;51(2):712-7 [1985788] Cell. 1991 Nov 15;67(4):701-16 [1934068] Mol Cell Biol. 1991 Dec;11(12):6026-33 [1658623] Nature. 1991 Nov 28;354(6351):311-4 [1956381] Science. 1992 Jan 31;255(5044):603-6 [1736363] Nature. 1992 Mar 26;356(6367):340-4 [1372395] J Biol Chem. 1995 May 19;270(20):11707-10 [7744811] Immunity. 1995 May;2(5):451-60 [7538439] J Biol Chem. 1995 Jul 7;270(27):15954-7 [7608150] Nat Genet. 1995 Jul;10(3):294-300 [7670467] Biochem J. 1995 Dec 15;312 ( Pt 3):661-6 [8554502] Bioessays. 1996 Jan;18(1):35-46 [8593162] Curr Opin Cell Biol. 1996 Apr;8(2):197-204 [8791426] Curr Opin Cell Biol. 1996 Apr;8(2):216-22 [8791419] J Biol Chem. 1996 Sep 27;271(39):24300-6 [8798677] Cancer Surv. 1996;27:87-100 [8909796] Oncogene. 1996 Nov 21;13(10):2055-65 [8950972] Curr Opin Genet Dev. 1997 Feb;7(1):75-9 [9024640] EMBO J. 1997 Feb 17;16(4):706-16 [9049300] Prog Biophys Mol Biol. 1996;66(1):1-41 [9107131] EMBO J. 1997 Mar 17;16(6):1351-9 [9135150] FEBS Lett. 1997 Apr 21;407(1):111-5 [9141492] Science. 1993 May 28;260(5112):1338-43 [8493579] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dynamic contact maps of protein structures. AN - 69986692; 9783253 AB - The two-dimensional contact map of interresidue distances is a visual analysis technique for protein structures. We present two standalone software tools designed to be used in combination to increase the versatility of this simple yet powerful technique. First, the program Structer calculates contact maps from three-dimensional molecular structural data. The contact map matrix can then be viewed in the graphical matrix-visualization program Dotter. Instead of using a predefined distance cutoff, we exploit Dotter's dynamic rendering control, allowing interactive exploration at varying distance cutoffs after calculating the matrix once. Structer can use a number of distance measures, can incorporate multiple chains in one contact map, and allows masking of user-defined residue sets. It works either directly with PDB files, or can use the MMDB network API for reading structures. JF - Journal of molecular graphics & modelling AU - Sonnhammer, E L AU - Wootton, J C AD - Computational Biology Branch, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 1 EP - 5, 33 VL - 16 IS - 1 SN - 1093-3263, 1093-3263 KW - Diphtheria Toxin KW - 0 KW - Histocompatibility Antigens Class II KW - Index Medicus KW - Histocompatibility Antigens Class II -- chemistry KW - Diphtheria Toxin -- chemistry KW - Humans KW - Software KW - Computer Simulation KW - Models, Molecular KW - Protein Conformation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69986692?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+graphics+%26+modelling&rft.atitle=Dynamic+contact+maps+of+protein+structures.&rft.au=Sonnhammer%2C+E+L%3BWootton%2C+J+C&rft.aulast=Sonnhammer&rft.aufirst=E&rft.date=1998-02-01&rft.volume=16&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+graphics+%26+modelling&rft.issn=10933263&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-30 N1 - Date created - 1998-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sex Differences in Marital and Social Adjustment AN - 60083254; 9905655 AB - A sample of 146 married Japanese men & women, ages 25-85, were interviewed to clarify the relationship between marital adjustment & social adjustment. For the whole sample, the total score of the Short Marital Adjustment Test (SMAT) & its subcategories, dyadic consensus & satisfaction, was significantly correlated with five subcategory scores of the Social Adjustment Scale-II: household adjustment (except the spouse), external family adjustment, work adjustment, social leisure adjustment, & general adjustment. For the men, these correlations were only present for social leisure & general adjustment. Among men, the dyadic consensus scores of the SMAT had stronger correlations with the social adjustment scores; among women, correlations with the marital satisfaction scores were stronger. Thus, marital adjustment may be a part of social adjustment for women, but the two may be discrete for men. 1 Table, 16 References. Adapted from the source document. JF - Journal of Social Psychology AU - Kitamura, Toshinori AU - Aoki, Mitsuka AU - Fujino, Masako AU - Ura, Chiaki AU - Watanabe, Mayumi AU - Watanabe, Kyoko AU - Fujihara, Shigeki AD - Dept Sociocultural Environmental Research NIMH, 1-7-3 Konodai Ichikawa Chiba 272 Japan Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 26 EP - 32 VL - 138 IS - 1 SN - 0022-4545, 0022-4545 KW - Husbands KW - Wives KW - Sex Differences KW - Marriage KW - Marital Satisfaction KW - Adjustment KW - Japan KW - article KW - 1941: the family and socialization; sociology of the family, marriage, & divorce KW - 0312: social psychology; personality & social roles (individual traits, social identity, adjustment, conformism, & deviance) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/60083254?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocabs&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Social+Psychology&rft.atitle=Sex+Differences+in+Marital+and+Social+Adjustment&rft.au=Kitamura%2C+Toshinori%3BAoki%2C+Mitsuka%3BFujino%2C+Masako%3BUra%2C+Chiaki%3BWatanabe%2C+Mayumi%3BWatanabe%2C+Kyoko%3BFujihara%2C+Shigeki&rft.aulast=Kitamura&rft.aufirst=Toshinori&rft.date=1998-02-01&rft.volume=138&rft.issue=1&rft.spage=26&rft.isbn=&rft.btitle=&rft.title=Journal+of+Social+Psychology&rft.issn=00224545&rft_id=info:doi/ LA - English DB - Sociological Abstracts N1 - Date revised - 2007-10-30 N1 - Last updated - 2016-09-28 N1 - CODEN - JSPSAG N1 - SubjectsTermNotLitGenreText - Adjustment; Marriage; Sex Differences; Japan; Marital Satisfaction; Husbands; Wives ER - TY - JOUR T1 - In vitro techniques for the assessment of neurotoxicity. AN - 21262698; 11702142 AB - Risk assessment is a process often divided into the following steps: a) hazard identification, b) dose-response assessment, c) exposure assessment, and d) risk characterization. Regulatory toxicity studies usually are aimed at providing data for the first two steps. Human case reports, environmental research, and in vitro studies may also be used to identify or to further characterize a toxic hazard. In this report the strengths and limitations of in vitro techniques are discussed in light of their usefulness to identify neurotoxic hazards, as well as for the subsequent dose-response assessment. Because of the complexity of the nervous system, multiple functions of individual cells, and our limited knowledge of biochemical processes involved in neurotoxicity, it is not known how well any in vitro system would recapitulate the in vivo system. Thus, it would be difficult to design an in vitro test battery to replace in vivo test systems. In vitro systems are well suited to the study of biological processes in a more isolated context and have been most successfully used to elucidate mechanisms of toxicity, identify target cells of neurotoxicity, and delineate the development and intricate cellular changes induced by neurotoxicants. Both biochemical and morphological end points can be used, but many of the end points used can be altered by pharmacological actions as well as toxicity. Therefore, for many of these end points it is difficult or impossible to set a criterion that allows one to differentiate between a pharmacological and a neurotoxic effect. For the process of risk assessment such a discrimination is central. Therefore, end points used to determine potential neurotoxicity of a compound have to be carefully selected and evaluated with respect to their potential to discriminate between an adverse neurotoxic effect and a pharmacologic effect. It is obvious that for in vitro neurotoxicity studies the primary end points that can be used are those affected through specific mechanisms of neurotoxicity. For example, in vitro systems may be useful for certain structurally defined compounds and mechanisms of toxicity, such as organophosphorus compounds and delayed neuropathy, for which target cells and the biochemical processes involved in the neurotoxicity are well known. For other compounds and the different types of neurotoxicity, a mechanism of toxicity needs to be identified first. Once identified, by either in vivo or in vitro methods, a system can be developed to detect and to evaluate predictive ability for the type of in vivo neurotoxicity produced. Therefore, in vitro tests have their greatest potential in providing information on basic mechanistic processes in order to refine specific experimental questions to be addressed in the whole animal. Images Figure 1 JF - Environmental Health Perspectives AU - Harry, G J AU - Billingsley, M AU - Bruinink, A AU - Campbell, I L AU - Classen, W AU - Dorman, D C AU - Galli, C AU - Ray, D AU - Smith, R A AU - Tilson, H A AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA., harry@niehs.nih.gov Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 131 EP - 158 PB - US Government Printing Office, Superintendent of Documents, P.O. Box 371954 Pittsburgh PA 15250-7954 USA VL - 106 IS - Suppl 1 SN - 0091-6765, 0091-6765 KW - Risk Abstracts; Pollution Abstracts; CSA Neurosciences Abstracts; Environment Abstracts KW - Risk assessment KW - discrimination KW - Data processing KW - Organophosphorus compounds KW - Biochemistry KW - Toxicity KW - Nervous system KW - Case reports KW - Dose-response effects KW - Neurotoxicity KW - Neuropathy KW - N3 11028:Neuropharmacology & toxicology KW - R2 23050:Environment KW - P 6000:TOXICOLOGY AND HEALTH KW - ENA 02:Toxicology & Environmental Safety UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21262698?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=In+vitro+techniques+for+the+assessment+of+neurotoxicity.&rft.au=Harry%2C+G+J%3BBillingsley%2C+M%3BBruinink%2C+A%3BCampbell%2C+I+L%3BClassen%2C+W%3BDorman%2C+D+C%3BGalli%2C+C%3BRay%2C+D%3BSmith%2C+R+A%3BTilson%2C+H+A&rft.aulast=Cao&rft.aufirst=Xing&rft.date=2015-11-01&rft.volume=186&rft.issue=&rft.spage=58&rft.isbn=&rft.btitle=&rft.title=Journal+of+Affective+Disorders&rft.issn=01650327&rft_id=info:doi/10.1016%2Fj.jad.2015.06.058 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-01-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Risk assessment; Nervous system; Organophosphorus compounds; Data processing; Case reports; Neurotoxicity; Neuropathy; discrimination; Biochemistry; Dose-response effects; Toxicity ER - TY - JOUR T1 - Validating new toxicology tests for regulatory acceptance AN - 1859129839; 9618321 AB - Before a new or revised toxicology test is considered acceptable for safety evaluation of new substances, the test users and the industrial and regulatory decision makers must feel comfortable with it, and the decisions it supports. Comfort with, and the acceptance of, a new test comes after knowing that it has been validated for its proposed use. The validation process is designed to determine the operational characteristics of a test, that is, its reliability and relevance, in addition to its strengths and limitations. The reliability of a test is measured by its reproducibility. Its relevance is judged by its mechanistic relationship to the health effects of concern, and its ability to predict or identify those effects. The U.S. government has recently formed the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) to work with federal agencies and test developers to coordinate the evaluation and adoption of new test methods. The ICCVAM will provide guidance to agencies and other stakeholders on criteria and processes for development, validation, and acceptance of tests; coordinate technical reviews of proposed new tests of interagency interest; facilitate information sharing among agencies; and serve as an interagency resource and communications link with parties outside of the federal government on matters of test method validation. Copyright 1998 Academic Press. JF - Regulatory toxicology and pharmacology : RTP AU - Zeiger AU - Stokes AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709, USA. Y1 - 1998/02// PY - 1998 DA - February 1998 SP - 32 EP - 37 VL - 27 IS - 1 Pt 2 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859129839?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Regulatory+toxicology+and+pharmacology+%3A+RTP&rft.atitle=Validating+new+toxicology+tests+for+regulatory+acceptance&rft.au=Zeiger%3BStokes&rft.aulast=Zeiger&rft.aufirst=&rft.date=1998-02-01&rft.volume=27&rft.issue=1+Pt+2&rft.spage=32&rft.isbn=&rft.btitle=&rft.title=Regulatory+toxicology+and+pharmacology+%3A+RTP&rft.issn=1096-0295&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 1998-06-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reducing Cigarette Sales to Minors in an Urban Setting: Issues and Opportunities for Merchant Intervention AN - 17387378; 4610173 AB - Intervention studies to reduce cigarette sales to minors have been conducted primarily in suburban settings. Little is known about sociocultural factors influencing cigarette sales to minors in urban settings. This study sought to determine sociodemographic and cultural factors that may play a role in cigarette sales and in efforts to reduce sales to minors in urban areas. Merchant education and follow-up surveys were conducted in small local stores in predominantly African-American urban census tracts in Baltimore. The stores had prior evidence of cigarette sales to minors. Merchants reported hostility (66%) and foul language (64%) when they requested youth identification. Youthful-oriented advertising of cigarettes was highly prevalent in all stores and moreso in stores owned and staffed by Asian merchants. Advertising with specific youthful content was predictive (OR = 3.97; 95% CI = 1.70, 9.23; P = .0014) of higher requests for cigarettes from minors. Youth-oriented cigarette advertising is a prevalent environmental risk for urban youth. Differences between Asian and African-American merchants suggest socioethnic factors may be an influential component of illegal sales and educational campaigns to reduce smoking among minors. JF - American Journal of Preventive Medicine AU - Voorhees, C C AU - Yanek, L R AU - Stillman, F A AU - Becker, D M AD - NHLBI/NIH, Division of Epidemiology and Clinical Applications, Prevention and Behavioral Medicine SRG, Rockledge 2, Room 8215, Bethesda, MD 20892-7936, USA Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 138 EP - 142 VL - 14 IS - 2 SN - 0749-3797, 0749-3797 KW - African Americans KW - USA, Maryland, Baltimore KW - advertising KW - disease control KW - marketing KW - Health & Safety Science Abstracts KW - Cigarette smoking KW - Adolescents KW - Urban areas KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17387378?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Preventive+Medicine&rft.atitle=Reducing+Cigarette+Sales+to+Minors+in+an+Urban+Setting%3A+Issues+and+Opportunities+for+Merchant+Intervention&rft.au=Voorhees%2C+C+C%3BYanek%2C+L+R%3BStillman%2C+F+A%3BBecker%2C+D+M&rft.aulast=Voorhees&rft.aufirst=C&rft.date=1998-02-01&rft.volume=14&rft.issue=2&rft.spage=138&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Preventive+Medicine&rft.issn=07493797&rft_id=info:doi/10.1016%2FS0749-3797%2897%2900024-X LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Urban areas; Adolescents; Cigarette smoking DO - http://dx.doi.org/10.1016/S0749-3797(97)00024-X ER - TY - JOUR T1 - An Inverse Relation between cagA super(+) Strains of Helicobacter pylori Infection and Risk of Esophageal and Gastric Cardia Adenocarcinoma AN - 17278179; 4493384 AB - Gastric colonization with Helicobacter pylori, especially cagA super(+) strains, is a risk factor for noncardia gastric adenocarcinoma, but its relationship with gastric cardia adenocarcinoma is unclear. Although incidence rates for noncardia gastric adenocarcinoma have declined steadily, paralleling a decline in H. pylori prevalence, rates for adenocarcinomas of esophagus and gastric cardia have sharply increased in industrialized countries in recent decades. To clarify the role of H. pylori infection in these tumors with divergent incidence trends, we analyzed serum IgG antibodies to H. pylori and to a recombinant fragment of CagA by antigen-specific ELISA among 129 patients newly diagnosed with esophageal/gastric cardia adenocarcinoma, 67 patients with noncardia gastric adenocarcinoma, and 224 population controls. Cancer risks were estimated by odds ratios (OR) and 95% confidence intervals (CI) using logistic regression models. Infection with cagA super(+) strains was not significantly related to risk for noncardia gastric cancers (OR, 1.4; CI, 0.7-2.8) but was significantly associated with a reduced risk for esophageal/cardia cancers (OR, 0.4; CI, 0.2-0.8). However, there was little association with cagA super(-) strains of H. pylori for either cancer site (OR, 1.0 and 1.1, respectively). These findings suggest that the effects of H. pylori strains on tumor development vary by anatomical site. Further studies are needed to confirm these results and to assess whether the decreasing prevalence of H. pylori, especially cagA super(+) strains, may be associated with the rising incidence of esophageal/gastric cardia adenocarcinomas in industrialized countries. JF - Cancer Research AU - Chow, W-H AU - Blaser, MJ AU - Blot, W J AU - Gammon, MD AU - Vaughan, T L AU - Risch, HA AU - Perez-Perez, GI AU - Schoenberg, J B AU - Stanford, J L AU - Rotterdam, H AU - West, AB AU - Fraumeni, JF Jr AD - National Cancer Institute, 6130 Executive Boulevard, EPN 418, Rockville, MD 20852, USA Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 588 EP - 590 VL - 58 IS - 4 SN - 0008-5472, 0008-5472 KW - cagA protein KW - gastric adenocarcinoma KW - Microbiology Abstracts B: Bacteriology KW - Intestinal microflora KW - Helicobacter pylori KW - Gastrointestinal tract diseases KW - Esophageal carcinoma KW - Carcinoma KW - J 02846:Gastrointestinal tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17278179?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Research&rft.atitle=An+Inverse+Relation+between+cagA+super%28%2B%29+Strains+of+Helicobacter+pylori+Infection+and+Risk+of+Esophageal+and+Gastric+Cardia+Adenocarcinoma&rft.au=Chow%2C+W-H%3BBlaser%2C+MJ%3BBlot%2C+W+J%3BGammon%2C+MD%3BVaughan%2C+T+L%3BRisch%2C+HA%3BPerez-Perez%2C+GI%3BSchoenberg%2C+J+B%3BStanford%2C+J+L%3BRotterdam%2C+H%3BWest%2C+AB%3BFraumeni%2C+JF+Jr&rft.aulast=Chow&rft.aufirst=W-H&rft.date=1998-02-01&rft.volume=58&rft.issue=4&rft.spage=588&rft.isbn=&rft.btitle=&rft.title=Cancer+Research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Helicobacter pylori; Esophageal carcinoma; Intestinal microflora; Carcinoma; Gastrointestinal tract diseases ER - TY - JOUR T1 - Nosocomial catheter-associated Flavobacterium odoratum bacteraemia in cancer patients AN - 16481093; 4287610 JF - Journal of Medical Microbiology AU - Spanik, S AU - Trupl, J AU - Krcmery, V AD - Department of Medicine, Microbiology and Pharmacology, National Cancer Institute and St. Elizabeth Cancer Institute, Heydukova 10, 812 50 Bratislava, Slovak Republic Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 183 VL - 47 IS - 2 SN - 0022-2615, 0022-2615 KW - Microbiology Abstracts B: Bacteriology KW - J 02855:Human Bacteriology: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16481093?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Health+Communication&rft.atitle=Social+support+functions+during+a+slowly-evolving+environmental+disaster%3A+The+case+of+amphibole+asbestos+exposure+in+Libby%2C+Montana&rft.au=Cline%2C+Rebecca+J.+W.%3BOrom%2C+Heather%3BChild%2C+Jeffrey+T.%3BHernandez%2C+Tanis%3BBlack%2C+Brad&rft.aulast=Cline&rft.aufirst=Rebecca+J.&rft.date=2015-11-01&rft.volume=30&rft.issue=11&rft.spage=1135&rft.isbn=&rft.btitle=&rft.title=Health+Communication&rft.issn=10410236&rft_id=info:doi/10.1080%2F10410236.2014.922456 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Serum caffeine and paraxanthine as markers for reported caffeine intake in pregnancy AN - 16457637; 4344162 AB - PURPOSE: Previous studies of maternal caffeine use and pregnancy outcome have relied on selfreported use. Even if these were perfectly accurate, inter-individual differences in caffeine metabolism result in a relatively weak correlation between caffeine intake and serum concentration. The purpose of this study was to determine whether the serum concentration of caffeine or its primary metabolite, paraxanthine, obtained at an unknown time during working hours, is useful to distinguish between pregnant women who report consuming small and large amounts of caffeine. METHODS: We selected from the Birmingham fetal growth study 60 women with normal pregnancy outcomes who reported consuming less than or equal to 0.8 mg/kg/day of caffeine in a 24-hour dietary recall, 60 who consumed 0.81-2.5 mg/kg/day, 60 who consumed 2.51-5.0 mg/kg/day and 59 who consumed greater than or equal to 5.01 mg/kg/day. These women had serum drawn for storage during regular clinic hours on the same day as the recall interview. Caffeine and paraxanthine were measured in the stored serum using high performance liquid chromatography. RESULTS: The weighted kappa coefficient between strata of caffeine intake and quartiles of serum paraxanthine was 0.58 among smokers and 0.53 among nonsmokers, versus 0.44 and 0.51, respectively, for quartiles of serum caffeine. The Pearson correlation coefficient between intake and paraxanthine was 0.50 for smokers and 0.53 for nonsmokers, and 0.37 and 0.51, respectively, for serum caffeine. These values are comparable to the correlation between reported smoking and serum cotinine in pregnancy. CONCLUSIONS: The serum concentrations of paraxanthine, and to a lesser degree, caffeine are useful to distinguish between women with varying levels of caffeine intake. JF - Annals of Epidemiology AU - Klebanoff, MA AU - Levine, R J AU - Dersimonian, R AU - Clemens, J D AU - Wilkins, D G AD - DESPR, NICHD, NIH, 6100 Bldg Room 7B03, Bethesda, MD 20892-7510, USA Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 107 EP - 111 VL - 8 IS - 2 SN - 1047-2797, 1047-2797 KW - caffeine KW - dietary intake KW - man KW - paraxanthine KW - pregnancy KW - serum levels KW - Toxicology Abstracts KW - X 24120:Food, additives & contaminants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16457637?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+Epidemiology&rft.atitle=Serum+caffeine+and+paraxanthine+as+markers+for+reported+caffeine+intake+in+pregnancy&rft.au=Klebanoff%2C+MA%3BLevine%2C+R+J%3BDersimonian%2C+R%3BClemens%2C+J+D%3BWilkins%2C+D+G&rft.aulast=Klebanoff&rft.aufirst=MA&rft.date=1998-02-01&rft.volume=8&rft.issue=2&rft.spage=107&rft.isbn=&rft.btitle=&rft.title=Annals+of+Epidemiology&rft.issn=10472797&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Tetravinyl-tetramethylcyclo-tetrasiloxane (tetravinyl D4) is a mutagen in Rat2 lambda lacI fibroblasts AN - 16417663; 4326156 AB - Small fragments of silicone gels injected intraperitoneally have been used to induce plasmacytomas in genetically susceptible mice. Silicone oils, in contrast to silicone gels, are apparently not tumorigenic in the mouse plasmacytoma system. The reason for this difference as well as the mechanism of silicone gel-induced plasmacytoma development is poorly understood. We chose to examine the possibility that low molecular wt silicone compounds such as siloxanes, leaking from the complex silicone gel matrix into the surrounding tissue, may be mutagenic. We postulate that this mutagenicity may be a critical determinant of the plasmacytoma inducing potency of silicone gels. Six siloxane compounds, either linear or cyclic di-, tri-, or tetrasiloxanes substituted with methyl or vinyl moieties, were selected as model compounds to study mutagenicity in Rat2 lambda lacI fibroblasts in vitro. Using phage lambda -derived lacI/lacZ genes as target/reporter genes to quantitate mutagenesis, and gamma -cyclodextrin as vehicle to effectively deliver siloxanes, we found that exposure to 50 mu M of tetravinyl-tetramethylcyclo-tetrasiloxane (tetravinyl D4) resulted in a modest 1.7-fold increase of mutant frequencies over controls in Rat2 lambda lacI cells. In related toxicity experiments, tetravinyl D4 was shown to perturb lipid membranes leading to a loss of cytosolic glutathione (GSH), which by itself resulted in a 1.5-fold increased mutant rate in Rat2 lambda lacI cells. We conclude that certain siloxanes may act as direct mutagens in mammalian cells. In addition, siloxane-induced mutagenicity may be enhanced by the depletion of intracellular GSH caused by the interaction of lipophilic siloxanes with cell membranes. JF - Carcinogenesis AU - Felix, K AU - Lin, S AU - Bornkamm, G-W AU - Janz, S AD - Laboratory of Genetics, DBS, NCI, NIH, Bethesda, MD 20892, USA, felixk@dc37a.nci.nih.gov Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 315 EP - 320 VL - 19 IS - 2 SN - 0143-3334, 0143-3334 KW - cell culture KW - glutathione KW - rats KW - siloxanes KW - tetravinyl D4 KW - Toxicology Abstracts KW - X 24155:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16417663?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Tetravinyl-tetramethylcyclo-tetrasiloxane+%28tetravinyl+D4%29+is+a+mutagen+in+Rat2+lambda+lacI+fibroblasts&rft.au=Felix%2C+K%3BLin%2C+S%3BBornkamm%2C+G-W%3BJanz%2C+S&rft.aulast=Felix&rft.aufirst=K&rft.date=1998-02-01&rft.volume=19&rft.issue=2&rft.spage=315&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Dry deposition modeling of nitrate and sulfate by using particle size distribution data AN - 16401356; 4315413 AB - Dry deposition and air sampling were undertaken simultaneously in the ambient air of Ping Tung area by using several dry deposition plates, two MOUDIs (Micro-orifice Uniform Deposit Impactors) and one NRI (Noll Rotary Impactor) from December 1995 to May 1996 in Southern Taiwan. The NRI and MOUDI were used to collect ambient coarse and fine particulate, respectively. Dry deposition plate was applied to collect particle deposition flux. An ion chromatography (Dionex 2000i/sP) equipped with 4 mm AG4A-SC and AS4A-SC column was employed to analyze the anion species (NO sub(3) super(-) and SO sub(4) super(2-)). The eluent solution is 1.8 mM sodium carbonate/1.7mM sodium bicarbonate. The calculated dry deposition flux for each particle size range was obtained by using measured mass-size distribution data between 0.18 and 100 mu m diameter and a dry deposition model. The mean modeled/measured (Md/Ma) ratio of dry deposition flux varied between 1.11 and 1.28, between 1.28 and 1.42 and between 0.88 and 0.97 for nitrate, sulfate and total particle mass, respectively. The results indicated that nitrate and sulfate were slightly overestimated by a dry deposition model, while total particle mass was slightly underestimated by this model. In general, by using the particle size distribution data, this dry deposition model can provide a good predication for the dry deposition flux of nitrate, sulfate and total particle mass. More than 87.5% of nitrate and more than 92.9% of sulfate dry deposition flux are contributed by particle diameters larger than 10 mu m. This is due to the fact that particle size larger than 10 mu m have higher dry deposition velocities (>4.65 cm/sec) and control the majority of the dry deposition flux. JF - Journal of Environmental Science and Health, Part A: Toxic/Hazardous Substances & Environmental Engineering AU - Chen, S J AU - Lin, C C AU - Chiu, S C AD - Department of Environmental Protection Technology, National Ping-Tung University of Science and Technology, Nei Pu 91207, Ping Tung, Taiwan Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 307 EP - 334 VL - A33 IS - 2 SN - 1093-4529, 1093-4529 KW - Taiwan, Ping Tung KW - Pollution Abstracts KW - P 0000:AIR POLLUTION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16401356?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Apollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Environmental+Science+and+Health%2C+Part+A%3A+Toxic%2FHazardous+Substances+%26+Environmental+Engineering&rft.atitle=Dry+deposition+modeling+of+nitrate+and+sulfate+by+using+particle+size+distribution+data&rft.au=Chen%2C+S+J%3BLin%2C+C+C%3BChiu%2C+S+C&rft.aulast=Chen&rft.aufirst=S&rft.date=1998-02-01&rft.volume=A33&rft.issue=2&rft.spage=307&rft.isbn=&rft.btitle=&rft.title=Journal+of+Environmental+Science+and+Health%2C+Part+A%3A+Toxic%2FHazardous+Substances+%26+Environmental+Engineering&rft.issn=10934529&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Drug testing with alternative matrices. I. Pharmacological effects and disposition of cocaine and codeine in plasma, sebum, and stratum corneum AN - 16392143; 4311870 AB - This study examined the disposition of cocaine, codeine, and metabolites in stratum corneum, sebum, and plasma collected from five African-American males after administrations of cocaine and codeine during a 10-week inpatient clinical study. The subjects were experienced, healthy drug users with a recent history of cocaine and heroin abuse. The first drug administration was delayed by three weeks to allow for the elimination of previously administered drugs from the body. Subjects received three 75 mg cocaine hydrochloride/70 kg doses by the subcutaneous route and three 60 mg codeine sulfate/70 kg doses by the oral route on alternating days beginning in week 4. The same dosing sequence was repeated in week 8 with doubled (x 2) doses. Pharmacological measures (heart rate, pupil diameter, subject "High" and "Liking") were obtained simultaneously with blood. Stratum corneum was collected by scraping regions of the back once each week. Sebum was collected periodically from the forehead by applying Sebutape super(TM) patches for 1-2-h intervals. Plasma, stratum corneum, and sebum were analyzed for cocaine, codeine, and metabolites by gas chromatography-mass spectrometry. Peak plasma cocaine concentrations occurred within the 30 min following dosing and followed peak pharmacological effects. Peak plasma codeine concentrations occurred within 1-2 h of dosing and before peak pharmacological effects. Cocaine and codeine were the primary analytes in sebum and stratum corneum. After dosing, these drugs appeared in sebum within 1-2 h and were detected for 1-2 days. Peak-drug concentrations in stratum corneum occurred one day after completion of dosing; elimination of the drugs continued over the next 1-2 weeks after dosing. Overall, no definitive relationship was observed between drug concentrations in sebum and stratum corneum compared with dose. Interpretation of drug distribution and elimination in sebum and stratum corneum was complicated by possible contamination of specimens with drugs from sweat. The mechanism(s) for deposition of cocaine and codeine in sebum and stratum corneum appeared to be complex and could involve the transfer of drugs between different body fluids (i.e., sebum and sweat) and other matrices (i.e., skin and hair). JF - Journal of Analytical Toxicology AU - Joseph, RE Jr AU - Oyler, J M AU - Wstadik, A T AU - Ohuoha, Chideha AU - Cone, E J AD - Addiction Research Center, Division of Intramural Research, National Institute on Drug Abuse, P.O. Box 5180, Baltimore, MD 21224, USA Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 6 EP - 17 VL - 22 IS - 1 SN - 0146-4760, 0146-4760 KW - cocaine KW - codeine KW - man KW - normal subjects KW - pharmacokinetics KW - Toxicology Abstracts KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16392143?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Analytical+Toxicology&rft.atitle=Drug+testing+with+alternative+matrices.+I.+Pharmacological+effects+and+disposition+of+cocaine+and+codeine+in+plasma%2C+sebum%2C+and+stratum+corneum&rft.au=Joseph%2C+RE+Jr%3BOyler%2C+J+M%3BWstadik%2C+A+T%3BOhuoha%2C+Chideha%3BCone%2C+E+J&rft.aulast=Joseph&rft.aufirst=RE&rft.date=1998-02-01&rft.volume=22&rft.issue=1&rft.spage=6&rft.isbn=&rft.btitle=&rft.title=Journal+of+Analytical+Toxicology&rft.issn=01464760&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Helicobacter pylori adheres selectively to Fusobacterium spp. AN - 16364791; 4270222 AB - Helicobacter pylori strains ATCC 43504 and ATCC 43629 were tested for their ability to coaggregate with 79 strains of bacteria representing 16 genera. All except two of the strains were of human origin, and most of the strains were isolated from the oral cavity. The helicobacters failed to coaggregate with all strains except the fusobacteria. Several coaggregations were partially or completely inhibited by lactose. Strong coaggregation was seen with each of four subspecies of Fusobacterium nucleatum and with Fusobacterium periodonticum ATCC 33693, all of human dental plaque origin. In contrast, the helicobacters failed to coaggregate with non-plaque isolates, Fusobacterium mortiferum ATCC 25557 and Fusobacterium ulcerans ATCC 49185. Heat treatment of the fusobacteria inactivated their ability to coaggregate, whereas heating of the helicobacter partners had no effect, suggesting the presence of an adhesin on the fusobacteria and a corresponding receptor on the helicobacters. The potential ability of H. pylori to colonize the oral cavity by adhering selectively to the ubiquitous fusobacteria gives credence to the possibility that dental plaque may serve as a reservoir for this pathogen outside of the stomach. JF - Oral Microbiology and Immunology AU - Andersen, R N AU - Ganeshkumar, N AU - Kolenbrander, P E AD - National Institutes of Health, Building 30, Room 310, 30 Convent Drive MSC 4350, Bethesda, MD 20892-4350, USA Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 51 EP - 54 VL - 13 IS - 1 SN - 0902-0055, 0902-0055 KW - bacteria KW - coaggregates KW - lactose KW - man KW - Microbiology Abstracts B: Bacteriology KW - J 02844:Dental and oral UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16364791?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oral+Microbiology+and+Immunology&rft.atitle=Helicobacter+pylori+adheres+selectively+to+Fusobacterium+spp.&rft.au=Andersen%2C+R+N%3BGaneshkumar%2C+N%3BKolenbrander%2C+P+E&rft.aulast=Andersen&rft.aufirst=R&rft.date=1998-02-01&rft.volume=13&rft.issue=1&rft.spage=51&rft.isbn=&rft.btitle=&rft.title=Oral+Microbiology+and+Immunology&rft.issn=09020055&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Population structure of the relapsing fever spirochete Borrelia hermsii as indicated by polymorphism of two multigene families that encode imunogenic outer surface lipoproteins AN - 16337136; 4270323 AB - The tick-borne relapsing fever spirochete Borrelia hermsii evades the mammalian immune system by periodically switching expression among members of two multigene families that encode immunogenic, antigenically distinct outer surface proteins. The type strain, B. hermsii HS1, has at least 40 complete genes and pseudogenes that participate in this multiphasic antigenic variation. Originally termed vmp (for variable major protein) genes, they have been reclassified as vsp (for variable small protein) and vlp (for variable large protein) genes, based on size and amino acid sequence similarities. To date, antigenic variation in B. hermsii has been studied only in the type strain, HS1. Nucleotide sequence comparisons of 23 B. hermsii HS1 genes revealed five distinct groups, the vsp gene family and four subfamilies of vlp genes. We used PCR with family- and subfamily-specific primers, followed by restriction fragment length polymorphism analysis, to compare the vsp and vlp repertoires of HS1 and seven other B. hermsii isolates from Washington, Idaho, and California. This analysis, together with pulsed-field gel electrophoresis genome profiles, revealed that the eight isolates formed three distinct groups, which likely represent clonal lineages. Members of the three groups coexisted in the same geographic area, but they could also be isolated across large geographical distances. This population structure may result from immune selection by the host, as has been proposed for other pathogens with polymorphic antigens. JF - Infection and Immunity AU - Hinnebusch, B J AU - Barbour, A G AU - Restrepo, B I AU - Schwan, T G AD - Laboratory of Microbial Structure and Function, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 S. 4th St., Hamilton, MT 59840, USA, joe_hinnebusch@nih.gov Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 432 EP - 440 VL - 66 IS - 2 SN - 0019-9567, 0019-9567 KW - nucleotide sequence KW - polymerase chain reaction KW - vlp gene KW - vmp gene KW - vsp gene KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - J 02725:DNA KW - G 07290:Population genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16337136?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Population+structure+of+the+relapsing+fever+spirochete+Borrelia+hermsii+as+indicated+by+polymorphism+of+two+multigene+families+that+encode+imunogenic+outer+surface+lipoproteins&rft.au=Hinnebusch%2C+B+J%3BBarbour%2C+A+G%3BRestrepo%2C+B+I%3BSchwan%2C+T+G&rft.aulast=Hinnebusch&rft.aufirst=B&rft.date=1998-02-01&rft.volume=66&rft.issue=2&rft.spage=432&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Partial purification and characterization of biological effects of a lipid toxin produced by Mycobacterium ulcerans AN - 16331974; 4270345 AB - Organisms in the genus Mycobacterium cause a variety of human diseases. One member of the genus, M. ulcerans, causes a necrotizing skin disease called Buruli ulcer. Buruli ulcer is unique among mycobacterial diseases in that the organisms at the site of infection are extracellular and there is little acute inflammatory response. Previous literature reported the presence of a toxin in the culture supernatant of M. ulcerans which causes a cytopathic effect on the mouse fibroblast cell line L929 in which the adherent cells round up and detach from the tissue culture plate. Here we report partial purification of a lipid toxin from the culture supernatant of M. ulcerans which is capable of causing the cytopathic effect on L929 cells. We also show that this cytopathic effect is a result of cytoskeletal rearrangement. The M. ulcerans toxin does not cause cell death but instead arrests cells in the G sub(1) phase of the cell cycle. JF - Infection and Immunity AU - George, K M AU - Barker, L P AU - Welty, D M AU - Small, PLC AD - Microscopy Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, 903 S. 4th St,, Hamilton, MT 59840, USA, katie_george@nih.gov Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 587 EP - 593 VL - 66 IS - 2 SN - 0019-9567, 0019-9567 KW - Toxicology Abstracts; Microbiology Abstracts B: Bacteriology KW - X 24171:Microbial KW - J 02843:Skin KW - J 02823:In vitro and in vivo effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16331974?accountid=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=Partial+purification+and+characterization+of+biological+effects+of+a+lipid+toxin+produced+by+Mycobacterium+ulcerans&rft.au=George%2C+K+M%3BBarker%2C+L+P%3BWelty%2C+D+M%3BSmall%2C+PLC&rft.aulast=George&rft.aufirst=K&rft.date=1998-02-01&rft.volume=66&rft.issue=2&rft.spage=587&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - A review of alcohol clearance in humans AN - 16327204; 4286193 AB - The level of blood or brain alcohol is considered to influence alcohol ingestion by causing subjective perceptions or neural activations that are reinforcing or rewarding. Alcohol-dependent people may try to maintain some desired tissue level, drinking to replace the millimolar levels that were cleared from the blood by metabolism. The biomedical literature describes many approaches to understanding the role of blood alcohol levels in human physiology and behavior, and this review examines some of the published results. They include the general kinetics of intake and removal of beverage alcohol as well as the characteristics of many different catalysts that can interact with alcohol. Because ingested alcohol creates blood levels that are a 1000-fold greater than those normally experienced during abstinence, ethanol may impose itself as an alternate substrate for the many oxidoreductases that act physiologically on other endogenous alcohols. Many enzymes that can act on millimolar ethanol have been isolated, and their structural genes are sequenced. Unfortunately, the genetic sequence does not indicate the physiological material upon which the translated gene product may act. In a sense, the set of enzymes with catalytic sites occupied by millimolar ethanol during alcohol drinking might constructively be regarded as "orphan gene products" whose physiological role remains to be clarified. This review is designed to indicate some of what is known, what is not known, and what needs to be known to improve the interpretations regarding adaptations to beverage alcohol and the ability of millimolar levels of alcohol to diminish dysphoria. The dysphoria may be influenced by ethanol, by ethanol metabolites, or by altered metabolism of currently unspecified endogenous substrates. A major challenge is to evaluate the multiple alternative variables within a context that stimulates curiosity and encourages quantitative tests of the relative contribution of each variable to the overall physiology of an individual. JF - Alcohol AU - Lands, WEM AD - National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Willco Building, Suite 400, 6000 Executive Boulevard, MSC 7003, Bethesda, MD 20892-7003, USA, wlands@willco.niaaa.nih.gov Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 147 EP - 160 VL - 15 IS - 2 SN - 0741-8329, 0741-8329 KW - man KW - pharmacokinetics KW - Toxicology Abstracts KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16327204?accountid=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=Alcohol&rft.atitle=A+review+of+alcohol+clearance+in+humans&rft.au=Lands%2C+WEM&rft.aulast=Lands&rft.aufirst=WEM&rft.date=1998-02-01&rft.volume=15&rft.issue=2&rft.spage=147&rft.isbn=&rft.btitle=&rft.title=Alcohol&rft.issn=07418329&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Development of a preliminary ground water flow model for water resources management in the Pingtung Plain, Taiwan AN - 16316607; 4249295 AB - Pingtung Plain is formed by Quaternary alluvial fan material from the three main rivers: Kaoping, Tungkang and Linpien. Ground water is the major water supply source on the plain. This is principally extracted from two aquifers. The natural ground water source is derived mainly from direct rainfall percolation and infiltration from the three rivers, with their catchments lying partly outside the plain. Rainfall characteristics are therefore the main factors controlling water resources availability. Pingtung Plain is an important primary production area for southern Taiwan, the comparatively warm climate allowing a long growing season, diversified cropping and the rearing of aquacultural produces. Approximately 75 percent of irrigation and domestic water supplies are derived from ground water. A water balance for the entire plain indicates that ground water resources, under optimized management, are sufficient to meet the existing multi-purpose uses. Development of a hydrogeological conceptual model is the first phase of a numerical ground water flow simulation. Preliminary results are encouraging, with the final simulations affording better insight to the hydraulic behavior of the aquifer system. Data input requirements for model operation fall into three categories: hydrological stresses, hydrogeological parameters and boundary conditions. After the model is built, the normal numerical modeling process requires significant calibration and sensitivity analyses for the hydrogeological parameters and stresses which are the most sensitive, but the least well defined. A well-calibrated simulation model can lead to a reliable and realistic management model. With this in mind, the calibration processes detailed are presented, and these data are introduced as initial values in the calibration process. JF - Ground Water AU - Ting, Cheh-Shyh AU - Zhou, Yangxiao AU - De Vries, JJ AU - Simmers, I AD - Dep. Civ. Eng., Natl. Pingtung Univ. Sci. and Technol., No. 1, Hseuh Fu Rd., Nei Pu Hsiang, Pingtung, Taiwan, ROC Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 20 EP - 36 VL - 36 IS - 1 SN - 0017-467X, 0017-467X KW - Water Resources Abstracts KW - SW 0840:Groundwater UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16316607?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Awaterresources&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ground+Water&rft.atitle=Development+of+a+preliminary+ground+water+flow+model+for+water+resources+management+in+the+Pingtung+Plain%2C+Taiwan&rft.au=Ting%2C+Cheh-Shyh%3BZhou%2C+Yangxiao%3BDe+Vries%2C+JJ%3BSimmers%2C+I&rft.aulast=Ting&rft.aufirst=Cheh-Shyh&rft.date=1998-02-01&rft.volume=36&rft.issue=1&rft.spage=20&rft.isbn=&rft.btitle=&rft.title=Ground+Water&rft.issn=0017467X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Contact: Ground Water Publishing Co., 6375 Riverside Dr, Dublin, OH, 43017 (USA). PH: (800) 332-2104. FAX: (614) 761-3446. N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - BIAcore for macromolecular interaction AN - 16293438; 4294717 AB - Examination of the literature for the period of this review revealed nearly two hundred citations that employed surface plasmon resonance (SPR) spectroscopy using BIAcore technology to evaluate biospecific interactions, demonstrating the increasing popularity of this powerful technique. Among these we noted the development of several new applications/modifications of standard techniques. In general, we find the qualitative aspects of the reported experiments to be excellent but the quantitative descriptions (k sub(T), k sub(on), k sub(off), and K sub(eq)) as well as the binding models still lagging behind. JF - Current Opinion in Biotechnology AU - Fivash, M AU - Towler, E M AU - Fisher, R J AD - Data Management Services, Inc., Protein Chemistry Laboratory, SAIC, Frederick NCI-Frederick Cancer Research and Development Center, PO Box B, Frederick, MD 21702, USA Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 97 EP - 101 VL - 9 IS - 1 SN - 0958-1669, 0958-1669 KW - BIAcore KW - reviews KW - surface plasmon resonance spectroscopy KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W 30965:Miscellaneous, Reviews KW - W3 33250:Methods: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16293438?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Opinion+in+Biotechnology&rft.atitle=BIAcore+for+macromolecular+interaction&rft.au=Fivash%2C+M%3BTowler%2C+E+M%3BFisher%2C+R+J&rft.aulast=Fivash&rft.aufirst=M&rft.date=1998-02-01&rft.volume=9&rft.issue=1&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=Current+Opinion+in+Biotechnology&rft.issn=09581669&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Cell cycle arrest in Era GTPase mutants: A potential growth rate-regulated checkpoint in Escherichia coli AN - 16282712; 4282155 AB - Era is a low-molecular-weight GTPase essential for Escherichia coli viability. The gene encoding Era is found in the rnc operon, and the synthesis of both RNase III and Era increases with growth rate. Mutants that are partially defective in Era GTPase activity or that are reduced in the synthesis of wild-type Era become arrested in the cell cycle at the predivisional two-cell stage. The partially defective Era GTPase mutation (era1) suppresses several temperature-sensitive lethal alleles that affect chromosome replication and chromosome partitioning but not cell division. Our results suggest that Era plays an important role in cell cycle progression at a specific point in the cycle, after chromosome partitioning but before cytokinesis. Possible functions for Era in cell cycle progression and the initiation of cell division are discussed. JF - Molecular Microbiology AU - Britton, R A AU - Powell, B S AU - Dasgupta, S AU - Sun, Qin AU - Margolin, W AU - Lupski, J R AU - Court, D L AD - Lab. Gene Regulation and Chromosome Biol., ABL-Basic Res. Prog., NCI/FCRDC, Frederick, MD 21702, USA Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 739 EP - 750 VL - 27 IS - 4 SN - 0950-382X, 0950-382X KW - Era protein KW - cell cycle KW - era gene KW - guanosinetriphosphatase KW - mutation KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - G 07210:Cell cycle KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16282712?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Microbiology&rft.atitle=Cell+cycle+arrest+in+Era+GTPase+mutants%3A+A+potential+growth+rate-regulated+checkpoint+in+Escherichia+coli&rft.au=Britton%2C+R+A%3BPowell%2C+B+S%3BDasgupta%2C+S%3BSun%2C+Qin%3BMargolin%2C+W%3BLupski%2C+J+R%3BCourt%2C+D+L&rft.aulast=Britton&rft.aufirst=R&rft.date=1998-02-01&rft.volume=27&rft.issue=4&rft.spage=739&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Carbon disulfide neurotoxicity in rats. VIII. Summary AN - 16272746; 4273296 AB - The carbon disulfide (CS sub(2)) studies reported here underscore the importance of addressing neurotoxicity issues by including a battery of biologic and mechanistic endpoints over both a dose and temporal range. In general, the continuum of effects was initiated in sensitive endpoints at the cellular level which progressed to behavioral alterations in the hindlimb and forelimb functioning followed by electrophysiological and morphological changes. JF - Neurotoxicology AU - Harry, G J AU - Graham, D G AU - Valentine, WM AU - Morgan, D L AU - Sills, R C AD - Environmental Toxicology Program (MD C1-04), National Institute of Environmental Health Sciences, Research Triangle Park, N.C. 27709, USA Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 159 EP - 162 VL - 19 IS - 1 SN - 0161-813X, 0161-813X KW - carbon disulfide KW - neurotoxicity KW - rats KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - N3 11104:Mammals (except primates) KW - X 24154:Pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16272746?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicology&rft.atitle=Carbon+disulfide+neurotoxicity+in+rats.+VIII.+Summary&rft.au=Harry%2C+G+J%3BGraham%2C+D+G%3BValentine%2C+WM%3BMorgan%2C+D+L%3BSills%2C+R+C&rft.aulast=Harry&rft.aufirst=G&rft.date=1998-02-01&rft.volume=19&rft.issue=1&rft.spage=159&rft.isbn=&rft.btitle=&rft.title=Neurotoxicology&rft.issn=0161813X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Carbon disulfide neurotoxicity in rats: I. Introduction and study design AN - 16267547; 4273300 AB - The toxicity of carbon disulfide (CS sub(2)) was first recognized in humans during the mid-nineteenth century in Europe where it was used in the cold vulcanization of rubber (Davidson and Feinlab, 1972). Human exposure may occur through the use of CS sub(2) in the production of rayon and cellophane or through the release of CS sub(2) from dithiocarbamates used as pesticides or therapeutic agents. With the development of the viscose rayon industry, numerous symptoms of CS sub(2) intoxication were reported. Acute exposure to high concentrations may result in euphoria, hallucinations, irritability, manic delirium and convulsions. Case reports suggested that exposure to CS sub(2) at levels between 150 and 300 ppm caused psychosis, polyneuritis, tremors, weakness of limbs, myopathy, and vertigo. Additional symptoms included tingling and numbness of the extremities, weakness of limbs, loss of appetite, weight loss, severe and localized headache, sexual dysfunction, impaired vision, and gastrointestinal disturbance. JF - Neurotoxicology AU - Sills, R C AU - Morgan, D L AU - Harry, G J AD - Environmental Toxicology Program (MD B3-08), National Institute of Environmental Health Sciences, Research Triangle Park, N.C. 27709, USA Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 83 EP - 88 VL - 19 IS - 1 SN - 0161-813X, 0161-813X KW - carbon disulfide KW - neurotoxicity KW - rats KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - X 24151:Acute exposure KW - N3 11104:Mammals (except primates) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16267547?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicology&rft.atitle=Carbon+disulfide+neurotoxicity+in+rats%3A+I.+Introduction+and+study+design&rft.au=Sills%2C+R+C%3BMorgan%2C+D+L%3BHarry%2C+G+J&rft.aulast=Sills&rft.aufirst=R&rft.date=1998-02-01&rft.volume=19&rft.issue=1&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=Neurotoxicology&rft.issn=0161813X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Carbon disulfide neurotoxicity in rats. V. Morphology of axonal swelling in the muscular branch of the posterior tibial nerve and spinal cord AN - 16267479; 4273298 AB - The study objectives were to examine the morphological progression and dose response of carbon disulfide (CS sub(2)) distal axonopathy in the muscular branch of the posterior tibial nerve (MBPTN) and spinal cord. Male and female F344 rats were exposed to 0, 50, 500 or 800 ppm CS sub(2) by inhalation, 6 hours/day, 5 days per week, for 2, 4, 8 or 13 weeks. At 8 weeks, in the MBPTN, single fascicles contained individual swollen axons. By 13 weeks, multiple fascicles had giant swollen axons with thin myelin sheaths and occasional degenerated and regenerated axons. At 8 weeks, in the spinal cord, white matter changes in cervical segments 1 and 2 consisted of prominent multifocal axonal swelling in the fasciculus gracilis nerve tracts. In lumbar segments 1 and 2, multifocal axonal swelling was first present at 8 weeks in the lateral and ventro-medial funiculus. By 13 weeks, axonal swelling was diffuse in the fasciculus gracilis nerve tracts of the cervical spinal cord and the lateral and ventral funiculus nerve tracts in the lumbar spinal cord. Compared to the spinal cord, where axonal swelling was present in rats exposed to 800 and 500 ppm, in the muscular branch of the posterior tibial nerve, axonal swelling was only present at 800 ppm at both 8 and 13 weeks. Electron microscopic examination demonstrated marked accumulations of neurofilaments in swollen axons in the spinal cord and MBPTN. Axonal swelling was not present in the spinal cord at 50 ppm, or in the MBPT at 50 and 500 ppm. Axonal swelling was not present at earlier time points of 2 and 4 weeks in either the spinal cord or MBPTN. JF - Neurotoxicology AU - Sills, R C AU - Harry, G J AU - Morgan, D L AU - Valentine, WM AU - Graham, D G AD - Environmental Toxicology Program (MD B3-08), National Institute of Environmental Health Sciences, Research Triangle Park, N.C. 27709, USA Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 117 EP - 128 VL - 19 IS - 1 SN - 0161-813X, 0161-813X KW - axons KW - carbon disulfide KW - neurotoxicity KW - peripheral nerves KW - posterior tibial nerve KW - rats KW - spinal cord KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - N3 11104:Mammals (except primates) KW - X 24154:Pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16267479?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicology&rft.atitle=Carbon+disulfide+neurotoxicity+in+rats.+V.+Morphology+of+axonal+swelling+in+the+muscular+branch+of+the+posterior+tibial+nerve+and+spinal+cord&rft.au=Sills%2C+R+C%3BHarry%2C+G+J%3BMorgan%2C+D+L%3BValentine%2C+WM%3BGraham%2C+D+G&rft.aulast=Sills&rft.aufirst=R&rft.date=1998-02-01&rft.volume=19&rft.issue=1&rft.spage=117&rft.isbn=&rft.btitle=&rft.title=Neurotoxicology&rft.issn=0161813X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Preclinical evaluation of 9-chloro-2-methylellipticinium acetate alone and in combination with conventional anticancer drugs for the treatment of human brain tumor xenografts AN - 1496897743; 16787489 AB - Some ellipticine derivative salts, including 9-chloro-2-methylellipticinium (CME), have been found to have a marked selectivity against all eight brain tumor cell lines of the U.S. National Cancer Institute's disease-oriented in vitro screen. We initiated in vivo antitumor studies to explore the feasibility for further development of this class of compounds. We found that CME was extremely toxic to nude mice when given i.p. at a dose of 25mg/kg for 3 consecutive days. Animals treated by this route experienced an increase in hepatic transaminases and histopathological changes in the liver, compatible with mitochondrial damage. In contrast, when the portal circulation was bypassed and the same dose of CME was given i.v., animals tolerated daily bolus injections for 5 consecutive days. This 5-day i.v. bolus schedule had consistent antitumor activity, with 28.1% growth delay on s.c. implanted human U251 gliomas. When the potentially high peaks of CME in the portal circulation were avoided by using a 3-day continuous infusion with osmotic minipumps implanted i.p. to release 3.4mgkg super(-1)h super(-1) or 6.6mgkg super(-1)h super(-1) CME, there were only modest increases in liver enzymes and leukopenia, but no meaningful antitumor activity was observed. In contrast, continuous infusion in the s.c. space was well tolerated and was accompanied by a demonstrable growth delay in s.c. U251 human gliomas of 37.8%. When CME was used in conjunction with carmustine, etoposide or cisplatin, no synergistic activities were observed, but additive effects were demonstrated. Our pharmacokinetic and disposition studies with CME argue against the notion that large and invasive tumors in the brain lack blood-brain barrier features. When CME was used in animals bearing orthotopically implanted U251 gliomas in the brain of nude mice, the survival of the treated animals was not better than vehicle controls, and the addition of CME to carmustine therapy did not improve the survival of those animals treated with carmustine alone. We conclude that, in spite of its marked cytotoxicity in vitro on a variety of human brain tumor cell lines, including U251 glioma cells, CME has a modest antitumor effect on extracranially implanted U251 glioma tumors, and no beneficial effect in animals bearing the same U251 tumor in the brain, owing to a poor penetration into the brain parenchyma. JF - Journal of Cancer Research and Clinical Oncology AU - Arguello, Francisco AU - Alexander, Mark A AU - Greene, John F, Jr AU - Stinson, Sherman F AU - Jorden, Jean L AU - Smith, Erik M AU - Kalavar, Naina T AU - Alvord, WGregory AU - Klabansky, Richard L AU - Sausville, Edward A AD - Division of Cancer Treatment, Diagnosis and Centers, Developmental Therapeutics Program, Laboratory of Drug Discovery, Research and Development, National Institutes of Health, National Cancer Institute-FCRDC, Building 1052, Room 121, Frederick, Maryland 21702, USA Fax: +1 301 846 6177, US Y1 - 1998/02// PY - 1998 DA - Feb 1998 SP - 19 EP - 26 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 124 IS - 1 SN - 0171-5216, 0171-5216 KW - CSA Neurosciences Abstracts; Biotechnology and Bioengineering Abstracts KW - Acetic acid KW - Brain tumors KW - W 30915:Pharmaceuticals & Vaccines KW - N3 11027:Neurology & neuropathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1496897743?accountid=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+Cancer+Research+and+Clinical+Oncology&rft.atitle=Preclinical+evaluation+of+9-chloro-2-methylellipticinium+acetate+alone+and+in+combination+with+conventional+anticancer+drugs+for+the+treatment+of+human+brain+tumor+xenografts&rft.au=Arguello%2C+Francisco%3BAlexander%2C+Mark+A%3BGreene%2C+John+F%2C+Jr%3BStinson%2C+Sherman+F%3BJorden%2C+Jean+L%3BSmith%2C+Erik+M%3BKalavar%2C+Naina+T%3BAlvord%2C+WGregory%3BKlabansky%2C+Richard+L%3BSausville%2C+Edward+A&rft.aulast=Arguello&rft.aufirst=Francisco&rft.date=1998-02-01&rft.volume=124&rft.issue=1&rft.spage=19&rft.isbn=&rft.btitle=&rft.title=Journal+of+Cancer+Research+and+Clinical+Oncology&rft.issn=01715216&rft_id=info:doi/10.1007%2Fs004320050128 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2014-02-01 N1 - Last updated - 2014-04-03 N1 - SubjectsTermNotLitGenreText - Brain tumors DO - http://dx.doi.org/10.1007/s004320050128 ER - TY - JOUR T1 - Isolation of a high-affinity stable single-chain Fv specific for mesothelin from DNA-immunized mice by phage display and construction of a recombinant immunotoxin with anti-tumor activity. AN - 79673305; 9435250 AB - Mesothelin is a differentiation antigen present on the surface of ovarian cancers, mesotheliomas, and several other types of human cancers. Because among normal tissues, mesothelin is present only on mesothelial cells, it represents a good target for antibody-mediated delivery of cytotoxic agents. In the present study mice were immunized with an eukaryotic expression vector coding for mesothelin. When high serum antibody titers were obtained, a phage display library was made from the splenic mRNA of these mice. After three rounds of panning on recombinant mesothelin, a single-chain Fv (scFv)-displaying phage was selected that bound specifically to recombinant mesothelin and mesothelin-positive cells. The scFv was used to construct an immunotoxin by genetically fusing it with a truncated mutant of Pseudomonas exotoxin A. The purified immunotoxin binds mesothelin with high affinity (Kd 11 nm), is stable for over 40 hr at 37 degrees C and is very cytotoxic to cells expressing mesothelin. It also produces regressions of tumors expressing mesothelin. This combination of selective cytotoxicity, high activity, and stability makes the immunotoxin a good candidate for development as a therapeutic agent. This work also shows that DNA immunization can be used to isolate and clone antibodies against epitopes present on human proteins in their native conformation. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Chowdhury, P S AU - Viner, J L AU - Beers, R AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1998/01/20/ PY - 1998 DA - 1998 Jan 20 SP - 669 EP - 674 VL - 95 IS - 2 SN - 0027-8424, 0027-8424 KW - Antibodies, Neoplasm KW - 0 KW - Antigens, Neoplasm KW - Exotoxins KW - GPI-Linked Proteins KW - Immunoglobulin Variable Region KW - Immunotoxins KW - Membrane Glycoproteins KW - Recombinant Proteins KW - mesothelin KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Humans KW - Recombinant Proteins -- immunology KW - Molecular Sequence Data KW - Mice KW - Recombinant Proteins -- genetics KW - Mice, Inbred BALB C KW - Immunization KW - Female KW - Gene Library KW - Immunoglobulin Variable Region -- genetics KW - Immunotoxins -- immunology KW - Immunoglobulin Variable Region -- immunology KW - DNA -- immunology KW - Antibodies, Neoplasm -- immunology KW - Antigens, Neoplasm -- genetics KW - Antigens, Neoplasm -- immunology KW - Membrane Glycoproteins -- immunology KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79673305?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=unknown&rft.jtitle=The+China+Quarterly&rft.atitle=Book+Reviews%3A+Out+to+Work%3A+Migration%2C+Gender+and+the+Changing+Lives+of+Rural+Women+in+Contemporary+China&rft.au=Goodburn%2C+Charlotte&rft.aulast=Goodburn&rft.aufirst=Charlotte&rft.date=2016-03-01&rft.volume=225&rft.issue=&rft.spage=271&rft.isbn=&rft.btitle=&rft.title=The+China+Quarterly&rft.issn=03057410&rft_id=info:doi/10.1017%2FS0305741016000138 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-24 N1 - Date created - 1998-02-24 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF035617; GENBANK N1 - SuppNotes - Cited By: J Biol Chem. 1980 Nov 10;255(21):10331-7 [7000776] Nat Biotechnol. 1996 Oct;14(10):1239-45 [9631086] Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8616-20 [1924323] Cancer Res. 1992 Jan 1;52(1):181-6 [1727378] Nature. 1992 Mar 12;356(6365):152-4 [1545867] Am J Surg Pathol. 1992 Mar;16(3):259-68 [1599018] J Biol Chem. 1992 Aug 15;267(23):16007-10 [1644788] Behring Inst Mitt. 1992 Apr;(91):6-12 [1524572] Anal Biochem. 1992 Sep;205(2):263-70 [1332541] N Engl J Med. 1993 Oct 21;329(17):1219-24 [7692295] J Biol Chem. 1994 Jan 14;269(2):805-8 [8288629] Cancer Res. 1994 May 15;54(10):2714-8 [8168102] Biochemistry. 1994 May 10;33(18):5451-9 [7910034] Biochim Biophys Acta. 1994 May 27;1198(1):27-45 [8199194] Int J Cancer. 1994 Jul 1;58(1):142-9 [8014011] J Biol Chem. 1994 Jul 15;269(28):18327-31 [7913461] J Immunol Methods. 1994 Dec 2;176(2):145-52 [7983375] J Immunol Methods. 1995 May 11;182(1):41-50 [7769243] Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):136-40 [8552591] Nat Med. 1996 Mar;2(3):350-3 [8612238] Proc Natl Acad Sci U S A. 1996 May 14;93(10):5141-5 [8643542] Science. 1996 Jul 19;273(5273):352-4 [8662521] J Med Primatol. 1996 Jun;25(3):242-50 [8892046] Int J Cancer. 1997 May 16;71(4):638-44 [9178820] Mol Immunol. 1997 Jan;34(1):9-20 [9182872] J Clin Oncol. 1997 Apr;15(4):1567-74 [9193354] Nature. 1989 Jun 1;339(6223):394-7 [2498664] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Deoxyhypusine synthase activity is essential for cell viability in the yeast Saccharomyces cerevisiae. AN - 79669597; 9430712 AB - Deoxyhypusine synthase catalyzes the first step in the posttranslational synthesis of an unusual amino acid, hypusine (N epsilon-(4-amino-2-hydroxybutyl)lysine), in the eukaryotic translation initiation factor 5A (eIF-5A) precursor protein. The null mutation in the single copy gene, yDHS, encoding deoxyhypusine synthase results in the loss of viability in the yeast Saccharomyces cerevisiae. Upon depletion of deoxyhypusine synthase, and consequently of eIF-5A, cessation of growth was accompanied by a marked enlargement of cells, suggesting a defect in cell cycle progression or in cell division. Two residues of the yeast enzyme, Lys308 and Lys350, corresponding to Lys287 and Lys329, respectively, known to be critical for the activity of the human enzyme, were targeted for site-directed mutagenesis. The chromosomal ydhs null mutation was complemented by the plasmid-borne yDHS wild-type gene, but not by mutated genes encoding inactive proteins, including that with Lys350-->Arg substitution or with substitutions at both Lys308 and Lys350. The mutated gene ydhs (K308R) encoding a protein with diminished activities (< 1% of wild type) could support growth but only to a very limited extent. These findings provide strong evidence that the hypusine modification is indeed essential for the survival of S. cerevisiae and imply a vital function for eIF-5A in all eukaryotes. JF - The Journal of biological chemistry AU - Park, M H AU - Joe, Y A AU - Kang, K R AD - Oral and Pharyngeal Cancer Branch, NIDR, National Institutes of Health, Bethesda, Maryland 20892-4340, USA. mpark@yoda.nidr.nih.gov Y1 - 1998/01/16/ PY - 1998 DA - 1998 Jan 16 SP - 1677 EP - 1683 VL - 273 IS - 3 SN - 0021-9258, 0021-9258 KW - Peptide Initiation Factors KW - 0 KW - RNA-Binding Proteins KW - eukaryotic translation initiation factor 5A KW - Oxidoreductases Acting on CH-NH Group Donors KW - EC 1.5.- KW - deoxyhypusine synthase KW - EC 1.5.1.- KW - Lysine KW - K3Z4F929H6 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Peptide Initiation Factors -- metabolism KW - Alleles KW - Humans KW - Cell Cycle KW - Lysine -- metabolism KW - Amino Acid Substitution KW - Cell Survival KW - Catalysis KW - Oxidoreductases Acting on CH-NH Group Donors -- metabolism KW - Oxidoreductases Acting on CH-NH Group Donors -- genetics KW - Saccharomyces cerevisiae -- enzymology KW - Saccharomyces cerevisiae -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79669597?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Deoxyhypusine+synthase+activity+is+essential+for+cell+viability+in+the+yeast+Saccharomyces+cerevisiae.&rft.au=Park%2C+M+H%3BJoe%2C+Y+A%3BKang%2C+K+R&rft.aulast=Park&rft.aufirst=M&rft.date=1998-01-16&rft.volume=273&rft.issue=3&rft.spage=1677&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-12 N1 - Date created - 1998-02-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recognition of an antigenic peptide derived from tyrosinase-related protein-2 by CTL in the context of HLA-A31 and -A33. AN - 79803133; 9551926 AB - Tumor-infiltrating lymphocytes (TILs) derived from tumor-bearing patients recognize tumor-associated Ags presented by MHC class I molecules. The infusion of TIL586 along with IL-2 into the autologous patient with metastatic melanoma resulted in the objective regression of tumor. Two T cell epitopes derived from tumor Ags, tyrosinase-related protein (TRP)-1 and TRP-2, were shown to be recognized by HLA-A31 restricted TIL586 and its T cell clones. In this study we tested the hypothesis that these two peptides can be recognized by CTL from non-HLA-A31 patients with melanoma. It was found that both peptides were capable of binding to HLA-A3, -A11, -A31, -A33, and -A68 of the HLA-A3 supertype. Importantly, we found that HLA-A33-positive TIL1244 and its T cell clones can recognize TRP197-205 presented by both HLA-A31 and -A33 molecules, suggesting that a single TCR can recognize peptide/A31 and peptide/A33 complexes. However, peptide titration experiments showed that the affinity of TCR receptor to peptide/A33 could be higher than that to the peptide/A31. These studies have important implications for the development of peptide-based cancer vaccines. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Wang, R F AU - Johnston, S L AU - Southwood, S AU - Sette, A AU - Rosenberg, S A AD - Surgery Branch, National Cancer Institute, Bethesda, MD 20892, USA. rongfu@pop.nci.nih.gov Y1 - 1998/01/15/ PY - 1998 DA - 1998 Jan 15 SP - 890 EP - 897 VL - 160 IS - 2 SN - 0022-1767, 0022-1767 KW - Antigens, Neoplasm KW - 0 KW - Epitopes, T-Lymphocyte KW - HLA-A Antigens KW - HLA-A*33 antigen KW - HLA-A31 antigen KW - Peptide Fragments KW - Intramolecular Oxidoreductases KW - EC 5.3.- KW - dopachrome isomerase KW - EC 5.3.3.12 KW - Abridged Index Medicus KW - Index Medicus KW - Clone Cells KW - Tumor Cells, Cultured KW - Humans KW - Cytotoxicity Tests, Immunologic KW - Antigens, Neoplasm -- metabolism KW - Protein Binding -- immunology KW - Lymphocytes, Tumor-Infiltrating -- enzymology KW - Peptide Fragments -- metabolism KW - Epitopes, T-Lymphocyte -- metabolism KW - Intramolecular Oxidoreductases -- metabolism KW - T-Lymphocytes, Cytotoxic -- immunology KW - HLA-A Antigens -- metabolism KW - Intramolecular Oxidoreductases -- immunology KW - T-Lymphocytes, Cytotoxic -- metabolism KW - Peptide Fragments -- immunology KW - T-Lymphocytes, Cytotoxic -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79803133?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=unknown&rft.jtitle=French+Politics%2C+Culture+%26+Society&rft.atitle=IS+INTEGRATION+A+ZERO-SUM+GAME%3F%3A+Negotiating+Space+for+Ethnic+Minorities+in+Europe&rft.au=Garrett%2C+Amanda&rft.aulast=Garrett&rft.aufirst=Amanda&rft.date=2015-12-01&rft.volume=33&rft.issue=3&rft.spage=116&rft.isbn=&rft.btitle=&rft.title=French+Politics%2C+Culture+%26+Society&rft.issn=15376370&rft_id=info:doi/10.3167%2Ffpcs.2015.330306 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-30 N1 - Date created - 1998-04-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic analysis of diagnostic systems of alcoholism in males. AN - 79694163; 9474446 AB - Research into genes involved in alcoholism could benefit from use of diagnostic systems most sensitive to detecting genetic influences. In this study, heritable influences were estimated in a single twin sample with commonly used criteria for alcoholism. Male twin probands ascertained through alcohol and drug abuse treatment programs and their same-sex cotwins (54 monozygotic and 65 dizygotic pairs) were diagnosed independently by DSM-III (alcohol dependence and alcohol abuse and/or dependence), Feighner (probable and definite alcoholism), and Cloninger (type 1 and type 2 alcoholism) systems. Using univariate structural equation modeling, heritability was estimated for each diagnostic system. The highest heritability estimates were obtained for Feighner probable alcoholism (h2 = .63), Cloninger type 2 alcoholism (h2 = .54), and DSM-III alcohol dependence (h2 = .52). Certain diagnostic systems appear to have greater sensitivity for detecting genetic influence and may therefore be more appropriate for use in molecular genetic studies attempting to find genes for alcoholism. JF - Biological psychiatry AU - van den Bree, M B AU - Johnson, E O AU - Neale, M C AU - Svikis, D S AU - McGue, M AU - Pickens, R W AD - Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. Y1 - 1998/01/15/ PY - 1998 DA - 1998 Jan 15 SP - 139 EP - 145 VL - 43 IS - 2 SN - 0006-3223, 0006-3223 KW - Index Medicus KW - Analysis of Variance KW - Psychiatric Status Rating Scales KW - Twins, Monozygotic KW - Models, Genetic KW - Humans KW - Adult KW - Twin Studies as Topic KW - Aged KW - Middle Aged KW - Twins, Dizygotic KW - Adolescent KW - Male KW - Alcoholism -- diagnosis KW - Alcoholism -- genetics KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79694163?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biological+psychiatry&rft.atitle=Genetic+analysis+of+diagnostic+systems+of+alcoholism+in+males.&rft.au=van+den+Bree%2C+M+B%3BJohnson%2C+E+O%3BNeale%2C+M+C%3BSvikis%2C+D+S%3BMcGue%2C+M%3BPickens%2C+R+W&rft.aulast=van+den+Bree&rft.aufirst=M&rft.date=1998-01-15&rft.volume=43&rft.issue=3&rft.spage=153&rft.isbn=&rft.btitle=&rft.title=Far+Eastern+Affairs&rft.issn=0206149X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-03 N1 - Date created - 1998-04-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Early induction of apoptosis in hematopoietic cell lines after exposure to flavopiridol. AN - 79665138; 9427698 AB - Flavopiridol (NSC 649890; Behringwerke L86-8275, Marburg, Germany), is a potent inhibitor of cyclin dependent kinases (CDKs) 1, 2, and 4. It has potent antiproliferative effects in vitro and is active in tumor models in vivo. While surveying the effect of flavopiridol on cell cycle progression in different cell types, we discovered that hematopoietic cell lines, including SUDHL4, SUDHL6 (B-cell lines), Jurkat, and MOLT4 (T-cell lines), and HL60 (myeloid), displayed notable sensitivity to flavopiridol-induced apoptosis. For example, after 100 nmol/L for 12 hours, SUDHL4 cells displayed a similar degree of DNA fragmentation to that shown by the apoptosis-resistant PC3 prostate carcinoma cells only after 3,000 nmol/L for 48 hours. After exposure to 1,000 nmol/L flavopiridol for 12 hours, typical apoptotic morphology was observed in SUDHL4 cells, but not in PC3 prostate carcinoma cells despite comparable potency (SUDHL4: 120 nmol/L; PC3: 203 nmol/L) in causing growth inhibition by 50% (IC50). Flavopiridol did not induce topoisomerase I or II cleavable complex activity. A relation of p53, bcl2, or bax protein levels to apoptosis in SUDHL4 was not appreciated. While flavopiridol caused cell cycle arrest with decline in CDK1 activity in PC3 cells, apoptosis of SUDHL4 cells occurred without evidence of cell cycle arrest. These results suggest that antiproliferative activity of flavopiridol (manifest by cell cycle arrest) may be separated in different cell types from a capacity to induce apoptosis. Cells from hematopoietic neoplasms appear in this limited sample to be very susceptible to flavopiridol-induced apoptosis and therefore clinical trials in hematopoietic neoplasms should be of high priority. JF - Blood AU - Parker, B W AU - Kaur, G AU - Nieves-Neira, W AU - Taimi, M AU - Kohlhagen, G AU - Shimizu, T AU - Losiewicz, M D AU - Pommier, Y AU - Sausville, E A AU - Senderowicz, A M AD - Laboratory of Biological Chemistry, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 1998/01/15/ PY - 1998 DA - 1998 Jan 15 SP - 458 EP - 465 VL - 91 IS - 2 SN - 0006-4971, 0006-4971 KW - Flavonoids KW - 0 KW - Growth Inhibitors KW - Piperidines KW - alvocidib KW - 45AD6X575G KW - Abridged Index Medicus KW - Index Medicus KW - Cells, Cultured KW - Humans KW - Male KW - Hematopoietic Stem Cells -- pathology KW - Hematopoiesis -- drug effects KW - Piperidines -- toxicity KW - Apoptosis -- drug effects KW - Prostate -- pathology KW - Hematopoietic Stem Cells -- drug effects KW - Growth Inhibitors -- toxicity KW - Flavonoids -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79665138?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Early+induction+of+apoptosis+in+hematopoietic+cell+lines+after+exposure+to+flavopiridol.&rft.au=Parker%2C+B+W%3BKaur%2C+G%3BNieves-Neira%2C+W%3BTaimi%2C+M%3BKohlhagen%2C+G%3BShimizu%2C+T%3BLosiewicz%2C+M+D%3BPommier%2C+Y%3BSausville%2C+E+A%3BSenderowicz%2C+A+M&rft.aulast=Parker&rft.aufirst=B&rft.date=1998-01-15&rft.volume=91&rft.issue=2&rft.spage=458&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-11 N1 - Date created - 1998-02-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Frequent nitric oxide synthase-2 expression in human colon adenomas: implication for tumor angiogenesis and colon cancer progression. AN - 79663161; 9443414 AB - An increased expression of nitric oxide synthase (NOS) has been observed in human colon carcinoma cell lines as well as in human gynecological, breast, and central nervous system tumors. This observation suggests a pathobiological role of tumor-associated NO production. Hence, we investigated NOS expression in human colon cancer in respect to tumor staging, NOS-expressing cell type(s), nitrotyrosine formation, inflammation, and vascular endothelial growth factor expression. Ca2+-dependent NOS activity was found in normal colon and in tumors but was significantly decreased in adenomas (P < 0.001) and carcinomas (Dukes' stages A-D: P < 0.002). Ca2+-independent NOS activity, indicating inducible NOS (NOS2), is markedly expressed in approximately 60% of human colon adenomas (P < 0.001 versus normal tissues) and in 20-25% of colon carcinomas (P < 0.01 versus normal tissues). Only low levels were found in the surrounding normal tissue. NOS2 activity decreased with increasing tumor stage (Dukes' A-D) and was lowest in colon metastases to liver and lung. NOS2 was detected in tissue mononuclear cells (TMCs), endothelium, and tumor epithelium. There was a statistically significant correlation between NOS2 enzymatic activity and the level of NOS2 protein detected by immunohistochemistry (P < 0.01). Western blot analysis of tumor extracts with Ca2+-independent NOS activity showed up to three distinct NOS2 protein bands at Mr 125,000-Mr 138,000. The same protein bands were heavily tyrosine-phosphorylated in some tumor tissues. TMCs, but not the tumor epithelium, were immunopositive using a polyclonal anti-nitrotyrosine antibody. However, only a subset of the NOS2-expressing TMCs stained positively for 3-nitrotyrosine, which is a marker for peroxynitrite formation. Furthermore, vascular endothelial growth factor expression was detected in adenomas expressing NOS2. These data are consistent with the hypothesis that excessive NO production by NOS2 may contribute to the pathogenesis of colon cancer progression at the transition of colon adenoma to carcinoma in situ. JF - Cancer research AU - Ambs, S AU - Merriam, W G AU - Bennett, W P AU - Felley-Bosco, E AU - Ogunfusika, M O AU - Oser, S M AU - Klein, S AU - Shields, P G AU - Billiar, T R AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 1998/01/15/ PY - 1998 DA - 1998 Jan 15 SP - 334 EP - 341 VL - 58 IS - 2 SN - 0008-5472, 0008-5472 KW - DNA Primers KW - 0 KW - DNA, Neoplasm KW - Endothelial Growth Factors KW - Lymphokines KW - Neoplasm Proteins KW - Vascular Endothelial Growth Factor A KW - Vascular Endothelial Growth Factors KW - 3-nitrotyrosine KW - 3604-79-3 KW - Tyrosine KW - 42HK56048U KW - NOS2 protein, human KW - EC 1.14.13.39 KW - Nitric Oxide Synthase KW - Nitric Oxide Synthase Type II KW - Index Medicus KW - Lymphokines -- metabolism KW - Endothelium, Vascular -- enzymology KW - Humans KW - Disease Progression KW - DNA, Neoplasm -- analysis KW - Polymerase Chain Reaction KW - Blotting, Western KW - Phosphorylation KW - Carcinoma -- blood supply KW - Carcinoma -- pathology KW - Colon -- enzymology KW - Endothelial Growth Factors -- metabolism KW - Carcinoma -- enzymology KW - Tyrosine -- metabolism KW - Tyrosine -- analogs & derivatives KW - Neoplasm Proteins -- analysis KW - Immunohistochemistry KW - DNA Primers -- chemistry KW - Adenoma -- enzymology KW - Colonic Neoplasms -- blood supply KW - Neovascularization, Pathologic -- enzymology KW - Nitric Oxide Synthase -- metabolism KW - Colonic Neoplasms -- pathology KW - Adenoma -- pathology KW - Adenoma -- blood supply KW - Colonic Neoplasms -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79663161?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Frequent+nitric+oxide+synthase-2+expression+in+human+colon+adenomas%3A+implication+for+tumor+angiogenesis+and+colon+cancer+progression.&rft.au=Ambs%2C+S%3BMerriam%2C+W+G%3BBennett%2C+W+P%3BFelley-Bosco%2C+E%3BOgunfusika%2C+M+O%3BOser%2C+S+M%3BKlein%2C+S%3BShields%2C+P+G%3BBilliar%2C+T+R%3BHarris%2C+C+C&rft.aulast=Ambs&rft.aufirst=S&rft.date=1998-01-15&rft.volume=58&rft.issue=2&rft.spage=334&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-04 N1 - Date created - 1998-02-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cross-resistance to methotrexate and metals in human cisplatin-resistant cell lines results from a pleiotropic defect in accumulation of these compounds associated with reduced plasma membrane binding proteins. AN - 79661325; 9443404 AB - Cross-resistance to a wide array of toxic chemicals is a common phenomenon in cisplatin-resistant cell lines. In this study, two independently isolated cisplatin-resistant cell lines derived from a human hepatoma and a cervical adenocarcinoma were shown to be cross-resistant to methotrexate (MTX) and several metal salts, such as sodium arsenite, sodium arsenate, antimony potassium tartrate, and cadmium chloride. A pleiotropic defect resulting in reduced accumulation of cisplatin, 3[H]MTX, 73As3+, and 73As5+ was found in both cisplatin-resistant cell lines. Analysis by immunoblot, indirect immunofluorescence, and Northern hybridization showed dramatically reduced expression of the folate binding protein that mediates MTX uptake in both human cisplatin-resistant cell lines. By photoaffinity labeling with UV irradiation, specific binding proteins of Mr 230,000 and Mr 48,000 for 73As3+ and Mr 190,000 for 73As5+ were found in enriched plasma membrane of both human cisplatin-sensitive parental cell lines. Expression of these specific binding proteins was decreased in cells selected for cisplatin resistance. A protein band at Mr 36,000 that binds to 73As3+ was overexpressed in both human cisplatin-resistant cell lines. The finding of loss of distinct binding proteins for MTX, arsenate, and arsenite in association with decreased accumulation of these agents in cisplatin-resistant cells suggests a pleiotropic, possibly regulatory, alteration in these cells. JF - Cancer research AU - Shen, D AU - Pastan, I AU - Gottesman, M M AD - Laboratory of Cell Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 1998/01/15/ PY - 1998 DA - 1998 Jan 15 SP - 268 EP - 275 VL - 58 IS - 2 SN - 0008-5472, 0008-5472 KW - Antineoplastic Agents KW - 0 KW - Arsenicals KW - Carrier Proteins KW - Folate Receptors, GPI-Anchored KW - Membrane Proteins KW - Metals KW - Neoplasm Proteins KW - Receptors, Cell Surface KW - Cisplatin KW - Q20Q21Q62J KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Liver Neoplasms -- metabolism KW - Blotting, Northern KW - Fluorescent Antibody Technique, Indirect KW - Membrane Proteins -- metabolism KW - Humans KW - Arsenicals -- pharmacology KW - Carcinoma, Squamous Cell -- metabolism KW - Drug Resistance, Neoplasm KW - Drug Resistance, Multiple KW - Tumor Cells, Cultured KW - Arsenicals -- pharmacokinetics KW - Carcinoma, Squamous Cell -- genetics KW - Membrane Proteins -- drug effects KW - Cell Membrane -- metabolism KW - Liver Neoplasms -- genetics KW - Receptors, Cell Surface -- metabolism KW - Carrier Proteins -- metabolism KW - Cisplatin -- toxicity KW - Carrier Proteins -- genetics KW - Neoplasm Proteins -- genetics KW - Antineoplastic Agents -- toxicity KW - Receptors, Cell Surface -- genetics KW - Methotrexate -- metabolism KW - Metals -- metabolism KW - Neoplasm Proteins -- metabolism KW - Methotrexate -- toxicity KW - Metals -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79661325?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+International+Migration+Review&rft.atitle=Migration%2C+Modernity%2C+and+Social+Transformation+in+South+Asia&rft.au=Mills%2C+Mary+Beth&rft.aulast=Mills&rft.aufirst=Mary&rft.date=2005-01-01&rft.volume=39&rft.issue=3&rft.spage=769&rft.isbn=&rft.btitle=&rft.title=The+International+Migration+Review&rft.issn=01979183&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-04 N1 - Date created - 1998-02-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Overlapping Sp1 and AP2 binding sites in a promoter element of the lens-specific MIP gene. AN - 79629065; 9421492 AB - The MIP gene, the founder of the MIP family of channel proteins, is specifically expressed in fiber cells of the ocular lens and expression is regulated temporally and spatially during development. We previously found that a DNA fragment containing 253 bp of 5'-flanking sequence and 42 bp of exon 1 of the human MIP gene contains regulatory elements responsible for lens-specific expression of the MIP gene. In this report we have analyzed the function of overlapping Sp1 and AP2 binding sites present in the MIP promoter. Using DNase I footprinting analysis we found that purified Sp1 and AP2 transcription factors interact with several domains of the human MIP promoter sequence -253/+42. Furthermore, addition of purified Sp1 to Drosophila nuclear extracts activates in vitro transcription from the MIP promoter -253/+42. This promoter activity is competed by oligonucleotides containing domains footprinted with Sp1. Using promoter-reporter gene ( CAT ) constructs we found that the sequence -39/-70 contains a cis regulatory element essential for promoter activity in transient assays in lens cells. EMSA analysis showed that lens nuclear extracts contain factors that bind to the MIP 5'-flanking sequence containing overlapping Sp1 and AP2 binding domains at positions -37/-65. Supershift experiments with lens nuclear extracts indicated that Sp3 is also able to interact with this regulatory element, suggesting that Sp1 and Sp3 may be involved in regulation of transcription of the MIP gene in the lens. JF - Nucleic acids research AU - Ohtaka-Maruyama, C AU - Wang, X AU - Ge, H AU - Chepelinsky, A B AD - Laboratory of Molecular and Developmental Biology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/01/15/ PY - 1998 DA - 1998 Jan 15 SP - 407 EP - 414 VL - 26 IS - 2 SN - 0305-1048, 0305-1048 KW - Bacterial Proteins KW - 0 KW - DNA-Binding Proteins KW - Membrane Proteins KW - Sp1 Transcription Factor KW - Transcription Factor AP-2 KW - Transcription Factors KW - DNA KW - 9007-49-2 KW - Immunophilins KW - EC 5.2.1.8 KW - Peptidylprolyl Isomerase KW - Index Medicus KW - Animals KW - Exons KW - Humans KW - Amino Acid Sequence KW - Binding Sites KW - Gene Deletion KW - Mutagenesis KW - Regulatory Sequences, Nucleic Acid KW - Base Sequence KW - Chickens KW - Transfection KW - DNA Footprinting KW - Molecular Sequence Data KW - Promoter Regions, Genetic KW - Bacterial Proteins -- genetics KW - Bacterial Proteins -- chemistry KW - Transcription Factors -- metabolism KW - Membrane Proteins -- chemistry KW - DNA -- metabolism KW - Sp1 Transcription Factor -- metabolism KW - DNA -- chemistry KW - Membrane Proteins -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79629065?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=Overlapping+Sp1+and+AP2+binding+sites+in+a+promoter+element+of+the+lens-specific+MIP+gene.&rft.au=Ohtaka-Maruyama%2C+C%3BWang%2C+X%3BGe%2C+H%3BChepelinsky%2C+A+B&rft.aulast=Ohtaka-Maruyama&rft.aufirst=C&rft.date=1998-01-15&rft.volume=30&rft.issue=6&rft.spage=479&rft.isbn=&rft.btitle=&rft.title=Gender+in+Management&rft.issn=17542413&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-26 N1 - Date created - 1998-02-26 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U36308; GENBANK N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1995 May 9;92(10):4676-80 [7753863] Oncogene. 1995 May 4;10(9):1841-8 [7753559] J Biol Chem. 1995 May 26;270(21):12737-44 [7759528] EMBO J. 1995 Jul 17;14(14):3510-9 [7628452] J Biol Chem. 1995 Oct 6;270(40):23511-9 [7559515] J Biol Chem. 1995 Oct 27;270(43):25402-10 [7592707] J Biol Chem. 1995 Oct 27;270(43):25879-84 [7592774] Cell. 1997 May 16;89(4):619-28 [9160753] J Biol Chem. 1997 Aug 22;272(34):21260-7 [9261136] J Biol Chem. 1997 Sep 19;272(38):24038-45 [9295357] Nucleic Acids Res. 1983 Mar 11;11(5):1475-89 [6828386] Nucleic Acids Res. 1985 Apr 25;13(8):2709-30 [2987864] Biochem Biophys Res Commun. 1986 Mar 28;135(3):965-71 [2421726] J Cell Biol. 1988 Mar;106(3):705-14 [3279052] Dev Biol. 1988 May;127(1):209-19 [2834246] Nucleic Acids Res. 1989 Apr 11;17(7):2639-53 [2717405] Nucleic Acids Res. 1989 Aug 11;17(15):6419 [2771659] Genes Dev. 1990 Oct;4(10):1811-22 [2123467] Genes Dev. 1991 Jan;5(1):105-19 [1989904] Mol Cell Biol. 1991 Apr;11(4):2189-99 [2005904] J Biol Chem. 1991 May 15;266(14):8907-15 [2026603] Development. 1991 Sep;113(1):283-93 [1722450] Genomics. 1991 Dec;11(4):981-90 [1840563] Nucleic Acids Res. 1992 Jul 11;20(13):3287-95 [1385862] Nucleic Acids Res. 1992 Jul 25;20(14):3701-12 [1641336] Exp Eye Res. 1995 Sep;61(3):351-62 [7556498] Exp Eye Res. 1995 Sep;61(3):293-301 [7556493] Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7452-6 [1502157] Gene. 1995 Dec 29;167(1-2):321-5 [8566800] Nat Genet. 1996 Feb;12(2):212-5 [8563764] Nature. 1996 May 16;381(6579):235-8 [8622765] Nature. 1996 May 16;381(6579):238-41 [8622766] EMBO J. 1996 Oct 15;15(20):5659-67 [8896459] J Biol Chem. 1996 Nov 15;271(46):28853-60 [8910531] J Biol Chem. 1997 Jan 10;272(2):1308-14 [8995437] Mol Cell Biol. 1997 Jun;17(6):3056-64 [9154804] Mol Cell Biol. 1992 Oct;12(10):4251-61 [1341900] Development. 1992 Aug;115(4):1149-64 [1451662] Nucleic Acids Res. 1992 Nov 11;20(21):5519-25 [1454515] J Biol Chem. 1993 Apr 15;268(11):8230-9 [8096519] Mol Cell Biol. 1993 Jul;13(7):4174-85 [8321221] Development. 1993 Oct;119(2):433-46 [7904558] J Biol Chem. 1994 Jan 14;269(2):1046-50 [8288559] Mol Cell Biol. 1994 Feb;14(2):1383-94 [8289814] J Biol Chem. 1994 Apr 15;269(15):11425-34 [7512565] Mol Cell Biol. 1994 Sep;14(9):5692-700 [8065305] Nature. 1994 Sep 1;371(6492):72-4 [8072529] Dev Biol. 1994 Sep;165(1):165-77 [8088434] Development. 1994 Sep;120(9):2369-83 [7525178] Mol Cell Biol. 1995 Feb;15(2):653-60 [7823934] J Biol Chem. 1995 Jan 20;270(3):1221-9 [7836383] J Biol Chem. 1995 Apr 14;270(15):8514-20 [7721749] J Biol Chem. 1995 Apr 14;270(15):9010-16 [7536742] J Biol Chem. 1995 Apr 21;270(16):9494-9 [7721877] EMBO J. 1995 Apr 3;14(7):1508-19 [7729426] Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):3953-7 [7732011] Dev Biol. 1995 May;169(1):1-14 [7750631] Proc Natl Acad Sci U S A. 1995 May 9;92(10):4681-5 [7753864] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Stereoselective actions of halothane at GABA(A) receptors. AN - 79785866; 9543259 AB - Isoflurane anesthesia exhibits stereoselectivity, and a corresponding stereoselectivity ((+)->(-)-isomer) has been reported at GABA(A) receptors in vitro. The objective of the present study was to determine if the positive modulatory actions of halothane at GABA(A) receptors exhibited a similar stereoselectivity. Both (R)- and (S)-halothane ((+)- and (-)- isomers, respectively) enhanced [3H]flunitrazepam binding to brain membranes in a concentration dependent manner without a significant difference in either potency (EC50) or efficacy (Emax). While both (R)- and (S)-halothane enhanced [3H]muscimol binding, the potency of the (+)-isomer was slightly greater than the corresponding (-)-isomer (0.91 +/- 0.17 versus 1.45 +/- 0.04% atmospheres, respectively (P < 0.02)). Thus, subtle structural differences between inhalational anesthetics can have a significant impact on the degree of stereoselectivity at the receptor level and may provide insights for the development of more specific drugs. JF - European journal of pharmacology AU - Harris, B D AU - Moody, E J AU - Skolnick, P AD - Laboratory of Neuroscience, NIDDK, National Institutes of Health, Bethesda, MD 20892-0008, USA. Y1 - 1998/01/12/ PY - 1998 DA - 1998 Jan 12 SP - 349 EP - 352 VL - 341 IS - 2-3 SN - 0014-2999, 0014-2999 KW - Anesthetics, Inhalation KW - 0 KW - GABA Agonists KW - GABA Modulators KW - Receptors, GABA-A KW - Muscimol KW - 2763-96-4 KW - Flunitrazepam KW - 620X0222FQ KW - Halothane KW - UQT9G45D1P KW - Index Medicus KW - Animals KW - Stereoisomerism KW - Drug Interactions KW - GABA Agonists -- pharmacology KW - GABA Modulators -- pharmacology KW - Binding, Competitive KW - Mice KW - Flunitrazepam -- pharmacology KW - Muscimol -- pharmacology KW - Male KW - Halothane -- pharmacology KW - Halothane -- chemistry KW - Anesthetics, Inhalation -- pharmacology KW - Anesthetics, Inhalation -- chemistry KW - Receptors, GABA-A -- metabolism KW - Receptors, GABA-A -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79785866?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+International+Migration+Review&rft.atitle=Cultures+in+Contact%3A+World+Migrations+in+the+Second+Millennium&rft.au=Triadafilopoulos%2C+Triadafilos&rft.aulast=Triadafilopoulos&rft.aufirst=Triadafilos&rft.date=2005-01-01&rft.volume=39&rft.issue=2&rft.spage=526&rft.isbn=&rft.btitle=&rft.title=The+International+Migration+Review&rft.issn=01979183&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retrograde transport of Golgi-localized proteins to the ER. AN - 79654066; 9425149 AB - The ER is uniquely enriched in chaperones and folding enzymes that facilitate folding and unfolding reactions and ensure that only correctly folded and assembled proteins leave this compartment. Here we address the extent to which proteins that leave the ER and localize to distal sites in the secretory pathway are able to return to the ER folding environment during their lifetime. Retrieval of proteins back to the ER was studied using an assay based on the capacity of the ER to retain misfolded proteins. The lumenal domain of the temperature-sensitive viral glycoprotein VSVGtsO45 was fused to Golgi or plasma membrane targeting domains. At the nonpermissive temperature, newly synthesized fusion proteins misfolded and were retained in the ER, indicating the VSVGtsO45 ectodomain was sufficient for their retention within the ER. At the permissive temperature, the fusion proteins were correctly delivered to the Golgi complex or plasma membrane, indicating the lumenal epitope of VSVGtsO45 also did not interfere with proper targeting of these molecules. Strikingly, Golgi-localized fusion proteins, but not VSVGtsO45 itself, were found to redistribute back to the ER upon a shift to the nonpermissive temperature, where they misfolded and were retained. This occurred over a time period of 15 min-2 h depending on the chimera, and did not require new protein synthesis. Significantly, recycling did not appear to be induced by misfolding of the chimeras within the Golgi complex. This suggested these proteins normally cycle between the Golgi and ER, and while passing through the ER at 40 degrees C become misfolded and retained. The attachment of the thermosensitive VSVGtsO45 lumenal domain to proteins promises to be a useful tool for studying the molecular mechanisms and specificity of retrograde traffic to the ER. JF - The Journal of cell biology AU - Cole, N B AU - Ellenberg, J AU - Song, J AU - DiEuliis, D AU - Lippincott-Schwartz, J AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/01/12/ PY - 1998 DA - 1998 Jan 12 SP - 1 EP - 15 VL - 140 IS - 1 SN - 0021-9525, 0021-9525 KW - G protein, vesicular stomatitis virus KW - 0 KW - KDEL receptor KW - Membrane Glycoproteins KW - Receptors, Peptide KW - Recombinant Fusion Proteins KW - Viral Envelope Proteins KW - Cycloheximide KW - 98600C0908 KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - Animals KW - Receptors, Peptide -- chemistry KW - COS Cells KW - Models, Molecular KW - Simian virus 40 -- genetics KW - Temperature KW - Cell Membrane -- physiology KW - Recombinant Fusion Proteins -- chemistry KW - Mutagenesis, Site-Directed KW - Receptors, Peptide -- biosynthesis KW - Transfection KW - Cycloheximide -- pharmacology KW - Protein Folding KW - CHO Cells KW - Cricetinae KW - Protein Conformation KW - Viral Envelope Proteins -- chemistry KW - Viral Envelope Proteins -- biosynthesis KW - Endoplasmic Reticulum -- physiology KW - Golgi Apparatus -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79654066?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+cell+biology&rft.atitle=Retrograde+transport+of+Golgi-localized+proteins+to+the+ER.&rft.au=Cole%2C+N+B%3BEllenberg%2C+J%3BSong%2C+J%3BDiEuliis%2C+D%3BLippincott-Schwartz%2C+J&rft.aulast=Cole&rft.aufirst=N&rft.date=1998-01-12&rft.volume=140&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+cell+biology&rft.issn=00219525&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-10 N1 - Date created - 1998-02-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Cell Biol. 1995 Aug;130(4):781-96 [7642697] Curr Opin Cell Biol. 1995 Aug;7(4):530-5 [7495573] J Biol Chem. 1995 Oct 20;270(42):25057-63 [7559636] EMBO J. 1995 Oct 2;14(19):4695-704 [7588599] J Cell Biol. 1995 Nov;131(4):895-912 [7490292] Biochem Soc Trans. 1995 Aug;23(3):541-4 [8566411] Mol Biol Cell. 1995 Jul;6(7):871-87 [7579700] J Cell Biol. 1995 Dec;131(6 Pt 2):1715-26 [8557739] J Cell Biol. 1996 Mar;132(6):985-98 [8601597] Science. 1996 Apr 12;272(5259):227-34 [8602507] Cell. 1996 Apr 19;85(2):205-15 [8612273] J Biol Chem. 1996 Feb 23;271(8):4031-7 [8626736] J Biol Chem. 1997 Aug 1;272(31):19554-61 [9235960] Nature. 1997 Sep 4;389(6646):81-5 [9288971] J Histochem Cytochem. 1977 Jul;25(7):935-41 [894009] Proc Natl Acad Sci U S A. 1981 Jan;78(1):293-7 [7017713] Cell. 1983 Apr;32(4):1026-8 [6340834] Nature. 1984 Oct 18-24;311(5987):626-31 [6090948] J Virol. 1985 May;54(2):374-82 [2985803] J Biol Chem. 1985 Jun 10;260(11):6654-62 [3922977] J Cell Biol. 1987 Nov;105(5):1957-69 [2824524] J Cell Biol. 1988 Jul;107(1):89-99 [2839523] Cell. 1989 Mar 10;56(5):801-13 [2647301] J Cell Biol. 1989 Jul;109(1):61-72 [2745557] Cell. 1989 Nov 17;59(4):591-601 [2573430] J Histochem Cytochem. 1989 Dec;37(12):1817-23 [2685110] J Histochem Cytochem. 1989 Dec;37(12):1835-44 [2584692] Annu Rev Cell Biol. 1989;5:247-75 [2688705] Annu Rev Cell Biol. 1989;5:277-307 [2688707] J Biol Chem. 1990 Apr 25;265(12):6879-83 [2157712] Cell. 1990 Jun 29;61(7):1349-57 [2194670] J Cell Biol. 1990 Sep;111(3):857-66 [1697299] Biochem J. 1990 Aug 15;270(1):97-102 [2204342] J Cell Biol. 1991 Feb;112(4):567-77 [1847146] J Cell Biol. 1991 Feb;112(4):579-88 [1993732] Nature. 1991 Aug 1;352(6334):441-4 [1861723] Nature. 1992 Jan 2;355(6355):33-45 [1731198] Cell. 1992 Jan 24;68(2):353-64 [1310258] J Cell Sci. 1991 Nov;100 ( Pt 3):415-30 [1808196] Cell. 1992 May 15;69(4):625-35 [1316805] J Cell Biol. 1993 Jan;120(1):5-13 [8416995] J Cell Biol. 1993 Jan;120(2):325-38 [8380600] J Cell Sci. 1992 Dec;103 ( Pt 4):875-80 [1336779] J Cell Biol. 1993 Mar;120(5):1123-35 [8436587] Virology. 1993 Apr;193(2):545-62 [8460475] J Cell Biol. 1993 Apr;121(2):317-33 [8468349] Cell. 1993 Jun 18;73(6):1079-90 [8513494] Eur J Cell Biol. 1993 Apr;60(2):371-5 [8330634] EMBO J. 1993 Jul;12(7):2821-9 [8392934] J Biol Chem. 1993 Sep 5;268(25):19092-100 [8395529] Science. 1993 Sep 3;261(5126):1280-1 [8362242] Science. 1994 Jan 21;263(5145):387-90 [8278814] Mol Biol Cell. 1996 Apr;7(4):631-50 [8730104] J Biol Chem. 1996 Jul 19;271(29):17183-9 [8663407] Mol Biol Cell. 1996 Mar;7(3):483-93 [8868475] J Cell Biol. 1996 Oct;135(2):341-54 [8896593] J Biol Chem. 1997 Jan 17;272(3):1970-5 [8999888] Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1828-33 [9050864] J Cell Biol. 1997 Jun 16;137(6):1211-28 [9182657] J Cell Biol. 1986 May;102(5):1558-66 [3084497] J Biol Chem. 1986 Nov 5;261(31):14681-9 [3021750] J Cell Biol. 1994 Apr;125(2):253-68 [8163544] J Cell Biol. 1994 May;125(3):557-71 [8175881] J Cell Sci. 1994 Mar;107 ( Pt 3):529-37 [8006071] J Cell Biol. 1994 Jul;126(1):41-52 [8027184] J Cell Biol. 1994 Sep;126(5):1157-72 [7914893] J Cell Biol. 1994 Nov;127(3):653-65 [7962050] Nature. 1994 Nov 3;372(6501):55-63 [7969419] Cell. 1994 Dec 30;79(7):1199-207 [8001155] J Cell Biol. 1994 Dec;127(6 Pt 1):1557-74 [7798312] J Biol Chem. 1995 Feb 24;270(8):3551-3 [7876089] EMBO J. 1995 Apr 3;14(7):1329-39 [7729411] J Cell Sci. 1995 Apr;108 ( Pt 4):1617-27 [7615680] J Biol Chem. 1986 Nov 5;261(31):14690-6 [3021751] Cell. 1987 Jul 17;50(2):289-300 [3594573] EMBO J. 1994 Apr 1;13(7):1696-705 [8157008] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The catalytic domain of PKC-epsilon, in reciprocal PKC-delta and -epsilon chimeras, is responsible for conferring tumorgenicity to NIH3T3 cells, whereas both regulatory and catalytic domains of PKC-epsilon contribute to in vitro transformation. AN - 79680514; 9467942 AB - Protein kinase C-epsilon (PKC-epsilon) has been shown to increase growth and cause malignant transformation when overexpressed in NIH3T3 cells, whereas PKC-delta reduced fibroblast growth. Two reciprocal chimeric proteins (PKC-epsilondelta and PKC-deltaepsilon were constructed by exchanging the regulatory and catalytic domains of PKC-delta and -epsilon and were stably overexpressed in NIH3T3 cells. Fibroblasts that overexpressed either chimera showed maximum cell density and morphology that were intermediate between cells overexpressing PKC-delta and those that overexpressed PKC-epsilon. Moreover, all lines that expressed chimeras were capable of anchorage-independent growth in the presence of TPA, which indicated that both the regulatory and catalytic domains of PKC-epsilon could independently induce NIH3T3 transformation, although the combination of both domains, as found in PKC-epsilon, was the most active form. In contrast, the translocation pattern and ability to induce tumors in nude mice was attributable to the catalytic domains exclusively. In particular, cells that expressed PKC-deltaepsilon retained PKC-epsilon's full potency of tumorgenicity when injected into nude mice. In sum, our findings not only reinforce the concept that only certain PKC isozymes contribute to carcinogenesis but also show that different domains of PKCs mediate the physiologically distinguishable events of transformation and tumorgenesis. JF - Oncogene AU - Wang, Q J AU - Acs, P AU - Goodnight, J AU - Blumberg, P M AU - Mischak, H AU - Mushinski, J F AD - Laboratory of Genetics, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1998/01/08/ PY - 1998 DA - 1998 Jan 08 SP - 53 EP - 60 VL - 16 IS - 1 SN - 0950-9232, 0950-9232 KW - Isoenzymes KW - 0 KW - Recombinant Fusion Proteins KW - Prkcd protein, mouse KW - EC 2.7.1.- KW - Prkce protein, mouse KW - Protein Kinase C KW - EC 2.7.11.13 KW - Protein Kinase C-delta KW - Protein Kinase C-epsilon KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - 3T3 Cells KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Mice, Nude KW - Mice KW - Cell Transformation, Neoplastic KW - Cell Division KW - Catalysis KW - Recombinant Fusion Proteins -- metabolism KW - Protein Kinase C -- metabolism KW - Protein Kinase C -- genetics KW - Recombinant Fusion Proteins -- genetics KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79680514?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=The+catalytic+domain+of+PKC-epsilon%2C+in+reciprocal+PKC-delta+and+-epsilon+chimeras%2C+is+responsible+for+conferring+tumorgenicity+to+NIH3T3+cells%2C+whereas+both+regulatory+and+catalytic+domains+of+PKC-epsilon+contribute+to+in+vitro+transformation.&rft.au=Wang%2C+Q+J%3BAcs%2C+P%3BGoodnight%2C+J%3BBlumberg%2C+P+M%3BMischak%2C+H%3BMushinski%2C+J+F&rft.aulast=Wang&rft.aufirst=Q&rft.date=1998-01-08&rft.volume=16&rft.issue=1&rft.spage=53&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-02 N1 - Date created - 1998-03-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Long-term feeding of sodium saccharin to nonhuman primates: implications for urinary tract cancer. AN - 79657187; 9428778 AB - It was observed in the early 1970s that saccharin produced bladder cancer in rats. However, it has been unclear whether sodium saccharin when consumed by humans poses a substantial carcinogenic hazard. Numerous epidemiologic studies have not shown any evidence of increased urothelial proliferation associated with ingestion of sodium saccharin. Our purpose was to determine the effects of long-term feeding of sodium saccharin to three species of nonhuman primates. Twenty monkeys of three species (six African green, seven rhesus, six cynomolgus, and one hybrid [of rhesus male and cynomolgus female parentage]) were treated with sodium saccharin (25 mg in the diet/kg body weight daily for 5 days a week) beginning within 24 hours after birth and continuing for up to 24 years. Sixteen monkeys (seven rhesus and nine cynomolgus) served as controls. During their last 2 years of life, urine was collected from selected treated and control animals and evaluated for various urinary chemistries and for the presence of calculi, microcrystalluria, and precipitate. Urinary bladders were examined by light microscopy and by scanning electron microscopy. Sodium saccharin treatment had no effect on the urine or urothelium in any of these monkeys. There was no evidence of increased urothelial cell proliferation, and there was no evidence of formation of solid material in the urine. Although the dose of sodium saccharin administered to these monkeys was only five to 10 times the allowable daily intake for humans, the results provide additional evidence that sodium saccharin is without a carcinogenic effect on the primate urinary tract. JF - Journal of the National Cancer Institute AU - Takayama, S AU - Sieber, S M AU - Adamson, R H AU - Thorgeirsson, U P AU - Dalgard, D W AU - Arnold, L L AU - Cano, M AU - Eklund, S AU - Cohen, S M AD - Division of Basic Sciences, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1998/01/07/ PY - 1998 DA - 1998 Jan 07 SP - 19 EP - 25 VL - 90 IS - 1 SN - 0027-8874, 0027-8874 KW - Carcinogens KW - 0 KW - Saccharin KW - FST467XS7D KW - Index Medicus KW - Animals KW - Cell Division -- drug effects KW - Ultrasonography KW - Male KW - Haplorhini KW - Female KW - Microscopy, Electron, Scanning KW - Saccharin -- administration & dosage KW - Urothelium -- drug effects KW - Carcinogens -- administration & dosage KW - Saccharin -- toxicity KW - Carcinogens -- toxicity KW - Urine -- chemistry KW - Urinary Bladder -- drug effects KW - Urinary Bladder -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79657187?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Long-term+feeding+of+sodium+saccharin+to+nonhuman+primates%3A+implications+for+urinary+tract+cancer.&rft.au=Takayama%2C+S%3BSieber%2C+S+M%3BAdamson%2C+R+H%3BThorgeirsson%2C+U+P%3BDalgard%2C+D+W%3BArnold%2C+L+L%3BCano%2C+M%3BEklund%2C+S%3BCohen%2C+S+M&rft.aulast=Takayama&rft.aufirst=S&rft.date=1998-01-07&rft.volume=90&rft.issue=1&rft.spage=19&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-01-22 N1 - Date created - 1998-01-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Natl Cancer Inst. 1998 Jan 7;90(1):2-3 [9428771] J Natl Cancer Inst. 1998 Jun 17;90(12):934-6 [9637144] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mammary carcinoma cells over-expressing tissue inhibitor of metalloproteinases-1 show enhanced vascular endothelial growth factor expression. AN - 79654506; 9426694 AB - The tissue inhibitor of metalloproteinases-1 (TIMP-1) has at least 2 independent functions, i.e., regulation of matrix metalloproteinases and erythroid-potentiating activity. We investigated the effects of TIMP-1 over-expression on tumor growth, using cloned lines derived from a TIMP-1-transfected rat breast carcinoma cell line. The in vitro growth rate of the TIMP-1-transfected clones was indistinguishable from that of the control. In contrast, the highest TIMP-1-producing clone (159.0 ng/ml), designated as T-H, formed 4.6-fold larger s.c. tumors than did the control after 14 days. Tumors derived from an intermediate TIMP-1-producing clone (45.4 ng/ml), designated as T-M, were 1.9-fold larger than the control. TIMP-1 over-expression was associated with increased vascular endothelial growth factor (VEGF) expression, vascularization and proliferative activity of the s.c. tumors. Similar to the rat breast carcinoma cells, transfection of TIMP-1 cDNA into the human breast carcinoma cell line MCF-7 resulted in up-regulation of VEGF, with a linear relationship between TIMP-1 and VEGF production in 9 cell clones examined. There was, however, no change in VEGF expression when the rat and human breast carcinoma cell lines were exposed to exogenous recombinant TIMP-1. Our findings suggest that over-expression of TIMP-1 confers growth advantage on breast carcinoma cells in vivo and that up-regulation of VEGF expression may play an important role in this TIMP-1-mediated, growth-stimulating effect. JF - International journal of cancer AU - Yoshiji, H AU - Harris, S R AU - Raso, E AU - Gomez, D E AU - Lindsay, C K AU - Shibuya, M AU - Sinha, C C AU - Thorgeirsson, U P AD - Tumor Biology and Carcinogenesis Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/01/05/ PY - 1998 DA - 1998 Jan 05 SP - 81 EP - 87 VL - 75 IS - 1 SN - 0020-7136, 0020-7136 KW - Endothelial Growth Factors KW - 0 KW - Lymphokines KW - Neoplasm Proteins KW - Tissue Inhibitor of Metalloproteinase-1 KW - Vascular Endothelial Growth Factor A KW - Vascular Endothelial Growth Factors KW - Index Medicus KW - Rats KW - Animals KW - Tumor Cells, Cultured KW - Transfection KW - Humans KW - Genetic Vectors -- genetics KW - Neovascularization, Pathologic -- pathology KW - Female KW - Cell Division KW - Lymphokines -- metabolism KW - Tissue Inhibitor of Metalloproteinase-1 -- metabolism KW - Endothelial Growth Factors -- metabolism KW - Neoplasm Proteins -- genetics KW - Mammary Neoplasms, Experimental -- blood supply KW - Mammary Neoplasms, Experimental -- genetics KW - Mammary Neoplasms, Experimental -- metabolism KW - Neoplasm Proteins -- metabolism KW - Tissue Inhibitor of Metalloproteinase-1 -- genetics KW - Mammary Neoplasms, Experimental -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79654506?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Mammary+carcinoma+cells+over-expressing+tissue+inhibitor+of+metalloproteinases-1+show+enhanced+vascular+endothelial+growth+factor+expression.&rft.au=Yoshiji%2C+H%3BHarris%2C+S+R%3BRaso%2C+E%3BGomez%2C+D+E%3BLindsay%2C+C+K%3BShibuya%2C+M%3BSinha%2C+C+C%3BThorgeirsson%2C+U+P&rft.aulast=Yoshiji&rft.aufirst=H&rft.date=1998-01-05&rft.volume=75&rft.issue=1&rft.spage=81&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-01-22 N1 - Date created - 1998-01-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Combinations of paclitaxel and vinblastine and their effects on tubulin polymerization and cellular cytotoxicity: characterization of a synergistic schedule. AN - 79653900; 9426691 AB - Paclitaxel (PTX) and vinblastine (VBL) represent 2 classes of drugs that target tubulin but have separate binding properties and opposing mechanisms of action. To evaluate the potential use of these agents together in a chemotherapeutic regimen, we investigated their effects on the dynamics of tubulin polymerization and cellular cytotoxicity, when administered singly or in combination. In human epidermoid carcinoma KB cells and MCF-7 breast carcinoma cells, we observed a time- and dose-dependent effect on cytoskeletal dynamics for both PTX and VBL. Tubulin polymerization induced by PTX was stable for more than 24 hr. When PTX treatment was followed by VBL, a time- and dose-dependent reversal of tubulin polymerization was observed. In contrast, rapid tubulin polymerization occurred when VBL was followed by PTX. When both agents were added simultaneously, a diminution of PTX-induced tubulin polymerization was observed with increasing doses of VBL; a maximum reduction was achieved when equal concentrations were used. Examination of the tubulin pattern by immunofluorescence in MCF-7 breast cancer cells confirmed and extended our findings. Bundle formation followed treatment with PTX. Addition of increasing concentrations of VBL prevented bundling; however, the normal cytoskeletal architecture was not restored. Cytotoxicity studies carried out using the median dose effect principles and the combination index analysis showed synergism when VBL and PTX were administered sequentially and antagonism for simultaneous administration. Our results demonstrate changes in tubulin dynamics following drug treatment and provide a rationale for combined PTX/VBL therapy after careful evaluation of the schedule of administration. JF - International journal of cancer AU - Giannakakou, P AU - Villalba, L AU - Li, H AU - Poruchynsky, M AU - Fojo, T AD - Medicine Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 1998/01/05/ PY - 1998 DA - 1998 Jan 05 SP - 57 EP - 63 VL - 75 IS - 1 SN - 0020-7136, 0020-7136 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Tubulin KW - Vinblastine KW - 5V9KLZ54CY KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Drug Screening Assays, Antitumor KW - Drug Interactions KW - Drug Administration Schedule KW - HeLa Cells -- drug effects KW - Tumor Cells, Cultured -- drug effects KW - Dose-Response Relationship, Drug KW - Humans KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacology KW - Vinblastine -- pharmacology KW - Paclitaxel -- administration & dosage KW - Tubulin -- drug effects KW - Vinblastine -- administration & dosage KW - Antineoplastic Agents, Phytogenic -- pharmacology KW - Paclitaxel -- pharmacology KW - Antineoplastic Agents, Phytogenic -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79653900?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Combinations+of+paclitaxel+and+vinblastine+and+their+effects+on+tubulin+polymerization+and+cellular+cytotoxicity%3A+characterization+of+a+synergistic+schedule.&rft.au=Giannakakou%2C+P%3BVillalba%2C+L%3BLi%2C+H%3BPoruchynsky%2C+M%3BFojo%2C+T&rft.aulast=Giannakakou&rft.aufirst=P&rft.date=1998-01-05&rft.volume=75&rft.issue=1&rft.spage=57&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-01-22 N1 - Date created - 1998-01-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Impaired learning in rats in a 14-unit T-maze by 7-nitroindazole, a neuronal nitric oxide synthase inhibitor, is attenuated by the nitric oxide donor, molsidomine. AN - 79707653; 9489851 AB - In previous experiments, it was demonstrated that systemic or central administration of the nitric oxide synthase (NO synthase) inhibitor, NG-nitro-L-arginine (N-Arg), produced dose-dependent learning impairments in rats in a 14-unit T-maze; and that sodium nitroprusside, a NO donor, could attenuate the impairment. Since N-Arg is not specific for neuronal NO synthase and produces hypertension, it is possible that effects on the cardiovasculature may have contributed to the impaired maze performance. In the present experiment, we have investigated the maze performance of 3-4 months old male Fischer-344 rats following treatment with 7-nitroindazole, a NO synthase inhibitor that is selective for neuronal NO synthase and does not produce hypertension. In addition, we examined the effects of the NO donor, molsidomine, which is much longer acting than sodium nitroprusside. Rats were pretrained to avoid footshock in a straight runway and received training in a 14-unit T-maze 24 h later. In an initial dose-response study, rats received intraperitoneal (i.p.) injections of either 7-nitroindazole (25, 50, or 65 mg/kg) or peanut oil 30 min prior to maze training. 7-nitroindazole produced significant, dose-dependent maze acquisition deficits, with 65 mg/kg producing the greatest learning impairment. This dose of 7-nitroindazole had no significant effect on systolic blood pressure. Following the dose-response study, rats were given i.p. injections of either 7-nitroindazole (70 mg/kg) plus saline, 7-nitroindazole (70 mg/kg) plus the NO donor, molsidomine (2 or 4 mg/kg), or peanut oil plus saline as controls. Both doses of molsidomine significantly attenuated the learning deficit induced by 7-nitroindazole relative to controls. These findings represent the first evidence that impaired learning produced by inhibition of neuronal NO synthase can be overcome by systemic administration of a NO donor. JF - European journal of pharmacology AU - Meyer, R C AU - Spangler, E L AU - Patel, N AU - London, E D AU - Ingram, D K AD - Molecular Physiology and Genetics Section, Nathan W. Shock Laboratories, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 1998/01/02/ PY - 1998 DA - 1998 Jan 02 SP - 17 EP - 22 VL - 341 IS - 1 SN - 0014-2999, 0014-2999 KW - Enzyme Inhibitors KW - 0 KW - Indazoles KW - Vasodilator Agents KW - Nitric Oxide KW - 31C4KY9ESH KW - Molsidomine KW - D46583G77X KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - 7-nitroindazole KW - UX0N37CMVH KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Dose-Response Relationship, Drug KW - Nitric Oxide Synthase -- antagonists & inhibitors KW - Neurons -- enzymology KW - Nitric Oxide -- biosynthesis KW - Blood Pressure -- drug effects KW - Drug Synergism KW - Male KW - Maze Learning -- drug effects KW - Indazoles -- administration & dosage KW - Enzyme Inhibitors -- administration & dosage KW - Indazoles -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Indazoles -- antagonists & inhibitors KW - Vasodilator Agents -- pharmacology KW - Molsidomine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79707653?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+pharmacology&rft.atitle=Impaired+learning+in+rats+in+a+14-unit+T-maze+by+7-nitroindazole%2C+a+neuronal+nitric+oxide+synthase+inhibitor%2C+is+attenuated+by+the+nitric+oxide+donor%2C+molsidomine.&rft.au=Meyer%2C+R+C%3BSpangler%2C+E+L%3BPatel%2C+N%3BLondon%2C+E+D%3BIngram%2C+D+K&rft.aulast=Meyer&rft.aufirst=R&rft.date=1998-01-02&rft.volume=341&rft.issue=1&rft.spage=17&rft.isbn=&rft.btitle=&rft.title=European+journal+of+pharmacology&rft.issn=00142999&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-29 N1 - Date created - 1998-04-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Coordinate transactivation of the interleukin-2 CD28 response element by c-Rel and ATF-1/CREB2. AN - 79633811; 9417115 AB - The interleukin-2 CD28 response element (CD28RE) acts as a composite enhancer, in conjunction with a 3'-12-O-tetradecanoylphorbol-13-acetate response element (TRE)-like element, to confer CD28 receptor-dependent inducibility to the interleukin-2 promoter in T-cells. When inserted as a single copy upstream of a basal promoter, this composite enhancer, termed the CD28RE-TRE, is both highly active and CD28-inducible in transactivation assays. A multicomponent nuclear protein complex that binds the CD28RE-TRE was isolated by DNA affinity chromatography from nuclear extracts of mitogen- and CD28 receptor-costimulated human T-cells. Immunological and biochemical analyses of this complex reveal the presence of c-Rel, ATF-1, and CREB2 as major DNA-binding components. Coexpression of c-Rel in combination with ATF-1, CREB2, or ATF-1/CREB2 leads to synergistic transactivation of a CD28RE-TRE reporter plasmid in quiescent Jurkat T-cells. Furthermore, CD28-dependent transactivation of the CD28RE-TRE is specifically inhibited by cAMP response element-binding protein (CREB) dominant-negative expression vectors. Moreover, mutant promoter constructs in which the internal 5'-CD28RE and 3'-TRE-like sequences have been topologically positioned 180 degrees out of phase with one another show loss of mitogen- and CD28-dependent inducibility. Finally, the addition of the CREB-binding transcriptional coactivator p300 leads to a dramatic CREB-dependent increase in both mitogen- and CD28-mediated transactivation of the CD28RE-TRE. These findings demonstrate that full physiological responsiveness to CD28 receptor stimulation in T-cells is dependent on topologically linked sequences within the CD28RE-TRE composite enhancer and provide strong support of a direct role for the CREB family of transcription factors and p300/CREB-binding protein coactivator proteins in cytokine gene induction during T-cell activation. JF - The Journal of biological chemistry AU - Butscher, W G AU - Powers, C AU - Olive, M AU - Vinson, C AU - Gardner, K AD - Laboratory of Pathology, NCI, National Institutes of Health, Bethesda, Maryland 20892-1500, USA. Y1 - 1998/01/02/ PY - 1998 DA - 1998 Jan 02 SP - 552 EP - 560 VL - 273 IS - 1 SN - 0021-9258, 0021-9258 KW - Activating Transcription Factor 1 KW - 0 KW - Antibodies, Monoclonal KW - Antigens, CD28 KW - DNA-Binding Proteins KW - Interleukin-2 KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-rel KW - Transcription Factors KW - Ionomycin KW - 56092-81-0 KW - DNA KW - 9007-49-2 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Humans KW - Jurkat Cells KW - Ionomycin -- pharmacology KW - Antibodies, Monoclonal -- immunology KW - Mutagenesis KW - Chromatography, Affinity KW - Antibody Specificity KW - T-Lymphocytes -- metabolism KW - Promoter Regions, Genetic KW - Genetic Vectors KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Up-Regulation KW - T-Lymphocytes -- drug effects KW - T-Lymphocytes -- immunology KW - Antigens, CD28 -- genetics KW - Transcription Factors -- metabolism KW - Antigens, CD28 -- isolation & purification KW - Proto-Oncogene Proteins -- metabolism KW - Interleukin-2 -- genetics KW - Transcriptional Activation KW - Antigens, CD28 -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79633811?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Coordinate+transactivation+of+the+interleukin-2+CD28+response+element+by+c-Rel+and+ATF-1%2FCREB2.&rft.au=Butscher%2C+W+G%3BPowers%2C+C%3BOlive%2C+M%3BVinson%2C+C%3BGardner%2C+K&rft.aulast=Butscher&rft.aufirst=W&rft.date=1998-01-02&rft.volume=273&rft.issue=1&rft.spage=552&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-03 N1 - Date created - 1998-02-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation and processing of non-anchored yapsin 1 (Yap3p). AN - 79631568; 9417119 AB - A C-terminally truncated form of yapsin 1 (yeast aspartic protease 3), the first member of the novel sub-class of aspartic proteases with specificity for basic residues (designated the Yapsins), was overexpressed and purified to apparent homogeneity, yielding approximately 1 microg of yapsin 1/g of wet yeast. N-terminal amino acid analysis of the purified protein confirmed that the propeptide was absent and that the mature enzyme began at Ala68. The mature enzyme was shown to be composed of approximately equimolar amounts of two subunits, designated alpha and beta, that were associated to each other by a disulfide bond. C-terminally truncated proyapsin 1 was also expressed in the baculovirus/Sf9 insect cell expression system and secreted as a zymogen that could be activated upon incubation at an acidic pH with an optimum at approximately 4.0. When expressed without its pro-region, it was localized intracellularly and lacked activity, indicating that the pro-region was required for the correct folding of the enzyme. The activation of proyapsin 1 in vitro exhibited linear kinetics and generated an intermediate form of yapsin 1 or pseudo-yapsin 1. JF - The Journal of biological chemistry AU - Cawley, N X AU - Olsen, V AU - Zhang, C F AU - Chen, H C AU - Tan, M AU - Loh, Y P AD - Section on Cellular Neurobiology, Laboratory of Developmental Neurobiology, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA.cawley@codon.nih.gov Y1 - 1998/01/02/ PY - 1998 DA - 1998 Jan 02 SP - 584 EP - 591 VL - 273 IS - 1 SN - 0021-9258, 0021-9258 KW - Enzyme Precursors KW - 0 KW - Fungal Proteins KW - Recombinant Proteins KW - Saccharomyces cerevisiae Proteins KW - aspartic proteinase A KW - EC 3.4.23 KW - Aspartic Acid Endopeptidases KW - EC 3.4.23.- KW - YPS1 protein, S cerevisiae KW - EC 3.4.23.25 KW - Index Medicus KW - Enzyme Precursors -- metabolism KW - Electrophoresis, Polyacrylamide Gel KW - Enzyme Activation KW - Amino Acid Sequence KW - Recombinant Proteins -- genetics KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- isolation & purification KW - Baculoviridae -- genetics KW - Blotting, Western KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Molecular Sequence Data KW - Enzyme Precursors -- isolation & purification KW - Substrate Specificity KW - Enzyme Precursors -- genetics KW - Fungal Proteins -- metabolism KW - Aspartic Acid Endopeptidases -- genetics KW - Protein Processing, Post-Translational KW - Aspartic Acid Endopeptidases -- isolation & purification KW - Aspartic Acid Endopeptidases -- metabolism KW - Fungal Proteins -- isolation & purification KW - Fungal Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79631568?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Activation+and+processing+of+non-anchored+yapsin+1+%28Yap3p%29.&rft.au=Cawley%2C+N+X%3BOlsen%2C+V%3BZhang%2C+C+F%3BChen%2C+H+C%3BTan%2C+M%3BLoh%2C+Y+P&rft.aulast=Cawley&rft.aufirst=N&rft.date=1998-01-02&rft.volume=273&rft.issue=1&rft.spage=584&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-03 N1 - Date created - 1998-02-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A novel ets-related transcription factor, ERT/ESX/ESE-1, regulates expression of the transforming growth factor-beta type II receptor. AN - 79631256; 9417054 AB - A 2.5-kilobase cDNA clone that encodes a 371-amino acid novel transcription factor was isolated from a human placenta cDNA library using a yeast one-hybrid system. The novel ets-related transcription factor (ERT) showed a homology with the ETS DNA-binding domain. Using constructs of the transforming growth factor-beta (TGF-beta) type II receptor (RII) promoter linked to the luciferase gene, we have demonstrated that ERT activates transcription of the TGF-beta RII gene through the 5'-TTTCCTGTTTCC-3' response element spanning nucleotides +13 to +24 and multiple additional ETS binding sites between -1816 and -82 of the TGF-beta RII promoter. A specific interaction between ERT and the ETS binding sites was also demonstrated using an electrophoretic mobility shift assay. Deletion mapping of ERT protein suggests that the transactivation domain resides in the amino terminus while the DNA-binding domain is localized to the carboxyl-terminal region. Our results suggest that ERT might be a major transcription factor involved in the transcriptional regulation of the TGF-beta RII gene. JF - The Journal of biological chemistry AU - Choi, S G AU - Yi, Y AU - Kim, Y S AU - Kato, M AU - Chang, J AU - Chung, H W AU - Hahm, K B AU - Yang, H K AU - Rhee, H H AU - Bang, Y J AU - Kim, S J AD - Laboratory of Cell Regulation and Carcinogenesis, NCI, National Institutes of Health, Bethesda, Maryland 20892-5055, USA. Y1 - 1998/01/02/ PY - 1998 DA - 1998 Jan 02 SP - 110 EP - 117 VL - 273 IS - 1 SN - 0021-9258, 0021-9258 KW - DNA, Complementary KW - 0 KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-ets KW - Receptors, Transforming Growth Factor beta KW - Transcription Factors KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - transforming growth factor-beta type II receptor KW - EC 2.7.11.30 KW - Index Medicus KW - Promoter Regions, Genetic KW - Humans KW - Molecular Sequence Data KW - Transcription, Genetic KW - Protein Binding KW - Cloning, Molecular KW - Receptors, Transforming Growth Factor beta -- genetics KW - Transcription Factors -- metabolism KW - Proto-Oncogene Proteins -- metabolism KW - Gene Expression Regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79631256?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=A+novel+ets-related+transcription+factor%2C+ERT%2FESX%2FESE-1%2C+regulates+expression+of+the+transforming+growth+factor-beta+type+II+receptor.&rft.au=Choi%2C+S+G%3BYi%2C+Y%3BKim%2C+Y+S%3BKato%2C+M%3BChang%2C+J%3BChung%2C+H+W%3BHahm%2C+K+B%3BYang%2C+H+K%3BRhee%2C+H+H%3BBang%2C+Y+J%3BKim%2C+S+J&rft.aulast=Choi&rft.aufirst=S&rft.date=1998-01-02&rft.volume=273&rft.issue=1&rft.spage=110&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-03 N1 - Date created - 1998-02-03 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF017307; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Language, Play, Emotional Availability, and Acceptance in Cocaine-Exposed and Non-Cocaine-Exposed Young Children and Their Mothers AN - 85513211; 200101017 AB - This study assessed language, play, emotional availability, & acceptance in cocaine-exposed & non-cocaine-exposed children & their mothers at 18 months. Although prenatal cocaine exposure is thought to put the developing nervous system at risk, & likewise drug-abusing mothers are thought to disadvantage their developing children, cocaine-exposed youngsters showed no systematic differences in measures of language, play, emotional availability, & acceptance from their demographically similar non-cocaine-exposed peers. More gender (& social class) effects than cocaine-exposure effects emerged in these measures. The implications of this pattern of findings for cognitive & socioemotional functioning in childhood & for social policy are discussed. 5 Tables, 72 References. Adapted from the source document JF - Revue PArole AU - Bornstein, Marc H AU - Mayes, Linda C AU - Park, Jaihyun AD - National Instit Child Health & Human Development, Bethesda, MD Marc_H_Bornstein@nih.gov Y1 - 1998///0, PY - 1998 DA - 0, 1998 SP - 235 EP - 260 VL - 7-8 SN - 0770-545X, 0770-545X KW - Parent Child Interaction (62760) KW - Emotions (21600) KW - Drug Effects (19900) KW - Language Acquisition (41600) KW - Cognitive Development (12850) KW - Interpersonal Behavior (37550) KW - article KW - 4015: psycholinguistics; child language acquisition UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85513211?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Allba&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Revue+PArole&rft.atitle=Language%2C+Play%2C+Emotional+Availability%2C+and+Acceptance+in+Cocaine-Exposed+and+Non-Cocaine-Exposed+Young+Children+and+Their+Mothers&rft.au=Bornstein%2C+Marc+H%3BMayes%2C+Linda+C%3BPark%2C+Jaihyun&rft.aulast=Bornstein&rft.aufirst=Marc&rft.date=1998-01-01&rft.volume=7-8&rft.issue=&rft.spage=235&rft.isbn=&rft.btitle=&rft.title=Revue+PArole&rft.issn=0770545X&rft_id=info:doi/ LA - English DB - Linguistics and Language Behavior Abstracts (LLBA) N1 - Date revised - 2003-10-01 N1 - Last updated - 2016-09-27 N1 - SubjectsTermNotLitGenreText - Language Acquisition (41600); Parent Child Interaction (62760); Drug Effects (19900); Interpersonal Behavior (37550); Emotions (21600); Cognitive Development (12850) ER - TY - JOUR T1 - Overview of human tremor physiology. AN - 85411604; pmid-9827594 AB - The physiology differs in the many forms of human tremor. Tremors may derive from mechanical oscillations, mechanical reflex oscillations, normal central oscillators, and pathologic central oscillators. Methods of studying tremor include accelerometry and electromyography (EMG). An excellent method consists of accelerometry and EMG combined with spectral analysis and weighting of the body part, which allows separation of tremors coming from mechanical reflex and central oscillators. Physiologic tremor is a mechanical tremor with a possible contribution of the normal 8-12 Hz central oscillator; exaggerated physiologic tremor is a mechanical reflex tremor. Essential tremor (ET) comes from a central oscillator that can be easily influenced with sensory input. The classic rest tremor of Parkinson's disease (PD) comes from a central oscillator that seems less easily influenced with sensory input but can be affected by transcranial magnetic stimulation. Other tremors with central oscillators are palatal tremor and orthostatic tremor. Other tremors whose physiology involves central loops includes cerebellar tremor and cortical tremor. Neuropathic tremors may be a result of delays in peripheral loops, but central oscillators play a role in some. JF - Movement disorders : official journal of the Movement Disorder Society AU - Hallett, M AD - National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892-1428, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 43 EP - 48 VL - 13 Suppl 3 SN - 0885-3185, 0885-3185 KW - Index Medicus KW - National Library of Medicine KW - Electromyography -- methods KW - Muscle Spindles -- physiology KW - Humans KW - Reflex, Stretch -- physiology KW - Biological Clocks -- physiology KW - Tremor -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85411604?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.atitle=Overview+of+human+tremor+physiology.&rft.au=Hallett%2C+M&rft.aulast=Hallett&rft.aufirst=M&rft.date=1998-01-01&rft.volume=13+Suppl+3&rft.issue=&rft.spage=43&rft.isbn=&rft.btitle=&rft.title=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.issn=08853185&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2008-01-14 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Assessing functional outcomes: an overview. AN - 85408545; pmid-9720127 AB - Assessment of functional outcomes requires, first, a good working definition and, second, sufficiently reliable and valid measures from which to choose. With the advent of new or refined conceptualizations of patient outcomes, the functional domain has expanded to address not only routine activities of daily life but also the richly diverse aspects believed to constitute quality of life. This article defines and places the concept of functional outcomes within a context of various published and proposed classification schemes, and supports an expanded definition on the basis of these schemes, emerging models of health care that combine biomedical with social science approaches, and the visionary contributions of respected colleagues in the field. JF - Seminars in speech and language AU - Frattali, C M AD - National Institutes of Health, W.G. Magnuson Clinical Center, Rehabilitation Medicine Department, Bethesda, Maryland 20892-1604, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 209 EP - 220 VL - 19 IS - 3 SN - 0734-0478, 0734-0478 KW - Index Medicus KW - National Library of Medicine KW - Humans KW - Communication Disorders -- diagnosis KW - Treatment Outcome KW - Activities of Daily Living KW - Quality of Life KW - Communication Disorders -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85408545?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+speech+and+language&rft.atitle=Assessing+functional+outcomes%3A+an+overview.&rft.au=Frattali%2C+C+M&rft.aulast=Frattali&rft.aufirst=C&rft.date=1998-01-01&rft.volume=19&rft.issue=3&rft.spage=209&rft.isbn=&rft.btitle=&rft.title=Seminars+in+speech+and+language&rft.issn=07340478&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2008-01-14 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Axial specification for sensory organs versus non-sensory structures of the chicken inner ear. AN - 85274777; pmid-9389659 AB - A mature inner ear is a complex labyrinth containing multiple sensory organs and nonsensory structures in a fixed configuration. Any perturbation in the structure of the labyrinth will undoubtedly lead to functional deficits. Therefore, it is important to understand molecularly how and when the position of each inner ear component is determined during development. To address this issue, each axis of the otocyst (embryonic day 2.5, E2.5, stage 16-17) was changed systematically at an age when axial information of the inner ear is predicted to be fixed based on gene expression patterns. Transplanted inner ears were analyzed at E4.5 for gene expression of BMP4 (bone morphogenetic protein), SOHo-1 (sensory organ homeobox-1), Otx1 (cognate of Drosophila orthodenticle gene), p75NGFR (nerve growth factor receptor) and Msx1 (muscle segment homeobox), or at E9 for their gross anatomy and sensory organ formation. Our results showed that axial specification in the chick inner ear occurs later than expected and patterning of sensory organs in the inner ear was first specified along the anterior/posterior (A/P) axis, followed by the dorsal/ventral (D/V) axis. Whereas the A/P axis of the sensory organs was fixed at the time of transplantation, the A/P axis for most non-sensory structures was not and was able to be re-specified according to the new axial information from the host. The D/V axis for the inner ear was not fixed at the time of transplantation. The asynchronous specification of the A/P and D/V axes of the chick inner ear suggests that sensory organ formation is a multi-step phenomenon, rather than a single inductive event. JF - Development (Cambridge, England) AU - Wu, Doris Kar-Wah AU - Nunes, F D AU - Choo, D AD - National Institute on Deafness and Other Communication Disorders PY - 1998 SP - 11 EP - 20 VL - 125 IS - 1 SN - 0950-1991, 0950-1991 KW - Saccule and Utricle KW - Labyrinth KW - Transplantation KW - Hair Cells KW - Homeodomain Proteins KW - Chick Embryo KW - Animal KW - Cell Differentiation KW - Nerve Tissue Proteins KW - Phenotype KW - In Situ Hybridization KW - Cochlear Duct KW - Semicircular Canals KW - Bone Morphogenetic Proteins KW - Immunohistochemistry KW - Receptor, Nerve Growth Factor KW - Receptors, Nerve Growth Factor KW - Body Patterning KW - Gene Expression Regulation, Developmental UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85274777?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Development+%28Cambridge%2C+England%29&rft.atitle=Axial+specification+for+sensory+organs+versus+non-sensory+structures+of+the+chicken+inner+ear.&rft.au=Wu%2C+Doris+Kar-Wah%3BNunes%2C+F+D%3BChoo%2C+D&rft.aulast=Wu&rft.aufirst=Doris&rft.date=1998-01-01&rft.volume=125&rft.issue=1&rft.spage=11&rft.isbn=&rft.btitle=&rft.title=Development+%28Cambridge%2C+England%29&rft.issn=09501991&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Transmission of spongiform encephalopathy through biological products. AN - 85258531; pmid-9737380 AB - The transmissible spongiform encephalopathies (TSE) are rare but fatal neurological diseases that exist in sporadic, familial, and environmentally acquired forms. Environmentally acquired disease has until now been mostly iatrogenic in origin, recognized as responsible for nearly 200 deaths during the past 20 years. The two most important causes have been contamination of cadaver-derived human growth hormone and dura mater grafts, but a few instances related to contaminated neurosurgical instruments and corneal grafts have also occurred. Currently, a great deal of concern is being voiced about the potential risk of acquiring disease through blood or blood products, and although there is no supporting epidemiological evidence for such a danger, experiments are underway to define which blood components or plasma derivatives might pose the greatest problem. JF - Developments in Biological Standardization AU - Brown, P AD - Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1998 SP - 73 EP - 78 VL - 93 SN - 0301-5149, 0301-5149 KW - Iatrogenic Disease KW - Human KW - Animal KW - Prion Diseases KW - Organ Transplantation KW - Biological Products UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85258531?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Developments+in+Biological+Standardization&rft.atitle=Transmission+of+spongiform+encephalopathy+through+biological+products.&rft.au=Brown%2C+P&rft.aulast=Brown&rft.aufirst=P&rft.date=1998-01-01&rft.volume=93&rft.issue=&rft.spage=73&rft.isbn=&rft.btitle=&rft.title=Developments+in+Biological+Standardization&rft.issn=03015149&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Linguistic processing during repetitive transcranial magnetic stimulation. AN - 85227304; pmid-9443476 AB - To determine if linguistic processing could be selectively disrupted with repetitive transcranial magnetic stimulation (rTMS), rTMS was performed during a picture-word verification task. Seven right-handed subjects were trained in two conditions: picture-word verification, which required the subject to verify whether the picture of an object matched the subtitle name on the same page, and frame verification, which required subjects to verify whether there was a rectangular frame around the combined object picture and subtitle. Half of the trials were performed during rTMS. The effects of rTMS on performance were evaluated at the following four scalp positions: left anterior (the area where rTMS produced speech arrest), a mirror site on the right, and two positions in the left and right parietal region. Stimulation over the left deltoid muscle served as a control. Subjects had less difficulty in making picture-word matching decisions during unstimulated compared with stimulated trials at the left anterior and posterior positions. No significant difference in accuracy was detected in the frame verification condition, but response times in the frame verification condition were longer with stimulation at the left anterior position. Because rTMS of the dominant hemisphere affected linguistic processing independent of speech motor output, we confirm that rTMS may be used to investigate language and other cognitive functions. JF - Neurology AU - Flitman, S S AU - Grafman, J AU - Wassermann, E M AU - Cooper, V AU - O'Grady, J AU - Pascual-Leone, A AU - Hallett, M AD - Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892-1440, USA. PY - 1998 SP - 175 EP - 181 VL - 50 IS - 1 SN - 0028-3878, 0028-3878 KW - Cerebral Cortex KW - Photic Stimulation KW - Form Perception KW - Human KW - Adult KW - Psychomotor Performance KW - Neuropsychological Tests KW - Electric Stimulation KW - Male KW - Female KW - Cognition KW - Reading KW - Magnetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85227304?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=Linguistic+processing+during+repetitive+transcranial+magnetic+stimulation.&rft.au=Flitman%2C+S+S%3BGrafman%2C+J%3BWassermann%2C+E+M%3BCooper%2C+V%3BO%27Grady%2C+J%3BPascual-Leone%2C+A%3BHallett%2C+M&rft.aulast=Flitman&rft.aufirst=S&rft.date=1998-01-01&rft.volume=50&rft.issue=1&rft.spage=175&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Asymmetry of chimpanzee planum temporale: humanlike pattern of Wernicke's brain language area homolog. AN - 85223865; pmid-9422693 AB - The anatomic pattern and left hemisphere size predominance of the planum temporale, a language area of the human brain, are also present in chimpanzees (Pan troglodytes). The left planum temporale was significantly larger in 94 percent (17 of 18) of chimpanzee brains examined. It is widely accepted that the planum temporale is a key component of Wernicke's receptive language area, which is also implicated in human communication-related disorders such as schizophrenia and in normal variations such as musical talent. However, anatomic hemispheric asymmetry of this cerebrocortical site is clearly not unique to humans, as is currently thought. The evolutionary origin of human language may have been founded on this basal anatomic substrate, which was already lateralized to the left hemisphere in the common ancestor of chimpanzees and humans 8 million years ago. JF - Science AU - Gannon, P J AU - Holloway, R L AU - Broadfield, D C AU - Braun, Allen R AD - Department of Otolaryngology and Arthur M. Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York, NY 10029, USA.; National Institute on Deafness and Other Communication Disorders PY - 1998 SP - 220 EP - 222 VL - 279 IS - 5348 SN - 0036-8075, 0036-8075 KW - Magnetic Resonance Imaging KW - Human KW - Temporal Lobe KW - Communication KW - Animal KW - Support, U.S. Gov't, Non-P.H.S. KW - Support, Non-U.S. Gov't KW - Laterality KW - Evolution KW - Hominidae KW - Pan troglodytes KW - Language KW - Dominance, Cerebral UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85223865?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science&rft.atitle=Asymmetry+of+chimpanzee+planum+temporale%3A+humanlike+pattern+of+Wernicke%27s+brain+language+area+homolog.&rft.au=Gannon%2C+P+J%3BHolloway%2C+R+L%3BBroadfield%2C+D+C%3BBraun%2C+Allen+R&rft.aulast=Gannon&rft.aufirst=P&rft.date=1998-01-01&rft.volume=279&rft.issue=5348&rft.spage=220&rft.isbn=&rft.btitle=&rft.title=Science&rft.issn=00368075&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - A phase II study of carboplatin, cisplatin, interferon-alpha, and tamoxifen for patients with metastatic melanoma. AN - 80034924; 9679527 AB - The purpose of this trial was to determine the toxicity and antineoplastic activity of cisplatin, carboplatin, tamoxifen, and interferon-alpha (IFN-alpha) in patients with advanced melanoma. Eleven patients with metastatic melanoma were enrolled. The patients received carboplatin 400 mg/m2 i.v. on day 0; cisplatin 25 mg/m2 i.v. on days 7, 14, and 21; tamoxifen 20 mg p.o. b.i.d. on days 0-27; and interferon-alpha 5 million units/m2 subcutaneously 3 times per week. Cycles were repeated every 28 days. Patients were assessed for tumor response at the end of 2 cycles. Toxicity was severe, with 14 of 24 cycles given requiring some form of dose reduction. Carboplatin dose reductions were related to bone-marrow toxicity, whereas IFN-alpha caused fatigue, arthralgias, myalgias, and fever. The overall response rate was 18% (2 partial responses [PRs]). The combination of cisplatin, carboplatin, tamoxifen, and IFN-alpha is active in advanced melanoma; however, the toxicity is unacceptable. JF - Cancer investigation AU - Gause, B L AU - Sharfman, W H AU - Janik, J E AU - Curti, B D AU - Steis, R G AU - Urba, W J AU - Smith, J W AU - Alvord, W G AU - Longo, D L AD - National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 374 EP - 380 VL - 16 IS - 6 SN - 0735-7907, 0735-7907 KW - Antineoplastic Agents KW - 0 KW - Interferon-alpha KW - Tamoxifen KW - 094ZI81Y45 KW - Carboplatin KW - BG3F62OND5 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Interferon-alpha -- administration & dosage KW - Humans KW - Carboplatin -- administration & dosage KW - Carboplatin -- adverse effects KW - Tamoxifen -- administration & dosage KW - Cisplatin -- administration & dosage KW - Interferon-alpha -- adverse effects KW - Adult KW - Treatment Outcome KW - Tamoxifen -- adverse effects KW - Middle Aged KW - Cisplatin -- adverse effects KW - Female KW - Male KW - Melanoma -- secondary KW - Melanoma -- drug therapy KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80034924?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+investigation&rft.atitle=A+phase+II+study+of+carboplatin%2C+cisplatin%2C+interferon-alpha%2C+and+tamoxifen+for+patients+with+metastatic+melanoma.&rft.au=Gause%2C+B+L%3BSharfman%2C+W+H%3BJanik%2C+J+E%3BCurti%2C+B+D%3BSteis%2C+R+G%3BUrba%2C+W+J%3BSmith%2C+J+W%3BAlvord%2C+W+G%3BLongo%2C+D+L&rft.aulast=Gause&rft.aufirst=B&rft.date=1998-01-01&rft.volume=16&rft.issue=6&rft.spage=374&rft.isbn=&rft.btitle=&rft.title=Cancer+investigation&rft.issn=07357907&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-06 N1 - Date created - 1998-08-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Cancer Invest. 1998;16(6):421-3 [9679534] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical trials with Pseudomonas exotoxin immunotoxins. AN - 80016337; 9670614 JF - Current topics in microbiology and immunology AU - Pai, L H AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 83 EP - 96 VL - 234 SN - 0070-217X, 0070-217X KW - Antibodies, Monoclonal KW - 0 KW - Exotoxins KW - Immunotoxins KW - Recombinant Fusion Proteins KW - Index Medicus KW - Antibodies, Monoclonal -- biosynthesis KW - Immunotherapy KW - Humans KW - Clinical Trials, Phase I as Topic KW - Adult KW - Aged KW - Middle Aged KW - Recombinant Fusion Proteins -- therapeutic use KW - Male KW - Female KW - Antibodies, Monoclonal -- therapeutic use KW - Immunotoxins -- therapeutic use KW - Immunotoxins -- administration & dosage KW - Pseudomonas aeruginosa KW - Neoplasms -- therapy KW - Exotoxins -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80016337?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+topics+in+microbiology+and+immunology&rft.atitle=Clinical+trials+with+Pseudomonas+exotoxin+immunotoxins.&rft.au=Pai%2C+L+H%3BPastan%2C+I&rft.aulast=Pai&rft.aufirst=L&rft.date=1998-01-01&rft.volume=234&rft.issue=&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=Current+topics+in+microbiology+and+immunology&rft.issn=0070217X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-06 N1 - Date created - 1998-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical applications of immunotoxins. Introduction. AN - 80016295; 9670609 JF - Current topics in microbiology and immunology AU - FitzGerald, D AU - Pastan, I AU - Robertus, J AD - Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 1 EP - 11 VL - 234 SN - 0070-217X, 0070-217X KW - Bacterial Toxins KW - 0 KW - Immunotoxins KW - Plant Proteins KW - Recombinant Proteins KW - Index Medicus KW - Animals KW - Plant Proteins -- therapeutic use KW - Plant Proteins -- chemistry KW - Bacterial Toxins -- metabolism KW - Recombinant Proteins -- biosynthesis KW - Recombinant Proteins -- metabolism KW - Bacterial Toxins -- therapeutic use KW - Bacterial Toxins -- chemistry KW - Mice KW - Plant Proteins -- metabolism KW - Recombinant Proteins -- therapeutic use KW - Immunotoxins -- chemistry KW - Immunotoxins -- therapeutic use KW - Immunotoxins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80016295?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+topics+in+microbiology+and+immunology&rft.atitle=Clinical+applications+of+immunotoxins.+Introduction.&rft.au=FitzGerald%2C+D%3BPastan%2C+I%3BRobertus%2C+J&rft.aulast=FitzGerald&rft.aufirst=D&rft.date=1998-01-01&rft.volume=234&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Current+topics+in+microbiology+and+immunology&rft.issn=0070217X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-06 N1 - Date created - 1998-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunotoxins for brain tumor therapy. AN - 80011527; 9670615 JF - Current topics in microbiology and immunology AU - Oldfield, E H AU - Youle, R J AD - Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 97 EP - 114 VL - 234 SN - 0070-217X, 0070-217X KW - Immunotoxins KW - 0 KW - Index Medicus KW - Rats KW - Animals KW - Prospective Studies KW - Humans KW - Adult KW - Clinical Trials as Topic KW - Middle Aged KW - Male KW - Haplorhini KW - Female KW - Blood-Brain Barrier KW - Immunotoxins -- pharmacokinetics KW - Brain Neoplasms -- therapy KW - Brain Neoplasms -- metabolism KW - Immunotoxins -- therapeutic use KW - Immunotoxins -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80011527?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+topics+in+microbiology+and+immunology&rft.atitle=Immunotoxins+for+brain+tumor+therapy.&rft.au=Oldfield%2C+E+H%3BYoule%2C+R+J&rft.aulast=Oldfield&rft.aufirst=E&rft.date=1998-01-01&rft.volume=234&rft.issue=&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=Current+topics+in+microbiology+and+immunology&rft.issn=0070217X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-06 N1 - Date created - 1998-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Potentiation of retinoic acid-induced differentiation of human acute promyelocytic leukemia NB4 cells by butyric acid, tributyrin, and hexamethylene bisacetamide. AN - 80008463; 9666515 AB - Cytodifferentiation therapy by all-trans-retinoic acid (RA) for acute promyelocytic leukemia patients is encouraging in spite of several limitations preventing better clinical outcomes. Most patients in complete remission induced by RA experience relapse and resist further treatment with RA. This resistance primarily is due to a systemic self-induced catabolism of RA, which interferes with the maintenance of effective plasma levels of RA. In this report we explored the possibility that treatment with combinations of RA and other differentiation agents may induce differentiation at lower RA concentrations, which in turn may produce diminished levels of resistance. We found that although n-butyric acid (BA), tributyrin (TB) (a prodrug of BA), or hexamethylene bisacetamide (HMBA) were inactive as sole agents they potentiated RA-induced differentiation of human acute promyelocytic NB4 cells. A measure of the effectiveness of these combinations was that the concentrations of RA in combination with BA and HMBA inducing half-maximal differentiation were 20- to 40-fold lower than those needed with RA alone. Furthermore, the concentrations of BA and HMBA in these combinations were at achievable plasma levels. Therefore, these combinations may have clinical utility for treatment of a variety of malignancies that are sensitive to RA alone. JF - Oncology research AU - Taimi, M AU - Chen, Z X AU - Breitman, T R AD - Laboratory of Biological Chemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 75 EP - 84 VL - 10 IS - 2 SN - 0965-0407, 0965-0407 KW - Acetamides KW - 0 KW - Antineoplastic Agents KW - Butyrates KW - Triglycerides KW - Butyric Acid KW - 107-92-6 KW - Tretinoin KW - 5688UTC01R KW - hexamethylene bisacetamide KW - LA133J59VU KW - tributyrin KW - S05LZ624MF KW - Index Medicus KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Drug Synergism KW - Tretinoin -- pharmacology KW - Acetamides -- pharmacology KW - Triglycerides -- pharmacology KW - Butyrates -- metabolism KW - Butyrates -- pharmacology KW - Antineoplastic Agents -- metabolism KW - Leukemia, Promyelocytic, Acute -- metabolism KW - Leukemia, Promyelocytic, Acute -- pathology KW - Cell Differentiation -- drug effects KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80008463?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncology+research&rft.atitle=Potentiation+of+retinoic+acid-induced+differentiation+of+human+acute+promyelocytic+leukemia+NB4+cells+by+butyric+acid%2C+tributyrin%2C+and+hexamethylene+bisacetamide.&rft.au=Taimi%2C+M%3BChen%2C+Z+X%3BBreitman%2C+T+R&rft.aulast=Taimi&rft.aufirst=M&rft.date=1998-01-01&rft.volume=10&rft.issue=2&rft.spage=75&rft.isbn=&rft.btitle=&rft.title=Oncology+research&rft.issn=09650407&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-15 N1 - Date created - 1998-09-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Women's drug use and HIV risk: findings from NIDA's Cooperative Agreement for Community-Based Outreach/Intervention Research Program. AN - 79959917; 9640631 JF - Women & health AU - Coyle, S L AD - Community Research Branch of National Institute on Drug Abuse, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 1 EP - 18 VL - 27 IS - 1-2 SN - 0363-0242, 0363-0242 KW - Index Medicus KW - AIDS/HIV KW - Multicenter Studies as Topic KW - Risk Factors KW - Humans KW - National Institutes of Health (U.S.) KW - Adult KW - Community-Institutional Relations KW - United States -- epidemiology KW - Research Design KW - Puerto Rico -- epidemiology KW - Female KW - Women's Health KW - HIV Infections -- prevention & control KW - Community Health Services -- methods KW - Substance-Related Disorders -- complications KW - HIV Infections -- epidemiology KW - Community Health Services -- organization & administration KW - Substance-Related Disorders -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79959917?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Women+%26+health&rft.atitle=Women%27s+drug+use+and+HIV+risk%3A+findings+from+NIDA%27s+Cooperative+Agreement+for+Community-Based+Outreach%2FIntervention+Research+Program.&rft.au=Coyle%2C+S+L&rft.aulast=Coyle&rft.aufirst=S&rft.date=1998-01-01&rft.volume=27&rft.issue=1-2&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Women+%26+health&rft.issn=03630242&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-10 N1 - Date created - 1998-09-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase II study of 5-aza-2'deoxycytidine (decitabine) in hormone independent metastatic (D2) prostate cancer. AN - 79917815; 9619724 AB - Decitabine (5-aza-2'-deoxycytidine) is an S-phase-specific pyrimidine analog with hypomethylation properties. In laboratory models of prostate cancer (PC-3 and DU-145), decitabine induces cellular differentiation and enhanced expression of genes involved in tumor suppression, immunogenicity, and programmed cell death. We conducted a phase II study of decitabine in 14 men with progressive, metastatic prostate cancer recurrent after total androgen blockade and flutamide withdrawal. Decitabine was administered at a dose of 75 mg/m2/dose i.v. as a 1 hour infusion every 8 hours for three doses. Cycles of therapy were repeated every 5 to 8 weeks to allow for resolution of toxicity. Two of 12 patients evaluable for response had stable disease with a time to progression of more than 10 weeks. This activity was seen in 2 of 3 African-American patients. Toxicity was similar to previously reported experience. No significant changes in urinary concentrations of the angiogenic factor bFGF, a potential biomarker of tumor activity, were identified over time in 7 unselected patients with progressive disease. We conclude that decitabine is a well tolerated regimen with modest clinical activity against hormone-independent prostate cancer. Further investigations in patients of African-American origin may be warranted. JF - Tumori AU - Thibault, A AU - Figg, W D AU - Bergan, R C AU - Lush, R M AU - Myers, C E AU - Tompkins, A AU - Reed, E AU - Samid, D AD - Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1998 SP - 87 EP - 89 VL - 84 IS - 1 SN - 0300-8916, 0300-8916 KW - Antimetabolites, Antineoplastic KW - 0 KW - Biomarkers, Tumor KW - Enzyme Inhibitors KW - Fibroblast Growth Factor 2 KW - 103107-01-3 KW - decitabine KW - 776B62CQ27 KW - DNA Modification Methylases KW - EC 2.1.1.- KW - Azacitidine KW - M801H13NRU KW - Index Medicus KW - Humans KW - Treatment Outcome KW - Aged KW - Predictive Value of Tests KW - Middle Aged KW - Male KW - Azacitidine -- therapeutic use KW - Enzyme Inhibitors -- therapeutic use KW - DNA Modification Methylases -- antagonists & inhibitors KW - Azacitidine -- analogs & derivatives KW - Prostatic Neoplasms -- blood KW - Fibroblast Growth Factor 2 -- blood KW - Prostatic Neoplasms -- drug therapy KW - Biomarkers, Tumor -- blood KW - Antimetabolites, Antineoplastic -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79917815?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Tumori&rft.atitle=A+phase+II+study+of+5-aza-2%27deoxycytidine+%28decitabine%29+in+hormone+independent+metastatic+%28D2%29+prostate+cancer.&rft.au=Thibault%2C+A%3BFigg%2C+W+D%3BBergan%2C+R+C%3BLush%2C+R+M%3BMyers%2C+C+E%3BTompkins%2C+A%3BReed%2C+E%3BSamid%2C+D&rft.aulast=Thibault&rft.aufirst=A&rft.date=1998-01-01&rft.volume=84&rft.issue=1&rft.spage=87&rft.isbn=&rft.btitle=&rft.title=Tumori&rft.issn=03008916&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-30 N1 - Date created - 1998-06-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dysregulation of apoptosis in hepatocellular carcinoma. AN - 79902356; 9606809 AB - The tightly controlled homeostatic mechanisms between cell growth and apoptosis that exist in normal liver tissue are disrupted during hepatocarcinogenesis. The TGF (transforming growth factor)-beta signaling system is a central component of the mechanisms by which cell growth and apoptosis are controlled in the liver. The recent delineation of the TGF-beta signaling pathway has provided a unique framework for analysis of the impact that disruption of individual components of this signaling pathway can have on apoptosis during hepatocarcinogenesis. Here we review recent data on involvement of the TGF-beta signaling pathway in the dysregulation of apoptosis frequently observed in hepatocellular carcinomas. The data indicate that disruption of the TGF-beta pathway at the pre-receptor, receptor, and post-receptor levels occurs in hepatocellular carcinomas and can cause dysregulation of apoptosis. Also, substantial evidence now exists that phosphatidylinositol-3-kinase (PI3K) may function as an important negative regulator of the TGF-beta 1-induced apoptosis in hepatocellular carcinomas. Taken together, the available evidence indicates that disruption of the TGF-beta 1-induced apoptosis as well as growth inhibition is an important and integral part of the multistage process of liver carcinogenesis. JF - Seminars in liver disease AU - Thorgeirsson, S S AU - Teramoto, T AU - Factor, V M AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 115 EP - 122 VL - 18 IS - 2 SN - 0272-8087, 0272-8087 KW - Transforming Growth Factor beta KW - 0 KW - Index Medicus KW - Transforming Growth Factor beta -- physiology KW - Humans KW - Signal Transduction KW - Liver Neoplasms -- pathology KW - Apoptosis -- physiology KW - Carcinoma, Hepatocellular -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79902356?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+liver+disease&rft.atitle=Dysregulation+of+apoptosis+in+hepatocellular+carcinoma.&rft.au=Thorgeirsson%2C+S+S%3BTeramoto%2C+T%3BFactor%2C+V+M&rft.aulast=Thorgeirsson&rft.aufirst=S&rft.date=1998-01-01&rft.volume=18&rft.issue=2&rft.spage=115&rft.isbn=&rft.btitle=&rft.title=Seminars+in+liver+disease&rft.issn=02728087&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-03 N1 - Date created - 1998-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alzheimer's disease. Cholinergic therapy and beyond. AN - 79864879; 9581222 AB - While much of the Alzheimer's disease (AD) research community turns its spotlight on genetics, molecular biology, and the neurotoxicity of beta-amyloid, there is a more subtle but equally significant shift in focus emerging within AD therapeutic circles. Once devoid of specific treatment options, the field now enjoys a choice of two Food and Drug Administration (FDA)-approved cholinesterase inhibitors and the prospect of several more in the near future. In addition, therapy for AD is rapidly expanding beyond the central cholinergic hypothesis to include neuroprotective agents and the possibility of interfering with basic mechanisms involved in the pathogenesis of this disorder. Clinically, we have entered the era of viable cholinergic therapies, and we are already moving beyond that starting point to an era of effective combination approaches. This article provides a clinical framework for these current and potential new therapies. JF - The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry AU - Sunderland, T AD - Geriatric Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892-1275, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - S56 EP - S63 VL - 6 IS - 2 Suppl 1 SN - 1064-7481, 1064-7481 KW - Cholinergic Agonists KW - 0 KW - Cholinesterase Inhibitors KW - Index Medicus KW - Aged, 80 and over KW - Humans KW - Aged KW - Middle Aged KW - Age Distribution KW - Alzheimer Disease -- genetics KW - Cholinesterase Inhibitors -- therapeutic use KW - Cholinergic Agonists -- therapeutic use KW - Alzheimer Disease -- therapy KW - Cognitive Therapy -- methods KW - Alzheimer Disease -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79864879?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+geriatric+psychiatry+%3A+official+journal+of+the+American+Association+for+Geriatric+Psychiatry&rft.atitle=Alzheimer%27s+disease.+Cholinergic+therapy+and+beyond.&rft.au=Sunderland%2C+T&rft.aulast=Sunderland&rft.aufirst=T&rft.date=1998-01-01&rft.volume=6&rft.issue=2+Suppl+1&rft.spage=S56&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+geriatric+psychiatry+%3A+official+journal+of+the+American+Association+for+Geriatric+Psychiatry&rft.issn=10647481&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-18 N1 - Date created - 1998-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular epidemiology of breast cancer. AN - 79841447; 9575425 AB - Molecular epidemiology evaluates cancer risk based upon environmental exposures and genetically determined susceptibilities. Biomarkers, molecular indicators of exposure or disease state, are used to stake out the progression of a disease along plausible mechanistic pathways. Connecting biomarkers of exposure, (e.g., carcinogen DNA adducts), effect (e.g., mutations in tumor suppressor genes), or disease (e.g., histological abnormalities) can clarify the etiology of cancer, improve risk estimates, and lead to better preventive strategies. In this review, the following evidence is used to evaluate the possible contribution of environmental carcinogens to breast cancer: a) genetic predispositions in familial breast cancer, b) mutational spectra of the p53 tumor suppressor gene, c) chemical carcinogenesis in breast cancer models, and d) genetic polymorphisms in sporadic breast cancer. JF - In vivo (Athens, Greece) AU - Goldman, R AU - Shields, P G AD - Division of Basic Research, National Cancer Institute, National Institute of Health, Bethesda, MD 20892-4255, USA. PY - 1998 SP - 43 EP - 48 VL - 12 IS - 1 SN - 0258-851X, 0258-851X KW - Carcinogens KW - 0 KW - Index Medicus KW - Smoking KW - Animals KW - Genes, p53 KW - Polymorphism, Genetic KW - Molecular Epidemiology KW - Risk Factors KW - Humans KW - Genetic Diseases, Inborn -- genetics KW - Mutation KW - Female KW - Breast Neoplasms -- genetics KW - Breast Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79841447?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=In+vivo+%28Athens%2C+Greece%29&rft.atitle=Molecular+epidemiology+of+breast+cancer.&rft.au=Goldman%2C+R%3BShields%2C+P+G&rft.aulast=Goldman&rft.aufirst=R&rft.date=1998-01-01&rft.volume=12&rft.issue=1&rft.spage=43&rft.isbn=&rft.btitle=&rft.title=In+vivo+%28Athens%2C+Greece%29&rft.issn=0258851X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-11 N1 - Date created - 1998-06-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacologic treatment of alcoholics with collateral depression: issues and future directions. AN - 79823878; 9564206 AB - Patients in treatment for alcoholism often suffer collateral depressive disorders. Fortunately, recent advances in medications development may significantly improve outcome for this population, but there remain several concerns about the clinical use of pharmacologic agents in these cases. These concerns are discussed, as are research findings that bear on them. Directions for future research are also identified. JF - Psychopharmacology bulletin AU - Litten, R Z AU - Allen, J P AD - Treatment Research Branch, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20892-7003, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 107 EP - 110 VL - 34 IS - 1 SN - 0048-5764, 0048-5764 KW - Index Medicus KW - Humans KW - Depressive Disorder -- drug therapy KW - Alcoholism -- complications KW - Depressive Disorder -- complications KW - Alcoholism -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79823878?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology+bulletin&rft.atitle=Pharmacologic+treatment+of+alcoholics+with+collateral+depression%3A+issues+and+future+directions.&rft.au=Litten%2C+R+Z%3BAllen%2C+J+P&rft.aulast=Litten&rft.aufirst=R&rft.date=1998-01-01&rft.volume=34&rft.issue=1&rft.spage=107&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology+bulletin&rft.issn=00485764&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - What you need to know: detecting alcohol problems in general medical practice. AN - 79809038; 9557105 AB - In the US, about 11% to 20% of patients presenting to general medical clinics are diagnosed as suffering from alcohol abuse or dependence. Alcohol screening in primary care settings, whether in the US or Singapore, can utilise various strategies for the early detection of alcohol problems. This paper briefly reviews several self-reports and screening procedures to assist general practitioners in identifying problem drinkers. The use of CAGE questionnaire, MAST, and its variation, SAAST and the AUDIT, are discussed and evaluated. Likewise, useful biochemical markers of excessive alcohol consumption like the liver enzymes (AST, ALT, GGT), MCV, CDT are described. They can be combined with each other to improve validity or used in conjunction with self-report screening tests for more accurate detection of problem drinkers. In particular, use of the AUDIT for routine screening of alcohol problems in primary care settings is recommended. Selective administration to those with at least two drinks per setting can overcome time constraints. Alternatively, sequential screening utilising the TRAUMA questionnaire with frequency and quantity questions administered to higher frequency drinkers can circumvent concerns about direct questioning. Use of self-reports and when possible, biochemical screening for alcohol problems should be a standard part of primary care practice. JF - Singapore medical journal AU - Allen, J AU - Litten, R Z AU - Lee, A AD - Treatment Research Branch, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892-7003, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 38 EP - 41 VL - 39 IS - 1 SN - 0037-5675, 0037-5675 KW - Biomarkers KW - 0 KW - Transferrin KW - Index Medicus KW - Family Practice -- standards KW - Humans KW - Biomarkers -- analysis KW - Transferrin -- analysis KW - Erythrocytes -- pathology KW - Liver -- enzymology KW - Alcoholism -- diagnosis KW - Surveys and Questionnaires KW - Alcoholism -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79809038?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Singapore+medical+journal&rft.atitle=What+you+need+to+know%3A+detecting+alcohol+problems+in+general+medical+practice.&rft.au=Allen%2C+J%3BLitten%2C+R+Z%3BLee%2C+A&rft.aulast=Allen&rft.aufirst=J&rft.date=1998-01-01&rft.volume=39&rft.issue=1&rft.spage=38&rft.isbn=&rft.btitle=&rft.title=Singapore+medical+journal&rft.issn=00375675&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-04 N1 - Date created - 1998-06-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular and cell biology of TGF-beta. AN - 79758415; 9525693 AB - The TGF-betas are a remarkable set of peptides consisting of three highly homologous isoforms, TGF-beta 1, 2, and 3. Distinguished initially for their ability to inhibit the growth of most epithelial and hematopoietic cells and to regulate the production of extracellular matrix by mesenchymal cells, these peptides are now known to act via autocrine, paracrine, and endocrine modes to control a wide variety of developmental processes and to play key roles in the pathogenesis of many diseases including especially fibrotic diseases, parasitic diseases, autoimmune diseases, and carcinogenesis. The activity of these peptides is under tight control by processes including regulation of the expression of the isoforms and their receptors and of the trafficking and activation of their latent forms. JF - Mineral and electrolyte metabolism AU - Roberts, A B AD - Laboratory of Chemoprevention, National Cancer Institute, Bethesda, MD 20892-5055, USA. robertsa@dce41.nci.nih.gov Y1 - 1998 PY - 1998 DA - 1998 SP - 111 EP - 119 VL - 24 IS - 2-3 SN - 0378-0392, 0378-0392 KW - Extracellular Matrix Proteins KW - 0 KW - Growth Inhibitors KW - Transforming Growth Factor beta KW - Index Medicus KW - Regulatory Sequences, Nucleic Acid KW - Animals KW - Epithelial Cells -- cytology KW - Humans KW - Hematopoietic Stem Cells -- cytology KW - Gene Expression KW - Extracellular Matrix Proteins -- biosynthesis KW - Cell Division KW - Transforming Growth Factor beta -- pharmacology KW - Transforming Growth Factor beta -- physiology KW - Transforming Growth Factor beta -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79758415?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mineral+and+electrolyte+metabolism&rft.atitle=Molecular+and+cell+biology+of+TGF-beta.&rft.au=Roberts%2C+A+B&rft.aulast=Roberts&rft.aufirst=A&rft.date=1998-01-01&rft.volume=24&rft.issue=2-3&rft.spage=111&rft.isbn=&rft.btitle=&rft.title=Mineral+and+electrolyte+metabolism&rft.issn=03780392&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-01 N1 - Date created - 1998-05-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase II study of suramin plus aminoglutethimide in two cohorts of patients with androgen-independent prostate cancer: simultaneous antiandrogen withdrawal and prior antiandrogen withdrawal. AN - 79744158; 9516950 AB - Management of prostate cancer progression after failure of initial hormonal therapy is controversial. Recently, the activity of the simple discontinuation of antiandrogen therapy has been established by several groups, as well as the enhanced activity when combined with adrenal suppression (i.e., aminoglutethimide and hydrocortisone). Furthermore, suramin has generated considerable interest following reports of response rates ranging from 17 to 70%. More recently, suramin response rates of 18 and 22% have been reported when the potential confounding variables of flutamide withdrawal and hydrocortisone were prospectively controlled. On the basis of the activity of combining aminoglutethimide with flutamide withdrawal, we designed a protocol in which suramin was combined with aminoglutethimide in two cohorts of patients (those with simultaneous antiandrogen withdrawal compared to those who had previously discontinued antiandrogen therapy). Eighty-one evaluable patients were enrolled in this study between June 1992 and November 1994. Patients were a priori divided into two cohorts, those receiving prior antiandrogen withdrawal (n = 56) and those receiving simultaneous antiandrogen withdrawal (n = 25) at the time the patients were enrolled into the trial. For the group that discontinued antiandrogen prior to enrolling in therapy, the partial response rate (> 50% decline in PSA for > 4 weeks) was 14.2%, whereas the partial response was 44% for those patients who discontinued their antiandrogen at the time of starting suramin and aminoglutethimide. The median time to progression was 3.9 months in patients failing prior antiandrogen withdrawal and 5.5 months in those patients having concomitant antiandrogen withdrawal (P = 0.36 for the overall difference). The progression-free survival estimate at 1 year for patients having prior antiandrogen withdrawal was 19.8% [95% confidence interval (CI), 11-32.9%]. For those patients who experienced antiandrogen withdrawal simultaneous with the treatment, the progression-free survival estimates at 1 and 2 years were 27.1 (95% CI, 13.2-47.6%) and 4.5% (95% CI, 0.8-21.6%). The median survival time for those patients having prior antiandrogen withdrawal was 14.2 months, whereas the median survival was 21.9 months for those having concomitant antiandrogen withdrawal (P = 0.029 for the overall difference). In conclusion, the partial response rate of 44% for those who had concomitant flutamide withdrawal with adrenal suppression was consistent with that of other reports using a similar maneuver. Although this study was not randomized and thus we should not over-interpret the results, flutamide withdrawal plus adrenal suppression appears to have greater activity than flutamide withdrawal alone. Furthermore, these data suggest that suramin adds little to the response rate observed for other adrenal suppressive agents in the presence of antiandrogen withdrawal. This interpretation is in agreement with those studies controlling for adrenal suppression and flutamide withdrawal prior to suramin administration, which noted modest activity of short duration. Given that antiandrogen withdrawal is now accepted as an active maneuver for a subset of patients progressing after maximum androgen blockade, we propose that future trials attempting to maximize response rates incorporate this maneuver whenever possible into prospectively designed regimens. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Dawson, N AU - Figg, W D AU - Brawley, O W AU - Bergan, R AU - Cooper, M R AU - Senderowicz, A AU - Headlee, D AU - Steinberg, S M AU - Sutherland, M AU - Patronas, N AU - Sausville, E AU - Linehan, W M AU - Reed, E AU - Sartor, O AD - Clinical Pharmacology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 37 EP - 44 VL - 4 IS - 1 SN - 1078-0432, 1078-0432 KW - Androgen Antagonists KW - 0 KW - Aminoglutethimide KW - 0O54ZQ14I9 KW - Suramin KW - 6032D45BEM KW - Index Medicus KW - Survival Rate KW - Aged, 80 and over KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Androgen Antagonists -- administration & dosage KW - Suramin -- adverse effects KW - Prostatic Neoplasms -- mortality KW - Aminoglutethimide -- administration & dosage KW - Suramin -- administration & dosage KW - Aminoglutethimide -- adverse effects KW - Prostatic Neoplasms -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79744158?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Phase+II+study+of+suramin+plus+aminoglutethimide+in+two+cohorts+of+patients+with+androgen-independent+prostate+cancer%3A+simultaneous+antiandrogen+withdrawal+and+prior+antiandrogen+withdrawal.&rft.au=Dawson%2C+N%3BFigg%2C+W+D%3BBrawley%2C+O+W%3BBergan%2C+R%3BCooper%2C+M+R%3BSenderowicz%2C+A%3BHeadlee%2C+D%3BSteinberg%2C+S+M%3BSutherland%2C+M%3BPatronas%2C+N%3BSausville%2C+E%3BLinehan%2C+W+M%3BReed%2C+E%3BSartor%2C+O&rft.aulast=Dawson&rft.aufirst=N&rft.date=1998-01-01&rft.volume=4&rft.issue=1&rft.spage=37&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-09 N1 - Date created - 1998-04-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Review of epidemiologic studies of alcohol and prostate cancer: 1971-1996. AN - 79732675; 9507506 AB - Prostate cancer is the most common cancer among American men, with few established risk factors. The association between prostate cancer and alcohol, a potentially modifiable risk factor, has been examined in numerous studies. We systematically reviewed the literature on alcohol and the incidence of prostate cancer by searching for published cohort and case-control studies using computerized databases, references, and experts, by evaluating studies for validity, and by summarizing the results and providing research recommendations. We found compelling evidence for no association between low-to-moderate alcohol consumption and prostate cancer. Most studies, however, did not assess the risk of heavy drinking, where there has been some suggestion of increased risk, or of lifetime patterns of drinking. None of the studies have used genetic markers, nor have they been conducted in populations with known familial risk. Further studies in some populations may be warranted. JF - Nutrition and cancer AU - Breslow, R A AU - Weed, D L AD - Division of Cancer Prevention and Control, National Cancer Institute, Bethesda, MD 20892, USA. BreslowR@dcpcepn.nci.nih.gov Y1 - 1998 PY - 1998 DA - 1998 SP - 1 EP - 13 VL - 30 IS - 1 SN - 0163-5581, 0163-5581 KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Risk Factors KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Ethanol -- adverse effects KW - Prostatic Neoplasms -- epidemiology KW - Prostatic Neoplasms -- chemically induced KW - Ethanol -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79732675?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nutrition+and+cancer&rft.atitle=Review+of+epidemiologic+studies+of+alcohol+and+prostate+cancer%3A+1971-1996.&rft.au=Breslow%2C+R+A%3BWeed%2C+D+L&rft.aulast=Breslow&rft.aufirst=R&rft.date=1998-01-01&rft.volume=30&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Nutrition+and+cancer&rft.issn=01635581&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-24 N1 - Date created - 1998-04-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The C3(1)/SV40 T antigen transgenic mouse model of prostate and mammary cancer. AN - 79722643; 9502400 JF - Toxicologic pathology AU - Shibata, M A AU - Jorcyk, C L AU - Liu, M L AU - Yoshidome, K AU - Gold, L G AU - Green, J E AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1998 SP - 177 EP - 182 VL - 26 IS - 1 SN - 0192-6233, 0192-6233 KW - Antigens, Polyomavirus Transforming KW - 0 KW - Index Medicus KW - Animals KW - Submandibular Gland Neoplasms -- pathology KW - Mice, Inbred C3H KW - Gene Expression KW - Bulbourethral Glands -- pathology KW - Prostate -- pathology KW - Mice KW - Prostatic Intraepithelial Neoplasia -- pathology KW - Urethral Neoplasms -- pathology KW - Male KW - Female KW - Prostatic Neoplasms -- pathology KW - Prostatic Neoplasms -- genetics KW - Mammary Neoplasms, Experimental -- genetics KW - Disease Models, Animal KW - Adenocarcinoma -- genetics KW - Antigens, Polyomavirus Transforming -- genetics KW - Mice, Transgenic -- genetics KW - Mammary Neoplasms, Experimental -- pathology KW - Adenocarcinoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79722643?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=The+C3%281%29%2FSV40+T+antigen+transgenic+mouse+model+of+prostate+and+mammary+cancer.&rft.au=Shibata%2C+M+A%3BJorcyk%2C+C+L%3BLiu%2C+M+L%3BYoshidome%2C+K%3BGold%2C+L+G%3BGreen%2C+J+E&rft.aulast=Shibata&rft.aufirst=M&rft.date=1998-01-01&rft.volume=26&rft.issue=1&rft.spage=177&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-09 N1 - Date created - 1998-04-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Family history of alcoholism and gender: their combined effects on DSM-IV alcohol dependence and major depression. AN - 79720848; 9498321 AB - Data from a representative sample of U.S. adults were used to assess the extent of familial alcoholism, to examine its association with the odds of DSM-IV lifetime alcohol dependence, major depression, and their comorbid occurrence, and to determine whether the magnitude of this association was different for men and women. Self-report data from a sample of 42,862 U.S. adults (25,043 women) 18 years of age and over were analyzed by means of multiple logistic regression models that predicted the odds of various combinations of DSM-IV alcohol dependence and major depression. After adjusting for potential confounders through multiple logistic regression, family history saturation was associated with increased odds of dependence only, depression only, and all primary-secondary-concurrent combinations of these two disorders. The estimated effects were greatest for comorbid dependence and depression, next highest for dependence only and lowest for depression only. Differences in odds ratios among these groups increased with degree of family history saturation but were statistically significant at all levels of saturation. The effects of family history were greater for men than women for the outcome of primary depression followed by secondary dependence, but only at the higher levels of saturation. Among persons with lifetime major depression, family history of alcoholism had a positive independent association with the conditional odds of having experienced comorbid alcohol dependence. It had a weaker but still significant association with the odds of comorbid depression, conditional upon having experienced dependence, and this association was stronger among men than among women. For most outcomes, family history effects were stronger for paternal male and maternal female relatives than for paternal female and maternal male relatives. These findings supported prior research showing more familial alcoholism among persons with comorbid dependence and depression than among those with dependence alone. Gender differences were supportive of the proposed distinction between pure depression and depressive-spectrum disease. JF - Journal of studies on alcohol AU - Dawson, D A AU - Grant, B F AD - Biometry Branch, Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-7003, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 97 EP - 106 VL - 59 IS - 1 SN - 0096-882X, 0096-882X KW - Index Medicus KW - Odds Ratio KW - Risk Factors KW - Models, Genetic KW - Humans KW - Adult KW - Longitudinal Studies KW - Male KW - Female KW - Comorbidity KW - Psychiatric Status Rating Scales KW - Depressive Disorder -- psychology KW - Alcoholism -- diagnosis KW - Child of Impaired Parents -- psychology KW - Depressive Disorder -- diagnosis KW - Depressive Disorder -- genetics KW - Gender Identity KW - Alcoholism -- genetics KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79720848?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+studies+on+alcohol&rft.atitle=Family+history+of+alcoholism+and+gender%3A+their+combined+effects+on+DSM-IV+alcohol+dependence+and+major+depression.&rft.au=Dawson%2C+D+A%3BGrant%2C+B+F&rft.aulast=Dawson&rft.aufirst=D&rft.date=1998-01-01&rft.volume=59&rft.issue=1&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=Journal+of+studies+on+alcohol&rft.issn=0096882X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-28 N1 - Date created - 1998-04-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Present imperfect: a critical review of animal models of the mnemonic impairments in Alzheimer's disease. AN - 79710837; 9491942 AB - This paper reviews the current literature on animal models of the memory impairments of Alzheimer's disease (AD). The authors suggest that modeling of the mnemonic deficits in AD be limited to the amnesia observed early in the course of the disease, to eliminate the influence of impairments in non-mnemonic processes. Tasks should be chosen for their specificity and selectivity to the behavioral phenomena observed in early-stage AD and not for their relevance to hypothetical mnemonic processes. Tasks that manipulate the delay between learning and remembering are better able to differentiate Alzheimer patients from persons with other disorders, and better able to differentiate effects of manipulations in animals. The most commonly used manipulations that attempt to model the amnesia of AD are reviewed within these constraints. The authors conclude that of the models examined, lesions of the medial septal nucleus produce behavioral deficits that are most similar to the mnemonic impairments in the earliest stage of AD. However, the parallel is not definitive and more work is needed to clarify the relationship between neurobiology and behavior in AD. JF - Neuroscience and biobehavioral reviews AU - McDonald, M P AU - Overmier, J B AD - Department of Psychology, University of Minnesota, Minneapolis 55455, USA. mikemc@codon.nih.gov Y1 - 1998 PY - 1998 DA - 1998 SP - 99 EP - 120 VL - 22 IS - 1 SN - 0149-7634, 0149-7634 KW - Index Medicus KW - Animals KW - Humans KW - Disease Models, Animal KW - Memory Disorders -- chemically induced KW - Alzheimer Disease -- psychology KW - Memory Disorders -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79710837?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience+and+biobehavioral+reviews&rft.atitle=Present+imperfect%3A+a+critical+review+of+animal+models+of+the+mnemonic+impairments+in+Alzheimer%27s+disease.&rft.au=McDonald%2C+M+P%3BOvermier%2C+J+B&rft.aulast=McDonald&rft.aufirst=M&rft.date=1998-01-01&rft.volume=22&rft.issue=1&rft.spage=99&rft.isbn=&rft.btitle=&rft.title=Neuroscience+and+biobehavioral+reviews&rft.issn=01497634&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-09 N1 - Date created - 1998-04-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mortality among United States radiologic technologists, 1926-90. AN - 79704641; 9486465 AB - The possible mortality risk from low level chronic exposures to ionizing radiation was evaluated among 143,517 United States radiologic technologists certified by the American Registry of Radiologic Technologists between 1926-80. This is one of the few occupational studies of primarily women (73 percent) exposed to radiation during their employment. More than 2.8 million person-years of follow-up were accrued through 1990, and 7,345 deaths were identified. A strong healthy-worker effect was observed (standardized mortality ratios [SMR] for all causes and all cancers were 0.69 and 0.79, respectively). Lung cancer (429 deaths) was not increased with available measures of radiation exposure and no significant associations were observed for acute, myelogenous, and monocytic leukemia (74 deaths). Relative to the general population, the standardized mortality ratio (SMR) for female breast cancer was 0.99 (based on 425 deaths); however, breast cancer was significantly elevated relative to all other cancers in a test of homogeneity of SMRs (ratio of SMRs = 1.3, P < 0.0001). Significant risks were correlated with employment before 1940 (SMR = 1.5; 95 percent confidence interval [CI] = 1.2-1.9), when radiation doses were likely highest, and among women certified for more than 30 years (SMR = 1.4, CI = 1.2-1.7) for whom the cumulative exposure was likely greatest. Using an internal referent group, risk increased with duration of certification among the 1,890 women certified before 1940 (P-trend < 0.001). While the findings for breast cancer are consistent with a radiation effect, possible misclassification in exposure (based on number of years certified) and potential confounding associated with reproductive histories preclude a causal conclusion. JF - Cancer causes & control : CCC AU - Doody, M M AU - Mandel, J S AU - Lubin, J H AU - Boice, J D AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 67 EP - 75 VL - 9 IS - 1 SN - 0957-5243, 0957-5243 KW - Index Medicus KW - Breast Neoplasms -- mortality KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Lung Neoplasms -- mortality KW - United States -- epidemiology KW - Time Factors KW - Male KW - Female KW - Cause of Death KW - Occupational Exposure KW - Mortality KW - Allied Health Personnel KW - Radiology -- manpower KW - Neoplasms, Radiation-Induced -- mortality KW - Radiation, Ionizing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79704641?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+causes+%26+control+%3A+CCC&rft.atitle=Mortality+among+United+States+radiologic+technologists%2C+1926-90.&rft.au=Doody%2C+M+M%3BMandel%2C+J+S%3BLubin%2C+J+H%3BBoice%2C+J+D&rft.aulast=Doody&rft.aufirst=M&rft.date=1998-01-01&rft.volume=9&rft.issue=1&rft.spage=67&rft.isbn=&rft.btitle=&rft.title=Cancer+causes+%26+control+%3A+CCC&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-07 N1 - Date created - 1998-04-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Aralkylation of guanosine with para-substituted styrene oxides. AN - 79693241; 9477225 AB - To probe mechanisms of nucleoside aralkylation, product distributions and product stereochemistries were determined in reactions of optically active p-methyl- and p-bromostyrene oxide with guanosine. The proportion of 7-, N2-, and O6-substituted guanosine products was approximately 0.32:0.62:0.06 in neutral, aqueous reactions with the (R)-p-methylstyrene oxide and approximately 0.85: 0.09:0.04 in reactions with the (R)-p-bromostyrene oxide. The exocyclic positions opened the epoxide at the alpha-carbon. Epoxide ring opening by the nitrogen at the 7-position showed little preference for the alpha- or beta-carbons in reactions with p-methylstyrene oxide. However, the p-bromostyrene oxide favored reaction at the beta-carbon almost 4-fold over reaction at the alpha-carbon. Almost total inversion of stereochemistry was found to occur in reactions at the 7-position. In contrast, the ratio of inversion to retention of configuration in N2- and O6-substituted products was approximately 2:1 and approximately 1:1 for reactions with the p-methylstyrene oxide and approximately 6:1 and approximately 3:1 for reactions with p-bromostyrene oxide, respectively. These experiments suggest that an SN2 mechanism is in effect with reactions at the 7-position, whereas substrates of an increasingly ionic nature are involved in reactions at the N2- and O6-positions, respectively. JF - Chemical research in toxicology AU - Barlow, T AU - Dipple, A AD - Chemistry of Carcinogenesis Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 44 EP - 53 VL - 11 IS - 1 SN - 0893-228X, 0893-228X KW - Carcinogens KW - 0 KW - DNA Adducts KW - Epoxy Compounds KW - Mutagens KW - Guanosine KW - 12133JR80S KW - styrene oxide KW - 9QH06NGT6O KW - Index Medicus KW - DNA Adducts -- chemistry KW - Carcinogens -- chemistry KW - Epoxy Compounds -- chemistry KW - Guanosine -- chemistry KW - Mutagens -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79693241?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Aralkylation+of+guanosine+with+para-substituted+styrene+oxides.&rft.au=Barlow%2C+T%3BDipple%2C+A&rft.aulast=Barlow&rft.aufirst=T&rft.date=1998-01-01&rft.volume=11&rft.issue=1&rft.spage=44&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-08 N1 - Date created - 1998-04-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cooperation of p53 loss of function and v-Ha-ras in transformation of mouse keratinocyte cell lines. AN - 79691206; 9473771 AB - We previously demonstrated that after transduction with the v-Ha-ras oncogene and grafting onto nude mouse hosts, primary epidermal keratinocytes with a null mutation in the p53 gene form tumors with increased growth rates and predisposition to malignant conversion relative to p53 wild-type keratinocytes (Weinberg WC, et al., Cancer Res 54:5584-5592, 1994). To further explore the cooperation between p53 loss of function and activation of the ras oncogene, cell lines were established from the normal epidermises of newborn and adult p53-null mice, and parallel subclones were reconstituted with the p53val135 temperature-sensitive mutant. Reconstituted lines C, G, N, and V demonstrated functional p53 transcriptional activator activity at the wild-type-permissive temperature of 32 degrees C, compared with the hygromycin-selected control line X and parental p53-null lines NHK4 and AK1b. Hygromycin-selected subclones, but not the parental lines, made normal skin in vivo; all cell lines made carcinomas after introduction of v-Ha-ras, independent of p53 status. These cell lines were compared in vitro at 32 degrees C to maximize the amount of p53val135 in the wild-type conformation. Expression of v-Ha-ras did not consistently alter p53-mediated transcriptional activity, suggesting tat ras acts downstream or independently of p53. No correlation was observed between p53-mediated transcriptional activity and in vitro growth rates, colony formation after exposure to ultraviolet light, or suppression by normal neighboring keratinocytes. However, keratinocyte cell lines devoid of p53 and expressing v-Ha-ras formed colonies in soft agar; this was blocked at 32 degrees C in all cell lines reconstituted with p53val135. These keratinocyte lines provide a model for exploring the role of p53 and the interaction of p53 and ras in keratinocyte transformation. JF - Molecular carcinogenesis AU - Azzoli, C G AU - Sagar, M AU - Wu, A AU - Lowry, D AU - Hennings, H AU - Morgan, D L AU - Weinberg, W C AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 50 EP - 61 VL - 21 IS - 1 SN - 0899-1987, 0899-1987 KW - Index Medicus KW - Animals KW - Ultraviolet Rays KW - Mice, Nude KW - Mice KW - Gene Expression Regulation KW - Cell Survival -- radiation effects KW - Cell Transplantation KW - Fluorescent Antibody Technique KW - Cell Division -- genetics KW - Gene Deletion KW - Keratinocytes -- radiation effects KW - Keratinocytes -- physiology KW - Cell Transformation, Neoplastic -- pathology KW - Genes, p53 -- physiology KW - Genes, ras -- physiology KW - Epidermis -- cytology KW - Genes, p53 -- genetics KW - Keratinocytes -- pathology KW - Keratinocytes -- metabolism KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79691206?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+carcinogenesis&rft.atitle=Cooperation+of+p53+loss+of+function+and+v-Ha-ras+in+transformation+of+mouse+keratinocyte+cell+lines.&rft.au=Azzoli%2C+C+G%3BSagar%2C+M%3BWu%2C+A%3BLowry%2C+D%3BHennings%2C+H%3BMorgan%2C+D+L%3BWeinberg%2C+W+C&rft.aulast=Azzoli&rft.aufirst=C&rft.date=1998-01-01&rft.volume=21&rft.issue=1&rft.spage=50&rft.isbn=&rft.btitle=&rft.title=Molecular+carcinogenesis&rft.issn=08991987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-02 N1 - Date created - 1998-03-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Altered expression of transforming growth factor betas during urethral and bulbourethral gland tumor progression in transgenic mice carrying the androgen-responsive C3(1) 5' flanking region fused to SV40 large T antigen. AN - 79691015; 9472712 AB - We demonstrate that targeted expression of SV40 large T antigen (TAg) to the urethral (periurethral) and bulbourethral gland epithelium leads to adenocarcinoma formation in these tissues after 7 months of age, which are extremely rare sites for spontaneous tumor formation in humans. The development of proliferative lesions in the urethral gland predictably follows a temporal course of progression with approximately one third of male animals developing urethral tumors by 1 year of age. Tumor progression in these organs correlates to the level of TAg and p53 expression. Immunoprecipitation confirmed that SV40 TAg protein was bound to p53 and Rb p110 in vivo. Expression of transforming growth factor beta (TGFbetas) was evaluated during tumor progression of urethral gland carcinomas. Elevations of intracellular and extracellular TGFbeta1 and extracellular TGFbeta3 were found in preneoplastic and neoplastic lesions, suggesting that increased TGFbetas may augment tumor growth. c-Met expression showed a tendency for increased expression in the urethral gland carcinomas. We speculate that the directed expression of SV40 TAg by the hormone responsive C3(1) gene and subsequent tumor formation in these organs is influenced by androgens, since these tissues and carcinomas express androgen receptor (AR) and arise only in male transgenic mice. Several cell lines established from the urethral carcinomas were also shown to express AR, but are not androgen dependent in culture. To our knowledge, this is the first transgenic animal model for urethral and bulbourethral carcinomas. This transgenic mouse model and the cell lines derived from it may provide a unique opportunity for dissecting molecular mechanisms involved in the tumorigenesis of these organs which otherwise rarely develop cancer. JF - Carcinogenesis AU - Shibata, M A AU - Jorcyk, C L AU - Devor, D E AU - Yoshidome, K AU - Rulong, S AU - Resau, J AU - Roche, N AU - Roberts, A B AU - Ward, J M AU - Green, J E AD - Laboratory of Cellular Regulation and Carcinogenesis, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 195 EP - 205 VL - 19 IS - 1 SN - 0143-3334, 0143-3334 KW - Androgen-Binding Protein KW - 0 KW - Antigens, Polyomavirus Transforming KW - Recombinant Fusion Proteins KW - Retinoblastoma Protein KW - Transforming Growth Factor beta KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Tumor Suppressor Protein p53 -- biosynthesis KW - Animals KW - Neoplasm Invasiveness KW - Recombinant Fusion Proteins -- biosynthesis KW - Aging KW - Mice KW - Liver Neoplasms -- secondary KW - Mice, Transgenic KW - Tumor Suppressor Protein p53 -- metabolism KW - Protein Binding KW - Liver Neoplasms -- pathology KW - Antigens, Polyomavirus Transforming -- biosynthesis KW - Simian virus 40 KW - Retinoblastoma Protein -- metabolism KW - Neoplasm Metastasis KW - Male KW - Transforming Growth Factor beta -- biosynthesis KW - Genital Neoplasms, Male -- pathology KW - Bulbourethral Glands KW - Genital Neoplasms, Male -- metabolism KW - Androgen-Binding Protein -- genetics KW - Urethral Neoplasms -- pathology KW - Urethral Neoplasms -- metabolism KW - Androgen-Binding Protein -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79691015?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Altered+expression+of+transforming+growth+factor+betas+during+urethral+and+bulbourethral+gland+tumor+progression+in+transgenic+mice+carrying+the+androgen-responsive+C3%281%29+5%27+flanking+region+fused+to+SV40+large+T+antigen.&rft.au=Shibata%2C+M+A%3BJorcyk%2C+C+L%3BDevor%2C+D+E%3BYoshidome%2C+K%3BRulong%2C+S%3BResau%2C+J%3BRoche%2C+N%3BRoberts%2C+A+B%3BWard%2C+J+M%3BGreen%2C+J+E&rft.aulast=Shibata&rft.aufirst=M&rft.date=1998-01-01&rft.volume=19&rft.issue=1&rft.spage=195&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-27 N1 - Date created - 1998-02-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Overexpression of phosphoinositide-specific phospholipase Cgamma in NIH 3T3 cells promotes transformation and tumorigenicity. AN - 79687993; 9472710 AB - Phosphoinositide-specific phospholipase Cgamma (PLCgamma) is a key regulatory enzyme that binds to the phosphoryl-tyrosine residues in the cytoplasmic domain of certain activated receptors and catalyses the hydrolysis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] forming IP3 and diacylglycerol (DAG) in response to several mitogenic factors. Previously, we determined that microinjected PLCgamma induces DNA synthesis in G0-arrested NIH 3T3 cells, suggesting the possibility that PLCgamma may have an oncogenic potential. In this report, we demonstrate that overexpression of PLCgamma in NIH 3T3 cells results in altered growth properties and cellular transformation. The PLCgamma/3T3 transfectants do not require serum growth factors to proliferate, display anchorage-independent growth in soft agar and induce tumors when transplanted into nude mice. These findings suggest that overexpression of PLCgamma facilitates the transformation of NIH 3T3 cells. Furthermore, PLCgamma expression and activity have been shown to be elevated in many human tumors. Thus, PLCgamma signaling may contribute to the promotion and/or progression of human cancers. JF - Carcinogenesis AU - Smith, M R AU - Court, D W AU - Kim, H K AU - Park, J B AU - Rhee, S G AU - Rhim, J S AU - Kung, H F AD - Intramural Research Support Program, SAIC Frederick, Laboratory of Biochemical Physiology, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702, USA. smithmr@mail.nclcrf.gov Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 177 EP - 185 VL - 19 IS - 1 SN - 0143-3334, 0143-3334 KW - Culture Media, Serum-Free KW - 0 KW - Isoenzymes KW - Recombinant Proteins KW - Type C Phospholipases KW - EC 3.1.4.- KW - Phospholipase C gamma KW - EC 3.1.4.3 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Humans KW - Mice KW - Mice, Nude KW - Neoplasms, Experimental -- pathology KW - Transfection KW - Flow Cytometry KW - Cell Cycle KW - Signal Transduction KW - Female KW - Cell Adhesion KW - Cell Division KW - Isoenzymes -- biosynthesis KW - Type C Phospholipases -- biosynthesis KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79687993?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Overexpression+of+phosphoinositide-specific+phospholipase+Cgamma+in+NIH+3T3+cells+promotes+transformation+and+tumorigenicity.&rft.au=Smith%2C+M+R%3BCourt%2C+D+W%3BKim%2C+H+K%3BPark%2C+J+B%3BRhee%2C+S+G%3BRhim%2C+J+S%3BKung%2C+H+F&rft.aulast=Smith&rft.aufirst=M&rft.date=1998-01-01&rft.volume=19&rft.issue=1&rft.spage=177&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-27 N1 - Date created - 1998-02-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Screening for alcohol problems in the military: recommended tests. AN - 79687529; 9465564 AB - This article suggests two new techniques for identifying alcohol problems in a military setting. The Alcohol Use Disorders Identification Test is a well validated self-report procedure and requires approximately 2 minutes for administration. Measurement of carbohydrate-deficient transferrin provides a useful biochemical index of recent heavy alcohol consumption. Employment of these tests could improve selection of individuals seeking entry to the military, aid recognition of current personnel in need of treatment, and assist in evaluating progress of patients in treatment. JF - Military medicine AU - Allen, J P AU - Cross, G M AU - Fertig, J B AU - Litten, R Z AD - National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892-7003, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 9 EP - 12 VL - 163 IS - 1 SN - 0026-4075, 0026-4075 KW - Biomarkers KW - 0 KW - Transferrin KW - carbohydrate-deficient transferrin KW - Index Medicus KW - Humans KW - Surveys and Questionnaires KW - Mass Screening -- methods KW - Biomarkers -- blood KW - Male KW - Female KW - Transferrin -- analogs & derivatives KW - Alcoholism -- diagnosis KW - Military Personnel KW - Transferrin -- analysis KW - Alcoholism -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79687529?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Military+medicine&rft.atitle=Screening+for+alcohol+problems+in+the+military%3A+recommended+tests.&rft.au=Allen%2C+J+P%3BCross%2C+G+M%3BFertig%2C+J+B%3BLitten%2C+R+Z&rft.aulast=Allen&rft.aufirst=J&rft.date=1998-01-01&rft.volume=163&rft.issue=1&rft.spage=9&rft.isbn=&rft.btitle=&rft.title=Military+medicine&rft.issn=00264075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-04 N1 - Date created - 1998-03-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Mil Med. 1998 Apr;163(4):ix [9575778] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regenerative hyperplasia is not required for liver tumor induction in female B6C3F1 mice exposed to trihalomethanes. AN - 79687353; 9465273 AB - Chloroform (TCM), a water disinfection by-product, induced liver tumors in female mice when administered by gavage in corn oil but not when given in drinking water at comparable daily doses. Because short-term studies showed that the gavage doses also induced liver toxicity, it has been suggested that the liver tumor response occurs secondary to cytotoxicity and consequent regenerative hyperplasia induced by oxidative metabolism of TCM to the toxic dihalocarbonyl intermediate. This study compares dose-response relationships of gavage-administered chlorinated/brominated trihalomethanes for hepatotoxicity, replicative DNA synthesis, and hepatocarcinogenicity in female B6C3F1 mice. The liver tumor data were obtained from previously published studies. Because bromine is a better leaving group than chlorine, metabolism of bromodichloromethane (BDCM) should produce the same intermediates as would be formed from TCM. Hence, the toxicity and carcinogenicity of BDCM was expected to be qualitatively similar to that of TCM. Dose responses for liver weight, serum sorbitol dehydrogenase and alanine aminotransferase (ALT) activities, hepatocyte degeneration, and hepatocyte labeling index (LI, a measure of replicative DNA synthesis) in female mice were similar following 3 weeks of gavage administration (once per day, 5 days per week) with TCM, BDCM, or chlorodibromomethane (CDBM). Fits of composite data for these trihalomethanes to a Hill equation model revealed sigmoidal dose responses for ALT activity and hepatocyte LI and a nearly linear low-dose response for liver tumor incidence. For this family of chemicals, the mouse liver tumor response was not associated with an elevated hepatocyte LI at doses of approximately 1 mmol/kg or less. High incidences of liver tumors were observed with BDCM and CDBM at doses that had a marginal effect or no effect on the hepatocyte LI. Thus, the carcinogenic effects of trihalomethanes are not simply a consequence of cytotoxicity and regenerative hyperplasia. The possible contributions from other activation pathways, including GSH conjugation and reductive metabolism, need to be considered in assessments of the carcinogenicity of the trihalomethanes. JF - Toxicology and applied pharmacology AU - Melnick, R L AU - Kohn, M C AU - Dunnick, J K AU - Leininger, J R AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. melnickr@niehs.nih.gov Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 137 EP - 147 VL - 148 IS - 1 SN - 0041-008X, 0041-008X KW - Carcinogens KW - 0 KW - Hydrocarbons, Brominated KW - Hydrocarbons, Halogenated KW - Trihalomethanes KW - chlorodibromomethane KW - 3T4AJR1H24 KW - bromodichloromethane KW - 7LN464CH2O KW - Chloroform KW - 7V31YC746X KW - L-Iditol 2-Dehydrogenase KW - EC 1.1.1.14 KW - Alanine Transaminase KW - EC 2.6.1.2 KW - bromoform KW - TUT9J99IMU KW - Index Medicus KW - Administration, Oral KW - Animals KW - Hyperplasia -- chemically induced KW - Alanine Transaminase -- blood KW - L-Iditol 2-Dehydrogenase -- blood KW - Dose-Response Relationship, Drug KW - Chloroform -- toxicity KW - Mice KW - Hydrocarbons, Brominated -- toxicity KW - Female KW - DNA Replication -- drug effects KW - Organ Size -- drug effects KW - Liver Neoplasms -- pathology KW - Liver -- pathology KW - Hydrocarbons, Halogenated -- toxicity KW - Liver -- drug effects KW - Liver Neoplasms -- enzymology KW - Liver Neoplasms -- chemically induced KW - Carcinogens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79687353?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Regenerative+hyperplasia+is+not+required+for+liver+tumor+induction+in+female+B6C3F1+mice+exposed+to+trihalomethanes.&rft.au=Melnick%2C+R+L%3BKohn%2C+M+C%3BDunnick%2C+J+K%3BLeininger%2C+J+R&rft.aulast=Melnick&rft.aufirst=R&rft.date=1998-01-01&rft.volume=148&rft.issue=1&rft.spage=137&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=0041008X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-24 N1 - Date created - 1998-02-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Toxicol Appl Pharmacol. 1998 Nov;153(1):133-6 [9875307] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An alternative test for trend in exposure-response analysis. AN - 79686535; 9470101 AB - The Mantel-extension chi-square test for overall trend is commonly used in evaluating dose-response relationships in epidemiologic studies. As illustrated by others, it is not an optimal test for a monotonic dose-response. In addition, the result of this test depends heavily upon the scores assigned to the exposure categories. The selection of the score may have a substantial impact on the test statistic and consequently, on the interpretation of the study results. A monotonic dose-response relationship exists when risk increases (or decreases) with increasing exposure. Although the Mantel-extension test is one of the most cited test for trend, it is not a sensitive test to reflect the incremental risk change of a dose-response relationship which may potentially generate misleading results. We propose an alternative test for the evaluation of monotonic dose-response, which reconfigurates the Mantel-Haenszel chi square test for dichotomous exposure series into a polychotomous exposure series. The proposed test generates chi values that are sensitive to incremental increase (or decrease) in risk at each exposure category and does not require exposure scores. The test is a simple summation of Mantel-Haenszel chi statistics obtained in for 2 x 2 tables over adjacent exposure categories (i.e., the sum of Mantel-Haenszel chi values between categories 1 and 2, 2 and 3, 3 and 4 and 1-1 and 1). Several examples are presented to illustrate that the proposed test generates more realistic chi values than those obtained by the Mantel-extension test for trend. JF - Journal of exposure analysis and environmental epidemiology AU - Dosemeci, M AU - Benichou, J AD - Epidemiology and Biostatistics Program, National Cancer Institute, Rockville, MD 20892, USA. DosemecM@epndce.nci.nih.gov PY - 1998 SP - 9 EP - 15 VL - 8 IS - 1 SN - 1053-4245, 1053-4245 KW - Environmental Pollutants KW - 0 KW - Index Medicus KW - Dose-Response Relationship, Drug KW - Humans KW - Chi-Square Distribution KW - Environmental Exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79686535?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+exposure+analysis+and+environmental+epidemiology&rft.atitle=An+alternative+test+for+trend+in+exposure-response+analysis.&rft.au=Dosemeci%2C+M%3BBenichou%2C+J&rft.aulast=Dosemeci&rft.aufirst=M&rft.date=1998-01-01&rft.volume=8&rft.issue=1&rft.spage=9&rft.isbn=&rft.btitle=&rft.title=Journal+of+exposure+analysis+and+environmental+epidemiology&rft.issn=10534245&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-04 N1 - Date created - 1998-03-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Safety of salivary gland-administered replication-deficient recombinant adenovirus in rats. AN - 79682696; 9466733 AB - We have examined the safety of a replication-deficient recombinant adenovirus administered at a single, high dose intraductally to rat submandibular glands or systemically via the femoral vein. The virus used directed the synthesis of human aquaporin-1, a water channel protein, and is termed AdhAQP1. Comparisons were made 1 and 9 days post-infection with animals administered either a similar virus encoding no transgene or the viral suspension buffer. Animals were specifically not given anti-inflammatory drugs to impede the well-known immunopathologic response to recombinant adenoviral administration. Serum chemistries and hematological parameters were monitored. Rats were subjected to complete gross necropsy and selected tissues were evaluated by histopathology. Most clinical chemistry and hematology values were within normal ranges; however, evidence of inflammation (e.g., elevated lactic dehydrogenase, total leukocyte count) was seen. Gross pathology was normal, as was histopathology, excepting rare focal areas of necrosis. The results show that intrasalivary gland or intravenous AdhAQP1 administration leads to low levels of toxicity in rats. JF - Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology AU - Delporte, C AU - Miller, G AU - Kagami, H AU - Lillibridge, C D AU - O'Connell, B C AU - Atkinson, J C AU - Baum, B J AD - Gene Therapy and Therapeutics Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 34 EP - 38 VL - 27 IS - 1 SN - 0904-2512, 0904-2512 KW - AQP1 protein, human KW - 0 KW - Aqp1 protein, rat KW - Aquaporins KW - Blood Group Antigens KW - Ion Channels KW - Aquaporin 1 KW - 146410-94-8 KW - Dentistry KW - Index Medicus KW - Animals KW - Humans KW - Safety KW - Submandibular Gland KW - Femoral Vein KW - Rats KW - Toxicity Tests KW - Inflammation -- etiology KW - Rats, Wistar KW - Immunohistochemistry KW - Male KW - Inflammation -- pathology KW - Genetic Vectors KW - Gene Transfer Techniques -- adverse effects KW - Ion Channels -- biosynthesis KW - Ion Channels -- genetics KW - Adenoviridae -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79682696?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+oral+pathology+%26+medicine+%3A+official+publication+of+the+International+Association+of+Oral+Pathologists+and+the+American+Academy+of+Oral+Pathology&rft.atitle=Safety+of+salivary+gland-administered+replication-deficient+recombinant+adenovirus+in+rats.&rft.au=Delporte%2C+C%3BMiller%2C+G%3BKagami%2C+H%3BLillibridge%2C+C+D%3BO%27Connell%2C+B+C%3BAtkinson%2C+J+C%3BBaum%2C+B+J&rft.aulast=Delporte&rft.aufirst=C&rft.date=1998-01-01&rft.volume=27&rft.issue=1&rft.spage=34&rft.isbn=&rft.btitle=&rft.title=Journal+of+oral+pathology+%26+medicine+%3A+official+publication+of+the+International+Association+of+Oral+Pathologists+and+the+American+Academy+of+Oral+Pathology&rft.issn=09042512&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-05 N1 - Date created - 1998-03-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reactive astrogliosis in neonatal rat spinal cord after exposure to cerebrospinal fluid from patients with amyotrophic lateral sclerosis. AN - 79681938; 9454639 AB - Previous studies have proposed the presence of circulating toxic factor(s) in the cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS). In the present study we show that there is an increased number of astrocytes intensely immunoreactive for glial fibrillary acidic protein (GFAP) in the gray matter of the spinal cords of neonatal rats exposed to ALS CSF. There is also increased expression of GFAP in the astrocytes of the white matter of neonatal rat spinal cords exposed to ALS CSF. Western blot analysis also confirmed the increased expression of GFAP. Accordingly, our study provides for the first time a clear evidence for the pathological response of glia to the circulating toxic factor(s) in the CSF of ALS patients. JF - Experimental neurology AU - Shahani, N AU - Nalini, A AU - Gourie-Devi, M AU - Raju, T R AD - Department of Neurophysiology, National Institute of Mental Health and Neurosciences, Bangalore, India. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 295 EP - 298 VL - 149 IS - 1 SN - 0014-4886, 0014-4886 KW - Glial Fibrillary Acidic Protein KW - 0 KW - Index Medicus KW - Rats KW - Animals KW - Humans KW - Rats, Wistar KW - Glial Fibrillary Acidic Protein -- metabolism KW - Immunologic Techniques KW - Cerebrospinal Fluid -- physiology KW - Gliosis -- pathology KW - Amyotrophic Lateral Sclerosis -- cerebrospinal fluid KW - Spinal Cord -- pathology KW - Astrocytes -- pathology KW - Animals, Newborn -- physiology KW - Astrocytes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79681938?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+neurology&rft.atitle=Reactive+astrogliosis+in+neonatal+rat+spinal+cord+after+exposure+to+cerebrospinal+fluid+from+patients+with+amyotrophic+lateral+sclerosis.&rft.au=Shahani%2C+N%3BNalini%2C+A%3BGourie-Devi%2C+M%3BRaju%2C+T+R&rft.aulast=Shahani&rft.aufirst=N&rft.date=1998-01-01&rft.volume=149&rft.issue=1&rft.spage=295&rft.isbn=&rft.btitle=&rft.title=Experimental+neurology&rft.issn=00144886&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-06 N1 - Date created - 1998-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transforming growth factor-betas in neurodegenerative disease. AN - 79677199; 9460794 AB - Transforming growth factors-betas (TGF-betas), a family of multifunctional peptide growth factors, affect cells of the central nervous system (CNS). The three mammalian TGF-beta isoforms, TGF-betas 1, 2 and 3, are expressed in adult human brain. Since neuronal degeneration is a defining feature of CNS degenerative diseases, TGF-beta may be important because it can influence neuronal survival. In vitro TGF-beta promotes survival of rat spinal cord motoneurons and dopaminergic neurons. In addition to direct effects on neuronal survival, TGF-beta treatment of cultured astrocytes induces a reactive phenotype. Thus, TGF-beta may also normalize the extracellular matrix environment in degenerative diseases. The expression of TGF-betas change in response to neuronal injury. TGF-beta 1 expression increases in astrocytes and microglia in animal models of cerebral ischemia, while TGF-beta 2 expression increases in activated astroglial cells in human neurodegenerative diseases. TGF-betas protect neurons from a variety of insults. TGF-beta maintains survival of chick telencephalic neurons made hypoxic by treatment with cyanide and decreases the area of infarction when administered in animal models of cerebral ischemia. In vitro TGF-beta protects neurons from damage induced by treatment with beta-amyloid peptide, FeSO4 (induces production of reactive oxygen species), Ca2+ ionophores, glutamate, glutamate receptor agonists and MPTP (toxic for dopaminergic neurons). TGF-beta maintains mitochondrial potential and Ca2+ homeostasis and inhibits apoptosis in neurons. TGF-beta does not prevent neuronal degeneration in a rat model of Parkinson's disease and has yet to be tested in newly developed transgenic mouse models of Alzheimer's disease. TGF-beta is a potent neuroprotective agent which may affect the pathogenesis of neurodegenerative diseases of the CNS. JF - Progress in neurobiology AU - Flanders, K C AU - Ren, R F AU - Lippa, C F AD - Laboratory of Chemoprevention, National Cancer Institute, Bethesda, MD 20892-5055, USA. FLANDERK@DCE41.NCI.NIH.GOV Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 71 EP - 85 VL - 54 IS - 1 SN - 0301-0082, 0301-0082 KW - Transforming Growth Factor beta KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Disease Models, Animal KW - Transforming Growth Factor beta -- physiology KW - Neurodegenerative Diseases -- metabolism KW - Neurodegenerative Diseases -- pathology KW - Transforming Growth Factor beta -- chemistry KW - Transforming Growth Factor beta -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79677199?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Progress+in+neurobiology&rft.atitle=Transforming+growth+factor-betas+in+neurodegenerative+disease.&rft.au=Flanders%2C+K+C%3BRen%2C+R+F%3BLippa%2C+C+F&rft.aulast=Flanders&rft.aufirst=K&rft.date=1998-01-01&rft.volume=54&rft.issue=1&rft.spage=71&rft.isbn=&rft.btitle=&rft.title=Progress+in+neurobiology&rft.issn=03010082&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-17 N1 - Date created - 1998-03-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protein kinase C regulation of organic anion transport in renal proximal tubule. AN - 79675871; 9458835 AB - Fluorescence microscopy and digital image analysis were used to examine the role of protein kinase C (PKC) in the control of organic anion (fluorescein, FL) transport in killifish renal proximal tubules. Phorbol ester (1-100 nM) reduced cellular and luminal accumulation of FL, and protein kinase inhibitors [staurosporine and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, 10-1,000 nM] increased cellular and luminal accumulation. Phorbol ester effects were blocked by staurosporine. The increases in tissue fluorescence caused by staurosporine were blocked by p-aminohippurate, indicating that they represent increased FL transport on the organic anion system. Neither phorbol ester nor staurosporine had any effects on the cell-to-lumen transport of a fluorescent organic anion that was generated intracellularly from a nonfluorescent, uncharged precursor. Finally, studies with a fluorescent PKC inhibitor showed that phorbol ester caused PKC translocation from cytoplasm to the plasma membrane. Together, these findings indicate that renal organic anion transport is negatively correlated with PKC activity and that PKC directly or indirectly controls the basolateral step in transport. JF - The American journal of physiology AU - Miller, D S AD - Intracellular Regulation Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - F156 EP - F164 VL - 274 IS - 1 Pt 2 SN - 0002-9513, 0002-9513 KW - Enzyme Inhibitors KW - 0 KW - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine KW - 84477-87-2 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Staurosporine KW - H88EPA0A3N KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Fluorescein KW - TPY09G7XIR KW - Index Medicus KW - Animals KW - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine -- pharmacology KW - Staurosporine -- pharmacology KW - Epithelial Cells -- physiology KW - Epithelial Cells -- drug effects KW - Killifishes KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Homeostasis KW - Models, Biological KW - Biological Transport -- drug effects KW - Protein Kinase C -- metabolism KW - Kidney Tubules, Proximal -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79675871?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+physiology&rft.atitle=Protein+kinase+C+regulation+of+organic+anion+transport+in+renal+proximal+tubule.&rft.au=Miller%2C+D+S&rft.aulast=Miller&rft.aufirst=D&rft.date=1998-01-01&rft.volume=274&rft.issue=1+Pt+2&rft.spage=F156&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+physiology&rft.issn=00029513&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-23 N1 - Date created - 1998-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fibrin sheath formation and chemotherapy extravasation: a case report. AN - 79674730; 9458537 AB - Fibrin sheath formation around venous access devices (VADs) frequently leads to persistent withdrawal occlusion (PWO). PWO is a common problem encountered with VADs. Although PWO is often easily managed with small doses of thrombolytic therapy (e.g., urokinase), it could result in a more serious complication, such as chemotherapy extravasation. Careful assessment of all VADs is important to identify complications such as fibrin sheath formation, which can potentially lead to extravasation. To rule out fibrin sheath formation, catheter dye studies need to be obtained when fibrinolytic therapy has failed to restore catheter function. The purpose of this paper is to illustrate a retrospective case report demonstrating drug extravasation caused by the development of fibrin sheath formation. JF - Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer AU - Mayo, D J AD - National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 51 EP - 56 VL - 6 IS - 1 SN - 0941-4355, 0941-4355 KW - Cyclophosphamide KW - 8N3DW7272P KW - Fibrin KW - 9001-31-4 KW - Plasminogen Activators KW - EC 3.4.21.- KW - Urokinase-Type Plasminogen Activator KW - EC 3.4.21.73 KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Breast Neoplasms -- drug therapy KW - Cyclophosphamide -- administration & dosage KW - Paclitaxel -- administration & dosage KW - Urokinase-Type Plasminogen Activator -- therapeutic use KW - Humans KW - Constriction, Pathologic -- etiology KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Equipment Failure KW - Plasminogen Activators -- therapeutic use KW - Constriction, Pathologic -- drug therapy KW - Middle Aged KW - Infusions, Intravenous -- instrumentation KW - Female KW - Catheterization, Central Venous -- adverse effects KW - Fibrin -- metabolism KW - Catheters, Indwelling -- adverse effects KW - Extravasation of Diagnostic and Therapeutic Materials -- etiology KW - Extravasation of Diagnostic and Therapeutic Materials -- drug therapy KW - Catheterization, Central Venous -- instrumentation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79674730?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Supportive+care+in+cancer+%3A+official+journal+of+the+Multinational+Association+of+Supportive+Care+in+Cancer&rft.atitle=Fibrin+sheath+formation+and+chemotherapy+extravasation%3A+a+case+report.&rft.au=Mayo%2C+D+J&rft.aulast=Mayo&rft.aufirst=D&rft.date=1998-01-01&rft.volume=6&rft.issue=1&rft.spage=51&rft.isbn=&rft.btitle=&rft.title=Supportive+care+in+cancer+%3A+official+journal+of+the+Multinational+Association+of+Supportive+Care+in+Cancer&rft.issn=09414355&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-19 N1 - Date created - 1998-03-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A high-risk lesion for invasive breast cancer, ductal carcinoma in situ, exhibits frequent overexpression of retinoid X receptor. AN - 79674122; 9456240 AB - The development of prevention strategies for breast cancer will require a molecular map of carcinogenesis. We have investigated gene expression patterns in premalignant and early carcinomatous human breast lesions that confer to the patient varying risks for developing invasive breast cancer. The relative expression levels of one of the retinoid receptors, retinoid X receptor (RXR), was determined by in situ hybridization to 58 biopsy specimens; RXR mRNA grain density over each lesion was compared to that over the normal ductal/lobular units in each section. Overexpression of RXR mRNA was observed in 66% of noncomedo ductal carcinoma in situ (DCIS), which confer a >8-fold increase in breast cancer risk, and 88% of comedo DCIS lesions, which are associated with a yet higher risk. In contrast, only 8% of lesions that confer little or no increase in breast cancer risk overexpressed RXR mRNA (P = 0.0008). Limited in situ hybridization data using retinoic acid receptor (RAR) riboprobes showed overexpression of RAR alpha, but not RAR beta or -gamma, in only a modest percentage (36%) of cases, suggesting that all members of the retinoid receptor superfamily are not similarly regulated. Immunohistochemistry performed on 52 DCIS specimens for alpha, beta, and gamma isoforms of RXR confirmed its overexpression at the protein level and implicate RXR alpha as the predominant overexpressed form. The data indicate that RXR overexpression is associated with an increased risk for the development of invasive breast cancer in human breast lesions and suggest the hypothesis that it is causally involved in breast oncogenesis. The implications for retinoid chemoprevention are discussed. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Lawrence, J A AU - Merino, M J AU - Simpson, J F AU - Manrow, R E AU - Page, D L AU - Steeg, P S AD - Chemprevention Branch, Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland 20892, USA. julial@helix.nih.gov Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 29 EP - 35 VL - 7 IS - 1 SN - 1055-9965, 1055-9965 KW - Biomarkers, Tumor KW - 0 KW - Receptors, Retinoic Acid KW - Retinoid X Receptors KW - Retinoids KW - Transcription Factors KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - Risk KW - Neoplasm Invasiveness KW - In Situ Hybridization KW - Retinoids -- therapeutic use KW - Humans KW - In Vitro Techniques KW - Cohort Studies KW - Up-Regulation KW - Female KW - Receptors, Retinoic Acid -- metabolism KW - Breast Neoplasms -- genetics KW - Biomarkers, Tumor -- metabolism KW - Carcinoma in Situ -- pathology KW - Carcinoma, Ductal, Breast -- pathology KW - Breast Neoplasms -- pathology KW - Transcription Factors -- metabolism KW - Carcinoma in Situ -- genetics KW - Carcinoma, Ductal, Breast -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79674122?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=A+high-risk+lesion+for+invasive+breast+cancer%2C+ductal+carcinoma+in+situ%2C+exhibits+frequent+overexpression+of+retinoid+X+receptor.&rft.au=Lawrence%2C+J+A%3BMerino%2C+M+J%3BSimpson%2C+J+F%3BManrow%2C+R+E%3BPage%2C+D+L%3BSteeg%2C+P+S&rft.aulast=Lawrence&rft.aufirst=J&rft.date=1998-01-01&rft.volume=7&rft.issue=1&rft.spage=29&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-03-11 N1 - Date created - 1998-03-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nuclear factor-kappa B contributes to excitotoxin-induced apoptosis in rat striatum. AN - 79671036; 9443930 AB - Excitotoxin-induced destruction of striatal neurons, proposed as a model of Huntington's disease, involves a process having the biochemical stigmata of apoptosis. Recent studies suggested that transcription factor nuclear factor (NF)-kappa B may be involved in excitotoxicity. To further analyze the contribution of NF kappa B to excitotoxic neuronal death in vivo, changes in binding activities of NF kappa B and other transcription factors as well as the consequences of inhibiting NF kappa B nuclear translocation were measured after the infusion of quinolinic acid (120 nmol) into rat striatum. Internucleosomal DNA fragmentation and terminal transferase-mediated dUTP digoxigenin nick end labeling-positive nuclei appeared 12 hr later and intensified over the next 12 hr. NF kappa B binding activity increased several-fold from 2 to 12 hr, then gradually declined during the next 12 hr. Other transcription factor changes included AP-1, whose binding peaked about 6 hr after quinolinic acid administration, and E2F-1, which was only modestly and transiently elevated. In contrast, quinolinic acid lead to a reduction in OCT-1, beginning after 12 hr, and briefly in SP-1 binding. The NF kappa B, AP-1, and OCT-1 changes were attenuated both by the N-methyl-D-aspartate receptor antagonist MK-801 and the protein synthesis inhibitor cycloheximide. Moreover, quinolinic acid-induced internucleosomal DNA fragmentation and striatal cell death were significantly reduced by the intrastriatal administration of NF kappa B SN50, a cell-permeable recombinant peptide that blocks NF kappa B nuclear translocation. These results illustrate the complex temporal pattern of transcription factor change attending the apoptotic destruction produced in rat striatum by quinolinic acid. They further suggest that NF kappa B activation contributes to the excitotoxin-induced death of striatal neurons. JF - Molecular pharmacology AU - Qin, Z H AU - Wang, Y AU - Nakai, M AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 33 EP - 42 VL - 53 IS - 1 SN - 0026-895X, 0026-895X KW - NF-kappa B KW - 0 KW - Neurotoxins KW - Nucleosomes KW - Receptors, N-Methyl-D-Aspartate KW - Transcription Factors KW - DNA KW - 9007-49-2 KW - Quinolinic Acid KW - F6F0HK1URN KW - Index Medicus KW - Rats KW - Receptors, N-Methyl-D-Aspartate -- biosynthesis KW - Animals KW - Rats, Sprague-Dawley KW - Transcription Factors -- metabolism KW - DNA Damage KW - Neurons -- drug effects KW - DNA -- metabolism KW - Nucleosomes -- metabolism KW - Neurons -- cytology KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Quinolinic Acid -- toxicity KW - Corpus Striatum -- cytology KW - Apoptosis -- physiology KW - Apoptosis -- drug effects KW - Corpus Striatum -- drug effects KW - NF-kappa B -- physiology KW - Neurotoxins -- toxicity KW - NF-kappa B -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79671036?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=Nuclear+factor-kappa+B+contributes+to+excitotoxin-induced+apoptosis+in+rat+striatum.&rft.au=Qin%2C+Z+H%3BWang%2C+Y%3BNakai%2C+M%3BChase%2C+T+N&rft.aulast=Qin&rft.aufirst=Z&rft.date=1998-01-01&rft.volume=53&rft.issue=1&rft.spage=33&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-20 N1 - Date created - 1998-02-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structure-activity analysis of the interaction of curacin A, the potent colchicine site antimitotic agent, with tubulin and effects of analogs on the growth of MCF-7 breast cancer cells. AN - 79670304; 9443933 AB - Originally purified as a major lipid component of a strain of the cyanobacterium Lyngbya majuscula isolated in Curaçao, curacin A is a potent inhibitor of cell growth and mitosis, binding rapidly and tightly at the colchicine site of tubulin. Because its molecular structure differs so greatly from that of colchicine and other colchicine site inhibitors, we prepared a series of curacin A analogs to determine the important structural features of the molecule. These modifications include reduction and E-to-Z transitions of the olefinic bonds in the 14-carbon side chain of the molecule; disruption of and configurational changes in the cyclopropyl moiety; disruption, oxidation, and configurational reversal in the thiazoline moiety; configurational reversal and substituent modifications at C13; and demethylation at C10. Inhibitory effects on tubulin assembly, the binding of colchicine to tubulin, and the growth of MCF-7 human breast carcinoma cells were examined. The most important portions of curacin A required for its interaction with tubulin seem to be the thiazoline ring and the side chain at least through C4, the portion of the side chain including the C9-C10 olefinic bond, and the C10 methyl group. Only two modifications totally eliminated the tubulin-drug interaction. The inactive compounds were a segment containing most of the side chain, including its two substituents, and analogs in which the methyl group at the C13 oxygen atom was replaced by a benzoate residue. Antiproliferative activity comparable with that observed with curacin A was only reproduced in compounds that were potent inhibitors of the binding of colchicine to tubulin. Molecular modeling and quantitative structure-activity relationship studies demonstrated that most active analogs overlapped extensively with curacin A but failed to provide an explanation for the apparent structural analogy between curacin A and colchicine. JF - Molecular pharmacology AU - Verdier-Pinard, P AU - Lai, J Y AU - Yoo, H D AU - Yu, J AU - Marquez, B AU - Nagle, D G AU - Nambu, M AU - White, J D AU - Falck, J R AU - Gerwick, W H AU - Day, B W AU - Hamel, E AD - Laboratory of Drug Discovery Research and Development, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 62 EP - 76 VL - 53 IS - 1 SN - 0026-895X, 0026-895X KW - Antineoplastic Agents KW - 0 KW - Cyclopropanes KW - DNA, Neoplasm KW - Thiazoles KW - Tubulin KW - curacin A KW - 155233-30-0 KW - Colchicine KW - SML2Y3J35T KW - Index Medicus KW - Animals KW - Drug Interactions KW - Models, Molecular KW - Humans KW - Cell Division -- drug effects KW - Structure-Activity Relationship KW - Binding Sites KW - G2 Phase -- physiology KW - Cattle KW - G2 Phase -- drug effects KW - Tumor Cells, Cultured KW - Mitosis KW - Models, Chemical KW - Molecular Conformation KW - DNA, Neoplasm -- metabolism KW - Thiazoles -- pharmacology KW - Breast Neoplasms -- drug therapy KW - Cyclopropanes -- metabolism KW - Breast Neoplasms -- pathology KW - Thiazoles -- metabolism KW - Antineoplastic Agents -- metabolism KW - Tubulin -- metabolism KW - Cyclopropanes -- pharmacology KW - Breast Neoplasms -- embryology KW - Antineoplastic Agents -- pharmacology KW - Colchicine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79670304?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=Structure-activity+analysis+of+the+interaction+of+curacin+A%2C+the+potent+colchicine+site+antimitotic+agent%2C+with+tubulin+and+effects+of+analogs+on+the+growth+of+MCF-7+breast+cancer+cells.&rft.au=Verdier-Pinard%2C+P%3BLai%2C+J+Y%3BYoo%2C+H+D%3BYu%2C+J%3BMarquez%2C+B%3BNagle%2C+D+G%3BNambu%2C+M%3BWhite%2C+J+D%3BFalck%2C+J+R%3BGerwick%2C+W+H%3BDay%2C+B+W%3BHamel%2C+E&rft.aulast=Verdier-Pinard&rft.aufirst=P&rft.date=1998-01-01&rft.volume=53&rft.issue=1&rft.spage=62&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-20 N1 - Date created - 1998-02-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bcl-2 immunohistochemistry in a surgical series of non-small cell lung cancer patients. AN - 79663434; 9445135 AB - The bcl-2 gene is implicated in oncogenesis by its ability to prolong cell survival through the inhibition of apoptosis, without increasing cell proliferation. An association between immunohistochemical staining for bcl-2 protein and the histological type and prognosis of non-small cell carcinoma was hypothesized by Pezzella et al. (N Engl J Med 329:690-694, 1993). In a case series, we stained formalin-fixed, paraffin-embedded tumor tissue from 106 surgical non-small cell lung cancer patients with an antibody to bcl-2 protein (DAKO clone 124, Carpinteria, CA). The resulting bcl-2 staining data were evaluated for associations with demographic, histological, immunohistochemical, and genetic features, including p53 mutations. Bcl-2 staining was observed in tumors from 29 of 106 (27%) of subjects, but was significantly less frequent in subjects' adenocarcinoma histology (8 of 55, 14.6%) (P = .007). This finding persisted after adjustment for age, gender, stage, grade, smoking history, and disease-free survival. In univariate analyses, no association was seen with age, weight, body mass index, gender, or pack-years smoking; tumor grade, stage, or patient performance status; p53 or c-erbB2 immunohistochemical staining, or p53 mutations. These data agree with earlier reports that bcl-2 staining is less common in adenocarcinomas; however, our data do not support the hypothesis that bcl-2 staining confers a better prognosis overall, in squamous cell carcinoma, or in an older patient population. JF - Human pathology AU - Fleming, M V AU - Guinee, D G AU - Chu, W S AU - Freedman, A N AU - Caporaso, N E AU - Bennett, W P AU - Colby, T V AU - Tazelaar, H AU - Abbondanzo, S L AU - Jett, J AU - Pairolero, P AU - Trastek, V AU - Liotta, L A AU - Harris, C C AU - Travis, W D AD - Laboratory of Human Carcinogenesis, NCI, NIH, Bethesda, MD, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 60 EP - 64 VL - 29 IS - 1 SN - 0046-8177, 0046-8177 KW - Proto-Oncogene Proteins c-bcl-2 KW - 0 KW - Tumor Suppressor Protein p53 KW - Receptor, ErbB-2 KW - EC 2.7.10.1 KW - Index Medicus KW - Adenocarcinoma -- metabolism KW - Tumor Suppressor Protein p53 -- analysis KW - Receptor, ErbB-2 -- metabolism KW - Humans KW - Genes, p53 -- genetics KW - Carcinoma, Squamous Cell -- metabolism KW - Middle Aged KW - Immunohistochemistry KW - Male KW - Female KW - Carcinoma, Large Cell -- metabolism KW - Carcinoma, Non-Small-Cell Lung -- metabolism KW - Proto-Oncogene Proteins c-bcl-2 -- analysis KW - Lung Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79663434?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+pathology&rft.atitle=Bcl-2+immunohistochemistry+in+a+surgical+series+of+non-small+cell+lung+cancer+patients.&rft.au=Fleming%2C+M+V%3BGuinee%2C+D+G%3BChu%2C+W+S%3BFreedman%2C+A+N%3BCaporaso%2C+N+E%3BBennett%2C+W+P%3BColby%2C+T+V%3BTazelaar%2C+H%3BAbbondanzo%2C+S+L%3BJett%2C+J%3BPairolero%2C+P%3BTrastek%2C+V%3BLiotta%2C+L+A%3BHarris%2C+C+C%3BTravis%2C+W+D&rft.aulast=Fleming&rft.aufirst=M&rft.date=1998-01-01&rft.volume=29&rft.issue=1&rft.spage=60&rft.isbn=&rft.btitle=&rft.title=Human+pathology&rft.issn=00468177&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-05 N1 - Date created - 1998-02-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The immunophilin FKBP65 forms an association with the serine/threonine kinase c-Raf-1. AN - 79660771; 9438387 AB - FKBP65 is a member of the FK506-binding protein class of immunophilins and is the only member reported to contain four peptidylprolyl cis-trans isomerase domains and an unrelated COOH-terminal domain. In this report, we show that the heat shock protein hsp90 and the serine/threonine protein kinase c-Raf-1 are components of FKBP65 immune complexes. The NH2-terminal regulatory domain of c-Raf-1 appears to be required for its interaction with FKBP65. Using GST-FKBP65 fusion protein and purified Raf proteins, we show that full-length FKBP65 can interact with c-Raf-1 but not B-Raf. The activation kinetics of c-Raf-1 after v-H-RasV12 injection of Xenopus oocytes appear to correlate with FKBP65/c-Raf-1 interaction, suggesting that FKBP65 may preferentially associate with forms of c-Raf-1 that are more posttranslationally modified. The interaction of FKBP65 with the c-Raf-heat shock protein 90 heterocomplex implicates this immunophilin in signal-transduction processes. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Coss, M C AU - Stephens, R M AU - Morrison, D K AU - Winterstein, D AU - Smith, L M AU - Simek, S L AD - Division of Basic Science, National Cancer Institute-Frederick Cancer Research and Development Center, NIH, Frederick, Maryland 21702-1201, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 41 EP - 48 VL - 9 IS - 1 SN - 1044-9523, 1044-9523 KW - Carrier Proteins KW - 0 KW - DNA-Binding Proteins KW - FK506-binding protein, Xenopus KW - HSP90 Heat-Shock Proteins KW - Recombinant Fusion Proteins KW - Xenopus Proteins KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Proto-Oncogene Proteins c-raf KW - EC 2.7.11.1 KW - Tacrolimus Binding Proteins KW - EC 5.2.1.- KW - Index Medicus KW - Recombinant Fusion Proteins -- metabolism KW - Xenopus laevis KW - Animals KW - Spodoptera KW - Glutathione Transferase -- metabolism KW - HSP90 Heat-Shock Proteins -- metabolism KW - Protein Binding KW - Mutagenesis KW - Carrier Proteins -- metabolism KW - Proto-Oncogene Proteins c-raf -- genetics KW - Proto-Oncogene Proteins c-raf -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79660771?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=The+immunophilin+FKBP65+forms+an+association+with+the+serine%2Fthreonine+kinase+c-Raf-1.&rft.au=Coss%2C+M+C%3BStephens%2C+R+M%3BMorrison%2C+D+K%3BWinterstein%2C+D%3BSmith%2C+L+M%3BSimek%2C+S+L&rft.aulast=Coss&rft.aufirst=M&rft.date=1998-01-01&rft.volume=9&rft.issue=1&rft.spage=41&rft.isbn=&rft.btitle=&rft.title=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10449523&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-06 N1 - Date created - 1998-02-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ethics of randomized clinical trials. AN - 79659755; 9440766 JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Emanuel, E J AU - Patterson, W B AD - Dana-Farber Cancer Institute, Boston, MA 02115-6084, USA. eemanuel@nih.gov Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 365 EP - 6; discussion 366-71 VL - 16 IS - 1 SN - 0732-183X, 0732-183X KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Paclitaxel KW - P88XT4IS4D KW - Cisplatin KW - Q20Q21Q62J KW - Fluorouracil KW - U3P01618RT KW - Methotrexate KW - YL5FZ2Y5U1 KW - Bioethics KW - Index Medicus KW - Biomedical and Behavioral Research KW - Professional Patient Relationship KW - Cyclophosphamide -- administration & dosage KW - Paclitaxel -- administration & dosage KW - Researcher-Subject Relations KW - Humans KW - Professional-Family Relations KW - Prognosis KW - Comprehension KW - Doxorubicin -- administration & dosage KW - Disclosure KW - Risk Assessment KW - Cisplatin -- administration & dosage KW - Fluorouracil -- administration & dosage KW - Uncertainty KW - Adult KW - Ethical Theory KW - Personal Autonomy KW - Methotrexate -- administration & dosage KW - Female KW - Breast Neoplasms -- drug therapy KW - Carcinoma, Ductal, Breast -- drug therapy KW - Carcinoma, Ductal, Breast -- psychology KW - Breast Neoplasms -- psychology KW - Patient Advocacy KW - Ethics, Medical KW - Randomized Controlled Trials as Topic -- psychology KW - Randomized Controlled Trials as Topic -- standards KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Therapeutic Human Experimentation KW - Physician-Patient Relations UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79659755?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Ethics+of+randomized+clinical+trials.&rft.au=Emanuel%2C+E+J%3BPatterson%2C+W+B&rft.aulast=Emanuel&rft.aufirst=E&rft.date=1998-01-01&rft.volume=16&rft.issue=1&rft.spage=365&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-01-27 N1 - Date created - 1998-01-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Clin Oncol. 1998 Jul;16(7):2570 [9667280] J Clin Oncol. 1998 Apr;16(4):1637 [9552081] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drinking water source and chlorination byproducts. II. Risk of colon and rectal cancers. AN - 79655388; 9430265 AB - We evaluated the association between chlorination byproducts and colon and rectal cancer risk in a population-based case-control study conducted in Iowa in 1986-1989. Data were gathered from 685 colon cancer cases, 655 rectal cancer cases, and 2,434 controls. We calculated odds ratios for the 560 colon cancer cases, 537 rectal cancer cases, and 1,983 controls for whom water exposure information was available for at least 70% of their lifetime. We estimated exposure to chlorination byproducts with two types of measures: duration of lifetime at residences served by chlorinated water and estimated lifetime trihalomethane exposure. For rectal cancer, we observed an association with duration of chlorinated surface water use, with adjusted odds ratios of 1.1, 1.6, 1.6, and 2.6 for 1-19, 20-39, 40-59, and > or =60 years of exposure, compared with no exposure. Rectal cancer risk was also associated with several different measures of estimated lifetime trihalomethane exposure. For colon cancer and subsites, we detected no important increase in risk associated with duration of chlorinated surface water, nor with trihalomethane estimates. When we evaluated chlorination byproducts jointly with other factors, we found larger relative risk estimates for rectal cancer among subjects with low dietary fiber intake. The risk related to > or =40 years of exposure to a chlorinated surface water source was 2.4 (95% confidence interval = 1.5-4.0) for persons with low fiber intake and 0.9 (95% confidence interval = 0.4-1.8) for persons with high fiber intake, relative to the risk of persons with high-fiber diets and no exposure to chlorinated surface water. We observed a similar risk differential for low and high levels of physical activity. JF - Epidemiology (Cambridge, Mass.) AU - Hildesheim, M E AU - Cantor, K P AU - Lynch, C F AU - Dosemeci, M AU - Lubin, J AU - Alavanja, M AU - Craun, G AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 29 EP - 35 VL - 9 IS - 1 SN - 1044-3983, 1044-3983 KW - Chlorofluorocarbons, Methane KW - 0 KW - Chlorine KW - 4R7X1O2820 KW - Index Medicus KW - Odds Ratio KW - Chlorofluorocarbons, Methane -- analysis KW - Dietary Fiber -- administration & dosage KW - Aged, 80 and over KW - Risk Factors KW - Humans KW - Adult KW - Case-Control Studies KW - Confidence Intervals KW - Aged KW - Middle Aged KW - Iowa -- epidemiology KW - Colonic Neoplasms -- epidemiology KW - Chlorine -- analysis KW - Colonic Neoplasms -- etiology KW - Water Supply KW - Rectal Neoplasms -- etiology KW - Chlorine -- adverse effects KW - Rectal Neoplasms -- epidemiology KW - Water Purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79655388?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epidemiology+%28Cambridge%2C+Mass.%29&rft.atitle=Drinking+water+source+and+chlorination+byproducts.+II.+Risk+of+colon+and+rectal+cancers.&rft.au=Hildesheim%2C+M+E%3BCantor%2C+K+P%3BLynch%2C+C+F%3BDosemeci%2C+M%3BLubin%2C+J%3BAlavanja%2C+M%3BCraun%2C+G&rft.aulast=Hildesheim&rft.aufirst=M&rft.date=1998-01-01&rft.volume=9&rft.issue=1&rft.spage=29&rft.isbn=&rft.btitle=&rft.title=Epidemiology+%28Cambridge%2C+Mass.%29&rft.issn=10443983&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-05 N1 - Date created - 1998-02-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drinking water source and chlorination byproducts. I. Risk of bladder cancer. AN - 79653318; 9430264 AB - We conducted a population-based case-control study of bladder cancer in Iowa in 1986-1989 to evaluate the risk posed by tapwater containing chlorination byproducts. We combined information about residential history, drinking water source, beverage intake, and other factors with historical data from water utilities and measured contaminant levels to create indices of past exposure to chlorination byproducts. The study comprised 1,123 cases and 1,983 controls who had data relating to at least 70% of their lifetime drinking water source. After we adjusted for potential confounders, we calculated odds ratios for duration of chlorinated surface water of 1.0 (referent), 1.0, 1.1, 1.2, and 1.5 for 0, 1-19, 20-39, 40-59, and > or =60 years of use. We also found associations with total and average lifetime byproduct intake, as represented by trihalomethane estimates. Positive findings were restricted to men and to ever-smokers. Among men, odds ratios were 1.0 (referent), 1.1, 1.3, 1.5, and 1.9, and among ever-smokers, 1.0, 1.1, 1.3, 1.8, and 2.2, after adjustment for intensity and timing of smoking. Among nonsmoking men and women, regardless of smoking habit, there was no association. Among men, smoking and exposure to chlorinated surface water mutually enhanced the risk of bladder cancer. The overall association of bladder cancer risk with duration of chlorinated surface water use that we found is consistent with the findings of other investigations, but the differences in risk between men and women, and between smokers and nonsmokers, have not been widely observed. JF - Epidemiology (Cambridge, Mass.) AU - Cantor, K P AU - Lynch, C F AU - Hildesheim, M E AU - Dosemeci, M AU - Lubin, J AU - Alavanja, M AU - Craun, G AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 21 EP - 28 VL - 9 IS - 1 SN - 1044-3983, 1044-3983 KW - Chlorofluorocarbons, Methane KW - 0 KW - Chlorine KW - 4R7X1O2820 KW - Index Medicus KW - Odds Ratio KW - Humans KW - Aged KW - Chlorofluorocarbons, Methane -- analysis KW - Aged, 80 and over KW - Risk Factors KW - Adult KW - Confounding Factors (Epidemiology) KW - Case-Control Studies KW - Middle Aged KW - Female KW - Iowa -- epidemiology KW - Male KW - Urinary Bladder Neoplasms -- etiology KW - Chlorine -- analysis KW - Urinary Bladder Neoplasms -- epidemiology KW - Water Supply KW - Chlorine -- adverse effects KW - Water Purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79653318?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epidemiology+%28Cambridge%2C+Mass.%29&rft.atitle=Drinking+water+source+and+chlorination+byproducts.+I.+Risk+of+bladder+cancer.&rft.au=Cantor%2C+K+P%3BLynch%2C+C+F%3BHildesheim%2C+M+E%3BDosemeci%2C+M%3BLubin%2C+J%3BAlavanja%2C+M%3BCraun%2C+G&rft.aulast=Cantor&rft.aufirst=K&rft.date=1998-01-01&rft.volume=9&rft.issue=1&rft.spage=21&rft.isbn=&rft.btitle=&rft.title=Epidemiology+%28Cambridge%2C+Mass.%29&rft.issn=10443983&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-05 N1 - Date created - 1998-02-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Epidemiology. 1998 Jan;9(1):7-8 [9430261] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Disruption of the pRb/E2F pathway and inhibition of apoptosis are major oncogenic events in liver constitutively expressing c-myc and transforming growth factor alpha. AN - 79641115; 9426068 AB - The oncogene c-myc and transforming growth factor (TGF) alpha are frequently coexpressed in human cancers, suggesting that their interaction may be a critical step in malignant growth. Consistent with this idea, we recently demonstrated in a transgenic mouse model that TGF-alpha dramatically enhances c-myc-induced hepatocarcinogenesis. To elucidate this synergistic effect, we have now investigated regulation of cell cycle and apoptosis during neoplastic development in the liver of c-myc and c-myc/TGFalpha transgenic mice. Both lines displayed dramatic increases of mitotic and apoptotic rates before the onset of hepatocellular carcinoma (HCC), but only c-myc/TGF-alpha livers showed significant levels of net proliferation (mitosis minus apoptosis). Subsequently, mitosis declined in peritumorous tissues, concomitant with the previously reported induction of TGF-beta1, whereas c-myc and c-myc/TGFalpha HCCs maintained mitotic hyperactivity. The c-myc/TGF-alpha HCCs were also characterized by a particularly strong expression of TGF-alpha and very low apoptotic index in contrast to high levels of apoptosis in peritumorous tissues and c-myc HCCs. The differential levels of cell proliferation in noncancerous and cancerous tissues correlated with a stronger induction of cyclin D1 mRNA and protein in c-myc/TGF-alpha and c-myc HCCs associated with intense pRb hyperphosphorylation. Severe deregulation of G1-S transition was also indicated by the dramatic up-regulation, particularly in the HCCs, of pRb-free E2F1-DP1 and E2F2-DP1 transcription factor heterodimers, as assessed by immunoprecipitation and immunohistochemistry. The existence of increased E2F activity during hepatocarcinogenesis was further indicated by the transcriptional induction of putative E2F target genes involved in cell cycle progression, such as endogenous c-myc, cyclin A, Cdc2, and E2F itself. Cdc2 overexpression and the elevated mitotic indices in the HCCs correlated also with induction of cyclin B steady-state levels. The data suggest that coexpression of c-myc and TGF-alpha leads to a selective growth advantage for hepatic (pre)neoplastic cells by disrupting the pRb/E2F pathway and by TGF-alpha-mediated reduction of apoptosis. JF - Cancer research AU - Santoni-Rugiu, E AU - Jensen, M R AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1998/01/01/ PY - 1998 DA - 1998 Jan 01 SP - 123 EP - 134 VL - 58 IS - 1 SN - 0008-5472, 0008-5472 KW - Arid4a protein, mouse KW - 0 KW - Carrier Proteins KW - Cell Cycle Proteins KW - DNA-Binding Proteins KW - E2F Transcription Factors KW - E2F1 Transcription Factor KW - E2F2 Transcription Factor KW - E2f1 protein, mouse KW - Neoplasm Proteins KW - Proto-Oncogene Proteins c-myc KW - Retinoblastoma Protein KW - Retinoblastoma-Binding Protein 1 KW - Tfdp1 protein, mouse KW - Transcription Factor DP1 KW - Transcription Factors KW - Transforming Growth Factor alpha KW - CDC2 Protein Kinase KW - EC 2.7.11.22 KW - Index Medicus KW - Animals KW - CDC2 Protein Kinase -- metabolism KW - Transgenes KW - S Phase KW - Mice KW - Mice, Transgenic KW - Cell Cycle Proteins -- metabolism KW - Phosphorylation KW - G1 Phase KW - Mitotic Index KW - Cell Division KW - Apoptosis KW - Transcription Factors -- metabolism KW - Liver Neoplasms, Experimental -- metabolism KW - Proto-Oncogene Proteins c-myc -- genetics KW - Proto-Oncogene Proteins c-myc -- metabolism KW - Transforming Growth Factor alpha -- metabolism KW - Transcription Factors -- genetics KW - Transforming Growth Factor alpha -- genetics KW - Liver Neoplasms, Experimental -- etiology KW - Liver Neoplasms, Experimental -- pathology KW - Neoplasm Proteins -- genetics KW - Retinoblastoma Protein -- metabolism KW - Neoplasm Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79641115?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Disruption+of+the+pRb%2FE2F+pathway+and+inhibition+of+apoptosis+are+major+oncogenic+events+in+liver+constitutively+expressing+c-myc+and+transforming+growth+factor+alpha.&rft.au=Santoni-Rugiu%2C+E%3BJensen%2C+M+R%3BThorgeirsson%2C+S+S&rft.aulast=Santoni-Rugiu&rft.aufirst=E&rft.date=1998-01-01&rft.volume=58&rft.issue=1&rft.spage=123&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-01-20 N1 - Date created - 1998-01-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interleukin-15 augments superoxide production and microbicidal activity of human monocytes against Candida albicans. AN - 79634997; 9423851 AB - Interleukin-15 (IL-15) is a newly described cytokine that shares biological activities with IL-2. We report here results demonstrating the ability of IL-15 to enhance superoxide production and antifungal activity of human monocytes. After 18 and 48 h of treatment with IL-15, human elutriated monocytes manifested enhanced superoxide production in response to either phorbol myristate acetate or opsonized Candida albicans blastoconidia. Similar results were obtained when monocytes were treated with IL-2, but to a lesser extent. Combination studies with IL-15 and IL-2 showed no additive or synergistic effects. Following incubation of monocytes with IL-15 for 18 h, there was no significant increase in mRNA transcripts for components of the NADPH oxidase complex, p40-phox, p47-phox, and gp91-phox, suggesting a posttranscriptional modulation of enhanced superoxide production. Antibodies against the gamma chain of the IL-2 receptor and, to a lesser extent, against the beta chain partially abrogated the IL-15-mediated enhanced superoxide production. Additionally, human monocytes showed enhanced killing activity against C. albicans after 18 h of incubation with IL-15 or IL-2, but this treatment did not enhance the ability of these cells to phagocytose the organism. In addition, the enhanced fungicidal activity seen after 18 h of treatment was no longer detectable after 48 h of cytokine treatment. Culture supernatants from the IL-15-treated monocytes were assayed for the presence of other proinflammatory cytokines. IL-15 treatment did not induce the release of detectable levels of tumor necrosis factor alpha, IL-1beta, or IL-12. Our results indicate that IL-15 upregulates the microbicidal activity of human monocytes against C. albicans. JF - Infection and immunity AU - Vázquez, N AU - Walsh, T J AU - Friedman, D AU - Chanock, S J AU - Lyman, C A AD - Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 145 EP - 150 VL - 66 IS - 1 SN - 0019-9567, 0019-9567 KW - CYBB protein, human KW - 0 KW - Culture Media, Conditioned KW - Interleukin-1 KW - Interleukin-15 KW - Interleukin-2 KW - Membrane Glycoproteins KW - Phosphoproteins KW - Receptors, Interleukin-2 KW - Tumor Necrosis Factor-alpha KW - neutrophil cytosol factor 40K KW - Superoxides KW - 11062-77-4 KW - Interleukin-12 KW - 187348-17-0 KW - NADPH Oxidase KW - EC 1.6.3.1 KW - neutrophil cytosolic factor 1 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - NADPH Oxidase -- metabolism KW - Interleukin-2 -- pharmacology KW - Humans KW - Phagocytosis -- immunology KW - Culture Media, Conditioned -- analysis KW - Receptors, Interleukin-2 -- immunology KW - Interleukin-12 -- metabolism KW - Interleukin-1 -- metabolism KW - Respiratory Burst -- immunology KW - Neutralization Tests KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cytotoxicity Tests, Immunologic KW - Interleukin-2 -- immunology KW - Tumor Necrosis Factor-alpha -- metabolism KW - Membrane Glycoproteins -- metabolism KW - Phosphoproteins -- metabolism KW - Superoxides -- metabolism KW - Monocytes -- immunology KW - Monocytes -- metabolism KW - Interleukin-15 -- pharmacology KW - Candida albicans -- immunology KW - Interleukin-15 -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79634997?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+immunity&rft.atitle=Interleukin-15+augments+superoxide+production+and+microbicidal+activity+of+human+monocytes+against+Candida+albicans.&rft.au=V%C3%A1zquez%2C+N%3BWalsh%2C+T+J%3BFriedman%2C+D%3BChanock%2C+S+J%3BLyman%2C+C+A&rft.aulast=V%C3%A1zquez&rft.aufirst=N&rft.date=1998-01-01&rft.volume=66&rft.issue=1&rft.spage=145&rft.isbn=&rft.btitle=&rft.title=Infection+and+immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-01-27 N1 - Date created - 1998-01-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cytokine. 1996 Jan;8(1):42-8 [8742065] Immunodeficiency. 1993;4(1-4):187-90 [8167697] EMBO J. 1996 Sep 16;15(18):4928-39 [8890166] Nat Med. 1997 Feb;3(2):189-95 [9018238] J Immunol. 1997 Jun 15;158(12):5978-87 [9190952] Blood. 1997 Oct 1;90(7):2804-9 [9326248] Biochim Biophys Acta. 1959 Jul;34:255-6 [14422133] J Clin Invest. 1975 Jun;55(6):1357-72 [166094] J Exp Med. 1983 Sep 1;158(3):670-89 [6411853] Cell Immunol. 1984 May;85(2):373-83 [6232002] Nature. 1987 Jan 15-21;325(6101):262-5 [3100957] J Immunol. 1987 Aug 15;139(4):1342-7 [3039002] Science. 1994 May 13;264(5161):965-8 [8178155] Proc Natl Acad Sci U S A. 1994 May 24;91(11):4935-9 [8197160] EMBO J. 1994 Jun 15;13(12):2822-30 [8026467] J Exp Med. 1994 Oct 1;180(4):1395-403 [7523571] Blood. 1995 Jan 1;85(1):38-42 [7803808] J Immunol. 1995 Jan 15;154(2):483-90 [7814861] J Leukoc Biol. 1995 Jan;57(1):13-9 [7829965] J Exp Med. 1995 Mar 1;181(3):1255-9 [7869044] J Immunol. 1995 Jul 15;155(2):785-95 [7608555] EMBO J. 1995 Aug 1;14(15):3654-63 [7641685] J Exp Med. 1995 Oct 1;182(4):1067-77 [7561680] Int J Immunopharmacol. 1995 May;17(5):385-92 [7591362] J Immunol. 1996 Jan 15;156(2):663-9 [8543818] J Immunol. 1996 Jan 15;156(2):735-41 [8543827] Exp Hematol. 1996 Mar;24(4):559-67 [8608807] Exp Hematol. 1996 Feb;24(2):151-7 [8641336] J Immunol. 1996 Sep 1;157(5):2103-8 [8757333] Immunobiology. 1988 Apr;177(1):32-9 [2838419] Proc Natl Acad Sci U S A. 1988 Jul;85(14):5215-9 [2839835] J Immunol. 1989 Jul 15;143(2):671-7 [2661688] J Infect Dis. 1990 May;161(5):999-1005 [2157774] J Biol Chem. 1990 Nov 25;265(33):20241-6 [2173701] Infect Immun. 1991 Oct;59(10):3393-7 [1894353] J Pediatr. 1991 Dec;119(6):845-57 [1660069] J Clin Invest. 1996 Mar 15;97(6):1373-81 [8617868] J Clin Invest. 1995 Dec;96(6):2578-82 [8675621] Cancer Res. 1992 May 1;52(9):2530-7 [1568222] Leuk Res. 1992 Jun-Jul;16(6-7):703-9 [1321933] Clin Infect Dis. 1992 Sep;15(3):508-24 [1520801] Am J Hematol. 1993 Aug;43(4):279-85 [8396850] Immunodeficiency. 1993;4(1-4):181-5 [8167696] Exp Hematol. 1996 Feb;24(2):169-75 [8641338] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Quinolinic acid in vivo synthesis rates, extracellular concentrations, and intercompartmental distributions in normal and immune-activated brain as determined by multiple-isotope microdialysis. AN - 79632584; 9422373 AB - Quinolinic acid (QUIN) kills neurons by activation of NMDA receptors that are accessed via the extracellular fluid (ECF). In vivo microdialysis was employed to quantify the dynamics of ECF QUIN levels. [(13)C7]QUIN was perfused through the probe for in vivo calibration to accurately quantify ECF QUIN concentrations. Osmotic pumps infused [(2H)3]QUIN subcutaneously to quantify blood contributions to ECF and tissue levels. Local QUIN production rates and influx and efflux rates across the blood-brain barrier were calculated from the extraction fraction of [(13)C7]QUIN, probe geometry, tissue diffusion coefficients, the extracellular volume fraction, and [(2)H3]QUIN/QUIN ratios in blood and dialysates. In normal brain, 85% of ECF QUIN levels (110 nM) originated from blood, whereas 59% of tissue homogenate QUIN (130 pmol/g) originated from local de novo synthesis. During systemic immune activation (intraperitoneal injection of endotoxin), blood QUIN levels increased (10.2-fold) and caused a rise in homogenate (10.8-fold) and ECF (18.5-fold) QUIN levels with an increase in the proportions of QUIN derived from blood. During CNS inflammation (local infusion of endotoxin), increases in brain homogenate (246-fold) and ECF (66-fold) QUIN levels occurred because of an increase in local synthesis rate (146-fold) and a reduction in efflux/influx ratio (by 53%). These results demonstrate that brain homogenate measures are a reflection of ECF concentrations, although there are quantitative differences in the values obtained. The mechanisms that maintain ECF QUIN levels at low values cannot do so when there are large increases in local brain synthesis or when there are large elevations in blood QUIN concentrations. JF - Journal of neurochemistry AU - Beagles, K E AU - Morrison, P F AU - Heyes, M P AD - Laboratory of Neurotoxicology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1262, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 281 EP - 291 VL - 70 IS - 1 SN - 0022-3042, 0022-3042 KW - Endotoxins KW - 0 KW - Isotopes KW - Quinolinic Acid KW - F6F0HK1URN KW - Index Medicus KW - Osmolar Concentration KW - Injections, Intraperitoneal KW - Animals KW - Gerbillinae KW - Reference Values KW - Corpus Striatum -- metabolism KW - Blood-Brain Barrier -- physiology KW - Encephalomyelitis -- chemically induced KW - Tissue Distribution KW - Endotoxins -- pharmacology KW - Microdialysis -- methods KW - Administration, Topical KW - Female KW - Encephalomyelitis -- metabolism KW - Quinolinic Acid -- metabolism KW - Extracellular Space -- metabolism KW - Brain -- metabolism KW - Brain -- immunology KW - Immune System -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79632584?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=Quinolinic+acid+in+vivo+synthesis+rates%2C+extracellular+concentrations%2C+and+intercompartmental+distributions+in+normal+and+immune-activated+brain+as+determined+by+multiple-isotope+microdialysis.&rft.au=Beagles%2C+K+E%3BMorrison%2C+P+F%3BHeyes%2C+M+P&rft.aulast=Beagles&rft.aufirst=K&rft.date=1998-01-01&rft.volume=70&rft.issue=1&rft.spage=281&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-02-02 N1 - Date created - 1998-02-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Blockade and recovery of spontaneous rhythmic activity after application of neurotransmitter antagonists to spinal networks of the chick embryo. AN - 79629190; 9412508 AB - We studied the regulation of spontaneous activity in the embryonic (day 10-11) chick spinal cord. After bath application of either an excitatory amino acid (AP-5 or CNQX) and a nicotinic cholinergic (DHbetaE or mecamylamine) antagonist, or glycine and GABA receptor (bicuculline, 2-hydroxysaclofen, and strychnine) antagonists, spontaneous activity was blocked for a period (30-90 min) but then reappeared in the presence of the drugs. The efficacy of the antagonists was assessed by their continued ability to block spinal reflex pathways during the reappearance of spontaneous activity. Spontaneous activity ceased over the 4-5 hour monitoring period when both sets of antagonists were applied together. After application of glycine and GABA receptor antagonists, the frequency of occurrence of spontaneous episodes slowed and became highly variable. By contrast, during glutamatergic and nicotinic cholinergic blockade, the frequency of occurrence of spontaneous episodes initially slowed and then recovered to stabilize near the predrug level of activity. Whole-cell recordings made from ventral spinal neurons revealed that this recovery was accompanied by an increase in the amplitude of spontaneously occurring synaptic events. We also measured changes in the apparent equilibrium potential of the rhythmic, synaptic drive of ventral spinal neurons using voltage or discontinuous current clamp. After excitatory blockade, the apparent equilibrium potential of the rhythmic synaptic drive shifted approximately 10 mV more negative to approximately -30 mV. In the presence of bicuculline, the apparent equilibrium potential of the synaptic drive shifted toward the glutamate equilibrium potential. Considered with other evidence, these findings suggest that spontaneous rhythmic output is a general property of developing spinal networks, and that GABA and glycinergic networks alter their function to compensate for the blockade of excitatory transmission. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Chub, N AU - O'Donovan, M J AD - Section on Developmental Neurobiology, Laboratory of Neural Control, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/01/01/ PY - 1998 DA - 1998 Jan 01 SP - 294 EP - 306 VL - 18 IS - 1 SN - 0270-6474, 0270-6474 KW - Cholinergic Antagonists KW - 0 KW - Excitatory Amino Acid Antagonists KW - GABA Antagonists KW - GABA-A Receptor Antagonists KW - Glycine Agents KW - Neurotransmitter Agents KW - Nicotinic Antagonists KW - phaclofen KW - 108351-35-5 KW - 2-hydroxysaclofen KW - 117354-64-0 KW - Dihydro-beta-Erythroidine KW - 23255-54-1 KW - Mecamylamine KW - 6EE945D3OK KW - 6-Cyano-7-nitroquinoxaline-2,3-dione KW - 6OTE87SCCW KW - 2-Amino-5-phosphonovalerate KW - 76726-92-6 KW - Baclofen KW - H789N3FKE8 KW - Strychnine KW - H9Y79VD43J KW - Glycine KW - TE7660XO1C KW - Bicuculline KW - Y37615DVKC KW - Index Medicus KW - Bicuculline -- pharmacology KW - Animals KW - Dihydro-beta-Erythroidine -- pharmacology KW - Chick Embryo KW - 6-Cyano-7-nitroquinoxaline-2,3-dione -- pharmacology KW - Evoked Potentials -- physiology KW - Mecamylamine -- pharmacology KW - Baclofen -- analogs & derivatives KW - Action Potentials -- drug effects KW - Cholinergic Antagonists -- pharmacology KW - GABA Antagonists -- pharmacology KW - Excitatory Amino Acid Antagonists -- pharmacology KW - 2-Amino-5-phosphonovalerate -- pharmacology KW - Glycine -- pharmacology KW - Nicotinic Antagonists -- pharmacology KW - Strychnine -- pharmacology KW - Neuronal Plasticity -- drug effects KW - Periodicity KW - Glycine Agents -- pharmacology KW - Baclofen -- pharmacology KW - Motor Neurons -- physiology KW - Neurotransmitter Agents -- physiology KW - Neurotransmitter Agents -- antagonists & inhibitors KW - Motor Neurons -- drug effects KW - Spinal Cord -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79629190?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.atitle=Blockade+and+recovery+of+spontaneous+rhythmic+activity+after+application+of+neurotransmitter+antagonists+to+spinal+networks+of+the+chick+embryo.&rft.au=Chub%2C+N%3BO%27Donovan%2C+M+J&rft.aulast=Chub&rft.aufirst=N&rft.date=1998-01-01&rft.volume=18&rft.issue=1&rft.spage=294&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=02706474&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-01-16 N1 - Date created - 1998-01-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Accounting for errors in dose estimates used in studies of workers exposed to external radiation. AN - 79628139; 9415578 AB - This paper discusses approaches for accounting for errors in dose estimates used in dose-response analyses of data from epidemiologic studies of workers exposed to external radiation and illustrates these approaches with analyses of data on workers at the Hanford site. In these analyses, estimates of the excess relative risk are corrected for bias in recorded doses as estimates of organ dose, and confidence intervals reflect uncertainty in the correction factors. For the Hanford data, these procedures did not greatly modify results for all cancer excluding leukemia, but the upper confidence limit for leukemia was increased by about 40%, a difference that is of some importance in comparing worker-based estimates and confidence intervals with estimates that serve as the basis of radiation protection standards. It is argued that aside from taking account of uncertainty in correction factors, no additional corrections are needed to address random errors resulting from variation in exposure energies and geometries. In addition, it is shown that because the larger cumulative doses, which are most influential in dose-response analyses, are the sums of large numbers of independent dosimeter readings, random errors resulting from variation in laboratory measurements are unlikely to be important for epidemiologic purposes. It is hoped that the approaches illustrated in this paper will be applied to future analyses of data from worker studies, especially combined analyses of data from several countries. Taking account of uncertainty in factors that correct for systematic bias will be especially important as uncertainty resulting from sampling variation decreases. JF - Health physics AU - Gilbert, E S AD - Radiation Epidemiology Branch, National Cancer Institute, Rockville, MD 20852, USA. Y1 - 1998/01// PY - 1998 DA - January 1998 SP - 22 EP - 29 VL - 74 IS - 1 SN - 0017-9078, 0017-9078 KW - Index Medicus KW - Humans KW - Dose-Response Relationship, Radiation KW - Bias (Epidemiology) KW - Occupational Exposure -- statistics & numerical data KW - Power Plants KW - Occupational Exposure -- adverse effects KW - Radiation Injuries -- epidemiology KW - Nuclear Reactors KW - Radiation Injuries -- mortality KW - Film Dosimetry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79628139?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Health+physics&rft.atitle=Accounting+for+errors+in+dose+estimates+used+in+studies+of+workers+exposed+to+external+radiation.&rft.au=Gilbert%2C+E+S&rft.aulast=Gilbert&rft.aufirst=E&rft.date=1998-01-01&rft.volume=74&rft.issue=1&rft.spage=22&rft.isbn=&rft.btitle=&rft.title=Health+physics&rft.issn=00179078&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-01-12 N1 - Date created - 1998-01-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Monoclonal antibodies to cytochromes P450. AN - 79619513; 14577233 JF - Methods in molecular biology (Clifton, N.J.) AU - Gelboin, H V AU - Shou, M AU - Goldfarb, I AU - Yang, T J AU - Krausz, K AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, MD, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 227 EP - 237 VL - 107 SN - 1064-3745, 1064-3745 KW - Antibodies, Monoclonal KW - 0 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Durapatite KW - 91D9GV0Z28 KW - Index Medicus KW - Animals KW - Chromatography KW - Ascitic Fluid -- immunology KW - Hybridomas -- immunology KW - Mice KW - Cytochrome P-450 Enzyme System -- immunology KW - Antibodies, Monoclonal -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79619513?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.atitle=Monoclonal+antibodies+to+cytochromes+P450.&rft.au=Gelboin%2C+H+V%3BShou%2C+M%3BGoldfarb%2C+I%3BYang%2C+T+J%3BKrausz%2C+K&rft.aulast=Gelboin&rft.aufirst=H&rft.date=1998-01-01&rft.volume=107&rft.issue=&rft.spage=227&rft.isbn=&rft.btitle=&rft.title=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.issn=10643745&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-11 N1 - Date created - 2003-10-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The relationship between cannabis use and DSM-IV cannabis abuse and dependence: results from the National Longitudinal Alcohol Epidemiologic Survey. AN - 79617214; 10689658 AB - The purpose of-this study was to determine the risk of Diagnostic and Statistical Manual of Mental Disorders--Fourth Edition (DSM-IV) cannabis abuse and dependence at different levels of cannabis use in a nationally representative sample of the U.S. general population. Two separate logistic regression analyses were conducted to determine the association between cannabis use, and abuse and dependence. The risk of cannabis abuse and dependence was found to increase with the frequency of smoking occasions and slightly decreased with age. More severe comorbidity was associated with dependence compared to abuse, suggesting that cannabis might be used to self-medicate major depression. The strength of the association between cannabis use and abuse was also increased as a function of the number of joints smoked among females, but not males. These results were discussed in terms of differential societal reactions, the self-medication hypothesis, and gender biases in diagnosing cannabis abuse. JF - Journal of substance abuse AU - Grant, B F AU - Pickering, R AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892-7003, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 255 EP - 264 VL - 10 IS - 3 SN - 0899-3289, 0899-3289 KW - Index Medicus KW - United States KW - Depressive Disorder, Major -- diagnosis KW - Sex Factors KW - Humans KW - Depressive Disorder, Major -- epidemiology KW - Longitudinal Studies KW - Psychometrics KW - Comorbidity KW - Self Medication -- psychology KW - Cross-Sectional Studies KW - Risk Factors KW - Depressive Disorder, Major -- psychology KW - Adult KW - Health Surveys KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - Marijuana Smoking -- psychology KW - Alcoholism -- epidemiology KW - Alcoholism -- diagnosis KW - Marijuana Smoking -- epidemiology KW - Marijuana Abuse -- diagnosis KW - Marijuana Abuse -- psychology KW - Marijuana Abuse -- epidemiology KW - Psychiatric Status Rating Scales -- statistics & numerical data KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79617214?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+substance+abuse&rft.atitle=The+relationship+between+cannabis+use+and+DSM-IV+cannabis+abuse+and+dependence%3A+results+from+the+National+Longitudinal+Alcohol+Epidemiologic+Survey.&rft.au=Grant%2C+B+F%3BPickering%2C+R&rft.aulast=Grant&rft.aufirst=B&rft.date=1998-01-01&rft.volume=10&rft.issue=3&rft.spage=255&rft.isbn=&rft.btitle=&rft.title=Journal+of+substance+abuse&rft.issn=08993289&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-21 N1 - Date created - 2000-03-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin binds to HSP90 and shares important biologic activities with geldanamycin. AN - 73930159; 9744771 AB - Benzoquinone ansamycins are antibiotics with anticancer potential. First described as tyrosine kinase inhibitors, they are now frequently used to target HSP90 chaperone function. While herbimycin A and geldanamycin (GA) have been widely used in preclinical studies, both drugs are poor candidates for clinical trials owing to their in vivo toxicity and lack of stability. We therefore examined the biologic effects of 17-allylamino-17-demethoxygeldanamycin (17-AG), an ansamycin derivative with lower in vivo toxicity than GA. Binding of 17-AG to HSP90 was studied in vitro using a GA-affinity beads competition assay. We analyzed the drug-induced destabilization of p185erbB2, Raf-1 and mutant p53 in SKBR3 breast cancer cells by Western blotting. The antiproliferative activities of 17-AG and GA were compared using the MTT assay. We found that, in a similar manner to GA itself, 17-AG bound specifically to HSP90. It also led to degradation of the receptor tyrosine kinase p185erbB2, the serine/threonine kinase Raf-1 and mutant p53. Both GA and 17-AG displayed comparable antiproliferative effects in SKBR3 and MCF7 cells. Even though HSP90 binding by 17-AG was weaker than by GA, 17-AG and GA caused biologic effects in tumor cells at similar doses. 17-AG shares the important biologic features of its parent compound GA. Since 17-AG has a better toxicity profile than GA, it is an interesting candidate benzoquinone ansamycin for clinical development. JF - Cancer chemotherapy and pharmacology AU - Schulte, T W AU - Neckers, L M AD - Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1928, USA. tschulte@helix.nih.gov Y1 - 1998 PY - 1998 DA - 1998 SP - 273 EP - 279 VL - 42 IS - 4 SN - 0344-5704, 0344-5704 KW - Antibiotics, Antineoplastic KW - 0 KW - Benzoquinones KW - Enzyme Inhibitors KW - HSP90 Heat-Shock Proteins KW - Lactams, Macrocyclic KW - Quinones KW - Tumor Suppressor Protein p53 KW - Rifabutin KW - 1W306TDA6S KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Receptor, ErbB-2 KW - Proto-Oncogene Proteins c-raf KW - EC 2.7.11.1 KW - geldanamycin KW - Z3K3VJ16KU KW - Index Medicus KW - Mutation -- drug effects KW - 3T3 Cells KW - Animals KW - Proto-Oncogene Proteins c-raf -- chemistry KW - Receptor, ErbB-2 -- metabolism KW - Humans KW - Cell Division -- drug effects KW - Proto-Oncogene Proteins c-raf -- metabolism KW - Mice KW - Tumor Suppressor Protein p53 -- metabolism KW - Protein-Tyrosine Kinases -- antagonists & inhibitors KW - Protein-Tyrosine Kinases -- genetics KW - Tumor Cells, Cultured KW - Tumor Suppressor Protein p53 -- chemistry KW - Receptor, ErbB-2 -- chemistry KW - Female KW - Antibiotics, Antineoplastic -- metabolism KW - Rifabutin -- analogs & derivatives KW - Antibiotics, Antineoplastic -- pharmacology KW - HSP90 Heat-Shock Proteins -- metabolism KW - Enzyme Inhibitors -- pharmacology KW - Enzyme Inhibitors -- metabolism KW - Quinones -- pharmacology KW - Quinones -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73930159?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+pharmacology&rft.atitle=The+benzoquinone+ansamycin+17-allylamino-17-demethoxygeldanamycin+binds+to+HSP90+and+shares+important+biologic+activities+with+geldanamycin.&rft.au=Schulte%2C+T+W%3BNeckers%2C+L+M&rft.aulast=Schulte&rft.aufirst=T&rft.date=1998-01-01&rft.volume=42&rft.issue=4&rft.spage=273&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+pharmacology&rft.issn=03445704&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-08 N1 - Date created - 1998-10-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical pharmacology of UCN-01: initial observations and comparison to preclinical models. AN - 73924600; 9750030 AB - UCN-01 (7-hydroxystaurosporine; NSC 638850) is a protein kinase antagonist selected for clinical trial based in part on evidence of efficacy in a preclinical renal carcinoma xenograft model. Schedule studies and in vitro studies suggested that a 72-h continuous infusion would be appropriate. In rats and dogs, maximum tolerated doses produced peak plasma concentrations of approximately 0.2-0.3 microM. However, concentrations 10-fold greater are well tolerated in humans, and the compound has a markedly prolonged T1/2. Specific binding to human alpha1-acidic glycoprotein has been demonstrated. These findings reinforce the need to consider actual clinical pharmacology data in "real time" with phase I studies. JF - Cancer chemotherapy and pharmacology AU - Sausville, E A AU - Lush, R D AU - Headlee, D AU - Smith, A C AU - Figg, W D AU - Arbuck, S G AU - Senderowicz, A M AU - Fuse, E AU - Tanii, H AU - Kuwabara, T AU - Kobayashi, S AD - DTP Clinical Trials Unit, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD, USA. sausville@dtpax2.ncifcrf.gov Y1 - 1998 PY - 1998 DA - 1998 SP - S54 EP - S59 VL - 42 Suppl SN - 0344-5704, 0344-5704 KW - Alkaloids KW - 0 KW - Antineoplastic Agents KW - Blood Proteins KW - Enzyme Inhibitors KW - 7-hydroxystaurosporine KW - 7BU5H4V94A KW - Protein Kinase C KW - EC 2.7.11.13 KW - Staurosporine KW - H88EPA0A3N KW - Index Medicus KW - Transplantation, Heterologous -- immunology KW - Animals KW - Infusions, Intravenous KW - Humans KW - Mice KW - Mice, Nude KW - Protein Binding KW - Staurosporine -- analogs & derivatives KW - Chromatography, High Pressure Liquid KW - Rats KW - Adult KW - Dogs KW - Blood Proteins -- metabolism KW - Protein Kinase C -- antagonists & inhibitors KW - Antineoplastic Agents -- pharmacokinetics KW - Enzyme Inhibitors -- toxicity KW - Alkaloids -- toxicity KW - Antineoplastic Agents -- toxicity KW - Enzyme Inhibitors -- pharmacology KW - Enzyme Inhibitors -- pharmacokinetics KW - Alkaloids -- pharmacology KW - Alkaloids -- pharmacokinetics KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73924600?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+pharmacology&rft.atitle=Clinical+pharmacology+of+UCN-01%3A+initial+observations+and+comparison+to+preclinical+models.&rft.au=Sausville%2C+E+A%3BLush%2C+R+D%3BHeadlee%2C+D%3BSmith%2C+A+C%3BFigg%2C+W+D%3BArbuck%2C+S+G%3BSenderowicz%2C+A+M%3BFuse%2C+E%3BTanii%2C+H%3BKuwabara%2C+T%3BKobayashi%2C+S&rft.aulast=Sausville&rft.aufirst=E&rft.date=1998-01-01&rft.volume=42+Suppl&rft.issue=&rft.spage=S54&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+pharmacology&rft.issn=03445704&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-07 N1 - Date created - 1998-10-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - National Cancer Institute Clinical Trials Program in Colorectal Cancer. AN - 73909158; 9750034 AB - Colorectal cancer will be diagnosed in approximately 150,000 patients in the USA this year. Chemotherapy has recently been shown to improve survival when given as adjuvant therapy to surgery in patients with stage III colorectal cancer. Demonstration of this benefit required large, randomized controlled trials. Either 5-fluorouracil (5-FU) and leucovorin for 6 months or 5-FU and levamisole for 12 months are currently considered standard adjuvant treatment for stage III colorectal cancer. However, current adjuvant trials are comparing continuous infusion and intravenous bolus 5-FU regimens and oral uracil/Ftorafur with intravenous 5-FU and leucovorin, as well as studying the timing of chemotherapy in the adjuvant setting. Subsequent adjuvant trials will examine newer regimens with activity in advanced colorectal cancer, as well as the efficacy of monoclonal antibodies. Other trials will study which type of surgery is optimal and whether adjuvant therapy is helpful in stage II colon cancer. Trials in metastatic disease will focus on combinations of newer agents which may improve survival in this patient group. Studies in rectal cancer will focus on determining which agents are optimal in combination with radiation therapy in the adjuvant setting. Molecular characteristics of tumor cells are being defined, which may guide therapy in the future. Careful, logically designed clinical trials will hopefully provide more efficacious therapy for this common cancer. JF - Cancer chemotherapy and pharmacology AU - Conley, B A AU - Kaplan, R S AU - Arbuck, S G AD - Clinical Investigations Branch, Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Rockville, MD 20852, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - S75 EP - S79 VL - 42 Suppl SN - 0344-5704, 0344-5704 KW - Antimetabolites, Antineoplastic KW - 0 KW - Antineoplastic Agents KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - United States KW - Humans KW - Fluorouracil -- therapeutic use KW - National Institutes of Health (U.S.) KW - Clinical Trials as Topic -- trends KW - Antineoplastic Agents -- therapeutic use KW - Colorectal Neoplasms -- drug therapy KW - Antimetabolites, Antineoplastic -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73909158?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+pharmacology&rft.atitle=National+Cancer+Institute+Clinical+Trials+Program+in+Colorectal+Cancer.&rft.au=Conley%2C+B+A%3BKaplan%2C+R+S%3BArbuck%2C+S+G&rft.aulast=Conley&rft.aufirst=B&rft.date=1998-01-01&rft.volume=42+Suppl&rft.issue=&rft.spage=S75&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+pharmacology&rft.issn=03445704&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-07 N1 - Date created - 1998-10-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of protein glycosylation inhibitors in the prevention of metastasis and therapy of cancer. AN - 73897784; 9727627 AB - Oligosaccharide moieties of cell-surface glycoproteins are thought to be involved in recognition events during cancer metastasis and invasion. Swainsonine, an inhibitor of the Golgi alpha-mannosidase II, has been shown to block pulmonary colonization by tumor cells and stimulate components of the immune system. Swainsonine also abrogates much of the toxicity of chemotherapeutic agents and stimulates bone marrow hematopoietic progenitor cells, suggesting additional therapeutic applications. We are currently characterizing the ability of swainsonine to modify cell growth in human and murine bone marrow progenitor cells. Furthermore, we are examining crucial steps in metastasis that depend upon cell surface molecules that play a role in cell-matrix interactions. Our work shows that tumor cell adhesion to collagen IV in vitro is rapidly stimulated by cis-polyunsaturated fatty acids and is dependent on protein kinase C activity. We are investigating the hypothesis that integrins are critical components of this adhesion and are examining potential signal transduction pathways that lead to the modulation of cell adhesion. JF - Cancer detection and prevention AU - Roberts, J D AU - Klein, J L AU - Palmantier, R AU - Dhume, S T AU - George, M D AU - Olden, K AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 455 EP - 462 VL - 22 IS - 5 SN - 0361-090X, 0361-090X KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Enzyme Inhibitors KW - Glycoproteins KW - Arachidonic Acid KW - 27YG812J1I KW - Protein Kinase C KW - EC 2.7.11.13 KW - Swainsonine KW - RSY4RK37KQ KW - Index Medicus KW - Protein Kinase C -- metabolism KW - Arachidonic Acid -- physiology KW - Animals KW - Protein Kinase C -- antagonists & inhibitors KW - Arachidonic Acid -- antagonists & inhibitors KW - Tumor Cells, Cultured KW - Glycosylation -- drug effects KW - Glycoproteins -- metabolism KW - Humans KW - Mice, Nude KW - Mice KW - Hematopoietic Stem Cells -- metabolism KW - Signal Transduction KW - Cell Adhesion KW - Neoplasms -- drug therapy KW - Neoplasms -- pathology KW - Enzyme Inhibitors -- therapeutic use KW - Antineoplastic Agents, Phytogenic -- therapeutic use KW - Swainsonine -- therapeutic use KW - Neoplasms -- physiopathology KW - Neoplasm Metastasis -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73897784?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+detection+and+prevention&rft.atitle=The+role+of+protein+glycosylation+inhibitors+in+the+prevention+of+metastasis+and+therapy+of+cancer.&rft.au=Roberts%2C+J+D%3BKlein%2C+J+L%3BPalmantier%2C+R%3BDhume%2C+S+T%3BGeorge%2C+M+D%3BOlden%2C+K&rft.aulast=Roberts&rft.aufirst=J&rft.date=1998-01-01&rft.volume=22&rft.issue=5&rft.spage=455&rft.isbn=&rft.btitle=&rft.title=Cancer+detection+and+prevention&rft.issn=0361090X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-11-10 N1 - Date created - 1998-11-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Age at smoking onset and its association with alcohol consumption and DSM-IV alcohol abuse and dependence: results from the National Longitudinal Alcohol Epidemiologic Survey. AN - 73871902; 9720007 AB - The major purpose of this study was to examine the relationship of early onset smoking with lifetime drinking and the subsequent development of DSM-IV alcohol abuse and dependence using a large representative sample of the U.S. general population. Prevalences of lifetime drinking, alcohol abuse and dependence, and their associated severity were compared among smoking groups defined by age at onset of smoking and among nonsmokers. Linear logistic regression analyses were conducted to assess the relationship between age at smoking onset and lifetime drinking, alcohol abuse and dependence, controlling for important covariates. Early onset smoking was a significant predictor of lifetime drinking and the subsequent development of lifetime alcohol abuse and dependence, a relationship that generally remained consistent for males, females, whites and blacks. Early onset smoking was significantly associated with more excessive alcohol consumption and more severe alcohol use disorders relative to late onset smokers and nonsmokers. Early onset smoking was also significantly associated with heavier and longer smoking careers compared to late onset smokers. Implications of these findings are discussed in terms of prevention of adolescent smoking and the need for further research on understanding the mechanisms underlying the associations between early onset smoking and lifetime drinking, alcohol abuse and dependence. JF - Journal of substance abuse AU - Grant, B F AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20852-7003, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 59 EP - 73 VL - 10 IS - 1 SN - 0899-3289, 0899-3289 KW - Index Medicus KW - Severity of Illness Index KW - Regression Analysis KW - Age of Onset KW - Chi-Square Distribution KW - Humans KW - Social Behavior KW - Aged KW - Longitudinal Studies KW - Adult KW - Interviews as Topic KW - Middle Aged KW - United States -- epidemiology KW - Female KW - Male KW - Prevalence KW - Alcoholism -- epidemiology KW - Smoking -- psychology KW - Alcohol Drinking -- epidemiology KW - Alcoholism -- psychology KW - Smoking -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73871902?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+substance+abuse&rft.atitle=Age+at+smoking+onset+and+its+association+with+alcohol+consumption+and+DSM-IV+alcohol+abuse+and+dependence%3A+results+from+the+National+Longitudinal+Alcohol+Epidemiologic+Survey.&rft.au=Grant%2C+B+F&rft.aulast=Grant&rft.aufirst=B&rft.date=1998-01-01&rft.volume=10&rft.issue=1&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=Journal+of+substance+abuse&rft.issn=08993289&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-11-30 N1 - Date created - 1998-11-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mortality of industrial workers exposed to acrylonitrile. AN - 73859585; 9714511 AB - This study was designed to evaluate the relationship between occupational exposure to acrylonitrile and cancer mortality. Workers (18079 white men, 4293 white women, 2191 nonwhite men, and 897 nonwhite women) employed in acrylonitrile production or use in the 1950s through 1983 were followed through 1989 for vital status and cause of death. Exposure-response relationships were evaluated from quantitative estimates of historical exposures. Tobacco use was determined for a sample of workers to assess potential confounding. Mortality rates between the exposed and unexposed workers in the cohort were compared using the Poisson regression. Analyses by cumulative, average, peak, intensity, duration, and lagged exposure revealed no elevated risk of cancers of the stomach, brain, breast, prostate or lymphatic and hematopoietic systems. Mortality from lung cancer was elevated for the highest quintile of cumulative exposure. When the decile categories were used, the relative risk did not continue to increase at higher levels. Adjustment for cigarette use reduced the risk for lung cancer only slightly. Separate analyses for wage and salaried workers, long-term and short-term workers, fiber and nonfiber plants, and individual plants revealed no clear exposure-response patterns. The results indicate that exposure to acrylonitrile at the levels studied is not associated with an increased relative risk for most cancers of a priori interest. The excess of lung cancer in the highest quintile of cumulative exposure may indicate carcinogenic activity at the highest levels of exposure, but analyses of exposure-response do not provide strong or consistent evidence for a causal association. JF - Scandinavian journal of work, environment & health AU - Blair, A AU - Stewart, P A AU - Zaebst, D D AU - Pottern, L AU - Zey, J N AU - Bloom, T F AU - Miller, B AU - Ward, E AU - Lubin, J AD - Occupational Epidemiology Branch, National Cancer Institute, Bethesda, Maryland 20892, United States. BLAIRA@epndce.nci.nih.gov Y1 - 1998 PY - 1998 DA - 1998 SP - 25 EP - 41 VL - 24 Suppl 2 SN - 0355-3140, 0355-3140 KW - Acrylonitrile KW - MP1U0D42PE KW - Index Medicus KW - Regression Analysis KW - Humans KW - Aged KW - Poisson Distribution KW - Smoking -- epidemiology KW - Age Distribution KW - Lung Neoplasms -- diagnosis KW - Survival Rate KW - Risk Factors KW - Adult KW - Cohort Studies KW - Case-Control Studies KW - Incidence KW - Middle Aged KW - Data Collection KW - Lung Neoplasms -- mortality KW - Lung Neoplasms -- chemically induced KW - United States -- epidemiology KW - Sex Distribution KW - Male KW - Female KW - Occupational Exposure -- statistics & numerical data KW - Neoplasms -- diagnosis KW - Acrylonitrile -- adverse effects KW - Neoplasms -- mortality KW - Neoplasms -- chemically induced KW - Occupational Exposure -- adverse effects KW - Chemical Industry -- statistics & numerical data KW - Cause of Death UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73859585?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scandinavian+journal+of+work%2C+environment+%26+health&rft.atitle=Mortality+of+industrial+workers+exposed+to+acrylonitrile.&rft.au=Blair%2C+A%3BStewart%2C+P+A%3BZaebst%2C+D+D%3BPottern%2C+L%3BZey%2C+J+N%3BBloom%2C+T+F%3BMiller%2C+B%3BWard%2C+E%3BLubin%2C+J&rft.aulast=Blair&rft.aufirst=A&rft.date=1998-01-01&rft.volume=24+Suppl+2&rft.issue=&rft.spage=25&rft.isbn=&rft.btitle=&rft.title=Scandinavian+journal+of+work%2C+environment+%26+health&rft.issn=03553140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-22 N1 - Date created - 1998-10-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Construction and analysis of multidrug resistance transgenic mice. AN - 73851278; 9711584 JF - Methods in enzymology AU - Evans, G L AD - Clinical Gene Therapy Branch, National Center for Human Genome Research, Bethesda, Maryland 20892, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 572 EP - 594 VL - 292 SN - 0076-6879, 0076-6879 KW - DNA Primers KW - 0 KW - DNA Probes KW - DNA, Complementary KW - P-Glycoprotein KW - RNA KW - 63231-63-0 KW - Verapamil KW - CJ0O37KU29 KW - Index Medicus KW - Animals KW - Homozygote KW - Humans KW - Leukocytes -- physiology KW - Transcription, Genetic KW - Organ Specificity KW - Mice KW - Mice, Transgenic KW - Leukopenia -- prevention & control KW - RNA -- biosynthesis KW - Leukopenia -- chemically induced KW - Polymerase Chain Reaction -- methods KW - In Situ Hybridization, Fluorescence -- methods KW - Time Factors KW - Verapamil -- toxicity KW - P-Glycoprotein -- genetics KW - P-Glycoprotein -- biosynthesis KW - Drug Resistance, Multiple -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73851278?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+enzymology&rft.atitle=Construction+and+analysis+of+multidrug+resistance+transgenic+mice.&rft.au=Evans%2C+G+L&rft.aulast=Evans&rft.aufirst=G&rft.date=1998-01-01&rft.volume=292&rft.issue=&rft.spage=572&rft.isbn=&rft.btitle=&rft.title=Methods+in+enzymology&rft.issn=00766879&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-16 N1 - Date created - 1998-09-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Purification and reconstitution of human P-glycoprotein. AN - 73851197; 9711577 AB - Human Pgp from the vinblastine-resistant cell line, KB-V1, can be purified by sequential conventional chromatography on DEAE-sepharose CL-6B resin followed by a wheat germ agglutinin column. By including glycerol (osmolyte protectant) and lipid during the solubilization and chromatography procedures most of the biological activity of Pgp can be retained. The activity of Pgp in the detergent extract or in the concentrated column fractions is stable for at least 8-10 months when stored at -80 degrees. However, repeated cycles of freezing and thawing of fractions result in considerable loss of activity. We have purified Pgp from KB-C1 (a subclone of KB 3-1 that is resistant to 1 microgram/ml colchicine) by following the same protocol. When this method was used for purification of Pgp from MDR1-transfected NIH 3T3 transfectants (N3-V2400, grown in the presence of 2.4 micrograms/ml vinblastine), the protein was eluted with 0.1 M NaCl from the DEAE-Sepharose CL-6B column as usual. However, during WGA lectin chromatography, the protein was eluted with a lower concentration of sugar (0.1 M instead of 0.25 M NAG). This altered elution pattern appears to be due to a difference in the glycosylation of human Pgp in mouse NIH 3T3 cells. This is consistent with the observation that human Pgp expressed in NIH 3T3 cells migrates faster compared to the protein from KB-V1 cells on 8-10% acrylamide gel. Similarly, other workers have purified Chinese hamster Pgp either by a single-step chromatography on Reactive Red 120 agarose or by a combination of anion exchange and immunoaffinity chromatography (see the article by Senior et al. for the purification and properties of ATPase activity of Chinese hamster Pgp). The high level of drug-stimulated ATP hydrolysis by Pgp (Table I), like other ion-transporting ATPases, indicates that this is a high-capacity pump that can function as an effective multidrug transporter. This is further supported by the qualitative demonstration of ATP-dependent vinblastine transport in proteoliposomes reconstituted with pure Pgp (see Fig. 2). Thus, these experiments provide strong evidence that purified Pgp retains its activity and that it functions as an ATP-dependent drug transporter. JF - Methods in enzymology AU - Ambudkar, S V AU - Lelong, I H AU - Zhang, J AU - Cardarelli, C AD - Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 492 EP - 504 VL - 292 SN - 0076-6879, 0076-6879 KW - Indicators and Reagents KW - 0 KW - Liposomes KW - P-Glycoprotein KW - Proteolipids KW - Recombinant Proteins KW - proteoliposomes KW - Vinblastine KW - 5V9KLZ54CY KW - Verapamil KW - CJ0O37KU29 KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - Colchicine KW - SML2Y3J35T KW - Daunorubicin KW - ZS7284E0ZP KW - Index Medicus KW - Clone Cells KW - KB Cells KW - 3T3 Cells KW - Animals KW - Solubility KW - Chromatography, Ion Exchange -- methods KW - Electrophoresis, Polyacrylamide Gel KW - Humans KW - Mice KW - Vinblastine -- toxicity KW - Verapamil -- pharmacology KW - Drug Resistance, Multiple KW - Daunorubicin -- pharmacology KW - Transfection -- methods KW - Recombinant Proteins -- isolation & purification KW - Colchicine -- pharmacology KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Chromatography, Affinity -- methods KW - Cricetinae KW - Adenosine Triphosphatases -- drug effects KW - P-Glycoprotein -- metabolism KW - Adenosine Triphosphatases -- metabolism KW - P-Glycoprotein -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73851197?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+enzymology&rft.atitle=Purification+and+reconstitution+of+human+P-glycoprotein.&rft.au=Ambudkar%2C+S+V%3BLelong%2C+I+H%3BZhang%2C+J%3BCardarelli%2C+C&rft.aulast=Ambudkar&rft.aufirst=S&rft.date=1998-01-01&rft.volume=292&rft.issue=&rft.spage=492&rft.isbn=&rft.btitle=&rft.title=Methods+in+enzymology&rft.issn=00766879&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-16 N1 - Date created - 1998-09-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HIV/AIDS and drug abuse: epidemiology and prevention. AN - 70117950; 9848034 AB - In the United States, the AIDS epidemic is a dynamic process with increasing rates of AIDS reported among women, minority populations, heterosexual men, and users of drugs by routes other than injection. The 1993 CDC AIDS definition change has created some difficulties in interpreting trends in the United States. Drug use continues to represent a significant problem among HIV-infected persons. Several strategies have been advanced to decrease transmission of HIV among drug users, their sexual partners and children. However, more effective and comprehensive prevention and treatment strategies are needed. JF - Journal of addictive diseases AU - Haverkos, H W AD - Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Rockville, MD, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 91 EP - 103 VL - 17 IS - 4 SN - 1055-0887, 1055-0887 KW - Index Medicus KW - AIDS/HIV KW - Needle-Exchange Programs KW - Humans KW - Infant, Newborn KW - Aged KW - Child KW - Community-Institutional Relations KW - Child, Preschool KW - Infant KW - Sexual Behavior KW - Public Health KW - Adult KW - Incidence KW - Middle Aged KW - Adolescent KW - United States -- epidemiology KW - Female KW - Male KW - Acquired Immunodeficiency Syndrome -- epidemiology KW - Risk-Taking KW - Acquired Immunodeficiency Syndrome -- transmission KW - Acquired Immunodeficiency Syndrome -- psychology KW - Substance-Related Disorders -- complications KW - Substance-Related Disorders -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70117950?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+addictive+diseases&rft.atitle=HIV%2FAIDS+and+drug+abuse%3A+epidemiology+and+prevention.&rft.au=Haverkos%2C+H+W&rft.aulast=Haverkos&rft.aufirst=H&rft.date=1998-01-01&rft.volume=17&rft.issue=4&rft.spage=91&rft.isbn=&rft.btitle=&rft.title=Journal+of+addictive+diseases&rft.issn=10550887&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-19 N1 - Date created - 1999-02-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The germ cell--the mother of all stem cells. AN - 70113388; 9853836 AB - The germline, uniquely amongst the lineages of the embryo, carries the genome from generation to generation and is therefore the only lineage which retains true developmental totipotency. Paradoxically, when mouse primordial germ cells (PGCs) are introduced into a host blastocyst, they do not contribute to either the germline or the soma, suggesting that they are restricted in developmental potency. Conversely, in vivo PGCs give rise to embryonal carcinoma (EC) cells, the pluripotent stem cells of teratomas, benign tumors containing derivatives of the three primary germ layers. Similarly, PGCs can be converted in vitro into embryonic germ (EG) cells, pluripotent stem cells capable of giving rise to somatic and germline chimeras. The ability of PGCs to form EC cells in vivo and EG cells in vitro suggests that developmental potency of PGCs is regulateable. The molecular mechanisms controlling PGC growth and differentiation are gradually being elucidated through the characterization of sterile mutants and through the use of in vitro culture systems. Understanding how a PGC can give rise to a pluripotent stem cell could give significant insights into the regulation of developmental totipotency as well as having important implications for male fertility and the etiology of testicular cancer. JF - The International journal of developmental biology AU - Donovan, P J AD - Cell Biology of Development and Differentiation Group, ABL-Basic Research Program, NCI-FCRDC, Frederick MD, USA. pdonovan@lac.jci.tju.edu Y1 - 1998 PY - 1998 DA - 1998 SP - 1043 EP - 1050 VL - 42 IS - 7 SN - 0214-6282, 0214-6282 KW - Index Medicus KW - Animals KW - Culture Techniques KW - Neoplastic Stem Cells KW - Teratoma -- pathology KW - Cell Differentiation KW - Mice KW - Embryo, Mammalian KW - Male KW - Female KW - Embryonal Carcinoma Stem Cells KW - Cell Division KW - Germ Cells KW - Stem Cells UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70113388?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+International+journal+of+developmental+biology&rft.atitle=The+germ+cell--the+mother+of+all+stem+cells.&rft.au=Donovan%2C+P+J&rft.aulast=Donovan&rft.aufirst=P&rft.date=1998-01-01&rft.volume=42&rft.issue=7&rft.spage=1043&rft.isbn=&rft.btitle=&rft.title=The+International+journal+of+developmental+biology&rft.issn=02146282&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-23 N1 - Date created - 1999-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevalence of anxiety disorders and their comorbidity with mood and addictive disorders. AN - 70070346; 9829013 AB - The co-occurrence of anxiety disorders with other mental, addictive, and physical disorders has important implications for treatment and for prediction of clinical course and associated morbidity. Cross-sectional and prospective data on 20,291 individuals from the Epidemiologic Catchment Area (ECA) study were analysed to determine one-month, current disorders, one-year incidence, and one-year and lifetime prevalence of anxiety, mood, and addictive disorders, and to identify the onset and offset of disorders within the one-year prospective period. Nearly half (47.2%) of those meeting lifetime criteria for major depression also have met criteria for a comorbid anxiety disorder. The average age of onset of any lifetime anxiety disorder (16.4 years) and social phobia (11.6 years) among those with major depression was much younger than the onset age for major depression (23.2 years) and panic disorder. Anxiety disorders, especially social and simple phobias, appear to have an early onset in adolescence with potentially severe consequences, predisposing those affected to greater vulnerability to major depression and addictive disorders. JF - The British journal of psychiatry. Supplement AU - Regier, D A AU - Rae, D S AU - Narrow, W E AU - Kaelber, C T AU - Schatzberg, A F AD - Division of Epidemiology and Services Research, National Institute of Mental Health, National Institutes of Health, Rockville, Maryland 20857, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 24 EP - 28 IS - 34 SN - 0960-5371, 0960-5371 KW - Index Medicus KW - Cross-Sectional Studies KW - Prospective Studies KW - Age of Onset KW - Humans KW - Adult KW - Retrospective Studies KW - Diagnosis, Dual (Psychiatry) KW - Aged KW - Middle Aged KW - Massachusetts -- epidemiology KW - Adolescent KW - Prevalence KW - Substance-Related Disorders -- etiology KW - Mood Disorders -- epidemiology KW - Anxiety Disorders -- epidemiology KW - Anxiety Disorders -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70070346?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+British+journal+of+psychiatry.+Supplement&rft.atitle=Prevalence+of+anxiety+disorders+and+their+comorbidity+with+mood+and+addictive+disorders.&rft.au=Regier%2C+D+A%3BRae%2C+D+S%3BNarrow%2C+W+E%3BKaelber%2C+C+T%3BSchatzberg%2C+A+F&rft.aulast=Regier&rft.aufirst=D&rft.date=1998-01-01&rft.volume=&rft.issue=34&rft.spage=24&rft.isbn=&rft.btitle=&rft.title=The+British+journal+of+psychiatry.+Supplement&rft.issn=09605371&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-03 N1 - Date created - 1998-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacokinetics of methyl palmoxirate, an inhibitor of beta-oxidation, in rats and humans. AN - 70063782; 9820128 AB - Recent studies from our laboratory have shown that methyl palmoxirate (MEP), an inhibitor of mitochondrial beta-oxidation of long chain fatty acids, can be used to increase incorporation of radiolabeled palmitic acid into brain lipids and reduce beta-oxidation of the fatty acid. Thus, MEP allows the use of carbon labeled palmitate for studying brain lipid metabolism in animals and humans by quantitative autoradiography or positron emission tomography (PET). As it is essential to pretreat human subjects with an acute dose of MEP prior to intravenous injection of [1-11C]palmitate for PET scanning, this study was undertaken to determine the plasma elimination half-life of MEP in rats and human subjects and to provide insight about the drug's absorption and metabolism. A gas chromatographic method was developed to measure MEP in body fluids. Following oral administration of MEP to rats (2.5 and 10 mg/kg) and to humans, the unmetabolized drug could not be detected in plasma or urine (sensitivity of detection was 1 ng). However, when MEP was injected intravenously (10 mg/kg) in rats, a peak initial concentration could be measured in plasma (7.7 microg/mL), the clearance of the drug from plasma was rapid (t1/2 = 0.6 min), which indicates that MEP readily enters tissue lipid pools or is metabolized like long-chain fatty acids. As no adverse experience occured in the 11 human subjects studied, oral administration of a single dose of MEP was safe under the conditions of this study and may be used to increase the incorporation of positron labeled palmitic acid for studying brain lipid metabolism in vivo by PET. JF - Life sciences AU - Chang, M C AU - Connolly, C AU - Hill, D AU - Purdon, A D AU - Hayakawa, T AU - Grimes, G AU - Shetty, H U AD - Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA. mcjchang@box-m.nih.gov Y1 - 1998 PY - 1998 DA - 1998 SP - PL297 EP - PL302 VL - 63 IS - 20 SN - 0024-3205, 0024-3205 KW - Epoxy Compounds KW - 0 KW - Hypoglycemic Agents KW - Propionates KW - methyl 2-tetradecylglycidate KW - NPL6006Y4B KW - Index Medicus KW - Rats KW - Administration, Oral KW - Animals KW - Rats, Inbred F344 KW - Oxidation-Reduction -- drug effects KW - Injections, Intravenous KW - Humans KW - Brain -- drug effects KW - Mitochondria -- drug effects KW - Mitochondria -- metabolism KW - Brain -- metabolism KW - Male KW - Epoxy Compounds -- adverse effects KW - Epoxy Compounds -- pharmacokinetics KW - Propionates -- pharmacokinetics KW - Hypoglycemic Agents -- administration & dosage KW - Hypoglycemic Agents -- adverse effects KW - Epoxy Compounds -- administration & dosage KW - Propionates -- adverse effects KW - Propionates -- administration & dosage KW - Hypoglycemic Agents -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70063782?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Life+sciences&rft.atitle=Pharmacokinetics+of+methyl+palmoxirate%2C+an+inhibitor+of+beta-oxidation%2C+in+rats+and+humans.&rft.au=Chang%2C+M+C%3BConnolly%2C+C%3BHill%2C+D%3BPurdon%2C+A+D%3BHayakawa%2C+T%3BGrimes%2C+G%3BShetty%2C+H+U&rft.aulast=Chang&rft.aufirst=M&rft.date=1998-01-01&rft.volume=63&rft.issue=20&rft.spage=PL297&rft.isbn=&rft.btitle=&rft.title=Life+sciences&rft.issn=00243205&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-01 N1 - Date created - 1998-12-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cigarette smoking during early cocaine abstinence. AN - 70046590; 9809135 AB - Use of cocaine has been reported to increase cigarette smoking, but there are no published studies of cigarette smoking during early cocaine abstinence. The authors assessed ad libitum cigarette smoking of 12 cocaine-dependent smokers housed on a closed research ward. Last cocaine use averaged 0.6 grams 1.8 days before admission. Smoking was measured indirectly with computerized cigarette dispensers. There was no significant difference between self-reported daily number of cigarettes smoked before admission and the number of cigarettes dispensed daily for the first 7 full days after admission. These findings suggest that early cocaine abstinence does not significantly alter cigarette smoking. JF - The American journal on addictions AU - Radzius, A AU - Gorelick, D A AU - Henningfield, J E AD - National Institute on Drug Abuse, Baltimore, MD 21224, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 305 EP - 308 VL - 7 IS - 4 SN - 1055-0496, 1055-0496 KW - Narcotics KW - 0 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Substance Withdrawal Syndrome KW - Humans KW - Adult KW - Cocaine -- pharmacology KW - Narcotics -- pharmacology KW - Male KW - Female KW - Smoking KW - Cocaine-Related Disorders -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70046590?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+on+addictions&rft.atitle=Cigarette+smoking+during+early+cocaine+abstinence.&rft.au=Radzius%2C+A%3BGorelick%2C+D+A%3BHenningfield%2C+J+E&rft.aulast=Radzius&rft.aufirst=A&rft.date=1998-01-01&rft.volume=7&rft.issue=4&rft.spage=305&rft.isbn=&rft.btitle=&rft.title=The+American+journal+on+addictions&rft.issn=10550496&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-29 N1 - Date created - 1999-01-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mammary gland carcinogenicity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in Sprague-Dawley rats on high- and low-fat diets. AN - 70014377; 9795967 AB - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a carcinogenic heterocyclic amine derived from cooked meat. Mammary gland tumors were induced in female Sprague-Dawley rats given 10 doses of PhIP (75 mg/kg po) once per day from 43 days of age and then placed on a defined high-fat (23.5% corn oil) or low-fat (5% corn oil) diet for 25 weeks. Mammary tumor incidence was 49% (44 of 90 rats) and 31% (27 of 88 rats) in the high- and low-fat groups, respectively. No tumors were found in vehicle control rats on the high-or the low-fat diet (n = 44 and 43, respectively). The higher tumor incidence in the high-fat group was due to an increase specifically in carcinomas (classified as tubulopapillary carcinomas) rather than benign tumors (tubular adenomas and fibroadenomas). The incidence of carcinomas was 45% and 24% in PhIP-treated rats on the high- and low-fat diets, respectively. In addition, the percentage of carcinomas showing stromal invasion was highest in the high-fat diet group (22% vs. 8%, high- vs. low-fat diet). Proliferating cell nuclear antigen immunostaining (PCNA) index revealed six times more proliferation in carcinomas from rats on the high-fat diet than in rats on the low-fat diet. Adenomas from rats on different diets had similar PCNA indexes. The tumor apoptotic index, quantitated by immunohistochemical detection (terminal deoxynucleotidyl transferase nick end labeling), was twice as high in carcinomas from rats on the high-fat diet as in carcinomas from rats on the low-fat diet but was similar between the two groups of adenomas. The PCNA-to-apoptosis ratio was 43 and 17 in carcinomas from rats on the high- and low-fat diets, respectively, indicating that the growth rate of carcinomas was greater in rats on the high-fat diet. The results from this study show that the high-fat diet increases the incidence, invasiveness, and growth of PhIP-induced mammary gland carcinomas. JF - Nutrition and cancer AU - Snyderwine, E G AU - Thorgeirsson, U P AU - Venugopal, M AU - Roberts-Thomson, S J AD - Division of Basic Sciences, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 160 EP - 167 VL - 31 IS - 3 SN - 0163-5581, 0163-5581 KW - Carcinogens KW - 0 KW - Dietary Fats KW - Imidazoles KW - Proliferating Cell Nuclear Antigen KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Meat -- adverse effects KW - Immunohistochemistry KW - Female KW - Mammary Neoplasms, Experimental -- chemically induced KW - Diet, Fat-Restricted KW - Dietary Fats -- adverse effects KW - Mammary Neoplasms, Experimental -- metabolism KW - Imidazoles -- adverse effects KW - Mammary Neoplasms, Experimental -- pathology KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70014377?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nutrition+and+cancer&rft.atitle=Mammary+gland+carcinogenicity+of+2-amino-1-methyl-6-phenylimidazo%5B4%2C5-b%5Dpyridine+in+Sprague-Dawley+rats+on+high-+and+low-fat+diets.&rft.au=Snyderwine%2C+E+G%3BThorgeirsson%2C+U+P%3BVenugopal%2C+M%3BRoberts-Thomson%2C+S+J&rft.aulast=Snyderwine&rft.aufirst=E&rft.date=1998-01-01&rft.volume=31&rft.issue=3&rft.spage=160&rft.isbn=&rft.btitle=&rft.title=Nutrition+and+cancer&rft.issn=01635581&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-29 N1 - Date created - 1998-12-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cocaine and GBR photoaffinity labels as probes of dopamine transporter structure. AN - 69976897; 9779451 AB - Several aspects of DAT structure and function have been elucidated using a combination of photoaffinity labeling, proteolysis, enzymatic deglycosylation, and epitope-specific immunoprecipitation. The two photolabels are incorporated in different regions of the protein, suggesting that the binding sites for the ligands are distinct or partially nonoverlapping, consistent with results produced by site-directed mutagenesis and analysis of chimeras. These studies have also verified several aspects of DAT structure previously hypothesized based only on theoretical considerations, including the presence of at least one transmembrane helix or other membrane-anchoring structure in two different regions of the protein, identification of the glycosylated domain, and some topological properties. It should be possible to extend and adapt these techniques to further delineate DAT structural properties and to identify other functional domains such as phosphorylation sites or active sulfhydryl moieties. JF - Methods in enzymology AU - Vaughan, R A AD - Molecular Neurobiology Branch, National Institute on Drug Abuse, Intramural Research Program, Baltimore, Maryland 21224, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 219 EP - 230 VL - 296 SN - 0076-6879, 0076-6879 KW - Affinity Labels KW - 0 KW - Azides KW - Carbohydrates KW - Carrier Proteins KW - Dopamine Plasma Membrane Transport Proteins KW - Iodine Radioisotopes KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Piperazines KW - Recombinant Proteins KW - SLC6A3 protein, human KW - 1-(2-(diphenylmethoxy)ethyl)-4-(2-(4-azido-3-iodophenyl)ethyl)piperazine KW - 123632-48-4 KW - RTI 82 KW - 141782-67-4 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Animals KW - Humans KW - Glycosylation KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Chromatography, Gel -- methods KW - Transfection KW - Recombinant Proteins -- metabolism KW - Recombinant Proteins -- chemistry KW - Radioligand Assay -- methods KW - Carbohydrates -- analysis KW - Chromatography, Affinity -- methods KW - Piperazines -- chemistry KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- chemistry KW - Cocaine -- chemistry KW - Brain -- metabolism KW - Azides -- chemistry KW - Carrier Proteins -- isolation & purification KW - Piperazines -- pharmacokinetics KW - Cocaine -- analogs & derivatives KW - Azides -- pharmacokinetics KW - Cocaine -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69976897?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+enzymology&rft.atitle=Cocaine+and+GBR+photoaffinity+labels+as+probes+of+dopamine+transporter+structure.&rft.au=Vaughan%2C+R+A&rft.aulast=Vaughan&rft.aufirst=R&rft.date=1998-01-01&rft.volume=296&rft.issue=&rft.spage=219&rft.isbn=&rft.btitle=&rft.title=Methods+in+enzymology&rft.issn=00766879&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-16 N1 - Date created - 1998-12-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Breast cancer risk among women under 55 years of age by joint effects of usage of oral contraceptives and hormone replacement therapy. AN - 69970184; 9774759 AB - To assess effects on breast cancer risk of exposure to both oral contraceptives and menopausal hormones, an increasingly common exposure. A case-control study of breast cancer among women under the age of 55 years in Atlanta, GA involving 1,031 cases and 919 population controls was conducted. Ever use of oral contraceptives was associated with a relative risk of 1.1 (95% 0.9-1.4), whereas the relative risk for hormone replacement therapy was 0.9 (95% CI 0.7-1.2). Seventeen percent of the cases versus 19% of the population controls reported exposure to both agents, resulting in a relative risk of 1.0 (95% CI 0.7-1.4) relative to those unexposed to either preparation. Although there was little variation in risk associated with joint effects by either age or race, there were statistically nonsignificant elevations in risk for this exposure among women who had experienced a natural menopause (relative risk = 2.0, 95% CI 0.7-5.6), were relatively thin (relative risk = 1.5, 0.8-3.0), or who had a first degree relative with breast cancer (relative risk = 2.0, 0.6-7.0). When joint effects of longer term use of both agents were considered, subjects who reported use of oral contraceptives for 10 or more years and hormone replacement for 3 or more years had a relative risk of 3.2 (95% CI 1.4-7.4) compared with nonusers of either preparation. Although our results must be cautiously interpreted given small numbers within subgroups, they raise concern and emphasize the need for further evaluation on breast cancer risk of the increasingly common exposure to both oral contraceptives and hormone replacement therapy. JF - Menopause (New York, N.Y.) AU - Brinton, L A AU - Brogan, D R AU - Coates, R J AU - Swanson, C A AU - Potischman, N AU - Stanford, J L AD - Environmental Epidemiology Branch, National Cancer Institute, Bethesda, Maryland 20892-7374, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 145 EP - 151 VL - 5 IS - 3 SN - 1072-3714, 1072-3714 KW - Contraceptives, Oral KW - 0 KW - Index Medicus KW - Body Weight KW - Age Factors KW - Georgia -- epidemiology KW - Risk Factors KW - Humans KW - Continental Population Groups KW - Adult KW - Case-Control Studies KW - Middle Aged KW - Body Constitution KW - Menopause KW - Female KW - Contraceptives, Oral -- adverse effects KW - Breast Neoplasms -- genetics KW - Estrogen Replacement Therapy -- adverse effects KW - Breast Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69970184?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Menopause+%28New+York%2C+N.Y.%29&rft.atitle=Breast+cancer+risk+among+women+under+55+years+of+age+by+joint+effects+of+usage+of+oral+contraceptives+and+hormone+replacement+therapy.&rft.au=Brinton%2C+L+A%3BBrogan%2C+D+R%3BCoates%2C+R+J%3BSwanson%2C+C+A%3BPotischman%2C+N%3BStanford%2C+J+L&rft.aulast=Brinton&rft.aufirst=L&rft.date=1998-01-01&rft.volume=5&rft.issue=3&rft.spage=145&rft.isbn=&rft.btitle=&rft.title=Menopause+%28New+York%2C+N.Y.%29&rft.issn=10723714&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-03 N1 - Date created - 1998-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effect of an antisense expression plasmid to the IGF-1 receptor on hamster mesothelioma proliferation. AN - 69963553; 9776253 AB - We have evaluated the effect of antisense IGF receptor transcripts on the proliferation and tumorigenicity in an SV40-induced, immunocompetent hamster mesothelioma model (H9A). Expression of IGF-1 and IGF-1 receptor (IGF-1 R) genes was identified from H9A RNA using RT-PCR and Northern blot analysis. H9A cells were electroporated with inducible expression vectors (under the transcriptional control of heat shock promotor HSP70) containing a cDNA fragment corresponding to bp 1-309 of IGF-1 R in the sense or antisense orientation to generate the respective clones A3 sense or B9 antisense. At 39 degrees C, the B9 antisense transfectants demonstrated significantly less proliferation than A3 sense transfectants (p2 < 0.02). At 34 degrees C, cell growth of A3 sense and B9 antisense transfected cells was not significantly different. The A3 sense clones resulted in greater numbers of tumours in vivo compared to the B9 antisense clone (p2 = 0.0001). The inhibitory effect of IGF-1R antisense transcripts on hamster mesothelioma demonstrated in this study by decreased growth and tumorigenicity in vitro and in vivo may have implications for the therapy of human mesothelioma. JF - Developments in biological standardization AU - Pass, H I AU - Mew, D J AU - Carbone, M AU - Donington, J S AU - Baserga, R AU - Steinberg, S M AD - Thoracic Oncology Section, NCI/NIH, Bethesda, MD, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 321 EP - 328 VL - 94 SN - 0301-5149, 0301-5149 KW - HSP70 Heat-Shock Proteins KW - 0 KW - Oligonucleotides, Antisense KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Receptor, IGF Type 1 KW - EC 2.7.10.1 KW - Index Medicus KW - Insulin-Like Growth Factor I -- biosynthesis KW - HSP70 Heat-Shock Proteins -- metabolism KW - Animals KW - Tumor Cells, Cultured KW - Simian virus 40 -- isolation & purification KW - Humans KW - Asbestosis -- complications KW - Cell Transformation, Neoplastic -- drug effects KW - Plasmids KW - Cricetinae KW - Receptor, IGF Type 1 -- physiology KW - Pleural Neoplasms -- virology KW - Mesothelioma -- etiology KW - Pleural Neoplasms -- pathology KW - Mesothelioma -- pathology KW - Receptor, IGF Type 1 -- genetics KW - Oligonucleotides, Antisense -- pharmacology KW - Mesothelioma -- virology KW - Pleural Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69963553?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Developments+in+biological+standardization&rft.atitle=The+effect+of+an+antisense+expression+plasmid+to+the+IGF-1+receptor+on+hamster+mesothelioma+proliferation.&rft.au=Pass%2C+H+I%3BMew%2C+D+J%3BCarbone%2C+M%3BDonington%2C+J+S%3BBaserga%2C+R%3BSteinberg%2C+S+M&rft.aulast=Pass&rft.aufirst=H&rft.date=1998-01-01&rft.volume=94&rft.issue=&rft.spage=321&rft.isbn=&rft.btitle=&rft.title=Developments+in+biological+standardization&rft.issn=03015149&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-22 N1 - Date created - 1998-12-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanisms of isoniazid resistance in Mycobacterium tuberculosis. AN - 69266388; 16904399 AB - Isoniazid (INH) is a widely used front-line antituberculous agent with bacteriocidal activity at concentrations as low as 150 nM against Mycobacterium tuberculosis. INH is a prodrug and requires activation by an endogenous mycobacterial enzyme, the catalase-peroxidase KatG, before exerting toxic effects on cellular targets. Resistance to INH develops primarily through failure to activate the prodrug due to point mutations in the katG gene. In addition to mutations in katG, mutations in several other loci, such as the alkylhydroperoxidase AhpC and the enoylreductase InhA, may contribute to INH resistance. Although these markers can be used to accurately predict clinical INH resistance in a large number of cases, the molecular mechanisms involved remain largely speculative and incomplete. JF - Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy AU - Barry, C E AU - Slayden, R A AU - Mdluli, K AD - Tuberculosis Research Unit, Rocky Mountain Laboratories, National Institutes for Allergy and Infectious Disease, National Institutes of Health, Hamilton, Montana 59840, USA. clifton_barry@nih.gov Y1 - 1998 PY - 1998 DA - 1998 SP - 128 EP - 134 VL - 1 IS - 2 SN - 1368-7646, 1368-7646 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69266388?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+resistance+updates+%3A+reviews+and+commentaries+in+antimicrobial+and+anticancer+chemotherapy&rft.atitle=Mechanisms+of+isoniazid+resistance+in+Mycobacterium+tuberculosis.&rft.au=Barry%2C+C+E%3BSlayden%2C+R+A%3BMdluli%2C+K&rft.aulast=Barry&rft.aufirst=C&rft.date=1998-01-01&rft.volume=1&rft.issue=2&rft.spage=128&rft.isbn=&rft.btitle=&rft.title=Drug+resistance+updates+%3A+reviews+and+commentaries+in+antimicrobial+and+anticancer+chemotherapy&rft.issn=13687646&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2007-06-28 N1 - Date created - 2006-08-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recent insights into the molecular basis of intrinsic resistance of colorectal cancer: new challenges for systemic therapeutic approaches. AN - 69203495; 10326673 JF - Cancer treatment and research AU - Grem, J L AD - Developmental Therapeutics Department, National Cancer Institute, National Naval Medical Center, Bethesda, MD 20889, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 293 EP - 338 VL - 98 SN - 0927-3042, 0927-3042 KW - Antimetabolites, Antineoplastic KW - 0 KW - Pyrimidines KW - Thymidylate Synthase KW - EC 2.1.1.45 KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Fluorouracil -- therapeutic use KW - Pyrimidines -- adverse effects KW - Thymidylate Synthase -- drug effects KW - Combined Modality Therapy KW - Humans KW - Cell Death -- drug effects KW - Antimetabolites, Antineoplastic -- therapeutic use KW - Drug Resistance, Neoplasm -- genetics KW - Colorectal Neoplasms -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69203495?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+treatment+and+research&rft.atitle=Recent+insights+into+the+molecular+basis+of+intrinsic+resistance+of+colorectal+cancer%3A+new+challenges+for+systemic+therapeutic+approaches.&rft.au=Grem%2C+J+L&rft.aulast=Grem&rft.aufirst=J&rft.date=1998-01-01&rft.volume=98&rft.issue=&rft.spage=293&rft.isbn=&rft.btitle=&rft.title=Cancer+treatment+and+research&rft.issn=09273042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-14 N1 - Date created - 1999-07-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Assignment of the cyclin I gene (Ccni) to mouse chromosome 5E3.3-F1. 3 by in situ hybridization. AN - 69186624; 10072591 JF - Cytogenetics and cell genetics AU - Jensen, M R AU - Audolfsson, T AU - Keck, C L AU - Zimonjic, D B AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD,USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 242 EP - 243 VL - 83 IS - 3-4 SN - 0301-0171, 0301-0171 KW - CCNI protein, human KW - 0 KW - Ccni protein, mouse KW - Cyclin I KW - Cyclins KW - DNA, Complementary KW - Index Medicus KW - Animals KW - Humans KW - In Situ Hybridization, Fluorescence KW - Mice KW - Chromosome Mapping KW - Chromosomes -- genetics KW - Cyclins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69186624?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytogenetics+and+cell+genetics&rft.atitle=Assignment+of+the+cyclin+I+gene+%28Ccni%29+to+mouse+chromosome+5E3.3-F1.+3+by+in+situ+hybridization.&rft.au=Jensen%2C+M+R%3BAudolfsson%2C+T%3BKeck%2C+C+L%3BZimonjic%2C+D+B%3BThorgeirsson%2C+S+S&rft.aulast=Jensen&rft.aufirst=M&rft.date=1998-01-01&rft.volume=83&rft.issue=3-4&rft.spage=242&rft.isbn=&rft.btitle=&rft.title=Cytogenetics+and+cell+genetics&rft.issn=03010171&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-30 N1 - Date created - 1999-03-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular epidemiology of human cancer. AN - 69178290; 10026991 AB - A challenging goal of molecular epidemiology is to identify an individual's risk of cancer. Molecular epidemiology integrates molecular biology, in vitro and in vivo laboratory models, biochemistry and epidemiology to infer individual cancer risk. Molecular dosimetry of carcinogen exposure is an important facet of molecular epidemiology and cancer risk assessment. Carcinogen macromolecular adduct levels, cytogenetic alterations and somatic cell mutations can be measured to determine the biologically effective doses of carcinogens. Molecular epidemiology also explores host cancer susceptibilities, such as carcinogen metabolism, DNA repair, and epigenetic and genetic alterations in tumor suppressor genes. p53 is a prototype tumor suppressor gene and is well suited for analysis of mutational spectrum in human cancer. The analyses of germ line and somatic mutation spectra of the p53 tumor suppressor gene provide important clues for cancer risk assessment in molecular epidemiology. For example, characteristic p53 mutation spectra have been associated with: dietary aflatoxin B1 exposure and hepatocellular carcinoma; sunlight exposure and skin carcinoma; and cigarette smoking and lung cancer. The mutation spectrum also reveals those p53 mutants that provide cells with a selective clonal expansion advantage during the multistep process of carcinogenesis. The p53 gene encodes a multifunctional protein involved in the cellular response to stress including DNA damage and hypoxia. Certain p53 mutants lose tumor suppressor activity and gain oncogenic activity, which is one explanation for the commonality of p53 mutations in human cancer. Molecular epidemiological results can be evaluated for causation by inference of the Bradford-Hill criteria, i.e., strength of association (consistency, specificity and temporality) and biological plausibility, which utilizes the "weight of the evidence principle." JF - Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer AU - Hussain, S P AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD 20892-4255, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 22 EP - 36 VL - 154 SN - 0080-0015, 0080-0015 KW - Carcinogens KW - 0 KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Tumor Suppressor Protein p53 -- physiology KW - Apoptosis KW - Molecular Epidemiology KW - Genes, Tumor Suppressor KW - Humans KW - Carcinogens -- toxicity KW - Tumor Suppressor Protein p53 -- chemistry KW - Genetic Predisposition to Disease KW - Neoplasms -- genetics KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69178290?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Recent+results+in+cancer+research.+Fortschritte+der+Krebsforschung.+Progres+dans+les+recherches+sur+le+cancer&rft.atitle=Molecular+epidemiology+of+human+cancer.&rft.au=Hussain%2C+S+P%3BHarris%2C+C+C&rft.aulast=Hussain&rft.aufirst=S&rft.date=1998-01-01&rft.volume=154&rft.issue=&rft.spage=22&rft.isbn=&rft.btitle=&rft.title=Recent+results+in+cancer+research.+Fortschritte+der+Krebsforschung.+Progres+dans+les+recherches+sur+le+cancer&rft.issn=00800015&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-05 N1 - Date created - 1999-03-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Translational control elements in the major human transforming growth factor-beta 1 mRNA. AN - 69164683; 9932227 AB - Polysome analysis indicates that the major 2.4 kb transforming growth factor-beta 1 (TGF-beta 1) transcript is poorly translated, both in cultured cells, and in vivo in mouse liver. In contrast, the TGF-beta 2 transcripts are efficiently translated. The contribution of the 5'- and 3'-untranslated regions (UTRs) to the translational inhibition of the full-length TGF-beta 1 transcript was studied by deletion analysis. Despite their high G + C content, both UTRs stimulated translation in vitro. However, polysome analysis of synthetic TGF-beta 1 mRNAs transfected into MCF-7 cells suggests that the cell contains a limited pool of trans-acting factors that interact with the 5'UTR to make it inhibitory in vivo. Further deletion analysis in vitro revealed multiple stimulatory and inhibitory regions in the 5'UTR. This has important implications for the translatability of the naturally occurring shorter TGF-beta 1 transcripts and provides a framework for higher resolution mapping studies. Overall, the poor translational efficiency of the major TGF-beta 1 mRNA in vivo appears to be due to a combination of poor initiation sequence context, and inhibitory interactions of limiting transacting factors with cis-inhibitory elements embedded in an otherwise stimulatory 5'UTR. JF - Growth factors (Chur, Switzerland) AU - Allison, R S AU - Mumy, M L AU - Wakefield, L M AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 89 EP - 100 VL - 16 IS - 2 SN - 0897-7194, 0897-7194 KW - 3' Untranslated Regions KW - 0 KW - 5' Untranslated Regions KW - RNA, Messenger KW - Transforming Growth Factor beta KW - Index Medicus KW - Regulatory Sequences, Nucleic Acid KW - Tumor Cells, Cultured KW - Open Reading Frames KW - Humans KW - Protein Biosynthesis KW - Transforming Growth Factor beta -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69164683?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Growth+factors+%28Chur%2C+Switzerland%29&rft.atitle=Translational+control+elements+in+the+major+human+transforming+growth+factor-beta+1+mRNA.&rft.au=Allison%2C+R+S%3BMumy%2C+M+L%3BWakefield%2C+L+M&rft.aulast=Allison&rft.aufirst=R&rft.date=1998-01-01&rft.volume=16&rft.issue=2&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=Growth+factors+%28Chur%2C+Switzerland%29&rft.issn=08977194&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-13 N1 - Date created - 1999-04-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Diet and mammary gland carcinogenesis. AN - 69161305; 9928542 AB - The variation in human breast cancer incidence rates worldwide suggests that lifestyle factors, especially diet, influence breast cancer risk. There is convincing evidence that diets associated with rapid growth and greater adult height increase breast cancer risk. In addition, diet and other lifestyle factors which lead to high body mass, especially during postmenopausal years, also appear to increase risk. Several dietary components have been evaluated in epidemiological and animal studies for their role in breast cancer. Dietary fat was once implicated in the high incidence of breast cancer in the Western world, but its role in breast cancer is now controversial. In contrast, alcohol consumption is currently recognized as the best-established dietary risk factor in this disease. Carcinogens that cause mammary gland cancer in rats such as heterocyclic amines and polycyclic aromatic hydrocarbons are found in cooked meat, but it is not yet known if these carcinogens are etiological factors in human breast cancer. Fruits and vegetables are rich in potential chemopreventive factors that may lower breast cancer risk. Practical approaches to dietary modification that include increasing fruit and vegetable consumption, eating a low fat diet, reducing cooked meat consumption, and avoiding alcohol are likely to be of potential overall benefit in lowering the risk of human breast cancer. JF - Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer AU - Snyderwine, E G AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 3 EP - 10 VL - 152 SN - 0080-0015, 0080-0015 KW - Carcinogens KW - 0 KW - Dietary Fats KW - Index Medicus KW - Animals KW - Dietary Fats -- adverse effects KW - Risk Factors KW - Humans KW - Energy Metabolism -- physiology KW - Incidence KW - Mammary Neoplasms, Experimental -- etiology KW - Female KW - Breast Neoplasms -- etiology KW - Breast Neoplasms -- epidemiology KW - Diet -- adverse effects KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69161305?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Recent+results+in+cancer+research.+Fortschritte+der+Krebsforschung.+Progres+dans+les+recherches+sur+le+cancer&rft.atitle=Diet+and+mammary+gland+carcinogenesis.&rft.au=Snyderwine%2C+E+G&rft.aulast=Snyderwine&rft.aufirst=E&rft.date=1998-01-01&rft.volume=152&rft.issue=&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Recent+results+in+cancer+research.+Fortschritte+der+Krebsforschung.+Progres+dans+les+recherches+sur+le+cancer&rft.issn=00800015&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-12 N1 - Date created - 1999-03-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo imaging of brain nicotinic acetylcholine receptors with 5-[123I]iodo-A-85380 using single photon emission computed tomography. AN - 69104257; 9870715 AB - The distribution and kinetics of 5-[123I]iodo-A-85380, a novel ligand for brain nicotinic acetylcholine receptors (nAChRs), were evaluated in the Rhesus monkey using single photon emission computed tomography (SPECT). Peak levels of radioactivity were measured in brain at 90 min after injection of the tracer. Accumulation of radioactivity was highest in the thalamus, intermediate in the frontal cortex and basal ganglia, and lowest in the cerebellum. The ratio of specific to nonspecific binding (V3") in the thalamus, estimated from the (thalamic-cerebellar)/cerebellar radioactivity ratio, reached a value of 6 at 4 h post-injection. Specific binding was reduced by subcutaneous injection of 1 mg/kg cytisine at 2.25 h after injection of radiotracer. At 2.5 h after cytisine administration, radioactivity in the thalamus was reduced by 84%, in the frontal cortex, by 76%, and in the basal ganglia, by 57% of the level measured at the time of cytisine administration, demonstrating that the binding was reversible. On the basis of these findings, together with other data indicating high affinity, receptor subtype selectivity, low nonspecific binding and lack of toxicity in animals, 5-[123I]iodo-A-85380 appears to be a promising ligand for SPECT imaging of nAChRs in the human brain. JF - Life sciences AU - Chefer, S I AU - Horti, A G AU - Lee, K S AU - Koren, A O AU - Jones, D W AU - Gorey, J G AU - Links, J M AU - Mukhin, A G AU - Weinberger, D R AU - London, E D AD - Brain Imaging Center, Intramural Research Program, National Institute on Drug Abuse, National Institute of Health, Baltimore, MD 21224, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - PL355 EP - PL360 VL - 63 IS - 25 SN - 0024-3205, 0024-3205 KW - A 85380 KW - 0 KW - Azetidines KW - Iodine Radioisotopes KW - Radiopharmaceuticals KW - Receptors, Nicotinic KW - Index Medicus KW - Animals KW - Tomography, Emission-Computed, Single-Photon KW - Macaca mulatta KW - Tissue Distribution KW - Male KW - Radiopharmaceuticals -- pharmacokinetics KW - Azetidines -- pharmacokinetics KW - Receptors, Nicotinic -- metabolism KW - Radiopharmaceuticals -- metabolism KW - Azetidines -- metabolism KW - Brain -- metabolism KW - Brain -- ultrastructure KW - Brain -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69104257?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Life+sciences&rft.atitle=In+vivo+imaging+of+brain+nicotinic+acetylcholine+receptors+with+5-%5B123I%5Diodo-A-85380+using+single+photon+emission+computed+tomography.&rft.au=Chefer%2C+S+I%3BHorti%2C+A+G%3BLee%2C+K+S%3BKoren%2C+A+O%3BJones%2C+D+W%3BGorey%2C+J+G%3BLinks%2C+J+M%3BMukhin%2C+A+G%3BWeinberger%2C+D+R%3BLondon%2C+E+D&rft.aulast=Chefer&rft.aufirst=S&rft.date=1998-01-01&rft.volume=63&rft.issue=25&rft.spage=PL355&rft.isbn=&rft.btitle=&rft.title=Life+sciences&rft.issn=00243205&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-08 N1 - Date created - 1999-01-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Age of onset of drug use and its association with DSM-IV drug abuse and dependence: results from the National Longitudinal Alcohol Epidemiologic Survey. AN - 69080038; 9854701 AB - The purpose of this study was to examine the relationship between early onset drug use and the development of lifetime DSM-IV drug abuse and dependence using a representative sample of the U.S. population. Prevalences of lifetime drug abuse and dependence were estimated for each year of age of onset of drug use from ages 13 and younger to 21 and older for the overall sample of drug users by race and gender. Linear logistic analyses were conducted to assess the relationship between age of drug use onset and lifetime drug use disorders controlling for important covariates. The major finding of this study was that early onset drug use is a significant predictor of the subsequent development of drug abuse over the life course. Early onset drug use was also a significant predictor of the subsequent development of lifetime alcohol dependence among males, females, and nonblacks, but not among blacks. After adjusting for important model covariates, the likelihood of lifetime drug abuse and dependence among the total sample of lifetime drug users was reduced by 4% and 5% with each year drug use onset was delayed. Implications of these findings are discussed in terms of the importance of collecting national data on drug use, abuse and dependence and the need for further research and its integration with prevention efforts. JF - Journal of substance abuse AU - Grant, B F AU - Dawson, D A AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20852-7003, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 163 EP - 173 VL - 10 IS - 2 SN - 0899-3289, 0899-3289 KW - Index Medicus KW - Regression Analysis KW - Age Factors KW - Sex Factors KW - Humans KW - African Americans -- statistics & numerical data KW - European Continental Ancestry Group -- psychology KW - Aged KW - European Continental Ancestry Group -- statistics & numerical data KW - Longitudinal Studies KW - Cross-Sectional Studies KW - African Americans -- psychology KW - Adult KW - Incidence KW - Middle Aged KW - Adolescent KW - United States -- epidemiology KW - Male KW - Female KW - Substance-Related Disorders -- diagnosis KW - Psychiatric Status Rating Scales KW - Alcoholism -- epidemiology KW - Alcoholism -- diagnosis KW - Substance-Related Disorders -- psychology KW - Alcoholism -- psychology KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69080038?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+substance+abuse&rft.atitle=Age+of+onset+of+drug+use+and+its+association+with+DSM-IV+drug+abuse+and+dependence%3A+results+from+the+National+Longitudinal+Alcohol+Epidemiologic+Survey.&rft.au=Grant%2C+B+F%3BDawson%2C+D+A&rft.aulast=Grant&rft.aufirst=B&rft.date=1998-01-01&rft.volume=10&rft.issue=2&rft.spage=163&rft.isbn=&rft.btitle=&rft.title=Journal+of+substance+abuse&rft.issn=08993289&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-16 N1 - Date created - 1999-03-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Symptoms and characteristics of individuals with different types of recovery from DSM-IV alcohol dependence. AN - 69079749; 9854699 AB - Symptoms and criteria for DSM-IV alcohol dependence and demographic and drinking characteristics are compared for three groups. Group I (N = 1,044) consists of persons who formerly met the criteria for dependence but were abstinent in the past year, Group II (N = 2,325) consists of persons who were formerly dependent but did not meet the criteria for abuse or dependence in the past year despite drinking, and Group III (N = 22,204) consists of persons who never met the criteria for dependence. Members of Group II lay between members of Groups I and III in terms of the numbers of prior dependence symptoms and criteria, past level of intake, degree of familial alcoholism and history of alcohol treatment. Both groups of former alcoholics were equally likely to have experienced withdrawal, drinking more/longer than intended and tolerance. The criteria that most strongly distinguished the groups were continued use despite physical or psychological consequences, time spent drinking and activities given up, all of which were far more common in Group I than in Group II. Members of Group II had earlier onsets of heavy drinking and dependence than members of Group I, supporting the existence of a developmentally limited subtype of alcoholism that is subject to spontaneous remission in early adulthood without treatment. The paper compares three options for tightening the criteria for dependence, all of which remove more members from Group II (28% to 41% depending on option) than from Group I (12% to 19%). JF - Journal of substance abuse AU - Dawson, D A AD - Division of Biometry and Epidemiology, National Institutes on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-7003, USA. Y1 - 1998 PY - 1998 DA - 1998 SP - 127 EP - 142 VL - 10 IS - 2 SN - 0899-3289, 0899-3289 KW - Index Medicus KW - Humans KW - Adult KW - Treatment Outcome KW - Alcohol Withdrawal Delirium -- diagnosis KW - Middle Aged KW - Follow-Up Studies KW - Male KW - Individuality KW - Female KW - Alcoholism -- rehabilitation KW - Psychiatric Status Rating Scales KW - Alcoholism -- diagnosis KW - Alcoholism -- classification KW - Alcoholism -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69079749?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+substance+abuse&rft.atitle=Symptoms+and+characteristics+of+individuals+with+different+types+of+recovery+from+DSM-IV+alcohol+dependence.&rft.au=Dawson%2C+D+A&rft.aulast=Dawson&rft.aufirst=D&rft.date=1998-01-01&rft.volume=10&rft.issue=2&rft.spage=127&rft.isbn=&rft.btitle=&rft.title=Journal+of+substance+abuse&rft.issn=08993289&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-16 N1 - Date created - 1999-03-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Working Sisters from Outside: Rural Chinese Household Workers in Beijing AN - 61433354; 9904131 AB - Draws on in-depth interviews & field observations of rural women migrating to Beijing, People's Republic of China, in search of work as housemaids in official & informal labor markets. This evidence is set in the larger context of economic reform & rural-urban migration patterns in China. The situation of the "working sisters from outside," as seen in an extended case study of one household worker, casts light on the rich-poor gap under improving economic conditions for the country as a whole. 28 References. Adapted from the source document. JF - Current Research on Occupations and Professions AU - Kejing, Dai AU - Dempsey, Paula R AD - Instit Sociology Chinese Academy Social Sciences, 5 Jianguomen Nei Da Jie 5 Hao Beijing Y1 - 1998///0, PY - 1998 DA - 0, 1998 SP - 11 EP - 29 VL - 10 KW - Economic Change KW - Domestics KW - Income Inequality KW - Rural Women KW - Peking, Peoples Republic of China KW - Rural to Urban Migration KW - article KW - 0621: complex organization; jobs, work organization, workplaces, & unions UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61433354?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocabs&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Research+on+Occupations+and+Professions&rft.atitle=Working+Sisters+from+Outside%3A+Rural+Chinese+Household+Workers+in+Beijing&rft.au=Kejing%2C+Dai%3BDempsey%2C+Paula+R&rft.aulast=Kejing&rft.aufirst=Dai&rft.date=1998-01-01&rft.volume=10&rft.issue=&rft.spage=11&rft.isbn=&rft.btitle=&rft.title=Current+Research+on+Occupations+and+Professions&rft.issn=&rft_id=info:doi/ LA - English DB - Sociological Abstracts N1 - Date revised - 2007-04-01 N1 - Last updated - 2016-09-28 N1 - CODEN - CROPEO N1 - SubjectsTermNotLitGenreText - Rural Women; Rural to Urban Migration; Peking, Peoples Republic of China; Domestics; Economic Change; Income Inequality ER - TY - JOUR T1 - Homology Model Building of Hho1p Supports its Role as a Yeast Histone H1 Protein AN - 20241661; 8720606 AB - Biochemical studies to date have not been able to identify the linker histone H1 protein in the budding yeast Saccharomyces cerevisiae. Database homology searching against the complete yeast genome has identified a gene, HHO1, (or YPL127C, formerly LPI17) which encodes a protein that has two regions that show similarity to the pea histone H1 globular domain. To determine whether Hho1p can assume the shape of an H1 protein, homology model building experiments were performed using the structure of chicken histone H5 globular domain as the basis for comparison. A statistically significant match between each of the two globular domains of Hho1p and the chicken histone H5 structure was obtained, and probability values indicate that there is a less than 1 in 100 chance that such a match would be the result of a random event. These findings support the proposal that Hho1p acts as an "H1 dimer" and could be responsible for the decreased linker DNA length observed between nucleosomal core particles. JF - In Silico Biology AU - Baxevanis, Andreas D AU - Landsman, David AD - Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA, e-mail: andy[at]nhgri.nih.gov Y1 - 1998 PY - 1998 DA - 1998 SP - 5 EP - 11 PB - IOS Press, Nieuwe Hemweg 6B VL - 1 IS - 1 SN - 1386-6338, 1386-6338 KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; Biochemistry Abstracts 2: Nucleic Acids; Biotechnology and Bioengineering Abstracts KW - histone H1 KW - HHO1 KW - homology model building KW - protein structure prediction KW - Y chromosome KW - Genomes KW - Databases KW - Histone H5 KW - Homology KW - Core particles KW - Statistical analysis KW - DNA KW - Histone H1 KW - Saccharomyces cerevisiae KW - Models KW - N 14820:DNA Metabolism & Structure KW - W 30960:Bioinformatics & Computer Applications KW - K 03310:Genetics & Taxonomy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20241661?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=In+Silico+Biology&rft.atitle=Homology+Model+Building+of+Hho1p+Supports+its+Role+as+a+Yeast+Histone+H1+Protein&rft.au=Baxevanis%2C+Andreas+D%3BLandsman%2C+David&rft.aulast=Baxevanis&rft.aufirst=Andreas&rft.date=1998-01-01&rft.volume=1&rft.issue=1&rft.spage=5&rft.isbn=&rft.btitle=&rft.title=In+Silico+Biology&rft.issn=13866338&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-12-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Genomes; Y chromosome; Databases; Histone H5; Homology; Core particles; DNA; Statistical analysis; Histone H1; Models; Saccharomyces cerevisiae ER - TY - JOUR T1 - Sources of Systematic Error in Functional Annotation of Genomes: Domain Rearrangement, Non-Orthologous Gene Displacement and Operon Disruption AN - 20128679; 8720604 AB - Functional annotation of proteins encoded in newly sequenced genomes can be expected to meet two conflicting objectives: (i) provide as much information as possible, and (ii) avoid erroneous functional assignments and over-predictions. The continuing exponential growth of the number of sequenced genomes makes the quality of sequence annotation a critical factor in the efforts to utilize this new information. When dubious functional assignments are used as a basis for subsequent predictions, they tend to proliferate, leading to "database explosion". It is therefore important to identify the common factors that hamper functional annotation. As a first step towards that goal, we have compared the annotations of the Mycoplasma genitalium and Methanococcus jannaschii genomes produced in several independent studies. The most common causes of questionable predictions appear to be: i) non-critical use of annotations from existing database entries; ii) taking into account only the annotation of the best database hit; iii) insufficient masking of low complexity regions (e.g. non-globular domains) in protein sequences, resulting in spurious database hits obscuring relevant ones; iv) ignoring multi-domain organization of the query proteins and/or the database hits; v) non-critical functional inferences on the basis of the functions of neighboring genes in an operon; vi) non-orthologous gene displacement, i.e. involvement of structurally unrelated proteins in the same function. These observations suggest that case by case validation of functional annotation by expert biologists remains crucial for productive genome analysis. JF - In Silico Biology AU - Galperin, Michael Y AU - Koonin, Eugene V AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA, E-mail: galperin[at]ncbi.nlm.nih.gov Y1 - 1998 PY - 1998 DA - 1998 SP - 55 EP - 67 PB - IOS Press, Nieuwe Hemweg 6B VL - 1 IS - 1 SN - 1386-6338, 1386-6338 KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts; Biotechnology and Bioengineering Abstracts KW - genome comparison KW - prediction of gene functions KW - systematic error KW - database annotation KW - automatic genome annotation, KW - manual genome annotation KW - low complexity KW - non-globular domains KW - multi-domain proteins KW - non-orthologous gene displacement KW - Genomes KW - Databases KW - Methanococcus KW - Mycoplasma genitalium KW - Information processing KW - gene rearrangement KW - Operons KW - J 02310:Genetics & Taxonomy KW - W 30960:Bioinformatics & Computer Applications KW - G 07770:Bacteria UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20128679?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=In+Silico+Biology&rft.atitle=Sources+of+Systematic+Error+in+Functional+Annotation+of+Genomes%3A+Domain+Rearrangement%2C+Non-Orthologous+Gene+Displacement+and+Operon+Disruption&rft.au=Galperin%2C+Michael+Y%3BKoonin%2C+Eugene+V&rft.aulast=Galperin&rft.aufirst=Michael&rft.date=1998-01-01&rft.volume=1&rft.issue=1&rft.spage=55&rft.isbn=&rft.btitle=&rft.title=In+Silico+Biology&rft.issn=13866338&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-12-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Genomes; Databases; gene rearrangement; Information processing; Operons; Methanococcus; Mycoplasma genitalium ER - TY - JOUR T1 - Cardiopulmonary effects of inhaled nitric oxide in normal dogs and during E. coli pneumonia and sepsis AN - 17286620; 4514926 AB - We investigated the effect of inhaled nitric oxide (NO) at increasing fractional inspired O sub(2) concentrations (FI sub(O2)) on hemodynamic and pulmonary function during Escherichia coli pneumonia. Thirty-eight conscious, spontaneously breathing, tracheotomized 2-yr-old beagles had intrabronchial inoculation with either 0.75 or 1.5 x 10 super(10) colony-forming units/kg of E. coli 0111:B4 (infected) or 0.9% saline (noninfected) in one or four pulmonary lobes. We found that neither the severity nor distribution (lobar vs. diffuse) of bacterial pneumonia altered the effects of NO. However, in infected animals, with increasing FI sub(O2) (0.08, 0.21, 0.50, and 0.85), NO (80 parts/million) progressively increased arterial PO sub(2) [-0.3 plus or minus 0.6, 3 plus or minus 1, 13 plus or minus 4, 10 plus or minus 9 (mean plus or minus SE) Torr, respectively] and decreased the mean arterial-alveolar O sub(2) gradient (0.5 plus or minus 0.3, 4 plus or minus 2, -8 plus or minus 7, -10 plus or minus 9 Torr, respectively). In contrast, in noninfected animals, the effect of NO was significantly different and opposite; NO progressively decreased mean PO sub(2) with increasing FI sub(O2) (2 plus or minus 1, -5 plus or minus 3, -2 plus or minus 3, and -12 plus or minus 5 Torr, respectively; P < 0.05 compared with infected animals) and increased mean arterial-alveolar O sub(2) gradient (0.3 plus or minus 0.04, 2 plus or minus 2, 1 plus or minus 3, 11 plus or minus 5 Torr; P < 0.05 compared with infected animals). In normal and infected animals alike, only at FI sub(O2) less than or equal to 0.21 did NO significantly lower mean pulmonary artery pressure, pulmonary artery occlusion pressure, and pulmonary vascular resistance index (all P < 0.01). However, inhaled NO had no significant effect on increases in mean pulmonay artery pressure associated with bacterial pneumonia. Thus, during bacterial pneumonia, inhaled NO had only modest effects on oxygenation dependent on high FI sub(O2) and did not affect sepsis-induced pulmonary hypertension. These data do not support a role for inhaled NO in bacterial pneumonia. Further studies are necessary to determine whether, in combination with ventilatory support, NO may have more pronounced effects. JF - Journal of Applied Physiology AU - Quezado, ZMN AU - Natanson, C AU - Karzai, W AU - Danner, R L AU - Koev, CA AU - Fitz, Y AU - Dolan, D P AU - Richmond, S AU - Banks, S M AU - Wilson, L AU - Eichacker, P Q AD - Critical Care Medicine Dept., National Institutes of Health, Bldg. 10, Rm. 7D43, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1998/01// PY - 1998 DA - Jan 1998 SP - 107 EP - 115 VL - 84 IS - 1 SN - 8750-7587, 8750-7587 KW - dogs KW - Microbiology Abstracts B: Bacteriology KW - Ventilation KW - Hemodynamics KW - Sepsis KW - Lung KW - Escherichia coli KW - Nitric oxide KW - Pneumonia KW - J 02855:Human Bacteriology: Others KW - J 02845:Ear, nose and respiratory tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17286620?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Applied+Physiology&rft.atitle=Cardiopulmonary+effects+of+inhaled+nitric+oxide+in+normal+dogs+and+during+E.+coli+pneumonia+and+sepsis&rft.au=Quezado%2C+ZMN%3BNatanson%2C+C%3BKarzai%2C+W%3BDanner%2C+R+L%3BKoev%2C+CA%3BFitz%2C+Y%3BDolan%2C+D+P%3BRichmond%2C+S%3BBanks%2C+S+M%3BWilson%2C+L%3BEichacker%2C+P+Q&rft.aulast=Quezado&rft.aufirst=ZMN&rft.date=1998-01-01&rft.volume=84&rft.issue=1&rft.spage=107&rft.isbn=&rft.btitle=&rft.title=Journal+of+Applied+Physiology&rft.issn=87507587&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Sepsis; Ventilation; Nitric oxide; Hemodynamics; Pneumonia; Lung ER - TY - CONF T1 - Mechanisms of axonal transport: Target sites for neurotoxicants AN - 17182274; 4480543 AB - The process of axonal transport is critical for maintenance of the axonal membrane and nerve endings. Various toxicants produce morphological alterations in the axon of the peripheral nervous system. Thus, alterations in axonal transport have been a major research focus in toxicant-induced peripheral axonopathies. Axonal transport can be altered at a specific step in the mechanism by the movement of a specific component, or by more general biochemical alterations. This manuscript presents basic principles of axonal transport in the nervous system and the complicated interdependent nature of the biological process. This information is presented to give a mechanistic framework in which one can evaluate data from in vitro studies. While information obtained about the process in either type of system is important in the understanding of the pathogenesis and progression of toxicant-induced neuropathies, an emphasis is placed on the need for in vivo studies to determine biological relevance and the causative nature of axonal transport deficits in peripheral neuropathies. JF - In Vitro & Molecular Toxicology AU - Harry, G J Y1 - 1998 PY - 1998 DA - 1998 SP - 83 EP - 93 PB - Mary Ann Liebert, Inc., 2 Madison Ave Larchmont NY 10538 USA VL - 11 IS - 1 KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - Axonal transport KW - Conferences KW - Reviews KW - Neurotoxicity KW - Peripheral nervous system KW - Neuropathy KW - N3 11101:General KW - N3 11430:Conference proceedings KW - X 24270:Proceedings UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17182274?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=In+Vitro+%26+Molecular+Toxicology&rft.atitle=Mechanisms+of+axonal+transport%3A+Target+sites+for+neurotoxicants&rft.au=Harry%2C+G+J&rft.aulast=Harry&rft.aufirst=G&rft.date=1998-01-01&rft.volume=11&rft.issue=1&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=In+Vitro+%26+Molecular+Toxicology&rft.issn=10979336&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Nucleotide excision repair and anti-cancer chemotherapy AN - 17153241; 4449034 AB - DNA repair is an important effector of anti-cancer drug resistance. In recent years, it has become apparent that DNA repair is an extremely complex process. Processes within DNA repair that may contribute to one or more drug resistance phenotypes include; O-6-alkyltransferase activity, base excision repair, mismatch repair, nucleotide excision repair, and gene specific repair. Clearly, several of these processes may show increased activity within any single cell, or tumor, at any one time. This review attempts to touch briefly upon the question of the distinctions between each of these specific pathways; and then seeks to expand on nucleotide excision repair as a possible effector of cellular and clinical resistance to platinum-based anticancer therapy. JF - Cytotechnology AU - Reed, E AD - Medical Ovarian Cancer Section, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Building 10, Room 12N226, Bethesda, MD 20892, USA, reed92@helix.nih.gov Y1 - 1998 PY - 1998 DA - 1998 SP - 187 EP - 201 VL - 27 IS - 1-3 SN - 0920-9069, 0920-9069 KW - nucleotide excision repair KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Chemotherapy KW - Reviews KW - DNA repair KW - Cancer KW - W 30965:Miscellaneous, Reviews KW - W3 33000:General topics and reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17153241?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytotechnology&rft.atitle=Nucleotide+excision+repair+and+anti-cancer+chemotherapy&rft.au=Reed%2C+E&rft.aulast=Reed&rft.aufirst=E&rft.date=1998-01-01&rft.volume=27&rft.issue=1-3&rft.spage=187&rft.isbn=&rft.btitle=&rft.title=Cytotechnology&rft.issn=09209069&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Special Issue: Multiple Drug Resistance in Cancer 2. Molecular, Cellular and Clinical Aspects. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - DNA repair; Reviews; Chemotherapy; Cancer ER - TY - JOUR T1 - Exposure assessment for a study of workers exposed to acrylonitrile AN - 17131497; 4435920 AB - Procedures used to develop estimates of exposure to acrylonitrile for a cohort study (>25 000 workers in 8 monomer, fiber, and resin companies from 1952 to 1983) are presented. Visits to the companies were made, interviews of workers were conducted, historical records were made, and measurements were taken. On the basis of similar tasks, locations, other exposures, and a similar distribution of exposures to acrylonitrile, 3600 exposure groups were formed. Special procedures were used to reduce the misclassification of workers performing tasks that varied in time but that were inadequately reflected in the job title. A software program organized and retained all exposure information on each exposure group. Quantitative estimates of acrylonitrile exposure were developed using a hierarchical approach in a software program that documented the derivation of each estimate and facilitated data review. Two of the estimation methods were evaluated in a comparison with measurement data. JF - Scandinavian Journal of Work, Environment & Health AU - Stewart, P A AU - Zaebst, D AU - Zey, J N AU - Herrick, R AU - Dosemeci, M AU - Hornung, R AU - Bloom, T AU - Pottern, L AU - Miller, BA AU - Blair, A AD - National Cancer Institute, EPN 418, 6130 Executive Boulevard MSC 7364, Bethesda, MD 20892-7364, USA Y1 - 1998 PY - 1998 DA - 1998 SP - 42 EP - 53 PB - Finnish Inst. of Occupational Health VL - 24 SN - 0355-3140, 0355-3140 KW - acrylonitrile KW - man KW - Toxicology Abstracts; Health & Safety Science Abstracts KW - Risk assessment KW - Mortality KW - Occupational exposure KW - H 1000:Occupational Safety and Health KW - X 24152:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17131497?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scandinavian+Journal+of+Work%2C+Environment+%26+Health&rft.atitle=Exposure+assessment+for+a+study+of+workers+exposed+to+acrylonitrile&rft.au=Stewart%2C+P+A%3BZaebst%2C+D%3BZey%2C+J+N%3BHerrick%2C+R%3BDosemeci%2C+M%3BHornung%2C+R%3BBloom%2C+T%3BPottern%2C+L%3BMiller%2C+BA%3BBlair%2C+A&rft.aulast=Stewart&rft.aufirst=P&rft.date=1998-01-01&rft.volume=24&rft.issue=&rft.spage=42&rft.isbn=&rft.btitle=&rft.title=Scandinavian+Journal+of+Work%2C+Environment+%26+Health&rft.issn=03553140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mortality; Occupational exposure; Risk assessment ER - TY - JOUR T1 - Tea and Coffee Consumption and Risk of Colon and Rectal Cancer in Middle-Aged Finnish Men AN - 16556803; 4376644 AB - The association between coffee and black tea consumption and the subsequent risk of colon and rectal cancer was investigated within a Finnish clinical trial cohort. One hundred eleven cases of colon cancer and 83 cases of rectal cancer were diagnosed over a median of 8.0 years of follow-up. Proportional hazards regression models were used to derive adjusted relative risks (RR) and 95% confidence intervals (CI) for the association between coffee and tea consumption and cancer incidence. After controlling for confounders, coffee was not significantly associated with colon or rectal cancer. A positive association was seen for increased consumption of tea drinking and colon cancer. Compared with persons who did not drink tea, those who consumed <1 cup/day had an RR of 1.40 (95% CI = 0.84-2.33) and those who consumed greater than or equal to 1 cup/day had an RR of 2.09 (95% CI = 1.34-3.26, p for trend = 0.001). In contrast, tea consumption had little effect on rectal cancer incidence. This study does not support the hypothesis that coffee and tea protect against colorectal cancer risk. However, given the strength of the tea-colon cancer association and the significant gradient of risk we observed across level of intake, further epidemiologic research of this relationship in other populations seems warranted. JF - Nutrition and Cancer AU - Hartman, T J AU - Tangrea, JA AU - Pietinen, P AU - Malila, N AU - Virtanen, M AU - Taylor, PR AU - Albanes, D AD - Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892, USA Y1 - 1998 PY - 1998 DA - 1998 SP - 41 EP - 48 VL - 31 IS - 1 SN - 0163-5581, 0163-5581 KW - Finland KW - beverages KW - coffee KW - colon KW - colorectal carcinoma KW - males KW - tea KW - Risk Abstracts KW - Food KW - Cancer KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16556803?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nutrition+and+Cancer&rft.atitle=Tea+and+Coffee+Consumption+and+Risk+of+Colon+and+Rectal+Cancer+in+Middle-Aged+Finnish+Men&rft.au=Hartman%2C+T+J%3BTangrea%2C+JA%3BPietinen%2C+P%3BMalila%2C+N%3BVirtanen%2C+M%3BTaylor%2C+PR%3BAlbanes%2C+D&rft.aulast=Hartman&rft.aufirst=T&rft.date=1998-01-01&rft.volume=31&rft.issue=1&rft.spage=41&rft.isbn=&rft.btitle=&rft.title=Nutrition+and+Cancer&rft.issn=01635581&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Food; Cancer ER - TY - JOUR T1 - Breast cancer risk and lifetime occupational history: employment in professional and managerial occupations AN - 16499124; 4397091 AB - In this case-control study, occupational histories were used to assess the relation between risk of breast cancer and employment in professional and managerial occupations while adjusting for reproductive and other risk factors. Incident, primary, female cases of breast cancer diagnosed between 1986 and 1991, and randomly selected controls were interviewed to obtain detailed medical, reproductive, and occupational histories. Mantel-Haenszel crude odds ratios (OR) and 95% confidence intervals (95% CIs) were used to estimate risk of breast cancer related to the job of longest duration. Unconditional logistic regression was used to estimate crude and adjusted ORs and 95% CIs associated with having ever been employed and duration of employment in a professional or managerial occupation. In this population, employment in professional and managerial occupations is not associated with post-menopausal risk of breast cancer, but seems to be related to a reduction in risk of premenopausal breast cancer. Methodological limitations of this study including response rates are discussed. JF - Occupational and Environmental Medicine AU - Petralia, SA AU - Vena, JE AU - Freudenheim, J L AU - Marshall, J R AU - Michalek, A AU - Brasure, J AU - Swanson, M AU - Graham, S AD - Occupational Epidemiology Branch, National Cancer Institute, Executive Plaza North, Rm 418, 6130 Executive Boulevard, Bethesda, MD 20892, USA Y1 - 1998/01// PY - 1998 DA - Jan 1998 SP - 43 EP - 48 VL - 55 IS - 1 SN - 1351-0711, 1351-0711 KW - Health & Safety Science Abstracts; Risk Abstracts KW - R2 23080:Industrial and labor KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16499124?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+Environmental+Medicine&rft.atitle=Breast+cancer+risk+and+lifetime+occupational+history%3A+employment+in+professional+and+managerial+occupations&rft.au=Petralia%2C+SA%3BVena%2C+JE%3BFreudenheim%2C+J+L%3BMarshall%2C+J+R%3BMichalek%2C+A%3BBrasure%2C+J%3BSwanson%2C+M%3BGraham%2C+S&rft.aulast=Petralia&rft.aufirst=SA&rft.date=1998-01-01&rft.volume=55&rft.issue=1&rft.spage=43&rft.isbn=&rft.btitle=&rft.title=Occupational+and+Environmental+Medicine&rft.issn=13510711&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996 AN - 16488457; 4366604 AB - Single-pulse transcranial magnetic stimulation (TMS) is a safe and useful tool for investigating various aspects of human neurophysiology, particularly corticospinal function, in health and disease. Repetitive TMS (rTMS), however, is a more powerful and potentially dangerous modality, capable of regionally blocking or facilitating cortical processes. Although there is evidence that rTMS is useful for treating clinical depression, and possibly other brain disorders, it had caused 7 known seizures by 1996 and could have other undesirable effects. In June 1996 a workshop was organized to review the available data on the safety of rTMS and to develop guidelines for its safe use. This article summarizes the workshop's deliberations. In addition to issues of risk and safety, it also addresses the principles and applications of rTMS, nomenclature, and potential therapeutic effects of rTMS. The guidelines for the use of rTMS, which are summarized in an appendix, cover the ethical issues, recommended limits on stimulation parameters, monitoring of subjects (both physiologically and neuropsychologically), expertise and function of the rTMS team, medical and psychosocial management of induced seizures, and contraindications to rTMS. JF - Evoked Potentials AU - Wassermann, E M AD - Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, Building 10, Room 5N226, National Institutes of Health, 10 Center Drive, MSC-1428, Bethesda, MD 20892-1428, USA, wassermann@nih.gov Y1 - 1998/01// PY - 1998 DA - Jan 1998 SP - 1 EP - 16 VL - 108 IS - 1 SN - 0168-5597, 0168-5597 KW - man KW - transcranial magnetic stimulation KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - X 24210:Radiation & radioactive materials KW - N3 11020:Neuroprotocols and apparatus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16488457?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Evoked+Potentials&rft.atitle=Risk+and+safety+of+repetitive+transcranial+magnetic+stimulation%3A+report+and+suggested+guidelines+from+the+International+Workshop+on+the+Safety+of+Repetitive+Transcranial+Magnetic+Stimulation%2C+June+5-7%2C+1996&rft.au=Wassermann%2C+E+M&rft.aulast=Wassermann&rft.aufirst=E&rft.date=1998-01-01&rft.volume=108&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Evoked+Potentials&rft.issn=01685597&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - A nested case-control study of dietary factors and the risk of incident cytological abnormalities of the cervix AN - 16451170; 4351699 AB - Several earlier case-control studies reported inverse associations of cervical squamous intraepithelial lesions (SIL) with high dietary or biomarker levels of carotenoids, folate, and vitamins C and E. However, most studies did not measure the primary causal factor, cancer-associated genital human papillomaviruses (HPV), now detected by sensitive viral DNA tests. This nested case-control study assessed whether high dietary intakes of these nutrients, plus zinc and vitamin A, reduced SIL risk in cancer-associated HPV DNA-positive women. Using a 60-item food-frequency questionnaire, nutrient estimates were obtained for 33 incident cases with high-grade lesions, 121 with low-grade lesions, 97 with equivocal SIL, and 806 cytologically normal controls sampled from a large prospective cohort study. Baseline cervicovaginal lavages were tested for HPV DNA by the polymerase chain reaction. Among DNA-positive cases (n = 68) and controls (n = 69), age-adjusted odds ratios (ORs) of SIL in the highest vs. the lowest nutrient quartiles were 1.4 [95% confidence interval (CI) = 0.5-4.2] for vitamin A, 0.6 (CI = 0.2-2.0) for beta -carotene, 1.3 (CI = 0.4-3.6) for vitamin C, 1.0 (CI = 0.4-3.6) for vitamin E, 0.7 (CI = 0.3-2.1) for folate, and 0.8 (CI = 0.3-2.2) for zinc. ORs in HPV DNA-negative women approximated 1.0, with the exception of vitamin E (OR = 0.5, CI = 0.3-0.9). These results do not support a protective role for the above nutrients against low-grade or equivocal SIL, which constituted the majority of diagnoses in this study. JF - Nutrition and Cancer AU - Wideroff, L AU - Potischman, N AU - Glass, A G AU - Greer, CE AU - Manos, M M AU - Scott AU - Burk, R D AU - Sherman, ME AU - Wacholder, S AU - Schiffman, M AD - Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA Y1 - 1998 PY - 1998 DA - 1998 SP - 130 EP - 136 VL - 30 IS - 2 SN - 0163-5581, 0163-5581 KW - cancer KW - cervix KW - cytology KW - diets KW - nutrition KW - papilloma KW - Health & Safety Science Abstracts KW - H 11000:Diseases/Injuries/Trauma UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16451170?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nutrition+and+Cancer&rft.atitle=A+nested+case-control+study+of+dietary+factors+and+the+risk+of+incident+cytological+abnormalities+of+the+cervix&rft.au=Wideroff%2C+L%3BPotischman%2C+N%3BGlass%2C+A+G%3BGreer%2C+CE%3BManos%2C+M+M%3BScott%3BBurk%2C+R+D%3BSherman%2C+ME%3BWacholder%2C+S%3BSchiffman%2C+M&rft.aulast=Wideroff&rft.aufirst=L&rft.date=1998-01-01&rft.volume=30&rft.issue=2&rft.spage=130&rft.isbn=&rft.btitle=&rft.title=Nutrition+and+Cancer&rft.issn=01635581&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Determining the structures of large proteins and protein complexes by NMR AN - 16442353; 4344280 AB - Recent advances in multidimensional NMR methodology to obtain super(1)H, super(15)N and super(13)C resonance assignments, interproton-distance and torsion-angle restraints, and restraints that characterize long-range order have, coupled with new methods of structure refinement, permitted solution structures of proteins in excess of 250 residues to be solved. These developments may permit the determination by NMR of the structures of macromolecules up to 50-60 kDa, thereby bringing into reach numerous systems of considerable biological interest, including a large variety of protein-protein and protein-nucleic-acid complexes. JF - Trends in Biotechnology AU - Clore, G M AU - Gronenborn, A M AD - The Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520, USA Y1 - 1998/01// PY - 1998 DA - Jan 1998 SP - 22 EP - 34 VL - 16 IS - 1 SN - 0167-7799, 0167-7799 KW - N.M.R. KW - protein structure KW - reviews KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Agricultural and Environmental Biotechnology Abstracts KW - W3 33340:Other proteins, peptides, amino acids KW - W2 32340:Other peptides, proteins, amino acids KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16442353?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+Biotechnology&rft.atitle=Determining+the+structures+of+large+proteins+and+protein+complexes+by+NMR&rft.au=Clore%2C+G+M%3BGronenborn%2C+A+M&rft.aulast=Clore&rft.aufirst=G&rft.date=1998-01-01&rft.volume=16&rft.issue=1&rft.spage=22&rft.isbn=&rft.btitle=&rft.title=Trends+in+Biotechnology&rft.issn=01677799&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Homologous DNA pairing domain peptides of RecA protein: intrinsic propensity to form beta -structures and filaments AN - 16407819; 4322092 AB - The 20 amino acid residue peptides derived from RecA loop L2 have been shown to be the pairing domain of RecA. The peptides bind to ss- and dsDNA, unstack ssDNA, and pair the ssDNA to its homologous target in a duplex DNA. As shown by circular dichroism, upon binding to DNA the disordered peptides adopt a beta -structure conformation. Here we show that the conformational change of the peptide from random coil to beta -structure is important in binding ss- and dsDNA. The beta -structure in the DNA pairing peptides can be induced by many environmental conditions such as high pH, high concentration, and non-micellar sodium dodecyl sulfate (6 mM). This behavior indicates an intrinsic property of these peptides to form a beta -structure. A beta -structure model for the loop L2 of RecA protein when bound to DNA is thus proposed. The fact that aromatic residues at the central position 203 strongly modulate the peptide binding to DNA and subsequent biochemical activities can be accounted for by the direct effect of the aromatic amino acids on the peptide conformational change. The DNA-pairing domain of RecA visualized by electron microscopy self-assembles into a filamentous structure like RecA. The relevance of such a peptide filamentous structure to the structure of RecA when bound to DNA is discussed. JF - Journal of Molecular Biology AU - Wang, Lijiang AU - Voloshin, ON AU - Stasiak, A AU - Camerini-Otero, R D AD - Bldg 10, Rm 9D20, Genetics and Biochemistry Branch National Institutes of Health Bethesda, MD 20892, USA Y1 - 1998 PY - 1998 DA - 1998 SP - 1 EP - 11 VL - 277 IS - 1 SN - 0022-2836, 0022-2836 KW - DNA-binding protein KW - RecA protein KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - J 02725:DNA KW - N 14940:Nucleic acid-binding proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16407819?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Biology&rft.atitle=Homologous+DNA+pairing+domain+peptides+of+RecA+protein%3A+intrinsic+propensity+to+form+beta+-structures+and+filaments&rft.au=Wang%2C+Lijiang%3BVoloshin%2C+ON%3BStasiak%2C+A%3BCamerini-Otero%2C+R+D&rft.aulast=Wang&rft.aufirst=Lijiang&rft.date=1998-01-01&rft.volume=277&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Paradoxical effect of GM-CSF gene transfer on the tumorigenicity and immunogenicity of murine tumors AN - 16400451; 4315982 AB - The effect of granulocyte/macrophage colony-stimulating factor (GM-CSF) gene transfer on the tumorigenicity and immunogenicity of 2 different murine tumor lines was determined. Transduction of B16 melanoma cells with the GM-CSF gene rendered the cells more immunogenic. In contrast, transduction of NG4TL4 fibrosarcoma in FVB/N mice (NG) with the GM-CSF gene showed increased tumorigenicity in a high producer line (NG-MGh). The parent NG or NG-MG cells induced the same level of cytotoxic T-lymphocyte (CTL) response and the same magnitude of tumor transplantation immunity. However, the proliferation of the NG-MGh cells was increased 2- to 10-fold. There was no increase in apoptosis in the NG cells and there was no increase of NG-MGh cells in S-phase, hence the increase of the proliferative activity appeared to be indeed inherent to the cells. Mixing the splenocytes from the NG-MGh tumor bearers with the NG tumor cells did not increase tumorigenicity but totally inhibited the growth of the NG tumor, indicating that suppressor cells were not present. Mixing 10,000 rad X-irradiated NG-MGh cells with viable NG tumor cells resulted in 3- to 10-fold increased NG tumor growth rate. The in vitro proliferation of NG cells was increased by adding both GM-CSFs and macrophages and not by either one alone, suggesting that interaction between macrophages and GM-CSFs resulted in the production of tumor growth enhancing factor(s). Our findings suggest that transduction of NG tumor cells with the GM-CSF gene increases tumorigenicity, which is attributed both to an increased inherent proliferative ability of the tumor cells and to the in vivo production of a tumor growth enhancing factor(s) at the tumor site. JF - International Journal of Cancer AU - Wang, Jie AU - Yang, Wen K AU - Yang, Yili AU - Wei, Sung-Jan AU - Yang, Den-Mei AU - Whang-Peng, J AU - Chen, Yuh-Min AU - Ting, Kai-Li AD - Bldg. 10, Room 4B17, National Institutes of Health, Bethesda, MD 20892-1360, USA, ct53j@nih.gov Y1 - 1998/01// PY - 1998 DA - Jan 1998 SP - 459 EP - 466 VL - 75 IS - 3 SN - 0020-7136, 0020-7136 KW - FVB/N mice KW - NG-MGh cells KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16400451?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Cancer&rft.atitle=Paradoxical+effect+of+GM-CSF+gene+transfer+on+the+tumorigenicity+and+immunogenicity+of+murine+tumors&rft.au=Wang%2C+Jie%3BYang%2C+Wen+K%3BYang%2C+Yili%3BWei%2C+Sung-Jan%3BYang%2C+Den-Mei%3BWhang-Peng%2C+J%3BChen%2C+Yuh-Min%3BTing%2C+Kai-Li&rft.aulast=Wang&rft.aufirst=Jie&rft.date=1998-01-01&rft.volume=75&rft.issue=3&rft.spage=459&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - The adhesion-associated sca operon in Streptococcus gordonii encodes an inducible high-affinity ABC transporter for Mn super(2+) uptake AN - 16363251; 4269449 AB - ScaA lipoprotein in Streptococcus gordonii is a member of the LraI family of homologous polypeptides found among streptococci, pneumococci, and enterococci. It is the product of the third gene within the scaCBA operon encoding the components of an ATP-binding cassette (ABC) transporter system. Inactivation of scaC (ATP-binding protein) or scaA (substrate-binding protein) genes resulted in both impaired growth of cells and >70% inhibition of super(54)Mn super(2+) uptake in media containing 20-fold in sca mutants. The addition of 0.1 mM Mn super(2+) to the transformation medium restored only partly the transformability of mutant cells, implying an alternate role for Sca proteins in the transformation process. Cells of sca mutants were unaffected in other binding properties tested and were unaffected in sensitivity to oxidants. The results show that Sca permease is a high-affinity mechanism for the acquisition of Mn super(2+) and is essential for growth of streptococci under Mn super(2+)-limiting conditions. JF - Journal of Bacteriology AU - Kolenbrander, P E AU - Andersen, R N AU - Baker, R A AU - Jenkinson, H F AD - Building 30, Room 310, 30 Convent Dr. MSC 4350, National Institutes of Health, Bethesda, MD 20892-4350, USA, kolenbrander@yoda.nidr.nih.gov Y1 - 1998/01// PY - 1998 DA - Jan 1998 SP - 290 EP - 295 VL - 180 IS - 2 SN - 0021-9193, 0021-9193 KW - ATP-binding casette KW - ATP-binding protein KW - ScaA protein KW - enterococci KW - manganese KW - pneumococci KW - scaA gene KW - Microbiology Abstracts B: Bacteriology KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16363251?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=The+adhesion-associated+sca+operon+in+Streptococcus+gordonii+encodes+an+inducible+high-affinity+ABC+transporter+for+Mn+super%282%2B%29+uptake&rft.au=Kolenbrander%2C+P+E%3BAndersen%2C+R+N%3BBaker%2C+R+A%3BJenkinson%2C+H+F&rft.aulast=Kolenbrander&rft.aufirst=P&rft.date=1998-01-01&rft.volume=180&rft.issue=2&rft.spage=290&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Subtracted differential display: Genes with amphetamine-altered expression patterns include calcineurin AN - 16295287; 4278904 AB - Genes whose expression changes with administration of abused substances provide candidate biochemical mechanisms for drug-induced long-term brain changes. To identify such genes, and to avoid the false-positive results frequently obtained from differential display PCR, we applied a subtracted differential display (SDD) approach. We subtracted single-stranded cDNA prepared from drug-treated animals with excess mRNA from saline-treated animals, and visa versa, prior to differential display amplifications. Two of initial amphetamine-regulated cDNAs identified in this fashion encoded calcineurin A, a neuron-specific protein phosphatase catalytic subunit whose striatal expression was upregulated ca. 1.5-fold. SDD may enhance the utility of differential display approaches to identifying regulated genes in tissues in which mRNA complexities are high. JF - Molecular Brain Research AU - Wang, X B AU - Uhl, G R AD - Molecular Neurobiology Branch, Intramural Research Program, National Institute on Drug Abuse, Box 5180, Baltimore, MD 21224, USA Y1 - 1998/01/01/ PY - 1998 DA - 1998 Jan 01 SP - 345 EP - 347 PB - Elsevier Science B.V. VL - 53 IS - 1-2 SN - 0169-328X, 0169-328X KW - subtracted differential display KW - Calcium & Calcified Tissue Abstracts; CSA Neurosciences Abstracts; Toxicology Abstracts KW - T 20058:Phosphatases KW - N3 11106:Neurobiology of drug abuse KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16295287?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Brain+Research&rft.atitle=Subtracted+differential+display%3A+Genes+with+amphetamine-altered+expression+patterns+include+calcineurin&rft.au=Wang%2C+X+B%3BUhl%2C+G+R&rft.aulast=Wang&rft.aufirst=X&rft.date=1998-01-01&rft.volume=53&rft.issue=1-2&rft.spage=345&rft.isbn=&rft.btitle=&rft.title=Molecular+Brain+Research&rft.issn=0169328X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - H2M3 super(wt)-restricted, Listeria monocytogenes-immune CD8 T cells respond to multiple formylated peptides and to a variety of gram-positive and gram-negative bacteria AN - 16285500; 4284532 AB - A subset of H2M3 super(wt)-restricted, Listeria monocytogenes (LM)-immune CD8 effectors recognize antigen-presenting cells (APC) preincubated with heat-killed LM. The responsible product, which we have previously designated heat-killed Listeria-associated antigen (HAA), is extremely hydrophobic and resistant to proteolytic degradation. Despite the protease resistance of HAA, we now report that HAA-immune clones are uniformly responsive to fMIGWII, a formylated oligopeptide derived from the recently described LM product, lemA. While fMIGWII was by far the most potent peptide tested, over half our clones also responded to the LM-derived peptide fMIVIL and cross-reactive responses to two other unrelated formylated peptides at concentrations of <1 mu M were frequently observed. One of these peptides (fBlaZ) did not share any amino acid in common with fMIGWII except N-formyl methionine at position 1. Unformylated variants of the same peptides were inactive. HAA-immune CD8 cells also responded in an H2M3 super(wt)-restricted manner to APC pretreated with heat-killed or live preparations of other Gram-positive and Gram-negative bacteria such as Streptococcus pyogenes (SP) and Proteus vulgaris (PV). Unlike fMIGWII which is water soluble and protease sensitive, the native antigens extracted from SP and PV, like HAA, were very hydrophobic and proteinase K resistant, presumably reflecting in each case the association of cross-reactive polypeptides with bacterial lipid or phospholipid. Thus, HAA/lemA-immune, H2M3 super(wt)-restricted effectors can respond to a variety of formylated peptides and bacterial antigens in vitro. Similar cross-reactions in vivo might have physiologically significant implications. JF - International Immunology AU - Nataraj, C AU - Huffman, G R AU - Kurlander, R J AD - Building 10/Rm 2C390, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892-1508, USA Y1 - 1998 PY - 1998 DA - 1998 SP - 7 EP - 15 VL - 10 IS - 1 SN - 0953-8178, 0953-8178 KW - CD8 antigen KW - Listeria monocytogenes KW - gram-negative bacteria KW - gram-positive bacteria KW - lymphocytes T KW - peptides KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16285500?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Immunology&rft.atitle=H2M3+super%28wt%29-restricted%2C+Listeria+monocytogenes-immune+CD8+T+cells+respond+to+multiple+formylated+peptides+and+to+a+variety+of+gram-positive+and+gram-negative+bacteria&rft.au=Nataraj%2C+C%3BHuffman%2C+G+R%3BKurlander%2C+R+J&rft.aulast=Nataraj&rft.aufirst=C&rft.date=1998-01-01&rft.volume=10&rft.issue=1&rft.spage=7&rft.isbn=&rft.btitle=&rft.title=International+Immunology&rft.issn=09538178&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - DNA adduct formation by polycyclic aromatic hydrocarbon dihydrodiol epoxides AN - 16283959; 4295675 AB - Classically, active metabolites of chemical carcinogens were identified by isolating various metabolites produced in experimental animals and determining which of these exhibited carcinogenic activity comparable to, or greater than, that of the parent compound. This approach was not successful for the polycyclic aromatic hydrocarbon carcinogens, however, because most metabolites examined with this approach were found to be much weaker carcinogens than the parent hydrocarbon from which they were derived. Metabolic activation of polycyclic aromatic hydrocarbons was clarified, however, by initially identifying metabolites that were responsible for covalent binding to DNA in cells or tissues [these were found to be vicinal dihydrodiol epoxides in which the epoxide is in a bay or fjord region] and, only thereafter, demonstrating that these metabolites exhibited high tumorigenic activities. It has been shown that this dihydrodiol epoxide route of activation applies to a fairly wide range of hydrocarbon structures, but other mechanisms of metabolic activation have also been investigated. For example, it has been suggested that the active metabolites of some polycyclic aromatic hydrocarbons may be radical cations that induce mutation through the intermediacy of apurinic sites in DNA, rather than through the DNA adducts themselves. The proposed radical cations are not stable enough to be isolated, and therefore, there is no direct evidence that these intermediates are carcinogenic. JF - Chemical Research in Toxicology AU - Szeliga, J AU - Dipple, A AD - Chem. Carcinogenesis Lab., ABL-Basic Res. Prog., NCI-Frederick Cancer Res. and Dev. Cent., Frederick, MD 21702, USA Y1 - 1998/01// PY - 1998 DA - Jan 1998 SP - 1 EP - 11 VL - 11 IS - 1 SN - 0893-228X, 0893-228X KW - DNA adducts KW - dihydrodiol epoxide KW - free radicals KW - metabolic activation KW - polycyclic aromatic hydrocarbons KW - Toxicology Abstracts KW - X 24190:Polycyclic hydrocarbons UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16283959?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+Research+in+Toxicology&rft.atitle=DNA+adduct+formation+by+polycyclic+aromatic+hydrocarbon+dihydrodiol+epoxides&rft.au=Szeliga%2C+J%3BDipple%2C+A&rft.aulast=Szeliga&rft.aufirst=J&rft.date=1998-01-01&rft.volume=11&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Chemical+Research+in+Toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Inhibition of HIV-1 replication by combined expression of gag dominant negative mutant and a human ribonuclease in a tightly controlled HIV-1 inducible vector AN - 16276048; 4283188 AB - An HIV-1-based expression vector has been constructed that produces protective genes tightly regulated by HIV-1 Tat and Rev proteins. The vector contains either a single protective gene (HIV-1 gag dominant negative mutant (delta-gag)) or a combination of two different protective genes (delta-gag and eosinophil-derived neurotoxin (EDN), a human ribonuclease) which are expressed from a dicistronic mRNA. After stable transfection of CEM T cells and following challenge with HIV-1, viral production was completely inhibited in cells transduced with the vector producing both delta-gag and EDN and delayed in cells producing delta-gag alone. In addition, cotransfection of HeLa-Tat cells with an infectious HIV-1 molecular clone and either protective vector demonstrated that the HIV-1 packaging signals present in the constructs were functional and allowed the efficient assembly of the protective RNAs into HIV-1 virions, thus potentially transmitting protection to the HIV-1 target cells. JF - Gene Therapy AU - Cara, A AU - Rybak, S M AU - Newton, D L AU - Crowley, R AU - Rottschafer, SE AU - Reitz, Jr AU - Gusella, G L AD - Lab. Biochem. Physiol., Bldg. 567, Rm. 152, Frederick, NCI-Frederick Cancer Res. and Dev. Cent., Frederick, MD 21702, USA Y1 - 1998/01// PY - 1998 DA - Jan 1998 SP - 65 EP - 75 VL - 5 IS - 1 SN - 0969-7128, 0969-7128 KW - HIV-1 KW - Rev protein KW - Tat protein KW - eosinophil-derived neurotoxin KW - expression vectors KW - gag gene KW - human immunodeficiency virus 1 KW - ribonuclease KW - virions KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33181:Gene therapy vectors KW - V 22002:AIDS: Molecular and in vitro aspects KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16276048?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gene+Therapy&rft.atitle=Inhibition+of+HIV-1+replication+by+combined+expression+of+gag+dominant+negative+mutant+and+a+human+ribonuclease+in+a+tightly+controlled+HIV-1+inducible+vector&rft.au=Cara%2C+A%3BRybak%2C+S+M%3BNewton%2C+D+L%3BCrowley%2C+R%3BRottschafer%2C+SE%3BReitz%2C+Jr%3BGusella%2C+G+L&rft.aulast=Cara&rft.aufirst=A&rft.date=1998-01-01&rft.volume=5&rft.issue=1&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Gene+Therapy&rft.issn=09697128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Interleukin-2-mediated modulation of plasma cell tumor growth in a model of multiple myeloma AN - 16273548; 4262463 AB - A number of studies have demonstrated that inoculation of certain types of cancer cells engineered for expression of the interleukin-2 (IL-2) gene results in reduced tumorigenicity and/or protection from subsequent challenge with a tumorigenic dose of wild-type cells. In the current studies, we have employed murine plasma cell tumors to examine IL-2-mediated tumor rejection as a possible model for therapeutic approaches to human myeloma or plasma cell leukemia. Two murine plasma cell tumor lines, S107 and X24, were infected with a retroviral vector expressing the human IL-2 gene, and the antitumor potential of IL-2-expressing infectants was characterized in syngeneic BALB/c and BALB/c nu/nu mice. Results demonstrate that tumorigenicity of both lines correlates inversely with the amount of IL-2 produced by the tumor cells. However, there are clear differences between the two lines in terms of reduced tumorigenicity and the ability to protect against co-injected parental tumor cells that appear unrelated to IL-2 levels. More importantly, intravenous immunization of animals with irradiated, IL-2 secreting cells from either line leads to significant protection from challenge with highly metastatic parental cells. These results suggest that such an approach may warrant consideration in the treatment of human plasma cell dyscrasias. JF - Human Gene Therapy AU - Kopantzev, E AU - Roschke, V AU - Rudikoff, S AD - National Cancer Institute, NIH, Bldg. 37, Rm. 2B15, 37 Convent Drive, MSC 4255, Bethesda, MD 20892-4255, USA Y1 - 1998/01/01/ PY - 1998 DA - 1998 Jan 01 SP - 13 EP - 19 VL - 9 IS - 1 SN - 1043-0342, 1043-0342 KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33170:Cellular based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16273548?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Interleukin-2-mediated+modulation+of+plasma+cell+tumor+growth+in+a+model+of+multiple+myeloma&rft.au=Kopantzev%2C+E%3BRoschke%2C+V%3BRudikoff%2C+S&rft.aulast=Kopantzev&rft.aufirst=E&rft.date=1998-01-01&rft.volume=9&rft.issue=1&rft.spage=13&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - On the antigenic determinants of the lipopolysaccharides of Vibrio cholerae O:1, serotypes Ogawa and Inaba AN - 16259753; 4272188 AB - Monoclonal, murine IgG sub(1)s S-20-4, A-20-6, and IgA 2D6, directed against Vibrio cholerae O:1 Ogawa-lipopolysaccharide exhibited the same fine specificities and similar affinities for the synthetic methyl alpha -glycosides of the (oligo)saccharide fragments mimicking the Ogawa O-polysaccharide (O-PS). They did not react with the corresponding synthetic fragments of Inaba O-PS. IgG sub(1)s S-20-4 and A-20-6 have absolute affinity constants for synthetic Ogawa mono- to hexasaccharides of from similar to 10 super(5) to similar to 10 super(6) M super(-1). For IgG sub(1)s S-20-4, A-20-6, and IgA 2D6, the nonreducing terminal residue of Ogawa O-PS is the dominant determinant, accounting for similar to 90% of the maximal binding energy shown by these antibodies. Binding studies of derivatives of the Ogawa monosaccharide and IgGs S-20-4 and A-20-6 revealed that the C-2 O-methyl group fits into a somewhat flexible antibody cavity and that hydrogen bonds involving the oxygen and, respectively, the OH at the 2- and 3-position of the sugar moiety as well as the 2'-position in the amide side chain are required. Monoclonal IgA ZAC-3 and IgG sub(3) I-24-2 are specific for V. cholerae O:1 serotypes Ogawa/Inaba-LPS. The former did not show binding with members of either series of the synthetic ligands related to the O-antigens of the Ogawa or Inaba serotypes, in agreement with its reported specificity for the lipid/core region (1). Inhibition studies revealed that the binding of purified IgG sub(3) I-24-2 to Ogawa-LPS might be mediated by a region in the junction of the OPS to the lipid-core region of the LPS. cDNA cloning and analysis of the anti-Ogawa antibodies S-20-4, A-20-6, and 2D6 revealed a very high degree of homology among the heavy chains. Among the light chains, no such homology between S-20-4 and A-20-6 on the one hand, and 2D6 on the other hand, exists. For the anti-Inaba/Ogawa antibodies I-24-2 and ZAC-3, their heavy chains are completely different, with some homology among the light chains. JF - Journal of Biological Chemistry AU - Wang, Jin AU - Villeneuve, S AU - Zhang, Jian AU - Lei, Ping-Sheng AU - Miller, CE AU - Lafaye, P AU - Nato, F AU - Szu, S C AU - Karpas, A AU - Bystricky, S AU - Robbins, J B AU - Kovac, P AU - Fournier, J-M AU - Glaudemans, CPJ AD - Laboratory of Medicinal Chemistry, NIDDK, NICHD, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 1998/01// PY - 1998 DA - Jan 1998 SP - 2777 EP - 2783 VL - 273 IS - 5 SN - 0021-9258, 0021-9258 KW - antigenic determinants KW - cholera KW - lipopolysaccharides KW - monoclonal antibodies KW - Microbiology Abstracts B: Bacteriology KW - J 02832:Antigenic properties and virulence KW - J 02730:Carbohydrates UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16259753?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=On+the+antigenic+determinants+of+the+lipopolysaccharides+of+Vibrio+cholerae+O%3A1%2C+serotypes+Ogawa+and+Inaba&rft.au=Wang%2C+Jin%3BVilleneuve%2C+S%3BZhang%2C+Jian%3BLei%2C+Ping-Sheng%3BMiller%2C+CE%3BLafaye%2C+P%3BNato%2C+F%3BSzu%2C+S+C%3BKarpas%2C+A%3BBystricky%2C+S%3BRobbins%2C+J+B%3BKovac%2C+P%3BFournier%2C+J-M%3BGlaudemans%2C+CPJ&rft.aulast=Wang&rft.aufirst=Jin&rft.date=1998-01-01&rft.volume=273&rft.issue=5&rft.spage=2777&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER -