TY - JOUR T1 - Role of intracortical mechanisms in the late part of the silent period to transcranial stimulation of the human motor cortex. AN - 85240952; pmid-8610491 AB - Transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES) of the human motor cortex produce a silent period (SP) following motor evoked potentials (MEPs). The early part of the SP can be explained by decreased alpha motor neuron excitability, whereas the late part is presumably due to suprasegmental mechanisms. In order to determine the level of the suprasegmental contribution of the generation of SPs, we recorded excitatory and inhibitory responses to TMS, TES and percutaneous electrical brainstem stimulation (PBS) in the voluntarily activated first dorsal interosseous muscle of the hand. Stimulus intensities were set so that PBS and TES induced MEPs with areas equal to or larger than those of MEPs obtained with TMS. This procedure revealed that SPs were 49% and 83% shorter with TES and PBS, respectively, than with TMS. As TMS is more effective than TES or PBS in activating cortical interneurons, these findings support the idea that a significant component of the SP arises from intracortical mechanisms. JF - Acta Neurologica Scandinavica AU - Brasil-Neto, J P AU - Cammarota, A AU - Valls-Solé J AU - Pascual-Leone, A AU - Hallett, M AU - Cohen, L G AD - Human Cortical Physiology Unit, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892-1428, USA. PY - 1995 SP - 383 EP - 386 VL - 92 IS - 5 SN - 0001-6314, 0001-6314 KW - H-Reflex KW - Motor Cortex KW - Evoked Potentials, Motor KW - Human KW - Adult KW - Brain Stem KW - Middle Age KW - Female KW - Male KW - Motor Neurons KW - Electric Stimulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85240952?accountid=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=Acta+Neurologica+Scandinavica&rft.atitle=Role+of+intracortical+mechanisms+in+the+late+part+of+the+silent+period+to+transcranial+stimulation+of+the+human+motor+cortex.&rft.au=Brasil-Neto%2C+J+P%3BCammarota%2C+A%3BValls-Sol%C3%A9+J%3BPascual-Leone%2C+A%3BHallett%2C+M%3BCohen%2C+L+G&rft.aulast=Brasil-Neto&rft.aufirst=J&rft.date=1995-11-01&rft.volume=92&rft.issue=5&rft.spage=383&rft.isbn=&rft.btitle=&rft.title=Acta+Neurologica+Scandinavica&rft.issn=00016314&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Effects of 9-aminocamptothecin on newly synthesized DNA in patient bone marrow samples. AN - 77953932; 9815930 AB - 9-Aminocamptothecin (9-AC) inhibited cell growth and DNA synthesis in HCT 116 human colon cancer cells in a concentration- and time-dependent manner. Interference with nascent DNA chain elongation was monitored using pH step alkaline elution. After a 3-day 9-AC exposure, 38% (10 nM) and 53% (50 nM) of the total [3H]DNA eluted with pH steps 11.3-11.7, compared to 9% in control cells. Effects on nascent DNA integrity were also evaluated by fixed elution with pH 12.1 buffer. After a 3-day exposure to 9-AC, 27% (10 nM) and 82.5% (50 nM) of the total [3H]DNA eluted relative to control. Paired bone marrow samples were then obtained in 10 patients before treatment and between 42 and 72 h of a continuous i. v. infusion of 9-AC (35-74 microgram/m2/h for 72 h). The mononuclear cells were incubated with [3H]dThd for 2 or 4 h, and then analyzed using either pH step or fixed pH alkaline elution, respectively. In seven patients receiving >/=47 microgram/m2/h 9-AC, 4% +/- 1.5% (mean +/- SE) of the total [3H]DNA eluted with pH steps /=59 microgram/m2/h 9-AC (n = 7). Since hematological toxicity is dose limiting on this 9-AC schedule, these cellular pharmacodynamic studies provide evidence of a DNA-directed cytotoxic effect of 9-AC in a sensitive host target tissue. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Geoffroy, F AU - Dahut, W AU - Takimoto, C H AU - Grem, J L AD - National Cancer Institute-Navy Medical Oncology Branch, Clinical Oncology Program, Division of Cancer Treatment, National Cancer Institute, National Naval Medical Center, Bethesda, Maryland 20889-5105, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 1345 EP - 1351 VL - 1 IS - 11 SN - 1078-0432, 1078-0432 KW - Antineoplastic Agents KW - 0 KW - 9-aminocamptothecin KW - 5MB77ICE2Q KW - DNA KW - 9007-49-2 KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Half-Life KW - Hydrogen-Ion Concentration KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Camptothecin -- pharmacology KW - Camptothecin -- metabolism KW - Antineoplastic Agents -- metabolism KW - Camptothecin -- analogs & derivatives KW - Bone Marrow -- metabolism KW - DNA -- biosynthesis KW - Bone Marrow -- drug effects KW - Antineoplastic Agents -- pharmacology KW - DNA -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77953932?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effects+of+9-aminocamptothecin+on+newly+synthesized+DNA+in+patient+bone+marrow+samples.&rft.au=Geoffroy%2C+F%3BDahut%2C+W%3BTakimoto%2C+C+H%3BGrem%2C+J+L&rft.aulast=Geoffroy&rft.aufirst=F&rft.date=1995-11-01&rft.volume=1&rft.issue=11&rft.spage=1345&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-09 N1 - Date created - 1999-02-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Serum zinc and serum lipid profiles in 778 adults. AN - 77888460; 8680613 AB - There has been increasing use of high-dosage zinc supplementation in the population, in particular as a potential treatment for age-related macular degeneration. We examined the relationship between fasting serum zinc and serum lipid levels in 778 adults, aged 22 to 80 years, who were control subjects in a multicenter, clinic-based case-control study. The samples were taken during 1987 to 1990, a time when vitamin/mineral supplementation was becoming increasingly common. We found that higher serum zinc levels, most notably those above the highest quintile, were associated with higher levels of total serum cholesterol, low-density-lipoprotein cholesterol, and triglycerides. No significant trend was noted for high-density-lipoprotein cholesterol. Previous studies demonstrated that high-dosage zinc supplements raise serum zinc levels. The possibility that use of such supplements can adversely affect serum lipid profiles suggests that chronic ingestion of such supplements should not be done without adequate medical supervision. JF - Annals of epidemiology AU - Hiller, R AU - Seigel, D AU - Sperduto, R D AU - Blair, N AU - Burton, T C AU - Farber, M D AU - Gragoudas, E S AU - Gunter, E W AU - Haller, J AU - Seddon, J M AD - Division of Biometry and Epidemiology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892-2510, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 490 EP - 496 VL - 5 IS - 6 SN - 1047-2797, 1047-2797 KW - Cholesterol, HDL KW - 0 KW - Cholesterol, LDL KW - Lipids KW - Triglycerides KW - Zinc KW - J41CSQ7QDS KW - Index Medicus KW - Triglycerides -- blood KW - Cholesterol, LDL -- blood KW - Cholesterol, HDL -- blood KW - Aged, 80 and over KW - Humans KW - Adult KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Cardiovascular Diseases -- chemically induced KW - Lipids -- blood KW - Zinc -- blood KW - Zinc -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77888460?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+epidemiology&rft.atitle=Serum+zinc+and+serum+lipid+profiles+in+778+adults.&rft.au=Hiller%2C+R%3BSeigel%2C+D%3BSperduto%2C+R+D%3BBlair%2C+N%3BBurton%2C+T+C%3BFarber%2C+M+D%3BGragoudas%2C+E+S%3BGunter%2C+E+W%3BHaller%2C+J%3BSeddon%2C+J+M&rft.aulast=Hiller&rft.aufirst=R&rft.date=1995-11-01&rft.volume=5&rft.issue=6&rft.spage=490&rft.isbn=&rft.btitle=&rft.title=Annals+of+epidemiology&rft.issn=10472797&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-22 N1 - Date created - 1996-08-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Determination of 2-oxohistidine by amino acid analysis. AN - 77803049; 8594998 AB - Oxidative modification of proteins has been implicated in aging, ischemia reperfusion, carcinogenesis, and other phenomena. Oxidation of the C-2 position of the imidazole ring of histidine converts the residue to 2-oxohistidine, a novel amino acid which may serve as a marker of oxidative modification of proteins (K. Uchida and S. Kawakishi, J. Biol. Chem. 269, 2405-2410, 1994). It has been identified in oxidatively modified proteins by electrochemical detection during reverse-phase high-pressure liquid chromatography, by mass spectrometry, and as the phenylthiohydantoin after Edman degradation, but not by amino acid analysis of protein hydrolysates. We now describe procedures for stabilizing 2-oxohistidine which allow its quantification by routine methods of amino acid analysis. These include classical ion exchange chromatography with postcolumn derivatization by o-phthaldialdehyde, reverse-phase chromatography with precolumn derivatization by o-phthaldialdehyde, and reverse-phase chromatography with precolumn derivatization by 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate. Using these techniques, a previously unidentified amino acid which appears during the oxidative inactivation of glutamine synthetase was shown to be 2-oxohistidine. One picomole of 2-oxohistidine was readily detected in a protein hydrolysate containing 1700 pmol total amino acids. JF - Analytical biochemistry AU - Lewisch, S A AU - Levine, R L AD - Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-0320, USA. Y1 - 1995/11/01/ PY - 1995 DA - 1995 Nov 01 SP - 440 EP - 446 VL - 231 IS - 2 SN - 0003-2697, 0003-2697 KW - Amino Acids KW - 0 KW - Biomarkers KW - 2-oxohistidine KW - 151436-49-6 KW - Histidine KW - 4QD397987E KW - Glutamate-Ammonia Ligase KW - EC 6.3.1.2 KW - Index Medicus KW - Sensitivity and Specificity KW - Oxidation-Reduction KW - Biomarkers -- chemistry KW - Glutamate-Ammonia Ligase -- chemistry KW - Chromatography, High Pressure Liquid -- methods KW - Chromatography, Ion Exchange KW - Oxidative Stress -- physiology KW - Histidine -- analysis KW - Amino Acids -- analysis KW - Histidine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77803049?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Analytical+biochemistry&rft.atitle=Determination+of+2-oxohistidine+by+amino+acid+analysis.&rft.au=Lewisch%2C+S+A%3BLevine%2C+R+L&rft.aulast=Lewisch&rft.aufirst=S&rft.date=1995-11-01&rft.volume=231&rft.issue=2&rft.spage=440&rft.isbn=&rft.btitle=&rft.title=Analytical+biochemistry&rft.issn=00032697&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-04-09 N1 - Date created - 1996-04-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The mathematics of radiation target analyses. AN - 77723922; 8528160 AB - Radiation target theory has been extended to complex biochemical systems. Mathematical analyses are presented for multiple forms of biological active proteins, for the presence of large inhibitors or activators, for compounds which regulate rate or affinity and for multiple-step reactions. Several predictions of these models have been verified experimentally. JF - Bulletin of mathematical biology AU - Kempner, E S AD - Laboratory of Physical Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 883 EP - 898 VL - 57 IS - 6 SN - 0092-8240, 0092-8240 KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Radiation KW - Radiation Effects KW - Models, Theoretical KW - Mathematics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77723922?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bulletin+of+mathematical+biology&rft.atitle=The+mathematics+of+radiation+target+analyses.&rft.au=Kempner%2C+E+S&rft.aulast=Kempner&rft.aufirst=E&rft.date=1995-11-01&rft.volume=57&rft.issue=6&rft.spage=883&rft.isbn=&rft.btitle=&rft.title=Bulletin+of+mathematical+biology&rft.issn=00928240&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-29 N1 - Date created - 1996-01-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Persistence of TCDD-induced hepatic cell proliferation and growth of enzyme altered foci after chronic exposure followed by cessation of treatment in DEN initiated female rats. AN - 77705270; 7586202 AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent tumor promoter in two-stage models of hepatocarcinogenesis. This study focuses on the persistence or reversibility of TCDD-mediated changes in livers after 30 weeks of treatment and cessation of treatment. Diethylnitrosamine (DEN) initiated animals (175 mg/kg) were promoted bi-weekly with TCDD at a dose equivalent to 125 ng/kg/day for 30 weeks without or with a following waiting period of 32 weeks before necropsy. 2,3,7,8-Tetrachlorodibenzo-p-dioxin liver concentration decreased 300-fold above background. Induction of CYP1A1 dependent enzyme activity decreased according to TCDD tissue levels. In contrast, cell proliferation, as measured by BrdU-labeling index, was still 2.8-fold increased over controls in the TCDD group with waiting period compared to a 4-fold increase over controls at the end of the 30 week dosing period. Enzyme altered hepatic foci expressing the placental form of glutathione S-transferase decreased in number but the remaining foci were significantly increased in size and the percent of liver occupied by foci was higher at the end of the waiting period as compared to livers at the end of the dosing period. Liver tumor incidence at the end of the waiting period was 71% (5 of 7 animals) and the livers showed an increase in bile duct lesions with only mild toxicity. There was pronounced bile duct proliferation in DEN/TCDD treated animals after the waiting period with intense expression of TGF alpha in bile duct epithelial cells at detected by immunohistochemical methods. In comparison, at the end of the 30 week dosing period the livers showed more severe toxicity and only mild bile duct proliferation. Also, one small hepatocellular adenoma was observed. It is concluded that as opposed to CYP1A1 induction the more complex biological responses, cell proliferation and selective growth of certain preneoplastic foci, are persistent after prolonged TCDD treatment within the experimental framework of our study. JF - Carcinogenesis AU - Tritscher, A M AU - Clark, G C AU - Sewall, C AU - Sills, R C AU - Maronpot, R AU - Lucier, G W AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 2807 EP - 2811 VL - 16 IS - 11 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - Polychlorinated Dibenzodioxins KW - Diethylnitrosamine KW - 3IQ78TTX1A KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Glutathione Transferase -- metabolism KW - Cell Division -- drug effects KW - Female KW - Liver -- pathology KW - Liver -- enzymology KW - Liver -- drug effects KW - Polychlorinated Dibenzodioxins -- toxicity KW - Carcinogens -- toxicity KW - Liver Neoplasms, Experimental -- chemically induced KW - Polychlorinated Dibenzodioxins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77705270?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Persistence+of+TCDD-induced+hepatic+cell+proliferation+and+growth+of+enzyme+altered+foci+after+chronic+exposure+followed+by+cessation+of+treatment+in+DEN+initiated+female+rats.&rft.au=Tritscher%2C+A+M%3BClark%2C+G+C%3BSewall%2C+C%3BSills%2C+R+C%3BMaronpot%2C+R%3BLucier%2C+G+W&rft.aulast=Tritscher&rft.aufirst=A&rft.date=1995-11-01&rft.volume=270&rft.issue=37&rft.spage=21722&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 - 1995-12-28 N1 - Date created - 1995-12-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lower levels of urinary 2-amino-3,8-dimethylimidazo[4,5-f]-quinoxaline (MeIQx) in humans with higher CYP1A2 activity. AN - 77701915; 7586210 AB - Heterocyclic aromatics amines (HAAs), such as 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), are metabolically activated by cytochrome P4501A2 (CYP1A2) and N-acetyltransferase (NAT2). We examined the relationship between CYP1A2 and NAT2 activity and the excretion of total unconjugated MeIQx in 66 healthy subjects. The subjects ate a control diet for 7 days containing lean ground beef cooked at low temperature. On day 8, they were tested for CYP1A2 and NAT2 activity by caffeine phenotyping. On the evening of day 8, subjects consumed lean ground beef cooked at high temperature containing 9.0 ng of MeIQx/g of meat. The subjects ate 3.1-4.0 g meat/kg body wt. Twelve-hour urine samples were collected and MeIQx was measured by gas chromatography-mass spectrometry. Using linear regression analyses, we found that higher CYP1A2 activity was associated with lower levels of total unconjugated MeIQx in the urine (P = 0.008) when adjusted for amount of meat eaten, while NAT2 activity showed no relationship with the latter. This suggest that a greater percentage of MeIQx is converted to metabolites such as the N-hydroxy derivative when CYP1A2 activity is higher. This finding supports the concept that inter-individual variation is CYP1A2 activity may be relevant for cancers associated with exposure to HAAs. JF - Carcinogenesis AU - Sinha, R AU - Rothman, N AU - Mark, S D AU - Murray, S AU - Brown, E D AU - Levander, O A AU - Davies, D S AU - Lang, N P AU - Kadlubar, F F AU - Hoover, R N AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20892, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 2859 EP - 2861 VL - 16 IS - 11 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - Mutagens KW - Quinoxalines KW - 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline KW - 77500-04-0 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Oxidoreductases KW - EC 1.- KW - Cytochrome P-450 CYP1A2 KW - EC 1.14.14.1 KW - Arylamine N-Acetyltransferase KW - EC 2.3.1.5 KW - Index Medicus KW - Humans KW - Adult KW - Middle Aged KW - Arylamine N-Acetyltransferase -- metabolism KW - Male KW - Female KW - Carcinogens -- metabolism KW - Oxidoreductases -- metabolism KW - Quinoxalines -- urine KW - Mutagens -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77701915?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Lower+levels+of+urinary+2-amino-3%2C8-dimethylimidazo%5B4%2C5-f%5D-quinoxaline+%28MeIQx%29+in+humans+with+higher+CYP1A2+activity.&rft.au=Sinha%2C+R%3BRothman%2C+N%3BMark%2C+S+D%3BMurray%2C+S%3BBrown%2C+E+D%3BLevander%2C+O+A%3BDavies%2C+D+S%3BLang%2C+N+P%3BKadlubar%2C+F+F%3BHoover%2C+R+N&rft.aulast=Sinha&rft.aufirst=R&rft.date=1995-11-01&rft.volume=16&rft.issue=11&rft.spage=2859&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-28 N1 - Date created - 1995-12-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Possible mechanisms for PhIP-DNA adduct formation in the mammary gland of female Sprague-Dawley rats. AN - 77701814; 7586192 AB - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most abundant heterocyclic amine in fried beef, is mammary gland carcinogen in rats. Using the 32P-postlabeling method, PhIP-DNA adduct levels were measured in mammary epithelial cells isolated from female Sprague-Dawley rats given 10 daily doses of PhIP (75 mg/kg, p.o.) according to a protocol previously shown to induce mammary gland cancer. At 24 h, 48 h, 1 week and 5 weeks after the last dose of PhIP, PhIP-DNA adduct levels [relative adduct labeling (RAL) x 10(7), mean +/- SD] were 10.2 +/- 0.7, 7.9 +/- 2.7, 2.2 +/- 0.6 and 0.9 +/- 0.03 respectively. When isolated rat mammary epithelial cells (from untreated rats) were incubated in vitro with N-hydroxy-PhIP (45 microM, 1 h, 37 degrees C), PhIP-DNA adducts were detected in cell DNA (RAL = approximately 97 x 10(7); however, no adducts were detected in cells incubated with PhIP (200 microM, 15 h, 37 degrees C). Incubating cells with pentachlorophenol, an inhibitor of acetyltransferase, or incubating cells at 0-4 degrees C, reduced N-hydroxy-PhIP adduct levels by 45 and 75% respectively, indicating that formation of N-hydroxy-PhIP adducts was largely due to metabolic activation. Further studies showed that rat mammary gland microsomes had little capacity to N-hydroxylate PhIP, as assayed by the mutagenic activation of PhIP in the Ames Salmonella assay. In contrast, N-hydroxy-PhIP was metabolically activated by cytosol-catalyzed PhIP-DNA adduct formation to calf thymus DNA incubated in vitro with N-hydroxy-PhIP (2 microM) in the presence of acetyl CoA. Notably, mammary cytosolic O-acetyltransferase activation of N-hydroxy-IQ or N-hydroxy-MeIQx. All three N-hydroxylamines were activated via cytosolic proline aminoacyl-tRNA synthetase and phosphorylase, although the activities of these enzymes were approximately 100-fold lower than O-acetyltransferase. No mammary cytosolic sulfotransferase activation could be detected with any of the N-hydroxylamines. Our results are consistent with the notion that PhIP-DNA adduct formation and initiation of carcinogenesis in the rat mammary gland may be associated with N-hydroxylation of PhIP outside the mammary gland, transport of the N-hydroxylamine to the mammary gland and subsequent in situ O-acetyltransferase-catalyzed activation of N-hydroxy-PhIP. JF - Carcinogenesis AU - Ghoshal, A AU - Davis, C D AU - Schut, H A AU - Snyderwine, E G AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 2725 EP - 2731 VL - 16 IS - 11 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - DNA Adducts KW - Imidazoles KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - Acetyltransferases KW - EC 2.3.1.- KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Acetyltransferases -- metabolism KW - Cytochrome P-450 Enzyme System -- physiology KW - Female KW - Carcinogens -- metabolism KW - Mammary Glands, Animal -- metabolism KW - Imidazoles -- metabolism KW - DNA Adducts -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77701814?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Residues+in+the+second+cysteine-rich+region+of+protein+kinase+C+delta+relevant+to+phorbol+ester+binding+as+revealed+by+site-directed+mutagenesis.&rft.au=Kazanietz%2C+M+G%3BWang%2C+S%3BMilne%2C+G+W%3BLewin%2C+N+E%3BLiu%2C+H+L%3BBlumberg%2C+P+M&rft.aulast=Kazanietz&rft.aufirst=M&rft.date=1995-09-15&rft.volume=270&rft.issue=37&rft.spage=21852&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 - 1995-12-28 N1 - Date created - 1995-12-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Osteoporosis is a toxic effect of long-term etretinate therapy. AN - 77687831; 7503569 AB - Osteoporosis has been observed with chronic hypervitaminosis A but has not been established as a toxic effect of synthetic retinoid therapy in humans. This cross-sectional study was designed to assess bone mineral density (BMD) during long-term therapy with the retinoids etretinate or isotretinoin. Twenty-four patients were evaluated for osteoporosis with the standard techniques: single- and dual-photon absorptiometry. They received 50 g or more of etretinate (15 patients) or isotretinoin (nine patients) for 2 years or longer for the treatment of skin disease (ichthyosis [nine patients], Darier's disease [six patients], xeroderma pigmentosum [four patients], skin cancer [three patients], or psoriasis [two patients]). In each of the two treatment groups, BMDs (measured in grams per square centimeter) were measured at five standard sites (ie, lumbar spine, femoral neck, trochanter, Ward's triangle, and radius) and evaluated against a standardized database to control for age, sex, and weight. In addition, for each measurement site, BMDs (controlled for age, sex, and weight) were compared between the two groups, as a direct control for each other. Compared with those of the age-, sex-, and weight-matched controls, the BMD values of the etretinate group were significantly decreased at four of the five measurement sites: femoral neck (90.6%, P = .0001), Ward's triangle (87.8%, P = .0001), trochanter (87.8%, P = .0012), and radius (85.0%, P = .039). In contrast, the BMDs in the isotretinoin group did not differ from control values except for an elevation at the lumbar spine (P = .039). When the two groups were compared, the mean BMDs were significantly lower in the etretinate group when measured at the lumbar spine, trochanter, and radius (P < .05). This study identified osteoporosis in patients who received long-term therapy with etretinate but not isotretinoin. Prospective studies of BMD would be useful to further define retinoid-associated osteoporosis. JF - Archives of dermatology AU - DiGiovanna, J J AU - Sollitto, R B AU - Abangan, D L AU - Steinberg, S M AU - Reynolds, J C AD - Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 1995/11// PY - 1995 DA - November 1995 SP - 1263 EP - 1267 VL - 131 IS - 11 SN - 0003-987X, 0003-987X KW - Keratolytic Agents KW - 0 KW - Etretinate KW - 65M2UDR9AG KW - Isotretinoin KW - EH28UP18IF KW - Abridged Index Medicus KW - Index Medicus KW - Bone Density -- drug effects KW - Cross-Sectional Studies KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Time Factors KW - Male KW - Female KW - Isotretinoin -- adverse effects KW - Etretinate -- adverse effects KW - Keratolytic Agents -- adverse effects KW - Osteoporosis -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77687831?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+dermatology&rft.atitle=Osteoporosis+is+a+toxic+effect+of+long-term+etretinate+therapy.&rft.au=DiGiovanna%2C+J+J%3BSollitto%2C+R+B%3BAbangan%2C+D+L%3BSteinberg%2C+S+M%3BReynolds%2C+J+C&rft.aulast=DiGiovanna&rft.aufirst=J&rft.date=1995-11-01&rft.volume=131&rft.issue=11&rft.spage=1263&rft.isbn=&rft.btitle=&rft.title=Archives+of+dermatology&rft.issn=0003987X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-17 N1 - Date created - 1996-01-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Arch Dermatol. 1995 Nov;131(11):1321-2 [7503578] Arch Dermatol. 1996 Jun;132(6):713; author reply 714 [8651729] Arch Dermatol. 1996 Jun;132(6):713-4 [8651730] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The H-ras oncogene interferes with retinoic acid signaling and metabolism in NIH3T3 cells. AN - 77617464; 7585519 AB - We have previously shown that retinoic acid (RA) fails to induce transglutaminase C in H-ras transformed NIH-3T3 cells. Therefore, we investigated the effect of the H-ras oncogene on the metabolism of RA and on the expression of the cellular RA-binding protein I mRNA. HPLC analysis of the media and cell extracts demonstrated that H-ras-transformed cells metabolize RA to a much lesser extent than control cells, resulting in a higher concentration of RA in H-ras cells. Although inactive in endogenous transglutaminase induction, H-ras cell-associated RA was shown to be biologically available to induce activation of a reporter construct containing a retinoid response element and in stimulating transglutaminase activity in nontransfected cells. Cellular RA-binding protein I mRNA, supposedly involved in RA storage, was significantly increased in the H-ras-transformed cells. These data demonstrate that, even though H-ras-transformed cells accumulate up to 20 fold the concentration of RA as NIH-3T3 cells, they fail to show transglutaminase induction, suggesting that H-ras interferes with signal transduction by RA. JF - Cancer research AU - Kósa, K AU - Jones, C S AU - De Luca, L M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1995/11/01/ PY - 1995 DA - 1995 Nov 01 SP - 4850 EP - 4854 VL - 55 IS - 21 SN - 0008-5472, 0008-5472 KW - Culture Media KW - 0 KW - RNA, Messenger KW - Receptors, Retinoic Acid KW - retinoic acid binding protein I, cellular KW - retinoic acid binding protein II, cellular KW - Tritium KW - 10028-17-8 KW - Tretinoin KW - 5688UTC01R KW - Index Medicus KW - Receptors, Retinoic Acid -- genetics KW - Animals KW - 3T3 Cells -- drug effects KW - Mice KW - RNA, Messenger -- genetics KW - Chromatography, High Pressure Liquid KW - Base Sequence KW - Transfection KW - 3T3 Cells -- physiology KW - Genes, Reporter KW - Molecular Sequence Data KW - Gene Expression Regulation -- drug effects KW - Tretinoin -- pharmacology KW - Signal Transduction -- physiology KW - Genes, ras -- drug effects KW - Genes, ras -- physiology KW - Signal Transduction -- drug effects KW - Tretinoin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77617464?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=The+H-ras+oncogene+interferes+with+retinoic+acid+signaling+and+metabolism+in+NIH3T3+cells.&rft.au=K%C3%B3sa%2C+K%3BJones%2C+C+S%3BDe+Luca%2C+L+M&rft.aulast=K%C3%B3sa&rft.aufirst=K&rft.date=1995-11-01&rft.volume=55&rft.issue=21&rft.spage=4850&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 - 1995-12-06 N1 - Date created - 1995-12-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Suppression of growth of renal carcinoma cells by the von Hippel-Lindau tumor suppressor gene. AN - 77614138; 7585510 AB - Clear cell renal carcinomas are most frequently characterized by loss of function of both copies of the von Hippel-Lindau (VHL) disease gene, suggesting that the VHL gene product plays an important role in regulating renal cell proliferation. To directly assess the function of the VHL gene product, we transfected the wild-type VHL gene into two renal carcinoma cell lines that lacked normal expression of the gene. Expression of the wild-type VHL gene led to a dramatic suppression of growth in two renal carcinoma cell lines, A498 and UMRC6 in vitro, as measured by colony formation and direct cell counting. Transfection of a naturally occurring mutant VHL gene (nucleotide 713 G to A, Arg to Gln) did not lead to growth suppression of these renal carcinoma cells, nor did transfection of the wild-type VHL gene into two non-renal tumor cell lines that expressed the endogenous wild-type VHL gene. Expression constructs, which included the first ATG at nucleotide 214, were sufficient to produce the strongest growth suppression. These experiments provide direct evidence that the VHL gene product functions to suppress the growth of renal carcinoma cells and also provide a model for mapping the domains of the VHL protein important in suppressing tumor growth. JF - Cancer research AU - Chen, F AU - Kishida, T AU - Duh, F M AU - Renbaum, P AU - Orcutt, M L AU - Schmidt, L AU - Zbar, B AD - Biological Carcinogenesis and Development Program, SAIC Frederick, National Cancer Institute, Maryland 21702, USA. Y1 - 1995/11/01/ PY - 1995 DA - 1995 Nov 01 SP - 4804 EP - 4807 VL - 55 IS - 21 SN - 0008-5472, 0008-5472 KW - Codon KW - 0 KW - DNA, Complementary KW - Index Medicus KW - Base Sequence KW - DNA, Complementary -- genetics KW - Tumor Cells, Cultured KW - Transfection KW - Open Reading Frames KW - Humans KW - Molecular Sequence Data KW - Gene Expression KW - Cell Division -- physiology KW - Cell Survival -- physiology KW - Kidney Neoplasms -- genetics KW - Carcinoma, Renal Cell -- pathology KW - Kidney Neoplasms -- therapy KW - Kidney Neoplasms -- pathology KW - Carcinoma, Renal Cell -- therapy KW - Genes, Tumor Suppressor KW - von Hippel-Lindau Disease -- genetics KW - Genetic Therapy KW - Carcinoma, Renal Cell -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77614138?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Suppression+of+growth+of+renal+carcinoma+cells+by+the+von+Hippel-Lindau+tumor+suppressor+gene.&rft.au=Chen%2C+F%3BKishida%2C+T%3BDuh%2C+F+M%3BRenbaum%2C+P%3BOrcutt%2C+M+L%3BSchmidt%2C+L%3BZbar%2C+B&rft.aulast=Chen&rft.aufirst=F&rft.date=1995-11-01&rft.volume=55&rft.issue=21&rft.spage=4804&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 - 1995-12-06 N1 - Date created - 1995-12-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Factors responsible for the Ca(2+)-dependent inactivation of calcineurin in brain. AN - 77657618; 7589543 AB - The Ca(2+)-dependent protein phosphatase activity of crude rat brain extracts measured in the presence of okadaic acid, exhibits the characteristic properties of the calmodulin-stimulated protein phosphatase, calcineurin. It is stimulated more than 200-fold by Ca2+ and inhibited by the calmodulin-binding peptide, M13, and by the immunosuppressive drug, FK506. It is insensitive to rapamycin at concentrations up to 1 microM. Its specific activity, based on calcineurin concentration determined by quantitative analysis of Western blots exposed to anti-bovine brain IgG, is ten to twenty times that of purified rat brain calcineurin assayed under similar conditions. Unlike the purified enzyme it is rapidly and irreversibly inactivated in a time-, temperature-, and Ca2+/calmodulin-dependent fashion without evidence of extensive proteolytic degradation. The enzyme is converted to a state which does not lose activity by removal of low molecular weight material by gel filtration. Reconstitution of a labile enzyme is achieved by the addition of the low molecular weight-containing fraction eluted from the gel filtration column. These observations indicate that calcineurin in crude brain extracts is under the control of Ca2+/calmodulin-dependent positive and negative regulatory mechanisms which involve unidentified endogenous factor(s). JF - FEBS letters AU - Stemmer, P M AU - Wang, X AU - Krinks, M H AU - Klee, C B AD - Laboratory of Biochemistry, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 1995/10/30/ PY - 1995 DA - 1995 Oct 30 SP - 237 EP - 240 VL - 374 IS - 2 SN - 0014-5793, 0014-5793 KW - Calmodulin KW - 0 KW - Calmodulin-Binding Proteins KW - Enzyme Inhibitors KW - Ethers, Cyclic KW - Immunosuppressive Agents KW - Polyenes KW - Tissue Extracts KW - Okadaic Acid KW - 1W21G5Q4N2 KW - Calcineurin KW - EC 3.1.3.16 KW - Phosphoprotein Phosphatases KW - Calcium KW - SY7Q814VUP KW - Sirolimus KW - W36ZG6FT64 KW - Tacrolimus KW - WM0HAQ4WNM KW - Index Medicus KW - Animals KW - Tacrolimus -- analogs & derivatives KW - Ethers, Cyclic -- pharmacology KW - Polyenes -- pharmacology KW - Immunosuppressive Agents -- pharmacology KW - Rats KW - Rats, Sprague-Dawley KW - Tacrolimus -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Calmodulin -- pharmacology KW - Male KW - Phosphoprotein Phosphatases -- antagonists & inhibitors KW - Brain -- enzymology KW - Calmodulin-Binding Proteins -- antagonists & inhibitors KW - Phosphoprotein Phosphatases -- metabolism KW - Calmodulin-Binding Proteins -- metabolism KW - Calcium -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77657618?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+chromatography.+A&rft.atitle=Gel+electrophoretic+analysis+of+cellular+and+secreted+proteins+from+resting+and+activated+rat+alveolar+macrophages+treated+with+pentamidine+isethionate.&rft.au=Selkirk%2C+J+K%3BHe%2C+C%3BMerrick%2C+B+A&rft.aulast=Selkirk&rft.aufirst=J&rft.date=1995-09-22&rft.volume=711&rft.issue=2&rft.spage=331&rft.isbn=&rft.btitle=&rft.title=Journal+of+chromatography.+A&rft.issn=00219673&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-28 N1 - Date created - 1995-12-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A Mg(2+)-dependent, Ca(2+)-inhibitable serine/threonine protein phosphatase from bovine brain. AN - 77580637; 7592734 AB - The Mg(2+)-dependent serine/threonine protein phosphatases, also known as type 2C phosphatases (PP2C), belong to a gene family distinct from the other serine/threonine phosphatases and tyrosine phosphatases. Here we report the purification to apparent homogeneity of a novel Mg(2+)-dependent, Ca(2+)-inhibitable serine/threonine protein phosphatase from bovine brain. It is a type 2C enzyme in view of its Mg2+ requirement, resistance to okadaic acid and calyculin A, inability to use phosphorylase alpha as substrate, and a segment of amino acid sequence typical of all PP2C type phosphatases known to date. However, it differs from the other PP2C enzymes, particularly the mammalian PP2C alpha and -beta isoforms, in that its molecular weight, 76,000, is considerably larger and that it is inhibited by Ca2+, NaF, and polycations, but not by orthovanadate. The Ca2+ inhibition may not be related to its cellular regulation because of Ki values in the 20-90 microM range, but this property permits distinction of this enzyme from the other phosphatases. Although the precise physiological role of this phosphatase is not yet known, its ability to dephosphorylate a wide variety of phosphoproteins and its broad distribution, as shown by a survey of mouse tissues for its activity, suggest that it may serve an important cellular function. JF - The Journal of biological chemistry AU - Wang, Y AU - Santini, F AU - Qin, K AU - Huang, C Y AD - Laboratory of Biochemistry, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/10/27/ PY - 1995 DA - 1995 Oct 27 SP - 25607 EP - 25612 VL - 270 IS - 43 SN - 0021-9258, 0021-9258 KW - Cations KW - 0 KW - Enzyme Inhibitors KW - Ethers, Cyclic KW - Nerve Tissue Proteins KW - Oxazoles KW - Saccharomyces cerevisiae Proteins KW - Okadaic Acid KW - 1W21G5Q4N2 KW - calyculin A KW - 7D07U14TK3 KW - Phosphorylase a KW - EC 2.4.1.- KW - Phosphorylase Kinase KW - EC 2.7.1.19 KW - PTC1 protein, S cerevisiae KW - EC 3.1.3.16 KW - Phosphoprotein Phosphatases KW - Ppm1a protein, mouse KW - Protein Phosphatase 2 KW - Protein Phosphatase 2C KW - Phosphoric Monoester Hydrolases KW - EC 3.1.3.2 KW - Magnesium KW - I38ZP9992A KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Phosphorylase Kinase -- metabolism KW - Amino Acid Sequence KW - Mice KW - Ethers, Cyclic -- pharmacology KW - Molecular Weight KW - Phosphoric Monoester Hydrolases -- antagonists & inhibitors KW - Phosphorylase a -- metabolism KW - Cattle KW - Oxazoles -- pharmacology KW - Molecular Sequence Data KW - Enzyme Inhibitors -- pharmacology KW - Substrate Specificity KW - Sequence Homology, Amino Acid KW - Cations -- pharmacology KW - Protein Conformation KW - Phosphoprotein Phosphatases -- antagonists & inhibitors KW - Nerve Tissue Proteins -- drug effects KW - Brain -- enzymology KW - Phosphoprotein Phosphatases -- drug effects KW - Phosphoprotein Phosphatases -- isolation & purification KW - Phosphoprotein Phosphatases -- metabolism KW - Nerve Tissue Proteins -- isolation & purification KW - Magnesium -- pharmacology KW - Nerve Tissue Proteins -- metabolism KW - Calcium -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77580637?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+Mg%282%2B%29-dependent%2C+Ca%282%2B%29-inhibitable+serine%2Fthreonine+protein+phosphatase+from+bovine+brain.&rft.au=Wang%2C+Y%3BSantini%2C+F%3BQin%2C+K%3BHuang%2C+C+Y&rft.aulast=Wang&rft.aufirst=Y&rft.date=1995-10-27&rft.volume=270&rft.issue=43&rft.spage=25607&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 - 1995-12-14 N1 - Date created - 1995-12-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytochrome P450 2A1, 2E1, and 2C9 cDNA-expression by insect cells and partial purification using hydrophobic chromatography. AN - 77690129; 7503803 AB - High-level expression of three cloned cytochrome P450 enzymes was accomplished using the baculovirus-insect cell expression system. The amount of enzyme expression was enhanced by cell infections in the presence of medium-supplements containing hemin and by growth in suspension cultures. Human cytochromes P450 2E1 and 2C9 and rat cytochrome P450 2A1 were partially purified from cell extracts using hydrophobic interaction and hydroxyapatite chromatography. The resulting enzymes were of estimated molecular masses similar to those reported previously and analyzed by PAGE. Reconstitution of enzyme activity resulted when the enzymes were incubated together with NADPH-cytochrome P450 reductase, phospholipid, NADPH, and appropriate substrates. The cytochrome P450 activity of the partially purified enzymes was comparable to that of the corresponding enzymes expressed in the vaccinia virus-Hep G2 system. These results provide evidence for a general means of obtaining cytochrome P450 enzymes for mechanistic, immunochemical, and biophysical investigations. JF - Biochemical pharmacology AU - Grogan, J AU - Shou, M AU - Andrusiak, E A AU - Tamura, S AU - Buters, J T AU - Gonzalez, F J AU - Korzekwa, K R AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/10/26/ PY - 1995 DA - 1995 Oct 26 SP - 1509 EP - 1515 VL - 50 IS - 9 SN - 0006-2952, 0006-2952 KW - DNA, Complementary KW - 0 KW - Recombinant Proteins KW - Sodium Dodecyl Sulfate KW - 368GB5141J KW - Hemin KW - 743LRP9S7N KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Steroid Hydroxylases KW - EC 1.14.- KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - Steroid 16-alpha-Hydroxylase KW - Oxidoreductases, N-Demethylating KW - EC 1.5.- KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Spodoptera KW - Electrophoresis, Polyacrylamide Gel KW - Chemistry, Physical KW - Humans KW - Oxidoreductases, N-Demethylating -- isolation & purification KW - Gene Expression KW - Steroid Hydroxylases -- biosynthesis KW - Rats KW - Hemin -- pharmacology KW - Recombinant Proteins -- isolation & purification KW - Tumor Cells, Cultured KW - Genetic Vectors KW - Steroid Hydroxylases -- isolation & purification KW - Steroid Hydroxylases -- genetics KW - Oxidoreductases, N-Demethylating -- genetics KW - Vaccinia virus -- genetics KW - Chromatography KW - Recombinant Proteins -- genetics KW - Oxidoreductases, N-Demethylating -- biosynthesis KW - Baculoviridae -- genetics KW - Chemical Phenomena KW - Cell Line KW - Catalysis KW - DNA, Complementary -- genetics KW - Cytochrome P-450 Enzyme System -- genetics KW - Cytochrome P-450 Enzyme System -- isolation & purification KW - Cytochrome P-450 Enzyme System -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77690129?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=Cytochrome+P450+2A1%2C+2E1%2C+and+2C9+cDNA-expression+by+insect+cells+and+partial+purification+using+hydrophobic+chromatography.&rft.au=Grogan%2C+J%3BShou%2C+M%3BAndrusiak%2C+E+A%3BTamura%2C+S%3BButers%2C+J+T%3BGonzalez%2C+F+J%3BKorzekwa%2C+K+R&rft.aulast=Grogan&rft.aufirst=J&rft.date=1995-10-26&rft.volume=50&rft.issue=9&rft.spage=1509&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-18 N1 - Date created - 1996-01-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparative assessment of metabolic enzyme levels in macrophage populations of the F344 rat. AN - 77685135; 7503801 AB - The immune system is a direct target for toxic insult by a number of drugs and other chemicals, many of which require activation to toxic metabolites by drug-metabolizing enzymes. We compared the induction of drug-metabolizing enzymes, including cytochrome P450 1A1 (CYP1A1) and aldehyde dehydrogenase (ALDH), which are differentially expressed in various macrophage populations following treatment of F344 rats with the inducer 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Kupffer cells, alveolar macrophages and splenic macrophages from TCDD-treated animals expressed elevated levels of inducible CYP1A1 as compared to other macrophage subpopulations or cells from control rats. TCDD treatment also resulted in increased ethoxyresorufin-O-deethylase (EROD) activity and total cytochrome P450 content in tissue-derived macrophages. Immunoreactive protein and mRNA transcripts for CYP1A1 were not detectable in resident peritoneal macrophages or peripheral blood monocytes. Examination of aromatic hydrocarbon receptor (AhR) levels in macrophage populations suggests that the ability of TCDD to induce metabolic enzymes in specific cell types correlates well with AhR expression. In vivo activation of macrophages, using either Bacillus of Calmette and Guérin, Mycobacterium tuberculosis (BCG) or polyinosinic:polycytidylic acid (Poly I:C), caused no significant alteration in the levels of induction of CYP1A1. ALDH-3 induction was similar in all macrophage populations examined. These studies indicate that macrophages, particularly those from portals of entry, may be induced to produce increased levels of specific enzymes, and the induction is dependent upon their maturational stage rather than their activation state. The metabolism of xenobiotics to toxic intermediates by immune cells and its role in immunosuppression are discussed. JF - Biochemical pharmacology AU - Germolec, D R AU - Adams, N H AU - Luster, M I AD - Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/10/26/ PY - 1995 DA - 1995 Oct 26 SP - 1495 EP - 1504 VL - 50 IS - 9 SN - 0006-2952, 0006-2952 KW - Polychlorinated Dibenzodioxins KW - 0 KW - Receptors, Aryl Hydrocarbon KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Oxidoreductases KW - EC 1.- KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - Aldehyde Dehydrogenase KW - EC 1.2.1.3 KW - Index Medicus KW - Animals KW - Immunoblotting KW - Spleen -- cytology KW - Polychlorinated Dibenzodioxins -- pharmacology KW - Macrophages, Alveolar -- enzymology KW - Kupffer Cells -- drug effects KW - Macrophages, Peritoneal -- drug effects KW - Macrophages, Alveolar -- drug effects KW - Macrophage Activation -- drug effects KW - Rats KW - Rats, Inbred F344 KW - Base Sequence KW - Oxidoreductases -- metabolism KW - Molecular Sequence Data KW - Kupffer Cells -- enzymology KW - Enzyme Induction KW - Receptors, Aryl Hydrocarbon -- metabolism KW - Female KW - Macrophages, Peritoneal -- enzymology KW - Macrophages -- enzymology KW - Cytochrome P-450 Enzyme System -- metabolism KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Aldehyde Dehydrogenase -- metabolism KW - Macrophages -- drug effects KW - Aldehyde Dehydrogenase -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77685135?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=Comparative+assessment+of+metabolic+enzyme+levels+in+macrophage+populations+of+the+F344+rat.&rft.au=Germolec%2C+D+R%3BAdams%2C+N+H%3BLuster%2C+M+I&rft.aulast=Germolec&rft.aufirst=D&rft.date=1995-10-26&rft.volume=50&rft.issue=9&rft.spage=1495&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-18 N1 - Date created - 1996-01-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hepatic failure and lactic acidosis due to fialuridine (FIAU), an investigational nucleoside analogue for chronic hepatitis B. AN - 77550732; 7565947 AB - We describe severe and unexpected multisystem toxicity that occurred during a study of the antiviral nucleoside analogue fialuridine (1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodouracil, or FIAU) as therapy for chronic hepatitis B virus infection. Fifteen patients with chronic hepatitis B were randomly assigned to receive fialuridine at a dose of either 0.10 or 0.25 mg per kilogram of body weight per day for 24 weeks and were monitored every 1 to 2 weeks by means of a physical examination, blood tests, and testing for hepatitis B virus markers. During the 13th week lactic acidosis and liver failure suddenly developed in one patient. The study was terminated on an emergency basis, and all treatment with fialuridine was discontinued. Seven patients were found to have severe hepatotoxicity, with progressive lactic acidosis, worsening jaundice, and deteriorating hepatic synthetic function despite the discontinuation of fialuridine. Three other patients had mild hepatotoxicity. Several patients also had pancreatitis, neuropathy, or myopathy. Of the seven patients with severe hepatotoxicity, five died and two survived after liver transplantation. Histologic analysis of liver tissue revealed marked accumulation of microvesicular and macrovesicular fat, with minimal necrosis of hepatocytes or architectural changes. Electron microscopy showed abnormal mitochondria and the accumulation of fat in hepatocytes. In patients with chronic hepatitis B, treatment with fialuridine induced a severe toxic reaction characterized by hepatic failure, lactic acidosis, pancreatitis, neuropathy, and myopathy. This toxic reaction was probably caused by widespread mitochondrial damage and may occur infrequently with other nucleoside analogues. JF - The New England journal of medicine AU - McKenzie, R AU - Fried, M W AU - Sallie, R AU - Conjeevaram, H AU - Di Bisceglie, A M AU - Park, Y AU - Savarese, B AU - Kleiner, D AU - Tsokos, M AU - Luciano, C AD - Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Y1 - 1995/10/26/ PY - 1995 DA - 1995 Oct 26 SP - 1099 EP - 1105 VL - 333 IS - 17 SN - 0028-4793, 0028-4793 KW - Antiviral Agents KW - 0 KW - DNA, Mitochondrial KW - DNA, Viral KW - Drugs, Investigational KW - Arabinofuranosyluracil KW - 3083-77-0 KW - fialuridine KW - 53T7IN77LC KW - Alanine Transaminase KW - EC 2.6.1.2 KW - Abridged Index Medicus KW - Index Medicus KW - Liver -- pathology KW - Humans KW - Jaundice -- chemically induced KW - Peripheral Nervous System Diseases -- chemically induced KW - Liver Transplantation KW - Alanine Transaminase -- blood KW - DNA, Mitochondrial -- drug effects KW - Liver -- drug effects KW - Adult KW - DNA, Viral -- blood KW - Middle Aged KW - Chronic Disease KW - Pancreatitis -- chemically induced KW - Female KW - Male KW - Antiviral Agents -- therapeutic use KW - Arabinofuranosyluracil -- therapeutic use KW - Liver Failure -- mortality KW - Acidosis, Lactic -- chemically induced KW - Arabinofuranosyluracil -- analogs & derivatives KW - Drugs, Investigational -- adverse effects KW - Hepatitis B -- drug therapy KW - Drugs, Investigational -- therapeutic use KW - Acidosis, Lactic -- surgery KW - Liver Failure -- surgery KW - Arabinofuranosyluracil -- adverse effects KW - Liver Failure -- chemically induced KW - Antiviral Agents -- adverse effects KW - Acidosis, Lactic -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77550732?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Hepatic+failure+and+lactic+acidosis+due+to+fialuridine+%28FIAU%29%2C+an+investigational+nucleoside+analogue+for+chronic+hepatitis+B.&rft.au=McKenzie%2C+R%3BFried%2C+M+W%3BSallie%2C+R%3BConjeevaram%2C+H%3BDi+Bisceglie%2C+A+M%3BPark%2C+Y%3BSavarese%2C+B%3BKleiner%2C+D%3BTsokos%2C+M%3BLuciano%2C+C&rft.aulast=McKenzie&rft.aufirst=R&rft.date=1995-10-26&rft.volume=333&rft.issue=17&rft.spage=1099&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 - 1995-10-26 N1 - Date created - 1995-10-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: N Engl J Med. 1996 Apr 25;334(17):1136; author reply 1137-8 [8598881] N Engl J Med. 1995 Oct 26;333(17):1146-8 [7565955] N Engl J Med. 1996 Apr 25;334(17):1136-7; author reply 1137-8 [8598883] N Engl J Med. 1996 Apr 25;334(17):1135-6; author reply 1137-8 [8598880] N Engl J Med. 1996 Apr 25;334(17):1136; author reply 1137-8 [8598882] N Engl J Med. 1996 Apr 25;334(17):1135; author reply 1137-8 [8598879] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - CGG repeats associated with DNA instability and chromosome fragility form structures that block DNA synthesis in vitro. AN - 77679521; 7479085 AB - A large increase in the length of a CGG tandem array is associated with a number of triplet expansion diseases, including fragile X syndrome, the most common cause of heritable mental retardation in humans. Expansion results in the appearance of a fragile site on the X chromosome in the region of the CGG array. We show here that CGG repeats readily form a series of barriers to DNA synthesis in vitro. There barriers form only when the (CGG)n strand is used as the template, are K(+)-dependent, template concentration-independent, and involve hydrogen bonding between guanines. Chemical modification experiments suggest these blocks to DNA synthesis result from the formation of a series of intrastrand tetraplexes. A number of lines of evidence suggest that both triplet expansion and chromosome fragility are the result of replication defects. Our data are discussed in the light of such evidence. JF - Nucleic acids research AU - Usdin, K AU - Woodford, K J AD - Section on Genomic Structure and Function, National Institute of Diabetes and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0830, USA. Y1 - 1995/10/25/ PY - 1995 DA - 1995 Oct 25 SP - 4202 EP - 4209 VL - 23 IS - 20 SN - 0305-1048, 0305-1048 KW - Alkylating Agents KW - 0 KW - Oligodeoxyribonucleotides KW - Sulfuric Acid Esters KW - bromoacetaldehyde KW - 17157-48-1 KW - Guanine KW - 5Z93L87A1R KW - DNA KW - 9007-49-2 KW - Acetaldehyde KW - GO1N1ZPR3B KW - dimethyl sulfate KW - JW5CW40Z50 KW - Potassium KW - RWP5GA015D KW - Index Medicus KW - Acetaldehyde -- analogs & derivatives KW - Potassium -- physiology KW - Base Sequence KW - Chromosome Fragile Sites KW - Molecular Sequence Data KW - Oligodeoxyribonucleotides -- chemical synthesis KW - Templates, Genetic KW - Nucleic Acid Conformation KW - Hydrogen Bonding KW - Guanine -- metabolism KW - DNA Replication -- genetics KW - DNA -- metabolism KW - DNA -- genetics KW - Chromosome Fragility KW - Trinucleotide Repeats -- genetics KW - DNA -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77679521?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=CGG+repeats+associated+with+DNA+instability+and+chromosome+fragility+form+structures+that+block+DNA+synthesis+in+vitro.&rft.au=Usdin%2C+K%3BWoodford%2C+K+J&rft.aulast=Usdin&rft.aufirst=K&rft.date=1995-10-25&rft.volume=23&rft.issue=20&rft.spage=4202&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-21 N1 - Date created - 1995-12-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1994 Jul 1;77(7):1083-92 [8020096] Hum Mol Genet. 1994 Mar;3(3):399-405 [8012351] J Biol Chem. 1994 Oct 28;269(43):27029-35 [7929444] Hum Mol Genet. 1994 Sep;3(9):1543-51 [7833909] J Med Genet. 1983 Jun;20(3):169-78 [6876108] Am J Hum Genet. 1983 Nov;35(6):1270-5 [6196967] Nucleic Acids Res. 1985 Jul 11;13(13):4811-24 [4022774] Am J Med Genet. 1986 Jan-Feb;23(1-2):457-66 [2937300] Proc Natl Acad Sci U S A. 1988 Jun;85(11):3781-5 [3375241] Am J Hum Genet. 1988 Sep;43(3):265-73 [3137811] Nature. 1990 Mar 29;344(6265):410-4 [2320109] Nature. 1990 Jun 28;345(6278):836-8 [2359461] Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):507-11 [1988950] Science. 1991 Jun 21;252(5013):1711-4 [1675488] Cell. 1991 Dec 20;67(6):1047-58 [1760838] J Biol Chem. 1992 Sep 15;267(26):18251-4 [1526964] J Mol Endocrinol. 1992 Dec;9(3):221-5 [1476609] Hum Mol Genet. 1993 Feb;2(2):197-200 [8499907] Biochemistry. 1993 Jun 8;32(22):5870-80 [8504107] Proc Natl Acad Sci U S A. 1994 May 24;91(11):4950-4 [8197163] Cell. 1994 Jun 17;77(6):853-61 [7911740] Science. 1994 Jun 24;264(5167):1938-41 [8009225] Am J Hum Genet. 1994 Jul;55(1):81-6 [8023854] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cloning and characterization of a cellular apoptosis susceptibility gene, the human homologue to the yeast chromosome segregation gene CSE1. AN - 77590513; 7479798 AB - We recently isolated human cDNA fragments that render MCF-7 breast cancer cells resistant to cell death caused by Pseudomonas exotoxin, Pseudomonas exotoxin-derived immunotoxins, diphtheria toxin, and tumor necrosis factor. We report here that one of these fragments is an antisense fragment of a gene homologous to the essential yeast chromosome segregation gene CSE1. Cloning and analysis of the full-length cDNA of the human CSE1 homologue, which we name CAS for cellular apoptosis susceptibility gene, reveals a protein coding region with similar length (971 amino acids for CAS, 960 amino acids for CSE1) and 59% overall protein homology to the yeast CSE1 protein. The conservation of this gene indicates it has an important function in human cells consistent with the essential role of CSE1 in yeast. CAS is highly expressed in human tumor cell lines and in human testis and fetal liver, tissues that contain actively dividing cells. Furthermore, CAS expression increases when resting human fibroblasts are induced to proliferate and decreases when they are growth-arrested. Thus, CAS appears to play an important role in both toxin and tumor necrosis factor-mediated cell death, as well as in cell proliferation. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Brinkmann, U AU - Brinkmann, E AU - Gallo, M AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institutes, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1995/10/24/ PY - 1995 DA - 1995 Oct 24 SP - 10427 EP - 10431 VL - 92 IS - 22 SN - 0027-8424, 0027-8424 KW - CSE1 protein, S cerevisiae KW - 0 KW - Cellular Apoptosis Susceptibility Protein KW - DNA, Complementary KW - Fungal Proteins KW - Nuclear Proteins KW - Nucleocytoplasmic Transport Proteins KW - Proteins KW - RNA, Messenger KW - Recombinant Proteins KW - Saccharomyces cerevisiae Proteins KW - Index Medicus KW - Fetus KW - Liver -- cytology KW - Testis -- metabolism KW - Recombinant Proteins -- biosynthesis KW - Humans KW - RNA, Messenger -- analysis KW - Liver -- metabolism KW - Breast Neoplasms KW - Organ Specificity KW - Amino Acid Sequence KW - RNA, Messenger -- biosynthesis KW - Chromosomes, Fungal KW - Cloning, Molecular KW - Tumor Cells, Cultured KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Repetitive Sequences, Nucleic Acid KW - Male KW - Cell Line KW - Female KW - Testis -- cytology KW - Cell Division KW - Protein Biosynthesis KW - Apoptosis -- genetics KW - Proteins -- chemistry KW - Genes, Fungal KW - Gene Expression KW - Fungal Proteins -- genetics KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77590513?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cloning+and+characterization+of+a+cellular+apoptosis+susceptibility+gene%2C+the+human+homologue+to+the+yeast+chromosome+segregation+gene+CSE1.&rft.au=Brinkmann%2C+U%3BBrinkmann%2C+E%3BGallo%2C+M%3BPastan%2C+I&rft.aulast=Brinkmann&rft.aufirst=U&rft.date=1995-10-24&rft.volume=92&rft.issue=22&rft.spage=10427&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 - 1995-11-30 N1 - Date created - 1995-11-30 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U33286; GENBANK N1 - SuppNotes - Cited By: J Biol Chem. 1987 Jun 25;262(18):8707-11 [2885323] Mol Cell Biol. 1993 Aug;13(8):4691-702 [8336709] J Mol Biol. 1990 Oct 5;215(3):403-10 [2231712] Mol Cell Biol. 1991 Jun;11(6):3317-25 [2038334] Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8616-20 [1924323] Cell. 1991 Nov 29;67(5):879-88 [1835668] Eur J Biochem. 1992 Apr 1;205(1):25-31 [1313365] FEBS Lett. 1992 Jun 15;304(2-3):170-8 [1319925] J Immunol. 1992 Sep 15;149(6):2089-94 [1517572] Exp Cell Res. 1993 Sep;208(1):296-302 [8359223] Mol Cell Biol. 1994 May;14(5):3320-8 [8164683] Science. 1994 Sep 30;265(5181):2091-3 [8091232] Science. 1994 Dec 16;266(5192):1821-8 [7997877] Cell. 1995 Apr 21;81(2):269-78 [7736579] Mol Med. 1995 Jan;1(2):206-16 [8529099] J Biol Chem. 1989 Sep 15;264(26):15261-7 [2768263] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutagenic analysis of functional domains of the mos proto-oncogene and identification of the sites important for MAPK activation and DNA binding. AN - 77587170; 7478569 AB - We constructed in-frame deletion/replacement mutations in the Xenopus mos proto-oncogene that lie within conserved Mos-specific codons, but outside of the regions that are conserved among the src kinase family of genes. All gene products were assayed in vitro for kinase activity and in vivo for their ability to induce oocyte maturation, embryonic cleavage arrest and cellular transformation. Most mutations in Mos eliminated both kinase and biological activity. However, a mutation in Mos that removed two basic amino acid residues (R94 and K97) downstream from the lysine at the ATP binding site (K90) markedly enhanced autophosphorylation activity. Moreover, this mutant displayed markedly reduced biological activity, lacked transforming activity, and failed to activate mitogen activated protein kinase (MAPK). A second mutant Mos product, lacking amino acids R45-A54, displayed a five-fold increase in cellular transforming activity. This Mos mutant specifically localized to the cytoplasm; in contrast to wild-type (wt) Mos that localized to both the nucleus and the cytoplasm. These data indicate that Mos transforming activity is mediated via signalling exerted in the cytoplasm, presumably through MAPK, and that nuclear localization of the oncogene product interferes with transforming activity. We also show that amino acids R45-A54 are important for Mos DNA binding activity. JF - Oncogene AU - Fukasawa, K AU - Zhou, R AU - Matten, W T AU - Armstrong, A J AU - Daar, I AU - Oskarsson, M AU - Sathyanarayana, B K AU - Maclvor, L AU - Wood, T G AU - Vande Woude, G F AD - ABL-Basic Research Program, NCI-Frederick Cancer Research, Maryland 21702, USA. Y1 - 1995/10/19/ PY - 1995 DA - 1995 Oct 19 SP - 1447 EP - 1457 VL - 11 IS - 8 SN - 0950-9232, 0950-9232 KW - DNA Primers KW - 0 KW - DNA-Binding Proteins KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Proto-Oncogene Proteins c-mos KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Mitogen-Activated Protein Kinase 1 KW - EC 2.7.11.24 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Protein-Serine-Threonine Kinases -- metabolism KW - DNA-Binding Proteins -- chemistry KW - Enzyme Activation KW - Fluorescent Antibody Technique, Indirect KW - Protein-Serine-Threonine Kinases -- genetics KW - Amino Acid Sequence KW - Mice KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Xenopus laevis KW - Base Sequence KW - Cytoplasm -- metabolism KW - Molecular Sequence Data KW - Oocytes KW - Signal Transduction KW - Cell Transformation, Neoplastic KW - Sequence Deletion KW - DNA Primers -- chemistry KW - DNA-Binding Proteins -- metabolism KW - Proto-Oncogene Proteins c-mos -- metabolism KW - Proto-Oncogene Proteins c-mos -- genetics KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Protein-Tyrosine Kinases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77587170?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutagenic+analysis+of+functional+domains+of+the+mos+proto-oncogene+and+identification+of+the+sites+important+for+MAPK+activation+and+DNA+binding.&rft.au=Fukasawa%2C+K%3BZhou%2C+R%3BMatten%2C+W+T%3BArmstrong%2C+A+J%3BDaar%2C+I%3BOskarsson%2C+M%3BSathyanarayana%2C+B+K%3BMaclvor%2C+L%3BWood%2C+T+G%3BVande+Woude%2C+G+F&rft.aulast=Fukasawa&rft.aufirst=K&rft.date=1995-10-19&rft.volume=11&rft.issue=8&rft.spage=1447&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-06 N1 - Date created - 1995-12-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - NMR solution structure of a nonanucleotide duplex with a dG mismatch opposite a 10S adduct derived from trans addition of a deoxyadenosine N6-amino group to (+)-(7R,8S,9S,10R)-7,8-dihydroxy-9,10-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene: an unusual syn glycosidic torsion angle at the modified dA. AN - 77576178; 7577946 AB - A nonanucleotide, d(G1G2T3C4[BaP]A5C6G7A8G9), in which (+)-(7R,8S,9S,10R)-7,8-dihydroxy-9,10-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene (7-hydroxyl group and epoxide oxygen are trans) is covalently bonded to the exocyclic N6-amino group of deoxyadenosine (dA5) through trans addition at C10 of the epoxide (to give a 10S adduct) has been synthesized. The solution structure of the duplex, d(G1G2T3C4[BaP]A5C6G7A8G9).d(C10T11C12G13G14G15A16C17C18+ ++), containing a dG mismatch opposite the modified dA (designated 10S-[BaP]dA.dG 9-mer duplex) has been investigated using a combination of 1D and 2D (including COSY, PECOSY, TOCSY, NOESY, and indirect detection of 1H-31P HETCOR) NMR spectroscopies. The NMR results together with restrained molecular dynamics/energy minimization calculations show that the modified dA5 adopts a syn glycosidic torsion angle whereas all other nucleotide residues adopt anti glycosidic torsion angles. The sugar ring of dA5 is in the C3'-endo conformation, and the sugar rings of the other residues are in the C2'-endo conformation. The hydrocarbon attached at dA5 orients toward the 3' end of the modified strand (i.e., dC6 direction) and intercalates between and parallel to bases of dG13 and dG14 of the complementary strand directly opposite dC6 and dA5, respectively. The edge of the hydrocarbon bearing H11 and H12 is positioned between the imino protons of dG13 and dG14 in the interior of the duplex, whereas H4 and H5 at the opposite edge are positioned near the sugar H1' and H2" protons of dG13 and facing the exterior of the duplex. The mismatched AG base pair is stabilized by dAsyn-dGanti base pairing in which the imino proton and the O6 of dG14 are hydrogen bonded to N7- and the single N6-amino proton, respectively, of the modified dA5. The modified DNA duplex remains in a right-handed helix, which bends at the site of intercalation about 20 to 30 degrees away from the helical axis and toward the direction of the modified strand. JF - Biochemistry AU - Yeh, H J AU - Sayer, J M AU - Liu, X AU - Altieri, A S AU - Byrd, R A AU - Lakshman, M K AU - Yagi, H AU - Schurter, E J AU - Gorenstein, D G AU - Jerina, D M AD - NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/10/17/ PY - 1995 DA - 1995 Oct 17 SP - 13570 EP - 13581 VL - 34 IS - 41 SN - 0006-2960, 0006-2960 KW - DNA Adducts KW - 0 KW - Deoxyadenosines KW - Glycosides KW - N(6)-(10-(7,8,9-trihydroxy-7,8,9,10-tetrahydrobenzo(a)pyrenyl))-2'-deoxyadenosine KW - Oligodeoxyribonucleotides KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide KW - 55097-80-8 KW - Deoxyglucose KW - 9G2MP84A8W KW - Index Medicus KW - Molecular Structure KW - Magnetic Resonance Spectroscopy -- methods KW - Base Sequence KW - Base Composition KW - Models, Molecular KW - Molecular Sequence Data KW - Molecular Conformation KW - Structure-Activity Relationship KW - Models, Theoretical KW - Mathematics KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- analogs & derivatives KW - DNA Adducts -- chemistry KW - Oligodeoxyribonucleotides -- chemistry KW - Deoxyadenosines -- chemistry KW - Nucleic Acid Conformation KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77576178?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=NMR+solution+structure+of+a+nonanucleotide+duplex+with+a+dG+mismatch+opposite+a+10S+adduct+derived+from+trans+addition+of+a+deoxyadenosine+N6-amino+group+to+%28%2B%29-%287R%2C8S%2C9S%2C10R%29-7%2C8-dihydroxy-9%2C10-epoxy-7%2C8%2C9%2C10-+tetrahydrobenzo%5Ba%5Dpyrene%3A+an+unusual+syn+glycosidic+torsion+angle+at+the+modified+dA.&rft.au=Yeh%2C+H+J%3BSayer%2C+J+M%3BLiu%2C+X%3BAltieri%2C+A+S%3BByrd%2C+R+A%3BLakshman%2C+M+K%3BYagi%2C+H%3BSchurter%2C+E+J%3BGorenstein%2C+D+G%3BJerina%2C+D+M&rft.aulast=Yeh&rft.aufirst=H&rft.date=1995-10-17&rft.volume=34&rft.issue=41&rft.spage=13570&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-14 N1 - Date created - 1995-12-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An acidic sequence within the cytoplasmic domain of furin functions as a determinant of trans-Golgi network localization and internalization from the cell surface. AN - 77663665; 7588625 AB - The mammalian endopeptidase, furin, is predominantly localized to the trans-Golgi network (TGN) at steady state. The localization of furin to this compartment seems to be the result of a dynamic process in which the protein undergoes cycling between the TGN and the plasma membrane. Both TGN localization and internalization from the plasma membrane are mediated by targeting information contained within the cytoplasmic domain of furin. Here, we report the results of a mutagenesis analysis aimed at identifying the source(s) of targeting information within the furin cytoplasmic domain. Our studies show that there are at least two cytoplasmic determinants that contribute to the steady-state localization and trafficking of furin. The first determinant corresponds to a canonical tyrosine-based motif, YKGL (residues 758-761), that functions mainly as an internalization signal. The second determinant consists of a strongly hydrophilic sequence (residues 766-783) that contains a large cluster of acidic residues (E and D) and is devoid of any tyrosine-based or di-leucine-based motifs. This second determinant is capable of conferring localization to the TGN as well as mediating internalization from the plasma membrane. Thus, these observations establish the existence of a novel, autonomous determinant distinct from sorting signals described previously. JF - The EMBO journal AU - Voorhees, P AU - Deignan, E AU - van Donselaar, E AU - Humphrey, J AU - Marks, M S AU - Peters, P J AU - Bonifacino, J S AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/10/16/ PY - 1995 DA - 1995 Oct 16 SP - 4961 EP - 4975 VL - 14 IS - 20 SN - 0261-4189, 0261-4189 KW - Amino Acids, Dicarboxylic KW - 0 KW - Antigens KW - Receptors, Interleukin-2 KW - Recombinant Fusion Proteins KW - Tyrosine KW - 42HK56048U KW - Subtilisins KW - EC 3.4.21.- KW - Furin KW - EC 3.4.21.75 KW - Index Medicus KW - HeLa Cells KW - Humans KW - Amino Acid Sequence KW - Precipitin Tests KW - Receptors, Interleukin-2 -- genetics KW - Structure-Activity Relationship KW - Recombinant Fusion Proteins -- metabolism KW - Antigens -- genetics KW - Molecular Sequence Data KW - Flow Cytometry KW - Fluorescent Antibody Technique KW - Sequence Deletion KW - Endocytosis KW - Golgi Apparatus -- enzymology KW - Cell Membrane -- enzymology KW - Golgi Apparatus -- ultrastructure KW - Cell Compartmentation KW - Cell Membrane -- ultrastructure KW - Subtilisins -- isolation & purification KW - Subtilisins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77663665?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+EMBO+journal&rft.atitle=An+acidic+sequence+within+the+cytoplasmic+domain+of+furin+functions+as+a+determinant+of+trans-Golgi+network+localization+and+internalization+from+the+cell+surface.&rft.au=Voorhees%2C+P%3BDeignan%2C+E%3Bvan+Donselaar%2C+E%3BHumphrey%2C+J%3BMarks%2C+M+S%3BPeters%2C+P+J%3BBonifacino%2C+J+S&rft.aulast=Voorhees&rft.aufirst=P&rft.date=1995-10-16&rft.volume=14&rft.issue=20&rft.spage=4961&rft.isbn=&rft.btitle=&rft.title=The+EMBO+journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-21 N1 - Date created - 1995-12-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1994 Nov 11;269(45):28263-9 [7961764] J Cell Biol. 1994 Dec;127(6 Pt 2):1829-42 [7806563] J Cell Sci. 1991 Apr;98 ( Pt 4):567-75 [1860903] J Biol Chem. 1991 Sep 5;266(25):16954-9 [1885622] Hybridoma. 1992 Feb;11(1):71-86 [1737642] Nature. 1970 Aug 15;227(5259):680-5 [5432063] Virology. 1973 Apr;52(2):456-67 [4705382] J Biol Chem. 1993 Oct 25;268(30):22853-62 [8226795] Annu Rev Cell Biol. 1993;9:129-61 [8280459] EMBO J. 1994 Jan 1;13(1):18-33 [7508380] J Biol Chem. 1994 Feb 18;269(7):4827-31 [8106453] J Cell Biol. 1994 Apr;125(2):253-68 [8163544] Cell. 1994 May 20;77(4):579-86 [8187177] Eur J Immunol. 1974 Feb;4(2):91-7 [4546942] J Immunol. 1981 Apr;126(4):1393-7 [6970774] Cell. 1983 Nov;35(1):321-30 [6313227] Nature. 1984 May 31-Jun 6;309(5967):418-25 [6328312] Cell. 1984 Jul;37(3):789-800 [6204769] Nature. 1984 Oct 18-24;311(5987):626-31 [6090948] Cell. 1984 Dec;39(2 Pt 1):267-74 [6094009] J Biol Chem. 1984 Dec 10;259(23):14576-9 [6594339] Hybridoma. 1985 Summer;4(2):91-102 [2408992] Proc Natl Acad Sci U S A. 1985 Nov;82(21):7314-8 [2997784] Proc Natl Acad Sci U S A. 1986 Mar;83(5):1463-6 [3081898] Science. 1986 Nov 14;234(4778):859-63 [3095922] J Biol Chem. 1987 Jan 25;262(3):1344-51 [3100530] Proc Natl Acad Sci U S A. 1987 Apr;84(8):2233-7 [2951738] Cell. 1987 Jul 17;50(2):181-92 [2954652] Proc Natl Acad Sci U S A. 1987 Aug;84(16):5575-9 [2441386] Nature. 1987 Sep 24-30;329(6137):301-7 [2957598] Nature. 1987 Oct 29-Nov 4;329(6142):840-2 [3313052] J Biol Chem. 1988 Feb 15;263(5):2553-62 [2963003] Science. 1988 Jan 29;239(4839):487-91 [2448875] FEBS Lett. 1988 Jul 18;234(2):464-70 [3292294] Nucleic Acids Res. 1988 Aug 11;16(15):7351-67 [3045756] Proc Natl Acad Sci U S A. 1988 Oct;85(20):7567-71 [2971973] Biochem Biophys Res Commun. 1988 Oct 14;156(1):246-54 [2845974] Proc Natl Acad Sci U S A. 1989 Mar;86(5):1434-8 [2646633] Proc Natl Acad Sci U S A. 1989 Mar;86(6):2112-6 [2928321] J Biol Chem. 1990 Feb 25;265(6):3116-23 [1968060] Nucleic Acids Res. 1990 Feb 11;18(3):664 [2408021] Biochem Biophys Res Commun. 1990 Jun 15;169(2):551-8 [2357221] Biochem J. 1990 Aug 15;270(1):97-102 [2204342] J Biol Chem. 1990 Nov 5;265(31):18833-42 [2172236] Proc Natl Acad Sci U S A. 1990 Dec;87(23):9378-82 [2251280] Cell. 1990 Nov 30;63(5):1061-72 [2257624] Cell. 1987 Aug 14;50(4):573-84 [3301004] J Biol Chem. 1990 Dec 25;265(36):22075-8 [2266110] J Cell Biol. 1990 Dec;111(6 Pt 2):2851-9 [2269657] J Exp Med. 1991 May 1;173(5):1099-109 [2022921] Cell. 1991 Jul 12;66(1):1-3 [2070411] Cell. 1992 Jun 26;69(7):1143-57 [1535555] J Biol Chem. 1992 Aug 25;267(24):17110-5 [1324923] J Biol Chem. 1992 Aug 25;267(24):17208-15 [1512259] Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8235-9 [1325651] J Cell Biol. 1992 Oct;119(1):69-83 [1527174] J Cell Biol. 1992 Oct;119(2):249-57 [1400571] Eur J Biochem. 1992 Nov 1;209(3):945-50 [1425701] Yeast. 1992 Sep;8(9):769-76 [1441754] J Cell Biol. 1992 Dec;119(6):1459-68 [1469044] Mol Biol Cell. 1992 Dec;3(12):1353-71 [1493334] J Cell Biol. 1993 Mar;120(5):1123-35 [8436587] EMBO J. 1993 May;12(5):2181-93 [8491206] EMBO J. 1993 May;12(5):2219-28 [8491209] J Cell Biol. 1993 Jun;121(6):1197-209 [8509444] Ann N Y Acad Sci. 1993 May 31;680:135-46 [8512214] FEBS Lett. 1993 Jul 26;327(2):165-71 [8335106] J Biol Chem. 1993 Aug 15;268(23):17108-13 [8349600] J Biol Chem. 1993 Oct 15;268(29):21470-3 [8407994] J Biol Chem. 1993 Oct 25;268(30):22338-46 [8226743] J Biol Chem. 1993 Oct 25;268(30):22552-6 [8226766] EMBO J. 1994 May 15;13(10):2305-12 [8194522] J Biol Chem. 1994 Jun 3;269(22):15732-9 [8195226] J Biol Chem. 1994 Jun 17;269(24):16529-32 [8206966] EMBO J. 1994 Jul 1;13(13):2963-9 [8039492] J Cell Biol. 1994 Aug;126(4):991-1004 [8051216] J Cell Biol. 1994 Sep;126(5):1157-72 [7914893] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I study of sequential versus concurrent interleukin-3 and granulocyte-macrophage colony-stimulating factor in advanced breast cancer patients treated with FLAC (5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide) chemotherapy. AN - 77574514; 7579383 AB - Cumulative thrombocytopenia is a dose-limiting toxicity of dose-intensive chemotherapy for advanced breast cancer. In this phase I study, we have studied the hematologic toxicity associated with sequential interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF; molgramostim) administration after multiple cycles of FLAC (5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide) chemotherapy compared with that after concurrent cytokine administration or to each cytokine administered alone. Ninety-three patients with advanced breast cancer were treated with five cycles of FLAC chemotherapy and either IL-3 alone, GM-CSF alone, sequential IL-3 and GM-CSF administered by schedule A (5 days of IL-3 followed by 10 days of GM-CSF) or schedule B (9 days of IL-3 followed by 6 days of GM-CSF), or concurrent administration of IL-3 and GM-CSF for 15 days. Cohorts of patients were treated with one of four dose levels of IL-3 (1,2.5, 5, and 10 micrograms/kg) administered subcutaneously for each schedule of cytokine administration. The GM-CSF dose in all schedules was 5 micrograms/kg/day. Sequential IL-3 and GM-CSF (schedule B) was associated with higher platelet nadirs, shorter durations of platelet counts less than 50,000/microL, and the need for fewer platelet transfusions over five cycles of FLAC chemotherapy compared with concurrent cytokines, sequential IL-3 and GM-CSF schedule A, and GM-CSF alone. Concurrent IL-3 and GM-CSF was associated with unexpected platelet toxicity. The duration of granulocytopenia after FLAC chemotherapy was significantly worse with IL-3 alone compared with each of the GM-CSF-containing cytokine regimens. Although no cycle 1 maximum tolerated dose for IL-3 was defined in this study, 5 micrograms/kg was well tolerated over multiple cycles of therapy and is recommended for future studies. The data from this phase I study suggest that sequential IL-3 and GM-CSF with IL-3 administered for 9 days before beginning GM-CSF may be superior to shorter durations of IL-3 administered sequentially with GM-CSF, to concurrent IL-3 and GM-CSF, and to either colony-stimulating factor alone in ameliorating the cumulative hematologic toxicity associated with multiple cycles of FLAC chemotherapy. Additional studies of sequential IL-3 and GM-CSF are warranted. JF - Blood AU - O'Shaughnessy, J A AU - Venzon, D J AU - Gossard, M AU - Noone, M H AU - Denicoff, A AU - Tolcher, A AU - Danforth, D AU - Jacobson, J AU - Keegan, P AU - Miller, L AU - Chow, C AU - Goldspiel, B AU - Cowan, K H AD - Medicine Branch, National Institutes of Health, Bethesda, MD, USA. Y1 - 1995/10/15/ PY - 1995 DA - 1995 Oct 15 SP - 2913 EP - 2921 VL - 86 IS - 8 SN - 0006-4971, 0006-4971 KW - Immunologic Factors KW - 0 KW - Interleukin-3 KW - Doxorubicin KW - 80168379AG KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Cyclophosphamide KW - 8N3DW7272P KW - Leucovorin KW - Q573I9DVLP KW - Fluorouracil KW - U3P01618RT KW - Abridged Index Medicus KW - Index Medicus KW - Fluorouracil -- administration & dosage KW - Cyclophosphamide -- administration & dosage KW - Fluorouracil -- adverse effects KW - Drug Interactions KW - Drug Administration Schedule KW - Doxorubicin -- adverse effects KW - Leucovorin -- administration & dosage KW - Humans KW - Injections, Subcutaneous KW - Leucovorin -- adverse effects KW - Doxorubicin -- administration & dosage KW - Female KW - Cyclophosphamide -- adverse effects KW - Breast Neoplasms -- drug therapy KW - Thrombocytopenia -- therapy KW - Immunologic Factors -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Interleukin-3 -- administration & dosage KW - Granulocyte-Macrophage Colony-Stimulating Factor -- therapeutic use KW - Interleukin-3 -- adverse effects KW - Granulocyte-Macrophage Colony-Stimulating Factor -- administration & dosage KW - Interleukin-3 -- therapeutic use KW - Breast Neoplasms -- mortality KW - Breast Neoplasms -- pathology KW - Immunologic Factors -- therapeutic use KW - Thrombocytopenia -- chemically induced KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Granulocyte-Macrophage Colony-Stimulating Factor -- adverse effects KW - Immunologic Factors -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77574514?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+phase+I+study+of+sequential+versus+concurrent+interleukin-3+and+granulocyte-macrophage+colony-stimulating+factor+in+advanced+breast+cancer+patients+treated+with+FLAC+%285-fluorouracil%2C+leucovorin%2C+doxorubicin%2C+cyclophosphamide%29+chemotherapy.&rft.au=O%27Shaughnessy%2C+J+A%3BVenzon%2C+D+J%3BGossard%2C+M%3BNoone%2C+M+H%3BDenicoff%2C+A%3BTolcher%2C+A%3BDanforth%2C+D%3BJacobson%2C+J%3BKeegan%2C+P%3BMiller%2C+L%3BChow%2C+C%3BGoldspiel%2C+B%3BCowan%2C+K+H&rft.aulast=O%27Shaughnessy&rft.aufirst=J&rft.date=1995-10-15&rft.volume=86&rft.issue=8&rft.spage=2913&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-29 N1 - Date created - 1995-11-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytotoxic effect of TNF and lymphotoxin on T lymphoblasts. AN - 77536685; 7561073 AB - Recombinant TNF and lymphotoxin trigger the apoptotic death of normal mouse and human T lymphocyte blasts in vitro. This cytotoxic effect does not involve the Fas death pathway and differs from the TNF-triggered death of tumor cells in several respects: 1) It is a slower process, requiring 2 to 3 days; 2) it is blocked, rather than enhanced, by cycloheximide; and 3) based on the agonistic effect of anti-TNF receptor Abs, it involves a synergistic effect of both the 55-kDa TNFR1 and the 75-kDa TNFR2, as opposed to the dominance of TNFR1 for tumor cytotoxicity. The TNF-induced death of blasts is potently inhibited by IL-2, as well as by IL-1, IL-4, IFN-gamma, and IL-12. Because activated T cells secrete both TNF and LT, these findings reveal a new pathway for Ag-induced down-modulation of T cell responses. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Sarin, A AU - Conan-Cibotti, M AU - Henkart, P A AD - Experimental Immunology Branch, NCI, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/10/15/ PY - 1995 DA - 1995 Oct 15 SP - 3716 EP - 3718 VL - 155 IS - 8 SN - 0022-1767, 0022-1767 KW - Antigens, CD95 KW - 0 KW - Antilymphocyte Serum KW - Cytokines KW - Lymphotoxin-alpha KW - Receptors, Tumor Necrosis Factor KW - Tumor Necrosis Factor-alpha KW - Abridged Index Medicus KW - Index Medicus KW - Lymphocyte Activation -- drug effects KW - Animals KW - Cytokines -- pharmacology KW - Receptors, Tumor Necrosis Factor -- immunology KW - Humans KW - Antigens, CD95 -- physiology KW - Antilymphocyte Serum -- pharmacology KW - Mice KW - Tumor Necrosis Factor-alpha -- toxicity KW - Cytotoxicity, Immunologic KW - Lymphotoxin-alpha -- toxicity KW - Apoptosis -- immunology KW - T-Lymphocytes -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77536685?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Cytotoxic+effect+of+TNF+and+lymphotoxin+on+T+lymphoblasts.&rft.au=Sarin%2C+A%3BConan-Cibotti%2C+M%3BHenkart%2C+P+A&rft.aulast=Sarin&rft.aufirst=A&rft.date=1995-10-15&rft.volume=155&rft.issue=8&rft.spage=3716&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 - 1995-11-22 N1 - Date created - 1995-11-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cellular proteins that bind the von Hippel-Lindau disease gene product: mapping of binding domains and the effect of missense mutations. AN - 77535915; 7553625 AB - The von Hippel-Lindau disease (VHL) gene is a novel tumor suppressor gene that plays a role in the pathogenesis of renal cell carcinomas and hemangioblastomas of the central nervous system. To begin an evaluation of the biological functions of the VHL gene product (pVHL), we prepared bacterial fusion protein between glutathione S-transferase and wild-type or mutant pVHLs. The fusion proteins were used to identify cellular proteins that bind to pVHL in vitro. Monkey kidney cells transfected with wild-type or mutant VHL cDNAs were used to identify cellular proteins that bind to pVHL in vivo. Wild-type pVHL consistently bound two cellular proteins with apparent molecular masses of 10 and 14 kilodaltons that were designated p10 and p14, respectively. Mapping studies with a panel of VHL deletion mutant proteins demonstrated that p10 and p14 bound to a 32-amino acid peptide located in the carboxy terminal portion of pVHL. Missense mutation located within this 32-amino acid peptide abrogated the ability of the VHL protein to bind p10 and p14. Of 67 VHL families with identified germline mutations, 42 families had mutations predicted to affect the p10/p14-binding region. Maintenance of the integrity of the p10/p14-binding region appears to be essential for cellular growth regulation by pVHL. JF - Cancer research AU - Kishida, T AU - Stackhouse, T M AU - Chen, F AU - Lerman, M I AU - Zbar, B AD - Laboratory of Immunobiology, National Cancer Institute-Frederick Cancer Research Facility and Development Center, Maryland 21702-1201, USA. Y1 - 1995/10/15/ PY - 1995 DA - 1995 Oct 15 SP - 4544 EP - 4548 VL - 55 IS - 20 SN - 0008-5472, 0008-5472 KW - Neoplasm Proteins KW - 0 KW - Nuclear Proteins KW - Recombinant Fusion Proteins KW - Tumor Suppressor Proteins KW - Ubiquitin-Protein Ligases KW - EC 2.3.2.27 KW - Von Hippel-Lindau Tumor Suppressor Protein KW - Ligases KW - EC 6.- KW - VHL protein, human KW - EC 6.3.2.- KW - Index Medicus KW - Animals KW - Humans KW - Neoplasm Proteins -- chemistry KW - Protein Binding KW - Molecular Weight KW - Structure-Activity Relationship KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Tumor Cells, Cultured KW - Cercopithecus aethiops KW - In Vitro Techniques KW - Point Mutation KW - Neoplasm Proteins -- metabolism KW - Genes, Tumor Suppressor KW - Nuclear Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77535915?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Cellular+proteins+that+bind+the+von+Hippel-Lindau+disease+gene+product%3A+mapping+of+binding+domains+and+the+effect+of+missense+mutations.&rft.au=Kishida%2C+T%3BStackhouse%2C+T+M%3BChen%2C+F%3BLerman%2C+M+I%3BZbar%2C+B&rft.aulast=Kishida&rft.aufirst=T&rft.date=1995-10-15&rft.volume=55&rft.issue=20&rft.spage=4544&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 - 1995-11-08 N1 - Date created - 1995-11-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - (+/-)-(N-alkylamino)benzazepine analogs: novel dopamine D1 receptor antagonists. AN - 77576821; 7473556 AB - (+/-)-(N-Alkylamino)benzazepine analogs were prepared as novel dopamine D1 receptor antagonists to further elucidate the role of these receptor subtypes in the pharmacology and toxicology of cocaine. In the first series of compounds, (+/-)-7-chloro-8-hydroxy-3- [6-(N,N-dimethylamino)-hexyl]-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepi ne (15) showed the highest affinity (Ki = 49.3 nM) and subtype-selectivity for dopamine D1 over dopamine D2, 5-HT2a, and 5-HT2c receptors. Compounds 7a [(+/-)-7-Chloro-8-hydroxy-3-[4-(N,N-dimethylamino)butyl]-1-phenyl- 2,3,4,5-tetrahydro-1H-3-benzazepine], 11 [(+/-)-7-chloro-8-hydroxy-3-[6-[(N,N-dimethylamino)hexyl]-1- phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-cyanoborane], and 15 were moderately potent dopamine D1 receptor antagonists as evidenced by their ability to block dopamine-stimulated adenylyl cyclase activity in rat caudate (predicted Ki values = 60, 34, and 21 nM, respectively). Compound 7a appears to be unique in that, despite its relatively potent inhibition of dopamine stimulated adenylyl cyclase, it demonstrated relatively weak binding affinity at the dopamine D1 receptors (Ki = 811 nM). Unlike previously reported N-alkylbenzazepines, where a significant loss in dopamine D1 receptor binding affinity was observed when successive increases in the alkyl side chain size at the benzazepine nitrogen were made, several of these novel N-alkylamino analogs demonstrated high-affinity binding with an optimal chain length of six carbons. This initial series of compounds appears to be identifying another binding domain on the dopamine D1 receptor protein that has not previously been characterized and that accepts an amino function. Further, these compounds may serve as templates for the design of peripherally active dopamine D1 receptor antagonists. JF - Journal of medicinal chemistry AU - Shah, J H AU - Izenwasser, S AU - Geter-Douglass, B AU - Witkin, J M AU - Newman, A H AD - Psychobiology Section, National Institutes of Health, National Institute on Drug Abuse-Division of Intramural Research, Baltimore, Maryland 21224, USA. Y1 - 1995/10/13/ PY - 1995 DA - 1995 Oct 13 SP - 4284 EP - 4293 VL - 38 IS - 21 SN - 0022-2623, 0022-2623 KW - 7-chloro-8-hydroxy-3-(4-(N,N-dimethylamino)butyl)-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine KW - 0 KW - 7-chloro-8-hydroxy-3-(6-(N,N-dimethylamino)hexyl)-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-cyanoborane KW - 7-chloro-8-hydroxy-3-(6-(dimethylamino)hexyl)-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine KW - Benzazepines KW - Borohydrides KW - Boron Compounds KW - Dopamine Antagonists KW - Indicators and Reagents KW - Receptors, Dopamine D1 KW - Receptors, Serotonin KW - sodium cyanoborohydride KW - C4I8C58P9T KW - Index Medicus KW - Molecular Structure KW - Animals KW - Caudate Nucleus -- metabolism KW - Mice KW - Receptors, Serotonin -- metabolism KW - Structure-Activity Relationship KW - Magnetic Resonance Spectroscopy KW - Spectrophotometry, Infrared KW - Rats KW - Rats, Sprague-Dawley KW - Putamen -- metabolism KW - Motor Activity -- drug effects KW - Cell Membrane -- metabolism KW - Methylation KW - Male KW - Boron Compounds -- metabolism KW - Dopamine Antagonists -- metabolism KW - Dopamine Antagonists -- chemical synthesis KW - Boron Compounds -- pharmacology KW - Benzazepines -- pharmacology KW - Receptors, Dopamine D1 -- antagonists & inhibitors KW - Dopamine Antagonists -- pharmacology KW - Benzazepines -- metabolism KW - Boron Compounds -- chemical synthesis KW - Benzazepines -- chemical synthesis KW - Benzazepines -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77576821?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+medicinal+chemistry&rft.atitle=%28%2B%2F-%29-%28N-alkylamino%29benzazepine+analogs%3A+novel+dopamine+D1+receptor+antagonists.&rft.au=Shah%2C+J+H%3BIzenwasser%2C+S%3BGeter-Douglass%2C+B%3BWitkin%2C+J+M%3BNewman%2C+A+H&rft.aulast=Shah&rft.aufirst=J&rft.date=1995-10-13&rft.volume=38&rft.issue=21&rft.spage=4284&rft.isbn=&rft.btitle=&rft.title=Journal+of+medicinal+chemistry&rft.issn=00222623&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-28 N1 - Date created - 1995-11-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Receptor-mediated internalization of insulin. Potential role of pp120/HA4, a substrate of the insulin receptor kinase. AN - 77568262; 7592607 AB - pp120/HA4 is a hepatocyte membrane glycoprotein phosphorylated by the insulin receptor tyrosine kinase. In this study, we have investigated the role of pp120/HA4 in insulin action. Transfection of antisense pp120/HA4 cDNA in H35 hepatoma cells resulted in inhibition of pp120/HA4 expression and was associated with a 2-3-fold decrease in the rate of insulin internalization. Furthermore, insulin internalization in NIH 3T3 fibroblasts co-transfected with insulin receptors and pp120/HA4 was increased 2-fold compared with cells expressing insulin receptors alone. In contrast, no effect on internalization was observed in cells overexpressing a naturally occurring splice variant of pp120/HA4 that lacks the phosphorylation sites in the intracellular domain. Insulin internalization was also unaffected in cells expressing three site-directed mutants of pp120/HA4 in which the sites of phosphorylation by the insulin receptor kinase had been removed (Y488F, Y488F/Y513F, and S503A). Our data suggest that pp120/HA4 is part of a complex of proteins required for receptor-mediated internalization of insulin. It is possible that this function is regulated by insulin-induced phosphorylation of the intracellular domain of pp120/HA4. JF - The Journal of biological chemistry AU - Formisano, P AU - Najjar, S M AU - Gross, C N AU - Philippe, N AU - Oriente, F AU - Kern-Buell, C L AU - Accili, D AU - Gorden, P AD - Diabetes Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/10/13/ PY - 1995 DA - 1995 Oct 13 SP - 24073 EP - 24077 VL - 270 IS - 41 SN - 0021-9258, 0021-9258 KW - Antibodies KW - 0 KW - Carrier Proteins KW - Insulin KW - Membrane Glycoproteins KW - Peptide Fragments KW - Platelet-Derived Growth Factor KW - RNA, Antisense KW - Recombinant Proteins KW - bile acid binding proteins KW - Hydroxysteroid Dehydrogenases KW - EC 1.1.- KW - AKR1C2 protein, human KW - EC 1.1.1.- KW - Receptor, Insulin KW - EC 2.7.10.1 KW - Receptors, Platelet-Derived Growth Factor KW - Thymidine KW - VC2W18DGKR KW - Index Medicus KW - Receptors, Platelet-Derived Growth Factor -- metabolism KW - Platelet-Derived Growth Factor -- metabolism KW - 3T3 Cells KW - Animals KW - Liver -- metabolism KW - Amino Acid Sequence KW - Mice KW - Thymidine -- metabolism KW - Rats KW - Mutagenesis, Site-Directed KW - Peptide Fragments -- chemistry KW - Phosphorylation KW - Transfection KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Molecular Sequence Data KW - Cell Cycle KW - Cell Division KW - Carrier Proteins -- metabolism KW - Insulin -- metabolism KW - Carrier Proteins -- biosynthesis KW - Receptor, Insulin -- metabolism KW - Membrane Glycoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77568262?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Receptor-mediated+internalization+of+insulin.+Potential+role+of+pp120%2FHA4%2C+a+substrate+of+the+insulin+receptor+kinase.&rft.au=Formisano%2C+P%3BNajjar%2C+S+M%3BGross%2C+C+N%3BPhilippe%2C+N%3BOriente%2C+F%3BKern-Buell%2C+C+L%3BAccili%2C+D%3BGorden%2C+P&rft.aulast=Formisano&rft.aufirst=P&rft.date=1995-10-13&rft.volume=270&rft.issue=41&rft.spage=24073&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 - 1995-12-04 N1 - Date created - 1995-12-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Maitotoxin-elicited calcium influx in cultured cells. Effect of calcium-channel blockers. AN - 77657145; 7488233 AB - Maitotoxin elicited a marked influx of 45Ca2+ into NIH 3T3 fibroblast cells. The influx was blocked by imidazoles (econazole, miconazole, SKF 96365, clotrimazole, calmidazolium) with IC50 values from 0.56 to 3 microM. Phenylalkylamines (verapamil, methoxyverapamil) and nitrendipine were less potent, and diltiazem was very weak. Among other calcium blockers, the diphenylbutylpiperidines fluspirilene and penfluridol, the diphenylpropylpiperidine loperamide, and the local anesthetic proadifen were quite active with IC50 values of 2-4 microM. The pattern of inhibition of maitotoxin-elicited calcium influx did not correspond to the ability of the agents to block elevation of calcium that ensues through calcium-release activated calcium (CRAC) channels after activation of phosphoinositide breakdown by ATP in HL-60 cells. The imidazoles did block CRAC channels, but fluspirilene, penfluridol, loperamide and proadifen were ineffective. Loperamide actually appeared to enhance influx of calcium via the activated CRAC channels. The imidazoles, in particular calmidazolium, caused an apparent influx of calcium and caused a stimulation of phosphoinositide breakdown in HL-60 cells. JF - Biochemical pharmacology AU - Daly, J W AU - Lueders, J AU - Padgett, W L AU - Shin, Y AU - Gusovsky, F AD - National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/10/12/ PY - 1995 DA - 1995 Oct 12 SP - 1187 EP - 1197 VL - 50 IS - 8 SN - 0006-2952, 0006-2952 KW - Calcium Channel Blockers KW - 0 KW - Calcium Channels KW - Calcium Radioisotopes KW - Imidazoles KW - Marine Toxins KW - Oxocins KW - Phosphatidylinositols KW - maitotoxin KW - 9P59GES78D KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Phosphatidylinositols -- metabolism KW - Animals KW - Imidazoles -- pharmacology KW - HL-60 Cells -- drug effects KW - 3T3 Cells -- drug effects KW - Humans KW - Mice KW - Calcium Channels -- biosynthesis KW - Marine Toxins -- pharmacology KW - Calcium -- metabolism KW - Calcium Channel Blockers -- pharmacology KW - Marine Toxins -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77657145?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=Maitotoxin-elicited+calcium+influx+in+cultured+cells.+Effect+of+calcium-channel+blockers.&rft.au=Daly%2C+J+W%3BLueders%2C+J%3BPadgett%2C+W+L%3BShin%2C+Y%3BGusovsky%2C+F&rft.aulast=Daly&rft.aufirst=J&rft.date=1995-10-12&rft.volume=50&rft.issue=8&rft.spage=1187&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-14 N1 - Date created - 1995-12-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytostatic activity of phenylacetate and derivatives against tumor cells. Correlation with lipophilicity and inhibition of protein prenylation. AN - 77647786; 7488244 AB - The aromatic fatty acid phenylacetate, a common metabolite of phenylalanine, shows promise as a relatively non-toxic drug for cancer treatment. This slowly metabolized fatty acid alters tumor cell lipid metabolism causing, among other effects, inhibition of protein prenylation critical to malignant growth. In pursuit of more potent analogues, we have examined the activity of related compounds against tumor cell lines established from patients with advanced prostatic carcinoma, glioblastomas, and malignant melanoma. Like phenylacetate, derivatives containing alpha-carbon or ring substitutions induced cytostasis and phenotypic reversion at non-toxic concentrations. Potency was correlated with the degree of calculated lipophilicity of the aromatic fatty acid, and the extent of inhibition of protein prenylation. Remarkably, a parallel cytostatic activity was reported in embryonic plant cells, which respond to phenylacetate and its analogues in the same concentration range and the same rank order of lipophilicity. These data suggest that phenylacetate and its analogues may act through common mechanisms to inhibit the growth of vastly divergent, undifferentiated cell types, and provide a basis for the development of new agents for the treatment of human malignancies. JF - Biochemical pharmacology AU - Hudgins, W R AU - Shack, S AU - Myers, C E AU - Samid, D AD - Clinical Pharmacology Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/10/12/ PY - 1995 DA - 1995 Oct 12 SP - 1273 EP - 1279 VL - 50 IS - 8 SN - 0006-2952, 0006-2952 KW - Antimetabolites, Antineoplastic KW - 0 KW - Phenylacetates KW - phenylacetic acid KW - ER5I1W795A KW - Index Medicus KW - Phenotype KW - Cell Survival -- drug effects KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Cell Line -- drug effects KW - Cell Division -- drug effects KW - Drug Design KW - Lipid Metabolism KW - Structure-Activity Relationship KW - Protein Prenylation -- drug effects KW - Phenylacetates -- pharmacology KW - Phenylacetates -- chemistry KW - Antimetabolites, Antineoplastic -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77647786?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=Cytostatic+activity+of+phenylacetate+and+derivatives+against+tumor+cells.+Correlation+with+lipophilicity+and+inhibition+of+protein+prenylation.&rft.au=Hudgins%2C+W+R%3BShack%2C+S%3BMyers%2C+C+E%3BSamid%2C+D&rft.aulast=Hudgins&rft.aufirst=W&rft.date=1995-10-12&rft.volume=50&rft.issue=8&rft.spage=1273&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-14 N1 - Date created - 1995-12-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isolation of the mouse homologue of BRCA1 and genetic mapping to mouse chromosome 11. AN - 77748717; 8575748 AB - The BRCA1 gene is in large part responsible for hereditary human breast and ovarian cancer. Here we report the isolation of the murine Brca1 homologue cDNA clones. In addition, we identified genomic P1 clones that contain most, if not all, of the mouse Brca1 locus. DNA sequence analysis revealed that the mouse and human coding regions are 75% identical at the nucleotide level while the predicted amino acid identity is only 58%. A DNA sequence variant in the Brca1 locus was identified and used to map this gene on a (Mus m. musculus Czech II x C57BL/KsJ)F1 x C57BL/KsJ intersubspecific backcross to distal mouse chromosome 11. The mapping of this gene to a region highly syntenic with human chromosome 17, coupled with Southern and Northern analyses, confirms that we isolated the murine Brca1 homologue rather than a related RING finger gene. The isolation of the mouse Brca1 homologue will facilitate the creation of mouse models for germline BRCA1 defects. JF - Genomics AU - Bennett, L M AU - Haugen-Strano, A AU - Cochran, C AU - Brownlee, H A AU - Fiedorek, F T AU - Wiseman, R W AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/10/10/ PY - 1995 DA - 1995 Oct 10 SP - 576 EP - 581 VL - 29 IS - 3 SN - 0888-7543, 0888-7543 KW - BRCA1 Protein KW - 0 KW - Brca1 protein, mouse KW - DNA Primers KW - Neoplasm Proteins KW - RNA, Messenger KW - Transcription Factors KW - Tumor Suppressor Proteins KW - Index Medicus KW - Breast Neoplasms -- genetics KW - Animals KW - Blotting, Northern KW - Ovarian Neoplasms -- genetics KW - Humans KW - RNA, Messenger -- analysis KW - Amino Acid Sequence KW - RNA, Messenger -- biosynthesis KW - Polymerase Chain Reaction KW - Mice, Inbred Strains KW - Base Sequence KW - Blotting, Southern KW - Molecular Sequence Data KW - Mice, Inbred C57BL KW - Crosses, Genetic KW - Sequence Homology, Amino Acid KW - Female KW - Male KW - Tumor Suppressor Proteins -- biosynthesis KW - Neoplasm Proteins -- biosynthesis KW - Chromosomes, Human, Pair 17 KW - Neoplasm Proteins -- genetics KW - Mice -- genetics KW - Tumor Suppressor Proteins -- genetics KW - Transcription Factors -- genetics KW - Transcription Factors -- biosynthesis KW - Chromosome Mapping UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77748717?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genomics&rft.atitle=Isolation+of+the+mouse+homologue+of+BRCA1+and+genetic+mapping+to+mouse+chromosome+11.&rft.au=Bennett%2C+L+M%3BHaugen-Strano%2C+A%3BCochran%2C+C%3BBrownlee%2C+H+A%3BFiedorek%2C+F+T%3BWiseman%2C+R+W&rft.aulast=Bennett&rft.aufirst=L&rft.date=1995-10-10&rft.volume=29&rft.issue=3&rft.spage=576&rft.isbn=&rft.btitle=&rft.title=Genomics&rft.issn=08887543&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-14 N1 - Date created - 1996-03-14 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U32446; GENBANK; U14680 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Endogenous D-factor activity partially mediates the toxic but not the therapeutic effects of tumor necrosis factor. AN - 77612110; 7591212 AB - We have earlier shown that passive immunization against differentiation-inducing factor/leukemia-inhibitory factor (D factor) activity improves the survival of endotoxemic mice, suggesting that D factor may contribute to the systemic toxicity associated with tumor necrosis factor (TNF). In the current experiments, TNF induced D-factor gene expression in various tissues of non-tumor-bearing female C57BI/6 mice. Passive immunization against D-factor significantly improved survival after a lethal TNF challenge in both non-tumor-bearing (p2 < 0.02) and tumor-bearing mice (p2 < 0.01). In mice bearing 10-day s.c. MCA 105 sarcomas, D-factor antibody alone had no effect on tumor growth as compared with control IgG. Tumor regression and regrowth in mice treated i.v. with TNF was not affected by pre-treatment with D-factor antibody, as compared with pre-treatment with IgG. However, TNF-treatment-related mortality was abrogated by pre-treatment with D-factor antibody (0% vs. 36% for IgG-pre-treated controls). These results indicate that endogenous D-factor activity contributes to the toxicity but not to the anti-tumor effects of TNF therapy. With renewed interest in the use of TNF for the treatment of patients with cancer, improved understanding of the role of D factor in mediating the effects of TNF may have important clinical benefits. JF - International journal of cancer AU - Block, M I AU - Fraker, D L AU - Strassmann, G AU - Billingsley, K G AU - Arnold, W S AU - Perlis, C AU - Alexander, H R AD - Surgical Metabolism Section, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 1995/10/09/ PY - 1995 DA - 1995 Oct 09 SP - 245 EP - 249 VL - 63 IS - 2 SN - 0020-7136, 0020-7136 KW - DNA Primers KW - 0 KW - Growth Inhibitors KW - Interleukin-6 KW - Leukemia Inhibitory Factor KW - Lif protein, mouse KW - Lymphokines KW - RNA, Messenger KW - Tumor Necrosis Factor-alpha KW - Index Medicus KW - Gene Expression -- drug effects KW - Animals KW - Base Sequence KW - Immunization, Passive KW - Molecular Sequence Data KW - Mice, Inbred C57BL KW - Mice KW - RNA, Messenger -- genetics KW - Female KW - DNA Primers -- chemistry KW - Tumor Necrosis Factor-alpha -- toxicity KW - Lymphokines -- toxicity KW - Lymphokines -- physiology KW - Growth Inhibitors -- physiology KW - Growth Inhibitors -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77612110?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Endogenous+D-factor+activity+partially+mediates+the+toxic+but+not+the+therapeutic+effects+of+tumor+necrosis+factor.&rft.au=Block%2C+M+I%3BFraker%2C+D+L%3BStrassmann%2C+G%3BBillingsley%2C+K+G%3BArnold%2C+W+S%3BPerlis%2C+C%3BAlexander%2C+H+R&rft.aulast=Block&rft.aufirst=M&rft.date=1995-10-09&rft.volume=63&rft.issue=2&rft.spage=245&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 - 1995-12-04 N1 - Date created - 1995-12-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A recombinant vaccinia virus expressing human prostate-specific antigen (PSA): safety and immunogenicity in a non-human primate. AN - 77610848; 7591210 AB - Prostate-specific antigen (PSA) is a serine protease secreted by prostatic epithelial cells and is widely used as a marker for prostate cancer. The tissue specificity of PSA makes it a potential target for active specific immunotherapy, especially in prostate cancer patients who have undergone prostatectomy and in whom the only PSA-expressing tissue in the body resides in metastatic deposits. We report here the cloning, construction and immunological consequences of immunization of rhesus monkeys with a recombinant vaccinia virus expressing human PSA (designated rV-PSA). The prostate gland of the rhesus is structurally and functionally similar to the human prostate. While rodent and other mammalian species do not share homology with human PSA, there is 94% homology between the amino acid sequences of rhesus and human PSA. Immunization of rhesus monkeys with wild-type vaccinia virus or rV-PSA elicited the usual low-grade constitutional symptoms of vaccinia virus infection. There was no evidence of any adverse effects in any immunized monkeys. A short-lived PSA-specific IgM antibody response was noted in all rV-PSA immunized monkeys regardless of dose level. All monkeys receiving the 10(8)pfu dose of rV-PSA demonstrated PSA-specific T-cell responses that were maintained up to 270 days. No differences in anti-PSA immune responses or toxicity were observed in animals that received prostatectomy prior to immunization. Our results thus demonstrate the safety and immunogenicity of rV-PSA in a non-human primate and have implications for potential specific immunotherapy protocols using PSA as a target. JF - International journal of cancer AU - Hodge, J W AU - Schlom, J AU - Donohue, S J AU - Tomaszewski, J E AU - Wheeler, C W AU - Levine, B S AU - Gritz, L AU - Panicali, D AU - Kantor, J A AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/10/09/ PY - 1995 DA - 1995 Oct 09 SP - 231 EP - 237 VL - 63 IS - 2 SN - 0020-7136, 0020-7136 KW - Antibodies, Neoplasm KW - 0 KW - DNA Primers KW - DNA, Complementary KW - Immunoglobulin M KW - Recombinant Proteins KW - Vaccines, Synthetic KW - Prostate-Specific Antigen KW - EC 3.4.21.77 KW - Index Medicus KW - Animals KW - DNA, Complementary -- genetics KW - Humans KW - Immunoglobulin M -- immunology KW - Antibodies, Neoplasm -- immunology KW - Cloning, Molecular KW - Lymphocyte Activation KW - Base Sequence KW - Vaccinia virus KW - Vaccines, Synthetic -- immunology KW - Molecular Sequence Data KW - Macaca mulatta KW - DNA Primers -- chemistry KW - Prostate-Specific Antigen -- immunology KW - Prostate-Specific Antigen -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77610848?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+recombinant+vaccinia+virus+expressing+human+prostate-specific+antigen+%28PSA%29%3A+safety+and+immunogenicity+in+a+non-human+primate.&rft.au=Hodge%2C+J+W%3BSchlom%2C+J%3BDonohue%2C+S+J%3BTomaszewski%2C+J+E%3BWheeler%2C+C+W%3BLevine%2C+B+S%3BGritz%2C+L%3BPanicali%2C+D%3BKantor%2C+J+A&rft.aulast=Hodge&rft.aufirst=J&rft.date=1995-10-09&rft.volume=63&rft.issue=2&rft.spage=231&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 - 1995-12-04 N1 - Date created - 1995-12-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - International renal-cell cancer study. VIII. Role of diuretics, other anti-hypertensive medications and hypertension. AN - 77610059; 7591207 AB - Risk of renal-cell cancer in relation to use of diuretics, other anti-hypertensive medications and hypertension was assessed in a multi-center, population-based, case-control study conducted in Australia, Denmark, Germany, Sweden and the United States, using a shared protocol and questionnaire. A total of 1,732 histologically confirmed cases and 2,309 controls, frequency-matched to cases by age and sex, were interviewed. The association between renal-cell cancer and the drugs was estimated by relative risks (RRs) and 95% confidence intervals (CIs). Risks were increased among users of diuretics and other anti-hypertensive medications. After adjustment for hypertension, risk for diuretics was reduced to unity, except among long-term (15+ years) users. Risk for use of non-diuretic anti-hypertensive drugs remained significantly elevated and increased further with duration of use. Overall risk was not enhanced when both classes of medications were used. Excess risk was not restricted to any specific type of diuretic or anti-hypertensive drug and no trend was observed with estimated lifetime consumption of any particular type of product. The RR for hypertension after adjustment for diuretics and other anti-hypertensive medications was 1.4 (95% CI = 1.2-1.7), although among non-users of any anti-hypertensive medications, there was little excess risk associated with a history of hypertension. Exclusion of drug use that first occurred within 5 years of cancer diagnosis or interview did not alter the associations. Our findings suggest small effects on renal-cell cancer risk associated with hypertension and use of diuretics and other anti-hypertensive medications. However, because of potential misclassifications of these highly correlated variables, it is difficult to distinguish the effect of treatment from its indication, hypertension. JF - International journal of cancer AU - McLaughlin, J K AU - Chow, W H AU - Mandel, J S AU - Mellemgaard, A AU - McCredie, M AU - Lindblad, P AU - Schlehofer, B AU - Pommer, W AU - Niwa, S AU - Adami, H O AD - National Cancer Institute, Bethesda, MD 20850, USA. Y1 - 1995/10/09/ PY - 1995 DA - 1995 Oct 09 SP - 216 EP - 221 VL - 63 IS - 2 SN - 0020-7136, 0020-7136 KW - Antihypertensive Agents KW - 0 KW - Diuretics KW - Index Medicus KW - Risk KW - Odds Ratio KW - Humans KW - Case-Control Studies KW - Hypertension -- complications KW - Diuretics -- adverse effects KW - Carcinoma, Renal Cell -- etiology KW - Diuretics -- classification KW - Antihypertensive Agents -- adverse effects KW - Kidney Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77610059?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=International+renal-cell+cancer+study.+VIII.+Role+of+diuretics%2C+other+anti-hypertensive+medications+and+hypertension.&rft.au=McLaughlin%2C+J+K%3BChow%2C+W+H%3BMandel%2C+J+S%3BMellemgaard%2C+A%3BMcCredie%2C+M%3BLindblad%2C+P%3BSchlehofer%2C+B%3BPommer%2C+W%3BNiwa%2C+S%3BAdami%2C+H+O&rft.aulast=McLaughlin&rft.aufirst=J&rft.date=1995-10-09&rft.volume=63&rft.issue=2&rft.spage=216&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 - 1995-12-04 N1 - Date created - 1995-12-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of residues that stabilize the single-chain Fv of monoclonal antibodies B3. AN - 77539985; 7559495 AB - B3(Fv)-PE38 is a recombinant single-chain immunotoxin in which the Fv portion of the B3 antibody in a single-chain form, which serves as the targeting moiety, is fused to PE38, a truncated form of Pseudomonas exotoxin A, which serves as the cytotoxic moiety. B3(Fv)-PE38 is specifically cytotoxic to many human cancer cell lines and is currently evaluated in a clinical trial. Monoclonal antibodies B3 (IgG1k) and B5 (IgMk) recognize related carbohydrate epitopes on human carcinoma cells. The Fv regions of these antibodies were previously cloned and expressed as the single-chain Fv-immunotoxins B3(Fv)-PE38 and B5(Fv)-PE38, respectively. The B3(Fv)-PE38 immunotoxin binds to antigen-positive cancer cells with a higher affinity than B5(Fv)-PE38 and is a more potent cytotoxic agent than B5(Fv)-PE38. However, it is less stable and rapidly aggregates upon incubation at 37 degrees C. The VL domains of the two Fvs are very similar, differing by only three residues, the fourth and seventh Fr1 residues and the fifth CDR1 residue. The VH domains of the two Fvs vary considerably. To investigate whether any of the different VL residues may influence the stability of the B3(Fv), we constructed a chimeric immunotoxin containing the B3VH and the B5VL. This chimera had an improved stability and a higher apparent antigen binding affinity and cytotoxic activity when compared with B3(Fv)-PE38. Site-specific mutagenesis was used to show that the VL M4L mutation has an important role in stabilizing B3(Fv), although residues VL Ser-7 and VL Ile-28 also play a role in the increased stability. When tested in an in vivo model system, the chimera containing the B3VH and the B5VL had an improved antitumor activity in a human xenograft mouse model. These studies indicate that the common use of degenerate ("family-specific") primers to clone Fv fragments may introduce destabilizing mutations. JF - The Journal of biological chemistry AU - Benhar, I AU - Pastan, I AD - Laboratory of Molecular Biology, NCI, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1995/10/06/ PY - 1995 DA - 1995 Oct 06 SP - 23373 EP - 23380 VL - 270 IS - 40 SN - 0021-9258, 0021-9258 KW - Antibodies, Monoclonal KW - 0 KW - Bacterial Toxins KW - DNA Primers KW - Exotoxins KW - Immunoglobulin Variable Region KW - Immunotoxins KW - Recombinant Fusion Proteins KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Drug Stability KW - Animals KW - Humans KW - Mice, Nude KW - Pseudomonas KW - Mice, Inbred BALB C KW - Recombinant Fusion Proteins -- chemistry KW - Immunotoxins -- chemistry KW - Recombinant Fusion Proteins -- genetics KW - Molecular Sequence Data KW - Immunotoxins -- genetics KW - Molecular Structure KW - Exotoxins -- genetics KW - Exotoxins -- pharmacology KW - DNA Primers -- genetics KW - Models, Molecular KW - Neoplasms, Experimental -- therapy KW - Exotoxins -- chemistry KW - Amino Acid Sequence KW - Mice KW - Cloning, Molecular KW - Cytotoxicity, Immunologic KW - Base Sequence KW - Recombinant Fusion Proteins -- pharmacology KW - Immunotoxins -- pharmacology KW - Female KW - Immunoglobulin Variable Region -- pharmacology KW - Immunoglobulin Variable Region -- genetics KW - Antibodies, Monoclonal -- genetics KW - Immunoglobulin Variable Region -- chemistry KW - Antibodies, Monoclonal -- pharmacology KW - Antibodies, Monoclonal -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77539985?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Identification+of+residues+that+stabilize+the+single-chain+Fv+of+monoclonal+antibodies+B3.&rft.au=Benhar%2C+I%3BPastan%2C+I&rft.aulast=Benhar&rft.aufirst=I&rft.date=1995-10-06&rft.volume=270&rft.issue=40&rft.spage=23373&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 - 1995-11-14 N1 - Date created - 1995-11-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enzymatic characterization of human immunodeficiency virus type 1 reverse transcriptase resistant to multiple 2',3'-dideoxynucleoside 5'-triphosphates. AN - 77535173; 7559526 AB - A set of five mutations (A62V, V75I, F77L, F116Y, and Q151M) in the polymerase domain of reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1), which confers on the virus a reduced sensitivity to multiple therapeutic dideoxynucleosides (ddNs), has been identified. In this study, we defined the biochemical properties of RT with such mutations by using site-directed mutagenesis, overproduction of recombinant RTs, and steady-state kinetic analyses. A single mutation, Q151M, which developed first among the five mutations in patients receiving therapy, most profoundly reduced the sensitivity of RT to multiple ddN 5'-triphosphate (ddNTPs). Addition of other mutations to Q151M further reduced the sensitivity of RT to ddNTPs. RT with the five mutations proved to be resistant by 65-fold to 3'-azido-2',3'-dideoxythymidine 5'-triphosphate (AZTTP), 12-fold to ddCTP, 8.8-fold to ddATP, and 3.3-fold to 2',3'-dideoxyguanosine 5'-triphosphate (ddGTP), compared with wild-type RT (RTwt). Steady-state kinetic studies revealed comparable catalytic efficiency (kcat/Km) of RTs carrying combined mutations as compared with that of RTwt (< 3-fold), although a marked difference was noted in inhibition constants (Ki) (e.g. Ki of a mutant RT carrying the five mutations was 62-fold higher for AZTTP than that of RTwt). Thus, we conclude that the alteration of RT's substrate recognition, caused by these mutations, accounts for the observed multi-ddN resistance of HIV-1. The features of multi-ddNTP-resistant RTs should provide insights into the molecular mechanism of RT discriminating ddNTPs from natural substrates. JF - The Journal of biological chemistry AU - Ueno, T AU - Shirasaka, T AU - Mitsuya, H AD - Experimental Retrovirology Section, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/10/06/ PY - 1995 DA - 1995 Oct 06 SP - 23605 EP - 23611 VL - 270 IS - 40 SN - 0021-9258, 0021-9258 KW - Antiviral Agents KW - 0 KW - DNA Primers KW - DNA, Viral KW - Deoxyadenine Nucleotides KW - Deoxyguanine Nucleotides KW - Deoxyribonucleotides KW - Dideoxynucleotides KW - Reverse Transcriptase Inhibitors KW - Thymine Nucleotides KW - 2',3'-dideoxyadenosine triphosphate KW - 24027-80-3 KW - Zidovudine KW - 4B9XT59T7S KW - 2',3'-dideoxyguanosine 5'-triphosphate KW - 68726-28-3 KW - 3'-azido-3'-deoxythymidine 5'-triphosphate KW - 6RGF96R053 KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - RNA-Directed DNA Polymerase KW - 2',3'-dideoxythymidine triphosphate KW - IA883WYU21 KW - Index Medicus KW - AIDS/HIV KW - Zidovudine -- analogs & derivatives KW - HIV Infections -- virology KW - DNA Primers -- genetics KW - Humans KW - Zidovudine -- pharmacology KW - Deoxyguanine Nucleotides -- pharmacology KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Kinetics KW - Antiviral Agents -- pharmacology KW - Thymine Nucleotides -- pharmacology KW - In Vitro Techniques KW - HIV Infections -- drug therapy KW - Point Mutation KW - Molecular Sequence Data KW - Binding Sites -- genetics KW - DNA, Viral -- genetics KW - Deoxyadenine Nucleotides -- pharmacology KW - Drug Resistance, Multiple -- genetics KW - HIV-1 -- genetics KW - Reverse Transcriptase Inhibitors -- pharmacology KW - HIV-1 -- enzymology KW - RNA-Directed DNA Polymerase -- metabolism KW - HIV-1 -- drug effects KW - Deoxyribonucleotides -- pharmacology KW - RNA-Directed DNA Polymerase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77535173?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Enzymatic+characterization+of+human+immunodeficiency+virus+type+1+reverse+transcriptase+resistant+to+multiple+2%27%2C3%27-dideoxynucleoside+5%27-triphosphates.&rft.au=Ueno%2C+T%3BShirasaka%2C+T%3BMitsuya%2C+H&rft.aulast=Ueno&rft.aufirst=T&rft.date=1995-10-06&rft.volume=270&rft.issue=40&rft.spage=23605&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 - 1995-11-14 N1 - Date created - 1995-11-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A gene for autosomal dominant nonsyndromic hereditary hearing impairment maps to 4p16.3. AN - 85281546; pmid-8595423 AB - Mapping genes for nonsyndromic hereditary hearing impairment may lead to identification of genes that are essential for the development and preservation of hearing. We studied a family with autosomal dominant, progressive, low frequency sensorineural hearing loss. Linkage analysis employing microsatellite polymorphic markers revealed a fully linked marker (D4S126) at 4p16.3, a gene-rich region containing IT15, the gene for Huntington's disease (HD). For D4S126, the logarithm-of-odds (lod) score was 3.64 at theta = 0, and the overall maximum lod score was 5.05 at theta = 0.05 for D4S412. Analysis of recombinant individuals maps the disease gene to a 1.7 million base pair (Mb) region between D4S412 and D4S432. Genes for two types of mutant mice with abnormal cochleovestibular function, tilted (tlt) and Bronx waltzer (bv), have been mapped to the syntenic region of human 4p16.3 on mouse chromosome 5. Further studies with the goals of cloning a gene for autosomal nonsyndromic hearing impairment and identifying the murine homologue may explain the role of this gene in the development and function of the cochlea. JF - Human Molecular Genetics AU - Lesperance, M M AU - Hall, J W AU - Bess, Fred Henry AU - Fukushima, K AU - Jain, P K AU - Ploplis, B AU - San Agustin T B AU - Skarka, H AU - Smith, R J AU - Wills, M AD - Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850-3227, USA.; Department of Otolaryngology-Head and Neck Surgery, University of Texas Medical School, Houston.; Bill Wilkerson Center for Otolaryngology and Communication Sciences, Vanderbilt University School of Medicine, Vanderbilt University Medical Center, Vanderbilt University PY - 1995 SP - 1967 EP - 1972 VL - 4 IS - 10 SN - 0964-6906, 0964-6906 KW - Pedigree KW - Linkage (Genetics) KW - Human KW - Animal KW - Genetic Markers KW - Mice KW - Child KW - Chromosome Mapping KW - Child, Preschool KW - Polymerase Chain Reaction KW - Hearing Disorders KW - Comparative Study KW - Genes, Dominant KW - Lod Score KW - Recombination, Genetic KW - Case Report KW - Adolescent KW - Female KW - Huntington Disease KW - Male KW - Chromosomes, Human, Pair 4 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85281546?accountid=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=Human+Molecular+Genetics&rft.atitle=A+gene+for+autosomal+dominant+nonsyndromic+hereditary+hearing+impairment+maps+to+4p16.3.&rft.au=Lesperance%2C+M+M%3BHall%2C+J+W%3BBess%2C+Fred+Henry%3BFukushima%2C+K%3BJain%2C+P+K%3BPloplis%2C+B%3BSan+Agustin+T+B%3BSkarka%2C+H%3BSmith%2C+R+J%3BWills%2C+M&rft.aulast=Lesperance&rft.aufirst=M&rft.date=1995-10-01&rft.volume=4&rft.issue=10&rft.spage=1967&rft.isbn=&rft.btitle=&rft.title=Human+Molecular+Genetics&rft.issn=09646906&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - DNA strand breakage, thymine glycol production, and hydroxyl radical generation induced by different samples of crystalline silica in vitro. AN - 77900379; 8757240 AB - Five preparations of alpha-quartz [Min-U-Sil 5 (MQZ), MQZ pretreated with hydrofluoric acid (HFMQZ), Chinese standard alpha-quartz (CSQZ), and two German samples, DQ-12 and F600] and two preparations of the crystalline silica polymorphs, cristobalite and tridymite, previously characterized for surface area and surface charge, were evaluated for their relative activities in the following assays: (i) in vitro assays of short duration (< or = 15 min) for oxygen consumption and for generation of hydroxyl radicals (measured by electron spin resonance spin trapping), and (ii) in vitro assays of longer duration for DNA strand breakage (measured using linear DNA as a detector molecule) and for production of the oxidized DNA base, thymine glycol (measured by gas chromatography-mass spectrometry). Marked differences among the samples were found for their levels of oxygen consumption and of hydroxyl radicals' generation. All samples caused increased formation of thymine glycol, with wide variations in activity among samples. When normalized for equal surface area, the samples produced different levels of DNA strand breakage. Addition of hydrogen peroxide strongly accelerated DNA damage--more for cristobalite than for the alpha-quartz samples. DNA damage by quartz was enhanced by ferric chloride and inhibited by iron chelators. The order of relative activity of the samples varied with different types of in vitro assays and was not directly correlated to surface area. Electrophoretic mobility, as measured by zeta potential, was not significantly different among samples. The results suggest that the ability of different crystalline silica samples to generate a rapid burst of oxygen free radicals is distinct from their ability to induce DNA damage and DNA base oxidation over longer time periods. The relative activities of the samples in cellular assays (hemolysis of human erythrocytes; cytotoxicity and neoplastic transformation of BALB/3T3/A31-1-1 cells) were in turn markedly different from those listed above, suggesting a more critical role for surface area. The mechanisms of carcinogenesis by crystalline silica need to be further investigated in relation to the underlying physicochemical characteristics. JF - Environmental research AU - Daniel, L N AU - Mao, Y AU - Wang, T C AU - Markey, C J AU - Markey, S P AU - Shi, X AU - Saffiotti, U AD - Laboratory of Experimental Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 60 EP - 73 VL - 71 IS - 1 SN - 0013-9351, 0013-9351 KW - thymine glycol KW - 2943-56-8 KW - Hydroxyl Radical KW - 3352-57-6 KW - Silicon Dioxide KW - 7631-86-9 KW - Thymine KW - QR26YLT7LT KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Crystallization KW - Animals KW - Humans KW - Electron Spin Resonance Spectroscopy KW - Gas Chromatography-Mass Spectrometry KW - Oxygen -- chemistry KW - Thymine -- analogs & derivatives KW - Hydroxyl Radical -- metabolism KW - DNA Damage KW - Silicon Dioxide -- toxicity KW - Thymine -- biosynthesis KW - Silicon Dioxide -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77900379?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+research&rft.atitle=DNA+strand+breakage%2C+thymine+glycol+production%2C+and+hydroxyl+radical+generation+induced+by+different+samples+of+crystalline+silica+in+vitro.&rft.au=Banks%2C+Aaron+L.&rft.aulast=Banks&rft.aufirst=Aaron&rft.date=2006-01-01&rft.volume=63&rft.issue=1&rft.spage=8&rft.isbn=&rft.btitle=&rft.title=Physical+Educator&rft.issn=00318981&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-18 N1 - Date created - 1996-11-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Acute pulmonary toxicity of copper gallium diselenide, copper indium diselenide, and cadmium telluride intratracheally instilled into rats. AN - 77890109; 8757234 AB - Acute toxicity studies were conducted on copper gallium diselenide (CGS), copper indium diselenide (CIS), and cadmium telluride (CT), three novel compounds used in the photovoltaic and semiconductor industries. Female Sprague-Dawley rats (six rats/dose) were administered 0, 12, 25, 50, or 100 mg/kg body wt of CGS, CIS, or CT by intratracheal instillation. At 72 hr after treatment, body weight gain was significantly decreased in the 100 mg/kg CIS group and in all CT dose groups. Lung weights were increased in most chemical-treated rats, with CT causing the greatest increase. Total numbers of cells in bronchoalveolar lavage fluid (BALF) were significantly increased in treated rats and were greatest in the 100 mg/kg CIS group. Differential cell counts of BALF demonstrated a marked decrease in the percentage of alveolar macrophages and an increase in the percentage of polymorphonuclear leukocytes in all dose groups of all three chemicals. Slight to moderate increases in lactate dehydrogenase activity were observed in BALF from CGS- and CIS-treated rats; marked increases were observed in CT-treated rats. BALF protein was significantly increased in rats treated with CIS and CT. Microscopic examination revealed lymphoid hyperplasia in lungs of rats treated with all three chemicals. CT caused necrosis of the terminal bronchiolar epithelium and epithelium of the alveolar duct region with inflammation, prominent fibrin exudates, and type II cell hyperplasia. CGS and CIS also caused intraalveolar inflammation and type II cell hyperplasia, but did not cause the necrosis and fibrin exudate observed in lungs of CT-treated rats. Based on changes in lung weight, BALF indices, and histopathology, CT was the most toxic for the lung; CIS had intermediate toxicity and CGS was the least toxic. The solubilities of CGS and CIS were relatively low and similar at both pH levels and do not readily explain the observed differences in pulmonary toxicity. The solubility of CdTe was considerably greater than that of CGS and CIS and likely contributed to the greater toxicity of this compound. JF - Environmental research AU - Morgan, D L AU - Shines, C J AU - Jeter, S P AU - Wilson, R E AU - Elwell, M P AU - Price, H C AU - Moskowitz, P D AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 16 EP - 24 VL - 71 IS - 1 SN - 0013-9351, 0013-9351 KW - Cadmium Compounds KW - 0 KW - copper gallium diselenide KW - copper indium diselenide KW - Indium KW - 045A6V3VFX KW - Copper KW - 789U1901C5 KW - Gallium KW - CH46OC8YV4 KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Selenium KW - H6241UJ22B KW - Tellurium KW - NQA0O090ZJ KW - cadmium telluride KW - STG188WO13 KW - Index Medicus KW - Rats KW - Body Weight KW - Animals KW - Rats, Sprague-Dawley KW - Dose-Response Relationship, Drug KW - Trachea KW - Organ Size KW - Bronchoalveolar Lavage Fluid -- cytology KW - L-Lactate Dehydrogenase -- metabolism KW - Female KW - Tellurium -- administration & dosage KW - Cadmium Compounds -- administration & dosage KW - Selenium -- toxicity KW - Indium -- toxicity KW - Tellurium -- toxicity KW - Lung -- drug effects KW - Cadmium Compounds -- toxicity KW - Gallium -- toxicity KW - Lung -- enzymology KW - Lung -- pathology KW - Copper -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77890109?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+research&rft.atitle=Acute+pulmonary+toxicity+of+copper+gallium+diselenide%2C+copper+indium+diselenide%2C+and+cadmium+telluride+intratracheally+instilled+into+rats.&rft.au=Morgan%2C+D+L%3BShines%2C+C+J%3BJeter%2C+S+P%3BWilson%2C+R+E%3BElwell%2C+M+P%3BPrice%2C+H+C%3BMoskowitz%2C+P+D&rft.aulast=Morgan&rft.aufirst=D&rft.date=1995-10-01&rft.volume=71&rft.issue=1&rft.spage=16&rft.isbn=&rft.btitle=&rft.title=Environmental+research&rft.issn=00139351&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-18 N1 - Date created - 1996-11-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ion channel hypothesis for Alzheimer amyloid peptide neurotoxicity. AN - 77875712; 8719038 AB - 1. Alzheimer's disease (AD) is a chronic dementia and neurodegenerative disorder affecting the oldest portions of the population. Brains of AD patients accumulate large amount of the A beta P peptide in amyloid plaques. 2. The A beta P[1-40] peptide is derived by proteolytic processing from a much larger amyloid precursor protein (APP), and has been circumstantially identified as the toxic principle causing cell damage in the disease. 4. The A beta P[1-40] peptide is able to form quite characteristic calcium channels in planar lipid bilayers. These channels have conductances in the nS range, and can dissipate ion gradients quickly. The peptide can also cause equivalent cation conductances in cells. 5. We suggest that amyloid channel blocking agents might be therapeutically useful in Alzheimer's Disease, and have constructed molecular models of the channels to aid in the design of such compounds. JF - Cellular and molecular neurobiology AU - Pollard, H B AU - Arispe, N AU - Rojas, E AD - Laboratory of Cell Biology and Genetics, NIDDSK, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 513 EP - 526 VL - 15 IS - 5 SN - 0272-4340, 0272-4340 KW - Amyloid beta-Peptides KW - 0 KW - Amyloid beta-Protein Precursor KW - Ion Channels KW - Neurotoxins KW - Index Medicus KW - Brain -- physiopathology KW - Animals KW - Amyloid beta-Protein Precursor -- chemistry KW - Models, Structural KW - Humans KW - Brain -- pathology KW - Molecular Sequence Data KW - Amyloid beta-Protein Precursor -- physiology KW - Amino Acid Sequence KW - Models, Neurological KW - Ion Channels -- chemistry KW - Protein Structure, Secondary KW - Amyloid beta-Peptides -- toxicity KW - Alzheimer Disease -- physiopathology KW - Amyloid beta-Peptides -- chemistry KW - Amyloid beta-Peptides -- physiology KW - Ion Channels -- physiology KW - Alzheimer Disease -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77875712?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+and+molecular+neurobiology&rft.atitle=Ion+channel+hypothesis+for+Alzheimer+amyloid+peptide+neurotoxicity.&rft.au=Pollard%2C+H+B%3BArispe%2C+N%3BRojas%2C+E&rft.aulast=Pollard&rft.aufirst=H&rft.date=1995-10-01&rft.volume=15&rft.issue=5&rft.spage=513&rft.isbn=&rft.btitle=&rft.title=Cellular+and+molecular+neurobiology&rft.issn=02724340&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-10 N1 - Date created - 1996-10-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Targeting Pseudomonas exotoxin to hematologic malignancies. AN - 77833525; 8562907 AB - Malignant cells of hematopoietic origin often express a variety of different growth factor receptors and antigens on their surface, at levels much higher than normal cells. These malignant cells can be selectively targeted with Pseudomonas exotoxin (PE) derivatives directed by interleukins 2, 4 and 6, and by Fv fragments of monoclonal antibodies to interleukin 2 receptor (IL2R) subunits, CD22 and other antigens present on these cells. Anti-Tac(Fv)-PE38, a single-chain recombinant immunotoxin which targets cells bearing the IL2Ra, is furthest along in preclinical development and is being prepared for clinical testing in patients with IL2Ra-positive leukemia, lymphoma and Hodgkin's disease. JF - Seminars in cancer biology AU - Kreitman, R J AU - Pastan, I AD - Division of Cancer Biology, Diagnosis and Centers, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 297 EP - 306 VL - 6 IS - 5 SN - 1044-579X, 1044-579X KW - Antibodies, Monoclonal KW - 0 KW - Bacterial Toxins KW - Exotoxins KW - Immunoglobulin Fragments KW - Immunotoxins KW - Receptors, Interleukin-2 KW - Virulence Factors KW - immunoglobulin Fv KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Immunoglobulin Fragments -- therapeutic use KW - Animals KW - Receptors, Interleukin-2 -- metabolism KW - Humans KW - Antibodies, Monoclonal -- therapeutic use KW - Lymphoma -- therapy KW - Leukemia -- therapy KW - Immunotoxins -- therapeutic use KW - Exotoxins -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77833525?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Global+Media+Journal+Turkish+Edition&rft.atitle=Factors+that+affect+media+literacy+level+of+university+students&rft.au=Sacan%2C+Selvinaz%3BAdibelli%2C+Derya&rft.aulast=Sacan&rft.aufirst=Selvinaz&rft.date=2016-04-01&rft.volume=6&rft.issue=12&rft.spage=27&rft.isbn=&rft.btitle=&rft.title=Global+Media+Journal+Turkish+Edition&rft.issn=13097601&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-07 N1 - Date created - 1996-03-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Micropreparative immobilized pH gradient two-dimensional electrophoresis in combination with protein microsequencing for the analysis of human liver proteins. AN - 77804914; 8586070 AB - Simplified methodology has been developed for the direct N-terminal amino acid microsequencing of human liver and hepatoma derived polypeptides, following micropreparative two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). Utilization of immobilized pH gradient (IPG) gel strips in the first dimension permitted protein loading of 0.5-2.0 mg with negligible diminution of polypeptide resolution. Following 2-D separation and electrotransfer to polyvinylidene difluoride (PVDF) membranes nearly 100 well resolved Ponceau S stained polypeptides were readily visualized, from which, 32 adult liver S-9 and 72 HepG2 nuclear cytosolic polypeptides were subjected to N-terminal microsequencing. Twenty normal adult liver and 54 HepG2 polypeptides yielded N-terminal sequence information, of which 17 and 19 polypeptides, respectively, exhibited high sequence homology to previously identified proteins. The initial yields of the proteins sequenced ranged from 2-14 pmols and yielded sequences of 14-26 amino acid residues. Many of the adult liver and HepG2 proteins contained inferred leader sequences since the first sequenced residue was several (20-30) residues from the methionine initiation site predicted by the cDNA of the adult liver. Quantitative comparison of 60 well characterized hepatic proteins between normal adult liver and two nontransformed, Chang and WRL-68, and four human hepatoma derived cell lines, HepG2, Huh-7, FOCUS, and SK-Hep, revealed a high homogeneity of protein expression both qualitatively and quantitatively in both whole cell lysate and purified nuclear preparations. Most notable differences include the previously characterized polypeptides: carbamoyl phosphate synthase, MER5 homologous protein, cytidylate kinase, phosphatidylethanolamine-binding protein and mitochondrial enoyl-CoA hydratase as well as three N-terminally blocked polypeptides: 11 (63 kDa/pI 7.00), 56 (26/6.45) and 59 (22/6.00) all of which were expressed at similar levels in normal adult liver tissue and each of the nontransformed, Chang and WRL-68, cell lines but not expressed or expressed at greatly decreased levels in each of tumor derived liver cell lines. Pyruvate carboxylase, superoxide dismutase, serotransferrin, liver fatty acid binding protein, 1-hydroxyprostaglandin dehydrogenase, NADH dehydrogenase (ubiquinone) as well as three N-terminally blocked polypeptides: 9 (57/6.00), 53 (24/4.90) and 63 (16/4.70) were detected only in whole adult liver tissue and not in any of the cultured cell lines. Two additional polypeptides: U35, (27/6.05) and 58 (22/5.70) yielded N-terminal partial amino acid sequences but were not identified in established protein databases. We have shown that micropreparative IPG 2-D PAGE In combination with protein microsequencing provides a convenient one step procedure to rapidly obtain partial amino acid sequence information for nearly 100 individual polypeptides directly from a single 2-D PAGE gel with numerous applications to a wide variety of biological model systems. JF - Electrophoresis AU - Wirth, P J AU - Hoang, T N AU - Benjamin, T AD - Biopolymer Chemistry Section, Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 1946 EP - 1960 VL - 16 IS - 10 SN - 0173-0835, 0173-0835 KW - Peptide Fragments KW - 0 KW - Proteins KW - Index Medicus KW - Liver Neoplasms KW - Peptide Fragments -- chemistry KW - Tumor Cells, Cultured KW - Carcinoma, Hepatocellular KW - Hydrogen-Ion Concentration KW - Humans KW - Adult KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Proteins -- chemistry KW - Electrophoresis, Gel, Two-Dimensional -- methods KW - Proteins -- isolation & purification KW - Sequence Analysis KW - Liver -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77804914?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Electrophoresis&rft.atitle=Micropreparative+immobilized+pH+gradient+two-dimensional+electrophoresis+in+combination+with+protein+microsequencing+for+the+analysis+of+human+liver+proteins.&rft.au=Wirth%2C+P+J%3BHoang%2C+T+N%3BBenjamin%2C+T&rft.aulast=Wirth&rft.aufirst=P&rft.date=1995-10-01&rft.volume=16&rft.issue=10&rft.spage=1946&rft.isbn=&rft.btitle=&rft.title=Electrophoresis&rft.issn=01730835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-22 N1 - Date created - 1996-03-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alterations in estrogen levels during development affects the skeleton: use of an animal model. AN - 77803297; 8593884 AB - Exposure to estrogens during various stages of development has been shown to irreversibly influence responsive target organs. The recent finding of the presence of estrogen receptor in both osteoblasts and osteoclasts has suggested a direct role of steroid hormones on bone tissue. Furthermore, estrogens have important effects on bone turnover in both humans and experimental animal models. Thus, this tissue is now regarded as a specific estrogen target tissue. To investigate whether a short-term developmental exposure to estrogens can influence bone tissue, we have injected female mice with diethylstilbestrol (DES) from day 1 through day 5 of life. Additionally, a group of pregnant female mice were injected with different doses of DES from day 9 through 16 of pregnancy. Mice were then weaned at 21 days of age, and effects on bone tissue of the female mice were evaluated in adulthood (7-12 months of age). These short-term treatments did not affect body weight of exposed mice. However, a dose-dependent increase in bone mass, both in the trabecular and compact compartments, was observed in the DES-exposed female offspring. Furthermore, femurs from DES-exposed females were shorter than femurs from controls. A normal skeletal mineralization accompanied these changes in the bone tissue. In fact, a parallel increase in total calcium content of the skeleton was found in concomitance with the increase in bone mass. Estrogen treatment induced an increase in the amount of mineralized skeleton when compared to untreated controls. In summary, this report shows that alterations of estrogen levels during development can influence the early phases of bone tissue development inducing permanent changes in the skeleton. These changes appear to be related to bone cell programming in early phases of life. JF - Environmental health perspectives AU - Migliaccio, S AU - Newbold, R R AU - McLachlan, J A AU - Korach, K S AD - Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 95 EP - 97 VL - 103 Suppl 7 SN - 0091-6765, 0091-6765 KW - Diethylstilbestrol KW - 731DCA35BT KW - Index Medicus KW - Bone Density -- drug effects KW - Animals KW - Dose-Response Relationship, Drug KW - Mice KW - Models, Biological KW - Female KW - Prenatal Exposure Delayed Effects KW - Pregnancy KW - Embryonic and Fetal Development -- drug effects KW - Diethylstilbestrol -- pharmacology KW - Bone Development -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77803297?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Alterations+in+estrogen+levels+during+development+affects+the+skeleton%3A+use+of+an+animal+model.&rft.au=Migliaccio%2C+S%3BNewbold%2C+R+R%3BMcLachlan%2C+J+A%3BKorach%2C+K+S&rft.aulast=Migliaccio&rft.aufirst=S&rft.date=1995-10-01&rft.volume=103+Suppl+7&rft.issue=&rft.spage=95&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 - 1996-04-09 N1 - Date created - 1996-04-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Natl Cancer Inst. 1981 Oct;67(4):761-7 [6944545] N Engl J Med. 1971 Apr 15;284(15):878-81 [5549830] Food Chem Toxicol. 1986 Sep;24(9):931-4 [3781439] Proc Natl Acad Sci U S A. 1987 Sep;84(17):6267-71 [2819869] Science. 1988 Jul 1;241(4861):81-4 [3164526] Science. 1988 Jul 1;241(4861):84-6 [3388021] Endocrinology. 1988 Aug;123(2):681-6 [3396505] J Bone Miner Res. 1987 Apr;2(2):115-22 [3455160] Proc Natl Acad Sci U S A. 1990 Mar;87(6):2172-6 [2315310] Cancer Res. 1990 Dec 1;50(23):7677-81 [2174729] Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6613-7 [1907373] Mol Endocrinol. 1991 Nov;5(11):1597-606 [1779966] Endocrinology. 1992 Mar;130(3):1756-8 [1537323] Reprod Toxicol. 1989;3(2):81-9 [2520515] Endocrinology. 1992 May;130(5):2617-24 [1572285] Endocrinology. 1992 Aug;131(2):883-9 [1639030] Bone Miner. 1992 Oct;19 Suppl 1:S3-14 [1422318] Endocr Rev. 1994 Jun;15(3):275-300 [8076582] J Natl Cancer Inst. 1981 Sep;67(3):653-62 [6944535] Lancet. 1976 May 15;1(7968):1038-41 [57448] Fundam Appl Toxicol. 1984 Oct;4(5):686-91 [6510599] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Techniques for detection of estrogenicity. AN - 77802619; 8593874 JF - Environmental health perspectives AU - Korach, K S AU - McLachlan, J A AD - Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 5 EP - 8 VL - 103 Suppl 7 SN - 0091-6765, 0091-6765 KW - Biomarkers KW - 0 KW - Estrogens KW - Vitellogenins KW - Lactoferrin KW - EC 3.4.21.- KW - Index Medicus KW - Biomarkers -- chemistry KW - Animals KW - Lactoferrin -- analysis KW - Humans KW - Cell Division -- drug effects KW - Biological Assay KW - Vitellogenins -- analysis KW - Estrogens -- pharmacology KW - Gene Expression Regulation -- drug effects KW - Estrogens -- analysis KW - Estrogens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77802619?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Techniques+for+detection+of+estrogenicity.&rft.au=Korach%2C+K+S%3BMcLachlan%2C+J+A&rft.aulast=Korach&rft.aufirst=K&rft.date=1995-10-01&rft.volume=103+Suppl+7&rft.issue=&rft.spage=5&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 - 1996-04-09 N1 - Date created - 1996-04-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer Res. 1990 Feb 15;50(4):1257-70 [2153455] Prog Clin Biol Res. 1989;318:345-51 [2626437] Endocrinology. 1991 Jul;129(1):75-84 [2055206] Mol Endocrinol. 1992 Mar;6(3):355-64 [1584212] Gen Comp Endocrinol. 1994 Apr;94(1):122-34 [8045362] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of D1 and D2 dopamine receptor antagonists and catecholamine depleting agents on the locomotor stimulation induced by dizocilpine in mice. AN - 77788232; 8561905 AB - Low doses of the uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) induce locomotor stimulation in mice, whereas higher doses are associated with ataxia, stereotyped behaviors and catalepsy. We investigated the role of dopamine receptors and presynaptic dopamine neurons in the locomotor effects of dizocilpine. For comparison, we studied several other drugs that induce locomotor stimulation in mice. Pretreatment of male mice with haloperidol (0.1 mg/kg, i.p.) completely prevented the stimulation of normally coordinated locomotion induced by a non-intoxicating dose of dizocilpine (0.1 mg/kg, i.p.); haloperidol also attenuated the locomotor stimulation produced by phencyclidine (PCP, 1 and 2 mg/kg, i.p.), d-amphetamine (2 and 5 mg/kg, i.p.) and diazepam (0.5 mg/kg, i.p.). Haloperidol (doses up to 2.5 mg/kg) did not attenuate the ataxia and decreased locomotion induced by higher doses of dizocilpine (1 and 2 mg/kg). The active cis isomer of flupenthixol (0.5 mg/kg, i.p.), an antagonist of both D1 and D2 dopamine receptors, also diminished the stimulant actions of all of the test drugs, whereas its inactive trans form did not. The selective D1 antagonist R(+/-)-SCH 23390 (0.1 mg/kg) and the selective D2 antagonist raclopride (1 mg/kg) had little effect on the stimulatory effect of dizocilpine, although they did reduce the stimulation produced by PCP, d-amphetamine and diazepam. However, pretreatment with a combination of R(+/-)SCH 23390 and raclopride completely prevented dizocilpine-induced locomotor stimulation. Pretreatment with alpha-methyl-p-tyrosine (AMPT, 50 and 250 mg/kg), an inhibitor of tyrosine hydroxylase, or with 6-hydroxydopamine (6-OH-DA, 50 micrograms, i.c.v.), a neurotoxin that destroys brain dopaminergic and noradrenergic neurons, did not attenuate the locomotor stimulation induced by dizocilpine, although these treatments did reduce the stimulant effects of d-amphetamine. In AMPT or 6-OH-DA pretreated mice, haloperidol (0.125 mg/kg) prevented the stimulatory effect of dizocilpine. These results support a role for dopamine receptors in the stimulation of normally coordinated locomotion by dizocilpine. However, the locomotor stimulant effect of dizocilpine, unlike that of d-amphetamine, can be expressed in the presence of D1 or D2 dopamine receptor blockade and does not appear to be dependent on intact presynaptic mechanisms. JF - Behavioural brain research AU - Lapin, I P AU - Rogawski, M A AD - Neuronal Excitability Section, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 145 EP - 151 VL - 70 IS - 2 SN - 0166-4328, 0166-4328 KW - Catecholamines KW - 0 KW - Dopamine Antagonists KW - Dopamine D2 Receptor Antagonists KW - Excitatory Amino Acid Antagonists KW - Receptors, Dopamine D1 KW - Receptors, N-Methyl-D-Aspartate KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - Oxidopamine KW - 8HW4YBZ748 KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Norepinephrine -- physiology KW - Mice, Inbred Strains KW - Animals KW - Brain Mapping KW - Dose-Response Relationship, Drug KW - Neurons -- drug effects KW - Brain -- drug effects KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Mice KW - Male KW - Catecholamines -- physiology KW - Receptors, Dopamine D1 -- antagonists & inhibitors KW - Dopamine Antagonists -- pharmacology KW - Stereotyped Behavior -- drug effects KW - Motor Activity -- drug effects KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Dizocilpine Maleate -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77788232?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Behavioural+brain+research&rft.atitle=Effects+of+D1+and+D2+dopamine+receptor+antagonists+and+catecholamine+depleting+agents+on+the+locomotor+stimulation+induced+by+dizocilpine+in+mice.&rft.au=Lapin%2C+I+P%3BRogawski%2C+M+A&rft.aulast=Lapin&rft.aufirst=I&rft.date=1995-10-01&rft.volume=70&rft.issue=2&rft.spage=145&rft.isbn=&rft.btitle=&rft.title=Behavioural+brain+research&rft.issn=01664328&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-05 N1 - Date created - 1996-03-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rectal methadone in cancer patients with pain. A preliminary clinical and pharmacokinetic study. AN - 77785858; 8589026 AB - Cancer pain can be treated in most cases with oral analgesics. However, during their clinical history, 53% to 70% of patients will need alternative routes of opioid administration. The rectal administration of opioids is a simple alternative route for many patients. There are no data in the literature regarding the pharmacodynamics and pharmacokinetics of rectal methadone. We evaluated the analgesia, tolerability and absorption profile of methadone hydrochloride in six opioid-naive cancer patients with pain. A blood sample was collected before administration of a single dose of drug (10 mg) and then again after fixed times. At these fixed times the patients were asked about pain, nausea and drowsiness by means of a visual analogue scale of 0-100 mm (VAS). Pain relief was statistically significant as early as 30 minutes and up to eight hours after methadone administration. None of the patients reported significant side effects. The pharmacokinetics of rectal methadone showed rapid and extensive distribution phases followed by a slow elimination phase. Rectal methadone can be considered an effective analgesic therapy for patients with cancer pain for whom oral and/or parenteral opioids are not indicated or available. JF - Annals of oncology : official journal of the European Society for Medical Oncology AU - Ripamonti, C AU - Zecca, E AU - Brunelli, C AU - Rizzio, E AU - Saita, L AU - Lodi, F AU - De Conno, F AD - Pain Therapy and Palliative Care Division, National Cancer Institute, Milan, Italy. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 841 EP - 843 VL - 6 IS - 8 SN - 0923-7534, 0923-7534 KW - Analgesics, Opioid KW - 0 KW - Methadone KW - UC6VBE7V1Z KW - Index Medicus KW - Humans KW - Adult KW - Middle Aged KW - Administration, Rectal KW - Male KW - Female KW - Colorectal Neoplasms -- complications KW - Pain -- etiology KW - Methadone -- adverse effects KW - Head and Neck Neoplasms -- blood KW - Pain -- drug therapy KW - Head and Neck Neoplasms -- complications KW - Pain -- blood KW - Methadone -- pharmacokinetics KW - Colorectal Neoplasms -- blood KW - Analgesics, Opioid -- pharmacokinetics KW - Analgesics, Opioid -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77785858?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+and+molecular+neurobiology&rft.atitle=Ion+channel+hypothesis+for+Alzheimer+amyloid+peptide+neurotoxicity.&rft.au=Pollard%2C+H+B%3BArispe%2C+N%3BRojas%2C+E&rft.aulast=Pollard&rft.aufirst=H&rft.date=1995-10-01&rft.volume=15&rft.issue=5&rft.spage=513&rft.isbn=&rft.btitle=&rft.title=Cellular+and+molecular+neurobiology&rft.issn=02724340&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-27 N1 - Date created - 1996-03-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ambulatory low-toxicity chemotherapy in non-small-cell lung carcinoma by continuous 28-day infusion of alternating cisplatin and 5-fluorouracil. AN - 77782477; 8589025 AB - One regimen consisting of a continuous infusion of cisplatin and fluorouracil was designed to be minimally toxic, and suitable for application with radiotherapy in non-small-cell lung carcinoma (NSCLC). Forty-four NSCLC patients received daily 8 mg/m2 of cisplatin on days 1-2, 8-9, 15-16, 22-23, and 300 mg/m2 of fluorouracil on days 3-7, 10-14, 17-21, 24-28 (35-day courses). Two patients experienced grade 3-4 toxicities. Eleven achieved objective responses. The median progression-free and observed survival was 22 and 39.5 weeks. The schedule management was fully ambulatory. Toxicity was negligible. The activity was moderate, but the combination with radiotherapy is advisable due to the radioenhancing properties of both of the drugs. JF - Annals of oncology : official journal of the European Society for Medical Oncology AU - Bedini, A V AU - Tavecchio, L AU - Lequaglie, C AU - Ravasi, G AD - National Cancer Institute, Milan, Italy. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 838 EP - 840 VL - 6 IS - 8 SN - 0923-7534, 0923-7534 KW - Cisplatin KW - Q20Q21Q62J KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Drug Administration Schedule KW - Infusions, Intravenous KW - Humans KW - Retrospective Studies KW - Aged KW - Cisplatin -- administration & dosage KW - Fluorouracil -- administration & dosage KW - Fluorouracil -- adverse effects KW - Radiotherapy, Adjuvant KW - Survival Rate KW - Adult KW - Middle Aged KW - Cisplatin -- adverse effects KW - Female KW - Male KW - Carcinoma, Non-Small-Cell Lung -- mortality KW - Lung Neoplasms -- drug therapy KW - Lung Neoplasms -- mortality KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Carcinoma, Non-Small-Cell Lung -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77782477?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Knowledge+Quest&rft.atitle=Capitalizing+on+the+School+Library%27s+Potential+to+Positively+Affect+Student+Achievement%3A+A+Sampling+of+Resources+for+Administrators.&rft.au=Hartzell%2C+Gary&rft.aulast=Hartzell&rft.aufirst=Gary&rft.date=2002-01-01&rft.volume=31&rft.issue=1&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Knowledge+Quest&rft.issn=10949046&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-27 N1 - Date created - 1996-03-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Guidelines for application of meta-analysis in environmental epidemiology. ISLI Risk Science Institute. AN - 77780915; 8577954 AB - The use of meta-analysis in environmental epidemiology can enhance the value of epidemiologic data in debates about environmental health risks. Meta-analysis may be particularly useful to formally examine sources of heterogeneity, to clarify the relationship between environmental exposures and health effects, and to generate information beyond that provided by individual studies or a narrative review. However, meta-analysis may not be useful when the relationship between exposure and disease is obvious, when there are only a few studies of the key health outcomes, or when there is substantial confounding or other biases which cannot be adjusted for in the analysis. Recent increases in the use of meta-analysis in environmental epidemiology have highlighted the need for guidelines for the application of the technique. Guidelines, in the form of desirable and undesirable attributes, are presented in this paper for various components of a meta-analysis including study identification and selection; data extraction and analysis; and interpretation, presentation, and communication of results. Also discussed are the appropriateness of the use of meta-analysis in environmental health studies and when meta-analysis should or should not be used. JF - Regulatory toxicology and pharmacology : RTP AU - Blair, A AU - Burg, J AU - Foran, J AU - Gibb, H AU - Greenland, S AU - Morris, R AU - Raabe, G AU - Savitz, D AU - Teta, J AU - Wartenberg, D AD - National Cancer Institute, Bethesda, Maryland, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 189 EP - 197 VL - 22 IS - 2 SN - 0273-2300, 0273-2300 KW - Index Medicus KW - Epidemiologic Methods KW - Environmental Exposure -- statistics & numerical data KW - Meta-Analysis as Topic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77780915?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Developmental+biology&rft.atitle=The+organizer-associated+chick+homeobox+gene%2C+Gnot1%2C+is+expressed+before+gastrulation+and+regulated+synergistically+by+activin+and+retinoic+acid.&rft.au=Knezevic%2C+V%3BRanson%2C+M%3BMackem%2C+S&rft.aulast=Knezevic&rft.aufirst=V&rft.date=1995-10-01&rft.volume=171&rft.issue=2&rft.spage=458&rft.isbn=&rft.btitle=&rft.title=Developmental+biology&rft.issn=00121606&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-14 N1 - Date created - 1996-03-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alternative leader sequences in insulin-like growth factor I mRNAs modulate translational efficiency and encode multiple signal peptides. AN - 77779185; 8544846 AB - Rat insulin-like growth factor I (IGF-I) mRNAs contain multiple 5'-untranslated regions due to the use of leader exons transcribed from several transcription initiation sites and to alternative splicing within leader exon 1. Synthetic RNAs with 5'-ends corresponding to the use of exon 1 transcription initiation sites were translated in vitro into prepro-IGF-I peptides initiated at a Met-48 codon in exon 1 or a Met-22 codon in exon 3, and RNAs with a 5'-end corresponding to the major exon 2 transcription start site were translated into a prepro-IGF-I peptide initiated at a Met-32 codon in exon 2. All forms of prepro-IGF-I were processed by canine pancreatic microsomes, suggesting that all these prepeptides function as signal peptides. The translational efficiency of IGF-I RNAs was inversely proportional to the length of the 5'-untranslated region. Mutation of the first of three upstream AUG codons in exon 1, which potentially initiates a 14-amino acid open reading frame, did not affect prepro-IGF-I translation. The other two AUG codons are immediately followed by stop codons. The absence of both upstream AUG codons in a completely spliced exon 1-derived RNA enhanced the in vitro and in vivo translatability of this RNA as compared with the full-length RNA. Mutation of the downstream initiation codon in particular increased translational efficiency in vitro and in intact cells, suggesting that an inefficient reinitiation event at the Met-48 codon contributes to the poorer translation of IGF-I mRNAs in which these upstream AUGUGA motifs occur. We conclude that IGF-I mRNAs potentially encode multiple forms of preproIGF and that specific differences in their 5'-untranslated regions provide a molecular basis for translational control of IGF-I biosynthesis. JF - Molecular endocrinology (Baltimore, Md.) AU - Yang, H AU - Adamo, M L AU - Koval, A P AU - McGuinness, M C AU - Ben-Hur, H AU - Yang, Y AU - LeRoith, D AU - Roberts, C T AD - Section on Molecular and Cellular Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 1380 EP - 1395 VL - 9 IS - 10 SN - 0888-8809, 0888-8809 KW - Protein Sorting Signals KW - 0 KW - RNA, Messenger KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Index Medicus KW - Rats KW - Mutagenesis, Site-Directed KW - Animals KW - Base Sequence KW - Sequence Analysis KW - Molecular Sequence Data KW - Dogs KW - Insulin-Like Growth Factor I -- genetics KW - Protein Biosynthesis KW - Protein Sorting Signals -- metabolism KW - RNA, Messenger -- metabolism KW - Protein Sorting Signals -- genetics KW - Insulin-Like Growth Factor I -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77779185?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Alternative+leader+sequences+in+insulin-like+growth+factor+I+mRNAs+modulate+translational+efficiency+and+encode+multiple+signal+peptides.&rft.au=Yang%2C+H%3BAdamo%2C+M+L%3BKoval%2C+A+P%3BMcGuinness%2C+M+C%3BBen-Hur%2C+H%3BYang%2C+Y%3BLeRoith%2C+D%3BRoberts%2C+C+T&rft.aulast=Yang&rft.aufirst=H&rft.date=1995-10-01&rft.volume=9&rft.issue=10&rft.spage=1380&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 - 1996-02-13 N1 - Date created - 1996-02-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic and cellular changes in colorectal cancer: proposed targets of chemopreventive agents. AN - 77776229; 8672984 AB - Progress in development of a genetic model for colorectal tumorigenesis and human chemoprevention research may allow the mechanism-based identification of targets and chemopreventive agents that will protect against colorectal cancer. For example, numerous mutagenic events can occur throughout colorectal carcinogenesis, including loss of heterozygosity in tumor suppressor genes such as APC, MCC, DCC, and p53, as well as in oncogenes such as K-ras. Chemopreventive agents that inhibit mutagenic activity such as N-acetyl-l-cysteine, oltipraz, and nonsteroidal anti-inflammatory drugs may protect against these mutations. Also, agents such as perillyl alcohol and lovastatin that interfere with protein isoprenylation and, hence, inhibit oncogene activation may protect against aberrant K-ras expression. Hyperproliferation in normal mucosa, leading to growth and progression of neoplasia, are also aspects of colorectal carcinogenesis that can be controlled by chemopreventive agents. Calcium is a chemopreventive agent for which there is both clinical and experimental evidence of inhibition of cell proliferation in colon mucosa. Other examples of antiproliferative agents with potential chemopreventive efficacy in colon are 2-difluoromethylornithine, dehydroepiandrosterone, and selenium. Differentiating agents such as retinoids and deltanoids also may slow proliferation and progression. Antioxidants have potential for interfering with both mutagenicity and proliferation (e.g., by preventing oxidative activation of carcinogens and scavenging activated oxygen species generated during inflammation). The same mechanistic principles apply to identification of dietary chemopreventive intervention for colorectal carcinogenesis. For example, lowering dietary fat and increasing dietary fiber lead to lower colorectal mucosal proliferation, and cruciferous vegetables contain agents such as indoles and dithiolthiones that have shown antimutagenic activity. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Greenwald, P AU - Kelloff, G J AU - Boone, C W AU - McDonald, S S AD - Division of Cancer Prevention and Control, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. PY - 1995 SP - 691 EP - 702 VL - 4 IS - 7 SN - 1055-9965, 1055-9965 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Mutation -- drug effects KW - Animals KW - Genes, Tumor Suppressor -- drug effects KW - Genes, Tumor Suppressor -- genetics KW - Humans KW - Cell Division -- drug effects KW - Diet KW - Colorectal Neoplasms -- pathology KW - Colorectal Neoplasms -- genetics KW - Antineoplastic Agents -- therapeutic use KW - Colorectal Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77776229?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genetic+and+cellular+changes+in+colorectal+cancer%3A+proposed+targets+of+chemopreventive+agents.&rft.au=Greenwald%2C+P%3BKelloff%2C+G+J%3BBoone%2C+C+W%3BMcDonald%2C+S+S&rft.aulast=Greenwald&rft.aufirst=P&rft.date=1995-10-01&rft.volume=4&rft.issue=7&rft.spage=691&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 - 1996-08-13 N1 - Date created - 1996-08-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comorbidity between DSM-IV alcohol use disorders and major depression: results of a national survey. AN - 77773359; 8556968 AB - The purpose of this study was to describe detailed patterns of comorbidity between Diagnostic and Statistical Manual of Mental Disorders--Fourth Edition (DSM-IV) alcohol use disorders and major depression using a representative sample of the United States. Comorbidity rates and associations between DSM-IV alcohol use disorders and major depression were expressed as odds ratios with confidence intervals adjusted for the complex design characteristics of the NLAES. Comorbidity analyses were presented by sex, ethnicity and age for past year, prior to past year and lifetime diagnoses. Virtually all odds ratios were significantly greater than 1.0, demonstrating that comorbidity of alcohol use disorders and major depression is pervasive in the general population. The magnitude of the association remained stable across the three time frames but diagnostic and subgroup variations in comorbidity were noted. The association between alcohol dependence and major depression was greater than the association between abuse and major depression and the association between alcohol abuse and major depression was consistently greater for females and blacks, compared to their male and non-black counterparts. Implications of the results are discussed in terms of professional help seeking, the self-medication hypothesis, and differential social control theory. JF - Drug and alcohol dependence AU - Grant, B F AU - Harford, T C AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892-7003, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 197 EP - 206 VL - 39 IS - 3 SN - 0376-8716, 0376-8716 KW - Index Medicus 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 - Comorbidity KW - Self Medication -- psychology 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 - Depressive Disorder -- epidemiology KW - Psychiatric Status Rating Scales KW - Alcoholism -- epidemiology KW - Depressive Disorder -- psychology KW - Alcoholism -- diagnosis KW - Depressive Disorder -- diagnosis KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77773359?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Comorbidity+between+DSM-IV+alcohol+use+disorders+and+major+depression%3A+results+of+a+national+survey.&rft.au=Grant%2C+B+F%3BHarford%2C+T+C&rft.aulast=Grant&rft.aufirst=B&rft.date=1995-10-01&rft.volume=39&rft.issue=3&rft.spage=197&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 - 1996-02-27 N1 - Date created - 1996-02-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Suramin treatment suppresses induction of experimental autoimmune uveoretinitis (EAU) in rodents. AN - 77765378; 8549154 AB - The experimental drug suramin has been shown to possess several immunosuppressive properties. In this study we investigated the effect of suramin on the development of experimental autoimmune uveoretinitis (EAU) in mice and in rats. EAU was induced either by active immunization with a uveitogenic protein or peptide, or by the adoptive transfer of a uveitogenic T cell line. The development of EAU was assessed by clinical evaluation as well as by histopathology. Immunological responses were measured by delayed type hypersensitivity (DTH), lymphocyte proliferation, and serum antibody levels to the immunizing antigen. Suramin treatment was most effective in suppressing EAU when started concurrently with immunization (afferent). Treatment was less effective in suppressing disease when first administered 7 days after immunization or when given to animals that received an adoptive transfer of uveitogenic T cells (efferent). The effect of suramin on DTH and lymphocyte proliferation roughly paralleled its effect on EAU. Aferent treatment of mice with suramin completely suppressed anti-IRBP antibody titers. Interestingly, animals receiving efferent treatment had unreduced IgM levels but little or no IgG, suggesting prevention of the IgM-to-IgG switch. Depressed in vitro lymphocyte proliferative responses in animals treated with suramin during the afferent stage suggested that the suppressive effect on disease was due at least in part to an inhibition of antigen priming. Our results suggest that suramin merits further investigation as a potential treatment for some types of uveitis. JF - Current eye research AU - Sartani, G AU - Silver, P B AU - Strassmann, G AU - Chan, C C AU - Caspi, R R AD - Laboratory of Immunology, National Eye Institute, NIH, Bethesda, MD 20892, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 887 EP - 896 VL - 14 IS - 10 SN - 0271-3683, 0271-3683 KW - Eye Proteins KW - 0 KW - Immunoglobulin G KW - Immunoglobulin M KW - Immunosuppressive Agents KW - Peptides KW - Retinol-Binding Proteins KW - interstitial retinol-binding protein KW - Suramin KW - 6032D45BEM KW - Index Medicus KW - Animals KW - Rats, Inbred Lew KW - Immunoglobulin M -- immunology KW - Hypersensitivity, Delayed -- prevention & control KW - Mice KW - Immunoglobulin G -- immunology KW - Hypersensitivity, Delayed -- immunology KW - Immunization KW - Rats KW - Lymphocyte Activation -- drug effects KW - Retinol-Binding Proteins -- immunology KW - Eye Proteins -- immunology KW - Lymphocyte Activation -- immunology KW - Immunotherapy, Adoptive KW - Female KW - Uveitis -- prevention & control KW - Autoimmune Diseases -- prevention & control KW - Uveitis -- pathology KW - Retinitis -- pathology KW - Retinitis -- immunology KW - Retinitis -- prevention & control KW - Uveitis -- immunology KW - Retinitis -- chemically induced KW - Autoimmune Diseases -- pathology KW - Autoimmune Diseases -- chemically induced KW - Immunosuppressive Agents -- therapeutic use KW - Uveitis -- chemically induced KW - Autoimmune Diseases -- immunology KW - Suramin -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77765378?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Techniques+for+detection+of+estrogenicity.&rft.au=Korach%2C+K+S%3BMcLachlan%2C+J+A&rft.aulast=Korach&rft.aufirst=K&rft.date=1995-10-01&rft.volume=103+Suppl+7&rft.issue=&rft.spage=5&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=08822689&rft_id=info:doi/10.1007%2Fs10862-011-9271-4 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-20 N1 - Date created - 1996-02-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Passive inhalation of cocaine. AN - 77761051; 8926734 AB - Six healthy male volunteers were exposed to the vapor of 100 and 200 mg freebase cocaine heated to a temperature of 200 degrees C in an unventilated room (12,600-L volume) for a period of 1 h. No pharmacological effects were detected as a result of the exposure. Blood specimens collected immediately following exposure were negative for cocaine and metabolites. Urine specimens analyzed by gas chromatography-mass spectrometry contained peak concentrations of benzoylecgonine that ranged from 22 to 123 ng/mL. The peak excretion time for benzoylecgonine following passive exposure was approximately 5 h. The amount of cocaine inhaled by the subjects during passive exposure was estimated from room air measurements of cocaine to be approximately 0.25 mg. The total amount of cocaine (cocaine plus metabolites) excreted in urine by the six subjects ranged from 0.04 to 0.21 mg. For comparison, the six subjects also received an intravenous injection of 1 mg cocaine hydrochloride. Four of six subjects screened positive (300-ng/mL cutoff concentration) following the injection, indicating that the minimum amount of cocaine in these subjects necessary to produce positive results was approximately 1 mg. A second passive inhalation study was undertaken in which specimens were collected from research staff who assisted in a series of experimental studies with "crack" (freebase cocaine) smokers. The research staff remained in close vicinity while the crack smokers smoked three doses of freebase cocaine (12.5, 25, and 50 mg) over a period of 4 h. As a result, staff members were passively exposed to sidestream smoke from crack pipes and to breath exhalation from the crack smokers. Urine specimens from the staff members contained a maximum of 6 ng/mL benzoylecgonine. Only traces (less than 1 ng/mL) of cocaine were detected in any specimen. Overall, these studies demonstrated that individuals exposed to cocaine smoke under naturalistic or artificial conditions absorbed small amounts of cocaine that were insufficient to produce positive urine specimens at standard Department of Health and Human Services cutoffs. However, passive exposure conditions that would result in absorption of cocaine in amounts exceeding 1 mg could result in the production of cocaine-positive urine specimens. JF - Journal of analytical toxicology AU - Cone, E J AU - Yousefnejad, D AU - Hillsgrove, M J AU - Holicky, B AU - Darwin, W D AD - Addiction Research Center, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 399 EP - 411 VL - 19 IS - 6 SN - 0146-4760, 0146-4760 KW - Narcotics KW - 0 KW - benzoylecgonine KW - 5353I8I6YS KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Occupational Exposure KW - Heart Rate -- drug effects KW - Injections, Intravenous KW - Double-Blind Method KW - Humans KW - Adult KW - Gas Chromatography-Mass Spectrometry KW - Middle Aged KW - Administration, Inhalation KW - Male KW - Female KW - Cocaine -- analogs & derivatives KW - Cocaine -- urine KW - Narcotics -- blood KW - Narcotics -- urine KW - Environmental Exposure KW - Narcotics -- administration & dosage KW - Cocaine -- blood KW - Cocaine -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77761051?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+analytical+toxicology&rft.atitle=Passive+inhalation+of+cocaine.&rft.au=Cone%2C+E+J%3BYousefnejad%2C+D%3BHillsgrove%2C+M+J%3BHolicky%2C+B%3BDarwin%2C+W+D&rft.aulast=Cone&rft.aufirst=E&rft.date=1995-10-01&rft.volume=19&rft.issue=6&rft.spage=399&rft.isbn=&rft.btitle=&rft.title=Journal+of+analytical+toxicology&rft.issn=01464760&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-21 N1 - Date created - 1996-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mitochondrial aldehyde dehydrogenase polymorphism in Asian and American Indian populations: detection of new ALDH2 alleles. AN - 77758541; 8561277 AB - Genetic deficiency of the mitochondrial aldehyde dehydrogenase (ALDH2) is frequent in Asian peoples where it is an important factor negatively regulating drinking behavior. To obtain additional information on gene geography of known ALDH2 alleles, and look for new variants, ALDH2 genes were evaluated in a Chinese population from Taiwan, a Yakut population of Siberia, and in five North American Indian populations. A novel approach based on a single-strand conformation polymorphism assay, and polymerase chain reaction-directed mutagenesis was developed for genotyping. In the Taiwan Chinese population, the ALDH2(2) allele frequency was 0.319 +/- 0.025, and this allele was not detected in the Yakut population nor in the five North American Indian populations. However, a new allele, ALDH2(3), was detected in Pima Indians at a frequency of 0.044 +/- 0.022, and this allele was also observed in 1 of 49 Pueblo samples. ALDH2(3) is a silent transition 1464 G-->A, and it possibly has a wide distribution among North American Indians. A new subtype of the ALDH2(2) allele, designated as ALDH2(2Taiwan), was found in 1 of 174 Chinese from Taiwan. ALDH2(2Taiwan) is characterized by two G-->A transitions at bases 1486 and 1510, resulting in Glu-->Lys substitutions at both the 479 and 487 positions. Thus, this second nonconservative ALDH2 substitution occurs within the sequence of the already inactive ALDH2(2) allele. JF - Alcoholism, clinical and experimental research AU - Novoradovsky, A AU - Tsai, S J AU - Goldfarb, L AU - Peterson, R AU - Long, J C AU - Goldman, D AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland 20892, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 1105 EP - 1110 VL - 19 IS - 5 SN - 0145-6008, 0145-6008 KW - Isoenzymes KW - 0 KW - DNA KW - 9007-49-2 KW - Aldehyde Dehydrogenase KW - EC 1.2.1.3 KW - Index Medicus KW - United States KW - Taiwan KW - Reference Values KW - Alleles KW - Gene Frequency KW - Humans KW - DNA -- genetics KW - Molecular Sequence Data KW - Base Composition -- genetics KW - Mitochondria, Liver -- enzymology KW - Aldehyde Dehydrogenase -- genetics KW - Alcoholism -- enzymology KW - Isoenzymes -- deficiency KW - Polymorphism, Genetic -- genetics KW - Alcoholism -- ethnology KW - Aldehyde Dehydrogenase -- deficiency KW - Alcoholism -- genetics KW - Isoenzymes -- genetics KW - Asian Continental Ancestry Group -- genetics KW - Indians, North American -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77758541?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mitochondrial+aldehyde+dehydrogenase+polymorphism+in+Asian+and+American+Indian+populations%3A+detection+of+new+ALDH2+alleles.&rft.au=Novoradovsky%2C+A%3BTsai%2C+S+J%3BGoldfarb%2C+L%3BPeterson%2C+R%3BLong%2C+J+C%3BGoldman%2C+D&rft.aulast=Novoradovsky&rft.aufirst=A&rft.date=1995-10-01&rft.volume=19&rft.issue=5&rft.spage=1105&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 - 1996-02-26 N1 - Date created - 1996-02-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The germ cell deficient locus maps to mouse chromosome 11A2-3. AN - 77755182; 8563166 AB - The autosomal recessive mouse mutation, germ cell deficient, gcd, manifests as infertility in both sexes owing to improper migration and/or proliferation of primordial germ cells during embryonic development. Mice harboring this mutation have been hypothesized to be animal models of the human syndromes, premature ovarian failure and Sertoli cell only syndrome. Since the gcd mutation arose from the insertion of over 100 kb of foreign DNA into the chromosome during a transgenic mouse experiment, fluorescent in situ hybridization with the transgene as a probe was used to determine the chromosomal position of the gcd locus. DAPI chromosomal banding in conjunction with double labeling with the alpha 1(I) collagen gene revealed that the gcd locus is situated on mouse Chromosome (Chr) 11A2-3. Two candidate genes, Lif and Oncostatin M, map near the gcd locus; however, Southern blot hybridization analysis revealed no gross rearrangements in these genes in gcd mice. The chromosomal position of the gcd locus will prove valuable in the search for other candidate genes as well as a landmark for positional cloning experiments. JF - Mammalian genome : official journal of the International Mammalian Genome Society AU - Duncan, M K AU - Lieman, J AU - Chada, K K AD - National Eye Institute, Laboratory of Molecular and Developmental Biology, Bethesda, Maryland 20892-2730, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 697 EP - 699 VL - 6 IS - 10 SN - 0938-8990, 0938-8990 KW - Globins KW - 9004-22-2 KW - Index Medicus KW - Animals KW - Mice, Inbred CBA KW - Cattle KW - Goats KW - Globins -- genetics KW - Mice, Inbred C57BL KW - Mice KW - Male KW - Female KW - Germ Cells KW - Infertility -- genetics KW - Chromosome Mapping KW - Mutagenesis, Insertional UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77755182?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mammalian+genome+%3A+official+journal+of+the+International+Mammalian+Genome+Society&rft.atitle=The+germ+cell+deficient+locus+maps+to+mouse+chromosome+11A2-3.&rft.au=Duncan%2C+M+K%3BLieman%2C+J%3BChada%2C+K+K&rft.aulast=Duncan&rft.aufirst=M&rft.date=1995-10-01&rft.volume=6&rft.issue=10&rft.spage=697&rft.isbn=&rft.btitle=&rft.title=Mammalian+genome+%3A+official+journal+of+the+International+Mammalian+Genome+Society&rft.issn=09388990&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-05 N1 - Date created - 1996-03-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isolation of homologous gene sequences by vectorette cloning. AN - 77751241; 8777041 JF - BioTechniques AU - Dyer, K D AU - Rosenberg, H F AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1886, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 550 EP - 552 VL - 19 IS - 4 SN - 0736-6205, 0736-6205 KW - DNA Primers KW - 0 KW - DNA, Viral KW - Neurotoxins KW - DNA KW - 9007-49-2 KW - Eosinophil-Derived Neurotoxin KW - EC 3.1.- KW - Ribonucleases KW - CTGCAG-specific type II deoxyribonucleases KW - EC 3.1.21.4 KW - Deoxyribonucleases, Type II Site-Specific KW - Ribonuclease, Pancreatic KW - EC 3.1.27.5 KW - Index Medicus KW - Humans KW - Neurotoxins -- genetics KW - Bacteriophages -- genetics KW - Nucleic Acid Hybridization KW - Polymerase Chain Reaction KW - Promoter Regions, Genetic KW - Base Sequence KW - Blotting, Southern KW - DNA, Viral -- analysis KW - Molecular Sequence Data KW - Ribonuclease, Pancreatic -- genetics KW - DNA -- isolation & purification KW - DNA -- chemistry KW - Cloning, Molecular -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77751241?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+homologous+gene+sequences+by+vectorette+cloning.&rft.au=Dyer%2C+K+D%3BRosenberg%2C+H+F&rft.aulast=Dyer&rft.aufirst=K&rft.date=1995-10-01&rft.volume=19&rft.issue=4&rft.spage=550&rft.isbn=&rft.btitle=&rft.title=BioTechniques&rft.issn=07366205&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-16 N1 - Date created - 1996-09-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 and K-ras in radon-associated lung adenocarcinoma. AN - 77748799; 8672998 AB - Mutations in the p53 tumor suppressor gene and the K-ras proto-oncogene are common genetic defects in lung cancer. Analysis of the patterns of damage in these genes may provide important insights into the mechanisms by which environmental mutagens initiate cancer. Previously, our laboratory found that a rare p53 codon 249 mutation (AGG(ARG) to ATG(MET) transversion) was present in 31% of a series of 52 large and squamous cell lung cancers from uranium miners, suggesting that this mutation might be a marker for radon exposure. In the current study, we analyzed 23 lung adenocarcinomas from the same cohort of highly exposed uranium miners. These tumors failed to show the codon 249 transversion, but 9 (39%) of 23 contained 1 or more mutations within hotspots in the K-ras gene. The results suggest that there is a histological tissue-type specificity for the codon 249 mutation; although this mutation was common in squamous and large cell tumors from very highly exposed uranium miners, it is rare in adenocarcinomas from the same cohort of miners. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - McDonald, J W AU - Taylor, J A AU - Watson, M A AU - Saccomanno, G AU - Devereux, T R AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. PY - 1995 SP - 791 EP - 793 VL - 4 IS - 7 SN - 1055-9965, 1055-9965 KW - Carcinogens, Environmental KW - 0 KW - Radon KW - Q74S4N8N1G KW - Index Medicus KW - Humans KW - Genes, ras -- genetics KW - Carcinogens, Environmental -- adverse effects KW - Genes, p53 -- genetics KW - Point Mutation KW - Lung Neoplasms -- genetics KW - Adenocarcinoma -- genetics KW - Radon -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77748799?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+research&rft.atitle=Acute+pulmonary+toxicity+of+copper+gallium+diselenide%2C+copper+indium+diselenide%2C+and+cadmium+telluride+intratracheally+instilled+into+rats.&rft.au=Morgan%2C+D+L%3BShines%2C+C+J%3BJeter%2C+S+P%3BWilson%2C+R+E%3BElwell%2C+M+P%3BPrice%2C+H+C%3BMoskowitz%2C+P+D&rft.aulast=Morgan&rft.aufirst=D&rft.date=1995-10-01&rft.volume=71&rft.issue=1&rft.spage=16&rft.isbn=&rft.btitle=&rft.title=Environmental+research&rft.issn=00139351&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-08-13 N1 - Date created - 1996-08-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Exposure to lead-acetate modulates the developmental expression of myelin genes in the rat frontal lobe. AN - 77739127; 8553899 AB - Postnatal exposure to high levels (4%) of lead (Pb) have been shown to disrupt myelin formation and result in abnormal conduction of nerve impulses, components necessary for information processing in the CNS. To investigate whether the pathological changes in myelin, due to Pb exposure, might be partially mediated by modulations of the expression of genes involved in CNS myelin, we have examined the developmental profiles of the proteolipid protein (PLP) and myelin basic protein (MBP), two major structural constituents of CNS myelin and 2',3'-cyclic nucleotide 3' phosphodiesterase (CNP), a non-structural enzyme associated with myelin formation. Rat pups were postnatally exposed, from birth to weaning, to moderate amounts of Pb (0.2%), in the drinking water of the dam, and their frontal cortices were assayed for changes in the expression profile of the above genes by Northern Analysis. On PND 20, Pb resulted in a dramatic stimulation of the mRNA levels of PLP and a small increase in MBP mRNA levels, but had no effect on the CNP message. These data suggest that moderate levels of Pb selectively interfere with the gene expression of structural proteins of CNS myelin and may thus influence the composition of myelin in this way. JF - International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience AU - Zawia, N H AU - Harry, G J AD - Laboratory of Biochemical Risk Assessment (LBRA), NIEHS, RTP, NC 27709, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 639 EP - 644 VL - 13 IS - 6 SN - 0736-5748, 0736-5748 KW - Myelin Basic Protein KW - 0 KW - Myelin Proteins KW - Myelin Proteolipid Protein KW - Organometallic Compounds KW - RNA, Messenger KW - 2',3'-Cyclic-Nucleotide Phosphodiesterases KW - EC 3.1.4.- KW - Phosphoric Diester Hydrolases KW - 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase KW - EC 3.1.4.37 KW - Cnp protein, rat KW - lead acetate KW - RX077P88RY KW - Index Medicus KW - Rats KW - Animals, Suckling KW - Animals, Newborn KW - Animals KW - Analysis of Variance KW - Myelin Basic Protein -- genetics KW - Weaning KW - 2',3'-Cyclic-Nucleotide Phosphodiesterases -- genetics KW - Myelin Proteolipid Protein -- genetics KW - Organometallic Compounds -- poisoning KW - RNA, Messenger -- metabolism KW - Frontal Lobe -- drug effects KW - Frontal Lobe -- metabolism KW - Frontal Lobe -- growth & development KW - Myelin Proteins -- genetics KW - Gene Expression Regulation, Developmental -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77739127?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+developmental+neuroscience+%3A+the+official+journal+of+the+International+Society+for+Developmental+Neuroscience&rft.atitle=Exposure+to+lead-acetate+modulates+the+developmental+expression+of+myelin+genes+in+the+rat+frontal+lobe.&rft.au=Zawia%2C+N+H%3BHarry%2C+G+J&rft.aulast=Zawia&rft.aufirst=N&rft.date=1995-10-01&rft.volume=13&rft.issue=6&rft.spage=639&rft.isbn=&rft.btitle=&rft.title=International+journal+of+developmental+neuroscience+%3A+the+official+journal+of+the+International+Society+for+Developmental+Neuroscience&rft.issn=07365748&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-22 N1 - Date created - 1996-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacokinetics and pharmacodynamics of cocaine. AN - 77736048; 8926741 AB - A dramatic shift has occurred over the last decade in the route of cocaine administration by drug abusers in the United States. The favored route has changed from intranasal and intravenous use to administration of cocaine ("crack") by the smoking route. The reasons for this shift are not well understood but may include social and environmental factors such as the ease and convenience of the smoking route, avoidance of needle-transmitted disease, and possible pharmacological differences produced by the different routes of administration. This study examined the influences exerted by changes in the route of administration on pharmacokinetic parameters and drug-induced behavioral and physiological effects of cocaine. Six male subjects who provided informed consent and had a recent history of cocaine use by the intravenous and smoked routes participated in a blind, double-dummy, crossover study conducted on a clinical research ward. On different occasions, subjects received single doses of cocaine by the intravenous (25 mg, cocaine HCl), intranasal (32 mg, cocaine HCl), and smoked (42 mg, cocaine base) routes. Physiological and behavioral measures were collected prior to and periodically after drug administration. Concurrent blood samples were collected and analyzed for cocaine and metabolites by gas chromatography-mass spectrometry, Plasma concentrations of cocaine and benzoylecgonine were fitted to pharmacokinetic models by nonlinear regression analysis. Behavioral measures of "good" drug effects and "liking" were higher by the smoked route than the intravenous route, but physiological changes were approximately equal at equivalent plasma concentrations of cocaine. Intranasal cocaine administration was characterized by lower cocaine plasma concentrations and a slower onset of pharmacological effects that were generally of lesser magnitude than those observed by other routes of administration. Overall, this study demonstrated that cocaine administration by the smoked route produced substantially higher behavioral responses than an equivalent dose of cocaine administered by the intravenous route. This finding suggests that smoked cocaine (crack) has a higher abuse liability and greater dependence-producing properties than equivalent doses of cocaine administered by the intravenous or intranasal route. JF - Journal of analytical toxicology AU - Cone, E J AD - Addiction Research Center, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 459 EP - 478 VL - 19 IS - 6 SN - 0146-4760, 0146-4760 KW - Street Drugs KW - 0 KW - benzoylecgonine KW - 5353I8I6YS KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Regression Analysis KW - Double-Blind Method KW - Injections, Intravenous KW - Humans KW - Biological Availability KW - Heart Rate -- drug effects KW - Administration, Intranasal KW - Adult KW - Cross-Over Studies KW - Gas Chromatography-Mass Spectrometry KW - Administration, Inhalation KW - Opioid-Related Disorders -- blood KW - Male KW - Cocaine -- analogs & derivatives KW - Cocaine -- pharmacokinetics KW - Cocaine -- pharmacology KW - Cocaine -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77736048?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+analytical+toxicology&rft.atitle=Pharmacokinetics+and+pharmacodynamics+of+cocaine.&rft.au=Cone%2C+E+J&rft.aulast=Cone&rft.aufirst=E&rft.date=1995-10-01&rft.volume=19&rft.issue=6&rft.spage=459&rft.isbn=&rft.btitle=&rft.title=Journal+of+analytical+toxicology&rft.issn=01464760&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-21 N1 - Date created - 1996-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intravenous cysteamine therapy for nephropathic cystinosis. AN - 77720603; 8559613 AB - A 4-y-old boy with nephropathic cystinosis and gastrointestinal dysmotility of unknown etiology was treated with i.v. cysteamine over a period of 10 mo. Thirty minutes after a dose of 10 mg/kg cysteamine free base, the leukocyte cystine value had fallen from 11.9 to 4.9 nmol of half-cystine/mg of protein. When cysteamine was given every 6 h, the leukocyte cystine concentration, measured 5-7 h after a dose, decreased with increasing cysteamine doses up to 17 mg/kg; at this dose the cystine value was 1.1 nmol of half-cystine/mg of protein, or 9% of the untreated value. Oral administration of approximately 16 mg/kg per dose every 6 h to this patient over the previous 3 y achieved similar leukocyte cystine depletion, to 1.2 nmol of half-cystine/mg of protein. The plasma cysteamine concentration 30 min after a dose of 10 mg/kg was 71 microM; 5-7 h after a dose of up to 20 mg/kg, the concentration was below 5 microM. Dimethylsulfide was elevated in the breath and urine of this boy after, but not before, the initiation of i.v. cysteamine therapy. Ten months after the start of therapy, the patient tolerated 250 mg (14 mg/kg) every 8 h. Adverse effects of this treatment included lethargy and increased nausea and vomiting when a schedule of therapy every 6 h was attempted. This investigation demonstrates that cysteamine given through a central venous catheter is effective in reducing leukocyte cystine levels. JF - Pediatric research AU - Gahl, W A AU - Ingelfinger, J AU - Mohan, P AU - Bernardini, I AU - Hyman, P E AU - Tangerman, A AD - Section on Human Biochemical Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-1830, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 579 EP - 584 VL - 38 IS - 4 SN - 0031-3998, 0031-3998 KW - Sulfides KW - 0 KW - Cystine KW - 48TCX9A1VT KW - Cysteamine KW - 5UX2SD1KE2 KW - dimethyl sulfide KW - QS3J7O7L3U KW - Index Medicus KW - Leukocytes -- metabolism KW - Gastrointestinal Diseases -- complications KW - Gastrointestinal Motility KW - Gastrointestinal Diseases -- pathology KW - Sulfides -- urine KW - Injections, Intravenous KW - Sulfides -- metabolism KW - Humans KW - Cystine -- blood KW - Microscopy, Electron KW - Male KW - Child, Preschool KW - Cysteamine -- administration & dosage KW - Cystinosis -- drug therapy KW - Cysteamine -- adverse effects KW - Cystinosis -- complications KW - Cysteamine -- therapeutic use KW - Cystinosis -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77720603?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatric+research&rft.atitle=Intravenous+cysteamine+therapy+for+nephropathic+cystinosis.&rft.au=Gahl%2C+W+A%3BIngelfinger%2C+J%3BMohan%2C+P%3BBernardini%2C+I%3BHyman%2C+P+E%3BTangerman%2C+A&rft.aulast=Gahl&rft.aufirst=W&rft.date=1995-10-01&rft.volume=38&rft.issue=4&rft.spage=579&rft.isbn=&rft.btitle=&rft.title=Pediatric+research&rft.issn=00313998&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-26 N1 - Date created - 1996-02-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Only controls: effect of handling, sham injection, and intraperitoneal injection of saline on behavior of mice in an elevated plus-maze. AN - 77702872; 8563035 AB - In male NIH-Swiss mice intraperitoneal injection of physiological saline significantly diminished (vs. naive mice) the ratio of the number of entries into open arms over the sum of entries into open and closed arms, and significantly prolonged time spent in closed arms. These two effects are considered to be typical for anxiety-inducing drugs (anxiogens). The time spent in open arms and at the intersection was unaffected. An equal number of entries into closed and also open arms was observed among fast- and slow-moving individuals. This is an argument against using the number of entries into arms as a measure of locomotor activity of mice. Additional measurement of locomotor activity in actometers is needed to check whether drugs used in experiments with elevated plus-maze alter locomotor activity. Injection of saline significantly shortened the latency of reaching one of the closed arms from the free end of an open arm. Handling, sham injection, and injection significantly diminished the shortening of latency in a second experiment (vs the latency in the first one), a parameter used as a criterion of memory and learning. Thus, saline-treated groups taken as controls in pharmacological experiments possess the behavioral profile of stressed and anxious animals in an elevated plus-maze, a device used as a model of anxiety and a model for studying memory and learning in mice and rats. JF - Journal of pharmacological and toxicological methods AU - Lapin, I P AD - Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 73 EP - 77 VL - 34 IS - 2 SN - 1056-8719, 1056-8719 KW - Sodium Chloride KW - 451W47IQ8X KW - Index Medicus KW - Injections, Intraperitoneal KW - Animals KW - Analysis of Variance KW - Mice KW - Male KW - Behavior, Animal -- drug effects KW - Maze Learning -- drug effects KW - Sodium Chloride -- toxicity KW - Sodium Chloride -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77702872?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+pharmacological+and+toxicological+methods&rft.atitle=Only+controls%3A+effect+of+handling%2C+sham+injection%2C+and+intraperitoneal+injection+of+saline+on+behavior+of+mice+in+an+elevated+plus-maze.&rft.au=Lapin%2C+I+P&rft.aulast=Lapin&rft.aufirst=I&rft.date=1995-10-01&rft.volume=34&rft.issue=2&rft.spage=73&rft.isbn=&rft.btitle=&rft.title=Journal+of+pharmacological+and+toxicological+methods&rft.issn=10568719&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-07 N1 - Date created - 1996-03-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Diagnostic analysis, clinical importance and molecular basis of dihydropyrimidine dehydrogenase deficiency. AN - 77656390; 7491709 JF - Trends in pharmacological sciences AU - Gonzalez, F J AU - Fernandez-Salguero, P AD - Laboratory of Molecular Carcinogenesis, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 325 EP - 327 VL - 16 IS - 10 SN - 0165-6147, 0165-6147 KW - Antineoplastic Agents KW - 0 KW - Oxidoreductases KW - EC 1.- KW - Dihydrouracil Dehydrogenase (NADP) KW - EC 1.3.1.2 KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Fluorouracil -- adverse effects KW - Humans KW - Antineoplastic Agents -- adverse effects KW - Oxidoreductases -- metabolism KW - Purine-Pyrimidine Metabolism, Inborn Errors -- enzymology KW - Oxidoreductases -- chemistry KW - Oxidoreductases -- deficiency KW - Purine-Pyrimidine Metabolism, Inborn Errors -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77656390?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Diagnostic+analysis%2C+clinical+importance+and+molecular+basis+of+dihydropyrimidine+dehydrogenase+deficiency.&rft.au=Gonzalez%2C+F+J%3BFernandez-Salguero%2C+P&rft.aulast=Gonzalez&rft.aufirst=F&rft.date=1995-10-01&rft.volume=16&rft.issue=10&rft.spage=325&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 - 1996-01-04 N1 - Date created - 1996-01-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Trends Pharmacol Sci. 1996 Mar;17(3):106-7 [8936346] Trends Pharmacol Sci. 1998 Jul;19(7):252 [9703754] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Binding of human prothymosin alpha to the leucine-motif/activation domains of HTLV-I Rex and HIV-1 Rev. AN - 77655647; 7588773 AB - Rex of human T-cell leukemia virus type I (HTLV-I) and Rev of human immunodeficiency virus 1 (HIV-1) are post-transcriptional regulators of viral gene expression. By means of affinity chromatography, we purified an 18-kDa cellular protein that bound to the conserved leucine-motif/activation domain of HTLV-I Rex or HIV-1 Rev. The protein that was purified through a Rev-affinity column was found to bind to Rex immunoprecipitated with anti-Rex IgG from an HTLV-I-producing cell line. We analyzed the purified approximately 18-kDa protein biochemically and identified it as prothymosin alpha. The binding activity of prothymosin alpha to Rev or Rex was completely abolished when the epsilon-amino groups of its lysine residues were chemically modified by N-succinimidyl-3-(4-hydroxy-3,5-diodo- phenyl)propionate. The functional relationship between the nuclear protein prothymosin alpha and Rex-Rev is discussed. JF - European journal of biochemistry AU - Kubota, S AU - Adachi, Y AU - Copeland, T D AU - Oroszlan, S AD - Laboratory of Molecular Virology and Carcinogenesis, NCI-Frederick Cancer Research and Development Center, MD 21702, USA. Y1 - 1995/10/01/ PY - 1995 DA - 1995 Oct 01 SP - 48 EP - 54 VL - 233 IS - 1 SN - 0014-2956, 0014-2956 KW - Carrier Proteins KW - 0 KW - Gene Products, rev KW - Gene Products, rex KW - Protein Precursors KW - prothymosin alpha KW - rev Gene Products, Human Immunodeficiency Virus KW - Thymosin KW - 61512-21-8 KW - Index Medicus KW - AIDS/HIV KW - Chromatography, Affinity KW - Carrier Proteins -- metabolism KW - Humans KW - Carrier Proteins -- genetics KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Precipitin Tests KW - Protein Binding KW - Cell Line KW - Carrier Proteins -- isolation & purification KW - Binding Sites KW - Gene Products, rex -- metabolism KW - HIV-1 -- genetics KW - HIV-1 -- chemistry KW - Protein Precursors -- metabolism KW - Human T-lymphotropic virus 1 -- chemistry KW - Protein Precursors -- genetics KW - Thymosin -- isolation & purification KW - Thymosin -- genetics KW - Human T-lymphotropic virus 1 -- metabolism KW - Gene Products, rev -- isolation & purification KW - Gene Products, rex -- isolation & purification KW - HIV-1 -- metabolism KW - Human T-lymphotropic virus 1 -- genetics KW - Gene Products, rev -- metabolism KW - Gene Products, rex -- genetics KW - Gene Products, rev -- genetics KW - Thymosin -- analogs & derivatives KW - Protein Precursors -- isolation & purification KW - Thymosin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77655647?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepatology+%28Baltimore%2C+Md.%29&rft.atitle=Expression+of+transforming+growth+factor+alpha+in+the+liver+before+and+after+interferon+alfa+therapy+for+chronic+hepatitis+B.&rft.au=Morimitsu%2C+Y%3BKleiner%2C+D+E%3BConjeevaram%2C+H+S%3BHsia%2C+C+C%3BDi+Bisceglie%2C+A+M%3BTabor%2C+E&rft.aulast=Morimitsu&rft.aufirst=Y&rft.date=1995-10-01&rft.volume=22&rft.issue=4+Pt+1&rft.spage=1021&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 - 1995-12-14 N1 - Date created - 1995-12-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of transforming growth factor alpha in the liver before and after interferon alfa therapy for chronic hepatitis B. AN - 77585133; 7557846 AB - The effect of interferon alfa (IFN-alpha) therapy on the expression of transforming growth factor alpha (TGF-alpha) in the liver during chronic hepatitis B was investigated. Serial liver biopsy specimens were evaluated from 35 patients who had participated in a randomized, controlled trial of recombinant human IFN-alpha for the treatment of chronic hepatitis B. Percutaneous liver biopsy specimens obtained before and 1 year after entry in the trial were sectioned and stained with a monoclonal antibody to TGF-alpha in an avidin-biotin-peroxidase-complex system. The expression of TGF-alpha in each section was evaluated blindly (with respect to treatment group and order of biopsies) and was numerically scored. There was no significant difference in TGF-alpha expression before or after therapy between 13 patients receiving daily IFN-alpha, 13 receiving alternate-day IFN-alpha, and 9 receiving no therapy. Sustained clearance of HBV-DNA and DNA polymerase activity occurred in 8 of 26 treated patients ("responders"); the 18 other patients were "nonresponders." Expression of TGF-alpha before IFN-alpha therapy was significantly higher in responders than in nonresponders; after IFN-alpha therapy, TGF-alpha expression decreased significantly among responders compared with nonresponders and untreated controls. Thus, the level of expression of TGF-alpha in the liver, which was correlated with the severity of inflammation in the liver in this study, appeared to be predictive of the response to IFN-alpha therapy in chronic hepatitis B, with a higher level of expression indicating a greater likelihood that the patient would respond. JF - Hepatology (Baltimore, Md.) AU - Morimitsu, Y AU - Kleiner, D E AU - Conjeevaram, H S AU - Hsia, C C AU - Di Bisceglie, A M AU - Tabor, E AD - Biological Carcinogenesis Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 1021 EP - 1026 VL - 22 IS - 4 Pt 1 SN - 0270-9139, 0270-9139 KW - Antiviral Agents KW - 0 KW - Hepatitis B Surface Antigens KW - Interferon Type I KW - Recombinant Proteins KW - Transforming Growth Factor alpha KW - Alanine Transaminase KW - EC 2.6.1.2 KW - Index Medicus KW - Alanine Transaminase -- blood KW - Hepatitis B Surface Antigens -- analysis KW - Humans KW - Adult KW - Middle Aged KW - Immunohistochemistry KW - Male KW - Female KW - Antiviral Agents -- therapeutic use KW - Liver -- virology KW - Liver -- pathology KW - Hepatitis B -- pathology KW - Hepatitis B -- metabolism KW - Interferon Type I -- therapeutic use KW - Liver -- metabolism KW - Transforming Growth Factor alpha -- metabolism KW - Hepatitis B -- virology KW - Hepatitis B -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77585133?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepatology+%28Baltimore%2C+Md.%29&rft.atitle=Expression+of+transforming+growth+factor+alpha+in+the+liver+before+and+after+interferon+alfa+therapy+for+chronic+hepatitis+B.&rft.au=Morimitsu%2C+Y%3BKleiner%2C+D+E%3BConjeevaram%2C+H+S%3BHsia%2C+C+C%3BDi+Bisceglie%2C+A+M%3BTabor%2C+E&rft.aulast=Morimitsu&rft.aufirst=Y&rft.date=1995-10-01&rft.volume=22&rft.issue=4+Pt+1&rft.spage=1021&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 - 1995-11-03 N1 - Date created - 1995-11-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Quantitative analysis of multiple phenotype enzyme-altered foci in rat hepatocarcinogenesis experiments: the multipath/multistage model. AN - 77584416; 7586158 AB - The promotional effect of phenobarbital and 1-hydroxymethyl-pyren on enzyme altered lesions in the rat liver were quantified within the framework of two separate multipath/multistage models. The experiment analyzed followed an initiation-promotion protocol in which female Wistar rats were initiated with a single dose of diethylnitrosamine at 0.15 mumol/g body wt followed by a 3 week treatment-free period. A promotor, 1-hydroxymethyl-pyren or phenobarbital was then administered continuously in the diet for 120 days. All animals were sacrificed 3 weeks after treatment and their livers were examined for enzyme histological changes. Focal lesions were classified into three phenotype categories: adenosine triphosphatase altered (ATPase), sulfotransferase altered (ST) and jointly altered lesions (ATPase and ST). Quantitative methods were used to analyze the data, which consisted of the number and sizes of these enzyme-altered lesions. Both multipath/multistage models fitted to the data clearly demonstrate that phenobarbital promotion produced more observable and larger foci than promotion via 1-hydroxymethyl-pyren and that the growth kinetics of the jointly altered lesions were elevated relative to the lesions expressing a single marker. It was not possible with these data to determine if there was a predominant sequence in the formation of jointly altered lesions. JF - Carcinogenesis AU - Sherman, C D AU - Portier, C J AD - Laboratory of Quantitative and Computational Biology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 2499 EP - 2506 VL - 16 IS - 10 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - Pyrenes KW - 1-hydroxymethylpyrene KW - 24463-15-8 KW - Sulfotransferases KW - EC 2.8.2.- KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Rats KW - Phenotype KW - Animals KW - Precancerous Conditions -- chemically induced KW - Rats, Wistar KW - Diet KW - Precancerous Conditions -- pathology KW - Precancerous Conditions -- enzymology KW - Female KW - Mathematics KW - Sulfotransferases -- genetics KW - Sulfotransferases -- metabolism KW - Liver -- enzymology KW - Liver -- pathology KW - Carcinogens -- administration & dosage KW - Adenosine Triphosphatases -- metabolism KW - Carcinogens -- toxicity KW - Liver Neoplasms, Experimental -- enzymology KW - Liver Neoplasms, Experimental -- chemically induced KW - Models, Biological KW - Phenobarbital -- administration & dosage KW - Pyrenes -- toxicity KW - Liver Neoplasms, Experimental -- pathology KW - Liver -- drug effects KW - Pyrenes -- administration & dosage KW - Phenobarbital -- toxicity KW - Adenosine Triphosphatases -- genetics KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77584416?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Quantitative+analysis+of+multiple+phenotype+enzyme-altered+foci+in+rat+hepatocarcinogenesis+experiments%3A+the+multipath%2Fmultistage+model.&rft.au=Sherman%2C+C+D%3BPortier%2C+C+J&rft.aulast=Sherman&rft.aufirst=C&rft.date=1995-10-01&rft.volume=16&rft.issue=10&rft.spage=2499&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-28 N1 - Date created - 1995-11-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of macrophage colony-stimulating factor on antifungal activity of mononuclear phagocytes against Aspergillus fumigatus. AN - 77581347; 7561176 AB - The effects of recombinant human macrophage colony-stimulating factor (M-CSF) on antifungal activity of human monocytes (MNC), MNC-derived macrophages (MDM), and rabbit pulmonary alveolar macrophages (PAM) against Aspergillus fumigatus were studied. MNC-induced hyphal damage was augmented by incubation with M-CSF (P = .027); PAM-induced hyphal damage was moderately enhanced by M-CSF (P = .046). Phagocytosis of Aspergillus conidia by MDM and PAM was strongly enhanced by M-CSF (P < .01). MNC pretreated with M-CSF exhibited enhanced superoxide anion production in response to PMA (P = .026). This effect was not associated with increased levels of mRNA transcripts of the components of NADPH oxidase, the enzyme responsible for superoxide anion production. M-CSF augments antifungal activity of mononuclear phagocytes against both conidia and hyphae of Aspergillus fumigatus partly by enhancement of oxidation-dependent mechanisms and may have an important immunomodulatory role in prevention and treatment of invasive aspergillosis in leukopenic patients. JF - The Journal of infectious diseases AU - Roilides, E AU - Sein, T AU - Holmes, A AU - Chanock, S AU - Blake, C AU - Pizzo, P A AU - Walsh, T J AD - Infectious Diseases Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 1028 EP - 1034 VL - 172 IS - 4 SN - 0022-1899, 0022-1899 KW - Recombinant Proteins KW - 0 KW - Superoxides KW - 11062-77-4 KW - Macrophage Colony-Stimulating Factor KW - 81627-83-0 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Superoxides -- metabolism KW - Recombinant Proteins -- pharmacology KW - Dose-Response Relationship, Drug KW - Humans KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Bronchoalveolar Lavage KW - Rabbits KW - Cell Separation KW - Macrophages, Alveolar -- drug effects KW - Aspergillosis -- immunology KW - Macrophage Colony-Stimulating Factor -- pharmacology KW - Phagocytes -- drug effects KW - Leukocytes, Mononuclear -- drug effects KW - Aspergillus fumigatus -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77581347?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Nodules+of+less-differentiated+tumor+within+or+adjacent+to+hepatocellular+carcinoma%3A+relative+expression+of+transforming+growth+factor-alpha+and+its+receptor+in+the+different+areas+of+tumor.&rft.au=Morimitsu%2C+Y%3BHsia%2C+C+C%3BKojiro%2C+M%3BTabor%2C+E&rft.aulast=Morimitsu&rft.aufirst=Y&rft.date=1995-10-01&rft.volume=26&rft.issue=10&rft.spage=1126&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 - 1995-11-03 N1 - Date created - 1995-11-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential in vivo mutagenicity of the carcinogen/non-carcinogen pair 2,4- and 2,6-diaminotoluene. AN - 77578912; 7586147 AB - The aromatic amines 2,4-diaminotoluene (2,4-DAT) and 2,6-diaminotoluene (2,6-DAT) are structural isomers that have been extensively studied for their mutagenic and carcinogenic characteristics. Both compounds are equally mutagenic in the Ames/Salmonella assay in the presence of S9. However, the differences in the results of chronic rodent carcinogen bioassays using these two compounds are significant, in that 2,4-DAT is a potent hepatocarcinogen, whereas 2,6-DAT does not produce an increased incidence of tumors in rats or mice at similar doses. The Big Blue transgenic B6C3F1 mouse carries multiple copies of bacteriophage lambda, each with a lacI mutational target gene, integrated into mouse chromosome 4. Our studies were designed to determine whether the Big Blue system could be used to detect differences in the in vivo mutagenic activity between the carcinogen/non-carcinogen pair 2,4- and 2,6-DAT and to determine whether the in vivo mutagenesis assay results correspond to the rodent carcinogen bioassay results. Male B6C3F1 transgenic mice were exposed to 2,4- or 2,6-DAT at 0 or 1000 p.p.m. in the diet for 30 and 90 days. Mice serving as positive controls were administered five daily i.p. injections of 6 mg/kg dimethylnitrosamine (DMN) in saline and were sacrificed 15 days following the last injection. Mutant frequencies at lacI were determined by recovering the genomically integrated lambda phage using an in vitro packaging reaction followed by infection of an appropriate Escherichia coli host. Complete non-sectored blue mutant plaques were scored against a background of clear non-mutant plaques. Mutant frequencies were nearly identical for all three groups at 30 days, while at 90 days the mutant frequency for the hepatocarcinogen 2,4-DAT (12.1 +/- 1.4 x 10(-5)) was significantly higher (P < 0.01) as compared with both age-matched (spontaneous) controls (5.7 +/- 2.9 x 10(-5)) and the 2,6-DAT-exposed group (5.7 +/- 2.4 x 10(-5)). Mutations at lacI arising ex vivo during replication in E. coli are observed in this system as sectored blue plaques. The sectored plaque frequency in this study was constant across all groups at approximately 9.0 x 10(-5). Results from this study demonstrate that the Big Blue transgenic mutation assay: (i) can distinguish differences in vivo between the mutagenic responses of a carcinogen and a non-carcinogen which elicited comparable mutagenic activity in S.typhimurium; (ii) is sensitive to mutagens through subchronic dietary exposure; and (iii) yields a differential response depending upon the length of time mice are exposed to a mutagen. JF - Carcinogenesis AU - Hayward, J J AU - Shane, B S AU - Tindall, K R AU - Cunningham, M L AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research, Triangle Park, NC 27709, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 2429 EP - 2433 VL - 16 IS - 10 SN - 0143-3334, 0143-3334 KW - Bacterial Proteins KW - 0 KW - Carcinogens KW - Escherichia coli Proteins KW - Lac Repressors KW - LacI protein, E coli KW - Mutagens KW - Phenylenediamines KW - Repressor Proteins KW - DNA KW - 9007-49-2 KW - 2,6-diaminotoluene KW - H838Q10551 KW - 2,4-diaminotoluene KW - IS1AKN4HYB KW - Dimethylnitrosamine KW - M43H21IO8R KW - Index Medicus KW - Repressor Proteins -- biosynthesis KW - Animals KW - Bacterial Proteins -- genetics KW - Genes, Bacterial KW - Bacterial Proteins -- biosynthesis KW - Bacteriophage lambda -- genetics KW - Dimethylnitrosamine -- toxicity KW - Microsomes, Liver -- metabolism KW - Escherichia coli -- genetics KW - Salmonella typhimurium -- drug effects KW - Mice KW - Virus Integration KW - Mice, Transgenic KW - Repressor Proteins -- genetics KW - DNA -- drug effects KW - Rats KW - Mice, Inbred Strains KW - DNA -- isolation & purification KW - Mutagenicity Tests KW - Neoplasms, Experimental -- chemically induced KW - Biotransformation KW - Male KW - Phenylenediamines -- toxicity KW - Carcinogens -- toxicity KW - Mutagens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77578912?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Differential+in+vivo+mutagenicity+of+the+carcinogen%2Fnon-carcinogen+pair+2%2C4-+and+2%2C6-diaminotoluene.&rft.au=Hayward%2C+J+J%3BShane%2C+B+S%3BTindall%2C+K+R%3BCunningham%2C+M+L&rft.aulast=Hayward&rft.aufirst=J&rft.date=1995-10-01&rft.volume=16&rft.issue=10&rft.spage=2429&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-28 N1 - Date created - 1995-11-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chromium(VI)-induced nuclear factor-kappa B activation in intact cells via free radical reactions. AN - 77578875; 7586142 AB - Incubation of chromium(VI) [Cr(VI)] with cultured Jurkat cells resulted in activation of DNA binding activity of the nuclear factor (NF)-kappa B. In a combination with glutathione reductase, a Cr(VI) reducing agent, Cr(VI) expressed an enhanced activity in induction of NF-kappa B. This activation of NF-kappa B was decreased by a metal chelator, diethylene-triaminepentaacetic acid or catalase, but increased by superoxide dismutase. Addition of Mn2+, which reacts with Cr(IV) and inhibits Cr(IV)-mediated hydroxyl radical (.OH) generation via Fenton-like reaction, attenuated the activation of NF-kappa B. Sodium formate, an .OH radical scavenger, also inhibited the activation. Electron spin resonance measurements showed that the incubation of Cr(VI) with intact Jurkat cells generated reactive Cr(V) intermediate. Glutathione reductase and NADPH enhanced Cr(V) generation. Electron spin resonance spin trapping measurements using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spin trapping agent provided evidence that the incubation of Cr(VI) with the Jurkat cells in the presence of glutathione reductase generated .OH radicals. H2O2 enhanced .OH radical generation and also enhanced Cr(V) formation, indicating the role of Cr(IV) in .OH radical generation. We conclude that Cr(VI) can activate NF-kappa B in vitro via Cr(IV)-mediated free radical reactions. We hypothesize that Cr(VI)-mediated NF-kappa B activation may be involved in the mechanism of Cr(VI)-induced carcinogenicity. JF - Carcinogenesis AU - Ye, J AU - Zhang, X AU - Young, H A AU - Mao, Y AU - Shi, X AD - Laboratory of Experimental Immunology, National Cancer Institute, Frederick, MD 21702, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 2401 EP - 2405 VL - 16 IS - 10 SN - 0143-3334, 0143-3334 KW - Cyclic N-Oxides KW - 0 KW - Formates KW - Free Radical Scavengers KW - Free Radicals KW - NF-kappa B KW - Oligodeoxyribonucleotides KW - Receptors, Interleukin-2 KW - Spin Labels KW - formic acid KW - 0YIW783RG1 KW - Hydroxyl Radical KW - 3352-57-6 KW - 5,5-dimethyl-1-pyrroline-1-oxide KW - 7170JZ1QF3 KW - Potassium Dichromate KW - T4423S18FM KW - Index Medicus KW - Hydroxyl Radical -- metabolism KW - Humans KW - Oligodeoxyribonucleotides -- chemical synthesis KW - Receptors, Interleukin-2 -- genetics KW - Free Radicals -- metabolism KW - Binding Sites KW - Promoter Regions, Genetic KW - Base Sequence KW - Tumor Cells, Cultured KW - Oligodeoxyribonucleotides -- chemistry KW - Electron Spin Resonance Spectroscopy KW - Molecular Sequence Data KW - Formates -- pharmacology KW - Oligodeoxyribonucleotides -- metabolism KW - Lymphoma KW - Cell Line KW - Free Radical Scavengers -- pharmacology KW - Potassium Dichromate -- pharmacology KW - NF-kappa B -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77578875?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chromium%28VI%29-induced+nuclear+factor-kappa+B+activation+in+intact+cells+via+free+radical+reactions.&rft.au=Ye%2C+J%3BZhang%2C+X%3BYoung%2C+H+A%3BMao%2C+Y%3BShi%2C+X&rft.aulast=Ye&rft.aufirst=J&rft.date=1995-10-01&rft.volume=16&rft.issue=10&rft.spage=2401&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-28 N1 - Date created - 1995-11-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytokine interactions in human immunodeficiency virus-infected individuals: roles of interleukin (IL)-2, IL-12, and IL-15. AN - 77578276; 7561680 AB - Cytokines have been shown to be powerful regulators of the immune response. In this study, we analyze the effect that the newly recognized cytokine interleukin (IL)-15 has on proliferation and cytokine induction using peripheral blood mononuclear cells (PBMCs) and purified CD4+ T cells from patients infected with human immunodeficiency virus (HIV) who are at various stages in their disease. We observed that IL-15 enhances the proliferative response in a dose-dependent manner from PBMCs of HIV-infected individuals when stimulated by polyclonal mitogen, tetanus toxoid, or HIV-specific antigen. The effects of exogenous IL-15 are substantially diminished by adding a neutralizing antibody to the beta chain of the IL-2 receptor. Moreover, the ability of IL-15 to increase proliferation is enhanced by the presence of endogenous IL-2 produced in the cultures. The effect that exogenous IL-15 had on IL-2, IL-4, and interferon (IFN)-gamma induction from PBMC's or CD4+ T cells in response to mitogen or tetanus toxoid was also examined. This was compared to the effect that exogenous IL-2 and IL-12 had under the same conditions. Addition of IL-2 or IL-15 to short-term in vitro cultures of either PBMCs or CD4+ T cells had little effect on IL-2, IL-4, or IFN-gamma production. By contrast, IL-12 caused substantial enhancement of both IL-2 and IFN-gamma production from these cultures. The role that endogenous cytokines have on IFN-gamma induction was also studied. Addition of a neutralizing antibody to the alpha chain of the IL-2 receptor or IL-12 to antigen stimulated cultures caused a striking decrease in IFN-gamma production. Neutralization of endogenous IL-15 also resulted in diminished IFN-gamma production from cultures stimulated with mitogen. IL-4 and IFN-gamma protein production by PBMCs and CD4+ T cells stimulated with mitogen was assessed to see if we could detect a specific bias of cytokine production. Small amounts of IL-4 were detected from CD4+ T cells but not PBMCs from most individuals tested. IFN-gamma and IL-2, however, were also produced from these same cultures. These results further elucidate the mechanism of cytokine regulation in HIV-infected individuals, and they provide evidence that IL-15 may be a useful immune modulator. JF - The Journal of experimental medicine AU - Seder, R A AU - Grabstein, K H AU - Berzofsky, J A AU - McDyer, J F AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/10/01/ PY - 1995 DA - 1995 Oct 01 SP - 1067 EP - 1077 VL - 182 IS - 4 SN - 0022-1007, 0022-1007 KW - HIV Antigens KW - 0 KW - Interleukin-15 KW - Interleukin-2 KW - Interleukins KW - Mitogens KW - Receptors, Interleukin-2 KW - Interleukin-12 KW - 187348-17-0 KW - Interferon-gamma KW - 82115-62-6 KW - Index Medicus KW - AIDS/HIV KW - Mitogens -- pharmacology KW - Interleukin-2 -- pharmacology KW - Drug Interactions KW - Humans KW - HIV Antigens -- pharmacology KW - Interleukin-2 -- biosynthesis KW - CD4-Positive T-Lymphocytes -- immunology KW - Interleukin-12 -- pharmacology KW - Receptors, Interleukin-2 -- immunology KW - Lymphocyte Activation -- drug effects KW - Interleukins -- pharmacology KW - HIV Infections -- immunology KW - Interferon-gamma -- biosynthesis KW - Leukocytes, Mononuclear -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77578276?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+experimental+medicine&rft.atitle=Cytokine+interactions+in+human+immunodeficiency+virus-infected+individuals%3A+roles+of+interleukin+%28IL%29-2%2C+IL-12%2C+and+IL-15.&rft.au=Seder%2C+R+A%3BGrabstein%2C+K+H%3BBerzofsky%2C+J+A%3BMcDyer%2C+J+F&rft.aulast=Seder&rft.aufirst=R&rft.date=1995-10-01&rft.volume=182&rft.issue=4&rft.spage=1067&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+experimental+medicine&rft.issn=00221007&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-20 N1 - Date created - 1995-11-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1976 Sep 10;193(4257):1007-8 [181845] J Immunol. 1995 Jul 15;155(2):785-95 [7608555] Am J Med. 1984 Jan;76(1):95-100 [6229182] Lancet. 1984 Mar 31;1(8379):698-702 [6143040] Clin Exp Immunol. 1984 Apr;56(1):14-7 [6609030] J Immunol. 1984 Sep;133(3):1313-7 [6235286] N Engl J Med. 1985 Jul 11;313(2):79-84 [2582258] Ann Intern Med. 1985 Nov;103(5):704-9 [2996403] N Engl J Med. 1985 Dec 5;313(23):1485-92 [3903508] Annu Rev Immunol. 1985;3:477-500 [2415141] J Immunol. 1986 Oct 15;137(8):2514-21 [3489767] Proc Natl Acad Sci U S A. 1989 Mar;86(6):1982-6 [2467293] Nature. 1989 Jun 1;339(6223):383-5 [2524668] J Infect Dis. 1992 Jun;165(6):1012-9 [1533867] J Clin Invest. 1993 Mar;91(3):759-65 [8450057] Immunol Today. 1993 Mar;14(3):107-11 [8096699] Science. 1993 Apr 23;260(5107):547-9 [8097338] Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10188-92 [7901851] Science. 1993 Dec 10;262(5140):1721-4 [7903123] J Exp Med. 1994 Apr 1;179(4):1273-83 [7908322] J Exp Med. 1994 Apr 1;179(4):1361-6 [7908324] Science. 1994 May 13;264(5161):965-8 [8178155] Science. 1994 Jul 8;265(5169):244-8 [8023142] Science. 1994 Jul 8;265(5169):248-52 [8023143] EMBO J. 1994 Jun 15;13(12):2822-30 [8026467] J Exp Med. 1994 Oct 1;180(4):1395-403 [7523571] Immunol Today. 1994 Oct;15(10):460-3 [7945769] J Immunol. 1994 Dec 1;153(11):5167-75 [7963574] Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12932-6 [7809149] N Engl J Med. 1995 Mar 2;332(9):567-75 [7646637] J Clin Immunol. 1983 Oct;3(4):332-40 [6606643] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Felbamate relieves several abnormal pain sensations in rats with an experimental peripheral neuropathy. AN - 77574725; 7562547 AB - The antiepileptic drug, felbamate, was tested in a rat model of painful peripheral neuropathy (the chronic constriction injury model). Intraperitoneal doses of 150, 300 and 600 mg/kg were given to animals with established heat-hyperalgesia, mechanohyperalgesia, mechano-allodynia and signs of spontaneous pain (hindpaw guarding). Postinjection tests were conducted 2, 6, 12, 24 and 48 h later. The 150 mg/kg dose had little or no effect on any measure. Significant reductions in all measures of abnormal pain were seen after the 300 and 600 mg/kg doses; relief lasted 2 to 12 h. Side effects were trivial or absent by 2 h postinjection. Felbamate's actions were generally antihyperalgesic and antiallodynic, rather than analgesic, in that the responsiveness of the control (sham-operated) hindpaw was unaffected. We conclude that felbamate suppresses neuropathic pain sensations and that its effectiveness may be due to multiple mechanisms of action. The recently discovered severe side-effect liability of felbamate is likely to preclude its clinical application. JF - The Journal of pharmacology and experimental therapeutics AU - Imamura, Y AU - Bennett, G J AD - Neurobiology and Anesthesiology Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 177 EP - 182 VL - 275 IS - 1 SN - 0022-3565, 0022-3565 KW - Analgesics KW - 0 KW - Anticonvulsants KW - Phenylcarbamates KW - Propylene Glycols KW - felbamate KW - X72RBB02N8 KW - Index Medicus KW - Rats KW - Behavior, Animal -- drug effects KW - Animals KW - Rats, Sprague-Dawley KW - Heating KW - Dose-Response Relationship, Drug KW - Pain Measurement -- drug effects KW - Hindlimb -- innervation KW - Hindlimb -- drug effects KW - Hyperalgesia KW - Male KW - Propylene Glycols -- pharmacology KW - Pain -- etiology KW - Anticonvulsants -- pharmacology KW - Pain -- drug therapy KW - Anticonvulsants -- adverse effects KW - Analgesics -- pharmacology KW - Peripheral Nervous System Diseases -- drug therapy KW - Analgesics -- adverse effects KW - Peripheral Nervous System Diseases -- complications KW - Propylene Glycols -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77574725?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Felbamate+relieves+several+abnormal+pain+sensations+in+rats+with+an+experimental+peripheral+neuropathy.&rft.au=Imamura%2C+Y%3BBennett%2C+G+J&rft.aulast=Imamura&rft.aufirst=Y&rft.date=1995-10-01&rft.volume=275&rft.issue=1&rft.spage=177&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-21 N1 - Date created - 1995-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Development of behavioral sensitization to cocaine: influence of kappa opioid receptor agonists. AN - 77574340; 7562544 AB - The effects of acute or repeated administrations of the selective kappa opioid receptor agonists U-69593 and U-50488H on cocaine-induced locomotor stimulation were examined in the rat. Acute administration of cocaine (10-30 mg/kg i.p.) produced a dose-dependent increase in locomotor activity. A single injection of U-69593 (0.04-0.32 mg/kg s.c.) or U-50488H (2.5-7.5 mg/kg s.c.) administered 15 min before cocaine did not modify the effects of an acute cocaine challenge. In contrast, repeated administration of U-69593 or U-50488H in combination with saline for 3 days prevented the acute locomotor-activating effects of cocaine. Repeated administration of cocaine (10-30 mg/kg i.p.) for 3 days resulted in an enhancement of its locomotor-activating effects, i.e., sensitization. No such sensitized responses were observed in animals that had received U-69593 or U-50488H in combination with the cocaine treatment regimen. Repeated administration of U-69593 (0.16 mg/kg s.c.) for 3 days failed to block the acute locomotor-activating effects of nicotine (0.6 mg/kg s.c.). Furthermore, when U-69593 was given in combination with nicotine, sensitized motor responses to a subsequent nicotine challenge were still observed. These data demonstrate that the repeated activation of kappa opioid receptors prevents the locomotor activation that occurs in response to an acute cocaine challenge as well as the sensitized motor responses that develop after the repeated administration of cocaine. JF - The Journal of pharmacology and experimental therapeutics AU - Heidbreder, C A AU - Babovic-Vuksanovic, D AU - Shoaib, M AU - Shippenberg, T S AD - National Institute on Drug Abuse, Intramural Research Program, Baltimore, Maryland, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 150 EP - 163 VL - 275 IS - 1 SN - 0022-3565, 0022-3565 KW - Analgesics KW - 0 KW - Benzeneacetamides KW - Pyrrolidines KW - Receptors, Opioid, kappa KW - Sodium Chloride KW - 451W47IQ8X KW - 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer KW - 67198-13-4 KW - Nicotine KW - 6M3C89ZY6R KW - Cocaine KW - I5Y540LHVR KW - U 69593 KW - J5S4K6TKTG KW - Index Medicus KW - Sensitivity and Specificity KW - Animals KW - Drug Administration Schedule KW - Drug Interactions KW - Dose-Response Relationship, Drug KW - Analgesics -- pharmacology KW - Locomotion -- drug effects KW - Rats KW - Rats, Sprague-Dawley KW - Nicotine -- pharmacology KW - Pyrrolidines -- pharmacology KW - Male KW - Sodium Chloride -- pharmacology KW - Behavior, Animal -- drug effects KW - Receptors, Opioid, kappa -- agonists KW - Cocaine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77574340?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Development+of+behavioral+sensitization+to+cocaine%3A+influence+of+kappa+opioid+receptor+agonists.&rft.au=Heidbreder%2C+C+A%3BBabovic-Vuksanovic%2C+D%3BShoaib%2C+M%3BShippenberg%2C+T+S&rft.aulast=Heidbreder&rft.aufirst=C&rft.date=1995-10-01&rft.volume=275&rft.issue=1&rft.spage=150&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-21 N1 - Date created - 1995-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Radon-exposed underground miners and inverse dose-rate (protraction enhancement) effects. AN - 77573566; 7558839 AB - Recent models for radon-induced lung cancer assume that at high levels of cumulative exposure, as experienced historically by many underground miners of uranium and other ores, the risk of lung cancer follows an inverse dose-rate (protraction enhancement) pattern. That is, for equal total dose, a greater risk is incurred by those whose total dose is accumulated at a lower rate over a longer duration than at a higher rate over a shorter duration. This inverse dose-rate effect is hypothesized to be the consequence of multiple traversals of the nucleus of a target cell by alpha particles. It has recently been concluded, however, that for low total doses, as in most residential settings, the inverse dose-rate effect should diminish and perhaps even disappear, since at very low doses the probability that more than one alpha particle would traverse a cell is small and there would be no possibility for interactions from multiple hits. Pooling original data from 11 cohort studies of underground miners, including nearly 1.2 million person-y of observation and 2,701 lung cancer deaths, we evaluate the presence of an inverse dose-rate effect and its modification by total dose. An inverse dose-rate effect was confirmed in each cohort, except one, and overall in the pooled data. There also appears to be a diminution of the inverse dose-rate effect below 50 Working Level Months (WLM), although analyses were necessarily hampered by a limited range of exposure rates at low total WLM. These data support both the presence of an inverse dose-rate effect, as well as its diminution at low total dose. As a consequence, assessment of risks of radon progeny exposure in homes (on average 15-20 WLM for a lifetime) using miner-based models should not assume an ever-increasing risk per unit dose. Rather, it is more appropriate to apply risk models that take into account protraction enhancement and its diminution. JF - Health physics AU - Lubin, J H AU - Boice, J D AU - Edling, C AU - Hornung, R W AU - Howe, G AU - Kunz, E AU - Kusiak, R A AU - Morrison, H I AU - Radford, E P AU - Samet, J M AD - Biostatistics Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 494 EP - 500 VL - 69 IS - 4 SN - 0017-9078, 0017-9078 KW - Radon KW - Q74S4N8N1G KW - Index Medicus KW - Radiation Dosage KW - Risk Factors KW - Humans KW - Lung Neoplasms -- etiology KW - Neoplasms, Radiation-Induced -- etiology KW - Occupational Exposure -- adverse effects KW - Mining KW - Radon -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77573566?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Radon-exposed+underground+miners+and+inverse+dose-rate+%28protraction+enhancement%29+effects.&rft.au=Lubin%2C+J+H%3BBoice%2C+J+D%3BEdling%2C+C%3BHornung%2C+R+W%3BHowe%2C+G%3BKunz%2C+E%3BKusiak%2C+R+A%3BMorrison%2C+H+I%3BRadford%2C+E+P%3BSamet%2C+J+M&rft.aulast=Lubin&rft.aufirst=J&rft.date=1995-10-01&rft.volume=69&rft.issue=4&rft.spage=494&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 - 1995-10-31 N1 - Date created - 1995-10-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A lysosomal targeting signal in the cytoplasmic tail of the beta chain directs HLA-DM to MHC class II compartments. AN - 77570256; 7593164 AB - In human B cells, class II molecules of the major histocompatibility complex (MHC-II) accumulate in an endosomal/lysosomal compartment, the MIIC, in which they may encounter and bind peptides. An additional molecule required for MHC-II peptide binding, HLA-DM (DM), has also been localized to the MIIC. Neither the relationship of the MIIC to the endosomal system nor the mechanisms by which DM localizes to the MIIC are understood. To address these issues, DM localization was analyzed in cells that do or do not express MHC-II. DM alpha beta heterodimers were localized in transfected MHC-II-negative HeLa and NRK cells, in the absence of the MHC-II-associated invariant chain, to a prelysosomal/lysosomal compartment by immunofluorescence microscopy. To identify a potential targeting determinant, we analyzed the localization of a chimeric protein, T-T-Mb, in which the cytoplasmic tail of murine DM beta (Mb) was appended to the lumenal and transmembrane domains of a cell surface protein, Tac. Like intact DM, T-T-Mb was localized to a lysosomal compartment in HeLa and NRK cells, as judged by immunofluorescence and immunoelectron microscopy. T-T-Mb was rapidly degraded in this compartment by a process that was blocked by inhibitors of lysosomal proteolysis. The DM beta cytoplasmic tail also mediated internalization of anti-Tac antibody from the cell surface and delivery to lysosomes. Deletion from the DM beta cytoplasmic tail of the tyrosine-based motif, YTPL, resulted in cell surface expression of T-T-Mb and a loss of both degradation and internalization; alanine scanning mutagenesis showed that the Y and L residues were critical for these functions. Similarly, mutation of the same Y residue within full-length DM beta resulted in cell surface expression of DM alpha beta heterodimers. Lastly, T-T-Mb was localized by immunoelectron microscopy to the MIIC in a human B lymphoblastoid cell line. Our results suggest that a motif, YTPL, in the cytoplasmic tail of the beta chain of DM is sufficient for targeting either to lysosomes or to the MIIC. JF - The Journal of cell biology AU - Marks, M S AU - Roche, P A AU - van Donselaar, E AU - Woodruff, L AU - Peters, P J AU - Bonifacino, J S AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 351 EP - 369 VL - 131 IS - 2 SN - 0021-9525, 0021-9525 KW - HLA-D Antigens KW - 0 KW - Histocompatibility Antigens Class II KW - Membrane Proteins KW - Recombinant Fusion Proteins KW - Index Medicus KW - Animals KW - Transfection KW - HeLa Cells KW - Fluorescent Antibody Technique, Indirect KW - Humans KW - Cell Compartmentation KW - Recombinant Fusion Proteins -- genetics KW - Biological Transport KW - Mice KW - Membrane Proteins -- genetics KW - Microscopy, Immunoelectron KW - Lysosomes -- physiology KW - Histocompatibility Antigens Class II -- ultrastructure KW - Lysosomes -- ultrastructure KW - Histocompatibility Antigens Class II -- physiology KW - HLA-D Antigens -- ultrastructure KW - HLA-D Antigens -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77570256?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=A+lysosomal+targeting+signal+in+the+cytoplasmic+tail+of+the+beta+chain+directs+HLA-DM+to+MHC+class+II+compartments.&rft.au=Marks%2C+M+S%3BRoche%2C+P+A%3Bvan+Donselaar%2C+E%3BWoodruff%2C+L%3BPeters%2C+P+J%3BBonifacino%2C+J+S&rft.aulast=Marks&rft.aufirst=M&rft.date=1995-10-01&rft.volume=131&rft.issue=4&rft.spage=524&rft.isbn=&rft.btitle=&rft.title=Substance+Abuse&rft.issn=08897077&rft_id=info:doi/10.1080%2F08897077.2014.995332 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-01 N1 - Date created - 1995-12-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Cell Biol. 1992 Sep;118(5):1027-40 [1512288] J Cell Biol. 1992 Nov;119(3):531-42 [1400590] J Biol Chem. 1993 Jan 25;268(3):1941-6 [8420968] J Cell Biol. 1993 Mar;120(5):1123-35 [8436587] J Exp Med. 1993 Mar 1;177(3):583-96 [8436902] Cell. 1993 Feb 26;72(4):635-48 [7679955] Blood. 1993 Mar 15;81(6):1607-13 [7680921] EMBO J. 1993 May;12(5):2219-28 [8491209] J Exp Med. 1993 Jun 1;177(6):1699-712 [8098731] Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8581-5 [8397411] J Biol Chem. 1988 Dec 15;263(35):18911-9 [3143719] J Biol Chem. 1988 Dec 15;263(35):18920-8 [3198605] J Biol Chem. 1989 Jan 25;264(3):1631-7 [2783582] EMBO J. 1989 Dec 1;8(12):3633-40 [2583113] Annu Rev Cell Biol. 1989;5:277-307 [2688707] J Cell Sci. 1989 Apr;92 ( Pt 4):701-12 [2689465] Science. 1990 Jan 5;247(4938):79-82 [2294595] Cell. 1990 Apr 6;61(1):171-83 [2156628] Nature. 1990 Jun 14;345(6276):615-8 [2190094] J Cell Biol. 1990 Sep;111(3):839-55 [2391366] J Cell Sci. 1993 Nov;106 ( Pt 3):831-46 [8308066] EMBO J. 1994 Feb 15;13(4):934-44 [8112308] J Biol Chem. 1994 Mar 11;269(10):7131-6 [8125922] Nature. 1994 Apr 7;368(6471):551-4 [8139689] Nature. 1994 Apr 7;368(6471):554-8 [8139690] J Cell Biol. 1994 May;125(3):595-605 [7909813] Nature. 1994 May 12;369(6476):113-20 [8177316] Nature. 1994 May 12;369(6476):120-6 [8177317] Nature. 1994 May 12;369(6476):147-51 [8177319] J Cell Biol. 1994 Jun;125(6):1225-37 [8207055] Annu Rev Immunol. 1994;12:259-93 [8011283] J Cell Biol. 1994 Jul;126(2):317-30 [8034737] J Immunol. 1994 Aug 15;153(4):1487-94 [8046228] J Cell Biol. 1994 Aug;126(4):979-89 [7519625] J Cell Biol. 1994 Sep;126(5):1157-72 [7914893] J Immunol. 1993 Oct 15;151(8):3988-98 [8409381] J Biol Chem. 1993 Oct 25;268(30):22853-62 [8226795] Annu Rev Cell Biol. 1993;9:129-61 [8280459] Cell. 1994 Jan 28;76(2):287-99 [8293464] Nature. 1970 Aug 15;227(5259):680-5 [5432063] Eur J Immunol. 1974 Feb;4(2):91-7 [4546942] Mol Immunol. 1979 Jan;16(1):51-60 [376435] J Immunol. 1981 Apr;126(4):1393-7 [6970774] Cell. 1982 May;29(1):61-9 [6955026] J Mol Appl Genet. 1982;1(4):327-41 [6286831] J Immunol. 1982 Dec;129(6):2564-9 [6982931] Science. 1983 Aug 5;221(4610):551-3 [6306768] Biochemistry. 1983 Jun 21;22(13):3206-13 [6576808] Hum Immunol. 1984 Jul;10(3):177-86 [6611328] J Cell Biol. 1985 Jun;100(6):1839-47 [3922993] Proc Natl Acad Sci U S A. 1985 Dec;82(23):8188-92 [2999796] Nature. 1987 Oct 29-Nov 4;329(6142):840-2 [3313052] Proc Natl Acad Sci U S A. 1988 Jun;85(11):3975-9 [3287381] Nucleic Acids Res. 1988 Aug 11;16(15):7351-67 [3045756] J Exp Med. 1994 Sep 1;180(3):1107-13 [8064228] Science. 1994 Dec 2;266(5190):1566-9 [7985027] Science. 1994 Dec 2;266(5190):1569-73 [7985028] EMBO J. 1995 Jan 3;14(1):37-49 [7530198] J Cell Biol. 1995 Feb;128(3):321-32 [7844146] Immunity. 1994 Dec;1(9):763-74 [7895165] J Biol Chem. 1995 May 5;270(18):10475-81 [7737982] J Exp Med. 1995 Jul 1;182(1):163-74 [7790816] Nature. 1995 Jun 29;375(6534):802-6 [7596415] Immunity. 1994 Oct;1(7):585-94 [7600287] Immunity. 1994 Oct;1(7):595-606 [7600288] Immunity. 1995 Jan;2(1):73-88 [7600303] Cell. 1995 Jul 14;82(1):155-65 [7606781] J Exp Med. 1995 Aug 1;182(2):325-34 [7629497] Immunity. 1995 Aug;3(2):197-205 [7648393] J Cell Biol. 1990 Sep;111(3):955-66 [2391371] Cell. 1990 Nov 16;63(4):707-16 [2121367] Nature. 1990 Nov 1;348(6296):39-44 [2234057] Nature. 1990 Dec 13;348(6302):600-5 [2250716] Cell. 1990 Nov 30;63(5):1061-72 [2257624] J Biol Chem. 1991 Feb 15;266(5):3239-45 [1993697] Nature. 1991 Feb 21;349(6311):669-76 [1847504] Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2346-50 [1900941] J Exp Med. 1991 May 1;173(5):1099-109 [2022921] Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5197-201 [1711220] Hum Immunol. 1991 Aug;31(4):229-35 [1655683] Nature. 1991 Oct 10;353(6344):571-3 [1922365] Nature. 1991 Oct 10;353(6344):573-6 [1922366] J Cell Biol. 1991 Dec;115(6):1573-84 [1757463] Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2282-6 [1549594] J Cell Biol. 1992 Apr;117(2):311-25 [1560028] Cell. 1992 Jun 26;69(7):1143-57 [1535555] EMBO J. 1992 Aug;11(8):2841-7 [1639058] EMBO J. 1992 Sep;11(9):3245-54 [1505516] J Biol Chem. 1992 Aug 25;267(24):17110-5 [1324923] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Engraftment of SCID mice by human bone marrow hematopoietic cells cultured in vitro: an in vivo model for human gene transfer. AN - 77569015; 7475312 AB - Demonstration of the ability of fresh human hematopoietic cells to engraft severe combined immuno-deficient (scid) mice has provided an in vivo assay for expansion and maturation of early human progenitor cells. However, engraftment of cultured hematopoietic cells has been difficult to achieve. We wished to further develop this model as an in vivo assay for efficiency of retroviral gene transfer and expression in the differentiated progeny of adult human bone marrow progenitor cells. Human bone marrow cells were cultured in vitro for six days under conditions suitable for infection by retroviral vectors prior to transfer to irradiated scid mice. Cultured human bone marrow cells introduced by both intravenous (i.v.) and intraperitoneal (i.p.) injection persisted in the bone marrow, spleen and peritoneum of recipient animals up to four weeks after transfer. Following irradiation scid mice receiving cultured human bone marrow cells by either i.v. or i.p. routes demonstrated engraftment of the bone marrow and spleen as determined by the growth of human hematopoietic progenitors in soft agar. By flow cytometric analysis human cells were also detected in the peritoneum of mice receiving cultured human bone marrow cells i.p. These results suggest that the transfer of cultured human bone marrow cells to scid mice with the subsequent engraftment of these cells in the bone marrow, spleen and peritoneum of recipients can routinely occur. This provides an in vivo model for retroviral gene transfer to human cells. JF - Leukemia AU - Spence, S E AU - Keller, J R AU - Ruscetti, F W AU - Czarra, K T AU - Gooya, J M AU - Funakoshi, S AU - Longo, D L AU - Murphy, W J AD - Biological Carcinogenesis and Development Program, Program Resources, Inc/DynCorp, National Cancer Institute, Frederick Cancer Research and Development Center, MD, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - S43 EP - S47 VL - 9 Suppl 1 SN - 0887-6924, 0887-6924 KW - Interleukin-3 KW - 0 KW - Recombinant Fusion Proteins KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Index Medicus KW - Animals KW - Spleen -- cytology KW - Fluorescent Antibody Technique, Indirect KW - Humans KW - Interleukin-3 -- pharmacology KW - Retroviridae KW - Mice KW - Dose-Response Relationship, Radiation KW - Granulocyte-Macrophage Colony-Stimulating Factor -- pharmacology KW - Models, Biological KW - Tissue Donors KW - Whole-Body Irradiation KW - Cells, Cultured KW - Adult KW - Recombinant Fusion Proteins -- pharmacology KW - Mice, SCID KW - Bone Marrow Cells KW - Gene Transfer Techniques KW - Hematopoietic Stem Cells -- cytology KW - Hematopoietic Stem Cell Transplantation KW - Transplantation, Heterologous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77569015?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Leukemia&rft.atitle=Engraftment+of+SCID+mice+by+human+bone+marrow+hematopoietic+cells+cultured+in+vitro%3A+an+in+vivo+model+for+human+gene+transfer.&rft.au=Spence%2C+S+E%3BKeller%2C+J+R%3BRuscetti%2C+F+W%3BCzarra%2C+K+T%3BGooya%2C+J+M%3BFunakoshi%2C+S%3BLongo%2C+D+L%3BMurphy%2C+W+J&rft.aulast=Spence&rft.aufirst=S&rft.date=1995-10-01&rft.volume=9+Suppl+1&rft.issue=&rft.spage=S43&rft.isbn=&rft.btitle=&rft.title=Leukemia&rft.issn=08876924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-30 N1 - Date created - 1995-11-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The NCI's AIDS antiviral drug screening program. AN - 77565034; 7475324 AB - The Developmental Therapeutics Program (DTP) in the National Cancer Institute has an unique mission by serving as a resource for all academic and private research institutions, the National Institutes of Health in the USA, and the global scientific community in the quest for effective therapeutic agents for treating patients with Acquired Immune Deficiency Syndrome (AIDS) as well as for cancer patients. This communication will concentrate on the developmental therapeutic program on anti-AIDS drug discovery. JF - Leukemia AU - Yang, S S AD - Antiviral Evaluation Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - S9 EP - 11 VL - 9 Suppl 1 SN - 0887-6924, 0887-6924 KW - Antiviral Agents KW - 0 KW - Index Medicus KW - AIDS/HIV KW - United States KW - Cell Survival -- drug effects KW - Cell Fusion KW - Virus Replication -- drug effects KW - Humans KW - HIV -- drug effects KW - National Institutes of Health (U.S.) KW - HIV Infections -- drug therapy KW - Acquired Immunodeficiency Syndrome -- drug therapy KW - HIV-1 -- physiology KW - Drug Evaluation, Preclinical -- methods KW - HIV-1 -- drug effects KW - Antiviral Agents -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77565034?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Leukemia&rft.atitle=The+NCI%27s+AIDS+antiviral+drug+screening+program.&rft.au=Yang%2C+S+S&rft.aulast=Yang&rft.aufirst=S&rft.date=1995-10-01&rft.volume=9+Suppl+1&rft.issue=&rft.spage=S9&rft.isbn=&rft.btitle=&rft.title=Leukemia&rft.issn=08876924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-30 N1 - Date created - 1995-11-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Polymorphism at position nine of the MHC class I heavy chain affects the stability of association with beta 2-microglobulin and presentation of a viral peptide. AN - 77555741; 7561043 AB - To identify residues that control the interactions between MHC-heavy chains and (beta 2m) sequence comparisons were made between murine class I MHC molecules with high (H-2Dd, H-2Kb) and low (H-2Ld, H-2Db) affinities for beta 2m. A single residue at position 9 was evaluated for its contribution to the stability of the complex. Mutagenesis of the glutamic acid at position 9 of H-2Ld to valine, as is found in H-2Dd and H-2Kb, resulted in both qualitative and quantitative effects on inter-chain interactions, intracellular transport, peptide binding, and peptide presentation. In in vitro translation and assembly studies, the E9V mutation resulted in a more stable association of beta 2m with the heavy chain after immunoprecipitation with the alpha 2 domain-specific Ab 30-5-7 in the presence of an H-2Ld-restricted peptide. E9V variant expressed in transfected L cells had similar surface expression compared with H-2Ld despite exhibiting a slower rate of maturation. However, cells expressing E9V were unable to present peptide Ag to a specific T cell hybridoma. H-2LdE9V in E-3 cells, which are defective in TAP-dependent peptide transport, was expressed at higher levels than H-2Ld and was stabilized more efficiently by the addition of exogenous human beta 2m. Thus, amino acid position 9 not only plays an important role in the interaction of the MHC-1 molecule with the beta 2m, it also qualitatively and quantitatively influences peptide binding and Ag presentation. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Ribaudo, R K AU - Margulies, D H AD - Molecular Biology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/10/01/ PY - 1995 DA - 1995 Oct 01 SP - 3481 EP - 3493 VL - 155 IS - 7 SN - 0022-1767, 0022-1767 KW - DNA, Complementary KW - 0 KW - Histocompatibility Antigens Class I KW - Viral Proteins KW - beta 2-Microglobulin KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Gene Transfer Techniques KW - Models, Molecular KW - Polymorphism, Genetic KW - Amino Acid Sequence KW - Mice KW - Receptor Aggregation KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Sequence Alignment KW - Molecular Sequence Data KW - Antigen Presentation -- genetics KW - Cell Line KW - Viral Proteins -- immunology KW - beta 2-Microglobulin -- immunology KW - Histocompatibility Antigens Class I -- immunology KW - Histocompatibility Antigens Class I -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77555741?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Neuropharmacology&rft.atitle=Can+cannabis+cause+psychosis%3F&rft.au=Michaels%2C+Timothy+I.%3BNovakovic%2C+Vladan&rft.aulast=Michaels&rft.aufirst=Timothy&rft.date=2015-03-01&rft.volume=38&rft.issue=2&rft.spage=63&rft.isbn=&rft.btitle=&rft.title=Clinical+Neuropharmacology&rft.issn=03625664&rft_id=info:doi/10.1097%2FWNF.0000000000000066 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-27 N1 - Date created - 1995-10-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular mechanisms of an inborn error of methionine pathway. Methionine adenosyltransferase deficiency. AN - 77552194; 7560086 AB - Methionine adenosyltransferase (MAT) is a key enzyme in transmethylation, transsulfuration, and the biosynthesis of polyamines. Genetic deficiency of alpha/beta-MAT causes isolated persistent hypermethioninemia and, in some cases, unusual breath odor or neural demyelination. However, the molecular mechanism(s) underlying this deficiency has not been clearly defined. In this study, we characterized the human alpha/beta-MAT transcription unit and identified several mutations in the gene of patients with enzymatically confirmed diagnosis of MAT deficiency. Site-directed mutagenesis and transient expression assays demonstrated that these mutations partially inactivate MAT activity. These results establish the molecular basis of this disorder and allow for the development of DNA-based methodologies to investigate and diagnose hypermethioninemic individuals suspected of having abnormalities at this locus. JF - The Journal of clinical investigation AU - Ubagai, T AU - Lei, K J AU - Huang, S AU - Mudd, S H AU - Levy, H L AU - Chou, J Y AD - Human Genetics Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 1943 EP - 1947 VL - 96 IS - 4 SN - 0021-9738, 0021-9738 KW - Methionine KW - AE28F7PNPL KW - Methionine Adenosyltransferase KW - EC 2.5.1.6 KW - Abridged Index Medicus KW - Index Medicus KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Transcription, Genetic KW - Mutation KW - Polymorphism, Single-Stranded Conformational KW - Female KW - Methionine Adenosyltransferase -- deficiency KW - Methionine -- metabolism KW - Amino Acid Metabolism, Inborn Errors -- genetics KW - Methionine Adenosyltransferase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77552194?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+investigation&rft.atitle=Molecular+mechanisms+of+an+inborn+error+of+methionine+pathway.+Methionine+adenosyltransferase+deficiency.&rft.au=Ubagai%2C+T%3BLei%2C+K+J%3BHuang%2C+S%3BMudd%2C+S+H%3BLevy%2C+H+L%3BChou%2C+J+Y&rft.aulast=Ubagai&rft.aufirst=T&rft.date=1995-10-01&rft.volume=96&rft.issue=4&rft.spage=1943&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+investigation&rft.issn=00219738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-13 N1 - Date created - 1995-11-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochem J. 1993 Jul 15;293 ( Pt 2):481-6 [8393662] Eur J Biochem. 1987 Dec 30;170(1-2):299-304 [3121322] J Biol Chem. 1988 Aug 15;263(23):11211-6 [3403522] Proc Natl Acad Sci U S A. 1989 Apr;86(8):2766-70 [2565038] Lancet. 1991 Dec 21-28;338(8782-8783):1550-4 [1683972] Biochem Int. 1991 Sep;25(1):81-90 [1772450] FEBS Lett. 1992 Nov 2;312(1):37-41 [1426236] FEBS Lett. 1993 Sep 20;330(3):307-11 [8375501] Pharmacol Ther. 1993 Aug;59(2):125-43 [8278461] J Biol Chem. 1953 Sep;204(1):403-16 [13084611] J Biol Chem. 1993 Jul 5;268(19):13978-86 [8314764] Science. 1974 Oct 4;186(4158):59-60 [4421454] Biochem Biophys Res Commun. 1975 Oct 27;66(4):1491-7 [1191305] Biochem Med. 1976 Dec;16(3):234-50 [13790] Arch Fr Pediatr. 1977 May;34(5):416-23 [889406] Biochemistry. 1981 Feb 17;20(4):934-40 [7213623] J Pediatr. 1981 May;98(5):734-41 [7229751] Nucleic Acids Res. 1982 Jan 22;10(2):459-72 [7063411] Biochemistry. 1983 Mar 29;22(7):1636-41 [6849873] J Biol Chem. 1985 Apr 10;260(7):3923-30 [3980460] Am J Hum Genet. 1987 Jan;40(1):39-49 [3812486] J Clin Invest. 1988 Feb;81(2):390-7 [3339126] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of Escherichia coli dnaE antimutator alleles in a proofreading-deficient mutD5 strain. AN - 77551675; 7592352 AB - We have previously isolated seven mutants of Escherichia coli which replicate their DNA with increased fidelity. These mutants were isolated as suppressors of the elevated mutability of a mismatch-repair-defective mutL strain. Each mutant was shown to contain a single amino acid substitution in the dnaE gene product, the alpha (i.e., polymerase) subunit of DNA polymerase III holoenzyme responsible for replicating the E. coli chromosome. The mechanism(s) by which these antimutators exert their effect is of interest. Here, we have examined the effects of the antimutator alleles in a mutD5 mutator strain. This strain carries a mutation in the dnaQ gene, which results in defective exonucleolytic proofreading. Our results show that dnaE mutations also confer a strong antimutator phenotype in this background, the effects being generally much greater than those observed previously in the mutL background. The results suggest that the dnaE antimutator alleles can exert their effect independently of exonucleolytic proofreading activity. The large magnitude of the antimutator effects in the mutD5 background can be ascribed, at least in part, to the (additional) restoration of DNA mismatch repair, which is generally impaired in mutD5 strains because of error saturation. The high mutability of mutD5 strains was exploited to isolate a strong new dnaE antimutator allele on the basis of its ability to suppress the high reversion rate of an A.T-->T.A transversion in this background. A model suggesting how the dnaE antimutator alleles might exert their effects in proofreading-proficient and -deficient backgrounds is presented. JF - Journal of bacteriology AU - Fijalkowska, I J AU - Schaaper, R M AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 5979 EP - 5986 VL - 177 IS - 20 SN - 0021-9193, 0021-9193 KW - Bacterial Proteins KW - 0 KW - Escherichia coli Proteins KW - MutL protein, E coli KW - DNA Polymerase III KW - EC 2.7.7.- KW - DNA polymerase III, alpha subunit KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - MutL Proteins KW - EC 3.6.1.3 KW - Index Medicus KW - Bacterial Proteins -- genetics KW - Alleles KW - Models, Genetic KW - Suppression, Genetic KW - Sequence Analysis, DNA KW - DNA Replication -- genetics KW - DNA Polymerase III -- genetics KW - Escherichia coli -- genetics KW - Mutagenesis -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77551675?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+bacteriology&rft.atitle=Effects+of+Escherichia+coli+dnaE+antimutator+alleles+in+a+proofreading-deficient+mutD5+strain.&rft.au=Fijalkowska%2C+I+J%3BSchaaper%2C+R+M&rft.aulast=Fijalkowska&rft.aufirst=I&rft.date=1995-10-01&rft.volume=177&rft.issue=20&rft.spage=5979&rft.isbn=&rft.btitle=&rft.title=Journal+of+bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-28 N1 - Date created - 1995-11-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Bacteriol. 1992 Mar;174(6):1974-82 [1548237] Cell. 1994 Sep 9;78(5):877-87 [8087854] J Bacteriol. 1992 Nov;174(21):6965-73 [1400246] Mutat Res. 1993 Aug;288(2):311-9 [7688092] Annu Rev Biochem. 1993;62:685-713 [7688945] Genetics. 1993 Aug;134(4):1023-30 [8375645] Genetics. 1993 Aug;134(4):1031-8 [8375646] Genetics. 1993 Aug;134(4):1039-44 [8375647] J Biol Chem. 1993 Nov 15;268(32):23762-5 [8226906] Mol Gen Genet. 1994 Feb;242(3):289-96 [8107676] J Bacteriol. 1974 Feb;117(2):477-87 [4590472] Mol Gen Genet. 1978 Jul 25;163(3):277-83 [355854] Genetics. 1982 Jan;100(1):7-18 [7047297] Proc Natl Acad Sci U S A. 1983 Apr;80(8):2189-92 [6340117] J Mol Biol. 1983 Jul 15;167(4):757-71 [6224021] Proc Natl Acad Sci U S A. 1983 Dec;80(23):7085-9 [6359162] Proc Natl Acad Sci U S A. 1984 Dec;81(24):7747-51 [6393125] J Biol Chem. 1985 Oct 25;260(24):12987-92 [2997151] Gene. 1985;39(2-3):181-9 [4092929] Proc Natl Acad Sci U S A. 1987 Sep;84(17):6220-4 [3306672] J Bacteriol. 1987 Dec;169(12):5735-44 [3316192] Science. 1988 Jan 29;239(4839):487-91 [2448875] Mutat Res. 1988 Jul-Aug;200(1-2):11-20 [3393157] Proc Natl Acad Sci U S A. 1988 Nov;85(21):8126-30 [3054881] Proc Natl Acad Sci U S A. 1988 Dec;85(23):9124-7 [3057500] Biochemistry. 1988 Sep 6;27(18):6716-25 [3058205] J Biol Chem. 1989 Feb 15;264(5):2898-905 [2521632] Genetics. 1989 Feb;121(2):205-12 [2659431] Proc Natl Acad Sci U S A. 1989 Jul;86(14):5345-9 [2501784] J Bacteriol. 1989 Aug;171(8):4494-7 [2666405] J Bacteriol. 1989 Oct;171(10):5572-80 [2551891] EMBO J. 1989 Nov;8(11):3511-6 [2555167] J Biol Chem. 1990 Feb 5;265(4):2338-46 [1688852] Biotechniques. 1989 Jul-Aug;7(7):696-8 [2631784] Mol Gen Genet. 1990 Apr;221(2):251-5 [2196432] Biochemistry. 1990 Jun 5;29(22):5226-31 [2166556] EMBO J. 1991 Jan;10(1):17-24 [1989882] Annu Rev Biochem. 1991;60:477-511 [1883202] J Biol Chem. 1991 Oct 15;266(29):19127-30 [1918028] Annu Rev Genet. 1991;25:229-53 [1812808] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intracellular signaling pathways required for rat vascular smooth muscle cell migration. Interactions between basic fibroblast growth factor and platelet-derived growth factor. AN - 77549918; 7560082 AB - Intracellular signaling pathways activated by both PDGF and basic fibroblast growth factor (bFGF) have been implicated in the migration of vascular smooth muscle cells (VSMC), a key step in the pathogenesis of many vascular diseases. We demonstrate here that, while bFGF is a weak chemoattractant for VSMCs, it is required for the PDGF-directed migration of VSMCs and the activation of calcium/calmodulin-dependent protein kinase II (CamKinase II), an intracellular event that we have previously shown to be important in the regulation of VSMC migration. Neutralizing antibodies to bFGF caused a dramatic reduction in the size of the intracellular calcium transient normally seen after PDGF stimulation and inhibited both PDGF-directed VSMC migration and CamKinase II activation. Partially restoring the calcium transient with ionomycin restored migration and CamKinase II activation as did the forced expression of a mutant CamKinase II that had been "locked" in the active state by site-directed mutagenesis. These results suggest that bFGF links PDGF receptor stimulation to changes in intracellular calcium and CamKinase II activation, reinforcing the central role played by CamKinase II in regulating VSMC migration. JF - The Journal of clinical investigation AU - Bilato, C AU - Pauly, R R AU - Melillo, G AU - Monticone, R AU - Gorelick-Feldman, D AU - Gluzband, Y A AU - Sollott, S J AU - Ziman, B AU - Lakatta, E G AU - Crow, M T AD - Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 1905 EP - 1915 VL - 96 IS - 4 SN - 0021-9738, 0021-9738 KW - Platelet-Derived Growth Factor KW - 0 KW - RNA, Messenger KW - Fibroblast Growth Factor 2 KW - 103107-01-3 KW - Calcium-Calmodulin-Dependent Protein Kinase Type 2 KW - EC 2.7.11.17 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - Calcium KW - SY7Q814VUP KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Cell Movement KW - Calcium -- metabolism KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Animals KW - Cells, Cultured KW - Humans KW - Rats, Wistar KW - RNA, Messenger -- analysis KW - Mice KW - Fibroblast Growth Factor 2 -- physiology KW - Muscle, Smooth, Vascular -- cytology KW - Platelet-Derived Growth Factor -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77549918?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+investigation&rft.atitle=Intracellular+signaling+pathways+required+for+rat+vascular+smooth+muscle+cell+migration.+Interactions+between+basic+fibroblast+growth+factor+and+platelet-derived+growth+factor.&rft.au=Bilato%2C+C%3BPauly%2C+R+R%3BMelillo%2C+G%3BMonticone%2C+R%3BGorelick-Feldman%2C+D%3BGluzband%2C+Y+A%3BSollott%2C+S+J%3BZiman%2C+B%3BLakatta%2C+E+G%3BCrow%2C+M+T&rft.aulast=Bilato&rft.aufirst=C&rft.date=1995-10-01&rft.volume=96&rft.issue=4&rft.spage=1905&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+investigation&rft.issn=00219738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-13 N1 - Date created - 1995-11-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cardiovasc Res. 1993 Jul;27(7):1199-203 [8252578] Circ Res. 1994 Mar;74(3):485-94 [8118957] Circ Res. 1994 Jun;74(6):1034-41 [8187273] Circ Res. 1994 Jul;75(1):41-54 [8013081] Exp Eye Res. 1977 Jul;25(1):75-89 [302215] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] Biochemistry. 1979 Nov 27;18(24):5294-9 [518835] J Cell Biol. 1981 Jun;89(3):568-78 [6454694] Proc Natl Acad Sci U S A. 1981 Jun;78(6):3669-72 [6943570] J Cell Physiol. 1983 Mar;114(3):284-90 [6300146] Proc Natl Acad Sci U S A. 1989 Nov;86(21):8412-6 [2813399] Proc Natl Acad Sci U S A. 1989 Dec;86(24):9911-5 [2481318] Proc Natl Acad Sci U S A. 1990 Feb;87(4):1273-7 [2154738] J Biol Chem. 1990 Mar 15;265(8):4315-20 [2155222] Am J Physiol. 1990 Feb;258(2 Pt 2):H574-86 [2309919] J Cell Physiol. 1990 May;143(2):232-42 [2159012] Growth Factors. 1990;2(4):313-20 [2337475] J Biol Chem. 1990 Oct 25;265(30):18055-8 [2211681] Circ Res. 1991 Jan;68(1):106-13 [1984855] Cell. 1991 Jan 25;64(2):281-302 [1846320] Biochem Biophys Res Commun. 1991 Feb 14;174(3):1260-6 [1996989] Proc Natl Acad Sci U S A. 1991 May 1;88(9):3739-43 [2023924] Prog Growth Factor Res. 1989;1(4):207-35 [2491263] J Cell Physiol. 1991 Aug;148(2):202-10 [1880150] Science. 1991 Sep 6;253(5024):1129-32 [1653454] Cancer Cells. 1991 Jun;3(6):239-43 [1911037] Cell Regul. 1991 Sep;2(9):719-26 [1742342] J Clin Invest. 1992 Feb;89(2):507-11 [1531345] Ann N Y Acad Sci. 1991;638:232-43 [1723854] J Cell Physiol. 1992 Apr;151(1):81-93 [1560052] Cell. 1992 May 1;69(3):413-23 [1374684] J Biol Chem. 1992 Jun 15;267(17):12197-201 [1318312] Nature. 1993 Jan 28;361(6410):315-25 [8381210] Growth Factors. 1993;8(1):61-75 [7680568] Nature. 1993 Apr 29;362(6423):801-9 [8479518] J Biol Chem. 1993 Jul 5;268(19):14443-9 [8390994] J Biol Chem. 1993 Aug 15;268(23):17397-403 [8349623] J Cell Physiol. 1993 Oct;157(1):133-44 [7691833] Am J Pathol. 1993 Oct;143(4):1024-31 [8213998] Am J Physiol. 1993 Oct;265(4 Pt 2):H1424-33 [8238429] Circ Res. 1994 Aug;75(2):261-7 [7518361] Circulation. 1995 Feb 15;91(4):1107-15 [7850948] Lab Invest. 1983 Sep;49(3):327-33 [6887785] Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991-5 [6326095] Nucleic Acids Res. 1985 Mar 11;13(5):1431-42 [2987824] J Biol Chem. 1986 Jan 5;261(1):32-5 [2416748] Proc Natl Acad Sci U S A. 1986 Apr;83(7):2091-5 [3008151] Science. 1986 Aug 1;233(4763):545-8 [2425435] Proc Natl Acad Sci U S A. 1986 Oct;83(19):7297-301 [2429303] Biochem Biophys Res Commun. 1987 Apr 29;144(2):705-12 [3579937] Cancer Res. 1987 Jun 15;47(12):3239-45 [2438036] Cancer Res. 1988 Aug 1;48(15):4266-71 [3260536] J Cell Biol. 1988 Sep;107(3):1199-205 [3417781] Biochem Biophys Res Commun. 1988 Nov 30;157(1):256-63 [3196337] J Cell Biol. 1989 Feb;108(2):671-82 [2465298] J Cell Biol. 1989 Jul;109(1):1-6 [2545723] J Cell Biol. 1989 Aug;109(2):823-31 [2760114] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Endothelin 1 stimulates Na+,K(+)-ATPase and Na(+)-K(+)-Cl- cotransport through ETA receptors and protein kinase C-dependent pathway in cerebral capillary endothelium. AN - 77541609; 7561853 AB - The effect of endothelins (ET-1 and ET-3) on 86Rb+ uptake as a measure of K+ uptake was investigated in cultured rat brain capillary endothelium. ET-1 or ET-3 dose-dependently enhanced K+ uptake (EC50 = 0.60 +/- 0.15 and 21.5 +/- 4.1 nM, respectively), which was inhibited by the selective ETA receptor antagonist BQ 123 (cyclo-D-Trp-D-Asp-Pro-D-Val-Leu). Neither the selective ETB agonists IRL 1620 [N-succinyl-(Glu9,-Ala11,15)-ET-1] and sarafotoxin S6c, nor the ETB receptor antagonist IRL 1038 [(Cys11,Cys15)-ET-1] had any effect on K+ uptake. Ouabain (inhibitor of Na+,K(+)-ATPase) and bumetanide (inhibitor of Na(+)-K(+)-Cl- cotransport) reduced (up to 40% and up to 70%, respectively) the ET-1-stimulated K+ uptake. Complete inhibition was seen with both agents. Phorbol 12-myristate 13-acetate (PMA), activator of protein kinase C (PKC), stimulated Na+,K(+)-ATPase and Na(+)-K(+)-Cl- cotransport. ET-1- but not PMA-stimulated K+ uptake was inhibited by 5-(N-ethyl-N-isopropyl)amiloride (inhibitor of Na+/H+ exchange system), suggesting a linkage of Na+/H+ exchange with ET-1-stimulated Na+,K(+)-ATPase and Na(+)-K(+)-Cl- cotransport activity that is not mediated by PKC. JF - Journal of neurochemistry AU - Kawai, N AU - Yamamoto, T AU - Yamamoto, H AU - McCarron, R M AU - Spatz, M AD - Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 1588 EP - 1596 VL - 65 IS - 4 SN - 0022-3042, 0022-3042 KW - Carrier Proteins KW - 0 KW - Endothelin Receptor Antagonists KW - Endothelins KW - Receptors, Endothelin KW - Sodium-Potassium-Chloride Symporters KW - Amiloride KW - 7DZO8EB0Z3 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Sodium-Potassium-Exchanging ATPase KW - EC 3.6.3.9 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Potassium KW - RWP5GA015D KW - Calcium KW - SY7Q814VUP KW - ethylisopropylamiloride KW - VW50CE070T KW - Index Medicus KW - Rats KW - Calcium -- metabolism KW - Animals KW - Extracellular Space -- metabolism KW - Cells, Cultured KW - Potassium -- pharmacokinetics KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Amiloride -- pharmacology KW - Capillaries -- metabolism KW - Amiloride -- analogs & derivatives KW - Endothelins -- pharmacology KW - Sodium-Potassium-Exchanging ATPase -- metabolism KW - Endothelium, Vascular -- metabolism KW - Carrier Proteins -- metabolism KW - Endothelium, Vascular -- cytology KW - Protein Kinase C -- physiology KW - Cerebrovascular Circulation KW - Receptors, Endothelin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77541609?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Endothelin+1+stimulates+Na%2B%2CK%28%2B%29-ATPase+and+Na%28%2B%29-K%28%2B%29-Cl-+cotransport+through+ETA+receptors+and+protein+kinase+C-dependent+pathway+in+cerebral+capillary+endothelium.&rft.au=Kawai%2C+N%3BYamamoto%2C+T%3BYamamoto%2C+H%3BMcCarron%2C+R+M%3BSpatz%2C+M&rft.aulast=Kawai&rft.aufirst=N&rft.date=1995-10-01&rft.volume=65&rft.issue=4&rft.spage=1588&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 - 1995-10-25 N1 - Date created - 1995-10-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nodules of less-differentiated tumor within or adjacent to hepatocellular carcinoma: relative expression of transforming growth factor-alpha and its receptor in the different areas of tumor. AN - 77539888; 7557946 AB - Expression of transforming growth factor-alpha (TGF-alpha) and its receptor, the epidermal growth factor receptor (EGFR), in hepatocellular carcinomas (HCCs) and adjacent nontumorous livers from 25 Japanese patients were examined using immunoperoxidase staining of paraffin-embedded sections. TGF-alpha was detected in 24 of 25 (96%) HCCs and 23 of 24 (96%) available adjacent nontumorous livers. EGFR was detected in 16 of 25 (64%) HCCs and 17 of 24 (71%) adjacent nontumorous livers. TGF-alpha and EGFR were not detected by immunohistochemical staining in normal livers. Fifteen of 25 HCCs contained an apparent area of a second tumor (two of the 15 also contained a third tumor) that had a less-differentiated histological grade developing within or adjacent to the first tumor. In those cases, staining in the less-differentiated area of tumor was usually less intense than in the more highly differentiated area (80% of cases for TGF-alpha; 91% for EGFR). These data confirm that increased expression of TGF-alpha and EGFR occur frequently in human HCC. Furthermore, the detection of greater staining in more highly differentiated portions of the tumors suggests that increased expression of TGF-alpha and EGFR may be events of the early stages of human hepatocarcinogenesis. JF - Human pathology AU - Morimitsu, Y AU - Hsia, C C AU - Kojiro, M AU - Tabor, E AD - Biological Carcinogenesis Program, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 1126 EP - 1132 VL - 26 IS - 10 SN - 0046-8177, 0046-8177 KW - Hepatitis B Surface Antigens KW - 0 KW - Transforming Growth Factor alpha KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Hepatitis B Surface Antigens -- analysis KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Female KW - Liver Neoplasms -- pathology KW - Liver Neoplasms -- chemistry KW - Carcinoma, Hepatocellular -- pathology KW - Carcinoma, Hepatocellular -- chemistry KW - Transforming Growth Factor alpha -- analysis KW - Receptor, Epidermal Growth Factor -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77539888?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Nodules+of+less-differentiated+tumor+within+or+adjacent+to+hepatocellular+carcinoma%3A+relative+expression+of+transforming+growth+factor-alpha+and+its+receptor+in+the+different+areas+of+tumor.&rft.au=Morimitsu%2C+Y%3BHsia%2C+C+C%3BKojiro%2C+M%3BTabor%2C+E&rft.aulast=Morimitsu&rft.aufirst=Y&rft.date=1995-10-01&rft.volume=26&rft.issue=10&rft.spage=1126&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 - 1995-11-13 N1 - Date created - 1995-11-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antioxidant activity of tetrandrine and its inhibition of quartz-induced lipid peroxidation. AN - 77537000; 7563220 AB - Tetrandrine is a benzylisoquinoline alkaloid that has been used in China as an antifibrotic drug to treat the lesions of silicosis. Its mechanism in the treatment of silicosis is unclear. Electron spin resonance (ESR) spin trapping was employed to investigate the antioxidant properties of tetrandrine. The spin trap used was 5,5-dimethyl-1-pyrroline N-oxide (DMPO). Tetrandine efficiently reacted with hydroxyl (.OH) radicals with a reaction rate of approximately 1.4 x 10(10) M-1 s-1. The .OH radicals were generated by the Fenton reaction [Fe(II) + H2O2) as well as by reaction of chromium(V) with H2O2. Similar results were obtained using .OH radicals generated by reaction of freshly fractured quartz particles with aqueous medium. Tetrandrine also scavenged superoxide (O2-) radicals produced from xanthine/xanthine oxidase. The effect of tetrandrine on lipid peroxidation induced by freshly fractured quartz particles was evaluated using linoleic acid as a model lipid. The results showed that tetrandrine caused a significant inhibition on freshly fractured quartz-induced lipid peroxidation. JF - Journal of toxicology and environmental health AU - Shi, X AU - Mao, Y AU - Saffiotti, U AU - Wang, L AU - Rojanasakul, Y AU - Leonard, S S AU - Vallyathan, V AD - Laboratory of Experimental Pathology, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 233 EP - 248 VL - 46 IS - 2 SN - 0098-4108, 0098-4108 KW - Alkaloids KW - 0 KW - Antioxidants KW - Benzylisoquinolines KW - Free Radical Scavengers KW - Quartz KW - 14808-60-7 KW - tetrandrine KW - 29EX23D5AJ KW - Index Medicus KW - Drug Interactions KW - Spin Trapping KW - Electron Spin Resonance Spectroscopy KW - In Vitro Techniques KW - Free Radical Scavengers -- pharmacology KW - Quartz -- pharmacology KW - Antioxidants -- pharmacology KW - Lipid Peroxidation -- drug effects KW - Alkaloids -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77537000?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Anxiety%2C+depression+and+risk+of+cannabis+use%3A+Examining+the+internalising+pathway+to+use+among+Chilean+adolescents&rft.au=Stapinski%2C+Lexine+A.%3BMontgomery%2C+Alan+A.%3BAraya%2C+Ricardo&rft.aulast=Stapinski&rft.aufirst=Lexine&rft.date=2016-09-01&rft.volume=166&rft.issue=&rft.spage=109&rft.isbn=&rft.btitle=&rft.title=Drug+and+Alcohol+Dependence&rft.issn=03768716&rft_id=info:doi/10.1016%2Fj.drugalcdep.2016.06.032 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-13 N1 - Date created - 1995-11-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The organizer-associated chick homeobox gene, Gnot1, is expressed before gastrulation and regulated synergistically by activin and retinoic acid. AN - 77535787; 7556928 AB - Gnot1, a Not (for notochord) family homeobox gene, is expressed in the chick pregastrulation blastoderm. Gnot1 expression in the epiblast is upregulated as the posteriorly derived hypoblast moves forward anteriorly to form a layer beneath it, which is of particular interest considering the known inductive role of the hypoblast in axis formation in the chick. Both activin and retinoic acid are able to activate Gnot1 expression in cultured blastodermal cells and show a strong synergistic effect when applied in combination. Strong superinduction of Gnot1 transcripts in the presence of cycloheximide also indicates the presence of a potent and labile intracellular inhibitor capable of modulating Gnot1 expression. During gastrulation, Gnot1 transcripts become localized specifically to tissues associated with "organizer" function (Hensen's node, head process, notochord). The expression data and the response to mesoderm inducing factors and axial "caudalizing" signals suggest that Gnot1 may be involved in specification of the embryonic body axis and could play a part in regulating features of the trunk/tail organizer in the chick embryo. JF - Developmental biology AU - Knezevic, V AU - Ranson, M AU - Mackem, S AD - Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 458 EP - 470 VL - 171 IS - 2 SN - 0012-1606, 0012-1606 KW - Avian Proteins KW - 0 KW - Gnot1 protein, chicken KW - Growth Substances KW - Homeodomain Proteins KW - Activins KW - 104625-48-1 KW - Tretinoin KW - 5688UTC01R KW - Inhibins KW - 57285-09-3 KW - Index Medicus KW - Animals KW - Base Sequence KW - Chick Embryo KW - Molecular Sequence Data KW - Drug Synergism KW - Blastoderm -- metabolism KW - Gastrula -- physiology KW - Tretinoin -- pharmacology KW - Genes, Homeobox KW - Homeodomain Proteins -- genetics KW - Growth Substances -- pharmacology KW - Inhibins -- pharmacology KW - Gene Expression Regulation, Developmental -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77535787?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Developmental+biology&rft.atitle=The+organizer-associated+chick+homeobox+gene%2C+Gnot1%2C+is+expressed+before+gastrulation+and+regulated+synergistically+by+activin+and+retinoic+acid.&rft.au=Knezevic%2C+V%3BRanson%2C+M%3BMackem%2C+S&rft.aulast=Knezevic&rft.aufirst=V&rft.date=1995-10-01&rft.volume=171&rft.issue=2&rft.spage=458&rft.isbn=&rft.btitle=&rft.title=Developmental+biology&rft.issn=00121606&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-08 N1 - Date created - 1995-11-08 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U23054; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of buspirone for treatment of cerebellar ataxia. An open-label study. AN - 77533067; 7575226 AB - To evaluate the efficacy of buspirone hydrochloride, a serotonin (5-hydroxytryptamine1A) agonist, in treating patients with cerebellar ataxia. Open-label study in which 20 patients (14 with cerebellar cortical atrophy and six with olivopontocerebellar atrophy) received buspirone hydrochloride, up to 60 mg/d, for 8 weeks. Research hospital. Clinical, physiological, and psychological assessment. Nine patients with mild or moderate cerebellar dysfunction who completed the study showed significant improvement in clinical and self-assessment ratings, but not in a motor performance test, posturography (data were incomplete), State-Trait Anxiety Inventory, and Beck Depression Inventory. Seven patients with severe cerebellar dysfunction who completed the study had no improvement on any measure. Buspirone may be effective in treating mild to moderate cerebellar ataxia. A double-blind study of the efficacy of buspirone in cerebellar ataxia is warranted. JF - Archives of neurology AU - Lou, J S AU - Goldfarb, L AU - McShane, L AU - Gatev, P AU - Hallett, M AD - Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Md, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 982 EP - 988 VL - 52 IS - 10 SN - 0003-9942, 0003-9942 KW - Anti-Anxiety Agents KW - 0 KW - Serotonin Receptor Agonists KW - Buspirone KW - TK65WKS8HL KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Adult KW - Anxiety -- drug therapy KW - Anti-Anxiety Agents -- therapeutic use KW - Depression -- drug therapy KW - Aged KW - Psychomotor Performance KW - Middle Aged KW - Self-Assessment KW - Male KW - Female KW - Cerebellar Ataxia -- drug therapy KW - Buspirone -- therapeutic use KW - Buspirone -- adverse effects KW - Serotonin Receptor Agonists -- therapeutic use KW - Cerebellar Ataxia -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77533067?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+neurology&rft.atitle=Use+of+buspirone+for+treatment+of+cerebellar+ataxia.+An+open-label+study.&rft.au=Lou%2C+J+S%3BGoldfarb%2C+L%3BMcShane%2C+L%3BGatev%2C+P%3BHallett%2C+M&rft.aulast=Lou&rft.aufirst=J&rft.date=1995-10-01&rft.volume=52&rft.issue=10&rft.spage=982&rft.isbn=&rft.btitle=&rft.title=Archives+of+neurology&rft.issn=00039942&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-08 N1 - Date created - 1995-11-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhanced glutathione peroxidase expression protects cells from hydroperoxides but not from radiation or doxorubicin. AN - 77506772; 7671261 AB - Both radiation and anthracycline antibiotics may produce reactive oxygen species to cause cytotoxicity, and it has been suggested that some cellular antioxidant enzymes may be important for resistance to these agents. The human breast adenocarcinoma cell line MCF-7WT has a low level of glutathione peroxidase (GPX) activity. We have transfected MCF-7WT cells with a plasmid that contains the cDNA for human GPX under the transcriptional control of the human metallothionein IIA promoter. One transfected clone, MCF-GPX-6, contained multiple copies of GPX cDNA/cell and, after exposure to heavy metals, expressed a level of GPX enzyme activity that was 40-fold higher than that present in MCF-7WT cells and comparable to the GPX activity contained in the doxorubicin-resistant MCF-7DOX cell line. No differences in levels of glutathione, catalase, superoxide dismutase, glutathione S-transferase, or glutathione reductase were noted in MCF-GPX-6 cells compared to MCF-7WT cells. MCF-GPX-6 cells were relatively resistant to hydrogen peroxide and tert-butylhydroperoxide compared to MCF-7WT cells, e.g., exposure of both cell lines to 750 microM H2O2 for 1 h resulted in a relative surviving fraction of 0.07 for MCF-7WT and 0.35 for MCF-GPX-6 cells. However, no difference in sensitivity to either radiation or doxorubicin was noted between MCF-7WT and MCF-GPX-6 cells. These results suggest that GPX is not important for the development of cellular resistance to either radiation or doxorubicin. JF - Cancer research AU - Liebmann, J AU - Fisher, J AU - Lipschultz, C AU - Kuno, R AU - Kaufman, D C AD - Radiation Biology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1995/10/01/ PY - 1995 DA - 1995 Oct 01 SP - 4465 EP - 4470 VL - 55 IS - 19 SN - 0008-5472, 0008-5472 KW - Antibiotics, Antineoplastic KW - 0 KW - Peroxides KW - RNA, Messenger KW - Doxorubicin KW - 80168379AG KW - tert-Butylhydroperoxide KW - 955VYL842B KW - Hydrogen Peroxide KW - BBX060AN9V KW - Glutathione Peroxidase KW - EC 1.11.1.9 KW - Glutathione KW - GAN16C9B8O KW - Zinc KW - J41CSQ7QDS KW - Index Medicus KW - Zinc -- pharmacology KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Breast Neoplasms -- pathology KW - DNA Damage KW - Humans KW - Glutathione -- analysis KW - RNA, Messenger -- analysis KW - Cell Survival -- radiation effects KW - Hydrogen Peroxide -- toxicity KW - Doxorubicin -- pharmacology KW - Antibiotics, Antineoplastic -- pharmacology KW - Peroxides -- toxicity KW - Glutathione Peroxidase -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77506772?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Enhanced+glutathione+peroxidase+expression+protects+cells+from+hydroperoxides+but+not+from+radiation+or+doxorubicin.&rft.au=Liebmann%2C+J%3BFisher%2C+J%3BLipschultz%2C+C%3BKuno%2C+R%3BKaufman%2C+D+C&rft.aulast=Liebmann&rft.aufirst=J&rft.date=1995-10-01&rft.volume=55&rft.issue=19&rft.spage=4465&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 - 1995-10-19 N1 - Date created - 1995-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Replication of avian leukosis viruses with mutations at the primer binding site: use of alternative tRNAs as primers. AN - 77503135; 7545245 AB - We have tested whether avian leukosis viruses (ALVs) can use tRNAs other than tRNATrp to initiate reverse transcription. The primer binding site (PBS) of a wild-type ALV provirus, which is complementary to the 3' end of tRNA(Trp), was replaced with sequences homologous to the 3' ends of six different chicken tRNAs (tRN(APro), tRNA(Lys), tRNA(Met), tRNA(Ile), tRNA(Phe), and tRNA(Ser)). Transfection of these proviruses into chicken embryo fibroblasts resulted in the production of infectious viruses, all of which apparently used the tRNA specified by the mutated PBS to replicate. However, growth of these viruses resulted in reversion to the wild-type (tRNA(Trp)) PBS. Some of the viruses revert quite quickly, while others are more stable. The relative stability of a given PBS correlated with the concentration of the corresponding tRNA in the virion. We determined the percentage of viral RNA that had a tRNA bound to the PBS and found that the occupancy rate is lower in the mutants than in the wild-type virus. We conclude that many different tRNAs can be used as primers to initiate reverse transcription in ALV. However, ALVs that use tRNA(Trp) have a growth advantage over ALVs that use other tRNAs. JF - Journal of virology AU - Whitcomb, J M AU - Ortiz-Conde, B A AU - Hughes, S H AD - ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA. Y1 - 1995/10// PY - 1995 DA - October 1995 SP - 6228 EP - 6238 VL - 69 IS - 10 SN - 0022-538X, 0022-538X KW - DNA Primers KW - 0 KW - RNA, Transfer, Amino Acid-Specific KW - RNA, Transfer, Trp KW - RNA, Viral KW - RNA-Directed DNA Polymerase KW - EC 2.7.7.49 KW - Index Medicus KW - Animals KW - Chick Embryo KW - Proviruses -- physiology KW - Plasmids KW - Binding Sites KW - Fibroblasts KW - RNA, Transfer, Trp -- metabolism KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Base Sequence KW - Transfection KW - Cells, Cultured KW - Genetic Vectors KW - Restriction Mapping KW - Molecular Sequence Data KW - Proviruses -- genetics KW - Virus Replication KW - RNA, Viral -- biosynthesis KW - Avian Leukosis Virus -- genetics KW - Transcription, Genetic KW - RNA-Directed DNA Polymerase -- metabolism KW - RNA, Transfer, Amino Acid-Specific -- metabolism KW - Avian Leukosis Virus -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77503135?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Replication+of+avian+leukosis+viruses+with+mutations+at+the+primer+binding+site%3A+use+of+alternative+tRNAs+as+primers.&rft.au=Whitcomb%2C+J+M%3BOrtiz-Conde%2C+B+A%3BHughes%2C+S+H&rft.aulast=Whitcomb&rft.aufirst=J&rft.date=1995-10-01&rft.volume=69&rft.issue=10&rft.spage=6228&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 - 1995-10-12 N1 - Date created - 1995-10-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1975 Jul;72(7):2535-9 [52156] Arch Virol Suppl. 1994;9:513-22 [8032280] J Mol Biol. 1976 Sep 5;106(1):109-31 [61277] J Virol. 1977 Mar;21(3):1031-41 [66325] Biochemistry. 1977 Aug 9;16(16):3625-32 [70221] Prog Nucleic Acid Res Mol Biol. 1977;20:131-60 [71747] J Virol. 1978 Mar;25(3):888-96 [205678] J Virol. 1978 May;26(2):214-20 [77907] J Biol Chem. 1979 Mar 25;254(6):1866-74 [84811] J Virol. 1979 Jan;29(1):328-35 [219227] Proc Natl Acad Sci U S A. 1979 Mar;76(3):1373-6 [286319] J Virol. 1979 Mar;29(3):863-71 [87521] J Biol Chem. 1975 May 10;250(9):3487-97 [164470] Nature. 1979 Nov 15;282(5736):339-41 [228201] J Virol. 1980 Nov;36(2):450-6 [6253670] J Virol. 1980 Dec;36(3):692-700 [6162035] Virology. 1984 Jul 15;136(1):89-99 [6330999] Cell. 1985 Jan;40(1):9-17 [2981635] Nature. 1985 Jan 24-30;313(6000):277-84 [2578615] J Virol. 1986 Jan;57(1):37-45 [2416955] J Biol Chem. 1987 Apr 15;262(11):4961-7 [2435721] EMBO J. 1988 Jun;7(6):1777-83 [2458920] Eur J Biochem. 1989 Sep 15;184(2):367-74 [2477248] Nucleic Acids Res. 1989 Oct 25;17(20):8387-8 [2478963] Virology. 1989 Nov;173(1):157-66 [2815581] EMBO J. 1989 Nov;8(11):3279-85 [2479543] J Virol. 1990 Feb;64(2):774-83 [2153242] Biotechniques. 1990 Apr;8(4):404-7 [2340178] Gene. 1990 Apr 16;88(2):293-6 [2347496] J Virol. 1990 Oct;64(10):4903-6 [1697909] J Virol. 1991 Jul;65(7):3728-37 [2041092] J Virol. 1991 Sep;65(9):4555-64 [1714513] J Virol. 1992 Apr;66(4):2464-72 [1548772] J Biol Chem. 1992 Apr 5;267(10):6689-95 [1551877] J Virol. 1992 Aug;66(8):4919-29 [1321278] J Virol. 1994 Oct;68(10):6198-206 [7521916] Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9490-4 [7524077] Annu Rev Cell Biol. 1992;8:275-306 [1282352] Virology. 1993 Apr;193(2):690-9 [8460481] J Virol. 1993 Jun;67(6):3246-53 [8497049] Nucleic Acids Res. 1993 May 25;21(10):2399-407 [8506135] Nucleic Acids Res. 1993 Jul 1;21(13):3011-5 [7687348] J Virol. 1993 Dec;67(12):7125-30 [7693968] J Biol Chem. 1993 Dec 5;268(34):25269-72 [7503978] J Virol. 1994 Mar;68(3):1605-14 [7508999] J Virol. 1994 Apr;68(4):2065-72 [7511167] J Virol. 1976 May;18(2):709-18 [58075] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mouse lactoferrin gene: a marker for estrogen and epidermal growth factor. AN - 36335152; 201002-31-0247372 (CE); 11701715 (EN) AB - Lactoferrin mRNA in the 21-day-old mouse uterus can be increased several hundredfold by estrogen. The physiological role of lactoferrin in mouse uterus is unclear; however, it can be a useful marker for the estrogen action in the uterus. The structural organization and the chromosome location of the lactoferrin gene are similar to members of the transferrin gene family. At the 5' flanking region of the lactoferrin gene, we have characterized two modules that respond to estrogen and growth factor stimulation. Each module is composed of either overlapping or multiple transcription factor-binding elements. The well-characterized estrogen and growth factor response modules in the mouse lactoferrin gene could serve as the foundation to understand the intricate molecular mechanisms of estrogen action and its relationship to growth factors. Images Figure 1. Figure 1. JF - Environmental Health Perspectives AU - Teng, C AD - Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, NC 27709, USA. PY - 1995 SP - 17 EP - 20 PB - U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES, NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES VL - 103 SN - 0091-6765, 0091-6765 KW - Civil Engineering (CE); Environmental Engineering (EN) KW - Estrogens KW - Genes KW - Growth factors KW - Uterus KW - Modules KW - Markers KW - Images KW - Stimulation KW - Article KW - EE 10:General Environmental Engineering (EN) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/36335152?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aenvironmentalengabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+and+Alcohol+Review&rft.atitle=Challenges+in+reducing+cannabis-related+harm+in+Australia&rft.au=Hall%2C+Wayne+D.&rft.aulast=Hall&rft.aufirst=Wayne&rft.date=2009-03-01&rft.volume=28&rft.issue=2&rft.spage=110&rft.isbn=&rft.btitle=&rft.title=Drug+and+Alcohol+Review&rft.issn=09595236&rft_id=info:doi/10.1111%2Fj.1465-3362.2008.00039.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-02-01 N1 - Last updated - 2011-11-14 ER - TY - JOUR T1 - Cellular and molecular effects of developmental exposure to diethylstilbestrol: implications for other environmental estrogens. AN - 21253385; 11701712 AB - Concerns have been raised regarding the role of environmental and dietary estrogens as possible contributors to an increased incidence of various abnormalities in estrogen-target tissues of both sexes. These abnormalities include breast cancer, endometriosis, fibroids, and uterine adenocarcinoma in females, as well as alterations in sex differentiation, decreased sperm concentrations, benign prostatic hyperplasia, prostatic cancer, testicular cancer, and reproductive problems in males. Whether these concerns are valid remains to be determined; however, studies with the potent synthetic estrogen diethylstilbestrol (DES) suggest that exogenous estrogen exposure during critical stages of development can result in permanent cellular and molecular alterations in the exposed organism. These alterations manifest themselves in the female and male as structural, functional, or long-term pathological changes including neoplasia. Although DES has potent estrogenic activity, it may be used as a model compound to study the effects of weaker environmental estrogens, many of which may fit into the category of endocrine disruptors. JF - Environmental Health Perspectives AU - Newbold, R AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/10// PY - 1995 DA - Oct 1995 SP - 83 EP - 87 PB - US Government Printing Office, Superintendent of Documents, P.O. Box 371954 Pittsburgh PA 15250-7954 USA VL - 103 IS - Suppl 7 SN - 0091-6765, 0091-6765 KW - Environment Abstracts; Health & Safety Science Abstracts KW - Diets KW - endocrine disruptors KW - Breast cancer KW - Cancer KW - estrogens KW - H 12000:Epidemiology and Public Health KW - ENA 02:Toxicology & Environmental Safety UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21253385?accountid=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=Environmental+Health+Perspectives&rft.atitle=Cellular+and+molecular+effects+of+developmental+exposure+to+diethylstilbestrol%3A+implications+for+other+environmental+estrogens.&rft.au=Newbold%2C+R&rft.aulast=Newbold&rft.aufirst=R&rft.date=1995-10-01&rft.volume=103&rft.issue=Suppl+7&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-01-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Diets; endocrine disruptors; Breast cancer; Cancer; estrogens ER - TY - JOUR T1 - High concentrations of the carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) occur in chicken but are dependent on the cooking method AN - 15910926; 4043598 AB - Heterocyclic aromatic amines (HAAs) are mutagenic and carcinogenic compounds found in meats cooked at high temperatures. Although chicken is consumed in large quantities in the United States, there is little information on its HAA content. The objective of this study was to measure the five predominant HAAs (IQ, MeIQ, MeIQx, DiMeIQx, and PhIP) in chicken cooked by various methods to different degrees of doneness. Chicken breasts were panfried, oven-broiled, or grilled/barbecued. Whole chickens were roasted or stewed. Skinless, boneless chicken breasts were cooked to three degrees of doneness: just until done, well done, or very well done. High levels of PhIP (ranging from 12 to 480 ng/g cooked meat) were found in chicken breasts when panfried, oven-broiled, and grilled /barbecued but not in whole roasted or stewed chicken. PhIP concentration increased in skinless, boneless chicken breast with longer cooking time, higher internal temperature, and greater degree of surface browning. PhIP concentration was also high in chicken breasts cooked with skin and bones. MeIQx and DiMeIQx levels increased with the degree of doneness, whereas IQ and MeIQ were not detectable in any of these chicken samples. Certain cooking methods produce PhIP, a known colon and breast carcinogen in rodents and possibly a human carcinogen, at substantially higher levels in chicken than has been reported previously in red meat. JF - Cancer Research AU - Sinha, R AU - Rothman, N AU - Brown, ED AU - Salmon, C P AU - Knize, M G AU - Swanson, CA AU - Rossi, S C AU - Mark, S D AU - Levander, O A AU - Felton, J S AD - Epidemiology and Biostatistics Program, National Cancer Institute, NIH, Executive Plaza North, Room 443, 6130 Executive Boulevard, Rockville, MD 20892, USA Y1 - 1995/10// PY - 1995 DA - Oct 1995 SP - 4516 EP - 4519 VL - 55 IS - 20 SN - 0008-5472, 0008-5472 KW - chickens KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - heterocyclic amines KW - Toxicology Abstracts KW - carcinogens KW - poultry KW - cooking KW - X 24120:Food, additives & contaminants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15910926?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3A&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=JAMA%3A+Journal+of+the+American+Medical+Association&rft.atitle=Destructive+periodontal+disease+and+tobacco+and+cannabis+smoking&rft.au=Hujoel%2C+Philippe+P.&rft.aulast=Hujoel&rft.aufirst=Philippe&rft.date=2008-02-01&rft.volume=299&rft.issue=5&rft.spage=574&rft.isbn=&rft.btitle=&rft.title=JAMA%3A+Journal+of+the+American+Medical+Association&rft.issn=00987484&rft_id=info:doi/10.1001%2Fjama.299.5.574 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - carcinogens; cooking; poultry ER - TY - JOUR T1 - Effects of second intracellular loop mutations on signal transduction and internalization of the gonadotropin-releasing hormone receptor. AN - 77581519; 7559413 AB - The gonadotropin-releasing hormone (GnRH) receptor belongs to the superfamily of heptahelical G protein coupled receptors, most of which have a highly conserved DRYXXV/IXXPL sequence in the second intracellular (2i) loop that has been implicated in G protein coupling. The predicted 2i loop of the GnRH receptor contains serine rather than tyrosine in the DRY sequence but retains the conserved hydrophobic Leu residue, which is required for G protein coupling and internalization of muscarinic receptors. The present study examined the effects of mutating the unique Ser140 to the conserved Tyr, and the conserved Leu147 to Ala or Asp, on agonist binding, internalization, and signal transduction. The S140Y mutant showed a 100% increase in agonist binding affinity, and its internalization was increased by 60% above that of the wild-type receptor. The binding characteristics of the Leu147 mutants were indistinguishable from those of the wild-type receptor, but their internalization was reduced by about 50%. The L147A and L147D mutants also showed significant impairment of GnRH-stimulated inositol phosphate production. These findings demonstrate that substitution of Ser140 by Tyr does not affect G protein coupling but significantly increases receptor affinity and internalization rate. In contrast, replacement of a conserved aliphatic residue (Leu147) impairs both G protein coupling and agonist-induced receptor internalization. JF - The Journal of biological chemistry AU - Arora, K K AU - Sakai, A 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 - 1995/09/29/ PY - 1995 DA - 1995 Sep 29 SP - 22820 EP - 22826 VL - 270 IS - 39 SN - 0021-9258, 0021-9258 KW - Receptors, LHRH KW - 0 KW - Recombinant Proteins KW - Guanosine 5'-O-(3-Thiotriphosphate) KW - 37589-80-3 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Humans KW - Amino Acid Sequence KW - Mice KW - Guanosine 5'-O-(3-Thiotriphosphate) -- pharmacology KW - Rats KW - Mutagenesis, Site-Directed KW - Cattle KW - Conserved Sequence KW - Transfection KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Cercopithecus aethiops KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Sequence Homology, Amino Acid KW - Cell Line KW - Receptors, LHRH -- physiology KW - Receptors, LHRH -- chemistry KW - Protein Structure, Secondary KW - GTP-Binding Proteins -- metabolism KW - Point Mutation KW - Receptors, LHRH -- biosynthesis KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77581519?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=JAMA%3A+Journal+of+the+American+Medical+Association&rft.atitle=Marijuana+use+starting+in+youth+linked+to+IQ+loss&rft.au=Kuehn%2C+Bridget+M.&rft.aulast=Kuehn&rft.aufirst=Bridget&rft.date=2012-09-26&rft.volume=308&rft.issue=12&rft.spage=&rft.isbn=&rft.btitle=&rft.title=JAMA%3A+Journal+of+the+American+Medical+Association&rft.issn=00987484&rft_id=info:doi/10.1001%2F2012.jama.12205 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-06 N1 - Date created - 1995-11-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Homodimers of chromosomal proteins HMG-14 and HMG-17 in nucleosome cores. AN - 77573380; 7563062 AB - In this work, we report that nucleosome core particles interact with an equimolar mixture of the chromosomal proteins HMG-14 and HMG-17 to form, exclusively, complexes containing two molecules of either HMG-14 or HMG-17 (homodimers). Analysis of the binding of various mixtures of wild-type proteins and their deletion mutants indicates that homodimer formation is not dependent on contacts between the nucleosome-bound HMG-14/-17 proteins themselves. We suggest that HMG-14/-17 proteins in nucleosomes cross-talk by inducing specific allosteric transitions in the chromatin subunit. JF - Journal of molecular biology AU - Postnikov, Y V AU - Trieschmann, L AU - Rickers, A AU - Bustin, M AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/09/29/ PY - 1995 DA - 1995 Sep 29 SP - 423 EP - 432 VL - 252 IS - 4 SN - 0022-2836, 0022-2836 KW - High Mobility Group Proteins KW - 0 KW - Nucleosomes KW - Recombinant Proteins KW - Index Medicus KW - Antibody Specificity KW - Recombinant Proteins -- metabolism KW - Humans KW - Allosteric Regulation KW - Protein Binding KW - Sequence Deletion KW - High Mobility Group Proteins -- genetics KW - Nucleosomes -- metabolism KW - High Mobility Group Proteins -- immunology KW - High Mobility Group Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77573380?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cancer+biology&rft.atitle=Targeting+Pseudomonas+exotoxin+to+hematologic+malignancies.&rft.au=Kreitman%2C+R+J%3BPastan%2C+I&rft.aulast=Kreitman&rft.aufirst=R&rft.date=1995-10-01&rft.volume=6&rft.issue=5&rft.spage=297&rft.isbn=&rft.btitle=&rft.title=Seminars+in+cancer+biology&rft.issn=1044579X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-02 N1 - Date created - 1995-11-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Correlation between catalytic activity and protein content for the polymorphically expressed dihydropyrimidine dehydrogenase in human lymphocytes. AN - 77570152; 7575656 AB - A TLC procedure was developed to determine dihydropyrimidine dehydrogenase (DPD) activity in human peripheral lymphocytes. The assay, which used radiolabeled uracil as a substrate, was validated using recombinant pig DPD in which it was demonstrated to yield kinetic constants similar to those found by methods that rely on either spectroscopic determination of NADPH oxidation or HPLC. DPD activity was measured in a group of human lymphocyte extracts, including an extract from a subject that actually presented toxicity to 5-fluorouracil treatment. Measurements of DPD protein content using western immunoblots revealed a significant correlation with activity levels in human lymphocytes. Thus, this correlation could be used to determine not only the levels of expression of this enzyme, which is the cause of an inherited genetic deficiency in pyrimidine catabolism, but also to estimate the degree of sensitivity to pyrimidine-based cancer drugs such as 5-fluorouracil. JF - Biochemical pharmacology AU - Fernandez-Salguero, P AU - Gonzalez, F J AU - Etienne, M C AU - Milano, G AU - Kimura, S AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/09/28/ PY - 1995 DA - 1995 Sep 28 SP - 1015 EP - 1020 VL - 50 IS - 7 SN - 0006-2952, 0006-2952 KW - Recombinant Proteins KW - 0 KW - Oxidoreductases KW - EC 1.- KW - Dihydrouracil Dehydrogenase (NADP) KW - EC 1.3.1.2 KW - Index Medicus KW - Swine KW - Animals KW - Liver -- enzymology KW - Blotting, Western KW - Polymorphism, Genetic KW - Kinetics KW - Humans KW - Escherichia coli -- enzymology KW - Recombinant Proteins -- analysis KW - Catalysis KW - Oxidoreductases -- isolation & purification KW - Chromatography, Thin Layer -- methods KW - Oxidoreductases -- genetics KW - Lymphocytes -- enzymology KW - Oxidoreductases -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77570152?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=Correlation+between+catalytic+activity+and+protein+content+for+the+polymorphically+expressed+dihydropyrimidine+dehydrogenase+in+human+lymphocytes.&rft.au=Fernandez-Salguero%2C+P%3BGonzalez%2C+F+J%3BEtienne%2C+M+C%3BMilano%2C+G%3BKimura%2C+S&rft.aulast=Fernandez-Salguero&rft.aufirst=P&rft.date=1995-09-28&rft.volume=50&rft.issue=7&rft.spage=1015&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-21 N1 - Date created - 1995-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased susceptibility of ras-transformed cells to phenylacetate is associated with inhibition of p21ras isoprenylation and phenotypic reversion. AN - 77529666; 7558439 AB - Alterations in the expression of ras oncogenes are characteristic of a wide variety of human neoplasms. Accumulating evidence has linked elevated ras expression with disease progression and with failure of tumors to respond to conventional therapies, including radiotherapy and certain chemotherapies. These observations led us to investigate the response of ras-transformed cells to the differentiation-inducer phenylacetate (PA). Using gene transfer models, we show that PA caused cytostasis in ras-transformed mesenchymal cells, associated with increased expression of 2',5'-oligoadenylate synthetase, an enzyme implicated in negative growth control. PA also induced phenotypic reversion characterized by loss of anchorage-independent growth, reduced invasiveness and increased expression of collagen alpha type I, a marker of cell differentiation. The anti-tumor activity of PA was observed in cases involving either Ha- or Ki-ras and was independent of the mode of oncogene activation. Interestingly, in contrast to their relative resistance to radiation and doxorubicin, ras-transformed cells were significantly more sensitive to PA than their parental cells. The profound changes in tumor cell and molecular biology were associated with reduced isoprenylation of the ras-encoded p21. Our results indicate that PA can suppress the growth of ras-transformed cells, resistant otherwise to free-radical based therapies, through interference with p21ras isoprenylation, critical to signal transduction and maintenance of the malignant phenotype. JF - International journal of cancer AU - Shack, S AU - Chen, L C AU - Miller, A C AU - Danesi, R AU - Samid, D AD - Clinical Pharmacology Branch, National Cancer Institute, Bethesda, MD, USA. Y1 - 1995/09/27/ PY - 1995 DA - 1995 Sep 27 SP - 124 EP - 129 VL - 63 IS - 1 SN - 0020-7136, 0020-7136 KW - Antimetabolites, Antineoplastic KW - 0 KW - Growth Inhibitors KW - Phenylacetates KW - HRAS protein, human KW - EC 3.6.5.2 KW - Proto-Oncogene Proteins p21(ras) KW - phenylacetic acid KW - ER5I1W795A KW - Index Medicus KW - Phenotype KW - Genes, ras KW - Animals KW - 3T3 Cells KW - Humans KW - Tumor Cells, Cultured -- pathology KW - Mice KW - Cell Differentiation -- drug effects KW - Proto-Oncogene Proteins p21(ras) -- metabolism KW - Protein Prenylation -- drug effects KW - Phenylacetates -- pharmacology KW - Cell Transformation, Neoplastic -- pathology KW - Growth Inhibitors -- pharmacology KW - Cell Transformation, Neoplastic -- drug effects KW - Antimetabolites, Antineoplastic -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77529666?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Increased+susceptibility+of+ras-transformed+cells+to+phenylacetate+is+associated+with+inhibition+of+p21ras+isoprenylation+and+phenotypic+reversion.&rft.au=Shack%2C+S%3BChen%2C+L+C%3BMiller%2C+A+C%3BDanesi%2C+R%3BSamid%2C+D&rft.aulast=Shack&rft.aufirst=S&rft.date=1995-09-27&rft.volume=63&rft.issue=1&rft.spage=124&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 - 1995-11-03 N1 - Date created - 1995-11-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hydrophobic cluster analysis predicts an amino-terminal domain of varicella-zoster virus open reading frame 10 required for transcriptional activation. AN - 77574817; 7568128 AB - Varicella-zoster virus open reading frame 10 (ORF10) protein, the homolog of the herpes simplex virus protein VP16, can transactivate immediate-early promoters from both viruses. A protein sequence comparison procedure termed hydrophobic cluster analysis was used to identify a motif centered at Phe-28, near the amino terminus of ORF10, that strongly resembles the sequence of the activating domain surrounding Phe-442 of VP16. With a series of GAL4-ORF10 fusion proteins, we mapped the ORF10 transcriptional-activation domain to the amino-terminal region (aa 5-79). Extensive mutagenesis of Phe-28 in GAL4-ORF10 fusion proteins demonstrated the importance of an aromatic or bulky hydrophobic amino acid at this position, as shown previously for Phe-442 of VP16. Transactivation by the native ORF10 protein was abolished when Phe-28 was replaced by Ala. Similar amino-terminal domains were identified in the VP16 homologs of other alphaherpesviruses. Hydrophobic cluster analysis correctly predicted activation domains of ORF10 and VP16 that share critical characteristics of a distinctive subclass of acidic activation domains. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Moriuchi, H AU - Moriuchi, M AU - Pichyangkura, R AU - Triezenberg, S J AU - Straus, S E AU - Cohen, J I AD - Medical Virology Section, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. Y1 - 1995/09/26/ PY - 1995 DA - 1995 Sep 26 SP - 9333 EP - 9337 VL - 92 IS - 20 SN - 0027-8424, 0027-8424 KW - DNA-Binding Proteins KW - 0 KW - Fungal Proteins KW - GAL4 protein, S cerevisiae KW - Herpes Simplex Virus Protein Vmw65 KW - ORF 10 protein, varicella-zoster virus KW - Recombinant Fusion Proteins KW - Saccharomyces cerevisiae Proteins KW - Trans-Activators KW - Transcription Factors KW - Viral Proteins KW - Phenylalanine KW - 47E5O17Y3R KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - Animals KW - Chloramphenicol O-Acetyltransferase -- biosynthesis KW - Herpes Simplex Virus Protein Vmw65 -- chemistry KW - Fungal Proteins -- biosynthesis KW - Viral Proteins -- biosynthesis KW - Amino Acid Sequence KW - Mutagenesis, Site-Directed KW - Transfection KW - Cercopithecus aethiops KW - Molecular Sequence Data KW - Vero Cells KW - Sequence Homology, Amino Acid KW - Cell Line KW - Protein Conformation KW - Herpesvirus 3, Human -- genetics KW - Trans-Activators -- biosynthesis KW - Trans-Activators -- genetics KW - Open Reading Frames KW - Trans-Activators -- chemistry KW - Herpesvirus 3, Human -- metabolism KW - Transcriptional Activation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77574817?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hydrophobic+cluster+analysis+predicts+an+amino-terminal+domain+of+varicella-zoster+virus+open+reading+frame+10+required+for+transcriptional+activation.&rft.au=Moriuchi%2C+H%3BMoriuchi%2C+M%3BPichyangkura%2C+R%3BTriezenberg%2C+S+J%3BStraus%2C+S+E%3BCohen%2C+J+I&rft.aulast=Moriuchi&rft.aufirst=H&rft.date=1995-09-26&rft.volume=92&rft.issue=20&rft.spage=9333&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 - 1995-10-27 N1 - Date created - 1995-10-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1993 Jul;67(7):4290-5 [8389928] J Virol. 1993 Jul;67(7):4246-51 [8389926] J Gen Virol. 1993 Sep;74 ( Pt 9):1837-45 [8397281] Cell. 1993 Nov 5;75(3):519-30 [8221891] J Virol. 1993 Dec;67(12):7573-81 [8230477] Virology. 1994 Jan;198(1):385-9 [8259676] Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):192-6 [8278363] Nucleic Acids Res. 1993 Dec 25;21(25):5987-96 [8290361] Virology. 1994 Apr;200(1):297-300 [8128631] J Virol. 1994 Aug;68(8):4890-7 [8035487] J Virol. 1994 Aug;68(8):4898-909 [8035488] C R Acad Sci III. 1994 Jul;317(7):597-606 [7882145] Nucleic Acids Res. 1985 Nov 11;13(21):7865-79 [2999707] Science. 1986 Feb 14;231(4739):699-704 [3080805] J Gen Virol. 1986 Sep;67 ( Pt 9):1759-816 [3018124] Genes Dev. 1988 Jun;2(6):718-29 [2843425] Nature. 1988 Oct 6;335(6190):563-4 [3047590] Nature. 1989 Mar 2;338(6210):39-44 [2521923] Gene. 1989 Apr 15;77(1):51-9 [2744487] EMBO J. 1989 Aug;8(8):2337-42 [2676518] Science. 1991 Jan 4;251(4989):87-90 [1846049] Biochimie. 1990 Aug;72(8):555-74 [2126461] J Virol. 1983 May;46(2):371-7 [6302308] Gene. 1991 Jul 22;103(2):235-8 [1653757] J Virol. 1991 Nov;65(11):5880-5 [1656076] J Virol. 1992 Jan;66(1):359-66 [1309252] Virology. 1992 Jul;189(1):304-16 [1318606] Gene. 1992 Oct 1;119(2):259-63 [1327963] Virology. 1992 Nov;191(1):346-54 [1329324] Protein Eng. 1992 Oct;5(7):629-35 [1480617] Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):883-7 [8381535] Cell. 1993 Feb 26;72(4):575-85 [8440021] J Virol. 1993 May;67(5):2739-46 [8386275] Mol Cell Biol. 1993 Sep;13(9):5233-44 [8395001] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tyrosine phosphorylation of protein kinase C-delta in response to the activation of the high-affinity receptor for immunoglobulin E modifies its substrate recognition. AN - 77566711; 7568083 AB - The delta isoform of protein kinase C is phosphorylated on tyrosine in response to antigen activation of the high-affinity receptor for immunoglobulin E. While protein kinase C-delta associates with and phosphorylates this receptor, immunoprecipitation of the receptor revealed that little, if any, tyrosine-phosphorylated protein kinase C-delta is receptor associated. In vitro kinase assays with immunoprecipitated tyrosine-phosphorylated protein kinase C-delta showed that the modified enzyme had diminished activity toward the receptor gamma-chain peptide as a substrate but not toward histones or myelin basic protein peptide. We propose a model in which the tyrosine phosphorylation of protein kinase C-delta regulates the kinase specificity toward a given substrate. This may represent a general mechanism by which in vivo protein kinase activities are regulated in response to external stimuli. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Haleem-Smith, H AU - Chang, E Y AU - Szallasi, Z AU - Blumberg, P M AU - Rivera, J AD - Section of Chemical Immunology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892-1820, USA. Y1 - 1995/09/26/ PY - 1995 DA - 1995 Sep 26 SP - 9112 EP - 9116 VL - 92 IS - 20 SN - 0027-8424, 0027-8424 KW - Antigens KW - 0 KW - Isoenzymes KW - Receptors, IgE KW - Phosphotyrosine KW - 21820-51-9 KW - Immunoglobulin E KW - 37341-29-0 KW - Tyrosine KW - 42HK56048U KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Immunoglobulin E -- pharmacology KW - Phosphotyrosine -- metabolism KW - Cell Membrane -- physiology KW - Leukemia, Basophilic, Acute KW - Antigens -- pharmacology KW - Rats KW - Cell Membrane -- immunology KW - Tumor Cells, Cultured KW - Phosphorylation KW - Kinetics KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Substrate Specificity KW - Cell Line KW - Signal Transduction KW - Protein Kinase C -- metabolism KW - Receptors, IgE -- metabolism KW - Isoenzymes -- isolation & purification KW - Receptors, IgE -- isolation & purification KW - Protein Kinase C -- isolation & purification KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77566711?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Tyrosine+phosphorylation+of+protein+kinase+C-delta+in+response+to+the+activation+of+the+high-affinity+receptor+for+immunoglobulin+E+modifies+its+substrate+recognition.&rft.au=Haleem-Smith%2C+H%3BChang%2C+E+Y%3BSzallasi%2C+Z%3BBlumberg%2C+P+M%3BRivera%2C+J&rft.aulast=Haleem-Smith&rft.aufirst=H&rft.date=1995-09-26&rft.volume=92&rft.issue=20&rft.spage=9112&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 - 1995-10-27 N1 - Date created - 1995-10-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Immunol. 1992 Oct 1;149(7):2428-36 [1388191] Anal Biochem. 1994 Aug 15;221(1):94-102 [7527191] J Biol Chem. 1993 Jan 25;268(3):1749-56 [8420951] J Biol Chem. 1993 Feb 5;268(4):2280-3 [8381401] J Biol Chem. 1993 Apr 5;268(10):7571-6 [8463287] J Biol Chem. 1993 Dec 15;268(35):26079-81 [8253722] J Biol Chem. 1994 Jan 21;269(3):2118-24 [8294465] J Biol Chem. 1994 Jan 28;269(4):2349-52 [7507923] Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7722-6 [8052650] J Biol Chem. 1994 Sep 16;269(37):23102-7 [8083212] Eur J Immunol. 1981 Apr;11(4):317-23 [6166481] Proc Natl Acad Sci U S A. 1985 Dec;82(23):8193-7 [2415983] Proc Natl Acad Sci U S A. 1988 Jun;85(11):3753-7 [3287375] J Immunol. 1988 Aug 1;141(3):942-7 [2969395] J Biol Chem. 1991 Aug 25;266(24):15771-81 [1874734] Nature. 1991 Oct 31;353(6347):855-8 [1834946] Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):222-6 [1530886] J Biol Chem. 1992 Mar 15;267(8):5434-41 [1372002] J Immunol. 1992 Aug 1;149(3):1031-7 [1378861] Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):9175-9 [7522330] Mol Cell Biol. 1994 Oct;14(10):6727-35 [7935392] Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11446-50 [1280826] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic transfer of a nonpeptide antagonist binding site to a previously unresponsive angiotensin receptor. AN - 77559060; 7568109 AB - Mutational analysis based on the pharmacological differences between mammalian and amphibian angiotensin II receptors (AT receptors) previously identified 7 aa residues located in transmembrane domains (TMs) III (Val-108), IV (Ala-163), V (Pro-192, Thr-198), VI (Ser-252), and VII (Leu-300, Phe-301) of the rat AT receptor type 1b (rAT1b receptor) that significantly influenced binding of the nonpeptide antagonist Losartan. Further studies have shown that an additional 6 residues in the rAT1b receptor TMs II (Ala-73), III (Ser-109, Ala-114, Ser-115), VI (Phe-248), and VII (Asn-295) are important in Losartan binding. The 13 residues required for Losartan binding in the mammalian receptor were exchanged for the corresponding amino acids in the Xenopus AT receptor type a (xATa receptor) to generate a mutant amphibian receptor that bound Losartan with the same affinity as the rAT1b receptor (Losartan IC50 values: rAT1b, 2.2 +/- 0.2 nM: xATa, > 50 microM; mutant, 2.0 +/- 0.1 nM). To our knowledge, this is the first report of a gain-of-function mutant in which the residues crucial to formation of a ligand binding site in a mammalian peptide hormone receptor were transferred to a previously unresponsive receptor by site-directed mutagenesis. Ala substitutions and comparison of mammalian and amphibian combinatorial mutants indicated that TM III in the rAT1b receptor plays a key role in Losartan binding. Identification of residues involved in nonpeptide ligand binding will facilitate studies aimed at elucidating the chemical basis for ligand recognition in the AT receptor and peptide hormone receptors in general. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Ji, H AU - Zheng, W AU - Zhang, Y AU - Catt, K J AU - Sandberg, K AD - Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/09/26/ PY - 1995 DA - 1995 Sep 26 SP - 9240 EP - 9244 VL - 92 IS - 20 SN - 0027-8424, 0027-8424 KW - Antihypertensive Agents KW - 0 KW - Biphenyl Compounds KW - Imidazoles KW - Ligands KW - Receptors, Angiotensin KW - Recombinant Proteins KW - Tetrazoles KW - Saralasin KW - H2AFV2HE66 KW - Losartan KW - JMS50MPO89 KW - Index Medicus KW - Animals KW - Protein Structure, Secondary KW - Recombinant Proteins -- biosynthesis KW - Mammals KW - DNA Mutational Analysis KW - Imidazoles -- metabolism KW - Amphibians KW - Saralasin -- metabolism KW - Amino Acid Sequence KW - Antihypertensive Agents -- metabolism KW - Binding Sites KW - Rats KW - Mutagenesis, Site-Directed KW - Tetrazoles -- metabolism KW - Kinetics KW - Binding, Competitive KW - Cercopithecus aethiops KW - Molecular Sequence Data KW - Kidney KW - Xenopus KW - Biphenyl Compounds -- metabolism KW - Cell Line KW - Receptors, Angiotensin -- chemistry KW - Transfection KW - Receptors, Angiotensin -- metabolism KW - Receptors, Angiotensin -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77559060?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genetic+transfer+of+a+nonpeptide+antagonist+binding+site+to+a+previously+unresponsive+angiotensin+receptor.&rft.au=Ji%2C+H%3BZheng%2C+W%3BZhang%2C+Y%3BCatt%2C+K+J%3BSandberg%2C+K&rft.aulast=Ji&rft.aufirst=H&rft.date=1995-09-26&rft.volume=92&rft.issue=20&rft.spage=9240&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 - 1995-10-27 N1 - Date created - 1995-10-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1994 Nov 11;269(45):28160-4 [7525569] Curr Opin Biotechnol. 1994 Aug;5(4):434-44 [7765177] Annu Rev Biochem. 1994;63:101-32 [7979235] Biochemistry. 1994 Dec 6;33(48):14543-9 [7981216] J Biol Chem. 1994 Dec 9;269(49):30953-9 [7983030] J Biol Chem. 1995 Feb 3;270(5):2284-9 [7530721] Nature. 1995 Mar 2;374(6517):74-7 [7532789] Biochem Biophys Res Commun. 1995 Apr 6;209(1):153-60 [7726829] Chem Biol. 1994 Dec;1(4):211-21 [9383393] FASEB J. 1989 May;3(7):1825-32 [2541037] Mol Pharmacol. 1991 Feb;39(2):120-3 [1996080] FEBS Lett. 1991 Jun 24;284(2):281-4 [2060651] Biochem J. 1992 Apr 1;283 ( Pt 1):1-19 [1314560] J Biol Chem. 1992 May 15;267(14):9455-8 [1374402] J Cell Biochem. 1992 Oct;50(2):159-64 [1429881] J Biol Chem. 1992 Dec 25;267(36):25664-7 [1281469] J Biol Chem. 1993 Feb 5;268(4):2319-23 [7679096] Nature. 1993 Mar 25;362(6418):345-8 [7681152] Mol Pharmacol. 1993 Jul;44(1):1-7 [8341266] Biochem Biophys Res Commun. 1993 Jul 30;194(2):756-62 [7688227] Pharmacol Rev. 1993 Jun;45(2):205-51 [8372104] J Biol Chem. 1994 Jan 21;269(3):1610-3 [8294406] Nature. 1994 Apr 14;368(6472):648-51 [8145852] J Biol Chem. 1994 Jun 17;269(24):16533-6 [8206967] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7046-50 [8041743] Mol Pharmacol. 1994 Oct;46(4):693-701 [7969048] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Development of a rapid approach to identification of tyrosine phosphorylation sites: application to PKC delta phosphorylated upon activation of the high affinity receptor for IgE in rat basophilic leukemia cells. AN - 77565829; 7575560 AB - In rat basophilic leukemia cells (RBL-2H3) activation of the high affinity receptor for IgE induces tyrosine phosphorylation of PKC delta. We carried out solid phase synthesis of 15 amino acid long oligopeptides corresponding to the sequences around each of the 19 tyrosine residues in PKC delta. Only three oligopeptides, corresponding to tyrosine 52, 155, and 565, were phosphorylated when exposed to lyn kinase. Single mutants in each of these three tyrosine residues of PKC delta were prepared. Upon expression in the RBL-2H3 cells, only the mutant in tryosine 52 showed abolition of the IgE-antigen induced tyrosine phosphorylation. JF - Biochemical and biophysical research communications AU - Szallasi, Z AU - Denning, M F AU - Chang, E Y AU - Rivera, J AU - Yuspa, S H AU - Lehel, C AU - Olah, Z AU - Anderson, W B AU - Blumberg, P M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/09/25/ PY - 1995 DA - 1995 Sep 25 SP - 888 EP - 894 VL - 214 IS - 3 SN - 0006-291X, 0006-291X KW - Isoenzymes KW - 0 KW - Oligopeptides KW - Receptors, IgE KW - Phosphotyrosine KW - 21820-51-9 KW - Tyrosine KW - 42HK56048U KW - lyn protein-tyrosine kinase KW - EC 2.7.10.2 KW - src-Family Kinases KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Rats KW - Animals KW - Receptors, IgE -- metabolism KW - Tumor Cells, Cultured KW - Phosphorylation KW - Phosphotyrosine -- analysis KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Substrate Specificity KW - Cell Line KW - Leukemia, Basophilic, Acute KW - Protein Kinase C -- metabolism KW - src-Family Kinases -- metabolism KW - Oligopeptides -- chemistry KW - Oligopeptides -- metabolism KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77565829?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=Development+of+a+rapid+approach+to+identification+of+tyrosine+phosphorylation+sites%3A+application+to+PKC+delta+phosphorylated+upon+activation+of+the+high+affinity+receptor+for+IgE+in+rat+basophilic+leukemia+cells.&rft.au=Szallasi%2C+Z%3BDenning%2C+M+F%3BChang%2C+E+Y%3BRivera%2C+J%3BYuspa%2C+S+H%3BLehel%2C+C%3BOlah%2C+Z%3BAnderson%2C+W+B%3BBlumberg%2C+P+M&rft.aulast=Szallasi&rft.aufirst=Z&rft.date=1995-09-25&rft.volume=214&rft.issue=3&rft.spage=888&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-02 N1 - Date created - 1995-11-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gel electrophoretic analysis of cellular and secreted proteins from resting and activated rat alveolar macrophages treated with pentamidine isethionate. AN - 77549828; 7581850 AB - Pneumocystic carinii pneumonia, which is a major cause of death among patients suffering from acquired immunodeficiency syndrome, has often been treated successfully with pentamidine isethionate. This study examines pentamidine effects on cellular and secreted proteins from rat alveolar macrophages by two-dimensional gel electrophoresis and computerized image analysis. Over 100 secreted proteins were detected by fluorography. Fluorography showed pentamidine diminished tumor necrosis factor and interleukin-1 release along with other proteins. Effects of combined bacterial lipopolysaccharide and pentamidine were more pronounced on secreted versus cellular proteins in protein amount and pattern difference. Thus pentamidine exhibited a general repressive effect on cellular and secreted protein expression in resting and activated macrophages. JF - Journal of chromatography. A AU - Selkirk, J K AU - He, C AU - Merrick, B A AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/09/22/ PY - 1995 DA - 1995 Sep 22 SP - 331 EP - 337 VL - 711 IS - 2 SN - 0021-9673, 0021-9673 KW - Antifungal Agents KW - 0 KW - Proteins KW - Pentamidine KW - 673LC5J4LQ KW - Index Medicus KW - AIDS/HIV KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Spectrometry, Fluorescence KW - Cells, Cultured KW - Female KW - Proteins -- secretion KW - Electrophoresis, Gel, Two-Dimensional -- methods KW - Antifungal Agents -- pharmacology KW - Pentamidine -- pharmacology KW - Macrophages, Alveolar -- chemistry KW - Proteins -- analysis KW - Macrophages, Alveolar -- drug effects KW - Macrophages, Alveolar -- secretion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77549828?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+chromatography.+A&rft.atitle=Gel+electrophoretic+analysis+of+cellular+and+secreted+proteins+from+resting+and+activated+rat+alveolar+macrophages+treated+with+pentamidine+isethionate.&rft.au=Selkirk%2C+J+K%3BHe%2C+C%3BMerrick%2C+B+A&rft.aulast=Selkirk&rft.aufirst=J&rft.date=1995-09-22&rft.volume=711&rft.issue=2&rft.spage=331&rft.isbn=&rft.btitle=&rft.title=Journal+of+chromatography.+A&rft.issn=00219673&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-29 N1 - Date created - 1995-11-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Anti-p53 antibodies in sera of workers occupationally exposed to vinyl chloride. AN - 77490889; 7658501 AB - The p53 tumor suppressor gene (also known as TP53) is often mutated in a wide variety of cancers, including angiosarcoma of the liver (ASL). Anti-p53 antibodies have been detected in the sera of patients with leukemia, childhood lymphoma, or cancers such as those of the breast, lung, colon, esophagus, and liver (hepatocellular carcinoma). The objective of this study was to determine the prevalence and time of appearance of serum anti-p53 antibodies during the pathogenesis of ASL associated with occupational exposure to vinyl chloride. Enzyme-linked immunoassay (EIA) was used to detect anti-p53 antibodies in 148 serum samples from 92 individuals occupationally exposed (in France or in Kentucky) to vinyl chloride; 15 of these individuals (six from France and nine from Kentucky) had ASL. A subset of coded EIA-positive and EIA-negative sera was further analyzed for anti-p53 antibodies by immunoblotting and immunoprecipitation. Nucleotide sequence analysis of exons 5-8 of the p53 gene was conducted on ASL DNA from six patients. We tested sera from 31 men who had no occupational exposure to vinyl chloride; they made up the control group. Statistical analyses were done using the Kruskal-Wallis chi-squared approximation and the Wilcoxon two-sample test for normal approximation. All P values result from two-sided tests. Fourteen serum samples (from nine individuals) were positive in the EIA. Five of the 15 individuals with ASL were positive for anti-p53 antibodies by EIA, immunoblotting, and immunoprecipitation: one individual at 11.3 and 10.8 years before diagnosis, another at 4 months before and shortly after diagnosis, and three when diagnosed or shortly thereafter. Four of the 77 vinyl chloride-exposed workers without diagnosed ASL were positive for anti-p53 antibodies; two of the four had symptoms related to vinyl chloride toxicity. Tumors from three of the six vinyl chloride-exposed workers from which sufficient DNA for analysis was obtained had A:T to T:A missense mutations of the p53 gene. Anti-p53 antibodies were detected in two of these individuals. Among the control group, two of 15 serum samples from 15 lung cancer patients and zero of 15 serum samples from control subjects without cancer had anti-p53 antibodies as substantially lower levels than the nine (10%) of 92 vinyl chloride-exposed workers who were positive for anti-p53 antibodies. Serum anti-p53 antibodies can predate clinical diagnosis of certain tumors, such as ASL, and may be useful in identifying individuals at high cancer risk, such as workers with occupational exposure to vinyl chloride. JF - Journal of the National Cancer Institute AU - Trivers, G E AU - Cawley, H L AU - DeBenedetti, V M AU - Hollstein, M AU - Marion, M J AU - Bennett, W P AU - Hoover, M L AU - Prives, C C AU - Tamburro, C C AU - Harris, C C AD - Laboratory of Human Carcinogenesis, Division of Cancer Etiology, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/09/20/ PY - 1995 DA - 1995 Sep 20 SP - 1400 EP - 1407 VL - 87 IS - 18 SN - 0027-8874, 0027-8874 KW - TP53 KW - Antibodies, Neoplasm KW - 0 KW - Vinyl Chloride KW - WD06X94M2D KW - Index Medicus KW - Immunoblotting KW - Aged, 80 and over KW - Humans KW - Adult KW - Enzyme-Linked Immunosorbent Assay KW - Aged KW - Middle Aged KW - Precipitin Tests KW - Time Factors KW - Male KW - Female KW - Occupational Exposure KW - Hemangiosarcoma -- immunology KW - Antibodies, Neoplasm -- drug effects KW - Vinyl Chloride -- adverse effects KW - Hemangiosarcoma -- genetics KW - Genes, p53 -- immunology KW - Liver Neoplasms -- immunology KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77490889?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Anti-p53+antibodies+in+sera+of+workers+occupationally+exposed+to+vinyl+chloride.&rft.au=Trivers%2C+G+E%3BCawley%2C+H+L%3BDeBenedetti%2C+V+M%3BHollstein%2C+M%3BMarion%2C+M+J%3BBennett%2C+W+P%3BHoover%2C+M+L%3BPrives%2C+C+C%3BTamburro%2C+C+C%3BHarris%2C+C+C&rft.aulast=Trivers&rft.aufirst=G&rft.date=1995-09-20&rft.volume=87&rft.issue=18&rft.spage=1400&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 - 1995-10-04 N1 - Date created - 1995-10-04 N1 - Date revised - 2017-01-13 N1 - Gene symbol - TP53 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sensitization and desensitization of the NMDA receptor complex. Implications for therapy. AN - 77626091; 7486630 JF - Annals of the New York Academy of Sciences AU - Fossom, L H AU - Skolnick, P AD - Laboratory of Neuroscience, NIDDK/NIH, Bethesda, Maryland 20892, USA. Y1 - 1995/09/15/ PY - 1995 DA - 1995 Sep 15 SP - 320 EP - 321 VL - 765 SN - 0077-8923, 0077-8923 KW - Ion Channels KW - 0 KW - Neuroprotective Agents KW - Neurotoxins KW - Receptors, N-Methyl-D-Aspartate KW - Index Medicus KW - Animals KW - Brain Ischemia -- drug therapy KW - Humans KW - Ion Channels -- physiology KW - Brain Ischemia -- physiopathology KW - Receptors, N-Methyl-D-Aspartate -- physiology KW - Receptors, N-Methyl-D-Aspartate -- agonists KW - Neurons -- drug effects KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Neurons -- physiology KW - Neuroprotective Agents -- therapeutic use KW - Neurotoxins -- toxicity KW - Neurotoxins -- antagonists & inhibitors KW - Neuroprotective Agents -- pharmacology KW - Neurons -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77626091?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Sensitization+and+desensitization+of+the+NMDA+receptor+complex.+Implications+for+therapy.&rft.au=Fossom%2C+L+H%3BSkolnick%2C+P&rft.aulast=Fossom&rft.aufirst=L&rft.date=1995-09-15&rft.volume=765&rft.issue=&rft.spage=320&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-06 N1 - Date created - 1995-12-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effects of nimodipine on the EEG of substance abusers. AN - 77622130; 7486602 AB - Cocaine abusers have increased EEG beta and areas of reduced cortical blood flow. Since, nimodipine has neuroprotective effects and increases blood flow, we investigated the efficacy of single and multiple doses of the nimodipine in normalizing the EEG of substance abusers. Fourteen subjects received single (0, 30, 60 mg) and eleven received multiple daily (up to 150 mg in 12 hours) doses of nimodipine to determine whether this drug would increase EEG alpha and decrease beta in substance abusers. The EEG was recorded from eight scalp locations (F3, C3, P3, O1, F4, C4, P4 and O2) for three minutes during eyes closed, and eyes open conditions. Single and multiple doses of nimodipine produced significant increases in EEG alpha and decreases in EEG beta in the eyes open condition. Thus, nimodipine may have potential therapeutic implications in the treatment of cocaine dependence. Chronic nimodipine dosing in cocaine-dependent individuals is now needed to confirm its efficacy in the treatment of cocaine dependence. JF - Annals of the New York Academy of Sciences AU - Herning, R I AU - Guo, X AU - Lange, W R AD - Molecular Neuropsychiatry Section, National Institutes of Health, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. Y1 - 1995/09/15/ PY - 1995 DA - 1995 Sep 15 SP - 143 EP - 51; discussion 160-2 VL - 765 SN - 0077-8923, 0077-8923 KW - Neuroprotective Agents KW - 0 KW - Nimodipine KW - 57WA9QZ5WH KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Analysis of Variance KW - Double-Blind Method KW - Humans KW - Heroin Dependence -- physiopathology KW - Heroin Dependence -- drug therapy KW - Adult KW - Alcoholism -- physiopathology KW - Male KW - Alcoholism -- drug therapy KW - Substance-Related Disorders -- physiopathology KW - Substance-Related Disorders -- drug therapy KW - Nimodipine -- therapeutic use KW - Electroencephalography -- drug effects KW - Neuroprotective Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77622130?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=The+effects+of+nimodipine+on+the+EEG+of+substance+abusers.&rft.au=Herning%2C+R+I%3BGuo%2C+X%3BLange%2C+W+R&rft.aulast=Herning&rft.aufirst=R&rft.date=1995-09-15&rft.volume=765&rft.issue=&rft.spage=143&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-06 N1 - Date created - 1995-12-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nimodipine improves information processing in substance abusers. AN - 77620495; 7486603 AB - We examined whether nimodipine can improve information processing in healthy drug abusers using cognitive event-related potential (ERP) methodology. Placebo and 30- and 60-mg doses of nimodipine were administered on separate days in a random double-blind design to twelve male subjects, who used cocaine and/or opiates as well as alcohol and marijuana. The subjects performed the auditory rare event monitoring (AREM) task and the paired letter version of the visual continuous performance task (CPT) before oral drug administration as well as one and two hours after drug ingestion. The EEG was recorded from 7 scalp locations. The P3 component of the ERPs to the target stimulus was reduced with repeated testing on the placebo day. The 30-mg dose of nimodipine blocked the decrease in P3, which reflects stimulus evaluation in both tasks. Chronic administration of nimodipine may alleviate the cognitive deficits observed in substance abusers during abstinence and prevent treatment relapse. JF - Annals of the New York Academy of Sciences AU - Herning, R I AU - Guo, X AU - Lange, W R AD - Molecular Neuropsychiatry Section, National Institutes of Health, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. Y1 - 1995/09/15/ PY - 1995 DA - 1995 Sep 15 SP - 152 EP - 9; discussion 160-2 VL - 765 SN - 0077-8923, 0077-8923 KW - Neuroprotective Agents KW - 0 KW - Nimodipine KW - 57WA9QZ5WH KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Analysis of Variance KW - Double-Blind Method KW - Humans KW - Heroin Dependence -- drug therapy KW - Heroin Dependence -- physiopathology KW - Electroencephalography -- drug effects KW - Alcoholism -- psychology KW - Alcoholism -- drug therapy KW - Evoked Potentials -- drug effects KW - Adult KW - Alcoholism -- physiopathology KW - Heroin Dependence -- psychology KW - Male KW - Substance-Related Disorders -- physiopathology KW - Substance-Related Disorders -- drug therapy KW - Nimodipine -- therapeutic use KW - Mental Processes -- drug effects KW - Substance-Related Disorders -- psychology KW - Neuroprotective Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77620495?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Nimodipine+improves+information+processing+in+substance+abusers.&rft.au=Herning%2C+R+I%3BGuo%2C+X%3BLange%2C+W+R&rft.aulast=Herning&rft.aufirst=R&rft.date=1995-09-15&rft.volume=765&rft.issue=&rft.spage=152&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-06 N1 - Date created - 1995-12-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional glycosylation sites of the rat luteinizing hormone receptor required for ligand binding. AN - 77506803; 7665591 AB - The contribution of N-linked glycosylation to the ligand binding activity of the rat luteinizing hormone receptor (LHR) was studied in wild-type and mutant LHR expressed in mammalian (COS1) cells and overexpressed in insect (Sf9) cells. The binding affinities of the holoreceptor and its truncated splice variant (form B) lacking the transmembrane domain were equivalent in both cell lines. Tunicamycin-treated transfected Sf9 cells expressed a carbohydrate-free LH receptor that lacked hormone binding activity. Functional carbohydrate chains essential for binding activity were localized to glycosylation sites at Asn-173 and Asn-152. Glycosidase treatment of the double mutant N173Q/N152Q revealed the presence of at least one additional carbohydrate chain at Asn-269, Asn-277, or Asn-291 that does not contribute to hormone binding. Asn-77 was not glycosylated, but its mutation to Gln reduced hormone binding. LHR expressed in insect cells contained only high mannose carbohydrate chains, and those located at Asn-173 and Asn-152 were sufficient for high-affinity hormone binding. Enzymatic cleavage of glycosyl chains indicated that only the proximal N-acetylglucosamine residue, which is common to high mannose and complex carbohydrate forms, is necessary for acquisition of the high affinity conformation of the receptor. The carbohydrate chains of the LHR appear to be involved in intramolecular folding of the nascent receptor rather than in its interaction with the hormone. JF - The Journal of biological chemistry AU - Zhang, R AU - Cai, H AU - Fatima, N AU - Buczko, E AU - Dufau, M L AD - Section of Molecular Endocrinology, NICHD, National Institutes of Health, Bethesda, Maryland 20892-4510, USA. Y1 - 1995/09/15/ PY - 1995 DA - 1995 Sep 15 SP - 21722 EP - 21728 VL - 270 IS - 37 SN - 0021-9258, 0021-9258 KW - Chorionic Gonadotropin KW - 0 KW - Ligands KW - Oligosaccharides KW - Receptors, LH KW - Recombinant Proteins KW - Glycoside Hydrolases KW - EC 3.2.1.- KW - Index Medicus KW - Animals KW - Spodoptera KW - Recombinant Proteins -- biosynthesis KW - Humans KW - Glycosylation KW - Mutagenesis, Site-Directed KW - Rats KW - Recombinant Proteins -- metabolism KW - Binding, Competitive KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Oligosaccharides -- chemistry KW - Carbohydrate Conformation KW - Amino Acid Sequence KW - Binding Sites KW - Transfection KW - Alternative Splicing KW - Chorionic Gonadotropin -- metabolism KW - Kinetics KW - Cercopithecus aethiops KW - Carbohydrate Sequence KW - Kidney KW - Female KW - Cell Line KW - Ovary -- metabolism KW - Protein Structure, Secondary KW - Receptors, LH -- chemistry KW - Receptors, LH -- biosynthesis KW - Receptors, LH -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77506803?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Functional+glycosylation+sites+of+the+rat+luteinizing+hormone+receptor+required+for+ligand+binding.&rft.au=Zhang%2C+R%3BCai%2C+H%3BFatima%2C+N%3BBuczko%2C+E%3BDufau%2C+M+L&rft.aulast=Zhang&rft.aufirst=R&rft.date=1995-09-15&rft.volume=270&rft.issue=37&rft.spage=21722&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 - 1995-10-12 N1 - Date created - 1995-10-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Eosinophil cationic protein and eosinophil-derived neurotoxin. Evolution of novel function in a primate ribonuclease gene family. AN - 77506605; 7665566 AB - Human eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) are members of a unique subfamily of rapidly evolving primate ribonuclease genes that emerged via a gene duplication event occurring after the divergence of Old World from New World monkeys (Rosenberg, H. F., Dyer, K. D., Tiffany, H. L., and Gonzalez, M. (1995) Nature Genet. 10, 219-223). In this work, we studied the activity of the protein encoded by the EDN/ECP homolog of the New World monkey, Saguinus oedipus (marmoset), a representative of the "ancestral" single sequences. Although the nucleotide sequence of the single marmoset gene (mEDN) was equally homologous (82%) to both human genes, the encoded amino acid sequence, calculated isoelectric point, and immunoreactivity all suggested a closer relationship with EDN. Furthermore, mEDN (at 0.3-1.0 microM concentrations) had no measurable anti-staphylococcal activity, suggesting functional as well as structural similarity to EDN. However, with yeast tRNA as substrate, mEDN had significantly less ribonuclease activity than EDN; Michaelis constants were nearly identical (Km (mEDN) = 0.67 microM; Km (EDN) = 0.70 microM), while turnover numbers differed by a factor of 100 (kcat (mEDN) = 0.91 s-1; kcat (EDN) = 0.64 x 10(-2) s-1). Thus, evolutionary constraints appear to have promoted two novel functions: increased cationicity/toxicity (ECP) and enhanced ribonuclease activity (EDN). The latter result is particularly intriguing, as it suggests a crucial role for ribonuclease activity in the (as yet to be determined) physiologic function of EDN. JF - The Journal of biological chemistry AU - Rosenberg, H F AU - Dyer, K D AD - Laboratory of Host Defenses, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/09/15/ PY - 1995 DA - 1995 Sep 15 SP - 21539 EP - 21544 VL - 270 IS - 37 SN - 0021-9258, 0021-9258 KW - Antibodies, Monoclonal KW - 0 KW - Blood Proteins KW - Eosinophil Granule Proteins KW - Neurotoxins KW - Eosinophil-Derived Neurotoxin KW - EC 3.1.- KW - Ribonucleases KW - Ribonuclease, Pancreatic KW - EC 3.1.27.5 KW - Index Medicus KW - Genetic Variation KW - Animals KW - Kinetics KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Ribonuclease, Pancreatic -- genetics KW - Neurotoxins -- biosynthesis KW - Callithrix -- genetics KW - Neurotoxins -- metabolism KW - Neurotoxins -- genetics KW - Multigene Family KW - Hominidae -- genetics KW - Primates -- genetics KW - Blood Proteins -- biosynthesis KW - Ribonucleases -- genetics KW - Blood Proteins -- metabolism KW - Ribonucleases -- metabolism KW - Blood Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77506605?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Eosinophil+cationic+protein+and+eosinophil-derived+neurotoxin.+Evolution+of+novel+function+in+a+primate+ribonuclease+gene+family.&rft.au=Rosenberg%2C+H+F%3BDyer%2C+K+D&rft.aulast=Rosenberg&rft.aufirst=H&rft.date=1995-09-15&rft.volume=270&rft.issue=37&rft.spage=21539&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 - 1995-10-12 N1 - Date created - 1995-10-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: J Biol Chem. 1995 Dec 15;270(50):30234 [8530435] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Residues in the second cysteine-rich region of protein kinase C delta relevant to phorbol ester binding as revealed by site-directed mutagenesis. AN - 77504886; 7665608 AB - Phorbol esters bind with high affinity to protein kinase C (PKC) isozymes as well as to two novel receptors, n-chimaerin and Unc-13. The cysteine-rich regions present in these proteins were identified as the binding sites for the phorbol ester tumor promoters and the lipophilic second messenger sn-diacylglycerol. A 50-amino-acid peptide comprising the second cysteine-rich region of PKC delta, expressed in Escherichia coli as a glutathione S-transferase (GST)-fusion protein, bound [3H]phorbol 12,13-dibutyrate (PDBu) with high affinity (Kd = 0.8 nM). Using the cDNA of that cysteine-rich region as a template, a series of 37 point mutations was generated by site-directed mutagenesis, and the mutated proteins were analyzed quantitatively for binding of [3H]PDBu and, as appropriate, for binding of the ultrapotent analog [3H]bryostatin 1. Mutants displayed one of three patterns of behavior: phorbol ester binding was completely abolished, binding affinity was reduced, or binding was not significantly modified. As expected, five of the six cysteines as well as the two histidines involved in Zn2+ coordination are critical for the interaction of the protein with the phorbol esters. In addition, mutations in several positions, including phenylalanine 3, tyrosine 8, proline 11, leucines 20, 21 and 24, tryptophan 21, glutamine 27, and valine 38 drastically reduced the interaction with the ligands. The effect of these mutations can be rationalized from the three-dimensional (NMR) structure of the cysteine-rich region. In particular, the C-terminal portion of the protein does not appear to be essential, and the loop comprising amino acids 20 to 28 is implicated in the binding activity. JF - The Journal of biological chemistry AU - Kazanietz, M G AU - Wang, S AU - Milne, G W AU - Lewin, N E AU - Liu, H L AU - Blumberg, P M AD - Molecular Mechanisms of Tumor Promotion Section, NCI, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1995/09/15/ PY - 1995 DA - 1995 Sep 15 SP - 21852 EP - 21859 VL - 270 IS - 37 SN - 0021-9258, 0021-9258 KW - Antineoplastic Agents KW - 0 KW - Bryostatins KW - Isoenzymes KW - Lactones KW - Macrolides KW - Oligodeoxyribonucleotides KW - Recombinant Fusion Proteins KW - Tritium KW - 10028-17-8 KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - bryostatin 1 KW - 37O2X55Y9E KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - Animals KW - Protein Structure, Secondary KW - Humans KW - Isoenzymes -- metabolism KW - Lactones -- metabolism KW - Recombinant Fusion Proteins -- chemistry KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Rats KW - Isoenzymes -- biosynthesis KW - Glutathione Transferase -- biosynthesis KW - Escherichia coli KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Isoenzymes -- chemistry KW - Models, Molecular KW - Antineoplastic Agents -- metabolism KW - Amino Acid Sequence KW - Mice KW - Cloning, Molecular KW - Binding Sites KW - Base Sequence KW - Kinetics KW - Restriction Mapping KW - Consensus Sequence KW - Protein Kinase C -- metabolism KW - Phorbol 12,13-Dibutyrate -- metabolism KW - Protein Kinase C -- chemistry KW - Point Mutation KW - Protein Kinase C -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77504886?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Residues+in+the+second+cysteine-rich+region+of+protein+kinase+C+delta+relevant+to+phorbol+ester+binding+as+revealed+by+site-directed+mutagenesis.&rft.au=Kazanietz%2C+M+G%3BWang%2C+S%3BMilne%2C+G+W%3BLewin%2C+N+E%3BLiu%2C+H+L%3BBlumberg%2C+P+M&rft.aulast=Kazanietz&rft.aufirst=M&rft.date=1995-09-15&rft.volume=270&rft.issue=37&rft.spage=21852&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 - 1995-10-12 N1 - Date created - 1995-10-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Aggregation of IgE receptors in rat basophilic leukemia 2H3 cells induces tyrosine phosphorylation of the cytosolic protein-tyrosine phosphatase HePTP. AN - 77495700; 7545170 AB - The cDNA encoding the rat equivalent of the human hematopoietic tyrosine phosphatase, also known as leukocyte phosphatase, was isolated from a rat basophilic leukemia mast cell cDNA library. By two-dimensional electrophoresis, the protein expressed in the mast cells was of a size (40 kDa) and pI (6.9) predicted from the deduced amino acid sequence. Thus, although previously shown to be preferentially expressed in T cells and B cells, the phosphatase is also found in mast cells. By immunofluorescence microscopy, rat hematopoietic tyrosine phosphatase localized to discrete, globular compartments within the cytoplasm and was not found either in the nucleus or associated with the cell surface membrane. Aggregation of high affinity IgE receptors in the mast cells induced tyrosine phosphorylation of the phosphatase. The tyrosine phosphorylation was mimicked by stimulation with calcium ionophore A23187 but not by direct activation of protein kinase C. Since phosphorylation of the phosphatase was dramatically reduced when the cells were activated in Ca(2+)-free media, it is dependent on a rise in intracellular Ca2+. These data strongly suggest that hematopoietic tyrosine phosphatase may be involved in the IgE receptor-mediated signaling cascade. JF - The Journal of biological chemistry AU - Swieter, M AU - Berenstein, E H AU - Swaim, W D AU - Siraganian, R P AD - Laboratory of Immunology, NIDR, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/09/15/ PY - 1995 DA - 1995 Sep 15 SP - 21902 EP - 21906 VL - 270 IS - 37 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - Intracellular Signaling Peptides and Proteins KW - RNA, Messenger KW - Receptors, IgE KW - Phosphotyrosine KW - 21820-51-9 KW - Calcimycin KW - 37H9VM9WZL KW - Tyrosine KW - 42HK56048U KW - PTPN6 protein, human KW - EC 3.1.3.48 KW - PTPN7 protein, human KW - Protein Tyrosine Phosphatase, Non-Receptor Type 6 KW - Protein Tyrosine Phosphatases KW - Protein Tyrosine Phosphatases, Non-Receptor KW - Ptpn6 protein, mouse KW - Ptpn6 protein, rat KW - Ptpn7 protein, rat KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Blotting, Northern KW - Cytosol -- enzymology KW - Calcimycin -- pharmacology KW - RNA, Messenger -- biosynthesis KW - Calcium -- metabolism KW - Rats KW - Tumor Cells, Cultured KW - Phosphorylation KW - Molecular Sequence Data KW - Immunoblotting KW - RNA, Messenger -- analysis KW - Amino Acid Sequence KW - Mice KW - Organ Specificity KW - Cloning, Molecular KW - Leukemia, Basophilic, Acute KW - Base Sequence KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Line KW - Protein Tyrosine Phosphatases -- biosynthesis KW - Brain -- enzymology KW - Protein Tyrosine Phosphatases -- metabolism KW - Gene Expression KW - Tyrosine -- metabolism KW - Tyrosine -- analogs & derivatives KW - Receptors, IgE -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77495700?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Aggregation+of+IgE+receptors+in+rat+basophilic+leukemia+2H3+cells+induces+tyrosine+phosphorylation+of+the+cytosolic+protein-tyrosine+phosphatase+HePTP.&rft.au=Swieter%2C+M%3BBerenstein%2C+E+H%3BSwaim%2C+W+D%3BSiraganian%2C+R+P&rft.aulast=Swieter&rft.aufirst=M&rft.date=1995-09-15&rft.volume=270&rft.issue=37&rft.spage=21902&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 - 1995-10-12 N1 - Date created - 1995-10-12 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U28356; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Acquired erythropoietin responsiveness of interleukin-2-dependent T lymphocytes retrovirally transduced with genes encoding chimeric erythropoietin/interleukin-2 receptors. AN - 77488548; 7662975 AB - Adoptive immunotherapy with tumor-infiltrating lymphocytes (TILs) causes regression of some human tumors. However, the sustained proliferation and antitumor activity of TILs requires the coadministration of potentially toxic amounts of interleukin-2 (IL-2). In an effort to overcome the requirement by T cells for IL-2, we have introduced alternative growth factor receptors that use the relatively nontoxic cytokine erythropoietin (Epo) as a ligand. In our model system, the coexpression of chimeric receptors consisting of the extracellular portion of the Epo receptor (EpoR) and the intracellular portions of the IL-2 receptor subunits, beta and gamma, conferred Epo responsiveness on a T-cell line. By contrast, cells expressing the wild-type EpoR did not proliferate in response to Epo. This suggested that Epo binding caused the activation of an IL-2 signal pathway mediated by the chimeric receptors. This approach can be used to minimize toxicity and potentially improve cancer immunotherapy with TILs. JF - Blood AU - Minamoto, S AU - Treisman, J AU - Hankins, W D AU - Sugamura, K AU - Rosenberg, S A AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/09/15/ PY - 1995 DA - 1995 Sep 15 SP - 2281 EP - 2287 VL - 86 IS - 6 SN - 0006-4971, 0006-4971 KW - Interleukin-2 KW - 0 KW - Receptors, Erythropoietin KW - Receptors, Interleukin-2 KW - Recombinant Fusion Proteins KW - Erythropoietin KW - 11096-26-7 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Base Sequence KW - Transfection KW - Humans KW - Molecular Sequence Data KW - Immunotherapy, Adoptive KW - Mice KW - Genetic Vectors -- genetics KW - Retroviridae -- genetics KW - Neoplasms -- therapy KW - Signal Transduction KW - Cell Line KW - Lymphocytes, Tumor-Infiltrating KW - Recombinant Fusion Proteins -- metabolism KW - Interleukin-2 -- pharmacology KW - T-Lymphocytes -- metabolism KW - Receptors, Interleukin-2 -- metabolism KW - Receptors, Erythropoietin -- metabolism KW - Erythropoietin -- pharmacology KW - Receptors, Erythropoietin -- genetics KW - T-Lymphocytes -- drug effects KW - Interleukin-2 -- toxicity KW - Receptors, Interleukin-2 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77488548?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Acquired+erythropoietin+responsiveness+of+interleukin-2-dependent+T+lymphocytes+retrovirally+transduced+with+genes+encoding+chimeric+erythropoietin%2Finterleukin-2+receptors.&rft.au=Minamoto%2C+S%3BTreisman%2C+J%3BHankins%2C+W+D%3BSugamura%2C+K%3BRosenberg%2C+S+A&rft.aulast=Minamoto&rft.aufirst=S&rft.date=1995-09-15&rft.volume=86&rft.issue=6&rft.spage=2281&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-12 N1 - Date created - 1995-10-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I trial of amifostine (WR-2721) and melphalan in children with refractory cancer. AN - 77486820; 7664282 AB - Melphalan has a steep dose-response curve, but the use of high doses results in unacceptable myelosuppression. Strategies to circumvent this dose-limiting myelosuppression would allow for the administration of higher, more effective doses of melphalan. Amifostine (WR-2721) has been shown in preclinical studies to protect the bone marrow from the myelotoxicity of melphalan, and in clinical trials, to protect from the myelotoxicity of other alkylating agents. A Phase I trial of the combination of amifostine and melphalan was performed in children with refractory cancers to: (a) define the acute toxicities of amifostine and its maximum tolerated dose (MTD); and (b) to determine whether the dose of melphalan could be safely escalated when administered in combination with amifostine. Amifostine was administered i.v. as a 15-min infusion 30 min before melphalan. The starting dose of amifostine was 750 mg/m2, with planned dose escalations in 30% increments. Melphalan was administered as a 5-min infusion using the previously defined MTD in heavily pretreated patients, 35 mg/m2, as the starting dose. The dose of melphalan was escalated by 30% increments. Nineteen patients, ranging in age from 3 to 24 years (median, 15 years), were entered on trial. The dose of amifostine was escalated to 2700 mg/m2, which is approximately 3-fold higher than the adult recommended dose, without reaching a MTD. Fifteen patients experienced nondose-limiting (< 25%), transient decreases in blood pressure after the amifostine infusion. Other nondose-limiting toxicities of amifostine included mild nausea and vomiting, flushing, anxiety, diarrhea, and urinary retention. Six patients, three each at the 2100 and 2700 mg/m2 amifostine dose levels were treated with an escalated dose of melphalan (45 mg/m2). All of these patients experienced grade 4 neutropenia (< 500/mm3), and five of six patients had grade 4 thrombocytopenia. The duration of this dose-limiting myelosuppression exceeded 7 days in four of six patients. Although no dose-limiting (grade 3 or 4) toxicity was attributed to amifostine, significant anxiety and reversible urinary retention occurred at the two highest amifostine dose levels. A dose of 1650 mg/m2 for pediatric Phase II trials is recommended. High doses of amifostine, however, do not appear to allow for escalation of melphalan beyond its single agent MTD of 35 mg/m2. JF - Cancer research AU - Adamson, P C AU - Balis, F M AU - Belasco, J E AU - Lange, B AU - Berg, S L AU - Blaney, S M AU - Craig, C AU - Poplack, D G AD - Pediatric Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1995/09/15/ PY - 1995 DA - 1995 Sep 15 SP - 4069 EP - 4072 VL - 55 IS - 18 SN - 0008-5472, 0008-5472 KW - Amifostine KW - M487QF2F4V KW - Melphalan KW - Q41OR9510P KW - Index Medicus KW - Humans KW - Adult KW - Child KW - Adolescent KW - Male KW - Female KW - Child, Preschool KW - Neoplasms -- drug therapy KW - Melphalan -- administration & dosage KW - Melphalan -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Amifostine -- adverse effects KW - Amifostine -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77486820?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=A+phase+I+trial+of+amifostine+%28WR-2721%29+and+melphalan+in+children+with+refractory+cancer.&rft.au=Adamson%2C+P+C%3BBalis%2C+F+M%3BBelasco%2C+J+E%3BLange%2C+B%3BBerg%2C+S+L%3BBlaney%2C+S+M%3BCraig%2C+C%3BPoplack%2C+D+G&rft.aulast=Adamson&rft.aufirst=P&rft.date=1995-09-15&rft.volume=55&rft.issue=18&rft.spage=4069&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 - 1995-10-06 N1 - Date created - 1995-10-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The 33-kDa C-terminal domain of Raf-1 protein kinase exhibits a Ras-independent serum- and phorbol ester-induced shift in gel mobility. AN - 77518127; 7545901 AB - Experiments were carried out to determine Raf-1 protein kinase domain fragments which exhibit a characteristic electrophoretic mobility shift noted with Raf-1 protein kinase in response to serum and phorbol ester (PMA) treatment of serum-deprived NIH 3T3 cells. Epsilon-epitope tagged 84 kDa Raf-1 holoenzyme (HR-epsilon), as well as the epsilon-epsilon pitope tagged 35 kDa N-terminal (RI-epsilon), 33 kDa mid-portion (RII-epsilon), and 33 kDa C-terminal (RIII-epsilon) fragments of Raf-1 were overexpressed in NIH 3T3 cells. The overexpressed HR-epsilon exhibited a serum- and PMA-induced shift in gel mobility similar to that noted with endogenous Raf-1. The C-terminal RIII-epsilon fragment exhibited a similar shift in gel mobility while the electrophoretic mobility of the N-terminal RI-epsilon fragment remained unchanged. These results suggest that modification(s) within the 33 kDa C-terminal portion of Raf-1 which occur independently of association with Ras may be responsible for the band shift observed with serum and PMA treatment of serum-deprived NIH 3T3 cells. JF - Biochemical and biophysical research communications AU - Oláh, Z AU - Ferrier, A AU - Lehel, C AU - Anderson, W B AD - Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/09/14/ PY - 1995 DA - 1995 Sep 14 SP - 340 EP - 347 VL - 214 IS - 2 SN - 0006-291X, 0006-291X KW - Culture Media KW - 0 KW - Culture Media, Serum-Free KW - DNA Primers KW - Epitopes KW - Peptide Fragments KW - Phosphates KW - Proto-Oncogene Proteins KW - Recombinant Proteins KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Proto-Oncogene Proteins c-raf KW - ras Proteins KW - EC 3.6.5.2 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Peptide Fragments -- metabolism KW - 3T3 Cells KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Peptide Fragments -- isolation & purification KW - Sequence Tagged Sites KW - Mice KW - Molecular Weight KW - Phosphates -- metabolism KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- isolation & purification KW - Polymerase Chain Reaction KW - Blood KW - Base Sequence KW - Transfection KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Protein-Serine-Threonine Kinases -- biosynthesis KW - Proto-Oncogene Proteins -- biosynthesis KW - Protein-Serine-Threonine Kinases -- metabolism KW - Protein-Serine-Threonine Kinases -- isolation & purification KW - Proto-Oncogene Proteins -- isolation & purification KW - Proto-Oncogene Proteins -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - ras Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77518127?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=The+33-kDa+C-terminal+domain+of+Raf-1+protein+kinase+exhibits+a+Ras-independent+serum-+and+phorbol+ester-induced+shift+in+gel+mobility.&rft.au=Ol%C3%A1h%2C+Z%3BFerrier%2C+A%3BLehel%2C+C%3BAnderson%2C+W+B&rft.aulast=Ol%C3%A1h&rft.aufirst=Z&rft.date=1995-09-14&rft.volume=214&rft.issue=2&rft.spage=340&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-19 N1 - Date created - 1995-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Focal cerebral ischemia induces CRH mRNA in rat cerebral cortex and amygdala. AN - 77721923; 8541482 AB - Corticotropin-releasing hormone (CRH) antagonism has neuroprotective effects in models of ischemia. We examined CRH mRNA by in situ hybridization in a well-established rat model of focal cerebral ischemia caused by permanent middle cerebral artery occlusion (MCAo). In ischemic cortex CRH mRNA levels were elevated 2.6-fold 60 min after MCAo, compared with sham operated animals. CRH mRNA was also induced in the amygdala, 60 min following ischemia, in a pattern which was qualitatively different from that of sham operated animals. This rapid and profound increase in CRH mRNA levels during focal cerebral ischemia is likely to be associated with neurotoxicity, as CRH antagonism has been reported to cause a significant reduction in neuronal loss during ischemia. JF - Neuroreport AU - Wong, M L AU - Loddick, S A AU - Bongiorno, P B AU - Gold, P W AU - Rothwell, N J AU - Licinio, J AD - Clinical Neuroendocrinology Branch, NIMH, NIH, Bethesda, Maryland 20892-1284, USA. Y1 - 1995/09/11/ PY - 1995 DA - 1995 Sep 11 SP - 1785 EP - 1788 VL - 6 IS - 13 SN - 0959-4965, 0959-4965 KW - RNA, Messenger KW - 0 KW - Corticotropin-Releasing Hormone KW - 9015-71-8 KW - Index Medicus KW - Rats KW - Ischemic Attack, Transient KW - Animals KW - Rats, Sprague-Dawley KW - Arterial Occlusive Diseases -- metabolism KW - Gene Expression KW - Male KW - Cerebral Arterial Diseases -- metabolism KW - Amygdala -- metabolism KW - Cerebral Cortex -- blood supply KW - Amygdala -- blood supply KW - Cerebral Cortex -- metabolism KW - Corticotropin-Releasing Hormone -- antagonists & inhibitors KW - RNA, Messenger -- biosynthesis KW - Corticotropin-Releasing Hormone -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77721923?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroreport&rft.atitle=Focal+cerebral+ischemia+induces+CRH+mRNA+in+rat+cerebral+cortex+and+amygdala.&rft.au=Wong%2C+M+L%3BLoddick%2C+S+A%3BBongiorno%2C+P+B%3BGold%2C+P+W%3BRothwell%2C+N+J%3BLicinio%2C+J&rft.aulast=Wong&rft.aufirst=M&rft.date=1995-09-11&rft.volume=6&rft.issue=13&rft.spage=1785&rft.isbn=&rft.btitle=&rft.title=Neuroreport&rft.issn=09594965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-13 N1 - Date created - 1996-02-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Self-report screening tests for alcohol problems in primary care. AN - 77480198; 7654105 AB - Considering the prevalence of excessive alcohol use, its adverse consequences on physical and emotional well-being, and the high degree of responsivity of early-stage drinking problems to brief intervention, screening for alcohol abuse is warranted in medical practice. We describe several practical self-report tests that can help primary care physicians screen their patients for alcohol abuse. Two of the more popular tests, the Michigan Alcoholism Screening Test and the CAGE (an acronym for questions about cutting down on drinking, annoyance at others' concern about drinking, feeling guilty about drinking, and using alcohol as an eye-opener in the morning), are comparable in sensitivity and specificity. Either test is appropriate, but the brevity of CAGE generally gives it an advantage in a busy medical office. Three new tests, the Alcohol Use Disorders Identification Test, the Adolescent Drinking Index, and the TWEAK also are promising. We offer guidelines for selection of screening tests for primary care practice. JF - Archives of internal medicine AU - Allen, J P AU - Maisto, S A AU - Connors, G J AD - National Institute on Alcohol Abuse and Alcoholism, Bethesda, Md, USA. Y1 - 1995/09/11/ PY - 1995 DA - 1995 Sep 11 SP - 1726 EP - 1730 VL - 155 IS - 16 SN - 0003-9926, 0003-9926 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Surveys and Questionnaires KW - Alcoholism -- diagnosis KW - Primary Health Care KW - Mass Screening -- methods KW - Alcoholism -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77480198?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+internal+medicine&rft.atitle=Self-report+screening+tests+for+alcohol+problems+in+primary+care.&rft.au=Allen%2C+J+P%3BMaisto%2C+S+A%3BConnors%2C+G+J&rft.aulast=Allen&rft.aufirst=J&rft.date=1995-09-11&rft.volume=155&rft.issue=16&rft.spage=1726&rft.isbn=&rft.btitle=&rft.title=Archives+of+internal+medicine&rft.issn=00039926&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-28 N1 - Date created - 1995-09-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A small modified hammerhead ribozyme and its conformational characteristics determined by mutagenesis and lattice calculation. AN - 19888625; 8741644 JF - Nucleic Acids Research AU - Lustig, B AU - Lin, N H AU - Smith, S M AU - Jernigan, R L AU - Jeang, K T AD - Laboratory of Mathematical Biology, NCI, NIAID, NIH, Bethesda, MD 20892-0460, USA. Y1 - 1995/09/11/ PY - 1995 DA - 1995 Sep 11 SP - 3531 EP - 3538 PB - Oxford University Press, Oxford Journals, Great Clarendon Street VL - 23 IS - 17 SN - 0305-1048, 0305-1048 KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Ribozymes KW - Mutagenesis KW - W 30940:Products KW - N 14830:RNA UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19888625?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+Acids+Research&rft.atitle=A+small+modified+hammerhead+ribozyme+and+its+conformational+characteristics+determined+by+mutagenesis+and+lattice+calculation.&rft.au=Lustig%2C+B%3BLin%2C+N+H%3BSmith%2C+S+M%3BJernigan%2C+R+L%3BJeang%2C+K+T&rft.aulast=Lustig&rft.aufirst=B&rft.date=1995-09-11&rft.volume=23&rft.issue=17&rft.spage=3531&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-12-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Ribozymes; Mutagenesis ER - TY - JOUR T1 - Inhibition of the human immunodeficiency virus-1 protease and human immunodeficiency virus-1 replication by bathocuproine disulfonic acid Cu1+. AN - 77538492; 7574666 AB - The protease encoded by the human immunodeficiency virus-1 (HIV-1) is essential for processing viral polyproteins which contain the enzymes and structural proteins required for the infectious virus. It was previously found that cupric chloride, in the presence of dithiothreitol or ascorbic acid, could inhibit the HIV-1 protease. It was suggested that a Cu1+ chelate was the moiety responsible for inhibition of the protease. This hypothesis has now been investigated directly by utilizing the stable Cu1+ chelate, bathocuproine disulfonic acid Cu1+ (BCDS-Cu1+). BCDS-Cu1+ inhibited the HIV-1 wild type protease as well as a mutant HIV-1 protease lacking cysteines. BCDS-Cu1+ was a competitive inhibitor of the mutant HIV-1 protease with an apparent Ki of 1 microM. Replication of HIV-1 in human lymphocytes and the cytotoxic effect of HIV-1 in CEM cells was inhibited by micromolar BCDS-Cu1+. Inhibition of the protease and of HIV replication by BCDS-Cu1+ was dependent on the presence of Cu1+ as BCDS alone was ineffective. EDTA blocked the inhibition of the protease by Cu1+ but was unable to block inhibition of the protease by BCDS-Cu1+, indicating that the Cu1+ complex was the inhibitory agent. The apparent IC50 for BCDS-Cu1+ on the inhibition of replication by primary isolates of HIV-1 was 5 microM. However, BCDS-Cu1+ did not affect polyprotein processing in an H9 cell line chronically infected with HIV-1, indicating that BCDS-Cu1+ acts by yet another mechanism to block HIV infection. Other possible targets for BCDS-Cu1+ include inhibition of viral adsorption and/or inhibition of the HIV-1 integrase. JF - Archives of biochemistry and biophysics AU - Davis, D A AU - Branca, A A AU - Pallenberg, A J AU - Marschner, T M AU - Patt, L M AU - Chatlynne, L G AU - Humphrey, R W AU - Yarchoan, R AU - Levine, R L AD - Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-0320, USA. Y1 - 1995/09/10/ PY - 1995 DA - 1995 Sep 10 SP - 127 EP - 134 VL - 322 IS - 1 SN - 0003-9861, 0003-9861 KW - Antiviral Agents KW - 0 KW - Chelating Agents KW - HIV Protease Inhibitors KW - Phenanthrolines KW - bathocuproine sulfonate KW - 73348-75-1 KW - Copper KW - 789U1901C5 KW - Edetic Acid KW - 9G34HU7RV0 KW - HIV Protease KW - EC 3.4.23.- KW - Renin KW - EC 3.4.23.15 KW - Index Medicus KW - AIDS/HIV KW - Mutagenesis, Site-Directed KW - Macrophages KW - HIV Protease -- genetics KW - Renin -- metabolism KW - Leukocytes, Mononuclear KW - Kinetics KW - Humans KW - Antiviral Agents -- pharmacology KW - In Vitro Techniques KW - Edetic Acid -- pharmacology KW - Cell Line KW - Chelating Agents -- pharmacology KW - Virus Replication -- drug effects KW - HIV-1 -- isolation & purification KW - Phenanthrolines -- pharmacology KW - HIV Protease Inhibitors -- pharmacology KW - HIV-1 -- physiology KW - Copper -- pharmacology KW - HIV-1 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77538492?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inhibition+of+the+human+immunodeficiency+virus-1+protease+and+human+immunodeficiency+virus-1+replication+by+bathocuproine+disulfonic+acid+Cu1%2B.&rft.au=Davis%2C+D+A%3BBranca%2C+A+A%3BPallenberg%2C+A+J%3BMarschner%2C+T+M%3BPatt%2C+L+M%3BChatlynne%2C+L+G%3BHumphrey%2C+R+W%3BYarchoan%2C+R%3BLevine%2C+R+L&rft.aulast=Davis&rft.aufirst=D&rft.date=1995-09-10&rft.volume=322&rft.issue=1&rft.spage=127&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 - 1995-10-23 N1 - Date created - 1995-10-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Research involving subjects with dementia and other cognitive impairments: experience at the NIH, and some unresolved ethical considerations. AN - 85252796; pmid-7675247 JF - Neurology AU - Wichman, A AU - Sandler, A L AD - Office of Human Subjects Research, National Institutes of Health, Bethesda, MD 20892-1154, USA. PY - 1995 SP - 1777 EP - 1778 VL - 45 IS - 9 SN - 0028-3878, 0028-3878 KW - United States KW - Government Regulation KW - Human KW - National Institutes of Health (U.S.) KW - Informed Consent KW - Research Subjects KW - Federal Government KW - Therapeutic Human Experimentation KW - Nontherapeutic Human Experimentation KW - Ethics Committees, Research KW - Human Experimentation KW - Ethics, Medical KW - Dementia UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85252796?accountid=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=Biochemical+pharmacology&rft.atitle=Maitotoxin-elicited+calcium+influx+in+cultured+cells.+Effect+of+calcium-channel+blockers.&rft.au=Daly%2C+J+W%3BLueders%2C+J%3BPadgett%2C+W+L%3BShin%2C+Y%3BGusovsky%2C+F&rft.aulast=Daly&rft.aufirst=J&rft.date=1995-10-12&rft.volume=50&rft.issue=8&rft.spage=1187&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Tamoxifen, uridine transport, and dome formation in human breast cancer cells. AN - 77958217; 9166472 JF - The cancer journal from Scientific American AU - Allegra, C J AD - NCI-Navy Medical Oncology Branch Clinical Oncology Program, National Cancer Institute, Bethesda, Maryland 20889-5105, USA. PY - 1995 SP - 182 EP - 183 VL - 1 IS - 3 SN - 1081-4442, 1081-4442 KW - Tamoxifen KW - 094ZI81Y45 KW - Fluorouracil KW - U3P01618RT KW - Uridine KW - WHI7HQ7H85 KW - Index Medicus KW - Drug Interactions KW - Humans KW - Cell Line, Tumor KW - Fluorouracil -- administration & dosage KW - Breast Neoplasms -- drug therapy KW - Tamoxifen -- pharmacology KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacokinetics KW - Breast Neoplasms -- metabolism KW - Uridine -- metabolism KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacology KW - Fluorouracil -- pharmacokinetics KW - Tamoxifen -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77958217?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+cancer+journal+from+Scientific+American&rft.atitle=Tamoxifen%2C+uridine+transport%2C+and+dome+formation+in+human+breast+cancer+cells.&rft.au=Allegra%2C+C+J&rft.aulast=Allegra&rft.aufirst=C&rft.date=1995-09-01&rft.volume=1&rft.issue=3&rft.spage=182&rft.isbn=&rft.btitle=&rft.title=The+cancer+journal+from+Scientific+American&rft.issn=10814442&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-10-03 N1 - Date created - 2006-09-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Cancer J Sci Am. 1995 Sep-Oct;1(3):210-4 [9166478] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of B1(Fv)PE38 and B1(dsFv)PE38: single-chain and disulfide-stabilized Fv immunotoxins with increased activity that cause complete remissions of established human carcinoma xenografts in nude mice. AN - 77955220; 9816075 AB - The mAb B1 (mouse IgG1 kappa) recognizes a carbohydrate epitope on human carcinoma cells (I. Pastan et al., Cancer Res., 51: 3781-3787, 1991). We have generated plasmids encoding immunotoxins in which the Fv domain of B1, either as a single-chain Fv or as a disulfide-stabilized Fv (dsFv), was fused to PE38, a truncated form of Pseudomonas exotoxin A. To compare the activities of the two types of recombinant immunotoxins, the proteins were prepared from cytoplasmic inclusion bodies produced in Escherichia coli. The immunotoxins were evaluated for stability, antigen binding, specific cytotoxicity, pharmacokinetics, and antitumor activity in a nude mouse model. Although the single-chain immunotoxin is relatively stable when incubated at 37 degreesC (t(1/2) approximately 4 h), the dsFv immunotoxin is much more stable, with no loss of activity after 8 h at 37 degreesC. The single-chain immunotoxin has a 2-fold better binding affinity and cytotoxicity toward antigen-positive cultured cells than the dsFv immunotoxin. The half-lives in the blood of mice of B1(Fv)PE38 (single-chain) and B1(dsFv)PE38 (disulfide-stabilized) are 23 and 27 min, respectively. Their therapeutic potential was evaluated in athymic nude mice bearing human epidermoid carcinoma xenografts. Both immunotoxins caused complete regressions of the s.c. (30-40 mm3) tumors when given i.v. in three doses of 0.025 mg/kg every other day. This is one-twentieth of the mouse LD50. Recombinant immunotoxins containing the B1(Fv) are 2-3-fold more potent antitumor agents than previously described immunotoxins containing the B3(Fv) (Brinkmann et al., Proc. Natl. Acad. Sci. USA, 88: 8616-8620, 1991), which also target LeY and related carbohydrates in human tumors, but have a similar toxicity in mice. Thus, their therapeutic window is 2-3-fold larger. In addition, B1(dsFv)PE38 has only a 50% decrease in the apparent binding affinity of B1(Fv)PE38, whereas B3(dsFv)PE38 has a much greater loss in antigen binding. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Benhar, I AU - Pastan, I AD - Laboratory of Molecular Biology, Division of Cancer Biology Diagnosis and Centers, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 1023 EP - 1029 VL - 1 IS - 9 SN - 1078-0432, 1078-0432 KW - Antibodies, Monoclonal KW - 0 KW - Bacterial Toxins KW - Exotoxins KW - Immunoglobulin Variable Region KW - Immunotoxins 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 - Drug Screening Assays, Antitumor KW - Animals KW - Humans KW - Transplantation, Heterologous KW - Mice, Nude KW - Mice KW - Remission Induction KW - Immunotoxins -- pharmacokinetics KW - Exotoxins -- chemistry KW - Exotoxins -- immunology KW - Antibodies, Monoclonal -- therapeutic use KW - Exotoxins -- pharmacokinetics KW - Immunotoxins -- chemistry KW - Immunotoxins -- immunology KW - Immunotoxins -- therapeutic use KW - Exotoxins -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77955220?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Characterization+of+B1%28Fv%29PE38+and+B1%28dsFv%29PE38%3A+single-chain+and+disulfide-stabilized+Fv+immunotoxins+with+increased+activity+that+cause+complete+remissions+of+established+human+carcinoma+xenografts+in+nude+mice.&rft.au=Benhar%2C+I%3BPastan%2C+I&rft.aulast=Benhar&rft.aufirst=I&rft.date=1995-09-01&rft.volume=1&rft.issue=9&rft.spage=1023&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-09 N1 - Date created - 1999-02-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Childhood cancer: overview of incidence trends and environmental carcinogens. AN - 77785741; 8549470 AB - An estimated 8000 children 0 to 14 years of age are diagnosed annually with cancer in the United States. Leukemia and brain tumors are the most common childhood malignancies, accounting for 30 and 20% of newly diagnosed cases, respectively. From 1975 to 1978 to 1987 to 1990, cancer among white children increased slightly from 12.8 to 14.1/100,000. Increases are suggested for leukemia, gliomas, and, to a much lesser extent, Wilms' tumor. There are a few well-established environmental causes of childhood cancer such as radiation, chemotherapeutic agents, and diethylstilbestrol. Many other agents such as electromagnetic fields, pesticides, and some parental occupational exposures are suspected of playing roles, but the evidence is not conclusive at this time. Some childhood exposures such as secondhand cigarette smoke may contribute to cancers that develop many years after childhood. For some exposures such as radiation and pesticides data suggest that children may be more susceptible to the carcinogenic effects than similarly exposed adults. JF - Environmental health perspectives AU - Zahm, S H AU - Devesa, S S AD - Epidemiology and Biostatistics Program, National Cancer Institute, Rockville, MD 20892, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 177 EP - 184 VL - 103 Suppl 6 SN - 0091-6765, 0091-6765 KW - Carcinogens KW - 0 KW - Environmental Pollutants KW - Index Medicus KW - Infant KW - Humans KW - Adult KW - Infant, Newborn KW - Incidence KW - Child KW - Child, Preschool KW - Neoplasms, Radiation-Induced -- epidemiology KW - Neoplasms -- chemically induced KW - Neoplasms -- epidemiology KW - Carcinogens -- analysis KW - Environmental Pollutants -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77785741?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Childhood+cancer%3A+overview+of+incidence+trends+and+environmental+carcinogens.&rft.au=Zahm%2C+S+H%3BDevesa%2C+S+S&rft.aulast=Zahm&rft.aufirst=S&rft.date=1995-09-01&rft.volume=103+Suppl+6&rft.issue=&rft.spage=177&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 - 1996-02-20 N1 - Date created - 1996-02-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Tumori. 1989 Aug 31;75(4):396-400 [2815346] JAMA. 1967 Sep 11;201(11):828-34 [6071896] N Engl J Med. 1978 Apr 6;298(14):763-7 [628409] Obstet Gynecol. 1978 Apr;51(4):453-8 [662228] Scand J Work Environ Health. 1978 Jun;4(2):137-50 [278225] N Engl J Med. 1979 Feb 22;300(8):397-402 [759916] N Engl J Med. 1979 Feb 22;300(8):431-2 [759921] Am J Epidemiol. 1979 Mar;109(3):273-84 [453167] Am J Epidemiol. 1979 Mar;109(3):309-19 [453168] J Urol. 1979 Jul;122(1):36-9 [37351] Am J Epidemiol. 1980 Mar;111(3):329-36 [7361757] JAMA. 1980 Sep 26;244(13):1464-5 [7420637] N Engl J Med. 1981 Mar 26;304(13):745-9 [7193288] J Occup Med. 1980 Dec;22(12):792-4 [7218055] Lancet. 1981 Aug 8;2(8241):300-1 [6114336] J Natl Cancer Inst. 1982 Jan;68(1):107-13 [6948120] J Epidemiol Community Health. 1981 Dec;35(4):245-50 [7338698] J Occup Med. 1982 Aug;24(8):578-84 [6750059] Am J Pediatr Hematol Oncol. 1982 Winter;4(4):438-9 [6963105] Br J Obstet Gynaecol. 1983 Nov;90(11):1007-17 [6357269] J Occup Med. 1984 Jun;26(6):427-35 [6330324] Lancet. 1984 Jul 14;2(8394):96-7 [6146025] CA Cancer J Clin. 1984 Sep-Oct;34(5):248-61 [6432238] J Natl Cancer Inst. 1984 Oct;73(4):831-4 [6592380] N Engl J Med. 1984 Nov 29;311(22):1393-8 [6493300] N Engl J Med. 1985 Feb 28;312(9):541-5 [3969117] N Engl J Med. 1985 Feb 28;312(9):576-7 [3969119] Am J Public Health. 1985 May;75(5):487-92 [3985235] Am J Epidemiol. 1985 Jun;121(6):924-9 [4014183] Arch Otolaryngol. 1985 Oct;111(10):639-42 [4041171] Br J Cancer. 1985 Dec;52(6):923-9 [4074645] Lancet. 1986 Feb 1;1(8475):266 [2868270] Br J Cancer. 1986 Feb;53(2):271-9 [3456788] Lancet. 1986 Jun 14;1(8494):1350-2 [2872471] Bioelectromagnetics. 1986;7(2):191-207 [3741493] Lancet. 1986 Aug 30;2(8505):519-20 [2875269] Am J Epidemiol. 1987 Jan;125(1):44-61 [3788954] N Engl J Med. 1987 Feb 26;316(9):514-6 [3807995] J Natl Cancer Inst. 1987 Mar;78(3):459-64 [3469460] Br Med J (Clin Res Ed). 1987 Mar 7;294(6572):603-7 [3103820] J Natl Cancer Inst. 1987 May;78(5):797-804 [3471992] J Natl Cancer Inst. 1989 Mar 15;81(6):409-14 [2783978] BMJ. 1990 Feb 17;300(6722):423-9 [2107892] Am J Epidemiol. 1990 May;131(5):776-80 [2321622] Lancet. 1990 Apr 28;335(8696):1008-12 [1970069] Cancer Res. 1990 May 1;50(9):2608-12 [2328486] Am J Epidemiol. 1990 Jun;131(6):995-1008 [2343871] Am J Epidemiol. 1990 Aug;132(2):275-92 [2372007] Lancet. 1990 Sep 8;336(8715):577-82 [1975376] Nature. 1990 Oct 25;347(6295):755-7 [2234049] Recent Results Cancer Res. 1990;120:166-80 [2236874] Tumori. 1990 Oct 31;76(5):413-9 [2256184] Am J Epidemiol. 1991 Jan 15;133(2):123-32 [1822074] JAMA. 1991 Mar 20;265(11):1403-8 [1999880] Am J Med. 1974 Apr;56(4):457-63 [4818412] Br J Prev Soc Med. 1974 May;28(2):98-100 [4853418] N Engl J Med. 1975 Aug 7;293(6):308 [1138190] Br J Cancer. 1975 Mar;31(3):271-87 [1156514] Lancet. 1976 Jul 17;2(7977):150 [59218] Br J Prev Soc Med. 1976 Jun;30(2):138-40 [953378] Ann N Y Acad Sci. 1976;271:311-23 [1069520] Obstet Gynecol. 1977 Jan;49(1):1-8 [318736] JAMA. 1977 Jul 25;238(4):334-5 [577539] Cancer. 1977 Nov;40(5 Suppl):2464-72 [200342] Lancet. 1976 Sep 4;1(7984):517 [74477] J Natl Cancer Inst. 1987 Jul;79(1):39-46 [3474448] N Engl J Med. 1987 Sep 3;317(10):588-93 [3475572] N Engl J Med. 1988 Jan 14;318(2):76-81 [3336397] Teratog Carcinog Mutagen. 1987;7(6):527-40 [2893466] Oncol Nurs Forum. 1988 Jan-Feb;15(1):67-77 [3278303] Am J Epidemiol. 1988 Jul;128(1):10-20 [3381818] Am J Epidemiol. 1988 Jul;128(1):21-38 [3164167] Cancer. 1988 Aug 1;62(3):635-44 [3164642] Lancet. 1988 Dec 10;2(8624):1323-7 [2904050] Am J Epidemiol. 1988 Dec;128(6):1256-65 [3195566] Br J Cancer. 1988 Dec;58(6):838-42 [3224086] Br J Cancer. 1991 Apr;63(4):626-9 [2021549] BMJ. 1991 Mar 23;302(6778):687-92 [2021742] Am J Epidemiol. 1991 Nov 1;134(9):923-37 [1843457] BMJ. 1991 Nov 30;303(6814):1357-62 [1760600] Med Hypotheses. 1991 Oct;36(2):172-7 [1779922] Am J Epidemiol. 1992 Jan 15;135(2):122-9 [1311140] Cancer Res. 1992 Apr 1;52(7 Suppl):2119s-2123s [1544150] Experientia. 1992 Mar 15;48(3):301-4 [1372266] Int J Cancer. 1992 Apr 22;51(1):38-41 [1314230] Cancer Causes Control. 1992 May;3(3):255-63 [1610972] Cancer Causes Control. 1992 May;3(3):283-8 [1610975] Rev Epidemiol Sante Publique. 1992;40 Suppl 1:S55-62 [1626106] Leukemia. 1992 Nov;6 Suppl 4:3-5 [1434828] Am J Epidemiol. 1992 Oct 15;136(8):916-24 [1456268] JAMA. 1993 Jan 13;269(2):195 [8417228] Am J Ind Med. 1993 Feb;23(2):343-54 [8427262] Cancer Causes Control. 1993 Jan;4(1):51-8 [8431531] Arch Environ Contam Toxicol. 1993 Jan;24(1):87-92 [8466294] Am J Epidemiol. 1993 Mar 15;137(6):620-8 [8470663] Am Ind Hyg Assoc J. 1993 Apr;54(4):197-204 [8480635] Cancer Epidemiol Biomarkers Prev. 1992 Nov-Dec;1(7):525-32 [1302564] Cancer Causes Control. 1993 May;4(3):217-24 [8318638] Cancer Epidemiol Biomarkers Prev. 1993 May-Jun;2(3):277-88 [8318881] Cancer. 1993 Aug 1;72(3):938-44 [8392906] Am J Ind Med. 1993 Dec;24(6):753-66 [8311105] Br Med J. 1958 Jun 28;1(5086):1495-508 [13546604] Acta Unio Int Contra Cancrum. 1964;20:1172-4 [14274726] J Natl Cancer Inst. 1962 May;28:1173-91 [14468031] Lancet. 1970 Nov 14;2(7681):1000-3 [4098041] N Engl J Med. 1971 Apr 15;284(15):878-81 [5549830] Semin Oncol Nurs. 1989 Feb;5(1):43-55 [2646668] AAOHN J. 1989 Mar;37(3):115-30 [2647086] J Natl Cancer Inst. 1989 May 10;81(10):745-57 [2654404] NCI Monogr. 1989;(8):17-23 [2785646] NCI Monogr. 1989;(8):29-33 [2785648] Cancer Res. 1989 Jul 15;49(14):4030-7 [2736544] Lancet. 1989 Jul 8;2(8654):99-100 [2567891] Cancer Res. 1989 Aug 1;49(15):4349-52 [2743324] Pediatrics. 1989 Aug;84(2):199-204 [2748244] Cancer. 1989 Sep 1;64(5):1169-76 [2547509] Cancer Res. 1989 Oct 15;49(20):5730-5 [2790788] Scand J Work Environ Health. 1989 Oct;15(5):360-3 [2477895] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Environmental poisoning of children--lessons from the past. AN - 77785585; 8549472 AB - Children have physiologic and behavioral characteristics that make them vulnerable to damage from environmental chemicals. In the past, there have been episodes in which children became ill or died from environmental exposures that spared adults or affected them less severely. Among the characteristics leading to children's sensitivity are their limited diets, dividing cells, differentiating organs and organ systems, slow or absent detoxification mechanisms, long life expectancy with the resulting ability to express damage with delayed consequences, and the severe metabolic demands of growth. There have been large outbreaks of poisonings involving children in Asia and Turkey, and some of the less obvious effects of chemicals have appeared in children in the United States. Although the United States has been spared a widespread outbreak of severe poisoning, such an incident is possible and would likely have greater consequences for children than adults. JF - Environmental health perspectives AU - Rogan, W J AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 19 EP - 23 VL - 103 Suppl 6 SN - 0091-6765, 0091-6765 KW - Environmental Pollutants KW - 0 KW - Index Medicus KW - Humans KW - Adult KW - Child KW - Environmental Pollutants -- poisoning UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77785585?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Environmental+poisoning+of+children--lessons+from+the+past.&rft.au=Rogan%2C+W+J&rft.aulast=Rogan&rft.aufirst=W&rft.date=1995-09-01&rft.volume=103+Suppl+6&rft.issue=&rft.spage=19&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 - 1996-02-20 N1 - Date created - 1996-02-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Public Health. 1983 Mar;73(3):281-5 [6297321] JAMA. 1983 Feb 25;249(8):1057-9 [6401824] Pediatrics. 1987 Jun;79(6):928-34 [3588147] Am J Public Health. 1987 Oct;77(10):1294-7 [3115123] Am J Epidemiol. 1987 Nov;126(5):893-900 [3661537] Science. 1988 Jul 15;241(4863):334-6 [3133768] JAMA. 1990 Feb 2;263(5):673-8 [2136923] JAMA. 1992 Dec 9;268(22):3213-8 [1433761] Am J Public Health. 1994 Mar;84(3):415-21 [8129058] Nature. 1967 Jul 8;215(5097):208-10 [6049131] Kurume Med J. 1972;19(1):43-51 [4481651] Residue Rev. 1976;61:37-112 [778957] Fed Proc. 1976 Oct;35(12):2400-3 [823051] Ann N Y Acad Sci. 1976;271:311-23 [1069520] Science. 1978 Mar 17;199(4334):1207-9 [204005] Arch Dermatol. 1980 Jan;116(1):46-50 [7352763] Environ Res. 1979 Dec;20(2):225-66 [121077] Environ Res. 1980 Apr;21(2):255-74 [6250815] J Pediatr. 1981 Jan;98(1):47-51 [6256513] Environ Health Perspect. 1985 Feb;59:5-10 [3921364] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Special susceptibility of the child to certain radiation-induced cancers. AN - 77780661; 8549487 AB - The carcinogenic effects of exposure to ionizing radiation vary markedly with age, as revealed by studies of Japanese atomic bomb survivors and of Marshall Islanders exposed to fallout from U.S. nuclear weapons tests in the South Pacific in 1954. An increase in cancers of adulthood after intrauterine exposure, as reported in 1988, has not been sustained. After childhood exposure, increases in leukemia, breast cancer, and thyroid cancer are well established. The carcinogenic effects of radiation on the young have been reported after intrauterine exposures and after exposures during childhood. Cancers with short latent periods such as leukemia occur during childhood, but those with long latent periods such as breast cancer occur in adulthood. JF - Environmental health perspectives AU - Miller, R W AD - Clinical Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 41 EP - 44 VL - 103 Suppl 6 SN - 0091-6765, 0091-6765 KW - Index Medicus KW - United States KW - Age Factors KW - Disease Susceptibility KW - Humans KW - Leukemia, Radiation-Induced -- etiology KW - Environmental Exposure KW - Breast Neoplasms -- etiology KW - Thyroid Neoplasms -- etiology KW - Child KW - Female KW - Prenatal Exposure Delayed Effects KW - Pregnancy KW - Neoplasms, Radiation-Induced -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77780661?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Special+susceptibility+of+the+child+to+certain+radiation-induced+cancers.&rft.au=Miller%2C+R+W&rft.aulast=Miller&rft.aufirst=R&rft.date=1995-09-01&rft.volume=103+Suppl+6&rft.issue=&rft.spage=41&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 - 1996-02-20 N1 - Date created - 1996-02-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Br J Cancer. 1975 Mar;31(3):271-87 [1156514] JAMA. 1982 Mar 19;247(11):1571-5 [7062458] N Engl J Med. 1985 Feb 28;312(9):576-7 [3969119] J Natl Cancer Inst. 1962 May;28:1173-91 [14468031] Radiat Res. 1994 May;138(2):209-23 [8183991] Lancet. 1956 Sep 1;271(6940):447 [13358242] Lancet. 1988 Sep 17;2(8612):665-9 [2901525] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronic phenytoin induced impairment of learning and memory with associated changes in brain acetylcholine esterase activity and monoamine levels. AN - 77761922; 7501653 AB - Groups of adult, male, Wistar rats were administered phenytoin (DPH) at 5, 12.5, 25, 50, or 75 mg/kg i.p. for 21 days. The learning and memory of these rats were assessed using the T-maze and passive avoidance tests. The plasma DPH levels, acetylcholine esterase (AChE) activity in different brain regions, and the levels of monoamines in the hippocampus were measured. The results indicate that DPH below the therapeutic plasma level did not significantly impair learning and memory. Correspondingly, no changes were noted in the brain 5-HT or AChE activity. However, DPH, at therapeutic plasma concentrations (i.e., 10.5 micrograms/ml in the dosage range of 50 and 75 mg/kg, respectively), significantly impaired learning and memory in rats. The impaired learning and memory functions were associated with increased 5-HT levels and decreased AChE activity in the hippocampus. With a dose of 75 mg/kg DPH, there was a reduction in the AChE activity in the striatum, in addition to hippocampus. It is conjectured that the neurochemical changes brought about by DPH at therapeutic plasma levels may account for the impairment of learning, memory, and cognitive functions in epilepsy. JF - Pharmacology, biochemistry, and behavior AU - Sudha, S AU - Lakshmana, M K AU - Pradhan, N AD - Department of Psychopharmacology, National Institute of Mental Health and Neurosciences, Bangalore, India. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 119 EP - 124 VL - 52 IS - 1 SN - 0091-3057, 0091-3057 KW - Biogenic Monoamines KW - 0 KW - Phenytoin KW - 6158TKW0C5 KW - Acetylcholinesterase KW - EC 3.1.1.7 KW - Index Medicus KW - Rats KW - Brain -- enzymology KW - Animals KW - Maze Learning -- drug effects KW - Brain -- drug effects KW - Rats, Wistar KW - Avoidance Learning -- drug effects KW - Male KW - Phenytoin -- pharmacology KW - Memory Disorders -- chemically induced KW - Brain Chemistry -- drug effects KW - Acetylcholinesterase -- metabolism KW - Learning Disorders -- psychology KW - Biogenic Monoamines -- metabolism KW - Memory Disorders -- psychology KW - Learning Disorders -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77761922?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacology%2C+biochemistry%2C+and+behavior&rft.atitle=Chronic+phenytoin+induced+impairment+of+learning+and+memory+with+associated+changes+in+brain+acetylcholine+esterase+activity+and+monoamine+levels.&rft.au=Sudha%2C+S%3BLakshmana%2C+M+K%3BPradhan%2C+N&rft.aulast=Sudha&rft.aufirst=S&rft.date=1995-09-01&rft.volume=52&rft.issue=1&rft.spage=119&rft.isbn=&rft.btitle=&rft.title=Pharmacology%2C+biochemistry%2C+and+behavior&rft.issn=00913057&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-16 N1 - Date created - 1996-01-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vitro anti-HIV-1 activity of HIV protease inhibitor KNI-272 in resting and activated cells: implications for its combined use with AZT or ddI. AN - 77741102; 8585758 AB - KNI-272, a conformationally constrained human immunodeficiency virus (HIV) protease inhibitor containing a P1 allophenylnorstatine (Apns) ((2S,3S)- 3-amino-2-hydroxy-4-phenylbutyric acid), has been shown to be a selective and potent inhibitor of the replication of a wide spectrum of HIV strains in vitro. When KNI-272 was tested in combination with 3'-azido-2',3'-dideoxythymidine (AZT) or 2',3'-dideoxyinosine (ddI) against a primary HIV-1 isolate in phytohemagglutin-activated peripheral blood mononuclear cells (PHA-PBM), its activity was identified to be additive, but not synergistic or antagonistic, as analyzed with the COMBO program package. When tested alone for anti-HIV-1 activity in resting PBM (R-PBM) and PHA-PBM, KNI-272 was found to be comparably potent against the virus in both target cell populations, whereas AZT was more potent in PHA-PBM than in R-PBM and ddI was more potent in R-PBM. These data suggest a potential clinical application of KNI-272 and its analogs. JF - Antiviral research AU - Chokekijchai, S AU - Shirasaka, T AU - Weinstein, J N AU - Mitsuya, H AD - Experimental Retrovirology Section, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 25 EP - 38 VL - 28 IS - 1 SN - 0166-3542, 0166-3542 KW - Antiviral Agents KW - 0 KW - HIV Protease Inhibitors KW - Oligopeptides KW - Phytohemagglutinins KW - kynostatin 272 KW - 147318-81-8 KW - Zidovudine KW - 4B9XT59T7S KW - Didanosine KW - K3GDH6OH08 KW - Index Medicus KW - AIDS/HIV KW - Molecular Structure KW - Drug Interactions KW - Cells, Cultured KW - Humans KW - Phytohemagglutinins -- pharmacology KW - Leukocytes, Mononuclear -- cytology KW - Antiviral Agents -- pharmacology KW - Zidovudine -- pharmacology KW - HIV Protease Inhibitors -- pharmacology KW - Oligopeptides -- pharmacology KW - HIV-1 -- enzymology KW - HIV-1 -- drug effects KW - Didanosine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77741102?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antiviral+research&rft.atitle=In+vitro+anti-HIV-1+activity+of+HIV+protease+inhibitor+KNI-272+in+resting+and+activated+cells%3A+implications+for+its+combined+use+with+AZT+or+ddI.&rft.au=Chokekijchai%2C+S%3BShirasaka%2C+T%3BWeinstein%2C+J+N%3BMitsuya%2C+H&rft.aulast=Chokekijchai&rft.aufirst=S&rft.date=1995-09-01&rft.volume=28&rft.issue=1&rft.spage=25&rft.isbn=&rft.btitle=&rft.title=Antiviral+research&rft.issn=01663542&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-20 N1 - Date created - 1996-03-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cryotherapy reduces fluorouracil-related side effects. AN - 77737226; 8532555 JF - Oncology nursing forum AU - McAtee, N AU - Brooks, C AU - Dela Rosa, T AD - National Cancer Institute, Navy Medical Oncology Branch, National Naval Medical Center, Bethesda, MD, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 1287 EP - 1288 VL - 22 IS - 8 SN - 0190-535X, 0190-535X KW - Antimetabolites, Antineoplastic KW - 0 KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Nursing KW - Colostomy -- adverse effects KW - Vaginitis -- prevention & control KW - Ulcer -- chemically induced KW - Humans KW - Adult KW - Ulcer -- prevention & control KW - Middle Aged KW - Skin Diseases -- prevention & control KW - Skin Diseases -- chemically induced KW - Vaginitis -- chemically induced KW - Male KW - Female KW - Fluorouracil -- adverse effects KW - Antimetabolites, Antineoplastic -- adverse effects KW - Cryotherapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77737226?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncology+nursing+forum&rft.atitle=Cryotherapy+reduces+fluorouracil-related+side+effects.&rft.au=McAtee%2C+N%3BBrooks%2C+C%3BDela+Rosa%2C+T&rft.aulast=McAtee&rft.aufirst=N&rft.date=1995-09-01&rft.volume=22&rft.issue=8&rft.spage=1287&rft.isbn=&rft.btitle=&rft.title=Oncology+nursing+forum&rft.issn=0190535X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-01 N1 - Date created - 1996-02-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of styrene hepatotoxicity in B6C3F1 and Swiss mice. AN - 77692919; 8529816 AB - Inhalation exposure to styrene at concentrations that cause metabolic saturation results in significantly greater hepatotoxicity in B6C3F1 mice than in Swiss mice; females of both strains are more susceptible than males. These studies were conducted to investigate the mouse strain and gender differences in susceptibility to hepatotoxicity caused by repeated exposure to styrene at concentrations that do not cause metabolic saturation. Male and female B6C3F1 and Swiss mice (8 weeks old) were exposed to 0, 150, or 200 ppm styrene for 6 hr/day, 5 days/week, for up to 2 weeks. Changes in body and liver weights, serum alanine aminotransferase (ALT) and sorbitol dehydrogenase (SDH) levels, liver histopathology, and total liver glutathione (GSH) were evaluated after 2, 3, 5, and 10 exposures (six mice/sex/strain/time point/concentration). Blood levels of styrene and styrene-7,8-oxide (SO) were measured in mice exposed to 200 ppm styrene for 2,3, or 5 days (six mice/sex/strain/time point/concentration). Serum ALT and SDH levels were significantly elevated only in female B6C3F1 mice after 3 exposures to 200 ppm styrene; enzyme levels had returned to control levels when measured after 5 and 10 exposures. Degeneration and coagulative necrosis of centrilobular hepatocytes were observed in female B6C3F1 mice exposed 2, 3, and 5 days to 150 or 200 ppm styrene; incidences of these lesions were greater in the 200 ppm than in the 150 ppm dose group. After 10 days of exposure to 150 or 200 ppm styrene, hepatocellular lesions had resolved, although a residual chronic inflammation was present in livers of most female B6C3F1 mice.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Morgan, D L AU - Mahler, J F AU - Moorman, M P AU - Wilson, R E AU - Price, H C AU - Richards, J H AU - O'Connor, R W AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 217 EP - 222 VL - 27 IS - 2 SN - 0272-0590, 0272-0590 KW - Epoxy Compounds KW - 0 KW - Styrenes KW - styrene oxide KW - 9QH06NGT6O KW - L-Iditol 2-Dehydrogenase KW - EC 1.1.1.14 KW - Alanine Transaminase KW - EC 2.6.1.2 KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Animals KW - Sex Characteristics KW - Alanine Transaminase -- metabolism KW - Glutathione -- metabolism KW - Mice KW - L-Iditol 2-Dehydrogenase -- metabolism KW - Mice, Inbred Strains KW - Epoxy Compounds -- blood KW - Body Weight -- drug effects KW - Species Specificity KW - Female KW - Male KW - Organ Size -- drug effects KW - Chemical and Drug Induced Liver Injury -- pathology KW - Styrenes -- blood KW - Styrenes -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77692919?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Comparison+of+styrene+hepatotoxicity+in+B6C3F1+and+Swiss+mice.&rft.au=Morgan%2C+D+L%3BMahler%2C+J+F%3BMoorman%2C+M+P%3BWilson%2C+R+E%3BPrice%2C+H+C%3BRichards%2C+J+H%3BO%27Connor%2C+R+W&rft.aulast=Morgan&rft.aufirst=D&rft.date=1995-09-01&rft.volume=27&rft.issue=2&rft.spage=217&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-01 N1 - Date created - 1996-02-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prostaglandin H synthase-catalyzed ring oxygenation of 2-naphthylamine: evidence for two distinct oxidation pathways. AN - 77690807; 7492737 AB - Previous studies showed that prostaglandin H synthase (PHS) cooxidizes 2-naphthylamine (2-NA) to ring-oxygenated products. These metabolites are atypical for a peroxidase-mediated reaction and are completely different from the polymeric nonoxygenated metabolites of 2-NA that are generated with the model peroxidase horseradish peroxidase (HRP). In this study, we investigated possible explanations for the PHS-catalyzed formation of ring-oxygenated 2-NA metabolites. We found that introduction of a peroxyl radical-generated cosubstrate into the HRP/2-NA system resulted in the formation of the same ring-oxygenated products observed in the PHS/2-NA system. 18O2 incorporation studies were utilized to further characterize the source of oxygen in the ring-oxygenated 2-NA metabolites. The data show that, in the case of PHS, ring oxygenation can occur both by peroxyl radical-mediated attack on 2-NA and by direct transfer of peroxide oxygen from PHS to 2-NA. JF - Chemical research in toxicology AU - Curtis, J F AU - Tomer, K AU - McGown, S AU - Eling, T E AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 875 EP - 883 VL - 8 IS - 6 SN - 0893-228X, 0893-228X KW - Carcinogens KW - 0 KW - 2-Naphthylamine KW - CKR7XL41N4 KW - Horseradish Peroxidase KW - EC 1.11.1.- KW - Prostaglandin-Endoperoxide Synthases KW - EC 1.14.99.1 KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Oxidation-Reduction KW - Mass Spectrometry KW - Animals KW - Sheep KW - Spectrophotometry, Ultraviolet KW - Models, Chemical KW - Horseradish Peroxidase -- chemistry KW - Male KW - Chromatography, High Pressure Liquid KW - 2-Naphthylamine -- metabolism KW - Carcinogens -- metabolism KW - Prostaglandin-Endoperoxide Synthases -- metabolism KW - Oxygen -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77690807?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Prostaglandin+H+synthase-catalyzed+ring+oxygenation+of+2-naphthylamine%3A+evidence+for+two+distinct+oxidation+pathways.&rft.au=Curtis%2C+J+F%3BTomer%2C+K%3BMcGown%2C+S%3BEling%2C+T+E&rft.aulast=Curtis&rft.aufirst=J&rft.date=1995-09-01&rft.volume=8&rft.issue=6&rft.spage=875&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 - 1996-01-11 N1 - Date created - 1996-01-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of thymic lymphoma in mice administered the dideoxynucleoside ddC. AN - 77686620; 8529822 AB - Groups of 10 male and 20 female B6C3F1 mice received 0, 500, or 1000 mg/kg/day 2'3'-dideoxycytidine (ddC) by gavage for 13 weeks. At the end of the 13-week exposure period all males and 10 females per group were necropsied while the remaining females were held for 1 month without further treatment. Thymic atrophy was present at the 13-week necropsy in male and female mice administered 1000 mg/kg/day and in females administered 500 mg/kg/day, but was not present in females following 1 month of recovery. Thymic lymphoma was present in 1 female that received 500 mg/kg/day and 1 female that received 1000 mg/kg/day. In a follow-up study groups of 70 female mice received 0, 500, or 1000 mg/kg/day for 13 weeks. At the end of the 13-week exposure period 20 mice per group were necropsied and the remaining animals held for 3 months without further treatment. Thymic atrophy was observed in ddC-exposed groups at the 13-week necropsy but not in mice allowed to recover for 13 weeks. Thymic lymphoma occurred in 3/50 mice that received 500 mg/kg/day and in 17/50 mice that received 1000 mg/kg/day but did not occur in mice from the vehicle control group. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Sanders, V M AU - Elwell, M R AU - Heath, J E AU - Collins, B J AU - Dunnick, J K AU - Rao, G N AU - Prejean, D AU - Lindamood, C AU - Irwin, R D AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 263 EP - 269 VL - 27 IS - 2 SN - 0272-0590, 0272-0590 KW - Antiviral Agents KW - 0 KW - Zalcitabine KW - 6L3XT8CB3I KW - Index Medicus KW - Atrophy -- chemically induced KW - Mice, Inbred Strains KW - Animals KW - Intubation, Gastrointestinal KW - Body Weight -- drug effects KW - Thymus Gland -- pathology KW - Mice KW - Atrophy -- pathology KW - Male KW - Female KW - Organ Size -- drug effects KW - Thymus Neoplasms -- chemically induced KW - Lymphoma -- chemically induced KW - Zalcitabine -- toxicity KW - Lymphoma -- pathology KW - Thymus Neoplasms -- pathology KW - Antiviral Agents -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77686620?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Induction+of+thymic+lymphoma+in+mice+administered+the+dideoxynucleoside+ddC.&rft.au=Sanders%2C+V+M%3BElwell%2C+M+R%3BHeath%2C+J+E%3BCollins%2C+B+J%3BDunnick%2C+J+K%3BRao%2C+G+N%3BPrejean%2C+D%3BLindamood%2C+C%3BIrwin%2C+R+D&rft.aulast=Sanders&rft.aufirst=V&rft.date=1995-09-01&rft.volume=27&rft.issue=2&rft.spage=263&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-01 N1 - Date created - 1996-02-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronic nephropathy and renal carcinogenicity of o-benzyl-p-chlorophenol in F344/N rats and B6C3F1 mice. AN - 77682055; 8529821 AB - o-Benzyl-p-chlorophenol, an aryl halide biocide, was evaluated in male and female F344/N rats and B6C3F1 mice in a series of subchronic and 2-year toxicity and carcinogenicity studies. Kidney was the primary target of toxicity in the 13-week gavage studies in rats and mice, with increased nephropathy noted as low as 240 mg/kg in male rats. Considering the nephropathy to be doselimiting, the chronic (2-year) study was conducted at lower doses (male rats: 30, 60, or 120 mg/kg; female rats: 60, 120, or 240 mg/kg; male and female mice: 120, 240, or 480 mg/kg; in corn oil; n = 50/group). Survival and body weights of dosed rats were similar to controls in the 2-year study. Survival of high-dose male and female mice, and body weights of all dosed male and mid- and high-dose female mice, were lower than controls. The incidence and severity of nephropathy increased with dose and length of treatment in both rats and mice. There was an increased incidence of renal tubule adenomas or carcinomas in both the mid- and high-dose male mice. Despite similar evidence of nephropathy, however, there were no increased incidences of neoplasms in female mice or in male or female rats. This study suggests therefore that while nephrotoxicity may have been a necessary component, factors other than the marked nephrotoxicity of o-benzyl-p-chlorophenol were critical to the development of renal carcinogenesis induced in only male mice. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Marsman, D S AU - Grumbein, S L AU - Haseman, J K AU - Hailey, J R AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 252 EP - 262 VL - 27 IS - 2 SN - 0272-0590, 0272-0590 KW - Disinfectants KW - 0 KW - clorophene KW - 7560BB0BO3 KW - Dichlorophen KW - T1J0JOU64O KW - Index Medicus KW - Eating -- drug effects KW - Hyperparathyroidism -- pathology KW - Animals KW - Kidney -- pathology KW - Intubation, Gastrointestinal KW - Survival KW - Mice KW - Rats KW - Mice, Inbred Strains KW - Rats, Inbred F344 KW - Body Weight -- drug effects KW - Hyperparathyroidism -- chemically induced KW - Blood Cell Count -- drug effects KW - Female KW - Male KW - Organ Size -- drug effects KW - Kidney Neoplasms -- pathology KW - Kidney Diseases -- pathology KW - Carcinoma -- pathology KW - Kidney Neoplasms -- chemically induced KW - Adenoma -- chemically induced KW - Dichlorophen -- analogs & derivatives KW - Adenoma -- pathology KW - Disinfectants -- toxicity KW - Dichlorophen -- toxicity KW - Kidney Diseases -- chemically induced KW - Carcinoma -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77682055?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Chronic+nephropathy+and+renal+carcinogenicity+of+o-benzyl-p-chlorophenol+in+F344%2FN+rats+and+B6C3F1+mice.&rft.au=Marsman%2C+D+S%3BGrumbein%2C+S+L%3BHaseman%2C+J+K%3BHailey%2C+J+R&rft.aulast=Marsman&rft.aufirst=D&rft.date=1995-09-01&rft.volume=27&rft.issue=2&rft.spage=252&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-01 N1 - Date created - 1996-02-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Negative regulation of chicken GATA-1 promoter activity mediated by a hormone response element. AN - 77677034; 7491106 AB - GATA-1 is a DNA-binding protein that regulates transcription of erythroid-specific genes and is required for the formation of mature erythroid cells. We show here that the GATA-1 hormone response-like element (GHRE) within the first intron of the gene functions as an inhibitory element in chicken erythroid precursor cells, as revealed by expression studies with mutants of the minimal GATA-1 promoter. We identify in these precursor cells the relevant proteins that interact with GHRE as a heterodimer of the thyroid hormone receptor alpha and the chicken ovalbumin upstream promoter transcription factor. Our results indicate that this novel complex can negatively regulate the GATA-1 promoter and suggest that GATA-1 can overcome this inhibitory action. We provide evidence that the viral gene product, v-erb A, can also reduce GATA-1 promoter activity through the GHRE site. JF - Molecular endocrinology (Baltimore, Md.) AU - Trainor, C D AU - Evans, T AU - Felsenfeld, G AD - Laboratory of Molecular Biology, National Institutes of Health Bethesda, Maryland 20892, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 1135 EP - 1146 VL - 9 IS - 9 SN - 0888-8809, 0888-8809 KW - COUP Transcription Factor I KW - 0 KW - DNA-Binding Proteins KW - Erythroid-Specific DNA-Binding Factors KW - Hormones KW - Receptors, Thyroid Hormone KW - Transcription Factors KW - Triiodothyronine KW - 06LU7C9H1V KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Triiodothyronine -- pharmacology KW - DNA -- metabolism KW - Receptors, Thyroid Hormone -- physiology KW - Erythroid Precursor Cells -- metabolism KW - Receptors, Thyroid Hormone -- immunology KW - Mutagenesis KW - Binding Sites KW - Base Sequence KW - Transfection KW - Binding, Competitive KW - Introns KW - Molecular Sequence Data KW - DNA -- chemistry KW - Chickens -- genetics KW - Transcription Factors -- physiology KW - Regulatory Sequences, Nucleic Acid KW - Promoter Regions, Genetic KW - Hormones -- pharmacology KW - DNA-Binding Proteins -- genetics KW - Gene Expression Regulation KW - DNA-Binding Proteins -- physiology KW - Transcription Factors -- immunology KW - Transcription Factors -- genetics KW - DNA-Binding Proteins -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77677034?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Negative+regulation+of+chicken+GATA-1+promoter+activity+mediated+by+a+hormone+response+element.&rft.au=Trainor%2C+C+D%3BEvans%2C+T%3BFelsenfeld%2C+G&rft.aulast=Trainor&rft.aufirst=C&rft.date=1995-09-01&rft.volume=9&rft.issue=9&rft.spage=1135&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 - 1996-01-04 N1 - Date created - 1996-01-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of the TATA box in transcription of the mouse mammary tumor virus long terminal repeat. AN - 77654183; 7491110 AB - An in vitro transcription system from mammary cells was established to study transcription of the long terminal repeat (LTR) of the mouse mammary tumor virus (MMTV). Experiments with progressive 5'-deletion constructs of the MMTV LTR revealed that a 19-base pair (bp) region from -41 to -23 bp, encompassing the TATA box and flanking DNA sequence, was as transcriptionally active as larger promoter constructs, both in nuclear extracts from human mammary cell lines (T47D and MCF7) and a nonmammary cell line (HeLa). The cell-free system was capable of supporting transcriptional induction by factors binding upstream of the TATA box, however, since purified glucocorticoid receptor-induced transcription in larger promoter constructs encompassing the MMTV hormone-responsive elements. Transcription from two other promoters, the adenovirus major late promoter and the human immunodeficiency virus LTR, also revealed a significant transcriptional contribution of upstream elements. The 19-bp TATA region from the MMTV LTR was shown to have considerably more activity in this transcription system than comparable TATA regions from other promoters. Sequences critical to the MMTV TATA region were evaluated by single base pair mutagenesis and found to comprise a consensus TATA box sequence, TATAAAA, as well as a single A just upstream of the TATAAAA sequence. Thus, the high level of basal transcription observed with the TATA region from MMTV is due to a perfect consensus TATA box sequence and a single base immediately 5' adjacent. It is likely that the high basal rate of transcription observed with this TATA box region on histone-free templates represents an inappropriate level of basal expression and that a complete evaluation of transactivation mechanisms in this system will require the recapitulation in vitro of the chromatin-mediated repressive state that exists in vivo. JF - Molecular endocrinology (Baltimore, Md.) AU - Kusk, P AU - Carlson, K E AU - Warren, B S AU - Hager, G L AD - Laboratory of Molecular Virology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 1180 EP - 1192 VL - 9 IS - 9 SN - 0888-8809, 0888-8809 KW - DNA, Viral KW - 0 KW - Nuclear Proteins KW - Index Medicus KW - AIDS/HIV KW - Promoter Regions, Genetic KW - Base Sequence KW - Tumor Cells, Cultured KW - HeLa Cells KW - Humans KW - Molecular Sequence Data KW - Breast Neoplasms KW - Binding Sites KW - DNA, Viral -- chemistry KW - Transcription, Genetic KW - Repetitive Sequences, Nucleic Acid KW - TATA Box KW - Mammary Tumor Virus, Mouse -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77654183?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Role+of+the+TATA+box+in+transcription+of+the+mouse+mammary+tumor+virus+long+terminal+repeat.&rft.au=Kusk%2C+P%3BCarlson%2C+K+E%3BWarren%2C+B+S%3BHager%2C+G+L&rft.aulast=Kusk&rft.aufirst=P&rft.date=1995-09-01&rft.volume=9&rft.issue=9&rft.spage=1180&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 - 1996-01-04 N1 - Date created - 1996-01-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of insulin-like growth factor I receptor gene expression by Sp1: physical and functional interactions of Sp1 at GC boxes and at a CT element. AN - 77653837; 7491107 AB - The insulin-like growth factor I (IGF-I) receptor mediates signal transduction by the IGFs and plays a critical role in growth and development. The proximal promoter region of the rat IGF-I receptor gene contains multiple Sp1 consensus-binding sites (GC boxes). Various promoter fragments fused to a luciferase reporter gene were transiently cotransfected together with an Sp1 expression vector into Drosophila Schneider cells, which lack endogenous Sp1. A proximal promoter fragment containing 476 nucleotides of 5'-flanking region and 640 nucleotides of 5'-untranslated region was strongly activated by Sp1 (an average of 116-fold), and progressive 5'-deletions of the promoter that sequentially removed GC boxes reduced Sp1 activation to 15-fold over basal promoter activity. DNase I footprinting studies with purified Sp1 protein revealed four GC boxes in the 5'-flanking region of the promoter and one homopurine/homopyrimidine motif (CT element) in the 5'-untranslated region that bound Sp1. Mutation of the CT element reduced Sp1 activation by 70%. Taken together, these results demonstrate that Sp1 can regulate expression of the IGF-I receptor promoter by acting both on GC boxes in the 5'-flanking region of the promoter and on a CT element in the 5'-untranslated region. JF - Molecular endocrinology (Baltimore, Md.) AU - Beitner-Johnson, D AU - Werner, H AU - Roberts, C T AU - LeRoith, D AD - Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 1147 EP - 1156 VL - 9 IS - 9 SN - 0888-8809, 0888-8809 KW - RNA, Messenger KW - 0 KW - Recombinant Fusion Proteins KW - Sp1 Transcription Factor KW - DNA KW - 9007-49-2 KW - Luciferases KW - EC 1.13.12.- KW - Receptor, IGF Type 1 KW - EC 2.7.10.1 KW - Deoxyribonuclease I KW - EC 3.1.21.1 KW - Index Medicus KW - Animals KW - DNA -- metabolism KW - Binding Sites KW - Rats KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Promoter Regions, Genetic KW - RNA, Messenger -- metabolism KW - DNA Footprinting KW - Molecular Sequence Data KW - DNA -- chemistry KW - Luciferases -- genetics KW - Regulatory Sequences, Nucleic Acid KW - Sp1 Transcription Factor -- pharmacology KW - Sp1 Transcription Factor -- metabolism KW - Receptor, IGF Type 1 -- genetics KW - Gene Expression Regulation -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77653837?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Regulation+of+insulin-like+growth+factor+I+receptor+gene+expression+by+Sp1%3A+physical+and+functional+interactions+of+Sp1+at+GC+boxes+and+at+a+CT+element.&rft.au=Beitner-Johnson%2C+D%3BWerner%2C+H%3BRoberts%2C+C+T%3BLeRoith%2C+D&rft.aulast=Beitner-Johnson&rft.aufirst=D&rft.date=1995-09-01&rft.volume=9&rft.issue=9&rft.spage=1147&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 - 1996-01-04 N1 - Date created - 1996-01-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibitors of the intracellular Ca(2+)-ATPase in cultured mouse keratinocytes reveal components of terminal differentiation that are regulated by distinct intracellular Ca2+ compartments. AN - 77653378; 8519694 AB - Differentiation of mammalian epidermis is associated with spatially and temporally coordinated changes in gene expression as cells migrate from the proliferative basal cell compartment through the nonproliferative spinous and granular cell layers where the terminal phase of maturation is completed. Previous studies have suggested that a gradient of Ca2+ in the epidermis in vivo and increased extracellular Ca2+ in vitro induce differentiation of mammalian epidermal keratinocytes. Chelation of intracellular free Ca2+ prevents this Ca(2+)-induced differentiation, but sites of action for intracellular Ca2+ remain undefined. In this study, thapsigargin (Tg) and cyclopiazonic acid (CPA), inhibitors of the endoplasmic reticulum Ca(2+)-ATPase, were used to evaluate the relative contribution of cytoplasmic and stored Ca2+ to Ca(2+)-induced terminal differentiation of cultured mouse keratinocytes. A sustained increase of both intracellular free Ca2+ (Cai) and ionomycin-sensitive Ca2+ stores is associated with Ca(2+)-induced keratinocyte terminal differentiation. Tg and CPA was used to change this coordinated regulation of free and stored Ca2+. In the absence of extracellular Ca2+, both Tg and CPA transiently increase Cai and deplete intracellular Ca2+ stores; while in the presence of extracellular Ca2+, Tg and CPA stimulate Ca2+ influx and cause a sustained increase in Cai while depleting stored Ca2+. In the presence of extracellular Ca2+, Tg (5 to 20 nM) and CPA (5 to 25 microM) inhibit Ca(2+)-induced morphological changes and stratification and prevent the suppression of DNA synthesis by Ca2+. Tg and CPA also inhibit the expression of mRNA and protein for specific epidermal spinous cell markers, keratins 1 (K1) and 10 (K10), prevent the redistribution of E-cadherin from a diffuse membranous pattern to concentration at cell-cell junctions, and inhibit the activation of a reporter gene regulated by a K1 enhancer element shown previously to be Ca2+ sensitive. These effects of Tg and CPA can be reversed by increasing the extracellular Ca2+ to levels that partially restore Ca2+ stores. In contrast, Tg and CPA enhance the expression of profilaggrin and loricrin mRNA and protein, markers of granular cell differentiation. These divergent actions of Tg and CPA on distinct components of the keratinocyte differentiation program suggest that adequate intracellular Ca2+ stores are important for the expression of spinous cell proteins and inhibition of DNA synthesis, while elevation of Cai stimulates the expression of markers of granular cell differentiation. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Li, L AU - Tucker, R W AU - Hennings, H AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 1171 EP - 1184 VL - 6 IS - 9 SN - 1044-9523, 1044-9523 KW - Enzyme Inhibitors KW - 0 KW - Indoles KW - Terpenes KW - Thapsigargin KW - 67526-95-8 KW - Calcium-Transporting ATPases KW - EC 3.6.3.8 KW - Calcium KW - SY7Q814VUP KW - cyclopiazonic acid KW - X9TLY4580Z KW - Index Medicus KW - Evaluation Studies as Topic KW - Cytosol -- metabolism KW - Animals KW - Cells, Cultured KW - Cell Compartmentation KW - Cell Division -- drug effects KW - Mice KW - Mice, Inbred BALB C KW - Cell Differentiation -- drug effects KW - Calcium -- metabolism KW - Keratinocytes -- enzymology KW - Enzyme Inhibitors -- pharmacology KW - Indoles -- pharmacology KW - Calcium-Transporting ATPases -- antagonists & inhibitors KW - Terpenes -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77653378?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cloning+and+characterization+of+a+cellular+apoptosis+susceptibility+gene%2C+the+human+homologue+to+the+yeast+chromosome+segregation+gene+CSE1.&rft.au=Brinkmann%2C+U%3BBrinkmann%2C+E%3BGallo%2C+M%3BPastan%2C+I&rft.aulast=Brinkmann&rft.aufirst=U&rft.date=1995-10-24&rft.volume=92&rft.issue=22&rft.spage=10427&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-25 N1 - Date created - 1996-01-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - EGF and TPA stimulate de novo synthesis of PGHS-1 and PGHS-2 through different signal transduction pathways. AN - 77647231; 7480087 AB - Epidermal growth factor (EGF) as well as phorbol 12-myristate 13-acetate (TPA) stimulate de novo synthesis of PGHS (prostaglandin H synthase)-1 and PGHS-2 mRNA, resulting in increased production of PGE2 in rat tracheal epithelial cells (RTE, EGV-6 cells). Stimulation of PGE2 production by TPA is more potent than that by EGF. Staurosporine and H-7, protein kinase C (PKC) inhibitors, suppressed the increase of mRNA and PGE2 levels caused by TPA, but not that caused by EGF. On the other hand, methyl 2,5-dihydroxycinnamate, a tyrosine kinase inhibitor (TKI), suppressed the increase of mRNA and PGE2 levels caused by EGF, but not that caused by TPA. These results indicate that EGF stimulates de novo synthesis of PGHS-1 and PGHS-2 mRNA through a signal transduction pathway which is independent from PKC-associated mechanisms but dependent upon the tyrosine kinase activity of the EGF receptor. JF - Prostaglandins, leukotrienes, and essential fatty acids AU - Hamasaki, Y AU - Eling, T E AD - Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 225 EP - 229 VL - 53 IS - 3 SN - 0952-3278, 0952-3278 KW - Alkaloids KW - 0 KW - Cinnamates KW - Enzyme Inhibitors KW - Isoquinolines KW - Piperazines KW - Protein Kinase Inhibitors KW - RNA, Messenger KW - Epidermal Growth Factor KW - 62229-50-9 KW - methyl 2,5-dihydroxycinnamate KW - 63177-57-1 KW - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine KW - 84477-87-2 KW - Prostaglandin-Endoperoxide Synthases KW - EC 1.14.99.1 KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Staurosporine KW - H88EPA0A3N KW - Dinoprostone KW - K7Q1JQR04M KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Dinoprostone -- biosynthesis KW - Piperazines -- pharmacology KW - Rats KW - Protein-Tyrosine Kinases -- antagonists & inhibitors KW - Isoquinolines -- pharmacology KW - RNA, Messenger -- metabolism KW - Cinnamates -- pharmacology KW - Alkaloids -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Epithelium -- metabolism KW - Trachea -- metabolism KW - Cell Line, Transformed KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Epidermal Growth Factor -- pharmacology KW - Signal Transduction KW - Prostaglandin-Endoperoxide Synthases -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77647231?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Prostaglandins%2C+leukotrienes%2C+and+essential+fatty+acids&rft.atitle=EGF+and+TPA+stimulate+de+novo+synthesis+of+PGHS-1+and+PGHS-2+through+different+signal+transduction+pathways.&rft.au=Hamasaki%2C+Y%3BEling%2C+T+E&rft.aulast=Hamasaki&rft.aufirst=Y&rft.date=1995-09-01&rft.volume=53&rft.issue=3&rft.spage=225&rft.isbn=&rft.btitle=&rft.title=Prostaglandins%2C+leukotrienes%2C+and+essential+fatty+acids&rft.issn=09523278&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-07 N1 - Date created - 1995-12-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neurotoxicity of the human immunodeficiency virus type 1 tat transactivator to PC12 cells requires the Tat amino acid 49-58 basic domain. AN - 77644546; 8531224 AB - The acquired immunodeficiency syndrome (AIDS) frequently involves the central nervous system (CNS) and manifests as dementia due to encephalitis or diffuse neurodegeneration. Human immunodeficiency virus type 1 (HIV-1) proteins, potentially transported into the CNS by mononuclear inflammatory cells, have been implicated in the etiology of this HIV-1 associated neurological dysfunction. Here we investigate the neurotoxicity of the essential HIV-1 regulator protein Tat in vivo after microinfusion into the rat brain and in vitro using PC12, NG108-15, and GT17 neuronal cell lines. Infusion of either chemically synthesized Tat (Tat86) or recombinant Tat (rTat) into the striatal gray matter in Sprague-Dawley rats resulted in postural deviation ipsilateral to the infusion, a clinical presentation in rats associated with complete striatal dysfunction. Histologic examination 3 days after infusion revealed massive necrosis in the area of the distribution of the infusion. Infusion of heat denatured rTat, peptide Tat49-58, or peptide Tat57-86 did not result in clinically or histologically detectable brain damage. After 3 days incubation in vitro, the lethal dose for half (LD50) of PC12 cells due to rTat was 5 micrograms/ml. The LD50 for Tat86 under the same conditions was 10 micrograms/ml. Tat49-58 and Tat57-86 peptides were not toxic in vitro even at 10-fold higher doses. At 5 micrograms/ml, rTat was toxic to 100% of GT17 cells after 24 hr. At 5 micrograms/ml, Tat86 was toxic to 90% of the NG108-15 cells after 7 days of treatment.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Journal of neuroscience research AU - Weeks, B S AU - Lieberman, D M AU - Johnson, B AU - Roque, E AU - Green, M AU - Loewenstein, P AU - Oldfield, E H AU - Kleinman, H K AD - Laboratory of Developmental Biology, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/09/01/ PY - 1995 DA - 1995 Sep 01 SP - 34 EP - 40 VL - 42 IS - 1 SN - 0360-4012, 0360-4012 KW - Amino Acids KW - 0 KW - Peptides KW - Trans-Activators KW - Index Medicus KW - AIDS/HIV KW - Rats KW - Animals KW - Dose-Response Relationship, Drug KW - Humans KW - Acquired Immunodeficiency Syndrome KW - Time Factors KW - PC12 Cells KW - Caudate Nucleus -- drug effects KW - HIV-1 KW - Amino Acids -- toxicity KW - Putamen -- drug effects KW - Peptides -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77644546?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neuroscience+research&rft.atitle=Neurotoxicity+of+the+human+immunodeficiency+virus+type+1+tat+transactivator+to+PC12+cells+requires+the+Tat+amino+acid+49-58+basic+domain.&rft.au=Weeks%2C+B+S%3BLieberman%2C+D+M%3BJohnson%2C+B%3BRoque%2C+E%3BGreen%2C+M%3BLoewenstein%2C+P%3BOldfield%2C+E+H%3BKleinman%2C+H+K&rft.aulast=Weeks&rft.aufirst=B&rft.date=1995-09-01&rft.volume=42&rft.issue=1&rft.spage=34&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuroscience+research&rft.issn=03604012&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-30 N1 - Date created - 1996-01-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HIV infection in healthcare workers: risk for infection and methods of prevention. AN - 77640498; 7488537 JF - Seminars in dermatology AU - Beekmann, S E AU - Henderson, D K AD - Hospital Epidemiology Service, National Institutes of Health, Bethesda, MD 20892. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 212 EP - 218 VL - 14 IS - 3 SN - 0278-145X, 0278-145X KW - Index Medicus KW - AIDS/HIV KW - Risk Factors KW - Humans KW - Infection Control KW - HIV Infections -- transmission KW - Occupational Diseases -- prevention & control KW - HIV Infections -- prevention & control KW - Infectious Disease Transmission, Patient-to-Professional -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77640498?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+dermatology&rft.atitle=HIV+infection+in+healthcare+workers%3A+risk+for+infection+and+methods+of+prevention.&rft.au=Beekmann%2C+S+E%3BHenderson%2C+D+K&rft.aulast=Beekmann&rft.aufirst=S&rft.date=1995-09-01&rft.volume=14&rft.issue=3&rft.spage=212&rft.isbn=&rft.btitle=&rft.title=Seminars+in+dermatology&rft.issn=0278145X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-04 N1 - Date created - 1996-01-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of photodynamic therapy for the management of pleural malignancies. AN - 77637153; 7569558 AB - Photodynamic therapy (PDT) is a surface oriented, locally cytotoxic intervention being investigated for oncologic therapy. Surfaces such as the pleura or the peritoneum are frequently involved with primary or metastatic cancer, and the chance for cure in such situations is low due to the inability to eradicate all the disease. A series of investigations have been performed at the National Cancer Institute since 1985 studying the possible use of PDT for large cavity treatment. This report details evolution of the methodology, toxicity, and overall feasibility of the delivery of intrapleural PDT to patients after debulking of primary and malignant chest neoplasms, with an emphasis on malignant pleural mesothelioma. These investigations have culminated in an ongoing Phase III trial to define the efficacy of intrapleural PDT. JF - Seminars in surgical oncology AU - Pass, H I AU - Donington, J S AD - Thoracic Oncology Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1995 SP - 360 EP - 367 VL - 11 IS - 5 SN - 8756-0437, 8756-0437 KW - Index Medicus KW - United States KW - Animals KW - Clinical Trials, Phase II as Topic KW - Clinical Trials, Phase III as Topic KW - Combined Modality Therapy KW - Humans KW - Mesothelioma -- surgery KW - Peritoneal Neoplasms -- drug therapy KW - Mesothelioma -- drug therapy KW - Feasibility Studies KW - Clinical Trials, Phase I as Topic KW - Peritoneal Neoplasms -- secondary KW - National Institutes of Health (U.S.) KW - Peritoneal Neoplasms -- surgery KW - Photochemotherapy -- adverse effects KW - Pleural Neoplasms -- secondary KW - Pleural Neoplasms -- drug therapy KW - Photochemotherapy -- methods KW - Pleural Neoplasms -- surgery UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77637153?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+surgical+oncology&rft.atitle=Use+of+photodynamic+therapy+for+the+management+of+pleural+malignancies.&rft.au=Pass%2C+H+I%3BDonington%2C+J+S&rft.aulast=Pass&rft.aufirst=H&rft.date=1995-09-01&rft.volume=11&rft.issue=5&rft.spage=360&rft.isbn=&rft.btitle=&rft.title=Seminars+in+surgical+oncology&rft.issn=87560437&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-21 N1 - Date created - 1995-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hepatic and pulmonary carcinogenicity of methylene chloride in mice: a search for mechanisms. AN - 77587840; 7482563 AB - An inhalation study utilizing over 1400 female B6C3F1 mice was undertaken to study mechanistic factors associated with liver and lung tumor induction following exposure to 2000 ppm of methylene chloride. Mice were exposed to methylene chloride (treated) or chamber air (controls) 6 h per day, for varying durations up to 104 weeks. Several interim sacrifices and 'stop exposures' were included. Exposure to 2000 ppm methylene chloride caused an increase in liver and lung neoplasia in the absence of overt cytotoxicity. Measurement of replicative DNA synthesis done after 13, 26, 52 and 78 weeks of exposure showed a significant decrease in the hepatocyte labeling index at 13 weeks. Replicative DNA synthesis in pulmonary airways after 1, 2, 3, 4, 13 and 26 weeks of exposure to methylene chloride was significantly lower than in air-exposed controls. Likewise, the increase in tumor induction in treated mice was not associated with increased replicative DNA synthesis in liver foci or in alveolar parenchyma. The frequency and pattern of H-ras gene activation were similar in control and methylene chloride-induced liver neoplasms. Similarly, the frequency and pattern of K-ras activation in lung neoplasms were not altered by exposure to methylene chloride. Early exposure to methylene chloride for only 26 weeks was sufficient to cause an increase in lung tumors by 2 years, suggesting that methylene chloride may cause early and persistent loss of growth control in lung cells. This implies that risk management strategies should be aimed at minimizing or eliminating exposure to methylene chloride. Liver neoplasms continued to increase in incidence and multiplicity as exposure continued, suggesting that methylene chloride-induced hepatocarcinogenesis is facilitated by continuing exposure to methylene chloride. Since methylene chloride is a more potent inducer of lung than liver neoplasia, it is recommended that health risk assessment be based on the lung data. While no novel molecular lesions have been found to explain the induction of lung and liver neoplasia in mice, ongoing studies may identify other molecular changes that are important in the genesis of these neoplasms. Hence, it may be necessary to revise risk assessment and management strategies in light of future research findings. JF - Toxicology AU - Maronpot, R R AU - Devereux, T R AU - Hegi, M AU - Foley, J F AU - Kanno, J AU - Wiseman, R AU - Anderson, M W AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/09/01/ PY - 1995 DA - 1995 Sep 01 SP - 73 EP - 81 VL - 102 IS - 1-2 SN - 0300-483X, 0300-483X KW - Methylene Chloride KW - 588X2YUY0A KW - Index Medicus KW - Space life sciences KW - Animals KW - Genes, ras -- drug effects KW - Dose-Response Relationship, Drug KW - Atmosphere Exposure Chambers KW - Mice KW - Administration, Inhalation KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Transcriptional Activation KW - Female KW - DNA Replication -- drug effects KW - Risk Assessment KW - Methylene Chloride -- toxicity KW - Liver Neoplasms, Experimental -- chemically induced KW - Methylene Chloride -- administration & dosage KW - Lung Neoplasms -- chemically induced KW - Lung Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77587840?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=Hepatic+and+pulmonary+carcinogenicity+of+methylene+chloride+in+mice%3A+a+search+for+mechanisms.&rft.au=Maronpot%2C+R+R%3BDevereux%2C+T+R%3BHegi%2C+M%3BFoley%2C+J+F%3BKanno%2C+J%3BWiseman%2C+R%3BAnderson%2C+M+W&rft.aulast=Maronpot&rft.aufirst=R&rft.date=1995-09-01&rft.volume=102&rft.issue=1-2&rft.spage=73&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-07 N1 - Date created - 1995-12-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biochemical mechanisms and cancer risk assessment models for dioxin. AN - 77585804; 7482548 AB - Biologically realistic mechanistic models of carcinogenesis by TCDD are composed of equations representing biochemical events leading to altered expression of proteins involved in the response or equations representing the kinetics of proliferation of clones of mutant cells. A biochemically augmented physiological dosimetry model reproduces the observed altered expression of liver proteins in female rats exposed to dioxin. The model suggests that oxidation of estradiol to DNA reactive quinones or semiquinones by CYP1A2 protein induced by TCDD may contribute to an increased mutational rate. It suggests that TCDD-stimulated production of a peptide ligand of the epidermal growth factor (EGF) receptor and subsequent activation of the receptor's tyrosine kinase activity may increase the rate of proliferation of susceptible cells. These calculated quantities can serve as indices of toxicity and can be used to predict tumor incidence as a function of exposure. JF - Toxicology AU - Kohn, M C AD - Laboratory of Quantitative and Computational Biology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/09/01/ PY - 1995 DA - 1995 Sep 01 SP - 133 EP - 138 VL - 102 IS - 1-2 SN - 0300-483X, 0300-483X KW - Carcinogens KW - 0 KW - Dioxins KW - Receptors, Aryl Hydrocarbon KW - Index Medicus KW - Receptors, Aryl Hydrocarbon -- drug effects KW - Rats KW - Animals KW - Dose-Response Relationship, Drug KW - Female KW - Risk Assessment KW - Liver Neoplasms, Experimental -- metabolism KW - Carcinogens -- toxicity KW - Liver Neoplasms, Experimental -- chemically induced KW - Dioxins -- toxicity KW - Models, Biological UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77585804?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=Biochemical+mechanisms+and+cancer+risk+assessment+models+for+dioxin.&rft.au=Kohn%2C+M+C&rft.aulast=Kohn&rft.aufirst=M&rft.date=1995-09-01&rft.volume=102&rft.issue=1-2&rft.spage=133&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-07 N1 - Date created - 1995-12-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - NIEHS perspectives on collaboration among government, academia, and industry. AN - 77574854; 7570666 JF - Toxicology letters AU - Olden, K AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 287 EP - 289 VL - 79 IS - 1-3 SN - 0378-4274, 0378-4274 KW - Index Medicus KW - United States KW - Government KW - Humans KW - Universities KW - Risk Assessment KW - Industry KW - Cooperative Behavior KW - Environmental Health KW - National Institutes of Health (U.S.) KW - Toxicology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77574854?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+letters&rft.atitle=NIEHS+perspectives+on+collaboration+among+government%2C+academia%2C+and+industry.&rft.au=Olden%2C+K&rft.aulast=Olden&rft.aufirst=K&rft.date=1995-09-01&rft.volume=79&rft.issue=1-3&rft.spage=287&rft.isbn=&rft.btitle=&rft.title=Toxicology+letters&rft.issn=03784274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-06 N1 - Date created - 1995-11-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Summary and recommendations for session B: activity classification and structure-activity relationship modeling for human health risk assessment of toxic substances. AN - 77574818; 7570664 AB - The major theme of Session B explored and assessed the current status of activity-classification (AC)1 and structure-activity-relationship (SAR) methods developed to model adverse health effects that can result when biological systems are exposed to various chemical substances. The output from such models is intended to be used as information that supports risk assessments performed on toxic substances. Speakers gave special attention to the requirements and applications of hazard identification models. Specific aspects of the broad subject matter were augmented and explicated by audience and panel discussions during the 1.5 days available. This format stimulated the exchange of a surprisingly broad range of information and stimulating ideas. In order to gather the diverse aspects of Session B in one place, the Rapporteurs agreed that this summary would aim at providing a comprehensive overview, while Dr. Feldman's would amplify selected points of general interest. JF - Toxicology letters AU - Bristol, D W AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, NIH/National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 265 EP - 280 VL - 79 IS - 1-3 SN - 0378-4274, 0378-4274 KW - Hazardous Substances KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Expert Systems KW - Risk Assessment KW - Hazardous Substances -- classification KW - Models, Biological KW - Structure-Activity Relationship KW - Hazardous Substances -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77574818?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+letters&rft.atitle=Summary+and+recommendations+for+session+B%3A+activity+classification+and+structure-activity+relationship+modeling+for+human+health+risk+assessment+of+toxic+substances.&rft.au=Bristol%2C+D+W&rft.aulast=Bristol&rft.aufirst=D&rft.date=1995-09-01&rft.volume=79&rft.issue=1-3&rft.spage=265&rft.isbn=&rft.btitle=&rft.title=Toxicology+letters&rft.issn=03784274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-06 N1 - Date created - 1995-11-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronic sodium azide treatment decreases membrane-bound protein kinase C activity in the rat hippocampus. AN - 77574365; 7582827 AB - Chronic administration of sodium azide in rats inhibits cytochrome oxidase and produces learning and memory deficits. The present experiment tested the hypothesis that chronic sodium azide treatment might also alter protein kinase C activation. Continuous infusion of sodium azide (400 micrograms/h, sc) in rats for 2 weeks significantly decreases membrane-bound protein kinase C in hippocampus, but not frontal cortex, temporal cortex, or cerebellum. Since protein kinase C activation is correlated with hippocampus-dependent learning, these results suggest a possible biochemical mechanism for azide-induced impairment of learning. JF - Neurobiology of learning and memory AU - Bennett, M C AU - Fordyce, D E AU - Rose, G M AU - Wehner, J M AD - National Institute of Aging, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 187 EP - 190 VL - 64 IS - 2 SN - 1074-7427, 1074-7427 KW - Azides KW - 0 KW - Mutagens KW - Sodium Azide KW - 968JJ8C9DV KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Rats KW - Temporal Lobe -- drug effects KW - Animals KW - Rats, Sprague-Dawley KW - Brain Mapping KW - Frontal Lobe -- drug effects KW - Dose-Response Relationship, Drug KW - Cerebellum -- drug effects KW - Enzyme Activation -- drug effects KW - Male KW - Protein Kinase C -- antagonists & inhibitors KW - Hippocampus -- physiology KW - Azides -- pharmacology KW - Mutagens -- pharmacology KW - Mental Recall -- drug effects KW - Synaptic Membranes -- drug effects KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77574365?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurobiology+of+learning+and+memory&rft.atitle=Chronic+sodium+azide+treatment+decreases+membrane-bound+protein+kinase+C+activity+in+the+rat+hippocampus.&rft.au=Bennett%2C+M+C%3BFordyce%2C+D+E%3BRose%2C+G+M%3BWehner%2C+J+M&rft.aulast=Bennett&rft.aufirst=M&rft.date=1995-09-01&rft.volume=64&rft.issue=2&rft.spage=187&rft.isbn=&rft.btitle=&rft.title=Neurobiology+of+learning+and+memory&rft.issn=10747427&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-18 N1 - Date created - 1995-12-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Age at menarche among diethylstilbestrol granddaughters. AN - 77549623; 7573253 AB - We interviewed 542 women whose mothers were in a randomized trial of diethylstilbestrol. Effects of diethylstilbestrol on the third generation were explored by ascertaining age at menarche for the women's daughters. A total of 123 daughters were > or = 10 years old (52 exposed and 71 unexposed). Age at menarche was unaffected by mother's prenatal diethylstilbestrol exposure. JF - American journal of obstetrics and gynecology AU - Wilcox, A J AU - Umbach, D M AU - Hornsby, P P AU - Herbst, A L AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 835 EP - 836 VL - 173 IS - 3 Pt 1 SN - 0002-9378, 0002-9378 KW - Diethylstilbestrol KW - 731DCA35BT KW - Abridged Index Medicus KW - Index Medicus KW - Randomized Controlled Trials as Topic KW - Age Factors KW - Double-Blind Method KW - Humans KW - Adult KW - Child KW - Adolescent KW - Female KW - Pregnancy KW - Diethylstilbestrol -- adverse effects KW - Menarche KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77549623?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+obstetrics+and+gynecology&rft.atitle=Age+at+menarche+among+diethylstilbestrol+granddaughters.&rft.au=Wilcox%2C+A+J%3BUmbach%2C+D+M%3BHornsby%2C+P+P%3BHerbst%2C+A+L&rft.aulast=Wilcox&rft.aufirst=A&rft.date=1995-09-01&rft.volume=173&rft.issue=3+Pt+1&rft.spage=835&rft.isbn=&rft.btitle=&rft.title=American+journal+of+obstetrics+and+gynecology&rft.issn=00029378&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-26 N1 - Date created - 1995-10-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Monocyte chemotactic protein-3 (MCP3) interacts with multiple leukocyte receptors: binding and signaling of MCP3 through shared as well as unique receptors on monocytes and neutrophils. AN - 77543945; 7589134 AB - The diversity of monocyte chemotactic protein (MCP)3 target cell types, as well as the capacity of MCP3 to desensitize leukocyte responses to other CC chemokines, suggested that MCP3 may interact with multiple CC chemokine receptors. The purpose of this study is to establish how MCP3 binds and activates monocytes and neutrophils. We show that human monocytes exhibit high-affinity binding for 125I-MCP3 with an estimated Kd of 1-3 nM and about 10,000 binding sites/cell. The binding of 125I-MCP3 to monocytes was progressively less well competed by CC chemokines macrophage inflammatory protein (MIP)1 alpha (Kd = 5-10 nM), RANTES (Kd = 5-10 nM), MCP1 (monocyte chemoattractant and activating factor, or MCAF) (Kd = 60 nM) and MIP1 beta (Kd > 100 nM). On the other hand, unlabeled MCP3 displaced the binding of radiolabeled MIP1 alpha, RANTES, MCP1 and MIP1 beta as effectively as the isologous CC chemokines. In agreement with the binding data, pretreatment of monocytes with MCP3 completely desensitized the calcium flux in response to MIP1 alpha and RANTES. However, MIP1 alpha and RANTES failed to desensitize the response of monocytes to MCP3. MCP3 and MCP1 partially desensitized each other's effects on monocytes. These binding and cross-desensitization results suggest that MCP3 binds and signals through other binding sites in addition to those shared with MIP1 alpha, RANTES and MCP1. The unidirectional competition for MIP1 beta binding and signaling by MCP3 suggests the existence of an as-yet unidentified site for MCP3 shared with MIP1 beta. The existence of another unique binding site(s) for MCP3 was further shown by the failure of any of the other CC chemokines to compete effectively for MCP3 binding on neutrophils. MCP3 in our study was also the only human CC chemokine that consistently chemoattracted neutrophils. These results suggest that MCP3 is a ligand that can bind and activate a broad range of target cells through receptors shared by other CC chemokines as well as its own receptor. JF - European journal of immunology AU - Xu, L L AU - McVicar, D W AU - Ben-Baruch, A AU - Kuhns, D B AU - Johnston, J AU - Oppenheim, J J AU - Wang, J M AD - Biological Carcinogenesis and Development Program, SAIC-Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 2612 EP - 2617 VL - 25 IS - 9 SN - 0014-2980, 0014-2980 KW - CCL7 protein, human KW - 0 KW - Chemokine CCL7 KW - Cytokines KW - Monocyte Chemoattractant Proteins KW - Receptors, Cytokine KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Calcium -- metabolism KW - Humans KW - Radioligand Assay KW - Signal Transduction KW - Neutrophils -- metabolism KW - Monocyte Chemoattractant Proteins -- metabolism KW - Monocytes -- metabolism KW - Receptors, Cytokine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77543945?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+immunology&rft.atitle=Monocyte+chemotactic+protein-3+%28MCP3%29+interacts+with+multiple+leukocyte+receptors%3A+binding+and+signaling+of+MCP3+through+shared+as+well+as+unique+receptors+on+monocytes+and+neutrophils.&rft.au=Xu%2C+L+L%3BMcVicar%2C+D+W%3BBen-Baruch%2C+A%3BKuhns%2C+D+B%3BJohnston%2C+J%3BOppenheim%2C+J+J%3BWang%2C+J+M&rft.aulast=Xu&rft.aufirst=L&rft.date=1995-09-01&rft.volume=25&rft.issue=9&rft.spage=2612&rft.isbn=&rft.btitle=&rft.title=European+journal+of+immunology&rft.issn=00142980&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-28 N1 - Date created - 1995-11-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Trifluoperazine modulates [3H]resiniferatoxin binding by human and rat vanilloid (capsaicin) receptors and affects 45Ca uptake by adult rat dorsal root ganglion neurones. AN - 77543041; 7562474 AB - Optimum treatment of neuropathic pain includes the use of adjuvant analgesics such as antipsychotic drugs and tricyclic antidepressants. Although the mechanism of their analgesic action is not known, it is possible that such agents act directly on pain pathways. The ability of capsaicin and its analogs to selectively deactivate primary afferent neurons provides a basis for their use in human therapy to relieve a number of chronic pain conditions. We examined whether the phenothiazine antipsychotic drug trifluoperazine (TFP) as well as other neuroleptics and tricyclic antidepressants have an effect on the agonist binding properties and the activation of the human and rat vanilloid receptors. Binding of [3H]resiniferatoxin (RTX) to membrane preparations of human dorsal horn and rat whole spinal cord was affected by TFP in a biphasic fashion, with an initial 25 and 65% enhancement of [3H]RTX binding, respectively, preceding inhibition. The apparent Ki values for inhibition were 3.93 +/- 0.13 microM for human dorsal horn and 7.91 +/- 0.62 microM for rat spinal cord. Scatchard analyses revealed that TFP affected both the affinity and the cooperativity of [3H]RTX binding by the receptors, leaving the receptor density unaltered. Similar effects on [3H]RTX binding to rat spinal cord membranes were also induced by other antipsychotic phenothiazines and other types of antipsychotics, by phenothiazines without antipsychotic actions, as well as by tricyclic antidepressants. In cultures of dorsal root ganglion neurones, TFP at concentrations that increased [3H]RTX binding (1-3 microM) also induced an increase in 45Ca uptake; this increase was absent in cultures prepared from capsaicin desensitized animals.(ABSTRACT TRUNCATED AT 250 WORDS) JF - The Journal of pharmacology and experimental therapeutics AU - Acs, G AU - Palkovits, M AU - Blumberg, P M AD - Molecular Mechanisms of Tumor Promotion Section, National Institute of Mental Health, Bethesda, Maryland, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 1090 EP - 1098 VL - 274 IS - 3 SN - 0022-3565, 0022-3565 KW - Antipsychotic Agents KW - 0 KW - Calcium Radioisotopes KW - Diterpenes KW - Neurotoxins KW - Receptors, Drug KW - Tritium KW - 10028-17-8 KW - Trifluoperazine KW - 214IZI85K3 KW - resiniferatoxin KW - A5O6P1UL4I KW - Capsaicin KW - S07O44R1ZM KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Neurons -- metabolism KW - Neurons -- drug effects KW - Humans KW - Neurons -- cytology KW - Hypothermia, Induced KW - Female KW - Ganglia, Spinal -- cytology KW - Calcium -- metabolism KW - Receptors, Drug -- metabolism KW - Neurotoxins -- metabolism KW - Trifluoperazine -- pharmacology KW - Receptors, Drug -- drug effects KW - Ganglia, Spinal -- metabolism KW - Antipsychotic Agents -- pharmacology KW - Capsaicin -- metabolism KW - Ganglia, Spinal -- drug effects KW - Diterpenes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77543041?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Trifluoperazine+modulates+%5B3H%5Dresiniferatoxin+binding+by+human+and+rat+vanilloid+%28capsaicin%29+receptors+and+affects+45Ca+uptake+by+adult+rat+dorsal+root+ganglion+neurones.&rft.au=Acs%2C+G%3BPalkovits%2C+M%3BBlumberg%2C+P+M&rft.aulast=Acs&rft.aufirst=G&rft.date=1995-09-01&rft.volume=274&rft.issue=3&rft.spage=1090&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-25 N1 - Date created - 1995-10-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Environmental health science research and human risk assessment. AN - 77530711; 7546220 AB - Environmental health science research, with its focus on fundamental science and disease prevention, is important for the development of rational and cost-effective public health and regulatory policies related to environmental protection. Environmentally related diseases are preventable, yet they impose a major burden on society in terms of human suffering and costs related to health care. Similarly, the expenditure of hundreds of billions of dollars for regulatory compliance is a major economic concern. There is considerable debate regarding current regulatory risk assessment practices for environmental agents. Implicit in all risk assessment schemes is the need to extrapolate from high-exposure studies to low-exposure situations and from known risks in rodents to probable risks in people. Both extrapolations are fraught with uncertainties. These uncertainties are accommodated in risk-assessment schemes by the incorporation of arbitrary "safety factors" and other default approaches. Since these factors are not derived experimentally, they may overestimate or under estimate actual risks. Risk-assessment methodology, its relevance to the human condition, and its use in protecting human health will greatly improve when our expanding knowledge of the basic biology of environmental effects is incorporated into toxicological testing and risk-assessment schemes. Moreover, exciting opportunities now exist to advance our understanding of the environmental and genetic bases of many common diseases and to design effective prevention and intervention strategies to combat their development. This report discusses some of the current opportunities and challenges. JF - Molecular carcinogenesis AU - Olden, K AU - Klein, J L AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709-2233, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 2 EP - 9 VL - 14 IS - 1 SN - 0899-1987, 0899-1987 KW - Environmental Pollutants KW - 0 KW - Index Medicus KW - United States KW - Environmental Monitoring KW - Genes KW - Environmental Pollutants -- toxicity KW - Cell Physiological Phenomena KW - DNA Damage KW - Humans KW - Cell Communication KW - Epidemiological Monitoring KW - Public Policy KW - Risk Assessment KW - Conservation of Natural Resources KW - Disease -- etiology KW - Epidemiology KW - Environmental Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77530711?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Environmental+health+science+research+and+human+risk+assessment.&rft.au=Olden%2C+K%3BKlein%2C+J+L&rft.aulast=Olden&rft.aufirst=K&rft.date=1995-09-01&rft.volume=14&rft.issue=1&rft.spage=2&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 - 1995-11-06 N1 - Date created - 1995-11-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bile duct-specific lectins, Dolichos biflorus agglutinin and peanut agglutinin, as probes in mouse hepatocarcinogenesis. AN - 77526426; 7564276 AB - It is well established that alterations in the expression of cell surface glycoproteins occur during the course of tumorigenesis and can be detected immunohistochemically. However, no consistent markers of malignancy in mouse hepatocellular tumors have yet been identified. Lectin histochemistry, using three bile duct-specific lectins, Dolichos biflorus agglutinin (DBA), peanut agglutinin (PNA) and soybean agglutinin (SBA), and anti-epidermal keratin immunohistochemistry, was conducted on formalin-fixed, paraffin-embedded tissues of a spectrum of benign and malignant hepatocellular proliferative lesions of mice, including hepatocholangiocarcinomas. DBA- and PNA-binding glycoproteins in normal livers and in bile and liver tumors of mice were verified by SDS-PAGE and Western blot analysis. Normal bile duct cells stained strongly with DBA but minimally to moderately with PNA and SBA. DBA-positive tumor cells were present in 96% of hepatocholangiocarcinomas, 89% of hepatocellular carcinomas, and 35% of hepatocellular adenomas. In comparison, 43% of hepatocholangiocarcinomas, 37% of hepatocellular carcinomas, and 24% of hepatocellular adenomas exhibited PNA staining. SBA did not specifically stain tumor cells. Normal hepatocytes and those in altered foci were consistently negative for these three lectins. Keratin-positive staining was found only in normal bile ductular cells and ductal elements in 70% of hepatocholangiocarcinomas. Electrophoresis and Western blot analysis demonstrated that, in normal livers, DBA and PNA bound to the 13- to 16-kDa and 27- to 30-kDa glycoproteins believed to be of bile duct cell origin and commonly present in hepatocellular adenomas, hepatocellular carcinomas, and hepatocholangiocarcinomas, with strongest expression in the last. In addition, hepatocholangiocarcinomas had the same high molecular mass glycoprotein (> 200 kDa) labeled with DBA as detected in bile. Our results suggest that some malignant hepatocytes, especially in mouse hepatocholangiocarcinomas, have the potential of biliary differentiation. DBA is a sensitive marker for malignant hepatocytes in mice. JF - Laboratory investigation; a journal of technical methods and pathology AU - Takahashi, K AU - Viviano, C J AU - Elwell, M R AU - Bakewell, W E AU - Kuwahara, M AU - Nakashima, N AU - Blackwell, B N AU - Maronpot, R R AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 424 EP - 432 VL - 73 IS - 3 SN - 0023-6837, 0023-6837 KW - Lectins KW - 0 KW - Molecular Probes KW - Peanut Agglutinin KW - Plant Lectins KW - dolichos biflorus agglutinin KW - Keratins KW - 68238-35-7 KW - Index Medicus KW - Animals KW - Cholangiocarcinoma -- diagnosis KW - Retrospective Studies KW - Mice KW - Keratins -- analysis KW - Mice, Inbred Strains KW - Carcinogenicity Tests -- methods KW - Precancerous Conditions -- diagnosis KW - Adenoma -- diagnosis KW - Immunohistochemistry KW - Female KW - Male KW - Bile Ducts -- chemistry KW - Lectins -- analysis KW - Carcinoma, Hepatocellular -- diagnosis KW - Molecular Probes -- analysis KW - Bile Ducts -- metabolism KW - Liver Neoplasms -- diagnosis KW - Lectins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77526426?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Laboratory+investigation%3B+a+journal+of+technical+methods+and+pathology&rft.atitle=Bile+duct-specific+lectins%2C+Dolichos+biflorus+agglutinin+and+peanut+agglutinin%2C+as+probes+in+mouse+hepatocarcinogenesis.&rft.au=Takahashi%2C+K%3BViviano%2C+C+J%3BElwell%2C+M+R%3BBakewell%2C+W+E%3BKuwahara%2C+M%3BNakashima%2C+N%3BBlackwell%2C+B+N%3BMaronpot%2C+R+R&rft.aulast=Takahashi&rft.aufirst=K&rft.date=1995-09-01&rft.volume=73&rft.issue=3&rft.spage=424&rft.isbn=&rft.btitle=&rft.title=Laboratory+investigation%3B+a+journal+of+technical+methods+and+pathology&rft.issn=00236837&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-20 N1 - Date created - 1995-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Spermatocyte toxicity of 2-methoxyethanol (ME) in rats and guinea pigs: evidence for the induction of apoptosis. AN - 77526309; 7676444 AB - 2-Methoxyethanol (ME) produces testicular lesions characterized by pachytene spermatocyte degeneration in rats and guinea pigs which differ in onset, severity, and morphological characteristics. In the rat, degenerating spermatocytes appear necrotic at 24 hr, while in the guinea pig they appear apoptotic 96 hr after the start of three daily doses. To further examine if the spermatocyte degeneration in both species represented necrosis or apoptosis, the extent and nature of nuclear DNA fragmentation after ME exposure were assessed both visually using an in situ nucleotide 3' end-labeling (ISEL) procedure and by DNA gel electrophoresis. Testes from rats given a single oral dose of ME (200 mg/kg) showed the expected pachytene spermatocyte degeneration 24 hr after dosing, with the nuclear chromatin degradation typical of necrosis. In contrast, testes from guinea pigs given daily oral doses of ME (200 mg/kg) showed spermatocyte degeneration at only 96 hr after the start of dosing, with marked peripheral nuclear chromatin condensation characteristic of apoptosis. Coincident with the appearance of morphologic changes, degenerating spermatocytes in both species contained fragmented DNA as revealed by the ISEL procedure. The pattern of DNA fragmentation on agarose gels in both species consisted of ordered multiples or "ladders" of approximately 200 base pairs, a hallmark of apoptosis, with their appearance coincident with the time course of morphologic spermatocyte degeneration and ISEL staining. Preliminary data reveal the appearance of divalent metal cation-dependent endonuclease activity at pH 7.0 in ME-treated immature (24-day-old) rat testis that produces a similar pattern of DNA fragmentation and which appears to be distinct from activity associated with the spontaneous germ cell degeneration observed in testes of this age. In summary, in vivo ME exposure induces spermatocyte apoptosis in both the rat and guinea pig despite differing morphological classifications and time of onset of cell death. Future studies will focus on further characterization of the testicular endonuclease in the rat and the potential role of increased intracellular Ca2+ as a "triggering" stimulus in ME-induced spermatocyte apoptosis. JF - Toxicology and applied pharmacology AU - Ku, W W AU - Wine, R N AU - Chae, B Y AU - Ghanayem, B I AU - Chapin, R E AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 100 EP - 110 VL - 134 IS - 1 SN - 0041-008X, 0041-008X KW - Ethylene Glycols KW - 0 KW - Immunosuppressive Agents KW - DNA KW - 9007-49-2 KW - Endonucleases KW - EC 3.1.- KW - methyl cellosolve KW - EK1L6XWI56 KW - Index Medicus KW - Rats KW - Endonucleases -- metabolism KW - DNA -- isolation & purification KW - Animals KW - Rats, Inbred F344 KW - Guinea Pigs KW - DNA Damage KW - Species Specificity KW - Male KW - Ethylene Glycols -- toxicity KW - Testis -- drug effects KW - Immunosuppressive Agents -- toxicity KW - Apoptosis -- drug effects KW - Spermatocytes -- drug effects KW - Spermatocytes -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77526309?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Spermatocyte+toxicity+of+2-methoxyethanol+%28ME%29+in+rats+and+guinea+pigs%3A+evidence+for+the+induction+of+apoptosis.&rft.au=Ku%2C+W+W%3BWine%2C+R+N%3BChae%2C+B+Y%3BGhanayem%2C+B+I%3BChapin%2C+R+E&rft.aulast=Ku&rft.aufirst=W&rft.date=1995-09-01&rft.volume=134&rft.issue=1&rft.spage=100&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 - 1995-10-19 N1 - Date created - 1995-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of vitamin A deficiency on the integrity of hepatocytes after partial hepatectomy. AN - 77522828; 7677181 AB - The effect of vitamin A deficiency on hepatic regeneration in male and female rats was studied after partial hepatectomy. A fourfold increase in the number of positive dUTP end-labeled nuclei was observed in the deficient animals as early as 30 minutes after partial hepatectomy and their number reached a peak by 8 hours after the operation. The bile duct cells were both morphologically and biochemically intact at all time points. Administration of retinyl palmitate 1 hour before partial hepatectomy significantly reduced the number of positive nuclei, and treatment with retinyl palmitate 24 or 48 hours before the operation reduced the number of positive cells to the level observed in control vitamin A-supplemented rats. The level of transcripts for c-jun, c-fos, c-myc, and transforming growth factor-beta 1 were increased for an extended period of time in livers of deficient animals, whereas the expression of both p53 and max were unchanged. Immunocytochemistry demonstrated the presence of latent transforming growth factor-beta 1 in cells showing evident apoptotic or necrotic changes in their nuclei. This study demonstrates the importance of vitamin A for the survival of hepatocytes both in intact vitamin A-deficient liver and after partial hepatectomy, whereas the ductal cells appear to be less sensitive to vitamin A deficiency. JF - The American journal of pathology AU - Evarts, R P AU - Hu, Z AU - Omori, N AU - Omori, M AU - Marsden, E R AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 699 EP - 706 VL - 147 IS - 3 SN - 0002-9440, 0002-9440 KW - Transforming Growth Factor beta KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Blotting, Northern KW - Apoptosis KW - Gene Expression KW - Postoperative Period KW - Transforming Growth Factor beta -- metabolism KW - Immunohistochemistry KW - Male KW - Genes, Immediate-Early KW - Female KW - Vitamin A Deficiency -- metabolism KW - Liver -- physiopathology KW - Liver -- pathology KW - Vitamin A Deficiency -- genetics KW - Hepatectomy -- methods KW - Liver -- metabolism KW - Vitamin A Deficiency -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77522828?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+pathology&rft.atitle=Effect+of+vitamin+A+deficiency+on+the+integrity+of+hepatocytes+after+partial+hepatectomy.&rft.au=Evarts%2C+R+P%3BHu%2C+Z%3BOmori%2C+N%3BOmori%2C+M%3BMarsden%2C+E+R%3BThorgeirsson%2C+S+S&rft.aulast=Evarts&rft.aufirst=R&rft.date=1995-09-01&rft.volume=147&rft.issue=3&rft.spage=699&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+pathology&rft.issn=00029440&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-17 N1 - Date created - 1995-10-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1987 Dec 17-23;330(6149):624-9 [2825036] J Cell Biol. 1987 Dec;105(6 Pt 2):2861-76 [3320058] Mol Endocrinol. 1989 Oct;3(10):1515-22 [2608047] Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3412-5 [2014262] J Immunol. 1991 May 15;146(10):3340-6 [1827483] Adv Cancer Res. 1991;56:1-48 [2028839] Mol Pharmacol. 1991 Jun;39(6):697-701 [1904980] Cancer Res. 1991 Dec 1;51(23 Pt 1):6304-11 [1933891] Biochim Biophys Acta. 1991 Dec 10;1072(2-3):129-57 [1751545] Genes Dev. 1992 Jan;6(1):71-80 [1730411] Cell. 1992 Apr 3;69(1):119-28 [1555236] Cancer Res. 1992 Aug 15;52(16):4313-9 [1353702] J Biol Chem. 1992 Sep 15;267(26):18278-83 [1526968] J Cell Biol. 1992 Nov;119(3):493-501 [1400587] Methods Enzymol. 1992;213:460-72 [1435314] EMBO J. 1993 Jan;12(1):371-7 [8428592] Br J Cancer. 1993 Mar;67(3):531-6 [8439503] Nature. 1993 Apr 29;362(6423):847-9 [8479522] Nature. 1993 Apr 29;362(6423):849-52 [8479523] Endocr Rev. 1993 Apr;14(2):133-51 [8325248] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6170-4 [8392190] J Cell Physiol. 1993 Aug;156(2):264-71 [7688370] Cell. 1993 Oct 22;75(2):241-51 [7503812] Am J Pathol. 1994 Feb;144(2):321-8 [7508684] Immunol Today. 1994 Jan;15(1):7-10 [8136014] Cancer. 1994 Apr 15;73(8):2013-26 [8156506] J Biol Chem. 1994 Apr 22;269(16):12084-91 [7512958] Lab Invest. 1994 Apr;70(4):511-6 [7513770] Oncogene. 1994 Aug;9(8):2305-11 [8036012] Cell Growth Differ. 1994 May;5(5):503-8 [7519440] Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7553-7 [7519782] Lab Invest. 1994 Aug;71(2):219-25 [8078301] Nature. 1980 Apr 10;284(5756):555-6 [6245367] Int Rev Cytol. 1980;68:251-306 [7014501] Nature. 1987 Dec 3-9;330(6147):444-50 [2825025] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cadmium-induced renal damage and proinflammatory cytokines: possible role of IL-6 in tubular epithelial cell regeneration. AN - 77522486; 7676455 AB - Cadmium exposure in humans and experimental animals produces renal damage characterized by degeneration and necrosis of tubular epithelial cells followed by interstitial inflammation and eventual regeneration of proximal tubular cells. Since chronic kidney diseases are often associated with the presence of inflammatory cytokines and cadmium has been reported to alter cytokine expression in monocytes and the Kupffer cells of the liver, we investigated the role of proinflammatory cytokines in cadmium-induced nephrotoxicity. Increases in TNF-alpha and IL-6 cytokine mRNA transcripts and secretion were observed in the kidney following exposure of LPS-primed mice to a total of 21 mg/kg body weight cadmium administered over a 14-week period. IL-6 was the predominant cytokine expressed and was found to be present in mesangial cells. Cadmium, in the presence of LPS, was able to induce IL-6 secretion in vitro from mouse glomerular mesangial cells. Proliferative cell nuclear antigen (PCNA) staining revealed increases in regeneration of tubular epithelial cells following cadmium exposure. Furthermore, renal tubular epithelial cells responded to IL-6 by marked proliferation. Taken together, these data suggest that cadmium-induced IL-6 secretion in the kidney may act to support the regeneration of renal tubular epithelial cells that occurs in the course of cadmium nephrotoxicity. JF - Toxicology and applied pharmacology AU - Kayama, F AU - Yoshida, T AU - Elwell, M R AU - Luster, M I AD - Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 26 EP - 34 VL - 134 IS - 1 SN - 0041-008X, 0041-008X KW - Interleukin-6 KW - 0 KW - Tumor Necrosis Factor-alpha KW - Cadmium KW - 00BH33GNGH KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Index Medicus KW - Animals KW - Mice KW - Rats KW - Mice, Inbred Strains KW - Polymerase Chain Reaction KW - Rats, Inbred F344 KW - Base Sequence KW - Culture Techniques KW - Body Weight -- drug effects KW - Molecular Sequence Data KW - L-Lactate Dehydrogenase -- secretion KW - Cell Line KW - Female KW - Organ Size -- drug effects KW - Kidney -- pathology KW - Interleukin-6 -- secretion KW - Kidney -- drug effects KW - Cadmium -- toxicity KW - Kidney -- immunology KW - Tumor Necrosis Factor-alpha -- secretion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77522486?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cadmium-induced+renal+damage+and+proinflammatory+cytokines%3A+possible+role+of+IL-6+in+tubular+epithelial+cell+regeneration.&rft.au=Kayama%2C+F%3BYoshida%2C+T%3BElwell%2C+M+R%3BLuster%2C+M+I&rft.aulast=Kayama&rft.aufirst=F&rft.date=1995-09-01&rft.volume=134&rft.issue=1&rft.spage=26&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 - 1995-10-19 N1 - Date created - 1995-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacologic variables associated with the development of neurologic toxicity in patients treated with suramin. AN - 77499578; 7666080 AB - To describe pharmacologic variables correlated with the development of neurologic toxicity in patients treated with suramin. Eighty-one patients were treated with suramin in a phase I study. The rate of drug infusion was continuously adjusted to maintain a preassigned plasma suramin concentration (175, 215, or 275 micrograms/mL) for a fixed duration (2 to 8 weeks). Eight patients developed grade III/IV neurologic motor impairment (predominantly motor axonal polyneuropathy). All were treated at the 275-micrograms/mL concentration. One patient treated at the 215-micrograms/mL concentration developed grade II motor dysfunction. In addition, seven of nine patients had sensory symptoms. Pharmacologic variables associated with the development of polyneuropathy included total cumulative suramin dose, duration of exposure to plasma concentrations greater than 200 micrograms/mL, and area under the curve (AUC) greater than 200 micrograms/mL. Significant neurologic toxicity can result from therapy with suramin, even when dosing is designed to avoid exposure to plasma concentrations greater than 350 micrograms/mL. Future clinical trials of suramin should be designed in such a way as to limit the total cumulative dose to or = 8 weeks, limit the period of exposure to plasma suramin concentrations greater than 200 micrograms/mL to < or = 25 days, and limit the AUC greater than 200 micrograms/mL to < or = 48,000 mg.h/AL. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Bitton, R J AU - Figg, W D AU - Venzon, D J AU - Dalakas, M C AU - Bowden, C AU - Headlee, D AU - Reed, E AU - Myers, C E AU - Cooper, M R AD - Clinical Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 2223 EP - 2229 VL - 13 IS - 9 SN - 0732-183X, 0732-183X KW - Suramin KW - 6032D45BEM KW - Index Medicus KW - Humans KW - Melanoma -- blood KW - Aged KW - Prostatic Neoplasms -- drug therapy KW - Sarcoma -- drug therapy KW - Multivariate Analysis KW - Aged, 80 and over KW - Logistic Models KW - Motor Neuron Disease -- chemically induced KW - Adult KW - Melanoma -- drug therapy KW - Prostatic Neoplasms -- blood KW - Middle Aged KW - Male KW - Sarcoma -- blood KW - Suramin -- adverse effects KW - Suramin -- pharmacokinetics KW - Suramin -- administration & dosage KW - Nervous System Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77499578?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Pharmacologic+variables+associated+with+the+development+of+neurologic+toxicity+in+patients+treated+with+suramin.&rft.au=Bitton%2C+R+J%3BFigg%2C+W+D%3BVenzon%2C+D+J%3BDalakas%2C+M+C%3BBowden%2C+C%3BHeadlee%2C+D%3BReed%2C+E%3BMyers%2C+C+E%3BCooper%2C+M+R&rft.aulast=Bitton&rft.aufirst=R&rft.date=1995-09-01&rft.volume=13&rft.issue=9&rft.spage=2223&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 - 1995-10-06 N1 - Date created - 1995-10-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - RAG-1 mutations that affect the target specificity of V(D)j recombination: a possible direct role of RAG-1 in site recognition. AN - 77496776; 7657170 AB - The RAG-1 protein plays an essential role in V(D)j recombination, but its exact function has not yet been defined. Here we report that a particular mutation in RAG-1 affects recombination by altering the specificity of target sequence usage. Recombination mediated by wild-type RAG-1 is tolerant of a wide range of coding sequences adjacent to the recombination signal. With the mutant RAG-1, recombination is much more demanding; efficient recombination is only found when particular dinucleotides are adjacent to the signal sequence heptamer. The mutant is also more sensitive than wild-type RAG-1 to certain alterations within the signal sequence. We suggest that the RAG-1 protein may interact physically with the target DNA at the coding-signal sequence border. JF - Genes & development AU - Sadofsky, M J AU - Hesse, J E AU - van Gent, D C AU - Gellert, M AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Bethesda, Maryland 20892, USA. Y1 - 1995/09/01/ PY - 1995 DA - 1995 Sep 01 SP - 2193 EP - 2199 VL - 9 IS - 17 SN - 0890-9369, 0890-9369 KW - RAG-1 KW - Homeodomain Proteins KW - 0 KW - Proteins KW - Receptors, Antigen, T-Cell KW - RAG-1 protein KW - 128559-51-3 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Transfection KW - Molecular Sequence Data KW - Plasmids KW - Mutation KW - Sequence Deletion KW - Recombination, Genetic KW - Genes, RAG-1 KW - Receptors, Antigen, T-Cell -- genetics KW - Proteins -- genetics KW - Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77496776?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes+%26+development&rft.atitle=RAG-1+mutations+that+affect+the+target+specificity+of+V%28D%29j+recombination%3A+a+possible+direct+role+of+RAG-1+in+site+recognition.&rft.au=Sadofsky%2C+M+J%3BHesse%2C+J+E%3Bvan+Gent%2C+D+C%3BGellert%2C+M&rft.aulast=Sadofsky&rft.aufirst=M&rft.date=1995-09-01&rft.volume=9&rft.issue=17&rft.spage=2193&rft.isbn=&rft.btitle=&rft.title=Genes+%26+development&rft.issn=08909369&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-04 N1 - Date created - 1995-10-04 N1 - Date revised - 2017-01-13 N1 - Gene symbol - RAG-1 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Infectious and immunosuppressive complications of purine analog therapy. AN - 77493581; 7666104 AB - The purine analogs fludarabine, cladribine, and pentostatin are active agents in the treatment of indolent lymphoid malignancies. This report reviews the pattern, severity, and consequences of the immunosuppression and myelotoxicity associated with these agents. The literature was searched using MedLine and Cancerline, as well as the bibliographies of published reports through the winter of 1994 and 1995. Each of these drugs induces profound lymphocytopenia. A marked decrease in CD4 cells may persist for several years, while other mononuclear-cell populations recover more rapidly. The spectrum of infections encountered in these patients appears to be altered to include a wide range of opportunistic organisms. Factors that increase the risk of these infections include concurrent corticosteroids, extensive prior therapy, particularly with another purine analog, and poor response to purine analog treatment. Because of the frequency of life-threatening infections with unusual pathogens that may occur in patients treated with purine analogs, aggressive and early diagnostic evaluation and appropriate use of myeloid growth factors may be necessary to ensure appropriate antimicrobial therapy. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Cheson, B D AD - Division of Cancer Treatment, National Cancer Institute, Bethesda, MD 20892-7436, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 2431 EP - 2448 VL - 13 IS - 9 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents KW - 0 KW - Purines KW - Pentostatin KW - 395575MZO7 KW - Cladribine KW - 47M74X9YT5 KW - Vidarabine KW - FA2DM6879K KW - fludarabine KW - P2K93U8740 KW - Index Medicus KW - Vidarabine -- analogs & derivatives KW - Cladribine -- adverse effects KW - Pentostatin -- adverse effects KW - Humans KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Vidarabine -- adverse effects KW - Bone Marrow -- drug effects KW - Infection -- etiology KW - Immune Tolerance -- drug effects KW - Purines -- adverse effects KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77493581?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Infectious+and+immunosuppressive+complications+of+purine+analog+therapy.&rft.au=Cheson%2C+B+D&rft.aulast=Cheson&rft.aufirst=B&rft.date=1995-09-01&rft.volume=13&rft.issue=9&rft.spage=2431&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 - 1995-10-06 N1 - Date created - 1995-10-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Processing of endoplasmic reticulum luminal antigens associated with halothane hepatitis in rat hepatocytes. AN - 77489924; 7657302 AB - In this study we have investigated the mechanism of the processing of trifluoroacetylated liver microsomal protein antigens associated with halothane hepatitis to learn how the immune system might come in contact with these proteins to form antibodies directed against them. Rats were treated with halothane and parenchymal (PC) and non-parenchymal cells (NPC) were isolated 16 hours later. Immunoblotting of the cell lysates with antisera directed against the trifluoroacetyl hapten showed the presence of high levels of trifluoroacetylated proteins in parenchymal cells, whereas none of these proteins were detected in endothelial or Kupffer cells that were isolated by centrifugal elutriation. The half-lives of 100-, 82-, 80-, 63-, 59-, 58-, and 57-kd trifluoroacetylated and native carrier proteins of the trifluoroacetyl hapten in cultures of rat primary parenchymal cells were approximately 1 day. The turnovers of all of these trifluoroacetylated proteins, except for that of the trifluoroacetylated 100-kd protein, were inhibited by treatment of the cells with ammonium chloride, leupeptin, 4-(2-aminoethyl)-benzenesulfonyl fluoride, or 3-methyl-adenine (3-MA). These results indicate that, in liver, the major source of the formation of trifluoroacetylated antigens associated with halothane hepatitis is the parenchymal cells, It appears that most of the trifluoroacetylated antigens and possibly the native carrier protein of the trifluoroacetyl haptens are transferred from the endoplasmic reticulum (ER) to an acidic compartment of PCs, where they are enzymatically degraded. The processing of the trifluoroacetylated proteins by this pathway may be a protective mechanism that prevents these covalently altered proteins from inducing an antibody response in most patients who are administered halothane. JF - Hepatology (Baltimore, Md.) AU - Amouzadeh, H R AU - Pohl, L R AD - Molecular and Cellular Toxicology Section, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1760, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 936 EP - 943 VL - 22 IS - 3 SN - 0270-9139, 0270-9139 KW - Antigens KW - 0 KW - Carrier Proteins KW - Haptens KW - Proteins KW - Trifluoroacetic Acid KW - E5R8Z4G708 KW - Halothane KW - UQT9G45D1P KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Haptens -- metabolism KW - Carrier Proteins -- metabolism KW - Half-Life KW - Trifluoroacetic Acid -- metabolism KW - Proteins -- metabolism KW - Female KW - Endoplasmic Reticulum -- metabolism KW - Liver -- pathology KW - Antigens -- metabolism KW - Chemical and Drug Induced Liver Injury -- pathology KW - Liver -- immunology KW - Liver -- metabolism KW - Antigens -- immunology KW - Endoplasmic Reticulum -- immunology KW - Chemical and Drug Induced Liver Injury -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77489924?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Processing+of+endoplasmic+reticulum+luminal+antigens+associated+with+halothane+hepatitis+in+rat+hepatocytes.&rft.au=Amouzadeh%2C+H+R%3BPohl%2C+L+R&rft.aulast=Amouzadeh&rft.aufirst=H&rft.date=1995-09-01&rft.volume=22&rft.issue=3&rft.spage=936&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 - 1995-10-04 N1 - Date created - 1995-10-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antibodies to CD40 prevent Epstein-Barr virus-mediated human B-cell lymphomagenesis in severe combined immune deficient mice given human peripheral blood lymphocytes. AN - 77484003; 7544649 AB - CD40 is expressed on both normal and neoplastic B lymphocytes. Signal transduction through CD40 in vitro has been shown to exert stimulatory effects on normal B cells and inhibitory effects on Epstein-Barr virus (EBV)-induced B-cell lymphoma lines and some other cell lines derived from patients with aggressive histology lymphoma. The transfer of normal human peripheral blood lymphocytes (huPBL) from EBV-seropositive donors into severe combined immune deficient (SCID) mice has been previously shown to result in the generation of human B-cell lymphomas. These tumors are similar to the highly aggressive EBV-induced lymphomas that can arise clinically after transplantation or in the setting of immunodeficiency. Treatment of huPBL-SCID chimeric mice with anti-CD40 or anti-CD20 monoclonal antibodies (MoAb) significantly delayed the development of EBV-induced B-cell lymphoma. However, the effects of the two MoAb were mechanistically distinct. Anti-CD40 treatment prevented lymphoma generation, while still allowing for functional human B-cell engraftment in the huPBL-SCID mice compared with mice receiving no treatment, all of which succumbed to lymphoma. By contrast, treatment with anti-CD20 significantly inhibited total human B-cell engraftment in the SCID recipients, which accounted for the absence of lymphomas. In vitro assays examining the transformation of human B cells by EBV also indicated that anti-CD40 could directly inhibit EBV-transformation, whereas anti-CD20 antibodies had no effect. Thus, anti-CD40 exerts selective effects to allow for the engraftment of normal human B cells and prevent the emergence of EBV lymphomas. Stimulation of CD40 by antibodies or its physiologic ligand may, therefore, be of significant clinical use in the prevention of EBV-induced B lymphomas that may arise when EBV-seropositive individuals receive immunosuppressive regimens after transplantation or in immune deficiency states, such as acquired immune deficiency syndrome. JF - Blood AU - Murphy, W J AU - Funakoshi, S AU - Beckwith, M AU - Rushing, S E AU - Conley, D K AU - Armitage, R J AU - Fanslow, W C AU - Rager, H C AU - Taub, D D AU - Ruscetti, F W AD - Biological Carcinogenesis and Development Program, Inc/DynCorp, NCI-FCRDC, MD 21702-1201, USA. Y1 - 1995/09/01/ PY - 1995 DA - 1995 Sep 01 SP - 1946 EP - 1953 VL - 86 IS - 5 SN - 0006-4971, 0006-4971 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD KW - Antigens, CD20 KW - Antigens, CD40 KW - Antigens, Differentiation, B-Lymphocyte KW - Diphtheria Toxin KW - HLA Antigens KW - HLA-DR Antigens KW - Immunoglobulins KW - Tetanus Toxin KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Diphtheria Toxin -- immunology KW - HLA-DR Antigens -- analysis KW - Humans KW - Mice KW - Tetanus Toxin -- immunology KW - Immunotherapy, Adoptive KW - Transplantation, Heterologous KW - Enzyme-Linked Immunosorbent Assay KW - HLA Antigens -- analysis KW - Immunoglobulins -- blood KW - Mice, SCID KW - Lymphoma, B-Cell -- immunology KW - Lymphocyte Transfusion KW - Lymphoma, B-Cell -- virology KW - Antigens, Differentiation, B-Lymphocyte -- immunology KW - Lymphoma, B-Cell -- prevention & control KW - B-Lymphocytes -- immunology KW - Herpesvirus 4, Human KW - Cell Transformation, Neoplastic KW - Antigens, CD -- immunology KW - Antibodies, Monoclonal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77484003?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Antibodies+to+CD40+prevent+Epstein-Barr+virus-mediated+human+B-cell+lymphomagenesis+in+severe+combined+immune+deficient+mice+given+human+peripheral+blood+lymphocytes.&rft.au=Murphy%2C+W+J%3BFunakoshi%2C+S%3BBeckwith%2C+M%3BRushing%2C+S+E%3BConley%2C+D+K%3BArmitage%2C+R+J%3BFanslow%2C+W+C%3BRager%2C+H+C%3BTaub%2C+D+D%3BRuscetti%2C+F+W&rft.aulast=Murphy&rft.aufirst=W&rft.date=1995-09-01&rft.volume=86&rft.issue=5&rft.spage=1946&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-03 N1 - Date created - 1995-10-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Leukemia inhibitory factor induces interleukin-8 and monocyte chemotactic and activating factor in human monocytes: differential regulation by interferon-gamma. AN - 77482481; 7655023 AB - Leukemia inhibitory factor (LIF) is a cytokine released at the site of injuries where there is a recruitment of monocytes and polymorphonuclear cells. We analyzed the effect of LIF on human monocytes, which are a major source of chemotactic factors. We showed that supernatants of monocytes treated with LIF (50 ng/mL) for 18 hours had chemotactic activity for neutrophils and monocytes that was neutralized by anti-interleukin-8 (anti-IL-8) and anti-monocyte chemotactic and activating factor (anti-MCAF) neutralizing antibodies. Northern blot analysis showed induction of IL-8 and MCAF RNA in monocytes treated with LIF. Both IL-8 and MCAF mRNA were induced within 3 hours of stimulation. IL-8 and MCAF mRNAs expression peaked at 6 hours and 18 hours, respectively. Interferon-gamma (IFN-gamma), a potent monocyte activator, inhibited IL-8 induction by LIF. On the contrary, IFN-gamma by itself induced MCAF and did not affect the LIF-induced MCAF. These results indicate that LIF released at the site of injury by inducing IL-8 and MCAF can play an important role in recruiting leukocytes and that IFN-gamma can differentially regulate this recruitment. JF - Blood AU - Musso, T AU - Badolato, R AU - Longo, D L AU - Gusella, G L AU - Varesio, L AD - PRI/DynCorp, NCI-FCRDC, Biological Carcinogenesis and Development Program, MD 21702-1201, USA. Y1 - 1995/09/01/ PY - 1995 DA - 1995 Sep 01 SP - 1961 EP - 1967 VL - 86 IS - 5 SN - 0006-4971, 0006-4971 KW - Chemokine CCL2 KW - 0 KW - Chemotactic Factors KW - Culture Media KW - Cytokines KW - Growth Inhibitors KW - Interleukin-6 KW - Interleukin-8 KW - LIF protein, human KW - Leukemia Inhibitory Factor KW - Lymphokines KW - RNA, Messenger KW - Recombinant Proteins KW - Tumor Necrosis Factor-alpha KW - Interferon-gamma KW - 82115-62-6 KW - Abridged Index Medicus KW - Index Medicus KW - Recombinant Proteins -- pharmacology KW - Blotting, Northern KW - Humans KW - RNA, Messenger -- analysis KW - Tumor Necrosis Factor-alpha -- biosynthesis KW - Chemotaxis, Leukocyte KW - RNA, Messenger -- biosynthesis KW - Cells, Cultured KW - Kinetics KW - Cell Communication KW - Neutrophils -- physiology KW - Interleukin-8 -- biosynthesis KW - Monocytes -- physiology KW - Chemotactic Factors -- biosynthesis KW - Monocytes -- immunology KW - Cytokines -- biosynthesis KW - Lymphokines -- pharmacology KW - Growth Inhibitors -- pharmacology KW - Monocytes -- drug effects KW - Interferon-gamma -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77482481?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Leukemia+inhibitory+factor+induces+interleukin-8+and+monocyte+chemotactic+and+activating+factor+in+human+monocytes%3A+differential+regulation+by+interferon-gamma.&rft.au=Musso%2C+T%3BBadolato%2C+R%3BLongo%2C+D+L%3BGusella%2C+G+L%3BVaresio%2C+L&rft.aulast=Musso&rft.aufirst=T&rft.date=1995-09-01&rft.volume=86&rft.issue=5&rft.spage=1961&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-03 N1 - Date created - 1995-10-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Steel factor (c-kit ligand) promotes the survival of hematopoietic stem/progenitor cells in the absence of cell division. AN - 77482373; 7544641 AB - It is known that the majority of primitive hematopoietic progenitors are in a noncycling quiescent state. In addition, normal hematopoietic progenitors and progenitor cell lines show an absolute dependence on growth factors for their survival in vitro, yet the effect of growth factors on progenitor cell survival has not been separated from effects on both proliferation and differentiation. Using an in vitro assay system, we examined whether growth factors could promote the survival of stem cells in culture in the absence of cell division. These studies show that steel factor (SLF) and, to a lesser extent, interleukin-3 (IL-3) directly promoted the survival of elutriated bone marrow progenitor cells (countercurrent centrifugal elutriation [CCE]-27) that are enriched for primitive hematopoietic progenitors that respond to the combination of SLF plus IL-3. Furthermore, SLF promoted the survival of short-term reconstituting cells (STRC), and long-term reconstituting cells (LTRC) with trilineage reconstitution potential in vivo. In comparison, granulocyte colony-stimulating factor (G-CSF), IL-6, leukemia inhibitory factor, IL-11, IL-1, granulocyte macrophage CSF (GM-CSF), and macrophage CSF (M-CSF) had no effect on the survival of these cells. In the presence of mitotic inhibitors (nocodazole or aphidicolin), SLF promoted the survival of CCE-27 progenitor cells that respond to the combination of SLF plus IL-3 in vitro and STRCs and LTRCs that are detected in vivo. Taken together, these data show that SLF can directly promote the survival of hematopoietic progenitor cells in the absence of cell division. JF - Blood AU - Keller, J R AU - Ortiz, M AU - Ruscetti, F W AD - Biological Carcinogenesis and Development Program, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201, USA. Y1 - 1995/09/01/ PY - 1995 DA - 1995 Sep 01 SP - 1757 EP - 1764 VL - 86 IS - 5 SN - 0006-4971, 0006-4971 KW - Colony-Stimulating Factors KW - 0 KW - Hematopoietic Cell Growth Factors KW - Interleukin-3 KW - Recombinant Proteins KW - Stem Cell Factor KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Macrophage Colony-Stimulating Factor KW - 81627-83-0 KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - DNA KW - 9007-49-2 KW - Thymidine KW - VC2W18DGKR KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Recombinant Proteins -- pharmacology KW - Culture Techniques -- methods KW - Interleukin-3 -- pharmacology KW - Humans KW - Macrophage Colony-Stimulating Factor -- pharmacology KW - Culture Techniques -- instrumentation KW - Mice KW - Mice, Inbred BALB C KW - Granulocyte Colony-Stimulating Factor -- pharmacology KW - Granulocyte-Macrophage Colony-Stimulating Factor -- pharmacology KW - DNA -- biosynthesis KW - Cell Separation -- methods KW - Flow Cytometry -- methods KW - Thymidine -- metabolism KW - Bone Marrow Cells KW - Cell Survival -- drug effects KW - Cells, Cultured KW - Mice, Inbred C57BL KW - Time Factors KW - Hematopoietic Stem Cells -- cytology KW - Hematopoietic Cell Growth Factors -- pharmacology KW - Colony-Stimulating Factors -- pharmacology KW - Hematopoietic Stem Cells -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77482373?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Steel+factor+%28c-kit+ligand%29+promotes+the+survival+of+hematopoietic+stem%2Fprogenitor+cells+in+the+absence+of+cell+division.&rft.au=Keller%2C+J+R%3BOrtiz%2C+M%3BRuscetti%2C+F+W&rft.aulast=Keller&rft.aufirst=J&rft.date=1995-09-01&rft.volume=86&rft.issue=5&rft.spage=1757&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-03 N1 - Date created - 1995-10-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Future contraceptives. AN - 77479730; 7652531 JF - Scientific American AU - Alexander, N J AD - Contraceptive Development Branch, National Institute of Child Health and Human Development, Bethesda, Md, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 136 EP - 141 VL - 273 IS - 3 SN - 0036-8733, 0036-8733 KW - Contraceptive Agents, Female KW - 0 KW - Spermatocidal Agents KW - Vaccines KW - Index Medicus KW - Population KW - Reproductive Tract Infections KW - Barrier Methods KW - Contraceptive Implants KW - Contraceptive Agents KW - Spermicidal Contraceptive Agents KW - Contraceptive Methods KW - Economic Factors KW - Condom KW - Contraception KW - Contraceptive Vaccines KW - Sexually Transmitted Diseases--prevention and control KW - Critique KW - Diseases KW - Contraception, Immunological KW - Family Planning KW - Research And Development KW - Technology KW - Infections KW - Contraception Research KW - Condoms KW - Humans KW - Sexually Transmitted Diseases -- prevention & control KW - Male KW - Female KW - Contraception -- trends UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77479730?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Possible+mechanisms+for+PhIP-DNA+adduct+formation+in+the+mammary+gland+of+female+Sprague-Dawley+rats.&rft.au=Ghoshal%2C+A%3BDavis%2C+C+D%3BSchut%2C+H+A%3BSnyderwine%2C+E+G&rft.aulast=Ghoshal&rft.aufirst=A&rft.date=1995-11-01&rft.volume=16&rft.issue=11&rft.spage=2725&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-27 N1 - Date created - 1995-09-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Somatostatin may participate in the antiinflammatory actions of glucocorticoids. AN - 77463980; 7544277 AB - Glucocorticoids are potent antiinflammatory agents. They inhibit leukocyte chemotaxis and vascular permeability and generally suppress the expression of many inflammatory mediators. Recent reports suggested that somatostatin (Sms) had significant immunomodulatory properties in vitro and in vivo. In this study we examined the effects of glucocorticoids on immunoreactive somatostatin expression in aseptic inflammatory sites of Sprague-Dawley rats given carrageenin sc. The progress of the inflammatory reaction was studied over a 7-h period with respect to the volume and cellularity of the exudate and the levels of the inflammatory mediators expressed in the inflammatory site, including immunoreactive substance P (sP), corticotropin-releasing hormone (CRH), and tumor necrosis factor-alpha (TNF alpha). Dexamethasone significantly reduced the volume and cellularity of the inflammatory exudates; in parallel, the levels of immunoreactive sP, CRH, and TNF alpha were significantly suppressed by this glucocorticoid. In contrast, immunoreactive Sms was stimulated by dexamethasone in a time-dependent fashion. These findings suggest another mechanism for suppression of the inflammatory reaction by glucocorticoids via stimulation of local Sms expression, which occurs in parallel to the inhibition of the local inflammatory mediators sP, CRH, and TNF alpha. JF - Endocrinology AU - Karalis, K AU - Mastorakos, G AU - Sano, H AU - Wilder, R L AU - Chrousos, G P AD - Developmental Endocrinology Branch, National Institutes of Child Health and Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 4133 EP - 4138 VL - 136 IS - 9 SN - 0013-7227, 0013-7227 KW - Anti-Inflammatory Agents KW - 0 KW - Glucocorticoids KW - Tumor Necrosis Factor-alpha KW - Substance P KW - 33507-63-0 KW - Somatostatin KW - 51110-01-1 KW - Dexamethasone KW - 7S5I7G3JQL KW - Carrageenan KW - 9000-07-1 KW - Corticotropin-Releasing Hormone KW - 9015-71-8 KW - Abridged Index Medicus KW - Index Medicus KW - Substance P -- analysis KW - Animals KW - Leukocytes -- chemistry KW - Macrophages -- chemistry KW - Corticotropin-Releasing Hormone -- physiology KW - Dexamethasone -- pharmacology KW - Skin -- metabolism KW - Skin -- pathology KW - Skin Diseases -- pathology KW - Corticotropin-Releasing Hormone -- metabolism KW - Rats KW - Granuloma -- drug therapy KW - Carrageenan -- toxicity KW - Fibroblasts -- pathology KW - Tumor Necrosis Factor-alpha -- analysis KW - Endothelium -- chemistry KW - Time Factors KW - Male KW - Skin Diseases -- drug therapy KW - Granuloma -- chemically induced KW - Substance P -- metabolism KW - Tumor Necrosis Factor-alpha -- physiology KW - Skin Diseases -- chemically induced KW - Substance P -- physiology KW - Endothelium -- pathology KW - Skin -- chemistry KW - Rats, Sprague-Dawley KW - Macrophages -- pathology KW - Granuloma -- pathology KW - Leukocytes -- pathology KW - Fibroblasts -- chemistry KW - Tumor Necrosis Factor-alpha -- metabolism KW - Immunohistochemistry KW - Corticotropin-Releasing Hormone -- analysis KW - Somatostatin -- analysis KW - Somatostatin -- physiology KW - Anti-Inflammatory Agents -- therapeutic use KW - Somatostatin -- metabolism KW - Glucocorticoids -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77463980?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Somatostatin+may+participate+in+the+antiinflammatory+actions+of+glucocorticoids.&rft.au=Karalis%2C+K%3BMastorakos%2C+G%3BSano%2C+H%3BWilder%2C+R+L%3BChrousos%2C+G+P&rft.aulast=Karalis&rft.aufirst=K&rft.date=1995-09-01&rft.volume=136&rft.issue=9&rft.spage=4133&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-22 N1 - Date created - 1995-09-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of adrenomedullin in normal human lung and in pulmonary tumors. AN - 77463929; 7649118 AB - Adrenomedullin (AM) is a potent hypotensive peptide recently discovered in extracts of human pheochromocytoma. In this report we present evidence, using reverse transcriptase-polymerase chain reaction, immunocytochemistry, and in situ reverse transcriptase-polymerase chain reaction, that AM is synthesized by several cell populations of the normal lung, tumor cell lines of pulmonary origin, and tumor specimens. Among the normal cell populations of the lung, we found AM expression in the columnar epithelium, some glands, neurons of the pulmonary parasympathetic nervous system, endothelial cells, chondrocytes, alveolar macrophages, and smooth muscle cells. In tumors, AM expression was located in most of the nonsmall cell lung carcinomas and in half of the small cell lung carcinomas studied. These findings suggest that AM may play a broad role in respiratory homeostasis and lung carcinogenesis. JF - Endocrinology AU - Martinez, A AU - Miller, M J AU - Unsworth, E J AU - Siegfried, J M AU - Cuttitta, F AD - Biomarkers and Prevention Research Branch, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20850-3300, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 4099 EP - 4105 VL - 136 IS - 9 SN - 0013-7227, 0013-7227 KW - DNA, Antisense KW - 0 KW - Oligonucleotides KW - Peptides KW - RNA, Messenger KW - Adrenomedullin KW - 148498-78-6 KW - Abridged Index Medicus KW - Index Medicus KW - Muscle, Smooth -- chemistry KW - Macrophages -- chemistry KW - Humans KW - RNA, Messenger -- genetics KW - DNA, Antisense -- analysis KW - Gene Expression Regulation, Neoplastic KW - Tumor Cells, Cultured KW - Blotting, Southern KW - Oligonucleotides -- chemistry KW - DNA, Antisense -- chemistry KW - Molecular Sequence Data KW - Epithelium -- chemistry KW - Oligonucleotides -- genetics KW - Macrophages -- cytology KW - Oligonucleotides -- analysis KW - RNA, Messenger -- chemistry KW - RNA, Messenger -- analysis KW - DNA, Antisense -- genetics KW - Amino Acid Sequence KW - Polymerase Chain Reaction KW - Blotting, Western KW - Base Sequence KW - Epithelial Cells KW - Muscle, Smooth -- cytology KW - Immunohistochemistry KW - Carcinoma, Small Cell -- pathology KW - Lung Neoplasms -- chemistry KW - Lung -- cytology KW - Lung -- chemistry KW - Peptides -- analysis KW - Adenocarcinoma -- chemistry KW - Adenocarcinoma -- genetics KW - Carcinoid Tumor -- chemistry KW - Adenocarcinoma, Bronchiolo-Alveolar -- genetics KW - Adenocarcinoma -- pathology KW - Adenocarcinoma, Bronchiolo-Alveolar -- chemistry KW - Carcinoid Tumor -- pathology KW - Adenocarcinoma, Bronchiolo-Alveolar -- pathology KW - Lung Neoplasms -- genetics KW - Carcinoid Tumor -- genetics KW - Peptides -- genetics KW - Carcinoma, Small Cell -- chemistry KW - Carcinoma, Small Cell -- genetics KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77463929?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Expression+of+adrenomedullin+in+normal+human+lung+and+in+pulmonary+tumors.&rft.au=Martinez%2C+A%3BMiller%2C+M+J%3BUnsworth%2C+E+J%3BSiegfried%2C+J+M%3BCuttitta%2C+F&rft.aulast=Martinez&rft.aufirst=A&rft.date=1995-09-01&rft.volume=136&rft.issue=9&rft.spage=4099&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-22 N1 - Date created - 1995-09-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HIV infection and AIDS risk behaviors among injecting drug users entering methadone treatment: an update. AN - 77461392; 7648291 AB - Trends in HIV infection and AIDS risk behaviors among injecting drug users (IDUs) were assessed through a series of nonblinded point-prevalence surveys conducted between 1987 and 1991 with admissions to methadone treatment in eight areas, including New York City; Asbury Park and Trenton, New Jersey; Philadelphia; Baltimore; Chicago; San Antonio, Texas; and Los Angeles County. Over the 5-year period, significant changes in HIV seropositivity were found in two of the eight cities, with seroprevalence decreasing in Asbury Park from 43.1 to 21.2% and increasing from 10.1 to 17.6% in Chicago. Initially high levels of injection-related risk behaviors decreased substantially across cohorts in most cities, except for San Antonio and Los Angeles, where risk levels remained high. Sexual risk behaviors continued at high levels in all cities, suggesting relatively little sexual risk reduction during the course of the study. JF - Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association AU - Battjes, R J AU - Pickens, R W AU - Brown, L S AD - National Institute on Drug Abuse, Rockville, Maryland 20857, USA. Y1 - 1995/09/01/ PY - 1995 DA - 1995 Sep 01 SP - 90 EP - 96 VL - 10 IS - 1 SN - 1077-9450, 1077-9450 KW - Methadone KW - UC6VBE7V1Z KW - Index Medicus KW - AIDS/HIV KW - Sexual Behavior KW - Odds Ratio KW - Methadone -- therapeutic use KW - Patient Compliance KW - Needle Sharing KW - Humans KW - Cohort Studies KW - United States -- epidemiology KW - National Health Programs KW - Risk-Taking KW - Substance Abuse, Intravenous -- drug therapy KW - HIV Seroprevalence -- trends KW - Substance Abuse, Intravenous -- complications KW - HIV Infections -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77461392?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+acquired+immune+deficiency+syndromes+and+human+retrovirology+%3A+official+publication+of+the+International+Retrovirology+Association&rft.atitle=HIV+infection+and+AIDS+risk+behaviors+among+injecting+drug+users+entering+methadone+treatment%3A+an+update.&rft.au=Battjes%2C+R+J%3BPickens%2C+R+W%3BBrown%2C+L+S&rft.aulast=Battjes&rft.aufirst=R&rft.date=1995-09-01&rft.volume=10&rft.issue=1&rft.spage=90&rft.isbn=&rft.btitle=&rft.title=Journal+of+acquired+immune+deficiency+syndromes+and+human+retrovirology+%3A+official+publication+of+the+International+Retrovirology+Association&rft.issn=10779450&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-28 N1 - Date created - 1995-09-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of the excitoprotective actions of N-methyl-D-aspartate in cultured cerebellar granule neurons. AN - 77451954; 7643085 AB - Exposure of cultured cerebellar granule neurons to subtoxic concentrations of N-methyl-D-aspartate (NMDA) has been shown previously to result in a neuroprotective state, as measured by subsequent exposure to toxic concentrations of glutamate. In the present study, we have further characterized the excitoprotective actions of NMDA in these neurons. NMDA-induced excitoprotection was concentration dependent (EC50 approximately 30 microM) and time dependent, with maximal protection observed following 16 h of preexposure to NMDA. NMDA-induced excitoprotection did not require continuous exposure to NMDA, as a 4-h preincubation was sufficient to induce full excitoprotection when measured 8 h later. Maximal protection was manifest as a "right shift" in the concentration-response relationship for glutamate toxicity of approximately three orders of magnitude (EC50 approximately 30 microM in untreated neurons compared with > or = 50 mM in NMDA-treated neurons). After removal of NMDA, complete reversal of the excitoprotective state was observed by 48 h (t1/2 approximately 24 h). The ability of NMDA to induce excitoprotection was observed in neurons maintained for up to 14 days in vitro (DIV) [postnatal day (PND) 22], but was absent at 21 and 32 DIV (PND 29-40), despite little to no difference in the toxicity of glutamate at any DIV examined. Preexposure of cerebellar granule neurons to a maximally excitoprotective concentration of NMDA (50 microM) failed to alter the density of NMDA receptors measured by the specific binding of [3H]MK-801.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Journal of neurochemistry AU - Damschroder-Williams, P AU - Irwin, R P AU - Lin, S Z AU - Paul, S M AD - Section of Molecular Pharmacology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 1069 EP - 1076 VL - 65 IS - 3 SN - 0022-3042, 0022-3042 KW - Receptors, N-Methyl-D-Aspartate KW - 0 KW - Glutamic Acid KW - 3KX376GY7L KW - N-Methylaspartate KW - 6384-92-5 KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - Cycloheximide KW - 98600C0908 KW - Kainic Acid KW - SIV03811UC KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Rats KW - Calcium -- metabolism KW - Animals KW - Rats, Sprague-Dawley KW - Dizocilpine Maleate -- metabolism KW - Down-Regulation KW - Dose-Response Relationship, Drug KW - Cells, Cultured KW - Kinetics KW - Cycloheximide -- pharmacology KW - Receptors, N-Methyl-D-Aspartate -- metabolism KW - Time Factors KW - Kainic Acid -- toxicity KW - Glutamic Acid -- toxicity KW - N-Methylaspartate -- pharmacology KW - Neurons -- drug effects KW - Cerebellum -- drug effects KW - N-Methylaspartate -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77451954?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Characterization+of+the+excitoprotective+actions+of+N-methyl-D-aspartate+in+cultured+cerebellar+granule+neurons.&rft.au=Damschroder-Williams%2C+P%3BIrwin%2C+R+P%3BLin%2C+S+Z%3BPaul%2C+S+M&rft.aulast=Damschroder-Williams&rft.aufirst=P&rft.date=1995-09-01&rft.volume=65&rft.issue=3&rft.spage=1069&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 - 1995-09-18 N1 - Date created - 1995-09-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Endothelium-specific in vivo gene transfer. AN - 77444412; 7641320 AB - Targeted expression of genetic material within the vascular endothelium is potentially a powerful tool for the investigation of endothelial cell (EC) biology. We developed, optimized, and characterized an efficient somatic transgenic model of EC-specific gene transfer. Rat carotid arteries were infused with adenovirus expressing a beta-galactosidase (beta-gal) gene. The level and cell-type specificity of recombinant gene expression were measured by assaying beta-gal activity in vessel extracts and by counting transduced cells in histological sections. Toxicity was evaluated by counting total ECs (3 days) and by measuring neointimal formation (14 days). Effects of transduction on the proliferation of vascular cells were measured with bromodeoxyuridine and [3H]thymidine. Maximum recombinant gene expression resulted from infusion of 1 x 10(10) to 1 x 10(11) plaque-forming units (pfu) per milliliter; approximately 35% of luminal ECs were transduced. A high degree of EC specificity (90% to 98% of total transduced cells) was maintained over this range of virus concentrations. More highly concentrated virus resulted in loss of beta-gal expression and a large decrease in luminal EC number (97% decrease, P < .001). Gene transfer at 4 x 10(10) pfu/mL was efficient, preserved EC integrity, and caused minimal neointimal formation. After gene transfer, there were early (3-day) increases in both EC and smooth muscle cell proliferation. At 14 days, only EC proliferation remained elevated (18% versus 1.4% in vehicle-infused arteries, P = .005). This animal model permits efficient highly EC-specific gene transfer. Vascular toxicity is minimal, although the EC proliferative index is elevated. This model will be useful in experiments that elucidate the biological role of EC gene products and define pathways of EC gene regulation and signal transduction in vivo. JF - Circulation research AU - Schulick, A H AU - Dong, G AU - Newman, K D AU - Virmani, R AU - Dichek, D A AD - Molecular Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md, USA. Y1 - 1995/09// PY - 1995 DA - September 1995 SP - 475 EP - 485 VL - 77 IS - 3 SN - 0009-7330, 0009-7330 KW - Recombinant Proteins KW - 0 KW - Luciferases KW - EC 1.13.12.- KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Recombinant Proteins -- biosynthesis KW - Muscle, Smooth, Vascular -- cytology KW - Luciferases -- genetics KW - Lac Operon KW - Male KW - Cell Division KW - Adenoviridae -- genetics KW - Endothelium, Vascular -- metabolism KW - Gene Transfer Techniques KW - Endothelium, Vascular -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77444412?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Circulation+research&rft.atitle=Endothelium-specific+in+vivo+gene+transfer.&rft.au=Schulick%2C+A+H%3BDong%2C+G%3BNewman%2C+K+D%3BVirmani%2C+R%3BDichek%2C+D+A&rft.aulast=Schulick&rft.aufirst=A&rft.date=1995-09-01&rft.volume=77&rft.issue=3&rft.spage=475&rft.isbn=&rft.btitle=&rft.title=Circulation+research&rft.issn=00097330&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-21 N1 - Date created - 1995-09-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Disparate actions of hydroxyurea in potentiation of purine and pyrimidine 2',3'-dideoxynucleoside activities against replication of human immunodeficiency virus. AN - 77509943; 7667290 AB - We and other groups have recently reported the potentiation by ribonucleotide reductase inhibitors such as hydroxyurea of the anti-human immunodeficiency virus type 1 (HIV-1) activity of purine and pyrimidine 2',3'-dideoxynucleosides in both resting and phytohemagglutinin-stimulated peripheral blood mononuclear cells. Little agreement prevails, however, as to the mechanism of the synergistic effects described. We report here that in phytohemagglutinin-stimulated peripheral blood mononuclear cells, two mechanisms exist for the potentiation of the anti-HIV-1 activity by low-dose hydroxyurea of the purine-based dideoxynucleoside 2',3'-dideoxyinosine and the pyrimidine-based dideoxynucleosides 3'-azido-3'-deoxythymidine and 2',3'-dideoxycytidine. For 2',3'-dideoxyinosine, the enhancement arises from a specific depletion of dATP by hydroxyurea, resulting in a favorable shift of the 2',3'-dideoxyadenosine 5'-triphosphate/dATP ratio. For the pyrimidine dideoxynucleosides 3'-azido-3'-deoxythymidine and 2',3'-dideoxycytidine, the more modest anti-HIV enhancement results from hydroxyurea-induced increases of pyrimidine kinase activities in the salvage pathway and, hence, increased 5'-phosphorylation of these drugs, while depletion of the corresponding deoxynucleoside 5'-triphosphates (dTTP and dCTP) plays no significant role. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Gao, W Y AU - Johns, D G AU - Chokekuchai, S AU - Mitsuya, H AD - Experimental Retrovirology Section, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/08/29/ PY - 1995 DA - 1995 Aug 29 SP - 8333 EP - 8337 VL - 92 IS - 18 SN - 0027-8424, 0027-8424 KW - Zidovudine KW - 4B9XT59T7S KW - Zalcitabine KW - 6L3XT8CB3I KW - Adenosine Kinase KW - EC 2.7.1.20 KW - Uridine Kinase KW - EC 2.7.1.48 KW - Didanosine KW - K3GDH6OH08 KW - Hydroxyurea KW - X6Q56QN5QC KW - Index Medicus KW - AIDS/HIV KW - Adenosine Kinase -- metabolism KW - Phosphorylation KW - Virus Replication -- drug effects KW - Uridine Kinase -- metabolism KW - Cells, Cultured KW - Humans KW - Proviruses -- genetics KW - Drug Synergism KW - Proviruses -- drug effects KW - DNA Replication -- drug effects KW - Zalcitabine -- metabolism KW - HIV-1 -- genetics KW - Zidovudine -- metabolism KW - Zidovudine -- pharmacology KW - Zalcitabine -- pharmacology KW - Hydroxyurea -- pharmacology KW - HIV-1 -- physiology KW - HIV-1 -- drug effects KW - Didanosine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77509943?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Disparate+actions+of+hydroxyurea+in+potentiation+of+purine+and+pyrimidine+2%27%2C3%27-dideoxynucleoside+activities+against+replication+of+human+immunodeficiency+virus.&rft.au=Gao%2C+W+Y%3BJohns%2C+D+G%3BChokekuchai%2C+S%3BMitsuya%2C+H&rft.aulast=Gao&rft.aufirst=W&rft.date=1995-08-29&rft.volume=92&rft.issue=18&rft.spage=8333&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 - 1995-10-12 N1 - Date created - 1995-10-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell Tissue Kinet. 1971 Jul;4(4):297-305 [5316024] Anal Biochem. 1994 Oct;222(1):116-22 [7856836] J Biol Chem. 1976 Jul 10;251(13):4055-61 [932021] J Biol Chem. 1980 Jul 25;255(14):6640-5 [6248528] Pharmacol Ther. 1984;26(2):191-207 [6398448] J Biol Chem. 1986 Dec 5;261(34):16037-42 [3536919] J Biol Chem. 1987 Jan 25;262(3):988-91 [2433280] Biochem Pharmacol. 1987 Nov 1;36(21):3757-61 [3314871] J Biol Chem. 1988 Jun 15;263(17):8350-8 [3372530] Virus Genes. 1989 May;2(3):241-51 [2474897] Mol Pharmacol. 1989 Aug;36(2):291-5 [2549385] Anal Biochem. 1989 Aug 1;180(2):222-6 [2554751] Eur J Biochem. 1989 Dec 22;186(3):689-94 [2606113] Cell. 1990 Apr 20;61(2):213-22 [2331748] J Clin Invest. 1993 May;91(5):2326-33 [8387546] Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6405-9 [8341646] Drug Metab Dispos. 1993 Jul-Aug;21(4):738-44 [7690699] Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):8925-8 [7692440] Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8403-7 [8078894] Adv Enzyme Regul. 1994;34:13-25 [7942271] Mol Pharmacol. 1994 Oct;46(4):767-72 [7969058] Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11017-21 [7972000] Science. 1994 Nov 4;266(5186):801-5 [7973634] Nature. 1995 Jan 12;373(6510):123-6 [7816094] Science. 1995 Jan 27;267(5197):483-9 [7824947] J Biol Chem. 1976 May 10;251(9):2600-4 [1063125] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Suppression of oro-facial movements by rolipram, a cAMP phosphodiesterase inhibitor, in rats chronically treated with haloperidol. AN - 77651907; 7498291 AB - We investigated the effects of rolipram, a selective cyclic adenosine 3',5'-monophosphate phosphodiesterase type IV inhibitor, and isobutylmethylxanthine, a nonselective phosphodiesterase inhibitor, on purposeless spontaneous chewing movements and tongue protrusions produced by 24 weeks treatment with haloperidol decanoate (25 mg/kg every 4 weeks i.m.) in rats, to examine our hypothesis that restoration of striatal cyclic adenosine 3',5'-monophosphate levels previously reduced due to dopamine D2 receptor supersensitivity, may suppress these movements. Tests were performed 8 weeks after the final injection. Haloperidol treatment significantly increased dyskinetic movements and striatal dopamine D2 receptor density compared with controls. Rolipram (0.1-1.0 mg/kg i.p.) suppressed these movements in a dose-dependent manner, whereas isobutylmethylxanthine (2 mg/kg i.p.) only slightly suppressed the syndrome and doses higher than 5 mg/kg i.p. produced other intensive movements. These results support our hypothesis and suggest that rolipram may have a therapeutic effect on tardive dyskinesia. JF - European journal of pharmacology AU - Sasaki, H AU - Hashimoto, K AU - Inada, T AU - Fukui, S AU - Iyo, M AD - Division of Drug Dependence and Psychotropic Drug Clinical Research, National Institute of Mental Health, National Center of Neurology and Psychiatry, Chiba, Japan. Y1 - 1995/08/25/ PY - 1995 DA - 1995 Aug 25 SP - 71 EP - 76 VL - 282 IS - 1-3 SN - 0014-2999, 0014-2999 KW - Antipsychotic Agents KW - 0 KW - Dopamine Antagonists KW - Enzyme Inhibitors KW - Phosphodiesterase Inhibitors KW - Pyrrolidinones KW - 3',5'-Cyclic-AMP Phosphodiesterases KW - EC 3.1.4.17 KW - Haloperidol KW - J6292F8L3D KW - Rolipram KW - K676NL63N7 KW - 1-Methyl-3-isobutylxanthine KW - TBT296U68M KW - Index Medicus KW - Rats KW - Phosphodiesterase Inhibitors -- pharmacology KW - Animals KW - Rats, Sprague-Dawley KW - Dyskinesia, Drug-Induced -- drug therapy KW - 1-Methyl-3-isobutylxanthine -- pharmacology KW - Male KW - Depression, Chemical KW - Haloperidol -- antagonists & inhibitors KW - Dopamine Antagonists -- pharmacology KW - Antipsychotic Agents -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - 3',5'-Cyclic-AMP Phosphodiesterases -- antagonists & inhibitors KW - Pyrrolidinones -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77651907?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Suppression+of+oro-facial+movements+by+rolipram%2C+a+cAMP+phosphodiesterase+inhibitor%2C+in+rats+chronically+treated+with+haloperidol.&rft.au=Sasaki%2C+H%3BHashimoto%2C+K%3BInada%2C+T%3BFukui%2C+S%3BIyo%2C+M&rft.aulast=Sasaki&rft.aufirst=H&rft.date=1995-08-25&rft.volume=282&rft.issue=1-3&rft.spage=71&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 - 1996-01-18 N1 - Date created - 1996-01-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evidence for alterations in presynaptic serotonergic function during withdrawal from chronic cocaine in rats. AN - 77646465; 7498293 AB - The effects of repeated cocaine administration on serotonin (5-hydroxytryptamine, 5-HT) function were investigated by comparing the corticosterone response to 5-HT receptor agonists in cocaine-treated and vehicle-treated rats. Male rats were fitted with indwelling jugular catheters and received cocaine (15 mg/kg i.p., b.i.d.) or saline for 7 days. Rats were challenged with either saline, the 5-HT releaser fenfluramine (1.2 mg/kg i.v.), the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 50 micrograms/kg i.v.), or the 5-HT2A/2C receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI; 100 micrograms/kg i.v.) 42 h and 8 days after the final chronic treatment. Repeated blood samples were withdrawn immediately before and at 15, 30 and 60 min after acute challenge injections. All 5-HT receptor agonists increased plasma corticosterone, but the fenfluramine-induced rise in corticosterone was significantly attenuated in cocaine-treated rats withdrawn for 42 h. This blunted response to fenfluramine exhibited only partial recovery when examined at 8 days postchronic treatment. Corticosterone responses to 8-OH-DPAT and DOI were not affected by cocaine exposure. Our data suggest that chronic cocaine produces deficits in presynaptic 5-HT function, and alterations in 5-HT neurotransmission may underlie the dysphoria experienced by abstinent cocaine users. Neuroendocrine challenge tests should be performed in human addicts to evaluate potential 5-HT dysfunction associated with cocaine abuse. JF - European journal of pharmacology AU - Baumann, M H AU - Becketts, K M AU - Rothman, R B AD - Clinical Psychopharmacology Section, National Institutes of Health, National Institutes on Drug Abuse Intramural Research Program, Baltimore, MD 21224, USA. Y1 - 1995/08/25/ PY - 1995 DA - 1995 Aug 25 SP - 87 EP - 93 VL - 282 IS - 1-3 SN - 0014-2999, 0014-2999 KW - Amphetamines KW - 0 KW - Serotonin Agents KW - Fenfluramine KW - 2DS058H2CF KW - Serotonin KW - 333DO1RDJY KW - 8-Hydroxy-2-(di-n-propylamino)tetralin KW - 78950-78-4 KW - Cocaine KW - I5Y540LHVR KW - 4-iodo-2,5-dimethoxyphenylisopropylamine KW - OOM10GW9UE KW - Corticosterone KW - W980KJ009P KW - Index Medicus KW - Rats KW - Corticosterone -- secretion KW - Animals KW - Rats, Sprague-Dawley KW - Amphetamines -- pharmacology KW - 8-Hydroxy-2-(di-n-propylamino)tetralin -- pharmacology KW - Serotonin Agents -- pharmacology KW - Humans KW - Fenfluramine -- pharmacology KW - Male KW - Presynaptic Terminals -- drug effects KW - Substance Withdrawal Syndrome KW - Serotonin -- physiology KW - Neurosecretory Systems -- physiology KW - Cocaine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77646465?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Evidence+for+alterations+in+presynaptic+serotonergic+function+during+withdrawal+from+chronic+cocaine+in+rats.&rft.au=Baumann%2C+M+H%3BBecketts%2C+K+M%3BRothman%2C+R+B&rft.aulast=Baumann&rft.aufirst=M&rft.date=1995-08-25&rft.volume=282&rft.issue=1-3&rft.spage=87&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 - 1996-01-18 N1 - Date created - 1996-01-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Long-term antidepressant treatments alter 5-HT2A and 5-HT2C receptor-mediated hyperthermia in Fawn-Hooded rats. AN - 77645388; 7498290 AB - We have recently demonstrated that hyperthermia induced by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and m-chlorophenylpiperazine (m-CPP) are separately mediated by selective stimulation of 5-HT2A and 5-HT2C receptors, respectively in Wistar rats. Furthermore, hyperthermia induced by either DOI or m-CPP was found to be significantly less in Fawn-Hooded rats (a rat strain suggested to represent a genetic model of depression) relative to Wistar rats. In the present study, we studied the effects of long-term antidepressant treatments on DOI (2.5 mg/kg)-induced and m-CPP (2.5 mg/kg)-induced hyperthermia in male Fawn-Hooded rats. Long-term (21 days) treatment with the tricyclic antidepressants, imipramine or clomipramine (each 5 mg/kg/day), attenuated DOI-induced hyperthermia, while m-CPP-induced hyperthermia was accentuated. On the other hand, long-term (21 days) treatment with the monoamine oxidase type-A inhibiting antidepressant, clorgyline (1 mg/kg/day), did not modify m-CPP-induced hyperthermia, but significantly attenuated DOI-induced hyperthermia. These findings demonstrate that long-term antidepressant treatments alter 5-HT2A and 5-HT2C receptor-mediated hyperthermia in a genetic animal model of depression. JF - European journal of pharmacology AU - Aulakh, C S AU - Mazzola-Pomietto, P AU - Murphy, D L AD - Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD 20892-1264, USA. Y1 - 1995/08/25/ PY - 1995 DA - 1995 Aug 25 SP - 65 EP - 70 VL - 282 IS - 1-3 SN - 0014-2999, 0014-2999 KW - Amphetamines KW - 0 KW - Antidepressive Agents KW - Piperazines KW - Serotonin Receptor Agonists KW - 4-iodo-2,5-dimethoxyphenylisopropylamine KW - OOM10GW9UE KW - 1-(3-chlorophenyl)piperazine KW - REY0CNO998 KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Animals KW - Adaptation, Physiological -- drug effects KW - Models, Genetic KW - Time Factors KW - Male KW - Serotonin Receptor Agonists -- pharmacology KW - Body Temperature Regulation -- drug effects KW - Antidepressive Agents -- pharmacology KW - Amphetamines -- pharmacology KW - Piperazines -- pharmacology KW - Alcoholism -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77645388?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Long-term+antidepressant+treatments+alter+5-HT2A+and+5-HT2C+receptor-mediated+hyperthermia+in+Fawn-Hooded+rats.&rft.au=Aulakh%2C+C+S%3BMazzola-Pomietto%2C+P%3BMurphy%2C+D+L&rft.aulast=Aulakh&rft.aufirst=C&rft.date=1995-08-25&rft.volume=282&rft.issue=1-3&rft.spage=65&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 - 1996-01-18 N1 - Date created - 1996-01-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutations in the ras proto-oncogene: clues to etiology and molecular pathogenesis of mouse liver tumors. AN - 77523877; 7676462 AB - The mouse liver is a frequent target organ for chemical carcinogenesis (Huff et al., 1988, 1991; Gold et al., 1989) and tumor development exhibits preferential strain sensitivity (Dragani et al., 1992; Drinkwater and Bennett, 1991). In some reports a positive correlation has been observed between the degree of spontaneous liver tumor incidence and the propensity to develop liver tumors after treatment with chemical carcinogens (Della Porta et al., 1967; Flaks, 1968; Dragani et al., 1984, 1987; Diwan et al., 1986; Drinkwater and Ginsler, 1986), but this is not always the case (Grasso and Hardy, 1975; Hanigan et al., 1988; Dragani et al., 1992). Thus, the interpretation of this endpoint in assessing potential health hazards to humans continues to be the subject of active debate. Studies of molecular and genetic factors that modulate the genesis of mouse liver tumors should enhance our understanding of the relevance of this response following exposure to genotoxic as well as nongenotoxic chemicals. To utilize intelligently animal models as surrogates for human carcinogenesis, the validity of rodent tumor endpoints in assessing potential human health hazards from chemical exposure remains an important issue. One approach has been to understand the animal system itself and the mechanisms by which chemicals induce tumors in the animal model. Information regarding the molecular events associated with tumor induction should make the relevance of results from rodent carcinogenicity studies to human risk easier to assess. Results to date have identified activation of ras proto-oncogenes as one early event and an important factor associated with chemical induction of mouse liver neoplasia (Reynolds et al., 1986, 1987; Wiseman et al., 1986), although ras-independent pathways appear to account for an appreciable proportion of some chemically induced mouse liver tumors (Fox et al., 1990; Buchmann et al., 1991). Available data emphasize the complexity of H-ras activation in murine hepatocarcinogenesis. Not only the genetic background of the mouse but also the dose of the carcinogen may influence significantly the number of tumors containing activated H-ras. Both high sensitivity and low sensitivity strains of mice can develop liver tumors which contain activated H-ras oncogenes, showing that the ability to activate this gene does not in itself determine susceptibility to hepatocarcinogenesis. Ras gene mutational profiles in chemically induced liver tumors may be different and distinguishable from those in spontaneous tumors. Since multiple genetic as well as nongenetic events are associated with tumor development, defining a precise role for ras gene mutations when they occur in mouse liver tumors is often difficult.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Toxicology AU - Maronpot, R R AU - Fox, T AU - Malarkey, D E AU - Goldsworthy, T L AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/08/25/ PY - 1995 DA - 1995 Aug 25 SP - 125 EP - 156 VL - 101 IS - 3 SN - 0300-483X, 0300-483X KW - Carcinogens KW - 0 KW - Codon KW - Index Medicus KW - Animals KW - Mice KW - Gene Expression Regulation -- drug effects KW - Species Specificity KW - Mutation KW - Liver Neoplasms, Experimental -- genetics KW - Genes, ras -- genetics KW - Liver Neoplasms, Experimental -- pathology KW - Genes, ras -- drug effects KW - Carcinogens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77523877?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=Mutations+in+the+ras+proto-oncogene%3A+clues+to+etiology+and+molecular+pathogenesis+of+mouse+liver+tumors.&rft.au=Maronpot%2C+R+R%3BFox%2C+T%3BMalarkey%2C+D+E%3BGoldsworthy%2C+T+L&rft.aulast=Maronpot&rft.aufirst=R&rft.date=1995-08-25&rft.volume=101&rft.issue=3&rft.spage=125&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-17 N1 - Date created - 1995-10-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of the effector-specifying domain of Rac involved in NADPH oxidase activation. AN - 77474736; 7649999 AB - Production of microbicidal oxidants by phagocytic leukocytes requires activation of a latent NADPH oxidase by the coordinated assembly of a membrane-associated flavocytochrome b558, with three cytosolic components, p47phox, p67phox, and the low molecular weight GTP-binding protein Rac. Rac1 and Rac2 have 92% sequence identity and are both active in supporting the oxidase, while CDC42Hs, the closest relative to Rac with 70% sequence identity, only weakly supports oxidase activation in vitro. We have used CDC42Hs as a foil to identify residues in Rac that are critical for oxidase activation. Most of the divergent sequences of CDC42Hs could be incorporated into Rac-CDC42Hs chimeric proteins without affecting cell-free NADPH oxidase activity. However, incorporation of the amino-terminal segment of CDC42Hs (residues 1-40), which differs from Rac1 by only four residues (positions 3, 27, 30, and 33), resulted in a marked loss of oxidase activation capacity. Point mutagenesis studies showed that this was due to changes at residues 27 and 30, but not residues 3 and 33. Conversely, incorporation of the amino terminus of Rac1 (residues 1-40) into CDC42Hs increased its activity to that of Rac1, indicating that this terminus contains the effector-specifying domain of Rac. Taken together, these studies show that the difference in the activity between CDC42Hs and Rac1 is due entirely to differences in amino acids at position 27 and 30. JF - The Journal of biological chemistry AU - Kwong, C H AU - Adams, A G AU - Leto, T L AD - Laboratory of Host Defenses, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/08/25/ PY - 1995 DA - 1995 Aug 25 SP - 19868 EP - 19872 VL - 270 IS - 34 SN - 0021-9258, 0021-9258 KW - Cell Cycle Proteins KW - 0 KW - Recombinant Fusion Proteins KW - NADH, NADPH Oxidoreductases KW - EC 1.6.- KW - NADPH Oxidase KW - EC 1.6.3.1 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - cdc42 GTP-Binding Protein KW - EC 3.6.5.2 KW - rac GTP-Binding Proteins KW - Index Medicus KW - Animals KW - Enzyme Activation KW - Humans KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Binding Sites KW - Cell Cycle Proteins -- metabolism KW - Recombinant Fusion Proteins -- metabolism KW - Oxidation-Reduction KW - Neutrophils -- metabolism KW - Cell Cycle Proteins -- genetics KW - In Vitro Techniques KW - Recombinant Fusion Proteins -- genetics KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Mutation KW - GTP-Binding Proteins -- metabolism KW - NADH, NADPH Oxidoreductases -- metabolism KW - GTP-Binding Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77474736?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Characterization+of+the+effector-specifying+domain+of+Rac+involved+in+NADPH+oxidase+activation.&rft.au=Kwong%2C+C+H%3BAdams%2C+A+G%3BLeto%2C+T+L&rft.aulast=Kwong&rft.aufirst=C&rft.date=1995-08-25&rft.volume=270&rft.issue=34&rft.spage=19868&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 - 1995-09-28 N1 - Date created - 1995-09-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of dietary Aroclor 1254 exposure on lung and kidney cytochromes P450 in female rats: evidence for P4501A2 expression in kidney. AN - 77504482; 7671339 AB - In this report, we have investigated the effect of dietary exposure to Aroclor 1254 (1-100 ppm) given chronically or discontinuously over an 84-day time interval to the female F344 rat. Cytochrome P4501A was quantified in lung and kidney by measuring the dealkylation of ethoxyresorufin substrate and by Western immunoblotting. P4501A displayed a dose- and time-dependent increase in both extrahepatic organs. The kidney appeared to be more responsive to induction than lung at all doses (maximum of 500-fold induction following 84 days exposure to 100 ppm). Further, there was evidence by enzymatic activity, immunoblotting and Northern analysis of total RNA for the presence of 1A2 in the most highly induced kidneys. The decline in 1A induction observed following discontinuous exposure was more prominent in the kidney than in the lung. These data demonstrate the sensitivity of kidney to P4501A induction capacity as compared to lung, although the persistence of the induction response was evident in lung and not kidney. JF - Chemico-biological interactions AU - Beebe, L E AU - Fornwald, L W AU - Alworth, W L AU - Dragnev, K H AU - Lubet, R A AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702, USA. Y1 - 1995/08/18/ PY - 1995 DA - 1995 Aug 18 SP - 215 EP - 227 VL - 97 IS - 3 SN - 0009-2797, 0009-2797 KW - Aroclors KW - 0 KW - Carcinogens KW - Naphthalenes KW - Chlorodiphenyl (54% Chlorine) KW - 11097-69-1 KW - 2-ethynylnaphthalene KW - 2949-26-0 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Polychlorinated Biphenyls KW - DFC2HB4I0K KW - Oxidoreductases KW - EC 1.- KW - methoxyresorufin-O-demethylase KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - Cytochrome P-450 CYP1A2 KW - Index Medicus KW - Naphthalenes -- pharmacology KW - Animals KW - Blotting, Northern KW - Polychlorinated Biphenyls -- toxicity KW - Microsomes -- enzymology KW - Polychlorinated Biphenyls -- administration & dosage KW - Rats KW - Rats, Inbred F344 KW - Base Sequence KW - Blotting, Western KW - Molecular Sequence Data KW - Enzyme Induction KW - Diet KW - Female KW - Oxidoreductases -- genetics KW - Carcinogens -- administration & dosage KW - Cytochrome P-450 Enzyme System -- genetics KW - Lung -- drug effects KW - Kidney -- enzymology KW - Kidney -- drug effects KW - Carcinogens -- toxicity KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Aroclors -- toxicity KW - Lung -- enzymology KW - Oxidoreductases -- biosynthesis KW - Aroclors -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77504482?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemico-biological+interactions&rft.atitle=Effect+of+dietary+Aroclor+1254+exposure+on+lung+and+kidney+cytochromes+P450+in+female+rats%3A+evidence+for+P4501A2+expression+in+kidney.&rft.au=Beebe%2C+L+E%3BFornwald%2C+L+W%3BAlworth%2C+W+L%3BDragnev%2C+K+H%3BLubet%2C+R+A&rft.aulast=Beebe&rft.aufirst=L&rft.date=1995-08-18&rft.volume=97&rft.issue=3&rft.spage=215&rft.isbn=&rft.btitle=&rft.title=Chemico-biological+interactions&rft.issn=00092797&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-13 N1 - Date created - 1995-10-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protein kinase C epsilon subcellular localization domains and proteolytic degradation sites. A model for protein kinase C conformational changes. AN - 77447967; 7642654 AB - Protein kinase C (PCK) epsilon has been found to have unique properties among the PCK isozymes in terms of its membrane association, oncogenic potential, and substrate specificity. Recently we have demonstrated that PKC epsilon localizes to the Golgi network via its zinc finger domain and that both the holoenzyme and its zinc finger region modulate Golgi function. To further characterize the relationship between the domain organization and the subcellular localization of PKC epsilon, a series of NIH 3T3 cell lines were created, each overexpressing a different truncated version of PKC epsilon. The overexpressed proteins each were designed to contain an epsilon-epitope tag peptide at the COOH terminus to allow ready detection with an antibody specific for the tag. The subcellular localization of the recombinant proteins was analyzed by in vivo phorbol ester binding, immunocytochemistry, and cell fractionation followed by immunoblotting. Results revealed several regions of PKC epsilon that contain putative subcellular localization signals. The presence either of the hinge region or of a 33-amino-acid region including the pseudosubstrate sequence in the recombinant proteins resulted in association with the plasma membrane and cytoskeletal components. The catalytic domain was found predominantly in the cytosolic fraction. The accessibility and thus the dominance of these localization signals is likely to be affected by the overall conformation of the recombinant proteins. Regions with putative proteolytic degradation sites also were identified. The susceptibility of the overexpressed proteins to proteolytic degradation was dependent on the protein conformation. Based on these observations, a model depicting the interaction and hierarchy of the suspected localization signals and proteolytic degradation sites is presented. JF - The Journal of biological chemistry AU - Lehel, C AU - Oláh, Z AU - Jakab, G AU - Szállási, Z AU - Petrovics, G AU - Harta, G AU - Blumberg, P M AU - Anderson, W B AD - Laboratory of Cellular Oncolgy, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/08/18/ PY - 1995 DA - 1995 Aug 18 SP - 19651 EP - 19658 VL - 270 IS - 33 SN - 0021-9258, 0021-9258 KW - Isoenzymes KW - 0 KW - Oligodeoxyribonucleotides KW - Recombinant Proteins KW - Prkce protein, mouse KW - EC 2.7.1.- KW - Protein Kinase C KW - EC 2.7.11.13 KW - Protein Kinase C-epsilon KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Biological Transport KW - Mice KW - Hydrolysis KW - Base Sequence KW - Blotting, Western KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Recombinant Proteins -- chemistry KW - Immunohistochemistry KW - Mutation KW - Protein Conformation KW - Protein Kinase C -- metabolism KW - Isoenzymes -- chemistry KW - Protein Kinase C -- chemistry KW - Subcellular Fractions -- enzymology KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77447967?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Protein+kinase+C+epsilon+subcellular+localization+domains+and+proteolytic+degradation+sites.+A+model+for+protein+kinase+C+conformational+changes.&rft.au=Lehel%2C+C%3BOl%C3%A1h%2C+Z%3BJakab%2C+G%3BSz%C3%A1ll%C3%A1si%2C+Z%3BPetrovics%2C+G%3BHarta%2C+G%3BBlumberg%2C+P+M%3BAnderson%2C+W+B&rft.aulast=Lehel&rft.aufirst=C&rft.date=1995-08-18&rft.volume=270&rft.issue=33&rft.spage=19651&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 - 1995-09-18 N1 - Date created - 1995-09-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reduced frameshift fidelity and processivity of HIV-1 reverse transcriptase mutants containing alanine substitutions in helix H of the thumb subdomain. AN - 77444931; 7543900 AB - We have analyzed two human immunodeficiency virus (HIV-1) reverse transcriptase mutants of helix H in the thumb subdomain suggested by x-ray crystallography to interact with the primer strand of the template-primer. These enzymes, G262A and W266A, were previously shown to have greatly elevated dissociation rate constants for template-primer and to be much less sensitive to inhibition by 3'-azidodeoxythymidine 5'-triphosphate. Here we describe their processivity and error specificity. The results reveal that: (i) both enzymes have reduced processivity and lower fidelity for template-primer slippage errors, (ii) they differ from each other in sequence-dependent termination of processive synthesis and in error specificity, and (iii) the magnitude of the mutator effect relative to wild-type enzyme for deletions in homopolymeric sequences decreases as the length of the run increases. Thus amino acid substitutions in a subdomain thought to interact with the duplex template-primer confer a strand slippage mutator phenotype to a replicative DNA polymerase. This suggests that interactions between specific amino acids and the primer stem at positions well removed from the active site are critical determinants of processivity and fidelity. These effects, obtained in aqueous solution during catalytic cycling, are consistent with and support the existing crystallographic structural model. JF - The Journal of biological chemistry AU - Bebenek, K AU - Beard, W A AU - Casas-Finet, J R AU - Kim, H R AU - Darden, T A AU - Wilson, S H AU - Kunkel, T A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/08/18/ PY - 1995 DA - 1995 Aug 18 SP - 19516 EP - 19523 VL - 270 IS - 33 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - RNA-Directed DNA Polymerase KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - AIDS/HIV KW - Protein Structure, Secondary KW - Spectrometry, Fluorescence KW - Circular Dichroism KW - Templates, Genetic KW - Protein Structure, Tertiary KW - Mutagenesis KW - Frameshift Mutation KW - Alanine -- metabolism KW - RNA-Directed DNA Polymerase -- chemistry KW - Protein Processing, Post-Translational KW - Alanine -- genetics KW - HIV-1 -- enzymology KW - RNA-Directed DNA Polymerase -- metabolism KW - RNA-Directed DNA Polymerase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77444931?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Reduced+frameshift+fidelity+and+processivity+of+HIV-1+reverse+transcriptase+mutants+containing+alanine+substitutions+in+helix+H+of+the+thumb+subdomain.&rft.au=Bebenek%2C+K%3BBeard%2C+W+A%3BCasas-Finet%2C+J+R%3BKim%2C+H+R%3BDarden%2C+T+A%3BWilson%2C+S+H%3BKunkel%2C+T+A&rft.aulast=Bebenek&rft.aufirst=K&rft.date=1995-08-18&rft.volume=270&rft.issue=33&rft.spage=19516&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 - 1995-09-18 N1 - Date created - 1995-09-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rotenone, an anticarcinogen, inhibits cellular proliferation but not peroxisome proliferation in mouse liver. AN - 77495300; 7656250 AB - In previous National Toxicology Program (NTP) studies, rotenone reduced the background incidence of hepatocellular carcinoma in male B6C3F1 mice. In the present studies, rotenone reduced the basal hepatic labeling index of male B6C3F1 mice in a dose-dependent fashion and inhibited hepatocellular proliferation, but not peroxisome proliferation, induced by the peroxisome proliferator Wy-14,643. These results indicate that reduction of hepatic tumors by rotenone may have been due to decreased liver cell replication, that peroxisome proliferation can be induced in the absence of hepatocellular proliferation and suggest rotenone as a potential tool in studies of relationships of cell proliferation, peroxisomal proliferation and hepatocarcinogenesis. JF - Cancer letters AU - Cunningham, M L AU - Soliman, M S AU - Badr, M Z AU - Matthews, H B AD - Chemistry Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/08/16/ PY - 1995 DA - 1995 Aug 16 SP - 93 EP - 97 VL - 95 IS - 1-2 SN - 0304-3835, 0304-3835 KW - Anticarcinogenic Agents KW - 0 KW - Growth Inhibitors KW - Rotenone KW - 03L9OT429T KW - Catalase KW - EC 1.11.1.6 KW - Index Medicus KW - Oxidation-Reduction KW - Catalase -- metabolism KW - Animals KW - Dose-Response Relationship, Drug KW - Liver Neoplasms -- chemically induced KW - Liver -- metabolism KW - Mice KW - Male KW - Cell Division -- drug effects KW - Microbodies -- drug effects KW - Rotenone -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77495300?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=Rotenone%2C+an+anticarcinogen%2C+inhibits+cellular+proliferation+but+not+peroxisome+proliferation+in+mouse+liver.&rft.au=Cunningham%2C+M+L%3BSoliman%2C+M+S%3BBadr%2C+M+Z%3BMatthews%2C+H+B&rft.aulast=Cunningham&rft.aufirst=M&rft.date=1995-08-16&rft.volume=95&rft.issue=1-2&rft.spage=93&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-04 N1 - Date created - 1995-10-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High dietary retinoic acid inhibits tumor promotion and malignant conversion in a two-stage skin carcinogenesis protocol using 7,12-dimethylbenz[a]anthracene as the initiator and mezerein as the tumor promoter in female SENCAR mice. AN - 77488794; 7656218 AB - We studied the effect of dietary retinoic acid (RA) in a two-stage protocol of skin carcinogenesis in female SENCAR mice. At 3 weeks of age mice were initiated with 7,12-dimethylbenz[a]anthracene (DMBA, 20 micrograms) and promoted with either 12-O-tetradecanoylphorbol-13-acetate (TPA, 2 micrograms) once per week or mezerein (MEZ, 4 micrograms) twice per week for 20 weeks. At the week of DMBA initiation mice were also put on a purified diet containing either 3 (physiological dose) or 30 micrograms (pharmacological dose) of RA/g of diet. High dietary RA significantly inhibited papilloma yield but not incidence in the MEZ-promoted group. Papilloma incidence and yield were also lower in the MEZ- than in the TPA-treated groups. Cumulative carcinoma incidence and yield, and conversion efficiency (= (carcinomas/maximal papillomas) x 100%), were all decreased by high dietary RA in both MEZ- and TPA-treated groups. These results demonstrate that high dietary RA inhibited skin carcinogenesis in MEZ-promoted mice at the stages of tumor promotion and malignant conversion, while this inhibition occurred only at the malignant conversion stage in TPA-promoted mice. JF - Cancer letters AU - Chen, L C AU - Tarone, R AU - Huynh, M AU - De Luca, L M AD - Differentiation Control Section, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/08/16/ PY - 1995 DA - 1995 Aug 16 SP - 113 EP - 118 VL - 95 IS - 1-2 SN - 0304-3835, 0304-3835 KW - Carcinogens KW - 0 KW - Diterpenes KW - Terpenes KW - mezerein KW - 34807-41-5 KW - Tretinoin KW - 5688UTC01R KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Index Medicus KW - Animals KW - Mice KW - Mice, Inbred SENCAR KW - Diet KW - Female KW - Papilloma -- prevention & control KW - Skin Neoplasms -- chemically induced KW - Tretinoin -- administration & dosage KW - Carcinoma -- prevention & control KW - Skin Neoplasms -- prevention & control KW - Papilloma -- chemically induced KW - Carcinoma -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77488794?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=High+dietary+retinoic+acid+inhibits+tumor+promotion+and+malignant+conversion+in+a+two-stage+skin+carcinogenesis+protocol+using+7%2C12-dimethylbenz%5Ba%5Danthracene+as+the+initiator+and+mezerein+as+the+tumor+promoter+in+female+SENCAR+mice.&rft.au=Chen%2C+L+C%3BTarone%2C+R%3BHuynh%2C+M%3BDe+Luca%2C+L+M&rft.aulast=Chen&rft.aufirst=L&rft.date=1995-08-16&rft.volume=95&rft.issue=1-2&rft.spage=113&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-04 N1 - Date created - 1995-10-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Development and persistence of placental glutathione-S-transferase-positive foci in livers of male F344 rats exposed to o-nitrotoluene. AN - 77488769; 7656226 AB - In a previous 13-week study of o-nitrotoluene, a chemical-related increase in liver weight, hepatocellular vacuolization, and oval cell hyperplasia in male F344 rats was reported. In this study, the occurrence and change in number and size of hepatic foci in male F344 rats fed a diet containing 5000 ppm o-nitrotoluene or a control diet for 13 weeks, 26 weeks, and 13 weeks followed by a 13-week recovery period (26-week stop-exposure) were evaluated. The livers were stained immunohistochemically for placental glutathione S-transferase (PGST), a marker of hepatic preneoplasia, and quantified stereologically using computer-assisted image analysis. Exposure to o-nitrotoluene induced PGST-positive (PGST-positive (PGST+) liver foci in all treatment groups. The 26-week continuous-exposure group produced more PGST+ liver foci (961.4 foci/cm3 versus 445.4 foci/cm3) and greater mean focus volume (4.34 microns3 versus 1.34 microns3) than the 13-week continuous-exposure group. In the 26-week stop-exposure group, there were fewer PGST+ liver foci (181.4 foci/cm3) than observed with continuous exposure at 13 weeks or 26 weeks; however, the mean focal volume in the stop-exposure group at 26 weeks (5.33 microns3) was greater than that at 13 weeks (1.34 microns3) or 26 weeks of continuous exposure (4.34 microns3). These findings demonstrate that (1) PGST+ foci are observed after only 13 weeks of exposure to o-nitrotoluene; (2) the number and size of foci increase with continued exposure for 26 weeks; and (3) although the number of PGST+ foci decreases with time after chemical exposure is discontinued, many PGST+ foci do not regress but increase in size during the recovery of 13 weeks. The persistence and increase in size of these foci, even in the absence of chemical exposure, suggest the potential for a hepatocarcinogenic effect in long-term studies for o-nitrotoluene. JF - Cancer letters AU - Ton, T T AU - Elwell, M R AU - Morris, R W AU - Maronpot, R R AD - National Institute of Environmental Health Sciences, Laboratory of Experimental Pathology, Research Triangle Park, NC 27709, USA. Y1 - 1995/08/16/ PY - 1995 DA - 1995 Aug 16 SP - 167 EP - 173 VL - 95 IS - 1-2 SN - 0304-3835, 0304-3835 KW - PGST KW - Carcinogens KW - 0 KW - Isoenzymes KW - Toluene KW - 3FPU23BG52 KW - 2-nitrotoluene KW - 6Q9N88YIAY KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Placenta KW - Liver Neoplasms -- enzymology KW - Body Weight -- drug effects KW - Male KW - Isoenzymes -- metabolism KW - Organ Size -- drug effects KW - Toluene -- analogs & derivatives KW - Toluene -- pharmacology KW - Precancerous Conditions -- chemically induced KW - Glutathione Transferase -- metabolism KW - Liver Neoplasms, Experimental -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77488769?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=Development+and+persistence+of+placental+glutathione-S-transferase-positive+foci+in+livers+of+male+F344+rats+exposed+to+o-nitrotoluene.&rft.au=Ton%2C+T+T%3BElwell%2C+M+R%3BMorris%2C+R+W%3BMaronpot%2C+R+R&rft.aulast=Ton&rft.aufirst=T&rft.date=1995-08-16&rft.volume=95&rft.issue=1-2&rft.spage=167&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-04 N1 - Date created - 1995-10-04 N1 - Date revised - 2017-01-13 N1 - Gene symbol - PGST N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The use of polyethylene glycol-modified interleukin-2 (PEG-IL-2) in the treatment of patients with metastatic renal cell carcinoma and melanoma. A phase I study and a randomized prospective study comparing IL-2 alone versus IL-2 combined with PEG-IL-2. AN - 77836994; 8625167 AB - Conjugation of polyethylene glycol to recombinant human interleukin-2 (IL-2) results in a compound, polyethylene glycol-modified IL-2 (PEG-IL-2) that retains the in vitro and in vivo activity of IL-2, but exhibits a markedly prolonged circulating half-life. In mice, one dose of PEG-IL-2 results in tumor regression comparable to that achieved with multiple bolus doses of IL-2. Based on these preclinical studies, a Phase I study with PEG-IL-2 was undertaken in patients with metastatic renal cell carcinoma (RCC) and melanoma. Then, to exploit the higher peak levels attained with IL-2 and the improved trough levels of PEG-IL-2, a combination regimen beginning with bolus IL-2 followed by low dose maintenance PEG-IL-2 was devised and tested for efficacy. Patients with measurable metastatic melanoma or RCC were entered in a Phase I dose escalation trial of PEG-IL-2 given once a week by intravenous bolus. This trial then was repeated using a twice-a-week schedule. After determining the maximum tolerated dose (MTD) and a safe outpatient regimen for PEG-IL-2, a hybrid regimen combining an initial high dose IL-2 cycle followed by chronic maintenance with weekly PEG-IL-2 was devised. This regimen was compared with a standard regimen consisting of two cycles of high dose unconjugated IL-2 in a randomized prospective clinical trial. When given by intravenous bolus once a week, the MTD of PEG-IL-2 was 12 million IU/m2, with toxicities similar to those of unconjugated IL-2. A twice-a-week schedule was less well tolerated. Of 28 patients given 32 treatment courses at varied dose levels, there were two partial responses and one minor response. A total of 124 patients with metastatic melanoma or RCC were randomized to either standard unconjugated IL-2 therapy or the hybrid regimen. There was no treatment-related mortality in either arm, and the use of PEG-IL-2 resulted in a significant decrease in the need for intensive-care-unit care. The response rates (partial response and complete response) for patients with RCC and melanoma were 19% and 15%, respectively, for IL-2 alone and 17% and 11%, respectively, for the IL-2 and PEG-IL-2 combination. The combination of high dose IL-2 followed by PEG-IL-2 is a well tolerated regimen with significant activity against RCC and melanoma, but it shows no significant increase in antitumor activity compared with high dose IL-2 alone. JF - Cancer AU - Yang, J C AU - Topalian, S L AU - Schwartzentruber, D J AU - Parkinson, D R AU - Marincola, F M AU - Weber, J S AU - Seipp, C A AU - White, D E AU - Rosenberg, S A AD - Surgery Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/08/15/ PY - 1995 DA - 1995 Aug 15 SP - 687 EP - 694 VL - 76 IS - 4 SN - 0008-543X, 0008-543X KW - Interleukin-2 KW - 0 KW - interleukin-2, polyethylene glycol-modified KW - Polyethylene Glycols KW - 30IQX730WE KW - Abridged Index Medicus KW - Index Medicus KW - Prospective Studies KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Neoplasm Metastasis KW - Aged KW - Middle Aged KW - Male KW - Female KW - Kidney Neoplasms -- drug therapy KW - Interleukin-2 -- adverse effects KW - Interleukin-2 -- administration & dosage KW - Interleukin-2 -- analogs & derivatives KW - Melanoma -- drug therapy KW - Carcinoma, Renal Cell -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77836994?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer&rft.atitle=The+use+of+polyethylene+glycol-modified+interleukin-2+%28PEG-IL-2%29+in+the+treatment+of+patients+with+metastatic+renal+cell+carcinoma+and+melanoma.+A+phase+I+study+and+a+randomized+prospective+study+comparing+IL-2+alone+versus+IL-2+combined+with+PEG-IL-2.&rft.au=Yang%2C+J+C%3BTopalian%2C+S+L%3BSchwartzentruber%2C+D+J%3BParkinson%2C+D+R%3BMarincola%2C+F+M%3BWeber%2C+J+S%3BSeipp%2C+C+A%3BWhite%2C+D+E%3BRosenberg%2C+S+A&rft.aulast=Yang&rft.aufirst=J&rft.date=1995-08-15&rft.volume=76&rft.issue=4&rft.spage=687&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-26 N1 - Date created - 1996-06-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prefrontal cortical and hippocampal modulation of haloperidol-induced catalepsy and apomorphine-induced stereotypic behaviors in the rat. AN - 77623480; 8547448 AB - Effects of prefrontal cortical or hippocampal excitotoxic lesions on behavioral parameters related to dopaminergic transmission in the basal ganglia were investigated in the rat. We examined haloperidol-induced catalepsy and apomorphine-induced stereotypic behaviors after ibotenic acid lesions of the medial prefrontal cortex (MPFC), dorsal (DH), or ventral hippocampus (VH) in adult rats. Haloperidol-induced (1 mg/kg) catalepsy was decreased in rats with either MPFC or VH but not DH lesions. While both DH and VH lesioned animals demonstrated a reduction in apomorphine-induced (0.75 mg/kg) stereotypic behaviors, the VH lesioned animals also showed an enhancement of locomotor activity. MPFC lesioned rats tended towards potentiation of stereotypic behaviors and reduced locomotion after apomorphine administration. These data indicate that loss of prefrontal cortical or hippocampal modulation leads to an enhancement of DA transmission within the basal ganglia, though the pattern of augmentation depends on the area lesioned. JF - Biological psychiatry AU - Lipska, B K AU - Jaskiw, G E AU - Braun, A R AU - Weinberger, D R AD - National Institute of Mental Health, Clinical Brain Disorders Branch, Washington, DC, USA. Y1 - 1995/08/15/ PY - 1995 DA - 1995 Aug 15 SP - 255 EP - 262 VL - 38 IS - 4 SN - 0006-3223, 0006-3223 KW - Antiparkinson Agents KW - 0 KW - Antipsychotic Agents KW - Haloperidol KW - J6292F8L3D KW - Apomorphine KW - N21FAR7B4S KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Animals KW - Dopamine -- metabolism KW - Locomotion -- drug effects KW - Basal Ganglia -- drug effects KW - Male KW - Antiparkinson Agents -- adverse effects KW - Haloperidol -- adverse effects KW - Apomorphine -- adverse effects KW - Catalepsy -- chemically induced KW - Antipsychotic Agents -- pharmacology KW - Apomorphine -- pharmacology KW - Prefrontal Cortex -- physiopathology KW - Stereotyped Behavior -- drug effects KW - Prefrontal Cortex -- drug effects KW - Hippocampus -- drug effects KW - Rats, Sprague-Dawley KW - Haloperidol -- pharmacology KW - Hippocampus -- physiopathology KW - Antiparkinson Agents -- pharmacology KW - Antipsychotic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77623480?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Prefrontal+cortical+and+hippocampal+modulation+of+haloperidol-induced+catalepsy+and+apomorphine-induced+stereotypic+behaviors+in+the+rat.&rft.au=Lipska%2C+B+K%3BJaskiw%2C+G+E%3BBraun%2C+A+R%3BWeinberger%2C+D+R&rft.aulast=Lipska&rft.aufirst=B&rft.date=1995-08-15&rft.volume=38&rft.issue=4&rft.spage=255&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 - 1996-02-20 N1 - Date created - 1996-02-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of mdr-1 in refractory lymphoma: quantitation by polymerase chain reaction and validation of the assay. AN - 77431981; 7632959 AB - Measurement of P-glycoprotein and the gene that encodes it, mdr-1, is an important tool for assessing the impact of multidrug resistance in clinical cancer. We evaluated mdr-1 expression by a quantitative polymerase chain reaction (PCR) assay in 78 biopsy samples from 48 patients with refractory lymphoma enrolled on a trial of infusional chemotherapy (EPOCH) in which R-verapamil was added as an antagonist of P-glycoprotein in a subset of patients whose tumors were unresponsive to treatment. Expression of mdr-1 was detectable in all biopsies at the time of enrollment on study, and a fourfold or greater increase in mdr-1 expression was noted in 42% of patients at the time of treatment failure. Expression of mdr-1 was also detectable in biopsies from patients at the time of diagnosis of lymphoma. An endogenous control gene, beta 2-microglobulin, was quantitated for normalization of the mdr-1 values. The use of beta 2-microglobulin expression for normalization was validated in a subset of samples by comparing Northern blots detecting beta 2-microglobulin, beta actin, and GAPDH gene expression. Immunoblot analysis suggested that no major discrepancy was present between mRNA expression and protein level. Immunophenotyping of lymphomatous lymph nodes showed that infiltration of tumor cells ranged from 8% to 95% and of normal T cells from 1% to 83%. Expression of mdr-1 in normal T cells and monocytes was also shown to be low. The mdr-1 levels in patient samples were independent of T-cell contamination, suggesting that the presence of normal cells has at best a small impact on mdr-1 measurements. Expression of mdr-1 in lymphoma can be quantitated by PCR, and wide variations in expression can be observed. Increased expression in patients with refractory disease supports an important role for Pgp in drug resistance in lymphoma. These studies will aid in the design and interpretation of clinical trials in lymphoma. JF - Blood AU - Kang, Y K AU - Zhan, Z AU - Regis, J AU - Alvarez, M AU - Robey, R AU - Meadows, B AU - Dickstein, B AU - Lee, J S AU - Otsuki, T AU - Stetler-Stevenson, M AD - Medicine Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/08/15/ PY - 1995 DA - 1995 Aug 15 SP - 1515 EP - 1524 VL - 86 IS - 4 SN - 0006-4971, 0006-4971 KW - mdr-1 KW - P-Glycoprotein KW - 0 KW - RNA, Messenger KW - RNA, Neoplasm KW - beta 2-Microglobulin KW - Vincristine KW - 5J49Q6B70F KW - Etoposide KW - 6PLQ3CP4P3 KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Prednisone KW - VB0R961HZT KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - RNA, Neoplasm -- genetics KW - RNA, Messenger -- genetics KW - beta 2-Microglobulin -- genetics KW - Gene Expression Regulation, Neoplastic KW - Polymerase Chain Reaction KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Immunophenotyping KW - Time Factors KW - P-Glycoprotein -- genetics KW - Lymphoma -- drug therapy KW - Lymphoma -- immunology KW - Lymphoma -- metabolism KW - Drug Resistance, Multiple UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77431981?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Expression+of+mdr-1+in+refractory+lymphoma%3A+quantitation+by+polymerase+chain+reaction+and+validation+of+the+assay.&rft.au=Kang%2C+Y+K%3BZhan%2C+Z%3BRegis%2C+J%3BAlvarez%2C+M%3BRobey%2C+R%3BMeadows%2C+B%3BDickstein%2C+B%3BLee%2C+J+S%3BOtsuki%2C+T%3BStetler-Stevenson%2C+M&rft.aulast=Kang&rft.aufirst=Y&rft.date=1995-08-15&rft.volume=86&rft.issue=4&rft.spage=1515&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-14 N1 - Date created - 1995-09-14 N1 - Date revised - 2017-01-13 N1 - Gene symbol - mdr-1 N1 - SuppNotes - Erratum In: Blood 1995 Dec 15;86(12):4710 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - IL-10 synergizes with multiple cytokines in enhancing HIV production in cells of monocytic lineage. AN - 77426075; 7627621 AB - Several cytokines, whose expression is increased in human immunodeficiency virus (HIV)-infected individuals, can enhance virus replication in CD4+ T lymphocytes and mononuclear phagocytes (MP). We have previously reported that interleukin (IL)-10 inhibited HIV replication in acutely infected monocyte-derived macrophages (MDM) at concentrations that completely blocked the production of endogenous tumor necrosis factor-alpha (TNF-alpha) and IL-6 from infected cells. In the present study, lower concentrations of IL-10, which were unable to completely suppress endogenous cytokines, paradoxically enhanced HIV replication in MDM induced by other cytokines. This synergistic induction of HIV expression by IL-10 in combination with TNF-alpha, IL-6, and other cytokines was also observed in the chronically infected promonocytic cell line, U1. The enhancing effect of IL-10 was correlated with an increase in HIV mRNA accumulation and potentiation of phorbol ester-induced long terminal repeat-driven transcription that was independent of the NF-kappa B and Sp1 transcription factors. Thus, IL-10 is a cytokine capable of exerting complex regulatory effects on HIV expression in MP as a function of its own concentration and of the presence of other HIV regulatory cytokines. JF - Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association AU - Weissman, D AU - Poli, G AU - Fauci, A S AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/08/15/ PY - 1995 DA - 1995 Aug 15 SP - 442 EP - 449 VL - 9 IS - 5 SN - 1077-9450, 1077-9450 KW - Cytokines KW - 0 KW - Interleukin-6 KW - RNA, Messenger KW - Tumor Necrosis Factor-alpha KW - Interleukin-10 KW - 130068-27-8 KW - Index Medicus KW - AIDS/HIV KW - Lymphocyte Activation KW - Blotting, Northern KW - Cells, Cultured KW - Humans KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Cell Division -- drug effects KW - Transcriptional Activation -- drug effects KW - Interleukin-6 -- pharmacology KW - Drug Synergism KW - RNA, Messenger -- biosynthesis KW - Cell Line KW - HIV -- drug effects KW - HIV -- physiology KW - Cytokines -- pharmacology KW - Virus Replication -- drug effects KW - Interleukin-10 -- pharmacology KW - Monocytes -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77426075?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+acquired+immune+deficiency+syndromes+and+human+retrovirology+%3A+official+publication+of+the+International+Retrovirology+Association&rft.atitle=IL-10+synergizes+with+multiple+cytokines+in+enhancing+HIV+production+in+cells+of+monocytic+lineage.&rft.au=Weissman%2C+D%3BPoli%2C+G%3BFauci%2C+A+S&rft.aulast=Weissman&rft.aufirst=D&rft.date=1995-08-15&rft.volume=9&rft.issue=5&rft.spage=442&rft.isbn=&rft.btitle=&rft.title=Journal+of+acquired+immune+deficiency+syndromes+and+human+retrovirology+%3A+official+publication+of+the+International+Retrovirology+Association&rft.issn=10779450&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-05 N1 - Date created - 1995-09-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Apoptosis and altered redox state induced by caffeic acid phenethyl ester (CAPE) in transformed rat fibroblast cells. AN - 77422707; 7543016 AB - Caffeic acid phenethyl ester (CAPE), which is derived from the propolis of bee hives, was shown previously to block tumor promoter- and carcinogen-generated oxidative processes in several assays and to engender differential toxicity to some transformed cells. To study the mechanisms of CAPE-induced differential cytotoxicity, nontumorigenic rat embryo fibroblasts (CREF) and adenovirus (type 5)-transformed CREF cells (Wt3A) were used. As shown by nucleosomal-length DNA degradation, morphological alterations by electron microscopy, in situ labeling of 3'-OH ends, and the appearance of a hypodiploid cell population by bivariant flow cytometry, cell death induced by CAPE in the transformed Wt3A cells was apoptosis. Under the same CAPE treatment conditions, CREF cells transiently growth arrested. Both CREF and Wt3A cells were radioresistant, suggesting deficiencies in the proteins controlling the G1 checkpoint. To explore possible mechanisms of CAPE-induced apoptosis, it was determined whether CAPE-induced toxicity was influenced by the redox state of the cells. Depletion of cellular glutathione (GSH) with buthionine sulfoximine before CAPE treatment caused CREF sensitive to CAPE-induced cell death. GSH levels were also determined in CAPE-treated CREF and Wt3A cells. The GSH level in the CREF cells was unaffected by CAPE, whereas the Wt3A cells showed a significant reduction. When the GSH levels were increased in Wt3A cells by treatment with the reducing agent, N-acetyl-cysteine before CAPE treatment, the Wt3A cells were partially rescued. Furthermore, Bcl2, which protects cells from oxidative stress, had a protective effect against CAPE-induced apoptosis in Wt3A cells. Finally, the sensitivity of Wt3A cells to a known oxidant, hydrogen peroxide (H2O2), was examined. Wt3A cells were killed by H2O2-induced apoptosis, whereas CREF cells remained resistant. When Wt3A cells were treated with catalase, a cellular enzyme that inactivates H2O2, CAPE-induced apoptosis in Wt3A cells was reduced, further proving that Wt3A cells were more sensitive than CREF cells to oxidative stress. These results suggest that CAPE can modulate the redox state of cells. Sensitivity of cells to CAPE-induced cell death may be determined by the loss of normal redox state regulation in transformed cells. JF - Cancer research AU - Chiao, C AU - Carothers, A M AU - Grunberger, D AU - Solomon, G AU - Preston, G A AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/08/15/ PY - 1995 DA - 1995 Aug 15 SP - 3576 EP - 3583 VL - 55 IS - 16 SN - 0008-5472, 0008-5472 KW - Caffeic Acids KW - 0 KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Catalase KW - EC 1.11.1.6 KW - caffeic acid phenethyl ester KW - G960R9S5SK KW - Glutathione KW - GAN16C9B8O KW - Phenylethyl Alcohol KW - ML9LGA7468 KW - Acetylcysteine KW - WYQ7N0BPYC KW - Index Medicus KW - Rats KW - Oxidation-Reduction KW - Catalase -- metabolism KW - Animals KW - Rats, Inbred F344 KW - Glutathione -- metabolism KW - Hydrogen Peroxide -- pharmacology KW - Acetylcysteine -- pharmacology KW - Proto-Oncogene Proteins -- physiology KW - Cell Line KW - Cell Cycle -- drug effects KW - DNA Damage -- drug effects KW - Cell Transformation, Neoplastic -- pathology KW - Phenylethyl Alcohol -- pharmacology KW - Phenylethyl Alcohol -- analogs & derivatives KW - Caffeic Acids -- pharmacology KW - Apoptosis -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77422707?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Apoptosis+and+altered+redox+state+induced+by+caffeic+acid+phenethyl+ester+%28CAPE%29+in+transformed+rat+fibroblast+cells.&rft.au=Chiao%2C+C%3BCarothers%2C+A+M%3BGrunberger%2C+D%3BSolomon%2C+G%3BPreston%2C+G+A%3BBarrett%2C+J+C&rft.aulast=Chiao&rft.aufirst=C&rft.date=1995-08-15&rft.volume=55&rft.issue=16&rft.spage=3576&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 - 1995-09-07 N1 - Date created - 1995-09-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Polyadenylation polymorphism in the acetyltransferase 1 gene (NAT1) increases risk of colorectal cancer. AN - 77422327; 7627961 AB - Exposure to carcinogens present in the diet, cigarette smoke, or the environment may be associated with increased risk of colorectal cancer. Aromatic amines (aryl- and heterocyclic) are a class of carcinogens that are important in these exposures. These compounds can be N- or O-acetylated by the NAT1 or NAT2 enzymes, resulting in activation or in some cases detoxification. Recent studies have shown that both NAT2 and NAT1 genes exhibit variation in human populations and that rapid acetylation by the NAT2 enzyme may be a risk factor for colorectal cancer. In this study we have analyzed for genetic polymorphism in both NAT1 and NAT2 in a group of 202 colorectal cancer patients and 112 control subjects from Staffordshire, England. We find significantly increased risk (odds ratio, 1.9; 95% confidence interval, 1.2-3.2; P = 0.009) associated with the NAT1*10 allele of NAT1, an allele that contains a variant polyadenylation signal. Individuals with higher stage tumors (Duke's C) were more likely to inherit this variant allele (odds ratio, 2.5; 95% confidence interval, 1.3-4.7; P = 0.005). In contrast, rapid acetylation genotypes of NAT2 were not a significant risk factor in this English population. However, we found that the risk associated with the NAT1 variant allele (NAT1*10) was most apparent among NAT2 rapid acetylators (odds ratio, 2.8; 95% confidence interval, 1.4-5.7; P = 0.003), suggesting a possible gene-gene interaction between NAT1 and NAT2 (test for interaction; P = 0.12). This is the first study to test for cancer risk associated with the NAT1 gene, and these positive findings suggest that NAT1 alleles may be important genetic determinents of colorectal cancer risk. JF - Cancer research AU - Bell, D A AU - Stephens, E A AU - Castranio, T AU - Umbach, D M AU - Watson, M AU - Deakin, M AU - Elder, J AU - Hendrickse, C AU - Duncan, H AU - Strange, R C AD - Laboratory of biochemical Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/08/15/ PY - 1995 DA - 1995 Aug 15 SP - 3537 EP - 3542 VL - 55 IS - 16 SN - 0008-5472, 0008-5472 KW - NAT1 KW - NAT2 KW - DNA, Neoplasm KW - 0 KW - Isoenzymes KW - Poly A KW - 24937-83-5 KW - Arylamine N-Acetyltransferase KW - EC 2.3.1.5 KW - N-acetyltransferase 1 KW - NAT2 protein, human KW - Index Medicus KW - Risk KW - Base Sequence KW - Gene Frequency KW - Polymorphism, Genetic KW - Risk Factors KW - Humans KW - Poly A -- genetics KW - Molecular Sequence Data KW - DNA, Neoplasm -- genetics KW - Middle Aged KW - Male KW - Female KW - Adenocarcinoma -- enzymology KW - Adenocarcinoma -- genetics KW - Colorectal Neoplasms -- genetics KW - Colorectal Neoplasms -- enzymology KW - Isoenzymes -- genetics KW - Arylamine N-Acetyltransferase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77422327?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Polyadenylation+polymorphism+in+the+acetyltransferase+1+gene+%28NAT1%29+increases+risk+of+colorectal+cancer.&rft.au=Bell%2C+D+A%3BStephens%2C+E+A%3BCastranio%2C+T%3BUmbach%2C+D+M%3BWatson%2C+M%3BDeakin%2C+M%3BElder%2C+J%3BHendrickse%2C+C%3BDuncan%2C+H%3BStrange%2C+R+C&rft.aulast=Bell&rft.aufirst=D&rft.date=1995-08-15&rft.volume=55&rft.issue=16&rft.spage=3537&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 - 1995-09-07 N1 - Date created - 1995-09-07 N1 - Date revised - 2017-01-13 N1 - Gene symbol - NAT1; NAT2 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The relation of gastroesophageal reflux disease and its treatment to adenocarcinomas of the esophagus and gastric cardia. AN - 77433277; 7629956 AB - To examine the relationship of gastrointestinal disorders and their treatment to the risk of adenocarcinomas of the esophagus and gastric cardia (AEC). A medical record-based case-control study, with data collected on a standardized form by a trained abstractor, blind to the case-control status. A large prepaid health plan. Case patients were plan members newly diagnosed with histologically confirmed AEC from 1986 to 1992. For each of the 196 eligible case patients, one control was selected who matched for membership at time of diagnosis, sex, year of birth, and duration of membership. Association between AEC and history of gastroesophageal conditions and their treatment. Conditional logistic regression procedures were used for calculation of odds ratios (ORs) and corresponding 95% confidence intervals (Cls), with adjustment for race, smoking status, and body mass index. Medications were grouped into H2 antagonists (cimetidine, ranitidine, famotidine, and nizatidine) and anticholinergics (propantheline bromide, dicyclomine hydrochloride, Donnatal [combination of atropine sulfate, hyoscyamine sulfate, phenobarbital, and scopolamine hydrobromide], and Librax [combination of chlordiazepoxide hydrochloride and clidinium bromide]). Significant twofold or greater risks of AEC were associated with a history of esophageal reflux, hiatal hernia, esophagitis/esophageal ulcer, and difficulty swallowing. The ORs increased with increasing number of these conditions. Although a fourfold risk was linked to four or more prescriptions for H2 antagonists, the risk was reduced to 1.5 (95% Cl, 0.4 to 5.4) after adjusting for the predisposing conditions. Further analysis revealed that the excess risk was restricted to persons with a history of gastroesophageal reflux and related conditions. No association was observed for overall use of anticholinergics. However, after adjustment for predisposing conditions, ORs decreased with increasing number of prescriptions for anticholinergics (P for trend = .08) This study provides reassuring findings that use of H2 antagonists and anticholinergics does not increase AEC risk. It also quantifies the elevated risk of AEC associated with gastroesophageal reflux disease. Further research into reflux disease and the production of premalignant epithelial changes may help elucidate carcinogenic mechanisms and measures aimed at early detection and prevention of AEC. JF - JAMA AU - Chow, W H AU - Finkle, W D AU - McLaughlin, J K AU - Frankl, H AU - Ziel, H K AU - Fraumeni, J F AD - Division of Cancer Etiology, National Cancer Institute, Bethesda, Md, USA. Y1 - 1995/08/09/ PY - 1995 DA - 1995 Aug 09 SP - 474 EP - 477 VL - 274 IS - 6 SN - 0098-7484, 0098-7484 KW - Cholinergic Antagonists KW - 0 KW - Drug Combinations KW - Histamine H2 Antagonists KW - Quinuclidines KW - Chlordiazepoxide KW - 6RZ6XEZ3CR KW - chlordiazepoxide, clidinium drug combination KW - 8015-20-1 KW - Abridged Index Medicus KW - Index Medicus KW - Causality KW - Humans KW - Esophageal Diseases -- drug therapy KW - Esophageal Diseases -- physiopathology KW - Quinuclidines -- therapeutic use KW - Aged KW - Hernia, Hiatal -- physiopathology KW - Esophagitis -- drug therapy KW - Logistic Models KW - Risk Factors KW - Chlordiazepoxide -- therapeutic use KW - Cardia KW - Case-Control Studies KW - Cholinergic Antagonists -- therapeutic use KW - Middle Aged KW - Esophagitis -- physiopathology KW - Histamine H2 Antagonists -- therapeutic use KW - Hernia, Hiatal -- drug therapy KW - Gastroesophageal Reflux -- physiopathology KW - Adenocarcinoma -- epidemiology KW - Adenocarcinoma -- etiology KW - Gastroesophageal Reflux -- drug therapy KW - Stomach Neoplasms -- epidemiology KW - Stomach Neoplasms -- etiology KW - Esophageal Neoplasms -- etiology KW - Esophageal Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77433277?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=JAMA&rft.atitle=The+relation+of+gastroesophageal+reflux+disease+and+its+treatment+to+adenocarcinomas+of+the+esophagus+and+gastric+cardia.&rft.au=Chow%2C+W+H%3BFinkle%2C+W+D%3BMcLaughlin%2C+J+K%3BFrankl%2C+H%3BZiel%2C+H+K%3BFraumeni%2C+J+F&rft.aulast=Chow&rft.aufirst=W&rft.date=1995-08-09&rft.volume=274&rft.issue=6&rft.spage=474&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-07 N1 - Date created - 1995-09-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bisimidazoacridones and related compounds: new antineoplastic agents with high selectivity against colon tumors. AN - 77438501; 7636867 AB - A new class of potent and highly selective antitumor agents has been synthesized. Bisimidazoacridones, where the tetracyclic ring systems are held together by either a N2-methyldiethylenetriamine or 3,3'-diamino-N-methyldipropylamine linker, and related asymmetrical compounds, where one of the imidazoacridone ring system was replaced by a triazoloacridone ring system, were found to be cytostatic and cytotoxic in vitro. Some of these compounds, such as 5,5'-[(methylimino)bis(3,1-propanediylimino)]bis[6H-imidazo[ 4,5,1-de]acridin-6-one] (4b) showed remarkably high activity and selectivity for colon cancer in the National Cancer Institute screen. This antitumor effect was also apparent in colony survival assays utilizing the colon cancer line, HCT-116, and in in vivo assays involving xenografts of tumor derived from HCT-116 in nude mice. The tested compounds exhibited relatively low acute toxicity and were well-tolerated by the treated animals. The bisimidazoacridones interact with nucleic acids in vitro but preliminary experimental and modeling data indicate that in spite of their structure, they may not be bis-intercalators. While the precise mode of action of these compounds is not yet understood, they appear to be excellent candidates for clinical development. JF - Journal of medicinal chemistry AU - Cholody, W M AU - Hernandez, L AU - Hassner, L AU - Scudiero, D A AU - Djurickovic, D B AU - Michejda, C J AD - Division of Cancer Treatment, National Cancer Institute--Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1995/08/04/ PY - 1995 DA - 1995 Aug 04 SP - 3043 EP - 3052 VL - 38 IS - 16 SN - 0022-2623, 0022-2623 KW - Aminoacridines KW - 0 KW - Antineoplastic Agents KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Neoplasm Transplantation KW - Drug Screening Assays, Antitumor KW - Animals KW - Base Sequence KW - Tumor Cells, Cultured KW - Humans KW - Computer Graphics KW - Molecular Sequence Data KW - Mice, Nude KW - Mice KW - Male KW - Structure-Activity Relationship KW - DNA -- drug effects KW - Colonic Neoplasms -- drug therapy KW - Aminoacridines -- chemistry KW - Colonic Neoplasms -- pathology KW - Antineoplastic Agents -- chemistry KW - Antineoplastic Agents -- pharmacology KW - Aminoacridines -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77438501?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+medicinal+chemistry&rft.atitle=Bisimidazoacridones+and+related+compounds%3A+new+antineoplastic+agents+with+high+selectivity+against+colon+tumors.&rft.au=Cholody%2C+W+M%3BHernandez%2C+L%3BHassner%2C+L%3BScudiero%2C+D+A%3BDjurickovic%2C+D+B%3BMichejda%2C+C+J&rft.aulast=Cholody&rft.aufirst=W&rft.date=1995-08-04&rft.volume=38&rft.issue=16&rft.spage=3043&rft.isbn=&rft.btitle=&rft.title=Journal+of+medicinal+chemistry&rft.issn=00222623&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-14 N1 - Date created - 1995-09-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A hPMS2 mutant cell line is defective in strand-specific mismatch repair. AN - 77426519; 7629132 AB - Human cells contain several homologs of the bacterial mutL gene required for mismatch repair, including a gene on chromosome 7 designated hPMS2. We have identified an endometrial carcinoma cell line, HEC-1-A, that has a C-->T mutation in hPMS2 that generates a nonsense codon and yields a protein truncated at the C terminus. No wild-type gene or gene product was detected. The missing amino acids in hPMS2 are highly conserved among PMS homologs, suggesting that they may be critical for function. In support of this, extracts of HEC-1-A cells are defective in repairing a variety of mismatched substrates. Moreover, di-, tri-, and tetranucleotide repeated sequences are highly unstable in single cell clones of HEC-1-A cells, and HEC-1-A cells are resistant to killing by N-methyl-N'-nitro-N-nitrosoguanidine. The results provide strong experimental support for the involvement of the hPMS2 gene product in mismatch repair in human cells and support the concept that a defective hPMS2 gene may lead to predisposition to certain forms of cancer. JF - The Journal of biological chemistry AU - Risinger, J I AU - Umar, A AU - Barrett, J C AU - Kunkel, T A AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/08/04/ PY - 1995 DA - 1995 Aug 04 SP - 18183 EP - 18186 VL - 270 IS - 31 SN - 0021-9258, 0021-9258 KW - hPMS2 KW - DNA, Satellite KW - 0 KW - DNA-Binding Proteins KW - Neoplasm Proteins KW - Methylnitronitrosoguanidine KW - 12H3O2UGSF KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - PMS2 protein, human KW - Mismatch Repair Endonuclease PMS2 KW - EC 3.6.1.3 KW - DNA Repair Enzymes KW - EC 6.5.1.- KW - Index Medicus KW - DNA, Satellite -- genetics KW - Base Sequence KW - Tumor Cells, Cultured KW - Methylnitronitrosoguanidine -- toxicity KW - Humans KW - Molecular Sequence Data KW - Chromosomes, Human, Pair 7 -- genetics KW - Repetitive Sequences, Nucleic Acid -- genetics KW - Female KW - DNA Repair -- genetics KW - Carcinoma -- etiology KW - Neoplasm Proteins -- genetics KW - Endometrial Neoplasms -- genetics KW - Mutation KW - Endometrial Neoplasms -- etiology KW - Carcinoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77426519?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+hPMS2+mutant+cell+line+is+defective+in+strand-specific+mismatch+repair.&rft.au=Risinger%2C+J+I%3BUmar%2C+A%3BBarrett%2C+J+C%3BKunkel%2C+T+A&rft.aulast=Risinger&rft.aufirst=J&rft.date=1995-08-04&rft.volume=270&rft.issue=31&rft.spage=18183&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 - 1995-09-07 N1 - Date created - 1995-09-07 N1 - Date revised - 2017-01-13 N1 - Gene symbol - hPMS2 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - What does it mean to be a cancer gene carrier? Problems in establishing causality from the molecular genetics of cancer. AN - 77519664; 7674316 AB - This article addresses the following question: What does it mean to be a cancer gene carrier? The existence of families prone to cancer has prompted an intense search for predisposing heritable gene mutations. Genes that impart susceptibility to colorectal, breast, and ovarian cancers have been recently identified. It is doubtful, however, that the action of a single mutant gene totally accounts for the development of malignant disease. The mutant gene likely causes cancer in these family members only in conjunction with other genes, environmental factors, or both. Furthermore, although an individual carrier of a mutant gene within a cancer-prone family has an increased risk of malignancy, nutritional, pharmacologic, or other interventions may still confer protection. Extrapolations from cancer-prone families to the general population are even more problematic. The excess risk of malignancy among carriers of mutant genes who are not members of cancer-prone families is unknown. Large-scale epidemiologic studies are needed to determine the magnitude (or even the existence) of such excess risk. JF - Journal of the National Cancer Institute AU - Schatzkin, A AU - Goldstein, A AU - Freedman, L S AD - Cancer Prevention Studies Branch, National Cancer Institute, Bethesda, MD, USA. Y1 - 1995/08/02/ PY - 1995 DA - 1995 Aug 02 SP - 1126 EP - 1130 VL - 87 IS - 15 SN - 0027-8874, 0027-8874 KW - Index Medicus KW - Risk KW - Humans KW - Environmental Exposure KW - Heterozygote KW - Neoplasms -- epidemiology KW - Mutation -- genetics KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77519664?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=What+does+it+mean+to+be+a+cancer+gene+carrier%3F+Problems+in+establishing+causality+from+the+molecular+genetics+of+cancer.&rft.au=Schatzkin%2C+A%3BGoldstein%2C+A%3BFreedman%2C+L+S&rft.aulast=Schatzkin&rft.aufirst=A&rft.date=1995-08-02&rft.volume=87&rft.issue=15&rft.spage=1126&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 - 1995-10-19 N1 - Date created - 1995-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Breast cancer among radiologic technologists. AN - 77406130; 7616635 AB - To evaluate the risk of breast cancer among women occupationally exposed to ionizing radiation. Case-control study. A health survey of 105,385 women radiologic technologists certified by the American Registry of Radiologic Technologists since 1926. Among 79,016 respondents, 600 breast cancer cases were identified. Each of 528 eligible subjects with breast cancer was matched to five control subjects based on age, year of certification, and follow-up time. Relative risk (RR) estimated as the relative odds ratio for breast cancer over categories of years worked as a radiologic technologist and according to personal and occupational exposure characteristics. Study subjects had been certified for a mean of 29 years; 63.8% of cases and 62.6% of controls worked as radiologic technologists for 10 years or more. Significant increased risks for breast cancer were associated with early age at menarche (for 14 alcoholic drinks per week: RR = 2.12; 95% CI, 1.06 to 4.27), thyroid cancer (RR = 5.36; 95% CI, 1.64 to 17.5), hyperthyroidism (RR = 1.66; 95% CI, 1.02 to 2.71), and residence in the northeastern United States (RR = 1.66; 95% CI, 1.19 to 2.30). Jobs involving radiotherapy, radioisotopes, or fluoroscopic equipment, however, were not linked to breast cancer risk, nor were personal exposures to fluoroscopy or multifilm procedures. Use of birth control pills, postmenopausal estrogens, or permanent hair dyes also were not risk factors. Based on dosimetry records for 35% of study subjects, cumulative exposures appeared low. Among women who worked more than 20 years, the RR for breast cancer was 1.13 (95% CI, 0.79 to 1.64). More than 50% of the reported breast cancers could be explained by established risk factors. Employment as a radiologic technologist, however, was not found to increase the risk of breast cancer. The contribution of prolonged exposure to relatively low doses of ionizing radiation to breast cancer risk was too small to be detectable at this time. JF - JAMA AU - Boice, J D AU - Mandel, J S AU - Doody, M M AD - Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/08/02/ PY - 1995 DA - 1995 Aug 02 SP - 394 EP - 401 VL - 274 IS - 5 SN - 0098-7484, 0098-7484 KW - Abridged Index Medicus KW - Index Medicus KW - Logistic Models KW - Risk Factors KW - Humans KW - Adult KW - Case-Control Studies KW - Occupational Exposure -- adverse effects KW - Middle Aged KW - Female KW - Radiation, Ionizing KW - Matched-Pair Analysis KW - Neoplasms, Radiation-Induced -- etiology KW - Technology, Radiologic -- statistics & numerical data KW - Neoplasms, Radiation-Induced -- epidemiology KW - Occupational Diseases -- etiology KW - Breast Neoplasms -- etiology KW - Occupational Diseases -- epidemiology KW - Breast Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77406130?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=JAMA&rft.atitle=Breast+cancer+among+radiologic+technologists.&rft.au=Boice%2C+J+D%3BMandel%2C+J+S%3BDoody%2C+M+M&rft.aulast=Boice&rft.aufirst=J&rft.date=1995-08-02&rft.volume=274&rft.issue=5&rft.spage=394&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-24 N1 - Date created - 1995-08-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: JAMA. 1996 Aug 7;276(5):369-70 [8683810] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Studies of cancer and radiation dose among atomic bomb survivors. The example of breast cancer. AN - 77405149; 7616636 AB - A comprehensive program of medical follow-up of survivors of the atomic bombings of Hiroshima and Nagasaki, Japan, by the Radiation Effects Research Foundation (RERF) has produced quantitative estimates of cancer risk from exposure to ionizing radiation. For breast cancer in women, in particular, the strength of the radiation dose response and the generally low level of population risk in the absence of radiation exposure have led to a clear description of excess risk and its variation by age at exposure and over time following exposure. Comparisons of RERF data with data from medically irradiated populations have yielded additional information on the influence of population and underlying breast cancer rates on radiation-related risk. Epidemiological investigations of breast cancer cases and matched controls among atomic bomb survivors have clarified the role of reproductive history as a modifier of the carcinogenic effects of radiation exposure. Finally, a pattern of radiation-related risk by attained age among the survivors exposed during childhood or adolescence suggests the possible existence of a radiation-susceptible subgroup. The hypothetical existence of such a group is lent plausibility by the results of recent family studies suggesting that heritable mutations in certain genes are associated with familial aggregations of breast cancer. The recent isolation and cloning of one such gene, BRCA1, makes it likely that the hypothesis can be tested using molecular assays of archival and other tissue obtained from atomic bomb survivor cases and controls. JF - JAMA AU - Land, C E AD - Radiation Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892-7362, USA. Y1 - 1995/08/02/ PY - 1995 DA - 1995 Aug 02 SP - 402 EP - 407 VL - 274 IS - 5 SN - 0098-7484, 0098-7484 KW - Abridged Index Medicus KW - Index Medicus KW - Causality KW - Age Factors KW - Humans KW - Linear Models KW - Survival KW - Aged KW - Child KW - Dose-Response Relationship, Radiation KW - Child, Preschool KW - Japan -- epidemiology KW - Infant KW - Risk KW - Radiometry KW - Adult KW - Incidence KW - Middle Aged KW - Adolescent KW - Environmental Exposure -- adverse effects KW - Female KW - Radiation, Ionizing KW - Breast Neoplasms -- genetics KW - Neoplasms, Radiation-Induced -- etiology KW - Nuclear Warfare KW - Neoplasms, Radiation-Induced -- epidemiology KW - Breast Neoplasms -- etiology KW - Neoplasms, Radiation-Induced -- genetics KW - Breast Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77405149?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=JAMA&rft.atitle=Studies+of+cancer+and+radiation+dose+among+atomic+bomb+survivors.+The+example+of+breast+cancer.&rft.au=Land%2C+C+E&rft.aulast=Land&rft.aufirst=C&rft.date=1995-08-02&rft.volume=274&rft.issue=5&rft.spage=402&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-24 N1 - Date created - 1995-08-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: JAMA. 1995 Aug 2;274(5):427-8 [7616641] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Usefulness of the LPC-Residue in Text-Independent Speaker Verification AN - 85329842; llba-9512360 AB - Speech analysis is considered by linear prediction & the recognition contribution of its two main resulting components - the synthesis filter & the residue. This study is motivated by the orthogonality property & the physiological significance of these two components, which suggest an improvement over current speaker recognition approaches based on the usual synthesis filter features is possible. A new representation of the residue is proposed, & its corresponding recognition performance is analyzed by experiments in the context of text-independent speaker verification. Experiments involving both known & new methods allow comparison of the recognition performance of the two components. Each method was tested on the same database & according to the same methodology, with strictly disjoint training & test data sets. Results indicate the usefulness of the residue when used alone, although it was less efficient than the synthesis filter; when both were combined, the residue error rate was reduced. 7 Tables, 11 Figures, 44 References. Adapted from the source document JF - Speech Communication AU - Thevenaz, Philippe AU - Hugli, Heinz AD - NCRR/BEIP National Instits Health, Bethesda MD 20892-5766 [Tel: 301-496-4426; Fax: 301-496-6608; mailto:thevenaz@helix.nih.gov] Y1 - 1995/08// PY - 1995 DA - Aug 1995 SP - 145 EP - 157 VL - 17 IS - 1-2 SN - 0167-6393, 0167-6393 KW - text-independent speaker recognition, synthesis filter/residue component recognition performance KW - experiments KW - *Voice Recognition (95250) KW - *Speech Perception (82700) KW - article KW - 6311: hearing-pathological and normal; auditory perception UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85329842?accountid=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=Speech+Communication&rft.atitle=Usefulness+of+the+LPC-Residue+in+Text-Independent+Speaker+Verification&rft.au=Thevenaz%2C+Philippe%3BHugli%2C+Heinz&rft.aulast=Thevenaz&rft.aufirst=Philippe&rft.date=1995-08-01&rft.volume=17&rft.issue=1-2&rft.spage=145&rft.isbn=&rft.btitle=&rft.title=Speech+Communication&rft.issn=01676393&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2003-10-01 N1 - Last updated - 2014-06-17 N1 - CODEN - SCOMDH N1 - SubjectsTermNotLitGenreText - *Speech Perception (82700); *Voice Recognition (95250) ER - TY - JOUR T1 - The relation of gastroesophageal reflux disease and its treatment to adenocarcinomas of the esophagus and gastric cardia. AN - 85310302; pmid-7629956 AB - OBJECTIVE--To examine the relationship of gastrointestinal disorders and their treatment to the risk of adenocarcinomas of the esophagus and gastric cardia (AEC). DESIGN--A medical record-based case-control study, with data collected on a standardized form by a trained abstractor, blind to the case-control status. SETTING--A large prepaid health plan. SUBJECTS--Case patients were plan members newly diagnosed with histologically confirmed AEC from 1986 to 1992. For each of the 196 eligible case patients, one control was selected who matched for membership at time of diagnosis, sex, year of birth, and duration of membership. MAIN OUTCOME MEASURES--Association between AEC and history of gastroesophageal conditions and their treatment. Conditional logistic regression procedures were used for calculation of odds ratios (ORs) and corresponding 95% confidence intervals (Cls), with adjustment for race, smoking status, and body mass index. Medications were grouped into H2 antagonists (cimetidine, ranitidine, famotidine, and nizatidine) and anticholinergics (propantheline bromide, dicyclomine hydrochloride, Donnatal [combination of atropine sulfate, hyoscyamine sulfate, phenobarbital, and scopolamine hydrobromide], and Librax [combination of chlordiazepoxide hydrochloride and clidinium bromide]). RESULTS--Significant twofold or greater risks of AEC were associated with a history of esophageal reflux, hiatal hernia, esophagitis/esophageal ulcer, and difficulty swallowing. The ORs increased with increasing number of these conditions. Although a fourfold risk was linked to four or more prescriptions for H2 antagonists, the risk was reduced to 1.5 (95% Cl, 0.4 to 5.4) after adjusting for the predisposing conditions. Further analysis revealed that the excess risk was restricted to persons with a history of gastroesophageal reflux and related conditions. No association was observed for overall use of anticholinergics. However, after adjustment for predisposing conditions, ORs decreased with increasing number of prescriptions for anticholinergics (P for trend = .08) CONCLUSIONS--This study provides reassuring findings that use of H2 antagonists and anticholinergics does not increase AEC risk. It also quantifies the elevated risk of AEC associated with gastroesophageal reflux disease. Further research into reflux disease and the production of premalignant epithelial changes may help elucidate carcinogenic mechanisms and measures aimed at early detection and prevention of AEC. JF - JAMA AU - Chow, W H AU - Finkle, W D AU - McLaughlin, J K AU - Frankl, H AU - Ziel, H K AU - Fraumeni, J F AD - Division of Cancer Etiology, National Cancer Institute, Bethesda, Md, USA. PY - 1995 SP - 474 EP - 477 VL - 274 IS - 6 SN - 0098-7484, 0098-7484 KW - Causality KW - Hernia, Hiatal KW - Cholinergic Antagonists KW - Humans KW - Esophageal Neoplasms KW - Aged KW - Gastroesophageal Reflux KW - Histamine H2 Antagonists KW - Drug Combinations KW - Research Support, U.S. Gov't, P.H.S. KW - Esophagitis KW - Quinuclidines KW - Logistic Models KW - Risk Factors KW - Stomach Neoplasms KW - Case-Control Studies KW - Cardia KW - Middle Aged KW - Esophageal Diseases KW - Chlordiazepoxide KW - Adenocarcinoma UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85310302?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=JAMA&rft.atitle=The+relation+of+gastroesophageal+reflux+disease+and+its+treatment+to+adenocarcinomas+of+the+esophagus+and+gastric+cardia.&rft.au=Chow%2C+W+H%3BFinkle%2C+W+D%3BMcLaughlin%2C+J+K%3BFrankl%2C+H%3BZiel%2C+H+K%3BFraumeni%2C+J+F&rft.aulast=Chow&rft.aufirst=W&rft.date=1995-08-01&rft.volume=274&rft.issue=6&rft.spage=474&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Amiloride-sensitive Na+ channel-like immunoreactivity in the luminal membrane of some non-sensory epithelia of the inner ear. AN - 85239289; pmid-8575996 AB - Some non-sensory epithelia of the inner ear were examined for the localization of immunoreactivity to polyclonal antibodies raised against amiloride-sensitive Na+ channels from the bovine kidney. The pre-embedding immunogold technique was used for this purpose. Labelings were found on the membrane of the endolymphatic surface of strial marginal cells, epithelial cells of spiral prominence and Reissner's membrane, and ampullar dark cells. In contrast, no labeling was found on the luminal membrane of mesothelial cells of Reissner's membrane, the cells lining the supra-strial perilymphatic space, transitional cells and ampullar ceiling cells. Since the antibodies used may also label non-selective cation channels and non-functional sodium channel precursors as suggested by others, it was not possible to determine the labelings are solely due to amiloride-sensitive Na+ channels. However, the observed result was consistent with the previous studies that amiloride blocks ion transport in strial marginal cells and the semicircular canal. It is therefore likely that the observed labeling includes amiloride-sensitive Na+ channels. These labeled ion channels in a variety of epithelial cells lining the endolymphatic space could be important in the inner ear fluid regulation. JF - Hearing Research AU - Mizuta, K AU - Iwasa, K H AU - Tachibana, M AU - Benos, D J AU - Lim, D J AD - Laboratory of Cellular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1995 SP - 199 EP - 205 VL - 88 IS - 1-2 SN - 0378-5955, 0378-5955 KW - Cochlea KW - Cattle KW - Antibodies KW - Comparative Study KW - Epithelial Cells KW - Endolymph KW - Guinea Pigs KW - Animal KW - Amiloride KW - Stria Vascularis KW - Epithelium KW - Spiral Ganglion KW - Immunohistochemistry KW - Female KW - Ion Transport KW - Sodium Channels UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85239289?accountid=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=Amiloride-sensitive+Na%2B+channel-like+immunoreactivity+in+the+luminal+membrane+of+some+non-sensory+epithelia+of+the+inner+ear.&rft.au=Mizuta%2C+K%3BIwasa%2C+K+H%3BTachibana%2C+M%3BBenos%2C+D+J%3BLim%2C+D+J&rft.aulast=Mizuta&rft.aufirst=K&rft.date=1995-08-01&rft.volume=88&rft.issue=1-2&rft.spage=199&rft.isbn=&rft.btitle=&rft.title=Hearing+Research&rft.issn=03785955&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Neuropsychological features of progressive supranuclear palsy. AN - 85219887; pmid-8546857 AB - Progressive supranuclear palsy (PSP) is the epitome of a subcortical dementia process. Due to its relative rarity, there is only a small literature on the neuropsychological consequences of PSP. The findings to date demonstrate that PSP patients have dramatically slowed information processing and motor execution, rapid forgetting, problems in orienting attentional resources, and difficulty in planning and shifting conceptual sets. The pattern and severity of these deficits are unique to PSP and suggest that the study of PSP patients can provide a special insight into brain-behavior relations. JF - Brain and Cognition AU - Grafman, J AU - Litvan, I AU - Stark, M AD - Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1995 SP - 311 EP - 320 VL - 28 IS - 3 SN - 0278-2626, 0278-2626 KW - Severity of Illness Index KW - Mental Disorders KW - Human KW - Supranuclear Palsy, Progressive KW - Brain KW - Cognition Disorders UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85219887?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+and+Cognition&rft.atitle=Neuropsychological+features+of+progressive+supranuclear+palsy.&rft.au=Grafman%2C+J%3BLitvan%2C+I%3BStark%2C+M&rft.aulast=Grafman&rft.aufirst=J&rft.date=1995-08-01&rft.volume=28&rft.issue=3&rft.spage=311&rft.isbn=&rft.btitle=&rft.title=Brain+and+Cognition&rft.issn=02782626&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Phenylacetate in chemoprevention: in vitro and in vivo suppression of 5-aza-2'-deoxycytidine-induced carcinogenesis. AN - 77965215; 9816056 AB - Differentiation inducers selected for their low cytotoxic and genotoxic potential could be of major value in chemoprevention and maintenance therapy. We focus here on phenylacetate, a naturally occurring plasma component recently shown to affect the growth and differentiation of established neoplasms in experimental models. The ability of phenylacetate to prevent carcinogenesis by the chemotherapeutic hypomethylating drug 5-aza-2'-deoxycytidine (5AzadC) was tested in vitro and in mice. Transient exposure of immortalized, but poorly tumorigenic ras-transformed 4C8 fibroblasts to 5AzadC resulted in neoplastic transformation manifested by loss of contact inhibition of growth, acquired invasiveness, and increased tumorigenicity in athymic mice. The latter was associated with elevation in ras expression and a decline in collagen biosynthesis. These profound phenotypic and molecular changes were prevented by a simultaneous treatment with phenylacetate. Protection from 5AzadC carcinogenesis by phenylacetate was: (a) highly efficient despite DNA hypomethylation by both drugs, (b) free of cytotoxic and genotoxic effects, (c) stable after treatment was discontinued, and (d) reproducible in vivo. Whereas athymic mice bearing 4C8 cells developed fibrosarcomas following a single i.p. injection with 5AzadC, tumor development was significantly inhibited by systemic treatment with nontoxic doses of phenylacetate. Phenylacetate and its precursor suitable for oral administration, phenylbutyrate, may thus represent a new class of chemopreventive agents, the efficacy and safety of which should be further evaluated. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Prasanna, P AU - Shack, S AU - Wilson, V L AU - Samid, D AD - Clinical Pharmacology Branch, Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 865 EP - 871 VL - 1 IS - 8 SN - 1078-0432, 1078-0432 KW - Anticarcinogenic Agents KW - 0 KW - Carcinogens KW - Drug Combinations KW - Laminin KW - Phenylacetates KW - Proteoglycans KW - matrigel KW - 119978-18-6 KW - decitabine KW - 776B62CQ27 KW - Collagen KW - 9007-34-5 KW - phenylacetic acid KW - ER5I1W795A KW - Azacitidine KW - M801H13NRU KW - Index Medicus KW - Clone Cells KW - 3T3 Cells KW - Animals KW - Cell Division -- drug effects KW - Mice KW - Mice, Nude KW - DNA Methylation -- drug effects KW - Female KW - Neoplasm Invasiveness -- prevention & control KW - Genes, ras KW - Phenylacetates -- pharmacology KW - Neoplasms, Experimental -- chemically induced KW - Azacitidine -- toxicity KW - Azacitidine -- analogs & derivatives KW - Anticarcinogenic Agents -- pharmacology KW - Carcinogens -- toxicity KW - Cell Transformation, Neoplastic -- drug effects KW - Neoplasms, Experimental -- prevention & control KW - Chemoprevention KW - Neoplasms, Experimental -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77965215?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phenylacetate+in+chemoprevention%3A+in+vitro+and+in+vivo+suppression+of+5-aza-2%27-deoxycytidine-induced+carcinogenesis.&rft.au=Prasanna%2C+P%3BShack%2C+S%3BWilson%2C+V+L%3BSamid%2C+D&rft.aulast=Prasanna&rft.aufirst=P&rft.date=1995-08-01&rft.volume=1&rft.issue=8&rft.spage=865&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-18 N1 - Date created - 1999-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunotoxins that target an oncogenic mutant epidermal growth factor receptor expressed in human tumors. AN - 77954917; 9816055 AB - Human cancers arise from a series of mutations, many of which direct the expression of mutant proteins with altered functions. These aberrant proteins are attractive targets for new therapeutic agents. One such protein is a mutant epidermal growth factor receptor (EGFRvIII) that has an in-frame deletion near the NH2 terminus of its extracellular domain. This protein was first identified in human gliomas, but has also been shown to be present in lung and breast carcinomas. The deletion results in a receptor with constitutive tyrosine kinase activity that enhances the tumorigenicity of glioblastomas in vivo. The deletion also creates a tumor-specific cell-surface sequence at the deletion junction. Three specific anti-EGFRvIII mAbs have been isolated following immunization with a mixture of a deletion junction synthetic peptide and EGFRvIII as present on cell membranes. We have constructed immunotoxins by conjugating a modified version of Pseudomonas exotoxin A to these mAbs. Immunotoxins were tested on cells that had been transfected with cDNA for the EGFRvIII receptor and expressed receptor protein at 5 x 10(5) receptors/cell. All three immunotoxins were cytotoxic to these cells, with 50% inhibition of protein synthesis occurring in a 15-50 pM range. The immunotoxins specifically targeted EGFRvIII, as their cytotoxicity could be blocked by their respective free antibody. They showed little or no cytotoxicity to cells expressing high levels of normal epidermal growth factor receptors, demonstrating that they are able to discriminate between cells expressing the mutant receptor and those expressing the wild-type receptor. Immunotoxins targeted to mutant epidermal growth factor receptors are promising candidates for further development as tumor cell-specific therapeutic agents. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Lorimer, I A AU - Wikstrand, C J AU - Batra, S K AU - Bigner, D D AU - Pastan, I AD - Laboratory of Molecular Biology, Division of Cancer Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 859 EP - 864 VL - 1 IS - 8 SN - 1078-0432, 1078-0432 KW - Antibodies, Monoclonal KW - 0 KW - Immunotoxins KW - Oligopeptides KW - Protein Sorting Signals KW - Recombinant Proteins KW - lysyl-aspartyl-glutamyl-leucine KW - 113516-56-6 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Breast Neoplasms -- genetics KW - Recombinant Proteins -- drug effects KW - 3T3 Cells KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Humans KW - Mice KW - Drug Design KW - Mutagenesis, Site-Directed KW - Transfection KW - Lung Neoplasms -- genetics KW - Glioma -- genetics KW - Female KW - Sequence Deletion KW - Receptor, Epidermal Growth Factor -- drug effects KW - Immunotoxins -- chemistry KW - Receptor, Epidermal Growth Factor -- genetics KW - Immunotoxins -- toxicity KW - Cell Survival -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77954917?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Immunotoxins+that+target+an+oncogenic+mutant+epidermal+growth+factor+receptor+expressed+in+human+tumors.&rft.au=Lorimer%2C+I+A%3BWikstrand%2C+C+J%3BBatra%2C+S+K%3BBigner%2C+D+D%3BPastan%2C+I&rft.aulast=Lorimer&rft.aufirst=I&rft.date=1995-08-01&rft.volume=1&rft.issue=8&rft.spage=859&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-18 N1 - Date created - 1999-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacokinetics of orally administered carboxyamido-triazole, an inhibitor of calcium-mediated signal transduction. AN - 77954825; 9816048 AB - Carboxyamido-triazole (CAI), inhibits proliferation, invasion, and metastatic potential of a number of cancer cell lines at concentrations greater than 0.4 microgram/ml. The objective of this study was to characterize the pharmacokinetic profile from the first Phase I clinical trial of CAI for the single test dose and multiple daily dosing schedule. Two different p.o. formulations (liquid and gelcap) of CAI were administered. Thirty-nine patients with cancer were enrolled. The dose escalation schema was 100, 125, and 150 mg/m2/day and 200 and 330 mg/m2 every other day of the liquid formulation, plus 100 and 125 mg/m2/day and 200 mg/m2 every other day of the gelcap. The CAI pharmacokinetics are best described by a two-compartment open linear model. The gelcap was more rapidly absorbed than the liquid [time to maximum plasma concentration (Tmax) = 2.06 +/- 1.02 versus 5.31 +/- 3.59 h, P2 = 0.0012] which resulted in higher peak plasma concentrations. There was no evidence of saturable elimination as the dose was increased. The mean steady-state peak concentration was 5.1 +/- 1.0 microgram/ml for the 150 mg/m2/day multiple daily dosing regimen. The terminal half-life of CAI was relatively prolonged, 111 h, and the total body p.o. clearance was low (1.87 liters/h). The peak concentration for all dose levels explored was greater than the targeted concentration suggested by in vitro data for activity. Thus, these data suggest that an effective cytostatic exposure of CAI may be obtained with daily or every other day dosing without severe toxicity. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Figg, W D AU - Cole, K A AU - Reed, E AU - Steinberg, S M AU - Piscitelli, S C AU - Davis, P A AU - Soltis, M J AU - Jacob, J AU - Boudoulas, S AU - Goldspiel, B AD - Clinical Pharmacology Branch and the Signal Transduction and Prevention Unit, Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 797 EP - 803 VL - 1 IS - 8 SN - 1078-0432, 1078-0432 KW - Antineoplastic Agents KW - 0 KW - Triazoles KW - carboxyamido-triazole KW - 99519-84-3 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Administration, Oral KW - Chemistry, Pharmaceutical KW - Dose-Response Relationship, Drug KW - Humans KW - Aged KW - Metabolic Clearance Rate KW - Models, Biological KW - Calcium -- metabolism KW - Adult KW - Middle Aged KW - Signal Transduction KW - Female KW - Male KW - Neoplasms -- drug therapy KW - Antineoplastic Agents -- administration & dosage KW - Antineoplastic Agents -- pharmacokinetics KW - Triazoles -- adverse effects KW - Triazoles -- pharmacokinetics KW - Triazoles -- administration & dosage KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77954825?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pharmacokinetics+of+orally+administered+carboxyamido-triazole%2C+an+inhibitor+of+calcium-mediated+signal+transduction.&rft.au=Figg%2C+W+D%3BCole%2C+K+A%3BReed%2C+E%3BSteinberg%2C+S+M%3BPiscitelli%2C+S+C%3BDavis%2C+P+A%3BSoltis%2C+M+J%3BJacob%2C+J%3BBoudoulas%2C+S%3BGoldspiel%2C+B&rft.aulast=Figg&rft.aufirst=W&rft.date=1995-08-01&rft.volume=1&rft.issue=8&rft.spage=797&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-18 N1 - Date created - 1999-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Second primary cancer after treatment for cervical cancer. An international cancer registries study. AN - 77862948; 8625126 AB - The pattern of second cancers after treatment for cervical cancer provides important information on the risk of radiation-induced malignancies. Large numbers of women survive many years and can be studied for late effects. Incident second cancers in 86,193 patients with cervical cancer reported to 13 population-based cancer registries in 5 countries were evaluated to estimate the risk of second cancer among very long term survivors. Overall, 7543 second cancers were observed versus 6015 cancers expected based on population rates (observed/expected = 1.2). Lung cancer accounted for nearly half of the excess cancers. Among the 49,828 women treated with radiation, 3750 survived 30 or more years and a two-fold risk of cancers of heavily irradiated organs was seen. Most of the excess cancers were of the rectum, vagina, vulva, ovary, and bladder. Patterns of risk over time since treatment were consistent with a radiation etiology. Significant increases of nonchronic lymphocytic leukemia and cancers of the bone and kidney were also linked to radiotherapy. Women treated surgically were also at significant risk of second cancers, in all likelihood related to cigarette smoking and risk factors similar to those of cervical cancer. Curative therapy for cervical cancer results in large numbers of long term survivors who develop second cancers very late in life. Radiation is an important cause of this increase and there is no evidence that risk returns to normal levels. JF - Cancer AU - Kleinerman, R A AU - Boice, J D AU - Storm, H H AU - Sparen, P AU - Andersen, A AU - Pukkala, E AU - Lynch, C F AU - Hankey, B F AU - Flannery, J T AD - Radiation Epidemiology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-7362, USA. Y1 - 1995/08/01/ PY - 1995 DA - 1995 Aug 01 SP - 442 EP - 452 VL - 76 IS - 3 SN - 0008-543X, 0008-543X KW - Abridged Index Medicus KW - Index Medicus KW - Risk Factors KW - Radiotherapy Dosage KW - Humans KW - SEER Program KW - Europe -- epidemiology KW - United States -- epidemiology KW - Female KW - Neoplasms, Radiation-Induced -- etiology KW - Neoplasms, Radiation-Induced -- epidemiology KW - Uterine Cervical Neoplasms -- radiotherapy KW - Radiotherapy -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77862948?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer&rft.atitle=Second+primary+cancer+after+treatment+for+cervical+cancer.+An+international+cancer+registries+study.&rft.au=Kleinerman%2C+R+A%3BBoice%2C+J+D%3BStorm%2C+H+H%3BSparen%2C+P%3BAndersen%2C+A%3BPukkala%2C+E%3BLynch%2C+C+F%3BHankey%2C+B+F%3BFlannery%2C+J+T&rft.aulast=Kleinerman&rft.aufirst=R&rft.date=1995-08-01&rft.volume=76&rft.issue=3&rft.spage=442&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-27 N1 - Date created - 1996-06-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antitumor activity of suramin in hormone-refractory prostate cancer controlling for hydrocortisone treatment and flutamide withdrawal as potentially confounding variables. AN - 77845352; 8625127 AB - A prospective Phase II clinical trial was conducted to assess the clinical activity of a pharmacokinetically guided suramin regimen in patients who had documented progression of metastatic prostate cancer after hydrocortisone plus antecedent or simultaneous withdrawal of flutamide. Fifty-four patients whose disease had progressed after castration and flutamide administration were enrolled on this trial. The study was divided into two parts. Initially, 52 patients received hydrocortisone (30 mg/day) and for those patients receiving flutamide, at study entry (34 patients) flutamide was simultaneously discontinued. Forty-three patients whose disease progressed on hydrocortisone received suramin for 6-8 weeks. Six patients who progressed on hydrocortisone became ineligible for suramin due to clinical deterioration, four patients are still responding to hydrocortisone at more than 1 year, and one patient elected to postpone initiation of suramin. Suramin was given as intermittent infusions at fixed doses on days 1-5 and thereafter dosing was guided by adaptive control with feedback to maintain plasma suramin concentrations between 300-175 micrograms/ml. Antitumor activity was assessed by prostate specific antigen (PSA) decline and soft-tissue disease response. Ten patients (19%; 95% CI, 9.6%-32.5%) responded to hydrocortisone therapy with either a 50% or greater PSA decline for at least 4 weeks (9 patients) and/or a partial response of measurable soft-tissue disease (2 patients). Five of these patients (10%) demonstrated a 80% or greater PSA decline. All responders to hydrocortisone had simultaneous flutamide withdrawal, and had been receiving flutamide as part of initial combined androgen blockade. Seven of 37 evaluable patients (19%; 95% CI, 8.0%-35.2%) responded to suramin with a 50% or greater decline in PSA for 4 weeks or longer. One patient (3%) had a 80% or greater decline in PSA. There were no soft-tissue disease responses to suramin. The median time to progression was 1.9 months for hydrocortisone therapy and 2.6 months for suramin therapy. The median survival for all patients was 14.6 months. Suramin has antitumor activity in metastatic prostate carcinoma independent of the therapeutic effect of hydrocortisone administration or flutamide withdrawal. The role of prior flutamide withdrawal and hydrocortisone replacement should be taken into account in future studies of suramin. JF - Cancer AU - Dawson, N A AU - Cooper, M R AU - Figg, W D AU - Headlee, D J AU - Thibault, A AU - Bergan, R C AU - Steinberg, S M AU - Sausville, E A AU - Myers, C E AU - Sartor, O AD - Clinical Pharmacology Branch, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 1995/08/01/ PY - 1995 DA - 1995 Aug 01 SP - 453 EP - 462 VL - 76 IS - 3 SN - 0008-543X, 0008-543X KW - Antineoplastic Agents KW - 0 KW - Suramin KW - 6032D45BEM KW - Flutamide KW - 76W6J0943E KW - Prostate-Specific Antigen KW - EC 3.4.21.77 KW - Hydrocortisone KW - WI4X0X7BPJ KW - Abridged Index Medicus KW - Index Medicus KW - Prostate-Specific Antigen -- analysis KW - Treatment Failure KW - Prospective Studies KW - Humans KW - Aged KW - Middle Aged KW - Male KW - Suramin -- adverse effects KW - Prostatic Neoplasms -- mortality KW - Prostatic Neoplasms -- diagnosis KW - Flutamide -- therapeutic use KW - Prostatic Neoplasms -- drug therapy KW - Antineoplastic Agents -- therapeutic use KW - Suramin -- therapeutic use KW - Hydrocortisone -- therapeutic use KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77845352?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer&rft.atitle=Antitumor+activity+of+suramin+in+hormone-refractory+prostate+cancer+controlling+for+hydrocortisone+treatment+and+flutamide+withdrawal+as+potentially+confounding+variables.&rft.au=Dawson%2C+N+A%3BCooper%2C+M+R%3BFigg%2C+W+D%3BHeadlee%2C+D+J%3BThibault%2C+A%3BBergan%2C+R+C%3BSteinberg%2C+S+M%3BSausville%2C+E+A%3BMyers%2C+C+E%3BSartor%2C+O&rft.aulast=Dawson&rft.aufirst=N&rft.date=1995-08-01&rft.volume=76&rft.issue=3&rft.spage=453&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-27 N1 - Date created - 1996-06-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carboxypeptidase-G2 rescue in a patient with high dose methotrexate-induced nephrotoxicity. AN - 77843583; 8625136 AB - High dose methotrexate (HDMTX) induced renal failure is a medical emergency, as methotrexate (MTX) is primarily eliminated by renal excretion. High doses of leucovorin (LV) do not necessarily prevent toxicity in the presence of sustained elevated plasma MTX concentrations. The bacterial enzyme carboxypeptidase-G2 (CPDG2) hydrolyzes MTX into inactive metabolites and has been demonstrated to lower plasma MTX concentrations to nontoxic levels rapidly in the nonhuman primate after HDMTX infusion. Therefore, CPDG2 was evaluated as a rescue agent in a patient with acute renal dysfunction secondary to HDMTX: A 16 year old patient with osteosarcoma experienced acute renal dysfunction after HDMTX administration, which resulted in markedly elevated and sustained plasma MTX concentrations. She received three doses of CPDG2 on the fifth day after HDMTX: Plasma MTX concentrations were determined before and after CPDG2 administration. The plasma MTX concentrations decreased from 60 to 1.2 microM within 15 minutes after the first dose of CPDG2. No rebound increase in plasma MTX concentrations or adverse reactions to the enzyme were observed. The patient developed only mild mucositis. Serum creatinine at the time of CPDG2 administration was 5 mg/dl and returned to normal within 7 weeks of enzyme administration. Carboxypeptidase-G2 rapidly, markedly, and persistently lowered plasma MTX concentrations to a level that could be rescued safely with LV. Based on the experience with this patient and on preclinical studies in nonhuman primates, CPDG2 appears to be more effective than hemodialysis or hemoperfusion, and may prove beneficial for patients at risk for life-threatening toxicity secondary to delayed excretion of MTX. JF - Cancer AU - Widemann, B C AU - Hetherington, M L AU - Murphy, R F AU - Balis, F M AU - Adamson, P C AD - Pediatric Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1995/08/01/ PY - 1995 DA - 1995 Aug 01 SP - 521 EP - 526 VL - 76 IS - 3 SN - 0008-543X, 0008-543X KW - Antimetabolites, Antineoplastic KW - 0 KW - gamma-Glutamyl Hydrolase KW - EC 3.4.19.9 KW - Methotrexate KW - YL5FZ2Y5U1 KW - Abridged Index Medicus KW - Index Medicus KW - Femoral Neoplasms -- drug therapy KW - Osteosarcoma -- drug therapy KW - Humans KW - Adolescent KW - Female KW - Methotrexate -- pharmacokinetics KW - gamma-Glutamyl Hydrolase -- pharmacology KW - Methotrexate -- adverse effects KW - Acute Kidney Injury -- drug therapy KW - Antimetabolites, Antineoplastic -- adverse effects KW - Acute Kidney Injury -- chemically induced KW - Methotrexate -- therapeutic use KW - gamma-Glutamyl Hydrolase -- therapeutic use KW - Antimetabolites, Antineoplastic -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77843583?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer&rft.atitle=Carboxypeptidase-G2+rescue+in+a+patient+with+high+dose+methotrexate-induced+nephrotoxicity.&rft.au=Widemann%2C+B+C%3BHetherington%2C+M+L%3BMurphy%2C+R+F%3BBalis%2C+F+M%3BAdamson%2C+P+C&rft.aulast=Widemann&rft.aufirst=B&rft.date=1995-08-01&rft.volume=76&rft.issue=3&rft.spage=521&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-27 N1 - Date created - 1996-06-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Malignant pleural mesothelioma: newer aspects of carcinogenesis, molecular genetics, and prospects for future therapies. AN - 77810215; 8528480 AB - Malignant pleural mesothelioma (MPM) is an asbestos-related disease which, although rare, is having a major social impact, and is, for the majority of cases, an incurable illness. There has been a surge of information regarding data on mesothelial transformation, mesothelioma molecular genetics and somatic gene therapy for this disease. This report summarizes the most recent investigations attempting to characterize the behaviour, on a cellular and molecular level, of MPM, with an emphasis on data from investigations performed at the National Cancer Institute with our collaborators. JF - Surgical oncology AU - Donington, J S AU - Mew, D J AU - Pass, H I AD - Thoracic Oncology Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 175 EP - 185 VL - 4 IS - 4 SN - 0960-7404, 0960-7404 KW - Cytokines KW - 0 KW - Reactive Oxygen Species KW - Index Medicus KW - Reactive Oxygen Species -- metabolism KW - Base Sequence KW - Chromosome Aberrations -- etiology KW - Genes, Tumor Suppressor KW - DNA Damage KW - Simian virus 40 -- genetics KW - Humans KW - Asbestosis -- complications KW - Molecular Sequence Data KW - Chromosome Disorders KW - Genetic Therapy KW - Cytokines -- metabolism KW - Mesothelioma -- therapy KW - Mesothelioma -- metabolism KW - Pleural Neoplasms -- virology KW - Mesothelioma -- etiology KW - Mesothelioma -- genetics KW - Pleural Neoplasms -- therapy KW - Pleural Neoplasms -- genetics KW - Mesothelioma -- virology KW - Pleural Neoplasms -- etiology KW - Pleural Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77810215?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Surgical+oncology&rft.atitle=Malignant+pleural+mesothelioma%3A+newer+aspects+of+carcinogenesis%2C+molecular+genetics%2C+and+prospects+for+future+therapies.&rft.au=Donington%2C+J+S%3BMew%2C+D+J%3BPass%2C+H+I&rft.aulast=Donington&rft.aufirst=J&rft.date=1995-08-01&rft.volume=4&rft.issue=4&rft.spage=175&rft.isbn=&rft.btitle=&rft.title=Surgical+oncology&rft.issn=09607404&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-01 N1 - Date created - 1996-02-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicokinetics of 4-methylimidazole in the male F344 rat. AN - 77778853; 8779228 AB - The toxicokinetics and metabolism of 4-methylimidazole (4-MZ) have been studied in the male F344 rat using 14C radiolabelled compound. Radioactivity in plasma and urine was profiled by hplc. After gavage administration of 50 mg/kg, about 85% of the administered radioactivity was recovered in urine within 48 h. The majority of the radioactivity in urine or plasma was associated with the parent compound and only one minor hydrophilic metabolite was present in urine and in plasma. Elimination of radioactivity via fecal, biliary or respiration was negligible. Elimination of 4-MZ after an i.v. dose of 5 mg/kg can be described by a two-compartment process with an estimated half-life of 1.8 h and an estimated apparent volume of distribution of 2.3 litre/kg. After gavage at doses of 5, 50 and 150 mg/kg, 4-MZ was readily absorbed with a estimated bioavailability of 60-70%. Urinary excretion data indicated that renal clearance of 4-MZ accounted for about 80% of total body plasma clearance. Based on the estimated AUC of metabolite and the estimated renal clearance of 4-MZ, the formation of metabolite and the renal clearance of 4-MZ appeared to be a saturable process. JF - Xenobiotica; the fate of foreign compounds in biological systems AU - Yuan, J H AU - Burka, L T AD - National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 885 EP - 894 VL - 25 IS - 8 SN - 0049-8254, 0049-8254 KW - Imidazoles KW - 0 KW - Sulfates KW - 4-methylimidazole KW - Q64GF9FV4I KW - Index Medicus KW - Sulfates -- metabolism KW - Rats KW - Administration, Oral KW - Animals KW - Rats, Inbred F344 KW - Injections, Intravenous KW - Glomerular Filtration Rate KW - Biotransformation KW - Male KW - Chromatography, High Pressure Liquid KW - Imidazoles -- pharmacokinetics KW - Imidazoles -- blood KW - Imidazoles -- toxicity KW - Imidazoles -- urine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77778853?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Xenobiotica%3B+the+fate+of+foreign+compounds+in+biological+systems&rft.atitle=Toxicokinetics+of+4-methylimidazole+in+the+male+F344+rat.&rft.au=Yuan%2C+J+H%3BBurka%2C+L+T&rft.aulast=Yuan&rft.aufirst=J&rft.date=1995-08-01&rft.volume=25&rft.issue=8&rft.spage=885&rft.isbn=&rft.btitle=&rft.title=Xenobiotica%3B+the+fate+of+foreign+compounds+in+biological+systems&rft.issn=00498254&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-17 N1 - Date created - 1996-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Assessment of nalmefene glucuronide as a selective gut opioid antagonist. AN - 77736419; 8529534 AB - Opioid use often causes troublesome constipation as a side-effect. Selective antagonism of the intestinal actions of opioids might be useful in the treatment of opioid-induced constipation. We tested the inactive metabolite of nalmefene, nalmefene glucuronide, which showed promise of gut selectivity in rodent models, by administering ascending doses in single-blind, placebo-controlled fashion to five methadone-maintained, opioid-dependent male volunteers. Assessment of whether systemic or gut-selective opioid antagonist effects occurred was measured by vital signs, pupillary diameter, opioid withdrawal symptom scales, and bowel function. Oral nalmefene glucuronide precipitated symptoms and signs consistent with the opioid abstinence syndrome in all five subjects a mean of 9.0 h after dosing. We conclude that nalmefene glucuronide does not appear to exert sufficient gut selectivity to be useful in antagonizing constipation due to exogenous opioid administration without antagonizing systemic opioid effects. JF - Drug and alcohol dependence AU - Cheskin, L J AU - Chami, T N AU - Johnson, R E AU - Jaffe, J H AD - National Institute on Drug Abuse, Intramural Research Program, Baltimore, MD, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 151 EP - 154 VL - 39 IS - 2 SN - 0376-8716, 0376-8716 KW - Narcotic Antagonists KW - 0 KW - Naltrexone KW - 5S6W795CQM KW - nalmefene KW - TOV02TDP9I KW - Methadone KW - UC6VBE7V1Z KW - Index Medicus KW - Substance Withdrawal Syndrome -- physiopathology KW - Methadone -- therapeutic use KW - Dose-Response Relationship, Drug KW - Humans KW - Autonomic Nervous System -- drug effects KW - Adult KW - Neurologic Examination -- drug effects KW - Constipation -- physiopathology KW - Autonomic Nervous System -- physiopathology KW - Male KW - Opioid-Related Disorders -- physiopathology KW - Narcotic Antagonists -- therapeutic use KW - Narcotic Antagonists -- adverse effects KW - Gastrointestinal Motility -- physiology KW - Arousal -- drug effects KW - Naltrexone -- adverse effects KW - Naltrexone -- analogs & derivatives KW - Arousal -- physiology KW - Opioid-Related Disorders -- rehabilitation KW - Gastrointestinal Motility -- drug effects KW - Naltrexone -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77736419?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Assessment+of+nalmefene+glucuronide+as+a+selective+gut+opioid+antagonist.&rft.au=Cheskin%2C+L+J%3BChami%2C+T+N%3BJohnson%2C+R+E%3BJaffe%2C+J+H&rft.aulast=Cheskin&rft.aufirst=L&rft.date=1995-08-01&rft.volume=39&rft.issue=2&rft.spage=151&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 - 1996-01-29 N1 - Date created - 1996-01-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Common genetic mechanisms in alcohol, drug, and mental disorder comorbidity. AN - 77732000; 8529532 AB - Comorbid drug and mental disorders were assessed in 63 monozygotic (MZ) and 67 dizygotic (DZ) twin pairs. DSM-III alcohol dependence was heritable in males when probands had a comorbid DSM-III drug or mental disorder but not when probands had only alcohol dependence. For males, significantly higher cross-MZ than cross-DZ correlations were found between alcohol dependence in probands and certain mental and drug disorders in cotwins. In contrast, females showed higher within-twin than cross-MZ correlations and similar cross-MZ and cross-DZ correlations between alcohol dependence and all mental and drug disorders. These results suggest comorbidity between alcohol and certain drug and mental disorders in males in epidemiological surveys may be due in part to genetic influences. JF - Drug and alcohol dependence AU - Pickens, R W AU - Svikis, D S AU - McGue, M AU - LaBuda, M C AD - Division of Intramural Research, National Institute on Drug Abuse, Baltimore, MD, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 129 EP - 138 VL - 39 IS - 2 SN - 0376-8716, 0376-8716 KW - Index Medicus KW - Phenotype KW - Twins, Dizygotic -- genetics KW - Risk Factors KW - Humans KW - Adult KW - Patient Admission -- statistics & numerical data KW - Twins, Dizygotic -- psychology KW - Middle Aged KW - Maryland -- epidemiology KW - Twins, Monozygotic -- genetics KW - Male KW - Female KW - Comorbidity KW - Twins, Monozygotic -- psychology KW - Mental Disorders -- genetics KW - Alcoholism -- epidemiology KW - Mental Disorders -- epidemiology KW - Mental Disorders -- psychology KW - Diseases in Twins -- psychology KW - Substance-Related Disorders -- psychology KW - Alcoholism -- genetics KW - Diseases in Twins -- genetics KW - Alcoholism -- psychology KW - Substance-Related Disorders -- genetics KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77732000?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Common+genetic+mechanisms+in+alcohol%2C+drug%2C+and+mental+disorder+comorbidity.&rft.au=Pickens%2C+R+W%3BSvikis%2C+D+S%3BMcGue%2C+M%3BLaBuda%2C+M+C&rft.aulast=Pickens&rft.aufirst=R&rft.date=1995-08-01&rft.volume=39&rft.issue=2&rft.spage=129&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 - 1996-01-29 N1 - Date created - 1996-01-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The HMG-14/-17 chromosomal protein family: architectural elements that enhance transcription from chromatin templates. AN - 77694097; 8562917 AB - Chromosomal proteins HMG-14 and HMG-17 enhance the transcriptional potential of chromatin when incorporated into nucleosomes during, but not after, chromatin assembly on replicating DNA. Two molecules of either HMG-14 or HMG-17 can bind to nucleosome cores, independently of the underlying DNA sequence, in a cooperative fashion to limit nucleosome mobility and stabilize the structure of the nucleosome core without stabilizing the higher order chromatin structure. By modifying the structure of nucleosomes, the proteins affect the local structure of the chromatin fiber leading to an increase in the rate of transcriptional elongation but not initiation. We suggest that HMG-14/-17 are architectural elements which assist in the assembly of an unfolded chromatin fiber thereby decreasing the repressive activity of histones and facilitating transcriptional processes. JF - Seminars in cell biology AU - Bustin, M AU - Trieschmann, L AU - Postnikov, Y V AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 247 EP - 255 VL - 6 IS - 4 SN - 1043-4682, 1043-4682 KW - Chromatin KW - 0 KW - High Mobility Group Proteins KW - Index Medicus KW - Animals KW - Protein Folding KW - High Mobility Group Proteins -- genetics KW - Transcription, Genetic -- genetics KW - High Mobility Group Proteins -- ultrastructure KW - Chromatin -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77694097?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Obesity+Surgery&rft.atitle=20th+IFSO+World+Congress&rft.au=&rft.aulast=&rft.aufirst=&rft.date=2015-08-01&rft.volume=25&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Obesity+Surgery&rft.issn=09608923&rft_id=info:doi/10.1007%2Fs11695-015-1750-3 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-01 N1 - Date created - 1996-03-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genomic prospecting. AN - 77680844; 7585171 JF - Nature medicine AU - O'Brien, S J AD - Laboratory of Viral Carcinogenesis National Cancer Institute Frederick, Maryland 21702, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 742 EP - 744 VL - 1 IS - 8 SN - 1078-8956, 1078-8956 KW - Index Medicus KW - Animals KW - Humans KW - Immunity, Innate KW - Major Histocompatibility Complex KW - Species Specificity KW - Heart Defects, Congenital KW - Ecosystem KW - Genetic Variation KW - Research KW - Genome UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77680844?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genomic+prospecting.&rft.au=O%27Brien%2C+S+J&rft.aulast=O%27Brien&rft.aufirst=S&rft.date=1995-08-01&rft.volume=1&rft.issue=8&rft.spage=742&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 - 1995-12-28 N1 - Date created - 1995-12-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Novel sulfonated and phosphonated analogs of distamycin which inhibit the replication of HIV. AN - 77635503; 8540754 AB - A series of novel distamycin-related polyanionic compounds were compared for their anti-HIV activity. Several were highly potent inhibitors of HIV virus-induced cell killing and viral replication of a wide variety of laboratory isolates, as well as a monocytotropic virus and a clinical isolate in human peripheral blood lymphocytes. These compounds are structurally different from other sulfonic acid containing compounds reported to be potent inhibitors of the human immunodeficiency virus (HIV) in two respects: (1) they are structurally related to the non-toxic minor groove DNA binder distamycin; and (2) a number of them contain the aromatic phosphonic acid group. The compounds that were evaluated can be categorized into monomeric or dimeric ureido structural classes incorporating the bisamido-N-methylpyrrolenaphthalene-sulfonic acid group, with differences in the number and position of the sulfonic acids on the naphthalene rings. Broader structure-activity studies were made possible through the synthesis and evaluation of the compounds containing only a single N-methylpyrrole unit, those incorporating the N-methylpyrazole structure, and compounds having the isosteric phosphonic acid group substituted for the sulfonic acid group. One of the most potent of the inhibitors was 2,2'[4,4'[[aminocarbonyl]amino]bis[N,4'-di[pyrrole-2-carboxamide- 1,1'-dimethyl]]-4,6,8 naphthalenetrisulfonic acid] hexasodium salt, NSC 651015. This compound, the phosphonic acid analog NSC 662162, and the monomeric compound NSC 651018 were studied to determine the mechanism of their inhibitory activity. Mechanistic studies revealed that inhibition was due to the disruption of virus attachment to CD(4+)-susceptible cells and a further restraint on fusion of virus and cell membranes. The relative tolerance of these compounds in mice suggests that sufficient antiviral concentrations could be reached in vivo and thus may prove valuable in the treatment of AIDS patients. JF - Antiviral research AU - Clanton, D J AU - Buckheit, R W AU - Terpening, S J AU - Kiser, R AU - Mongelli, N AU - Borgia, A L AU - Schultz, R AU - Narayanan, V AU - Bader, J P AU - Rice, W G AD - Anti-AIDS Virus Drug Screening Laboratory, Program Resources, Inc./Dyncorp, NCI-Frederick Cancer Research and Development Center, MD 21702-1201, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 335 EP - 354 VL - 27 IS - 4 SN - 0166-3542, 0166-3542 KW - Antiviral Agents KW - 0 KW - Distamycins KW - Sulfur KW - 70FD1KFU70 KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Virus Replication -- drug effects KW - Humans KW - Molecular Sequence Data KW - Mice KW - Amino Acid Sequence KW - Cell Line KW - Structure-Activity Relationship KW - Distamycins -- chemistry KW - Antiviral Agents -- pharmacology KW - Antiviral Agents -- chemistry KW - HIV-2 -- drug effects KW - HIV-1 -- physiology KW - HIV-1 -- drug effects KW - HIV-2 -- physiology KW - Distamycins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77635503?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antiviral+research&rft.atitle=Novel+sulfonated+and+phosphonated+analogs+of+distamycin+which+inhibit+the+replication+of+HIV.&rft.au=Clanton%2C+D+J%3BBuckheit%2C+R+W%3BTerpening%2C+S+J%3BKiser%2C+R%3BMongelli%2C+N%3BBorgia%2C+A+L%3BSchultz%2C+R%3BNarayanan%2C+V%3BBader%2C+J+P%3BRice%2C+W+G&rft.aulast=Clanton&rft.aufirst=D&rft.date=1995-08-01&rft.volume=27&rft.issue=4&rft.spage=335&rft.isbn=&rft.btitle=&rft.title=Antiviral+research&rft.issn=01663542&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-08 N1 - Date created - 1996-02-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Perils and pitfalls on the path to normal potential: the role of impaired attention. Homage to Herbert G. Birch. AN - 77600211; 7593470 AB - The research of Herbert Birch and colleagues, conducted 30 years ago in a rural area of Guatemala, called attention to the permanent noxious effects on cognitive development associated with conditions of poverty. Half of the world's population, including millions of persons in the United States, are still afflicted by these conditions. Included among these are malnutrition, disease, toxic agents, perinatal injury, and lack of intellectual/social stimulation. Recent research findings on the cognitive effects of these poverty-related variables are presented; the effects appear to be expressed in a reduction of the brain's capacity to engage in attentive behavior. Neuropsychologists, by virtue of their interests and training, are in a position to develop methods of assessing and correcting these deficits, and must become advocates of improved conditions to foster better brain development for all of the world's children. JF - Journal of clinical and experimental neuropsychology AU - Mirsky, A F AD - Laboratory of Psychology and Psychopathology, NIMH, NIH, Bethesda, MD 20892-1366, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 481 EP - 498 VL - 17 IS - 4 SN - 1380-3395, 1380-3395 KW - Index Medicus KW - History of medicine KW - Birch KW - History, 20th Century KW - Rural Population KW - Humans KW - Guatemala KW - Infant, Newborn KW - Child KW - Pregnancy KW - Child, Preschool KW - Infant KW - Adult KW - Adolescent KW - Neuropsychological Tests KW - Urban Population KW - Female KW - Male KW - Prenatal Exposure Delayed Effects KW - Poverty -- history KW - Protein-Energy Malnutrition -- psychology KW - Protein-Energy Malnutrition -- etiology KW - Learning Disorders -- history KW - Learning Disorders -- psychology KW - Protein-Energy Malnutrition -- history KW - Learning Disorders -- etiology KW - Attention KW - Poverty -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77600211?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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+and+experimental+neuropsychology&rft.atitle=Perils+and+pitfalls+on+the+path+to+normal+potential%3A+the+role+of+impaired+attention.+Homage+to+Herbert+G.+Birch.&rft.au=Mirsky%2C+A+F&rft.aulast=Mirsky&rft.aufirst=A&rft.date=1995-08-01&rft.volume=17&rft.issue=4&rft.spage=481&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+and+experimental+neuropsychology&rft.issn=13803395&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-28 N1 - Date created - 1995-12-28 N1 - Date revised - 2017-01-13 N1 - People - Birch N1 - Last updated - 2017-01-18 N1 - SubjectsTermNotLitGenreText - Birch ER - TY - JOUR T1 - Cellular signals in alcohol-induced liver injury: a review. AN - 77582056; 7485841 JF - Alcoholism, clinical and experimental research AU - Lands, W E AD - Division of Basic Research, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, Maryland 20892-7003, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 928 EP - 938 VL - 19 IS - 4 SN - 0145-6008, 0145-6008 KW - Cytokines KW - 0 KW - Endotoxins KW - Platelet Activating Factor KW - Ethanol KW - 3K9958V90M KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Oxidoreductases, N-Demethylating KW - EC 1.5.- KW - Index Medicus KW - Animals KW - Humans KW - Kupffer Cells -- physiology KW - Kupffer Cells -- drug effects KW - Endothelium, Vascular -- physiopathology KW - Oxidoreductases, N-Demethylating -- physiology KW - Endothelium, Vascular -- drug effects KW - Platelet Activating Factor -- physiology KW - Liver Cirrhosis, Alcoholic -- physiopathology KW - Cytochrome P-450 Enzyme System -- physiology KW - Cytokines -- physiology KW - Fatty Liver, Alcoholic -- physiopathology KW - Endotoxins -- blood KW - Signal Transduction -- physiology KW - Ethanol -- pharmacokinetics KW - Signal Transduction -- drug effects KW - Liver Diseases, Alcoholic -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77582056?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cellular+signals+in+alcohol-induced+liver+injury%3A+a+review.&rft.au=Lands%2C+W+E&rft.aulast=Lands&rft.aufirst=W&rft.date=1995-08-01&rft.volume=19&rft.issue=4&rft.spage=928&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 - 1995-12-18 N1 - Date created - 1995-12-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The reproductive and neural toxicities of acrylamide and three analogues in Swiss mice, evaluated using the continuous breeding protocol. AN - 77581719; 7589932 AB - Acrylamide is a known genetic, reproductive, and neural toxicant, although it is not known if one effect is predominant. The toxicities of several structural analogues of acrylamide have been incompletely characterized, and the relative sensitivity of the second generation is not known. The present studies were designed to explore the relationship between neurotoxicity and reproductive toxicity, to further characterize the toxicities of three acrylamide analogues, and to evaluate the relative sensitivity of a second generation to these compounds. For the F0 generation, male and female Swiss CD-1 mice were provided drinking water containing acrylamide (ACR; 3, 10, 30 ppm), N,N'-methylenebisacrylamide (MBA; 10, 30, 60 ppm), N-(hydroxymethyl)acrylamide (HMA; 60, 180, 360 ppm), or methacrylamide (MACR; 24, 80, 240 ppm) during and after a 14-week cohabitation. The last litter was reared and dosed after weaning until mating at 74 +/- 10 days of age with the same level of compound given to the parents Neurotoxicity was assessed at several times in both generations by measuring forelimb and hindlimb grip strength. In the F0 generation, ACR caused an 11% decrease in pup number without measurable neurotoxicity; female fertility was not affected. Although both generations consumed the same amount of ACR, there were larger changes in the fertility-related endpoints in the F1 mice than in the F0's, with no concomitant change in organ weights or sperm parameters. In F0 mice, MBA reduced the number of live pups and their adjusted weight, with no neurotoxicity and no change in F0 female reproduction. MBA caused greater adverse effects in the second generation, concomitant with increased consumption. In the F0 generation, HMA caused the largest decrease in pup number during cohabitation (26%) together with a small effect on grip strength. Female reproduction was not affected. The second generation consumed more HMA and showed slightly greater toxic effects. In both generations, MACR was negative for both neurotoxicity and reproductive toxicity. Dominant-lethal studies showed that the fertility effects for ACR, MBA, and HMA could be explained by a male-mediated increase in postimplantation loss. These studies found that dominant lethality occurred without structural effects on the reproductive system in the presence of only minor effects on grip strength and without detectable neural histopathology. Female reproduction was not significantly affected by these compounds at the doses used. Thus, these data confirm the male as the affected gender and that the reproductive toxicity was greater than motoneuron toxicity when measured as grip strength. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Chapin, R E AU - Fail, P A AU - George, J D AU - Grizzle, T B AU - Heindel, J J AU - Harry, G J AU - Collins, B J AU - Teague, J AD - National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 9 EP - 24 VL - 27 IS - 1 SN - 0272-0590, 0272-0590 KW - Acrylamides KW - 0 KW - Acrylamide KW - 20R035KLCI KW - N-methylolacrylamide KW - 924-42-5 KW - N,N'-methylenebisacrylamide KW - EDK4RIE19C KW - methacrylamide KW - K67NG89J77 KW - Index Medicus KW - Animals KW - Hand Strength KW - Mice KW - Male KW - Female KW - Pregnancy KW - Germ-Line Mutation -- drug effects KW - Reproduction -- drug effects KW - Acrylamides -- toxicity KW - Nervous System -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77581719?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=The+reproductive+and+neural+toxicities+of+acrylamide+and+three+analogues+in+Swiss+mice%2C+evaluated+using+the+continuous+breeding+protocol.&rft.au=Chapin%2C+R+E%3BFail%2C+P+A%3BGeorge%2C+J+D%3BGrizzle%2C+T+B%3BHeindel%2C+J+J%3BHarry%2C+G+J%3BCollins%2C+B+J%3BTeague%2C+J&rft.aulast=Chapin&rft.aufirst=R&rft.date=1995-08-01&rft.volume=27&rft.issue=1&rft.spage=9&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-07 N1 - Date created - 1995-12-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Epidemiologic studies on the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM). AN - 77579657; 8549007 AB - The diagnostic criteria of the US National Diabetes Data Group and the World Health Organization have stimulated a major increase throughout the world in epidemiologic studies on the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM). They have established that much of NIDDM is undiagnosed, that onset of NIDDM occurs at least 7 y before its diagnosis, and that significant morbidity and premature mortality occur in subjects with undiagnosed diabetes. New studies have shown that rural or traditional-living populations are experiencing a major increase in the burden of NIDDM as they move to urban or nontraditional situations, often with 5- to 10-fold increases in NIDDM prevalence. Epidemiologic studies have documented that major risk factors for NIDDM include increasing age, greater obesity, longer duration of obesity, unfavourable body fat distribution, physical inactivity, and hyperinsulinemia. All these factors interact with unknown genetic factors to produce NIDDM. Studies have shown that genes for diabetes, as yet undetermined, are a necessary cause of NIDDM. Hyperinsulinemia exists in childhood in populations at high risk for NIDDM. Stimulated by obesity, upper body obesity, and physical inactivity, insulin resistance develops, accompanied by impaired glucose tolerance. The pressure of the NIDDM risk factors continues this process of insulin resistance/hyperinsulinemia/hyperglycemia, until glucose toxicity to the beta cell results in inability to secrete sufficient insulin, resulting in decompensated fasting hyperglycemia. JF - Clinical and investigative medicine. Medecine clinique et experimentale AU - Harris, M I AD - National Diabetes Data Group, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 231 EP - 239 VL - 18 IS - 4 SN - 0147-958X, 0147-958X KW - Index Medicus KW - Risk Factors KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - United States -- epidemiology KW - Male KW - Female KW - Prevalence KW - Diabetes Mellitus, Type 2 -- epidemiology KW - Diabetes Mellitus, Type 2 -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77579657?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+and+investigative+medicine.+Medecine+clinique+et+experimentale&rft.atitle=Epidemiologic+studies+on+the+pathogenesis+of+non-insulin-dependent+diabetes+mellitus+%28NIDDM%29.&rft.au=Harris%2C+M+I&rft.aulast=Harris&rft.aufirst=M&rft.date=1995-08-01&rft.volume=18&rft.issue=4&rft.spage=231&rft.isbn=&rft.btitle=&rft.title=Clinical+and+investigative+medicine.+Medecine+clinique+et+experimentale&rft.issn=0147958X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-22 N1 - Date created - 1996-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identifying alcoholism vulnerability alleles. AN - 77569788; 7485826 AB - Identification of vulnerability alleles is one starting point for elucidating the web of interactions leading to alcoholism so that treatment and prevention can be improved. Heritability studies indicate that vulnerability alleles exist. Two molecular approaches for identifying them, direct analysis of candidate genes and genetic linkage, are highlighted in this review. Methodological problems that have been partially addressed and limitations for the applicability of the genetic findings are discussed. JF - Alcoholism, clinical and experimental research AU - Goldman, D AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland 20852, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 824 EP - 831 VL - 19 IS - 4 SN - 0145-6008, 0145-6008 KW - Genetic Markers KW - 0 KW - Isoenzymes KW - Receptors, Dopamine D2 KW - Receptors, Serotonin KW - Monoamine Oxidase KW - EC 1.4.3.4 KW - Index Medicus KW - Animals KW - Genetic Markers -- genetics KW - Risk Factors KW - Models, Genetic KW - Humans KW - Linkage Disequilibrium -- genetics KW - Receptors, Dopamine D2 -- genetics KW - Receptors, Serotonin -- genetics KW - Isoenzymes -- genetics KW - Monoamine Oxidase -- genetics KW - Phenotype KW - Alleles KW - Alcoholism -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77569788?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Identifying+alcoholism+vulnerability+alleles.&rft.au=Goldman%2C+D&rft.aulast=Goldman&rft.aufirst=D&rft.date=1995-08-01&rft.volume=19&rft.issue=4&rft.spage=824&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 - 1995-12-18 N1 - Date created - 1995-12-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of the carboxy-terminal residues of the alpha-subunit in the expression and bioactivity of human thyroid-stimulating hormone. AN - 77567338; 7476992 AB - The glycoprotein hormones TSH, CG, LH, and FSH are heterodimers consisting of a hormone-specific beta-subunit and a common alpha-subunit. The aim of the present study was to investigate the role of the carboxy terminus of the common alpha-subunit (amino acids Tyr89-His90-Lys91-Ser92), which has been shown to be important for human (h) CG and hFSH, for the activity of hTSH. Successive truncations of the alpha-carboxy terminus by site-directed mutagenesis revealed a stepwise reduction of bioactivity occurring at residues alpha Ser92 and alpha His90 to 64% and 13%, respectively. This contrasts with previous findings for hCG and hFSH, where loss of bioactivity occurred in a single step with the deletion of alpha Lys91 but alpha Ser92 was not important. The decreased bioactivities of the hTSH alpha-truncation mutants were reflected by concomitant reductions of cAMP production, thyroid hormone synthesis and cell growth and were accompanied by a loss of receptor binding. Substitution of residues alpha Lys91 or alpha His90 with either a hydrophobic or a bulkier residues resulted in a reduction of receptor binding and signal transduction, indicating that the alpha-carboxy terminus of hTSH may interact with the TSH receptor in a tight contact area. Conversely, substitution of alpha His90 with smaller residues enhanced bioactivity. In addition, the integrity of the alpha-carboxy terminus was essential for hTSH expression. Thus, we showed common and different roles of the alpha-carboxy-terminal residues for the glycoprotein hormones. The unique role of alpha Ser92 in hTSH activity explains the evolutionary constraint to preserve the alpha-carboxy-terminal Ser92 in all glycoprotein hormones. JF - Molecular endocrinology (Baltimore, Md.) AU - Grossmann, M AU - Szkudlinski, M W AU - Zeng, H AU - Kraiem, Z AU - Ji, I AU - Tropea, J E AU - Ji, T H AU - Weintraub, B D AD - Molecular and Cellular Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1758, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 948 EP - 958 VL - 9 IS - 8 SN - 0888-8809, 0888-8809 KW - Receptors, Thyrotropin KW - 0 KW - Recombinant Proteins KW - Triiodothyronine KW - 06LU7C9H1V KW - Thyrotropin KW - 9002-71-5 KW - Cyclic AMP KW - E0399OZS9N KW - Index Medicus KW - Animals KW - Cyclic AMP -- biosynthesis KW - Humans KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Rats KW - Receptors, Thyrotropin -- physiology KW - Triiodothyronine -- secretion KW - Cells, Cultured KW - Molecular Sequence Data KW - Signal Transduction KW - Cell Division KW - Thyrotropin -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77567338?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Role+of+the+carboxy-terminal+residues+of+the+alpha-subunit+in+the+expression+and+bioactivity+of+human+thyroid-stimulating+hormone.&rft.au=Grossmann%2C+M%3BSzkudlinski%2C+M+W%3BZeng%2C+H%3BKraiem%2C+Z%3BJi%2C+I%3BTropea%2C+J+E%3BJi%2C+T+H%3BWeintraub%2C+B+D&rft.aulast=Grossmann&rft.aufirst=M&rft.date=1995-08-01&rft.volume=9&rft.issue=8&rft.spage=948&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 - 1995-12-06 N1 - Date created - 1995-12-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cerebral glucose utilization in polysubstance abuse. AN - 77558048; 8526968 AB - Regional cerebral glucose metabolism in subjects with histories of polysubstance abuse was compared to that in control subjects who were drawn from the same community. The substance abuse group showed lower absolute metabolic rates for glucose in lateral occipital gyrus and higher normalized metabolic rates in temporal and frontal areas, including orbitofrontal cortex. It is suggested that some patterns of brain function associated with polysubstance abuse may represent consequences of drug exposure, or they could reflect pre-existing differences that may be relevant to the etiology and maintenance of polysubstance abuse. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Stapleton, J M AU - Morgan, M J AU - Phillips, R L AU - Wong, D F AU - Yung, B C AU - Shaya, E K AU - Dannals, R F AU - Liu, X AU - Grayson, R L AU - London, E D AD - Division of Intramural Research, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 21 EP - 31 VL - 13 IS - 1 SN - 0893-133X, 0893-133X KW - Glucose KW - IY9XDZ35W2 KW - Index Medicus KW - Brain Mapping KW - Humans KW - Brain Chemistry KW - Adult KW - Occipital Lobe -- metabolism KW - Frontal Lobe -- metabolism KW - Tomography, Emission-Computed KW - Male KW - Glucose -- metabolism KW - Substance-Related Disorders KW - Brain -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77558048?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.atitle=Cerebral+glucose+utilization+in+polysubstance+abuse.&rft.au=Stapleton%2C+J+M%3BMorgan%2C+M+J%3BPhillips%2C+R+L%3BWong%2C+D+F%3BYung%2C+B+C%3BShaya%2C+E+K%3BDannals%2C+R+F%3BLiu%2C+X%3BGrayson%2C+R+L%3BLondon%2C+E+D&rft.aulast=Stapleton&rft.aufirst=J&rft.date=1995-08-01&rft.volume=13&rft.issue=1&rft.spage=21&rft.isbn=&rft.btitle=&rft.title=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.issn=0893133X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-29 N1 - Date created - 1996-01-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cortical maldevelopment, anti-psychotic drugs, and schizophrenia: a search for common ground. AN - 77555254; 7577773 AB - Two of the favorite hypotheses of schizophrenia research-maldevelopment of cerebral cortex and malfunction of brain dopamine systems-have often seemed difficult to reconcile. This article reviews recent research that suggests a heuristically useful reconciliation centered on the functional neuroanatomical concept of prefrontal-temporolimbic cortical connectivity. Anatomical findings from postmortem studies and neuropsychological and neuroimaging studies of brain function in patients with schizophrenia have implicated a developmental 'dysconnection' of temporolimbic-prefrontal cortices. The possibility that such dysconnection can account for the principal phenomenology of the illness, including its delayed onset and its treatment, is suggested by neurologic disease analogies such as metachromatic leukodystrophy and by recent studies in animals with developmental cortical lesions. Studies mapping neuronal gene expression indicate that all antipsychotic drugs modulate DNA transcription in a region of the nucleus accumbens that receives converging inputs from prefrontal and temporolimbic cortices, suggesting that indirect compensation for dysfunctional communication between prefrontal and temporolimbic cortices is a therapeutic mechanism of these drugs. Treatments aimed at direct cortical compensation may be more effective. JF - Schizophrenia research AU - Weinberger, D R AU - Lipska, B K AD - Clinical Brain Disorders Branch, National Institute of Mental Health, NIH, Neurosciences Center at Saint Elizabeths, Washington, DC 20032, USA. Y1 - 1995/08/01/ PY - 1995 DA - 1995 Aug 01 SP - 87 EP - 110 VL - 16 IS - 2 SN - 0920-9964, 0920-9964 KW - Antipsychotic Agents KW - 0 KW - Receptors, Dopamine KW - Index Medicus KW - Neural Pathways -- physiopathology KW - Neural Pathways -- abnormalities KW - Animals KW - Brain Mapping KW - Humans KW - Disease Models, Animal KW - Neural Pathways -- drug effects KW - Receptors, Dopamine -- drug effects KW - Receptors, Dopamine -- physiology KW - Cerebral Cortex -- drug effects KW - Cerebral Cortex -- abnormalities KW - Antipsychotic Agents -- therapeutic use KW - Schizophrenic Psychology KW - Schizophrenia -- drug therapy KW - Antipsychotic Agents -- adverse effects KW - Schizophrenia -- physiopathology KW - Cerebral Cortex -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77555254?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Schizophrenia+research&rft.atitle=Cortical+maldevelopment%2C+anti-psychotic+drugs%2C+and+schizophrenia%3A+a+search+for+common+ground.&rft.au=Weinberger%2C+D+R%3BLipska%2C+B+K&rft.aulast=Weinberger&rft.aufirst=D&rft.date=1995-08-01&rft.volume=16&rft.issue=2&rft.spage=87&rft.isbn=&rft.btitle=&rft.title=Schizophrenia+research&rft.issn=09209964&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-06 N1 - Date created - 1995-12-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of fibroblast growth factor receptors flg and bek during hepatic ontogenesis and regeneration in the rat. AN - 77543975; 8547216 AB - Fibroblast growth factors (FGFs) mediate their cellular responses through specific cell surface receptors. Previous studies have indicated that acidic FGF is involved in liver regeneration and hepatic differentiation via the stem cell compartment, as well as in liver development (Marsden et al., Lab. Invest. 67:427-433, 1992). To further define the role of acidic FGF and its receptor systems in the liver, we examined the expression and cellular localization of FGF receptor-1 (flg) and FGF receptor-2 (bek) in the liver by Northern blot analysis and in situ hybridization techniques during liver regeneration, hepatic differentiation, and ontogenesis. In the normal adult liver, flg is absent in hepatocytes, whereas a low level of bek can be detected. The transcripts for bek increased, while flg exhibited little change during liver regeneration after partial hepatectomy. Both flg and bek were expressed at high levels in the developing liver. flg was expressed at a high level in embryonic liver and further increased after birth, whereas a significant increase of bek occurred at the postnatal stage of liver development. In the 2-acetylaminofluorene/partial hepatectomy model, both flg and bek are expressed at high levels during the period of active proliferation and differentiation of oval cells. In situ hybridization showed that flg was mainly localized in oval cells, whereas bek was highly expressed in both oval and Ito cells. The data suggest that bek is involved in the proliferation of mature hepatocyte proliferation during liver regeneration, while flg is characteristic of primitive hepatic cells.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Hu, Z AU - Evarts, R P AU - Fujio, K AU - Marsden, E R AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 1019 EP - 1025 VL - 6 IS - 8 SN - 1044-9523, 1044-9523 KW - Receptors, Fibroblast Growth Factor KW - 0 KW - Fgfr3 protein, rat KW - 144590-76-1 KW - Fgfr2 protein, rat KW - EC 2.7.10.1 KW - Protein-Tyrosine Kinases KW - Receptor Protein-Tyrosine Kinases KW - Receptor, Fibroblast Growth Factor, Type 2 KW - Receptor, Fibroblast Growth Factor, Type 3 KW - Index Medicus KW - Rats KW - Animals KW - Reference Values KW - Rats, Inbred F344 KW - Cell Differentiation -- physiology KW - Embryonic and Fetal Development -- physiology KW - Stem Cells -- physiology KW - Male KW - Receptors, Fibroblast Growth Factor -- physiology KW - Liver -- growth & development KW - Receptor Protein-Tyrosine Kinases -- analysis KW - Receptor Protein-Tyrosine Kinases -- physiology KW - Liver Regeneration -- physiology KW - Liver -- chemistry KW - Liver -- embryology KW - Receptors, Fibroblast Growth Factor -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77543975?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Expression+of+fibroblast+growth+factor+receptors+flg+and+bek+during+hepatic+ontogenesis+and+regeneration+in+the+rat.&rft.au=Hu%2C+Z%3BEvarts%2C+R+P%3BFujio%2C+K%3BMarsden%2C+E+R%3BThorgeirsson%2C+S+S&rft.aulast=Hu&rft.aufirst=Z&rft.date=1995-08-01&rft.volume=6&rft.issue=8&rft.spage=1019&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 - 1996-02-20 N1 - Date created - 1996-02-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An economic evaluation of manic-depressive illness--1991. AN - 77533493; 7482006 AB - In 1991, the costs for manic-depressive illness, which has a lifetime prevalence of 1.3% among adult Americans, totaled $45 billion. Costs were broken down into their direct and indirect components. Direct costs totaling $7 billion consist of expenditures for inpatient and outpatient care, which are treatment related, as well as nontreatment-related expenditures such as those for the criminal justice system used by individuals with manic-depressive illness. Indirect costs, which were $38 billion, include the lost productivity of both wage-earners ($17 billion) and homemakers ($3 billion), individuals who are in institutions ($3 billion) or who have committed suicide ($8 billion), and caregivers who take care of manic-depressive family members ($6 billion). The method for determining each expenditure is provided, and the implications of these staggering costs are discussed. These calculations rely heavily on methods and data bases that were developed for the accompanying paper on the costs of schizophrenia. JF - Social psychiatry and psychiatric epidemiology AU - Wyatt, R J AU - Henter, I AD - Neuropsychiatry Branch, National Institute of Mental Health, Neuroscience Research Center at St. Elizabeths, Washington, DC 20032, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 213 EP - 219 VL - 30 IS - 5 SN - 0933-7954, 0933-7954 KW - Index Medicus KW - United States KW - Employment, Supported KW - Nursing Homes -- economics KW - Suicide, Attempted KW - Humans KW - Research -- economics KW - Substance-Related Disorders KW - Suicide KW - Ambulatory Care -- economics KW - Hospitalization -- economics KW - Bipolar Disorder -- therapy KW - Bipolar Disorder -- economics KW - Health Care Costs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77533493?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Social+psychiatry+and+psychiatric+epidemiology&rft.atitle=An+economic+evaluation+of+manic-depressive+illness--1991.&rft.au=Wyatt%2C+R+J%3BHenter%2C+I&rft.aulast=Wyatt&rft.aufirst=R&rft.date=1995-08-01&rft.volume=30&rft.issue=5&rft.spage=213&rft.isbn=&rft.btitle=&rft.title=Social+psychiatry+and+psychiatric+epidemiology&rft.issn=09337954&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-07 N1 - Date created - 1995-12-07 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Neuroprotective actions of 1-aminocyclopropanecarboxylic acid (ACPC): a partial agonist at strychnine-insensitive glycine sites. AN - 77521284; 7477740 AB - 1-Aminocyclopropanecarboxylic acid is a high affinity ligand with partial agonist properties at strychnine-insensitive glycine sites associated with the N-methyl-D-aspartate subtype of glutamate receptors. Since occupation of these sites appears required for operation of N-methyl-D-aspartate, receptor coupled cation channels, it was hypothesized that a glycine partial agonist could function as an N-methyl-D-aspartate antagonist. This hypothesis was examined by evaluating the in vivo and in vitro neuroprotective actions of 1-aminocyclopropanecarboxylic acid. 1-Aminocyclopropanecarboxlic acid (150-600 mg kg-1) administered to gerbils five minutes following twenty minutes of forebrain ischemia significantly improved seven day survival; the optimal dose (300 mg kg-1) increased 7 days survival > 4-fold, from 20% to 92%. Survival of hippocampal CA1 neurons (quantitated 7 days post-ischemia) was significantly (approximately 3-fold) increased by the 600 mg kg-1 dose. Seven day survival was not significantly increased when the interval between reperfusion and drug administration (300 mg kg-1) was increased from 5 to 30 min. In cerebellar granule cell cultures, NMDA combined with a saturating concentration of glycine (10 microM) resulted in a 500% increase in cGMP levels. cGMP levels were increased by 100% over basal when NMDA was combined with a saturating (10 microM) concentration of ACPC, indicating that in this measure, the efficacy of ACPC relative to glycine was approximately 0.2. Consistent with previous findings, 1-aminocyclopropanecarboxylic acid significantly reduced glutamate-induced neurotoxicity in cerebellar granule cell cultures. ACPC was most effective in blocking neurotoxicity at glutamate concentrations producing low to moderate levels of cell death.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Neurological research AU - Fossom, L H AU - Von Lubitz, D K AU - Lin, R C AU - Skolnick, P AD - Laboratory of Neuroscience, NIDDK, National Institutes of Health, Bethesda, MD 20892-0008, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 265 EP - 269 VL - 17 IS - 4 SN - 0161-6412, 0161-6412 KW - Neuroprotective Agents KW - 0 KW - Receptors, Glycine KW - Cycloleucine KW - 0TQU7668EI KW - Strychnine KW - H9Y79VD43J KW - Index Medicus KW - Rats KW - Gerbillinae KW - Animals KW - Rats, Sprague-Dawley KW - Cells, Cultured KW - Brain Ischemia -- prevention & control KW - Female KW - Cycloleucine -- therapeutic use KW - Receptors, Glycine -- agonists KW - Strychnine -- pharmacology KW - Neuroprotective Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77521284?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurological+research&rft.atitle=Neuroprotective+actions+of+1-aminocyclopropanecarboxylic+acid+%28ACPC%29%3A+a+partial+agonist+at+strychnine-insensitive+glycine+sites.&rft.au=Fossom%2C+L+H%3BVon+Lubitz%2C+D+K%3BLin%2C+R+C%3BSkolnick%2C+P&rft.aulast=Fossom&rft.aufirst=L&rft.date=1995-08-01&rft.volume=17&rft.issue=4&rft.spage=265&rft.isbn=&rft.btitle=&rft.title=Neurological+research&rft.issn=01616412&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-27 N1 - Date created - 1995-12-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pulmonary disease in AIDS: implications for respiratory care practitioners. AN - 77471393; 10144743 JF - Respiratory care AU - Medin, D L AU - Ognibene, F P AD - Warren G Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 832 EP - 854 VL - 40 IS - 8 SN - 0020-1324, 0020-1324 KW - Health administration KW - AIDS/HIV KW - United States KW - Respiratory Function Tests KW - Occupational Exposure -- prevention & control KW - Humans KW - AIDS-Related Opportunistic Infections -- pathology KW - Pneumocystis KW - Ethics, Medical KW - Mycobacterium tuberculosis KW - Lung Diseases -- etiology KW - Lung Diseases -- diagnosis KW - Acquired Immunodeficiency Syndrome -- therapy KW - Acquired Immunodeficiency Syndrome -- complications KW - Respiratory Therapy KW - Acquired Immunodeficiency Syndrome -- transmission UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77471393?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Respiratory+care&rft.atitle=Pulmonary+disease+in+AIDS%3A+implications+for+respiratory+care+practitioners.&rft.au=Medin%2C+D+L%3BOgnibene%2C+F+P&rft.aulast=Medin&rft.aufirst=D&rft.date=1995-08-01&rft.volume=40&rft.issue=8&rft.spage=832&rft.isbn=&rft.btitle=&rft.title=Respiratory+care&rft.issn=00201324&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-28 N1 - Date created - 1995-09-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of reverse ligation-PCR to identify transcriptional start sites in GC-rich TATA-less genes: application to the rat IGFBP-2 gene. AN - 77460809; 7544133 AB - TATA-less genes are often GC-rich in the region of transcriptional initiation and the corresponding mRNAs are prone to the formation of secondary structure. These properties have made it difficult to determine unambigously the start sites of transcription for some of these genes by conventional assays such as primer extension and nuclease protection. Using the TATA-less rat IGFBP-2 gene, we demonstrate that tobacco acid pyrophosphatase-reverse ligation polymerase chain reaction (TAP-RLPCR), a novel and sensitive assay, can be used to map the start sites of these genes. First, the validity of TAP-RLPCR was demonstrated by mapping the transcription start site of the rat insulin-like growth factor 1 (IGFBP-1) gene to the correct position (nucleotides -173 relative to ATG, +1). Using total RNA obtained from the rat liver cell line BRL-3A, the transcription start sites of the rat IGFBP-2 gene were mapped to a narrow cluster extending from nucleotides -86 to -90 (ATG, +1), 39 bp downstream of three adjacent GC boxes that are essential to the transcriptional activity of the gene. The assay was also used to map the start sites of a luciferase reporter gene driven by the fragment -1,295 to -32 of the rat IGFBP-2 promoter after transfection in the human embryonic kidney cell line 293. The hybrid gene utilized the same transcription start sites as the rat IGFBP-2 gene, indicating that the elements required for positioning of the transcription initiation complex are contained within the 3' end terminating at nucleotide -32.(ABSTRACT TRUNCATED AT 250 WORDS) JF - DNA and cell biology AU - Boisclair, Y R AU - Brown, A L AD - Growth and Development Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 731 EP - 739 VL - 14 IS - 8 SN - 1044-5498, 1044-5498 KW - Carrier Proteins KW - 0 KW - Insulin-Like Growth Factor Binding Protein 1 KW - Insulin-Like Growth Factor Binding Protein 2 KW - Luciferases KW - EC 1.13.12.- KW - Pyrophosphatases KW - EC 3.6.1.- KW - Index Medicus KW - Tobacco -- enzymology KW - Animals KW - Liver -- cytology KW - Kidney -- embryology KW - Rats KW - Plants, Toxic KW - Base Sequence KW - Genes, Reporter -- genetics KW - Molecular Sequence Data KW - Luciferases -- genetics KW - Cell Line KW - Carrier Proteins -- genetics KW - Polymerase Chain Reaction -- methods KW - Transcription, Genetic -- genetics KW - Promoter Regions, Genetic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77460809?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=DNA+and+cell+biology&rft.atitle=Use+of+reverse+ligation-PCR+to+identify+transcriptional+start+sites+in+GC-rich+TATA-less+genes%3A+application+to+the+rat+IGFBP-2+gene.&rft.au=Boisclair%2C+Y+R%3BBrown%2C+A+L&rft.aulast=Boisclair&rft.aufirst=Y&rft.date=1995-08-01&rft.volume=14&rft.issue=8&rft.spage=731&rft.isbn=&rft.btitle=&rft.title=DNA+and+cell+biology&rft.issn=10445498&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-25 N1 - Date created - 1995-09-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo induction of liver P-glycoprotein expression by xenobiotics in monkeys. AN - 77458030; 7645023 AB - P-glycoprotein (pgp), the protein product of the multidrug resistance (mdr) gene family, can confer a multidrug resistance (mdr) phenotype to cells in which it is expressed. One member of the pgp family, pgp2, is located on the hepatocyte biliary pole where it may have a role in biliary excretion. Using primates we sought to determine if mdr gene expression and pgp levels were affected by xenobiotics excreted via the bile in man. Five drugs were studied in male and female rhesus monkeys: erythromycin, rifampicin, tamoxifen, diethylstilbesterol (DES), and probenecid. For each xenobiotic, with the exception of DES, an increase in mdr2 mRNA was observed. The results suggest that expression of mdr2 is responsive to xenobiotics, or their metabolites, that require biliary excretion. We speculate that the mdr2 gene may be a member of a class of xenobiotic responsive genes coding for proteins that actively excrete xenobiotics and/or their metabolites into the bile. JF - Toxicology and applied pharmacology AU - Gant, T W AU - O'Connor, C K AU - Corbitt, R AU - Thorgeirsson, U AU - Thorgeirsson, S S AD - National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 269 EP - 276 VL - 133 IS - 2 SN - 0041-008X, 0041-008X KW - mdr1 KW - mdr2 KW - P-Glycoprotein KW - 0 KW - RNA, Messenger KW - Tamoxifen KW - 094ZI81Y45 KW - Erythromycin KW - 63937KV33D KW - Diethylstilbestrol KW - 731DCA35BT KW - Probenecid KW - PO572Z7917 KW - Rifampin KW - VJT6J7R4TR KW - Index Medicus KW - Tamoxifen -- toxicity KW - Animals KW - Probenecid -- administration & dosage KW - Electrophoresis, Polyacrylamide Gel KW - Diethylstilbestrol -- toxicity KW - Probenecid -- toxicity KW - Tamoxifen -- administration & dosage KW - Erythromycin -- administration & dosage KW - Rifampin -- toxicity KW - RNA, Messenger -- metabolism KW - Body Weight -- drug effects KW - Macaca mulatta KW - Rifampin -- administration & dosage KW - Diethylstilbestrol -- administration & dosage KW - Erythromycin -- toxicity KW - Female KW - Male KW - Densitometry KW - Organ Size -- drug effects KW - P-Glycoprotein -- genetics KW - Liver -- drug effects KW - Liver -- metabolism KW - Gene Expression Regulation -- drug effects KW - P-Glycoprotein -- biosynthesis KW - Gene Expression Regulation -- genetics KW - Drug Resistance, Multiple -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77458030?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=In+vivo+induction+of+liver+P-glycoprotein+expression+by+xenobiotics+in+monkeys.&rft.au=Gant%2C+T+W%3BO%27Connor%2C+C+K%3BCorbitt%2C+R%3BThorgeirsson%2C+U%3BThorgeirsson%2C+S+S&rft.aulast=Gant&rft.aufirst=T&rft.date=1995-08-01&rft.volume=133&rft.issue=2&rft.spage=269&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 - 1995-09-21 N1 - Date created - 1995-09-21 N1 - Date revised - 2017-01-13 N1 - Gene symbol - mdr1; mdr2 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Four-day paclitaxel infusion with cisplatin for patients with lung cancer. AN - 77454997; 7544027 AB - Lung cancer cell lines are between seven and 1,000 times more sensitive to paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ) when exposed for 120 hours (5 days) compared with 3-hour exposure. A phase I study of 4-day infusion of paclitaxel plus bolus cisplatin for patients with lung cancer has defined the recommended phase II dose. In this study, paclitaxel infused at 30 mg/m2/d for 4 days followed by a cisplatin bolus of 80 mg/m2 after infusion completion was associated with acceptable hematologic toxicity. Nine of the 16 patients with non-small cell lung cancer treated with at least two cycles of this regimen attained an objective tumor response (one complete response and eight partial responses; overall response rate, 56%). The recommended phase II dose of a 4-day infusion of paclitaxel plus bolus cisplatin followed by the administration of granulocyte colony-stimulating factor has not yet been determined. JF - Seminars in oncology AU - Georgiadis, M S AU - Schuler, B AU - Johnson, B E AD - National Cancer Institute-Navy Medical Oncology Branch, National Cancer Institute, Bethesda, MD 20889-5105, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 67 EP - 69 VL - 22 IS - 4 Suppl 9 SN - 0093-7754, 0093-7754 KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Paclitaxel KW - P88XT4IS4D KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Tumor Cells, Cultured KW - Neoplasm Staging KW - Injections, Intravenous KW - Infusions, Intravenous KW - Granulocyte Colony-Stimulating Factor -- therapeutic use KW - Dose-Response Relationship, Drug KW - Humans KW - Neutropenia -- chemically induced KW - Follow-Up Studies KW - Remission Induction KW - Paclitaxel -- administration & dosage KW - Paclitaxel -- adverse effects KW - Lung Neoplasms -- drug therapy KW - Cisplatin -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Carcinoma, Non-Small-Cell Lung -- drug therapy KW - Cisplatin -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77454997?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+oncology&rft.atitle=Four-day+paclitaxel+infusion+with+cisplatin+for+patients+with+lung+cancer.&rft.au=Georgiadis%2C+M+S%3BSchuler%2C+B%3BJohnson%2C+B+E&rft.aulast=Georgiadis&rft.aufirst=M&rft.date=1995-08-01&rft.volume=22&rft.issue=4+Suppl+9&rft.spage=67&rft.isbn=&rft.btitle=&rft.title=Seminars+in+oncology&rft.issn=00937754&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-21 N1 - Date created - 1995-09-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of free radicals and p53 in neuron apoptosis in vivo. AN - 77450712; 7643225 AB - Apoptosis is a mechanism of cell death operative in the normal development and regulation of vertebrate tissues and organ cellularity. During the postnatal development of the mouse cerebellum, extensive granule neuron apoptosis occurs that may regulate the final granule cell to Purkinje cell stoichiometry observed in the adult. Cerebellar granule cells are highly sensitive to genotoxic agents such as gamma-irradiation and methylazoxymethanol during the first 2 weeks of postnatal development. We demonstrate that ionizing radiation induces extensive cerebellar granule cell death via apoptosis in vivo. In p53 null mice, however, the cerebellar granule cells do not undergo apoptosis in response to gamma-irradiation. In mice heterozygous for the p53 allele, the granule cells apoptosis is delayed, indicating an intermediate response. The developmental apoptosis of cerebellar granule cells, however, occurs similarly in wild-type and p53 null mice. Therefore, neurons undergo p53-dependent and p53-independent apoptosis, depending upon the initiating stimulus that triggers DNA fragmentation. In contrast to x-ray damage, the extensive death of cerebellar granule cells induced by methylazoxymethanol was found to be independent of the DNA fragmentation characteristic of apoptosis, and was also independent of expression of p53. Ablation of neuron progenitor cells with genotoxic agents may occur by p53-dependent apoptosis or by p53-independent mechanisms not associated with DNA fragmentation. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Wood, K A AU - Youle, R J AD - Biochemistry Section, National Institutes of Health, Bethesda, Maryland 20892-1414, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 5851 EP - 5857 VL - 15 IS - 8 SN - 0270-6474, 0270-6474 KW - Free Radicals KW - 0 KW - Tumor Suppressor Protein p53 KW - Methylazoxymethanol Acetate KW - 592-62-1 KW - methylazoxymethanol KW - JGG19N3YDQ KW - Index Medicus KW - Animals KW - DNA Damage KW - Mice KW - Mice, Transgenic KW - Cerebellum -- metabolism KW - X-Rays KW - Cerebellum -- cytology KW - Heterozygote KW - Methylazoxymethanol Acetate -- analogs & derivatives KW - Methylazoxymethanol Acetate -- pharmacology KW - Immunohistochemistry KW - Cerebellum -- radiation effects KW - Tumor Suppressor Protein p53 -- physiology KW - Neurons -- drug effects KW - Apoptosis -- physiology KW - Neurons -- radiation effects KW - Apoptosis -- drug effects KW - Neurons -- physiology KW - Tumor Suppressor Protein p53 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77450712?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.atitle=The+role+of+free+radicals+and+p53+in+neuron+apoptosis+in+vivo.&rft.au=Wood%2C+K+A%3BYoule%2C+R+J&rft.aulast=Wood&rft.aufirst=K&rft.date=1995-08-01&rft.volume=15&rft.issue=8&rft.spage=5851&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 - 1995-09-20 N1 - Date created - 1995-09-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synthetic omega-conopeptides applied to the site of nerve injury suppress neuropathic pains in rats. AN - 77447818; 7636726 AB - In patients and animals with painful peripheral neuropathies, spontaneous ectopic discharge from injured primary afferents is hypothesized to maintain a central state of hyperexcitability that underlies hyperalgesia and allodynia. Temporary suppression of this discharge allows the central state to normalize, such that hyperalgesia and allodynia are absent or reduced until the resumption of the discharge rekindles central hyperexcitability. Previous work suggests that Ca++ channels are involved in the genesis of spontaneous discharge from injured afferents. We applied SNX-111 and SNX-124 (0.1-3.0 micrograms), synthetic homologs of omega-conopeptides (MVIIA and GVIA, respectively) and potent blockers of neuronal N-type voltage-sensitive Ca++ channels, to the site of nerve injury via chronically implanted perineural cannulae in rats with an experimental painful peripheral neuropathy (the chronic constriction injury model). Heat-hyperalgesia and mechano-allodynia were reduced for at least 3 hr. Drug application to a normal nerve had no effect on responses to heat or mechanical stimuli. These results suggest that N-type Ca++ channel blockers may be useful in the treatment of the abnormal pains that occur after nerve injury. JF - The Journal of pharmacology and experimental therapeutics AU - Xiao, W H AU - Bennett, G J AD - Neurobiology and Anesthesiology Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 666 EP - 672 VL - 274 IS - 2 SN - 0022-3565, 0022-3565 KW - Calcium Channel Blockers KW - 0 KW - Peptides KW - omega-Conotoxins KW - ziconotide KW - 7I64C51O16 KW - omega-Conotoxin GVIA KW - 92078-76-7 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Sciatic Nerve -- physiology KW - Sciatic Nerve -- drug effects KW - Male KW - Hyperalgesia -- drug therapy KW - Pain -- drug therapy KW - Calcium Channel Blockers -- pharmacology KW - Peptides -- pharmacology KW - Peripheral Nervous System Diseases -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77447818?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Synthetic+omega-conopeptides+applied+to+the+site+of+nerve+injury+suppress+neuropathic+pains+in+rats.&rft.au=Xiao%2C+W+H%3BBennett%2C+G+J&rft.aulast=Xiao&rft.aufirst=W&rft.date=1995-08-01&rft.volume=274&rft.issue=2&rft.spage=666&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-08 N1 - Date created - 1995-09-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - ENV-specific cytotoxic T lymphocyte responses in HIV seronegative health care workers occupationally exposed to HIV-contaminated body fluids. AN - 77443009; 7635981 AB - Identification of the components of protective immunity are crucial for the development of effective prophylactic and therapeutic vaccine strategies. Analysis of HIV-specific responses in exposed but uninfected individuals might thus provide a unique resource to elucidate the components and correlates of protective immunity to HIV. In the present study we analyzed HIV-specific cytotoxic and helper T lymphocyte responses in health care workers (HCW) exposed to body fluids from HIV-positive individuals. HCW exposed to blood from HIV-negative individuals as well as healthy donors served as controls. Cytotoxic T lymphocyte (CTL) responses to HIV envelope (env) peptides were detected in 7/20 (35%) HCW exposed to HIV-positive blood and in none of the 20 health care workers exposed to uninfected blood or the seven healthy blood donors studied. HIV-specific CTL responses were detected only after in vitro stimulation, and were MHC class I restricted. No MHC class I restriction elements were uniformly identified among the different responders. 21/28 (75%) HCW exposed to contaminated blood responded to env as measured by IL-2 production to the peptides, in contrast to only 9/38 (24%) HCW exposed to HIV seronegative blood and 3/35 (9%) healthy blood donors. All the HIV exposed individuals were seronegative on repeated ELISA tests, and no evidence of infection was obtained by PCR analysis. These findings indicate that a single exposure to HIV can induce CTL immunity to HIV antigens, in the absence of other evidence of infection. JF - The Journal of clinical investigation AU - Pinto, L A AU - Sullivan, J AU - Berzofsky, J A AU - Clerici, M AU - Kessler, H A AU - Landay, A L AU - Shearer, G M AD - Experimental Immunology Branche, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 867 EP - 876 VL - 96 IS - 2 SN - 0021-9738, 0021-9738 KW - ENV KW - Gene Products, env KW - 0 KW - Medical Waste KW - Zidovudine KW - 4B9XT59T7S KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Zidovudine -- therapeutic use KW - HIV Infections -- transmission KW - Needlestick Injuries -- drug therapy KW - Humans KW - Amino Acid Sequence KW - Blood Donors KW - Needlestick Injuries -- immunology KW - Prospective Studies KW - Adult KW - HIV Infections -- prevention & control KW - Proviruses -- isolation & purification KW - Molecular Sequence Data KW - Follow-Up Studies KW - Female KW - Male KW - Occupational Exposure KW - HIV-1 -- immunology KW - HIV-1 -- isolation & purification KW - Body Fluids -- virology KW - Health Personnel KW - Gene Products, env -- immunology KW - T-Lymphocytes, Cytotoxic -- immunology KW - HIV Seronegativity -- immunology KW - Accidents, Occupational UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77443009?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+investigation&rft.atitle=ENV-specific+cytotoxic+T+lymphocyte+responses+in+HIV+seronegative+health+care+workers+occupationally+exposed+to+HIV-contaminated+body+fluids.&rft.au=Pinto%2C+L+A%3BSullivan%2C+J%3BBerzofsky%2C+J+A%3BClerici%2C+M%3BKessler%2C+H+A%3BLanday%2C+A+L%3BShearer%2C+G+M&rft.aulast=Pinto&rft.aufirst=L&rft.date=1995-08-01&rft.volume=96&rft.issue=2&rft.spage=867&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+investigation&rft.issn=00219738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-11 N1 - Date created - 1995-09-11 N1 - Date revised - 2017-01-13 N1 - Gene symbol - ENV N1 - SuppNotes - Cited By: Nature. 1987 Jul 23-29;328(6128):345-8 [3496541] AIDS Res Hum Retroviruses. 1992 Aug;8(8):1355-9 [1466956] Science. 1988 Apr 1;240(4848):64-6 [2451288] J Virol. 1993 Feb;67(2):694-702 [7678303] J Exp Med. 1993 Feb 1;177(2):249-56 [8093890] J Virol. 1993 Apr;67(4):1772-7 [8095306] Lancet. 1993 Apr 3;341(8849):860-1 [8096564] J Immunol. 1993 Apr 15;150(8 Pt 1):3569-81 [8096852] J Exp Med. 1993 Jul 1;178(1):27-47 [8315383] J Acquir Immune Defic Syndr. 1993 Sep;6(9):969-76 [8340900] Eur J Immunol. 1993 Aug;23(8):2022-5 [8344368] Semin Immunol. 1993 Jun;5(3):215-23 [8394161] Int Immunol. 1993 Aug;5(8):849-57 [8398980] Science. 1993 Nov 12;262(5136):1059-61 [8235625] JAMA. 1994 Jan 5;271(1):42-6 [8258885] J Exp Med. 1994 Jan 1;179(1):317-21 [8270876] AIDS. 1993 Nov;7(11):1401-10 [8280406] AIDS. 1993 Nov;7(11):1427-33 [8280407] J Exp Med. 1994 Feb 1;179(2):463-72 [8294860] J Clin Invest. 1994 Mar;93(3):1293-7 [8132769] J Infect Dis. 1994 Jun;169(6):1236-43 [7910835] J Exp Med. 1994 Jun 1;179(6):1933-43 [8195718] J Virol. 1994 Jul;68(7):4650-5 [8207839] Adv Immunol. 1979;27:51-177 [92183] J Exp Med. 1986 Apr 1;163(4):903-21 [3485173] Nature. 1986 Aug 21-27;322(6081):687-9 [3489186] AIDS Res. 1986 Summer;2(3):163-74 [3489470] Curr Top Microbiol Immunol. 1986;128:1-54 [3533447] Clin Immunol Immunopathol. 1986 Dec;41(3):305-13 [2946499] Proc Natl Acad Sci U S A. 1987 Jun;84(12):4249-53 [2438696] Nature. 1994 Jun 23;369(6482):648-52 [7516038] J Immunol. 1994 Aug 1;153(3):996-1003 [8027569] AIDS Res Hum Retroviruses. 1994 Apr;10(4):395-403 [8068417] Curr Biol. 1994 Jun 1;4(6):499-505 [7922370] Clin Lab Med. 1994 Jun;14(2):271-99 [7924192] Curr Opin Immunol. 1994 Aug;6(4):530-8 [7946039] Curr Opin Immunol. 1994 Aug;6(4):545-52 [7946041] Curr Opin Immunol. 1994 Aug;6(4):553-9 [7524536] J Infect Dis. 1994 Nov;170(5):1296-9 [7963731] AIDS. 1994 Aug;8(8):1123-8 [7986410] AIDS. 1994 Oct;8(10):1391-5 [7818809] Proc Natl Acad Sci U S A. 1988 May;85(9):3105-9 [2452443] Nature. 1988 May 19;333(6170):215 [3368000] Cell. 1988 Sep 9;54(6):777-85 [3261634] J Immunol. 1989 Jan 1;142(1):270-3 [2521235] J Immunol. 1989 Jan 15;142(2):452-62 [2463308] J Exp Med. 1989 Apr 1;169(4):1255-64 [2784483] Blood. 1989 May 15;73(7):1909-14 [2785419] Nature. 1989 Jun 1;339(6223):383-5 [2524668] Nature. 1989 Nov 30;342(6249):561-4 [2586628] J Clin Invest. 1989 Dec;84(6):1892-9 [2574188] Cell. 1990 Apr 6;61(1):171-83 [2156628] AIDS Res Hum Retroviruses. 1990 May;6(5):673-8 [2113821] Ann Intern Med. 1990 Nov 15;113(10):740-6 [2240876] J Immunol. 1991 Mar 15;146(6):1862-7 [2005381] J Immunol. 1991 Apr 1;146(7):2214-9 [1826020] Int Immunol. 1989;1(4):409-15 [2484961] J Infect Dis. 1991 Jul;164(1):178-82 [1829105] Nature. 1991 Sep 12;353(6340):180-4 [1832488] J Infect Dis. 1992 Jun;165(6):1012-9 [1533867] Mol Aspects Med. 1991;12(4):283-96 [1726016] Eur J Immunol. 1992 Sep;22(9):2211-7 [1381309] J Med Primatol. 1992 Feb-May;21(2-3):99-107 [1433273] J Exp Med. 1988 Mar 1;167(3):914-23 [3127528] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immortalized rat whisker dermal papilla cells cooperate with mouse immature hair follicle buds to activate type IV procollagenases in collagen matrix coculture: correlation with ability to promote hair follicle development in nude mouse grafts. AN - 77442592; 7636298 AB - An in vivo nude mouse graft model and an in vitro collagen matrix culture system were used to study interactions of immature hair follicle buds from newborn mice with clonally derived AdE1A-12S-immortalized rat whisker dermal papilla cell lines. Of the 19 available dermal papilla cell lines, four consistently supported good hair follicle development and hair growth in grafts. Seven cell lines were clearly negative in this assay, and the remaining eight cell lines yielded poor to moderate hair growth. As a correlate to in vivo extracellular matrix remodeling accompanying hair follicle development, type IV collagenase activity in the medium from cocultures of dermal papilla cells and hair follicle buds was analyzed by gelatin zymography. Hair follicle buds cultured alone secrete primarily the 92-kDa type IV procollagenase. Cocultivation of hair follicle buds with eight of the dermal papilla cell lines resulted in activation of this proenzyme and activation of the 72-kDa and 92-kDa type IV procollagenases produced by the dermal papilla cells. Seven of these eight dermal papilla cell lines support hair growth in the graft system. In the absence of dermal papilla cells, several growth factors induced activation of the 92-kDa procollagenase secreted by hair follicle buds cultured in serum-free medium: epidermal growth factor, transforming growth factor alpha, acidic fibroblast growth factor, and keratinocyte growth factor. The current working hypothesis is that a) hair follicle epithelial cells interact with dermal papilla cells in coculture by mutual induction of growth factors and cytokines that stimulate the release and activation of matrix remodeling proteases; and b) the ability of dermal papilla cells to interact with hair follicle epithelial cells in this way may be crucial for controlled dermal matrix remodelling during HF development. JF - The Journal of investigative dermatology AU - Scandurro, A B AU - Wang, Q AU - Goodman, L AU - Ledbetter, S AU - Dooley, T P AU - Yuspa, S H AU - Lichti, U AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 177 EP - 183 VL - 105 IS - 2 SN - 0022-202X, 0022-202X KW - Enzyme Precursors KW - 0 KW - Collagen KW - 9007-34-5 KW - Collagenases KW - EC 3.4.24.- KW - procollagenase KW - Index Medicus KW - Rats KW - Animals KW - Cytological Techniques KW - Enzyme Activation KW - Cells, Cultured KW - Mice, Inbred C57BL KW - Mice, Nude KW - Mice KW - Cell Line, Transformed KW - Vibrissae -- cytology KW - Hair -- growth & development KW - Enzyme Precursors -- metabolism KW - Collagen -- metabolism KW - Skin Transplantation KW - Collagenases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77442592?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+investigative+dermatology&rft.atitle=Immortalized+rat+whisker+dermal+papilla+cells+cooperate+with+mouse+immature+hair+follicle+buds+to+activate+type+IV+procollagenases+in+collagen+matrix+coculture%3A+correlation+with+ability+to+promote+hair+follicle+development+in+nude+mouse+grafts.&rft.au=Scandurro%2C+A+B%3BWang%2C+Q%3BGoodman%2C+L%3BLedbetter%2C+S%3BDooley%2C+T+P%3BYuspa%2C+S+H%3BLichti%2C+U&rft.aulast=Scandurro&rft.aufirst=A&rft.date=1995-08-01&rft.volume=105&rft.issue=2&rft.spage=177&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+investigative+dermatology&rft.issn=0022202X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-12 N1 - Date created - 1995-09-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Occult caffeine as a source of sleep problems in an older population. AN - 77441219; 7636092 AB - To evaluate the impact of caffeine in medication on sleep complaints in a community population of persons aged 67 or older. Cross-sectional analysis. Iowa 65+ Rural Health Study. Those who completed their own interview, including a section on the use of medications, during the third annual in-person follow-up in 1984-1985. trouble falling asleep or other sleep complaints. Covariates: use of caffeine-containing medication, spasmolytic, or sympathomimetic drug; number of drugs used; depressive symptoms; self-perceived health; comorbidity, hip fracture, arthritis, ulcer of stomach or intestines; and consumption of caffeinated beverages. The prevalence of caffeinated medication use by participants was 5.4%. Those reporting the use of any caffeine-containing medication were at an increased risk of having trouble falling asleep (Odds Ratio [OR] = 1.79, 95% confidence interval [CI] = 1.19-2.68). There was no significant risk of other reported nighttime or daytime sleep problems associated with use of caffeine-containing drugs. Even after adjusting for other factors that could interfere with initiation of sleep, such as painful disease, depressive symptoms, polypharmacy, use of specific medications known to interfere with sleep, and coffee consumption, the use of caffeine-containing medication still presented a significantly increased risk of having trouble falling asleep (OR = 1.60, CI = 1.04-2.46). Although those participants using over-the-counter analgesic medication containing caffeine had an increased risk of trouble falling asleep (OR = 1.88, CI = 1.22-2.90), there was no significant risk of trouble falling asleep for those who took similar noncaffeinated OTC analgesic drugs (OR = 1.26, CI = 0.87-1.83). The use of caffeine-containing medication is associated with sleep problems. Healthcare providers should be aware of potential problems associated with over-the-counter medications containing caffeine and should counsel patients about the potential of sleep problems. Older patients should be encouraged to read the label on medications and to select drugs that are caffeine-free when that is possible. JF - Journal of the American Geriatrics Society AU - Brown, S L AU - Salive, M E AU - Pahor, M AU - Foley, D J AU - Corti, M C AU - Langlois, J A AU - Wallace, R B AU - Harris, T B AD - Epidemiology, Demography, and Biometry Program, National Institute on Aging, Bethesda, Maryland, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 860 EP - 864 VL - 43 IS - 8 SN - 0002-8614, 0002-8614 KW - Caffeine KW - 3G6A5W338E KW - Index Medicus KW - Rural Health KW - Cross-Sectional Studies KW - Logistic Models KW - Humans KW - Drug-Related Side Effects and Adverse Reactions KW - Surveys and Questionnaires KW - Diet Surveys KW - Aged KW - Follow-Up Studies KW - Male KW - Iowa -- epidemiology KW - Female KW - Sleep Wake Disorders -- chemically induced KW - Caffeine -- adverse effects KW - Sleep Wake Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77441219?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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+Geriatrics+Society&rft.atitle=Occult+caffeine+as+a+source+of+sleep+problems+in+an+older+population.&rft.au=Brown%2C+S+L%3BSalive%2C+M+E%3BPahor%2C+M%3BFoley%2C+D+J%3BCorti%2C+M+C%3BLanglois%2C+J+A%3BWallace%2C+R+B%3BHarris%2C+T+B&rft.aulast=Brown&rft.aufirst=S&rft.date=1995-08-01&rft.volume=43&rft.issue=8&rft.spage=860&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Geriatrics+Society&rft.issn=00028614&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-11 N1 - Date created - 1995-09-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I/II study of intermittent all-trans-retinoic acid, alone and in combination with interferon alfa-2a, in patients with epidemic Kaposi's sarcoma. AN - 77440877; 7636537 AB - A phase I/II study of oral all-trans-retinoic acid (ATRA; tretinoin), administered every other week alone and then in combination with interferon (IFN) alfa-2a, was undertaken to evaluate the activity, toxicity, and pharmacokinetics of this regimen in patients with human immunodeficiency virus (HIV)-associated Kaposi's sarcoma (KS). Thirteen patients with HIV-associated KS, eight of whom had more than 100 CD4 cells/microL, were entered. The protocol initially called for patients to receive 150 mg/m2/d of ATRA every other week. However, this regimen was associated with headaches, and the initial dose of ATRA was reduced to 40 mg/m2/d orally in three divided doses, increasing to a maximum of 100 mg/m2/d. After 12 weeks, IFN alfa-2a could be added. The principal toxicities from ATRA were headaches (12 patients) and dry skin or lip (seven patients). Of 12 assessable patients, 10 had progressive disease and two had stable disease on ATRA alone. One of eight assessable patients who went on to receive ATRA plus IFN alfa-2a had partial response (PR). There were no overall changes in the serum HIV p24 antigen (Ag) level or CD4 count during treatment with ATRA alone. Peak ATRA levels decreased during the week of continuous ATRA therapy, but rebounded when treatment was resumed after a week without the drug. Intermittent ATRA therapy was reasonably well tolerated and provided a means to circumvent the low plasma exposure found with continuous ATRA therapy. However, we were unable to document antitumor activity in patients with HIV-associated KS. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Bailey, J AU - Pluda, J M AU - Foli, A AU - Saville, M W AU - Bauza, S AU - Adamson, P C AU - Murphy, R F AU - Cohen, R B AU - Broder, S AU - Yarchoan, R AD - Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 1966 EP - 1974 VL - 13 IS - 8 SN - 0732-183X, 0732-183X KW - Interferon-alpha KW - 0 KW - Recombinant Proteins KW - interferon alfa-2a KW - 47RRR83SK7 KW - Tretinoin KW - 5688UTC01R KW - Index Medicus KW - AIDS/HIV KW - Regression Analysis KW - HIV -- drug effects KW - Drug Administration Schedule KW - Combined Modality Therapy KW - Humans KW - HIV -- physiology KW - Headache -- chemically induced KW - HIV Infections -- complications KW - Virus Replication -- drug effects KW - Adult KW - Least-Squares Analysis KW - Middle Aged KW - Male KW - Remission Induction KW - Sarcoma, Kaposi -- drug therapy KW - Interferon-alpha -- therapeutic use KW - Tretinoin -- administration & dosage KW - Sarcoma, Kaposi -- virology KW - Tretinoin -- pharmacokinetics KW - Sarcoma, Kaposi -- therapy KW - Tretinoin -- adverse effects KW - Sarcoma, Kaposi -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77440877?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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%2FII+study+of+intermittent+all-trans-retinoic+acid%2C+alone+and+in+combination+with+interferon+alfa-2a%2C+in+patients+with+epidemic+Kaposi%27s+sarcoma.&rft.au=Bailey%2C+J%3BPluda%2C+J+M%3BFoli%2C+A%3BSaville%2C+M+W%3BBauza%2C+S%3BAdamson%2C+P+C%3BMurphy%2C+R+F%3BCohen%2C+R+B%3BBroder%2C+S%3BYarchoan%2C+R&rft.aulast=Bailey&rft.aufirst=J&rft.date=1995-08-01&rft.volume=13&rft.issue=8&rft.spage=1966&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 - 1995-09-11 N1 - Date created - 1995-09-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Paclitaxel activity in heavily pretreated breast cancer: a National Cancer Institute Treatment Referral Center trial. AN - 77439997; 7543562 AB - To provide paclitaxel, an investigational drug at the inception of this study, to women with chemotherapy-refractory metastatic breast cancer and to evaluate response and toxicity in these patients. Two hundred sixty-seven patients with progressive disease (PD) following at least two chemotherapy regimens for metastatic breast cancer and a contraindication to further doxorubicin treatment received paclitaxel either at 175 mg/m2 intravenously (IV) over 24 hours or at 135 mg/m2 if they had prior irradiation to 30% of marrow-bearing bone or a cumulative dose of mitomycin > or = 20 mg/m2. In a subgroup of patients (n = 172) with measurable disease, four complete responses (CRs) and 36 partial responses (PRs) occurred, for an overall response rate of 23% (95% confidence interval [CI], 17% to 30%). No differences in response rates were noted according either to the number of prior chemotherapy regimens received or to whether patients were considered refractory to doxorubicin. The dose and schedule used in this trial resulted in febrile neutropenia in 45% of patients and a hospitalization rate of 49%. Paclitaxel's activity in this multiinstitutional trial in heavily pretreated patients confirms the encouraging results attained in single-institution trials. Although at this dose and schedule paclitaxel may be considered too myelosuppressive for palliative care, supportive measures such as colony-stimulating factors and antibiotics were not used prophylactically. Current research efforts are focusing on whether paclitaxel's activity against breast cancer is dose- and/or schedule-dependent, and on what role it has in patients with less advanced disease. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Abrams, J S AU - Vena, D A AU - Baltz, J AU - Adams, J AU - Montello, M AU - Christian, M AU - Onetto, N AU - Desmond-Hellmann, S AU - Canetta, R AU - Friedman, M A AD - Division of Cancer Treatment, National Cancer Institute, Bethesda, MD 20892-7436, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 2056 EP - 2065 VL - 13 IS - 8 SN - 0732-183X, 0732-183X KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - United States KW - Disease-Free Survival KW - Granulocyte Colony-Stimulating Factor -- therapeutic use KW - Chi-Square Distribution KW - Humans KW - Referral and Consultation KW - Neutropenia -- prevention & control KW - Aged KW - Neutropenia -- chemically induced KW - Aged, 80 and over KW - Adult KW - National Institutes of Health (U.S.) KW - Neoplasm Metastasis KW - Middle Aged KW - Female KW - Remission Induction KW - Paclitaxel -- administration & dosage KW - Breast Neoplasms -- drug therapy KW - Paclitaxel -- adverse effects KW - Breast Neoplasms -- pathology KW - Paclitaxel -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77439997?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Paclitaxel+activity+in+heavily+pretreated+breast+cancer%3A+a+National+Cancer+Institute+Treatment+Referral+Center+trial.&rft.au=Abrams%2C+J+S%3BVena%2C+D+A%3BBaltz%2C+J%3BAdams%2C+J%3BMontello%2C+M%3BChristian%2C+M%3BOnetto%2C+N%3BDesmond-Hellmann%2C+S%3BCanetta%2C+R%3BFriedman%2C+M+A&rft.aulast=Abrams&rft.aufirst=J&rft.date=1995-08-01&rft.volume=13&rft.issue=8&rft.spage=2056&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 - 1995-09-11 N1 - Date created - 1995-09-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - IL-4 inhibits IL-2-induced tumoricidal activity and secretory functions of human monocytes. Modulation of IL-2 binding and IL-2 receptor beta gamma chain expression. AN - 77439368; 7636206 AB - Human monocytes express functional IL-2 receptors (IL-2R) and are directly activated by IL-2 to exert effector and secretory functions. In this study, we show that IL-4 selectively suppressed, in a dose-dependent manner, IL-2-induced monocyte tumoricidal activity, without affecting IFN-gamma-dependent cytotoxicity. This effect was specific because a neutralizing anti-IL-4 mAb completely restored IL-2-activated cytolysis. Furthermore, IL-4 effectively blocked the secretion of proinflammatory cytokines by IL-2-stimulated monocytes. Binding studies with biotin-conjugated IL-2 demonstrated that monocyte stimulation with IL-2 increased IL-2 binding to the cell surface, and that treatment with IL-4 inhibited this augmentation, providing a possible explanation for the decreased responsiveness of monocytes to IL-2 in the presence of IL-4. However, IL-4 suppressive effects could not be ascribed to the down-regulation of the individual components of the IL-2R complex. In fact, co-treatment of monocytes with IL-2 and IL-4 increased the expression of IL-2R gamma chain above the levels induced by IL-2 alone, whereas it did not significantly affect the expression of IL-2R beta chain. Thus, the inhibition of IL-2 binding by IL-4 may be due to the recruitment of the gamma chain into the IL-4-IL-4R system, making it unavailable for participation in the formation of IL-2 binding sites. These findings provide the first evidence of the ability of IL-4 to suppress IL-2-mediated activation of human monocytes and suggest that IL-4 may play an important role in vivo as an inhibitory signal that controls the response of monocytes to IL-2. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Bosco, M C AU - Pulkki, K AU - Rowe, T K AU - Zea, A H AU - Musso, T AU - Longo, D L AU - Varesio, L AU - Espinoza-Delgado, I AD - Laboratory of Experimental Immunology, Inc/DynCorp, NCI-FCRDC, Frederick, MD 21702, USA. Y1 - 1995/08/01/ PY - 1995 DA - 1995 Aug 01 SP - 1411 EP - 1419 VL - 155 IS - 3 SN - 0022-1767, 0022-1767 KW - c-fms KW - Antibodies, Monoclonal KW - 0 KW - Cytokines KW - Interleukin-2 KW - Receptors, Interleukin-2 KW - Interleukin-4 KW - 207137-56-2 KW - Abridged Index Medicus KW - Index Medicus KW - Tumor Cells, Cultured KW - Carcinoma -- pathology KW - Protein Binding -- drug effects KW - Humans KW - Cytokines -- secretion KW - Cytotoxicity Tests, Immunologic KW - Antibodies, Monoclonal -- pharmacology KW - Down-Regulation -- drug effects KW - Colonic Neoplasms -- pathology KW - Antibodies, Monoclonal -- immunology KW - Interleukin-2 -- antagonists & inhibitors KW - Receptors, Interleukin-2 -- metabolism KW - Interleukin-2 -- metabolism KW - Monocytes -- physiology KW - Interleukin-4 -- pharmacology KW - Monocytes -- drug effects KW - Gene Expression Regulation -- drug effects KW - Cytotoxicity, Immunologic -- drug effects KW - Receptors, Interleukin-2 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77439368?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=IL-4+inhibits+IL-2-induced+tumoricidal+activity+and+secretory+functions+of+human+monocytes.+Modulation+of+IL-2+binding+and+IL-2+receptor+beta+gamma+chain+expression.&rft.au=Bosco%2C+M+C%3BPulkki%2C+K%3BRowe%2C+T+K%3BZea%2C+A+H%3BMusso%2C+T%3BLongo%2C+D+L%3BVaresio%2C+L%3BEspinoza-Delgado%2C+I&rft.aulast=Bosco&rft.aufirst=M&rft.date=1995-08-01&rft.volume=155&rft.issue=3&rft.spage=1411&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 - 1995-09-12 N1 - Date created - 1995-09-12 N1 - Date revised - 2017-01-13 N1 - Gene symbol - c-fms N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The neurokinin1 receptor antagonist CP-99,994 reduces catalepsy produced by the dopamine D2 receptor antagonist raclopride: correlation with extracellular acetylcholine levels in striatum. AN - 77438799; 7636756 AB - The ability of the substance P (NK1) receptor antagonist CP-99,994 to alter catalepsy induced by a dopamine D1 or D2 receptor antagonist and the ability of CP-99,994 to influence acetylcholine (ACh) release in the striatum were investigated in rats. Catalepsy produced by the D1 antagonist SCH 23390 (0.5 mg/kg s.c.) was not altered by CP-99,994 (0.5, 2.5, or 10 mg/kg s.c.). In contrast, catalepsy induced by the D2 antagonist raclopride (2.5 mg/kg i.p.) was attenuated by CP-99,994 (2.5 and 10 mg/kg). CP-99,994 (10 mg/kg) did not stimulate locomotion when given alone. The less active enantiomer of CP-99,994, CP-100,263 (10 mg/kg), did not alter raclopride-induced catalepsy. Both systemic administration and intrastriatal perfusion of CP-99,994 alone decreased striatal ACh release. Bilateral intrastriatal perfusion of CP-99,994 (40 and 100 microM) reduced catalepsy produced by raclopride and attenuated raclopride-induced increases in striatal ACh release. The reductions in the duration of catalepsy and decreases in striatal ACh release associated with CP-99,994 perfusion were positively correlated. These findings suggest that blockade of striatal NK1 receptors reduces catalepsy induced by a dopamine D2 antagonist, an effect mediated, at least in part, by reducing striatal ACh release. Striatal NK1 receptors, therefore, may be a new therapeutic target for developing drugs that alleviate motor side effects associated with antipsychotic treatment. JF - The Journal of pharmacology and experimental therapeutics AU - Anderson, J J AU - Randall, S AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 928 EP - 936 VL - 274 IS - 2 SN - 0022-3565, 0022-3565 KW - Benzazepines KW - 0 KW - Neurokinin-1 Receptor Antagonists KW - Piperidines KW - Salicylamides KW - 3-(2-methoxybenzylamino)-2-phenylpiperidine KW - 136982-36-0 KW - Raclopride KW - 430K3SOZ7G KW - Acetylcholine KW - N9YNS0M02X KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Benzazepines -- pharmacology KW - Male KW - Piperidines -- pharmacology KW - Corpus Striatum -- secretion KW - Catalepsy -- chemically induced KW - Catalepsy -- prevention & control KW - Salicylamides -- pharmacology KW - Corpus Striatum -- drug effects KW - Acetylcholine -- secretion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77438799?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=The+neurokinin1+receptor+antagonist+CP-99%2C994+reduces+catalepsy+produced+by+the+dopamine+D2+receptor+antagonist+raclopride%3A+correlation+with+extracellular+acetylcholine+levels+in+striatum.&rft.au=Anderson%2C+J+J%3BRandall%2C+S%3BChase%2C+T+N&rft.aulast=Anderson&rft.aufirst=J&rft.date=1995-08-01&rft.volume=274&rft.issue=2&rft.spage=928&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-08 N1 - Date created - 1995-09-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of R-verapamil on the pharmacokinetics of paclitaxel in women with breast cancer. AN - 77438230; 7636546 AB - To study the effect of the multidrug-resistance reversal agent R-verapamil on the pharmacokinetic behavior of paclitaxel. Six women with breast cancer who received paclitaxel as a 3-hour infusion with and without R-verapamil were monitored with frequent plasma sampling up to 24 hours postinfusion. Paclitaxel concentrations were measured using a reverse-phase high-pressure liquid chromatography assay. Concomitant administration of R-verapamil resulted in a decrease in mean (+/- SD) paclitaxel clearance from 179 +/- 67 mL/min/m2 to 90 +/- 34 mL/min/m2 (P < .03) and in a twofold increase in paclitaxel exposure (area under the curve [AUC]). The mean end-infusion paclitaxel concentration was also twofold higher: 5.1 +/- 1.8 mumol/L versus 11.3 +/- 4.1 mumol/L (P < .03). The alteration in paclitaxel pharmacokinetics when paclitaxel and R-verapamil are coadministered complicates the interpretation of response and toxicity data from clinical trials of this drug combination. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Berg, S L AU - Tolcher, A AU - O'Shaughnessy, J A AU - Denicoff, A M AU - Noone, M AU - Ognibene, F P AU - Cowan, K H AU - Balis, F M AD - Pediatric Branch, National Cancer Institute, Bethesda, MD, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 2039 EP - 2042 VL - 13 IS - 8 SN - 0732-183X, 0732-183X KW - Verapamil KW - CJ0O37KU29 KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Drug Therapy, Combination KW - Humans KW - Metabolic Clearance Rate -- drug effects KW - Cross-Over Studies KW - Female KW - Chromatography, High Pressure Liquid KW - Breast Neoplasms -- drug therapy KW - Paclitaxel -- pharmacokinetics KW - Paclitaxel -- therapeutic use KW - Verapamil -- therapeutic use KW - Breast Neoplasms -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77438230?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Obesity+Surgery&rft.atitle=Abstracts+from+the+19th+World+Congress+of+the+International+Federation+for+the+Surgery+of+Obesity+%26amp%3B+Metabolic+Disorders+%28IFSO%29%2C+Montreal%2C+Canada+26-30+August+2014&rft.au=Anonymous&rft.aulast=Anonymous&rft.aufirst=&rft.date=2014-08-01&rft.volume=24&rft.issue=8&rft.spage=1136&rft.isbn=&rft.btitle=&rft.title=Obesity+Surgery&rft.issn=09608923&rft_id=info:doi/10.1007%2Fs11695-014-1292-0 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-11 N1 - Date created - 1995-09-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - H-ras oncogene mutation spectra in B6C3F1 and C57BL/6 mouse liver tumors provide evidence for TCDD promotion of spontaneous and vinyl carbamate-initiated liver cells. AN - 77438127; 7634393 AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent environmental toxin which has been found to be non-genotoxic in short term in vitro tests but strongly carcinogenic in two stage models of hepatocellular carcinogenesis in female rats. Many recent studies have shown that after treatment of mice with various genotoxic or non-genotoxic compounds, the H-ras oncogene mutational patterns exhibited by hepatocellular tumors appear to vary specifically with the chemical. To gain insight into the mechanism of TCDD-associated carcinogenesis, susceptible B6C3F1 mice and resistant C57BL/6 mice were treated with a single dose of vinyl carbamate (VC) or vehicle, and TCDD was administered once every 2 weeks for 1 year to half of the animals in each group. Liver tumor prevalence was assessed and found to be highest in the VC + TCDD treatment groups, reaching nearly 100% at 600 days in both sexes and both strains of mice. DNA was isolated from 20 or more frozen liver tumors (if available) from each exposure group and analyzed for H-ras mutations in codon 61 by sequencing after PCR amplification of exon 2. Fifty-one percent of tumors analyzed from B6C3F1 mice treated with TCDD alone had H-ras codon 61 mutations with a pattern similar to that detected in spontaneous tumors. Seventy-eight percent of tumors from B6C3F1 mice treated with both VC and TCDD had codon 61 mutations, and most mutations were A-->T transversions in the second base as observed similarly with VC alone. In the C57BL/6 strain comparable results were found in the respective exposure groups. These data suggest that TCDD is acting as a promoter of lesions previously initiated either spontaneously or by VC. Moreover, the intrinsic resistance of both male and female C57BL/6 mice to liver tumor formation seemed to disappear after treatment with TCDD. JF - Carcinogenesis AU - Watson, M A AU - Devereux, T R AU - Malarkey, D E AU - Anderson, M W AU - Maronpot, R R AD - Environmental Carcinogenesis Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 1705 EP - 1710 VL - 16 IS - 8 SN - 0143-3334, 0143-3334 KW - H-ras KW - Polychlorinated Dibenzodioxins KW - 0 KW - Urethane KW - 3IN71E75Z5 KW - vinyl carbamate KW - 7Y2431GOM5 KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - Animals KW - Base Sequence KW - Molecular Sequence Data KW - Mice, Inbred C57BL KW - Mice, Inbred C3H KW - Mice KW - Male KW - Female KW - Genes, ras KW - Liver Neoplasms, Experimental -- genetics KW - Urethane -- analogs & derivatives KW - Polychlorinated Dibenzodioxins -- toxicity KW - Liver Neoplasms, Experimental -- chemically induced KW - Urethane -- toxicity KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77438127?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=H-ras+oncogene+mutation+spectra+in+B6C3F1+and+C57BL%2F6+mouse+liver+tumors+provide+evidence+for+TCDD+promotion+of+spontaneous+and+vinyl+carbamate-initiated+liver+cells.&rft.au=Watson%2C+M+A%3BDevereux%2C+T+R%3BMalarkey%2C+D+E%3BAnderson%2C+M+W%3BMaronpot%2C+R+R&rft.aulast=Watson&rft.aufirst=M&rft.date=2013-03-01&rft.volume=33&rft.issue=2&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Annals+of+Saudi+Medicine&rft.issn=02564947&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-14 N1 - Date created - 1995-09-14 N1 - Date revised - 2017-01-13 N1 - Gene symbol - H-ras N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I and pharmacokinetic study of the multidrug resistance modulator dexverapamil with EPOCH chemotherapy. AN - 77437605; 7636539 AB - Dexverapamil is a competitive inhibitor of the P-glycoprotein (Pgp) efflux pump, a potent mechanism of multidrug resistance (mdr-1) in vitro. We performed a phase I study to determine the maximum-tolerated dose (MTD) and pharmacokinetics of dexverapamil with etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (EPOCH) chemotherapy. Eligible patients had relapsed or refractory lymphoma or sarcoma. Patients initially received EPOCH alone, and those with stable or progressive disease were crossed-over to received dexverapamil on subsequent cycles of EPOCH. Dexverapamil was administered orally for 6 days and escalated over eight dose levels ranging from 240 to 1,200 mg/m2/d. Pharmacokinetics of dexverapamil and its active metabolite, nor-dexverapamil, were obtained in most patients. In seven patients, pharmacokinetics of doxorubicin, doxorubicinol, and etoposide were determined on paired cycles of EPOCH with or without dexverapamil. Sixty-five patients received 130 cycles of dexverapamil/EPOCH chemotherapy. The MTD of dexverapamil was 150 mg/m2 every 4 hours (900 mg/m2/d), and hypotension was the principal dose-limiting toxicity. The dexverapamil area under the curve (AUC) increased proportionally with dexverapamil dose, but significant interpatient variation occurred. At the MTD, the median plasma average concentrations of dexverapamil and nor-dexverapamil were 1.2 and 1.4 mumol/L, respectively. Dexverapamil did not affect the steady-state concentration (Css) of etoposide, but increased the Css of doxorubicin and doxorubicinol nearly twofold. The absolute neutrophil and platelet nadirs were significantly lower on the dexverapamil cycles compared with cycles of EPOCH alone, but other chemotherapy-related toxicities did not change. The phase II recommended dose of dexverapamil with EPOCH is 150 mg/m2 every 4 hours. This dose was well tolerated on an outpatient basis and achieved plasma concentrations of dexverapamil and nor-dexverapamil within the effective range for Pgp inhibition in vitro. Although dexverapamil increased the hematopoietic toxicity of EPOCH, it was mild, readily reversible, and offset by EPOCH dose reductions. Dexverapamil should be considered for further study. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Wilson, W H AU - Jamis-Dow, C AU - Bryant, G AU - Balis, F M AU - Klecker, R W AU - Bates, S E AU - Chabner, B A AU - Steinberg, S M AU - Kohler, D R AU - Wittes, R E AD - Medicine Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 1985 EP - 1994 VL - 13 IS - 8 SN - 0732-183X, 0732-183X KW - Vincristine KW - 5J49Q6B70F KW - Etoposide KW - 6PLQ3CP4P3 KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - norverapamil KW - 957Z3K3R56 KW - Verapamil KW - CJ0O37KU29 KW - Prednisone KW - VB0R961HZT KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Hypotension -- chemically induced KW - Doxorubicin -- pharmacokinetics KW - Stereoisomerism KW - Etoposide -- pharmacokinetics KW - Vincristine -- adverse effects KW - Humans KW - Aged KW - Platelet Count -- drug effects KW - Drug Resistance, Multiple KW - Prednisone -- adverse effects KW - Neutrophils KW - Adult KW - Lymphoma -- blood KW - Lymphoma -- drug therapy KW - Male KW - Prednisone -- administration & dosage KW - Doxorubicin -- adverse effects KW - Vincristine -- administration & dosage KW - Doxorubicin -- administration & dosage KW - Sarcoma -- drug therapy KW - Cyclophosphamide -- adverse effects KW - Leukocyte Count -- drug effects KW - Etoposide -- administration & dosage KW - Cross-Over Studies KW - Etoposide -- adverse effects KW - Middle Aged KW - Female KW - Sarcoma -- blood KW - Verapamil -- blood KW - Verapamil -- analogs & derivatives KW - Verapamil -- administration & dosage KW - Verapamil -- adverse effects KW - Verapamil -- pharmacokinetics KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77437605?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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+and+pharmacokinetic+study+of+the+multidrug+resistance+modulator+dexverapamil+with+EPOCH+chemotherapy.&rft.au=Wilson%2C+W+H%3BJamis-Dow%2C+C%3BBryant%2C+G%3BBalis%2C+F+M%3BKlecker%2C+R+W%3BBates%2C+S+E%3BChabner%2C+B+A%3BSteinberg%2C+S+M%3BKohler%2C+D+R%3BWittes%2C+R+E&rft.aulast=Wilson&rft.aufirst=W&rft.date=1995-08-01&rft.volume=13&rft.issue=8&rft.spage=1985&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-11 N1 - Date created - 1995-09-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Controlled trial of dexverapamil, a modulator of multidrug resistance, in lymphomas refractory to EPOCH chemotherapy. AN - 77437505; 7636540 AB - Overexpression of the multidrug resistance gene (mdr-1) is present in up to 60% of relapsed lymphomas. To study its role in lymphomas, we conducted a controlled trial of dexverapamil, an inhibitor of the mdr-1 gene product, P-glycoprotein (Pgp), in lymphomas refractory to etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (EPOCH) chemotherapy. Eligible patients had recurrent Hodgkin's (HD) or non-Hodgkin's lymphomas (NHL) and measurable disease. Patients initially received EPOCH alone and those with stable tumor over two cycles or progressive disease crossed over to receive dexverapamil and EPOCH on subsequent cycles. Dexverapamil was escalated eight dose levels, from 240 to 1,200 mg/m2/d. When possible, serial biopsies were obtained to measure mdr-1 expression by quantitative polymerase chain reaction (PCR). Of 154 patients entered onto the trial, 109 had NHL and 45 had HD. The median age was 44 years, 67% had stage IV disease, and the median number of prior regimens was two (range, one to 12) in NHL and one (range, one to four) in HD. Sixty-four patients (42%) crossed over, of which eight were not assessable. The maximum-tolerated dose of dexverapamil was 900 mg/m2/d. Among 41 NHL patients (excluding mycosis fungoides), there were three complete responses (CRs) and two partial responses (PRs) (12%) and five minor responses (MRs); two of 10 HD patients achieved PRs. The mdr-1 level was measured in 44 biopsies from 19 patients. Pretherapy, mdr-1 was low (median, 2.5 U) but increased (median, 12.2 U) at crossover. Of six patients with mdr-1 levels greater than 15 U, three responded to dexverapamil, while only one of eight patients with mdr-1 levels less than 15 U responded. EPOCH and dexverapamil were well tolerated, but compared with EPOCH alone, produced more hematologic toxicity. These results suggest that Pgp plays a role in clinical drug resistance of lymphomas. However, they also suggest that mechanisms other than Pgp are prominent in heavily pretreated patients and that, although Pgp inhibition may be necessary, it is probably insufficient. Earlier intervention with dexverapamil may be more effective and warrants further study. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Wilson, W H AU - Bates, S E AU - Fojo, A AU - Bryant, G AU - Zhan, Z AU - Regis, J AU - Wittes, R E AU - Jaffe, E S AU - Steinberg, S M AU - Herdt, J AD - Medicine Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 1995 EP - 2004 VL - 13 IS - 8 SN - 0732-183X, 0732-183X KW - P-Glycoprotein KW - 0 KW - Vincristine KW - 5J49Q6B70F KW - Etoposide KW - 6PLQ3CP4P3 KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Verapamil KW - CJ0O37KU29 KW - Prednisone KW - VB0R961HZT KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Stereoisomerism KW - Vincristine -- adverse effects KW - Humans KW - Aged KW - Drug Resistance, Multiple KW - Lymphoma, Non-Hodgkin -- drug therapy KW - Prednisone -- adverse effects KW - P-Glycoprotein -- metabolism KW - Hodgkin Disease -- drug therapy KW - Adult KW - Male KW - Prednisone -- administration & dosage KW - Doxorubicin -- adverse effects KW - Hodgkin Disease -- metabolism KW - Vincristine -- administration & dosage KW - Doxorubicin -- administration & dosage KW - Cyclophosphamide -- adverse effects KW - Lymphoma, Non-Hodgkin -- metabolism KW - Polymerase Chain Reaction KW - Etoposide -- administration & dosage KW - Cross-Over Studies KW - Etoposide -- adverse effects KW - Middle Aged KW - Female KW - Remission Induction KW - Verapamil -- adverse effects KW - Lymphoma -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Lymphoma -- metabolism KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Verapamil -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77437505?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Controlled+trial+of+dexverapamil%2C+a+modulator+of+multidrug+resistance%2C+in+lymphomas+refractory+to+EPOCH+chemotherapy.&rft.au=Wilson%2C+W+H%3BBates%2C+S+E%3BFojo%2C+A%3BBryant%2C+G%3BZhan%2C+Z%3BRegis%2C+J%3BWittes%2C+R+E%3BJaffe%2C+E+S%3BSteinberg%2C+S+M%3BHerdt%2C+J&rft.aulast=Wilson&rft.aufirst=W&rft.date=1995-08-01&rft.volume=13&rft.issue=8&rft.spage=1995&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 - 1995-09-11 N1 - Date created - 1995-09-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Diphenylhydantoin induces apoptotic cell death of cultured rat cerebellar granule neurons. AN - 77437410; 7636763 AB - Apoptosis is one form of physiological or programmed cell death responsible for the selective elimination of various cell types during development. We have observed and characterized a delayed-type of neurotoxicity induced in cultured cerebellar granule neurons by diphenylhydantoin. Diphenylhydantoin toxicity of cerebellar granule neurons is time and concentration dependent. Morphological studies using Nomarski optics and staining with the fluorescent dye Hoechst 33258 demonstrate that diphenylhydantoin-induced neurotoxicity of cerebellar granule neurons is associated with cytoplasmic blebbing, heterochromatic clumping and condensation of chromatin that precede cell death. Unlike glutamate toxicity (excitotoxicity) diphenylhydantoin-induced neurotoxicity of cerebellar granule neurons is attenuated by actinomycin D and cycloheximide, and is associated with nucleosomal size DNA fragmentation. Since we have previously reported that depolarization of cultured cerebellar granule neurons with high concentrations of K+ promotes the survival of these neurons by blocking apoptosis, we examined the effects of diphenylhydantoin on the K(+)-evoked increase in intracellular calcium. Using microfluorimetry and fura-2 to measure intracellular calcium we found that neurotoxic concentrations of diphenylhydantoin markedly reduce the increase in intracellular calcium associated with elevated extracellular potassium. Taken together, these data demonstrate that exposure of cultured cerebellar granule neurons to pharmacologically relevant concentrations of diphenylhydantoin results in a delayed type of neurotoxicity characterized by the biochemical and morphological features of apoptosis. JF - The Journal of pharmacology and experimental therapeutics AU - Yan, G M AU - Irwin, R P AU - Lin, S Z AU - Weller, M AU - Wood, K A AU - Paul, S M AD - Section on Molecular Pharmacology, NIMH, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 983 EP - 990 VL - 274 IS - 2 SN - 0022-3565, 0022-3565 KW - Dactinomycin KW - 1CC1JFE158 KW - Phenytoin KW - 6158TKW0C5 KW - DNA KW - 9007-49-2 KW - Cycloheximide KW - 98600C0908 KW - Potassium KW - RWP5GA015D KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Rats KW - Calcium -- metabolism KW - Dactinomycin -- pharmacology KW - Animals KW - Rats, Sprague-Dawley KW - Cells, Cultured KW - Neurons -- drug effects KW - DNA -- metabolism KW - Cycloheximide -- pharmacology KW - Potassium -- pharmacology KW - Phenytoin -- pharmacology KW - Cerebellum -- cytology KW - Cerebellum -- drug effects KW - Apoptosis -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77437410?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Diphenylhydantoin+induces+apoptotic+cell+death+of+cultured+rat+cerebellar+granule+neurons.&rft.au=Yan%2C+G+M%3BIrwin%2C+R+P%3BLin%2C+S+Z%3BWeller%2C+M%3BWood%2C+K+A%3BPaul%2C+S+M&rft.aulast=Yan&rft.aufirst=G&rft.date=1995-08-01&rft.volume=274&rft.issue=2&rft.spage=983&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-08 N1 - Date created - 1995-09-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of sulpiride and SCH 23390 on methamphetamine-induced changes in body temperature and lethality. AN - 77436524; 7636758 AB - Data from human and animal studies suggest that hyperpyrexia contributes to both the neurotoxic and the lethal effects of stimulant drugs such as methamphetamine (METH). Because many of the effects of METH involve the release of dopamine from CNS neurons, we examined the effects of D1 and D2 dopamine receptor antagonists on METH-induced lethality and determined whether these effects correlated with changes in body temperature. In the first set of experiments, we found that the D2 antagonist sulpiride (SUL; 20, 40 or 80 mg/kg) potentiated the lethality caused by a single injection of METH (10 mg/kg). Pretreatment with the D1 antagonist SCH 23390 (SCH; 0.5 mg/kg) reduced the lethality induced by METH alone or by SUL/METH. Other D2 or 5-hydroxytryptamine antagonists prevented, rather than potentiated, METH-induced lethality. In a second set of experiments, rectal temperatures were recorded in METH-injected animals pretreated with SCH or SUL. METH caused a significant increase (i.e., above vehicle-injected levels) in body temperature at 2.5 hr after injection. The effects of SCH or SUL pretreatment on METH-induced changes in body temperature suggest that the lethality-potentiating and -protective effects of SUL and SCH, respectively, were not due to altered thermoregulatory responses. These data support the idea that D1 receptor activation is an important event in the lethality caused by METH and that SUL may potentiate D1 receptor activation by augmenting METH-induced DA release. JF - The Journal of pharmacology and experimental therapeutics AU - Bronstein, D M AU - Hong, J S AD - Laboratory of Molecular and Integrative Neuroscience, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 943 EP - 950 VL - 274 IS - 2 SN - 0022-3565, 0022-3565 KW - Benzazepines KW - 0 KW - Methamphetamine KW - 44RAL3456C KW - Sulpiride KW - 7MNE9M8287 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Rats, Inbred F344 KW - Male KW - Sulpiride -- pharmacology KW - Benzazepines -- pharmacology KW - Body Temperature -- drug effects KW - Methamphetamine -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77436524?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Effects+of+sulpiride+and+SCH+23390+on+methamphetamine-induced+changes+in+body+temperature+and+lethality.&rft.au=Bronstein%2C+D+M%3BHong%2C+J+S&rft.aulast=Bronstein&rft.aufirst=D&rft.date=1995-08-01&rft.volume=274&rft.issue=2&rft.spage=943&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-08 N1 - Date created - 1995-09-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prolactin activates Ras via signaling proteins SHC, growth factor receptor bound 2, and son of sevenless. AN - 77423330; 7628388 AB - Identification of the signal transduction pathways used by PRL is essential for understanding the role of PRL receptors in growth and differentiation processes. Early cellular mediators of PRL receptor activation include tyrosine kinases of the Janus kinase (JAK) and SRC families, with rapid nuclear signaling via tyrosine phosphorylated signal transducers and activators of transcription. In the present study we provide the first demonstration of PRL-induced activation of Ras, an oncogenic protein that supports an alternative signaling route from the membrane to the nucleus. PRL stimulated Ras in rat Nb2-SP lymphoma cells, as detected by a 2.0-fold increase in the GTP-bound state of the molecule (P < 0.01). This activation was associated with marked tyrosine phosphorylation and increased membrane association of the 52-kilodalton form of SHC. Moreover, PRL induced binding of SHC to growth factor receptor bound 2 and the guanine-nucleotide exchange factor son of sevenless, a common method used by growth factor receptors to activate Ras. In contrast, no apparent regulation by PRL of Ras via VAV or p120 Ras-guanosine triphosphatase-activating protein was detected, based upon an absence of PRL-inducible tyrosine phosphorylation of these proteins. Collectively, these results provide a molecular bridge between activation of PRL receptor-associated tyrosine kinases and subsequent stimulation of the serine/threonine kinase Raf-1, an established Ras target that was recently shown to be activated by PRL in Nb2 cells. We conclude that PRL is able to activate Ras via recruitment of the signaling proteins SHC, growth factor receptor bound 2, and son of sevenless in Nb2 cells. Moreover, PRL induced tyrosine phosphorylation of SHC in two of three PRL-responsive human breast cancer cell lines, suggesting that SHC-mediated Ras activation is a commonly used signaling strategy by PRL. JF - Endocrinology AU - Erwin, R A AU - Kirken, R A AU - Malabarba, M G AU - Farrar, W L AU - Rui, H AD - Biological Carcinogenesis and Development Program, Program Resources, Inc./DynCorp, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 3512 EP - 3518 VL - 136 IS - 8 SN - 0013-7227, 0013-7227 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - GRB2 Adaptor Protein KW - GRB2 protein, human KW - Grb2 protein, rat KW - Membrane Proteins KW - Protein Sorting Signals KW - Proteins KW - Son of Sevenless Proteins KW - Prolactin KW - 9002-62-4 KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Animals KW - Tumor Cells, Cultured KW - Sheep KW - Humans KW - Protein Sorting Signals -- physiology KW - Genes, ras -- drug effects KW - Gene Expression Regulation -- drug effects KW - Prolactin -- pharmacology KW - Proteins -- physiology KW - Membrane Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77423330?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Prolactin+activates+Ras+via+signaling+proteins+SHC%2C+growth+factor+receptor+bound+2%2C+and+son+of+sevenless.&rft.au=Erwin%2C+R+A%3BKirken%2C+R+A%3BMalabarba%2C+M+G%3BFarrar%2C+W+L%3BRui%2C+H&rft.aulast=Erwin&rft.aufirst=R&rft.date=1995-08-01&rft.volume=136&rft.issue=8&rft.spage=3512&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-01 N1 - Date created - 1995-09-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gonadotropin-releasing hormone-induced sensitization of calcium-dependent exocytosis in pituitary gonadotrophs. AN - 77421560; 7628375 AB - Agonist-induced increases in cytoplasmic calcium concentration ([Ca2+]i) play a pivotal role in regulated exocytosis by promoting the fusion of secretory vesicles with the plasma membrane. In permeabilized and ATP-primed pituitary cells, increases in ambient [Ca2+]i stimulated the release of LH from gonadotrophs with an EC50 of 2-3 microM. In contrast, the responses of intact gonadotrophs to agonist stimulation by GnRH were characterized by transient [Ca2+]i elevations of up to 1.5 microM, followed by a plateau of 300-400 nM. The sensitivity of the exocytotic response of permeabilized cells to [Ca2+]i was significantly increased by GnRH, which reduced the EC50 for [Ca2+]i to the submicromolar concentration range. The stimulatory action of GnRH on LH release in permeabilized cells was not a consequence of intracellular Ca2+ release, but was associated with increased cytidine diphosphate diacylglycerol production. Activation of protein kinase C by phorbol esters caused a similar increase in the Ca2+ sensitivity of LH release from permeabilized cells, and this effect was not additive to that of GnRH. Furthermore, the GnRH-induced increase in the sensitivity of the exocytotic response to Ca2+ was attenuated by inhibitors of protein kinase C. These findings indicate that although elevated [Ca2+]i per se can promote LH release from permeabilized gonadotrophs, concomitant activation of protein kinase C is necessary to support exocytosis at the physiological [Ca2+]i levels that prevail in GnRH-stimulated intact cells. Such sensitization of the Ca(2+)-dependent secretory mechanism by protein kinase C may be an important step in the agonist-induced release of LH from pituitary gonadotrophs. JF - Endocrinology AU - Jobin, R M AU - Tomić, M AU - Zheng, L AU - Stojilkovic, S S 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 - 1995/08// PY - 1995 DA - August 1995 SP - 3398 EP - 3405 VL - 136 IS - 8 SN - 0013-7227, 0013-7227 KW - Phorbol Esters KW - 0 KW - Gonadotropin-Releasing Hormone KW - 33515-09-2 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Luteinizing Hormone KW - 9002-67-9 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Calcium KW - SY7Q814VUP KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Protein Kinase C -- metabolism KW - Phorbol Esters -- pharmacology KW - Animals KW - Rats, Sprague-Dawley KW - Protein Kinase C -- antagonists & inhibitors KW - Adenosine Triphosphate -- physiology KW - Cells, Cultured KW - Signal Transduction -- drug effects KW - Cell Membrane Permeability KW - Female KW - Luteinizing Hormone -- secretion KW - Exocytosis -- drug effects KW - Pituitary Gland, Anterior -- physiology KW - Calcium -- physiology KW - Pituitary Gland, Anterior -- cytology KW - Gonadotropin-Releasing Hormone -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77421560?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Gonadotropin-releasing+hormone-induced+sensitization+of+calcium-dependent+exocytosis+in+pituitary+gonadotrophs.&rft.au=Jobin%2C+R+M%3BTomi%C4%87%2C+M%3BZheng%2C+L%3BStojilkovic%2C+S+S%3BCatt%2C+K+J&rft.aulast=Jobin&rft.aufirst=R&rft.date=1995-08-01&rft.volume=136&rft.issue=8&rft.spage=3398&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-01 N1 - Date created - 1995-09-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The association between alcohol and breast cancer: popular press coverage of research. AN - 77420794; 7625500 AB - This study was undertaken to examine popular press reports of the association between alcohol and breast cancer. Articles from scientific journals and stories from newspapers and magazines published from January 1, 1985, to July 1, 1992, were retrieved from six on-line databases. Lay press stories were analyzed to determine which medical articles were publicized and what information was reported. Fifty-eight scientific articles on the relationship of alcohol and breast cancer were found, and 64 newspaper and 23 magazine stories were retrieved. The press cited 11 studies, 19% of those published during the study period. Three studies were featured in 77% of popular press stories. No scientific review articles were reported. Behavioral recommendations were given to the public in 63% of stories. The vast majority of scientific studies on alcohol and breast cancer were ignored in press reports. We encourage researchers and the popular press to give the public a broader understanding of public health issues. JF - American journal of public health AU - Houn, F AU - Bober, M A AU - Huerta, E E AU - Hursting, S D AU - Lemon, S AU - Weed, D L AD - National Cancer Institute, Bethesda, Md 20892, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 1082 EP - 1086 VL - 85 IS - 8 Pt 1 SN - 0090-0036, 0090-0036 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Female KW - Alcohol Drinking -- adverse effects KW - Breast Neoplasms -- chemically induced KW - Mass Media UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77420794?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+public+health&rft.atitle=The+association+between+alcohol+and+breast+cancer%3A+popular+press+coverage+of+research.&rft.au=Houn%2C+F%3BBober%2C+M+A%3BHuerta%2C+E+E%3BHursting%2C+S+D%3BLemon%2C+S%3BWeed%2C+D+L&rft.aulast=Houn&rft.aufirst=F&rft.date=1995-08-01&rft.volume=85&rft.issue=8+Pt+1&rft.spage=1082&rft.isbn=&rft.btitle=&rft.title=American+journal+of+public+health&rft.issn=00900036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-30 N1 - Date created - 1995-08-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Lancet. 1983 Sep 24;2(8352):724-6 [6136850] Lancet. 1983 Sep 10;2(8350):626-7 [6136775] Am J Epidemiol. 1984 Sep;120(3):350-7 [6475912] Am J Epidemiol. 1984 Nov;120(5):676-83 [6496448] Health Aff (Millwood). 1985 Spring;4(1):5-23 [3997047] J Natl Cancer Inst. 1985 Jul;75(1):61-5 [3859697] JAMA. 1986 Mar 14;255(10):1323-7 [3944950] J Natl Cancer Inst. 1987 Feb;78(2):229-34 [3468286] J Natl Cancer Inst. 1987 Apr;78(4):657-61 [3104648] N Engl J Med. 1987 May 7;316(19):1169-73 [3574367] N Engl J Med. 1987 May 7;316(19):1174-80 [3574368] N Engl J Med. 1987 May 7;316(19):1211-3 [3574371] Cancer Res. 1988 Apr 15;48(8):2284-7 [3349491] Int J Cancer. 1988 May 15;41(5):695-9 [3366491] JAMA. 1988 May 20;259(19):2867-71 [3367453] JAMA. 1988 Aug 5;260(5):652-6 [3392790] J Natl Cancer Inst. 1989 Jan 4;81(1):31-5 [2908919] Am J Epidemiol. 1989 Nov;130(5):867-77 [2683749] JAMA. 1990 Mar 9;263(10):1385-9 [2406472] Med Oncol Tumor Pharmacother. 1990;7(2-3):143-51 [2146449] Lancet. 1991 Apr 13;337(8746):867-72 [1672966] JAMA. 1991 Oct 2;266(13):1824-6 [1890712] Breast Cancer Res Treat. 1991 Nov;19(3):221-31 [1838016] JAMA. 1992 Aug 26;268(8):1026-7 [1501310] J Natl Cancer Inst. 1993 Jun 2;85(11):892-7 [8492317] N Engl J Med. 1994 Jul 21;331(3):189-90 [8008033] J Commun. 1975 Summer;25(3):171-3 [1184780] Can Med Assoc J. 1980 Feb 23;122(4):450-2 [7370849] Lancet. 1982 Jan 30;1(8266):267-70 [6120284] Lancet. 1982 Apr 3;1(8275):799-800 [6121249] Lancet. 1983 Feb 5;1(8319):293-4 [6130308] JAMA. 1983 Oct 28;250(16):2137 [6620517] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparative immunogenicity of conjugates composed of Escherichia coli O111 O-specific polysaccharide, prepared by treatment with acetic acid or hydrazine, bound to tetanus toxoid by two synthetic schemes. AN - 77412343; 7542631 AB - Escherichia coli O111, of various H types and virulence factors, causes enteritis throughout the world, especially in young children. This O type is found rarely in healthy individuals. Serum antibodies to the O-specific polysaccharide of O111 lipopolysaccharide (LPS) protect mice and dogs against infection with this E. coli serotype. The O111 O-specific polysaccharide is composed of a pentasaccharide repeat unit with two colitoses bound to the C-3 and C-6 of glucose in a trisaccharide backbone; this structure is identical to that of Salmonella adelaide (O35), another enteric pathogen. Nonpyrogenic O111 O-specific polysaccharide was prepared by treatment of its LPS with acetic acid (O-SP) or the organic base hydrazine (DeA-LPS). The O-SP had a reduced concentration of colitose. These products were derivatized with adipic acid dihydrazide (ADH) or thiolated with N-succinimidyl-3(2-pyridyldithio) propionate (SPDP). The four derivatives were covalently bound to tetanus toxoid (TT) by carbodiimide-mediated condensation or with SPDP to form conjugates. Immunization of BALB/c and general-purpose mice by a clinically acceptable route showed that DeA-LPS-TTADH, of the four conjugates, elicited the highest level of LPS antibodies. Possible reasons to explain this differential immunogenicity between the four conjugates are discussed. JF - Infection and immunity AU - Gupta, R K AU - Egan, W AU - Bryla, D A AU - Robbins, J B AU - Szu, S C AD - National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 2805 EP - 2810 VL - 63 IS - 8 SN - 0019-9567, 0019-9567 KW - Acetates KW - 0 KW - Antigens, Bacterial KW - Bacterial Vaccines KW - Hydrazines KW - Lipopolysaccharides KW - O Antigens KW - Polysaccharides, Bacterial KW - Tetanus Toxoid KW - hydrazine KW - 27RFH0GB4R KW - Acetic Acid KW - Q40Q9N063P KW - Index Medicus KW - Animals KW - Chemistry, Physical KW - Lipopolysaccharides -- chemistry KW - Mice KW - Mice, Inbred BALB C KW - Lipopolysaccharides -- immunology KW - Chemical Phenomena KW - Molecular Sequence Data KW - Acetates -- chemistry KW - Carbohydrate Sequence KW - Hydrazines -- chemistry KW - Female KW - Tetanus Toxoid -- immunology KW - Polysaccharides, Bacterial -- chemistry KW - Bacterial Vaccines -- immunology KW - Escherichia coli -- immunology KW - Polysaccharides, Bacterial -- immunology KW - Antigens, Bacterial -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77412343?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Comparative+immunogenicity+of+conjugates+composed+of+Escherichia+coli+O111+O-specific+polysaccharide%2C+prepared+by+treatment+with+acetic+acid+or+hydrazine%2C+bound+to+tetanus+toxoid+by+two+synthetic+schemes.&rft.au=Gupta%2C+R+K%3BEgan%2C+W%3BBryla%2C+D+A%3BRobbins%2C+J+B%3BSzu%2C+S+C&rft.aulast=Gupta&rft.aufirst=R&rft.date=1995-08-01&rft.volume=63&rft.issue=8&rft.spage=2805&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 - 1995-08-25 N1 - Date created - 1995-08-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Infect Immun. 1994 Jan;62(1):210-4 [8262629] Infect Immun. 1993 Sep;61(9):3678-87 [8359890] Infect Immun. 1994 Aug;62(8):3282-8 [8039899] Biochem Biophys Res Commun. 1965 Dec 21;21(6):638-43 [5326027] J Biol Chem. 1975 Apr 25;250(8):2911-19 [804483] Eur J Biochem. 1980;107(1):145-53 [6156828] J Bacteriol. 1982 Sep;151(3):1210-21 [6179923] Infect Immun. 1983 Apr;40(1):245-56 [6601061] Infect Immun. 1984 Jul;45(1):113-7 [6203836] J Bacteriol. 1984 Sep;159(3):877-82 [6207166] Epidemiol Rev. 1984;6:31-51 [6386503] Infect Immun. 1985 Aug;49(2):365-70 [2410365] J Exp Med. 1985 Sep 1;162(3):877-89 [3897448] J Biol Stand. 1986 Jan;14(1):25-33 [2420803] Infect Immun. 1986 Nov;54(2):448-55 [3095243] Infect Immun. 1994 Nov;62(11):5048-54 [7927787] Acta Pathol Microbiol Scand. 1950;27(4):552-64 [14770850] J Lab Clin Med. 1952 Aug;40(2):252-4 [14946461] Pediatrics. 1953 Oct;12(4):377-83 [13099908] J Biol Chem. 1959 Aug;234(8):1971-5 [13672998] Am J Hyg. 1962 Jul;76:27-43 [14455415] J Exp Med. 1987 Nov 1;166(5):1510-24 [3681191] Infect Immun. 1988 Jul;56(7):1829-30 [2454893] J Infect Dis. 1988 Aug;158(2):301-11 [3042872] Infect Immun. 1988 Sep;56(9):2292-8 [3410538] J Infect Dis. 1988 Nov;158(5):1135-6 [3053926] J Immunol. 1989 Apr 1;142(7):2464-8 [2784464] J Clin Microbiol. 1989 Jun;27(6):1307-11 [2568996] J Infect Dis. 1989 Sep;160(3):452-9 [2668429] J Trop Pediatr. 1990 Aug;36(4):176-9 [2213982] Lancet. 1990 Oct 6;336(8719):831-4 [1976876] J Infect Dis. 1991 Apr;163(4):769-72 [2010630] J Immunol. 1991 Jun 15;146(12):4308-14 [2040803] Zentralbl Bakteriol. 1991 Jan;274(4):496-506 [1863318] Infect Immun. 1991 Dec;59(12):4450-8 [1937803] J Infect Dis. 1992 Jan;165(1):34-45 [1727896] Infect Immun. 1992 Feb;60(2):584-9 [1730492] Infect Immun. 1992 Aug;60(8):3201-8 [1639490] Clin Infect Dis. 1992 Aug;15(2):346-61 [1381621] Can J Microbiol. 1992 Jul;38(7):699-704 [1382824] Infect Immun. 1993 May;61(5):1619-29 [7682992] J Infect Dis. 1994 Mar;169(3):553-61 [7512609] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo antitumor activity of T cells redirected with chimeric antibody/T-cell receptor genes. AN - 77399284; 7614473 AB - In an effort to broaden the applicability of adoptive cellular immunotherapy toward nonmelanoma cancers, we have designed chimeric antibody/T-cell receptor genes composed of the variable domains from mAbs joined to T-cell receptor-signaling chains. We have demonstrated that T cells retrovirally transduced with these genes can recognize antibody-defined antigens and that this recognition leads to T-cell activation, specific lysis, and cytokine release. In this study, we have examined the in vivo activity of murine T cells transduced with a chimeric receptor gene (MOv-gamma) derived from the mAb MOv18, which binds to a folate-binding protein overexpressed on most human ovarian adenocarcinomas. Nude mice that were given i.p. implants of human ovarian cancer (IGROV) cells were treated 3 days later with i.p. murine tumor-infiltrating lymphocytes (TIL) derived from an unrelated tumor. Mice treated with MOv-gamma-transduced TIL (MOv-TIL) had significantly increased survival compared to mice treated with saline only, nontransduced TIL, or TIL transduced with a control anti-trinitrophenyl chimeric receptor gene (TNP-TIL). In another model, C57BL/6 mice were given i.v. injections of a syngeneic methylcholanthrene-induced sarcoma transduced with the folate-binding protein (FBP) gene. Three days later, mice were treated i.v. with various transduced murine TIL (derived from an unrelated tumor), followed by low-dose systemic interleukin 2. Eleven days after tumor injection, mice were sacrificed, and lung metastases were counted. In multiple experiments, mice receiving MOv-TIL had significantly fewer lung metastases than did mice treated with interleukin 2 alone, nontransduced TIL, or TNP-TIL. These studies indicate that T cells can be gene modified to react in vivo against tumor antigens, defined by mAbs. This approach is potentially applicable to a number of neoplastic and infectious diseases and may allow adoptive immunotherapy against types of cancer not previously amenable to cellular immunotherapy. JF - Cancer research AU - Hwu, P AU - Yang, J C AU - Cowherd, R AU - Treisman, J AU - Shafer, G E AU - Eshhar, Z AU - Rosenberg, S A AD - Surgery Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1995/08/01/ PY - 1995 DA - 1995 Aug 01 SP - 3369 EP - 3373 VL - 55 IS - 15 SN - 0008-5472, 0008-5472 KW - Antibodies, Monoclonal KW - 0 KW - Immunoglobulin Variable Region KW - Interleukin-2 KW - Receptors, Antigen, T-Cell KW - Recombinant Fusion Proteins KW - Methylcholanthrene KW - 56-49-5 KW - Interferon-gamma KW - 82115-62-6 KW - Index Medicus KW - Animals KW - Ovarian Neoplasms -- metabolism KW - Sarcoma, Experimental -- chemically induced KW - Humans KW - Lung Neoplasms -- secondary KW - Lung Neoplasms -- therapy KW - Mice KW - Mice, Nude KW - Ovarian Neoplasms -- therapy KW - Sarcoma, Experimental -- therapy KW - Tumor Cells, Cultured KW - Transfection KW - Sarcoma, Experimental -- metabolism KW - Interferon-gamma -- metabolism KW - Mice, Inbred C57BL KW - Female KW - Lymphocytes, Tumor-Infiltrating -- immunology KW - Interleukin-2 -- therapeutic use KW - Immunoglobulin Variable Region -- immunology KW - Immunotherapy, Adoptive -- methods KW - Immunoglobulin Variable Region -- therapeutic use KW - Recombinant Fusion Proteins -- therapeutic use KW - Antibodies, Monoclonal -- therapeutic use KW - Antibodies, Monoclonal -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77399284?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=In+vivo+antitumor+activity+of+T+cells+redirected+with+chimeric+antibody%2FT-cell+receptor+genes.&rft.au=Hwu%2C+P%3BYang%2C+J+C%3BCowherd%2C+R%3BTreisman%2C+J%3BShafer%2C+G+E%3BEshhar%2C+Z%3BRosenberg%2C+S+A&rft.aulast=Hwu&rft.aufirst=P&rft.date=1995-08-01&rft.volume=55&rft.issue=15&rft.spage=3369&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 - 1995-08-22 N1 - Date created - 1995-08-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased antitumor activity of a circularly permuted interleukin 4-toxin in mice with interleukin 4 receptor-bearing human carcinoma. AN - 77399216; 7614471 AB - We reported previously that circularly permuted interleukin-4 (IL4), composed of amino acids 38-129 of IL4 connected by a linker peptide GGNGG to amino acids 1-37, is preferable to native IL4 for fusing to the amino terminus of truncated Pseudomonas exotoxin (PE) to make a recombinant toxin, because the new ligand-toxin junction results in improved IL4 receptor (IL4R)-binding (R. J. Kreitman et al., Proc. Natl. Acad. Sci. USA, 91: 6889-6893, 1994). We now report that the improved binding of circularly permuted IL4-toxin is associated with improved antitumor activity in tumor-bearing mice. For in vivo testing, we made an improved circularly permuted IL4-toxin, termed IL4(38-37)-PE38KDEL. It contains an N38D mutation at the amino terminus, allowing improved expression and large-scale production in Escherichia coli. It also contains the truncated toxin PE38KDEL, which is composed of amino acids 253-364 and 381-608 of PE, followed by KDEL. To evaluate antitumor activity, nude mice carrying s.c. tumors composed of IL4R-bearing human A431 epidermoid carcinoma cells were injected with recombinant toxins i.v. every other day for three doses. IL4(38-37)-PE38KDEL induced complete remissions in 80% of mice receiving 50 micrograms/kg x 3 and 100% of mice receiving 100 micrograms/kg x 3, while only 70% of mice receiving 200 micrograms/kg x 3 of the native IL4-toxin IL4-PE38KDEL obtained complete remission. Disease-free survival after obtaining complete remissions was higher in mice treated with IL4(38-37)-PE38KDEL 50 micrograms/Kg QOD x 3 than with IL4-PE38KDEL 200 micrograms/Kg QOD x 3 (P < 0.03). IL4(38-37)-PE38KDEL and IL4-PE38KDEL exhibited similar toxicity and pharmacokinetics in the mice, indicating that the improved antitumor activity of the circularly permuted IL4-toxin was due to its improved binding to the IL4R on the target cells. JF - Cancer research AU - Kreitman, R J AU - Puri, R K AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1995/08/01/ PY - 1995 DA - 1995 Aug 01 SP - 3357 EP - 3363 VL - 55 IS - 15 SN - 0008-5472, 0008-5472 KW - Bacterial Toxins KW - 0 KW - Exotoxins KW - Immunotoxins KW - Peptide Fragments KW - Recombinant Fusion Proteins KW - Virulence Factors KW - Interleukin-4 KW - 207137-56-2 KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Drug Screening Assays, Antitumor KW - Animals KW - Peptide Fragments -- therapeutic use KW - Peptide Fragments -- chemistry KW - Cells, Cultured KW - Humans KW - Escherichia coli -- drug effects KW - Mice, Nude KW - Mice KW - Peptide Fragments -- pharmacokinetics KW - Female KW - Immunotoxins -- pharmacokinetics KW - Recombinant Fusion Proteins -- pharmacokinetics KW - Exotoxins -- chemistry KW - Interleukin-4 -- therapeutic use KW - Recombinant Fusion Proteins -- chemistry KW - Exotoxins -- pharmacokinetics KW - Immunotoxins -- chemistry KW - Interleukin-4 -- pharmacokinetics KW - Bacterial Toxins -- pharmacokinetics KW - Carcinoma -- drug therapy KW - Bacterial Toxins -- therapeutic use KW - Bacterial Toxins -- chemistry KW - Immunotoxins -- therapeutic use KW - Carcinoma -- metabolism KW - Exotoxins -- therapeutic use KW - Recombinant Fusion Proteins -- therapeutic use KW - Interleukin-4 -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77399216?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Increased+antitumor+activity+of+a+circularly+permuted+interleukin+4-toxin+in+mice+with+interleukin+4+receptor-bearing+human+carcinoma.&rft.au=Kreitman%2C+R+J%3BPuri%2C+R+K%3BPastan%2C+I&rft.aulast=Kreitman&rft.aufirst=R&rft.date=1995-08-01&rft.volume=55&rft.issue=15&rft.spage=3357&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 - 1995-08-22 N1 - Date created - 1995-08-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chromosome microdissection identifies cryptic sites of DNA sequence amplification in human ovarian carcinoma. AN - 77398552; 7614475 AB - DNA sequence amplification contributes to the multistep process of carcinogenesis, and overexpression of amplified genes has been shown to contribute to the malignant phenotype. Cytogenetic analyses of human tumor cells, including ovarian malignancies, frequently show cytological evidence of DNA amplification in the form of double minutes and homogeneously staining regions. In this report, we have combined the techniques of chromosome microdissection and fluorescence in situ hybridization (P. S. Meltzer et al., Nat. Genet., 1: 24-28, 1992) to identify the composition and chromosomal origin of seven homogeneously staining regions from seven cases of ovarian cancer. Twelve specific chromosome band regions were identified as amplified including 11q, 12p, 16p, 19p, and 19q. These results provide important insights into the organization of amplified sequences within ovarian malignancies and add further to our recognition of regions likely to harbor genes important to the development or progression of ovarian cancer. JF - Cancer research AU - Guan, X Y AU - Cargile, C B AU - Anzick, S L AU - Thompson, F H AU - Meltzer, P S AU - Bittner, M L AU - Taetle, R AU - McGill, J R AU - Trent, J M AD - Laboratory of Cancer Genetics, National Center for Human Genome Research, NIH, Bethesda, Maryland 20892-4470, USA. Y1 - 1995/08/01/ PY - 1995 DA - 1995 Aug 01 SP - 3380 EP - 3385 VL - 55 IS - 15 SN - 0008-5472, 0008-5472 KW - Index Medicus KW - Karyotyping KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Aged KW - Middle Aged KW - Female KW - Ovarian Neoplasms -- genetics KW - Nucleic Acid Amplification Techniques KW - In Situ Hybridization, Fluorescence UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77398552?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chromosome+microdissection+identifies+cryptic+sites+of+DNA+sequence+amplification+in+human+ovarian+carcinoma.&rft.au=Guan%2C+X+Y%3BCargile%2C+C+B%3BAnzick%2C+S+L%3BThompson%2C+F+H%3BMeltzer%2C+P+S%3BBittner%2C+M+L%3BTaetle%2C+R%3BMcGill%2C+J+R%3BTrent%2C+J+M&rft.aulast=Guan&rft.aufirst=X&rft.date=1995-08-01&rft.volume=55&rft.issue=15&rft.spage=3380&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 - 1995-08-22 N1 - Date created - 1995-08-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Proteins and cis-acting elements associated with transactivation of the varicella-zoster virus (VZV) immediate-early gene 62 promoter by VZV open reading frame 10 protein. AN - 77397428; 7609034 AB - Varicella-zoster virus (VZV) open reading frame 10 (ORF10) protein, the homolog of herpes simplex virus type 1 (HSV-1) VP16, is a virion-associated transactivator of the VZV immediate-early (IE) gene 62 (IE62) promoter. VP16 forms a complex with cellular factors (Oct1 and host cell factor [HCF]) and TAATGARAT elements (found in all HSV-1 IE promoter/enhancer sequences) to mediate stimulation of IE transcription. The VZV IE62 promoter also contains three TAATGARAT-like elements. Mutagenesis studies of the VZV IE62 promoter indicated that TAATGARAT-like elements contribute to transactivation of the VZV IE62 promoter by ORF10 protein. Other cis-acting elements such as GA-rich and cyclic AMP-responsive elements were also needed for full transactivation by ORF10 protein. In mobility shift assays, ORF10 protein formed a complex with either of two TAATGARAT-like elements that lack an overlapping octamer-binding motif (octa-/TAATGARAT) but not with a TAATGARAT element with an overlapping octamer-binding motif (octa+/TAATGARAT). In contrast, VP16 formed a high-affinity ternary complex with an octa+/TAATGARAT element and a low-affinity complex with octa-/TAATGARAT elements. Addition of antibodies to ORF10 protein, Oct1, or HCF disrupted the complexes, demonstrating that ORF10 protein interacts with Oct1 and HCF. These results suggest that transactivation of the VZV IE62 gene by ORF10 protein and HSV IE genes by VP16 require similar cellular proteins but distinct cis-acting elements. JF - Journal of virology AU - Moriuchi, H AU - Moriuchi, M AU - Cohen, J I AD - Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA. Y1 - 1995/08// PY - 1995 DA - August 1995 SP - 4693 EP - 4701 VL - 69 IS - 8 SN - 0022-538X, 0022-538X KW - IE62 KW - DNA-Binding Proteins KW - 0 KW - IE62 protein, Human herpesvirus 3 KW - Immediate-Early Proteins KW - ORF 10 protein, varicella-zoster virus KW - Oligodeoxyribonucleotides KW - Trans-Activators KW - Transcription Factors KW - Viral Envelope Proteins KW - Index Medicus KW - Base Sequence KW - Tumor Cells, Cultured KW - Transcription Factors -- metabolism KW - Humans KW - Molecular Sequence Data KW - Cell Line KW - Promoter Regions, Genetic KW - Immediate-Early Proteins -- genetics KW - Trans-Activators -- genetics KW - DNA-Binding Proteins -- genetics KW - Trans-Activators -- physiology KW - Transcriptional Activation KW - Viral Envelope Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77397428?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Proteins+and+cis-acting+elements+associated+with+transactivation+of+the+varicella-zoster+virus+%28VZV%29+immediate-early+gene+62+promoter+by+VZV+open+reading+frame+10+protein.&rft.au=Moriuchi%2C+H%3BMoriuchi%2C+M%3BCohen%2C+J+I&rft.aulast=Moriuchi&rft.aufirst=H&rft.date=1995-08-01&rft.volume=69&rft.issue=8&rft.spage=4693&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 - 1995-08-11 N1 - Date created - 1995-08-11 N1 - Date revised - 2017-01-13 N1 - Gene symbol - IE62 N1 - SuppNotes - Cited By: J Virol. 1974 Jul;14(1):8-19 [4365321] Neuron. 1991 Sep;7(3):381-90 [1654947] J Virol. 1983 May;46(2):371-7 [6302308] Nature. 1991 Oct 10;353(6344):569-71 [1922364] J Virol. 1992 Jan;66(1):359-66 [1309252] J Virol. 1992 Jun;66(6):3899-903 [1316489] Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6958-62 [1495986] J Virol. 1992 Sep;66(9):5298-304 [1323696] Virology. 1992 Nov;191(1):346-54 [1329324] J Virol. 1992 Dec;66(12):7303-8 [1366099] Intervirology. 1992;34(2):74-85 [1338062] J Virol. 1993 May;67(5):2739-46 [8386275] J Virol. 1993 Jul;67(7):4290-5 [8389928] Cell. 1993 Jul 16;74(1):115-25 [8392914] Virology. 1993 Oct;196(2):888-91 [8396817] Biochim Biophys Acta. 1993 Sep 23;1174(3):221-33 [8373801] Cell. 1993 Nov 5;75(3):519-30 [8221891] J Virol. 1994 Mar;68(3):1987-92 [8107260] Virology. 1994 Apr;200(1):297-300 [8128631] Mol Cell Biol. 1994 May;14(5):3484-93 [8164693] J Virol. 1994 Jun;68(6):3570-81 [8189496] J Virol. 1994 Aug;68(8):4898-909 [8035488] Nucleic Acids Res. 1986 Jan 24;14(2):929-43 [3003700] J Gen Virol. 1986 Sep;67 ( Pt 9):1759-816 [3018124] Proc Natl Acad Sci U S A. 1987 Jan;84(1):71-5 [3025864] Cell. 1988 Feb 12;52(3):425-34 [2830986] Proc Natl Acad Sci U S A. 1988 Sep;85(17):6347-51 [2842768] Genes Dev. 1988 Jun;2(6):718-29 [2843425] Genes Dev. 1988 Jun;2(6):730-42 [2843426] Gene Anal Tech. 1988 Mar-Apr;5(2):22-31 [3192155] Nucleic Acids Res. 1988 Dec 9;16(23):11047-56 [3264609] Nature. 1989 Mar 2;338(6210):39-44 [2521923] EMBO J. 1988 Dec 20;7(13):4231-8 [2854058] J Virol. 1989 Jun;63(6):2798-812 [2542590] Gene. 1989 Apr 15;77(1):51-9 [2744487] EMBO J. 1989 Aug;8(8):2337-42 [2676518] Nature. 1989 Oct 19;341(6243):624-30 [2571937] Virology. 1989 Dec;173(2):700-9 [2556848] Cell. 1990 Feb 9;60(3):375-86 [2302733] Neuron. 1990 Feb;4(2):215-22 [2155008] J Gen Virol. 1990 Apr;71 ( Pt 4):897-906 [2157801] Mol Cell Biol. 1990 Sep;10(9):4974-7 [2167442] Nucleic Acids Res. 1990 Sep 25;18(18):5495-503 [2216722] Nature. 1991 Jun 13;351(6327):588-90 [1646402] Science. 1991 Aug 16;253(5021):762-8 [1876833] J Virol. 1991 Oct;65(10):5289-96 [1654442] J Virol. 1974 Sep;14(3):640-51 [4369085] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of naloxone infusions in patients with the pruritus of cholestasis. A double-blind, randomized, controlled trial. AN - 77363997; 7598296 AB - To determine whether endogenous opioids contribute to the pruritus of cholestasis by studying the effect of the opiate antagonist naloxone on the perception of pruritus and on scratching activity in patients with this form of pruritus. Double-blind, placebo-controlled, crossover trial with four periods. Clinical research referral center. 29 pruritic patients with liver diseases of various causes. Each patient received as many as two naloxone and two placebo solution infusions consecutively in random order. Each infusion lasted 24 hours. During the infusions, visual analog scores of pruritus were recorded every 4 hours while patients were awake; scratching activity independent of limb movements was recorded continuously. One patient had a mild reaction consistent with a naloxone-precipitated syndrome similar to opiate withdrawal. A significant 24-hour rhythm of scratching activity was seen in 7 of 11 patients for whom complete 96-hour data were collected. The mean of a visual analog score of the perception of pruritus (maximum, 10.0) recorded during naloxone infusions was 0.582 lower than that recorded during placebo infusions (95% CI, 0.176 to 0.988; P < 0.01). Furthermore, the ratio of the geometric mean hourly scratching activity during naloxone infusions to that during placebo infusions was 0.727 (CI, 0.612 to 0.842; P < 0.001) and was greater than 1.0 in only five patients. Naloxone administration is associated with amelioration of the perception of pruritus and reduction of scratching activity in cholestatic patients. Because of the opioid receptor specificity of the action of naloxone, these findings support the hypothesis that a mechanism underlying the pruritus of cholestasis is modulated by endogenous opioids and suggest that opiate antagonists may have a role in the management of this complication of cholestasis. JF - Annals of internal medicine AU - Bergasa, N V AU - Alling, D W AU - Talbot, T L AU - Swain, M G AU - Yurdaydin, C AU - Turner, M L AU - Schmitt, J M AU - Walker, E C AU - Jones, E A AD - National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1995/08/01/ PY - 1995 DA - 1995 Aug 01 SP - 161 EP - 167 VL - 123 IS - 3 SN - 0003-4819, 0003-4819 KW - Naloxone KW - 36B82AMQ7N KW - Abridged Index Medicus KW - Index Medicus KW - Drug Administration Schedule KW - Infusions, Intravenous KW - Double-Blind Method KW - Humans KW - Motor Activity KW - Adult KW - Treatment Outcome KW - Cross-Over Studies KW - Aged KW - Middle Aged KW - Male KW - Female KW - Cholestasis -- complications KW - Pruritus -- drug therapy KW - Naloxone -- administration & dosage KW - Naloxone -- therapeutic use KW - Pruritus -- etiology KW - Naloxone -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77363997?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=American+Quarterly&rft.atitle=Never-ending+biography+--+Edgar+A.+Poe%3A+Mournful+and+Never-Ending+Remembrance+by+Kenneth+Silverman&rft.au=Rosenheim%2C+Shawn&rft.aulast=Rosenheim&rft.aufirst=Shawn&rft.date=1993-06-01&rft.volume=45&rft.issue=2&rft.spage=312&rft.isbn=&rft.btitle=&rft.title=American+Quarterly&rft.issn=00030678&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-03 N1 - Date created - 1995-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Both VH and VL chains of polyreactive IgM antibody are required for polyreactivity: expression of Fab in Escherichia coli AN - 1468384155; 18831332 AB - Monoclonal polyreactive antibodies can bind to many structurally dissimilar self and non-self antigens. Neither the precise antigen-binding site on the polyreactive antibody molecule nor the molecular basis of polyreactivity has been elucidated. The present study was initiated to see whether antibody genes encoding the Fab fragment of a human monoclonal polyreactive IgM antibody (MoAb 67) could be efficiently expressed in Escherichia coli, and whether the bacterially expressed Fab fragments possessed biological activity. cDNA encoding the variable domains of the heavy and light chains of MoAb 67 were cloned, amplified by polymerase chain reaction (PCR) and expressed in E. coli. Neither the recombinant heavy nor light chain showed antigen-binding activity. In contrast, the recombinant Fab 67 fragment showed the same antigen-binding reactivity profile as the native IgM antibody. It is concluded that the antigen-binding activity of polyreactive antibodies resides in the Fab fragment, and that both the heavy and light chains are required for activity. JF - Clinical and Experimental Immunology AU - Cheung, S C AU - Takeda, S AU - NOTKINS, AL AD - Laboratory of Oral Medicine, National Institute of Dental Research, National Institutes of Health, Bethesda, MD, USA Y1 - 1995/08// PY - 1995 DA - Aug 1995 SP - 383 EP - 386 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 101 IS - 2 SN - 0009-9104, 0009-9104 KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Light chains KW - Monoclonal antibodies KW - Escherichia coli KW - Polymerase chain reaction KW - Self KW - Fab KW - Immunoglobulin M KW - Autoantigens KW - F 06960:Molecular Immunology KW - J 02350:Immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1468384155?accountid=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+and+Experimental+Immunology&rft.atitle=Both+VH+and+VL+chains+of+polyreactive+IgM+antibody+are+required+for+polyreactivity%3A+expression+of+Fab+in+Escherichia+coli&rft.au=Cheung%2C+S+C%3BTakeda%2C+S%3BNOTKINS%2C+AL&rft.aulast=Cheung&rft.aufirst=S&rft.date=1995-08-01&rft.volume=101&rft.issue=2&rft.spage=383&rft.isbn=&rft.btitle=&rft.title=Clinical+and+Experimental+Immunology&rft.issn=00099104&rft_id=info:doi/10.1111%2Fj.1365-2249.1995.tb08368.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2013-12-01 N1 - Last updated - 2014-05-02 N1 - SubjectsTermNotLitGenreText - Light chains; Monoclonal antibodies; Self; Polymerase chain reaction; Fab; Autoantigens; Immunoglobulin M; Escherichia coli DO - http://dx.doi.org/10.1111/j.1365-2249.1995.tb08368.x ER - TY - JOUR T1 - Effect of MPTP on dopaminergic neurons in the goldfish brain: a light and electron microscope study. AN - 77569306; 7583312 AB - The neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) causes a Parkinsonian syndrome in the goldfish (Carassius auratus), characterized by transient bradykinesia, the accumulation of MPP+ in the brain, and a decrease in the forebrain and midbrain content of catecholamines (Pollard et al., FASEB J., 6 (1992) 3108-3116). Using light and electron microscopy, we studied the effect of MPTP on the distribution and ultrastructure of tyrosine hydroxylase (TH)-immunoreactive, dopaminergic neurons, and on the ultrastructure of other selected areas of the goldfish brain. Goldfish were treated with MPTP (50 mg/kg) in the absence or presence of L-deprenyl (10 mg/kg) or clorgyline (10 mg/kg). In the medial part of the central telencephalon, the nucleus telencephali, pars medialis, MPTP caused a decrease in the number of TH-immunoreactive neurons and distortions in their labelling pattern. Electron microscopic observations showed that MPTP caused swelling of cell processes, changes in neuronal nuclear profiles, dilation of endoplasmic reticulum, intracellular vacuolization and membrane distortions, and degeneration of neuronal fibers in this brain area. MPTP also caused a small reduction and some diffuseness in the labelling of dopaminergic neurons in several diencephalic periventricular nuclei. Moreover, MPTP induced cell swelling and degeneration in the subependymal cell layers along the forebrain ventricles. In all areas, L-deprenyl appeared to partially prevent the MPTP-induced degenerative changes. We conclude that in the goldfish MPTP causes marked histochemical changes in selected dopaminergic brain systems coincident with the Parkinson-like locomotor and neurochemical deficits. JF - Brain research AU - Goping, G AU - Pollard, H B AU - Adeyemo, O M AU - Kuijpers, G A AD - Laboratory of Cell Biology and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/07/31/ PY - 1995 DA - 1995 Jul 31 SP - 35 EP - 52 VL - 687 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Dopamine Agents KW - 0 KW - Monoamine Oxidase Inhibitors KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Tyrosine 3-Monooxygenase -- metabolism KW - Telencephalon -- drug effects KW - Telencephalon -- physiology KW - Telencephalon -- cytology KW - Microscopy, Electron KW - Immunohistochemistry KW - Monoamine Oxidase Inhibitors -- pharmacology KW - Dopamine Agents -- toxicity KW - Brain -- cytology KW - Neurons -- drug effects KW - MPTP Poisoning KW - Goldfish -- physiology KW - Dopamine -- physiology KW - Neurons -- enzymology KW - Brain -- ultrastructure KW - Neurons -- ultrastructure KW - Brain -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77569306?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research&rft.atitle=Effect+of+MPTP+on+dopaminergic+neurons+in+the+goldfish+brain%3A+a+light+and+electron+microscope+study.&rft.au=Goping%2C+G%3BPollard%2C+H+B%3BAdeyemo%2C+O+M%3BKuijpers%2C+G+A&rft.aulast=Goping&rft.aufirst=G&rft.date=1995-07-31&rft.volume=687&rft.issue=1-2&rft.spage=35&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 - 1995-12-14 N1 - Date created - 1995-12-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retinoic acid and methotrexate specifically increase PHA-E-lectin binding to a 67-kDa glycoprotein in LA-N-1 human neuroblastoma cells. AN - 77431170; 7543081 AB - Retinoic acid (RA) decreased growth and increased morphologic differentiation of human neuroblastoma LA-N-1 cells. These phenomena correlated with a specific enhancement of PHA-E lectin binding to a glycoprotein of MW 67 kDa (gp67). Gp67 was found susceptible to N-glycanase and displayed BSA binding by affinity chromatography analysis. The chemotherapeutic agent methotrexate (MTX) also reduced growth and induced differentiation of LA-N-1 cells. In addition, the cells responded to MTX as well as to doxorubicin by a marked increase in PHA-E binding to gp67. We conclude that reduced growth and induction of morphological differentiation of LA-N-1 cells correlates with increased binding of PHA-E to gp67. JF - International journal of cancer AU - Ross, S A AU - Jones, C S AU - De Luca, L M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/07/28/ PY - 1995 DA - 1995 Jul 28 SP - 303 EP - 308 VL - 62 IS - 3 SN - 0020-7136, 0020-7136 KW - Antibodies KW - 0 KW - Lectins KW - Membrane Glycoproteins KW - Neoplasm Proteins KW - Phytohemagglutinins KW - Serum Albumin, Bovine KW - erythroagglutinating phytohemagglutinin KW - Tretinoin KW - 5688UTC01R KW - Sepharose KW - 9012-36-6 KW - Amidohydrolases KW - EC 3.5.- KW - Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase KW - EC 3.5.1.52 KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Sensitivity and Specificity KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Staining and Labeling -- methods KW - Cell Division -- drug effects KW - Cell Division -- physiology KW - Chromatography, Affinity KW - Cell Differentiation -- physiology KW - Serum Albumin, Bovine -- immunology KW - Protein Binding -- drug effects KW - Amidohydrolases -- pharmacology KW - Cell Differentiation -- drug effects KW - Lectins -- metabolism KW - Neuroblastoma -- pathology KW - Tretinoin -- pharmacology KW - Methotrexate -- pharmacology KW - Phytohemagglutinins -- metabolism KW - Neuroblastoma -- metabolism KW - Neoplasm Proteins -- metabolism KW - Membrane Glycoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77431170?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Retinoic+acid+and+methotrexate+specifically+increase+PHA-E-lectin+binding+to+a+67-kDa+glycoprotein+in+LA-N-1+human+neuroblastoma+cells.&rft.au=Ross%2C+S+A%3BJones%2C+C+S%3BDe+Luca%2C+L+M&rft.aulast=Ross&rft.aufirst=S&rft.date=1995-07-28&rft.volume=62&rft.issue=3&rft.spage=303&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 - 1995-09-07 N1 - Date created - 1995-09-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cinnamic acid: a natural product with potential use in cancer intervention. AN - 77429863; 7628877 AB - Cinnamic acid, a naturally occurring aromatic fatty acid of low toxicity, has a long history of human exposure. We now show that cinnamic acid induces cytostasis and a reversal of malignant properties of human tumor cells in vitro. The concentration causing a 50% reduction of cell proliferation (IC50) ranged from 1 to 4.5 mM in glioblastoma, melanoma, prostate and lung carcinoma cells. Using melanoma cells as a model, we found that cinnamic acid induces cell differentiation as evidenced by morphological changes and increased melanin production. Moreover, treated cells had reduced invasive capacity associated with modulation of expression of genes implicated in tumor metastasis (collagenase type IV, and tissue inhibitor metalloproteinase 2) and immunogenicity (HLA-A3, class-I major histocompatibility antigen). Further molecular analysis indicated that the anti-tumor activity of cinnamic acid may be due in part to the inhibition of protein isoprenylation known to block mitogenic signal transduction. The results presented here identify cinnamic acid as a new member of the aromatic fatty acid class of differentiation-inducers with potential use in cancer intervention. JF - International journal of cancer AU - Liu, L AU - Hudgins, W R AU - Shack, S AU - Yin, M Q AU - Samid, D AD - Differentiation Section, Clinical Pharmacology Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/07/28/ PY - 1995 DA - 1995 Jul 28 SP - 345 EP - 350 VL - 62 IS - 3 SN - 0020-7136, 0020-7136 KW - Antineoplastic Agents KW - 0 KW - Cinnamates KW - Neoplasm Proteins KW - cinnamic acid KW - U14A832J8D KW - Index Medicus KW - Pigmentation -- drug effects KW - Gene Expression -- drug effects KW - Neoplasm Invasiveness KW - Drug Screening Assays, Antitumor KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Lung Neoplasms -- drug therapy KW - Cell Division -- drug effects KW - Glioblastoma -- drug therapy KW - Melanoma -- metabolism KW - Protein Prenylation -- drug effects KW - Melanoma -- pathology KW - Glioblastoma -- pathology KW - Glioblastoma -- metabolism KW - Melanoma -- drug therapy KW - Cell Differentiation -- drug effects KW - Neoplasm Proteins -- metabolism KW - Lung Neoplasms -- metabolism KW - Lung Neoplasms -- pathology KW - Neoplasms -- drug therapy KW - Neoplasms -- pathology KW - Cinnamates -- pharmacology KW - Antineoplastic Agents -- pharmacology KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77429863?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Apqrl&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=unknown&rft.jtitle=Sewanee+Review&rft.atitle=A+Definitive+Poor+Edgar+--+Edgar+A.+Poe%3A+Mournful+and+Never-Ending+Remembrance+by+Kenneth+Silverman&rft.au=Galligan%2C+Edward+L&rft.aulast=Galligan&rft.aufirst=Edward&rft.date=1992-07-01&rft.volume=100&rft.issue=3&rft.spage=lxxvii&rft.isbn=&rft.btitle=&rft.title=Sewanee+Review&rft.issn=00373052&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-07 N1 - Date created - 1995-09-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mapping of single amino acid residues required for selective activation of Gq/11 by the m3 muscarinic acetylcholine receptor. AN - 77426295; 7629074 AB - Each G protein-coupled receptor can interact only with a limited number of the many structurally similar G proteins expressed within a cell. This study was undertaken to identify single amino acids required for selectively coupling the m3 muscarinic acetylcholine receptor to G proteins of the Gq/11 family. To this goal, distinct intracellular segments/amino acids of the m3 receptor were systematically substituted into the structurally closely related m2 muscarinic receptor, which couples to Gi/o proteins, not Gq/11 proteins. The resultant mutant receptors were expressed in COS-7 cells and studied for their ability to induce agonist-dependent stimulation of phosphatidylinositol hydrolysis, a response known to be mediated by G proteins of the Gq/11 class. Using this approach, we were able to identify four amino acids in the second intracellular loop and four amino acids at the C terminus of the third intracellular loop of the m3 muscarinic receptor that are essential for efficient Gq/11 activation. We could demonstrate that these amino acids, together with a short segment at the N terminus of the third intracellular loop, fully account for the G protein coupling preference of the m3 muscarinic receptor. Taken together, our data strongly suggest that only a limited number of amino acids, located on different intracellular regions, are required to determine the functional profile of a given G protein-coupled receptor. JF - The Journal of biological chemistry AU - Blin, N AU - Yun, J AU - Wess, J AD - Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/07/28/ PY - 1995 DA - 1995 Jul 28 SP - 17741 EP - 17748 VL - 270 IS - 30 SN - 0021-9258, 0021-9258 KW - Amino Acids KW - 0 KW - Phosphatidylinositols KW - Receptors, Muscarinic KW - Carbachol KW - 8Y164V895Y KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Phosphatidylinositols -- metabolism KW - Animals KW - Sequence Alignment KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Hydrolysis KW - Carbachol -- pharmacology KW - Cell Line KW - GTP-Binding Proteins -- metabolism KW - GTP-Binding Proteins -- chemistry KW - Amino Acids -- metabolism KW - Receptors, Muscarinic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77426295?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Mapping+of+single+amino+acid+residues+required+for+selective+activation+of+Gq%2F11+by+the+m3+muscarinic+acetylcholine+receptor.&rft.au=Blin%2C+N%3BYun%2C+J%3BWess%2C+J&rft.aulast=Blin&rft.aufirst=N&rft.date=1995-07-28&rft.volume=270&rft.issue=30&rft.spage=17741&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 - 1995-09-05 N1 - Date created - 1995-09-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Administration of disulfide-stabilized Fv-immunotoxins B1(dsFv)-PE38 and B3(dsFv)-PE38 by continuous infusion increases their efficacy in curing large tumor xenografts in nude mice. AN - 77426073; 7628878 AB - B1 (dsFv)-PE38 and B3(dsFv)-PE38 are recombinant immunotoxins in which the Fv fragments of MAbs B1 and B3, respectively, are stabilized by an engineered interchain disulfide bond and are fused at their C-termini to a modified Pseudomonas exotoxin from which the cell-binding domain has been deleted (PE38). Both immunotoxins have been shown to be specifically cytotoxic toward human cancer cell lines which express Le gamma-related carbohydrates on their surface, and when given i.v., eradicated 30- to 50-mm3 s.c. A431 tumors growing in nude mice. A major advantage of dsFv-immunotoxins is their stability at 37 degrees C compared with the relatively unstable single-chain Fvs. This allows them to be given continuously by osmotic pumps placed in the peritoneal cavity. In an attempt to increase the therapeutic index of the immunotoxins, we have now delivered them continuously for 6 days through mini-osmotic pumps placed in the peritoneal cavity of tumor-bearing nude mice. Using this mode of administration, we were able to maintain a constant level of immunotoxin in the serum which was non-toxic to the mice, but caused complete regressions of large 150- to 200-mm3 tumors which lasted for over a month at 1/11 of the LD50 with B1(dsFv)-PE38 and 1/6 of the LD50 with B3(dsFv)-PE38. Complete regression of tumors of similar size could also be achieved by i.v. bolus injections of these immunotoxins at 1/7 of the LD50 with B1(dsFv)-PE38) and 1/3 of the LD50 with B3(dsFv)-PE38. These results suggest that in patients it may be advantageous to administer dsFv-immunotoxins by continuous infusion, since a larger therapeutic index is achieved. JF - International journal of cancer AU - Benhar, I AU - Reiter, Y AU - Pai, L H AU - Pastan, I AD - Division of Cancer Biology, Diagnosis and Centers, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1995/07/28/ PY - 1995 DA - 1995 Jul 28 SP - 351 EP - 355 VL - 62 IS - 3 SN - 0020-7136, 0020-7136 KW - Antibodies, Monoclonal KW - 0 KW - Bacterial Toxins KW - Disulfides KW - Exotoxins KW - Immunoglobulin Fragments KW - Immunoglobulin Heavy Chains KW - Immunoglobulin Light Chains KW - Immunoglobulin Variable Region KW - Immunotoxins 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 - Immunoglobulin Light Chains -- administration & dosage KW - Animals KW - Drug Stability KW - Injections, Intravenous KW - Dose-Response Relationship, Drug KW - Humans KW - Infusion Pumps, Implantable KW - Mice, Nude KW - Mice KW - Infusions, Parenteral KW - Antibodies, Monoclonal -- administration & dosage KW - Neoplasm Transplantation KW - Immunoglobulin Heavy Chains -- administration & dosage KW - Immunoglobulin Fragments -- administration & dosage KW - Immunoglobulin Variable Region -- administration & dosage KW - Transplantation, Heterologous KW - Immunoglobulin Fragments -- immunology KW - Female KW - Immunotoxins -- chemistry KW - Exotoxins -- administration & dosage KW - Disulfides -- chemistry KW - Exotoxins -- blood KW - Disulfides -- administration & dosage KW - Neoplasms, Experimental -- therapy KW - Exotoxins -- chemistry KW - Immunotoxins -- administration & dosage KW - Immunotoxins -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77426073?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Administration+of+disulfide-stabilized+Fv-immunotoxins+B1%28dsFv%29-PE38+and+B3%28dsFv%29-PE38+by+continuous+infusion+increases+their+efficacy+in+curing+large+tumor+xenografts+in+nude+mice.&rft.au=Benhar%2C+I%3BReiter%2C+Y%3BPai%2C+L+H%3BPastan%2C+I&rft.aulast=Benhar&rft.aufirst=I&rft.date=1995-07-28&rft.volume=62&rft.issue=3&rft.spage=351&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 - 1995-09-07 N1 - Date created - 1995-09-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Kinetic characterization and cross-resistance patterns of HIV-1 protease mutants selected under drug pressure. AN - 77419272; 7626598 AB - Eleven different recombinant, drug-resistant HIV-1 protease (HIV PR) mutants--R8Q, V32I, M46I, V82A, V82F, V82I, I84V, V32I/I84V, M46I/V82F, M46I/I84V, and V32I/K45I/F53L/A71V/I84V/L89M--were generated on the basis of results of in vitro selection experiments using the inhibitors A-77003, A-84538, and KNI-272. Kinetic parameters of mutant and wild-type (WT) enzymes were measured along with inhibition constants (Ki) toward the inhibitors A-77003, A-84538, KNI-272, L-735,524, and Ro31-8959. The catalytic efficiency, kcat/Km, for the mutants decreased relative to WT by a factor of 1.2-14.8 and was mainly due to the elevation of Km. The effects of specific mutations on Ki values were unique with respect to both inhibitor and mutant enzyme. A new property, termed vitality, defined as the ratio (Kikcat/Km)mutant/(Kikcat/Km)WT was introduced to compare the selective advantage of different mutants in the presence of a given inhibitor. High vitality values were generally observed with mutations that emerged during in vitro selection studies. The kinetic model along with the panel of mutants described here should be useful for evaluating and predicting patterns of resistance for HIV PR inhibitors and may aid in the selection of inhibitor combinations to combat drug resistance. JF - Biochemistry AU - Gulnik, S V AU - Suvorov, L I AU - Liu, B AU - Yu, B AU - Anderson, B AU - Mitsuya, H AU - Erickson, J W AD - SAIC-Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA. Y1 - 1995/07/25/ PY - 1995 DA - 1995 Jul 25 SP - 9282 EP - 9287 VL - 34 IS - 29 SN - 0006-2960, 0006-2960 KW - A 84538 KW - 0 KW - Carbamates KW - HIV Protease Inhibitors KW - Isoquinolines KW - Methylurea Compounds KW - Oligopeptides KW - Pyridines KW - Quinolines KW - Recombinant Proteins KW - Thiazoles KW - Abbott 77003 KW - 134878-17-4 KW - kynostatin 272 KW - 147318-81-8 KW - Indinavir KW - 5W6YA9PKKH KW - HIV Protease KW - EC 3.4.23.- KW - Saquinavir KW - L3JE09KZ2F KW - Index Medicus KW - AIDS/HIV KW - Carbamates -- pharmacology KW - Methylurea Compounds -- pharmacology KW - Drug Resistance, Microbial KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Binding Sites KW - Cloning, Molecular KW - Thiazoles -- pharmacology KW - Mutagenesis, Site-Directed KW - Isoquinolines -- pharmacology KW - Quinolines -- pharmacology KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Oligopeptides -- pharmacology KW - Pyridines -- pharmacology KW - Point Mutation KW - HIV Protease Inhibitors -- pharmacology KW - HIV-1 -- enzymology KW - HIV Protease -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77419272?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Kinetic+characterization+and+cross-resistance+patterns+of+HIV-1+protease+mutants+selected+under+drug+pressure.&rft.au=Gulnik%2C+S+V%3BSuvorov%2C+L+I%3BLiu%2C+B%3BYu%2C+B%3BAnderson%2C+B%3BMitsuya%2C+H%3BErickson%2C+J+W&rft.aulast=Gulnik&rft.aufirst=S&rft.date=1995-07-25&rft.volume=&rft.issue=4652&rft.spage=5&rft.isbn=&rft.btitle=&rft.title=TLS%2C+the+Times+Literary+Supplement&rft.issn=0307661X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-07 N1 - Date created - 1995-09-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Insulin-stimulated phosphorylation of recombinant pp120/HA4, an endogenous substrate of the insulin receptor tyrosine kinase. AN - 77418013; 7626603 AB - Insulin binding to the alpha-subunit of its receptor stimulates the receptor tyrosine kinase to phosphorylate the beta-subunit and several endogenous protein substrates, including pp120/HA4, a liver-specific plasma membrane glycoprotein of M(r) 20,000. Analysis of the deduced amino acid sequence of rat liver pp120/HA4 revealed two potential sites for tyrosine phosphorylation in the cytoplasmic domain (Tyr488 and Tyr513), as well as a potential cAMP-dependent protein kinase phosphorylation site (Ser503). To determine which of these sites is phosphorylated in response to insulin, each of these amino acid residues was altered by site-directed mutagenesis. Mutant cDNAs were then expressed by stable transfection in NIH 3T3 cells. Two mutations (Phe488 and Ala503) impaired insulin-induced phosphorylation of pp120/HA4, suggesting that pp120/HA4 undergoes multisite phosphorylation. It seems likely that Tyr488 is phosphorylated by the insulin receptor kinase, and phosphorylation of Ser513 may contribute to the regulation of tyrosine phosphorylation. Since pp120/HA4 is believed to be associated with a Ca2+/Mg(2+)-dependent ecto-ATPase activity, we determined the effects of insulin-induced phosphorylation on this enzymatic activity. In NIH 3T3 cells co-expressing the insulin receptor and pp120/HA4, insulin caused a 2-fold increase in ecto-ATPase activity. Moreover, elimination of the phosphorylation sites of pp120/HA4 impaired the ability of insulin to stimulate the ecto-ATPase activity. These data suggest that tyrosine phosphorylation of pp120/HA4 may regulate Ca2+/Mg(2+)-dependent ecto-ATPase activity. JF - Biochemistry AU - Najjar, S M AU - Philippe, N AU - Suzuki, Y AU - Ignacio, G A AU - Formisano, P AU - Accili, D AU - Taylor, S I AD - Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/07/25/ PY - 1995 DA - 1995 Jul 25 SP - 9341 EP - 9349 VL - 34 IS - 29 SN - 0006-2960, 0006-2960 KW - DNA Primers KW - 0 KW - Insulin KW - Macromolecular Substances KW - Membrane Glycoproteins KW - Recombinant Fusion Proteins KW - Recombinant Proteins KW - Phenylalanine KW - 47E5O17Y3R KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Receptor, Insulin KW - Focal Adhesion Kinase 1 KW - EC 2.7.10.2 KW - Focal Adhesion Protein-Tyrosine Kinases KW - PTK2 protein, human KW - Ptk2 protein, mouse KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - ectoATPase KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - 3T3 Cells KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Humans KW - Adenosine Triphosphatases -- metabolism KW - Mice KW - Amino Acid Sequence KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Base Sequence KW - Phosphorylation KW - Transfection KW - Recombinant Proteins -- metabolism KW - Point Mutation KW - Molecular Sequence Data KW - Substrate Specificity KW - Cell Membrane -- metabolism KW - Receptor, Insulin -- biosynthesis KW - Liver -- metabolism KW - Protein-Tyrosine Kinases -- isolation & purification KW - Insulin -- pharmacology KW - Protein-Tyrosine Kinases -- metabolism KW - Receptor, Insulin -- metabolism KW - Membrane Glycoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77418013?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Insulin-stimulated+phosphorylation+of+recombinant+pp120%2FHA4%2C+an+endogenous+substrate+of+the+insulin+receptor+tyrosine+kinase.&rft.au=Najjar%2C+S+M%3BPhilippe%2C+N%3BSuzuki%2C+Y%3BIgnacio%2C+G+A%3BFormisano%2C+P%3BAccili%2C+D%3BTaylor%2C+S+I&rft.aulast=Najjar&rft.aufirst=S&rft.date=1995-07-25&rft.volume=34&rft.issue=29&rft.spage=9341&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-07 N1 - Date created - 1995-09-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A study of the intracellular routing of cytotoxic ribonucleases. AN - 77402633; 7542240 AB - Several ribonucleases serve as cytotoxic agents in host defense and in physiological cell death pathways. Although certain members of the pancreatic ribonuclease A superfamily can be toxic when applied to the outside of cells, they become thousands of times more toxic when artificially introduced into the cytosol, indicating that internalization is the rate-limiting step for cytotoxicity. We have used three agents that disrupt the Golgi apparatus by distinct mechanisms, retinoic acid, brefeldin A, and monensin, to probe the intracellular pathways ribonucleases take to reach the cytosol. Retinoic acid and monensin potentiate the cytotoxicity of bovine seminal RNase, Onconase, angiogenin, and human ribonuclease A 100 times or more. Retinoic acid-mediated potentiation of ribonucleases is completely blocked by brefeldin A. Ribonucleases appear to route more efficiently into the cytosol through the Golgi apparatus disrupted by monensin or retinoic acid. Intracellular RNA degradation by BS-RNase increased more than 100 times in the presence of retinoic acid confirming that the RNase reaches the cytosol and indicating that degradation of RNA is the intracellular lesion causing toxicity. As retinoic acid alone and Onconase are in clinical trials for cancer therapy, combinations of RNases and retinoic acid in vivo may offer new clinical utility. JF - The Journal of biological chemistry AU - Wu, Y AU - Saxena, S K AU - Ardelt, W AU - Gadina, M AU - Mikulski, S M AU - De Lorenzo, C AU - D'Alessio, G AU - Youle, R J AD - Biochemistry Section, NINDS, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/07/21/ PY - 1995 DA - 1995 Jul 21 SP - 17476 EP - 17481 VL - 270 IS - 29 SN - 0021-9258, 0021-9258 KW - Antineoplastic Agents KW - 0 KW - Cyclopentanes KW - Egg Proteins KW - Proteins KW - Brefeldin A KW - 20350-15-6 KW - Tretinoin KW - 5688UTC01R KW - RNA KW - 63231-63-0 KW - Monensin KW - 906O0YJ6ZP KW - Ribonucleases KW - EC 3.1.- KW - angiogenin KW - EC 3.1.27.- KW - Ribonuclease, Pancreatic KW - EC 3.1.27.5 KW - ranpirnase KW - ZE15FIT23E KW - Index Medicus KW - Tretinoin -- pharmacology KW - Animals KW - Golgi Apparatus -- drug effects KW - Humans KW - Amino Acid Sequence KW - Monensin -- pharmacology KW - Rats KW - Proteins -- pharmacology KW - Base Sequence KW - Cattle KW - Cyclopentanes -- pharmacology KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - RNA -- metabolism KW - Molecular Sequence Data KW - Egg Proteins -- pharmacology KW - Ribonucleases -- pharmacology KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77402633?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+study+of+the+intracellular+routing+of+cytotoxic+ribonucleases.&rft.au=Wu%2C+Y%3BSaxena%2C+S+K%3BArdelt%2C+W%3BGadina%2C+M%3BMikulski%2C+S+M%3BDe+Lorenzo%2C+C%3BD%27Alessio%2C+G%3BYoule%2C+R+J&rft.aulast=Wu&rft.aufirst=Y&rft.date=1995-07-21&rft.volume=64&rft.issue=2&rft.spage=373&rft.isbn=&rft.btitle=&rft.title=American+Literature&rft.issn=00029831&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-22 N1 - Date created - 1995-08-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Murine txk: a protein tyrosine kinase gene regulated by T cell activation. AN - 77420018; 7542761 AB - To identify genes involved in signal transduction pathways that regulate T cell activation and development, murine fetal thymocytes were screened for expression of protein tyrosine kinase family members by the polymerase chain reaction. Using this approach, a non-receptor protein tyrosine kinase, txk, was identified and cloned. Tsk is expressed in thymocytes as early as fetal day 13.5 and its expression at the mRNA level continues throughout development. Txk transcripts are present in thymocytes, peripheral T cells and mast cell lines, but are not detectable in B cell macrophage/monocyte cell lines or in non-hematopoietic fetal or adult tissues. In both thymocytes and T cells, txk transcripts are down-regulated after activation with PMA and ionomycin, concanavalin A or T cell receptor cross-linking. Sequence analysis indicates that txk contains SH2, SH3 and kinase catalytic domains and belongs to the tec family of cytoplasmic protein tyrosine kinases which includes tec, itk and btk. Its unique N-terminus contains a proline-rich region, but unlike the other tec family members, does not contain a pleckstrin homology domain. The restricted expression pattern of txk and its regulation by T cell activation make it an excellent candidate for involvement in signal transduction during thymocyte development. JF - Oncogene AU - Sommers, C L AU - Huang, K AU - Shores, E W AU - Grinberg, A AU - Charlick, D A AU - Kozak, C A AU - Love, P E AD - Laboratory of Mammalian Genes and Development, NICHD, NIH, Bethesda, Maryland 20892, USA. Y1 - 1995/07/20/ PY - 1995 DA - 1995 Jul 20 SP - 245 EP - 251 VL - 11 IS - 2 SN - 0950-9232, 0950-9232 KW - hP13K KW - htxk KW - m3BP1 KW - m3BP2 KW - mbtk KW - mformin KW - mitk KW - mtecII KW - mtxk KW - Antigens, CD4 KW - 0 KW - Antigens, CD8 KW - DNA Primers KW - DNA, Complementary KW - Phorbol Esters KW - RNA, Messenger KW - Ionomycin KW - 56092-81-0 KW - RNA KW - 63231-63-0 KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Index Medicus KW - Animals KW - Embryo, Mammalian -- physiology KW - Blotting, Northern KW - Antigens, CD8 -- physiology KW - Gene Expression Regulation -- immunology KW - Humans KW - Ionomycin -- pharmacology KW - Chromosome Mapping KW - Antigens, CD4 -- physiology KW - Lymphocyte Activation KW - Antigens, CD4 -- drug effects KW - Molecular Sequence Data KW - Mast Cells -- physiology KW - Thymus Gland -- enzymology KW - Thymus Gland -- embryology KW - Sequence Homology, Amino Acid KW - RNA -- genetics KW - DNA, Complementary -- genetics KW - RNA, Messenger -- physiology KW - RNA, Messenger -- analysis KW - Antigens, CD8 -- drug effects KW - Mast Cells -- enzymology KW - Amino Acid Sequence KW - Mice KW - Cloning, Molecular KW - Phorbol Esters -- pharmacology KW - Base Sequence KW - Conserved Sequence KW - Polymerase Chain Reaction -- methods KW - Embryo, Mammalian -- cytology KW - Crosses, Genetic KW - RNA -- chemistry KW - Thymus Gland -- physiology KW - Cell Line KW - Protein-Tyrosine Kinases -- genetics KW - Protein-Tyrosine Kinases -- blood KW - T-Lymphocytes -- drug effects KW - T-Lymphocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77420018?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Murine+txk%3A+a+protein+tyrosine+kinase+gene+regulated+by+T+cell+activation.&rft.au=Sommers%2C+C+L%3BHuang%2C+K%3BShores%2C+E+W%3BGrinberg%2C+A%3BCharlick%2C+D+A%3BKozak%2C+C+A%3BLove%2C+P+E&rft.aulast=Sommers&rft.aufirst=C&rft.date=1995-07-20&rft.volume=11&rft.issue=2&rft.spage=245&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-31 N1 - Date created - 1995-08-31 N1 - Date revised - 2017-01-13 N1 - Gene symbol - hP13K; htxk; m3BP1; m3BP2; mbtk; mformin; mitk; mtecII; mtxk N1 - Genetic sequence - U19607; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A splice variant of alpha 6 integrin is associated with malignant conversion in mouse skin tumorigenesis. AN - 77421334; 7624366 AB - The epithelial-specific integrin alpha 6 beta 4 is suprabasally expressed in benign skin tumors (papillomas) and is diffusely expressed in carcinomas associated with an increase in the proliferating compartment. Analysis of RNA samples by reverse transcriptase-PCR and DNA sequencing revealed that chemically or oncogenically induced papillomas (n = 8) expressed a single transcript of the alpha 6 subunit, identified as the alpha 6 A splice variant. In contrast, carcinomas (n = 13) expressed both alpha 6A and an alternatively spliced form, alpha 6B. Primary keratinocytes and a number of keratinocyte cell lines that vary in biological potential from normal skin, to benign papillomas, to well-differentiated slowly growing carcinomas exclusively expressed alpha 6A. However, I7, an oncogene-induced cell line that produces highly invasive carcinomas, expressed both alpha 6A and alpha 6B transcript and protein. The expression of alpha 6B in I7 cells was associated with increased attachment to a laminin matrix compared to cell lines exclusively expressing alpha 6A. Furthermore, introduction of an alpha 6B expression vector into a papilloma cell line expressing alpha 6A increased laminin attachment. When a papilloma cell line was converted to an invasive carcinoma by introduction of the v-fos oncogene, the malignant cells expressed both alpha 6A and alpha 6B, while the parent cell line and cells transduced with v-jun or c-myc, which retained the papilloma phenotype, expressed only alpha 6A. Comparative analysis of alpha 6B expression in cell lines and their derived tumors indicate that alpha 6B transcripts are more abundant in tumors than cell lines, and alpha 6B is expressed to a greater extent in poorly differentiated tumors. These results establish a link between malignant conversion and invasion of squamous tumor cells and the regulation of transcript processing of the alpha 6 beta 4 integrin. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Tennenbaum, T AU - Belanger, A J AU - Glick, A B AU - Tamura, R AU - Quaranta, V AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/07/18/ PY - 1995 DA - 1995 Jul 18 SP - 7041 EP - 7045 VL - 92 IS - 15 SN - 0027-8424, 0027-8424 KW - Integrin alpha6 KW - 0 KW - Integrins KW - Oncogene Proteins v-fos KW - RNA, Messenger KW - Index Medicus KW - Animals KW - Precancerous Conditions KW - Mice KW - Oncogene Proteins v-fos -- genetics KW - RNA, Messenger -- genetics KW - Mice, Inbred BALB C KW - Papilloma -- genetics KW - Neoplasms, Experimental KW - Polymerase Chain Reaction KW - Blotting, Western KW - Fluorescent Antibody Technique KW - Cell Adhesion KW - Skin Neoplasms -- genetics KW - Carcinoma -- etiology KW - Alternative Splicing KW - Skin Neoplasms -- etiology KW - Skin Neoplasms -- chemically induced KW - Integrins -- genetics KW - Cell Transformation, Neoplastic -- genetics KW - Integrins -- biosynthesis KW - Carcinoma -- genetics KW - Carcinoma -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77421334?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+splice+variant+of+alpha+6+integrin+is+associated+with+malignant+conversion+in+mouse+skin+tumorigenesis.&rft.au=Tennenbaum%2C+T%3BBelanger%2C+A+J%3BGlick%2C+A+B%3BTamura%2C+R%3BQuaranta%2C+V%3BYuspa%2C+S+H&rft.aulast=Tennenbaum&rft.aufirst=T&rft.date=1995-07-18&rft.volume=92&rft.issue=15&rft.spage=7041&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 - 1995-08-31 N1 - Date created - 1995-08-31 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochemistry. 1979 Nov 27;18(24):5294-9 [518835] J Biol Chem. 1993 Sep 5;268(25):18427-30 [8360143] Cancer Res. 1980 Dec;40(12):4694-703 [7438101] J Invest Dermatol. 1981 Feb;76(2):144-6 [7462678] Cell. 1987 Feb 27;48(4):549-54 [3028640] Cancer Res. 1988 Jan 1;48(1):165-9 [3121168] Proc Natl Acad Sci U S A. 1989 Jul;86(14):5415-8 [2787511] Mol Carcinog. 1988;1(2):134-43 [2475137] Proc Natl Acad Sci U S A. 1990 Jan;87(2):643-7 [2153961] Annu Rev Immunol. 1990;8:365-400 [2188667] Science. 1990 Aug 10;249(4969):677-9 [1696397] J Cell Biol. 1990 Oct;111(4):1593-604 [1976638] J Cell Biol. 1990 Dec;111(6 Pt 2):3141-54 [2269668] Bioessays. 1990 Dec;12(12):583-90 [2080913] Cell. 1991 Apr 5;65(1):13-24 [1707342] J Cell Biol. 1991 May;113(4):907-17 [2026654] Cell Regul. 1991 Jun;2(6):427-38 [1883873] J Cell Biol. 1991 Nov;115(3):843-50 [1833411] Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10183-7 [1946438] Cancer Res. 1992 Mar 15;52(6):1439-44 [1540951] Cell. 1992 Apr 3;69(1):11-25 [1555235] Cancer Res. 1992 May 15;52(10):2966-76 [1533815] J Biol Chem. 1993 Sep 5;268(25):19019-24 [8360188] Cancer Res. 1993 Oct 15;53(20):4803-10 [8402665] J Biol Chem. 1993 Dec 5;268(34):25865-75 [8245021] J Biol Chem. 1993 Dec 15;268(35):26773-83 [8253814] Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):609-13 [8290571] J Cell Biol. 1994 Mar;124(6):1047-59 [7510712] J Cell Biol. 1994 Apr;125(1):205-14 [8138572] Mol Carcinog. 1994 Feb;9(2):61-6 [8142009] Cell Adhes Commun. 1993 May;1(1):33-53 [8081870] Genes Dev. 1994 Oct 15;8(20):2429-40 [7958907] J Cell Biol. 1993 Apr;121(1):179-91 [7681434] J Biol Chem. 1993 May 25;268(15):11401-8 [8496190] J Cell Biol. 1993 Jul;122(1):223-33 [8314843] J Cell Biol. 1993 Jul;122(2):431-42 [8320265] Cell. 1980 Jan;19(1):245-54 [6153576] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Escherichia coli adenylyl cyclase complex: requirement of PTS proteins for stimulation by nucleotides. AN - 77410869; 7619794 AB - GTP, as well as other nucleoside triphosphates, stimulates the activity of Escherichia coli adenylyl cyclase in permeable cells; the stimulatory effect is lost when the cells are disrupted by passage through a French pressure cell. These data suggested that the allosteric regulation by GTP of adenylyl cyclase activity requires an interaction of the enzyme with other protein factors. Strains deleted for genes encoding proteins of the phosphoenolpyruvate:sugar phosphotransferase system (PTS) failed to show an activity stimulation by GTP. With a view to localizing the site of interaction of GTP with the adenylyl cyclase complex, a variety of studies using purified PTS proteins were performed using the photoaffinity labeling reagent, 8-azidoGTP. These studies showed that 8-azidoGTP bound specifically to HPr. A species specificity study showed that the photoaffinity reagent labeled E. coli HPr but not HPr proteins from Mycoplasma capricolum or Bacillus subtilis. A variety of site-directed mutations of E. coli HPr were evaluated for interaction with GTP by photoaffinity labeling as well as by nuclear magnetic resonance; the results of these studies indicate that the lysine residues at positions 24 and 27, serine-46, the threonine at position 36, and the aspartate at position 69 are important for the binding of GTP to HPr. Molecular modeling has been used to formulate a model for the binding of GTP to HPr involving electrostatic interaction of the phosphate groups of the nucleotide with the side chains of lysine residues 27 and 45 and serine-43, interaction of the sugar with serine-46, and interaction of the base with lysine-24. From these data, it is hypothesized that the binding of GTP to HPr is required for the GTP-dependent stimulation of the activity of the adenylyl cyclase complex. JF - Biochemistry AU - Peterkofsky, A AU - Seok, Y J AU - Amin, N AU - Thapar, R AU - Lee, S Y AU - Klevit, R E AU - Waygood, E B AU - Anderson, J W AU - Gruschus, J AU - Huq, H AD - Laboratory of Biochemical Genetics, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892, USA. Y1 - 1995/07/18/ PY - 1995 DA - 1995 Jul 18 SP - 8950 EP - 8959 VL - 34 IS - 28 SN - 0006-2960, 0006-2960 KW - Affinity Labels KW - 0 KW - Bacterial Proteins KW - DNA Primers KW - DNA, Bacterial KW - Guanosine Triphosphate KW - 86-01-1 KW - Phosphoenolpyruvate Sugar Phosphotransferase System KW - EC 2.7.1.- KW - phosphocarrier protein HPr KW - Adenylyl Cyclases KW - EC 4.6.1.1 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Models, Molecular KW - DNA Primers -- genetics KW - DNA, Bacterial -- genetics KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Models, Biological KW - Protein Conformation KW - Magnetic Resonance Spectroscopy KW - Binding Sites KW - Escherichia coli -- metabolism KW - Phosphoenolpyruvate Sugar Phosphotransferase System -- genetics KW - Guanosine Triphosphate -- chemistry KW - Phosphoenolpyruvate Sugar Phosphotransferase System -- chemistry KW - Phosphoenolpyruvate Sugar Phosphotransferase System -- metabolism KW - Adenylyl Cyclases -- metabolism KW - Escherichia coli -- genetics KW - Escherichia coli -- enzymology KW - Guanosine Triphosphate -- pharmacology KW - Guanosine Triphosphate -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77410869?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asoutheastnews&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=unknown&rft.jtitle=The+Atlanta+Journal+the+Atlanta+Constitution&rft.atitle=Non-Fiction+Digest--Edgar+A.+Poe%3A+Mournful+and+Never-Ending+Remembrance&rft.au=&rft.aulast=&rft.aufirst=&rft.date=1991-12-29&rft.volume=&rft.issue=&rft.spage=K9&rft.isbn=&rft.btitle=&rft.title=The+Atlanta+Journal+the+Atlanta+Constitution&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-30 N1 - Date created - 1995-08-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhancement by hydroxyurea of the anti-human immunodeficiency virus type 1 potency of 2'-beta-fluoro-2',3'-dideoxyadenosine in peripheral blood mononuclear cells. AN - 77435714; 7632173 AB - Ribonucleotide reductase inhibitors such as hydroxyurea (HU) and related compounds, at low, non-toxic doses, enhance the anti-human immunodeficiency virus type 1 (HIV-1) potency of both purine and pyrimidine 2',3'-dideoxynucleosides (ddNs) in human lymphocytes and macrophages. The most marked enhancement of inhibition of HIV-1 replication reported to date has been seen with the purine ddN 2',3'-dideoxyinosine (ddIno): a low level of HU (0.1 mM) permitted a 4.5-fold reduction in optimal ddIno dosage with no decrease in therapeutic effect or increase in toxicity. We report here even more marked enhancement by HU of the potency of the purine ddN 2'-beta-fluoro-2',3'-dideoxyadenosine (2'-beta-F-ddAdo), where the addition of 0.1 mM HU permitted a 7.1-fold reduction in the optimal dose of 2'-beta-F-ddAdo in the phytohemagglutinin-activated peripheral blood mononuclear cell HIV-1 test system. JF - Biochemical pharmacology AU - Gao, W Y AU - Mitsuya, H AU - Driscoll, J S AU - Johns, D G AD - Experimental Retrovirology Section, NCI, National Institutes of Health, Bethesda, MD 20982, USA. Y1 - 1995/07/17/ PY - 1995 DA - 1995 Jul 17 SP - 274 EP - 276 VL - 50 IS - 2 SN - 0006-2952, 0006-2952 KW - Antiviral Agents KW - 0 KW - HIV Core Protein p24 KW - lodenosine KW - 3WB2LGT4R1 KW - Dideoxyadenosine KW - 4Q86AH641A KW - Hydroxyurea KW - X6Q56QN5QC KW - Index Medicus KW - AIDS/HIV KW - Cells, Cultured KW - Humans KW - HIV Core Protein p24 -- analysis KW - Drug Synergism KW - Antiviral Agents -- pharmacology KW - Dideoxyadenosine -- pharmacology KW - Monocytes -- drug effects KW - Hydroxyurea -- pharmacology KW - Monocytes -- virology KW - HIV-1 -- drug effects KW - Dideoxyadenosine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77435714?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=Enhancement+by+hydroxyurea+of+the+anti-human+immunodeficiency+virus+type+1+potency+of+2%27-beta-fluoro-2%27%2C3%27-dideoxyadenosine+in+peripheral+blood+mononuclear+cells.&rft.au=Gao%2C+W+Y%3BMitsuya%2C+H%3BDriscoll%2C+J+S%3BJohns%2C+D+G&rft.aulast=Gao&rft.aufirst=W&rft.date=1995-07-17&rft.volume=62&rft.issue=1&rft.spage=144&rft.isbn=&rft.btitle=&rft.title=Journal+of+Investigative+Medicine&rft.issn=10815589&rft_id=info:doi/10.2310%2FJIM.0000000000000033 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-01 N1 - Date created - 1995-09-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical toxicity of peripheral nerve to intraoperative radiotherapy in a canine model. AN - 77387718; 7607923 AB - The clinical late effects of intraoperative radiotherapy (IORT) on peripheral nerve were investigated in a foxhound model. Between 1982 and 1987, 40 animals underwent laparotomy with intraoperative radiotherapy of doses from 0-75 Gy administered to the right lumbosacral plexus. Subsequently, all animals were monitored closely and sacrificed to assess clinical effects to peripheral nerve. This analysis reports final clinical results of all animals, with follow-up to 5 years. All animals treated with > or = 25 Gy developed ipsilateral neuropathy. An inverse relationship was noted between intraoperative radiotherapy dose and time to neuropathy, with an effective dose for 50% paralysis (ED50) of 17.2 Gy. One of the animals treated with 15 Gy IORT developed paralysis, after a much longer latency than the other animals. Doses of 15 Gy delivered intraoperatively may be accompanied by peripheral neuropathy with long-term follow-up. This threshold is less than that reported with shorter follow-up. The value of ED50 determined here is in keeping with data from other animal trials, and from clinical trials in humans. JF - International journal of radiation oncology, biology, physics AU - Johnstone, P A AU - DeLuca, A M AU - Bacher, J D AU - Hampshire, V A AU - Terrill, R E AU - Anderson, W J AU - Kinsella, T J AU - Sindelar, W F AD - Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/07/15/ PY - 1995 DA - 1995 Jul 15 SP - 1031 EP - 1034 VL - 32 IS - 4 SN - 0360-3016, 0360-3016 KW - Index Medicus KW - Radiation Dosage KW - Animals KW - Peripheral Nervous System Diseases -- etiology KW - Dogs KW - Follow-Up Studies KW - Intraoperative Period KW - Time Factors KW - Radiotherapy -- adverse effects KW - Paralysis -- etiology KW - Peripheral Nerves -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77387718?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+radiation+oncology%2C+biology%2C+physics&rft.atitle=Clinical+toxicity+of+peripheral+nerve+to+intraoperative+radiotherapy+in+a+canine+model.&rft.au=Johnstone%2C+P+A%3BDeLuca%2C+A+M%3BBacher%2C+J+D%3BHampshire%2C+V+A%3BTerrill%2C+R+E%3BAnderson%2C+W+J%3BKinsella%2C+T+J%3BSindelar%2C+W+F&rft.aulast=Johnstone&rft.aufirst=P&rft.date=1995-07-15&rft.volume=32&rft.issue=4&rft.spage=1031&rft.isbn=&rft.btitle=&rft.title=International+journal+of+radiation+oncology%2C+biology%2C+physics&rft.issn=03603016&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-17 N1 - Date created - 1995-08-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Radiation dose-response of human tumors. AN - 77385250; 7607946 AB - The dose of radiation that locally controls human tumors treated electively or for gross disease is rarely well defined. These doses can be useful in understanding the dose requirements of novel therapies featuring inhomogeneous dosimetry and in an adjuvant setting. The goal of this study was to compute the dose of radiation that locally controls 50% (TCD50) of tumors in human subjects. Logit regression was used with data collected from single institutions or from combinations of local control data accumulated from several institutions treating the same disease. 90 dose response curves were calculated; 62 of macroscopic tumor therapy, 28 of elective therapy with surgery for primary control. The mean and median TCD50 for gross disease were 50.0 and 51.9 Gy, respectively. The mean and median TCD50 for microscopic disease control were 39.3 and 37.9 Gy, respectively. At the TCD50, an additional dose of 1 Gy controlled an additional 2.5% (median) additional patients with macroscopic disease and 4.2% (median) additional patients with microscopic disease. For both macro- and microscopic disease, an increase of 1% of dose at the TCD50 increased control rates approximately 1% (median) or 2-3% (mean). A predominance of dose response curves had shallow slopes accounting for the discrepancy between mean and median values. Doses to control microscopic disease are approximately 12 Gy less than that required to control macroscopic disease, and are about 79% of the dose required to control macroscopic disease. The percentage increase in cures expected for a 1% increase in dose is similar for macroscopic microscopic disease, with a median value of approximately 1%/% and a mean of approximately 2.7%/%. JF - International journal of radiation oncology, biology, physics AU - Okunieff, P AU - Morgan, D AU - Niemierko, A AU - Suit, H D AD - Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/07/15/ PY - 1995 DA - 1995 Jul 15 SP - 1227 EP - 1237 VL - 32 IS - 4 SN - 0360-3016, 0360-3016 KW - Index Medicus KW - Humans KW - Neoplasms -- pathology KW - Neoplasms -- radiotherapy KW - Dose-Response Relationship, Radiation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77385250?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+radiation+oncology%2C+biology%2C+physics&rft.atitle=Radiation+dose-response+of+human+tumors.&rft.au=Okunieff%2C+P%3BMorgan%2C+D%3BNiemierko%2C+A%3BSuit%2C+H+D&rft.aulast=Okunieff&rft.aufirst=P&rft.date=1995-07-15&rft.volume=32&rft.issue=4&rft.spage=1227&rft.isbn=&rft.btitle=&rft.title=International+journal+of+radiation+oncology%2C+biology%2C+physics&rft.issn=03603016&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-17 N1 - Date created - 1995-08-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dosimetric considerations in treating mediastinal disease with mantle fields: characterization of the dose under mantle blocks. AN - 77384076; 7607929 AB - While the rationale for using mantle fields is well understood and the prescription of these fields is straightforward, the underlying complexity of the dose distributions that result is not generally appreciated. This is especially true in the choice of lung block design, which affects the dose to both the target volume as well as to the normal lung tissue. The key to the design of optimal lung blocks is the physician's perception of the complex relationship between the geometric and dosimetric aspects of heavily modified fields, as well as how the physical and anatomical properties of the target volume and the shape of the patient's lungs relate to the images visualized on simulator films. Depth doses and cross-beam profiles of blocks ranging in width from 1 cm to 10 cm were taken using an automated beam scanning system. These data were then converted to "shadow fields." The results were compared to open fields of the same size using standard methodology. Shadow fields behave quite similarly to small, open fields in terms of x-ray-light field congruence, flatness, symmetry, and penumbra. There is a 2-3 mm rim between the edge of the block and the point at which it becomes nominally effective. The dose at the center of a block, which gives the normalization of the shadow fields, is given by a block transmission factor (BTF), which produces results in excellent agreement with measurements over a wide variety of block sizes and tissue depths. The radiation dose under shielding blocks can be considerably higher than expected, and care must be exercised when drawing blocks close to critical structures. The effects of blocks can be described in terms of normalized shadow fields, which behave similar to narrow, open fields, but with a divergence characteristic of their position relative to the radiation source. The normalization value for these fields, which gives the relative dose under the block, can be obtained from a straightforward analytical expression, the BTF. JF - International journal of radiation oncology, biology, physics AU - Miller, R W AU - van de Geijn, J AU - Raubitschek, A A AU - Orr, K AU - Okunieff, P AU - Glatstein, E AD - Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/07/15/ PY - 1995 DA - 1995 Jul 15 SP - 1083 EP - 1095 VL - 32 IS - 4 SN - 0360-3016, 0360-3016 KW - Index Medicus KW - Lung -- anatomy & histology KW - Radiation Protection KW - Radiotherapy Dosage KW - Mediastinal Neoplasms -- radiotherapy KW - Lung -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77384076?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+radiation+oncology%2C+biology%2C+physics&rft.atitle=Dosimetric+considerations+in+treating+mediastinal+disease+with+mantle+fields%3A+characterization+of+the+dose+under+mantle+blocks.&rft.au=Miller%2C+R+W%3Bvan+de+Geijn%2C+J%3BRaubitschek%2C+A+A%3BOrr%2C+K%3BOkunieff%2C+P%3BGlatstein%2C+E&rft.aulast=Miller&rft.aufirst=R&rft.date=1995-07-15&rft.volume=32&rft.issue=4&rft.spage=1083&rft.isbn=&rft.btitle=&rft.title=International+journal+of+radiation+oncology%2C+biology%2C+physics&rft.issn=03603016&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-17 N1 - Date created - 1995-08-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA adducts of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in colon, bladder, and kidney of congenic mice differing in Ah responsiveness and N-acetyltransferase genotype. AN - 77378287; 7606725 AB - Heterocyclic amines, suspected as cancer initiators, require metabolic activation to exert genotoxicity. The food carcinogen 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ) undergoes activation via N-hydroxylation by cytochrome P450 1A2, followed by O-esterification by N-acetyltransferase. We examined the effects of the Ah locus and acetylator polymorphisms (implicated in human colon and bladder cancer risk) on levels of 32P-postlabeled IQ-DNA adducts in C57BL/6 mice congenic for slow acetylation and/or Ah nonresponsiveness. Some were pretreated with beta-naphthoflavone (beta NF), an inducer of cytochromes P450 1A. Guanine adducts were detected in all organs, the predominant one corresponding to N2-(deoxyguanosine-8-yl)-IQ. In the kidney, beta NF pretreatment reduced total adducts by 50% in Ah-responsive animals (P = 0.021); the Ah or acetylator phenotype did not otherwise affect total adducts. In the colon of Ah-nonresponsive animals, rapid acetylators had 3-fold more adducts than slow acetylators (P = 0.0001, vehicle-pretreated; P = 0.0031, beta NF-pretreated). In Ah-responsive mice of either acetylator phenotype, beta NF pretreatment reduced total adducts in the colon by 70% (P = 0.0003). A significant interaction of phenotypes occurred in the bladder; beta NF-pretreatment caused a 2.5-fold increase in adducts but only in the Ah-responsive, rapid acetylator mice. In sum, these polymorphisms influenced the level of IQ-DNA adducts in the kidney, urinary bladder, and colon in complex ways. JF - Cancer research AU - Nerurkar, P V AU - Schut, H A AU - Anderson, L M AU - Riggs, C W AU - Snyderwine, E G AU - Thorgeirsson, S S AU - Weber, W W AU - Rice, J M AU - Levy, G N AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702-1201, USA. Y1 - 1995/07/15/ PY - 1995 DA - 1995 Jul 15 SP - 3043 EP - 3049 VL - 55 IS - 14 SN - 0008-5472, 0008-5472 KW - Ah KW - CYP1A2 KW - NAT1 KW - NAT2 KW - Carcinogens KW - 0 KW - DNA Adducts KW - Quinolines KW - Receptors, Aryl Hydrocarbon KW - 2-amino-3-methylimidazo(4,5-f)quinoline KW - 30GL3D3T0G KW - DNA KW - 9007-49-2 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Oxidoreductases KW - EC 1.- KW - Cytochrome P-450 CYP1A2 KW - EC 1.14.14.1 KW - Arylamine N-Acetyltransferase KW - EC 2.3.1.5 KW - Index Medicus KW - Animals KW - Polymorphism, Genetic KW - Cytochrome P-450 Enzyme System -- genetics KW - Cytochrome P-450 Enzyme System -- metabolism KW - Mice KW - Mice, Inbred DBA KW - Phenotype KW - Genotype KW - Acetylation KW - Oxidoreductases -- genetics KW - Oxidoreductases -- metabolism KW - Mice, Inbred C57BL KW - Female KW - Urinary Bladder -- metabolism KW - Quinolines -- toxicity KW - DNA Adducts -- biosynthesis KW - Kidney -- metabolism KW - Quinolines -- metabolism KW - DNA -- metabolism KW - Colon -- drug effects KW - Carcinogens -- toxicity KW - Kidney -- drug effects KW - Arylamine N-Acetyltransferase -- metabolism KW - Urinary Bladder -- drug effects KW - DNA -- drug effects KW - Carcinogens -- metabolism KW - Colon -- metabolism KW - Receptors, Aryl Hydrocarbon -- genetics KW - Arylamine N-Acetyltransferase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77378287?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=DNA+adducts+of+2-amino-3-methylimidazo%5B4%2C5-f%5Dquinoline+%28IQ%29+in+colon%2C+bladder%2C+and+kidney+of+congenic+mice+differing+in+Ah+responsiveness+and+N-acetyltransferase+genotype.&rft.au=Nerurkar%2C+P+V%3BSchut%2C+H+A%3BAnderson%2C+L+M%3BRiggs%2C+C+W%3BSnyderwine%2C+E+G%3BThorgeirsson%2C+S+S%3BWeber%2C+W+W%3BRice%2C+J+M%3BLevy%2C+G+N&rft.aulast=Nerurkar&rft.aufirst=P&rft.date=1995-07-15&rft.volume=55&rft.issue=14&rft.spage=3043&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 - 1995-08-17 N1 - Date created - 1995-08-17 N1 - Date revised - 2017-01-13 N1 - Gene symbol - Ah; CYP1A2; NAT1; NAT2 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Psychosocial dimensions of work and the risk of drug dependence among adults. AN - 77364398; 7598118 AB - The authors used prospectively gathered data to study whether different psychosocial work environments might signal increased risk of drug dependence syndromes. Adult participants were selected by probability sampling from households in five metropolitan areas of the United States. Subjects were sorted into risk sets defined by age and census tracts. Incident cases were identified using case definitions for drug abuse/dependence syndromes involving controlled substances, assessed by the Diagnostic Interview Schedule (DIS) administered during a baseline interview and at follow-up one year later. When the data were adjusted for baseline sociodemographic risk factors, history of alcoholism, and selected work conditions, increased risk of drug abuse/dependence was observed in subjects characterized by high levels of physical demands and low levels of skill discretion (high strain jobs) (relative odds (RO) = 4.92) and in subjects characterized by high levels of physical demands and decision authority (RO = 5.26). Findings from the present study underscore the importance of previously observed associations linking psychosocial work environments to mental health, and the results extend the range of findings to the drug dependence syndromes. JF - American journal of epidemiology AU - Muntaner, C AU - Anthony, J C AU - Crum, R M AU - Eaton, W W AD - Laboratory of Socio-environmental Studies, National Institute of Mental Health, Bethesda, MD, USA. Y1 - 1995/07/15/ PY - 1995 DA - 1995 Jul 15 SP - 183 EP - 190 VL - 142 IS - 2 SN - 0002-9262, 0002-9262 KW - Index Medicus KW - Socioeconomic Factors KW - Prospective Studies KW - Logistic Models KW - Risk Factors KW - Humans KW - Stress, Psychological KW - Adult KW - Middle Aged KW - Male KW - Female KW - Social Environment KW - Occupational Health KW - Substance-Related Disorders KW - Mental Health KW - Workplace UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77364398?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+epidemiology&rft.atitle=Psychosocial+dimensions+of+work+and+the+risk+of+drug+dependence+among+adults.&rft.au=Muntaner%2C+C%3BAnthony%2C+J+C%3BCrum%2C+R+M%3BEaton%2C+W+W&rft.aulast=Muntaner&rft.aufirst=C&rft.date=1995-07-15&rft.volume=142&rft.issue=2&rft.spage=183&rft.isbn=&rft.btitle=&rft.title=American+journal+of+epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-01 N1 - Date created - 1995-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effects of end point overdispersions on the validity of single-dose tumorigenicity assays. AN - 77409635; 7621426 AB - Overdispersion can be found in tumor incidence and tumor latency end point values obtained by the conventional assays that are being used to assess the tumorigenicity of neoplastic cells growing in tissue culture. Failure to account for such wide variations in end point data can lead to incorrect assessments of the neoplastic cell tumorigenic phenotype and misinterpretations of data relating genetic functions to tumor-forming capacity. This problem suggests the need for more detailed analyses of the relationships that exist between tumor cell dose and the parameters being used to measure tumorigenicity. JF - Cancer letters AU - Lewis, A M AU - Banks, S M AU - Soddu, S AU - Cook, J L AD - Viral Pathogenesis Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/07/13/ PY - 1995 DA - 1995 Jul 13 SP - 179 EP - 186 VL - 93 IS - 2 SN - 0304-3835, 0304-3835 KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured KW - Reproducibility of Results KW - Cell Count KW - Mice KW - Cell Line, Transformed KW - Mice, Inbred BALB C KW - Cricetinae KW - Neoplasm Transplantation -- methods KW - Carcinogenicity Tests -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77409635?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=The+effects+of+end+point+overdispersions+on+the+validity+of+single-dose+tumorigenicity+assays.&rft.au=Lewis%2C+A+M%3BBanks%2C+S+M%3BSoddu%2C+S%3BCook%2C+J+L&rft.aulast=Lewis&rft.aufirst=A&rft.date=1995-07-13&rft.volume=93&rft.issue=2&rft.spage=179&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-28 N1 - Date created - 1995-08-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Potentiation of 5-HT3 receptor-mediated responses by protein kinase C activation. AN - 77743330; 7488749 AB - The effect of agents that activate or inhibit protein kinase C (PKC) on the function of recombinant 5-HT3 receptors expressed in Xenopus oocytes was studied. The PKC activator phorbol 12-myristate 13-acetate (PMA) induced a long-lasting increase in the amplitude of 5-HT-activated ion current. The potentiation was maximal at 20 min and had a duration of approximately 60 min. The inactive phorbol ester, 4 alpha-PMA, had no effect on 5-HT3 receptor-mediated current. The PMA-induced potentiation was concentration-dependent over the concentration range 0.1-300 nM. The percentage potentiation by PMA was maximal at low 5-HT concentrations and decreased with increasing concentrations of 5-HT. For current activated by 0.1 microM 5-HT, maximal potentiation (Emax) was 667% of control, the EC50 was 15 nM and the apparent Hill coefficient was 0.99. The PKC inhibitor, staurosporin, antagonized the PMA potentiation; whereas, inhibitors of protein kinase A (PKA) or tyrosine kinase had no effect on this potentiation. The observations show that PMA can potentiate 5-HT3 receptor-mediated responses and suggest that this potentiation is mediated by activation of PKC. JF - Neuroreport AU - Zhang, L AU - Oz, M AU - Weight, F F AD - Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD 20852, USA. Y1 - 1995/07/10/ PY - 1995 DA - 1995 Jul 10 SP - 1464 EP - 1468 VL - 6 IS - 10 SN - 0959-4965, 0959-4965 KW - Alkaloids KW - 0 KW - Enzyme Inhibitors KW - Receptors, Serotonin KW - Serotonin Receptor Agonists KW - Protein Kinase C KW - EC 2.7.11.13 KW - Staurosporine KW - H88EPA0A3N KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Serotonin Receptor Agonists -- pharmacology KW - Animals KW - Enzyme Activation -- physiology KW - Electrophysiology KW - Tetradecanoylphorbol Acetate -- antagonists & inhibitors KW - Xenopus laevis KW - Patch-Clamp Techniques KW - Oocytes -- metabolism KW - Enzyme Activation -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Alkaloids -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Female KW - Receptors, Serotonin -- drug effects KW - Protein Kinase C -- metabolism KW - Protein Kinase C -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77743330?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroreport&rft.atitle=Potentiation+of+5-HT3+receptor-mediated+responses+by+protein+kinase+C+activation.&rft.au=Zhang%2C+L%3BOz%2C+M%3BWeight%2C+F+F&rft.aulast=Zhang&rft.aufirst=L&rft.date=1995-07-10&rft.volume=6&rft.issue=10&rft.spage=1464&rft.isbn=&rft.btitle=&rft.title=Neuroreport&rft.issn=09594965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-02 N1 - Date created - 1996-01-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transforming growth factor beta induces a beta-responsive calcium fluxes in neurons. AN - 77736692; 7488741 AB - The beta-amyloid (a beta) peptide is a neurotoxic peptide that accumulates in the brains of Alzheimer patients, but is also present in body fluids at subnanomolar levels. The potential effects of these low levels of a beta are unclear. We have recently shown that physiologic levels of a beta increase tyrosine phosphorylation and induce increases in cytosolic calcium. The basement membrane mixture, Matrigel, is required for observation of the a beta-induced calcium response. We now show that transforming growth factor beta (TGF beta) is the active component in Matrigel eliciting the a beta/calcium response. The response to the type of TGF beta varies depending on the cell type with TGF beta 1 eliciting a beta responsiveness in olfactory neuroblasts, and TGF beta 2 eliciting a beta responsiveness in PC12 cells. JF - Neuroreport AU - Wolozin, B AU - Hirashima, N AU - Luo, Y AU - Li, Y H AU - Alkon, D L AU - Etcheberrigaray, R AU - Sunderland, T AD - Section on Geriatric Psychiatry, NIMH, Bethesda, MD 20892-1264, USA. Y1 - 1995/07/10/ PY - 1995 DA - 1995 Jul 10 SP - 1429 EP - 1433 VL - 6 IS - 10 SN - 0959-4965, 0959-4965 KW - Amyloid beta-Peptides KW - 0 KW - Extracellular Matrix Proteins KW - Neurotoxins KW - Transforming Growth Factor beta KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Rats KW - Olfactory Nerve -- cytology KW - Animals KW - Extracellular Matrix Proteins -- metabolism KW - Signal Transduction -- drug effects KW - Olfactory Nerve -- drug effects KW - Olfactory Nerve -- metabolism KW - PC12 Cells KW - Calcium -- metabolism KW - Transforming Growth Factor beta -- pharmacology KW - Neurons -- metabolism KW - Neurons -- drug effects KW - Amyloid beta-Peptides -- pharmacology KW - Neurotoxins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77736692?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroreport&rft.atitle=Transforming+growth+factor+beta+induces+a+beta-responsive+calcium+fluxes+in+neurons.&rft.au=Wolozin%2C+B%3BHirashima%2C+N%3BLuo%2C+Y%3BLi%2C+Y+H%3BAlkon%2C+D+L%3BEtcheberrigaray%2C+R%3BSunderland%2C+T&rft.aulast=Wolozin&rft.aufirst=B&rft.date=1995-07-10&rft.volume=6&rft.issue=10&rft.spage=1429&rft.isbn=&rft.btitle=&rft.title=Neuroreport&rft.issn=09594965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-02 N1 - Date created - 1996-01-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Conserved kappa B element located downstream of the tumor necrosis factor alpha gene: distinct NF-kappa B binding pattern and enhancer activity in LPS activated murine macrophages. AN - 77419074; 7624137 AB - Transcriptional activation of various genes by lipopolysaccharide (LPS) is known to be mediated, at least in part, by the NF-kappa B/Rel family of transcription factors. We have identified a novel kappa B element located immediately downstream of the TNF-alpha gene that is conserved together with its flanking sequences across species lines and can act as an LPS-responsive enhancer for reporter gene constructs driven by the minimal TNF promoter. In extracts from activated murine macrophages and macrophage cell lines this element binds several non-canonical NF-kappa B/Rel complexes, in addition to p50 (NFKB1) homodimer and p50-p65 (NKFB1-RelA) heterodimer. Combination of high-resolution electrophoretic mobility shift assays (EMSA) with monospecific antibodies and u.v.-cross-linking indicates that the prominent slow migrating complex III contain p65 homodimer and c-Rel. The appearance of complex III in EMSA parallels the translocation of p65 and c-Rel into the nucleus and occurs shortly after LPS induction. Transfection experiments with reporter constructs driven by this kappa B element indicate strong inducibility by LPS and p65, moderate inducibility by c-Rel and repression by p50. Functional activity of sandwich TNF-CAT-TNF constructs further suggests that LPS-inducible transcriptional activation of the TNF gene in murine macrophages may be partly mediated by a downstream enhancer. JF - Oncogene AU - Kuprash, D V AU - Udalova, I A AU - Turetskaya, R L AU - Rice, N R AU - Nedospasov, S A AD - Biological Carcinogenesis and Development Program, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland, 21702-1201, USA. Y1 - 1995/07/06/ PY - 1995 DA - 1995 Jul 06 SP - 97 EP - 106 VL - 11 IS - 1 SN - 0950-9232, 0950-9232 KW - TNF-&agr; KW - Lipopolysaccharides KW - 0 KW - NF-kappa B KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-rel KW - Tumor Necrosis Factor-alpha KW - DNA KW - 9007-49-2 KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Index Medicus KW - Chloramphenicol O-Acetyltransferase -- genetics KW - Animals KW - Base Sequence KW - Conserved Sequence KW - Biological Evolution KW - Lipopolysaccharides -- pharmacology KW - Macrophage Activation KW - Proto-Oncogene Proteins -- metabolism KW - Molecular Sequence Data KW - Mice KW - Protein Binding KW - Regulatory Sequences, Nucleic Acid KW - Enhancer Elements, Genetic KW - Macrophages -- drug effects KW - Tumor Necrosis Factor-alpha -- genetics KW - NF-kappa B -- metabolism KW - Macrophages -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77419074?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Conserved+kappa+B+element+located+downstream+of+the+tumor+necrosis+factor+alpha+gene%3A+distinct+NF-kappa+B+binding+pattern+and+enhancer+activity+in+LPS+activated+murine+macrophages.&rft.au=Kuprash%2C+D+V%3BUdalova%2C+I+A%3BTuretskaya%2C+R+L%3BRice%2C+N+R%3BNedospasov%2C+S+A&rft.aulast=Kuprash&rft.aufirst=D&rft.date=1995-07-06&rft.volume=11&rft.issue=1&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-29 N1 - Date created - 1995-08-29 N1 - Date revised - 2017-01-13 N1 - Gene symbol - TNF-&agr; N1 - Genetic sequence - X54859; GENBANK; Z14137; M16441; L00981; U06950 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analgesics and cancers of the renal pelvis and ureter. AN - 77378885; 7601560 AB - To evaluate renal pelvis and ureter (RPU) cancer risk in relation to lifetime use of analgesics, a population-based case-control study was carried out in 3 areas of the United States. Among 502 cases and 496 controls diagnosed and interviewed during 1983-1986, no significant increases in risk were found for any of the non-prescription and prescription analgesics evaluated or among regular users of phenacetin, acetaminophen or aspirin. Neither cumulative lifetime ingestion nor duration of regular use of these 3 drugs, whether alone or in combination, was associated with significantly increased risk of RPU cancer, although a slight excess was observed among long-term users of acetaminophen. Risk was not increased among persons reporting highest cumulative dose and/or longest duration of phenacetin use. Although our study of RPU cancer is the largest to date, it was nonetheless limited by the small number of regular analgesic users and the relatively low response rates. Because of the relatively recent onset of widespread use of acetaminophen, its pharmacologic similarity to phenacetin, a known urothelial carcinogen, and the elevation in risk seen in long-term users, further surveillance of this analgesic is warranted. JF - International journal of cancer AU - Linet, M S AU - Chow, W H AU - McLaughlin, J K AU - Wacholder, S AU - Yu, M C AU - Schoenberg, J B AU - Lynch, C AU - Fraumeni, J F AD - Division of Cancer Etiology, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/07/04/ PY - 1995 DA - 1995 Jul 04 SP - 15 EP - 18 VL - 62 IS - 1 SN - 0020-7136, 0020-7136 KW - Analgesics KW - 0 KW - Acetaminophen KW - 362O9ITL9D KW - Phenacetin KW - ER0CTH01H9 KW - Aspirin KW - R16CO5Y76E KW - Index Medicus KW - Phenacetin -- adverse effects KW - Aspirin -- adverse effects KW - Humans KW - Adult KW - Acetaminophen -- adverse effects KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Male KW - Female KW - Kidney Neoplasms -- chemically induced KW - Kidney Pelvis KW - Ureteral Neoplasms -- chemically induced KW - Analgesics -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77378885?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Analgesics+and+cancers+of+the+renal+pelvis+and+ureter.&rft.au=Linet%2C+M+S%3BChow%2C+W+H%3BMcLaughlin%2C+J+K%3BWacholder%2C+S%3BYu%2C+M+C%3BSchoenberg%2C+J+B%3BLynch%2C+C%3BFraumeni%2C+J+F&rft.aulast=Linet&rft.aufirst=M&rft.date=1995-07-04&rft.volume=62&rft.issue=1&rft.spage=15&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 - 1995-08-10 N1 - Date created - 1995-08-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Double-blind trial of botulinum toxin for treatment of focal hand dystonia. AN - 85268749; pmid-7565828 AB - Ten patients with focal dystonia of the hand, all of whom had benefited in an open-label study of botulinum toxin, were treated with botulinum toxin-A in a double-blind study. Response was assessed by three measures: (a) subjective rating, provided by patients' reports of the effect of the injections on the dystonia; (b) objective testing, consisting of manual muscle testing (MRC scale) to measure muscle strength in all patients, timing of a writing sample and counting the number of errors of writing off-the-line in six patients with writer's cramp, counting the number of errors on a standard test of transcription in two patients with stenographer's cramp, and rating by professional musicians of the performances of two patients with musician's cramp; and (c) physicians' rating, provided by a review of the patients' videotaped performance by neurologists who were unaware of which treatment was administered. Eight of the 10 patients had greater subjective improvement with botulinum toxin than with placebo, and this impression was verified by at least one objective test in six patients. Two patients failed to have a better response to botulinum toxin than to placebo, and their reports were verified by the objective tests. This study confirms the efficacy of botulinum toxin in many patients with focal hand dystonia. JF - Movement Disorders AU - Cole, R AU - Hallett, M AU - Cohen, L G AD - Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1995 SP - 466 EP - 471 VL - 10 IS - 4 SN - 0885-3185, 0885-3185 KW - Handwriting KW - Double-Blind Method KW - Human KW - Injections, Intramuscular KW - Electromyography KW - Neurologic Examination KW - Dystonia KW - Muscle Cramp KW - Muscle, Skeletal KW - Botulinum Toxins KW - Music KW - Psychomotor Disorders KW - Hand Strength KW - Occupational Diseases KW - Hand UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85268749?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Movement+Disorders&rft.atitle=Double-blind+trial+of+botulinum+toxin+for+treatment+of+focal+hand+dystonia.&rft.au=Cole%2C+R%3BHallett%2C+M%3BCohen%2C+L+G&rft.aulast=Cole&rft.aufirst=R&rft.date=1995-07-01&rft.volume=10&rft.issue=4&rft.spage=466&rft.isbn=&rft.btitle=&rft.title=Movement+Disorders&rft.issn=08853185&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Cytomegalovirus enteritis after treatment with 5-fluorouracil, leukovorin, cisplatin, and alpha-interferon. AN - 85229866; pmid-7611225 JF - The American Journal of Gastroenterology AU - Theodossiou, C AU - Temeck, B AU - Vargas, H AU - Yang, J AU - Vargas, M AU - Hahn, S AU - Pass, H AD - Warren Magnuson Grant Clinical Center, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. PY - 1995 SP - 1174 EP - 1176 VL - 90 IS - 7 SN - 0002-9270, 0002-9270 KW - Interferon-alpha KW - Cisplatin KW - Ileitis KW - Enteritis KW - Esophageal Neoplasms KW - Fluorouracil KW - Humans KW - Antineoplastic Combined Chemotherapy Protocols KW - Cytomegalovirus Infections KW - Leucovorin KW - Middle Aged KW - Male UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85229866?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+Journal+of+Gastroenterology&rft.atitle=Cytomegalovirus+enteritis+after+treatment+with+5-fluorouracil%2C+leukovorin%2C+cisplatin%2C+and+alpha-interferon.&rft.au=Theodossiou%2C+C%3BTemeck%2C+B%3BVargas%2C+H%3BYang%2C+J%3BVargas%2C+M%3BHahn%2C+S%3BPass%2C+H&rft.aulast=Theodossiou&rft.aufirst=C&rft.date=1995-07-01&rft.volume=90&rft.issue=7&rft.spage=1174&rft.isbn=&rft.btitle=&rft.title=The+American+Journal+of+Gastroenterology&rft.issn=00029270&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Evolving strategies for the treatment of adenocarcinoma of the pancreas. A review. AN - 85204546; pmid-7560834 AB - Adenocarcinoma of the pancreas has an incidence of only 0.01%, yet is the fourth leading cause of cancer death for American men and women. Despite this dismal outlook, new strategies for staging and therapy for pancreatic cancer have emerged over the last few years. Laparoscopy with cytologic evaluation of peritoneal washings, and more recently, although still investigational, endoscopic and intracorporeal ultrasonography have provided more detailed staging information. The result of improved staging is earlier, more accurate selection of treatment most appropriate for stage of disease. For those patients with clinically localized disease, laparotomy with an attempt at resection is indicated, particularly with the recent trend in declining morbidity and operative mortality the recent trend in declining morbidity and operative mortality associated with pancreatectomy. With clinically unresectable disease, patients may potentially be spared the morbidity of laparotomy. Advances in therapeutic endoscopic and percutaneous manipulation of the obstructed biliary tree have provided an alternative to surgery and improved quality of life for patients with abbreviated life spans. Gastroduodenal obstruction has traditionally been managed by laparotomy, although with improved technology and surgical skill, a laparoscopic approach may become standard. Because even at presentation pancreatic cancer is rarely a localized process but is a disseminated disease, surgery alone is unlikely to increase survival rates in the absence of adjuvant therapies. Present and future strategies for treatment include the addition of neoadjuvant regimens and adjuvant modalities including intraoperative radiation, photodynamic therapy, intraperitoneal therapies, and pancreatic and splanchnic perfusion. Clearly, the greatest strides in treatment of pancreatic cancer will come with development of new agents with significantly greater antitumor efficacy. JF - Journal of Clinical Gastroenterology AU - Ettinghausen, S E AU - Schwartzentruber, D J AU - Sindelar, W F AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1995 SP - 48 EP - 60 VL - 21 IS - 1 SN - 0192-0790, 0192-0790 KW - Radiotherapy, Adjuvant KW - Neoplasm Staging KW - Human KW - Pancreatic Neoplasms KW - Adenocarcinoma KW - Chemotherapy, Adjuvant KW - Female KW - Male UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85204546?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Clinical+Gastroenterology&rft.atitle=Evolving+strategies+for+the+treatment+of+adenocarcinoma+of+the+pancreas.+A+review.&rft.au=Ettinghausen%2C+S+E%3BSchwartzentruber%2C+D+J%3BSindelar%2C+W+F&rft.aulast=Ettinghausen&rft.aufirst=S&rft.date=1995-07-01&rft.volume=21&rft.issue=1&rft.spage=48&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Gastroenterology&rft.issn=01920790&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Palliation of regional symptoms of advanced extremity melanoma by isolated limb perfusion with melphalan and high-dose tumor necrosis factor. AN - 77972549; 9166465 AB - Bulky, symptomatic melanoma of the extremity is a difficult management problem. In some patients, slowly progressive yet extensive regional disease can produce pain, edema, bleeding, and immobility. The use of hyperthermic isolated limb perfusion may provide good regional palliation even in the presence of distant metastatic disease. This study evaluates the ability of isolated limb perfusion using melphalan and high-dose tumor necrosis factor to palliate regional symptoms of locally advanced extremity melanoma. Fifteen patients with symptomatic extremity melanoma were treated for 90 minutes with isolated limb perfusion using mild hyperthermia, tumor necrosis factor at a dose of 4 mg (n = 8) or 6 mg (n = 7) given at the initiation of perfusion, and melphalan, 10 mg/L limb volume, given at 30 minutes into the perfusion. Eleven patients also received three courses of low-dose gamma-interferon, 0.2 mg subcutaneously, once a day for the 2 days preceding surgery and at the initiation of perfusion. Symptomatic improvement was achieved in 9 of 11 patients who had pain, 6 of 6 patients with edema, 5 of 6 patients with decreased extremity mobility, and 5 of 6 with bleeding or severe ulceration. The objective response rate in 14 evaluable patients was 100%, with a complete response rate in 5 of 14. Twelve of 15 patients achieved local control of advanced extremity melanoma after isolated limb perfusion. Treatment-related systemic toxicities were minimal and short lived. Isolated limb perfusion with melphalan and tumor necrosis factor is an effective and safe palliative treatment of locally advanced symptomatic melanoma of the extremity. JF - The cancer journal from Scientific American AU - Fraker, D L AU - Alexander, H R AU - Andrich, M AU - Rosenberg, S A AD - Surgical Metabolism Section, Surgery Branch, National Cancer Institute, Clinical Center, National Institutes of Health, Bethesda, MD 20892-1502, USA. PY - 1995 SP - 122 EP - 130 VL - 1 IS - 2 SN - 1081-4442, 1081-4442 KW - Tumor Necrosis Factor-alpha KW - 0 KW - Interferon-gamma KW - 82115-62-6 KW - Melphalan KW - Q41OR9510P KW - Index Medicus KW - Tumor Necrosis Factor-alpha -- administration & dosage KW - Combined Modality Therapy KW - Humans KW - Palliative Care KW - Aged KW - Extremities KW - Aged, 80 and over KW - Melphalan -- administration & dosage KW - Adult KW - Treatment Outcome KW - Interferon-gamma -- administration & dosage KW - Middle Aged KW - Hypothermia, Induced KW - Female KW - Male KW - Chemotherapy, Cancer, Regional Perfusion KW - Melanoma -- therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77972549?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+cancer+journal+from+Scientific+American&rft.atitle=Palliation+of+regional+symptoms+of+advanced+extremity+melanoma+by+isolated+limb+perfusion+with+melphalan+and+high-dose+tumor+necrosis+factor.&rft.au=Fraker%2C+D+L%3BAlexander%2C+H+R%3BAndrich%2C+M%3BRosenberg%2C+S+A&rft.aulast=Fraker&rft.aufirst=D&rft.date=1995-07-01&rft.volume=1&rft.issue=2&rft.spage=122&rft.isbn=&rft.btitle=&rft.title=The+cancer+journal+from+Scientific+American&rft.issn=10814442&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-10-17 N1 - Date created - 2006-09-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Cancer J Sci Am. 1995 Jul-Aug;1(2):104-5 [9166460] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Homozygous deletions at chromosome 9p21 and mutation analysis of p16 and p15 in microdissected primary non-small cell lung cancers. AN - 77963706; 9816033 AB - Loss of heterozygosity on chromosome 9p has been detected in many primary human tumors and cell lines, suggesting that this chromosomal arm harbors one or more tumor suppressor genes. The recently cloned p16 and p15 genes, mapped to 9p21, are likely candidates for such tumor suppressors. To map the deletion at chromosome 9p21 in non-small cell lung tumors, we analyzed DNA from 25 tumors and matching normal DNAs at six microsatellite markers that flank the region occupied by the p16 and p15 genes. Loss of heterozygosity of at least one microsatellite marker on chromosome 9p21 was detected in 13 (52%) of 25 tumors, including one tumor that exhibited homozygous deletion of both human IFNalpha and D9S171. Six tumors analyzed by a comparative multiplex PCR technique showed homozygous deletions of the sequence tag site marker c5.1 (within p16). Screening for mutations in p16 and p15 revealed one tumor with a non-sense mutation in exon 2 of p16, but no mutations were detected in p15 in any of the tumors. Thus, in these analyses approximately one-half of the non-small cell lung tumors had loss of heterozygosity at chromosome 9p21, and of these tumors, one-half had homozygous deletions of the region that includes p16. This appears to confirm the importance of a locus in this region critical to growth control in lung. The apparent lack of other mutations in p16 and p15 in the tumors with loss of heterozygosity leaves open the possibility of an unidentified gene in this region that may function as a tumor suppressor. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Packenham, J P AU - Taylor, J A AU - White, C M AU - Anna, C H AU - Barrett, J C AU - Devereux, T R AD - Environmental Carcinogenesis Program and Environmental Biology and Medicine Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/07// PY - 1995 DA - July 1995 SP - 687 EP - 690 VL - 1 IS - 7 SN - 1078-0432, 1078-0432 KW - CDKN2B protein, human KW - 0 KW - Cell Cycle Proteins KW - Cyclin-Dependent Kinase Inhibitor p15 KW - Genetic Markers KW - Interferon-alpha KW - Transcription Factors KW - Tumor Suppressor Proteins KW - Index Medicus KW - Polymerase Chain Reaction KW - Homozygote KW - Genes, Tumor Suppressor KW - Humans KW - DNA Mutational Analysis KW - Carcinoma, Adenosquamous -- genetics KW - Carcinoma, Squamous Cell -- genetics KW - Carcinoma, Large Cell -- genetics KW - Sequence Tagged Sites KW - Interferon-alpha -- genetics KW - Adenocarcinoma -- genetics KW - Chromosome Mapping KW - Chromosome Deletion KW - Carcinoma, Non-Small-Cell Lung -- genetics KW - Lung Neoplasms -- genetics KW - Chromosomes, Human, Pair 9 KW - Genes, p16 KW - Transcription Factors -- genetics KW - Lung Neoplasms -- pathology KW - Carcinoma, Non-Small-Cell Lung -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77963706?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Homozygous+deletions+at+chromosome+9p21+and+mutation+analysis+of+p16+and+p15+in+microdissected+primary+non-small+cell+lung+cancers.&rft.au=Packenham%2C+J+P%3BTaylor%2C+J+A%3BWhite%2C+C+M%3BAnna%2C+C+H%3BBarrett%2C+J+C%3BDevereux%2C+T+R&rft.aulast=Packenham&rft.aufirst=J&rft.date=1995-07-01&rft.volume=1&rft.issue=7&rft.spage=687&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-18 N1 - Date created - 1999-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of mutations at position 184 in reverse transcriptase of human immunodeficiency virus type 1. AN - 77739965; 7492119 AB - We have analyzed recombinant human immunodeficiency virus type 1 reverse transcriptases that contain mutations at position 184. These variants retain high levels of RNA-dependent DNA polymerase activity and show resistance to ddITP. However, the mutants varied in their ability to polymerize processively. The variants Met184Ile and Met184Val showed slight reductions in processivity relative to that of the wild-type enzyme; the variants Met184Ala and Met184Leu showed considerable reductions in their processivity. JF - Antimicrobial agents and chemotherapy AU - Boyer, P L AU - Hughes, S H AD - Advanced BioScience Laboratories-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA. Y1 - 1995/07// PY - 1995 DA - July 1995 SP - 1624 EP - 1628 VL - 39 IS - 7 SN - 0066-4804, 0066-4804 KW - Recombinant Proteins KW - 0 KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - RNA-Directed DNA Polymerase KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Index Medicus KW - AIDS/HIV KW - Escherichia coli -- metabolism KW - Base Sequence KW - Recombinant Proteins -- metabolism KW - DNA Mutational Analysis KW - Molecular Sequence Data KW - Escherichia coli -- genetics KW - Recombinant Proteins -- genetics KW - Mutagenesis, Insertional KW - DNA-Directed DNA Polymerase -- genetics KW - DNA-Directed DNA Polymerase -- metabolism KW - Binding Sites KW - RNA-Directed DNA Polymerase -- metabolism KW - Mutation KW - RNA-Directed DNA Polymerase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77739965?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Analysis+of+mutations+at+position+184+in+reverse+transcriptase+of+human+immunodeficiency+virus+type+1.&rft.au=Boyer%2C+P+L%3BHughes%2C+S+H&rft.aulast=Boyer&rft.aufirst=P&rft.date=1995-07-01&rft.volume=39&rft.issue=7&rft.spage=1624&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 - 1996-01-02 N1 - Date created - 1996-01-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1991 Sep 27;253(5027):1557-9 [1716788] EMBO J. 1991 Dec;10(12):3905-11 [1718745] J Biol Chem. 1991 Dec 5;266(34):23003-9 [1720776] J Virol. 1992 Feb;66(2):1031-9 [1370546] Nature. 1992 May 7;357(6373):85-9 [1374166] Science. 1992 Jun 26;256(5065):1783-90 [1377403] Science. 1986 Mar 14;231(4743):1289-91 [2418504] Proc Natl Acad Sci U S A. 1988 Feb;85(4):1218-22 [2448794] EMBO J. 1988 Jan;7(1):239-43 [2452083] Science. 1988 Jun 10;240(4858):1427-35 [3287617] Q Rev Biol. 1989 Mar;64(1):1-30 [2469098] Proc Natl Acad Sci U S A. 1989 Jul;86(13):4803-7 [2472634] EMBO J. 1989 Dec 1;8(12):3867-74 [2555175] Eur J Biochem. 1990 Jan 26;187(2):307-14 [1688798] AIDS Res Hum Retroviruses. 1990 Jun;6(6):753-64 [1694680] FEBS Lett. 1991 May 6;282(2):231-4 [1709876] J Virol. 1992 Nov;66(11):6806-12 [1383571] J Virol. 1992 Dec;66(12):7128-35 [1279198] J Virol. 1992 Dec;66(12):7533-7 [1279205] J Biol Chem. 1993 May 15;268(14):10312-23 [7683674] Antimicrob Agents Chemother. 1993 Apr;37(4):875-81 [7684216] Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5653-6 [7685907] Antimicrob Agents Chemother. 1993 Jun;37(6):1207-13 [8328771] Antimicrob Agents Chemother. 1993 Jun;37(6):1390-2 [8392313] Biochemistry. 1993 Sep 21;32(37):9745-53 [7690592] Antimicrob Agents Chemother. 1993 Oct;37(10):2231-4 [7504909] Biochem Pharmacol. 1994 Jan 20;47(2):155-69 [7508227] J Gen Virol. 1994 May;75 ( Pt 5):951-7 [7513745] Proc Natl Acad Sci U S A. 1994 May 24;91(11):4882-6 [7515182] J Mol Biol. 1994 Oct 28;243(3):369-87 [7525966] Nucleic Acids Res. 1995 Mar 11;23(5):803-10 [7535923] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [The diffusion of information on the carcinogenicity of asbestos in the Italian scientific community before 1965]. TT - La diffusione delle informazioni sulla cancerogenicità dell'amianto nella comunità scientifica italiana prima del 1965. AN - 77719069; 7500899 AB - The spreading of information on asbestos carcinogenicity within the Italian scientific community before 1965. The paper deals with the development of recognition of asbestos carcinogenicity within the Italian scientific community. This development was difficult in Italy as in other countries. Articles and other papers in handbooks and congress proceedings, by Italian authors, published in the period 1934-1965, were considered. The first cases of lung cancer in Italian workers exposed to asbestos were observed in 1955-56, the first cases of malignant mesothelioma in 1965. The cases observed were very few, but knowledge on asbestos carcinogenicity became widespread within the Italian scientific community during the fifties (from 1953 on wards) with the publication of several handbooks of occupational medicine. JF - La Medicina del lavoro AU - Carnevale, F AU - Chellini, E AD - Servizio di Prevenzione Igiene e Sicurezza nei Luoghi di Lavoro, Azienda USL n 10 di Firenze. PY - 1995 SP - 295 EP - 302 VL - 86 IS - 4 SN - 0025-7818, 0025-7818 KW - Carcinogens KW - 0 KW - Asbestos KW - 1332-21-4 KW - Index Medicus KW - History of medicine KW - Lung Neoplasms -- history KW - Lung Neoplasms -- etiology KW - History, 20th Century KW - Publishing -- history KW - Humans KW - Asbestosis -- complications KW - Asbestosis -- history KW - Italy KW - Asbestos -- history KW - Asbestos -- adverse effects KW - Information Services -- history KW - Carcinogens -- history KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77719069?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=La+Medicina+del+lavoro&rft.atitle=%5BThe+diffusion+of+information+on+the+carcinogenicity+of+asbestos+in+the+Italian+scientific+community+before+1965%5D.&rft.au=Carnevale%2C+F%3BChellini%2C+E&rft.aulast=Carnevale&rft.aufirst=F&rft.date=1995-07-01&rft.volume=86&rft.issue=4&rft.spage=295&rft.isbn=&rft.btitle=&rft.title=La+Medicina+del+lavoro&rft.issn=00257818&rft_id=info:doi/ LA - Italian DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-16 N1 - Date created - 1996-01-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Work-related accidents in minors in Lombardy]. TT - Gli infortuni sul lavoro nei minori in Lombardia. AN - 77715510; 7500903 AB - Work-related injuries in children and adolescents represent a negative indication of more general inequities of the society in which events occur. Their characteristics are not well described, particularly in Italy, and this paper is aimed at highlighting some fundamental aspects of these injuries. The case in point is represented by the injuries that received compensation and occurred in the Lombardy Region (Italy) between 1984 and 1989 and involved people under the age of eighteen. The injuries occurring in the same period and area in workers over eighteen were used for comparison. Work related injuries in minors were more frequent in crafts activities than in industry, but their gravity (in terms of deaths or permanent consequences) was lower than in the corresponding adult workers. Ninety percent of the events in young workers occurred in males, in each age category, and about 5% of the cases pertains to very young workers (less than 15 years). Cuts/lacerations are the most frequent type of lesion (49.9%) and the hands represent the site most frequently involved (55.5%). The great majority of the observed injuries pertains to a limited number of economic activity sectors: about 75% of the cases occurred in ten sectors. Metal manufacturing, construction and machine production scored first, with interesting correlations with the same sectors in adult workers. Ten specific occupations represent over fifty percent of the cases, with mechanics and bricklayers at the top. The description of the accident in terms of mode of occurrence and the agents involved was less informative and not specific.(ABSTRACT TRUNCATED AT 250 WORDS) JF - La Medicina del lavoro AU - Pianosi, G AU - Zocchetti, C AD - Unità Operativa Tutela della Salute nei Luoghi di Lavoro, USSL 34, Legnano. PY - 1995 SP - 332 EP - 340 VL - 86 IS - 4 SN - 0025-7818, 0025-7818 KW - Index Medicus KW - Humans KW - Adult KW - Incidence KW - Occupations -- statistics & numerical data KW - Child KW - Italy -- epidemiology KW - Adolescent KW - Sex Distribution KW - Male KW - Female KW - Prevalence KW - Age Distribution KW - Wounds and Injuries -- epidemiology KW - Accidents, Occupational -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77715510?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=La+Medicina+del+lavoro&rft.atitle=%5BWork-related+accidents+in+minors+in+Lombardy%5D.&rft.au=Pianosi%2C+G%3BZocchetti%2C+C&rft.aulast=Pianosi&rft.aufirst=G&rft.date=1995-07-01&rft.volume=86&rft.issue=4&rft.spage=332&rft.isbn=&rft.btitle=&rft.title=La+Medicina+del+lavoro&rft.issn=00257818&rft_id=info:doi/ LA - Italian DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-16 N1 - Date created - 1996-01-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Early modeling of drinking behavior by Native American elementary school children playing drunk. AN - 77696898; 7591357 AB - A report of games played by elementary school children on a Native American reservation in the United States illustrates how intoxicated adult behavior is perceived as funny. Only later does one develop an awareness that the consequences of misuse can be injury, illness, and death. Prevention messages targeted at elementary school children need to provide positive alternatives to the humor in drunkenness and may need to be culturally adapted. Examples of some culturally specific approaches are discussed. JF - The International journal of the addictions AU - Mail, P D AD - NIH/NIAAA/Willco 505, Rockville, Maryland 20892-7003, USA. Y1 - 1995/07// PY - 1995 DA - July 1995 SP - 1187 EP - 1197 VL - 30 IS - 9 SN - 0020-773X, 0020-773X KW - Index Medicus KW - Wit and Humor as Topic KW - Humans KW - Child of Impaired Parents -- psychology KW - Adult KW - Health Knowledge, Attitudes, Practice KW - Child KW - Personality Development KW - Peer Group KW - Health Education KW - Male KW - Female KW - Automobile Driving KW - Alcoholic Intoxication -- psychology KW - Alcoholic Intoxication -- prevention & control KW - Indians, North American -- psychology KW - Play and Playthings KW - Alcoholism -- psychology KW - Alcoholism -- prevention & control KW - Imitative Behavior UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77696898?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+the+addictions&rft.atitle=Early+modeling+of+drinking+behavior+by+Native+American+elementary+school+children+playing+drunk.&rft.au=Mail%2C+P+D&rft.aulast=Mail&rft.aufirst=P&rft.date=1995-07-01&rft.volume=30&rft.issue=9&rft.spage=1187&rft.isbn=&rft.btitle=&rft.title=The+International+journal+of+the+addictions&rft.issn=0020773X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-06 N1 - Date created - 1995-12-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dopamine transporter, alcoholism and other diseases. AN - 77696555; 7585136 JF - Nature medicine AU - Goldman, D AD - Laboratory of Neurogenetics, Natn. Inst. on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland 20852, USA. Y1 - 1995/07// PY - 1995 DA - July 1995 SP - 624 EP - 625 VL - 1 IS - 7 SN - 1078-8956, 1078-8956 KW - Carrier Proteins KW - 0 KW - Dopamine Plasma Membrane Transport Proteins KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Receptors, Dopamine D2 KW - Ethanol KW - 3K9958V90M KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Tomography, Emission-Computed, Single-Photon KW - Ethanol -- pharmacology KW - Humans KW - Brain Chemistry KW - Gene Expression Regulation -- drug effects KW - Receptors, Dopamine D2 -- physiology KW - Genetic Predisposition to Disease KW - Disease Susceptibility -- metabolism KW - Carrier Proteins -- genetics KW - Alcoholism -- classification KW - Dopamine -- physiology KW - Carrier Proteins -- physiology KW - Alcoholism -- metabolism KW - Alcoholism -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77696555?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dopamine+transporter%2C+alcoholism+and+other+diseases.&rft.au=Goldman%2C+D&rft.aulast=Goldman&rft.aufirst=D&rft.date=1995-07-01&rft.volume=1&rft.issue=7&rft.spage=624&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 - 1995-12-28 N1 - Date created - 1995-12-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Nat Med. 1995 Jul;1(7):654-7 [7585146] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [The risk of the carpal tunnel syndrome in some work activities]. TT - Rischio di sindrome del tunnel carpale in alcune attività lavorative. AN - 77693063; 7500904 AB - The aim of the study was to generate hypotheses on what could be the ISTAT (National Institute of Statistics) job classes with a major risk of carpal tunnel syndrome in order to plan more specific analytic epidemiology studies and apply more correct ergonomic solutions. A case-control cross-sectional survey without matching was carried out. The source of data were the computerized medical records of a large regional hospital: 833 carpal tunnel syndrome cases (mean age 48, SD 9.33) and 3222 controls (mean age 43.5, SD 13.22) hospitalized for other diseases, were selected. The odds ratio (OR) and 95% confidence limits, controlled for age and gender by a logistic linear regression model, were calculated as measures of association for the comparison between non-exposed managerial/administrative staff and industrial workers. The analysis showed a statistically significant risk for some ISTAT job classes, in particular class 53 (spinners, weavers, dyers and similar jobs) (OR = 2.65; C.L. 1.52-4.62) class 54 (knitters, tailors, hatmakers, upholsterers and similar jobs) (OR = 1.69; C.L. 1.06-2.71), 55 (tanners, shoemakers, leather manufacture workers and similar jobs) (OR = 2.74; C.L. 1.66-4.53) and group 742 (Hotel and restaurant cooks) (OR = 2.99; C.L. 1.45-6.13). Job classes 45 (carpenters, welders and similar jobs). 62 (electricians, electrotechnicians, radio engineers and similar jobs), 63 (gasfitters, plumbers, heating engineers and similar jobs) and 85 (porters and other jobs involving manual handling of loads) showed ORs higher than 2 but without statistical significance. The results are valid for planning further studies, especially in the textile and shoe and leather manufacturing sectors. JF - La Medicina del lavoro AU - Baldasseroni, A AU - Tartaglia, R AU - Carnevale, F AD - Servizio di Prevenzione, Igiene e Sicurezza nei Luoghi di Layoro, USL. 10/D, Firenze. PY - 1995 SP - 341 EP - 351 VL - 86 IS - 4 SN - 0025-7818, 0025-7818 KW - Index Medicus KW - Odds Ratio KW - Humans KW - Linear Models KW - Age Distribution KW - Cross-Sectional Studies KW - Risk Factors KW - Adult KW - Case-Control Studies KW - Confidence Intervals KW - Middle Aged KW - Occupations -- statistics & numerical data KW - Italy -- epidemiology KW - Sex Distribution KW - Female KW - Male KW - Carpal Tunnel Syndrome -- etiology KW - Carpal Tunnel Syndrome -- epidemiology KW - Occupational Diseases -- etiology KW - Occupational Diseases -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77693063?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=La+Medicina+del+lavoro&rft.atitle=%5BThe+risk+of+the+carpal+tunnel+syndrome+in+some+work+activities%5D.&rft.au=Baldasseroni%2C+A%3BTartaglia%2C+R%3BCarnevale%2C+F&rft.aulast=Baldasseroni&rft.aufirst=A&rft.date=1995-07-01&rft.volume=86&rft.issue=4&rft.spage=341&rft.isbn=&rft.btitle=&rft.title=La+Medicina+del+lavoro&rft.issn=00257818&rft_id=info:doi/ LA - Italian DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-16 N1 - Date created - 1996-01-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A reinvestigation of Maprounea triterpenes. AN - 77650070; 7561897 AB - Anti-HIV activity and the inhibition of phorbol ester receptor binding activity in two species of Maprounea were traced to small amounts of highly potent phorbol esters of the daphnane type. The triterpenes previously isolated from this genus were found to be devoid of biological activity when scrupulously purified. Four new triterpene esters were elucidated; two [3,4] were found in M. africana, while three [4,6,7] were found in M. membranacea. Nmr assignments have also been made for two previously known compounds [2,5] in this group. JF - Journal of natural products AU - Beutler, J A AU - Kashman, Y AU - Tischler, M AU - Cardellina, J H AU - Gray, G N AU - Currens, M J AU - Wall, M E AU - Wani, M C AU - Boyd, M R AD - Laboratory of Drug Discovery Research and Development, National Cancer Institute, Frederick, Maryland 21702-1201, USA. Y1 - 1995/07// PY - 1995 DA - July 1995 SP - 1039 EP - 1046 VL - 58 IS - 7 SN - 0163-3864, 0163-3864 KW - Reverse Transcriptase Inhibitors KW - 0 KW - Triterpenes KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Brain -- drug effects KW - Binding, Competitive -- drug effects KW - Brain -- metabolism KW - Hydrolysis KW - Chromatography, High Pressure Liquid KW - Magnetic Resonance Spectroscopy KW - Phorbol 12,13-Dibutyrate -- pharmacology KW - Rats KW - Acetylation KW - In Vitro Techniques KW - Gas Chromatography-Mass Spectrometry KW - Species Specificity KW - HIV -- drug effects KW - Triterpenes -- chemistry KW - Triterpenes -- pharmacology KW - Triterpenes -- isolation & purification KW - Plants, Medicinal -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77650070?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+natural+products&rft.atitle=A+reinvestigation+of+Maprounea+triterpenes.&rft.au=Beutler%2C+J+A%3BKashman%2C+Y%3BTischler%2C+M%3BCardellina%2C+J+H%3BGray%2C+G+N%3BCurrens%2C+M+J%3BWall%2C+M+E%3BWani%2C+M+C%3BBoyd%2C+M+R&rft.aulast=Beutler&rft.aufirst=J&rft.date=1995-07-01&rft.volume=58&rft.issue=7&rft.spage=1039&rft.isbn=&rft.btitle=&rft.title=Journal+of+natural+products&rft.issn=01633864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-20 N1 - Date created - 1995-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Familial depression versus depression identified in a control group: are they the same? AN - 77647286; 7480457 AB - Subjects who meet the criteria for an affective syndrome possibly are aetiologically heterogeneous. An approach to this possibility involves examining affectively ill subjects obtained by different methods of ascertainment. This study compares depressed and manic subjects who are related to affectively ill probands with affectively ill subjects who were obtained from a study of a control population, and, therefore, were less likely to be familial. The subjects were identified in a large collaborative study of depression where both family members as well as controls were personally interviewed and followed up for 6 years after admission to the study. Data were obtained on subtypes of affective disorder using the Research Diagnostic Criteria and information was gathered about psychiatric hospitalizations, suicide attempts, alcoholism and psychological functioning prior to admission. Similar assessments were made for the comparison groups for the 6 year period between intake and follow-up. Relatives of bipolar I/schizoaffective manic probands were more likely to show mania than affectively ill controls or relatives of unipolar/schizoaffective depressed probands. Affectively ill controls were less likely to be hospitalized and less likely to suffer from an incapacitating depression. They were also likely to have functioned in a more healthy fashion than the affectively ill relatives of the bipolars and unipolars, in the 5 years before admission to the study. In the 6 year follow-up, both the subjects themselves and raters assessed the depressed controls as functioning better than the affectively ill relatives of the probands. Further, assessment of global adjustment during the 6 year period was worse for the relatives of affectively ill probands than for the depressed controls. Length of major depression was longer in relatives of bipolar and unipolar probands than in controls. Though all of the subjects in this study met research criteria for an affective illness, there were marked differences in the qualitative aspects of these illnesses with the relatives of affectively ill probands, who functioned less well and had longer and more severe episodes and more hospitalizations. JF - Psychological medicine AU - Winokur, G AU - Coryell, W AU - Endicott, J AU - Akiskal, H AU - Keller, M AU - Maser, J D AU - Warshaw, M AD - National Institute of Mental Health Collaborative Program on the Psychobiology of Depression-Clinical Studies, Iowa City, USA. Y1 - 1995/07// PY - 1995 DA - July 1995 SP - 797 EP - 806 VL - 25 IS - 4 SN - 0033-2917, 0033-2917 KW - Index Medicus KW - Suicide, Attempted -- psychology KW - Alcoholism -- diagnosis KW - Humans KW - Alcoholism -- genetics KW - Alcoholism -- psychology KW - Comorbidity KW - Psychiatric Status Rating Scales KW - Adaptation, Psychological KW - Adult KW - Follow-Up Studies KW - Middle Aged KW - Personality Assessment KW - Female KW - Male KW - Bipolar Disorder -- diagnosis KW - Patient Admission KW - Depressive Disorder -- psychology KW - Depressive Disorder -- diagnosis KW - Bipolar Disorder -- genetics KW - Depressive Disorder -- genetics KW - Bipolar Disorder -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77647286?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychological+medicine&rft.atitle=Familial+depression+versus+depression+identified+in+a+control+group%3A+are+they+the+same%3F&rft.au=Winokur%2C+G%3BCoryell%2C+W%3BEndicott%2C+J%3BAkiskal%2C+H%3BKeller%2C+M%3BMaser%2C+J+D%3BWarshaw%2C+M&rft.aulast=Winokur&rft.aufirst=G&rft.date=1995-07-01&rft.volume=25&rft.issue=4&rft.spage=797&rft.isbn=&rft.btitle=&rft.title=Psychological+medicine&rft.issn=00332917&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-28 N1 - Date created - 1995-12-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional consequences of sustained sleep deprivation in the rat. AN - 77637393; 7546317 AB - Sleep deprivation disrupts vital biological processes that are necessary for cognitive ability and physical health, but the physiological changes that underlie these outward effects are largely unknown. The purpose of the present studies in the laboratory rat is to prolong sleep deprivation to delineate the pathophysiology and to determine its mediation. In the rat, the course of prolonged sleep deprivation has a syndromic nature and eventuates in a life-threatening state. An early and central symptom of sleep deprivation is a progressive increase in peripheral energy expenditure to nearly double normal levels. An attempt to alleviate this negative energy balance by feeding rats a balanced diet that is high in its efficiency of utilization prolongs survival and attenuates or delays development of malnutrition-like symptoms, indicating that several symptoms can be manipulated to some extent by energy and nutrient consumption. Most changes in neuroendocrine parameters appear to be responses to metabolic demands, such as increased plasma catecholamines indicating sympathetic activation. Plasma total thyroid hormones, however, decline to severely low levels; a metabolic complication that is associated with other sleep deprivation-induced symptoms, such as a decline in body temperature to hypothermic levels despite increased energy expenditure. Metabolic mapping of the brain revealed a dissociation between the energy metabolism of the brain and that of the body. Sleep deprivation's effects on cerebral structures are heterogeneous and unidirectional toward decreased functional activity. The hypometabolic brain structures are concentrated in the hypothalamus, thalamus and limbic systems, whereas few regions in the rest of the brain and none in the medulla, are affected. Correspondence can be found between some of the affected cerebral structures and several of the peripheral symptoms, such as hyperphagia and possible heat retention problems. The factor predisposing to mortality is a decreased resistance to infection. Lethal opportunistic organisms are permitted to infect the bloodstream, which presumably results in a cascade of toxic-like reactions. Host defense is thus the first system to fail. There is neither fever nor marked tissue inflammatory reactions typical of infectious disease states, suggesting that sleep deprivation is immunosuppressive. Each of the four abnormalities identified--(1) a deep negative energy balance and associated malnutrition; (2) heterogeneous decreases in cerebral function; (3) low thyroid hormone concentrations; and (4) decrease resistance to infection--can be viewed as having an early origin during the sleep deprivation process to signify the foremost pathogenic situation to which the other abnormalities might be secondarily related.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Behavioural brain research AU - Everson, C A AD - Clinical Psychobiology Branch, National Institutes of Health, National Institute of Mental Health, Bethesda, MD 20892, USA. PY - 1995 SP - 43 EP - 54 VL - 69 IS - 1-2 SN - 0166-4328, 0166-4328 KW - Index Medicus KW - Rats KW - Immunity -- physiology KW - Animals KW - Adaptation, Physiological -- physiology KW - Brain -- physiology KW - Sleep Deprivation -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77637393?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Behavioural+brain+research&rft.atitle=Functional+consequences+of+sustained+sleep+deprivation+in+the+rat.&rft.au=Everson%2C+C+A&rft.aulast=Everson&rft.aufirst=C&rft.date=1995-07-01&rft.volume=69&rft.issue=1-2&rft.spage=43&rft.isbn=&rft.btitle=&rft.title=Behavioural+brain+research&rft.issn=01664328&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-22 N1 - Date created - 1995-11-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mitochondrial membrane potential in single living adult rat cardiac myocytes exposed to anoxia or metabolic inhibition. AN - 77637018; 7562625 AB - 1. The relation between mitochondrial membrane potential (delta psi m) and cell function was investigated in single adult rat cardiac myocytes during anoxia and reoxygenation. delta psi m was studied by loading myocytes with JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'- tetra-ethylbenzimidazolylcarbocyanine iodide), a fluorescent probe characterized by two emission peaks (539 and 597 nm with excitation at 490 nm) corresponding to monomer and aggregate forms of the dye. 2. De-energizing conditions applied to mitochondria, cell suspensions or single cells decreased the aggregate emission and increased the monomer emission. This latter result cannot be explained by changes of JC-1 concentration in the aqueous mitochondrial matrix phase indicating that hydrophobic interaction of the probe with membranes has to be taken into account to explain JC-1 fluorescence properties in isolated mitochondria or intact cells. 3. A different sensitivity of the two JC-1 forms to delta psi m changes was shown in isolated mitochondria by the effects of ADP and FCCP and the calibration with K+ diffusion potentials. The monomer emission was responsive to values of delta psi m below 140 mV, which hardly modified the aggregate emission. Thus JC-1 represents a unique double sensor which can provide semi-quantitative information in both low and high potential ranges. 4. At the onset of glucose-free anoxia the epifluorescence of individual myocytes studied in the single excitation (490 nm)-double emission (530 and 590 nm) mode showed a gradual decline of the aggregate emission, which reached a plateau while electrically stimulated (0.2 Hz) contraction was still retained. The subsequent failure of contraction was followed by the rise of the emission at 530 nm, corresponding to the monomer form of the dye, concomitantly with the development of rigor contracture. 5. The onset of the rigor was preceded by the increase in intracellular Mg2+ concentration ([Mg2+]i) monitored by mag-indo-1 epifluorescence. Since under these experimental conditions intracellular [Ca2+] and pH are fairly stable, the increase in [Mg2+]i was likely to be produced by a decrease in ATP content. 6. The inhibition of mitochondrial ATPase induced by oligomycin during anoxia was associated with a rapid and simultaneous change of both the components of JC-1 fluorescence, suggesting that delta psi m, instead of producing ATP, is generated by glycolytic ATP during anoxia. 7. The readmission of oxygen induced a rapid decrease of the monomer emission and a slower increase of the aggregate emission. These fluorescence changes were not necessarily associated with the recovery of mechanical function.(ABSTRACT TRUNCATED AT 400 WORDS) JF - The Journal of physiology AU - Di Lisa, F AU - Blank, P S AU - Colonna, R AU - Gambassi, G AU - Silverman, H S AU - Stern, M D AU - Hansford, R G AD - Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA. Y1 - 1995/07/01/ PY - 1995 DA - 1995 Jul 01 SP - 1 EP - 13 VL - 486 ( Pt 1) SN - 0022-3751, 0022-3751 KW - Antimetabolites KW - 0 KW - Benzimidazoles KW - Carbocyanines KW - Fluorescent Dyes KW - 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine KW - 21527-78-6 KW - Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone KW - 370-86-5 KW - Adenosine Diphosphate KW - 61D2G4IYVH KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - Magnesium KW - I38ZP9992A KW - Potassium KW - RWP5GA015D KW - Index Medicus KW - Space life sciences KW - Rats KW - Magnesium -- metabolism KW - Animals KW - Fluorescence KW - Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone -- pharmacology KW - Rats, Wistar KW - Adenosine Triphosphatases -- antagonists & inhibitors KW - Membrane Potentials -- drug effects KW - Adenosine Diphosphate -- pharmacology KW - Potassium -- metabolism KW - Antimetabolites -- pharmacology KW - Myocardium -- cytology KW - Mitochondria, Heart -- physiology KW - Myocardium -- enzymology KW - Mitochondria, Heart -- drug effects KW - Cell Hypoxia -- physiology KW - Myocardium -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77637018?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+physiology&rft.atitle=Mitochondrial+membrane+potential+in+single+living+adult+rat+cardiac+myocytes+exposed+to+anoxia+or+metabolic+inhibition.&rft.au=Di+Lisa%2C+F%3BBlank%2C+P+S%3BColonna%2C+R%3BGambassi%2C+G%3BSilverman%2C+H+S%3BStern%2C+M+D%3BHansford%2C+R+G&rft.aulast=Di+Lisa&rft.aufirst=F&rft.date=1995-07-01&rft.volume=486+%28+Pt+1%29&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+physiology&rft.issn=00223751&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-22 N1 - Date created - 1995-11-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Methods Enzymol. 1979;55:547-69 [37402] J Mol Cell Cardiol. 1980 Apr;12(4):387-408 [7381944] Circ Res. 1981 Nov;49(5):1119-28 [7296779] Am J Physiol. 1983 Jun;244(6):H743-8 [6305212] J Biol Chem. 1983 Aug 25;258(16):9657-61 [6224783] Circ Res. 1984 Dec;55(6):816-24 [6499136] J Biol Chem. 1985 Nov 15;260(26):14325-34 [2414295] Science. 1986 Aug 8;233(4764):640-5 [3726553] Arch Biochem Biophys. 1986 Jul;248(1):305-23 [3015029] J Gen Physiol. 1986 Nov;88(5):589-613 [3783125] J Physiol. 1994 May 1;476(3):459-71 [8057254] Circ Res. 1988 Jul;63(1):1-15 [3383370] Proc Natl Acad Sci U S A. 1988 Sep;85(18):6954-8 [3413129] Am J Physiol. 1987 Apr;252(4 Pt 1):C356-61 [3565556] Biophys J. 1989 Dec;56(6):1053-69 [2611324] Am J Physiol. 1990 Feb;258(2 Pt 2):H574-86 [2309919] Biochem J. 1990 Feb 15;266(1):33-9 [2106875] Biochim Biophys Acta. 1990 Apr 5;1016(2):244-52 [2317483] Biochem J. 1991 Feb 15;274 ( Pt 1):133-7 [1900416] Biochemistry. 1991 May 7;30(18):4480-6 [2021638] Proc Natl Acad Sci U S A. 1991 May 1;88(9):3671-5 [2023917] Circ Res. 1991 Jul;69(1):196-208 [2054932] J Biol Chem. 1992 May 5;267(13):8834-9 [1374381] Circulation. 1992 Jul;86(1):1-11 [1617762] J Mol Cell Cardiol. 1992 Mar;24(3):213-8 [1625346] Circ Res. 1992 Sep;71(3):605-13 [1499108] J Physiol. 1992 May;450:33-61 [1432712] Am J Physiol. 1993 Mar;264(3 Pt 1):C709-14 [8460673] Cardiovasc Res. 1993 Oct;27(10):1790-4 [8275525] Am J Physiol. 1994 Jan;266(1 Pt 1):C222-33 [8304418] Am J Pathol. 1972 Jun;67(3):417-40 [5033257] Eur J Biochem. 1969 Jan;7(3):418-26 [5797439] J Biol Chem. 1966 Apr 25;241(8):1882-9 [4223456] Eur J Biochem. 1979 Mar 15;95(1):1-20 [378655] Biochem J. 1978 Feb 15;170(2):285-95 [637843] J Biol Chem. 1977 Dec 10;252(23):8731-9 [925018] Annu Rev Cell Biol. 1988;4:155-81 [3058159] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemo- and dietary prevention of colorectal cancer. AN - 77632197; 7577021 AB - Because of the substantial morbidity and mortality associated with colorectal cancer, and the limitations and costs of treating this disease, prevention remains a desirable (if elusive) goal. In this paper, we discuss both chemo- and dietary prevention strategies for colorectal cancer, recognising the overlap and cross-fertilisation between these two approaches. Chemopreventive compounds are drugs and are developed for clinical use like other pharmaceuticals. A formal sequential multi-phase programme for development of chemopreventive agents has been instituted by the National Cancer Institute, U.S.A. This involves both preclinical efficacy and clinical studies. Such studies increasingly employ preneoplastic intermediate markers (such as proliferation measures) as well as neoplastic adenomas as endpoints. Promising chemopreventive agents include calcium, aspirin and other non-steroidal anti-inflammatory drugs, vitamins (such as vitamin E and folate), 2-dimethylfluorornithine (DFMO), oltipraz and ursodeoxycholic acid. Several lines of evidence implicate diet in colorectal carcinogenesis. Key hypotheses in diet and colorectal cancer (which are amenable to prevention, research and action), in addition to those pertaining to the micronutrient chemopreventives, include dietary fat and fibre, food mutagens, red meat, and overall low-fat, high-fibre, high fruit and vegetable dietary patterns and cuisines. Several adenomatous polyp recurrence studies with fibre supplement, macronutrient or dietary pattern interventions have been undertaken internationally. We review early findings from this new generation of studies, and anticipate the future results from these investigations and the ambitious Women's Health initiative in the U.S.A. Results from these studies may convert the promise of colorectal cancer prevention into reality. JF - European journal of cancer (Oxford, England : 1990) AU - Schatzkin, A AU - Kelloff, G AD - Cancer Prevention Studies Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. PY - 1995 SP - 1198 EP - 1204 VL - 31A IS - 7-8 SN - 0959-8049, 0959-8049 KW - Vitamins KW - 0 KW - Index Medicus KW - Randomized Controlled Trials as Topic KW - Vitamins -- therapeutic use KW - Humans KW - Adenoma -- prevention & control KW - Aged KW - Middle Aged KW - Female KW - Dietary Fiber -- therapeutic use KW - Diet KW - Colorectal Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77632197?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+cancer+%28Oxford%2C+England+%3A+1990%29&rft.atitle=Chemo-+and+dietary+prevention+of+colorectal+cancer.&rft.au=Schatzkin%2C+A%3BKelloff%2C+G&rft.aulast=Schatzkin&rft.aufirst=A&rft.date=1995-07-01&rft.volume=31A&rft.issue=7-8&rft.spage=1198&rft.isbn=&rft.btitle=&rft.title=European+journal+of+cancer+%28Oxford%2C+England+%3A+1990%29&rft.issn=09598049&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-28 N1 - Date created - 1995-11-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of interferon-alpha as a modulator of fluorouracil and leucovorin. AN - 77625649; 7577043 AB - Several preclinical studies have demonstrated that interferon-alpha (IFN-alpha) may enhance the cytotoxicity of fluoropyrimidines in a greater-than-additive manner in a variety of human cancer cell lines. The underlying mechanism(s) have varied in different cancer cell lines, and include increased fluorouracil anabolism to fluorodeoxyuridine monophosphate, further inhibition of thymidylate synthase, stimulation of thymidine and uridine phosphorylase activities, greater DNA damage, and enhanced natural killer cell-mediated lysis of tumour targets. These preclinical studies stimulated clinical evaluation of IFN-alpha in combination with 5-fluorouracil (5-FU) with and without leucovorin (LV), and the initial clinical results appeared promising. We summarise preclinical research concerning the interaction of 5-FU and IFN-alpha. The rationale for combining 5-FU with IFN-alpha and LV is discussed, and we describe our clinical experience with the combination of 5-FU, LV and IFN-alpha-2a. The insights and unresolved questions concerning the clinical application of this combination are also discussed. JF - European journal of cancer (Oxford, England : 1990) AU - Grem, J L AU - van Groeningen, C J AU - Ismail, A A AU - Johnston, P G AU - Alexander, H R AU - Allegra, C J AD - NCI-NMOB, National Naval Medical Center, Bethesda, Maryland 20889-5105, USA. PY - 1995 SP - 1316 EP - 1320 VL - 31A IS - 7-8 SN - 0959-8049, 0959-8049 KW - Antidotes KW - 0 KW - Antimetabolites, Antineoplastic KW - Interferon-alpha KW - Leucovorin KW - Q573I9DVLP KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Combined Modality Therapy KW - Humans KW - Drug Synergism KW - Interferon-alpha -- pharmacology KW - Antimetabolites, Antineoplastic -- administration & dosage KW - Interferon-alpha -- administration & dosage KW - Antidotes -- administration & dosage KW - Leucovorin -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacology KW - Antimetabolites, Antineoplastic -- pharmacology KW - Fluorouracil -- administration & dosage KW - Colorectal Neoplasms -- therapy KW - Fluorouracil -- pharmacology KW - Leucovorin -- pharmacology KW - Antidotes -- pharmacology KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77625649?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+cancer+%28Oxford%2C+England+%3A+1990%29&rft.atitle=The+role+of+interferon-alpha+as+a+modulator+of+fluorouracil+and+leucovorin.&rft.au=Grem%2C+J+L%3Bvan+Groeningen%2C+C+J%3BIsmail%2C+A+A%3BJohnston%2C+P+G%3BAlexander%2C+H+R%3BAllegra%2C+C+J&rft.aulast=Grem&rft.aufirst=J&rft.date=1995-07-01&rft.volume=31A&rft.issue=7-8&rft.spage=1316&rft.isbn=&rft.btitle=&rft.title=European+journal+of+cancer+%28Oxford%2C+England+%3A+1990%29&rft.issn=09598049&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-28 N1 - Date created - 1995-11-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Magnetic resonance imaging reveals no ventriculomegaly in polydrug abusers. AN - 77618396; 7572068 AB - Previous studies of cerebral structure in substance abusers yielded controversial results, largely due to issues of subject selection and/or limitations of experimental techniques. The purpose of the present study was to assess whether the ventricle-to-brain ratio (VBR), determined volumetrically by magnetic resonance imaging (MRI), differed in polysubstance abusers (n = 10), as compared with age-matched controls (n = 10). Subjects were male volunteers 21-39 years of age. The values of VBR in the polydrug abuse group were not larger than those in control group, nor was there any tendency toward relative ventriculomegaly in the substance abusers. Therefore, the present findings provide no evidence that polysubstance abuse produces abnormalities of gross brain structure in relatively young and physically healthy men. JF - Acta neurologica Scandinavica AU - Liu, X AU - Phillips, R L AU - Resnick, S M AU - Villemagne, V L AU - Wong, D F AU - Stapleton, J M AU - London, E D AD - Division of Intramural Research, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 1995/07// PY - 1995 DA - July 1995 SP - 83 EP - 90 VL - 92 IS - 1 SN - 0001-6314, 0001-6314 KW - Psychotropic Drugs KW - 0 KW - Street Drugs KW - Index Medicus KW - Reference Values KW - Hypertrophy KW - Alcoholism -- diagnosis KW - Humans KW - Brain -- pathology KW - Brain -- drug effects KW - Adult KW - Image Processing, Computer-Assisted KW - Male KW - Magnetic Resonance Imaging KW - Substance-Related Disorders -- diagnosis KW - Cerebral Ventricles -- pathology KW - Cerebral Ventricles -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77618396?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neurologica+Scandinavica&rft.atitle=Magnetic+resonance+imaging+reveals+no+ventriculomegaly+in+polydrug+abusers.&rft.au=Liu%2C+X%3BPhillips%2C+R+L%3BResnick%2C+S+M%3BVillemagne%2C+V+L%3BWong%2C+D+F%3BStapleton%2C+J+M%3BLondon%2C+E+D&rft.aulast=Liu&rft.aufirst=X&rft.date=1995-07-01&rft.volume=92&rft.issue=1&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=Acta+neurologica+Scandinavica&rft.issn=00016314&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-09 N1 - Date created - 1995-11-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The carcinogenesis bioassay in perspective: application in identifying human cancer hazards. AN - 77571696; 7588478 AB - The selection process for chemicals tested in the rodent carcinogenicity bioassay has been biased toward chemicals suspected of potential carcinogenicity. Results from carcinogenicity bioassays of 400 chemicals tested by the National Cancer Institute/National Toxicology Program (NCI/NTP) were analyzed to determine the dependence of positive results on chemical selection criteria: those suspected of being carcinogenic and those selected based on large volumes produced and widespread exposures. Of these chemicals, 210 (52%) induced carcinogenicity in at least one organ of one sex of one species of the four sex/species groups typically used by NCI/NTP. Only 92 of the 400 chemicals (23%) were positive in two species and thus by international criteria are considered likely to pose a carcinogenic hazard to humans. A total of 267 chemicals (67%) were selected as suspect carcinogens, and 187 (68%) of these were carcinogenic. Suspect chemicals account for 86% of chemicals with at least one positive result and account for 90% of chemicals considered positive in two species. The International Agency for Research on Cancer (IARC) lists only 5 of the 400 chemicals as carcinogenic to humans (group 1) and 10 as probably carcinogenic to humans (group 2A). The majority (80%) of the 133 chemicals selected only on production/exposure considerations were not carcinogenic in animals, even when tested at the maximum tolerated (or minimally toxic) dose. Only 9 (6.8%) were positive in two species, and none is listed in IARC groups 1 or 2A. Thus, on the basis of our analyses we predict that less than 5-10% of the 75,000 chemicals in commercial use might be reasonably anticipated to be carcinogenic to humans. JF - Environmental health perspectives AU - Fung, V A AU - Barrett, J C AU - Huff, J AD - National Toxicology Program, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1995 SP - 680 EP - 683 VL - 103 IS - 7-8 SN - 0091-6765, 0091-6765 KW - Carcinogens KW - 0 KW - Index Medicus KW - Rats KW - Animals KW - Humans KW - Carcinogenicity Tests KW - Mice KW - Environmental Exposure -- adverse effects KW - Neoplasms, Experimental -- chemically induced KW - Carcinogens -- classification KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77571696?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+carcinogenesis+bioassay+in+perspective%3A+application+in+identifying+human+cancer+hazards.&rft.au=Fung%2C+V+A%3BBarrett%2C+J+C%3BHuff%2C+J&rft.aulast=Fung&rft.aufirst=V&rft.date=1995-07-01&rft.volume=103&rft.issue=7-8&rft.spage=680&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 - 1995-12-04 N1 - Date created - 1995-12-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Ann N Y Acad Sci. 1988;534:1-30 [3291703] Cancer Res. 1987 Jun 1;47(11):3012-31 [3105872] Mutagenesis. 1990 Jan;5(1):3-14 [2184307] Pharmacol Ther. 1990;46(3):469-86 [2188272] Science. 1990 Aug 31;249(4972):970-1 [2136249] Environ Health Perspect. 1990 Jun;86:313-21 [2205492] Cancer Res. 1990 Dec 1;50(23):7415-21 [2174724] Science. 1991 Jan 25;251(4992):387-8 [1989073] Annu Rev Pharmacol Toxicol. 1991;31:621-52 [2064387] Scand J Work Environ Health. 1992;18 Suppl 1:31-7 [1411375] Scand J Work Environ Health. 1992;18 Suppl 1:83-9 [1411384] Mutat Res. 1993 Mar;286(1):111-8 [7678907] Pharmacol Toxicol. 1993;72 Suppl 1:12-27 [8474975] Mol Carcinog. 1993;7(3):135-8 [8489710] In Vivo. 1993 Jan-Feb;7(1):65-72 [8504209] Fundam Appl Toxicol. 1993 May;20(4):413-36 [8314458] Environ Health Perspect. 1993 Apr;100:201-10 [8354167] Environ Health Perspect. 1993 Apr;100:9-20 [8354184] Toxicol Ind Health. 1993 May-Jun;9(3):415-38 [8367884] Environ Health Perspect. 1993 Oct;101(5):444-5 [8119256] Environ Health Perspect. 1993 Dec;101 Suppl 5:3-7 [7912189] Environ Health Perspect. 1993 Dec;101 Suppl 5:45-53 [8013424] Am J Ind Med. 1995 Feb;27(2):293-300 [7755018] Annu Rev Pharmacol Toxicol. 1979;19:511-30 [378109] J Toxicol Environ Health. 1981 Jul-Aug;8(1-2):251-80 [7328708] Prog Exp Tumor Res. 1983;26:187-201 [6342045] Carcinogenesis. 1986 Nov;7(11):1853-63 [3769134] Jpn J Cancer Res. 1989 Sep;80(9):795-807 [2513295] N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Baculovirus and insect cell gene expression: review of baculovirus biotechnology. AN - 77562932; 7588489 AB - The BEVS continues to evolve as a powerful, flexible tool for molecular biology, protein function, and biomedical research. Future developments offer the promise of replacement of hazardous chemical insecticides with environmentally safe biopesticides, construction of baculovirus vectors which encode genes for specific post-translational modifications, and establishment of efficient, stably transformed insect cell lines. FDA approval of BEVS-produced products offer the prospect of new biopharmaceuticals, in particular human therapeutics and vaccines, to improve human health and increase the quality of life for millions of people. JF - Environmental health perspectives AU - Patterson, R M AU - Selkirk, J K AU - Merrick, B A Y1 - 1995 PY - 1995 DA - 1995 SP - 756 EP - 759 VL - 103 IS - 7-8 KW - Recombinant Proteins KW - 0 KW - Viral Vaccines KW - Index Medicus KW - Animals KW - Humans KW - Pest Control, Biological KW - Baculoviridae -- genetics KW - Genetic Vectors KW - Insects -- virology KW - Biotechnology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77562932?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Baculovirus+and+insect+cell+gene+expression%3A+review+of+baculovirus+biotechnology.&rft.au=Patterson%2C+R+M%3BSelkirk%2C+J+K%3BMerrick%2C+B+A&rft.aulast=Patterson&rft.aufirst=R&rft.date=1995-07-01&rft.volume=103&rft.issue=7-8&rft.spage=756&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 - 1995-12-04 N1 - Date created - 1995-12-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Alcohol Use Disorder and Associated Disabilities Interview schedule (AUDADIS): reliability of alcohol and drug modules in a general population sample. AN - 77528979; 7587973 AB - Using a representative sample of the general population, the test-retest reliability of the alcohol and drug modules of the Alcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS) was examined. The AUDADIS showed good to excellent reliability for measures of alcohol consumption and use of sedatives, tranquilizers, amphetamines, opioids (other than heroin), cannabis and cocaine. Equally good reliability was demonstrated for diagnoses of alcohol, cannabis, cocaine and heroin abuse or harmful use and dependence defined in terms of the International Classification of Diseases-Tenth Revision (ICD-10) and the Diagnostic and Statistical Manual of Mental Disorders-Third Edition-Revised (DSM-III-R) and Fourth Edition (DSM-IV). Results are discussed in terms of the need for future research on the psychometric properties of the AUDADIS in clinical and general population samples. JF - Drug and alcohol dependence AU - Grant, B F AU - Harford, T C AU - Dawson, D A AU - Chou, P S AU - Pickering, R P AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892-7003, USA. Y1 - 1995/07// PY - 1995 DA - July 1995 SP - 37 EP - 44 VL - 39 IS - 1 SN - 0376-8716, 0376-8716 KW - Psychotropic Drugs KW - 0 KW - Street Drugs KW - Index Medicus KW - Mass Screening KW - Cross-Sectional Studies KW - New Jersey -- epidemiology KW - Reproducibility of Results KW - Humans KW - Adult KW - Sampling Studies KW - Incidence KW - Aged KW - Middle Aged KW - Adolescent KW - Psychometrics KW - Male KW - Female KW - Substance-Related Disorders -- diagnosis KW - Alcoholism -- epidemiology KW - Personality Assessment -- statistics & numerical data KW - Alcoholism -- diagnosis KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77528979?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+and+alcohol+dependence&rft.atitle=The+Alcohol+Use+Disorder+and+Associated+Disabilities+Interview+schedule+%28AUDADIS%29%3A+reliability+of+alcohol+and+drug+modules+in+a+general+population+sample.&rft.au=Grant%2C+B+F%3BHarford%2C+T+C%3BDawson%2C+D+A%3BChou%2C+P+S%3BPickering%2C+R+P&rft.aulast=Grant&rft.aufirst=B&rft.date=1995-07-01&rft.volume=39&rft.issue=1&rft.spage=37&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 - 1995-12-06 N1 - Date created - 1995-12-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA synthesis errors associated with double-strand-break repair. AN - 77526195; 7672595 AB - Repair of a site-specific double-strand DNA break (DSB) resulted in increased reversion frequency for a nearby allele. Site-specific DSBs were introduced into the genome of Saccharomyces cerevisiae by the endonuclease encoded by the HO gene. Expression of the HO gene from a galactose-inducible promoter allowed efficient DNA cleavage at a single site in large populations of cells. To determine whether the DNA synthesis associated with repair of DSBs has a higher error rate than that associated with genome duplication, HO-induced DSBs were generated 0.3 kb from revertible alleles of trp1. The reversion rate of the trp1 alleles was approximately 100-fold higher among cells that had experienced an HO cut than among uninduced cells. The reverted allele was found predominantly on the chromosome that experienced the DNA cleavage. JF - Genetics AU - Strathern, J N AU - Shafer, B K AU - McGill, C B AD - Laboratory of Eukaryotic Gene Expression, NCI-Frederick Cancer Research and Development Center, ABL-Basic Research Program, Maryland 21702-1201, USA. Y1 - 1995/07// PY - 1995 DA - July 1995 SP - 965 EP - 972 VL - 140 IS - 3 SN - 0016-6731, 0016-6731 KW - HO KW - trp1 KW - DNA, Fungal KW - 0 KW - Oligodeoxyribonucleotides KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Index Medicus KW - Genes, Fungal KW - Amino Acid Sequence KW - Chromosomes, Fungal KW - Mutagenesis KW - Genotype KW - Alleles KW - Base Sequence KW - Haploidy KW - Restriction Mapping KW - Molecular Sequence Data KW - Crosses, Genetic KW - Crossing Over, Genetic KW - Diploidy KW - Saccharomyces cerevisiae -- genetics KW - Frameshift Mutation KW - Saccharomyces cerevisiae -- metabolism KW - DNA Repair KW - DNA-Directed DNA Polymerase -- metabolism KW - DNA, Fungal -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77526195?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=DNA+synthesis+errors+associated+with+double-strand-break+repair.&rft.au=Strathern%2C+J+N%3BShafer%2C+B+K%3BMcGill%2C+C+B&rft.aulast=Strathern&rft.aufirst=J&rft.date=1995-07-01&rft.volume=140&rft.issue=3&rft.spage=965&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-13 N1 - Date created - 1995-10-13 N1 - Date revised - 2017-01-13 N1 - Gene symbol - HO; trp1 N1 - SuppNotes - Cited By: Microbiol Rev. 1988 Mar;52(1):70-102 [3280967] Mol Cell Biol. 1995 Apr;15(4):2173-9 [7891712] Bioessays. 1988 Aug-Sep;9(2-3):61-4 [3066359] Mol Cell Biol. 1989 Feb;9(2):365-76 [2651896] Cell. 1989 May 5;57(3):459-67 [2541914] Science. 1989 Jul 14;245(4914):160-4 [2665076] J Mol Biol. 1989 Jun 5;207(3):527-41 [2668534] Proc Natl Acad Sci U S A. 1989 Aug;86(16):6225-9 [2668958] EMBO J. 1990 Mar;9(3):663-73 [2178924] Curr Genet. 1990 Jul;18(1):29-39 [2173978] Methods Enzymol. 1991;194:319-29 [2005796] Genetics. 1991 Jan;127(1):61-73 [2016047] Annu Rev Genet. 1991;25:229-53 [1812808] Genetics. 1992 Aug;131(4):833-50 [1325387] Mol Cell Biol. 1993 Feb;13(2):1051-8 [8423775] Curr Genet. 1993;23(4):305-14 [8467528] Proc Natl Acad Sci U S A. 1982 Jul;79(13):4128-32 [7051004] Annu Rev Genet. 1982;16:439-500 [6760802] Cold Spring Harb Symp Quant Biol. 1984;49:97-104 [6397325] Cell. 1986 Aug 29;46(5):733-40 [3527443] Proc Natl Acad Sci U S A. 1986 Oct;83(20):7831-5 [3020559] EMBO J. 1987 Apr;6(4):1121-7 [2954815] Curr Genet. 1993 May-Jun;23(5-6):430-4 [8319299] Q Rev Biophys. 1993 Aug;26(3):225-331 [8022969] Mol Cell Biol. 1988 Sep;8(9):3918-28 [3065627] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evolutionary conservation of ten microsatellite loci in four species of Felidae. AN - 77481151; 7658003 AB - Short tandem repeat polymorphisms (STRP), or microsatellites, are widespread among vertebrate genomes and are useful in gene mapping and population studies due to a high level of length polymorphism. We describe here the isolation, characterization, and PCR amplification of 10 microsatellite loci from the domestic cat, Felis catus. The flanking primer sequences were conserved among other Felidae species, and amplification products demonstrated abundant polymorphism in puma, lion, cheetah, and domestic cat. The cheetah sample exhibited the lowest level of polymorphism for these loci among felid species. JF - The Journal of heredity AU - Menotti-Raymond, M A AU - O'Brien, S J AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702-1201, USA. PY - 1995 SP - 319 EP - 322 VL - 86 IS - 4 SN - 0022-1503, 0022-1503 KW - DNA Primers KW - 0 KW - DNA, Satellite KW - Index Medicus KW - Pedigree KW - Animals KW - Base Sequence KW - Conserved Sequence KW - Polymorphism, Genetic KW - Heterozygote KW - Molecular Sequence Data KW - Male KW - Female KW - Cats -- genetics KW - Biological Evolution KW - Repetitive Sequences, Nucleic Acid UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77481151?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Evolutionary+conservation+of+ten+microsatellite+loci+in+four+species+of+Felidae.&rft.au=Menotti-Raymond%2C+M+A%3BO%27Brien%2C+S+J&rft.aulast=Menotti-Raymond&rft.aufirst=M&rft.date=1995-07-01&rft.volume=86&rft.issue=4&rft.spage=319&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 - 1995-10-03 N1 - Date created - 1995-10-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhanced tumor growth in brain dopamine-depleted mice following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. AN - 77454537; 7642739 AB - Brain dopamine influences immune functions and the role of immune functions in tumor growth is well established. Therefore, a study has been carried out to evaluate the correlation, if any, between brain dopamine and tumor growth. MPTP selectively destroys dopaminergic neurons in the brain. In the present study, Ehrlich carcinoma growth was evaluated in MPTP-treated mice. Results showed a correlation between depletion of striatal dopamine and enhanced tumor growth. Since in the present study striatal dopamine depletion in mice was associated with significantly decreased immune responses, the suggested correlation between brain dopamine and tumor growth was possibly mediated by the immune system. JF - Journal of neuroimmunology AU - Basu, S AU - Dasgupta, P S AU - Chowdhury, J R AD - Department of Medical Oncology, Chittaranjan National Cancer Institute, Calcutta, India. Y1 - 1995/07// PY - 1995 DA - July 1995 SP - 1 EP - 8 VL - 60 IS - 1-2 SN - 0165-5728, 0165-5728 KW - Immunoglobulins KW - 0 KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - 9P21XSP91P KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - T-Lymphocytes, Cytotoxic -- physiology KW - Neoplasm Transplantation KW - Lymphocyte Activation -- drug effects KW - Mice, Inbred Strains KW - Immunoglobulins -- analysis KW - Animals KW - Thigh KW - Cell Division -- drug effects KW - Spleen -- pathology KW - Spleen -- immunology KW - Antibody Formation KW - Mice KW - Killer Cells, Natural -- physiology KW - Carcinoma, Ehrlich Tumor -- metabolism KW - Dopamine -- deficiency KW - Carcinoma, Ehrlich Tumor -- pathology KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine -- pharmacology KW - Carcinoma, Ehrlich Tumor -- immunology KW - Brain -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77454537?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neuroimmunology&rft.atitle=Enhanced+tumor+growth+in+brain+dopamine-depleted+mice+following+1-methyl-4-phenyl-1%2C2%2C3%2C6-tetrahydropyridine+%28MPTP%29+treatment.&rft.au=Basu%2C+S%3BDasgupta%2C+P+S%3BChowdhury%2C+J+R&rft.aulast=Basu&rft.aufirst=S&rft.date=1995-07-01&rft.volume=60&rft.issue=1-2&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuroimmunology&rft.issn=01655728&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-20 N1 - Date created - 1995-09-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Correlates of drug abuse among homeless and transient people in the Washington, DC, metropolitan area in 1991. AN - 77441399; 7638333 AB - Sociodemographic correlates of drug use among the general household population may have less accuracy and utility for describing risk factors for drug use among non household populations like the homeless and transient. This analysis examines correlates of past year use of marijuana, cocaine, and needles among homeless and transient people in the Washington, DC, metropolitan statistical area (DC MSA) and discusses them vis-a-vis traditional indicators of drug use among the general household population. Data are from a study conducted in the DC MSA in 1991 that used a multistage sampling design and surveyed a random sample of 908 homeless and transient people ages 12 years and older. The analysis uses multiple logistic regression to assess the independent effect of demographic and other predictors on selected drug use measures among this population. Three key socioeconomic correlates of drug use among the general household population (educational attainment, employment status, and marital status) were nonsignificant predictors of drug use among the homeless. However, other factors were significant, including past year institutionalization, location within the DC MSA, and stage of homelessness. The age group at greatest risk for use of marijuana and cocaine in the past year were the homeless ages 26 to 34, but the oldest group (35 years and older) had the highest risk of needle use. Although men were more likely to have used marijuana and cocaine in the past year, there were no sex differences in the use of needles in the past year. Only past year use of cocaine differed significantly by race or ethnicity, with a greater likelihood among homeless blacks than among homeless whites. Measures of social achievement and socioeconomic status related to the prevalence and risks of drug use among the general household population have but limited applicability in predicting drug use among people who are homeless and transient. Along with other indicators of behavioral and health risks,history of institutionalization, urbanization, and chronicity of homelessness should be considered to improve the epidemiologic assessment of this population. JF - Public health reports (Washington, D.C. : 1974) AU - Lambert, E Y AU - Caces, M F AD - Community Research Branch, National Institute on Drug Abuse, Rockville, MD 20857, USA. PY - 1995 SP - 455 EP - 461 VL - 110 IS - 4 SN - 0033-3549, 0033-3549 KW - Cocaine KW - I5Y540LHVR KW - Abridged Index Medicus KW - Index Medicus KW - Age Factors KW - Sex Factors KW - Humans KW - Substance Abuse, Intravenous -- epidemiology KW - Socioeconomic Factors KW - Logistic Models KW - Risk Factors KW - Adult KW - District of Columbia -- epidemiology KW - Adolescent KW - Female KW - Male KW - Prevalence KW - Cannabis KW - Transients and Migrants KW - Homeless Persons KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77441399?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Public+health+reports+%28Washington%2C+D.C.+%3A+1974%29&rft.atitle=Correlates+of+drug+abuse+among+homeless+and+transient+people+in+the+Washington%2C+DC%2C+metropolitan+area+in+1991.&rft.au=Lambert%2C+E+Y%3BCaces%2C+M+F&rft.aulast=Lambert&rft.aufirst=E&rft.date=1995-07-01&rft.volume=110&rft.issue=4&rft.spage=455&rft.isbn=&rft.btitle=&rft.title=Public+health+reports+%28Washington%2C+D.C.+%3A+1974%29&rft.issn=00333549&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-12 N1 - Date created - 1995-09-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Psychiatry. 1983 Jun;140(6):734-9 [6846631] Hosp Community Psychiatry. 1990 Mar;41(3):306-10 [2312077] Am Psychol. 1991 Nov;46(11):1115-28 [1772149] Am Psychol. 1991 Nov;46(11):1149-58 [1772152] Am J Public Health. 1994 Feb;84(2):303-4 [8296961] JAMA. 1993 Feb 24;269(8):993-7 [8429605] JAMA. 1994 Jan 12;271(2):115-20 [8264065] JAMA. 1994 Jan 12;271(2):121-7 [8264066] Am J Public Health. 1994 Feb;84(2):265-70 [8296951] Int J Addict. 1992 Mar;27(3):317-30 [1563888] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Magnetic field effects on the photohemolysis of human erythrocytes by ketoprofen and protoporphyrin IX. AN - 77438081; 7638268 AB - Application of a static magnetic field (3350 G) during UV-irradiation (> 300 nm) reduced the time for 50% photohemolysis of human erythrocytes by the phototoxic drug ketoprofen (3-benzoyl-alpha-methylbenzoacetic acid) from 96 min to 78 min. This observation can be attributed to a magnetic field induced decrease in the rate of intersystem crossing (kISC) of the geminate triplet radical pair generated by the reduction of ketoprofen in its triplet excited state by erythrocyte membrane constituents, probably lipids. The decrease in kISC results in an increase in the concentration and/or lifetime of free radicals that escape from the triplet radical pair. Thus the critical radical concentration needed to cause membrane damage cell lysis is reached sooner in the presence of the magnetic field. In contrast, the photohemolysis induced by the photodynamic agent protoporphyrin IX was not affected by the magnetic field. Protoporphyrin IX photohemolysis, which is initiated by singlet oxygen, does not involve the initial generation of a triplet radical pair and so is not influenced by the magnetic field. The example of a magnetic field effect on a toxicological process involving free radicals. JF - Photochemistry and photobiology AU - Chignell, C F AU - Sik, R H AD - National Institutes of Health, National Institutes of Environmental Health Sciences, Laboratory of Molecular Biophysics, Research Triangle Park, NC 22709, USA. Y1 - 1995/07// PY - 1995 DA - July 1995 SP - 205 EP - 207 VL - 62 IS - 1 SN - 0031-8655, 0031-8655 KW - Protoporphyrins KW - 0 KW - Ketoprofen KW - 90Y4QC304K KW - protoporphyrin IX KW - C2K325S808 KW - Index Medicus KW - Photolysis KW - Ultraviolet Rays KW - Humans KW - Erythrocytes -- drug effects KW - Magnetics KW - Protoporphyrins -- pharmacology KW - Erythrocytes -- radiation effects KW - Erythrocytes -- cytology KW - Hemolysis -- radiation effects KW - Ketoprofen -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77438081?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Photochemistry+and+photobiology&rft.atitle=Magnetic+field+effects+on+the+photohemolysis+of+human+erythrocytes+by+ketoprofen+and+protoporphyrin+IX.&rft.au=Chignell%2C+C+F%3BSik%2C+R+H&rft.aulast=Chignell&rft.aufirst=C&rft.date=1995-07-01&rft.volume=62&rft.issue=1&rft.spage=205&rft.isbn=&rft.btitle=&rft.title=Photochemistry+and+photobiology&rft.issn=00318655&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-11 N1 - Date created - 1995-09-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Elevated expression of mitochondrial cytochrome b and NADH dehydrogenase subunit 4/4L genes in senescent human cells. AN - 77431063; 7628554 AB - In order to isolate cDNAs expressed differentially in senescent cells, we constructed a cDNA library from poly(A)+ RNA of senescent human fibroblast cells and screened cDNAs by the differential screening method. We isolated five cDNA clones expressed preferentially in the senescent cells. These five cDNA clones fell into two groups by cross-hybridization. Sequence analysis revealed that these cDNA clones were homologous to the human mitochondrial genes for cytochrome b (cytb) and NADH dehydrogenase subunit 4/4L (ND4/4L). Northern blot analysis demonstrated that the expression of these two mitochondrial genes were elevated in senescent cells compared to young cells. However, the expression of the mitochondrial cytochrome oxidase I gene was similar between young and senescent cells, implying that the preferential expression of the mitochondrial genes in the senescent cells was selective for cytb and ND4/4L genes. The results suggest that expressions of mitochondrial cytb and ND4/4L genes are regulated by a senescence-dependent mechanism. JF - Experimental cell research AU - Kodama, S AU - Yamada, H AU - Annab, L 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 - 1995/07// PY - 1995 DA - July 1995 SP - 82 EP - 86 VL - 219 IS - 1 SN - 0014-4827, 0014-4827 KW - Cytochrome b Group KW - 0 KW - DNA Primers KW - DNA, Complementary KW - Macromolecular Substances KW - RNA, Messenger KW - NADH Dehydrogenase KW - EC 1.6.99.3 KW - Index Medicus KW - Blotting, Northern KW - Humans KW - DNA, Complementary -- isolation & purification KW - Fibroblasts -- cytology KW - RNA, Messenger -- biosynthesis KW - Cloning, Molecular KW - Fibroblasts -- physiology KW - Polymerase Chain Reaction KW - Base Sequence KW - Lung KW - Cell Aging KW - Molecular Sequence Data KW - Embryo, Mammalian KW - Cell Line KW - Gene Library KW - Gene Expression KW - Mitochondria -- metabolism KW - NADH Dehydrogenase -- biosynthesis KW - Cytochrome b Group -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77431063?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+cell+research&rft.atitle=Elevated+expression+of+mitochondrial+cytochrome+b+and+NADH+dehydrogenase+subunit+4%2F4L+genes+in+senescent+human+cells.&rft.au=Kodama%2C+S%3BYamada%2C+H%3BAnnab%2C+L%3BBarrett%2C+J+C&rft.aulast=Kodama&rft.aufirst=S&rft.date=1995-07-01&rft.volume=219&rft.issue=1&rft.spage=82&rft.isbn=&rft.btitle=&rft.title=Experimental+cell+research&rft.issn=00144827&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-01 N1 - Date created - 1995-09-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of drinking pattern on the peak/trough blood concentrations in drinking water studies. AN - 77429711; 7628792 AB - The effects of changes in drinking patterns on the expected peak/trough blood concentrations of test compounds were examined during rodent dosed drinking water studies. They were based on the assumption that the kinetics of the test compound is linear and time-invariant. Results indicate that drinking patterns have minor effects on the expected peak/trough concentrations and the time to reach these concentrations. If a 12-hr light/dark cycle starting at 7.00 is used for all the drinking patterns studied, the peak and trough concentrations will occur in the early morning and late afternoon, respectively. A comparison of the predicted versus experimentally determined pentachlorophenol (PCP) plasma concentrations in a 1-wk rat drinking water study revealed that using a circadian rhythm drinking pattern in the model generated the most satisfactory prediction. Predictions based on a square wave drinking pattern with 90% drinking activities in the night phase were also excellent. Triangular or sinusoidal drinking patterns were least accurate in predictions. JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association AU - Yuan, J AD - National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/07// PY - 1995 DA - July 1995 SP - 565 EP - 571 VL - 33 IS - 7 SN - 0278-6915, 0278-6915 KW - Water Pollutants, Chemical KW - 0 KW - Water KW - 059QF0KO0R KW - Pentachlorophenol KW - D9BSU0SE4T KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Computer Simulation KW - Half-Life KW - Circadian Rhythm KW - Water Pollutants, Chemical -- analysis KW - Kinetics KW - Tissue Distribution KW - Models, Biological KW - Male KW - Biological Availability KW - Pentachlorophenol -- pharmacokinetics KW - Drinking Behavior -- physiology KW - Water -- chemistry KW - Pentachlorophenol -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77429711?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effects+of+drinking+pattern+on+the+peak%2Ftrough+blood+concentrations+in+drinking+water+studies.&rft.au=Yuan%2C+J&rft.aulast=Yuan&rft.aufirst=J&rft.date=1995-07-01&rft.volume=33&rft.issue=7&rft.spage=565&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 - 1995-09-05 N1 - Date created - 1995-09-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemotherapy-induced changes in uterine volume: CT study. AN - 77416470; 7622690 AB - The goal of this study was to quantify changes in uterine volume during and after chemotherapy for breast cancer. Fifty-eight patients (mean age 42 years) with advanced breast cancer undergoing treatment with FLAC (5-fluorouracil, leucovorin, Adriamycin, and cyclophosphamide) were studied with serial pelvic CT. The transverse, anteroposterior, and sagittal measurements of the uterus were taken in each of the CT scans. The uterine volumes were calculated, normalized to baseline volumes, and graphically displayed for each patient. The temporal changes in uterine volume were correlated to the dates of chemotherapy administration and menstrual status. There was a striking and consistent loss of uterine volume with chemotherapy. This phenomenon was observed in 55 (95%) of the 58 patients. The mean minimum uterine volume was 58.3 +/- 20.2% compared with the baseline. This loss of uterine volume began after the administration of the first cycle of chemotherapy and progressed during subsequent cycles. It coincided with loss of normal menses in all patients. After completion of chemotherapy, there was a recovery of the uterine volume in 12 of the 16 patients who had follow-up CT. The mean recovery uterine volume was 108.4 +/- 49.8% of baseline. Menses recovered in four of these. Chemotherapy causes loss of uterine volume, which usually recovers after the withdrawal of chemotherapy in premenopausal women. This change should not be mistaken for a therapeutic response of primary or secondary malignancy within the uterus or be confused with subsequent uterine changes due to tamoxifen. JF - Journal of computer assisted tomography AU - Kolachana, P AU - Cowan, K AU - Denicoff, A AU - Jones, E C AU - Choyke, P L AD - Diagnostic Radiology Department/Henry M. Jackson Foundation, Warren Grant Magnuson Clinical Center, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1995 SP - 592 EP - 595 VL - 19 IS - 4 SN - 0363-8715, 0363-8715 KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Leucovorin KW - Q573I9DVLP KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Breast Neoplasms -- drug therapy KW - Cyclophosphamide -- administration & dosage KW - Humans KW - Leucovorin -- administration & dosage KW - Tomography, X-Ray Computed KW - Retrospective Studies KW - Doxorubicin -- administration & dosage KW - Hysterosalpingography -- drug effects KW - Fluorouracil -- administration & dosage KW - Doxorubicin -- pharmacology KW - Adult KW - Fluorouracil -- pharmacology KW - Leucovorin -- pharmacology KW - Female KW - Cyclophosphamide -- pharmacology KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacology KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Uterus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77416470?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+computer+assisted+tomography&rft.atitle=Chemotherapy-induced+changes+in+uterine+volume%3A+CT+study.&rft.au=Kolachana%2C+P%3BCowan%2C+K%3BDenicoff%2C+A%3BJones%2C+E+C%3BChoyke%2C+P+L&rft.aulast=Kolachana&rft.aufirst=P&rft.date=1995-07-01&rft.volume=19&rft.issue=4&rft.spage=592&rft.isbn=&rft.btitle=&rft.title=Journal+of+computer+assisted+tomography&rft.issn=03638715&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-30 N1 - Date created - 1995-08-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Studies of the biogenic amine transporters. VI. Characterization of a novel cocaine binding site, identified with [125I]RTI-55, in membranes prepared from whole rat brain minus caudate. AN - 77406779; 7616423 AB - Previous studies showed that the cocaine analog [125I]RTI-55 labels dopamine and serotonergic (5-HT) biogenic amine transporters (BATs) with high affinity. Here we characterized [125I]RTI-55 binding to membranes prepared from whole rat brain minus the caudate nuclei. Paroxetine (50 nM) was used to block [125I]RTI-55 binding to 5-HT transporter sites. Initial experiments identified drugs that displaced [125I]RTI-55 binding with moderately low slope factors. Binding surface analysis of the interaction of 3 beta-(4-chlorophenyl)tropan-2 beta-carboxylic acid phenyl ester hydrochloride (RTI-113) and 3 beta-(4-iodophenyl)tropan-2 beta-carboxylic acid phenyl ester hydrochloride (RTI-122) with [125I]RTI-55 binding sites readily resolved two binding sites for [125I]RTI-55 with Kd values of 0.44 nM and 17 nM and Bmax values of 31 and 245 fmol/mg protein. Potent 5-HT and noradrenergic uptake inhibitors had low affinity for both sites. Whereas cocaine, CFT and WIN35,065-2 were 6.0-, 25- and 14-fold selective for the first site, benztropine, PCP and the novel pyrrole, (+-)-(2RS,3aSR,8bRS)-1,2,3,3a,4,8b-hexahydro- 2-benzyl-1-methylindeno-[1,2-b]pyrrole resorcylate [(+-)-HBMP, formerly called (+-)-RTI-4793-14], were moderately selective for the second site. A single binding site with the characteristics of site 1 was resolved using COS cells transiently expressing the cloned rat dopamine transporter. Lesion studies with 6-hydroxydopamine and 5,7-dihydroxytryptamine were conducted to test the hypothesis that site 1 and site 2 are physically distinct. The data showed that these neurotoxins differentially decreased [125I]RTI-55 binding to sites 1 and 2. The differential distribution of sites 1 and 2 in rat brain provides further support for this hypothesis. Viewed collectively, these data show that [125I]RTI-55 labels a novel binding site in rat brain membranes, termed DATsite2, which is not associated with the classic dopamine, serotonin or norepinephrine transporters. JF - The Journal of pharmacology and experimental therapeutics AU - Rothman, R B AU - Silverthorn, M L AU - Baumann, M H AU - Goodman, C B AU - Cadet, J L AU - Matecka, D AU - Rice, K C AU - Carroll, F I AU - Wang, J B AU - Uhl, G R AD - Clinical Pharmacology Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, USA. Y1 - 1995/07// PY - 1995 DA - July 1995 SP - 385 EP - 395 VL - 274 IS - 1 SN - 0022-3565, 0022-3565 KW - Carrier Proteins KW - 0 KW - Dopamine Plasma Membrane Transport Proteins KW - Iodine Radioisotopes KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Serotonin Plasma Membrane Transport Proteins KW - Slc6a4 protein, rat KW - Tritium KW - 10028-17-8 KW - Serotonin KW - 333DO1RDJY KW - 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane KW - 4H1Z7121WS KW - Cocaine KW - I5Y540LHVR KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Caudate Nucleus KW - Dopamine -- metabolism KW - Radioligand Assay KW - Binding Sites KW - Rats KW - Rats, Sprague-Dawley KW - In Vitro Techniques KW - Nerve Tissue Proteins -- metabolism KW - Serotonin -- metabolism KW - Male KW - Cocaine -- analogs & derivatives KW - Carrier Proteins -- metabolism KW - Brain -- metabolism KW - Cocaine -- metabolism KW - Membrane Glycoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77406779?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Studies+of+the+biogenic+amine+transporters.+VI.+Characterization+of+a+novel+cocaine+binding+site%2C+identified+with+%5B125I%5DRTI-55%2C+in+membranes+prepared+from+whole+rat+brain+minus+caudate.&rft.au=Rothman%2C+R+B%3BSilverthorn%2C+M+L%3BBaumann%2C+M+H%3BGoodman%2C+C+B%3BCadet%2C+J+L%3BMatecka%2C+D%3BRice%2C+K+C%3BCarroll%2C+F+I%3BWang%2C+J+B%3BUhl%2C+G+R&rft.aulast=Rothman&rft.aufirst=R&rft.date=1995-07-01&rft.volume=274&rft.issue=1&rft.spage=385&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-18 N1 - Date created - 1995-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metabolic abnormalities in skeletal muscle of patients receiving zidovudine therapy observed by 31P in vivo magnetic resonance spectroscopy. AN - 77404083; 7615782 AB - Patients on long-term zidovudine (AZT) therapy experience muscle fatigue and weakness attributed to AZT-induced mitochondrial toxicity in skeletal muscle. To determine if the clinico-pathological abnormalities in these patients correspond to abnormal muscle energy metabolism, we used 31P in vivo magnetic resonance spectroscopy to follow phosphorylated metabolites during exercise. We studied 19 normal volunteers, 6 HIV-positive patients never treated with AZT, and 9 HIV-positive patients who had been treated with AZT for a mean period of 33 mo (range 12-48 mo) and had muscle biopsy-proven AZT-myopathy with abnormal mitochondria. Changes in phosphocreatine, ATP, and intracellular pH in the gastrocnemius muscle were followed during a graded steady state exercise protocol, and the recovery of phosphocreatine was followed on cessation of exercise. We found that graded steady state exercise produced a greater depletion of muscle phosphocreatine levels in the AZT-treated patients, compared to either HIV-positive patients who were not treated with AZT or normal controls. No differences in the effects of steady state exercise on muscle phosphocreatine levels were observed between the control group and the HIV-positive patients who had not been treated with AZT. The results suggest that the effect of AZT on muscle energy metabolism is significant, and similar to the effect observed in patients with known mitochondrial myopathies. Using a well-known model for control of mitochondrial metabolism, the observed differences in steady state phosphocreatine levels during exercise suggest that AZT treatment decreases the maximal work output and the maximal rate of muscle ATP synthesis. JF - The Journal of clinical investigation AU - Sinnwell, T M AU - Sivakumar, K AU - Soueidan, S AU - Jay, C AU - Frank, J A AU - McLaughlin, A C AU - Dalakas, M C AD - National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/07// PY - 1995 DA - July 1995 SP - 126 EP - 131 VL - 96 IS - 1 SN - 0021-9738, 0021-9738 KW - Phosphocreatine KW - 020IUV4N33 KW - Zidovudine KW - 4B9XT59T7S KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Hydrogen-Ion Concentration KW - Humans KW - HIV Infections -- drug therapy KW - HIV Infections -- metabolism KW - Adenosine Triphosphate -- analysis KW - Phosphocreatine -- analysis KW - Male KW - Magnetic Resonance Spectroscopy KW - Zidovudine -- adverse effects KW - Muscle, Skeletal -- metabolism KW - Muscle, Skeletal -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77404083?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+investigation&rft.atitle=Metabolic+abnormalities+in+skeletal+muscle+of+patients+receiving+zidovudine+therapy+observed+by+31P+in+vivo+magnetic+resonance+spectroscopy.&rft.au=Sinnwell%2C+T+M%3BSivakumar%2C+K%3BSoueidan%2C+S%3BJay%2C+C%3BFrank%2C+J+A%3BMcLaughlin%2C+A+C%3BDalakas%2C+M+C&rft.aulast=Sinnwell&rft.aufirst=T&rft.date=1995-07-01&rft.volume=96&rft.issue=1&rft.spage=126&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+investigation&rft.issn=00219738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-24 N1 - Date created - 1995-08-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochem Pharmacol. 1989 Apr 1;38(7):1033-6 [2706007] Am J Physiol. 1988 Apr;254(4 Pt 1):C548-53 [3354652] J Clin Invest. 1990 Sep;86(3):751-8 [2394829] Neurology. 1991 Jan;41(1):114-20 [1985275] J Neurol. 1990 Nov;237(7):399-404 [2125637] Lancet. 1991 Mar 2;337(8740):508-10 [1671889] Ann Neurol. 1991 Jun;29(6):606-14 [1892364] Neurology. 1991 Oct;41(10):1603-7 [1922802] Hum Pathol. 1991 Dec;22(12):1281-8 [1748434] Neurology. 1992 Jan;42(1):229-34 [1370862] Neurology. 1992 Mar;42(3 Pt 1):619-23 [1549225] J Clin Invest. 1992 Apr;89(4):1354-60 [1556193] Muscle Nerve. 1992 Mar;15(3):344-8 [1557082] J Appl Physiol (1985). 1993 Aug;75(2):813-9 [8226486] J Physiol. 1993 Jun;465:203-22 [8024651] J Biol Chem. 1973 Oct 25;248(20):7276-8 [4743524] J Biol Chem. 1979 Jul 25;254(14):6538-47 [36399] NMR Biomed. 1993 Sep-Oct;6(5):302-10 [8268062] Ann Neurol. 1994 Apr;35(4):482-7 [8154877] Magn Reson Q. 1994 Mar;10(1):43-63 [8161485] Nat Med. 1995 May;1(5):417-22 [7585087] J Biol Chem. 1955 Nov;217(1):383-93 [13271402] Proc Natl Acad Sci U S A. 1981 Nov;78(11):6714-8 [6947247] Nature. 1982 Feb 18;295(5850):608-9 [6799841] Am J Physiol. 1982 Jan;242(1):C1-11 [7058872] Proc Natl Acad Sci U S A. 1982 Dec;79(24):7714-8 [6218501] Mol Biol Med. 1983 Jul;1(1):77-94 [6679873] Circulation. 1985 Jan;71(1):57-62 [3964722] J Gen Physiol. 1985 Jul;86(1):135-65 [4031824] Ann Neurol. 1985 Aug;18(2):189-96 [4037759] Proc Natl Acad Sci U S A. 1985 Dec;82(24):8384-8 [3866229] Science. 1986 Aug 8;233(4764):640-5 [3726553] Fed Proc. 1986 Dec;45(13):2915-20 [3780995] Neurology. 1987 Feb;37(2):257-62 [3808305] N Engl J Med. 1990 Apr 19;322(16):1098-105 [2320079] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hyperglycosylation of eosinophil ribonucleases in a promyelocytic leukemia cell line and in differentiated peripheral blood progenitor cells. AN - 77402587; 7616105 AB - We evaluated two independent models of eosinophil differentiation for their ability to synthesize the ribonuclease toxins eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP). Cells from the clone 15 subline of HL-60 (human promyelocytic leukemia) produced both EDN and ECP; production of EDN increased in response to butyric acid (BA). CD34+ peripheral blood progenitor cells (PBPCs) grown with cytokines promoting eosinophil differentiation also produced EDN. EDN from both the clone 15 and PBPCs was more heterogeneous and heavily glycosylated (approximately 22-45 kDa) than EDN from the mature peripheral blood eosinophils (18-25 kDa). The heterogeneity of EDN from the clone 15 cells was not altered by endoglycosidase Hf, whereas treatment with peptide-N-glycosidase F (PNGase F) produced a single-band immunoreactive band (approximately 15 kDa). In contrast, only the highest molecular weight forms of EDN from differentiated PBPCs were eliminated by PNTGase F (reduced to 22-35 kDa), suggesting the presence of uncharacteristic forms of posttranslational modification. Synthesis of hyperglycosylated proteins has not been previously reported in PBPCs and is a feature shared with tumor cells and cell lines. JF - Journal of leukocyte biology AU - Tiffany, H L AU - Li, F AU - Rosenberg, H F AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/07// PY - 1995 DA - July 1995 SP - 49 EP - 54 VL - 58 IS - 1 SN - 0741-5400, 0741-5400 KW - Butyrates KW - 0 KW - Neurotoxins KW - Butyric Acid KW - 107-92-6 KW - Eosinophil-Derived Neurotoxin KW - EC 3.1.- KW - Ribonucleases KW - Index Medicus KW - Humans KW - Butyrates -- pharmacology KW - Protein Processing, Post-Translational KW - In Vitro Techniques KW - Leukemia, Myeloid -- enzymology KW - Glycosylation KW - Cell Differentiation -- drug effects KW - Cell Line KW - Neurotoxins -- metabolism KW - Eosinophils -- enzymology KW - Hematopoietic Stem Cells -- enzymology KW - Eosinophils -- cytology KW - Ribonucleases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77402587?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Hyperglycosylation+of+eosinophil+ribonucleases+in+a+promyelocytic+leukemia+cell+line+and+in+differentiated+peripheral+blood+progenitor+cells.&rft.au=Tiffany%2C+H+L%3BLi%2C+F%3BRosenberg%2C+H+F&rft.aulast=Tiffany&rft.aufirst=H&rft.date=1995-07-01&rft.volume=58&rft.issue=1&rft.spage=49&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 - 1995-08-22 N1 - Date created - 1995-08-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of zidovudine and didanosine treatment on heart function in children infected with human immunodeficiency virus. AN - 77399911; 7608800 AB - Human immunodeficiency virus (HIV) infection in children can be complicated by the development of cardiac disease. Decreased left ventricular function has been temporally associated with the use of zidovudine (azidothymidine; AZT) in adults with HIV and has been associated with changes in cardiac muscle mitochondria in animal models. This study was done in an attempt to determine whether the cardiac disease is related to the antiretroviral therapy or to progressive HIV infection. We retrospectively reviewed echocardiograms, clinical records, and laboratory data from 137 HIV-infected children who were being treated by the Pediatric Branch, National Cancer Institute, and who were receiving AZT or didanosine, both drugs, or no antiretroviral therapy. Despite correction of the echocardiographic results for HIV disease severity with markers such as CD4+ lymphocyte count, time since infection, mode of acquisition of HIV, and age, children who were treated with AZT had a lower average fractional shortening than those who were not treated with AZT (p < 0.00001). There was a nonlinear relation between days of AZT use and this There was a nonlinear relation between days of AZT use and this decrease in fractional shortening. The odds that a cardiomyopathy would develop was 8.4 times greater in children who had previously used AZT than in those who had never taken AZT (95% confidence interval, 1.7 to 42.0). Didanosine was not associated with the development of a cardiomyopathy. Treatment of HIV-infected children with AZT may be associated with the development of a cardiomyopathy; didanosine does not appear to increase the risk of cardiomyopathy. The continued use of AZT in a child in whom a cardiomyopathy develops should be carefully assessed, and all children receiving AZT should be followed by serial cardiac examination and echocardiograms. JF - The Journal of pediatrics AU - Domanski, M J AU - Sloas, M M AU - Follmann, D A AU - Scalise, P P AU - Tucker, E E AU - Egan, D AU - Pizzo, P A AD - Cardiology Branch, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA. Y1 - 1995/07// PY - 1995 DA - July 1995 SP - 137 EP - 146 VL - 127 IS - 1 SN - 0022-3476, 0022-3476 KW - Zidovudine KW - 4B9XT59T7S KW - Zalcitabine KW - 6L3XT8CB3I KW - Didanosine KW - K3GDH6OH08 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Severity of Illness Index KW - Medical Records KW - Cardiomyopathies -- etiology KW - Dose-Response Relationship, Drug KW - Cardiomyopathies -- diagnosis KW - Humans KW - Echocardiography KW - Retrospective Studies KW - Infant, Newborn KW - CD4 Lymphocyte Count KW - Child, Preschool KW - Infant KW - Cardiomyopathies -- physiopathology KW - Female KW - Male KW - Zidovudine -- therapeutic use KW - Didanosine -- therapeutic use KW - Zidovudine -- adverse effects KW - Zidovudine -- pharmacology KW - Zalcitabine -- pharmacology KW - Heart -- drug effects KW - Acquired Immunodeficiency Syndrome -- drug therapy KW - Zalcitabine -- therapeutic use KW - HIV KW - Heart -- physiopathology KW - Didanosine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77399911?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pediatrics&rft.atitle=Effect+of+zidovudine+and+didanosine+treatment+on+heart+function+in+children+infected+with+human+immunodeficiency+virus.&rft.au=Domanski%2C+M+J%3BSloas%2C+M+M%3BFollmann%2C+D+A%3BScalise%2C+P+P%3BTucker%2C+E+E%3BEgan%2C+D%3BPizzo%2C+P+A&rft.aulast=Domanski&rft.aufirst=M&rft.date=1995-07-01&rft.volume=127&rft.issue=1&rft.spage=137&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pediatrics&rft.issn=00223476&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-11 N1 - Date created - 1995-08-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Pediatr. 1996 May;128(5 Pt 1):721 [8627455] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased frequency of K-ras mutations in lung neoplasms from female B6C3F1 mice exposed to ozone for 24 or 30 months. AN - 77398382; 7614698 AB - The National Toxicology Program recently completed long-term ozone inhalation studies in B6C3F1 mice and F344/N rats. Mice and rats were exposed to 0, 0.5 or 1.0 p.p.m. ozone by inhalation for 24 or 30 months. There was an increased incidence of lung neoplasms in B6C3F1 mice. However, there was no evidence of carcinogenicity in F344/N rats. The objectives of this study were to (i) evaluate benign and malignant lung neoplasms from B6C3F1 mice for mutations in the K-ras gene at codons 12, 13 and 61, (ii) determine if the frequency and spectra of K-ras mutations were unique for ozone-induced lung neoplasms, (iii) determine if specific K-ras mutations were associated with the size and morphological patterns of lung neoplasms or ozone exposure concentrations and (iv) screen lung neoplasms by immunohistochemical methods for the p53 protein. K-ras mutations were detected by single-strand conformation analysis and identified by direct sequencing of polymerase chain reaction-amplified DNA isolated from formalin-fixed, paraffin-embedded neoplasms. K-ras mutations were detected in 73% of ozone-induced neoplasms, as compared with 33% of lung neoplasms from controls. The predominant mutations consisted of A-->T transversions at codon 61 (8/19) and G-->T transversions at codon 12 (7/19). Specific K-ras mutations in lung neoplasms were not associated with various morphological patterns. Our data suggests that ozone may cause direct and/or indirect DNA damage in the K-ras proto-oncogene of B6C3F1 mice. JF - Carcinogenesis AU - Sills, R C AU - Hong, H L AU - Greenwell, A AU - Herbert, R A AU - Boorman, G A AU - Devereux, T R AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/07// PY - 1995 DA - July 1995 SP - 1623 EP - 1628 VL - 16 IS - 7 SN - 0143-3334, 0143-3334 KW - K-ras KW - p53 KW - Codon KW - 0 KW - Tumor Suppressor Protein p53 KW - Ozone KW - 66H7ZZK23N KW - Index Medicus KW - Sensitivity and Specificity KW - Evaluation Studies as Topic KW - Mice, Inbred Strains KW - Animals KW - Tumor Suppressor Protein p53 -- analysis KW - Genes, p53 -- drug effects KW - Dose-Response Relationship, Drug KW - Mice KW - Time Factors KW - Immunohistochemistry KW - Female KW - Genes, ras -- drug effects KW - Adenocarcinoma, Bronchiolo-Alveolar -- genetics KW - Genes, ras -- genetics KW - Adenocarcinoma, Bronchiolo-Alveolar -- chemically induced KW - Adenocarcinoma, Bronchiolo-Alveolar -- pathology KW - Adenoma -- chemically induced KW - Lung Neoplasms -- genetics KW - Lung Neoplasms -- chemically induced KW - Adenoma -- genetics KW - Adenoma -- pathology KW - Mutation KW - Ozone -- toxicity KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77398382?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Increased+frequency+of+K-ras+mutations+in+lung+neoplasms+from+female+B6C3F1+mice+exposed+to+ozone+for+24+or+30+months.&rft.au=Sills%2C+R+C%3BHong%2C+H+L%3BGreenwell%2C+A%3BHerbert%2C+R+A%3BBoorman%2C+G+A%3BDevereux%2C+T+R&rft.aulast=Sills&rft.aufirst=R&rft.date=1995-07-01&rft.volume=16&rft.issue=7&rft.spage=1623&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-24 N1 - Date created - 1995-08-24 N1 - Date revised - 2017-01-13 N1 - Gene symbol - K-ras; p53 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of a transfected DNA repair gene (XPA) in xeroderma pigmentosum group A cells restores normal DNA repair and mutagenesis of UV-treated plasmids. AN - 77398293; 7614689 AB - The XPA gene was initially cloned based on the ability of its cDNA to improve survival of cells from xeroderma pigmentosum complementation group A (XP-A) patients following irradiation of the cells with UV. We used plasmid host cell reactivation assays to compare UV mutagenesis and the proficiency of DNA repair in a cell line from an XP-A patient, XP2OS(SV40), two derivative cell lines stably expressing XPA cDNAs and in a DNA repair proficient human cell line. Expression of XPA protein in XP2OS cells allowed them to repair UV-treated plasmid pRSVCAT, increasing activity of the damaged CAT marker gene > 100-fold to levels produced by similarly damaged plasmids in normal cells. Expression of the XPA protein in XP2OS cells improved replication of the UV-treated shuttle vector pSP189, increasing plasmid survival and decreasing plasmid mutation frequency to the levels measured in normal cells. The sequence locations of most mutation hotspots in the plasmid marker gene were similar for the three cell lines and the differences did not correlate with the DNA repair status of the cells. This suggests that the location of mutation hotspots is not directly influenced by DNA repair. Expression of the XPA protein did cause a shift in the types of mutations seen in the plasmid gene. In the XP2OS cells > 95% of the plasmid mutations were G:C-->A:T transition mutations. In contrast, XP2OS cells expressing XPA produced other types of mutations: three times as many transversion mutations and a 12-fold increase in mutations at A:T base pairs. Furthermore, the distribution of these types of mutations was similar to the proportions measured in normal cells. Strikingly similar patterns of transition and transversion mutations were found by examination of reports of XP and non-XP skin carcinomas containing mutations in the p53 tumor suppressor gene, suggesting that the repair status of the cells influenced mutagenesis associated with these skin cancers. Our data suggest that loss of XPA gene function may be sufficient to effect the quantitative and qualitative changes in mutagenesis associated with the large increase in skin cancers seen in XP-A patients. JF - Carcinogenesis AU - Levy, D D AU - Saijo, M AU - Tanaka, K AU - Kraemer, K H AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/07// PY - 1995 DA - July 1995 SP - 1557 EP - 1563 VL - 16 IS - 7 SN - 0143-3334, 0143-3334 KW - ERCC2 KW - SupF KW - XPA KW - XPD KW - p53 KW - DNA, Complementary KW - 0 KW - DNA-Binding Proteins KW - Genetic Markers KW - XPA protein, human KW - Xeroderma Pigmentosum Group A Protein KW - Index Medicus KW - Ultraviolet Rays KW - DNA, Complementary -- genetics KW - DNA Damage KW - Humans KW - DNA-Binding Proteins -- genetics KW - Gene Expression KW - Fibroblasts -- physiology KW - Base Sequence KW - Transfection KW - Molecular Sequence Data KW - Cell Survival -- radiation effects KW - Mutation KW - Xeroderma Pigmentosum -- pathology KW - DNA Repair -- genetics KW - Plasmids -- genetics KW - Xeroderma Pigmentosum -- genetics KW - Plasmids -- radiation effects KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77398293?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Expression+of+a+transfected+DNA+repair+gene+%28XPA%29+in+xeroderma+pigmentosum+group+A+cells+restores+normal+DNA+repair+and+mutagenesis+of+UV-treated+plasmids.&rft.au=Levy%2C+D+D%3BSaijo%2C+M%3BTanaka%2C+K%3BKraemer%2C+K+H&rft.aulast=Levy&rft.aufirst=D&rft.date=1995-07-01&rft.volume=16&rft.issue=7&rft.spage=1557&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-24 N1 - Date created - 1995-08-24 N1 - Date revised - 2017-01-13 N1 - Gene symbol - ERCC2; SupF; XPA; XPD; p53 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular characterization of two proximal deletion breakpoint regions in both Prader-Willi and Angelman syndrome patients. AN - 77397981; 7611294 AB - Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct mental retardation syndromes caused by paternal and maternal deficiencies, respectively, in chromosome 15q11-q13. Approximately 70% of these patients have a large deletion of approximately 4 Mb extending from D15S9 (ML34) through D15S12 (IR10). To further characterize the deletion breakpoints proximal to D15S9, three new polymorphic microsatellite markers were developed that showed observed heterozygosities of 60%-87%. D15S541 and D15S542 were isolated from YAC A124A3 containing the D15S18 (IR39) locus. D15S543 was isolated from a cosmid cloned from the proximal right end of YAC 254B5 containing the D15S9 (ML34) locus. Gene-centromere mapping of these markers, using a panel of ovarian teratomas of known meiotic origin, extended the genetic map of chromosome 15 by 2-3 cM toward the centromere. Analysis of the more proximal S541/S542 markers on 53 Prader-Willi and 33 Angelman deletion patients indicated two classes of patients: 44% (35/80) of the informative patients were deleted for these markers (class I), while 56% (45/80) were not deleted (class II), with no difference between PWS and AS. In contrast, D15S543 was deleted in all informative patients (13/48) or showed the presence of a single allele (in 35/48 patients), suggesting that this marker is deleted in the majority of PWS and AS cases. These results confirm the presence of two common proximal deletion breakpoint regions in both Prader-Willi and Angelman syndromes and are consistent with the same deletion mechanism being responsible for paternal and maternal deletions. One breakpoint region lies between D15S541/S542 and D15S543, with an additional breakpoint region being proximal to D15S541/S542. JF - American journal of human genetics AU - Christian, S L AU - Robinson, W P AU - Huang, B AU - Mutirangura, A AU - Line, M R AU - Nakao, M AU - Surti, U AU - Chakravarti, A AU - Ledbetter, D H AD - Diagnostic Development Branch, National Institutes of Health, Bethesda, MD 20892-0940, USA. Y1 - 1995/07// PY - 1995 DA - July 1995 SP - 40 EP - 48 VL - 57 IS - 1 SN - 0002-9297, 0002-9297 KW - DNA, Satellite KW - 0 KW - Genetic Markers KW - Index Medicus KW - Teratoma -- genetics KW - Polymerase Chain Reaction KW - Base Sequence KW - Polymorphism, Genetic KW - Ovarian Neoplasms -- genetics KW - Lod Score KW - Humans KW - Molecular Sequence Data KW - Chromosome Mapping KW - Female KW - DNA, Satellite -- analysis KW - Angelman Syndrome -- genetics KW - Chromosomes, Human, Pair 15 -- genetics KW - Prader-Willi Syndrome -- genetics KW - Sequence Deletion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77397981?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+human+genetics&rft.atitle=Molecular+characterization+of+two+proximal+deletion+breakpoint+regions+in+both+Prader-Willi+and+Angelman+syndrome+patients.&rft.au=Christian%2C+S+L%3BRobinson%2C+W+P%3BHuang%2C+B%3BMutirangura%2C+A%3BLine%2C+M+R%3BNakao%2C+M%3BSurti%2C+U%3BChakravarti%2C+A%3BLedbetter%2C+D+H&rft.aulast=Christian&rft.aufirst=S&rft.date=1995-07-01&rft.volume=57&rft.issue=1&rft.spage=40&rft.isbn=&rft.btitle=&rft.title=American+journal+of+human+genetics&rft.issn=00029297&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-15 N1 - Date created - 1995-08-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Hum Genet. 1995 Feb;95(2):161-70 [7532149] J Med Genet. 1994 Oct;31(10):798-803 [7837257] J Med Genet. 1993 Jun;30(6):529-31 [8326502] Hum Mol Genet. 1993 Jul;2(7):921-4 [8364575] Biotechniques. 1993 Aug;15(2):280-4 [8373596] Genomics. 1993 Dec;18(3):546-52 [8307564] Hum Mol Genet. 1993 Dec;2(12):2019-30 [7906587] Am J Hum Genet. 1994 May;54(5):741-7 [8178815] Hum Mol Genet. 1994 Feb;3(2):223-8 [8004087] Hum Mol Genet. 1994 Feb;3(2):309-15 [8004100] Eur J Hum Genet. 1993;1(1):37-50 [8069650] J Med Genet. 1983 Aug;20(4):290-9 [6620330] Proc Natl Acad Sci U S A. 1986 Jun;83(12):4408-12 [3012567] Am J Med Genet. 1987 Dec;28(4):791-802 [3688017] Prog Clin Biol Res. 1989;311:45-79 [2771999] Nature. 1989 Nov 16;342(6247):281-5 [2812027] Am J Med Genet. 1990 Mar;35(3):319-32 [2309779] Cell. 1990 May 18;61(4):603-10 [2344613] Am J Hum Genet. 1990 Jul;47(1):149-54 [1971993] Am J Hum Genet. 1990 Oct;47(4):635-43 [2220805] Am J Hum Genet. 1990 Oct;47(4):644-55 [1977308] Genomics. 1990 Oct;8(2):263-70 [2249849] Am J Hum Genet. 1991 Jan;48(1):16-21 [1985457] Genomics. 1990 Dec;8(4):614-22 [2276735] Am J Hum Genet. 1991 Mar;48(3):621-7 [1998344] Am J Hum Genet. 1991 Dec;49(6):1219-34 [1684085] Lancet. 1992 Feb 8;339(8789):366-7 [1346439] Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5457-61 [1608955] J Med Genet. 1992 Jun;29(6):412-5 [1619637] Hum Genet. 1993 Jan;90(5):489-95 [8094063] Hum Genet. 1993 Mar;91(2):181-4 [8462978] Hum Mol Genet. 1992 Sep;1(6):417-25 [1363801] Am J Med Genet. 1993 Apr 1;46(1):7-11 [8098583] Hum Mol Genet. 1992 Jul;1(4):221-7 [1303191] Nat Genet. 1992 Dec;2(4):292-300 [1303282] Hum Mol Genet. 1994 Jun;3(6):853-60 [7951227] Genomics. 1994 Jul 1;22(1):189-97 [7959766] Hum Mol Genet. 1994 Aug;3(8):1409-13 [7987324] Nat Genet. 1994 Sep;8(1):52-8 [7987392] Am J Med Genet. 1994 Aug 15;52(2):158-63 [7802001] J Med Genet. 1994 Aug;31(8):585-94 [7815414] Eur J Hum Genet. 1994;2(3):193-203 [7834280] Hum Mol Genet. 1993 Feb;2(2):143-51 [8499903] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytochromes P450 in cynomolgus monkeys mutagenically activate 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) but not 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). AN - 77395627; 7614688 AB - The promutagenic and procarcinogenic heterocyclic amines (HAs) found in cooked meats are N-hydroxylated by microsomal cytochrome P450 enzymes as the first step in their metabolic activation. In cynomolgus monkeys, one of the HAs, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), has been shown to be a potent hepatocarcinogen. However, the structurally similar HA 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) lacks this potency to induce hepatocellular carcinoma in monkeys. Liver microsomes from cynomolgus monkeys show a striking substrate specificity for the metabolic activation of IQ and MeIQx, the former being a far better substrate for N-hydroxylation. Western blot analysis showed that cynomolgus monkey hepatic microsomes constitutively express P450s immunologically related to the human CYP3A, CYP2C, and low levels of CYP1A1. For comparison, Western blot analysis of rat, human and patas monkey microsomes was also carried out. Treatment of cynomolgus monkeys with rifampicin induced hepatic cytochromes P450 related to human CYP3A4 and CYP2C9/10 without inducing CYP1A1 or CYP1A2. Immunoblot analysis also showed that chronic exposure of cynomolgus monkeys to IQ induced hepatic microsomal cytochrome CYP1A1 and CYP1A2, similarly but lesser in magnitude to that observed with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCCD) induction. Using the Ames Salmonella mutagenicity assay, we examined the effect of the inducers on the mutagenic activation (i.e. N-hydroxylation) of IQ and MeIQx by cynomolgus monkey hepatic microsomes. We also examined the mutagenic activation of these HAs by rat, human and patas monkey liver microsomes. Microsomes from cynomolgus monkeys treated with rifampicin showed a 3-fold increase in the mutagenic activation of IQ but showed no increase in the mutagenic activation of MeIQx. Since cytochromes P4503A and/or P4502C are constitutively expressed in cynomolgus monkey hepatic microsomes, and upon induction with rifampicin are associated with an increased metabolic activation of IQ but not MeIQx, it appears that CYP3A and/or CYP2C are the isoform(s) showing the selective substrate specificity in the metabolic activation of IQ over MeIQx. Treatment of monkeys with TCDD significantly increased the mutagenic activation of both IQ and MeIQx, concomitant with an induction of CYP1A isozymes. Thus, it appears that TCDD-inducible CYP1A enzymes N-hydroxylate both substrates without selectivity. Together, these findings suggest that CYP3A and CYP2C are the principal isoforms in the cynomolgus monkey, associated with the metabolic activation implicated in the induction of hepatocarcinogenicity by IQ. Furthermore, the poor metabolic activation of MeIQx by CYP3A and CYP2C, coupled with low constitutive levels of CYP1A isozymes, provide a metabolic explanation for the low hepatocarcinogenic potency of MeIQx in cynomolgus monkeys. JF - Carcinogenesis AU - Sadrieh, N AU - Snyderwine, E G AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1995/07// PY - 1995 DA - July 1995 SP - 1549 EP - 1555 VL - 16 IS - 7 SN - 0143-3334, 0143-3334 KW - Isoenzymes KW - 0 KW - Mutagens KW - Polychlorinated Dibenzodioxins KW - Quinolines KW - Quinoxalines KW - 2-amino-3-methylimidazo(4,5-f)quinoline KW - 30GL3D3T0G KW - 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline KW - 77500-04-0 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Rifampin KW - VJT6J7R4TR KW - Index Medicus KW - Animals KW - Immunoblotting KW - Macaca fascicularis KW - Humans KW - Polychlorinated Dibenzodioxins -- pharmacology KW - Hydroxylation KW - Rats KW - Mutagenicity Tests KW - Biotransformation KW - Microsomes, Liver -- enzymology KW - Microsomes, Liver -- drug effects KW - Enzyme Induction KW - Substrate Specificity KW - Rifampin -- pharmacology KW - Erythrocebus patas KW - Species Specificity KW - Female KW - Male KW - Quinolines -- toxicity KW - Quinolines -- metabolism KW - Quinoxalines -- metabolism KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Cytochrome P-450 Enzyme System -- metabolism KW - Mutagens -- toxicity KW - Mutagens -- pharmacokinetics KW - Isoenzymes -- metabolism KW - Isoenzymes -- biosynthesis KW - Mutagens -- metabolism KW - Quinoxalines -- toxicity KW - Quinoxalines -- pharmacokinetics KW - Quinolines -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77395627?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cytochromes+P450+in+cynomolgus+monkeys+mutagenically+activate+2-amino-3-methylimidazo%5B4%2C5-f%5Dquinoline+%28IQ%29+but+not+2-amino-3%2C8-dimethylimidazo%5B4%2C5-f%5Dquinoxaline+%28MeIQx%29.&rft.au=Sadrieh%2C+N%3BSnyderwine%2C+E+G&rft.aulast=Sadrieh&rft.aufirst=N&rft.date=1995-07-01&rft.volume=16&rft.issue=7&rft.spage=1549&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-24 N1 - Date created - 1995-08-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of the multiple antibiotic resistance (mar) regulon by marORA sequences in Escherichia coli. AN - 77394074; 7608098 AB - The mar operon and adjacent sequences were subcloned on a low-copy-number plasmid to identify essential regulatory elements. A 1.1-kbp fragment containing 133 bp of the operator-promoter region (marO), the full marRA gene sequences, and only 10 of 72 marB codons provided a dela mar strain with normal repressibility and inducibility and the ability to beget mar constitutive mutants. JF - Journal of bacteriology AU - Martin, R G AU - Nyantakyi, P S AU - Rosner, J L AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892-0560, USA. Y1 - 1995/07// PY - 1995 DA - July 1995 SP - 4176 EP - 4178 VL - 177 IS - 14 SN - 0021-9193, 0021-9193 KW - marA KW - marO KW - marR KW - Bacterial Proteins KW - 0 KW - DNA-Binding Proteins KW - Escherichia coli Proteins KW - MarA protein, E coli KW - MarR protein, E coli KW - Repressor Proteins KW - Transcription Factors KW - Index Medicus KW - Operator Regions, Genetic -- genetics KW - Bacterial Proteins -- genetics KW - DNA Mutational Analysis KW - Promoter Regions, Genetic -- genetics KW - Transcription Factors -- genetics KW - Repressor Proteins -- genetics KW - Sequence Deletion KW - Mutagenesis KW - Gene Expression Regulation, Bacterial KW - Drug Resistance, Microbial -- genetics KW - Escherichia coli -- genetics KW - Regulon -- genetics KW - Drug Resistance, Multiple -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77394074?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+bacteriology&rft.atitle=Regulation+of+the+multiple+antibiotic+resistance+%28mar%29+regulon+by+marORA+sequences+in+Escherichia+coli.&rft.au=Martin%2C+R+G%3BNyantakyi%2C+P+S%3BRosner%2C+J+L&rft.aulast=Martin&rft.aufirst=R&rft.date=1995-07-01&rft.volume=177&rft.issue=14&rft.spage=4176&rft.isbn=&rft.btitle=&rft.title=Journal+of+bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-15 N1 - Date created - 1995-08-15 N1 - Date revised - 2017-01-13 N1 - Gene symbol - marA; marO; marR N1 - SuppNotes - Cited By: J Bacteriol. 1983 Aug;155(2):541-8 [6307967] Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5456-60 [7777530] J Bacteriol. 1987 Jul;169(7):3001-6 [2954947] Genetics. 1987 Aug;116(4):513-21 [2957272] J Bacteriol. 1988 Dec;170(12):5416-22 [2848006] J Bacteriol. 1991 Jul;173(14):4433-9 [1648558] J Bacteriol. 1991 Sep;173(17):5532-8 [1715857] J Bacteriol. 1992 Mar;174(5):1537-43 [1537798] J Bacteriol. 1993 Mar;175(5):1484-92 [8383113] J Bacteriol. 1993 May;175(10):2888-94 [8491710] J Bacteriol. 1993 Dec;175(24):7856-62 [7504664] J Bacteriol. 1994 Jan;176(1):143-8 [8282690] J Bacteriol. 1994 Oct;176(20):6262-9 [7928997] J Bacteriol. 1994 Dec;176(24):7754-6 [8002604] J Mol Biol. 1986 Nov 20;192(2):275-85 [3560217] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A comparison of failure modes of glutaraldehyde-treated versus antibiotic-preserved mitral valve allografts implanted in sheep. AN - 77391380; 7609546 AB - Morphologic studies and calcium analyses were made on mitral valve allografts from 12 juvenile sheep surviving 12 to 24 weeks after mitral valve replacement. Before implantation, the allografts were treated with 0.625% glutaraldehyde (group I, n = 4) or with cold antibiotic solution (group II, n = 8). Three group I animals died 12 to 19 weeks after implantation because of dysfunction of calcified valves; the surviving animal also had extensive allograft calcification. One group II animal died of mitral regurgitation; the valves of the other seven (including five with regurgitation shown by Doppler and ventriculographic studies) were explanted at 19 to 24 weeks. Chordal rupture related to calcific deposits was found in all group I valves. Leaflet perforations (n = 4) and ruptured chordae (n = 4), each caused by connective tissue deterioration, were found in group II valves. Inflammatory reaction was absent or minimal in group I valves but moderate or severe in group II valves. Fibrous sheaths were thicker in group II than in group I valves. Calcium levels were much higher in group I than in group II valves. Calcification in group I valves was diffuse and involved collagen, elastic fibers, and connective tissue cells and matrix; in group II valves, it was localized in connective tissue cells. Thus glutaraldehyde-treated allografts failed because of extensive calcification, whereas antibiotic-preserved allografts underwent deterioration of connective tissue and infiltration by inflammatory cells. JF - The Journal of thoracic and cardiovascular surgery AU - Tamura, K AU - Jones, M AU - Yamada, I AU - Ferrans, V J AD - Pathology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md. 20892, USA. Y1 - 1995/07// PY - 1995 DA - July 1995 SP - 224 EP - 238 VL - 110 IS - 1 SN - 0022-5223, 0022-5223 KW - Anti-Bacterial Agents KW - 0 KW - Collagen KW - 9007-34-5 KW - Calcium KW - SY7Q814VUP KW - Glutaral KW - T3C89M417N KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Collagen -- drug effects KW - Prosthesis Failure KW - Calcinosis -- pathology KW - Sheep KW - Calcinosis -- diagnostic imaging KW - Collagen -- ultrastructure KW - Calcinosis -- chemically induced KW - Transplantation, Homologous KW - Chordae Tendineae -- pathology KW - Calcium -- metabolism KW - Endothelium -- ultrastructure KW - Microscopy, Electron KW - Radiography KW - Female KW - Male KW - Bioprosthesis KW - Mitral Valve -- drug effects KW - Glutaral -- pharmacology KW - Tissue Preservation -- methods KW - Graft Rejection -- etiology KW - Mitral Valve -- metabolism KW - Heart Valve Prosthesis KW - Anti-Bacterial Agents -- pharmacology KW - Mitral Valve -- pathology KW - Mitral Valve -- transplantation KW - Postoperative Complications -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77391380?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+thoracic+and+cardiovascular+surgery&rft.atitle=A+comparison+of+failure+modes+of+glutaraldehyde-treated+versus+antibiotic-preserved+mitral+valve+allografts+implanted+in+sheep.&rft.au=Tamura%2C+K%3BJones%2C+M%3BYamada%2C+I%3BFerrans%2C+V+J&rft.aulast=Tamura&rft.aufirst=K&rft.date=1995-07-01&rft.volume=110&rft.issue=1&rft.spage=224&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+thoracic+and+cardiovascular+surgery&rft.issn=00225223&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-11 N1 - Date created - 1995-08-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The epidemiology of nonfatal injuries among US children and youth. AN - 77382302; 7604916 AB - National data are not routinely available regarding the incidence of and associated risk factors for nonfatal injuries in children and youth. The Child Health Supplement to the 1988 National Health Interview Survey provided an opportunity to determine accurate national estimates of childhood injury morbidity by demographic factors, location, external cause, nature of injury, and other factors. The closest adult for 17,110 sampled children was asked whether the child had had an injury, accident, or poisoning during the preceding 12 months and about the cause, location, and consequences of the event. An analysis for potential underreporting from 12 months of recall provided adjustments of annual rates to those for a 1-month recall period. On the basis of 2772 reported injuries, the national estimated annual rate for children 0 to 17 years of age was 27 per 100 children after adjustment to 1-month recall. Boys experienced significantly higher rates than girls (risk ratio [RR] = 1.52, 95% confidence interval [CI] = 1.37, 1.68), and adolescents experienced the highest overall rate (38 per 100 children) and proportion of serious injuries. Approximately one fourth of US children experience a medically attended injury each year, but the risks vary considerably depending on the characteristics of subgroups and the injury cause. JF - American journal of public health AU - Scheidt, P C AU - Harel, Y AU - Trumble, A C AU - Jones, D H AU - Overpeck, M D AU - Bijur, P E AD - National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. Y1 - 1995/07// PY - 1995 DA - July 1995 SP - 932 EP - 938 VL - 85 IS - 7 SN - 0090-0036, 0090-0036 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Child KW - Age Distribution KW - Child, Preschool KW - Socioeconomic Factors KW - Infant KW - Risk Factors KW - Sampling Studies KW - Multiple Trauma -- epidemiology KW - Adolescent KW - United States -- epidemiology KW - Trauma Severity Indices KW - Sex Distribution KW - Female KW - Male KW - Wounds and Injuries -- epidemiology KW - Wounds and Injuries -- classification KW - Wounds and Injuries -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77382302?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+public+health&rft.atitle=The+epidemiology+of+nonfatal+injuries+among+US+children+and+youth.&rft.au=Scheidt%2C+P+C%3BHarel%2C+Y%3BTrumble%2C+A+C%3BJones%2C+D+H%3BOverpeck%2C+M+D%3BBijur%2C+P+E&rft.aulast=Scheidt&rft.aufirst=P&rft.date=1995-07-01&rft.volume=85&rft.issue=7&rft.spage=932&rft.isbn=&rft.btitle=&rft.title=American+journal+of+public+health&rft.issn=00900036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-10 N1 - Date created - 1995-08-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Public Health. 1984 May;74(5):473-8 [6711722] Am J Public Health. 1983 Jul;73(7):746-51 [6859356] Pediatrics. 1985 Mar;75(3):456-62 [3975114] Am J Dis Child. 1988 Jun;142(6):612-7 [3369399] Public Health Rep. 1988 Jul-Aug;103(4):399-405 [3136499] Paediatr Perinat Epidemiol. 1989 Apr;3(2):174-88 [2734235] Am J Dis Child. 1990 Jun;144(6):625-6 [2346145] Am J Dis Child. 1990 Jun;144(6):649-52 [2346146] Pediatrics. 1991 Oct;88(4):783-8 [1896283] Am J Public Health. 1991 Nov;81(11):1408-14 [1951796] JAMA. 1992 Jun 17;267(23):3166-71 [1593737] Pediatrics. 1992 Nov;90(5 Pt 2):798-807 [1437410] Am J Public Health. 1994 Apr;84(4):587-92 [8154561] Am J Public Health. 1994 Apr;84(4):599-605 [8154563] Am J Public Health Nations Health. 1949 Apr;39(4):504-15 [18118990] Am J Public Health. 1984 Dec;74(12):1340-7 [6507685] IMJ Ill Med J. 1973 Dec;144(6):570-3 [4149103] N Z Med J. 1981 May 27;93(684):344-7 [6942297] Am J Public Health. 1982 Apr;72(4):392-3 [7065320] Am J Dis Child. 1982 Jun;136(6):502-6 [7091061] Comment In: Am J Public Health. 1996 Jun;86(6):892-3 [8659678] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of HIV-associated Kaposi's sarcoma with paclitaxel. AN - 77372500; 7603142 AB - We investigated whether paclitaxel was active in AIDS-associated Kaposi's sarcoma. We gave 135 mg/m2 intravenously over 3 hours every 21 days. Follow-up is available on the first 20 patients, most of whom had advanced Kaposi's sarcoma and severe immunocompromise. Neutropenia was the most frequent dose-limiting toxic effect; novel toxic effects included late fevers, rash, and eosinophilia. Creatinine increased in 2 patients and 1 patient had cardiomyopathy. There were 13 partial responses (65%, 95% CI 41-85%). All 5 patients with pulmonary involvement responded. Paclitaxel appears to be active against Kaposi's sarcoma as a single agent. Further studies, including a randomised trial, are warranted. JF - Lancet (London, England) AU - Saville, M W AU - Lietzau, J AU - Pluda, J M AU - Feuerstein, I AU - Odom, J AU - Wilson, W H AU - Humphrey, R W AU - Feigal, E AU - Steinberg, S M AU - Broder, S AD - National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/07/01/ PY - 1995 DA - 1995 Jul 01 SP - 26 EP - 28 VL - 346 IS - 8966 SN - 0140-6736, 0140-6736 KW - Dexamethasone KW - 7S5I7G3JQL KW - Cimetidine KW - 80061L1WGD KW - Diphenhydramine KW - 8GTS82S83M KW - Paclitaxel KW - P88XT4IS4D KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Drug Therapy, Combination KW - Acquired Immunodeficiency Syndrome -- complications KW - Diphenhydramine -- administration & dosage KW - Humans KW - Adult KW - Dexamethasone -- administration & dosage KW - Cimetidine -- administration & dosage KW - Middle Aged KW - Male KW - Paclitaxel -- administration & dosage KW - Sarcoma, Kaposi -- drug therapy KW - Paclitaxel -- adverse effects KW - HIV Infections -- complications KW - Lung Neoplasms -- drug therapy KW - HIV-1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77372500?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lancet+%28London%2C+England%29&rft.atitle=Treatment+of+HIV-associated+Kaposi%27s+sarcoma+with+paclitaxel.&rft.au=Saville%2C+M+W%3BLietzau%2C+J%3BPluda%2C+J+M%3BFeuerstein%2C+I%3BOdom%2C+J%3BWilson%2C+W+H%3BHumphrey%2C+R+W%3BFeigal%2C+E%3BSteinberg%2C+S+M%3BBroder%2C+S&rft.aulast=Saville&rft.aufirst=M&rft.date=1995-07-01&rft.volume=346&rft.issue=8966&rft.spage=26&rft.isbn=&rft.btitle=&rft.title=Lancet+%28London%2C+England%29&rft.issn=01406736&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-04 N1 - Date created - 1995-08-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of proinflammatory cytokines in acetaminophen hepatotoxicity. AN - 77367760; 7597709 AB - Acetaminophen (APAP) intoxication has been shown to activate Kupffer cells. Kupffer cell activation is also associated with the release of proinflammatory cytokines which can induce a variety of pathophysiological responses. These studies examined whether proinflammatory cytokines are produced in response to a hepatotoxic dose of APAP, and if so, the role they play in the observed pathological response. Female B6C3F1 mice received 500 mg APAP/kg in the presence and absence of antibodies against tumor necrosis factor-alpha (TNF-alpha), interleukin-1-alpha (IL-1 alpha), and IL-1 receptor antagonist (IL-1ra). Serum TNF-alpha, IL-1 alpha, and liver-associated enzyme levels were measured. In addition, the levels of mRNA transcripts for IL-1 alpha, IL-6, and TNF-alpha from livers of treated mice were examined by reverse transcription-polymerase chain reaction (RT-PCR). Administration of APAP resulted in an immediate reduction in body temperature as well as elevated serum levels of IL-1 alpha and TNF-alpha that reached a peak at 12 and 16 hr, respectively. The reduction in body temperature was partially blocked by injection of antibodies against TNF-alpha or IL-1 alpha. Furthermore, neutralization of TNF-alpha delayed the increase in serum IL-1 alpha and liver enzyme levels. In contrast, pretreatment with IL-1ra antisera exacerbated the effect of APAP on body temperature and increased the release of liver enzymes. These data suggest that TNF-alpha and IL-1 alpha are released in response to APAP intoxication and are responsible for certain pathological manifestations of APAP-induced hepatotoxicity. JF - Toxicology and applied pharmacology AU - Blazka, M E AU - Wilmer, J L AU - Holladay, S D AU - Wilson, R E AU - Luster, M I AD - Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/07// PY - 1995 DA - July 1995 SP - 43 EP - 52 VL - 133 IS - 1 SN - 0041-008X, 0041-008X KW - Cytokines KW - 0 KW - Il1rn protein, mouse KW - Interleukin 1 Receptor Antagonist Protein KW - Interleukin-1 KW - Sialoglycoproteins KW - Tumor Necrosis Factor-alpha KW - Acetaminophen KW - 362O9ITL9D KW - Index Medicus KW - Interleukin-1 -- physiology KW - Gene Expression -- drug effects KW - Animals KW - Base Sequence KW - Sialoglycoproteins -- pharmacology KW - Molecular Sequence Data KW - Mice, Inbred C57BL KW - Mice, Inbred C3H KW - Tumor Necrosis Factor-alpha -- physiology KW - Mice KW - Female KW - Cytokines -- genetics KW - Liver -- drug effects KW - Cytokines -- physiology KW - Acetaminophen -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77367760?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Role+of+proinflammatory+cytokines+in+acetaminophen+hepatotoxicity.&rft.au=Blazka%2C+M+E%3BWilmer%2C+J+L%3BHolladay%2C+S+D%3BWilson%2C+R+E%3BLuster%2C+M+I&rft.aulast=Blazka&rft.aufirst=M&rft.date=1995-07-01&rft.volume=133&rft.issue=1&rft.spage=43&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 - 1995-08-03 N1 - Date created - 1995-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mouse skin tumor progression results in differential expression of retinoic acid and retinoid X receptors. AN - 77359978; 7540949 AB - Retinoids are powerful regulators of epidermal cell growth and differentiation and are widely used in the prevention and treatment of skin disorders and cancers in humans. Since many of the effects of retinoids on cell growth and differentiation are mediated by nuclear retinoid receptors (RARs and RXRs), we were interested in determining RAR and RXR gene expression during mouse skin tumor progression. The two-stage system of mouse skin carcinogenesis was used to generate papillomas and carcinomas, and the different stages of malignant progression (papillomas, differentiated squamous cell carcinomas, undifferentiated squamous cell carcinomas, and spindle cell carcinomas) were characterized in each tumor by specific keratin expression prior to receptor characterization. Using in situ hybridization analysis, we show that the two major RAR isoforms (alpha 1 and gamma 1), which account for most of RARs in the skin, were expressed in both the basal and suprabasal layers in mouse epidermis. In contrast, RXR alpha transcripts were compartmentalized to the basal cell layers and concentrated in hair follicles. During skin tumor progression, RAR (alpha 1 and gamma 1) transcripts were down-modulated in malignant tumor cells, whereas RXR (alpha and beta) transcript expression was expanded in papillomas and carcinomas as the number of undifferentiated cells also increased. RXR gamma was not detected in the skin or at any stage during skin tumor progression. Spindle cell tumors lacked markers of the keratinocyte phenotype and lost RAR expression, yet retained expression of RXR alpha and beta. The increased abundance of transcripts for RXRs and decreased presence of RARs in skin tumor progression may favor other nuclear signal transduction pathways requiring RXR for heterodimer formation and contribute to phenotypic progression of cancer cells. JF - Cancer research AU - Darwiche, N AU - Celli, G AU - Tennenbaum, T AU - Glick, A B AU - Yuspa, S H AU - De Luca, L M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1995/07/01/ PY - 1995 DA - 1995 Jul 01 SP - 2774 EP - 2782 VL - 55 IS - 13 SN - 0008-5472, 0008-5472 KW - Receptors, Retinoic Acid KW - 0 KW - Retinoid X Receptors KW - Transcription Factors KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Keratins KW - 68238-35-7 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Keratins -- genetics KW - Animals KW - In Situ Hybridization KW - Cell Compartmentation KW - Epidermis -- metabolism KW - Mice KW - Receptors, Retinoic Acid -- metabolism KW - Transcription Factors -- metabolism KW - Carcinoma -- metabolism KW - Skin Neoplasms -- metabolism KW - Papilloma -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77359978?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mouse+skin+tumor+progression+results+in+differential+expression+of+retinoic+acid+and+retinoid+X+receptors.&rft.au=Darwiche%2C+N%3BCelli%2C+G%3BTennenbaum%2C+T%3BGlick%2C+A+B%3BYuspa%2C+S+H%3BDe+Luca%2C+L+M&rft.aulast=Darwiche&rft.aufirst=N&rft.date=1995-07-01&rft.volume=55&rft.issue=13&rft.spage=2774&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 - 1995-08-01 N1 - Date created - 1995-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Seroprevalence of human T cell lymphotropic virus type II infection, with or without human immunodeficiency virus type 1 coinfection, among US intravenous drug users. AN - 77357487; 7797946 AB - Seroprevalence of human T lymphotropic virus (HTLV) and human immunodeficiency virus type 1 (HIV-1) was determined among 7841 intravenous drug users (IVDUs) from drug treatment centers in Baltimore, Chicago, Los Angeles, New Jersey (Asbury Park and Trenton), New York City (Brooklyn and Harlem), Philadelphia, and San Antonio, Texas; 20.9% had evidence of HTLV infection, as determined using a p21e EIA for screening and p21e blot for confirmation. With a type-specific EIA and blot used in combination, HTLV-II was identified in 97.6% of HTLV-positive IVDUs whose sera could be subtyped. HIV-1 seroprevalence was 13.2%. HTLV-II without HIV-1 was most common in Los Angeles and San Antonio. HIV-1 without HTLV-II was most common in New York, New Jersey, and Baltimore. Dual infection was most common in New York and New Jersey. Logistic regression analysis revealed that seroprevalence of HTLV-II was significantly greater with HIV-1 infection and increasing age and among women, blacks, and Mexican-Americans. In conclusion, it appears that among US IVDUs, nearly all HTLV infection is attributable to HTLV-II, and HTLV-II infection is associated with HIV-1 and sociodemographic background. JF - The Journal of infectious diseases AU - Briggs, N C AU - Battjes, R J AU - Cantor, K P AU - Blattner, W A AU - Yellin, F M AU - Wilson, S AU - Ritz, A L AU - Weiss, S H AU - Goedert, J J AD - National Cancer Institute, National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1995/07// PY - 1995 DA - July 1995 SP - 51 EP - 58 VL - 172 IS - 1 SN - 0022-1899, 0022-1899 KW - HIV Antibodies KW - 0 KW - HTLV-II Antibodies KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Age Factors KW - Sex Factors KW - Humans KW - Continental Population Groups KW - African Americans KW - HIV-1 KW - Demography KW - HIV Antibodies -- blood KW - HIV Seroprevalence KW - Ethnic Groups KW - Adult KW - HTLV-II Antibodies -- blood KW - Mexican Americans KW - Adolescent KW - Urban Population KW - United States -- epidemiology KW - Male KW - Female KW - Acquired Immunodeficiency Syndrome -- complications KW - Acquired Immunodeficiency Syndrome -- epidemiology KW - HIV Infections -- complications KW - HTLV-II Infections -- epidemiology KW - HTLV-II Infections -- complications KW - HIV Infections -- epidemiology KW - Substance Abuse, Intravenous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77357487?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+infectious+diseases&rft.atitle=Seroprevalence+of+human+T+cell+lymphotropic+virus+type+II+infection%2C+with+or+without+human+immunodeficiency+virus+type+1+coinfection%2C+among+US+intravenous+drug+users.&rft.au=Briggs%2C+N+C%3BBattjes%2C+R+J%3BCantor%2C+K+P%3BBlattner%2C+W+A%3BYellin%2C+F+M%3BWilson%2C+S%3BRitz%2C+A+L%3BWeiss%2C+S+H%3BGoedert%2C+J+J&rft.aulast=Briggs&rft.aufirst=N&rft.date=1995-07-01&rft.volume=172&rft.issue=1&rft.spage=51&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+infectious+diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-01 N1 - Date created - 1995-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The CCK-B antagonist CI-988 increases dopamine levels in microdialysate from the rat nucleus accumbens via a tetrodotoxin- and calcium-independent mechanism. AN - 77353270; 7790862 AB - CI-988, a water-soluble, selective cholecystokinin-B antagonist, was perfused through a microdialysis probe into the anterior nucleus accumbens, posterior nucleus accumbens, or caudate nucleus of anesthetized rats. High concentrations of CI-988 produced three- to fivefold increases in dopamine overflow, at all three sites, that were temporally correlated with the CI-988 perfusion and returned to baseline levels upon cessation of CI-988 perfusion. However, the cholecystokinin-A antagonist CAM-1481, and the relatively inactive enantiomer of CI-988, CAM-1241, also increased dopamine overflow in the nucleus accumbens. Furthermore, the ability of CI-988 to increase dopamine overflow persisted in the absence of calcium in the perfusate and was not sensitive to tetrodotoxin treatment. The mechanism by which locally administered CI-988 increases dopamine overflow appears not to be anatomically specific, not selective for one cholecystokinin receptor subtype, and may be nonvesicular. JF - Journal of neurochemistry AU - Corwin, R L AU - Jörn, A AU - Hardy, M AU - Crawley, J N AD - Section on Behavioral Neuropharmacology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1380, USA. Y1 - 1995/07// PY - 1995 DA - July 1995 SP - 208 EP - 217 VL - 65 IS - 1 SN - 0022-3042, 0022-3042 KW - Dopamine Antagonists KW - 0 KW - Indoles KW - PD 134308 KW - 130404-91-0 KW - Tetrodotoxin KW - 4368-28-9 KW - Meglumine KW - 6HG8UB2MUY KW - Cholecystokinin KW - 9011-97-6 KW - Calcium KW - SY7Q814VUP KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Microdialysis KW - Animals KW - Rats, Sprague-Dawley KW - Male KW - Dopamine Antagonists -- pharmacology KW - Meglumine -- analogs & derivatives KW - Cholecystokinin -- antagonists & inhibitors KW - Nucleus Accumbens -- metabolism KW - Dopamine -- metabolism KW - Indoles -- pharmacology KW - Calcium -- pharmacology KW - Tetrodotoxin -- pharmacology KW - Meglumine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77353270?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=The+CCK-B+antagonist+CI-988+increases+dopamine+levels+in+microdialysate+from+the+rat+nucleus+accumbens+via+a+tetrodotoxin-+and+calcium-independent+mechanism.&rft.au=Corwin%2C+R+L%3BJ%C3%B6rn%2C+A%3BHardy%2C+M%3BCrawley%2C+J+N&rft.aulast=Corwin&rft.aufirst=R&rft.date=1995-07-01&rft.volume=65&rft.issue=1&rft.spage=208&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 - 1995-07-26 N1 - Date created - 1995-07-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interleukin 6 is essential for in vivo development of B lineage neoplasms. AN - 77351918; 7790819 AB - Interleukin (IL) 6 has been suggested to be the major cytokine responsible for proliferation of neoplastic plasma cells in both human myeloma and mouse plasmacytoma. Much of the evidence supporting this suggestion is derived from in vitro studies in which the survival or proliferation of some plasma cell tumors has been found to be IL-6 dependent. However, it remains unclear whether this dependency is the consequence of in vivo or in vitro selective pressures that preferentially expand IL-6-responsive tumor cells, or whether it reflects a critical in vivo role for IL-6 in plasma cell neoplasia. To address this question, we have attempted to induce plasma cell tumors in normal mice and in IL-6-deficient mice generated by introduction of a germline-encoded null mutation in the IL-6 gene. The results demonstrate that mice homozygous (+/+) or heterozygous (+/-) for the wild-type IL-6 allele yield the expected incidences of plasma cell tumors. In contrast, mice homozygous for the IL-6-null allele (-/-) are completely resistant to plasma cell tumor development. These studies define the essential role of IL-6 in the development of B lineage tumors in vivo and provide experimental support for continued efforts to modulate this cytokine in the treatment of appropriate human B cell malignancies. JF - The Journal of experimental medicine AU - Hilbert, D M AU - Kopf, M AU - Mock, B A AU - Köhler, G AU - Rudikoff, S AD - Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/07/01/ PY - 1995 DA - 1995 Jul 01 SP - 243 EP - 248 VL - 182 IS - 1 SN - 0022-1007, 0022-1007 KW - myc KW - raf KW - Interleukin-6 KW - 0 KW - Terpenes KW - pristane KW - 26HZV48DT1 KW - Index Medicus KW - Animals KW - Tumor Virus Infections -- virology KW - Lymphoma, B-Cell -- etiology KW - Lymphoma, T-Cell -- physiopathology KW - Mice, Inbred BALB C KW - Mice, Knockout KW - Gammaretrovirus -- genetics KW - Alleles KW - In Situ Hybridization KW - Oncogenes KW - Lymphoma, T-Cell -- etiology KW - Gammaretrovirus -- physiology KW - Molecular Sequence Data KW - Flow Cytometry KW - Genetic Predisposition to Disease KW - Male KW - Cell Division KW - Terpenes -- toxicity KW - Cocarcinogenesis KW - Mice KW - Neoplasm Transplantation KW - Genotype KW - Polymerase Chain Reaction KW - Mice, Inbred Strains KW - Base Sequence KW - Lymphoma, B-Cell -- physiopathology KW - Mice, Inbred C57BL KW - Crosses, Genetic KW - Female KW - Plasmacytoma -- etiology KW - Multiple Myeloma -- etiology KW - Interleukin-6 -- physiology KW - Interleukin-6 -- genetics KW - Plasmacytoma -- physiopathology KW - Interleukin-6 -- deficiency KW - B-Lymphocytes -- physiology KW - Multiple Myeloma -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77351918?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+experimental+medicine&rft.atitle=Interleukin+6+is+essential+for+in+vivo+development+of+B+lineage+neoplasms.&rft.au=Hilbert%2C+D+M%3BKopf%2C+M%3BMock%2C+B+A%3BK%C3%B6hler%2C+G%3BRudikoff%2C+S&rft.aulast=Hilbert&rft.aufirst=D&rft.date=1995-07-01&rft.volume=182&rft.issue=1&rft.spage=243&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+experimental+medicine&rft.issn=00221007&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-25 N1 - Date created - 1995-07-25 N1 - Date revised - 2017-01-13 N1 - Gene symbol - myc; raf N1 - SuppNotes - Cited By: Blood. 1991 Oct 15;78(8):1996-2004 [1912582] Blood. 1991 Sep 1;78(5):1198-204 [1715218] J Immunol. 1991 Dec 1;147(11):3679-89 [1682380] Immunol Rev. 1992 Jun;127:25-50 [1380488] Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):2060-4 [8446628] Oncogene. 1993 Jul;8(7):1993-2000 [7685514] Cell. 1994 Jan 28;76(2):253-62 [8293462] Nature. 1994 Mar 24;368(6469):339-42 [8127368] Blood. 1994 Apr 1;83(7):1903-8 [8142657] J Exp Med. 1994 Apr 1;179(4):1337-42 [8145045] J Exp Med. 1994 Apr 1;179(4):1343-7 [8145046] Science. 1994 Apr 22;264(5158):561-3 [8160012] Blood. 1994 Jun 15;83(12):3654-63 [8204890] Blood. 1994 Oct 1;84(7):2269-77 [7919345] Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):649-53 [7846031] J Exp Med. 1979 Sep 19;150(3):580-96 [90108] Proc Natl Acad Sci U S A. 1985 Aug;82(16):5490-4 [2410927] Science. 1986 Aug 1;233(4763):566-9 [3726549] J Exp Med. 1987 Mar 1;165(3):641-9 [3493321] Proc Natl Acad Sci U S A. 1987 Dec;84(24):9035-9 [3501121] Nature. 1988 Mar 3;332(6159):83-5 [3258060] J Exp Med. 1989 Jan 1;169(1):339-44 [2783335] Blood. 1989 Feb;73(2):517-26 [2783861] J Exp Med. 1989 Jun 1;169(6):2133-48 [2786548] J Exp Med. 1989 Aug 1;170(2):613-8 [2787832] J Immunol. 1989 Oct 15;143(8):2514-9 [2571638] J Immunol. 1989 Oct 15;143(8):2520-4 [2794507] J Clin Invest. 1989 Dec;84(6):2008-11 [2592570] J Immunol. 1989 Dec 15;143(12):4019-24 [2480384] Proc Natl Acad Sci U S A. 1989 Dec;86(24):9941-5 [2690079] Oncogene. 1990 Apr;5(4):577-82 [2183159] Annu Rev Immunol. 1990;8:253-78 [2188664] J Exp Med. 1990 Sep 1;172(3):997-1000 [2388041] Immunol Today. 1990 Dec;11(12):443-9 [2127356] Eur J Immunol. 1991 Apr;21(4):1069-72 [1902175] Ann Hematol. 1991 Feb-Mar;62(2-3):54-8 [2031968] Int Immunol. 1991 Sep;3(9):907-16 [1834163] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alterations in the molecular response to DNA damage during cellular aging of cultured fibroblasts: reduced AP-1 activation and collagenase gene expression. AN - 77349978; 7790398 AB - Transcriptional activation of c-fos in response to both serum stimulation and DNA damage requires the serum response element. The inability of in vitro aged or senescent fibroblasts to proliferate in response to serum has been shown to be associated with repressed c-fos expression and reduced AP-1 binding activity. In contrast, we have observed similar levels of c-fos mRNA and protein expression in young (early passage) and old (late passage) cells following their treatment with ultraviolet (UV) irradiation or methyl methanesulfonate (MMS). Thus, the early events in the signal transduction pathway leading to transcriptional activation of c-fos following DNA damage are distinct from those mediating the gene's expression in response to mitogenic stimulation. Despite normal levels of c-fos expression, we observed a reduced level of AP-1 binding activity in old cells relative to young cells treated with UV irradiation or MMS. Reduced AP-1 binding activity is associated with reduced expression of the AP-1-dependent gene, collagenase, in old cells treated with DNA damaging agents. Since other DNA damage-inducible genes also contain an AP-1 regulatory element presumed to play a role in their expression, reduced AP-1 binding activity is likely to have a major impact on the old cell's ability to respond appropriately to DNA damage. JF - Journal of cellular physiology AU - Choi, A M AU - Pignolo, R J AU - apRhys, C M AU - Cristofalo, V J AU - Holbrook, N J AD - Gene Expression and Aging Section, National Institute on Aging, Baltimore, Maryland 21224, USA. Y1 - 1995/07// PY - 1995 DA - July 1995 SP - 65 EP - 73 VL - 164 IS - 1 SN - 0021-9541, 0021-9541 KW - Oligonucleotide Probes KW - 0 KW - Transcription Factor AP-1 KW - Methyl Methanesulfonate KW - AT5C31J09G KW - Collagenases KW - EC 3.4.24.- KW - Index Medicus KW - Ultraviolet Rays KW - Base Sequence KW - Oligonucleotide Probes -- genetics KW - Cells, Cultured KW - Cell Aging KW - Humans KW - Molecular Sequence Data KW - Genes, fos KW - Methyl Methanesulfonate -- pharmacology KW - Genes, jun KW - Gene Expression -- drug effects KW - Collagenases -- genetics KW - Fibroblasts -- drug effects KW - DNA Damage KW - Fibroblasts -- radiation effects KW - Transcription Factor AP-1 -- physiology KW - Gene Expression -- radiation effects KW - Fibroblasts -- physiology KW - Collagenases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77349978?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+physiology&rft.atitle=Alterations+in+the+molecular+response+to+DNA+damage+during+cellular+aging+of+cultured+fibroblasts%3A+reduced+AP-1+activation+and+collagenase+gene+expression.&rft.au=Choi%2C+A+M%3BPignolo%2C+R+J%3BapRhys%2C+C+M%3BCristofalo%2C+V+J%3BHolbrook%2C+N+J&rft.aulast=Choi&rft.aufirst=A&rft.date=1995-07-01&rft.volume=164&rft.issue=1&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+physiology&rft.issn=00219541&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-26 N1 - Date created - 1995-07-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Resiniferatoxin-amide and analogues as ligands for protein kinase C and vanilloid receptors and determination of their biological activities as vanilloids. AN - 77349909; 7790875 AB - The naturally occurring diterpene resiniferatoxin (RTX) is an ultrapotent analogue of capsaicin. Acting on polymodal afferent neurons, RTX induces a generally similar pattern of responses as does capsaicin. However, the two compounds, as well as other vanilloid derivatives, display different relative potencies for different responses. In the present study, we examined the vanilloid-like activities of two new derivatives, the amide analogue of RTX and phorbol 12,13-dibenzoate 20-homovanillylamide. Structurally, RTX-amide resembles capsaicin more closely than does RTX, and after cleavage of the amide bond the resulting amine would be predicted to not bind to protein kinase C in contrast to resiniferonol 9,13,14-orthophenylacetate, the parent diterpene of RTX. In contrast to our expectations the binding potency of the RTX-amide for the vanilloid receptor present in rat spinal cord was 450-fold lower than that of RTX (Ki values for the RTX-amide and RTX were 10.4 +/- 0.7 nM and 23.1 +/- 3.2 pM, respectively). In the case of phorbol 12,13-dibenzoate 20-homovanillylamide, there was a further loss of affinity for the vanilloid receptor compared with RTX; nonetheless, the Ki (8.56 +/- 0.61 microM) was comparable with that of capsaicin (5.31 +/- 0.37 microM). Computer fitting of the binding data yielded Hill coefficient values of 2.25 +/- 0.03, 2.33 +/- 0.03, and 1.84 +/- 0.05 for RTX, RTX-amide, and phorbol 12,13-dibenzoate 20-homovanillylamide, respectively, indicating that both new compounds induced apparent positive cooperativity among vanilloid binding sites.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Journal of neurochemistry AU - Acs, G AU - Lee, J AU - Marquez, V E AU - Wang, S AU - Milne, G W AU - Du, L AU - Lewin, N E AU - Blumberg, P M AD - Molecular Mechanisms of Tumor Promotion Section, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1995/07// PY - 1995 DA - July 1995 SP - 301 EP - 318 VL - 65 IS - 1 SN - 0022-3042, 0022-3042 KW - Ligands KW - 0 KW - Receptors, Drug KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Capsaicin KW - S07O44R1ZM KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Spinal Cord -- metabolism KW - Phorbol 12,13-Dibutyrate -- metabolism KW - Binding, Competitive KW - Female KW - Protein Kinase C -- metabolism KW - Receptors, Drug -- metabolism KW - Capsaicin -- analogs & derivatives KW - Capsaicin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77349909?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Resiniferatoxin-amide+and+analogues+as+ligands+for+protein+kinase+C+and+vanilloid+receptors+and+determination+of+their+biological+activities+as+vanilloids.&rft.au=Acs%2C+G%3BLee%2C+J%3BMarquez%2C+V+E%3BWang%2C+S%3BMilne%2C+G+W%3BDu%2C+L%3BLewin%2C+N+E%3BBlumberg%2C+P+M&rft.aulast=Acs&rft.aufirst=G&rft.date=1995-07-01&rft.volume=65&rft.issue=1&rft.spage=301&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 - 1995-07-26 N1 - Date created - 1995-07-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A UV-responsive G2 checkpoint in rodent cells. AN - 77349299; 7791779 AB - We have studied the effect of UV irradiation on the cell cycle progression of synchronized Chinese hamster ovary cells. Synchronization of cells in S or G2 phase was accomplished by the development of a novel protocol using mimosine, which blocks cell cycle progression at the G1/S boundary. After removal of mimosine, cells proceed synchronously through the S and G2 phases, allowing manipulation of cells at specific points in either phase. Synchronization of cells in G1 was achieved by release of cells after a period of serum starvation. Cells synchronized by these methods were UV irradiated at defined points in G1, S, and G2, and their subsequent progression through the cell cycle was monitored. UV irradiation of G1-synchronized cells caused a dose-dependent delay in entry into S phase. Irradiation of S-phase-synchronized cells inhibited progression through S phase and then resulted in accumulation of cells for a prolonged interval in G2. Apoptosis of a subpopulation of cells during this extended period was noted. UV irradiation of G2-synchronized cells caused a shorter G2 arrest. The arrest itself and its duration were dependent upon the timing (within G2 phase) of the irradiation and the UV dose, respectively. We have thus defined a previously undescribed (in mammalian cells) UV-responsive checkpoint in G2 phase. The implications of these findings with respect to DNA metabolism are discussed. JF - Molecular and cellular biology AU - Orren, D K AU - Petersen, L N AU - Bohr, V A AD - Laboratory of Molecular Genetics, National Institute on Aging, Baltimore, Maryland 21224, USA. Y1 - 1995/07// PY - 1995 DA - July 1995 SP - 3722 EP - 3730 VL - 15 IS - 7 SN - 0270-7306, 0270-7306 KW - Pyrimidine Dimers KW - 0 KW - Mimosine KW - 500-44-7 KW - Index Medicus KW - S Phase -- radiation effects KW - DNA Repair -- physiology KW - Animals KW - S Phase -- drug effects KW - DNA Damage -- physiology KW - Pyrimidine Dimers -- metabolism KW - Apoptosis -- radiation effects KW - Mimosine -- pharmacology KW - CHO Cells KW - G1 Phase -- drug effects KW - Dose-Response Relationship, Radiation KW - G1 Phase -- radiation effects KW - Cricetinae KW - G2 Phase -- physiology KW - Ultraviolet Rays KW - G2 Phase -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77349299?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+UV-responsive+G2+checkpoint+in+rodent+cells.&rft.au=Orren%2C+D+K%3BPetersen%2C+L+N%3BBohr%2C+V+A&rft.aulast=Orren&rft.aufirst=D&rft.date=1995-07-01&rft.volume=15&rft.issue=7&rft.spage=3722&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 - 1995-07-27 N1 - Date created - 1995-07-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Mol Biol. 1972 May 28;66(3):319-37 [5037019] Nature. 1975 Mar 20;254(5497):245-7 [46594] Nature. 1980 Apr 10;284(5756):555-6 [6245367] Proc Natl Acad Sci U S A. 1980 Dec;77(12):7315-7 [6938978] Radiat Environ Biophys. 1980;18(4):257-66 [7220791] Proc Natl Acad Sci U S A. 1981 Jan;78(1):110-4 [6165985] Biophys J. 1979 Sep;27(3):359-70 [95567] J Mol Biol. 1981 Jun 25;149(2):171-87 [7310880] Cancer Res. 1982 Apr;42(4):1473-8 [6174225] Mol Cell Biol. 1981 Dec;1(12):1069-76 [7346712] Mol Cell Biol. 1984 Sep;4(9):1689-94 [6092932] Cell. 1985 Feb;40(2):359-69 [3838150] Mutat Res. 1985 Jan-Mar;145(1-2):63-9 [3974604] Biochim Biophys Acta. 1985 Nov 13;826(2-3):121-8 [4052429] Mol Cell Biol. 1986 Oct;6(10):3443-50 [3025594] Mol Cell Biol. 1990 Sep;10(9):4678-84 [2201899] Mol Cell Biol. 1990 Dec;10(12):6554-64 [2247073] J Biol Chem. 1990 Dec 5;265(34):21330-6 [2250027] Anal Biochem. 1990 Nov 15;191(1):41-6 [2077941] Cell. 1991 Oct 18;67(2):293-302 [1655277] Cancer Res. 1991 Dec 1;51(23 Pt 1):6304-11 [1933891] EMBO J. 1992 Apr;11(4):1335-42 [1563349] EMBO J. 1992 Apr;11(4):1343-50 [1563350] Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4952-6 [1594599] Mutat Res. 1992 Aug;274(2):93-101 [1378211] Biochemistry. 1992 Jul 28;31(29):6794-800 [1637815] Mol Cell Biol. 1992 Oct;12(10):4375-83 [1406627] Cell. 1992 Nov 13;71(4):543-6 [1423612] Cell. 1992 Nov 13;71(4):587-97 [1423616] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10696-700 [1438266] Cell. 1992 Dec 24;71(7):1081-91 [1473146] J Biol Chem. 1993 Jan 25;268(3):1650-7 [8420940] Nature. 1993 Apr 29;362(6423):847-9 [8479522] Nature. 1993 Apr 29;362(6423):849-52 [8479523] Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5742-6 [8516323] Mol Cell Biol. 1993 Jul;13(7):4242-50 [8321226] Cancer Res. 1993 Sep 15;53(18):4164-8 [8364909] Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):7985-9 [8367452] Cell. 1993 Nov 19;75(4):765-78 [8242748] Mutat Res. 1994 Jan;314(1):67-76 [7504193] Mol Cell Biol. 1994 Mar;14(3):1815-23 [8114714] Mol Cell Biol. 1995 Jul;15(7):3731-7 [7791780] Proc Natl Acad Sci U S A. 1961 Aug;47:1181-91 [13787093] Biophys J. 1963 Jan;3:11-33 [13980635] Cell. 1987 Oct 23;51(2):241-9 [3664636] Nucleic Acids Res. 1988 Feb 11;16(3):1215 [3344216] Science. 1988 Jul 15;241(4863):317-22 [3291120] Annu Rev Biochem. 1988;57:29-67 [3052275] Photochem Photobiol. 1988 Jul;48(1):51-7 [3217442] Mutat Res. 1989 Sep;218(2):87-94 [2770767] Nature. 1989 Nov 2;342(6245):95-8 [2554145] Exp Cell Res. 1990 Feb;186(2):332-9 [2153561] Cancer Res. 1990 Jun 15;50(12):3761-6 [2187601] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glucocorticoid and/or glucocorticoid antagonist effects in inflammatory disease-susceptible Lewis rats and inflammatory disease-resistant Fischer rats. AN - 77344681; 7789338 AB - Lewis (LEW/N) and Fischer (F344) rats are inbred strains that respond antithetically to administration of several inflammatory stimuli. Thus, in response to streptococcal cell wall-derived peptidoglycan/polysaccharide, 6-week-old female Lewis rats develop acute and chronic polyarthritis, whereas age- and sex-matched Fischer rats are arthritis-resistant. The susceptibility of Lewis rats to development of chronic severe inflammatory disease has been attributed to their inability to appropriately activate their hypothalamic-pituitary-adrenal axis in response to inflammatory stimuli, leading to a functional glucocorticoid deficiency. To investigate whether the acute neurogenic inflammatory response was also different in the two strains, we studied the air-pouch model of carrageenin-induced neurogenic inflammation in adult male Lewis and Fischer rats. Both the volume and the leukocyte concentration of the inflammatory exudate were significantly higher in Lewis than in Fischer rats, suggesting that the known differences in the handling of chronic inflammation between the two strains pertain to the acute neurogenic type of inflammation as well. To confirm that glucocorticoids play a major role in the differential response of the two strains to this inflammatory stimulus, we administered graded doses of the glucocorticoid agonist dexamethasone or antagonist RU 486 to both strains and examined their responses to concomitantly administered carrageenin. RU 486 increased, whereas dexamethasone decreased, the inflammatory response of Fischer and Lewis rats, respectively, to approach the magnitude of each other's natural response, suggesting that glucocorticoids are involved in this phenomenon as well. To rule out any differences in end-organ sensitivity to glucocorticoids between the two strains, we evaluated dose-response relations of whole body, thymus, spleen, and adrenal weights after 1 week daily administration of graded doses of dexamethasone. We found similar ED50 for both Lewis and Fischer rats. We conclude that the differences in the susceptibility to acute, carrageenin-induced, neurogenic inflammation between the LEW/N and F344 rat strains are similar to those of chronic inflammatory responses in these strains and likewise glucocorticoid-dependent. No apparent major differences exist in the sensitivity of target tissues to exogenous glucocorticoids between Lewis and Fischer rats. JF - Endocrinology AU - Karalis, K AU - Crofford, L AU - Wilder, R L AU - Chrousos, G P AD - Developmental Endocrinology Branch, National Institute of Child Health and Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/07// PY - 1995 DA - July 1995 SP - 3107 EP - 3112 VL - 136 IS - 7 SN - 0013-7227, 0013-7227 KW - Peptidoglycan KW - 0 KW - Polysaccharides, Bacterial KW - Mifepristone KW - 320T6RNW1F KW - Dexamethasone KW - 7S5I7G3JQL KW - Carrageenan KW - 9000-07-1 KW - Abridged Index Medicus KW - Index Medicus KW - Spleen -- anatomy & histology KW - Animals KW - Rats, Inbred Lew KW - Streptococcus -- chemistry KW - Arthritis -- chemically induced KW - Rats KW - Adrenal Glands -- anatomy & histology KW - Rats, Inbred F344 KW - Thymus Gland -- anatomy & histology KW - Genetic Predisposition to Disease KW - Male KW - Organ Size -- drug effects KW - Disease Susceptibility KW - Dexamethasone -- pharmacology KW - Inflammation -- etiology KW - Dexamethasone -- administration & dosage KW - Mifepristone -- administration & dosage KW - Mifepristone -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77344681?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Glucocorticoid+and%2For+glucocorticoid+antagonist+effects+in+inflammatory+disease-susceptible+Lewis+rats+and+inflammatory+disease-resistant+Fischer+rats.&rft.au=Karalis%2C+K%3BCrofford%2C+L%3BWilder%2C+R+L%3BChrousos%2C+G+P&rft.aulast=Karalis&rft.aufirst=K&rft.date=1995-07-01&rft.volume=136&rft.issue=7&rft.spage=3107&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-21 N1 - Date created - 1995-07-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dose-finding study of 5'-deoxy-5-fluorouridine in combination with fixed doses of cisplatin and L-folinic acid for the treatment of advanced or recurrent squamous cell carcinoma of the head and neck. AN - 77325412; 7777248 AB - In order to assess the maximum tolerated dose of 5'-deoxy-5-fluorouridine (5dFUR) combined with a cisplatin (20 mg/m2 i.v.) and L-folinic acid (100 mg/m2 i.v.), 5-day schedule 19 consecutive chemotherapy-naive patients affected by advanced or recurrent carcinoma of the head and neck were entered in this phase I trial. Doses of 5dFUR were escalated from a starting level of 2,000 mg/m2/day up to 3,000 and 5,000 mg/m2/day. At the latter step the dose-limiting acute toxicities were stomatitis and diarrhea, which were of WHO grade 3-4 and occurred in 3 and 1 out of 4 evaluated patients, respectively. Other grade 3 acute toxicities were leukopenia, anemia, renal impairment, and neurologic symptoms, observed in 1 patient each. Furthermore, one possibly treatment-related death was registered among patients entered in the highest dose level. Eleven out of 19 patients (58%; 95% CI:34-80%) showed a complete (2 cases) or partial (9 cases) response to this treatment, regardless of the 5dFUR dosage employed. From our results we may define the maximum tolerated dose of 5dFUR to be associated with cisplatin and L-folin acid used in this trial as 3,000 mg/m2/day x 5 days. Assessment of the real activity of this combination chemotherapy deserves further studies. JF - Oncology AU - Comella, P AU - Biglietto, M AU - Della Vittoria Scarpati, M AU - Stampino, C G AU - Pandolfi, A AU - Palmieri, G AU - Carteni, G AU - Catalano, G AU - Comella, G AD - Division of Medical Oncology A, National Cancer Institute, Milan, Italy. PY - 1995 SP - 326 EP - 330 VL - 52 IS - 4 SN - 0030-2414, 0030-2414 KW - Floxuridine KW - 039LU44I5M KW - Cisplatin KW - Q20Q21Q62J KW - Leucovorin KW - Q573I9DVLP KW - doxifluridine KW - V1JK16Y2JP KW - Index Medicus KW - Humans KW - Leucovorin -- administration & dosage KW - Aged KW - Leucovorin -- adverse effects KW - Cisplatin -- administration & dosage KW - Stomatitis -- chemically induced KW - Floxuridine -- administration & dosage KW - Diarrhea -- chemically induced KW - Middle Aged KW - Cisplatin -- adverse effects KW - Female KW - Male KW - Floxuridine -- adverse effects KW - Neoplasm Recurrence, Local -- drug therapy KW - Carcinoma, Squamous Cell -- pathology KW - Head and Neck Neoplasms -- pathology KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Head and Neck Neoplasms -- drug therapy KW - Carcinoma, Squamous Cell -- drug therapy KW - Neoplasm Recurrence, Local -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77325412?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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&rft.atitle=Dose-finding+study+of+5%27-deoxy-5-fluorouridine+in+combination+with+fixed+doses+of+cisplatin+and+L-folinic+acid+for+the+treatment+of+advanced+or+recurrent+squamous+cell+carcinoma+of+the+head+and+neck.&rft.au=Comella%2C+P%3BBiglietto%2C+M%3BDella+Vittoria+Scarpati%2C+M%3BStampino%2C+C+G%3BPandolfi%2C+A%3BPalmieri%2C+G%3BCarteni%2C+G%3BCatalano%2C+G%3BComella%2C+G&rft.aulast=Comella&rft.aufirst=P&rft.date=1995-07-01&rft.volume=52&rft.issue=4&rft.spage=326&rft.isbn=&rft.btitle=&rft.title=Oncology&rft.issn=00302414&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-13 N1 - Date created - 1995-07-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant toxins: new therapeutic agents for cancer. AN - 77422035; 7625703 JF - Annals of the New York Academy of Sciences AU - Pastan, I H AU - Pai, L H AU - Brinkmann, U AU - Fitzgerald, D J AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/06/30/ PY - 1995 DA - 1995 Jun 30 SP - 345 EP - 354 VL - 758 SN - 0077-8923, 0077-8923 KW - Antibodies, Monoclonal KW - 0 KW - Bacterial Toxins KW - Exotoxins KW - Immunotoxins KW - Virulence Factors KW - immunotoxin LMB-7 KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Animals KW - Humans KW - Bacterial Toxins -- therapeutic use KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Exotoxins -- therapeutic use KW - Immunotoxins -- therapeutic use KW - Neoplasms, Experimental -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77422035?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Recombinant+toxins%3A+new+therapeutic+agents+for+cancer.&rft.au=Pastan%2C+I+H%3BPai%2C+L+H%3BBrinkmann%2C+U%3BFitzgerald%2C+D+J&rft.aulast=Pastan&rft.aufirst=I&rft.date=1995-06-30&rft.volume=758&rft.issue=&rft.spage=345&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-31 N1 - Date created - 1995-08-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of a constitutive mutant of iron regulatory protein 1 abolishes iron homeostasis in mammalian cells. AN - 77364262; 7541043 AB - Iron regulatory proteins (IRPs) are iron-sensing proteins that bind to RNA stem-loop sequences known as iron-responsive elements (IREs) when cells are depleted of iron. Although IRPs have been shown to bind to IREs derived from ferritin and transferrin receptor (TfR) mRNAs in vitro, there has not been a direct demonstration of the impact of a recombinant IRP on the expression of endogenous IRE-containing transcripts. In this study, we evaluate the impact of expression of C437S, a mutant of IRP1 that binds IREs regardless of cellular iron status, on the regulation of biosynthesis of ferritin and TfR. Despite being made iron-replete, cells expressing C437S continue to synthesize and express high amounts of TfR, while the synthesis of ferritin is repressed. Thus, a single mutant IRP can prevent the usual homeostatic changes in ferritin and TfR biosynthesis. Cells expressing the mutant protein would therefore be predicted to be unable to defend against iron overload. Preliminary results show that cells treated with iron have diminished cell survival when C437S is expressed, and we have thus created a tissue culture model system for the study of iron toxicity. JF - The Journal of biological chemistry AU - DeRusso, P A AU - Philpott, C C AU - Iwai, K AU - Mostowski, H S AU - Klausner, R D AU - Rouault, T A AD - Cell Biology and Metabolism Branch, NICHHD, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/06/30/ PY - 1995 DA - 1995 Jun 30 SP - 15451 EP - 15454 VL - 270 IS - 26 SN - 0021-9258, 0021-9258 KW - Iron-Regulatory Proteins KW - 0 KW - RNA-Binding Proteins KW - Receptors, Transferrin KW - RNA KW - 63231-63-0 KW - Ferritins KW - 9007-73-2 KW - Iron KW - E1UOL152H7 KW - Iron Regulatory Protein 1 KW - EC 4.2.1.3 KW - Index Medicus KW - Receptors, Transferrin -- analysis KW - Tumor Cells, Cultured KW - RNA -- metabolism KW - Humans KW - Mutation KW - Ferritins -- biosynthesis KW - RNA-Binding Proteins -- physiology KW - Homeostasis KW - Iron -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77364262?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Expression+of+a+constitutive+mutant+of+iron+regulatory+protein+1+abolishes+iron+homeostasis+in+mammalian+cells.&rft.au=DeRusso%2C+P+A%3BPhilpott%2C+C+C%3BIwai%2C+K%3BMostowski%2C+H+S%3BKlausner%2C+R+D%3BRouault%2C+T+A&rft.aulast=DeRusso&rft.aufirst=P&rft.date=1995-06-30&rft.volume=270&rft.issue=26&rft.spage=15451&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 - 1995-08-01 N1 - Date created - 1995-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transcriptional regulation of human CYP2C genes: functional comparison of CYP2C9 and CYP2C18 promoter regions. AN - 77351416; 7794915 AB - The cytochrome P4502C subfamily comprises a group of constitutive microsomal hemoproteins which are expressed primarily in liver. In humans, this subfamily is responsible for metabolism of a variety of therapeutic drugs such as warfarin, mephenytoin, omeprazole, and antiinflammatory drugs. In the present study, we analyzed the promoter activity of the 5'-flanking region of two human CYP2C genes, CYP2C9 and CYP2C18. The ability of the 2.2-kb 5'-flanking region of the CYP2C9 gene to direct expression of a luciferase reporter gene in HepG2 cells was 25 times greater than that of the 1.3-kb 5'-flanking region of CYP2C18. Deletional analysis of CYP2C9 indicated that the minimal promoter was located between the translation start site and nucleotide -155, and an HPF-1 domain consensus sequence was identified in this region. Gel shift analysis demonstrated that nuclear proteins from HepG2 cells had a high binding affinity for a 20-bp oligonucleotide containing the HPF-1 site of CYP2C9. Antiserum to rat HNF-4 supershifted this DNA--protein complex, and an oligonucleotide derived from an HNF-4 motif present in the human apolipoprotein CIII promoter competed for the supershifted complex. Cotransfection with an HNF-4 expression plasmid increased transcriptional activity of the CYP2C9 minimal promoter (approximately 2-fold) in HepG2 cells and elevated activity more substantially in nonhepatic NIH3T3 cells (26-fold) and Cos 1 cells (9-fold).(ABSTRACT TRUNCATED AT 250 WORDS) JF - Biochemistry AU - Ibeanu, G C AU - Goldstein, J A AD - National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/06/27/ PY - 1995 DA - 1995 Jun 27 SP - 8028 EP - 8036 VL - 34 IS - 25 SN - 0006-2960, 0006-2960 KW - Basic Helix-Loop-Helix Leucine Zipper Transcription Factors KW - 0 KW - DNA-Binding Proteins KW - Hepatocyte Nuclear Factor 4 KW - MLX protein, human KW - Phosphoproteins KW - Tcfl4 protein, mouse KW - Transcription Factors KW - DNA KW - 9007-49-2 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Steroid Hydroxylases KW - EC 1.14.- KW - CYP2C9 protein, human KW - EC 1.14.13.- KW - Cytochrome P-450 CYP2C9 KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - CYP2C18 protein, human KW - Steroid 16-alpha-Hydroxylase KW - Index Medicus KW - Animals KW - Transcription Factors -- metabolism KW - Carcinoma, Hepatocellular KW - DNA -- metabolism KW - Humans KW - Transcriptional Activation KW - Haplorhini KW - Binding Sites KW - Gene Deletion KW - Mutagenesis, Site-Directed KW - Liver Neoplasms KW - Transcription Factors -- pharmacology KW - Base Sequence KW - Tumor Cells, Cultured KW - Transfection KW - Molecular Sequence Data KW - DNA -- chemistry KW - Promoter Regions, Genetic KW - Cytochrome P-450 Enzyme System -- genetics KW - Transcription, Genetic KW - Steroid Hydroxylases -- genetics KW - Gene Expression Regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77351416?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Transcriptional+regulation+of+human+CYP2C+genes%3A+functional+comparison+of+CYP2C9+and+CYP2C18+promoter+regions.&rft.au=Ibeanu%2C+G+C%3BGoldstein%2C+J+A&rft.aulast=Ibeanu&rft.aufirst=G&rft.date=1995-06-27&rft.volume=34&rft.issue=25&rft.spage=8028&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-01 N1 - Date created - 1995-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA binding and regulatory effects of transcription factors SP1 and USF at the rat amyloid precursor protein gene promoter. AN - 77385183; 7610052 AB - Two DNA elements which we have termed SAA and GAG have been shown to control expression of the rat amyloid precursor protein (APP) gene, and the region containing the SAA element has been shown to interact with nuclear proteins [Hoffman and Chernak (1994) Biochem. Biophys. Res. Commun. 201, 610-617]. In this report we study DNA sequences and proteins which influence the activity of the SAA element. An oligonucleotide containing the SAA element is specifically bound by nuclear proteins derived from rat PC12 cells, consistently forming four complexes designated C25, C30, C35 and C40 in electrophoretic mobility shift assays (EMSAs). We demonstrate that the C25, C30 and C40 complexes involve the binding of nuclear proteins to an SP1 consensus sequence located within the SAA element and that the C25 complex contains a protein antigenically related to the human SP1 protein. We establish further that the C35 complex requires a USF recognition site located within the SAA element and contains a protein antigenically related to the human upstream stimulatory factor (USF) protein. Using APP promoter/luciferase reporter gene constructs, we demonstrate that both the SP1 and the USF sites can play a role in the transcriptional activity of the SAA element. Finally, we show that complexes similar to the C25, C30 and C35 complexes are formed by rat cortex nuclear extracts and the SAA element in EMSA experiments, suggesting the relevance of our in vitro observations to the in vivo functioning of the rat APP promoter. JF - Nucleic acids research AU - Hoffman, P W AU - Chernak, J M AD - Molecular Physiology and Genetics Section, National Institute on Aging, Baltimore, MD 21224, USA. Y1 - 1995/06/25/ PY - 1995 DA - 1995 Jun 25 SP - 2229 EP - 2235 VL - 23 IS - 12 SN - 0305-1048, 0305-1048 KW - Amyloid beta-Protein Precursor KW - 0 KW - DNA-Binding Proteins KW - Nuclear Proteins KW - Recombinant Fusion Proteins KW - Sp1 Transcription Factor KW - Transcription Factors KW - Upstream Stimulatory Factors KW - Usf1 protein, rat KW - DNA KW - 9007-49-2 KW - Luciferases KW - EC 1.13.12.- KW - Index Medicus KW - Animals KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Rats KW - Base Sequence KW - Cerebral Cortex -- chemistry KW - Binding, Competitive KW - Rats, Wistar KW - Molecular Sequence Data KW - Luciferases -- genetics KW - Nuclear Proteins -- metabolism KW - Male KW - PC12 Cells KW - Transcription Factors -- pharmacology KW - Promoter Regions, Genetic KW - Sp1 Transcription Factor -- pharmacology KW - Transcription Factors -- metabolism KW - DNA -- metabolism KW - Sp1 Transcription Factor -- metabolism KW - DNA -- chemistry KW - Amyloid beta-Protein Precursor -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77385183?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=DNA+binding+and+regulatory+effects+of+transcription+factors+SP1+and+USF+at+the+rat+amyloid+precursor+protein+gene+promoter.&rft.au=Hoffman%2C+P+W%3BChernak%2C+J+M&rft.aulast=Hoffman&rft.aufirst=P&rft.date=1995-06-25&rft.volume=23&rft.issue=12&rft.spage=2229&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-11 N1 - Date created - 1995-08-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1987 Jan 22-28;325(6102):368-72 [3027570] J Biol Chem. 1994 Aug 19;269(33):21229-33 [8063744] Nature. 1988 Apr 7;332(6164):557-61 [2833704] Proc Natl Acad Sci U S A. 1988 Dec;85(24):9811-5 [2904679] Proc Natl Acad Sci U S A. 1989 Oct;86(19):7606-10 [2508093] Gene. 1990 Mar 15;87(2):257-63 [2110105] FEBS Lett. 1990 Sep 3;269(2):305-10 [2205513] Trends Pharmacol Sci. 1991 Oct;12(10):383-8 [1763432] Nucleic Acids Res. 1983 Mar 11;11(5):1475-89 [6828386] Cell. 1983 Nov;35(1):79-87 [6313230] Cell. 1985 Nov;43(1):165-75 [4075392] Cell. 1986 Dec 5;47(5):767-76 [3779841] Gene. 1992 Mar 15;112(2):189-95 [1555768] Alzheimer Dis Assoc Disord. 1992 Spring;6(1):7-34 [1605946] Mol Cell Biol. 1992 Oct;12(10):4251-61 [1341900] Biochem Biophys Res Commun. 1993 Jan 29;190(2):637-47 [8427604] Nat Genet. 1992 Jul;1(4):233-4 [1363811] Gene. 1993 Nov 15;133(2):255-60 [8224912] Biochem Biophys Res Commun. 1994 Jun 15;201(2):610-7 [8002993] Methods Enzymol. 1987;154:367-82 [3323813] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human lung carcinogen-DNA adduct levels mediated by genetic polymorphisms in vivo. AN - 77499395; 7666479 AB - Cancer risk from exposure to tobacco smoke varies widely from person to person, depending in part on the status of particular genes and acquired susceptibilities. Certain genes determine how cells activate and detoxify carcinogens. Activated carcinogen metabolites may bind to DNA and form DNA adducts (e.g., 7-methyl-2'-deoxyguanosine-3'-monophosphate [7-methyl-dGMP] and polycyclic aromatic hydrocarbons-dGMP [PAHs-dGMP]), many of which can induce genetic mutations. Thus, if individuals have an increased capacity to activate carcinogens, they might form more carcinogen-DNA adducts and subsequently have an increased risk of cancer. Using DNA-adduct detection methods specific for 7-methyl-dGMP and PAH-dGMP, we sought to determine whether an inherited genetic susceptibility to cancer associated with certain carcinogen-metabolizing and detoxifying genes (e.g., cytochrome P450 and glutathione S-transferase) is related to DNA adduct formation in lung tissue. Human lung tissues were collected randomly from 90 autopsy donors who were free of cancer. Levels of 7-methyl-dGMP, a metabolic product of N-nitrosamines, and PAH-dGMP adducts were determined in lung tissue specimens by use of micropreparative DNA purification steps combined with a 32P-postlabeling assay. Genetic polymorphisms (the presence of different genes and/or alleles) were determined for the cytochrome P450 genes, CYP2D6, CYP2E1, and CYP1A1, as well as for glutathione S-transferase M1 (GSTM1). Statistical differences among adduct levels for the study variables, including genotypes, were assessed by the two-sided Student's t test or the Mann-Whitney U test. Higher 7-methyl-dGMP adduct levels were associated with CYP2D6 genotypes (P = .01), consistent with the reports of the increased risk of lung cancer associated with this genotype. Higher adduct levels were also associated with CYP2E1 minor alleles (P = .05). In both cases, the association was attributed mostly to individuals with low serum cotinine levels (P = .004 and P = .05, respectively), suggesting that the effect of the genotypes is mostly in nonsmokers exposed to either passive tobacco smoke or to N-nitrosamine exposures other than tobacco smoke or to N-nitrosamine exposures other than tobacco smoke. Separately, the presence of PAH-dGMP adducts was associated with the GSTM1 null genotype (absence of the gene) (odds ratio = 8.6; 95% confidence interval = 1.03-100). This study finds that the levels of two different carcinogen-DNA adducts vary in lung tissue (an important target tissue) in association with three separate genetic polymorphisms (i.e., CYP2D6, CYP2E1, and GSTM1). CYP2D6 and CYP2E1 genotypes are associated with higher 7-methyl-dGMP levels, while the GSTM1 null genotype is associated with higher numbers of PAH-dGMP adducts. These findings suggest that genetic polymorphisms are predictive of carcinogen-DNA adduct levels and would thus be predictive of an individual's lifetime response to carcinogen exposure. JF - Journal of the National Cancer Institute AU - Kato, S AU - Bowman, E D AU - Harrington, A M AU - Blomeke, B AU - Shields, P G AD - Division of Cancer Etiology, National Cancer Institute, Bethesda, Md 20892, USA. Y1 - 1995/06/21/ PY - 1995 DA - 1995 Jun 21 SP - 902 EP - 907 VL - 87 IS - 12 SN - 0027-8874, 0027-8874 KW - CYP1A1 KW - CYP2D6 KW - CYP2E1 KW - GSTM1 KW - Deoxyguanine Nucleotides KW - 0 KW - Polycyclic Compounds KW - 7-methyl-2'-deoxyguanosine 3'-monophosphate KW - 123497-14-3 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Cotinine KW - K5161X06LL KW - Index Medicus KW - Cytochrome P-450 Enzyme System -- genetics KW - Humans KW - Cotinine -- blood KW - Aged KW - Glutathione Transferase -- genetics KW - Smoking -- genetics KW - Base Sequence KW - Smoking -- blood KW - Aged, 80 and over KW - Adult KW - Molecular Sequence Data KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - Deoxyguanine Nucleotides -- metabolism KW - Polymorphism, Genetic KW - Deoxyguanine Nucleotides -- genetics KW - Lung -- enzymology KW - Polycyclic Compounds -- metabolism KW - Lung -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77499395?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Human+lung+carcinogen-DNA+adduct+levels+mediated+by+genetic+polymorphisms+in+vivo.&rft.au=Kato%2C+S%3BBowman%2C+E+D%3BHarrington%2C+A+M%3BBlomeke%2C+B%3BShields%2C+P+G&rft.aulast=Kato&rft.aufirst=S&rft.date=1995-06-21&rft.volume=87&rft.issue=12&rft.spage=902&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 - 1995-10-06 N1 - Date created - 1995-10-06 N1 - Date revised - 2017-01-13 N1 - Gene symbol - CYP1A1; CYP2D6; CYP2E1; GSTM1 N1 - SuppNotes - Comment In: J Natl Cancer Inst. 1995 Jun 21;87(12):861-2 [7666471] Erratum In: J Natl Cancer Inst 1996 Nov 6;88(21):1595 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hypersensitivity reactions to chemotherapy agents in patients receiving chemoimmunotherapy with high-dose interleukin 2. AN - 77494676; 7666481 AB - Treatment with the immune system modulator interleukin 2 (IL-2) can result in a number of immunologic abnormalities ranging from suppression of delayed-type hypersensitivity responses and neutrophil activity to autoimmune thyroiditis and hypersensitivity reactions against iodine-containing radiographic contrast media. There are a number of published reports of chemoimmunotherapy using IL-2 in combination with various chemotherapeutic agents to treat patients with certain cancers, but none have described hypersensitivity responses to the chemotherapeutic agents given. In the early stages of an ongoing clinical trial of the efficacy of combination chemoimmunotherapy for the treatment of patients with metastatic melanoma, we discovered that a number of the patients experienced unexpected hypersensitivity reactions after receiving chemotherapy. We therefore decided to examine these hypersensitivity reactions in detail. During the period of March 1993 through February 1994, 31 patients with metastatic melanoma were treated either by chemotherapy (dacarbazine, cisplatin, and tamoxifen) or by chemoimmunotherapy (the same drug regimen plus interferon alfa and high-dose IL-2). Twelve patients were treated in a non-randomized pilot study, with six receiving chemotherapy and six receiving chemoimmunotherapy. The six patients who received chemotherapy also received carmustine (BCNU). Nineteen subsequent patients were treated in a prospective, randomized study to compare the two therapeutic approaches. In total, 15 of the 31 patients were treated by chemotherapy alone, and 16 were treated by combination chemoimmunotherapy. Overall, the patients in the two groups were balanced in terms of age, sex, and stage of disease. Ten of 16 chemoimmunotherapy patients exhibited type I hypersensitivity reactions during chemotherapy administration, ranging from pruritus, erythema, and edema to hypotension with hemodynamic instability that required pressor therapy. None of the 15 patients on the chemotherapy regimen exhibited hypersensitivity reactions. All patients in the chemoimmunotherapy group gained weight and had elevated white blood cell and eosinophil counts during chemotherapy; these effects were more prominent in those with hypersensitivity reactions. Hypersensitivity reactions occurred within several hours after chemotherapy administration in patients who had previously received one to two cycles of high-dose IL-2, suggesting that prior IL-2 therapy sensitized patients to cisplatin or dacarbazine. This is the first report of IL-2-induced hypersensitivity to chemotherapy agents. JF - Journal of the National Cancer Institute AU - Heywood, G R AU - Rosenberg, S A AU - Weber, J S AD - Division of Cancer Treatment, National Cancer Institute, Bethesda, Md., USA. Y1 - 1995/06/21/ PY - 1995 DA - 1995 Jun 21 SP - 915 EP - 922 VL - 87 IS - 12 SN - 0027-8874, 0027-8874 KW - Interferon-alpha KW - 0 KW - Interleukin-2 KW - Index Medicus KW - Edema -- chemically induced KW - Skin -- drug effects KW - Humans KW - Adult KW - Middle Aged KW - Blood Pressure -- drug effects KW - Male KW - Female KW - Interleukin-2 -- adverse effects KW - Interleukin-2 -- administration & dosage KW - Interferon-alpha -- adverse effects KW - Interferon-alpha -- administration & dosage KW - Drug Hypersensitivity -- physiopathology KW - Drug Hypersensitivity -- etiology KW - Melanoma -- secondary KW - Melanoma -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77494676?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Hypersensitivity+reactions+to+chemotherapy+agents+in+patients+receiving+chemoimmunotherapy+with+high-dose+interleukin+2.&rft.au=Heywood%2C+G+R%3BRosenberg%2C+S+A%3BWeber%2C+J+S&rft.aulast=Heywood&rft.aufirst=G&rft.date=1995-06-21&rft.volume=87&rft.issue=12&rft.spage=915&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 - 1995-10-06 N1 - Date created - 1995-10-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Catalytic domain of human immunodeficiency virus type 1 integrase: identification of a soluble mutant by systematic replacement of hydrophobic residues. AN - 77376363; 7597080 AB - The integrase protein of human immunodeficiency virus type 1 is necessary for the stable integration of the viral genome into host DNA. Integrase catalyzes the 3' processing of the linear viral DNA and the subsequent DNA strand transfer reaction that inserts the viral DNA ends into host DNA. Although full-length integrase is required for 3' processing and DNA strand transfer activities in vitro, the central core domain of integrase is sufficient to catalyze an apparent reversal of the DNA strand transfer reaction, termed disintegration. This catalytic core domain, as well as the full-length integrase, has been refractory to structural studies by x-ray crystallography or NMR because of its low solubility and propensity to aggregate. In an attempt to improve protein solubility, we used site-directed mutagenesis to replace hydrophobic residues within the core domain with either alanine or lysine. The single substitution of lysine for phenylalanine at position 185 resulted in a core domain that was highly soluble, monodisperse in solution, and retained catalytic activity. This amino acid change has enabled the catalytic domain of integrase to be crystallized and the structure has been solved to 2.5-A resolution [Dyda, F., Hickman, A. B., Jenkins, T. M., Engelman, A., Craigie, R. & Davies, D. R. (1994) Science 266, 1981-1986]. Systematic replacement of hydrophobic residues may be a useful strategy to improve the solubility of other proteins to facilitate structural and biochemical studies. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Jenkins, T M AU - Hickman, A B AU - Dyda, F AU - Ghirlando, R AU - Davies, D R AU - Craigie, R AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892-0560, USA. Y1 - 1995/06/20/ PY - 1995 DA - 1995 Jun 20 SP - 6057 EP - 6061 VL - 92 IS - 13 SN - 0027-8424, 0027-8424 KW - Macromolecular Substances KW - 0 KW - Recombinant Proteins KW - Histidine KW - 4QD397987E KW - DNA Nucleotidyltransferases KW - EC 2.7.7.- KW - Integrases KW - Index Medicus KW - AIDS/HIV KW - Solubility KW - Electrophoresis, Polyacrylamide Gel KW - Models, Molecular KW - Sequence Tagged Sites KW - Amino Acid Sequence KW - Virus Integration KW - Binding Sites KW - Recombinant Proteins -- isolation & purification KW - Chromatography, Gel KW - Recombinant Proteins -- metabolism KW - Enzyme Stability KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Catalysis KW - Mutagenesis, Site-Directed KW - HIV-1 -- genetics KW - Point Mutation KW - DNA Nucleotidyltransferases -- isolation & purification KW - HIV-1 -- enzymology KW - DNA Nucleotidyltransferases -- chemistry KW - Protein Conformation KW - DNA Nucleotidyltransferases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77376363?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Catalytic+domain+of+human+immunodeficiency+virus+type+1+integrase%3A+identification+of+a+soluble+mutant+by+systematic+replacement+of+hydrophobic+residues.&rft.au=Jenkins%2C+T+M%3BHickman%2C+A+B%3BDyda%2C+F%3BGhirlando%2C+R%3BDavies%2C+D+R%3BCraigie%2C+R&rft.aulast=Jenkins&rft.aufirst=T&rft.date=1995-06-20&rft.volume=92&rft.issue=13&rft.spage=6057&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 - 1995-08-03 N1 - Date created - 1995-08-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1983 Nov 10-16;306(5939):155-60 [6316141] Science. 1994 Dec 23;266(5193):1981-6 [7801124] Virology. 1984 Sep;137(2):358-70 [6091334] Proc Natl Acad Sci U S A. 1984 Oct;81(20):6461-5 [6208550] Proc Natl Acad Sci U S A. 1984 Dec;81(24):7885-9 [6083562] Cell. 1985 Sep;42(2):573-80 [4028161] Eur J Biochem. 1986 May 15;157(1):169-80 [3709531] J Mol Biol. 1986 May 5;189(1):113-30 [3537305] J Virol. 1987 Jun;61(6):1999-2008 [3033327] Gene. 1987;56(1):125-35 [3315856] J Mol Biol. 1988 Jan 5;199(1):47-59 [3351923] Cell. 1988 Aug 12;54(4):497-504 [3401925] Nucleic Acids Res. 1988 Aug 11;16(15):7351-67 [3045756] Proc Natl Acad Sci U S A. 1989 Apr;86(8):2525-9 [2539592] Proc Natl Acad Sci U S A. 1990 Jul;87(13):5119-23 [2164223] Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1339-43 [1847518] Nucleic Acids Res. 1991 Feb 25;19(4):851-60 [1850126] J Virol. 1991 Oct;65(10):5624-30 [1895409] Methods Enzymol. 1991;202:390-411 [1723781] Science. 1992 Feb 7;255(5045):723-6 [1738845] Mol Cell Biol. 1992 May;12(5):2331-8 [1314954] J Virol. 1992 Nov;66(11):6361-9 [1404595] Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9598-602 [1409671] Annu Rev Cell Biol. 1992;8:275-306 [1282352] Annu Rev Genet. 1992;26:527-44 [1482125] Nucleic Acids Res. 1993 Mar 25;21(6):1419-25 [8464733] Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3428-32 [8386373] EMBO J. 1993 Aug;12(8):3269-75 [8344264] J Biol Chem. 1994 Nov 18;269(46):29279-87 [7961898] Cell. 1984 Jul;37(3):1043-52 [6204767] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Brain mitochondrial cytochromes P450: xenobiotic metabolism, presence of multiple forms and their selective inducibility. AN - 77351869; 7793987 AB - The capability of rat brain mitochondria to metabolize a variety of xenobiotics was examined. The presence of cytochrome P450 (P450) and associated monooxygenase activities were estimated in isolated rat brain mitochondria and compared with the corresponding activities in microsomes. Total P450 content in brain mitochondria from naive rats was twice that of the corresponding microsomal level. The ability of brain mitochondria to metabolize the potent carcinogen N-nitrosodimethylamine was more than twofold that of the corresponding microsomal activity, while the 7-ethoxycoumarin-O-deethylase activity was significantly lower in mitochondria. Immunoblot experiments using antisera to purified rat liver microsomal P450s, namely P450 (2B1/2B2), P4501A1, and P4502E1, and purified phenobarbital-inducible rat brain P450, revealed the presence of immunoreactive bands in isolated brain mitochondria. These various antibodies to P450 inhibited the brain mitochondrial monooxygenase activities to significant, though varying extent. The addition of antiserum to microsomal NADPH cytochrome P450 reductase did not affect the mitochondrial P450 associated monooxygenase activities, although it completely inhibited the corresponding microsomal activities. Chronic ethanol administration resulted in twofold induction of total P450 content and the monooxygenase activities known to be mediated by P4502E1, such as N-nitrosodimethylamine-N-demethylase and p-nitrophenol hydroxylase in brain mitochondria. Pretreatment of animals with phenobarbital resulted in the induction of aminopyrine N-demethylase activity in brain mitochondria. The study demonstrates the presence of multiple forms of P450 in the rat brain mitochondria, their inducibility, and their capability to metabolize xenobiotics. JF - Archives of biochemistry and biophysics AU - Bhagwat, S V AU - Boyd, M R AU - Ravindranath, V AD - Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences, Bangalore, India. Y1 - 1995/06/20/ PY - 1995 DA - 1995 Jun 20 SP - 73 EP - 83 VL - 320 IS - 1 SN - 0003-9861, 0003-9861 KW - Cytochrome P-450 Enzyme Inhibitors KW - 0 KW - Xenobiotics KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - 7-Alkoxycoumarin O-Dealkylase KW - EC 1.14.13.- KW - Cytochrome P-450 CYP2E1 KW - Oxidoreductases, N-Demethylating KW - EC 1.5.- KW - Aminopyrine N-Demethylase KW - EC 1.5.3.- KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Animals KW - 7-Alkoxycoumarin O-Dealkylase -- antagonists & inhibitors KW - 7-Alkoxycoumarin O-Dealkylase -- metabolism KW - Alcoholism -- metabolism KW - Microsomes -- ultrastructure KW - Rats KW - Phenobarbital -- pharmacology KW - Mixed Function Oxygenases -- metabolism KW - Mixed Function Oxygenases -- antagonists & inhibitors KW - Mitochondria -- ultrastructure KW - Aminopyrine N-Demethylase -- metabolism KW - Enzyme Induction -- drug effects KW - Microsomes -- metabolism KW - In Vitro Techniques KW - Rats, Wistar KW - Mitochondria -- metabolism KW - Aminopyrine N-Demethylase -- antagonists & inhibitors KW - Oxidoreductases, N-Demethylating -- antagonists & inhibitors KW - Microscopy, Electron KW - Oxidoreductases, N-Demethylating -- metabolism KW - Male KW - Xenobiotics -- metabolism KW - Brain -- drug effects KW - Cytochrome P-450 Enzyme System -- metabolism KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Brain -- metabolism KW - Brain -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77351869?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Brain+mitochondrial+cytochromes+P450%3A+xenobiotic+metabolism%2C+presence+of+multiple+forms+and+their+selective+inducibility.&rft.au=Bhagwat%2C+S+V%3BBoyd%2C+M+R%3BRavindranath%2C+V&rft.aulast=Bhagwat&rft.aufirst=S&rft.date=1995-06-20&rft.volume=320&rft.issue=1&rft.spage=73&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 - 1995-07-27 N1 - Date created - 1995-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structural change in dopamine D2 receptor gene in a patient with neuroleptic malignant syndrome. AN - 77589154; 7573176 AB - Dysfunction of the dopaminergic system has been suggested as a pathogenic mechanism in neuroleptic malignant syndrome. Therefore, we examined the complete coding sequences of the dopamine D2 receptor (DRD2) gene for structural abnormalities in 12 patients with a history of NMS, including two cases of familial NMS. Mutational analysis was performed by denaturing gradient gel electrophoresis (DGGE), a highly sensitive technique for detecting sequences differences. We found in one patient with a history of NMS a nucleotide substitution at codon 310 (CCG-->TCG) of exon 7 of the DRD2 gene which predicts the replacement of proline to serine in the third cytoplasmic loop of the receptor, a part of the receptor that interacts with G-proteins. A larger series of patients with NMS needs to be investigated to establish whether this allele is associated with an increased susceptibility to NMS. JF - American journal of medical genetics AU - Ram, A AU - Cao, Q AU - Keck, P E AU - Pope, H G AU - Otani, K AU - Addonizio, G AU - McElroy, S L AU - Kaneko, S AU - Redlichova, M AU - Gershon, E S AD - Clinical Neurogenetics Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/06/19/ PY - 1995 DA - 1995 Jun 19 SP - 228 EP - 230 VL - 60 IS - 3 SN - 0148-7299, 0148-7299 KW - Receptors, Dopamine D2 KW - 0 KW - Index Medicus KW - Base Sequence KW - Alleles KW - Sequence Analysis KW - Humans KW - Adult KW - Molecular Sequence Data KW - Mutation KW - Male KW - Female KW - Neuroleptic Malignant Syndrome -- genetics KW - Receptors, Dopamine D2 -- genetics KW - Neuroleptic Malignant Syndrome -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77589154?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Structural+change+in+dopamine+D2+receptor+gene+in+a+patient+with+neuroleptic+malignant+syndrome.&rft.au=Ram%2C+A%3BCao%2C+Q%3BKeck%2C+P+E%3BPope%2C+H+G%3BOtani%2C+K%3BAddonizio%2C+G%3BMcElroy%2C+S+L%3BKaneko%2C+S%3BRedlichova%2C+M%3BGershon%2C+E+S&rft.aulast=Ram&rft.aufirst=A&rft.date=1995-06-19&rft.volume=60&rft.issue=3&rft.spage=228&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 - 1995-11-07 N1 - Date created - 1995-11-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DRD4 dopamine receptor genotype and CSF monoamine metabolites in Finnish alcoholics and controls. AN - 77587751; 7573171 AB - The DRD4 dopamine receptor is thus far unique among neurotransmitter receptors in having a highly polymorphic gene structure that has been reported to produce altered receptor functioning. These allelic variations are caused by a 48-bp segment in exon III of the coding region which may be repeated from 2-10 times. Varying the numbers of repeated segments changes the length, structure, and, possibly, the functional efficiency of the receptor, which makes this gene an intriguing candidate for variations in dopamine-related behaviors, such as alcoholism and drug abuse. Thus far, these DRD4 alleles have been investigated for association with schizophrenia, bipolar disorder, Parkinson's disease, and chronic alcoholism, and all have been largely negative for a direct association. We evaluated the DRD4 genotype in 226 Finish adult males, 113 of whom were alcoholics, many of the early onset type with features of impulsivity and antisocial traits. Genotype frequencies were compared to 113 Finnish controls who were free of alcohol abuse, substance abuse, and major mental illness. In 70 alcoholics and 20 controls, we measured CSF homovanillic acid (HVA), the major metabolite of dopamine, and 5-hydroxyindoleacetic acid (5-HIAA). No association was found between a particular DRD4 dopamine receptor allele and alcoholism. CSF concentrations of the monoamine metabolites showed no significant difference among the DRD4 genotypes. This study of the DRD4 dopamine receptor in alcoholics is the first to be conducted in a clinically and ethnically homogeneous population and to relate the DRD4 genotype to CSF monoamine concentrations. The results indicate that there is no association of the DRD4 receptor with alcoholism. JF - American journal of medical genetics AU - Adamson, M D AU - Kennedy, J AU - Petronis, A AU - Dean, M AU - Virkkunen, M AU - Linnoila, M AU - Goldman, D AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, DICBR, Rockville, MD 20852, USA. Y1 - 1995/06/19/ PY - 1995 DA - 1995 Jun 19 SP - 199 EP - 205 VL - 60 IS - 3 SN - 0148-7299, 0148-7299 KW - Amines KW - 0 KW - DRD4 protein, human KW - Receptors, Dopamine KW - Receptors, Dopamine D2 KW - Receptors, Dopamine D4 KW - 137750-34-6 KW - Homovanillic Acid KW - X77S6GMS36 KW - Index Medicus KW - Polymerase Chain Reaction KW - Base Sequence KW - Alleles KW - Polymorphism, Genetic KW - Finland KW - Humans KW - Adult KW - Molecular Sequence Data KW - Male KW - Homovanillic Acid -- cerebrospinal fluid KW - Amines -- metabolism KW - Receptors, Dopamine -- genetics KW - Alcoholism -- metabolism KW - Alcoholism -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77587751?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=DRD4+dopamine+receptor+genotype+and+CSF+monoamine+metabolites+in+Finnish+alcoholics+and+controls.&rft.au=Adamson%2C+M+D%3BKennedy%2C+J%3BPetronis%2C+A%3BDean%2C+M%3BVirkkunen%2C+M%3BLinnoila%2C+M%3BGoldman%2C+D&rft.aulast=Adamson&rft.aufirst=M&rft.date=1995-06-19&rft.volume=60&rft.issue=3&rft.spage=199&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 - 1995-11-07 N1 - Date created - 1995-11-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selective metabolic activation by apomorphine in striosomes of denervated striatum in MPTP-induced hemiparkinsonian monkeys. AN - 77498824; 7669997 AB - Results of previous studies have suggested differences in the regulatory mechanisms in striatal striosomes and matrix following interruption of dopaminergic input to the striatum by MPTP in the monkey. In the present study we have investigated the possibility that stimulation of dopamine receptors by apomorphine modifies glucose metabolism differentially in the two striatal compartments of unilaterally MPTP-lesioned monkeys. Apomorphine treatment was found to result in higher rates of glucose utilization in the denervated striatum than in the intact hemisphere. Furthermore, the effect was more robust in the striosomes than in the matrix, thus providing evidence for differential functional and/or metabolic regulation in striatal striosomes and matrix in parkinsonian syndromes. JF - Neuroreport AU - Pontieri, F E AU - Viola, J J AU - Sokoloff, L AU - Porrino, L J AD - Laboratory of Cerebral Metabolism, National Institute of Mental Health, Bethesda, MD, USA. Y1 - 1995/06/19/ PY - 1995 DA - 1995 Jun 19 SP - 1330 EP - 1332 VL - 6 IS - 9 SN - 0959-4965, 0959-4965 KW - Receptors, Dopamine KW - 0 KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - 9P21XSP91P KW - Glucose KW - IY9XDZ35W2 KW - Apomorphine KW - N21FAR7B4S KW - Index Medicus KW - Receptors, Dopamine -- drug effects KW - Parkinson Disease, Secondary -- chemically induced KW - Animals KW - Glucose -- metabolism KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine -- pharmacology KW - Macaca mulatta KW - Autoradiography KW - Male KW - Female KW - Apomorphine -- pharmacology KW - Corpus Striatum -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77498824?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroreport&rft.atitle=Selective+metabolic+activation+by+apomorphine+in+striosomes+of+denervated+striatum+in+MPTP-induced+hemiparkinsonian+monkeys.&rft.au=Pontieri%2C+F+E%3BViola%2C+J+J%3BSokoloff%2C+L%3BPorrino%2C+L+J&rft.aulast=Pontieri&rft.aufirst=F&rft.date=1995-06-19&rft.volume=6&rft.issue=9&rft.spage=1330&rft.isbn=&rft.btitle=&rft.title=Neuroreport&rft.issn=09594965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-19 N1 - Date created - 1995-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metabolic activation and toxicity of some chemical agents to lung tissue and cells. AN - 77395849; 7598733 JF - Biochemical pharmacology AU - Gram, T E AD - Division of Cancer Treatment, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/06/16/ PY - 1995 DA - 1995 Jun 16 SP - 1721 EP - 1727 VL - 49 IS - 12 SN - 0006-2952, 0006-2952 KW - Xenobiotics KW - 0 KW - Index Medicus KW - Rats KW - Animals KW - Biotransformation KW - Rabbits KW - Mice KW - Lung Neoplasms -- chemically induced KW - Male KW - Female KW - Xenobiotics -- pharmacokinetics KW - Lung -- cytology KW - Lung -- drug effects KW - Xenobiotics -- toxicity KW - Lung -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77395849?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=Metabolic+activation+and+toxicity+of+some+chemical+agents+to+lung+tissue+and+cells.&rft.au=Gram%2C+T+E&rft.aulast=Gram&rft.aufirst=T&rft.date=1995-06-16&rft.volume=49&rft.issue=12&rft.spage=1721&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-03 N1 - Date created - 1995-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Low affinity binding of phorbol esters to protein kinase C and its recombinant cysteine-rich region in the absence of phospholipids. AN - 77334544; 7782331 AB - Binding of phorbol esters to protein kinase C (PKC) has been regarded as dependent on phospholipids, with phosphatidylserine being the most effective for reconstituting binding. By using a purified single cysteine-rich region from PKC delta expressed in Escherichia coli we were able to demonstrate that specific binding of [3H]phorbol 12,13-dibutyrate to the receptor still takes place in the absence of the phospholipid cofactor. However, [3H]phorbol 12,13-dibutyrate bound to the cysteine-rich region with 80-fold lower affinity in the absence than in the presence of 100 micrograms/ml phosphatidylserine. Similar results were observed with the intact recombinant PKC delta isolated from insect cells. When different phorbol derivatives were examined, distinct structure-activity relations for the cysteine-rich region were found in the presence and absence of phospholipid. Our results have potential implications for PKC translocation, for inhibitor design, and for PKC structural determination. JF - The Journal of biological chemistry AU - Kazanietz, M G AU - Barchi, J J AU - Omichinski, J G AU - Blumberg, P M AD - Molecular Mechanisms of Tumor Promotion Section, NCI, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1995/06/16/ PY - 1995 DA - 1995 Jun 16 SP - 14679 EP - 14684 VL - 270 IS - 24 SN - 0021-9258, 0021-9258 KW - Isoenzymes KW - 0 KW - Oligodeoxyribonucleotides KW - Phospholipids KW - Recombinant Proteins KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Protein Kinase C-delta KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Animals KW - Spodoptera KW - Escherichia coli -- genetics KW - Recombinant Proteins -- genetics KW - Protein Binding KW - Cloning, Molecular KW - Baculoviridae -- genetics KW - Base Sequence KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Cell Line KW - Protein Kinase C -- metabolism KW - Isoenzymes -- chemistry KW - Cysteine -- metabolism KW - Cysteine -- chemistry KW - Phorbol 12,13-Dibutyrate -- metabolism KW - Protein Kinase C -- genetics KW - Phospholipids -- metabolism KW - Protein Kinase C -- chemistry KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77334544?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Low+affinity+binding+of+phorbol+esters+to+protein+kinase+C+and+its+recombinant+cysteine-rich+region+in+the+absence+of+phospholipids.&rft.au=Kazanietz%2C+M+G%3BBarchi%2C+J+J%3BOmichinski%2C+J+G%3BBlumberg%2C+P+M&rft.aulast=Kazanietz&rft.aufirst=M&rft.date=1995-06-16&rft.volume=270&rft.issue=24&rft.spage=14679&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 - 1995-07-17 N1 - Date created - 1995-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Crystal structure of the cys2 activator-binding domain of protein kinase C delta in complex with phorbol ester. AN - 77330329; 7781068 AB - Protein kinase Cs (PKCs) are a ubiquitous family of regulatory enzymes that associate with membranes and are activated by diacylglycerol or tumor-promoting agonists such as phorbol esters. The structure of the second activator-binding domain of PKC delta has been determined in complex with phorbol 13-acetate, which binds in a groove between two pulled-apart beta strands at the tip of the domain. The C3, C4, and C20 phorbol oxygens form hydrogen bonds with main-chain groups whose orientation is controlled by a set of highly conserved residues. Phorbol binding caps the groove and forms a contiguous hydrophobic surface covering one-third of the domain, explaining how the activator promotes insertion of PKC into membranes. JF - Cell AU - Zhang, G AU - Kazanietz, M G AU - Blumberg, P M AU - Hurley, J H AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0580, USA. Y1 - 1995/06/16/ PY - 1995 DA - 1995 Jun 16 SP - 917 EP - 924 VL - 81 IS - 6 SN - 0092-8674, 0092-8674 KW - Isoenzymes KW - 0 KW - Macromolecular Substances KW - Phorbol Esters KW - Prkcd protein, mouse KW - EC 2.7.1.- KW - PRKCD protein, human KW - EC 2.7.11.13 KW - Protein Kinase C KW - Protein Kinase C-delta KW - Index Medicus KW - Molecular Structure KW - Membranes -- chemistry KW - Phorbol Esters -- chemistry KW - Animals KW - Phorbol Esters -- metabolism KW - Models, Molecular KW - Enzyme Activation KW - Humans KW - Mice KW - Amino Acid Sequence KW - Binding Sites KW - Membranes -- enzymology KW - In Vitro Techniques KW - Molecular Sequence Data KW - Crystallography KW - Sequence Homology, Amino Acid KW - Electrochemistry KW - Hydrogen Bonding KW - Protein Conformation KW - Protein Kinase C -- metabolism KW - Isoenzymes -- chemistry KW - Protein Kinase C -- genetics KW - Protein Kinase C -- chemistry KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77330329?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell&rft.atitle=Crystal+structure+of+the+cys2+activator-binding+domain+of+protein+kinase+C+delta+in+complex+with+phorbol+ester.&rft.au=Zhang%2C+G%3BKazanietz%2C+M+G%3BBlumberg%2C+P+M%3BHurley%2C+J+H&rft.aulast=Zhang&rft.aufirst=G&rft.date=1995-06-16&rft.volume=81&rft.issue=6&rft.spage=917&rft.isbn=&rft.btitle=&rft.title=Cell&rft.issn=00928674&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-19 N1 - Date created - 1995-07-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53-mediated transcriptional activity increases in differentiating epidermal keratinocytes in association with decreased p53 protein. AN - 77335102; 7784075 AB - The regulation of p53 protein synthesis and p53-mediated gene transactivation were evaluated in cultured mouse keratinocytes maintained as basal cells or induced to differentiate by Ca2+ > 0.1 mM. p53 protein half-life, p53 protein synthesis and the level of p53 mRNA decreased during terminal differentiation, as detected by immunoprecipitation with a panel of p53-specific antibodies and Northern blotting. Thus differentiating keratinocytes have lower levels of p53 protein. This decline is not observed following growth arrest alone, or in papilloma cell lines which do not terminally differentiate in response to Ca2+. In contrast, the ability of endogenous p53 to transactivate transcription from the PG13 CAT plasmid increased during differentiation in vitro. This change in activity cannot be explained by changes in p53 conformation or nuclear localization. Consistent with these findings, mRNA for the p53-mediated genes WAF1 and mdm-2 increased with Ca(2+)-induced differentiation in a time dependent manner, suggesting activation of p53 contributes to the differentiated phenotype. However, p53-null mice exhibit histologically normal skin and epidermal keratinocytes from these mice express the appropriate markers of differentiation and suppression of DNA synthesis in vitro when the [Ca2+] is > 0.1 mM. The observation that proliferating cells have higher levels of p53 protein which is less active for its function than differentiated cell types could have a consequence for the selection of p53 gene mutations during carcinogenesis, depending upon the stage of differentiation of the tumor cell type. JF - Oncogene AU - Weinberg, W C AU - Azzoli, C G AU - Chapman, K AU - Levine, A J AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1995/06/15/ PY - 1995 DA - 1995 Jun 15 SP - 2271 EP - 2279 VL - 10 IS - 12 SN - 0950-9232, 0950-9232 KW - p53 KW - RNA, Messenger KW - 0 KW - Transforming Growth Factor beta KW - Tumor Suppressor Protein p53 KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Calcium -- metabolism KW - Transforming Growth Factor beta -- pharmacology KW - Animals KW - Cells, Cultured KW - Cell Nucleus -- metabolism KW - RNA, Messenger -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Differentiation -- genetics KW - Transcription, Genetic KW - Mice KW - Up-Regulation KW - Chloramphenicol O-Acetyltransferase -- metabolism KW - RNA, Messenger -- biosynthesis KW - Tumor Suppressor Protein p53 -- biosynthesis KW - Keratinocytes -- drug effects KW - Tumor Suppressor Protein p53 -- drug effects KW - Keratinocytes -- cytology KW - Keratinocytes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77335102?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=p53-mediated+transcriptional+activity+increases+in+differentiating+epidermal+keratinocytes+in+association+with+decreased+p53+protein.&rft.au=Weinberg%2C+W+C%3BAzzoli%2C+C+G%3BChapman%2C+K%3BLevine%2C+A+J%3BYuspa%2C+S+H&rft.aulast=Weinberg&rft.aufirst=W&rft.date=1995-06-15&rft.volume=10&rft.issue=12&rft.spage=2271&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-18 N1 - Date created - 1995-07-18 N1 - Date revised - 2017-01-13 N1 - Gene symbol - p53 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Continuous infusion of the anti-CD22 immunotoxin IgG-RFB4-SMPT-dgA in patients with B-cell lymphoma: a phase I study. AN - 77328811; 7780133 AB - IgG-RFB4-SMPT-dgA consists of deglycosylated ricin A chain (dgA) coupled to the monoclonal antihuman CD22 antibody, RFB4. This study determined the maximally tolerated dose (MTD) of this immunotoxin (IT) administered as a continuous 8-day infusion to 18 patients with B-cell lymphoma (30% CD22+ tumor cells) over 8 days. The MTD was 19.2 mg/m2/192 h (maximum toxicity grade 1), with vascular leak syndrome (VLS) as dose-limiting toxicity (DLT) at 28.8 mg/m2/192 h (grades 3 through 5 in 7 of 11 patients). Predictors of severe VLS included serum IT concentrations greater than 1,000 ng/mL and the absence of circulating tumor cells. Decreased urine sodium excreted in 24 hours provided evidence for mild VLS without notable changes in serum albumin. Four partial responses, 3 minor responses, 6 stable disease, and 3 progression of disease were observed. The mean maximal serum concentration (Cmax) in initial courses at the MTD (19.2 mg/m2) was 443 +/- 144 ng/mL (n = 3; range, 326 to 604). At 28.8 mg/m2/192 h, the Cmax was highly variable (n = 11; mean, 1,102 +/- 702; range, 9.6 to 2,032 ng/mL). Human antimouse or antiricin antibodies developed in 6 of 16 (37.5%) patients after one course of IT. However, 10 eligible patients received multiple courses of IT. Changes in serum cytokines and cytokine receptors did not correlate with toxicity but decreased soluble interleukin-2 receptor concentrations correlated with clinical response. Comparison to a prior study with the same IT administered by intermittent bolus infusions (Amlot et al, Blood 82:2624, 1993) suggests similar clinical response, toxicity, and immunogenicity. JF - Blood AU - Sausville, E A AU - Headlee, D AU - Stetler-Stevenson, M AU - Jaffe, E S AU - Solomon, D AU - Figg, W D AU - Herdt, J AU - Kopp, W C AU - Rager, H AU - Steinberg, S M AD - Laboratory of Biological Chemistry, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 1995/06/15/ PY - 1995 DA - 1995 Jun 15 SP - 3457 EP - 3465 VL - 85 IS - 12 SN - 0006-4971, 0006-4971 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD KW - Antigens, Differentiation, B-Lymphocyte KW - CD22 protein, human KW - Cell Adhesion Molecules KW - Immunotoxins KW - Lectins KW - Sialic Acid Binding Ig-like Lectin 2 KW - Ricin KW - 9009-86-3 KW - Abridged Index Medicus KW - Index Medicus KW - Infusion Pumps KW - Ricin -- administration & dosage KW - Aged, 80 and over KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Female KW - Immunotoxins -- pharmacokinetics KW - Lymphoma, B-Cell -- therapy KW - Antigens, Differentiation, B-Lymphocyte -- immunology KW - Immunotoxins -- adverse effects KW - Antibodies, Monoclonal -- adverse effects KW - Immunotoxins -- administration & dosage KW - Antigens, CD -- immunology KW - Antibodies, Monoclonal -- administration & dosage KW - Antibodies, Monoclonal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77328811?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Continuous+infusion+of+the+anti-CD22+immunotoxin+IgG-RFB4-SMPT-dgA+in+patients+with+B-cell+lymphoma%3A+a+phase+I+study.&rft.au=Sausville%2C+E+A%3BHeadlee%2C+D%3BStetler-Stevenson%2C+M%3BJaffe%2C+E+S%3BSolomon%2C+D%3BFigg%2C+W+D%3BHerdt%2C+J%3BKopp%2C+W+C%3BRager%2C+H%3BSteinberg%2C+S+M&rft.aulast=Sausville&rft.aufirst=E&rft.date=1995-06-15&rft.volume=85&rft.issue=12&rft.spage=3457&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-20 N1 - Date created - 1995-07-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutations of the K-ras and p53 genes in gastric adenocarcinomas from a high-incidence region around Florence, Italy. AN - 77323228; 7780983 AB - K-ras and p53 gene mutations in intestinal-type gastric carcinomas from a high-incidence area around Florence, Italy, were studied by single strand conformation polymorphism and DNA sequencing analysis. Single-strand conformation polymorphism analysis of K-ras indicated aberrant bands in 13 of 34 cases. Sequencing revealed point mutations in 7 (including two at a previously unreported site in codon 11), a significantly higher frequency than reported in countries other than Japan. No K-ras mutations were identified in stage III tumors. Single-strand conformation polymorphisms in p53 exons 5-8 occurred in 30 of 34 cases, with mutations identifiable by direct sequencing in 65% of the cases. Of these, 91% were base substitutions, a value similar to that usually reported, but the percentage of G:C to A:T transitions (90% in this study, 89% in all published European cases combined) differed significantly from that in Oriental cases (48%). The percentage of A:T to G:C transitions was greater in Oriental (22%) than European cases (2%), as was also true for transversions (30% in Oriental tumors, 9% in European tumors). The frequency of mutations at CpG sites (14%) varied significantly from the 67% in cases from a neighboring region in Italy. Helicobacter pylori infection was established in 19 cases and was somewhat more common in cases lacking a p53 mutation. JF - Cancer research AU - Hongyo, T AU - Buzard, G S AU - Palli, D AU - Weghorst, C M AU - Amorosi, A AU - Galli, M AU - Caporaso, N E AU - Fraumeni, J F AU - Rice, J M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1995/06/15/ PY - 1995 DA - 1995 Jun 15 SP - 2665 EP - 2672 VL - 55 IS - 12 SN - 0008-5472, 0008-5472 KW - K-ras KW - p53 KW - DNA Primers KW - 0 KW - DNA, Neoplasm KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Helicobacter Infections -- diagnosis KW - Tumor Suppressor Protein p53 -- biosynthesis KW - Neoplasm Staging KW - Polymorphism, Genetic KW - Exons KW - Humans KW - DNA, Neoplasm -- analysis KW - Europe KW - Helicobacter Infections -- epidemiology KW - Japan -- epidemiology KW - Polymerase Chain Reaction KW - Helicobacter pylori -- isolation & purification KW - Tumor Suppressor Protein p53 -- analysis KW - Alleles KW - Base Sequence KW - Point Mutation KW - Molecular Sequence Data KW - Incidence KW - Italy -- epidemiology KW - Geography KW - Immunohistochemistry KW - Genes, ras KW - Stomach Neoplasms -- pathology KW - Adenocarcinoma -- epidemiology KW - Genes, p53 KW - Stomach Neoplasms -- genetics KW - Adenocarcinoma -- genetics KW - Stomach Neoplasms -- epidemiology KW - Mutation KW - Adenocarcinoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77323228?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutations+of+the+K-ras+and+p53+genes+in+gastric+adenocarcinomas+from+a+high-incidence+region+around+Florence%2C+Italy.&rft.au=Hongyo%2C+T%3BBuzard%2C+G+S%3BPalli%2C+D%3BWeghorst%2C+C+M%3BAmorosi%2C+A%3BGalli%2C+M%3BCaporaso%2C+N+E%3BFraumeni%2C+J+F%3BRice%2C+J+M&rft.aulast=Hongyo&rft.aufirst=T&rft.date=1995-06-15&rft.volume=55&rft.issue=12&rft.spage=2665&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 - 1995-07-19 N1 - Date created - 1995-07-19 N1 - Date revised - 2017-01-13 N1 - Gene symbol - K-ras; p53 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I study of phenylacetate administered twice daily to patients with cancer. AN - 77306026; 7773944 AB - The growth-inhibiting and differentiating effects of sodium phenylacetate against hematopoietic and solid tumor cell lines has aroused clinical interest in its use as an anticancer drug. In an earlier Phase I trial of phenylacetate aimed at maintaining serum drug concentrations in the range that proved active in vitro (> 250 micrograms/ml) for 2 consecutive weeks, infusion rates approached the maximum velocity of drug elimination and commonly resulted in drug accumulation and reversible dose-limiting neurologic toxicity. In this study, the authors described the nonlinear pharmacokinetics, metabolism, toxicity, and clinical activity of phenylacetate. The treatment regimen of this Phase I study was designed to expose patients intermittently to drug concentrations exceeding 250 micrograms/ml and to allow time for drug elimination to occur between doses to minimize accumulation. Sodium phenylacetate was administered as a 1-hour infusion twice daily (8 a.m., 5 p.m.) at two dose levels of 125 and 150 mg/kg for a 2-week period. Therapy was repeated at 4-week intervals for patients who did not experience dose-limiting toxicity or disease progression. Eighteen patients (4 of whom previously were treated with phenylacetate by continuous intravenous infusion) received 27 cycles of therapy. Detailed pharmacokinetic studies for eight patients indicated that phenylacetate induced its own clearance by a factor of 27% in a 2-week period. Dose-limiting toxicity, consisting of reversible central nervous system depression, was observed for three patients at the second dose level. One patient with refractory malignant glioma had a partial response, and one with hormone-independent prostate cancer achieved a 50% decline in prostate specific antigen level, which was maintained for 1 month. Phenylacetate administered at a dose of 125 mg/kg twice daily for 2 consecutive weeks is well tolerated. High grade gliomas and advanced prostate cancer are reasonable targets for Phase II clinical trials. JF - Cancer AU - Thibault, A AU - Samid, D AU - Cooper, M R AU - Figg, W D AU - Tompkins, A C AU - Patronas, N AU - Headlee, D J AU - Kohler, D R AU - Venzon, D J AU - Myers, C E AD - Clinical Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1576, USA. Y1 - 1995/06/15/ PY - 1995 DA - 1995 Jun 15 SP - 2932 EP - 2938 VL - 75 IS - 12 SN - 0008-543X, 0008-543X KW - Antineoplastic Agents KW - 0 KW - Phenylacetates KW - phenylacetic acid KW - ER5I1W795A KW - Abridged Index Medicus KW - Index Medicus KW - Drug Administration Schedule KW - Infusions, Intravenous KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Female KW - Phenylacetates -- administration & dosage KW - Phenylacetates -- pharmacokinetics KW - Neoplasms -- drug therapy KW - Antineoplastic Agents -- administration & dosage KW - Antineoplastic Agents -- pharmacokinetics KW - Phenylacetates -- toxicity KW - Antineoplastic Agents -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77306026?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer&rft.atitle=Phase+I+study+of+phenylacetate+administered+twice+daily+to+patients+with+cancer.&rft.au=Thibault%2C+A%3BSamid%2C+D%3BCooper%2C+M+R%3BFigg%2C+W+D%3BTompkins%2C+A+C%3BPatronas%2C+N%3BHeadlee%2C+D+J%3BKohler%2C+D+R%3BVenzon%2C+D+J%3BMyers%2C+C+E&rft.aulast=Thibault&rft.aufirst=A&rft.date=1995-06-15&rft.volume=75&rft.issue=12&rft.spage=2932&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-07 N1 - Date created - 1995-07-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - One-electron reduction of arenediazonium compounds by physiological electron donors generates aryl radicals. An EPR and spin trapping investigation. AN - 77275785; 7750162 AB - Arenediazonium compounds (ArN2+) are strong oxidizing agents, which upon one-electron reduction decompose, releasing aryl radicals (Ar.). The present studies were undertaken to determine whether reductive fragmentation of ArN2+ can be induced by biologically relevant electron donors. We found that 4-X-Ph-N2+ (where X: -NO2, -Br, -Cl, -OMe and -N(Et)2) decomposes to the respective aryl radicals when reduced by ascorbate, NADH, potassium ferrocyanide, catechol or p-hydroquinone in aqueous solutions. Radical identification was based on analysis of the EPR spectra of spin adducts formed by reaction of these radicals with spin traps 2-methyl-2-nitrosopropane (MNP), 3,5-dibromo-4-nitrosobenzene sulphonate (DBNBS) or 5,5-dimethyl-1-pyrroline N-oxide (DMPO). This study shows that reduction of arenediazonium ions can be a convenient method for generating aryl radicals in aqueous solutions. In addition, this investigation confirms that biological reducing agents are capable of inducing fragmentation of ArN2+ into aryl radicals. This reaction may be pertinent to some biological actions of arenediazonium compounds. JF - Chemico-biological interactions AU - Reszka, K J AU - Chignell, C F AD - Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, NC 27709, USA. Y1 - 1995/06/14/ PY - 1995 DA - 1995 Jun 14 SP - 223 EP - 234 VL - 96 IS - 3 SN - 0009-2797, 0009-2797 KW - Diazonium Compounds KW - 0 KW - Free Radicals KW - Nitroso Compounds KW - Oxidants KW - Spin Labels KW - tert-nitrosobutane KW - JGX6N17V2U KW - Ascorbic Acid KW - PQ6CK8PD0R KW - Index Medicus KW - Oxidation-Reduction KW - Electron Spin Resonance Spectroscopy KW - Nitroso Compounds -- chemistry KW - Ascorbic Acid -- chemistry KW - Oxidants -- chemistry KW - Diazonium Compounds -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77275785?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemico-biological+interactions&rft.atitle=One-electron+reduction+of+arenediazonium+compounds+by+physiological+electron+donors+generates+aryl+radicals.+An+EPR+and+spin+trapping+investigation.&rft.au=Reszka%2C+K+J%3BChignell%2C+C+F&rft.aulast=Reszka&rft.aufirst=K&rft.date=1995-06-14&rft.volume=96&rft.issue=3&rft.spage=223&rft.isbn=&rft.btitle=&rft.title=Chemico-biological+interactions&rft.issn=00092797&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-22 N1 - Date created - 1995-06-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular cloning of cDNA encoding the small subunit of Drosophila transcription initiation factor TFIIF. AN - 19356715; 8731115 AB - Transcription initiation factor TFIIF is a tetramer consisting of two large subunits (TFIIF alpha or RAP74) and two small subunits (TFIIF beta or RAP30). We report here the molecular cloning of a Drosophila cDNA encoding TFIIF beta. The cDNA clone contains an open-reading frame encoding a 277 amino acid polypeptide having a calculated molecular mass of 32,107 Da. Comparison of the deduced amino acid sequence with the corresponding sequences from vertebrates showed only 50% identity, with four insertion/deletion points. For transcription activity in a TFIIF-depleted Drosophila nuclear extract, both TFIIF alpha and TFIIF beta are essential. Moreover, Drosophila TFIIF beta interacts with both Drosophila and human TFIIF alpha in vitro. Thus we conclude that isolated cDNA encodes bona fide TFIIF beta. The structural domains of TFIIF beta and its sequence similarity to bacterial delta factors are discussed. Images JF - Nucleic Acids Research AU - Gong, D W AU - Mortin, M A AU - Horikoshi, M AU - Nakatani, Y AD - National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/06/11/ PY - 1995 DA - 1995 Jun 11 SP - 1882 EP - 1886 PB - Oxford University Press, Oxford Journals, Great Clarendon Street VL - 23 IS - 11 SN - 0305-1048, 0305-1048 KW - Microbiology Abstracts B: Bacteriology; Entomology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Clonal deletion KW - Insertion KW - Transcription initiation factor TFIIF KW - Drosophila KW - Amino acid sequence KW - J 02310:Genetics & Taxonomy KW - N 14815:Nucleotide Sequence KW - Z 05360:Genetics and Evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19356715?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+Acids+Research&rft.atitle=Molecular+cloning+of+cDNA+encoding+the+small+subunit+of+Drosophila+transcription+initiation+factor+TFIIF.&rft.au=Gong%2C+D+W%3BMortin%2C+M+A%3BHorikoshi%2C+M%3BNakatani%2C+Y&rft.aulast=Gong&rft.aufirst=D&rft.date=1995-06-11&rft.volume=23&rft.issue=11&rft.spage=1882&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-12-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Clonal deletion; Insertion; Transcription initiation factor TFIIF; Amino acid sequence; Drosophila ER - TY - JOUR T1 - Site-directed mutagenesis identifies residues involved in ligand recognition in the human A2a adenosine receptor. AN - 77309785; 7775460 AB - The A2a adenosine receptor is a member of the G-protein coupled receptor family, and its activation stimulates cyclic AMP production. To determine the residues which are involved in ligand binding, several residues in transmembrane domains 5-7 were individually replaced with alanine and other amino acids. The binding properties of the resultant mutant receptors were determined in transfected COS-7 cells. To study the expression levels in COS-7 cells, mutant receptors were tagged at their amino terminus with a hemagglutinin epitope, which allowed their immunological detection in the plasma membrane by the monoclonal antibody 12CA5. The functional properties of mutant receptors were determined by measuring stimulation of adenylate cyclase. Specific binding of [3H]CGS 21680 (15 nM) and [3H]XAC (4 nM), an A2a agonist and antagonist, respectively, was absent in the following Ala mutants: F182A, H250A, N253A, I274A, H278A, and S281A, although they were well expressed in the plasma membrane. The hydroxy group of Ser-277 is required for high affinity binding of agonists, but not antagonists. An N181S mutant lost affinity for adenosine agonists substituted at N6 or C-2, but not at C-5'. The mutant receptors I274A, S277A, and H278A showed full stimulation of adenylate cyclase at high concentrations of CGS 21680. The functional agonist potencies at mutant receptors that lacked radioligand binding were > 30-fold less than those at the wild type receptor. His-250 appears to be a required component of a hydrophobic pocket, and H-bonding to this residue is not essential. On the other hand, replacement of His-278 with other aromatic residues was not tolerated in ligand binding. Thus, some of the residues targeted in this study may be involved in the direct interaction with ligands in the human A2a adenosine receptor. A molecular model based on the structure of rhodopsin, in which the 5'-NH in NECA is hydrogen bonded to Ser-277 and His-278, was developed in order to visualize the environment of the ligand binding site. JF - The Journal of biological chemistry AU - Kim, J AU - Wess, J AU - van Rhee, A M AU - Schöneberg, T AU - Jacobson, K A AD - Molecular Recognition Section, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/06/09/ PY - 1995 DA - 1995 Jun 09 SP - 13987 EP - 13997 VL - 270 IS - 23 SN - 0021-9258, 0021-9258 KW - Ligands KW - 0 KW - Receptors, Purinergic P1 KW - Histidine KW - 4QD397987E KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Models, Molecular KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Histidine -- metabolism KW - Structure-Activity Relationship KW - Binding Sites KW - Receptors, Purinergic P1 -- chemistry KW - Receptors, Purinergic P1 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77309785?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Site-directed+mutagenesis+identifies+residues+involved+in+ligand+recognition+in+the+human+A2a+adenosine+receptor.&rft.au=Kim%2C+J%3BWess%2C+J%3Bvan+Rhee%2C+A+M%3BSch%C3%B6neberg%2C+T%3BJacobson%2C+K+A&rft.aulast=Kim&rft.aufirst=J&rft.date=1995-06-09&rft.volume=270&rft.issue=23&rft.spage=13987&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 - 1995-07-10 N1 - Date created - 1995-07-10 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - P28647; SWISSPROT; P11616; P30543; P11617; P30542; P33765; P08483; P29275; P25103; P29274; P28190; P04274; U04201; GENBANK N1 - SuppNotes - Cited By: Neuroscience. 1994 Dec;63(3):765-73 [7898676] J Biol Chem. 1994 Nov 11;269(45):27900-6 [7961722] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] Mol Cell Biol. 1983 Feb;3(2):280-9 [6300662] Mol Pharmacol. 1983 May;23(3):576-84 [6306429] Mol Pharmacol. 1985 Jun;27(6):595-9 [2987658] Methods Enzymol. 1987;152:684-704 [3657593] J Biol Chem. 1989 Aug 15;264(23):13572-8 [2547766] Proc Natl Acad Sci U S A. 1989 Sep;86(17):6572-6 [2771944] J Pharmacol Exp Ther. 1989 Dec;251(3):888-93 [2600819] J Mol Biol. 1990 Jun 20;213(4):899-929 [2359127] Physiol Rev. 1990 Jul;70(3):761-845 [2194223] Biochem Biophys Res Commun. 1990 Dec 31;173(3):1169-78 [2125216] Mol Pharmacol. 1991 Jul;40(1):1-7 [1857334] Mol Pharmacol. 1991 Jul;40(1):8-15 [1649965] EMBO J. 1991 Dec;10(12):3729-34 [1657592] J Med Chem. 1992 Feb 7;35(3):407-22 [1738138] Mol Pharmacol. 1992 Feb;41(2):352-9 [1311411] J Recept Res. 1992;12(2):149-69 [1583620] J Biol Chem. 1992 May 25;267(15):10764-70 [1587851] Mol Pharmacol. 1992 Jul;42(1):123-33 [1635550] Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7432-6 [1323836] Drug Des Discov. 1992;9(1):49-67 [1457698] EMBO J. 1993 Apr;12(4):1693-703 [8385611] Nature. 1993 Apr 22;362(6422):770-2 [8469290] Pharmacol Biochem Behav. 1993 Aug;45(4):951-8 [8105493] J Biol Chem. 1994 Jan 28;269(4):2373-6 [8300561] J Biol Chem. 1994 Jan 28;269(4):2728-32 [8300604] J Med Chem. 1994 Mar 4;37(5):636-46 [8126704] Mol Pharmacol. 1994 May;45(5):871-7 [8190104] Mol Pharmacol. 1994 Jun;45(6):1101-11 [8022403] J Neurochem. 1994 Oct;63(4):1477-84 [7931300] J Biol Chem. 1994 Jul 22;269(29):18870-6 [8034642] Eur J Pharmacol. 1994 May 2;256(3):263-8 [8045270] J Biol Chem. 1994 Jul 8;269(27):18016-20 [8027060] Prog Neuropsychopharmacol Biol Psychiatry. 1994 May;18(3):545-53 [8078988] Eur J Pharmacol. 1994 Jun 15;268(1):95-104 [7925617] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutagens from heated Chinese and U.S. cooking oils. AN - 77352763; 7791233 AB - The lung cancer incidence in Chinese women is among the highest in the world, but tobacco smoking accounts for only a minority of the cancers. Epidemiologic investigations of lung cancer among Chinese women have implicated exposure to indoor air pollution from wok cooking, where the volatile emissions from unrefined cooking oils are mutagenic. This study was conducted to identify and quantify the potentially mutagenic substances emitted from a variety of cooking oils heated to the temperatures typically used in wok cooking. Several cooking oils and fatty acids were heated in a wok to boiling, at temperatures (for the cooking oils) that ranged from 240 degrees C to 280 degrees C (typical cooking temperatures in Shanghai, China). The oils tested were unrefined Chinese rapeseed, refined U.S. rapeseed (known as canola), Chinese soybean, and Chinese peanut in addition to linolenic, linoleic, and erucic fatty acids. Condensates of the emissions were collected and tested in the Salmonella mutation assay (using Salmonella typhimurium tester strains TA98 and TA104). Volatile decomposition products also were subjected to gas chromatography and mass spectroscopy. Aldehydes were detected using high-performance liquid chromatography and UV spectroscopy. 1,3-Butadiene, benzene, acrolein, formaldehyde, and other related compounds were qualitatively and quantitatively detected, with emissions tending to be highest for unrefined Chinese rapeseed oil and lowest for peanut oil. The emission of 1,3-butadiene and benzene was approximately 22-fold and 12-fold higher, respectively, from heated unrefined Chinese rapeseed oil than from heated peanut oil. Lowering the cooking temperatures or adding an antioxidant, such as butylated hydroxyanisole, before cooking decreased the amount of these volatile emissions. Among the individual fatty acids tested, heated linolenic acid produced the greatest quantities of 1,3-butadiene, benzene, and acrolein. Separately, the mutagenicity of individual volatile emission condensates was correlated with linolenic acid content (r = .83; P = .0004). Condensates from heated linolenic acid, but not linoleic or erucic acid, were highly mutagenic. These studies, combined with experimental and epidemiologic findings, suggest that high-temperature wok cooking with unrefined Chinese rapeseed oil may increase lung cancer risk. This study indicates methods that may reduce that risk. The common use of wok cooking in China might be an important but controllable risk factor in the etiology of lung cancer. In the United States, where cooking oils are usually refined for purity, additional studies should be conducted to further quantify the potential risks of such methods of cooking. JF - Journal of the National Cancer Institute AU - Shields, P G AU - Xu, G X AU - Blot, W J AU - Fraumeni, J F AU - Trivers, G E AU - Pellizzari, E D AU - Qu, Y H AU - Gao, Y T AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Md 20892, USA. Y1 - 1995/06/07/ PY - 1995 DA - 1995 Jun 07 SP - 836 EP - 841 VL - 87 IS - 11 SN - 0027-8874, 0027-8874 KW - Fatty Acids KW - 0 KW - Mutagens KW - Oils, Volatile KW - Index Medicus KW - Humans KW - China -- epidemiology KW - Cooking KW - Gas Chromatography-Mass Spectrometry KW - United States -- epidemiology KW - Time Factors KW - Female KW - Hot Temperature KW - Lung Neoplasms -- epidemiology KW - Fatty Acids -- adverse effects KW - Oils, Volatile -- adverse effects KW - Lung Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77352763?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Mutagens+from+heated+Chinese+and+U.S.+cooking+oils.&rft.au=Shields%2C+P+G%3BXu%2C+G+X%3BBlot%2C+W+J%3BFraumeni%2C+J+F%3BTrivers%2C+G+E%3BPellizzari%2C+E+D%3BQu%2C+Y+H%3BGao%2C+Y+T%3BHarris%2C+C+C&rft.aulast=Shields&rft.aufirst=P&rft.date=1995-06-07&rft.volume=87&rft.issue=11&rft.spage=836&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 - 1995-07-27 N1 - Date created - 1995-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lung cancer in radon-exposed miners and estimation of risk from indoor exposure. AN - 77352724; 7791231 AB - Radioactive radon is an inert gas that can migrate from soils and rocks and accumulate in enclosed areas, such as homes and underground mines. Studies of miners show that exposure to radon decay products causes lung cancer. Consequently, it is of public health interest to estimate accurately the consequences of daily, low-level exposure in homes to this known carcinogen. Epidemiologic studies of residential radon exposure are burdened by an inability to estimate exposure accurately, low total exposure, and subsequent small excess risks. As a result, the studies have been inconclusive to date. Estimates of the hazard posed by residential radon have been based on analyses of data on miners, with recent estimates based on a pooling of four occupational cohort studies of miners, including 360 lung cancer deaths. To more fully describe the lung cancer risk in radon-exposed miners, we pooled original data from 11 studies of radon-exposed underground miners, conducted a comprehensive analysis, and developed models for estimating radon-associated lung cancer risk. We pooled original data from 11 cohort studies of radon-exposed underground miners, including 65,000 men and more than 2700 lung cancer deaths, and fit various relative risk (RR) regression models. The RR relationship for cumulative radon progeny exposure was consistently linear in the range of miner exposures, suggesting that exposures at lower levels, such as in homes, would carry some risk. The exposure-response trend for never-smokers was threefold the trend for smokers, indicating a greater RR for exposure in never-smokers. The RR from exposure diminished with time since the exposure occurred. For equal total exposure, exposures of long duration (and low rate) were more harmful than exposures of short duration (and high rate). In the miners, about 40% of all lung cancer deaths may be due to radon progeny exposure, 70% of lung cancer deaths in never-smokers, and 39% of lung cancer deaths in smokers. In the United States, 10% of all lung cancer deaths might be due to indoor radon exposure, 11% of lung cancer deaths in smokers, and 30% of lung cancer deaths in never-smokers. This risk model estimates that reducing radon in all homes exceeding the U. S. Environmental Protection Agency's recommended action level may reduce lung cancer deaths about 2%-4%. These estimates should be interpreted with caution, because concomitant exposures of miners to agents such as arsenic or diesel exhaust may modify the radon effect and, when considered together with other differences between homes and mines, might reduce the generalizability of findings in miners. JF - Journal of the National Cancer Institute AU - Lubin, J H AU - Boice, J D AU - Edling, C AU - Hornung, R W AU - Howe, G R AU - Kunz, E AU - Kusiak, R A AU - Morrison, H I AU - Radford, E P AU - Samet, J M AD - Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer Institute, Bethesda, Md 20892-7368, USA. Y1 - 1995/06/07/ PY - 1995 DA - 1995 Jun 07 SP - 817 EP - 827 VL - 87 IS - 11 SN - 0027-8874, 0027-8874 KW - Radon KW - Q74S4N8N1G KW - Index Medicus KW - Risk KW - Humans KW - Adult KW - Smoking -- adverse effects KW - Aged KW - Middle Aged KW - Mining KW - Time Factors KW - Sex Distribution KW - Male KW - Air Pollution, Indoor -- adverse effects KW - Occupational Exposure -- adverse effects KW - Lung Neoplasms -- mortality KW - Lung Neoplasms -- chemically induced KW - Radon -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77352724?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Lung+cancer+in+radon-exposed+miners+and+estimation+of+risk+from+indoor+exposure.&rft.au=Lubin%2C+J+H%3BBoice%2C+J+D%3BEdling%2C+C%3BHornung%2C+R+W%3BHowe%2C+G+R%3BKunz%2C+E%3BKusiak%2C+R+A%3BMorrison%2C+H+I%3BRadford%2C+E+P%3BSamet%2C+J+M&rft.aulast=Lubin&rft.aufirst=J&rft.date=1995-06-07&rft.volume=87&rft.issue=11&rft.spage=817&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 - 1995-07-27 N1 - Date created - 1995-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oral contraceptives and breast cancer risk among younger women. AN - 77350010; 7791232 AB - Several studies have suggested a link between oral contraceptive use and breast cancer in younger women, but it is possible that chance or bias, including selective screening of contraceptive users, contributed to the putative association. Given that oral contraceptives were first marketed in the United States in the early 1960s, we conducted a population-based case-control study to examine the relationship between use of oral contraceptives and breast cancer among women in a recently assembled cohort, focusing on women younger than 45 years of age who had the opportunity for exposure throughout their entire reproductive years. Breast cancer patients and healthy control subjects were identified, the latter group by random-digit dialing, in Atlanta, Ga., Seattle/Puget Sound, Wash., and central New Jersey. In Seattle and New Jersey, the study was confined to women 20 through 44 years of age; in Atlanta the age range was extended through 54 years. Patients included women with in situ or invasive breast cancer newly diagnosed during the period of May 1, 1990, through December 31, 1992. In-person interviews were completed by 2203 (86.4%) of 2551 eligible patients and 2009 (78.1%) of 2571 eligible control subjects. Analyses focused on women younger than 45 years of age (1648 patients and 1505 control subjects) to maximize opportunities for extended exposure. Logistic regression analyses were used to obtain maximum likelihood estimates of relative risks (RRs) and their 95% confidence intervals (CIs). Among women younger than 45 years, oral contraceptive use for 6 months or longer was associated with an RR for breast cancer of 1.3 (95% CI = 1.1-1.5). Risks were enhanced for breast cancers occurring prior to age 35 years (RR = 1.7; 95% CI = 1.2-2.6), with the RR rising to 2.2 (95% CI = 1.2-4.1) for users of 10 or more years. The RR for breast cancer for those whose oral contraceptive use began early (before age 18 years) and continued long-term (> 10 years) was even higher (RR = 3.1; 95% CI = 1.4-6.7). The RRs observed for those who used oral contraceptives within 5 years of cancer diagnosis were higher than for those who had not, with the effect most marked for women younger than age 35 years (RR = 2.0; 95% CI = 1.3-3.1). Oral contraceptive associations were also strongest for cancers diagnosed at advanced stages. Evaluation of screening histories and methods of diagnosis failed to support the speculation that associations could be due to selective screening. Among women 45 years of age and older, no associations of risk with use of oral contraceptives were noted. The relationship between oral contraceptives and breast cancer in young women appears to have a biologic basis rather than to be an artifact or the result of bias. JF - Journal of the National Cancer Institute AU - Brinton, L A AU - Daling, J R AU - Liff, J M AU - Schoenberg, J B AU - Malone, K E AU - Stanford, J L AU - Coates, R J AU - Gammon, M D AU - Hanson, L AU - Hoover, R N AD - Environmental Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/06/07/ PY - 1995 DA - 1995 Jun 07 SP - 827 EP - 835 VL - 87 IS - 11 SN - 0027-8874, 0027-8874 KW - Contraceptives, Oral, Hormonal KW - 0 KW - Index Medicus KW - Population KW - United States KW - Age Factors KW - Research Methodology KW - Breast Cancer KW - Oral Contraceptives KW - Contraceptive Methods KW - Correlation Studies KW - Developed Countries KW - Risk Assessment KW - Evaluation KW - Population Characteristics KW - Demographic Factors KW - Diseases KW - Family Planning KW - North America KW - Americas KW - Statistical Studies KW - Studies KW - Cancer KW - Case Control Studies KW - Northern America KW - Neoplasms KW - Contraception KW - Risk KW - Neoplasm Invasiveness KW - Carcinoma in Situ -- chemically induced KW - Logistic Models KW - Risk Factors KW - Humans KW - Adult KW - Case-Control Studies KW - Time Factors KW - Female KW - Breast Neoplasms -- pathology KW - Contraceptives, Oral, Hormonal -- adverse effects KW - Breast Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77350010?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Oral+contraceptives+and+breast+cancer+risk+among+younger+women.&rft.au=Brinton%2C+L+A%3BDaling%2C+J+R%3BLiff%2C+J+M%3BSchoenberg%2C+J+B%3BMalone%2C+K+E%3BStanford%2C+J+L%3BCoates%2C+R+J%3BGammon%2C+M+D%3BHanson%2C+L%3BHoover%2C+R+N&rft.aulast=Brinton&rft.aufirst=L&rft.date=1995-06-07&rft.volume=87&rft.issue=11&rft.spage=827&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 - 1995-07-27 N1 - Date created - 1995-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pax5 (BSAP) regulates the murine immunoglobulin 3' alpha enhancer by suppressing binding of NF-alpha P, a protein that controls heavy chain transcription. AN - 77325780; 7777508 AB - The Pax5 transcription factor BSAP (B-cell-specific activator protein) is known to bind to and repress the activity of the immunoglobulin heavy chain 3' alpha enhancer. We have detected an element--designated alpha P--that lies approximately 50 bp downstream of the BSAP binding site 1 and is required for maximal enhancer activity. In vitro binding experiments suggest that the 40-kDa protein that binds to this element (NF-alpha P) is a member of the Ets family present in both B-cell and plasma-cell nuclei. However, in vivo footprint analysis suggests that the alpha P site is occupied only in plasma cells, whereas the BSAP site is occupied in B cells but not in plasma cells. When Pax5 binding to the enhancer in B cells was blocked in vivo by transfection with a triple-helix-forming oligonucleotide an alpha P footprint appeared and endogenous immunoglobulin heavy chain transcripts increased. The triple-helix-forming oligonucleotide also increased enhancer activity of a transfected construct in B cells, but only when the alpha P site was intact. Pax5 thus regulates the 3' alpha enhancer and immunoglobulin gene transcription by blocking activation by NF-alpha P. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Neurath, M F AU - Max, E E AU - Strober, W AD - Mucosal Immunity Section, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892-1890, USA. Y1 - 1995/06/06/ PY - 1995 DA - 1995 Jun 06 SP - 5336 EP - 5340 VL - 92 IS - 12 SN - 0027-8424, 0027-8424 KW - DNA Primers KW - 0 KW - DNA-Binding Proteins KW - Immunoglobulin Heavy Chains KW - Nuclear Proteins KW - PAX5 Transcription Factor KW - Pax5 protein, mouse KW - RNA, Messenger KW - Transcription Factors KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Plasmacytoma -- genetics KW - Base Sequence KW - Tumor Cells, Cultured KW - Molecular Sequence Data KW - Mice KW - RNA, Messenger -- biosynthesis KW - Binding Sites KW - Transcription Factors -- metabolism KW - Enhancer Elements, Genetic KW - Genes, Immunoglobulin KW - Transcription, Genetic KW - Nuclear Proteins -- metabolism KW - Immunoglobulin Heavy Chains -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77325780?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pax5+%28BSAP%29+regulates+the+murine+immunoglobulin+3%27+alpha+enhancer+by+suppressing+binding+of+NF-alpha+P%2C+a+protein+that+controls+heavy+chain+transcription.&rft.au=Neurath%2C+M+F%3BMax%2C+E+E%3BStrober%2C+W&rft.aulast=Neurath&rft.aufirst=M&rft.date=1995-06-06&rft.volume=92&rft.issue=12&rft.spage=5336&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 - 1995-07-12 N1 - Date created - 1995-07-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1994 Jun 3;77(5):737-47 [8205622] J Biol Chem. 1994 May 27;269(21):15310-7 [8195169] Genes Dev. 1994 Sep 15;8(18):2212-26 [7958890] Cell. 1994 Dec 2;79(5):901-12 [8001127] Immunol Rev. 1986 Oct;93:35-51 [3491037] Science. 1989 Nov 10;246(4931):810-3 [2814502] Mol Cell Biol. 1989 Dec;9(12):5594-601 [2511438] Nature. 1990 Mar 8;344(6262):165-8 [2106628] Eur J Immunol. 1991 Jun;21(6):1499-504 [1904361] Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):8227-31 [1896473] Mol Cell Biol. 1991 Nov;11(11):5551-61 [1922063] Proc Natl Acad Sci U S A. 1992 Feb 1;89(3):1021-5 [1736283] J Immunol. 1992 May 1;148(9):2909-17 [1349323] Mol Cell Biol. 1992 Jun;12(6):2662-72 [1375324] Hybridoma. 1992 Jun;11(3):277-94 [1500064] Genes Dev. 1992 Sep;6(9):1589-607 [1516825] Mol Cell Biol. 1993 Mar;13(3):1547-53 [8441396] Science. 1993 Jul 2;261(5117):82-6 [8316859] Mol Cell Biol. 1993 Oct;13(10):5957-69 [8413200] J Immunol. 1994 Mar 15;152(6):2904-11 [8144891] J Exp Med. 1994 Apr 1;179(4):1099-108 [7511679] J Immunol. 1994 Jul 15;153(2):730-42 [8021508] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The orphan receptor TAK1 acts as a repressor of RAR-, RXR- and T3R-mediated signaling pathways. AN - 77321490; 7779113 AB - Recently, we reported the cloning and characterization of the novel orphan receptor TAK1. In this study, we analyze the interaction of TAK1 with a variety of response elements (RE's) and demonstrate that TAK1 binds effectively to RE's composed of the core motif PuGGTCA configured in direct repeats spaced by one or more nucleotides. TAK1 bound poorly to palindromic or inverted palindromic motifs and was unable to bind to a single core motif, suggesting that a dimeric site is required for binding. Transfection experiments with CV-1 cells revealed that TAK1 is able to repress retinoid- and thyroid-hormone-induced transactivation through a subset of retinoid and thyroid hormone RE's. Our studies indicate that the antagonism of RAR-mediated transactivation does not involve the formation of heterodimers between TAK1 and RAR or RXR but is due to the competition of TAK1 homodimers with RAR-RXR heterodimers and RXR homodimers for binding to RARE and RXRE, respectively. Our results suggest that the orphan receptor TAK1 can be a negative modulator of the regulation of gene expression mediated by retinoid and thyroid hormone signaling pathways. JF - Biochemical and biophysical research communications AU - Hirose, T AU - Apfel, R AU - Pfahl, M AU - Jetten, A M AD - Cell Biology Section, National Institute of Environmental Health and Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/06/06/ PY - 1995 DA - 1995 Jun 06 SP - 83 EP - 91 VL - 211 IS - 1 SN - 0006-291X, 0006-291X KW - DNA-Binding Proteins KW - 0 KW - NR2C2 protein, human KW - Oligonucleotide Probes KW - Receptors, Retinoic Acid KW - Receptors, Steroid KW - Receptors, Thyroid Hormone KW - Recombinant Proteins KW - Repressor Proteins KW - Retinoid X Receptors KW - Transcription Factors KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Humans KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Transfection KW - Recombinant Proteins -- metabolism KW - Cercopithecus aethiops KW - Molecular Sequence Data KW - Cell Line KW - DNA-Binding Proteins -- metabolism KW - Transcription Factors -- physiology KW - Repressor Proteins -- biosynthesis KW - Receptors, Retinoic Acid -- physiology KW - Receptors, Retinoic Acid -- biosynthesis KW - Receptors, Thyroid Hormone -- biosynthesis KW - Repressor Proteins -- metabolism KW - Receptors, Thyroid Hormone -- physiology KW - Receptors, Thyroid Hormone -- metabolism KW - Receptors, Steroid -- metabolism KW - Transcription Factors -- biosynthesis KW - Signal Transduction KW - Receptors, Steroid -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77321490?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=The+orphan+receptor+TAK1+acts+as+a+repressor+of+RAR-%2C+RXR-+and+T3R-mediated+signaling+pathways.&rft.au=Hirose%2C+T%3BApfel%2C+R%3BPfahl%2C+M%3BJetten%2C+A+M&rft.aulast=Hirose&rft.aufirst=T&rft.date=1995-06-06&rft.volume=211&rft.issue=1&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-10 N1 - Date created - 1995-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fluency changes in persons who stutter following a double blind trial of clomipramine and desipramine. AN - 85160837; pmid-7674643 AB - This study compared fluency changes in adult developmental stuttering speakers treated with two tricyclic antidepressants, clomipramine and desipramine. Clomipramine is primarily a serotonergic reuptake inhibitor, and desipramine, primarily a noradrenergic reuptake inhibitor. Sixteen subjects who stuttered participated in a single-blind placebo, double-blind active drug crossover study lasting 12 weeks. Speech rate and percent fluency did not significantly improve in placebo compared to baseline. Speech rate significantly increased while repeating, reading or constructing sentences, and during a telephone conversation, but no significant changes in percent fluency were found under clomipramine compared to placebo. Speech rate during a telephone conversation and percent fluency while speaking in front of an audience of four to seven listeners significantly increased under clomipramine compared to desipramine. No significant improvements in percent fluency or speech rate were found for any speaking task under desipramine compared to placebo. Twelve of 16 subjects reported improved fluency compared to baseline using clomipramine, whereas 6 reported improvement using desipramine. Because more evidence of improvement was found under clomipramine compared to desipramine, fluency improvement may be related to clomipramine's greater selectivity for serotonergic reuptake inhibition. JF - Journal of Speech and Hearing Research AU - Stager, S V AU - Ludlow, C L AU - Gordon, C T AU - Cotelingam, M AU - Rapoport, J L AD - Voice and Speech Section, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, USA. PY - 1995 SP - 516 EP - 525 VL - 38 IS - 3 SN - 0022-4685, 0022-4685 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85160837?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Speech+and+Hearing+Research&rft.atitle=Fluency+changes+in+persons+who+stutter+following+a+double+blind+trial+of+clomipramine+and+desipramine.&rft.au=Stager%2C+S+V%3BLudlow%2C+C+L%3BGordon%2C+C+T%3BCotelingam%2C+M%3BRapoport%2C+J+L&rft.aulast=Stager&rft.aufirst=S&rft.date=1995-06-01&rft.volume=38&rft.issue=3&rft.spage=516&rft.isbn=&rft.btitle=&rft.title=Journal+of+Speech+and+Hearing+Research&rft.issn=00224685&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - N-(4-hydroxyphenyl)retinamide (Fenretinide) in combination with retinoic acid enhances differentiation and retinoylation of proteins. AN - 77953310; 9816026 AB - The synthetic retinoid, N-(4-hydroxyphenyl)retinamide (4-HPR; Fenretinide), is a cancer chemopreventive and antiproliferative agent whose mechanism of action is unknown. 4-HPR alone is a poor inducer of differentiation of HL-60 cells compared to all-trans-retinoic acid (RA). Here, we found that combinations of 4-HPR and RA synergistically induced differentiation of HL-60 cells. In addition, 4-HPR increased the level of retinoylation, the covalent binding of RA to proteins. Retinoylation occurs in many eukaryotic cell lines and may be involved in RA-induced differentiation. These results suggest that 4-HPR may be a member of a class of retinoids that are active because they displace RA from extracellular and intracellular sites or because they inhibit RA catabolism. On the basis of these proposed mechanisms, retinoids that do not cause differentiation as sole agents may have utility in the clinic in combination with RA. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Takahashi, N AU - Sausville, E A AU - Breitman, T R AD - Laboratory of Biological Chemistry, Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 637 EP - 642 VL - 1 IS - 6 SN - 1078-0432, 1078-0432 KW - Anticarcinogenic Agents KW - 0 KW - Neoplasm Proteins KW - Fenretinide KW - 187EJ7QEXL KW - Tretinoin KW - 5688UTC01R KW - Index Medicus KW - HL-60 Cells KW - Kinetics KW - Humans KW - Drug Synergism KW - Tretinoin -- pharmacology KW - Fenretinide -- pharmacology KW - Anticarcinogenic Agents -- pharmacology KW - Tretinoin -- metabolism KW - Cell Differentiation -- drug effects KW - Neoplasm Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77953310?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=N-%284-hydroxyphenyl%29retinamide+%28Fenretinide%29+in+combination+with+retinoic+acid+enhances+differentiation+and+retinoylation+of+proteins.&rft.au=Takahashi%2C+N%3BSausville%2C+E+A%3BBreitman%2C+T+R&rft.aulast=Takahashi&rft.aufirst=N&rft.date=1995-06-01&rft.volume=1&rft.issue=6&rft.spage=637&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-08 N1 - Date created - 1999-02-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Suppression of pulmonary P4502b and induction of hepatic, intestinal and kidney P4501a-1 and 1a-2 in the Ah-responsive and non-responsive mouse by Aroclor 1254. AN - 77736210; 7483655 AB - 1. Investigations in our laboratory have demonstrated a rapid suppression of the P4502b isoform in mouse lung, concomitant with significant induction of this enzyme in liver from these same animals. The current study was designed to determine whether the suppression by polychlorinated biphenyls of pulmonary P4502b required the presence of a functional Ah receptor, and additionally to delineate the time course of the induction responses to Aroclor 1254 in the liver, kidney, and intestine of the AH-responsive and non-responsive mouse. 2. P450s were quantified by specific enzyme assay and immunoblot in liver (1a-1, 1a-2, 2b), lung (1a-1, 1a-2), kidney (1a-1, 1a-2, 2b) and small intestine (1a-1, 2b) of C57 and DBA animals at varying times (48 h-12 weeks) following a single intraperitoneal dose of Aroclor 1254 (250 mg/kg). 3. The suppression of constitutive P4502b in the lung by Aroclor was observed in both strains, but was more prominent over a longer time course in the non-responsive animals. P4502b enzyme activity was increased in the liver and intestine of both strains of mouse; however, there was a significantly greater response to Aroclor in the C57 animals. These data indicate that the AH receptor does not participate in the suppression of pulmonary P4502b, and suggests that the regulation of inducible P4502b in liver and intestine is quantitatively different between these two strains of mouse. 4. P4501a was predictably induced in all tissues examined from the C57 animal, but was largely unaffected by PCBs in the DBA strain. P4501a-2, which is also regulated by the Ah receptor, was highly induced in the liver of the responsive strain, and also increased approximately two-fold in the liver of the non-responsive animals. Kidney P4501a-2 was also modestly increased by Aroclor, only in the responsive mouse. JF - Xenobiotica; the fate of foreign compounds in biological systems AU - Beebe, L E AU - Fornwald, L W AU - Riggs, C W AU - Anderson, L M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 541 EP - 551 VL - 25 IS - 6 SN - 0049-8254, 0049-8254 KW - Aroclors KW - 0 KW - Environmental Pollutants KW - Receptors, Aryl Hydrocarbon KW - Chlorodiphenyl (54% Chlorine) KW - 11097-69-1 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Injections, Intraperitoneal KW - Animals KW - Liver -- enzymology KW - Environmental Pollutants -- toxicity KW - Kidney -- enzymology KW - Mice KW - Mice, Inbred DBA KW - Enzyme Repression -- drug effects KW - Blotting, Western KW - Enzyme Induction -- drug effects KW - Mice, Inbred C57BL KW - Time Factors KW - Male KW - Intestine, Small -- enzymology KW - Receptors, Aryl Hydrocarbon -- physiology KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Aroclors -- toxicity KW - Lung -- enzymology KW - Aroclors -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77736210?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Xenobiotica%3B+the+fate+of+foreign+compounds+in+biological+systems&rft.atitle=Suppression+of+pulmonary+P4502b+and+induction+of+hepatic%2C+intestinal+and+kidney+P4501a-1+and+1a-2+in+the+Ah-responsive+and+non-responsive+mouse+by+Aroclor+1254.&rft.au=Beebe%2C+L+E%3BFornwald%2C+L+W%3BRiggs%2C+C+W%3BAnderson%2C+L+M&rft.aulast=Beebe&rft.aufirst=L&rft.date=1995-06-01&rft.volume=25&rft.issue=6&rft.spage=541&rft.isbn=&rft.btitle=&rft.title=Xenobiotica%3B+the+fate+of+foreign+compounds+in+biological+systems&rft.issn=00498254&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-27 N1 - Date created - 1995-12-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Disposition of the plasmacytomagenic alkane pristane (2,6,10,14-tetramethylpentadecane) in mice. AN - 77698024; 8536217 AB - The intraperitoneal administration of pristane (2,6,10,14-tetramethylpentadecane) induces peritoneal plasmacytomas in genetically susceptible BALB/c mice. The purpose of this study was to estimate the disposition of an amount of intraperitoneally injected pristane that would conventionally be used in a tumor induction protocol. The distribution of 3H-labeled pristane in various tissues was monitored by liquid scintillation counting at different times after injection. The data show that pristane is present in the blood and detectable in all tested tissues during an observation period of one to 64 days. The levels of pristane fluctuate in some tissues such as lymph node and bone marrow but show a clear tendency to accumulate in others such as liver, spleen and kidney. Evidence is also presented for the in vivo metabolism of pristane based on the observed urinary excretion of tritium and on the high levels of radioactivity in the gall bladder fluid. It is concluded that intraperitoneally administered pristane is distributed throughout the mouse and is stored in tissues in sufficient amounts to allow interactions with the cells residing there. JF - Cancer biochemistry biophysics AU - Janz, S AU - Shacter, E AD - Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 25 EP - 34 VL - 15 IS - 1 SN - 0305-7232, 0305-7232 KW - Carcinogens KW - 0 KW - Terpenes KW - Tritium KW - 10028-17-8 KW - pristane KW - 26HZV48DT1 KW - Index Medicus KW - Injections, Intraperitoneal KW - Animals KW - Mice KW - Tissue Distribution KW - Mice, Inbred BALB C KW - Female KW - Mice, Inbred DBA KW - Terpenes -- toxicity KW - Peritoneal Neoplasms -- chemically induced KW - Terpenes -- pharmacokinetics KW - Plasmacytoma -- chemically induced KW - Carcinogens -- pharmacokinetics KW - Carcinogens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77698024?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+biochemistry+biophysics&rft.atitle=Disposition+of+the+plasmacytomagenic+alkane+pristane+%282%2C6%2C10%2C14-tetramethylpentadecane%29+in+mice.&rft.au=Janz%2C+S%3BShacter%2C+E&rft.aulast=Janz&rft.aufirst=S&rft.date=1995-06-01&rft.volume=15&rft.issue=1&rft.spage=25&rft.isbn=&rft.btitle=&rft.title=Cancer+biochemistry+biophysics&rft.issn=03057232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-07 N1 - Date created - 1996-02-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of SCH 32615, an enkephalinase inhibitor, on D-1 and D-2 dopamine receptor-mediated behaviors. AN - 77639170; 7566505 AB - Striatal enkephalin-containing neurons receive dopaminergic inputs from the substantia nigra and project to the external segment of globus pallidus. These neurons express primarily dopamine (DA) D-2 receptors. Accordingly, stimulation of enkephalinergic transmission might be expected to influence mainly D-2 receptor agonist or antagonist effects on motor function. To test this hypothesis, the effects of SCH 32615, an enkephalinase inhibitor, on DA antagonist-induced catalepsy, DA D-1 agonist-induced non-stereotyped grooming, and DA D-2 agonist-induced stereotyped behavior were studied. The administration of SCH 32615 (3 mg/kg) decreased both D-1 and D-2 antagonist-induced catalepsy. In contrast, SCH 32615 (0.3 mg/kg) increased D-1 agonist-induced non-stereotyped grooming and D-2 agonist-induced stereotypies. These results suggest that a DA agonist-like, mostly D-2 activity may be involved in enkephalinergic-mediated functions. JF - Neuropharmacology AU - Marin, C AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institute of Health, Bethesda, MD 20892, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 677 EP - 682 VL - 34 IS - 6 SN - 0028-3908, 0028-3908 KW - Dipeptides KW - 0 KW - Protease Inhibitors KW - Receptors, Dopamine D1 KW - Receptors, Dopamine D2 KW - SCH 32615 KW - 83861-02-3 KW - Neprilysin KW - EC 3.4.24.11 KW - Index Medicus KW - Rats KW - Behavior, Animal -- drug effects KW - Animals KW - Rats, Sprague-Dawley KW - Catalepsy -- chemically induced KW - Grooming KW - Dose-Response Relationship, Drug KW - Neprilysin -- drug effects KW - Motor Activity -- drug effects KW - Male KW - Protease Inhibitors -- pharmacology KW - Receptors, Dopamine D2 -- drug effects KW - Receptors, Dopamine D1 -- drug effects KW - Dipeptides -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77639170?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropharmacology&rft.atitle=Effects+of+SCH+32615%2C+an+enkephalinase+inhibitor%2C+on+D-1+and+D-2+dopamine+receptor-mediated+behaviors.&rft.au=Marin%2C+C%3BChase%2C+T+N&rft.aulast=Marin&rft.aufirst=C&rft.date=1995-06-01&rft.volume=34&rft.issue=6&rft.spage=677&rft.isbn=&rft.btitle=&rft.title=Neuropharmacology&rft.issn=00283908&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-14 N1 - Date created - 1995-11-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 100 years of ibogaine: neurochemical and pharmacological actions of a putative anti-addictive drug. AN - 77591100; 7568327 JF - Pharmacological reviews AU - Popik, P AU - Layer, R T AU - Skolnick, P AD - Laboratory of Neuroscience, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 235 EP - 253 VL - 47 IS - 2 SN - 0031-6997, 0031-6997 KW - Hallucinogens KW - 0 KW - Neurotoxins KW - Receptors, GABA KW - Receptors, Glutamate KW - Receptors, Opioid KW - Serotonin KW - 333DO1RDJY KW - Ibogaine KW - 3S814I130U KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Receptors, GABA -- drug effects KW - Receptors, Opioid -- metabolism KW - Humans KW - Receptors, Glutamate -- drug effects KW - Receptors, Opioid -- drug effects KW - Receptors, Glutamate -- metabolism KW - Neurotoxins -- toxicity KW - Calcium -- metabolism KW - Receptors, GABA -- metabolism KW - Substance-Related Disorders -- drug therapy KW - Neurotoxins -- adverse effects KW - Serotonin -- metabolism KW - Hallucinogens -- pharmacokinetics KW - Synaptic Transmission -- drug effects KW - Ibogaine -- therapeutic use KW - Substance Withdrawal Syndrome -- drug therapy KW - Ibogaine -- chemistry KW - Hallucinogens -- pharmacology KW - Hallucinogens -- chemistry KW - Substance Withdrawal Syndrome -- mortality KW - Ibogaine -- pharmacology KW - Ibogaine -- pharmacokinetics KW - Hallucinogens -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77591100?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=100+years+of+ibogaine%3A+neurochemical+and+pharmacological+actions+of+a+putative+anti-addictive+drug.&rft.au=Popik%2C+P%3BLayer%2C+R+T%3BSkolnick%2C+P&rft.aulast=Popik&rft.aufirst=P&rft.date=1995-06-01&rft.volume=47&rft.issue=2&rft.spage=235&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 - 1995-11-07 N1 - Date created - 1995-11-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The U.S. Advisory Committee on Human Radiation Experiments. AN - 77574711; 7556311 JF - European journal of nuclear medicine AU - Neumann, R AD - Department of Nuclear Medicine, National Institutes of Health, Bethesda, MD, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 589 EP - 591 VL - 22 IS - 6 SN - 0340-6997, 0340-6997 KW - Index Medicus KW - History of medicine KW - United States KW - History, 20th Century KW - Humans KW - Ethics, Medical -- history KW - Radiation Injuries -- history KW - Human Experimentation -- history UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77574711?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+nuclear+medicine&rft.atitle=The+U.S.+Advisory+Committee+on+Human+Radiation+Experiments.&rft.au=Neumann%2C+R&rft.aulast=Neumann&rft.aufirst=R&rft.date=1995-06-01&rft.volume=22&rft.issue=6&rft.spage=589&rft.isbn=&rft.btitle=&rft.title=European+journal+of+nuclear+medicine&rft.issn=03406997&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-02 N1 - Date created - 1995-11-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neonatal excitotoxic ventral hippocampal damage alters dopamine response to mild repeated stress and to chronic haloperidol. AN - 77539054; 7570341 AB - The effects of neonatal excitotoxic ventral hippocampus (VH) lesions on dopamine release in response to repeated stress (saline injections) and to chronic haloperidol treatment were investigated in Sprague-Dawley rats infused with ibotenic acid or vehicle into the VH on day 7 of postnatal life (PD7). Beginning on PD35, lesioned and sham-operated rats were injected i.p. with saline (INJ) once daily for 3 weeks or were not treated (NO INJ). Another cohort of rats was given haloperidol (HAL, 0.4 mg/kg, i.p.) or vehicle beginning on PD35 and thereafter once daily for 3 weeks. 3-Methoxytyramine (3-MT) was measured by combined gas chromatography/mass spectrometry in the frontal cortex (FC), nucleus accumbens (NAcc), and striatum (STR) at PD56 following MAO inhibition with pargyline. At baseline (NO INJ), 3-MT was reduced in STR of lesioned rats. Repeated saline injections resulted in a further 3-MT reduction in STR, FC, and NAcc of lesioned animals, but had no effect in sham rats. Chronic HAL, compared with vehicle, suppressed locomotor activity, and increased 3-MT accumulation in the FC, NAcc, and STR in sham and lesioned rats. This increase was enhanced in the FC of lesioned rats. These data show that mild repeated stress attenuates dopamine release in FC, NAcc, and STR of lesioned rats, while chronic HAL augments it in FC of lesioned animals versus controls. We conclude that the neonatal excitotoxic lesion of VH alters the functioning of midbrain dopamine systems during environmental and pharmacological challenge. JF - Synapse (New York, N.Y.) AU - Lipska, B K AU - Chrapusta, S J AU - Egan, M F AU - Weinberger, D R AD - Clinical Brain Disorders Branch, National Institute of Mental Health, NIH, Washington, DC 20032, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 125 EP - 130 VL - 20 IS - 2 SN - 0887-4476, 0887-4476 KW - Neurotoxins KW - 0 KW - Ibotenic Acid KW - 2552-55-8 KW - Sodium Chloride KW - 451W47IQ8X KW - Pargyline KW - 9MV14S8G3E KW - Haloperidol KW - J6292F8L3D KW - 3-methoxytyramine KW - JCH2767EDP KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Handling (Psychology) KW - Animals KW - Rats, Sprague-Dawley KW - Pargyline -- pharmacology KW - Corpus Striatum -- metabolism KW - Sodium Chloride -- administration & dosage KW - Frontal Lobe -- metabolism KW - Female KW - Ibotenic Acid -- pharmacology KW - Dopamine -- analogs & derivatives KW - Nerve Degeneration -- drug effects KW - Stress, Psychological -- metabolism KW - Hippocampus -- physiology KW - Haloperidol -- pharmacology KW - Neurotoxins -- pharmacology KW - Dopamine -- metabolism KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77539054?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Synapse+%28New+York%2C+N.Y.%29&rft.atitle=Neonatal+excitotoxic+ventral+hippocampal+damage+alters+dopamine+response+to+mild+repeated+stress+and+to+chronic+haloperidol.&rft.au=Lipska%2C+B+K%3BChrapusta%2C+S+J%3BEgan%2C+M+F%3BWeinberger%2C+D+R&rft.aulast=Lipska&rft.aufirst=B&rft.date=1995-06-01&rft.volume=20&rft.issue=2&rft.spage=125&rft.isbn=&rft.btitle=&rft.title=Synapse+%28New+York%2C+N.Y.%29&rft.issn=08874476&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-26 N1 - Date created - 1995-10-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biochemical characterization of human GCF transcription factor in tumor cells. AN - 77507369; 7669724 AB - GCF is a transcriptional regulator that was found to repress transcription of the epidermal growth factor (EGF) receptor and several other genes and is encoded by a 3-kb mRNA (R. Kageyama and I. Pastan, Cell, 59: 815-825, 1989; A. C. Johnson et al., J. Biol. Chem., 267: 1689-1694, 1992). To identify and characterize the GCF gene product at the cellular level, we have developed antibodies against a bacterially expressed GCF fusion protein. GCF antibodies recognize GCF present in extracts from human cells and causes a "supershift" of a protein DNA complex containing a GCF oligonucleotide binding site. The major form of GCF has a molecular weight of approximately M(r) 97,000, identical to that of GCF transiently expressed in CV1 cells by the vaccinia virus system. In addition, other less abundant species with slightly higher and lower apparent molecular weight are specifically recognized, suggesting extensive posttranslational modification. GCF is highly expressed in EGF receptor-negative human cell lines (HUT102, U266, and CA46) and in lower amounts in several EGF receptor-expressing cells (KB, A431, TMK, and HeLa). Cell fractionation studies indicate that GCF is predominantly localized in the nucleus. GCF is a stable protein with a relatively long half-life. In addition, GCF is a phosphoprotein, and the phosphorylated form is found to be associated with the nuclear compartment in both HUT102 and KB cells. Phosphorylation occurs on serine and threonine residues and is stimulated by okadaic acid, phorbol myristate acetate, and cyclic AMP, but not vanadate.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Beguinot, L AU - Yamazaki, H AU - Pastan, I AU - Johnson, A C AD - Division of Cancer Biology, Diagnosis and Centers, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 699 EP - 706 VL - 6 IS - 6 SN - 1044-9523, 1044-9523 KW - DNA, Complementary KW - 0 KW - Ethers, Cyclic KW - GCFC2 protein, human KW - Immune Sera KW - RNA, Messenger KW - Recombinant Fusion Proteins KW - Repressor Proteins KW - Okadaic Acid KW - 1W21G5Q4N2 KW - Cyclic AMP KW - E0399OZS9N KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Protein Processing, Post-Translational -- drug effects KW - Animals KW - Fibroblasts -- drug effects KW - Protein-Serine-Threonine Kinases -- metabolism KW - DNA, Complementary -- genetics KW - 3T3 Cells -- drug effects KW - Tumor Cells, Cultured -- drug effects KW - Recombinant Fusion Proteins -- immunology KW - Humans KW - Rabbits KW - Mice KW - Ethers, Cyclic -- pharmacology KW - RNA, Messenger -- genetics KW - RNA, Messenger -- biosynthesis KW - Molecular Weight KW - Phosphorylation -- drug effects KW - Recombinant Fusion Proteins -- metabolism KW - Cercopithecus aethiops KW - Cyclic AMP -- pharmacology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Line, Transformed KW - Down-Regulation -- drug effects KW - Repressor Proteins -- biosynthesis KW - Receptor, Epidermal Growth Factor -- genetics KW - Repressor Proteins -- immunology KW - Repressor Proteins -- genetics KW - Repressor Proteins -- chemistry KW - Receptor, Epidermal Growth Factor -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77507369?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Biochemical+characterization+of+human+GCF+transcription+factor+in+tumor+cells.&rft.au=Beguinot%2C+L%3BYamazaki%2C+H%3BPastan%2C+I%3BJohnson%2C+A+C&rft.aulast=Beguinot&rft.aufirst=L&rft.date=1995-06-01&rft.volume=6&rft.issue=6&rft.spage=699&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 - 1995-10-19 N1 - Date created - 1995-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nutritional supplement use and age-related macular degeneration. AN - 77504782; 10150867 AB - Age-related macular degeneration is one of the leading causes of visual loss among people aged 65 years or older. The causes and factors associated with the progression of age-related macular degeneration are unknown presently. Basic research and epidemiologic data support the hypotheses that higher levels of antioxidant vitamins and minerals may protect the eye from the development of age-related macular degeneration. For this reason and also because of the lack of effective treatment for most cases of age-related macular degeneration, nutritional supplements with antioxidants have emerged as possible therapy for age-related macular degeneration. Nutritional supplements are not proven therapy for age-related macular degeneration. The potential beneficial effects and adverse side effects of the nutritional supplements have not yet been fully evaluated in carefully conducted clinical trials. Several randomized placebo-controlled clinical trials are presently underway. Results of these studies will provide important data to clarify the potential beneficial and adverse effects of such treatment. Until these results are available, it would be premature to make recommendations in favor of vitamin or mineral supplements. JF - Current opinion in ophthalmology AU - Chew, E Y AD - National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 19 EP - 24 VL - 6 IS - 3 SN - 1040-8738, 1040-8738 KW - Antioxidants KW - 0 KW - Minerals KW - Vitamins KW - Health technology assessment KW - Fundus Oculi KW - Antioxidants -- adverse effects KW - Animals KW - Randomized Controlled Trials as Topic KW - Vitamins -- therapeutic use KW - Humans KW - Antioxidants -- therapeutic use KW - Clinical Trials as Topic KW - Macula Lutea -- pathology KW - Aged KW - Retina -- pathology KW - Minerals -- therapeutic use KW - Macular Degeneration -- prevention & control KW - Macular Degeneration -- pathology KW - Macular Degeneration -- etiology KW - Macular Degeneration -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77504782?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+opinion+in+ophthalmology&rft.atitle=Nutritional+supplement+use+and+age-related+macular+degeneration.&rft.au=Chew%2C+E+Y&rft.aulast=Chew&rft.aufirst=E&rft.date=1995-06-01&rft.volume=6&rft.issue=3&rft.spage=19&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+ophthalmology&rft.issn=10408738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-13 N1 - Date created - 1995-10-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Generation of free radicals by Cr(IV) from lipid hydroperoxides and its inhibition by chelators. AN - 77503566; 7663436 AB - The generation of free radicals by Cr(IV) from lipid hydroperoxides was investigated by ESR spin trapping. The spin trap used was 5,5-dimethyl-1-pyrroline N-oxide (DMPO). Reaction of Cr(VI) with ascorbate was used as a source of Cr(IV). Incubation of Cr(VI) with ascorbate generated Cr(IV) and Cr(V). Addition of cumene hydroperoxide generated DMPO/R adduct with an enhancement of Cr(V) signal. Addition of Mn(II), whose function is to remove Cr(IV), caused dose-dependent inhibition of DMPO/R formation. Similar results were obtained using t-butyl hydroperoxide. Metal ion chelators, deferoxamine, 1,10-phenanthroline and diethylenetriaminepentaacetic acid inhibited DMPO/R formation in the order of deferoxamine > 1,10-phenanthroline > diethylenetriaminepentaacetic acid. The results suggest the possible role of Cr(IV) and its mediated free radical generation from lipid hydroperoxides in the mechanism of Cr(VI) carcinogenesis. JF - Biochemistry and molecular biology international AU - Mao, Y AU - Zang, L AU - Shi, X AD - Laboratory of Experimental Pathology, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 327 EP - 337 VL - 36 IS - 2 SN - 1039-9712, 1039-9712 KW - Benzene Derivatives KW - 0 KW - Chelating Agents KW - Cyclic N-Oxides KW - Free Radicals KW - Lipid Peroxides KW - Peroxides KW - Spin Labels KW - Chromium KW - 0R0008Q3JB KW - Manganese KW - 42Z2K6ZL8P KW - 5,5-dimethyl-1-pyrroline-1-oxide KW - 7170JZ1QF3 KW - tert-Butylhydroperoxide KW - 955VYL842B KW - cumene hydroperoxide KW - PG7JD54X4I KW - Ascorbic Acid KW - PQ6CK8PD0R KW - Index Medicus KW - Manganese -- pharmacology KW - Electron Spin Resonance Spectroscopy KW - Cyclic N-Oxides -- metabolism KW - Ascorbic Acid -- metabolism KW - Free Radicals -- metabolism KW - Chelating Agents -- pharmacology KW - Peroxides -- metabolism KW - Chromium -- antagonists & inhibitors KW - Benzene Derivatives -- metabolism KW - Chromium -- metabolism KW - Lipid Peroxides -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77503566?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry+and+molecular+biology+international&rft.atitle=Generation+of+free+radicals+by+Cr%28IV%29+from+lipid+hydroperoxides+and+its+inhibition+by+chelators.&rft.au=Mao%2C+Y%3BZang%2C+L%3BShi%2C+X&rft.aulast=Mao&rft.aufirst=Y&rft.date=1995-06-01&rft.volume=36&rft.issue=2&rft.spage=327&rft.isbn=&rft.btitle=&rft.title=Biochemistry+and+molecular+biology+international&rft.issn=10399712&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-12 N1 - Date created - 1995-10-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rapid evolution of a unique family of primate ribonuclease genes. AN - 77501548; 7663519 AB - We have traced the rapid molecular evolution of eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP), two host defense proteins that are members of the mammalian ribonuclease gene family. The EDN/ECP gene pair arose from a recent duplication event that occurred after the divergence of New World and Old World monkeys. Since duplication, the genes encoding EDN and ECP have accumulated non-silent mutations at rates exceeding those of all other functional coding sequences studied in primates, while retaining both the structural and catalytic components required for ribonuclease activity. These results suggest that both EDN and ECP may be responding to unusual evolutionary constraints, which has prompted a reexamination of their physiologic function. JF - Nature genetics AU - Rosenberg, H F AU - Dyer, K D AU - Tiffany, H L AU - Gonzalez, M AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 219 EP - 223 VL - 10 IS - 2 SN - 1061-4036, 1061-4036 KW - Amino Acids KW - 0 KW - Blood Proteins KW - Eosinophil Granule Proteins KW - Inflammation Mediators KW - Neurotoxins KW - Eosinophil-Derived Neurotoxin KW - EC 3.1.- KW - Ribonucleases KW - Ribonuclease, Pancreatic KW - EC 3.1.27.5 KW - Index Medicus KW - Space life sciences KW - Rats KW - Animals KW - Neurotoxins -- genetics KW - Humans KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Mutation KW - Chromosome Mapping KW - Blood Proteins -- genetics KW - Ribonuclease, Pancreatic -- genetics KW - Biological Evolution KW - Primates -- genetics KW - Ribonucleases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77501548?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+genetics&rft.atitle=Rapid+evolution+of+a+unique+family+of+primate+ribonuclease+genes.&rft.au=Rosenberg%2C+H+F%3BDyer%2C+K+D%3BTiffany%2C+H+L%3BGonzalez%2C+M&rft.aulast=Rosenberg&rft.aufirst=H&rft.date=1995-06-01&rft.volume=10&rft.issue=2&rft.spage=219&rft.isbn=&rft.btitle=&rft.title=Nature+genetics&rft.issn=10614036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-12 N1 - Date created - 1995-10-12 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - M30683; GENBANK; X64177; M14743; L22862; X16447; A06925; M15818; X51890; X73323; X76717; M31134; J00105; K00485; K00484; X71340; M18189; M12807; L14590; Z27245; L14592; X02157; L14587; L14589; X71338; X71337; X71336; Y00443; X71335; X07862; X71334 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 modulation of TFIIH-associated nucleotide excision repair activity. AN - 77496062; 7663514 AB - p53 has pleiotropic functions including control of genomic plasticity and integrity. Here we report that p53 can bind to several transcription factor IIH-associated factors, including transcription-repair factors, XPD (Rad3) and XPB, as well as CSB involved in strand-specific DNA repair, via its C-terminal domain. We also found that wild-type, but not Arg273His mutant p53 inhibits XPD (Rad3) and XPB DNA helicase activities. Moreover, repair of UV-induced dimers is slower in Li-Fraumeni syndrome cells (heterozygote p53 mutant) than in normal human cells. Our findings indicate that p53 may play a direct role in modulating nucleotide excision repair pathways. JF - Nature genetics AU - Wang, X W AU - Yeh, H AU - Schaeffer, L AU - Roy, R AU - Moncollin, V AU - Egly, J M AU - Wang, Z AU - Freidberg, E C AU - Evans, M K AU - Taffe, B G AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 188 EP - 195 VL - 10 IS - 2 SN - 1061-4036, 1061-4036 KW - DNA-Binding Proteins KW - 0 KW - Nucleotides KW - Proteins KW - Saccharomyces cerevisiae Proteins KW - Transcription Factors KW - Transcription Factors, TFII KW - Tumor Suppressor Protein p53 KW - XPBC-ERCC-3 protein KW - 146045-44-5 KW - Transcription Factor TFIIH KW - 148710-81-0 KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - Rad3 protein, S cerevisiae KW - DNA Helicases KW - EC 3.6.4.- KW - ERCC6 protein, human KW - EC 3.6.4.12 KW - Xeroderma Pigmentosum Group D Protein KW - ERCC2 protein, human KW - EC 5.99.- KW - DNA Repair Enzymes KW - EC 6.5.1.- KW - Index Medicus KW - Protein Structure, Secondary KW - DNA Helicases -- metabolism KW - Models, Molecular KW - Enzyme Activation KW - Humans KW - Adenosine Triphosphatases -- metabolism KW - DNA-Binding Proteins -- genetics KW - Xeroderma Pigmentosum -- genetics KW - Amino Acid Sequence KW - Proteins -- metabolism KW - Proteins -- genetics KW - Li-Fraumeni Syndrome -- genetics KW - Chromosome Mapping KW - Li-Fraumeni Syndrome -- enzymology KW - Xeroderma Pigmentosum -- enzymology KW - Tumor Cells, Cultured KW - Cockayne Syndrome -- genetics KW - Molecular Sequence Data KW - DNA Helicases -- genetics KW - Cockayne Syndrome -- enzymology KW - Adenosine Triphosphatases -- genetics KW - DNA-Binding Proteins -- metabolism KW - Transcription Factors -- physiology KW - Tumor Suppressor Protein p53 -- physiology KW - DNA Repair KW - Transcription Factors -- metabolism KW - Tumor Suppressor Protein p53 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77496062?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+genetics&rft.atitle=p53+modulation+of+TFIIH-associated+nucleotide+excision+repair+activity.&rft.au=Wang%2C+X+W%3BYeh%2C+H%3BSchaeffer%2C+L%3BRoy%2C+R%3BMoncollin%2C+V%3BEgly%2C+J+M%3BWang%2C+Z%3BFreidberg%2C+E+C%3BEvans%2C+M+K%3BTaffe%2C+B+G&rft.aulast=Wang&rft.aufirst=X&rft.date=1995-06-01&rft.volume=10&rft.issue=2&rft.spage=188&rft.isbn=&rft.btitle=&rft.title=Nature+genetics&rft.issn=10614036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-12 N1 - Date created - 1995-10-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of new selenocysteine tRNA[SER]SEC isoacceptors in human cell lines. AN - 77495393; 7663446 AB - The selenocysteine tRNA population was examined in a human T-cell line and in a human monocytic cell line for the occurrence of additional species of selenocysteine tRNA. At least three additional (and possibly more) selenocysteine isoacceptors were found which occur in minor levels as compared to the two major selenocysteine isoacceptors previously characterized. The possible significance of these newly observed species are discussed. JF - Biochemistry and molecular biology international AU - Ohama, T AU - Jung, J E AU - Park, S I AU - Clouse, K A AU - Lee, B J AU - Hatfield, D AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 421 EP - 427 VL - 36 IS - 2 SN - 1039-9712, 1039-9712 KW - Codon KW - 0 KW - RNA, Transfer, Amino Acid-Specific KW - RNA, Transfer, Amino Acyl KW - tRNA, selenocysteine- KW - Index Medicus KW - Ribosomes -- metabolism KW - Tumor Cells, Cultured KW - Chromatography KW - Humans KW - Cell Line KW - T-Lymphocytes -- chemistry KW - RNA, Transfer, Amino Acyl -- metabolism KW - RNA, Transfer, Amino Acyl -- chemistry KW - Monocytes -- chemistry KW - RNA, Transfer, Amino Acyl -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77495393?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry+and+molecular+biology+international&rft.atitle=Identification+of+new+selenocysteine+tRNA%5BSER%5DSEC+isoacceptors+in+human+cell+lines.&rft.au=Ohama%2C+T%3BJung%2C+J+E%3BPark%2C+S+I%3BClouse%2C+K+A%3BLee%2C+B+J%3BHatfield%2C+D&rft.aulast=Ohama&rft.aufirst=T&rft.date=1995-06-01&rft.volume=36&rft.issue=2&rft.spage=421&rft.isbn=&rft.btitle=&rft.title=Biochemistry+and+molecular+biology+international&rft.issn=10399712&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-12 N1 - Date created - 1995-10-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A model for estimating the potency and survival of human gametes in vivo. AN - 77489490; 7662833 AB - Sperm and ova are sensitive to numerous toxicants in animal studies; however, human vulnerability has been far more difficult to assess, due in part to a lack of methods for measuring the viable survival of human gametes in vivo. We present a parametric model for fertility, which assumes that the viable lifetime of the ovum is fixed while that of sperm is exponentially distributed. By reducing the number of parameters that must be estimated, compared to a previous approach, the model leads to improved tests for differences in sperm and egg survival between exposed and unexposed couples. Since it assumes that batches of sperm introduced on different days present independent competing "risks" (of fertilization) to the ovum, the model also provides for estimation of the age distribution, in days, of the sperm which actually fertilized the ova. This allows us to consider whether older sperm are more likely to produce defective embryos. We apply this model to data from a group of women who were intensively studied, beginning when they discontinued contraception in order to start a pregnancy. Participants kept daily records of intercourse. Daily urine specimens allowed the day of ovulation to be estimated and conceptions to be identified, based on assays of excreted hormones. Applying the parametric model to these data, the estimated mean viable lifetime for sperm is 1.4 days, while the lifetime of the ovum appears to be less than a day.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Biometrics AU - Weinberg, C R AU - Wilcox, A J AD - Statistics and Biomathematics Branch, National Institute of Environmental Health Sciences, North Carolina 27709, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 405 EP - 412 VL - 51 IS - 2 SN - 0006-341X, 0006-341X KW - Index Medicus KW - Sperm-Ovum Interactions KW - Humans KW - Coitus KW - Male KW - Female KW - Mathematics KW - Ovum -- physiology KW - Spermatozoa -- physiology KW - Fertilization KW - Spermatozoa -- cytology KW - Models, Statistical KW - Models, Biological KW - Ovum -- cytology KW - Cell Survival UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77489490?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+model+for+estimating+the+potency+and+survival+of+human+gametes+in+vivo.&rft.au=Weinberg%2C+C+R%3BWilcox%2C+A+J&rft.aulast=Weinberg&rft.aufirst=C&rft.date=1995-06-01&rft.volume=51&rft.issue=2&rft.spage=405&rft.isbn=&rft.btitle=&rft.title=Biometrics&rft.issn=0006341X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-10 N1 - Date created - 1995-10-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cellular functions during activation and damage by pathogens: immunogold studies of the interaction of bacterial endotoxins with target cells. AN - 77484036; 7655088 AB - Bacterial endotoxins (lipopolysaccharides or LPS) are active components of Gram-negative bacteria that act on numerous cellular functions through the processes of cell activation and damage. The molecular mechanisms involved in the "endotoxic phenomenon" are not defined yet, although extensive studies have been carried out. Immunogold and electron microscopy (EM) have contributed to identify the primary target cells of endotoxins and the subcellular systems that receive the direct action of these bacterial agents. Here, we review our studies on immunogold detection of endotoxins in cellular and subcellular systems. The analysis of the interaction between endotoxins and cells was focussed on the following aspects: (1) morphological characteristics of the LPS aqueous suspensions used in experimental work; (2) binding of endotoxins to the plasma membrane of type II pneumocytes and alveolar macrophages (two of their cellular targets), and influence of the state of aggregation of the LPS; (3) movement and distribution of endotoxins inside the cell, from the plasma membrane to the nucleoplasm; and (4) interaction of LPS with microtubules and its effects on the integrity of the microtubular network. These approaches provide information at the molecular level as well as data for the establishment of physiological models of endotoxicity. JF - Microscopy research and technique AU - Risco, C AU - Pinto da Silva, P AD - Biological Carcinogenesis and Development Program, NCI-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA. Y1 - 1995/06/01/ PY - 1995 DA - 1995 Jun 01 SP - 141 EP - 158 VL - 31 IS - 2 SN - 1059-910X, 1059-910X KW - Lipopolysaccharides KW - 0 KW - Index Medicus KW - Animals KW - Freeze Fracturing KW - Cell Membrane -- drug effects KW - Cell Membrane -- ultrastructure KW - Cell Membrane -- metabolism KW - Microscopy, Immunoelectron KW - Immunohistochemistry KW - Microtubules -- ultrastructure KW - Macrophages, Alveolar -- ultrastructure KW - Lipopolysaccharides -- pharmacology KW - Lipopolysaccharides -- metabolism KW - Microtubules -- metabolism KW - Lung -- ultrastructure KW - Lung -- drug effects KW - Escherichia coli KW - Macrophages, Alveolar -- drug effects KW - Lung -- physiology KW - Macrophages, Alveolar -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77484036?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Microscopy+research+and+technique&rft.atitle=Cellular+functions+during+activation+and+damage+by+pathogens%3A+immunogold+studies+of+the+interaction+of+bacterial+endotoxins+with+target+cells.&rft.au=Risco%2C+C%3BPinto+da+Silva%2C+P&rft.aulast=Risco&rft.aufirst=C&rft.date=1995-06-01&rft.volume=31&rft.issue=2&rft.spage=141&rft.isbn=&rft.btitle=&rft.title=Microscopy+research+and+technique&rft.issn=1059910X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-05 N1 - Date created - 1995-10-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicity and carcinogenicity of 2,3-dibromo-1-propanol in F344/N rats and B6C3F1 mice. AN - 77482316; 7657061 AB - 2,3-Dibromo-1-propanol is a metabolite of the flame retardant tris(2,3-dibromopropyl) phosphate, previously shown to be a mutagen and carcinogen in experimental animals. Toxicology and carcinogenesis studies of 2,3-dibromo-1-propanol were conducted by applying the chemical in 95% ethanol to the interscapular skin of male and female F344/N rats and B6C3F1 mice 5 days a week for 13 weeks in the prechronic study and 48-55 weeks (rats) or 36-42 weeks (mice) in the carcinogenicity study. In the 13-week study, 10 rats and 10 mice of each sex received doses of 0, 44, 88, 177, 375, or 750 mg/kg. Deaths associated with chemical application occurred only in the high-dose (750 mg/kg) male mice. Chemical-related lesions were seen in the kidney of male rats, liver of female rats, and liver and lung of both sexes of mice. Based on the toxicity observed in the 13-week study, 50 rats of each sex received doses of 0, 188, or 375 mg/kg and 50 mice of each sex received 0, 88, or 177 mg/kg in the carcinogenicity study. The planned 2-year study was terminated early because of reduced survival of rats related to chemical-induced neoplasia and because of the appearance of antibodies to lymphocytic choriomeningitis virus in sentinel mice. Nearly all dosed rats had malignant neoplasms at one or more sites, while only one control male and one control female had malignant neoplasms. In rats, neoplasms induced by 2,3-dibromo-1-propanol occurred in the skin, nasal mucosa, Zymbal's gland, oral mucosa, esophagus, forestomach, intestines, liver, kidney, mammary gland (females), clitoral gland (females), spleen (males), and mesothelium (males). In mice, chemical-induced neoplasms occurred in the skin, forestomach, liver (males), and lung (males). JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Eustis, S L AU - Haseman, J K AU - Mackenzie, W F AU - Abdo, K M AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 41 EP - 50 VL - 26 IS - 1 SN - 0272-0590, 0272-0590 KW - Propanols KW - 0 KW - 1-Propanol KW - 96F264O9SV KW - 2,3-dibromopropanol KW - C0YBW1OA2I KW - Index Medicus KW - Rats KW - Gastrointestinal Neoplasms -- chemically induced KW - Mice, Inbred Strains KW - Animals KW - Rats, Inbred F344 KW - Administration, Cutaneous KW - Skin Neoplasms -- chemically induced KW - 1-Propanol -- toxicity KW - 1-Propanol -- administration & dosage KW - Mice KW - Male KW - Female KW - Neoplasms, Experimental -- chemically induced KW - Carcinogenicity Tests UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77482316?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Toxicity+and+carcinogenicity+of+2%2C3-dibromo-1-propanol+in+F344%2FN+rats+and+B6C3F1+mice.&rft.au=Eustis%2C+S+L%3BHaseman%2C+J+K%3BMackenzie%2C+W+F%3BAbdo%2C+K+M&rft.aulast=Eustis&rft.aufirst=S&rft.date=1995-06-01&rft.volume=26&rft.issue=1&rft.spage=41&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-02 N1 - Date created - 1995-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risk of renal cell cancer in relation to diuretics, antihypertensive drugs, and hypertension. AN - 77481858; 7655326 AB - Although recent data have suggested an association between renal cell cancer and the use of diuretics, it remains unclear whether these medications or hypertension is the important risk factor. In a population-based case-control study including 440 renal cell cancer cases, spouses of an additional 151 cases, and 691 controls, we assessed renal cell cancer risk associated with hypertension and use of diuretics and other antihypertensive medications. Risks increased with the use of diuretics or other drugs that lower blood pressure, especially among persons who reported no history of hypertension. After adjustment for hypertension, the use of diuretics alone was associated with a 40% excess risk (OR = 1.4; 95% CI = 0.8-2.2), while use of other antihypertensive drugs was linked to a 2-fold risk (OR = 2.0; 95% CI = 1.2-3.3). The excess risk was not restricted to any specific products, and no trend was observed with estimated lifetime consumption of any product. Furthermore, risk was not potentiated by the presence of both hypertension and the use of antihypertensive drugs. Among persons who did not use antihypertensive drugs, a history of hypertension was associated with a significant 40-50% excess risk of renal cell cancer. Excluding subjects with hypertension diagnosed within 5 years of cancer diagnosis or interview had only a small effect on risk. These findings suggest small effects on renal cell cancer risk associated with hypertensive disease and with the use of diuretics and other antihypertensive drugs, but it is difficult to disentangle the separate effects due to potential misclassification of highly correlated events.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Chow, W H AU - McLaughlin, J K AU - Mandel, J S AU - Wacholder, S AU - Niwa, S AU - Fraumeni, J F AD - Epidemiology and Biostatistics Program, National Cancer Institute, Bethesda, Maryland 20852, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 327 EP - 331 VL - 4 IS - 4 SN - 1055-9965, 1055-9965 KW - Antihypertensive Agents KW - 0 KW - Diuretics KW - Index Medicus KW - Risk Factors KW - Humans KW - Adult KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Male KW - Female KW - Hypertension -- complications KW - Diuretics -- adverse effects KW - Carcinoma, Renal Cell -- etiology KW - Antihypertensive Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77481858?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=Risk+of+renal+cell+cancer+in+relation+to+diuretics%2C+antihypertensive+drugs%2C+and+hypertension.&rft.au=Chow%2C+W+H%3BMcLaughlin%2C+J+K%3BMandel%2C+J+S%3BWacholder%2C+S%3BNiwa%2C+S%3BFraumeni%2C+J+F&rft.aulast=Chow&rft.aufirst=W&rft.date=1995-06-01&rft.volume=4&rft.issue=4&rft.spage=327&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 - 1995-10-05 N1 - Date created - 1995-10-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - D1-D2 dopamine receptor synergy in striatum: effects of intrastriatal infusions of dopamine agonists and antagonists on immediate early gene expression. AN - 77472473; 7651617 AB - Manipulations of D1- or D2-dopamine receptors have differential and selective effects on the striatonigral and striatopallidal output pathways of the striatum, respectively. However, combined stimulation of these receptors produces synergistic responses. To examine the locus of this interaction in vivo, we infused D1- or D2-receptor agents into the striatum of freely moving, dopamine-depleted rats given systemic injections of the D1 agonist SKF 38393 and the D2 agonist quinpirole. Expression of the immediate early genes zif268 and c-fos, as determined by in situ hybridization histochemistry, was used as a measure of changes in the function of striatal neurons. Systemic administration of SKF 38393 produced a dose-dependent increase in the expression of immediate early genes in the dopamine-depleted striatum. Quinpirole, on the other hand, decreased the basal expression of zif268 in both the lesioned and intact striatum. However, combined administration of quinpirole with SKF 38393 significantly enhanced immediate early gene expression in the dopamine-depleted striatum relative to that seen with SKF 38393 alone. Intrastriatal infusion of SKF 38393 produced a concentration-dependent increase in immediate early gene expression in the striatum. Furthermore, intrastriatal application of the D1-receptor antagonist SCH 23390 blocked the induction of immediate early genes by SKF 38393 given systemically either alone or with quinpirole. The induction of immediate early genes by co-administration of SKF 38393 and quinpirole was also significantly attenuated by intrastriatal administration of the D2-receptor antagonist eticlopride. These data show that D1-D2 synergy is operative in the dopamine-depleted striatum, is reflected in increases in the expression of the immediate early genes zif268 and c-fos, and is a consequence of activation of both D1 and D2 receptors within the striatum rather than in extrastriatal sites. The data further suggest that the enhanced induction of immediate early genes in the dopamine-depleted striatum of rats receiving SKF 38393 with quinpirole reflects a D2-mediated potentiation of a D1-dependent process. JF - Neuroscience AU - Keefe, K A AU - Gerfen, C R AD - Section of Neuroanatomy, National Institute of Mental Health, Bethesda, MD 20892, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 903 EP - 913 VL - 66 IS - 4 SN - 0306-4522, 0306-4522 KW - Dopamine D2 Receptor Antagonists KW - 0 KW - Receptors, Dopamine D1 KW - Receptors, Dopamine D2 KW - 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine KW - 67287-49-4 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - In Situ Hybridization KW - Dopamine -- pharmacology KW - Gene Expression KW - Drug Synergism KW - 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine -- pharmacology KW - Male KW - Receptors, Dopamine D1 -- physiology KW - Receptors, Dopamine D1 -- agonists KW - Genes, Immediate-Early -- drug effects KW - Receptors, Dopamine D1 -- antagonists & inhibitors KW - Receptors, Dopamine D2 -- agonists KW - Genes, Immediate-Early -- genetics KW - Corpus Striatum -- drug effects KW - Receptors, Dopamine D2 -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77472473?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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&rft.atitle=D1-D2+dopamine+receptor+synergy+in+striatum%3A+effects+of+intrastriatal+infusions+of+dopamine+agonists+and+antagonists+on+immediate+early+gene+expression.&rft.au=Keefe%2C+K+A%3BGerfen%2C+C+R&rft.aulast=Keefe&rft.aufirst=K&rft.date=1995-06-01&rft.volume=66&rft.issue=4&rft.spage=903&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-27 N1 - Date created - 1995-09-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A role for calcium release-activated current (CRAC) in cholinergic modulation of electrical activity in pancreatic beta-cells. AN - 77464970; 7647236 AB - S. Bordin and colleagues have proposed that the depolarizing effects of acetylcholine and other muscarinic agonists on pancreatic beta-cells are mediated by a calcium release-activated current (CRAC). We support this hypothesis with additional data, and present a theoretical model which accounts for most known data on muscarinic effects. Additional phenomena, such as the biphasic responses of beta-cells to changes in glucose concentration and the depolarizing effects of the sarco-endoplasmic reticulum calcium ATPase pump poison thapsigargin, are also accounted for by our model. The ability of this single hypothesis, that CRAC is present in beta-cells, to explain so many phenomena motivates a more complete characterization of this current. JF - Biophysical journal AU - Bertram, R AU - Smolen, P AU - Sherman, A AU - Mears, D AU - Atwater, I AU - Martin, F AU - Soria, B AD - Mathematical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 2323 EP - 2332 VL - 68 IS - 6 SN - 0006-3495, 0006-3495 KW - Cholinergic Agents KW - 0 KW - Insulin KW - Terpenes KW - Thapsigargin KW - 67526-95-8 KW - Carbachol KW - 8Y164V895Y KW - Calcium-Transporting ATPases KW - EC 3.6.3.8 KW - Glucose KW - IY9XDZ35W2 KW - Acetylcholine KW - N9YNS0M02X KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Endoplasmic Reticulum -- enzymology KW - Animals KW - Sarcoplasmic Reticulum -- enzymology KW - Membrane Potentials -- physiology KW - Acetylcholine -- pharmacology KW - Calcium-Transporting ATPases -- antagonists & inhibitors KW - Insulin -- secretion KW - Mice KW - Mathematics KW - Glucose -- pharmacology KW - Kinetics KW - Membrane Potentials -- drug effects KW - Terpenes -- pharmacology KW - Time Factors KW - Carbachol -- pharmacology KW - Calcium -- metabolism KW - Islets of Langerhans -- drug effects KW - Islets of Langerhans -- physiology KW - Cholinergic Agents -- pharmacology KW - Models, Biological UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77464970?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biophysical+journal&rft.atitle=A+role+for+calcium+release-activated+current+%28CRAC%29+in+cholinergic+modulation+of+electrical+activity+in+pancreatic+beta-cells.&rft.au=Bertram%2C+R%3BSmolen%2C+P%3BSherman%2C+A%3BMears%2C+D%3BAtwater%2C+I%3BMartin%2C+F%3BSoria%2C+B&rft.aulast=Bertram&rft.aufirst=R&rft.date=1995-06-01&rft.volume=68&rft.issue=6&rft.spage=2323&rft.isbn=&rft.btitle=&rft.title=Biophysical+journal&rft.issn=00063495&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-25 N1 - Date created - 1995-09-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1984 Sep 20-26;311(5983):269-71 [6090929] Fed Proc. 1984 Jun;43(9):2368-72 [6327396] FEBS Lett. 1985 Oct 21;191(1):102-6 [3902500] Endocrinology. 1987 Sep;121(3):1025-33 [3304975] Endocrinology. 1988 May;122(5):2134-42 [3282876] FEBS Lett. 1988 Apr 11;231(1):143-7 [2452098] Pflugers Arch. 1988 Apr;411(4):401-9 [2456515] FEBS Lett. 1989 Jun 5;249(2):411-7 [2567680] J Biol Chem. 1989 Jul 25;264(21):12266-71 [2663854] Nature. 1989 Sep 21;341(6239):197-205 [2550825] FEBS Lett. 1989 Dec 18;259(1):19-23 [2689228] J Biol Chem. 1990 Sep 5;265(25):15010-4 [2394710] Prog Biophys Mol Biol. 1989;54(2):87-143 [2484976] J Clin Invest. 1972 Aug;51(8):2047-59 [4559946] Physiol Rev. 1974 Jul;54(3):596-619 [4601624] Diabetologia. 1974 Oct;10(5):431-8 [4375640] Horm Metab Res. 1976 Jan;8(1):11-6 [814075] J Physiol (Paris). 1977 Jul;73(2):201-17 [330839] Cell Calcium. 1990 Nov-Dec;11(10):611-24 [1965707] J Membr Biol. 1991 Jan;119(2):187-95 [1710672] Pflugers Arch. 1991 May;418(4):417-22 [1876486] Nature. 1991 Oct 31;353(6347):849-52 [1719424] Nature. 1992 Jan 23;355(6358):353-6 [1309940] Endocrinology. 1992 Jul;131(1):127-31 [1611991] J Membr Biol. 1992 Apr;127(1):9-19 [1328645] Pflugers Arch. 1993 Feb;422(5):443-8 [8474849] J Biol Chem. 1993 May 15;268(14):9953-6 [8387528] J Biol Chem. 1993 May 25;268(15):10808-12 [8098704] Cell Calcium. 1993 May;14(5):397-410 [8390921] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6295-9 [8392195] Nature. 1993 Aug 26;364(6440):809-14 [8355806] Nature. 1993 Aug 26;364(6440):814-8 [8395025] J Biol Chem. 1993 Oct 25;268(30):22265-8 [8226733] Endocrinology. 1994 Apr;134(4):1771-81 [8137742] J Theor Biol. 1994 Feb 21;166(4):461-73 [8176949] J Biol Chem. 1994 May 20;269(20):14359-62 [8182038] J Biol Chem. 1994 Jun 24;269(25):17095-103 [8006014] Endocrinology. 1994 Jul;135(1):365-72 [8013370] Am J Physiol. 1994 Nov;267(5 Pt 1):E769-74 [7977729] J Biol Chem. 1985 Mar 25;260(6):3440-50 [3838314] J Physiol. 1978 May;278:117-39 [353252] Diabetes. 1981 Jul;30(7):558-61 [7018962] Comment In: Biophys J. 1995 Jun;68(6):2216-7 [7647228] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Calcium tracer kinetics show decreased irreversible flow to bone in glucocorticoid treated patients. AN - 77464897; 7648481 AB - Osteopenia resulting from pharmacologic doses of glucocorticoids is well known. Previously, there has been no satisfactory quantitative model describing the kinetics of calcium flow in subjects on chronic steroid use. A mathematical model of calcium isotope interaction with bone is described and applied to determine an estimate of kinetic parameters characterizing these changes. Calcium tracer dilution kinetics after a bolus injection of 42Ca were measured in 14 subjects with juvenile dermatomyositis, 6 on prednisone regimens and 8 on treatment regimens without prednisone. Irreversible tracer loss from plasma bone is found to be significantly reduced (P = 0.043) in the glucocorticoid-treated patients compared with patients on nonsteroid regimens. Reversible flow to bone is noted to be similar in the two groups. These results suggest a direct effect of glucocorticoids on osteoblast function. JF - Calcified tissue international AU - Goans, R E AU - Weiss, G H AU - Abrams, S A AU - Perez, M D AU - Yergey, A L AD - Laboratory of Theoretical and Physical Biology, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 533 EP - 535 VL - 56 IS - 6 SN - 0171-967X, 0171-967X KW - Calcium Isotopes KW - 0 KW - Glucocorticoids KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Osteoblasts -- drug effects KW - Dermatomyositis -- drug therapy KW - Humans KW - Bone Diseases, Metabolic -- chemically induced KW - Indicator Dilution Techniques KW - Child KW - Dermatomyositis -- physiopathology KW - Adolescent KW - Models, Biological KW - Male KW - Female KW - Calcium -- metabolism KW - Glucocorticoids -- adverse effects KW - Bone and Bones -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77464897?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Calcified+tissue+international&rft.atitle=Calcium+tracer+kinetics+show+decreased+irreversible+flow+to+bone+in+glucocorticoid+treated+patients.&rft.au=Goans%2C+R+E%3BWeiss%2C+G+H%3BAbrams%2C+S+A%3BPerez%2C+M+D%3BYergey%2C+A+L&rft.aulast=Goans&rft.aufirst=R&rft.date=1995-06-01&rft.volume=56&rft.issue=6&rft.spage=533&rft.isbn=&rft.btitle=&rft.title=Calcified+tissue+international&rft.issn=0171967X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-25 N1 - Date created - 1995-09-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Late renal damage after total body irradiation and bone marrow transplantation in a mouse model: effect of radiation fractionation. AN - 77464570; 7646934 AB - In response to the accumulating evidence that renal damage is now becoming an important late complication after total body irradiation (TBI) and bone marrow transplantation (BMT), we have tested the effect of fractionated and hyperfractionated TBI on late kidney damage in a mouse model. TBI was given as fractionated (three fractions in 3 days, Fx 3), or hyperfractionated (nine fractions in 3 days, Fx 9) treatment. Kidney damage was evaluated using [51Cr]EDTA residual activity, blood urea nitrogen (BUN) and percentage haematocrit (%Hct) as end-points. We were able to detect progressive renal damage with no evidence of recovery or plateau in the Fx 3 and Fx 9 schedules. The time latency before the expression of renal damage was dependent on both total dose and end-point and it was shorter the higher the dose. [51Cr]EDTA detected renal damage at the same doses as BUN but earlier in time whereas %Hct detected renal damage at doses lower than both BUN and [51Cr]EDTA. Reducing the dose per fraction spared the kidney from TBI damage. The dose-response curves for renal damage (using the [51Cr]EDTA end-point) were steep, and tended to shift towards lower doses with longer follow-up times. The dose-modifying factors defined as the dose needed to cause renal damage in 50% of the animals (ED50) using single fraction TBI divided by the ED50 using fractionated TBI were 1.3 and 1.9 for the Fx 3 and Fx 9, respectively. These results may indicate that patients treated with TBI and BMT should be assessed for late kidney damage and that fractionation and particularly hyperfractionation may protect the kidneys from TBI-induced renal damage. JF - European journal of cancer (Oxford, England : 1990) AU - Safwat, A AU - Nielsen, O S AU - el-Badawy, S AU - Overgaard, J AD - Department of Radiotherapy, National Cancer Institute, Fom El-Khalig, Cairo, Egypt. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 987 EP - 992 VL - 31A IS - 6 SN - 0959-8049, 0959-8049 KW - Edetic Acid KW - 9G34HU7RV0 KW - Index Medicus KW - Animals KW - Hematocrit KW - Disease Models, Animal KW - Mice KW - Edetic Acid -- metabolism KW - Dose-Response Relationship, Radiation KW - Blood Urea Nitrogen KW - Male KW - Whole-Body Irradiation -- methods KW - Whole-Body Irradiation -- adverse effects KW - Bone Marrow Transplantation -- adverse effects KW - Kidney Diseases -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77464570?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+cancer+%28Oxford%2C+England+%3A+1990%29&rft.atitle=Late+renal+damage+after+total+body+irradiation+and+bone+marrow+transplantation+in+a+mouse+model%3A+effect+of+radiation+fractionation.&rft.au=Safwat%2C+A%3BNielsen%2C+O+S%3Bel-Badawy%2C+S%3BOvergaard%2C+J&rft.aulast=Safwat&rft.aufirst=A&rft.date=1995-06-01&rft.volume=31A&rft.issue=6&rft.spage=987&rft.isbn=&rft.btitle=&rft.title=European+journal+of+cancer+%28Oxford%2C+England+%3A+1990%29&rft.issn=09598049&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-27 N1 - Date created - 1995-09-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - United States non-Hodgkin's lymphoma surveillance by occupation 1984-1989: a twenty-four state death certificate study. AN - 77462142; 7645576 AB - Death certificates from 23,890 male and female non-Hodgkin's lymphoma (NHL) cases and 119,450 noncancer controls from 24 states for the period 1984-1989 were used to generate hypotheses regarding occupational associations. Cases were frequency matched by age, race, and gender with five controls per case. Odds ratios were calculated for 231 industries and 509 occupations. Significant associations were observed for a variety of white-collar professionals (i.e., real estate agents, secretaries, bookkeepers, teachers, postal employees, business agents, engineers, chemists, and medical professionals) and blue-collar occupations (i.e., firefighters, farm managers, aircraft mechanics, electronic repairers, mining machine operators, and crane and tower operators). JF - American journal of industrial medicine AU - Figgs, L W AU - Dosemeci, M AU - Blair, A AD - Occupational Studies Section, Environmental Epidemiology Branch, National Cancer Institute, Rockville, MD 20892, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 817 EP - 835 VL - 27 IS - 6 SN - 0271-3586, 0271-3586 KW - Index Medicus KW - Odds Ratio KW - Sex Factors KW - Risk Factors KW - Humans KW - European Continental Ancestry Group KW - Adult KW - Case-Control Studies KW - Aged KW - African Americans KW - Middle Aged KW - Residence Characteristics KW - United States -- epidemiology KW - Male KW - Female KW - Occupational Exposure -- statistics & numerical data KW - Sentinel Surveillance KW - Lymphoma, Non-Hodgkin -- mortality KW - Death Certificates KW - Occupations UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77462142?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=United+States+non-Hodgkin%27s+lymphoma+surveillance+by+occupation+1984-1989%3A+a+twenty-four+state+death+certificate+study.&rft.au=Figgs%2C+L+W%3BDosemeci%2C+M%3BBlair%2C+A&rft.aulast=Figgs&rft.aufirst=L&rft.date=1995-06-01&rft.volume=27&rft.issue=6&rft.spage=817&rft.isbn=&rft.btitle=&rft.title=American+journal+of+industrial+medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-21 N1 - Date created - 1995-09-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The loss of regenerated host axons in nerve allografts after stopping immunosuppression with cyclosporin A is related to immune effects on allogeneic Schwann cells. AN - 77460517; 7649224 AB - After immunosuppressive therapy with Cyclosporin A (Cy-A) is stopped, nerve allograft rejection occurs. In addition to the loss of allogeneic perineurial, vascular, and Schwann cells, host axons that regenerate into the allograft disappear despite the fact that the axons are not foreign tissue. The present experiment was performed to correlate immune events and allogeneic cell and host axonal loss in nerve allografts after terminating Cy-A treatment. Nerve grafts (4 cm long) were taken from American Cancer Institute (ACI) rats and joined to the peroneal nerves of Fischer (FR) or ACI rats that received a daily dose of Cy-A (10 mg/kg, intraperitoneally). After one week, Cy-A therapy was stopped and the grafts were examined 2-6 weeks postoperatively by light and electron microscopy. No immune reaction nor destruction of perineural, vascular, or Schwann cells was found in 2- or 3-week-old allografts (i.e., ACI to FR grafts). These grafts underwent Wallerian degeneration and were invaded proximally by regenerating host axons, some of which were thinly myelinated. At 4 weeks, the perineurium of each allograft became infiltrated by mononuclear cells and was destroyed. Many of the endoneurial blood vessels of these grafts were occluded and their endothelial cells were degenerating or missing. Despite the immune reaction, allogeneic Schwann cells remained and continued to myelinate or ensheath host axons that had now grown up to 3 cm into the grafts.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Experimental neurology AU - Zalewski, A A AU - Azzam, N A AU - Azzam, R N AD - Laboratory of Neural Control, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-4120, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 189 EP - 197 VL - 133 IS - 2 SN - 0014-4886, 0014-4886 KW - Cyclosporine KW - 83HN0GTJ6D KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Substance Withdrawal Syndrome KW - Cyclosporine -- pharmacology KW - Microscopy, Electron KW - Transplantation, Homologous KW - Rats, Inbred ACI KW - Male KW - Immunosuppression KW - Schwann Cells -- immunology KW - Nerve Regeneration KW - Axons -- ultrastructure KW - Graft Rejection -- immunology KW - Nerve Tissue -- transplantation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77460517?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+neurology&rft.atitle=The+loss+of+regenerated+host+axons+in+nerve+allografts+after+stopping+immunosuppression+with+cyclosporin+A+is+related+to+immune+effects+on+allogeneic+Schwann+cells.&rft.au=Zalewski%2C+A+A%3BAzzam%2C+N+A%3BAzzam%2C+R+N&rft.aulast=Zalewski&rft.aufirst=A&rft.date=1995-06-01&rft.volume=133&rft.issue=2&rft.spage=189&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 - 1995-09-22 N1 - Date created - 1995-09-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicity studies and distribution dynamics of retroviral vectors following intrathecal administration of retroviral vector-producer cells. AN - 77413526; 7621261 AB - The use of intrathecal, retroviral-mediated transfer of the herpes simplex thymidine kinase (HStk) gene and subsequent ganciclovir (GCV) administration has recently been shown to improve survival in a rat model of leptomeningeal carcinomatosis. Clinical application of this approach is attractive because access to the cerebrospinal fluid (CSF) space is relatively noninvasive and distribution of producer cells and vectors may be facilitated by circulation of CSF, overcoming distribution problems inherent in solid tumors. However, meningeal inflammation, transduction and injury to normal CNS tissue, proliferation of the xenogeneic producer cells in the subarachnoid space, immune-mediated injury, and development of hydrocephalus are possible complications of intraventricular or intrathecal administration of vector-producer cells. In addition, the dynamics of producer cell and vector distribution in the CSF are unknown. To address these issues, we evaluated the safety of this approach for gene delivery and assessed the dynamics of distribution of producer cells and retroviral vectors in rats and non-human primates. In rats, transduction of normal central nervous system (CNS) structures surrounding the subarachnoid space was evaluated after intrathecal and intraventricular injections of beta-galactosidase and HStk vector-producer cells, with and without GCV. In primates, beta-galactosidase and HStk vector-producer cells were injected intraventricularly and GCV was administered either intrathecally or intravenously. Toxicity was evaluated by neurologic examination, serial gadolinium-enhanced MRI scans of the brain, and blood and CSF profiles. A subgroup of monkeys received repeated intraventricular injection of vector-producer cells and intravenous GCV. The titer of retroviral-vector was measured in cisternal and lumbar CSF samples after repeated producer cell injection.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Cancer gene therapy AU - Oshiro, E M AU - Viola, J J AU - Oldfield, E H AU - Walbridge, S AU - Bacher, J AU - Frank, J A AU - Blaese, R M AU - Ram, Z AD - Surgical Neurology Branch, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 87 EP - 95 VL - 2 IS - 2 SN - 0929-1903, 0929-1903 KW - HStk KW - NeoR KW - lacZ KW - Recombinant Fusion Proteins KW - 0 KW - Viral Proteins KW - Thymidine Kinase KW - EC 2.7.1.21 KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Ganciclovir KW - P9G3CKZ4P5 KW - Index Medicus KW - Magnetic Resonance Imaging KW - Animals KW - Rats -- blood KW - Simplexvirus -- enzymology KW - Mice KW - Tissue Distribution KW - Simplexvirus -- immunology KW - Rats -- cerebrospinal fluid KW - Injections, Intraventricular KW - Macaca mulatta -- blood KW - Subarachnoid Space KW - Choroid Plexus -- metabolism KW - Choroid Plexus -- virology KW - Graft Survival KW - Injections, Spinal KW - Simplexvirus -- genetics KW - Genes, Reporter KW - Macaca mulatta -- cerebrospinal fluid KW - Moloney murine leukemia virus -- genetics KW - beta-Galactosidase -- biosynthesis KW - Brain Diseases -- etiology KW - Choroid Plexus -- pathology KW - Viral Proteins -- immunology KW - Viral Proteins -- genetics KW - Viral Proteins -- therapeutic use KW - Genetic Vectors -- administration & dosage KW - Genetic Vectors -- toxicity KW - Thymidine Kinase -- therapeutic use KW - Recombinant Fusion Proteins -- metabolism KW - Thymidine Kinase -- immunology KW - 3T3 Cells -- transplantation KW - Ganciclovir -- toxicity KW - Genetic Therapy -- methods KW - Genetic Vectors -- pharmacokinetics KW - Recombinant Fusion Proteins -- therapeutic use KW - Thymidine Kinase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77413526?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+gene+therapy&rft.atitle=Toxicity+studies+and+distribution+dynamics+of+retroviral+vectors+following+intrathecal+administration+of+retroviral+vector-producer+cells.&rft.au=Oshiro%2C+E+M%3BViola%2C+J+J%3BOldfield%2C+E+H%3BWalbridge%2C+S%3BBacher%2C+J%3BFrank%2C+J+A%3BBlaese%2C+R+M%3BRam%2C+Z&rft.aulast=Oshiro&rft.aufirst=E&rft.date=1995-06-01&rft.volume=2&rft.issue=2&rft.spage=87&rft.isbn=&rft.btitle=&rft.title=Cancer+gene+therapy&rft.issn=09291903&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-31 N1 - Date created - 1995-08-31 N1 - Date revised - 2017-01-13 N1 - Gene symbol - HStk; NeoR; lacZ N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of interleukin-1 alpha on DNA repair in human ovarian carcinoma (NIH:OVCAR-3) cells: implications in the mechanism of sensitization of cis-diamminedichloroplatinum(II). AN - 77375914; 7603468 AB - The cytokine interleukin-1 alpha (IL-1 alpha) showed a cytostatic effect on human ovarian carcinoma cells and significantly enhanced the antiproliferative activity of cis-diamminedichloroplatinum(II) (cisplatin) toward the NIH:OVCAR-3 tumor cell line in culture. The factor of sensitization was 15-20-fold. The maximum levels of sensitization were observed both with simultaneous exposure to cisplatin and IL-1 alpha and with 24-hr pretreatment with IL-1 alpha. Synergy between these agents was diminished when cells were pretreated with an IL-1 alpha-specific receptor antagonist, indicating that synergistic interaction was receptor mediated. Using atomic absorption spectroscopy, we evaluated the cellular accumulation of cisplatin and the DNA platination; the results showed that IL-1 alpha increased cellular accumulation of cisplatin and DNA platination. Cisplatin did not affect IL-1 alpha accumulation in NIH:OVCAR-3 cells. Further studies showed that IL-1 alpha reduced the removal of platinum from DNA. These results strongly suggest that IL-1 alpha inhibits DNA repair, and this decrease in DNA repair may explain, in part, the strong synergistic interaction between IL-1 alpha and cisplatin in NIH:OVCAR-3 cells. JF - Molecular pharmacology AU - Benchekroun, M N AU - Parker, R AU - Dabholkar, M AU - Reed, E AU - Sinha, B K AD - Clinical Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 1255 EP - 1260 VL - 47 IS - 6 SN - 0026-895X, 0026-895X KW - DNA Adducts KW - 0 KW - IL1RN protein, human KW - Interleukin 1 Receptor Antagonist Protein KW - Interleukin-1 KW - Sialoglycoproteins KW - cisplatin-DNA adduct KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Glutathione KW - GAN16C9B8O KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Sialoglycoproteins -- pharmacology KW - Tumor Cells, Cultured KW - Humans KW - Glutathione -- metabolism KW - Glutathione Transferase -- metabolism KW - Drug Synergism KW - Female KW - Interleukin-1 -- pharmacology KW - Ovarian Neoplasms -- genetics KW - Ovarian Neoplasms -- pathology KW - Cisplatin -- pharmacology KW - DNA Repair -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77375914?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effects+of+interleukin-1+alpha+on+DNA+repair+in+human+ovarian+carcinoma+%28NIH%3AOVCAR-3%29+cells%3A+implications+in+the+mechanism+of+sensitization+of+cis-diamminedichloroplatinum%28II%29.&rft.au=Benchekroun%2C+M+N%3BParker%2C+R%3BDabholkar%2C+M%3BReed%2C+E%3BSinha%2C+B+K&rft.aulast=Benchekroun&rft.aufirst=M&rft.date=1995-06-01&rft.volume=47&rft.issue=6&rft.spage=1255&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 - 1995-08-04 N1 - Date created - 1995-08-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of v-Ha-ras and v-fos oncogene transduction into a mouse epidermal cell line with "initiated" phenotype in culture but normal skin phenotype in vivo. AN - 77373799; 7605585 AB - Cell line SCR722 was derived from adult SENCAR mouse epidermal cells initiated in culture by treatment with the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine and selection for foci proliferating in medium with calcium levels that induce terminal differentiation in normal cells. Expansion of one of these foci and two additional cell clonings produced cell line SCR722, which was near-tetraploid and formed normal skin when grafted to athymic nude mouse hosts. However, unlike normal keratinocytes, SCR722 cells fail to suppress papilloma formation when grafted along with papilloma cell line SP-1. For optimum growth in culture, SCR722 cells required fibroblast-conditioned medium and 0.5 mM Ca2+. SCR722 cells had a wild-type c-Ha-ras gene but had lost their requirement for conditioned medium in culture and produced dysplastic papillomas in grafts when transduced with the v-Ha-ras gene. SCR722 cells stably expressing the v-fos gene produced normal epidermis in grafts, but when these cells were transduced with the v-Ha-ras gene, they produced carcinomas. Clones with greater expression of the transfected v-fos gene had a more invasive phenotype in vivo. These results indicate that carcinogen treatment of epithelial cells can result in an altered but nontumorigenic phenotype that may be at risk for becoming a more advanced neoplastic state with additional genetic alterations. JF - Molecular carcinogenesis AU - Ueda, M AU - Kawamura, H AU - Sutter, C AU - Glick, A AU - Yuspa, S H AU - Strickland, J E AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 96 EP - 103 VL - 13 IS - 2 SN - 0899-1987, 0899-1987 KW - v-Ha-ras KW - v-fos KW - Methylnitronitrosoguanidine KW - 12H3O2UGSF KW - Index Medicus KW - Animals KW - Mice KW - Mice, Nude KW - Skin Neoplasms -- genetics KW - Evaluation Studies as Topic KW - Phenotype KW - Base Sequence KW - Skin -- drug effects KW - Skin Neoplasms -- chemically induced KW - Molecular Sequence Data KW - Mice, Inbred SENCAR KW - Ploidies KW - Cell Line KW - Genes, ras KW - Skin Physiological Phenomena KW - Transduction, Genetic KW - Genes, fos UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77373799?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+carcinogenesis&rft.atitle=Analysis+of+v-Ha-ras+and+v-fos+oncogene+transduction+into+a+mouse+epidermal+cell+line+with+%22initiated%22+phenotype+in+culture+but+normal+skin+phenotype+in+vivo.&rft.au=Ueda%2C+M%3BKawamura%2C+H%3BSutter%2C+C%3BGlick%2C+A%3BYuspa%2C+S+H%3BStrickland%2C+J+E&rft.aulast=Ueda&rft.aufirst=M&rft.date=1995-06-01&rft.volume=13&rft.issue=2&rft.spage=96&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 - 1995-08-15 N1 - Date created - 1995-08-15 N1 - Date revised - 2017-01-13 N1 - Gene symbol - v-Ha-ras; v-fos N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Paclitaxel, cisplatin, and cyclophosphamide in human ovarian cancer: molecular rationale and early clinical results. AN - 77362091; 7541159 AB - The three most active types of agents in the treatment of cancer of the ovary are platinum compounds (cisplatin or carboplatin), bifunctional alkylating agents (cyclophosphamide, melphalan, etc), and the recently developed natural product paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ). In an effort to improve long-term disease-free survival in patients with advanced disease, we have developed a three-drug regimen consisting of cisplatin, paclitaxel, and cyclophosphamide. Granulocyte-colony stimulating factor is given as bone marrow support using a flexible dosing approach. The molecular basis for this approach is founded in the positive molecular interactions between cisplatin and bifunctional alkylating agents and between paclitaxel and DNA-damaging agents. Cisplatin and cyclophosphamide damage DNA by two very different mechanisms; the respective importance of DNA strand "kinking" versus DNA strand "cross-linking" may explain the positive cell kill interaction between these two drugs. Paclitaxel appears to markedly slow the repair of DNA lesions caused by DNA-damaging agents, which may include radiation-induced lesions, cisplatin adducts, and cyclophosphamide cross-links. Clinical data to date from several different groups strongly suggest that these molecular interactions translate into positive clinical benefit in human ovarian cancer. Preliminary data from our clinical trial show that these three agents are well tolerated in the doses administered and that this combination shows exceptional promise as a possible therapeutic advance in this disease. JF - Seminars in oncology AU - Reed, E AU - Kohn, E C AU - Sarosy, G AU - Dabholkar, M AU - Davis, P AU - Jacob, J AU - Maher, M AD - Medical Ovarian Cancer Section, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 90 EP - 96 VL - 22 IS - 3 Suppl 6 SN - 0093-7754, 0093-7754 KW - DNA, Neoplasm KW - 0 KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Cyclophosphamide KW - 8N3DW7272P KW - Paclitaxel KW - P88XT4IS4D KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Paclitaxel -- administration & dosage KW - Granulocyte Colony-Stimulating Factor -- therapeutic use KW - Humans KW - Clinical Trials as Topic KW - Paclitaxel -- pharmacology KW - Cell Survival KW - Cisplatin -- administration & dosage KW - Tumor Cells, Cultured KW - Cisplatin -- pharmacology KW - Drug Synergism KW - Female KW - Cyclophosphamide -- pharmacology KW - DNA, Neoplasm -- drug effects KW - DNA Repair KW - DNA Damage KW - Ovarian Neoplasms -- pathology KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacology KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Ovarian Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77362091?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+oncology&rft.atitle=Paclitaxel%2C+cisplatin%2C+and+cyclophosphamide+in+human+ovarian+cancer%3A+molecular+rationale+and+early+clinical+results.&rft.au=Reed%2C+E%3BKohn%2C+E+C%3BSarosy%2C+G%3BDabholkar%2C+M%3BDavis%2C+P%3BJacob%2C+J%3BMaher%2C+M&rft.aulast=Reed&rft.aufirst=E&rft.date=1995-06-01&rft.volume=22&rft.issue=3+Suppl+6&rft.spage=90&rft.isbn=&rft.btitle=&rft.title=Seminars+in+oncology&rft.issn=00937754&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-31 N1 - Date created - 1995-07-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Promotion of N-nitrosodimethylamine-initiated mouse lung tumors following single or multiple low dose exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. AN - 77348164; 7788853 AB - The environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is highly toxic to several rodent species and may have adverse health effects in exposed human populations. Further, TCDD has been shown to be a potent liver tumor promoter in the rat after repeated administration. These studies were conducted to determine the tumor promoting capability of TCDD in the Swiss mouse following single or multiple exposures. Following tumor initiation with N-nitrosodimethylamine (NDMA; 25 mg/kg), animals were given either a single dose (1.6, 16 or 48 micrograms/kg) or repeated injections (0.05 microgram/kg/week for 20 weeks) of TCDD and sacrificed at 52 weeks of age. Neither NDMA nor TCDD caused an increase in incidence of liver tumors. NDMA induced lung tumors in 100% of animals, with 12 +/- 0.1 tumors/mouse. The multiplicity of lung tumors was significantly increased by low dose TCDD treatment, with 20 +/- 2.6 tumors/mouse following a single 1.6 micrograms/kg dose (P = 0.016) and 18 +/- 1.7 (P = 0.031) following repeated 0.05 microgram/kg doses (x 20). Higher doses of TCDD did not increase multiplicity of lung tumors and, in fact, may have been toxic to the lungs of NDMA-treated mice, as evidenced by the infiltration of pigmented macrophages. These data demonstrate the potent tumor promoting capability of TCDD in mouse lung. JF - Carcinogenesis AU - Beebe, L E AU - Anver, M R AU - Riggs, C W AU - Fornwald, L W AU - Anderson, L M AD - Laboratory of Comparative Carcinogenesis, PRI/DynCorp, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 1345 EP - 1349 VL - 16 IS - 6 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - Polychlorinated Dibenzodioxins KW - Dimethylnitrosamine KW - M43H21IO8R KW - Index Medicus KW - Animals KW - Mice KW - Male KW - Polychlorinated Dibenzodioxins -- administration & dosage KW - Lung Neoplasms -- chemically induced KW - Neoplasms, Multiple Primary -- chemically induced KW - Dimethylnitrosamine -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77348164?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Promotion+of+N-nitrosodimethylamine-initiated+mouse+lung+tumors+following+single+or+multiple+low+dose+exposure+to+2%2C3%2C7%2C8-tetrachlorodibenzo-p-dioxin.&rft.au=Beebe%2C+L+E%3BAnver%2C+M+R%3BRiggs%2C+C+W%3BFornwald%2C+L+W%3BAnderson%2C+L+M&rft.aulast=Beebe&rft.aufirst=L&rft.date=1995-06-01&rft.volume=16&rft.issue=6&rft.spage=1345&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-26 N1 - Date created - 1995-07-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nitric oxide protects against alkyl peroxide-mediated cytotoxicity: further insights into the role nitric oxide plays in oxidative stress. AN - 77344379; 7786021 AB - Endogenously formed nitric oxide (NO) possesses diverse properties such as regulating physiological functions, exerting specific toxic effects, and protecting against various toxic substances. Recent studies suggest that in the presence of reactive oxygen species, NO can serve as an antioxidant. We show here that NO delivered from the NO donor compound, PAPA/NO (NH2(C3H6)(N[N(O)NO](C3H7)), protects Chinese hamster V79 lung fibroblasts from the cytotoxicity of t-butyl hydroperoxide and cumene hydroperoxide. In contrast, the other end products of PAPA/NO degradation in aqueous solution, NH2(C3H6)NH(C3H7) and nitrite, did not protect. The NONOate DEA/NO releases NO six times faster than PAPA/NO, yet did not afford protection, which implies that NO must be present throughout the alkyl hydroperoxide exposure. Measurements of NO concentrations released from PAPA/NO suggest that micromolar levels protect against cytotoxicity induced by alkyl hydroperoxides. These findings demonstrate that the flux of NO sustained over the duration of the peroxide exposure determines protection and not the total of NO delivered. These results suggest that concentrations of NO produced in the microenvironment of endothelial cells are high enough to protect cells from Fenton-type-mediated toxicity and support the premise that NO may exert a salutary effect in certain diseases associated with membrane damage. JF - Archives of biochemistry and biophysics AU - Wink, D A AU - Cook, J A AU - Krishna, M C AU - Hanbauer, I AU - DeGraff, W AU - Gamson, J AU - Mitchell, J B AD - Chemistry Section, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1995/06/01/ PY - 1995 DA - 1995 Jun 01 SP - 402 EP - 407 VL - 319 IS - 2 SN - 0003-9861, 0003-9861 KW - Alkylating Agents KW - 0 KW - Peroxides KW - Nitric Oxide KW - 31C4KY9ESH KW - Index Medicus KW - Animals KW - Cricetulus KW - Cell Line -- drug effects KW - Oxidative Stress KW - Cell Death KW - Cricetinae KW - Cell Survival KW - Peroxides -- pharmacology KW - Alkylating Agents -- pharmacology KW - Nitric Oxide -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77344379?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Nitric+oxide+protects+against+alkyl+peroxide-mediated+cytotoxicity%3A+further+insights+into+the+role+nitric+oxide+plays+in+oxidative+stress.&rft.au=Wink%2C+D+A%3BCook%2C+J+A%3BKrishna%2C+M+C%3BHanbauer%2C+I%3BDeGraff%2C+W%3BGamson%2C+J%3BMitchell%2C+J+B&rft.aulast=Wink&rft.aufirst=D&rft.date=1995-06-01&rft.volume=319&rft.issue=2&rft.spage=402&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 - 1995-07-17 N1 - Date created - 1995-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metabolism of the food-derived carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in nonhuman primates. AN - 77341480; 7788858 AB - The metabolism and disposition of the food mutagen and rodent carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline was investigated in cynomolgus monkeys. Monkeys were administered a single dose of radiolabeled [14C]MeIQx (2.2 or 50 mumol/kg). Peak blood levels of radioactivity were observed within 1-3 h after dosing and declined rapidly thereafter. By 72 h after dosing, approximately 50% and 70% of the 2.2 mumol/kg, and 50 mumol/kg dose, respectively, was excreted in the urine. Approximately 15-20% of either dose was recovered in the feces. Eight metabolites and the parent compound were detected in urine by HPLC. The parent compound accounted for approximately 15-25% of the dose excreted in the urine. Seven MeIQx urinary metabolites were identified. Five metabolites were identical to MeIQx metabolites previously found in rats: MeIQx-N2-glucuronide, MeIQx-N2-sulfamate, MeIQx-5-sulfate, MeIQx-5-O-glucuronide, and 8-CH2OH-MeIQx-5-sulfate. Cynomolgus monkeys, however, metabolized MeIQx to a novel glucuronide conjugate of MeIQx not found in rats. Based upon mass spectroscopy and proton NMR analyses, the structure of this metabolite was consistent with an N1-glucuronide of MeIQx. This metabolite was the major urinary metabolite found in monkeys, accounting for 31-37% of the dose excreted in the urine over a 24 h period. One additional metabolite identified in urine and feces of MeIQx treated cynomolgus monkeys, that has not been found previously in any other animal model, was 7-oxo-MeIQx, a likely enteric bacterial metabolite of MeIQx. 7-Oxo-MeIQx accounted for 20-25% of the dose of MeIQx found in the urine and was the major fecal metabolite. The N2-glucuronide conjugate of the carcinogenic metabolite 2-hydroxyamino-3,8-dimethylimidazo[4,5-f]quinoxaline (NHOH-MeIQx) was not detected in urine or bile of monkeys, even after 10 daily doses of MeIQx (100 mumol/kg) were given. The results indicate that MeIQx is metabolically processed in monkeys via multiple pathways of detoxification. However, MeIQx is poorly metabolically activated via cytochrome P450 mediated N-oxidation. The in vivo metabolism of MeIQx in cynomolgus monkeys is different from that of the structurally related food-derived mutagen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), which is readily metabolically activated by this species and in contrast to MeIQx, has been shown to be a powerful hepatic carcinogen. JF - Carcinogenesis AU - Snyderwine, E G AU - Welti, D H AU - Davis, C D AU - Fay, L B AU - Turesky, R J AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 1377 EP - 1384 VL - 16 IS - 6 SN - 0143-3334, 0143-3334 KW - Quinoxalines KW - 0 KW - 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline KW - 77500-04-0 KW - Index Medicus KW - Animals KW - Macaca fascicularis KW - Biotransformation KW - Female KW - Magnetic Resonance Spectroscopy KW - Quinoxalines -- urine KW - Quinoxalines -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77341480?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Metabolism+of+the+food-derived+carcinogen+2-amino-3%2C8-dimethylimidazo%5B4%2C5-f%5Dquinoxaline+%28MeIQx%29+in+nonhuman+primates.&rft.au=Snyderwine%2C+E+G%3BWelti%2C+D+H%3BDavis%2C+C+D%3BFay%2C+L+B%3BTuresky%2C+R+J&rft.aulast=Snyderwine&rft.aufirst=E&rft.date=1995-06-01&rft.volume=16&rft.issue=6&rft.spage=1377&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-26 N1 - Date created - 1995-07-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alterations in thyroid function in female Sprague-Dawley rats following chronic treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin. AN - 77337901; 7540335 AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a multisite carcinogen. Although the hepatocarcinogenic actions of TCDD have received the most attention, it has been demonstrated in several rodent carcinogenicity bioassays that TCDD causes a dose-related increase in thyroid follicular cell adenomas and carcinomas. The purpose of the present experiment was to investigate the dose-response relationship for thyroid function alterations in female Sprague-Dawley rats following chronic treatment with TCDD. TCDD was administered via oral gavage biweekly for 30 weeks at average daily equivalent doses of 0.1-125 ng/kg/day, thereby more than encompassing the dose range historically used in previous TCDD rodent bioassays. The endpoints examined include serum levels of thyroxine (T4), triiodothyronine (T3), and thyroid-stimulating hormone (TSH). In addition, the induction of the dioxin-responsive genes UDP-glucuronosyltransferase-1 (UGT1) and cytochrome P450 1A1 (CYP1A1) in liver were measured using reverse-transcriptase-polymerase chain reaction (RT-PCR). In agreement with previous hypotheses, TCDD appears to alter thyroid function via a secondary mechanism, namely increased excretion of T4-glucuronide resulting from TCDD induction of UGT1. The observed follicular cell hyperplasia and hypertrophy are consistent with the observed elevated TSH levels and may represent the early stages in the progression of thyroid carcinogenesis. Therefore, TCDD induces alterations in thyroid hormone function, probably as a result of chronic perturbations of liver-pituitary-thyroid axis. JF - Toxicology and applied pharmacology AU - Sewall, C H AU - Flagler, N AU - Vanden Heuvel, J P AU - Clark, G C AU - Tritscher, A M AU - Maronpot, R M AU - Lucier, G W AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 237 EP - 244 VL - 132 IS - 2 SN - 0041-008X, 0041-008X KW - Antithyroid Agents KW - 0 KW - Polychlorinated Dibenzodioxins KW - RNA, Messenger KW - Thyroid Hormones KW - Triiodothyronine KW - 06LU7C9H1V KW - Thyrotropin KW - 9002-71-5 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Glucuronosyltransferase KW - EC 2.4.1.17 KW - Thyroxine KW - Q51BO43MG4 KW - Index Medicus KW - Animals KW - Glucuronosyltransferase -- genetics KW - Triiodothyronine -- antagonists & inhibitors KW - Thyroid Gland -- pathology KW - Cytochrome P-450 Enzyme System -- genetics KW - Thyroxine -- biosynthesis KW - Triiodothyronine -- biosynthesis KW - Antithyroid Agents -- metabolism KW - Enzyme Induction -- genetics KW - Radioimmunoassay KW - Gene Expression Regulation -- genetics KW - Rats KW - Polymerase Chain Reaction KW - Rats, Sprague-Dawley KW - Base Sequence KW - Thyroid Gland -- drug effects KW - RNA, Messenger -- metabolism KW - Thyroxine -- antagonists & inhibitors KW - Molecular Sequence Data KW - Female KW - Thyroid Hormones -- biosynthesis KW - Thyrotropin -- biosynthesis KW - Polychlorinated Dibenzodioxins -- toxicity KW - Polychlorinated Dibenzodioxins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77337901?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Alterations+in+thyroid+function+in+female+Sprague-Dawley+rats+following+chronic+treatment+with+2%2C3%2C7%2C8-tetrachlorodibenzo-p-dioxin.&rft.au=Sewall%2C+C+H%3BFlagler%2C+N%3BVanden+Heuvel%2C+J+P%3BClark%2C+G+C%3BTritscher%2C+A+M%3BMaronpot%2C+R+M%3BLucier%2C+G+W&rft.aulast=Sewall&rft.aufirst=C&rft.date=1995-06-01&rft.volume=132&rft.issue=2&rft.spage=237&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 - 1995-07-17 N1 - Date created - 1995-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of p53 mutants on wild-type p53-mediated transactivation are cell type dependent. AN - 77335015; 7784055 AB - The spectrum of p53 mutations differs among human cancer types. We have hypothesized that the p53 mutational spectrum observed in particular tumor types reflects the functional ability of different p53 mutants to modulate wild-type (WT) p53-dependent gene transcription. Missense p53 mutants representing several mutational hotspot codons were cotransfected with WT p53 and analysed for their effects on p53-dependent transactivation of a reporter construct containing a specific p53 binding sequence (PG13-CAT) in human tumor cell lines lacking endogenous p53. Our results show that the ability of p53 mutants to inhibit WT p53-mediated transactivation is cell type dependent. In cell lines derived from a lung adenocarcinoma and a mesothelioma, the transactivation function of WT p53 was strongly inhibited by all p53 mutants examined. However, in cell lines derived from a prostate carcinoma and an osteosarcoma, the mutants examined generally had only minimal dominant negative effects. In cell lines derived from a hepatocellular carcinoma and an ovarian carcinoma, two mutants (248trp and 273his) enhanced WT p53-mediated transactivation of the reporter construct. Additional mutants retained the ability to inhibit WT p53-mediated transactivation in these cell lines. In addition, in a series of four breast tumor cell lines, the p53 mutants examined had similar effects on WT p53 transactivation ability including enhanced transactivation activity in the 273his cotransfectants. The p53 mutants were incapable of transactivating the PG13-CAT reporter in the absence of WT p53 expression. Therefore, the dominant negative effects of p53 mutants on WT p53 function may vary depending on the particular cell type. In addition, mutants with stronger inhibitory capabilities may confer a selective advantage during the tumorigenic process. JF - Oncogene AU - Forrester, K AU - Lupold, S E AU - Ott, V L AU - Chay, C H AU - Band, V AU - Wang, X W AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1995/06/01/ PY - 1995 DA - 1995 Jun 01 SP - 2103 EP - 2111 VL - 10 IS - 11 SN - 0950-9232, 0950-9232 KW - Oligodeoxyribonucleotides KW - 0 KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Base Sequence KW - Tumor Cells, Cultured KW - Humans KW - Molecular Sequence Data KW - Mutation KW - Protein Conformation KW - Neoplasms -- pathology KW - Tumor Suppressor Protein p53 -- chemistry KW - Transcriptional Activation -- genetics KW - Tumor Suppressor Protein p53 -- genetics KW - Tumor Suppressor Protein p53 -- metabolism KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77335015?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effects+of+p53+mutants+on+wild-type+p53-mediated+transactivation+are+cell+type+dependent.&rft.au=Forrester%2C+K%3BLupold%2C+S+E%3BOtt%2C+V+L%3BChay%2C+C+H%3BBand%2C+V%3BWang%2C+X+W%3BHarris%2C+C+C&rft.aulast=Forrester&rft.aufirst=K&rft.date=1995-06-01&rft.volume=10&rft.issue=11&rft.spage=2103&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-14 N1 - Date created - 1995-07-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - TCDD reduces rat hepatic epidermal growth factor receptor: comparison of binding, immunodetection, and autophosphorylation. AN - 77334496; 7785053 AB - Administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent tumor promoter, to rats resulted in a dose-dependent decrease in hepatic plasma membrane epidermal growth factor receptor (EGFR). The present study is the first to quantify and compare alterations in hepatic EGFR levels in female Sprague-Dawley rats 7 days after a single oral gavage dose of TCDD (0, 1, 5, 25, and 50 micrograms/kg) using three different techniques: (1) equilibrium receptor binding, (2) EGF induced receptor autophosphorylation, and (3) Western blot detection with a rabbit anti-rat EGFR polyclonal antibody. All three methods similarly demonstrated that the level of hepatic EGFR is significantly decreased at a dose of TCDD as low as 1 micrograms/kg. We showed that the immunoblot technique is a sensitive and quantitative alternative to radioligand binding assays. It is concluded that TCDD decreased total EGFR protein and maximum binding capacity without altering ligand binding affinity (Kd). The results demonstrated that ligand-induced autophosphorylation capacity and basal phosphotyrosine residues of plasma membrane EGFR were both decreased parallel with the decrease in EGFR protein, suggesting no TCDD-related alteration in the inherent functional ability of the receptor to undergo activation. Furthermore, it was found that the dose-response curve for EGFR protein level determined by Western blot analysis was similar for both male and female Sprague-Dawley rats. JF - Toxicology and applied pharmacology AU - Sewall, C H AU - Clark, G C AU - Lucier, G W AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 263 EP - 272 VL - 132 IS - 2 SN - 0041-008X, 0041-008X KW - Bile Acids and Salts KW - 0 KW - Enzymes KW - Polychlorinated Dibenzodioxins KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Animals KW - Sex Factors KW - Cytochrome P-450 Enzyme System -- metabolism KW - Bile Acids and Salts -- analysis KW - Organ Size KW - Phosphorylation -- drug effects KW - Rats KW - Cytochrome P-450 Enzyme System -- blood KW - Rats, Sprague-Dawley KW - Blotting, Western KW - Enzymes -- blood KW - Protein Binding -- drug effects KW - Enzyme Induction KW - Female KW - Male KW - Receptor, Epidermal Growth Factor -- drug effects KW - Liver -- ultrastructure KW - Liver -- anatomy & histology KW - Receptor, Epidermal Growth Factor -- metabolism KW - Liver -- drug effects KW - Receptor, Epidermal Growth Factor -- immunology KW - Polychlorinated Dibenzodioxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77334496?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=TCDD+reduces+rat+hepatic+epidermal+growth+factor+receptor%3A+comparison+of+binding%2C+immunodetection%2C+and+autophosphorylation.&rft.au=Sewall%2C+C+H%3BClark%2C+G+C%3BLucier%2C+G+W&rft.aulast=Sewall&rft.aufirst=C&rft.date=1995-06-01&rft.volume=132&rft.issue=2&rft.spage=263&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 - 1995-07-17 N1 - Date created - 1995-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effect of dose and interval between 5-fluorouracil and leucovorin on the formation of thymidylate synthase ternary complex in human cancer cells. AN - 77317832; 7779703 AB - We examined the importance of dosing interval between leucovorin (LCV) and 5-fluorouracil (5-FU) on intracellular thymidylate synthase (TS) ternary complex, free TS and total TS protein levels in human MCF-7 breast and NCI H630 colon cancer cell lines. A 2- to 3-fold increase in total TS was noted when either cell line was exposed to 5-FU 10 microM plus LCV (0.01-10 microM) compared with a 1.4- to 1.6-fold increase in total TS due to 5-FU 10 microM alone. The amount of TS ternary complex formed was 2- to 3-fold higher in both cell lines treated with the combination of 5-FU and LCV compared with 5-FU alone. TS complex formation and total TS protein increased with LCV dose (0.1-10 microM). In MCF-7 cells, the maximal increase in total TS protein and TS ternary complex formation was observed when 5-FU was delayed for 4 h after the start of LCV exposure. In NCI H630 cells, maximal total TS protein and ternary complex formation occurred when 5-FU was delayed for 18 h after the start of LCV exposure. The amount of free TS did not change in either cell line whether 5-FU was given concurrently with LCV or delayed for up to 24 h. The accumulation rate of intracellular folates in the form of higher glutamates Glu3-Glu5 was rapid in MCF-7 cells (maximal formation after 4 h), whereas in H630 cells accumulation of higher polyglutamates continued to increase up to 18 h. The time of peak folate polyglutamate (Glu3-Glu5) formation coincided with the time of peak TS complex formation and total TS protein in each cell line. In these human carcinoma cell lines, the LCV dose and interval between 5-FU and LCV play a role in increased TS total protein and TS ternary complex; however, the amount of free TS is independent of the interval between 5-FU and LCV. The time-and dose-dependent increases in TS ternary complex and TS total protein are associated with differences in the accumulation of folate polyglutamates in these cell lines. JF - British journal of cancer AU - Drake, J C AU - Voeller, D M AU - Allegra, C J AU - Johnston, P G AD - NCI-Navy Medical Oncology Branch, Bethesda, Maryland 20889-5105, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 1145 EP - 1150 VL - 71 IS - 6 SN - 0007-0920, 0007-0920 KW - Macromolecular Substances KW - 0 KW - Thymidylate Synthase KW - EC 2.1.1.45 KW - Leucovorin KW - Q573I9DVLP KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Drug Interactions KW - Blotting, Western KW - Tumor Cells, Cultured KW - Dose-Response Relationship, Drug KW - Kinetics KW - Humans KW - Breast Neoplasms KW - Time Factors KW - Colonic Neoplasms KW - Cell Line KW - Thymidylate Synthase -- chemistry KW - Fluorouracil -- pharmacology KW - Leucovorin -- pharmacology KW - Thymidylate Synthase -- metabolism KW - Thymidylate Synthase -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77317832?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+effect+of+dose+and+interval+between+5-fluorouracil+and+leucovorin+on+the+formation+of+thymidylate+synthase+ternary+complex+in+human+cancer+cells.&rft.au=Drake%2C+J+C%3BVoeller%2C+D+M%3BAllegra%2C+C+J%3BJohnston%2C+P+G&rft.aulast=Drake&rft.aufirst=J&rft.date=1995-06-01&rft.volume=71&rft.issue=6&rft.spage=1145&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 - 1995-07-19 N1 - Date created - 1995-07-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1970 Aug 15;227(5259):680-5 [5432063] J Natl Cancer Inst. 1988 Dec 7;80(19):1560-4 [2973527] Biochemistry. 1974 Jan 29;13(3):471-81 [4203910] Anal Biochem. 1976 May 7;72:248-54 [942051] Biochim Biophys Acta. 1977 Dec 23;473(2):73-92 [145246] Proc Natl Acad Sci U S A. 1978 Feb;75(2):980-3 [147465] N Engl J Med. 1978 Nov 9;299(19):1049-52 [360064] J Biol Chem. 1979 Dec 25;254(24):12285-8 [115883] Cancer Res. 1981 Jan;41(1):144-9 [7448754] Cancer Res. 1984 Sep;44(9):4144-50 [6744325] J Clin Oncol. 1986 May;4(5):685-96 [3517242] Cancer Res. 1986 Oct;46(10):5229-35 [2944577] Cancer Treat Rep. 1987 Apr;71(4):381-9 [2950995] J Clin Oncol. 1989 Jul;7(7):890-9 [2661735] J Clin Oncol. 1989 Oct;7(10):1407-18 [2476530] J Clin Oncol. 1989 Oct;7(10):1427-36 [2789272] Cancer Res. 1990 Jun 15;50(12):3493-502 [2140289] Cancer Res. 1991 Feb 1;51(3):789-93 [1988119] Cancer Res. 1991 Sep 1;51(17):4618-23 [1831402] Cancer Res. 1991 Dec 15;51(24):6668-76 [1720706] J Natl Cancer Inst. 1991 Dec 18;83(24):1806-12 [1744924] Cancer Res. 1992 Jan 1;52(1):36-44 [1370075] J Natl Cancer Inst. 1992 Mar 4;84(5):321-7 [1738182] Mol Pharmacol. 1993 Apr;43(4):527-33 [8474431] Anticancer Drugs. 1993 Aug;4(4):431-5 [8400344] J Clin Oncol. 1993 Oct;11(10):1879-87 [8410113] J Clin Oncol. 1987 Oct;5(10):1559-65 [2443619] Cancer Res. 1987 Dec 15;47(24 Pt 1):6710-8 [3479249] J Clin Oncol. 1988 Mar;6(3):469-75 [3280741] J Clin Oncol. 1988 Jul;6(7):1184-91 [3260621] J Natl Cancer Inst. 1973 Nov;51(5):1409-16 [4357757] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I/II study of 2'-deoxy-3'-thiacytidine (lamivudine) in patients with advanced human immunodeficiency virus infection. AN - 77301789; 7769277 AB - In a phase I/II trial assessing the toxicity, pharmacokinetics, and activity of the (-)enantiomer of 2'-deoxy-3'-thiacytidine (3TC, lamivudine), 97 patients with AIDS or advanced human immunodeficiency virus (HIV) disease were administered 3TC at 0.5-20.0 mg/kg/day. The cohort's median entry CD4 cell count was 128/mm3 (range, 7-357). A toxic dose was not reached, although some patients reported mild headache, insomnia, and abdominal symptoms, and there was a general downward trend in neutrophil counts at the highest doses. Although subjective and difficult to interpret, increases in energy and appetite were noted, particularly in patients receiving > or = 8.0 mg/kg/day. Immunologic and virologic parameters showed evidence of at least transient anti-HIV activity at those higher doses. Although further studies of 3TC as monotherapy are needed, its favorable toxicity profile, evidence of at least transient clinical activity, and results of in vitro resistance experiments support further clinical testing in combination therapy. JF - The Journal of infectious diseases AU - Pluda, J M AU - Cooley, T P AU - Montaner, J S AU - Shay, L E AU - Reinhalter, N E AU - Warthan, S N AU - Ruedy, J AU - Hirst, H M AU - Vicary, C A AU - Quinn, J B AD - Medicine Branch, National Cancer Institute, Bethesda, MD 20852, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 1438 EP - 1447 VL - 171 IS - 6 SN - 0022-1899, 0022-1899 KW - HIV Core Protein p24 KW - 0 KW - beta 2-Microglobulin KW - Lamivudine KW - 2T8Q726O95 KW - Zalcitabine KW - 6L3XT8CB3I KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - HIV Core Protein p24 -- blood KW - beta 2-Microglobulin -- metabolism KW - Humans KW - Adult KW - Middle Aged KW - Time Factors KW - Male KW - Female KW - HIV Infections -- drug therapy KW - Zalcitabine -- pharmacokinetics KW - Acquired Immunodeficiency Syndrome -- drug therapy KW - Zalcitabine -- therapeutic use KW - Zalcitabine -- analogs & derivatives KW - Zalcitabine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77301789?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+infectious+diseases&rft.atitle=A+phase+I%2FII+study+of+2%27-deoxy-3%27-thiacytidine+%28lamivudine%29+in+patients+with+advanced+human+immunodeficiency+virus+infection.&rft.au=Pluda%2C+J+M%3BCooley%2C+T+P%3BMontaner%2C+J+S%3BShay%2C+L+E%3BReinhalter%2C+N+E%3BWarthan%2C+S+N%3BRuedy%2C+J%3BHirst%2C+H+M%3BVicary%2C+C+A%3BQuinn%2C+J+B&rft.aulast=Pluda&rft.aufirst=J&rft.date=1995-06-01&rft.volume=171&rft.issue=6&rft.spage=1438&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+infectious+diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-05 N1 - Date created - 1995-07-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular mapping of a recombination hotspot located in the second intron of the human TAP2 locus. AN - 77299528; 7762558 AB - Recombination across the HLA class II region is not randomly distributed, as indicated by both strong linkage disequilibrium within the 100 kb encompassing the DRB1-DQA1-DQB1 loci and complete equilibrium between TAP1 and TAP2, the closest variant sites of which are < 15 kb. In an attempt to explain these observations, 39 novel polymorphic markers in a region encompassing the TAP, LMP, and DOB genes were used to delineate the site of crossover in 11 class II recombinant chromosomes. SSCP demonstrated that two recombination events occurred within an 850-bp interval in the second intron of TAP2, which separates the variant sites of TAP1 and TAP2. These data indicate the presence of a recombination hotspot, the first to be identified from the analysis of familial transmission in the human major histocompatibility complex. The region of crossover was cloned and sequenced from one of the recombinants, further defining the crossover site to a 138-bp segment nested within the 850-bp region. This represents the most precisely defined region of recombination in the human genome. JF - American journal of human genetics AU - Cullen, M AU - Erlich, H AU - Klitz, W AU - Carrington, M AD - Biological Carcinogenesis and Development Program, NCI-Frederick Cancer Research and Development Program, MD 21702, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 1350 EP - 1358 VL - 56 IS - 6 SN - 0002-9297, 0002-9297 KW - TAP2 KW - Antigen Peptide Transporter-2 KW - 0 KW - HLA-D Antigens KW - TAP2 protein, human KW - 145892-13-3 KW - Index Medicus KW - Pedigree KW - Genetic Variation KW - Humans KW - Sequence Analysis, DNA KW - Chromosome Mapping KW - Genes, MHC Class II -- genetics KW - Cloning, Molecular KW - Polymerase Chain Reaction KW - Base Sequence KW - HLA-D Antigens -- genetics KW - Molecular Sequence Data KW - Female KW - Male KW - ATP-Binding Cassette Transporters -- genetics KW - Crossing Over, Genetic -- genetics KW - Introns -- genetics KW - Chromosomes, Human -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77299528?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+human+genetics&rft.atitle=Molecular+mapping+of+a+recombination+hotspot+located+in+the+second+intron+of+the+human+TAP2+locus.&rft.au=Cullen%2C+M%3BErlich%2C+H%3BKlitz%2C+W%3BCarrington%2C+M&rft.aulast=Cullen&rft.aufirst=M&rft.date=1995-06-01&rft.volume=56&rft.issue=6&rft.spage=1350&rft.isbn=&rft.btitle=&rft.title=American+journal+of+human+genetics&rft.issn=00029297&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-28 N1 - Date created - 1995-06-28 N1 - Date revised - 2017-01-13 N1 - Gene symbol - TAP2 N1 - Genetic sequence - S78269; GENBANK N1 - SuppNotes - Cited By: Cell. 1981 May;24(2):429-36 [6453653] J Immunol. 1988 Aug 15;141(4):1365-8 [3135331] Am J Hum Genet. 1984 Nov;36(6):1239-58 [6097112] Nature. 1985 Mar 7-13;314(6006):67-73 [3856104] J Immunol. 1986 Feb 1;136(3):1112-6 [3001187] Proc Natl Acad Sci U S A. 1986 Feb;83(4):1045-9 [3006026] Cell. 1986 Mar 28;44(6):895-904 [3754180] J Exp Med. 1986 Jun 1;163(6):1518-28 [3011948] Science. 1986 Oct 10;234(4773):173-9 [3018929] J Immunol. 1986 Dec 15;137(12):4004-9 [2878047] Mol Cell Biol. 1986 Nov;6(11):3934-47 [3540602] Immunogenetics. 1988;27(2):96-101 [2891614] Proc Natl Acad Sci U S A. 1988 Apr;85(8):2701-5 [2895928] Tissue Antigens. 1989 Jan;33(1):38-40 [2711370] J Mol Cell Immunol. 1984;1(2):125-35 [6152893] Am J Hum Genet. 1989 Sep;45(3):368-72 [2570527] Cell. 1990 Jan 12;60(1):95-103 [2295091] Immunogenetics. 1990;31(2):79-88 [1968049] Proc Natl Acad Sci U S A. 1990 Jun;87(12):4823-7 [1972281] Immunogenetics. 1991;33(2):132-40 [1847899] EMBO J. 1991 Mar;10(3):681-6 [2001681] Nucleic Acids Res. 1991 Mar 11;19(5):1154 [2020552] J Immunol. 1992 Jan 1;148(1):249-58 [1727870] Immunogenetics. 1992;35(4):235-40 [1541483] Mamm Genome. 1992;2(2):123-9 [1347471] Hum Immunol. 1992 Mar;33(3):208-12 [1618658] J Mol Biol. 1992 Nov 20;228(2):433-41 [1453454] Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11594-7 [1360671] Immunogenetics. 1993;37(4):266-73 [8267790] Immunogenetics. 1993;37(5):331-6 [8428766] Immunogenetics. 1993;37(5):373-80 [8428770] Nucleic Acids Res. 1993 Jul 1;21(13):3117-8 [8332533] Immunogenetics. 1993;38(6):446-9 [8406617] Hum Mol Genet. 1994 Jan;3(1):218 [8162046] Hum Immunol. 1994 Jan;39(1):31-40 [7910160] Immunogenetics. 1994;39(6):381-9 [7910587] Nat Genet. 1994 Jul;7(3):420-4 [7920662] Hum Immunol. 1994 Nov;41(3):234-40 [7868379] Hum Mol Genet. 1995 Mar;4(3):423-8 [7795597] Biochem Genet. 1987 Aug;25(7-8):513-26 [2895998] Proc Natl Acad Sci U S A. 1983 Aug;80(15):4808-12 [6348773] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Targeted disruption of the alpha isoform of the peroxisome proliferator-activated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators. AN - 77297025; 7539101 AB - To gain insight into the function of peroxisome proliferator-activated receptor (PPAR) isoforms in rodents, we disrupted the ligand-binding domain of the alpha isoform of mouse PPAR (mPPAR alpha) by homologous recombination. Mice homozygous for the mutation lack expression of mPPAR alpha protein and yet are viable and fertile and exhibit no detectable gross phenotypic defects. Remarkably, these animals do not display the peroxisome proliferator pleiotropic response when challenged with the classical peroxisome proliferators, clofibrate and Wy-14,643. Following exposure to these chemicals, hepatomegaly, peroxisome proliferation, and transcriptional-activation of target genes were not observed. These results clearly demonstrate that mPPAR alpha is the major isoform required for mediating the pleiotropic response resulting from the actions of peroxisome proliferators. mPPAR alpha-deficient animals should prove useful to further investigate the role of this receptor in hepatocarcinogenesis, fatty acid metabolism, and cell cycle regulation. JF - Molecular and cellular biology AU - Lee, S S AU - Pineau, T AU - Drago, J AU - Lee, E J AU - Owens, J W AU - Kroetz, D L AU - Fernandez-Salguero, P M AU - Westphal, H AU - Gonzalez, F J AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 3012 EP - 3022 VL - 15 IS - 6 SN - 0270-7306, 0270-7306 KW - DNA, Complementary KW - 0 KW - Pyrimidines KW - Receptors, Cytoplasmic and Nuclear KW - Transcription Factors KW - RNA KW - 63231-63-0 KW - pirinixic acid KW - 86C4MRT55A KW - Clofibrate KW - HPN91K7FU3 KW - Index Medicus KW - Animals KW - Pyrimidines -- pharmacology KW - RNA -- analysis KW - Mice KW - Liver -- physiology KW - Clofibrate -- pharmacology KW - Mice, Knockout KW - Liver -- ultrastructure KW - Base Sequence KW - Mice, Inbred C57BL KW - Molecular Sequence Data KW - Microscopy, Electron KW - Transcription Factors -- deficiency KW - Receptors, Cytoplasmic and Nuclear -- genetics KW - Microbodies -- ultrastructure KW - Receptors, Cytoplasmic and Nuclear -- deficiency KW - Microbodies -- physiology KW - Microbodies -- drug effects KW - Transcription Factors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77297025?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Targeted+disruption+of+the+alpha+isoform+of+the+peroxisome+proliferator-activated+receptor+gene+in+mice+results+in+abolishment+of+the+pleiotropic+effects+of+peroxisome+proliferators.&rft.au=Lee%2C+S+S%3BPineau%2C+T%3BDrago%2C+J%3BLee%2C+E+J%3BOwens%2C+J+W%3BKroetz%2C+D+L%3BFernandez-Salguero%2C+P+M%3BWestphal%2C+H%3BGonzalez%2C+F+J&rft.aulast=Lee&rft.aufirst=S&rft.date=1995-06-01&rft.volume=15&rft.issue=6&rft.spage=3012&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 - 1995-06-28 N1 - Date created - 1995-06-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1993 Jun 15;268(17):12939-45 [8389766] Biochem Pharmacol. 1993 May 25;45(10):2045-53 [7685601] Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5723-7 [8390676] Biol Cell. 1993;77(1):67-76 [8390886] FEBS Lett. 1993 Jul 26;327(2):219-23 [8335112] Horm Res. 1992;38(5-6):269-77 [1339170] Biochem Biophys Res Commun. 1993 Oct 29;196(2):671-7 [8240342] J Biol Chem. 1993 Dec 25;268(36):26817-20 [8262913] Biochem Biophys Res Commun. 1994 Feb 28;199(1):255-63 [8123021] Cell Struct Funct. 1993 Oct;18(5):267-77 [8168153] J Cell Biol. 1969 Nov;43(2):275-88 [4186511] Endocrinology. 1994 Aug;135(2):798-800 [8033830] J Biol Chem. 1994 Jul 22;269(29):18767-72 [7913466] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7355-9 [8041794] Genes Dev. 1994 May 15;8(10):1224-34 [7926726] Genes Dev. 1994 May 1;8(9):1007-18 [7926783] J Biol Chem. 1994 Oct 28;269(43):26754-8 [7929410] Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11012-6 [7971999] Cell. 1994 Dec 30;79(7):1147-56 [8001151] Am J Pathol. 1974 Apr;75(1):103-18 [4825610] J Cell Biol. 1974 May;61(2):344-58 [4208071] Experientia. 1974 Oct 15;30(10):1110-1 [4435102] Science. 1975 Nov 21;190(4216):787-9 [1198095] Arch Int Pharmacodyn Ther. 1977 Jan;225(1):51-7 [851495] Am J Pathol. 1978 Feb;90(2):435-46 [623209] Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350-4 [388439] Biochim Biophys Acta. 1980 Jan 18;617(1):1-11 [6101540] Biochem J. 1980 Jan 15;186(1):369-71 [7370018] Histochemistry. 1981;71(1):33-44 [6262282] J Biochem. 1981 Dec;90(6):1691-6 [7334004] Ann N Y Acad Sci. 1982;386:13-29 [6953843] Crit Rev Toxicol. 1983;12(1):1-58 [6360536] J Biol Chem. 1985 Jul 25;260(15):8905-10 [4019459] Proc Natl Acad Sci U S A. 1986 Mar;83(6):1747-51 [3456610] EMBO J. 1986 May;5(5):891-7 [3755102] J Biol Chem. 1987 Jan 15;262(2):801-10 [3027069] Environ Health Perspect. 1986 Dec;70:211-9 [3104023] J Biol Chem. 1987 Jun 15;262(17):8131-7 [3036800] J Biol Chem. 1987 Jun 15;262(17):8151-8 [3036803] Biochem Pharmacol. 1988 Apr 1;37(7):1203-6 [3355594] Science. 1988 May 13;240(4854):889-95 [3283939] Annu Rev Pharmacol Toxicol. 1989;29:145-63 [2658768] DNA. 1989 Sep;8(7):517-25 [2766933] Biochem Pharmacol. 1989 Dec 1;38(23):4291-7 [2688656] J Biol Chem. 1990 Mar 15;265(8):4600-6 [2307679] Electrophoresis. 1990 May;11(5):355-60 [2194789] Nature. 1990 Oct 18;347(6294):645-50 [2129546] Biochem J. 1991 Mar 15;274 ( Pt 3):745-51 [2012603] Biochem J. 1991 Apr 1;275 ( Pt 1):247-52 [2018479] Biochem Biophys Res Commun. 1991 Mar 29;175(3):866-71 [2025260] Nucleic Acids Res. 1991 Aug 11;19(15):4293 [1870982] EMBO J. 1992 Feb;11(2):433-9 [1537328] Cell. 1992 Mar 6;68(5):879-87 [1312391] Proc Natl Acad Sci U S A. 1992 May 15;89(10):4653-7 [1316614] Cell. 1992 Jun 12;69(6):915-26 [1606615] Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7541-5 [1502166] Nature. 1992 Aug 27;358(6389):771-4 [1324435] FEBS Lett. 1992 Aug 31;309(1):37-40 [1324848] J Biol Chem. 1992 Sep 25;267(27):19051-3 [1326542] FEBS Lett. 1992 Sep 28;310(2):193-6 [1397271] Biochem Biophys Res Commun. 1992 Oct 30;188(2):799-806 [1280124] Mol Endocrinol. 1992 Oct;6(10):1634-41 [1333051] Biochem Soc Trans. 1992 Nov;20(4):824-7 [1487072] Biochim Biophys Acta. 1993 Jan 23;1171(3):263-71 [8424950] Biochem Biophys Res Commun. 1993 Apr 15;192(1):37-45 [8386511] J Biol Chem. 1993 May 5;268(13):9593-603 [8486647] Biochim Biophys Acta. 1993 Jun 6;1177(2):183-90 [8499488] Biochemistry. 1993 Jun 1;32(21):5598-604 [7684926] Biochimie. 1993;75(3-4):251-6 [8389594] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The cytotoxicity of decays of tritium and iodine-125 incorporated in DNA of mammalian cells. Implications for the low-LET dosimetry of incorporated nuclides. AN - 77295546; 7761582 AB - To quantify the toxicity of low-LET radiation from incorporated radionuclides, we have determined the toxicity of decays of [3H]dThd pulse-incorporated into CHO cells in early S phase, with the cells frozen for decay accumulation at 30, 120 or 360 min after the pulse. D37 values of 1500, 2000 and 2100 decays were found by colony formation assay, corresponding to average nuclear doses of 4.6 and 2.7 Gy at the 30- and 360-min times. As D37 for external irradiation (60Co, 2.2 Gy/min) under these conditions is approximately 18 Gy, these results confirm the inadequacy of the dosimetry used for external irradiation to predict the biological effects of the low-LET radiation from incorporated radionuclides. We also determined the toxicity of 125IdU administered as above, and have confirmed the previously reported finding that D37 falls dramatically from 165 decays at 30 min to 40 decays at 360 min. Using the data for tritium to estimate the effect of the dose of 125I low-LET radiation, we conclude that even at 30 min, most of the toxicity of the 125I decays is due to the high-LET portion of the 125I electron spectrum, not the low-LET portion as reported previously. JF - Radiation research AU - Geselowitz, D A AU - McManaway, M E AU - Hofer, K G AU - Neumann, R D AD - Department of Nuclear Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892-1180, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 321 EP - 326 VL - 142 IS - 3 SN - 0033-7587, 0033-7587 KW - Cobalt Radioisotopes KW - 0 KW - Iodine Radioisotopes KW - Tritium KW - 10028-17-8 KW - DNA KW - 9007-49-2 KW - Thymidine KW - VC2W18DGKR KW - Index Medicus KW - Space life sciences KW - Animals KW - Kinetics KW - S Phase KW - CHO Cells KW - Dose-Response Relationship, Radiation KW - Time Factors KW - Cricetinae KW - Thymidine -- metabolism KW - Cell Survival -- radiation effects KW - Linear Energy Transfer KW - DNA -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77295546?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Radiation+research&rft.atitle=The+cytotoxicity+of+decays+of+tritium+and+iodine-125+incorporated+in+DNA+of+mammalian+cells.+Implications+for+the+low-LET+dosimetry+of+incorporated+nuclides.&rft.au=Geselowitz%2C+D+A%3BMcManaway%2C+M+E%3BHofer%2C+K+G%3BNeumann%2C+R+D&rft.aulast=Geselowitz&rft.aufirst=D&rft.date=1995-06-01&rft.volume=142&rft.issue=3&rft.spage=321&rft.isbn=&rft.btitle=&rft.title=Radiation+research&rft.issn=00337587&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-29 N1 - Date created - 1995-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neuronal cyclin-dependent kinase-5 phosphorylation sites in neurofilament protein (NF-H) are dephosphorylated by protein phosphatase 2A. AN - 77294870; 7760048 AB - Neurofilament (NF) protein [high molecular mass (NF-H)] is extensively phosphorylated in vivo. The phosphorylation occurs mainly in its characteristic KSP (Lys-Ser-Pro) repeat motifs. There are two major types of KSP motifs in the NF-H tail domain: KSPXKX and KSPXXX. Recent studies by two different laboratories have demonstrated the presence of a cdc2-like kinase [cyclin-dependent kinase-5 (cdk5)] in nervous tissue that selectively phosphorylates KSPXKX and XS/TXK motifs in NF-H and lysine-rich histone (H1). This article describes the identification of phosphatases dephosphorylating three different substrates: histone (H1), NF-H in a NF preparation, and a bacterially expressed C-terminal tail domain of NF-H, each containing KSPXKX repeats phosphorylated in vitro by cdk5. Among various phosphatases identified, protein phosphatase (PP) 2A from rabbit skeletal muscle appeared to be the most effective phosphatase in in vitro assays. Three phosphatase activity peaks--P1, P2, and P3--were partially purified from frozen rat spinal cord by ion exchange and size exclusion column chromatography and then characterized on the basis of biochemical, pharmacological, and immunochemical studies. One of the three peaks was identified as PP2A, whereas the others were mixtures of both PP2A and PP1. These three peaks could dephosphorylate cdk5-phosphorylated 32P-histone (H1), 32P-NF-H in the NF preparation, and 32P-NF-H tail fusion protein. These studies suggest the involvement of PP2A or a PP2A-like activity in the regulation of the phosphorylation state of KSPXKX motifs in NF-H. JF - Journal of neurochemistry AU - Veeranna AU - Shetty, K T AU - Link, W T AU - Jaffe, H AU - Wang, J AU - Pant, H C AD - Laboratory of Neurochemistry, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 2681 EP - 2690 VL - 64 IS - 6 SN - 0022-3042, 0022-3042 KW - Ethers, Cyclic KW - 0 KW - Histones KW - Microcystins KW - Neurofilament Proteins KW - Peptides, Cyclic KW - neurofilament protein H KW - 108688-71-7 KW - Okadaic Acid KW - 1W21G5Q4N2 KW - microcystin KW - 77238-39-2 KW - Cyclin-Dependent Kinase 5 KW - EC 2.7.11.1 KW - Protein-Serine-Threonine Kinases KW - Cdk5 protein, rat KW - EC 2.7.11.22 KW - Cyclin-Dependent Kinases KW - Phosphoprotein Phosphatases KW - EC 3.1.3.16 KW - Protein Phosphatase 2 KW - Phosphoric Monoester Hydrolases KW - EC 3.1.3.2 KW - Index Medicus KW - Rats KW - Animals KW - Phosphorylation KW - Spinal Cord -- enzymology KW - Histones -- metabolism KW - Ethers, Cyclic -- pharmacology KW - Repetitive Sequences, Nucleic Acid KW - Peptides, Cyclic -- pharmacology KW - Phosphoric Monoester Hydrolases -- metabolism KW - Phosphoprotein Phosphatases -- antagonists & inhibitors KW - Protein-Serine-Threonine Kinases -- metabolism KW - Neurofilament Proteins -- genetics KW - Phosphoprotein Phosphatases -- metabolism KW - Neurons -- enzymology KW - Neurofilament Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77294870?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Neuronal+cyclin-dependent+kinase-5+phosphorylation+sites+in+neurofilament+protein+%28NF-H%29+are+dephosphorylated+by+protein+phosphatase+2A.&rft.au=Veeranna%3BShetty%2C+K+T%3BLink%2C+W+T%3BJaffe%2C+H%3BWang%2C+J%3BPant%2C+H+C&rft.aulast=Veeranna&rft.aufirst=&rft.date=1995-06-01&rft.volume=64&rft.issue=6&rft.spage=2681&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 - 1995-06-28 N1 - Date created - 1995-06-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 14-3-3 is not essential for Raf-1 function: identification of Raf-1 proteins that are biologically activated in a 14-3-3- and Ras-independent manner. AN - 77292888; 7760835 AB - Recent reports have demonstrated the in vivo association of Raf-1 with members of the 14-3-3 protein family. To address the significance of the Raf-1-14-3-3 interaction, we investigated the enzymatic activity and biological function of Raf-1 in the presence and absence of associated 14-3-3. The interaction between these two molecules was disrupted in vivo and in vitro with a combination of molecular and biochemical techniques. Biochemical studies demonstrated that the enzymatic activities of Raf-1 were equivalent in the presence and absence of 14-3-3. Furthermore, mixing of purified Raf-1 and 14-3-3 in vitro was not sufficient to activate Raf-1. With a molecular approach, Cys-165 and Cys-168 as well as Ser-259 were identified as residues of Raf-1 required for the interaction with 14-3-3. Cys-165 and Cys-168 are located within the conserved cysteine-rich region of the CR1 domain, and Ser-259 is a conserved site of serine phosphorylation found within the CR2 domain. Mutation of either Cys-165 and Cys-168 or Ser-259 prevented the stable interaction of Raf-1 with 14-3-3 in vivo. Consistent with the model in which a site of serine phosphorylation is involved in the Raf-1-14-3-3 interaction, dephosphorylated Raf-1 was unable to associate with 14-3-3 in vitro. Phosphorylation may represent a general mechanism mediating 14-3-3 binding, because dephosphorylation of the Bcr kinase (known to interact with 14-3-3) also eliminated its association with 14-3-3. Finally, mutant Raf-1 proteins unable to stably interact with 14-3-3 exhibited enhanced enzymatic activity in human 293 cells and Xenopus oocytes and were biologically activated, as demonstrated by their ability to induced meiotic maturation of Xenopus oocytes. However, in contrast to wild-type Raf-1, activation of these mutants was independent of Ras. Our results therefore indicate that interaction with 14-3-3 is not essential for Raf-1 function. JF - Molecular and cellular biology AU - Michaud, N R AU - Fabian, J R AU - Mathes, K D AU - Morrison, D K AD - Molecular Mechanisms of Carcinogenesis Laboratory, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 3390 EP - 3397 VL - 15 IS - 6 SN - 0270-7306, 0270-7306 KW - 14-3-3 Proteins KW - 0 KW - Proteins KW - Proto-Oncogene Proteins KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Proto-Oncogene Proteins c-raf KW - Index Medicus KW - Animals KW - Phosphorylation KW - Enzyme Activation KW - Humans KW - Xenopus KW - Mutation KW - Cell Line KW - Protein-Serine-Threonine Kinases -- chemistry KW - Protein-Serine-Threonine Kinases -- metabolism KW - Proto-Oncogene Proteins -- chemistry KW - Proto-Oncogene Proteins -- metabolism KW - Protein-Serine-Threonine Kinases -- genetics KW - Proto-Oncogene Proteins -- genetics KW - Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77292888?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=14-3-3+is+not+essential+for+Raf-1+function%3A+identification+of+Raf-1+proteins+that+are+biologically+activated+in+a+14-3-3-+and+Ras-independent+manner.&rft.au=Michaud%2C+N+R%3BFabian%2C+J+R%3BMathes%2C+K+D%3BMorrison%2C+D+K&rft.aulast=Michaud&rft.aufirst=N&rft.date=1995-06-01&rft.volume=15&rft.issue=6&rft.spage=3390&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 - 1995-06-28 N1 - Date created - 1995-06-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell Biol. 1989 Feb;9(2):639-47 [2710120] Science. 1994 Sep 16;265(5179):1716-9 [8085159] Nature. 1994 Oct 13;371(6498):612-4 [7935795] Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9544-8 [7937802] Science. 1994 Oct 7;266(5182):126-9 [7939632] Science. 1994 Oct 7;266(5182):129-33 [7939633] Science. 1994 Oct 7;266(5182):56-7 [7939645] Biochem J. 1994 Oct 1;303 ( Pt 1):105-12 [7945229] Mol Cell Biol. 1995 Jan;15(1):398-406 [7799948] Science. 1994 Sep 16;265(5179):1713-6 [8085158] Cell. 1978 Jul;14(3):725-31 [210957] Nucleic Acids Res. 1984 Sep 25;12(18):7057-70 [6207484] Nature. 1986 Apr 10-16;320(6062):540-3 [2938016] Mol Cell Biol. 1990 Jun;10(6):2503-12 [2188091] Cancer Cells. 1990 Dec;2(12):377-82 [2150916] Oncogene. 1991 Apr;6(4):495-500 [2030909] Adv Cancer Res. 1992;58:53-73 [1312290] Oncogene. 1992 Sep;7(9):1867-73 [1386920] Nature. 1992 Dec 10;360(6404):534-5 [1334231] Nature. 1992 Dec 10;360(6404):600-3 [1461284] Trends Biochem Sci. 1992 Dec;17(12):498-501 [1471260] Cell. 1993 Feb 12;72(3):407-14 [8381718] Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2320-4 [8460141] Nature. 1993 May 13;363(6425):133-40 [8483497] Trends Biochem Sci. 1993 Apr;18(4):128-31 [8388132] Science. 1993 Jun 11;260(5114):1658-61 [8503013] Nature. 1993 Jul 15;364(6434):249-52 [8321321] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6213-7 [8327501] Nature. 1993 Jul 22;364(6435):308-13 [8332187] Nature. 1993 Jul 22;364(6435):352-5 [8332195] Biochem Biophys Res Commun. 1993 Jul 15;194(1):144-9 [8101440] Cell. 1993 Jul 16;74(1):205-14 [8334704] J Cell Biol. 1993 Aug;122(3):645-52 [8335690] J Biol Chem. 1993 Jul 25;268(21):16009-19 [8340422] J Biol Chem. 1993 Aug 15;268(23):17309-16 [8349614] Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8683-6 [8378348] Mol Cell Biol. 1993 Nov;13(11):7170-9 [7692235] J Biol Chem. 1994 Feb 11;269(6):3913-6 [8307946] Trends Genet. 1994 Feb;10(2):44-8 [8191584] Nature. 1994 Jun 2;369(6479):411-4 [8196769] Science. 1994 Jun 3;264(5164):1463-7 [7811320] Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):5982-6 [8016101] J Biol Chem. 1994 Jul 1;269(26):17749-55 [7517401] Science. 1994 Jul 22;265(5171):533-5 [8036497] Cell. 1992 Mar 20;68(6):1041-50 [1312393] Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2922-6 [1372995] Science. 1994 Jul 22;265(5171):535-7 [8036498] Cold Spring Harb Symp Quant Biol. 1988;53 Pt 1:173-84 [2978288] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intensive immunosuppression with antithymocyte globulin and cyclosporine as treatment for severe acquired aplastic anemia. AN - 77291222; 7756640 AB - Immunosuppressive therapy can produce hematologic improvement in a large proportion of patients with severe aplastic anemia. Antithymocyte globulin (ATG) is the current treatment of choice for patients who do not have histocompatible sibling donors or who are otherwise inegligible for allogeneic bone marrow transplantation. About 50% of patients respond to an initial course of ATG, and many nonresponders can be salvaged by subsequent treatment with cyclosporine (CsA). To determine whether simultaneous administration of these agents could further improve response rates, we enrolled 55 patients in a therapeutic trial of 4 days of ATG and 6 months of CsA. Among the 51 patients who had not received previous courses of ATG or CsA, 67% had responded by 3 months, and 78% had responded by 1 year (response was defined as an increase in peripheral blood counts sufficient that a patient no longer met the criteria for severe disease). There was a high incidence of relapse (36% actuarial risk at 2 years), but most relapsed patients responded to additional courses of immunosuppression, and relapse was not associated with a significant survival disadvantage. Evolution to myelodysplastic syndromes and acute leukemia was rare (1 of 51 patients), but the later appearance of paroxysmal nocturnal hemoglobinuria was more common (5 of 51 patients). Actuarial survival was 86% at 1 year and 72% at 2 years. These data support the use of a combination immunosuppressive regimen containing both ATG and CsA as first-line therapy for severe aplastic anemia. JF - Blood AU - Rosenfeld, S J AU - Kimball, J AU - Vining, D AU - Young, N S AD - Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/06/01/ PY - 1995 DA - 1995 Jun 01 SP - 3058 EP - 3065 VL - 85 IS - 11 SN - 0006-4971, 0006-4971 KW - Antilymphocyte Serum KW - 0 KW - Cyclosporine KW - 83HN0GTJ6D KW - Abridged Index Medicus KW - Index Medicus KW - Disease-Free Survival KW - Humans KW - Salvage Therapy KW - Prognosis KW - Aged KW - Child KW - Hemoglobinuria, Paroxysmal -- etiology KW - Child, Preschool KW - Life Tables KW - Survival Rate KW - Adult KW - Leukemia, Myeloid, Acute -- etiology KW - Treatment Outcome KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - Cyclosporine -- adverse effects KW - Anemia, Aplastic -- mortality KW - Cyclosporine -- therapeutic use KW - Antilymphocyte Serum -- therapeutic use KW - Anemia, Aplastic -- therapy KW - T-Lymphocytes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77291222?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Intensive+immunosuppression+with+antithymocyte+globulin+and+cyclosporine+as+treatment+for+severe+acquired+aplastic+anemia.&rft.au=Rosenfeld%2C+S+J%3BKimball%2C+J%3BVining%2C+D%3BYoung%2C+N+S&rft.aulast=Rosenfeld&rft.aufirst=S&rft.date=1995-06-01&rft.volume=85&rft.issue=11&rft.spage=3058&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-23 N1 - Date created - 1995-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Iron and reactive oxygen species in the asbestos-induced tumor necrosis factor-alpha response from alveolar macrophages. AN - 77290368; 7539275 AB - Free radicals and other reactive oxygen species (ROS) are important mediators in asbestos-induced lung toxicity. Asbestos fibers are thought to stimulate cells to generate ROS via iron that is present on fibrous silicates. The pathophysiologic responses in the lung after asbestos exposure are characterized by the accumulation of macrophages at the site of fiber deposition and the release of growth factors and proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha). We have examined the role of iron-catalyzed ROS in asbestos induction of TNF-alpha from rat alveolar macrophages. Treatment of alveolar macrophage cultures with asbestos stimulated dose-dependently TNF-alpha secretion, which was inhibited by the addition of deferoxamine, an iron chelator. Asbestos fibers, pretreated with deferoxamine to remove iron from the fibers before addition to alveolar macrophages, also significantly reduced the TNF-alpha response. Consistent with the role of iron on asbestos fibers in catalyzing hydroxyl radical generation, membrane-permeable hydroxyl radical scavengers (tetramethylthiourea, dimethyl sulfoxide) inhibited the asbestos-induced TNF-alpha response. The asbestos-induced increase in TNF-alpha, as well as in interleukin-1 alpha, and their inhibition by tetramethylthiourea occurred at the transcriptional level. The role of ROS in signaling TNF-alpha stimulation was confirmed by use of free radical-generating systems (hypoxanthine-xanthine oxidase, hydrogen peroxide, glucose-glucose oxidase, or ferrous plus hydrogen peroxide). These results suggest that intracellularly generated ROS can stimulate TNF-alpha in alveolar macrophages and that asbestos-induced TNF-alpha gene expression and secretion are mediated by iron-catalyzed product of ROS. JF - American journal of respiratory cell and molecular biology AU - Simeonova, P P AU - Luster, M I AD - Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 676 EP - 683 VL - 12 IS - 6 SN - 1044-1549, 1044-1549 KW - DNA Primers KW - 0 KW - Reactive Oxygen Species KW - Tumor Necrosis Factor-alpha KW - Asbestos KW - 1332-21-4 KW - RNA KW - 63231-63-0 KW - Iron KW - E1UOL152H7 KW - Index Medicus KW - Rats KW - Polymerase Chain Reaction KW - Animals KW - Rats, Inbred F344 KW - Base Sequence KW - Dose-Response Relationship, Drug KW - Cells, Cultured KW - Oxidative Stress KW - Molecular Sequence Data KW - RNA -- analysis KW - Gene Expression Regulation KW - Macrophages, Alveolar -- metabolism KW - Reactive Oxygen Species -- metabolism KW - Asbestos -- pharmacology KW - Tumor Necrosis Factor-alpha -- secretion KW - Iron -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77290368?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Iron+and+reactive+oxygen+species+in+the+asbestos-induced+tumor+necrosis+factor-alpha+response+from+alveolar+macrophages.&rft.au=Simeonova%2C+P+P%3BLuster%2C+M+I&rft.aulast=Simeonova&rft.aufirst=P&rft.date=1995-06-01&rft.volume=12&rft.issue=6&rft.spage=676&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 - 1995-07-06 N1 - Date created - 1995-07-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanism of action of bisimidazoacridones, new drugs with potent, selective activity against colon cancer. AN - 77288985; 7757985 AB - Antitumor bisimidazoacridones are bifunctional DNA binders which have recently been shown to selectively target human colon carcinoma cells in vitro and in vivo and appear to be excellent candidates for clinical development. We have studied the mechanism of action of one bisimidazoacridone, WMC26, which is 1,000-10,000 times more toxic to human colon carcinoma cells (HCT116) than to melanoma cells (SKMEL2) in vitro. Plasmid DNA exposed to WMC26 showed enhanced digestion by DNase I at A-T-rich sites, suggesting alterations in DNA conformation upon drug binding. These results led us to investigate whether WMC26 was selectively toxic due to a specific recognition of DNA bends by repair excinucleases, as has been demonstrated with the DNA bisintercalator, ditercalinium. Both prokaryotic and eukaryotic cells with intact repair capacity were shown to be selectively sensitive to WMC26, strongly indicating that excision repair plays a role in its toxicity. Confocal microscopy studies utilizing fluorescence of the WMC26 chromophore showed compound localization in the perinuclear cytoplasmic area, as had been previously noted for ditercalinium, indicating that cytoplasmic DNA could be the target. This irreversible accumulation of compound was gradually followed by vacuolization of the cytoplasm and cell death. Cell cycle analysis of both lines treated with WMC26 or with ditercalinium showed that, while the latter induced HCT116 growth arrest at G1-G0, WMC26 also blocked the cell cycle at G2-M; SKMEL2 cells did not undergo any changes in cell cycle as a result of either treatment. Our data show that WMC26 is 10-100 times more cytotoxic than ditercalinium in vitro. Like ditercalinium, WMC26 appears to exert its toxicity via cytoplasmic elements, through a mechanism involving excision repair processes. However, its highly selective cytotoxicity may stem from additional undefined targets in sensitive colon cancer cells. JF - Cancer research AU - Hernandez, L AU - Cholody, W M AU - Hudson, E A AU - Resau, J H AU - Pauly, G AU - Michejda, C J AD - Molecular Aspects of Drug Design, Macromolecular Structure Laboratory, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1995/06/01/ PY - 1995 DA - 1995 Jun 01 SP - 2338 EP - 2345 VL - 55 IS - 11 SN - 0008-5472, 0008-5472 KW - Aminoacridines KW - 0 KW - Antineoplastic Agents KW - Carbazoles KW - DNA, Mitochondrial KW - DNA, Neoplasm KW - Intercalating Agents KW - WMC 25 KW - WMC 26 KW - ditercalinium KW - VFS4ZUK33P KW - Index Medicus KW - Animals KW - Drug Screening Assays, Antitumor KW - Fluorescence KW - Tumor Cells, Cultured -- drug effects KW - DNA Damage KW - Humans KW - Cell Division -- drug effects KW - Mice, Nude KW - Mice KW - Cell Death -- drug effects KW - Neoplasm Transplantation KW - DNA, Neoplasm -- drug effects KW - DNA, Mitochondrial -- drug effects KW - DNA, Mitochondrial -- metabolism KW - Carbazoles -- pharmacology KW - DNA, Neoplasm -- metabolism KW - Male KW - Cell Cycle -- drug effects KW - Intercalating Agents -- pharmacology KW - Colonic Neoplasms -- drug therapy KW - Colonic Neoplasms -- pathology KW - Antineoplastic Agents -- pharmacology KW - Aminoacridines -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77288985?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mechanism+of+action+of+bisimidazoacridones%2C+new+drugs+with+potent%2C+selective+activity+against+colon+cancer.&rft.au=Hernandez%2C+L%3BCholody%2C+W+M%3BHudson%2C+E+A%3BResau%2C+J+H%3BPauly%2C+G%3BMichejda%2C+C+J&rft.aulast=Hernandez&rft.aufirst=L&rft.date=1995-06-01&rft.volume=55&rft.issue=11&rft.spage=2338&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 - 1995-06-29 N1 - Date created - 1995-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Loss of heterozygosity occurs centromeric to RB without associated abnormalities in the retinoblastoma gene in tumors from patients with metastatic renal cell carcinoma. AN - 77287490; 7752392 AB - Tumor suppressor genes have been found to have loss of function in a number of malignancies. This loss of function is believed to contribute to malignant transformation or metastatic spread. In the present study, expression of the retinoblastoma (RB) tumor suppressor gene was examined in cell lines and tumor tissue obtained from primary renal and metastatic sites in patients with metastatic renal cell carcinoma. Three of fifteen (20%) of informative renal carcinoma cell lines had loss of heterozygosity (LOH) in the RB gene (intron 20) detected by polymerase chain reaction analysis. Using restriction fragment length polymorphism (RFLP) analysis, 7 of 22 (32%) informative cell lines had LOH centromeric to the RB gene at the D13S1 locus. No LOH (0 of 7) was seen telomeric to the RB gene at the D13S2 locus. None of the 28 cell lines examined had decreased RB mRNA expression compared with short-term cultures of proximal renal tubular cells. Western blotting demonstrated phosphorylated and unphosphorylated forms of RB protein of expected molecular weight in all 41 cell lines (33 primary and 8 metastatic) examined. Twenty-nine primary cell lines and 6 metastatic cell lines all demonstrated normal immunohistochemical staining. Loss of RB immunohistochemical staining in paraffin-embedded tissue was detected in none of the primary tumors (0 of 30) or metastatic tumors (0 of 12). The absence of abnormalities of RB expression detected in these renal cell carcinomas suggests that abnormalities of the RB gene are not central to malignant transformation or progression in this tumor type; however, another tumor suppressor gene centromeric to the RB locus may be important in renal cell carcinogenesis. JF - The Journal of urology AU - Walther, M M AU - Gnarra, J R AU - Elwood, L AU - Xu, H J AU - Florence, C AU - Anglard, P AU - Hu, S X AU - King, C AU - Trahan, E AU - Hurley, K AD - Urologic Oncology Section, COP, DCT, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 2050 EP - 2054 VL - 153 IS - 6 SN - 0022-5347, 0022-5347 KW - Abridged Index Medicus KW - Index Medicus KW - Base Sequence KW - Tumor Cells, Cultured KW - Humans KW - Heterozygote KW - Molecular Sequence Data KW - Kidney Neoplasms -- genetics KW - Kidney Neoplasms -- pathology KW - Carcinoma, Renal Cell -- secondary KW - Genes, Retinoblastoma -- genetics KW - Carcinoma, Renal Cell -- genetics KW - Gene Expression Regulation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77287490?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+urology&rft.atitle=Loss+of+heterozygosity+occurs+centromeric+to+RB+without+associated+abnormalities+in+the+retinoblastoma+gene+in+tumors+from+patients+with+metastatic+renal+cell+carcinoma.&rft.au=Walther%2C+M+M%3BGnarra%2C+J+R%3BElwood%2C+L%3BXu%2C+H+J%3BFlorence%2C+C%3BAnglard%2C+P%3BHu%2C+S+X%3BKing%2C+C%3BTrahan%2C+E%3BHurley%2C+K&rft.aulast=Walther&rft.aufirst=M&rft.date=1995-06-01&rft.volume=153&rft.issue=6&rft.spage=2050&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+urology&rft.issn=00225347&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-16 N1 - Date created - 1995-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Two mechanisms of antigen-specific apoptosis of myelin basic protein (MBP)-specific T lymphocytes derived from multiple sclerosis patients and normal individuals. AN - 77286318; 7538545 AB - Several stimuli induce mature T cells to undergo apoptosis or programmed cell death (PCD) including specific Ag. We have demonstrated previously that Ag induces the death of encephalitogenic T cells in vitro and deletion in vivo, leading to amelioration of autoimmune encephalomyelitis. We have now examined whether activated, myelin basic protein (MBP)-specific human T cells may be eliminated by Ag-induced PCD. We demonstrate that activated MBP-specific T cell lines (TCL) undergo the classic nuclear morphologic changes and DNA fragmentation characteristic of apoptosis when given a TCR challenge. We found evidence that two mechanisms led to apoptosis: a propriocidal mechanism that was highly Ag-specific and dependent on the dose of exogenously added rIL-2, and a cytolytic mechanism in which MBP-specific TCL lysed B cell targets and engaged in considerable "fratricidal" cytolysis of other MBP-specific T cells. These two pathways leading to MBP-specific apoptotic death could be distinguished by their glucocorticoid sensitivity. Glucocorticoid treatment significantly blocked MBP-induced propriocidal apoptosis but had no effect on T cell cytolysis of B cell targets. Although it has been proposed that autoimmune disease could result from the failure of normal deletional mechanisms, this preliminary survey of MBP-reactive mature TCL from multiple sclerosis patients revealed that such cells are highly susceptible to TCR-induced PCD and comparable with TCL from normal subjects. Thus, therapeutic strategies based on Ag-induced PCD of T lymphocytes may be feasible in man. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Pelfrey, C M AU - Tranquill, L R AU - Boehme, S A AU - McFarland, H F AU - Lenardo, M J AD - Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/06/01/ PY - 1995 DA - 1995 Jun 01 SP - 6191 EP - 6202 VL - 154 IS - 11 SN - 0022-1767, 0022-1767 KW - Autoantigens KW - 0 KW - Glucocorticoids KW - Lymphokines KW - Myelin Basic Protein KW - Abridged Index Medicus KW - Index Medicus KW - Lymphokines -- immunology KW - Humans KW - Cytotoxicity Tests, Immunologic KW - Cell Survival -- immunology KW - Glucocorticoids -- pharmacology KW - Cell Line KW - Autoantigens -- immunology KW - Apoptosis -- immunology KW - Multiple Sclerosis -- immunology KW - T-Lymphocytes -- drug effects KW - T-Lymphocytes -- immunology KW - Myelin Basic Protein -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77286318?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Two+mechanisms+of+antigen-specific+apoptosis+of+myelin+basic+protein+%28MBP%29-specific+T+lymphocytes+derived+from+multiple+sclerosis+patients+and+normal+individuals.&rft.au=Pelfrey%2C+C+M%3BTranquill%2C+L+R%3BBoehme%2C+S+A%3BMcFarland%2C+H+F%3BLenardo%2C+M+J&rft.aulast=Pelfrey&rft.aufirst=C&rft.date=1995-06-01&rft.volume=154&rft.issue=11&rft.spage=6191&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 - 1995-06-22 N1 - Date created - 1995-06-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The relationship between plasma and brain quinolinic acid levels and the severity of hepatic encephalopathy in animal models of fulminant hepatic failure. AN - 77286259; 7760040 AB - Quinolinic acid is an excitatory, neurotoxic tryptophan metabolite proposed to play a role in the pathogenesis of hepatic encephalopathy. This involvement was investigated in rat and rabbit models of fulminant hepatic failure at different stages of hepatic encephalopathy. Although plasma and brain tryptophan levels were significantly increased in all stages of hepatic encephalopathy, quinolinic acid levels increased three-to sevenfold only in the plasma, CSF, and brain regions of animals in stage IV hepatic encephalopathy. Plasma-CSF and plasma-brain quinolinic acid levels in rats and rabbits with fulminant hepatic failure were strongly correlated, with CSF and brain concentrations approximately 10% those of plasma levels. Moreover, there was no significant regional difference in brain quinolinic acid concentrations in either model. Extrahepatic indoleamine-2,3-dioxygenase activity was not altered in rats in stage IV hepatic encephalopathy, but hepatic L-tryptophan-2,3-dioxygenase activity was increased. These results suggest that quinolinic acid synthesized in the liver enters the plasma and then accumulates in the CNS after crossing a permeabilized blood-brain barrier in the end stages of liver failure. Furthermore, the observation of low brain concentrations of quinolinic acid only in stage IV encephalopathy suggests that the contribution of quinolinic acid to the pathogenesis of hepatic encephalopathy in these animal models is minor. JF - Journal of neurochemistry AU - Basile, A S AU - Saito, K AU - Li, Y AU - Heyes, M P AD - Laboratory of Neuroscience, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 2607 EP - 2614 VL - 64 IS - 6 SN - 0022-3042, 0022-3042 KW - Thioacetamide KW - 075T165X8M KW - Galactosamine KW - 7535-00-4 KW - Quinolinic Acid KW - F6F0HK1URN KW - Index Medicus KW - Rats KW - Osmolar Concentration KW - Galactosamine -- pharmacology KW - Animals KW - Rats, Sprague-Dawley KW - Thioacetamide -- pharmacology KW - Rabbits KW - Male KW - Quinolinic Acid -- metabolism KW - Quinolinic Acid -- blood KW - Hepatic Encephalopathy -- physiopathology KW - Brain -- metabolism KW - Hepatic Encephalopathy -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77286259?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=The+relationship+between+plasma+and+brain+quinolinic+acid+levels+and+the+severity+of+hepatic+encephalopathy+in+animal+models+of+fulminant+hepatic+failure.&rft.au=Basile%2C+A+S%3BSaito%2C+K%3BLi%2C+Y%3BHeyes%2C+M+P&rft.aulast=Basile&rft.aufirst=A&rft.date=1995-06-01&rft.volume=64&rft.issue=6&rft.spage=2607&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 - 1995-06-28 N1 - Date created - 1995-06-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retrovirally marked CD34-enriched peripheral blood and bone marrow cells contribute to long-term engraftment after autologous transplantation. AN - 77282153; 7538814 AB - We report here on a preliminary human autologous transplantation study of retroviral gene transfer to bone marrow (BM) and peripheral blood (PB)-derived CD34-enriched cells. Eleven patients with multiple myeloma or breast cancer had cyclophosphamide and filgrastim-mobilized PB cells CD34-enriched and transduced with a retroviral marking vector containing the neomycin resistance gene, and CD34-enriched BM cells transduced with a second marking vector also containing a neomycin resistance gene. After high-dose conditioning therapy, both transduced cell populations were reinfused and patients were followed over time for the presence of the marker gene and any adverse effects related to the gene-transfer procedure. All 10 evaluable patients had the marker gene detected at the time of engraftment, and 3 of 9 patients had persistence of the marker gene for greater than 18 months posttransplantation. The marker gene was detected in multiple lineages, including granulocytes, T cells, and B cells. The source of the marking was both the transduced PB graft and the BM graft, with a suggestion of better long-term marking originating from the PB graft. The steady-state levels of marking were low, with only 1:1000 to 1:10,000 cells positive. There was no toxicity noted, and patients did not develop detectable replication-competent helper virus at any time posttransplantation. These results suggest that mobilized PB cells may be preferable to BM for gene therapy applications and that progeny of mobilized peripheral blood cells can contribute long-term to engraftment of multiple lineages. JF - Blood AU - Dunbar, C E AU - Cottler-Fox, M AU - O'Shaughnessy, J A AU - Doren, S AU - Carter, C AU - Berenson, R AU - Brown, S AU - Moen, R C AU - Greenblatt, J AU - Stewart, F M AD - Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1652, USA. Y1 - 1995/06/01/ PY - 1995 DA - 1995 Jun 01 SP - 3048 EP - 3057 VL - 85 IS - 11 SN - 0006-4971, 0006-4971 KW - Antigens, CD KW - 0 KW - Antigens, CD34 KW - Genetic Markers KW - Recombinant Proteins KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Cyclophosphamide KW - 8N3DW7272P KW - Phosphotransferases (Alcohol Group Acceptor) KW - EC 2.7.1.- KW - Kanamycin Kinase KW - EC 2.7.1.95 KW - Filgrastim KW - PVI5M0M1GW KW - Melphalan KW - Q41OR9510P KW - Fluorouracil KW - U3P01618RT KW - Abridged Index Medicus KW - Index Medicus KW - Recombinant Proteins -- pharmacology KW - Humans KW - Genetic Therapy KW - Granulocyte Colony-Stimulating Factor -- pharmacology KW - Melphalan -- pharmacology KW - Hematopoietic Stem Cells -- drug effects KW - Whole-Body Irradiation KW - Graft Survival KW - Treatment Outcome KW - Genes, Reporter KW - Fluorouracil -- pharmacology KW - Middle Aged KW - Follow-Up Studies KW - Recombinant Proteins -- analysis KW - Phosphotransferases (Alcohol Group Acceptor) -- analysis KW - Male KW - Female KW - Cyclophosphamide -- pharmacology KW - Antigens, CD -- analysis KW - Breast Neoplasms -- pathology KW - Multiple Myeloma -- pathology KW - Multiple Myeloma -- therapy KW - Hematopoietic Stem Cell Transplantation KW - Breast Neoplasms -- therapy KW - Bone Marrow Transplantation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77282153?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Retrovirally+marked+CD34-enriched+peripheral+blood+and+bone+marrow+cells+contribute+to+long-term+engraftment+after+autologous+transplantation.&rft.au=Dunbar%2C+C+E%3BCottler-Fox%2C+M%3BO%27Shaughnessy%2C+J+A%3BDoren%2C+S%3BCarter%2C+C%3BBerenson%2C+R%3BBrown%2C+S%3BMoen%2C+R+C%3BGreenblatt%2C+J%3BStewart%2C+F+M&rft.aulast=Dunbar&rft.aufirst=C&rft.date=1995-06-01&rft.volume=85&rft.issue=11&rft.spage=3048&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-23 N1 - Date created - 1995-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Radiation exposure and other factors that predispose to human thyroid neoplasia. AN - 77276889; 7747246 AB - Radiation exposure is the only known etiologic factor clearly associated with an increased risk of thyroid cancer. External beam radiation treatment for medical therapy, acute gamma ray exposure from environmental sources (nuclear weapons, nuclear power plant accidents), and ingestion of short-lived radioactive iodine isotopes are the primary sources of radiation exposure, which increases the risk of benign and malignant thyroid neoplasia. Relative risk is directly proportional to the exposure dose and is inversely proportional to the age at exposure. JF - The Surgical clinics of North America AU - Fraker, D L AD - Surgical Metabolism Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1995/06// PY - 1995 DA - June 1995 SP - 365 EP - 375 VL - 75 IS - 3 SN - 0039-6109, 0039-6109 KW - Radioactive Pollutants KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Risk Factors KW - Radioactive Pollutants -- adverse effects KW - Nuclear Warfare KW - Humans KW - Child KW - Radionuclide Imaging -- adverse effects KW - Radiotherapy -- adverse effects KW - Neoplasms, Radiation-Induced -- etiology KW - Thyroid Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77276889?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Surgical+clinics+of+North+America&rft.atitle=Radiation+exposure+and+other+factors+that+predispose+to+human+thyroid+neoplasia.&rft.au=Fraker%2C+D+L&rft.aulast=Fraker&rft.aufirst=D&rft.date=1995-06-01&rft.volume=75&rft.issue=3&rft.spage=365&rft.isbn=&rft.btitle=&rft.title=The+Surgical+clinics+of+North+America&rft.issn=00396109&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-15 N1 - Date created - 1995-06-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Prevalence of Dental Fluorosis in a School-based Program of Fluoride Mouthrinsing, Fluoride Tablets, and Both Procedures Combined AN - 21132066; 11162187 AB - Objectives: The objective of the study was to describe and compare the prevalence and severity of dental fluorosis in children who participated in an eight-year clinical trial of the effectiveness of school-based fluoride procedures according to three treatment regimens and age of regimen initiation. Methods: At baseline in 1981, 1,640 kindergarten and first grade children residing in a fluoride-deficient community (Springfield, OH) were assigned randomly to a group that(1) rinsed once a week with a 0.2 percent neutral NaF solution; (2) chewed, rinsed, and swallowed daily a neutral 2.2 mg NaF tablet; or (3) carried out both procedures. DMFS examinations were conducted at baseline and after two, five, and eight years of treatment. As a follow-up in 1992, fluorosis examinations using Dean's index were conducted on 448 remaining subjects. Results: Overall, the prevalence of fluorosis was 4.4 percent with 20 children classified as having some definitive level of the condition. No statistically significant differences existed in the prevalence or severity of fluorosis: (1) among the preventive regimens; (2) among children who began the regimens at ages 5, 6, or 7; or (3) by eruptive status of teeth. Conclusion: These results reiterate the safety of school-based fluoride mouthrinse, fluoride tablet, or combined regimens in communities with fluoride-deficient water supplies. Manuscript received: 3/21/94; returned to authors for revision: 7/18/94; accepted for publication: 12/12/94. JF - Journal of Public Health Dentistry AU - Nowjack-Raymer, Ruth E AU - Selwitz, Robert H AU - Kingman, Albert AU - Driscoll, William S AD - Ms. Nowjack-Raymer, National Institute of Dental Research, Epidemiology and Oral Disease Prevention Program, Natcher Building, Room 3AN-38B, 45 Center Drive, MSC 6401, Bethesda, MD 20892-6401. Internet: nowjackr sub(e)45.nidr.nih.gov. Drs. Selwitz, Kingman, and Driscoll (now retired) also are affiliated with the Epidemiology and Oral Disease Prevention Program, NIDR., nowjackr@de45.nidr.nih.gov Y1 - 1995/06// PY - 1995 DA - Jun 1995 SP - 165 EP - 170 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 USA VL - 55 IS - 3 SN - 0022-4006, 0022-4006 KW - Health & Safety Science Abstracts; Calcium & Calcified Tissue Abstracts KW - Teeth KW - Age KW - Statistical analysis KW - Tablets KW - Dentistry KW - clinical trials KW - Clinical trials KW - Water supplies KW - Public health KW - Fluorosis KW - Fluoride KW - Dental fluorosis KW - Mouthwashes KW - Children KW - teeth KW - dentistry KW - USA, Illinois, Springfield KW - T 2045:Teeth KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21132066?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Public+Health+Dentistry&rft.atitle=The+Prevalence+of+Dental+Fluorosis+in+a+School-based+Program+of+Fluoride+Mouthrinsing%2C+Fluoride+Tablets%2C+and+Both+Procedures+Combined&rft.au=Nowjack-Raymer%2C+Ruth+E%3BSelwitz%2C+Robert+H%3BKingman%2C+Albert%3BDriscoll%2C+William+S&rft.aulast=Nowjack-Raymer&rft.aufirst=Ruth&rft.date=1995-06-01&rft.volume=55&rft.issue=3&rft.spage=165&rft.isbn=&rft.btitle=&rft.title=Journal+of+Public+Health+Dentistry&rft.issn=00224006&rft_id=info:doi/10.1111%2Fj.1752-7325.1995.tb02361.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - USA, Illinois, Springfield; Fluoride; Children; Age; clinical trials; Water supplies; teeth; dentistry; Tablets; Fluorosis; Dental fluorosis; Public health; Mouthwashes; Teeth; Clinical trials; Statistical analysis; Dentistry DO - http://dx.doi.org/10.1111/j.1752-7325.1995.tb02361.x ER - TY - JOUR T1 - Interactions between PRP-T vaccine against Haemophilus influenzae type b and conventional infant vaccines. Lessons for future studies of simultaneous immunization and combined vaccines. AN - 77420806; 7625660 JF - Annals of the New York Academy of Sciences AU - Clemens, J AU - Brenner, R AU - Rao, M AD - Division of Epidemiology, Statistics, and Prevention Research, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA. Y1 - 1995/05/31/ PY - 1995 DA - 1995 May 31 SP - 255 EP - 266 VL - 754 SN - 0077-8923, 0077-8923 KW - Antibodies, Bacterial KW - 0 KW - Diphtheria-Tetanus-Pertussis Vaccine KW - Haemophilus Vaccines KW - Vaccines, Conjugate KW - Index Medicus KW - Infant KW - Diphtheria-Tetanus-Pertussis Vaccine -- immunology KW - Diphtheria-Tetanus-Pertussis Vaccine -- administration & dosage KW - Drug Interactions KW - Humans KW - Chile KW - Antibodies, Bacterial -- biosynthesis KW - Immunization Schedule KW - Vaccines, Conjugate -- administration & dosage KW - Haemophilus Vaccines -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77420806?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Interactions+between+PRP-T+vaccine+against+Haemophilus+influenzae+type+b+and+conventional+infant+vaccines.+Lessons+for+future+studies+of+simultaneous+immunization+and+combined+vaccines.&rft.au=Clemens%2C+J%3BBrenner%2C+R%3BRao%2C+M&rft.aulast=Clemens&rft.aufirst=J&rft.date=1995-05-31&rft.volume=754&rft.issue=&rft.spage=255&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-25 N1 - Date created - 1995-08-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Physiological levels of beta-amyloid increase tyrosine phosphorylation and cytosolic calcium. AN - 77585849; 7552293 AB - The a beta peptide is a neurotoxic peptide that accumulates in the brains of Alzheimer patients, but is also present in body fluids at subnanomolar levels. The potential effects of these low levels of a beta are unclear. We now show that one such action is to increase tyrosine phosphorylation in PC12 cells and olfactory neuroblasts. Application of a beta 25-35 or a beta 1-40 induces a dose-dependent increase in the tyrosine phosphorylation in both whole cells and in vitro. The increase in tyrosine phosphorylation is both rapid and sensitive, being stimulated by picomolar doses of a beta and occurring within 1 min of application. Calcium imaging experiments provide further support for the role of tyrosine phosphorylation in the action of a beta. While a beta does not alter calcium metabolism under basal conditions, the addition of a beta induces a rapid increase in cytoplasmic calcium in olfactory neuroblasts that have been treated with the tyrosine phosphatase inhibitor, sodium orthovanadate or in PC12 cells treated with nerve growth factor. These responses could be blocked by the tyrosine kinase inhibitor, herbimycin. These calcium responses displayed an obligate requirement for the presence of matrix proteins. The identification of a rapid, sensitive assay for the action of a beta may facilitate investigations of its mechanism of action. JF - Brain research AU - Luo, Y Q AU - Hirashima, N AU - Li, Y H AU - Alkon, D L AU - Sunderland, T AU - Etcheberrigaray, R AU - Wolozin, B AD - Section on Geriatric Psychiatry, NIMH, Bethesda, MD 20892-1264, USA. Y1 - 1995/05/29/ PY - 1995 DA - 1995 May 29 SP - 65 EP - 74 VL - 681 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Amyloid beta-Peptides KW - 0 KW - Fluorescent Dyes KW - Tyrosine KW - 42HK56048U KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Calcium KW - SY7Q814VUP KW - Fura-2 KW - TSN3DL106G KW - Index Medicus KW - Rats KW - Immunoblotting KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Animals KW - Neurons -- metabolism KW - Phosphorylation KW - Neurons -- drug effects KW - Kinetics KW - Olfactory Bulb -- drug effects KW - Precipitin Tests KW - Olfactory Bulb -- metabolism KW - Olfactory Bulb -- cytology KW - PC12 Cells KW - Calcium -- metabolism KW - Cytosol -- metabolism KW - Cytosol -- drug effects KW - Amyloid beta-Peptides -- pharmacology KW - Tyrosine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77585849?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Physiological+levels+of+beta-amyloid+increase+tyrosine+phosphorylation+and+cytosolic+calcium.&rft.au=Luo%2C+Y+Q%3BHirashima%2C+N%3BLi%2C+Y+H%3BAlkon%2C+D+L%3BSunderland%2C+T%3BEtcheberrigaray%2C+R%3BWolozin%2C+B&rft.aulast=Luo&rft.aufirst=Y&rft.date=1995-05-29&rft.volume=681&rft.issue=1-2&rft.spage=65&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 - 1995-11-06 N1 - Date created - 1995-11-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rapid changes in cytochrome P4502E1 (CYP2E1) activity and other P450 isozymes following ethanol withdrawal in rats. AN - 77347687; 7786308 AB - This study describes the effects of chronic ethanol (ETOH) treatment and withdrawal on the rat hepatic mixed-function mono-oxygenase system. Male Sprague-Dawley rats (150-200 g, 10 per group) were administered ETOH as part of the Lieber-deCarli liquid diet for 3 weeks. Ethanol was removed, and the animals were euthanized at 0, 24, 48, 72 and 168 hr post-withdrawal. Microsomes were prepared, and ethanol-inducible cytochrome P4502E1 (CYP2E1) activity was measured using the enzyme markers N-nitrosodimethylamine demethylase (NDMAd), p-nitrophenol hydroxylase (PNPH) and aniline hydroxylase (AH). Activities were found to be induced significantly after chronic ETOH feeding using all three assays (NDMAd, 5-fold; PNPH, 3.5-fold; AH, 9-fold). Upon ETOH withdrawal, all three activities dropped markedly, with NDMAd and PNPH at control values at 24 hr and all subsequent time points. AH activity remained 3-fold higher than controls at 24, 48 and 72 hr. Western blot analyses showed that immunoreactive CYP2E1 returned to control at 24 hr, consonant with NDMAd and PNPH activities. The prolonged induction of AH activity following ETOH withdrawal indicates that it is not a specific marker of CYP2E1-catalyzed reactions. Collectively, these data are suggestive of a rapid mechanism of CYP2E1 degradation in the rat liver. Of the other parameters investigated in this study, total cytochrome P450 content was increased 2.5-fold after ETOH feeding, with levels dropping markedly 24 hr post-withdrawal. NADPH-dependent cytochrome c reductase activity was unchanged throughout the course of the study. CYP1A1, CYP2B1 and CYP3A activities were assessed by the substrate probes ethoxyresorufin O-dealkylase (EROD), pentoxyresorufin O-dealkylase (PROD) and erythromycin N-demethylase (ERNd). EROD and PROD were induced significantly by ETOH administration (2-fold) at 0 hr, with EROD remaining elevated over controls 24 hr post-withdrawal. Quantitative western blot analysis of CYP1A1 and CYP2B1 revealed a pattern of immunostaining generally consistent with but less variable than levels predicted by the respective substrate markers. Both proteins were induced significantly by chronic ethanol administration (CYP1A1, 1.9-fold; CYP2B1, 4-fold). Induction of these P450 isoforms persisted for several days following withdrawal. In contrast, immunoreactive CYP1A2 was found to decrease significantly (by 30-40%) during ethanol withdrawal (24, 48, 72, 168 hr). ERNd activity was induced significantly by chronic ETOH feeding (2.5-fold) and remained so for 24 hr into the withdrawal period (2-fold). Immunoreactive CYP3A1 was also induced significantly following ETOH administration (0 hr) and 24 hr following withdrawal.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Biochemical pharmacology AU - Roberts, B J AU - Shoaf, S E AU - Song, B J AD - Laboratory of Clinical Studies and Laboratory of Neurogenetics, DICBR, NIAAA, Bethesda, MD 20892, USA. Y1 - 1995/05/26/ PY - 1995 DA - 1995 May 26 SP - 1665 EP - 1673 VL - 49 IS - 11 SN - 0006-2952, 0006-2952 KW - Isoenzymes KW - 0 KW - Ethanol KW - 3K9958V90M KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Oxidoreductases KW - EC 1.- KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - Cytochrome P-450 CYP1A1 KW - Cytochrome P-450 CYP1A2 KW - Cytochrome P-450 CYP2B1 KW - Cytochrome P-450 CYP3A KW - Oxidoreductases, N-Demethylating KW - EC 1.5.- KW - NADH Dehydrogenase KW - EC 1.6.99.3 KW - Index Medicus KW - Animals KW - Alcohol Drinking -- metabolism KW - Oxidoreductases -- analysis KW - Rats KW - Rats, Sprague-Dawley KW - Time Factors KW - Male KW - NADH Dehydrogenase -- analysis KW - Cytochrome P-450 Enzyme System -- analysis KW - Ethanol -- blood KW - Ethanol -- adverse effects KW - Substance Withdrawal Syndrome -- enzymology KW - Ethanol -- administration & dosage KW - Cytochrome P-450 Enzyme System -- metabolism KW - Oxidoreductases, N-Demethylating -- metabolism KW - Oxidoreductases, N-Demethylating -- analysis KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77347687?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=Rapid+changes+in+cytochrome+P4502E1+%28CYP2E1%29+activity+and+other+P450+isozymes+following+ethanol+withdrawal+in+rats.&rft.au=Roberts%2C+B+J%3BShoaf%2C+S+E%3BSong%2C+B+J&rft.aulast=Roberts&rft.aufirst=B&rft.date=1995-05-26&rft.volume=49&rft.issue=11&rft.spage=1665&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-14 N1 - Date created - 1995-07-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A double-blind, placebo-controlled trial of high-dose prednisone for the treatment of post-poliomyelitis syndrome. AN - 77397956; 7611639 JF - Annals of the New York Academy of Sciences AU - Dinsmore, S AU - Dambrosia, J AU - Dalakas, M C AD - Medical Neurology Branch, NINDS, NIH, Bethesda, MD 20892-1382, USA. Y1 - 1995/05/25/ PY - 1995 DA - 1995 May 25 SP - 303 EP - 313 VL - 753 SN - 0077-8923, 0077-8923 KW - Prednisone KW - VB0R961HZT KW - Index Medicus KW - Double-Blind Method KW - Humans KW - Middle Aged KW - Muscles -- physiopathology KW - Male KW - Female KW - Fatigue -- drug therapy KW - Postpoliomyelitis Syndrome -- physiopathology KW - Prednisone -- adverse effects KW - Postpoliomyelitis Syndrome -- drug therapy KW - Prednisone -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77397956?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=A+double-blind%2C+placebo-controlled+trial+of+high-dose+prednisone+for+the+treatment+of+post-poliomyelitis+syndrome.&rft.au=Dinsmore%2C+S%3BDambrosia%2C+J%3BDalakas%2C+M+C&rft.aulast=Dinsmore&rft.aufirst=S&rft.date=1995-05-25&rft.volume=753&rft.issue=&rft.spage=303&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-15 N1 - Date created - 1995-08-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fertility in men exposed prenatally to diethylstilbestrol. AN - 77230389; 7723797 AB - Prenatal exposure to diethylstilbestrol causes infertility in male mice and has been associated with malformations of the genital tract in men. However, little is known about the fertility of men who have been exposed prenatally to diethylstilbestrol. In 1950 through 1952, 1646 pregnant women were enrolled in a randomized, placebo-controlled clinical trial of diethylstilbestrol at Chicago Lying-in Hospital. We interviewed men who were born to the women during that study about their fertility. Four decades after their birth, we were able to trace 548 of the surviving sons (68 percent). Ninety percent consented to be interviewed (253 who had been exposed to diethylstilbestrol in utero and 241 who had not been exposed). Congenital malformations of the genitalia were reported three times as often by the diethylstilbestrol-exposed men as by the sons of the women in the placebo group. Within the exposed group, malformations were reported twice as often among those exposed to diethylstilbestrol before the 11th week of gestation as among those exposed later (P = 0.05). Men with genital malformations were nonetheless as fertile as other men. The diethylstilbestrol-exposed men (with or without genital malformations) had no impairment of fertility by any measure, including whether they had ever impregnated a women, age at the birth of their first child, average number of children, medical diagnosis of a fertility problem, or length of time to conception in the most recent pregnancy of the female partner. Finally, diethylstilbestrol-exposed men had no impairment of sexual function, as indicated, for example, by the frequency of intercourse or reported episodes of decreased libido. High doses of diethylstilbestrol did not lead to impairment of fertility or sexual function in adult men who had been exposed to the drug in utero. JF - The New England journal of medicine AU - Wilcox, A J AU - Baird, D D AU - Weinberg, C R AU - Hornsby, P P AU - Herbst, A L AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, N.C. 27709, USA. Y1 - 1995/05/25/ PY - 1995 DA - 1995 May 25 SP - 1411 EP - 1416 VL - 332 IS - 21 SN - 0028-4793, 0028-4793 KW - Diethylstilbestrol KW - 731DCA35BT KW - Abridged Index Medicus KW - Index Medicus KW - Probability KW - Randomized Controlled Trials as Topic KW - Humans KW - Adult KW - Genitalia, Male -- abnormalities KW - Middle Aged KW - Infertility, Male -- chemically induced KW - Abnormalities, Drug-Induced -- etiology KW - Male KW - Female KW - Sexual Behavior -- drug effects KW - Pregnancy KW - Diethylstilbestrol -- adverse effects KW - Prenatal Exposure Delayed Effects KW - Fertility -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77230389?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Fertility+in+men+exposed+prenatally+to+diethylstilbestrol.&rft.au=Wilcox%2C+A+J%3BBaird%2C+D+D%3BWeinberg%2C+C+R%3BHornsby%2C+P+P%3BHerbst%2C+A+L&rft.aulast=Wilcox&rft.aufirst=A&rft.date=1995-05-25&rft.volume=332&rft.issue=21&rft.spage=1411&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 - 1995-05-25 N1 - Date created - 1995-05-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neonatal lethality associated with respiratory distress in mice lacking cytochrome P450 1A2. AN - 77292066; 7761462 AB - Cytochrome P450 1A2 (CYP1A2) is a constitutively expressed hepatic enzyme that is highly conserved among mammals. This protein is primarily involved in oxidative metabolism of xenobiotics and is capable of metabolically activating numerous procarcinogens including aflatoxin B1, arylamines, heterocyclic amine food mutagens, and polycylic aromatic hydrocarbons. Expression of CYP1A2 is induced after exposure to certain aromatic hydrocarbons (i.e., 2,3,7,8-tetrachlorodibenzo-p-dioxin). Direct evidence for a role of CYP1A2 in any physiological or developmental pathway has not been documented. We now demonstrate that mice homozygous for a targeted mutation in the Cyp1a-2 gene are nonviable. Lethality occurs shortly after birth with symptoms of severe respiratory distress. Mutant neonates display impaired respiratory function associated with histological signs of lung immaturity, lack of air in alveoli at birth, and changes in expression of surfactant apoprotein in alveolar type II cells. The penetrance of the phenotype is not complete (19 mutants survived to adulthood out of 599 mice). Surviving animals, although lacking expression of CYP1A2, appear to be normal and are able to reproduce. These findings establish that CYP1A2 is critical for neonatal survival by influencing the physiology of respiration in neonates, thus offering etiological insights for neonatal respiratory distress syndrome. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Pineau, T AU - Fernandez-Salguero, P AU - Lee, S S AU - McPhail, T AU - Ward, J M AU - Gonzalez, F J AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/05/23/ PY - 1995 DA - 1995 May 23 SP - 5134 EP - 5138 VL - 92 IS - 11 SN - 0027-8424, 0027-8424 KW - Cyp1a-2 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Oxidoreductases KW - EC 1.- KW - Cytochrome P-450 CYP1A2 KW - EC 1.14.14.1 KW - Index Medicus KW - Animals KW - Pulmonary Alveoli -- pathology KW - Liver -- enzymology KW - Death KW - Mammals KW - Humans KW - Stem Cells -- physiology KW - Phenotype KW - Stem Cells -- cytology KW - Recombination, Genetic KW - Lung -- enzymology KW - Embryo, Mammalian KW - Liver -- pathology KW - Thyroid Gland -- pathology KW - Exons KW - Infant, Newborn KW - Mice KW - Lung -- pathology KW - Animals, Newborn KW - Mice, Mutant Strains KW - Restriction Mapping KW - Enzyme Induction KW - Thyroid Gland -- enzymology KW - Gallbladder -- pathology KW - Respiratory Distress Syndrome, Newborn -- pathology KW - Respiratory Distress Syndrome, Newborn -- enzymology KW - Oxidoreductases -- genetics KW - Cytochrome P-450 Enzyme System -- deficiency KW - Respiratory Distress Syndrome, Newborn -- genetics KW - Cytochrome P-450 Enzyme System -- genetics KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Oxidoreductases -- deficiency KW - Oxidoreductases -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77292066?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Neonatal+lethality+associated+with+respiratory+distress+in+mice+lacking+cytochrome+P450+1A2.&rft.au=Pineau%2C+T%3BFernandez-Salguero%2C+P%3BLee%2C+S+S%3BMcPhail%2C+T%3BWard%2C+J+M%3BGonzalez%2C+F+J&rft.aulast=Pineau&rft.aufirst=T&rft.date=1995-05-23&rft.volume=92&rft.issue=11&rft.spage=5134&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 - 1995-06-29 N1 - Date created - 1995-06-29 N1 - Date revised - 2017-01-13 N1 - Gene symbol - Cyp1a-2 N1 - SuppNotes - Cited By: Endocrinology. 1990 Jun;126(6):3101-6 [2161748] J Biol Chem. 1985 Apr 25;260(8):5040-9 [3988744] Nucleic Acids Res. 1991 Aug 11;19(15):4293 [1870982] FASEB J. 1992 Jan 6;6(2):669-73 [1537454] Mol Pharmacol. 1992 May;41(5):856-64 [1588920] Nature. 1992 Jun 4;357(6377):407-10 [1594045] Cell. 1992 Jun 12;69(6):915-26 [1606615] Mol Pharmacol. 1992 Dec;42(6):1027-32 [1282662] DNA Cell Biol. 1993 Jan-Feb;12(1):1-51 [7678494] Drug Metab Dispos. 1993 Jan-Feb;21(1):1-6 [8095200] Biochem Pharmacol. 1993 Apr 6;45(7):1373-86 [8471063] Mol Pharmacol. 1993 May;43(5):722-5 [8502229] Mol Cell Biol. 1994 Apr;14(4):2404-10 [8139544] EMBO J. 1994 Jun 15;13(12):2876-85 [7913017] Mol Carcinog. 1989;1(4):253-9 [2789689] Pediatrics. 1974 Oct;54(4):423-8 [4479315] Obstet Gynecol. 1980 Apr;55(4):439-43 [6892726] J Biol Chem. 1984 Sep 10;259(17):10705-13 [6547952] J Histochem Cytochem. 1985 Jun;33(6):564-8 [3889141] J Biol Chem. 1985 Nov 5;260(25):13607-12 [4055750] Mol Cell Biol. 1986 May;6(5):1471-7 [3785172] Cell. 1987 Nov 6;51(3):503-12 [2822260] Mol Biol Evol. 1987 Nov;4(6):572-93 [3484338] Nature. 1988 Nov 24;336(6197):348-52 [3194019] Trends Genet. 1990 Jun;6(6):182-6 [2196721] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Further studies of the role of Ser-16 in the regulation of the activity of phenylalanine hydroxylase. AN - 77289677; 7761394 AB - It was previously proposed that the activation of rat liver phenylalanine hydroxylase (EC 1.14.16.1) by cAMP-dependent protein kinase-mediated phosphorylation of Ser-16 is due to the introduction of the negatively charged phosphate group. To explore the validity of this proposal, we have applied site-directed mutagenesis to specifically replace Ser-16 with negatively charged amino acids, glutamic and aspartic; with polar uncharged amino acids, asparagine and glutamine; with the positively charged amino acid lysine; and with the nonpolar hydrophobic amino acid alanine. The wild-type and mutant enzymes were purified to homogeneity, and the importance of Ser-16 in the activation of phenylalanine hydroxylase was examined by comparing the state of activation of the phosphorylated form of the wild-type hydroxylase with that of the mutants. The kinetic studies carried out on the wild-type phosphorylated hydroxylase showed that all the activation could be accounted for by an increase in Vmax with no change in Km for either phenylalanine or the pterin cofactor. Replacement of Ser-16 with a negatively charged residue, glutamate of aspartate, resulted in the activation of the hydroxylase by 2- to 4-fold, whereas replacement with glutamine, asparagine, lysine, or alanine resulted in a much more modest increase. Further, lysolecithin was found to stimulate the phosphorylated hydroxylase and the mutant enzymes S16E and S16D by a factor of 6-7. In contrast, the mutants S16Q, S16N, and S16A all showed the same magnitude of activation as the wild-type with lysolecithin. Therefore, this study demonstrates that activation of the enzyme by phosphorylation of Ser-16 by cAMP-dependent protein kinase is due to the introduction of negative charge(s) and strongly suggests the involvement of electrostatic interaction between the regulatory and catalytic domains of the hydroxylase. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Kowlessur, D AU - Yang, X J AU - Kaufman, S AD - Laboratory of Neurochemistry, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/05/23/ PY - 1995 DA - 1995 May 23 SP - 4743 EP - 4747 VL - 92 IS - 11 SN - 0027-8424, 0027-8424 KW - DNA Primers KW - 0 KW - Lysophosphatidylcholines KW - Recombinant Proteins KW - Serine KW - 452VLY9402 KW - Phenylalanine Hydroxylase KW - EC 1.14.16.1 KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Index Medicus KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Animals KW - Electrophoresis, Polyacrylamide Gel KW - Enzyme Activation KW - Amino Acid Sequence KW - Mutagenesis, Site-Directed KW - Rats KW - Recombinant Proteins -- isolation & purification KW - Base Sequence KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Restriction Mapping KW - Lysophosphatidylcholines -- pharmacology KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Liver -- enzymology KW - Phenylalanine Hydroxylase -- isolation & purification KW - Phenylalanine Hydroxylase -- chemistry KW - Phenylalanine Hydroxylase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77289677?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Further+studies+of+the+role+of+Ser-16+in+the+regulation+of+the+activity+of+phenylalanine+hydroxylase.&rft.au=Kowlessur%2C+D%3BYang%2C+X+J%3BKaufman%2C+S&rft.aulast=Kowlessur&rft.aufirst=D&rft.date=1995-05-23&rft.volume=92&rft.issue=11&rft.spage=4743&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 - 1995-06-29 N1 - Date created - 1995-06-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] Adv Enzyme Regul. 1986;25:37-64 [3028051] J Biol Chem. 1979 Nov 25;254(22):11300-6 [500646] J Biol Chem. 1980 May 25;255(10):4793-800 [7372612] Biochem Biophys Res Commun. 1980 Mar 28;93(2):403-8 [7387651] J Biol Chem. 1981 Jul 10;256(13):6876-82 [7240248] Proc Natl Acad Sci U S A. 1985 Jan;82(2):488-92 [3881765] Methods Enzymol. 1987;142:3-17 [3600372] Protein Expr Purif. 1992 Apr;3(2):93-100 [1422220] Biochem Biophys Res Commun. 1994 Jan 14;198(1):174-80 [7904815] J Biol Chem. 1952 Feb;194(2):503-11 [14927641] J Biol Chem. 1952 May;196(1):227-33 [12980961] Eur J Biochem. 1969 Jan;7(3):360-9 [5791581] Nature. 1970 Aug 15;227(5259):680-5 [5432063] J Biol Chem. 1970 Sep 25;245(18):4751-9 [5456148] Biochim Biophys Acta. 1971 Aug 20;242(2):345-54 [5160150] J Biol Chem. 1972 Apr 10;247(7):2250-2 [5062822] J Biol Chem. 1973 Jun 25;248(12):4345-53 [4145799] J Biol Chem. 1976 Sep 10;251(17):5310-4 [182695] J Biol Chem. 1986 Feb 15;261(5):2051-6 [3944127] J Biol Chem. 1978 Oct 10;253(19):6657-9 [690116] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Decreased sensitivity to nerve growth factor of dorsal root ganglion neurons cultured from mouse trisomy 16, a model of Down's syndrome. AN - 77489884; 7663966 AB - The effect of NGF was studied on the adhesion of mouse dorsal root ganglion (DRG) neurons to a laminin-coated surface and on their subsequent survival in primary culture. DRG neurons were obtained both from normal diploid mice and trisomy 16 mice. The latter are considered a model of human trisomy 21, Down's syndrome. Whereas both diploid and trisomy DRG neurons depended on NGF for adhesion, the sensitivity of trisomy 16 neurons to NGF was significantly reduced (P < 0.05). This suggests that excess expression of genes on mouse chromosome 16 alters NGF-regulated adhesion to laminin. Survival of neurons that had attached to laminin in culture did not appear dependent on NGF for either diploid or trisomy 16 neurons. JF - Brain research AU - Pearce, R AU - Galdzicki, Z AU - Rapoport, S I AD - Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/05/22/ PY - 1995 DA - 1995 May 22 SP - 108 EP - 116 VL - 680 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Nerve Growth Factors KW - 0 KW - Index Medicus KW - Animals KW - Drug Resistance -- genetics KW - Microscopy, Phase-Contrast KW - Cell Count KW - Cells, Cultured KW - Mice KW - Diploidy KW - Nerve Growth Factors -- poisoning KW - Down Syndrome -- physiopathology KW - Nerve Growth Factors -- pharmacology KW - Neurons -- drug effects KW - Ganglia, Spinal -- pathology KW - Trisomy KW - Ganglia, Spinal -- drug effects KW - Down Syndrome -- genetics KW - Down Syndrome -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77489884?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Decreased+sensitivity+to+nerve+growth+factor+of+dorsal+root+ganglion+neurons+cultured+from+mouse+trisomy+16%2C+a+model+of+Down%27s+syndrome.&rft.au=Pearce%2C+R%3BGaldzicki%2C+Z%3BRapoport%2C+S+I&rft.aulast=Pearce&rft.aufirst=R&rft.date=1995-05-22&rft.volume=680&rft.issue=1-2&rft.spage=108&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 - 1995-10-10 N1 - Date created - 1995-10-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structure-function analysis of human glucose-6-phosphatase, the enzyme deficient in glycogen storage disease type 1a. AN - 77257833; 7744838 AB - Glucose-6-phosphatase (G6Pase) is the enzyme deficient in glycogen storage disease type 1a, an autosomal recessive disorder. We have previously identified six mutations in the G6Pase gene of glycogen storage disease type 1a patients and demonstrated that these mutations abolished or greatly reduced enzymatic activity of G6Pase, a hydrophobic protein of 357 amino acids. Of these, four mutations (R83C, R295C, G222R, and Q347X) are missense and one (Q347X) generates a truncated G6Pase of 346 residues. To further understand the roles and structural requirements of amino acids 83, 222, 295, and those at the carboxyl terminus in G6Pase catalysis, we characterized mutant G6Pases generated by near-saturation mutagenesis of the aforementioned amino acids. Substitution of Arg-83 with amino acids of diverse structures including Lys, a conservative change, yielded mutant G6Pase with no enzymatic activity. On the other hand, substitution of Arg-295 with Lys (R295K) retained high activity, and R295N, R295S, and R295Q exhibited moderate activity. All other substitutions of Arg-295 had no G6Pase activity, suggesting that the role of Arg-295 is to stabilize the protein either by salt bridge or hydrogen-bond formation. Substitution of Gly-222, however, remained functional unless a basic (Arg or Lys), acidic (Asp), or large polar (Gln) residue was introduced, consistent with the hydrophobic requirement of codon 222, which is predicted to be in the fourth membrane-spanning domain. It is possible that Arg-83 is involved in stabilizing the enzyme (His)-phosphate intermediate formed during G6Pase catalysis. There exist 9 conserved His residues in human G6Pase. His-9, His-119, His-252, and His-353 reside on the same side of the endoplasmic reticulum membrane as Arg-83. Whereas H119A mutant G6Pase had no enzymatic activity, H9A, H252A, and H353A mutant G6Pases retained significant activity. Substitution of His-119 with amino acids of diverse structures also yielded mutant G6Pase with no activity, suggesting that His-119 is the phosphate acceptor in G6Pase catalysis. We also present data demonstrating that the carboxyl-terminal 8 residues in human G6Pase are not essential for G6Pase catalysis. JF - The Journal of biological chemistry AU - Lei, K J AU - Pan, C J AU - Liu, J L AU - Shelly, L L AU - Chou, J Y AD - Human Genetics Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/05/19/ PY - 1995 DA - 1995 May 19 SP - 11882 EP - 11886 VL - 270 IS - 20 SN - 0021-9258, 0021-9258 KW - Amino Acids KW - 0 KW - Codon KW - Recombinant Fusion Proteins KW - Glucose-6-Phosphatase KW - EC 3.1.3.9 KW - Index Medicus KW - Endoplasmic Reticulum -- enzymology KW - Animals KW - Codon -- genetics KW - Humans KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Hot Temperature KW - Base Sequence KW - Amino Acids -- chemistry KW - Cercopithecus aethiops KW - Molecular Sequence Data KW - Cell Line, Transformed KW - Catalysis KW - Glucose-6-Phosphatase -- metabolism KW - Glucose-6-Phosphatase -- chemistry KW - Glycogen Storage Disease Type I -- genetics KW - Glycogen Storage Disease Type I -- enzymology KW - Glucose-6-Phosphatase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77257833?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Structure-function+analysis+of+human+glucose-6-phosphatase%2C+the+enzyme+deficient+in+glycogen+storage+disease+type+1a.&rft.au=Lei%2C+K+J%3BPan%2C+C+J%3BLiu%2C+J+L%3BShelly%2C+L+L%3BChou%2C+J+Y&rft.aulast=Lei&rft.aufirst=K&rft.date=1995-05-19&rft.volume=270&rft.issue=20&rft.spage=11882&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 - 1995-06-12 N1 - Date created - 1995-06-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evidence in support of a role for human T-cell leukemia virus type I Tax in activating NF-kappa B via stimulation of signaling pathways. AN - 77257671; 7744820 AB - The human T-cell leukemia virus type I Tax protein activates NF-kappa B transcription factors from preformed cytoplasmic pools, including those pools that are retained by the I kappa B-alpha inhibitory protein. Degradation of I kappa B-alpha is enhanced by Tax, resulting in the liberation of some NF-kappa B, which then translocates into the nucleus. Here we have investigated the mechanism by which Tax causes degradation of I kappa B-alpha. Two I kappa B-alpha mutants defective in extracellular signal-induced degradation of I kappa B-alpha also blocked Tax-mediated kappa B-dependent transactivation when cotransfected into Jurkat T cells. Cotransfected wild-type I kappa B-alpha or an irrelevant mutant did not significantly effect transactivation induced by Tax. The signal-defective I kappa B-alpha proteins are mutated at either of two closely spaced serines in the N terminus of the protein (Ser32 and Ser36). In wild-type I kappa B-alpha, one or both of these serines are inducibly phosphorylated with extracellular stimuli, and such phosphorylation appears necessary for subsequent degradation and thus activation of NF-kappa B. These results suggest that Tax triggers I kappa B-alpha degradation and thus NF-kappa B activation by a mechanism that converges with that induced by extracellular stimulation such as phorbol 12-myristate 13-acetate/ionomycin or tumor necrosis factor alpha. A role for Tax in activating signal transduction pathways upstream of I kappa B-alpha is implied. JF - The Journal of biological chemistry AU - Kanno, T AU - Brown, K AU - Siebenlist, U AD - Laboratory of Immunoregulation, NIAID, National Institutes of Health, Bethesda, Maryland 20892-1876, USA. Y1 - 1995/05/19/ PY - 1995 DA - 1995 May 19 SP - 11745 EP - 11748 VL - 270 IS - 20 SN - 0021-9258, 0021-9258 KW - Gene Products, tax KW - 0 KW - NF-kappa B KW - Proto-Oncogene Proteins KW - RELB protein, human KW - Recombinant Fusion Proteins KW - Transcription Factors KW - Tumor Necrosis Factor-alpha KW - Transcription Factor RelB KW - 147337-75-5 KW - Serine KW - 452VLY9402 KW - Ionomycin KW - 56092-81-0 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - AIDS/HIV KW - Humans KW - Leukemia-Lymphoma, Adult T-Cell KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Protein Processing, Post-Translational KW - Ionomycin -- pharmacology KW - Serine -- chemistry KW - Mutagenesis, Site-Directed KW - Recombinant Fusion Proteins -- metabolism KW - T-Lymphocytes -- metabolism KW - Tumor Cells, Cultured KW - Phosphorylation KW - Transfection KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Human T-lymphotropic virus 1 -- physiology KW - Human T-lymphotropic virus 1 -- genetics KW - Signal Transduction -- drug effects KW - Proto-Oncogene Proteins -- metabolism KW - Transcriptional Activation -- drug effects KW - Gene Expression Regulation -- drug effects KW - NF-kappa B -- physiology KW - Proto-Oncogene Proteins -- genetics KW - Gene Products, tax -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77257671?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Evidence+in+support+of+a+role+for+human+T-cell+leukemia+virus+type+I+Tax+in+activating+NF-kappa+B+via+stimulation+of+signaling+pathways.&rft.au=Kanno%2C+T%3BBrown%2C+K%3BSiebenlist%2C+U&rft.aulast=Kanno&rft.aufirst=T&rft.date=1995-05-19&rft.volume=270&rft.issue=20&rft.spage=11745&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 - 1995-06-12 N1 - Date created - 1995-06-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cloning, expression, sequence analysis, and site-directed mutagenesis of the Tn5306-encoded N5-(carboxyethyl)ornithine synthase from Lactococcus lactis K1. AN - 77257462; 7744873 AB - The gene (ceo) encoding N5-(carboxyethyl)ornithine synthase (EC 1.5.1.24) has been isolated from the sucrose-nisin transposon Tn5306 of Lactococcus lactis K1, sequenced, and expressed at high level in Escherichia coli. The cloned enzyme has allowed the synthesis of the novel N omega-carboxypropyl amino acids N5-(1-carboxypropyl)-L-ornithine and N6-(1-carboxypropyl)-L-lysine. Comparison of the deduced amino acid sequence of N5-(1-carboxyethyl)-L-ornithine synthase (M(r) = 35,323) to the functionally analogous octopine and nopaline synthases from crown gall tumors showed surprisingly little similarity. However, N5-(1-carboxyethyl)-L-ornithine synthase and yeast saccharopine dehydrogenase exhibit homology at their N and C termini, which suggests that these two proteins constitute a distinct branch of the amino acid dehydrogenase superfamily. A centrally located 9-amino acid segment (GSGNVAQGA) in N5-(1-carboxyethyl)-L-ornithine synthase is virtually identical with a sequence present in the beta alpha beta-fold of the nucleotide binding domain of several microbial NADPH-dependent glutamate dehydrogenases. A much longer sequence of approximately 80 residues has significant similarity to alanine dehydrogenase. Substitution of arginine 15 of N5-(1-carboxyethyl)-L-ornithine synthase by lysine resulted in loss of enzyme activity. JF - The Journal of biological chemistry AU - Donkersloot, J A AU - Thompson, J AD - Laboratory of Microbial Ecology, NIDR, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/05/19/ PY - 1995 DA - 1995 May 19 SP - 12226 EP - 12234 VL - 270 IS - 20 SN - 0021-9258, 0021-9258 KW - ceo KW - Bacterial Proteins KW - 0 KW - DNA Transposable Elements KW - Amino Acid Oxidoreductases KW - EC 1.4.- KW - Alanine Dehydrogenase KW - EC 1.4.1.1 KW - Glutamate Dehydrogenase KW - EC 1.4.1.2 KW - Saccharopine Dehydrogenases KW - EC 1.5.1.- KW - nopaline synthase KW - D-octopine dehydrogenase KW - EC 1.5.1.11 KW - N(5)-(carboxyethyl)ornithine synthase KW - EC 1.5.1.24 KW - Index Medicus KW - Genes, Bacterial KW - Escherichia coli -- genetics KW - Amino Acid Sequence KW - Saccharopine Dehydrogenases -- chemistry KW - Cloning, Molecular KW - Mutagenesis, Site-Directed KW - Oxidation-Reduction KW - Base Sequence KW - Sequence Alignment KW - Glutamate Dehydrogenase -- chemistry KW - Molecular Sequence Data KW - DNA Transposable Elements -- genetics KW - Genetic Vectors -- genetics KW - Sequence Homology, Amino Acid KW - Amino Acid Oxidoreductases -- genetics KW - Lactococcus lactis -- genetics KW - Bacterial Proteins -- genetics KW - Bacterial Proteins -- biosynthesis KW - Amino Acid Oxidoreductases -- biosynthesis KW - Amino Acid Oxidoreductases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77257462?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Cloning%2C+expression%2C+sequence+analysis%2C+and+site-directed+mutagenesis+of+the+Tn5306-encoded+N5-%28carboxyethyl%29ornithine+synthase+from+Lactococcus+lactis+K1.&rft.au=Donkersloot%2C+J+A%3BThompson%2C+J&rft.aulast=Donkersloot&rft.aufirst=J&rft.date=1995-05-19&rft.volume=270&rft.issue=20&rft.spage=12226&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 - 1995-06-12 N1 - Date created - 1995-06-12 N1 - Date revised - 2017-01-13 N1 - Gene symbol - ceo N1 - Genetic sequence - U23376; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of apoptosis in lymph nodes of HIV-infected persons. Intensity of apoptosis correlates with the general state of activation of the lymphoid tissue and not with stage of disease or viral burden. AN - 77244225; 7730654 AB - The occurrence of in vivo apoptosis was investigated in lymph node sections obtained from HIV-infected persons at different stages of disease. The degree of apoptosis in lymph nodes from HIV-infected individuals was compared with that observed in lymph nodes obtained from HIV-negative individuals. Apoptosis was readily detected in lymph nodes obtained from both HIV-negative and HIV-positive persons; however, the degree of apoptosis in lymph nodes obtained from HIV-positive persons was three to four times higher than that observed in the lymph nodes obtained from HIV-negative persons. In contrast to HIV-negative lymph nodes in which apoptosis was confined largely to germinal centers, in HIV-positive lymph nodes all functional compartments of the lymph node (i.e., cortex, paracortex, and sinuses) were extensively involved by this phenomenon. Furthermore, a significant correlation was observed between intensity of apoptosis and degree of activation of the lymphoid tissue associated with HIV infection. In contrast, intensity of apoptosis correlated neither with the clinical stage of HIV disease nor with the viral burden in the lymph node. Finally, apoptosis was not restricted only to CD4+ T cells; both B cells and CD8+ T cells were found to undergo apoptosis. Taken together, these results indicate that the increased intensity of the apoptotic phenomenon in HIV infection is caused by the general state of immune activation, and is independent of the progression of HIV disease and of the levels of viral load. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Muro-Cacho, C A AU - Pantaleo, G AU - Fauci, A S AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/05/15/ PY - 1995 DA - 1995 May 15 SP - 5555 EP - 5566 VL - 154 IS - 10 SN - 0022-1767, 0022-1767 KW - DNA, Viral KW - 0 KW - Acridine Orange KW - F30N4O6XVV KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Polymerase Chain Reaction KW - HIV-1 -- immunology KW - HIV-1 -- isolation & purification KW - DNA, Viral -- analysis KW - DNA Damage KW - Humans KW - Electrophoresis, Agar Gel KW - Leukocytes, Mononuclear -- immunology KW - Lymph Nodes -- virology KW - HIV Infections -- virology KW - HIV Infections -- immunology KW - Apoptosis -- immunology KW - Lymph Nodes -- cytology KW - Lymph Nodes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77244225?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Analysis+of+apoptosis+in+lymph+nodes+of+HIV-infected+persons.+Intensity+of+apoptosis+correlates+with+the+general+state+of+activation+of+the+lymphoid+tissue+and+not+with+stage+of+disease+or+viral+burden.&rft.au=Muro-Cacho%2C+C+A%3BPantaleo%2C+G%3BFauci%2C+A+S&rft.aulast=Muro-Cacho&rft.aufirst=C&rft.date=1995-05-15&rft.volume=154&rft.issue=10&rft.spage=5555&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 - 1995-05-31 N1 - Date created - 1995-05-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Diethylstilbestrol revisited: a review of the long-term health effects. AN - 77220184; 7717601 AB - To review the literature on the long-term health effects of exposure to diethylstilbestrol (DES) among women prescribed DES during pregnancy (DES mothers), among their children exposed inutero to the drug (DES sons and daughters) and among the progeny of these exposed sons and daughters (DES grandchildren). English-language articles were identified through MEDLINE and CANCERLIT searches and through review of the bibliographies of identified articles. All human studies relevant to long-term health effects of exposure to DES were reviewed. Descriptive data on existing DES cohorts were extracted from early publications. Risk estimates for health effects were extracted from published reports. An estimated 5 to 10 million Americans received DES during pregnancy or were exposed to the drug in utero. Exposure to DES has been associated with an increased risk for breast cancer in DES mothers (relative risk, < 2.0) and with a lifetime risk of clear-cell cervicovaginal cancer in DES daughters of 1/1000 to 1/10,000. The association between DES exposure and testicular cancer in DES sons remains controversial. Exposure to DES has also been linked to reproductive tract abnormalities in DES sons and daughters that consist of immune system disorders and psychosexual effects. No evidence for transgenerational effects currently exists. Recommendations for screening persons exposed to DES are reviewed. Further research is needed to define long-term health effects related to DES exposure. Such research would provide a basis for counseling persons exposed to DES and would further understanding of environmental and pharmacologic compounds similar to DES. JF - Annals of internal medicine AU - Giusti, R M AU - Iwamoto, K AU - Hatch, E E AD - Division of Cancer Treatment, National Cancer Institute, Bethesda, MD 20892-2440, USA. Y1 - 1995/05/15/ PY - 1995 DA - 1995 May 15 SP - 778 EP - 788 VL - 122 IS - 10 SN - 0003-4819, 0003-4819 KW - Diethylstilbestrol KW - 731DCA35BT KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Urogenital Abnormalities KW - Risk Factors KW - Humans KW - Testicular Neoplasms -- etiology KW - Breast Neoplasms -- etiology KW - Male KW - Female KW - Pregnancy KW - Genital Neoplasms, Female -- etiology KW - Diethylstilbestrol -- adverse effects KW - Diethylstilbestrol -- toxicity KW - Diethylstilbestrol -- pharmacology KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77220184?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+internal+medicine&rft.atitle=Diethylstilbestrol+revisited%3A+a+review+of+the+long-term+health+effects.&rft.au=Giusti%2C+R+M%3BIwamoto%2C+K%3BHatch%2C+E+E&rft.aulast=Giusti&rft.aufirst=R&rft.date=1995-05-15&rft.volume=122&rft.issue=10&rft.spage=778&rft.isbn=&rft.btitle=&rft.title=Annals+of+internal+medicine&rft.issn=00034819&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-16 N1 - Date created - 1995-05-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - KAI1, a metastasis suppressor gene for prostate cancer on human chromosome 11p11.2. AN - 77279839; 7754374 AB - A gene from human chromosome 11p11.2 was isolated and was shown to suppress metastasis when introduced into rat AT6.1 prostate cancer cells. Expression of this gene, designated KAI1, was reduced in human cell lines derived from metastatic prostate tumors. KAI1 specifies a protein of 267 amino acids, with four hydrophobic and presumably transmembrane domains and one large extracellular hydrophilic domain with three potential N-glycosylation sites. KAI1 is evolutionarily conserved, is expressed in many human tissues, and encodes a member of a structurally distinct family of leukocyte surface glycoproteins. Decreased expression of this gene may be involved in the malignant progression of prostate and other cancers. JF - Science (New York, N.Y.) AU - Dong, J T AU - Lamb, P W AU - Rinker-Schaeffer, C W AU - Vukanovic, J AU - Ichikawa, T AU - Isaacs, J T AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, NC 27709, USA. Y1 - 1995/05/12/ PY - 1995 DA - 1995 May 12 SP - 884 EP - 886 VL - 268 IS - 5212 SN - 0036-8075, 0036-8075 KW - KAI1 KW - Antigens, CD KW - 0 KW - Antigens, CD82 KW - CD82 protein, human KW - Cd82 antigen, mouse KW - Cd82 protein, rat KW - Membrane Glycoproteins KW - Proto-Oncogene Proteins KW - Index Medicus KW - Animals KW - Biological Evolution KW - Humans KW - Gene Expression KW - Amino Acid Sequence KW - Mice KW - Rats KW - Base Sequence KW - Tumor Cells, Cultured KW - Transfection KW - Molecular Sequence Data KW - Mice, SCID KW - Male KW - Prostatic Neoplasms -- pathology KW - Membrane Glycoproteins -- chemistry KW - Antigens, CD -- physiology KW - Neoplasm Metastasis -- genetics KW - Membrane Glycoproteins -- physiology KW - Genes, Tumor Suppressor KW - Antigens, CD -- chemistry KW - Prostatic Neoplasms -- genetics KW - Antigens, CD -- genetics KW - Membrane Glycoproteins -- genetics KW - Chromosomes, Human, Pair 11 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77279839?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+%28New+York%2C+N.Y.%29&rft.atitle=KAI1%2C+a+metastasis+suppressor+gene+for+prostate+cancer+on+human+chromosome+11p11.2.&rft.au=Dong%2C+J+T%3BLamb%2C+P+W%3BRinker-Schaeffer%2C+C+W%3BVukanovic%2C+J%3BIchikawa%2C+T%3BIsaacs%2C+J+T%3BBarrett%2C+J+C&rft.aulast=Dong&rft.aufirst=J&rft.date=1995-05-12&rft.volume=268&rft.issue=5212&rft.spage=884&rft.isbn=&rft.btitle=&rft.title=Science+%28New+York%2C+N.Y.%29&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-16 N1 - Date created - 1995-06-16 N1 - Date revised - 2017-01-13 N1 - Gene symbol - KAI1 N1 - Genetic sequence - U20770; GENBANK N1 - SuppNotes - Comment In: Science. 1995 May 12;268(5212):799-800 [7754364] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Azatoxin derivatives with potent and selective action on topoisomerase II. AN - 77293840; 7763310 AB - Azatoxin was rationally designed as a DNA topoisomerase II (top2) inhibitor [Leteurtre et al., Cancer Res 52: 4478-4483, 1992] and was also found to inhibit tubulin polymerization. Its cytotoxicity is due to action on tubulin at lower concentrations and on top2 at higher concentrations. At intermediate concentrations, the combination of the two mechanisms appears antagonistic [Solary et al., Biochem Pharmacol 45: 2449-2456, 1993]. The aim of this study was to design azatoxin derivatives that would act only on tubulin or on top2. Selective targeting of top2 or tubulin was tested using top2-mediated DNA cleavage assays, and tubulin polymerization and tubulin proteolysis assays, as well as COMPARE analyses of cytotoxicity assays in the National Cancer Institute in vitro Drug Screening Program. Selective inhibitors of top2 and tubulin polymerization have been obtained. Top2 inhibition, abolished by methylation at position 4', was enhanced by the addition of a bulky group at position 11. Bulky substitution at position 11 determined different patterns of top2 cleavage sites and suppressed the action on tubulin. Selective inhibition of tubulin was obtained with 4'-methylazatoxin that was found to bind to the colchicine site. These results are consistent with those obtained in the podophyllotoxin family to which azatoxin is structurally related. Some azatoxin derivatives are under consideration for further preclinical development. JF - Biochemical pharmacology AU - Leteurtre, F AU - Sackett, D L AU - Madalengoitia, J AU - Kohlhagen, G AU - MacDonald, T AU - Hamel, E AU - Paull, K D AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, DTP, DCT, NCI, NIH, Bethesda, Maryland 20892, USA. Y1 - 1995/05/11/ PY - 1995 DA - 1995 May 11 SP - 1283 EP - 1290 VL - 49 IS - 9 SN - 0006-2952, 0006-2952 KW - 4'-methylazatoxin KW - 0 KW - Antineoplastic Agents KW - Indoles KW - Topoisomerase II Inhibitors KW - Tubulin Modulators KW - fluoroanilinoazatoxin KW - azatoxin KW - 129564-92-7 KW - Index Medicus KW - Drug Screening Assays, Antitumor KW - Base Sequence KW - Molecular Sequence Data KW - Structure-Activity Relationship KW - Indoles -- toxicity KW - Indoles -- pharmacology KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77293840?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=Azatoxin+derivatives+with+potent+and+selective+action+on+topoisomerase+II.&rft.au=Leteurtre%2C+F%3BSackett%2C+D+L%3BMadalengoitia%2C+J%3BKohlhagen%2C+G%3BMacDonald%2C+T%3BHamel%2C+E%3BPaull%2C+K+D%3BPommier%2C+Y&rft.aulast=Leteurtre&rft.aufirst=F&rft.date=1995-05-11&rft.volume=49&rft.issue=9&rft.spage=1283&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-27 N1 - Date created - 1995-06-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Study of the role of retinoblastoma protein in terminal differentiation of murine erythroleukemia cells. AN - 77282776; 7753788 AB - Hexamethylenebisacetamide-induced terminal differentiation of Friend virus-transformed murine erythroleukemia (MEL) cells can be inhibited by okadaic acid, an inhibitor of type 1 and type 2A protein phosphatases. The inhibition is shown to be correlated with prevention of dephosphorylation of retinoblastoma protein (pRB) in cells and bypass of G1 prolongation in the cell cycle. These results suggest that pRB-mediated G1 prolongation is necessary for MEL cells to commit to terminal differentiation. However, further experiments demonstrate that the simple cell cycle exit is not sufficient for commitment to terminal differentiation. Induction of dephosphorylation of pRB and subsequent G1 prolongation by forskolin does not lead MEL cells to differentiate. Additional pRB has been expressed in MEL cells by transfection with a neo-resistant plasmid containing RB cDNA under the control of a cytomegalovirus promoter. Exogenously expressed pRB is hyperphosphorylated in logarithmically growing MEL cells without any noticeable change in growth rate between the transfected cell line and the parental cell line. This result suggests that pRB in MEL cells is regulated by protein kinases and protein phosphatases and not by transcription. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Zhuo, S AU - Fan, S AU - Huang, S AU - Kaufman, S AD - Laboratory of Neurochemistry, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/05/09/ PY - 1995 DA - 1995 May 09 SP - 4234 EP - 4238 VL - 92 IS - 10 SN - 0027-8424, 0027-8424 KW - Acetamides KW - 0 KW - Antineoplastic Agents KW - Ethers, Cyclic KW - Retinoblastoma Protein KW - Okadaic Acid KW - 1W21G5Q4N2 KW - Phosphoprotein Phosphatases KW - EC 3.1.3.16 KW - hexamethylene bisacetamide KW - LA133J59VU KW - Index Medicus KW - Phosphoprotein Phosphatases -- antagonists & inhibitors KW - Animals KW - Leukemia, Erythroblastic, Acute KW - Tumor Cells, Cultured KW - Kinetics KW - Gene Expression KW - Mice KW - G1 Phase KW - Friend murine leukemia virus KW - Ethers, Cyclic -- pharmacology KW - Cell Line, Transformed KW - Cell Line KW - Acetamides -- pharmacology KW - Cell Differentiation -- physiology KW - Cell Cycle -- physiology KW - Retinoblastoma Protein -- metabolism KW - Retinoblastoma Protein -- biosynthesis KW - Cell Differentiation -- drug effects KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77282776?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Study+of+the+role+of+retinoblastoma+protein+in+terminal+differentiation+of+murine+erythroleukemia+cells.&rft.au=Zhuo%2C+S%3BFan%2C+S%3BHuang%2C+S%3BKaufman%2C+S&rft.aulast=Zhuo&rft.aufirst=S&rft.date=1995-05-09&rft.volume=92&rft.issue=10&rft.spage=4234&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 - 1995-06-16 N1 - Date created - 1995-06-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Natl Cancer Inst Monogr. 1966 Sep;22:505-22 [5923328] Cell. 1994 Nov 4;79(3):487-96 [7954814] Proc Natl Acad Sci U S A. 1979 Sep;76(9):4511-5 [291983] Cancer Res. 1987 Jan 15;47(2):617-23 [3791246] Proc Natl Acad Sci U S A. 1987 Aug;84(15):5282-6 [3474654] Proc Natl Acad Sci U S A. 1989 Sep;86(17):6474-8 [2671991] Cell. 1989 Sep 22;58(6):1097-105 [2673543] Cell. 1989 Sep 22;58(6):1193-8 [2673546] Science. 1989 Nov 3;246(4930):603-8 [2683075] Cell. 1990 Feb 9;60(3):387-96 [2154332] EMBO J. 1990 Jun;9(6):1815-22 [2189724] EMBO J. 1991 Apr;10(4):857-64 [2009861] Cell. 1991 Jun 14;65(6):1053-61 [1828392] Cell. 1991 Jun 14;65(6):1063-72 [1828393] Cell. 1991 Jun 14;65(6):1073-82 [1828394] Nature. 1991 Jun 6;351(6326):494-7 [1710781] Nature. 1991 Aug 8;352(6335):541-4 [1865909] Cell. 1991 Oct 18;67(2):293-302 [1655277] EMBO J. 1991 Dec;10(13):4279-90 [1756735] Nature. 1992 Jul 23;358(6384):331-4 [1641004] Nature. 1992 Sep 24;359(6393):270-1 [1406928] Nature. 1992 Sep 24;359(6393):288-94 [1406932] Nature. 1992 Sep 24;359(6393):295-300 [1406933] Nature. 1992 Sep 24;359(6393):328-30 [1406937] Cell Growth Differ. 1992 Jul;3(7):413-20 [1419904] Mol Cell Biol. 1993 Jan;13(1):367-72 [8380224] Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):388-92 [8380637] Cell. 1993 Feb 12;72(3):309-24 [8381715] Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6746-50 [8341693] Cell. 1993 Nov 19;75(4):779-90 [8242749] Cancer Res. 1994 Apr 15;54(8):2245-50 [8174134] Proc Natl Acad Sci U S A. 1994 May 10;91(10):4165-9 [8183886] Cell. 1994 Oct 7;79(1):119-30 [7923370] Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10251-4 [7937935] Cancer Res. 1994 Nov 15;54(22):5824-30 [7954409] Proc Natl Acad Sci U S A. 1977 Jan;74(1):248-52 [64982] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Basic fibroblast growth factor can mediate the early inductive events in renal development. AN - 77278818; 7753867 AB - The earliest characterized events during induction of tubulogenesis in renal anlage include the condensation or compaction of metanephrogenic mesenchyme with the concurrent upregulation of WT1, the gene encoding the Wilms tumor transcriptional activator/suppressor. We report that basic fibroblast growth factor (FGF2) can mimic the early effects of an inductor tissue by promoting the condensation of mesenchyme and inhibiting the tissue degeneration associated with the absence of an inductor tissue. By in situ hybridization, FGF2 was also found to mediate the transcriptional activation of WT1 and of the hepatocyte growth factor receptor gene, c-met. Although FGF2 can induce these early events of renal tubulogenesis, it cannot promote the epithelial conversion associated with tubule formation in metanephrogenic mesenchyme. For this, an undefined factor(s) from pituitary extract in combination with FGF2 can cause tubule formation in uninduced mesenchyme. These findings support the concept that induction in kidney is a multiphasic process that is mediated by more than a single comprehensive inductive factor and that soluble molecules can mimic these inductive activities in isolated uninduced metanephrogenic mesenchyme. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Perantoni, A O AU - Dove, L F AU - Karavanova, I AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702, USA. Y1 - 1995/05/09/ PY - 1995 DA - 1995 May 09 SP - 4696 EP - 4700 VL - 92 IS - 10 SN - 0027-8424, 0027-8424 KW - WT1 KW - c-met KW - Tissue Extracts KW - 0 KW - Fibroblast Growth Factor 2 KW - 103107-01-3 KW - Proto-Oncogene Proteins c-met KW - EC 2.7.10.1 KW - Receptor Protein-Tyrosine Kinases KW - Index Medicus KW - Animals KW - Transcription, Genetic -- drug effects KW - Pituitary Gland KW - Humans KW - Tissue Extracts -- pharmacology KW - Proto-Oncogenes KW - Embryonic and Fetal Development -- drug effects KW - Pregnancy KW - Rats KW - Rats, Inbred F344 KW - Cattle KW - In Situ Hybridization KW - Kidney Tubules -- drug effects KW - Organ Culture Techniques KW - Receptor Protein-Tyrosine Kinases -- biosynthesis KW - Female KW - Kidney Tubules -- ultrastructure KW - Male KW - Fibroblast Growth Factor 2 -- pharmacology KW - Kidney -- metabolism KW - Genes, Wilms Tumor KW - Kidney -- embryology KW - Kidney -- drug effects KW - Gene Expression Regulation -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77278818?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Basic+fibroblast+growth+factor+can+mediate+the+early+inductive+events+in+renal+development.&rft.au=Perantoni%2C+A+O%3BDove%2C+L+F%3BKaravanova%2C+I&rft.aulast=Perantoni&rft.aufirst=A&rft.date=1995-05-09&rft.volume=92&rft.issue=10&rft.spage=4696&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 - 1995-06-16 N1 - Date created - 1995-06-16 N1 - Date revised - 2017-01-13 N1 - Gene symbol - WT1; c-met N1 - SuppNotes - Cited By: Dev Biol. 1993 Aug;158(2):475-86 [8393815] Dev Suppl. 1992;:143-9 [1299359] J Cell Biol. 1993 Oct;123(1):223-35 [8408200] Cancer Res. 1993 Nov 15;53(22):5355-60 [7693339] Science. 1994 Jan 7;263(5143):98-101 [7505952] J Cell Biol. 1993 Dec;123(6 Pt 2):1857-65 [8276903] Nature. 1994 Jan 27;367(6461):380-3 [8114940] Science. 1994 Apr 1;264(5155):104-7 [7908145] Dev Biol. 1994 Jun;163(2):525-9 [8200486] Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5286-90 [8202482] Development. 1994 Aug;120(8):2225-34 [7925023] Nature. 1994 Dec 15;372(6507):679-83 [7990960] Nature. 1953 Nov 7;172(4384):869-70 [13111219] Dev Biol. 1969 Jan;19(1):41-51 [5767094] Dev Biol. 1970 Apr;21(4):547-56 [5444151] Adv Morphog. 1973;10:1-39 [4581327] J Cell Physiol. 1982 Feb;110(2):219-29 [7040427] Proc Natl Acad Sci U S A. 1984 Nov;81(22):6963-7 [6594674] Proc Natl Acad Sci U S A. 1985 Oct;82(19):6507-11 [3863109] Regul Pept. 1985 Nov 7;12(3):201-13 [4081126] J Cell Biol. 1986 Sep;103(3):1101-7 [2427526] Nature. 1987 Mar 12-18;326(6109):197-200 [3821895] Biochemistry. 1987 Sep 8;26(18):5844-7 [3676295] Philos Trans R Soc Lond B Biol Sci. 1990 Mar 12;327(1239):171-86 [1969657] Dev Biol. 1990 Jun;139(2):338-48 [2140104] Biochem Biophys Res Commun. 1990 May 16;168(3):1194-200 [2346483] EMBO J. 1990 Sep;9(9):2685-92 [1697263] Cell. 1991 Feb 22;64(4):841-8 [1847668] Dev Biol. 1991 Apr;144(2):248-61 [2010031] J Cell Biol. 1991 Jun;113(6):1447-53 [2045421] Science. 1991 Oct 25;254(5031):571-3 [1658930] Differentiation. 1991 Sep;48(1):25-31 [1743431] Am J Physiol. 1992 Apr;262(4 Pt 2):F523-32 [1566866] Am J Physiol. 1992 Apr;262(4 Pt 2):F533-9 [1566867] Kidney Int. 1992 Mar;41(3):657-64 [1573843] Development. 1991 Dec;113(4):1419-34 [1667382] Dev Biol. 1992 Aug;152(2):221-32 [1644217] Dev Biol. 1992 Aug;152(2):293-303 [1644221] J Cell Biol. 1992 Dec;119(5):1327-33 [1447305] Mech Dev. 1993 Jan;40(1-2):85-97 [8382938] Cell. 1993 Aug 27;74(4):679-91 [8395349] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of sodium and potassium ions in regulation of glucose metabolism in cultured astroglia. AN - 77271636; 7753851 AB - Effects of increasing extracellular K+ or intracellular Na+ concentrations on glucose metabolism in cultures of rat astroglia and neurons were examined. Cells were incubated in bicarbonate buffer, pH 7.2, containing 2 mM glucose, tracer amounts of [14C]deoxyglucose ([14C]dGlc), and 5.4, 28, or 56 mM KCl for 10, 15, or 30 min, and then for 5 min in [14C]dGlc-free buffer to allow efflux of unmetabolized [14C]dGlc. Cells were then digested and assayed for labeled products, which were shown to consist of 96-98% [14C]deoxyglucose 6-phosphate. Increased K+ concentrations significantly raised [14C]deoxyglucose 6-phosphate accumulation in both neuronal and mixed neuronal-astroglial cultures at 15 and 30 min but did not raise it in astroglial cultures. Veratridine (75 microM), which opens voltage-dependent Na+ channels, significantly raised rates of [14C]dGlc phosphorylation in astroglial cultures (+20%), and these elevations were blocked by either 1 mM ouabain, a specific inhibitor of Na+,K(+)-ATPase (EC 3.6.1.37), or 10 microM tetrodotoxin, which blocks Na+ channels. The carboxylic sodium ionophore, monensin (10 microM), more than doubled [14C]dGlc phosphorylation; this effect was only partially blocked by ouabain and unaffected by tetrodotoxin. L-Glutamate (500 microM) also stimulated [14C]dGlc phosphorylation in astroglia--not through N-methyl-D-aspartate or non-N-methyl-D-aspartate receptor mechanisms but via a Na(+)-dependent glutamate-uptake system. These results indicate that increased uptake of Na+ can stimulate energy metabolism in astroglial cells. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Takahashi, S AU - Driscoll, B F AU - Law, M J AU - Sokoloff, L AD - Laboratory of Cerebral Metabolism, National Institute of Mental Health, Bethesda, MD 20892-4030, USA. Y1 - 1995/05/09/ PY - 1995 DA - 1995 May 09 SP - 4616 EP - 4620 VL - 92 IS - 10 SN - 0027-8424, 0027-8424 KW - Carbon Radioisotopes KW - 0 KW - Glutamic Acid KW - 3KX376GY7L KW - Tetrodotoxin KW - 4368-28-9 KW - Ouabain KW - 5ACL011P69 KW - Bucladesine KW - 63X7MBT2LQ KW - 6-Cyano-7-nitroquinoxaline-2,3-dione KW - 6OTE87SCCW KW - Veratridine KW - 71-62-5 KW - 2-Amino-5-phosphonovalerate KW - 76726-92-6 KW - Monensin KW - 906O0YJ6ZP KW - Deoxyglucose KW - 9G2MP84A8W KW - Sodium KW - 9NEZ333N27 KW - Glucose KW - IY9XDZ35W2 KW - Potassium KW - RWP5GA015D KW - Index Medicus KW - Animals KW - Fetus KW - Neurons -- metabolism KW - Neurons -- drug effects KW - 6-Cyano-7-nitroquinoxaline-2,3-dione -- pharmacology KW - Gestational Age KW - Monensin -- pharmacology KW - Bucladesine -- pharmacology KW - Glutamic Acid -- pharmacology KW - Pregnancy KW - Rats KW - Rats, Sprague-Dawley KW - Phosphorylation KW - 2-Amino-5-phosphonovalerate -- pharmacology KW - Cells, Cultured KW - Kinetics KW - Neurons -- cytology KW - Tetrodotoxin -- pharmacology KW - Veratridine -- pharmacology KW - Time Factors KW - Ouabain -- pharmacology KW - Female KW - Corpus Striatum -- cytology KW - Astrocytes -- cytology KW - Glucose -- metabolism KW - Corpus Striatum -- metabolism KW - Astrocytes -- drug effects KW - Potassium -- pharmacology KW - Sodium -- pharmacology KW - Deoxyglucose -- metabolism KW - Astrocytes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77271636?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Role+of+sodium+and+potassium+ions+in+regulation+of+glucose+metabolism+in+cultured+astroglia.&rft.au=Takahashi%2C+S%3BDriscoll%2C+B+F%3BLaw%2C+M+J%3BSokoloff%2C+L&rft.aulast=Takahashi&rft.aufirst=S&rft.date=1995-05-09&rft.volume=92&rft.issue=10&rft.spage=4616&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 - 1995-06-16 N1 - Date created - 1995-06-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Cereb Blood Flow Metab. 1981;1(2):143-53 [6120175] Nature. 1982 Jan 7;295(5844):59-61 [7057874] Annu Rev Pharmacol Toxicol. 1982;22:465-90 [7044290] Neuron. 1994 Sep;13(3):713-25 [7917301] Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10625-9 [7938003] Prog Neurobiol. 1994 May;43(1):37-71 [7972852] Dev Neurosci. 1993;15(3-5):194-206 [7805571] Brain Res. 1994 Nov 7;663(1):168-72 [7850466] Brain Res. 1993 Dec 17;631(1):1-11 [8298981] Can J Physiol Pharmacol. 1992;70 Suppl:S145-57 [1295665] J Neurophysiol. 1993 Mar;69(3):819-31 [7681866] J Neurochem. 1971 Aug;18(8):1599-603 [4255236] Brain Res. 1972 Aug 25;43(2):437-43 [4262289] Nature. 1973 Jan 19;241(5386):203-4 [4349559] Annu Rev Physiol. 1975;37:163-90 [1092250] J Neurochem. 1977 May;28(5):897-916 [864466] J Neurochem. 1977 May;28(5):967-75 [68101] Pharmacol Rev. 1977 Mar;29(1):35-65 [928502] Brain Res. 1978 Feb 10;141(2):305-23 [146537] Brain Res. 1978 Apr 21;145(1):202-8 [638779] Brain Res. 1979 Jul 6;170(1):190-3 [223720] J Biol Chem. 1966 Sep 10;241(17):4110-2 [4224144] Proc Natl Acad Sci U S A. 1983 Jul;80(13):4179-83 [6575402] Nature. 1984 Oct 18-24;311(5987):656-9 [6148706] J Neurochem. 1985 Feb;44(2):473-9 [2578179] J Cell Biol. 1985 Feb;100(2):384-96 [3881455] Proc Natl Acad Sci U S A. 1985 Sep;82(17):6010-3 [3862113] Anal Biochem. 1985 Oct;150(1):76-85 [3843705] J Neurosci. 1986 Mar;6(3):859-66 [3958797] J Neurochem. 1989 Oct;53(4):1149-55 [2788714] Neuron. 1989 Apr;2(4):1375-88 [2560639] Brain Res Mol Brain Res. 1990 Jun;8(1):69-75 [2166202] J Neurophysiol. 1966 Jul;29(4):788-806 [5966435] J Neurosci. 1991 Aug;11(8):2410-21 [1869922] Glia. 1991;4(3):293-304 [1716608] J Neurosci. 1991 Dec;11(12):3685-94 [1720814] Biochem J. 1992 Feb 15;282 ( Pt 1):225-30 [1540138] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10955-9 [1279699] Physiol Rev. 1992 Oct;72(4 Suppl):S15-48 [1332090] Nature. 1992 Dec 3;360(6403):464-7 [1448170] Nature. 1992 Dec 3;360(6403):467-71 [1280334] J Neurochem. 1979 Sep;33(3):779-85 [479891] J Neurochem. 1980 Jan;34(1):213-5 [7452237] J Neurocytol. 1981 Aug;10(4):693-708 [7310471] J Cereb Blood Flow Metab. 1981;1(1):7-36 [7035471] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gut bacteria provide precursors of benzodiazepine receptor ligands in a rat model of hepatic encephalopathy. AN - 77460867; 7648264 AB - Benzodiazepine receptor (BZR) ligands are elevated in animals and humans with fulminant hepatic failure (FHF) and contribute to the pathogenesis of the associated hepatic encephalopathy (HE). As gut factors are proposed to play a role in the pathogenesis of HE, we investigated gut flora as a source of BZR ligands. Rats received daily oral neomycin, vancomycin and metronidazole (AB +) or saline (AB -) before and concurrent with the induction of FHF with thioacetamide. BZR ligands were extracted from brain and plasma and quantified using radiometric techniques. Plasma BZR ligand concentrations in AB(+) and AB(-) rats with HE were higher than AB(+) and AB(-) control rats. Brain BZR ligand concentrations increased in AB(+) and AB(-) rats with HE. Stool cultures from antibiotic treated rats with HE indicated the presence of multidrug resistant Acinetobacter lwoffii. Although no significant concentrations of BZR ligands were detected in culture media inoculated with A. lwoffii, administering A. lwoffii to normal rats significantly elevated BZR ligand levels in brain, but not plasma. Thus, antibiotic treatment of rats is associated with the growth of a resistant strain of bacterium which produces an inactive BZR ligand precursor. BZR ligands may be synthesized from these precursors in the brain and efficiently cleared by a normal liver following brain-to-plasma transfer. Impairment of this clearance process in FHF facilitates their accumulation, enabling agonist BZR ligands to contribute to the pathogenesis of HE by further enhancing GABAergic neurotransmission. JF - Brain research AU - Yurdaydin, C AU - Walsh, T J AU - Engler, H D AU - Ha, J H AU - Li, Y AU - Jones, E A AU - Basile, A S AD - Liver Diseases Section, NIDDK, Bethesda, MD 20892, USA. Y1 - 1995/05/08/ PY - 1995 DA - 1995 May 08 SP - 42 EP - 48 VL - 679 IS - 1 SN - 0006-8993, 0006-8993 KW - Ligands KW - 0 KW - Receptors, GABA-A KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Analysis of Variance KW - Disease Models, Animal KW - Male KW - Receptors, GABA-A -- metabolism KW - Hepatic Encephalopathy -- metabolism KW - Intestines -- microbiology KW - Hepatic Encephalopathy -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77460867?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Gut+bacteria+provide+precursors+of+benzodiazepine+receptor+ligands+in+a+rat+model+of+hepatic+encephalopathy.&rft.au=Yurdaydin%2C+C%3BWalsh%2C+T+J%3BEngler%2C+H+D%3BHa%2C+J+H%3BLi%2C+Y%3BJones%2C+E+A%3BBasile%2C+A+S&rft.aulast=Yurdaydin&rft.aufirst=C&rft.date=1995-05-08&rft.volume=679&rft.issue=1&rft.spage=42&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 - 1995-09-27 N1 - Date created - 1995-09-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immune system impairment and hepatic fibrosis in mice lacking the dioxin-binding Ah receptor. AN - 77256460; 7732381 AB - The aryl hydrocarbon (Ah) receptor (AHR) mediates many carcinogenic and teratogenic effects of environmentally toxic chemicals such as dioxin. An AHR-deficient (Ahr-/-) mouse line was constructed by homologous recombination in embryonic stem cells. Almost half of the mice died shortly after birth, whereas survivors reached maturity and were fertile. The Ahr-/- mice showed decreased accumulation of lymphocytes in the spleen and lymph nodes, but not in the thymus. The livers of Ahr-/- mice were reduced in size by 50 percent and showed bile duct fibrosis Ahr-/- mice were also nonresponsive with regard to dioxin-mediated induction of genes encoding enzymes that catalyze the metabolism of foreign compounds. Thus, the AHR plays an important role in the development of the liver and the immune system. JF - Science (New York, N.Y.) AU - Fernandez-Salguero, P AU - Pineau, T AU - Hilbert, D M AU - McPhail, T AU - Lee, S S AU - Kimura, S AU - Nebert, D W AU - Rudikoff, S AU - Ward, J M AU - Gonzalez, F J AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/05/05/ PY - 1995 DA - 1995 May 05 SP - 722 EP - 726 VL - 268 IS - 5211 SN - 0036-8075, 0036-8075 KW - Ahr KW - Receptors, Aryl Hydrocarbon KW - 0 KW - Index Medicus KW - Animals KW - Lymphoid Tissue -- pathology KW - Gene Expression Regulation -- physiology KW - Mice, Inbred C57BL KW - Liver Cirrhosis, Experimental -- genetics KW - Mice KW - Liver Cirrhosis, Experimental -- pathology KW - Male KW - Female KW - Mice, Knockout KW - Immunity -- physiology KW - Receptors, Aryl Hydrocarbon -- physiology KW - Receptors, Aryl Hydrocarbon -- genetics KW - Liver -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77256460?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+%28New+York%2C+N.Y.%29&rft.atitle=Immune+system+impairment+and+hepatic+fibrosis+in+mice+lacking+the+dioxin-binding+Ah+receptor.&rft.au=Fernandez-Salguero%2C+P%3BPineau%2C+T%3BHilbert%2C+D+M%3BMcPhail%2C+T%3BLee%2C+S+S%3BKimura%2C+S%3BNebert%2C+D+W%3BRudikoff%2C+S%3BWard%2C+J+M%3BGonzalez%2C+F+J&rft.aulast=Fernandez-Salguero&rft.aufirst=P&rft.date=1995-05-05&rft.volume=268&rft.issue=5211&rft.spage=722&rft.isbn=&rft.btitle=&rft.title=Science+%28New+York%2C+N.Y.%29&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-30 N1 - Date created - 1995-05-30 N1 - Date revised - 2017-01-13 N1 - Gene symbol - Ahr N1 - SuppNotes - Comment In: Science. 1996 Jan 12;271(5246):223-4 [8539627] Science. 1995 May 5;268(5211):638-9 [7732370] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of the cysteine-rich region of the Caenorhabditis elegans protein Unc-13 as a high affinity phorbol ester receptor. Analysis of ligand-binding interactions, lipid cofactor requirements, and inhibitor sensitivity. AN - 77249929; 7537738 AB - The Caenorhabditis elegans Unc-13 protein is a novel member of the phorbol ester receptor family having a single cysteine-rich region with high homology to those present in protein kinase C (PKC) isozymes and the chimaerins. We expressed the cysteine-rich region of Unc-13 in Escherichia coli and quantitatively analyzed its interactions with phorbol esters and related analogs, its phospholipid requirements, and its inhibitor sensitivity. [3H]Phorbol 12,13-dibutyrate [3H]PDBu bound with high affinity to the cysteine-rich region of Unc-13 (Kd = 1.3 +/- 0.2 nM). This affinity is similar to that of other single cysteine-rich regions from PKC isozymes as well as n-chimaerin. As also described for PKC isozymes and n-chimaerin, Unc-13 bound diacylglycerol with an affinity about 2 orders of magnitude weaker than [3H]PDBu. Structure-activity analysis revealed significant but modest differences between recombinant cysteine-rich regions of Unc-13 and PKC delta. In addition, Unc-13 required slightly higher concentrations of phospholipid for reconstitution of [3H]PDBu binding. Calphostin C, a compound described as a selective inhibitor of PKC, was also able to inhibit [3H]PDBu binding to Unc-13, suggesting that this inhibitor is not able to distinguish between different classes of phorbol ester receptors. In conclusion, although our results revealed some differences in ligand and lipid cofactor sensitivities, Unc-13 represents a high affinity cellular target for the phorbol esters as well as for the lipid second messenger diacylglycerol, at least in C. elegans. The use of phorbol esters or some "specific" antagonists of PKC does not distinguish between cellular pathways involving different PKC isozymes or novel phorbol ester receptors such as n-chimaerin or Unc-13. JF - The Journal of biological chemistry AU - Kazanietz, M G AU - Lewin, N E AU - Bruns, J D AU - Blumberg, P M AD - Molecular Mechanisms of Tumor Promotion Section, NCI, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1995/05/05/ PY - 1995 DA - 1995 May 05 SP - 10777 EP - 10783 VL - 270 IS - 18 SN - 0021-9258, 0021-9258 KW - Unc-13 KW - Bryostatins KW - 0 KW - Caenorhabditis elegans Proteins KW - Carrier Proteins KW - DNA Primers KW - Helminth Proteins KW - Lactones KW - Ligands KW - Macrolides KW - Naphthalenes KW - Phospholipids KW - Polycyclic Compounds KW - Receptors, Drug KW - Recombinant Proteins KW - phorbol ester binding protein KW - phorbol ester receptor KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - bryostatin 1 KW - 37O2X55Y9E KW - Protein Kinase C KW - EC 2.7.11.13 KW - calphostin C KW - I271P23G24 KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Animals KW - Phorbol 12,13-Dibutyrate -- metabolism KW - Phospholipids -- metabolism KW - Polycyclic Compounds -- pharmacology KW - Amino Acid Sequence KW - Lactones -- metabolism KW - Base Sequence KW - Caenorhabditis elegans KW - Molecular Sequence Data KW - DNA Primers -- chemistry KW - Protein Kinase C -- metabolism KW - Helminth Proteins -- metabolism KW - Receptors, Drug -- metabolism KW - Protein Kinase C -- chemistry KW - Receptors, Drug -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77249929?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Characterization+of+the+cysteine-rich+region+of+the+Caenorhabditis+elegans+protein+Unc-13+as+a+high+affinity+phorbol+ester+receptor.+Analysis+of+ligand-binding+interactions%2C+lipid+cofactor+requirements%2C+and+inhibitor+sensitivity.&rft.au=Kazanietz%2C+M+G%3BLewin%2C+N+E%3BBruns%2C+J+D%3BBlumberg%2C+P+M&rft.aulast=Kazanietz&rft.aufirst=M&rft.date=1995-05-05&rft.volume=270&rft.issue=18&rft.spage=10777&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 - 1995-06-05 N1 - Date created - 1995-06-05 N1 - Date revised - 2017-01-13 N1 - Gene symbol - Unc-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytokines in the central nervous system: regulatory roles in neuronal function, cell death and repair. AN - 77854672; 8646560 AB - Recent evidence suggests that neurons and glia can synthesize and secrete cytokines, which play critical roles in maintaining homeostasis in the central nervous system (CNS) by mediating the interaction between cells via autocrine or paracrine mechanisms. Circulating cytokines and soluble receptors also regulate neuronal function via endocrine mechanisms. Disturbance of the cytokine-mediated interaction between cells may lead to neuronal dysfunction and/or cell death and contribute to the pathogenesis of the CNS diseases (e.g., ischemia, Alzheimer's disease and HIV encephalopathy). Defining the molecular pathways of cytokine dysregulation and neurotoxicity may help to elucidate potential therapeutic interventions for many devastating CNS diseases. JF - Neuroimmunomodulation AU - Sei, Y AU - Vitković, L AU - Yokoyama, M M AD - Laboratory of Neuroscience, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Md 20892, USA. PY - 1995 SP - 121 EP - 133 VL - 2 IS - 3 SN - 1021-7401, 1021-7401 KW - Cytokines KW - 0 KW - Neurotransmitter Agents KW - Receptors, Cytokine KW - Arachidonic Acid KW - 27YG812J1I KW - Quinolinic Acid KW - F6F0HK1URN KW - Index Medicus KW - Receptors, Cytokine -- physiology KW - Animals KW - Neurons -- metabolism KW - Central Nervous System Diseases -- physiopathology KW - Quinolinic Acid -- metabolism KW - Apoptosis -- physiology KW - Humans KW - Long-Term Potentiation -- drug effects KW - Homeostasis KW - Neurons -- secretion KW - Arachidonic Acid -- metabolism KW - Neuroglia -- metabolism KW - Neurotransmitter Agents -- metabolism KW - Long-Term Potentiation -- physiology KW - Neuroglia -- secretion KW - Cytokines -- pharmacology KW - Central Nervous System -- physiology KW - Neuroimmunomodulation -- physiology KW - Cytokines -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77854672?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroimmunomodulation&rft.atitle=Cytokines+in+the+central+nervous+system%3A+regulatory+roles+in+neuronal+function%2C+cell+death+and+repair.&rft.au=Sei%2C+Y%3BVitkovi%C4%87%2C+L%3BYokoyama%2C+M+M&rft.aulast=Sei&rft.aufirst=Y&rft.date=1995-05-01&rft.volume=2&rft.issue=3&rft.spage=121&rft.isbn=&rft.btitle=&rft.title=Neuroimmunomodulation&rft.issn=10217401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-19 N1 - Date created - 1996-07-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Circularly permuted interleukin 4 retains proliferative and binding activity. AN - 77829119; 8589260 AB - In human interleukin 4(IL-4), the carboxyl and amino termini of the 129 amino acid hormone are close to each other and this region is believed to be important for binding to the IL-4 receptor (IL-4r). We constructed plasmids encoding circularly permuted IL-4 mutants with the peptide Gly-Gly-Asn-Gly-Gly (GGNGG) joining the carboxyl to the amino terminus and with new amino and carboxyl termini elsewhere. Mutant IL-4(38-37) is composed of IL-4 residues 38-129 GGNGG and 1-37. Mutant IL-4(105-104) is composed of IL-4 residues 105-129, GGNGG and 1-104. IL-4(38-37) and IL-4(105-104) were purified from E. coli to near homogeneity and retained 50-100% of the binding and proliferative activity of IL-4, and in addition retained the ability to upregulate CD23 on Burkitt's lymphoma cells. Circular dichroism studies indicated that the tertiary structures of both IL-4(38-37) and IL-4(105-104) were retained, with the former molecule most similar to native IL-4. We conclude that while both native termini of IL-4 may be near its binding site, neither is required to be free for optimum activity. JF - Cytokine AU - Kreitman, R J AU - Puri, R K AU - McPhie, P AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 311 EP - 318 VL - 7 IS - 4 SN - 1043-4666, 1043-4666 KW - Receptors, IgE KW - 0 KW - Recombinant Fusion Proteins KW - Interleukin-4 KW - 207137-56-2 KW - Index Medicus KW - Humans KW - Cell Division -- drug effects KW - Circular Dichroism KW - Amino Acid Sequence KW - B-Lymphocytes -- immunology KW - Burkitt Lymphoma -- pathology KW - Recombinant Fusion Proteins -- chemistry KW - Receptors, IgE -- biosynthesis KW - Mutagenesis KW - B-Lymphocytes -- drug effects KW - Polymerase Chain Reaction KW - Base Sequence KW - Tumor Cells, Cultured KW - Escherichia coli KW - Molecular Sequence Data KW - Recombinant Fusion Proteins -- pharmacology KW - Protein Structure, Tertiary KW - Interleukin-4 -- analogs & derivatives KW - Interleukin-4 -- pharmacology KW - Interleukin-4 -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77829119?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytokine&rft.atitle=Circularly+permuted+interleukin+4+retains+proliferative+and+binding+activity.&rft.au=Kreitman%2C+R+J%3BPuri%2C+R+K%3BMcPhie%2C+P%3BPastan%2C+I&rft.aulast=Kreitman&rft.aufirst=R&rft.date=1995-05-01&rft.volume=7&rft.issue=4&rft.spage=311&rft.isbn=&rft.btitle=&rft.title=Cytokine&rft.issn=10434666&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-25 N1 - Date created - 1996-03-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo system for the detection of low level activity barnase mutants. AN - 77559715; 8532672 AB - We report the design of a new tightly controlled barnase system which allows the existence of the barnase gene in host cells without a signal sequence. When expression of barnase is turned on by gene inversion in vivo, the lethal effect of barnase (or its mutants) is not compromised either by coexpression of its polypeptide inhibitor (barstar), or by extracellular secretion. This serves as a rapid, sensitive in vivo test for the detection of any very low residual activity of the barnase mutants. Active-site mutants His102Lys, Glu73Asp and Arg87Lys, and a mutant which greatly reduces the stability and yield of protein, Arg83Lys, produce enough activity to be detectable by this test. In contrast, when expressed on a secretion vector, these mutants do not yield detectable activity in a solution assay. Truly inactive mutants, such as those of His102 to Gly, Ala or Leu, were completely harmless when expressed in this system. JF - Protein engineering AU - Jucovic, M AU - Hartley, R W AD - Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 497 EP - 499 VL - 8 IS - 5 SN - 0269-2139, 0269-2139 KW - DNA Primers KW - 0 KW - Ribonucleases KW - EC 3.1.- KW - Bacillus amyloliquefaciens ribonuclease KW - EC 3.1.4.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Gene Expression Regulation, Bacterial KW - Polymerase Chain Reaction KW - Base Sequence KW - Molecular Sequence Data KW - Chromosome Inversion KW - Plasmids KW - Binding Sites KW - Protein Engineering KW - Ribonucleases -- genetics KW - Ribonucleases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77559715?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+engineering&rft.atitle=In+vivo+system+for+the+detection+of+low+level+activity+barnase+mutants.&rft.au=Jucovic%2C+M%3BHartley%2C+R+W&rft.aulast=Jucovic&rft.aufirst=M&rft.date=1995-05-01&rft.volume=8&rft.issue=5&rft.spage=497&rft.isbn=&rft.btitle=&rft.title=Protein+engineering&rft.issn=02692139&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-01 N1 - Date created - 1996-02-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic susceptibility and occupational cancer. AN - 77544894; 7565279 AB - This review describes statistical models for the biological interaction of susceptibility genes and environmental exposures, as observed in epidemiologic studies. The importance of metabolic transformation of industrial carcinogens and the potential role of genetic polymorphisms in metabolic enzyme activity are outlined. Several genetic polymorphisms have been associated with cancer risk, but the link with the relevant exposures has only infrequently been specified. For example, studies show that slow N-acetylation increased bladder cancer risk among workers exposed to some arylamines, as found among dye workers in England, but that this effect does not hold for benzidine exposure. This link of a genetic susceptibility factor with cancer risk due to some aromatic amines, but not to others, illustrated the specific nature of metabolic environment/gene interactions. Epidemiologic studies to investigate the role of genetic susceptibility in cancer development promise to further the identification of human carcinogens by focusing on susceptible individuals and, in turn, to enhance understanding of human cancer by relating cancer risk in populations to underlying biologic processes. Occupational studies are key to this effort. JF - La Medicina del lavoro AU - Hayes, R B AD - Epidemiology and Biostatistics Program, U.S. National Cancer Institute, Bethesda, MD 20895, USA. PY - 1995 SP - 206 EP - 213 VL - 86 IS - 3 SN - 0025-7818, 0025-7818 KW - Carcinogens KW - 0 KW - Index Medicus KW - Carcinogens -- metabolism KW - Polymorphism, Genetic KW - Risk Factors KW - Humans KW - Occupational Exposure -- adverse effects KW - Models, Statistical KW - Occupational Diseases -- metabolism KW - Occupational Diseases -- genetics KW - Neoplasms -- chemically induced KW - Genetic Predisposition to Disease KW - Occupational Diseases -- chemically induced KW - Neoplasms -- genetics KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77544894?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=La+Medicina+del+lavoro&rft.atitle=Genetic+susceptibility+and+occupational+cancer.&rft.au=Hayes%2C+R+B&rft.aulast=Hayes&rft.aufirst=R&rft.date=1995-05-01&rft.volume=86&rft.issue=3&rft.spage=206&rft.isbn=&rft.btitle=&rft.title=La+Medicina+del+lavoro&rft.issn=00257818&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-22 N1 - Date created - 1995-11-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of case-control studies in the general population and in occupational cohorts to study genetic susceptibility and cancer risk. AN - 77538158; 7565281 JF - La Medicina del lavoro AU - Rothman, N AD - NIH/NCI EPN 418, Occupational Studies Section, Bethesda, MD USA 20892. PY - 1995 SP - 221 EP - 225 VL - 86 IS - 3 SN - 0025-7818, 0025-7818 KW - Carcinogens KW - 0 KW - Genetic Markers KW - Index Medicus KW - Occupational Exposure KW - Polymorphism, Genetic KW - Urinary Bladder Neoplasms -- epidemiology KW - Humans KW - Urinary Bladder Neoplasms -- genetics KW - Genotype KW - Phenotype KW - Alleles KW - Risk Factors KW - Cohort Studies KW - Case-Control Studies KW - Urinary Bladder Neoplasms -- chemically induced KW - Occupational Diseases -- genetics KW - Neoplasms -- chemically induced KW - Neoplasms -- epidemiology KW - Occupational Diseases -- epidemiology KW - Genetic Predisposition to Disease KW - Occupational Diseases -- chemically induced KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77538158?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=La+Medicina+del+lavoro&rft.atitle=Use+of+case-control+studies+in+the+general+population+and+in+occupational+cohorts+to+study+genetic+susceptibility+and+cancer+risk.&rft.au=Rothman%2C+N&rft.aulast=Rothman&rft.aufirst=N&rft.date=1995-05-01&rft.volume=86&rft.issue=3&rft.spage=221&rft.isbn=&rft.btitle=&rft.title=La+Medicina+del+lavoro&rft.issn=00257818&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-22 N1 - Date created - 1995-11-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic susceptibility in the occupational setting: introduction to the workshop. AN - 77535572; 7565278 JF - La Medicina del lavoro AU - Caporaso, N AD - Genetic Epidemiology Branch, National Cancer Institute, Bethesda, MD, USA 20892. PY - 1995 SP - 199 EP - 206 VL - 86 IS - 3 SN - 0025-7818, 0025-7818 KW - Carcinogens KW - 0 KW - Genetic Markers KW - Index Medicus KW - Phenotype KW - Genotype KW - Metabolism, Inborn Errors -- epidemiology KW - Polymorphism, Genetic KW - Humans KW - Metabolism, Inborn Errors -- genetics KW - Occupational Exposure -- adverse effects KW - Occupational Diseases -- genetics KW - Neoplasms -- epidemiology KW - Occupational Diseases -- epidemiology KW - Genetic Predisposition to Disease KW - Pharmacogenetics KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77535572?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=La+Medicina+del+lavoro&rft.atitle=Genetic+susceptibility+in+the+occupational+setting%3A+introduction+to+the+workshop.&rft.au=Caporaso%2C+N&rft.aulast=Caporaso&rft.aufirst=N&rft.date=1995-05-01&rft.volume=86&rft.issue=3&rft.spage=199&rft.isbn=&rft.btitle=&rft.title=La+Medicina+del+lavoro&rft.issn=00257818&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-22 N1 - Date created - 1995-11-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Singlet oxygen generation in the superoxide reaction. AN - 77502487; 7663419 AB - ESR spin trapping was utilized to study the singlet oxygen (1O2) generation in the reaction of superoxide (O2) with H2O2. The spin trap used was 2,2,6,6-tetramethyl-4-piperdone. Incubation of xanthine, xanthine oxidase and H2O2 generated 1O2 spin adduct signal. Omission of xanthine, xanthine oxidase or H2O2 caused a sharp decrease in 1O2 generation. 1O2 scavenger, sodium azide, inhibited 1O2 generation while .OH scavenger, ethanol, only slightly decreased the signal intensity. Potassium superoxide (KO2) decomposition generated 1O2. Catalase and sodium azide inhibited 1O2 generation and H2O2 enhanced it. The results demonstrate that O2 is capable of generating 1O2 upon reaction with H2O2. JF - Biochemistry and molecular biology international AU - Mao, Y AU - Zang, L AU - Shi, X AD - Laboratory of Experimental Pathology, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 227 EP - 232 VL - 36 IS - 1 SN - 1039-9712, 1039-9712 KW - Azides KW - 0 KW - Free Radicals KW - Spin Labels KW - Xanthines KW - Superoxides KW - 11062-77-4 KW - Singlet Oxygen KW - 17778-80-2 KW - Xanthine KW - 1AVZ07U9S7 KW - Hydroxyl Radical KW - 3352-57-6 KW - Sodium Azide KW - 968JJ8C9DV KW - Hydrogen Peroxide KW - BBX060AN9V KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Xanthine Oxidase KW - EC 1.17.3.2 KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Xanthine Oxidase -- metabolism KW - Hydroxyl Radical -- metabolism KW - Hydrogen Peroxide -- metabolism KW - Electron Spin Resonance Spectroscopy KW - Azides -- pharmacology KW - Superoxide Dismutase -- metabolism KW - Xanthines -- metabolism KW - Free Radicals -- metabolism KW - Superoxides -- metabolism KW - Oxygen -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77502487?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry+and+molecular+biology+international&rft.atitle=Singlet+oxygen+generation+in+the+superoxide+reaction.&rft.au=Mao%2C+Y%3BZang%2C+L%3BShi%2C+X&rft.aulast=Mao&rft.aufirst=Y&rft.date=1995-05-01&rft.volume=36&rft.issue=1&rft.spage=227&rft.isbn=&rft.btitle=&rft.title=Biochemistry+and+molecular+biology+international&rft.issn=10399712&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-10 N1 - Date created - 1995-10-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Incidence of nonneoplastic lesions in historical control male and female Fischer-344 rats from 90-day toxicity studies. AN - 77499840; 7659956 AB - The incidence of all spontaneously occurring histologic lesions was determined for control Fischer-344 (F-344) rats from 90-day (13-wk) prechronic National Toxicology Program (NTP) toxicity studies. A total of 319 rats, represented by control groups of 10 males and 10 females each from dosed feed (n = 8), inhalation (n = 4), and gavage (n = 4) studies were included in the review. All protocol required tissues routinely collected for evaluation were reexamined for potential nonneoplastic and neoplastic lesions. Histopathologic findings in tissues included a spectrum of degenerative and inflammatory lesions. The most common lesions in male rats were nephropathy [145/160 (90.6%)] and cardiomyopathy [125/158 (79.1%)]. These changes were also present in the female rats, however, at much lower incidence rates [nephropathy = 30/157 (19.1%); cardiomyopathy = 36/158 (22.8%)]. Other less frequently occurring lesions included inflammation of the preputial [36/152 (23.7%)] and clitoral [34/155 (21.9%)] glands and inflammation of the liver consisting of either foci of mononuclear inflammatory cells [19/159 (11.9%) in males and 33/159 (20.8%) in females] or focal granulomatous inflammation [1/159 (0.6%) in males and 14/159 (8.8%) in females]. Pancreatic acinar cell atrophy occurred in both males [11/160 (6.9%)] and females [8/159 (5.0%)]. A variety of other less common nonneoplastic lesions were identified in both sexes of rats. Also recorded in this review are histologic changes generally considered to be components of the normal morphology of a particular tissue or organ for the F-344 rat (i.e., extramedullary hematopoiesis and hemosiderin deposition in the spleen, renal mineralization, uterine dilation, etc.). These findings were included and discussed due to potential treatment effects that may result in an increase or decrease in these changes compared to controls. Neoplasms were not observed in rats from the prechronic studies evaluated. JF - Toxicologic pathology AU - Dixon, D AU - Heider, K AU - Elwell, M R AD - Experimental Carcinogenesis Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. PY - 1995 SP - 338 EP - 348 VL - 23 IS - 3 SN - 0192-6233, 0192-6233 KW - Index Medicus KW - Animals KW - Male Urogenital Diseases KW - Lung Diseases -- veterinary KW - Rats KW - Endocrine System Diseases -- veterinary KW - Cardiovascular Diseases -- veterinary KW - Cohort Studies KW - Rodentia KW - Female Urogenital Diseases -- veterinary KW - Gastrointestinal Diseases -- veterinary KW - Skin Diseases -- veterinary KW - Female KW - Male KW - Nervous System Diseases -- veterinary KW - Rats, Inbred F344 KW - Toxicology -- methods KW - Rodent Diseases -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77499840?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Incidence+of+nonneoplastic+lesions+in+historical+control+male+and+female+Fischer-344+rats+from+90-day+toxicity+studies.&rft.au=Dixon%2C+D%3BHeider%2C+K%3BElwell%2C+M+R&rft.aulast=Dixon&rft.aufirst=D&rft.date=1995-05-01&rft.volume=23&rft.issue=3&rft.spage=338&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 - 1995-10-02 N1 - Date created - 1995-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 1,2,3-Trichloropropane: a multisite carcinogen in rats and mice. AN - 77493711; 7665008 AB - 1,2,3-Trichloropropane was evaluated in 2-year toxicology and carcinogenesis studies by the National Toxicology Program. The selection of this chemical for study was based on the potential for human exposure, its positive in vitro genotoxicity, and the carcinogenicity of structurally related chemicals. During the 2-year study 1,2,3-trichloropropane was administered in corn oil by gavage 5 days per week; groups of 60 F344/N rats received 0, 3, 10, or 30 mg/kg, while groups of 60 B6C3F1 mice received 0,6,20, or 60 mg/kg. Because of reduced survival associated with the development of chemical-related neoplasms, rats that received 30 mg/kg were terminated at 65 weeks (females) or 76 weeks (males). Similarly, mice that received 60 mg/kg were terminated at 73 weeks (females) or 79 weeks (males), while groups of mice that received 20 mg/kg were terminated at 88 weeks. 1,2,3-Trichloropropane induced benign and/or malignant neoplasms at multiple sites in both rats and mice; this included increased incidences of benign and malignant neoplasms of the squamous epithelium of the oral mucosa and forestomach of male and female rats, benign neoplasms of the kidney and pancreas and benign or malignant neoplasms of the preputial gland in male rats, malignant neoplasms of the mammary gland, and benign or malignant neoplasms of the clitoral gland in female rats. In mice, 1,2,3-trichloropropane induced a low incidence of malignant neoplasms of the oral mucosa in females, high incidences of benign and malignant neoplasms of the forestomach in males and females, benign neoplasms of the liver and harderian gland of males and females, and uterine neoplasms in females. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Irwin, R D AU - Haseman, J K AU - Eustis, S L AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 241 EP - 252 VL - 25 IS - 2 SN - 0272-0590, 0272-0590 KW - Carcinogens KW - 0 KW - 1,2,3-trichloropropane KW - 3MJ7QCK0Z0 KW - Propane KW - T75W9911L6 KW - Index Medicus KW - Animals KW - Mouth Neoplasms -- chemically induced KW - Uterine Neoplasms -- chemically induced KW - Pancreatic Neoplasms -- chemically induced KW - Liver Neoplasms -- chemically induced KW - Mice KW - Rats KW - Mammary Neoplasms, Experimental -- chemically induced KW - Stomach Neoplasms -- chemically induced KW - Harderian Gland KW - Skin Neoplasms -- chemically induced KW - Body Weight -- drug effects KW - Intestinal Neoplasms -- chemically induced KW - Female KW - Male KW - Propane -- toxicity KW - Propane -- analogs & derivatives KW - Carcinogens -- toxicity KW - Carcinogenicity Tests UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77493711?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=1%2C2%2C3-Trichloropropane%3A+a+multisite+carcinogen+in+rats+and+mice.&rft.au=Irwin%2C+R+D%3BHaseman%2C+J+K%3BEustis%2C+S+L&rft.aulast=Irwin&rft.aufirst=R&rft.date=1995-05-01&rft.volume=25&rft.issue=2&rft.spage=241&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-10 N1 - Date created - 1995-10-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Molecular mechanisms of environmental carcinogenesis. AN - 77493320; 7656881 JF - Environmental health perspectives AU - Rhodes, N AU - Paules, R S AU - Roberts, J D Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 504 EP - 506 VL - 103 IS - 5 KW - Carcinogens, Environmental KW - 0 KW - Index Medicus KW - Oncogenes KW - Molecular Biology KW - Environmental Health KW - Humans KW - Male KW - Female KW - Carcinogens, Environmental -- adverse effects KW - Neoplasms -- genetics KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77493320?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Molecular+mechanisms+of+environmental+carcinogenesis.&rft.au=Rhodes%2C+N%3BPaules%2C+R+S%3BRoberts%2C+J+D&rft.aulast=Rhodes&rft.aufirst=N&rft.date=1995-05-01&rft.volume=103&rft.issue=5&rft.spage=504&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 - 1995-10-02 N1 - Date created - 1995-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A cohort study of the effects of Vietnam service on testicular pathology of U.S. military working dogs. AN - 77481394; 7659215 AB - Using histopathologic diagnoses made on necropsy material from 3,024 military working dogs (MWDs) who died from 1968 to 1973, we analyzed the effect of military service in the Republic of Vietnam on testicular pathology. Among 1,048 MWDs that died in Vietnam and had no reported developmental risk factors for testicular disease, significant excesses of testicular hemorrhage, epididymitis/orchitis, sperm granuloma, testicular degeneration, and seminoma were evident. Among 126 MWDs with prior Vietnam service who died at other duty stations outside Vietnam from 1968 to 1973, significant excesses of testicular degeneration and seminoma were likewise evident. Among 136 MWDs with prior Vietnam service that later died from 1974 to 1980, seminoma continued to be diagnosed in significant excess. In each instance, the odds ratio for the association between Vietnam service and seminoma was 2.0 or greater. Analysis of ever service by Corps Tactical Zones showed significant excesses of seminoma with each Corps area of service compared to Vietnam-era MWDs, but risk was highest in I Corps, particularly at Da Nang Port and Da Nang Air Base. This finding with respect to I Corps is consistent with certain human studies in Vietnam veterans and points to the need for further investigation of possible environmental exposures, particularly those associated to a greater extent with service in I Corps. JF - Military medicine AU - Hayes, H M AU - Tarone, R E AU - Casey, H W AD - Environmental Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 248 EP - 255 VL - 160 IS - 5 SN - 0026-4075, 0026-4075 KW - Index Medicus KW - United States KW - Animals KW - Odds Ratio KW - Risk Factors KW - Cohort Studies KW - Environmental Exposure KW - Dogs KW - Vietnam -- epidemiology KW - Male KW - Testicular Diseases -- mortality KW - Dog Diseases -- mortality KW - Testicular Diseases -- diagnosis KW - Veterinary Service, Military KW - Testis -- pathology KW - Testicular Diseases -- veterinary KW - Dog Diseases -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77481394?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+cohort+study+of+the+effects+of+Vietnam+service+on+testicular+pathology+of+U.S.+military+working+dogs.&rft.au=Hayes%2C+H+M%3BTarone%2C+R+E%3BCasey%2C+H+W&rft.aulast=Hayes&rft.aufirst=H&rft.date=1995-05-01&rft.volume=160&rft.issue=5&rft.spage=248&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 - 1995-09-29 N1 - Date created - 1995-09-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase II trial investigating primary immunochemotherapy for malignant pleural mesothelioma and the feasibility of adjuvant immunochemotherapy after maximal cytoreduction. AN - 77446427; 7641017 AB - The treatment of malignant pleural mesothelioma (MPM) continues to be inadequate with the use of standard techniques, including surgery, radiotherapy and chemotherapy. We initiated a phase II trial of immunochemotherapy with cisplatinum (25 mg/m2 four times weekly), interferon-alpha (5 mU/m2 s.c. three times weekly, and tamoxifen (20 mg orally twice a day for 35 days) (CIT) based on in vitro and in vivo data suggesting interrelating efficacy of this combination. Since July 1991, 36 patients have been evaluable for response after receiving one to five cycles of CIT. Ten additional patients had debulking surgery followed by two cycles of postoperative adjuvant CIT commencing a mean of 6 weeks after surgery. Toxicity was acceptable (4% grade III/IV). One treatment-related death (2%) occurred, from myocardial infarction. A 19% partial response rate, objectively quantified using three-dimensional computerized tomographic (CT) measurement of solid disease volume, was recorded. The median survival for the seven responders was 14.7 months, whereas that of the nonresponders was 8 months (p2 = 0.2). Median survival for the entire group was 8.7 months. Preoperative size, platelet count > 360,000/ml, and nonepithelial histology were associated with shortened survival. The CIT regimen has some activity in MPM and can be delivered after debulking resection. In good-risk patients, as defined by favorable prognostic factors, a randomized trial using this combination may be warranted. JF - Annals of surgical oncology AU - Pass, H W AU - Temeck, B K AU - Kranda, K AU - Steinberg, S M AU - Pass, H I AD - Thoracic Oncology Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 214 EP - 220 VL - 2 IS - 3 SN - 1068-9265, 1068-9265 KW - Interferon-alpha KW - 0 KW - Tamoxifen KW - 094ZI81Y45 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Feasibility Studies KW - Immunotherapy KW - Humans KW - Adult KW - Treatment Outcome KW - Aged KW - Middle Aged KW - Male KW - Female KW - Chemotherapy, Adjuvant KW - Survival Analysis KW - Proportional Hazards Models KW - Mesothelioma -- drug therapy KW - Tamoxifen -- pharmacology KW - Interferon-alpha -- pharmacology KW - Cisplatin -- therapeutic use KW - Interferon-alpha -- therapeutic use KW - Tamoxifen -- therapeutic use KW - Mesothelioma -- surgery KW - Cisplatin -- pharmacology KW - Pleural Neoplasms -- drug therapy KW - Pleural Neoplasms -- surgery UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77446427?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+surgical+oncology&rft.atitle=A+phase+II+trial+investigating+primary+immunochemotherapy+for+malignant+pleural+mesothelioma+and+the+feasibility+of+adjuvant+immunochemotherapy+after+maximal+cytoreduction.&rft.au=Pass%2C+H+W%3BTemeck%2C+B+K%3BKranda%2C+K%3BSteinberg%2C+S+M%3BPass%2C+H+I&rft.aulast=Pass&rft.aufirst=H&rft.date=1995-05-01&rft.volume=2&rft.issue=3&rft.spage=214&rft.isbn=&rft.btitle=&rft.title=Annals+of+surgical+oncology&rft.issn=10689265&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-18 N1 - Date created - 1995-09-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A transgenic mouse assay for agouti protein activity. AN - 77446091; 7635291 AB - The mouse agouti gene encodes an 131 amino acid paracrine signaling molecule that instructs hair follicle melanocytes to switch from making black to yellow pigment. Expression of agouti during the middle part of the hair growth cycle in wild-type mice produces a yellow band on an otherwise black hair. The ubiquitous unregulated expression of agouti in mice carrying dominant yellow alleles is associated with pleiotropic effects including increased yellow pigment in the coat, obesity, diabetes and increased tumor susceptibility. Agouti shows no significant homology to known genes, and the molecular analysis of agouti alleles has shed little new light on the important functional elements of the agouti protein. In this paper, we show that agouti expression driven by the human beta-ACTIN promoter produces obese yellow transgenic mice and that this can be used as an assay for agouti activity. We used this assay to evaluate a point mutation associated with the a16H allele within the region encoding agouti's putative signal sequence and our results suggest that this mutation is sufficient to cause the a16H phenotype. Thus, in vitro mutagenesis followed by the generation of transgenic mice should allow us to identify important functional elements of the agouti protein. JF - Genetics AU - Perry, W L AU - Hustad, C M AU - Swing, D A AU - Jenkins, N A AU - Copeland, N G AD - Mammalian Genetics Laboratory, NCI-Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 267 EP - 274 VL - 140 IS - 1 SN - 0016-6731, 0016-6731 KW - ASIP protein, human KW - 0 KW - Actins KW - Agouti Signaling Protein KW - DNA, Complementary KW - Intercellular Signaling Peptides and Proteins KW - Proteins KW - Recombinant Fusion Proteins KW - nonagouti protein, mouse KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - Animals KW - Humans KW - Mice, Transgenic KW - Phenotype KW - Hair Color -- genetics KW - Promoter Regions, Genetic KW - Genes KW - Obesity -- genetics KW - Recombinant Fusion Proteins -- genetics KW - Mice, Inbred C3H KW - Molecular Sequence Data KW - Point Mutation KW - Gene Expression Regulation KW - Genes, Lethal KW - Male KW - Protein Biosynthesis KW - DNA, Complementary -- genetics KW - Mice KW - Mice, Inbred DBA KW - Base Sequence KW - Mice, Mutant Strains KW - Actins -- genetics KW - Mice, Inbred C57BL KW - Female KW - Proteins -- analysis KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77446091?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genetics&rft.atitle=A+transgenic+mouse+assay+for+agouti+protein+activity.&rft.au=Perry%2C+W+L%3BHustad%2C+C+M%3BSwing%2C+D+A%3BJenkins%2C+N+A%3BCopeland%2C+N+G&rft.aulast=Perry&rft.aufirst=W&rft.date=1995-05-01&rft.volume=140&rft.issue=1&rft.spage=267&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-13 N1 - Date created - 1995-09-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Natl Cancer Inst. 1968 Jun;40(6):1161-6 [4298250] Genetics. 1987 Sep;117(1):85-92 [2822532] Physiol Rev. 1971 Jul;51(3):598-646 [5162297] Biochemistry. 1979 Nov 27;18(24):5294-9 [518835] J Virol. 1982 Jul;43(1):26-36 [6287001] Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991-5 [6326095] Genet Res. 1985 Aug;46(1):95-9 [4065569] Mol Cell Biol. 1986 Jul;6(7):2382-91 [3537718] Science. 1988 Jan 29;239(4839):487-91 [2448875] Int J Obes. 1988;12(4):305-20 [3058616] Oncogene. 1991 Feb;6(2):323-32 [1705690] Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6447-51 [1650469] Nucleic Acids Res. 1992 Feb 11;20(3):623 [1741307] Biotechniques. 1992 Aug;13(2):214-20 [1327007] Cell. 1992 Dec 24;71(7):1195-204 [1473152] Genes Dev. 1993 Mar;7(3):454-67 [8449404] Transgenic Res. 1991 Dec;1(1):31-7 [1844573] Genes Dev. 1993 Jul;7(7A):1203-13 [8319910] Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2562-6 [8146154] FASEB J. 1994 May;8(8):479-88 [8181666] Genes Dev. 1994 Jun 15;8(12):1463-72 [7926745] Bioessays. 1994 Oct;16(10):705-7 [7980472] Genetics. 1995 May;140(1):255-65 [7635290] Metabolism. 1963 Jun;12:527-36 [13953596] Science. 1947 May 9;105(2732):496-8 [17796172] J Hered. 1969 Jan-Feb;60(1):20-5 [5798139] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular genetic characterization of six recessive viable alleles of the mouse agouti locus. AN - 77445822; 7635290 AB - The agouti locus on mouse chromosome 2 encodes a secreted cysteine-rich protein of 131 amino acids that acts as a molecular switch to instruct the melanocyte to make either yellow pigment (phaeomelanin) or black pigment (eumelanin). Mutations that up-regulate agouti expression are dominant to those causing decreased expression and result in yellow coat color. Other associated effects are obesity, diabetes, and increased susceptibility to tumors. To try to define important functional domains of the agouti protein, we have analyzed the molecular defects present in a series of recessive viable agouti mutations. In total, six alleles (amJ, au, ada, a16H, a18H, ae) were examined at both the RNA and DNA level. Two of the alleles, a16H and ae, result from mutations in the agouti coding region. Four alleles (amJ, au, a18H, and ada) appear to represent regulatory mutations that down-regulate agouti expression. Interestingly, one of these mutations, a18H, also appears to cause an immunological defect in the homozygous condition. This immunological defect is somewhat analogous to that observed in motheaten (me) mutant mice. Short and long-range restriction enzyme analyses of homozygous a18H DNA are consistent with the hypothesis that a18H results from a paracentric inversion where one end of the inversion maps in the 5' regulatory region of agouti and the other end in or near a gene that is required for normal immunological function. Cloning the breakpoints of this putative inversion should allow us to identify the gene that confers this interesting immunological disorder. JF - Genetics AU - Hustad, C M AU - Perry, W L AU - Siracusa, L D AU - Rasberry, C AU - Cobb, L AU - Cattanach, B M AU - Kovatch, R AU - Copeland, N G AU - Jenkins, N A AD - Mammalian Genetics Laboratory, NCI-Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 255 EP - 265 VL - 140 IS - 1 SN - 0016-6731, 0016-6731 KW - Hcph KW - me KW - Agouti Signaling Protein KW - 0 KW - Intercellular Signaling Peptides and Proteins KW - Melanins KW - Proteins KW - RNA, Messenger KW - nonagouti protein, mouse KW - phaeomelanin KW - 12627-61-1 KW - eumelanin KW - 12627-86-0 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Transcription, Genetic KW - Mice KW - RNA, Messenger -- genetics KW - Chromosome Mapping KW - Mutagenesis KW - Lung Diseases, Interstitial -- genetics KW - Phenotype KW - Lymphoproliferative Disorders -- genetics KW - Melanins -- biosynthesis KW - Base Sequence KW - Hair Color -- genetics KW - DNA -- genetics KW - Molecular Sequence Data KW - Mice, Inbred C57BL KW - Mice, Inbred C3H KW - Chromosome Inversion KW - Gene Expression Regulation KW - Male KW - Alleles KW - Mice, Mutant Strains -- genetics KW - Proteins -- genetics KW - Genes, Recessive UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77445822?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+characterization+of+six+recessive+viable+alleles+of+the+mouse+agouti+locus.&rft.au=Hustad%2C+C+M%3BPerry%2C+W+L%3BSiracusa%2C+L+D%3BRasberry%2C+C%3BCobb%2C+L%3BCattanach%2C+B+M%3BKovatch%2C+R%3BCopeland%2C+N+G%3BJenkins%2C+N+A&rft.aulast=Hustad&rft.aufirst=C&rft.date=1995-05-01&rft.volume=140&rft.issue=1&rft.spage=255&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-13 N1 - Date created - 1995-09-13 N1 - Date revised - 2017-01-13 N1 - Gene symbol - Hcph; me N1 - Genetic sequence - S78889; GENBANK N1 - SuppNotes - Cited By: J Immunol. 1978 Dec;121(6):2392-8 [363946] Biochemistry. 1979 Nov 27;18(24):5294-9 [518835] J Virol. 1982 Jul;43(1):26-36 [6287001] Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991-5 [6326095] Anal Biochem. 1984 Feb;137(1):266-7 [6329026] Am J Pathol. 1984 Aug;116(2):179-92 [6380298] Annu Rev Microbiol. 1985;39:615-48 [3904614] Genet Res. 1985 Aug;46(1):95-9 [4065569] Mol Cell Biol. 1986 Jul;6(7):2382-91 [3537718] Science. 1986 Dec 19;234(4783):1582-5 [3538420] Int J Obes. 1988;12(4):305-20 [3058616] Mol Cell Biol. 1992 Feb;12(2):836-46 [1732748] Cell. 1992 Oct 30;71(3):399-410 [1339316] Cell. 1992 Dec 24;71(7):1195-204 [1473152] Genes Dev. 1993 Mar;7(3):454-67 [8449404] Genes Dev. 1993 Jul;7(7A):1203-13 [8319910] Cell. 1993 Jul 2;73(7):1445-54 [8324828] Nat Genet. 1993 Jun;4(2):124-9 [8348149] Genes Dev. 1994 Feb 15;8(4):481-90 [8125260] Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2562-6 [8146154] FASEB J. 1994 May;8(8):479-88 [8181666] Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5667-71 [8202545] Development. 1994 Jun;120(6):1695-708 [8050375] Genes Dev. 1994 Jun 15;8(12):1463-72 [7926745] Trends Genet. 1994 Dec;10(12):423-8 [7871591] Metabolism. 1963 Jun;12:527-36 [13953596] Nucleic Acids Res. 1990 Jul 11;18(13):4028 [2374739] Vet Pathol. 1978 Mar;15(2):170-8 [664185] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Local hyperthermia and systemic chemotherapy for treatment of recurrent melanoma. AN - 77440641; 7638988 AB - Thirty-two patients with recurrent (skin) or metastatic (skin, node, or both) melanoma have been treated with a hyperthermia-cisplatin regimen. The hyperthermic treatment was carried out for 60 minutes at 43 degrees C with the MHS-SMA and the Sapic SVO3 ALENIA devices once a week. When the tumor temperature reached 42 degrees C, cisplatin was administered at a dosage of 50 mg/m2 given by intravenous bolus infusion. The treatment was repeated four times and the tumor response evaluated 4 weeks after the last treatment. Significant systemic or local toxicity was not seen. In terms of results, there were 9 patients with complete responses (28.1%), 13 with partial responses (40.6%), 8 with no change (25.0%), and two with disease progression (6.3%). The objective response rate was 68.7%. The response duration for those with complete responses ranged from 4 to 49 months (median 20 months). The median time to progression for patients with partial responses and those with no change was 6 and 5 months, respectively, with ranges of 1-7 and 1-10 months, respectively. The 4-year actuarial survival rates were 47.6% and 20.3% for the complete and incomplete responders, respectively. These results can be considered satisfactory, taking into account that most patients were pretreated with radiotherapy, chemotherapy or both, confirming the therapeutic potential of the hyperthermia and cisplatin regimen. JF - World journal of surgery AU - Di Filippo, F AU - Carlini, S AU - Garinei, R AU - Perri, P AU - Anzà, M AU - Ferranti, F AU - Saracca, E AU - Schiratti, M AU - Cavaliere, F AU - Cavaliere, R AD - First Department of Surgery, Regina Elena National Cancer Institute, Rome, Italy. PY - 1995 SP - 359 EP - 362 VL - 19 IS - 3 SN - 0364-2313, 0364-2313 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Survival Rate KW - Infusions, Intravenous KW - Lymphatic Metastasis KW - Humans KW - Adult KW - Prognosis KW - Aged KW - Pilot Projects KW - Middle Aged KW - Male KW - Female KW - Chemotherapy, Adjuvant KW - Cisplatin -- therapeutic use KW - Melanoma -- mortality KW - Melanoma -- secondary KW - Hyperthermia, Induced KW - Skin Neoplasms -- therapy KW - Skin Neoplasms -- pathology KW - Neoplasm Recurrence, Local -- therapy KW - Melanoma -- therapy KW - Skin Neoplasms -- mortality KW - Neoplasm Recurrence, Local -- mortality KW - Cisplatin -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77440641?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=World+journal+of+surgery&rft.atitle=Local+hyperthermia+and+systemic+chemotherapy+for+treatment+of+recurrent+melanoma.&rft.au=Di+Filippo%2C+F%3BCarlini%2C+S%3BGarinei%2C+R%3BPerri%2C+P%3BAnz%C3%A0%2C+M%3BFerranti%2C+F%3BSaracca%2C+E%3BSchiratti%2C+M%3BCavaliere%2C+F%3BCavaliere%2C+R&rft.aulast=Di+Filippo&rft.aufirst=F&rft.date=1995-05-01&rft.volume=19&rft.issue=3&rft.spage=359&rft.isbn=&rft.btitle=&rft.title=World+journal+of+surgery&rft.issn=03642313&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-14 N1 - Date created - 1995-09-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alcohol use in combination with cocaine, heroin and methadone by medical examiner cases. AN - 77413138; 7623474 AB - The purpose of this review of all appropriate, available medical examiner (ME) studies is to provide information on cases with positive toxicologies for cocaine, morphine (the heroin metabolite) and methadone that have positive blood or brain alcohol concentrations (BACs). Criteria for inclusion of U.S. ME studies in this review are (1) at least 20 cases with a positive toxicology for cocaine, morphine or methadone and (2) BAC test findings according to specific drug positivity. Only 19 studies conducted from 1969 to 1992 met these criteria; most studies reviewed were not included primarily because of their failure to present or link available BAC test findings with positive toxicologies for these other drugs. The BAC-positive ranges were similar for cocaine and heroin. In reports on both heroin and methadone or on all three drugs, heroin-positive cases had the highest proportions and methadone-positive cases had the lowest proportions with positive BACs. Published data confirm the substantial presence of alcohol in combination with cocaine, heroin and methadone among ME cases. Future ME studies should endeavor to link BAC and toxicology findings for other drugs according to drug-induced or drug-related manner of death. These data would advance our knowledge about the role of alcohol in drug deaths and provide additional information on substance abuse trends. JF - Journal of studies on alcohol AU - Haberman, P W AU - Noble, J A AU - Dufour, M C AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-7003, USA. Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 344 EP - 347 VL - 56 IS - 3 SN - 0096-882X, 0096-882X KW - Ethanol KW - 3K9958V90M KW - Heroin KW - 70D95007SX KW - Cocaine KW - I5Y540LHVR KW - Methadone KW - UC6VBE7V1Z KW - Index Medicus KW - Ethanol -- pharmacokinetics KW - Heroin -- pharmacokinetics KW - Coroners and Medical Examiners KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Child KW - Adolescent KW - United States -- epidemiology KW - Male KW - Female KW - Comorbidity KW - Alcoholism -- rehabilitation KW - Methadone -- adverse effects KW - Methadone -- therapeutic use KW - Alcoholism -- mortality KW - Substance-Related Disorders -- mortality KW - Heroin Dependence -- rehabilitation KW - Cocaine -- pharmacokinetics KW - Substance-Related Disorders -- rehabilitation KW - Heroin Dependence -- mortality KW - Cocaine -- adverse effects KW - Cause of Death KW - Alcoholism -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77413138?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Alcohol+use+in+combination+with+cocaine%2C+heroin+and+methadone+by+medical+examiner+cases.&rft.au=Haberman%2C+P+W%3BNoble%2C+J+A%3BDufour%2C+M+C&rft.aulast=Haberman&rft.aufirst=P&rft.date=1995-05-01&rft.volume=56&rft.issue=3&rft.spage=344&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 - 1995-08-31 N1 - Date created - 1995-08-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic susceptibility biomarkers in studies of occupational and environmental cancer: methodologic issues. AN - 77405769; 7618141 AB - When using biomarkers to assess genetic susceptibility for cancer risk, the following issues should be recognized: (i) exposure assessment should receive as much attention as marker measurement; (ii) it is critical to study cases with a wide range of exposure patterns; (iii) each approach to evaluating susceptibility has its own potential biases; (iv) it is important to demonstrate the biologic plausibility of gene-exposure interactions detected in epidemiologic studies. JF - Toxicology letters AU - Rothman, N AD - Occupational Studies Section, NIH/NCI EPN 418, Bethesda, MD 20892, USA. Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 221 EP - 225 VL - 77 IS - 1-3 SN - 0378-4274, 0378-4274 KW - Biomarkers KW - 0 KW - Environmental Pollutants KW - Index Medicus KW - Humans KW - Toxicology -- methods KW - Biomarkers -- analysis KW - Neoplasms -- epidemiology KW - Occupational Exposure -- adverse effects KW - Genetic Predisposition to Disease KW - Neoplasms -- genetics KW - Neoplasms -- etiology KW - Environmental Pollutants -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77405769?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+letters&rft.atitle=Genetic+susceptibility+biomarkers+in+studies+of+occupational+and+environmental+cancer%3A+methodologic+issues.&rft.au=Rothman%2C+N&rft.aulast=Rothman&rft.aufirst=N&rft.date=1995-05-01&rft.volume=77&rft.issue=1-3&rft.spage=221&rft.isbn=&rft.btitle=&rft.title=Toxicology+letters&rft.issn=03784274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-22 N1 - Date created - 1995-08-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Esophageal cancer and occupation in a cohort of Swedish men. AN - 77397564; 7611309 AB - Using the Cancer Environment Registry of Sweden, which links the 1960 census information on employment with cancer incidence data from 1961-1979, we conducted a systematic, population-based assessment of esophageal cancer incidence by industry and occupation for men in Sweden. A general reduction in esophageal cancer incidence was found among agricultural and professional workers, whereas excess incidence was found among business, sales, and some craftsmen and production jobs. Elevated incidence was associated with several specific industries, including the food (SIR = 1.3, p < 0.05), beverage and tobacco (SIR = 1.8, p < 0.05) industries, vulcanizing shops within the rubber industry (SIR = 4.7, p < 0.01), and certain automotive building industries. Incidence also was increased among brewery workers (SIR = 4.2, p < 0.01) and butchers (SIR = 2.1, p < 0.01), and among individuals with certain service jobs, particularly waiters in the hotel and restaurant industry (SIR = 3.1, p < 0.01). Some of the occupational associations may be explained by lifestyle factors such as alcohol drinking and smoking, whereas others are specific and tend to support those of earlier investigations. This study adds to the evidence of a small but possibly important role of occupation in esophageal cancer etiology. JF - American journal of industrial medicine AU - Chow, W H AU - McLaughlin, J K AU - Malker, H S AU - Linet, M S AU - Weiner, J A AU - Stone, B J AD - Division of Cancer Etiology, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 749 EP - 757 VL - 27 IS - 5 SN - 0271-3586, 0271-3586 KW - Index Medicus KW - Registries KW - Risk Factors KW - Humans KW - Cohort Studies KW - Sweden -- epidemiology KW - Industry -- statistics & numerical data KW - Incidence KW - Male KW - Adenocarcinoma -- epidemiology KW - Carcinoma, Squamous Cell -- etiology KW - Carcinoma, Squamous Cell -- epidemiology KW - Adenocarcinoma -- etiology KW - Occupational Diseases -- epidemiology KW - Esophageal Neoplasms -- etiology KW - Esophageal Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77397564?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=Esophageal+cancer+and+occupation+in+a+cohort+of+Swedish+men.&rft.au=Chow%2C+W+H%3BMcLaughlin%2C+J+K%3BMalker%2C+H+S%3BLinet%2C+M+S%3BWeiner%2C+J+A%3BStone%2C+B+J&rft.aulast=Chow&rft.aufirst=W&rft.date=1995-05-01&rft.volume=27&rft.issue=5&rft.spage=749&rft.isbn=&rft.btitle=&rft.title=American+journal+of+industrial+medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-14 N1 - Date created - 1995-08-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Suppression of endometrial carcinoma cell tumorigenicity by human chromosome 18. AN - 77378330; 7541639 AB - Presumptive tumor suppressor genes may be localized to specific chromosomes by the procedure of microcell fusion, whereby individual chromosomes derived from normal human cells are introduced into tumor cells. Allelic loss on chromosome 18 is commonly seen in endometrial carcinoma, and the DCC gene on chromosome 18q is a potential human tumor suppressor gene. In this study, we investigated the hypothesis that a gene on chromosome 18, possibly DCC, is capable of suppressing the tumorigenicity of endometrial carcinoma cells. Microcells from the mouse A9 cell clone containing one human chromosome 18 tagged with the pSV2-neo plasmid were fused with the highly tumorigenic endometrial carcinoma cell lines HHUA and Ishikawa, and G418-resistant microcell hybrids containing and extra copy of chromosome 18 were isolated. Clones isolated from the HHUA cell line were completely suppressed for tumorigenicity in nude mice, and clones from the Ishikawa line were suppressed or inhibited for tumorigenicity. In contrast, growth rates in vitro were not significantly affected in clones from either parental cell line. DCC expression was elevated in most of the suppressed hybrids. These results indicate that a gene on human chromosome 18 is capable of suppressing the tumorigenicity of endometrial carcinoma cells, and that DCC is a candidate for this endometrial carcinoma tumor suppressor gene. JF - Genes, chromosomes & cancer AU - Yamada, H AU - Sasaki, M AU - Honda, T AU - Wake, N AU - Boyd, J AU - Oshimura, M 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 - 1995/05// PY - 1995 DA - May 1995 SP - 18 EP - 24 VL - 13 IS - 1 SN - 1045-2257, 1045-2257 KW - pSV2-neo KW - Cell Adhesion Molecules KW - 0 KW - DCC protein, human KW - Dcc protein, mouse KW - Genetic Markers KW - Receptors, Cell Surface KW - Tumor Suppressor Proteins KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Cell Adhesion Molecules -- genetics KW - Chromosome Banding KW - Humans KW - DNA -- analysis KW - Mice, Nude KW - Mice KW - Polymerase Chain Reaction KW - Base Sequence KW - Tumor Cells, Cultured KW - Cell Fusion KW - Blotting, Southern KW - Molecular Sequence Data KW - Cell Adhesion Molecules -- biosynthesis KW - Cell Transformation, Neoplastic -- genetics KW - Female KW - Gene Expression Regulation, Neoplastic KW - Chromosomes, Human, Pair 18 KW - Genes, DCC -- genetics KW - Endometrial Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77378330?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes%2C+chromosomes+%26+cancer&rft.atitle=Suppression+of+endometrial+carcinoma+cell+tumorigenicity+by+human+chromosome+18.&rft.au=Yamada%2C+H%3BSasaki%2C+M%3BHonda%2C+T%3BWake%2C+N%3BBoyd%2C+J%3BOshimura%2C+M%3BBarrett%2C+J+C&rft.aulast=Yamada&rft.aufirst=H&rft.date=1995-05-01&rft.volume=13&rft.issue=1&rft.spage=18&rft.isbn=&rft.btitle=&rft.title=Genes%2C+chromosomes+%26+cancer&rft.issn=10452257&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-11 N1 - Date created - 1995-08-11 N1 - Date revised - 2017-01-13 N1 - Gene symbol - pSV2-neo N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vasopressin Vla receptor-stimulated phospholipase D: differential regulation of transphosphatidylation and phospholipid hydrolysis by protein kinase C [corrected]. AN - 77369936; 7603588 AB - Phospholipase D belongs to a group of membrane associated phospholipases which have been shown to be activated by G-protein coupled neurotransmitter receptors. Phosphatidylcholine is the primary substrate for phospholipase D generating phosphatidic acid (PA) and choline. In the presence of 1% ethanol, phospholipase D catalyzes a transphosphatidylation reaction generating phosphatidylethanol (PEt) which is an indicator of phospholipase D activation. In the present study, we utilized Chinese hamster ovary (CHO) cells stably transfected with and expressing a rat V1a vasopressin receptor to study the regulation of phospholipase D by protein kinase C and calcium. Arginine-vasopressin (AVP) stimulated the release of 3H-PEt and 3H-PA in cells pre-labelled overnight with 3H-palmitic acid. The phorbol ester, phorbol 12-myristate 13-acetate (PMA), stimulated the release of PEt and PA that was additive with AVP over 15 min. However, long-term stimulation with PMA, which desensitizes protein kinase C, decreased PEt production while simultaneously increasing PA production. Differential regulation of PEt and PA production by PMA suggests the existence of more than one phospholipase D isoenzyme. Though differentially regulated by protein kinase C, both AVP-stimulated PEt and PA production required extracellular and not intracellular calcium. JF - Neuropeptides AU - Garces, Y AU - Briley, E M AU - Felder, C C AD - Howard Hughes Medical Scholars Program, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 277 EP - 285 VL - 28 IS - 5 SN - 0143-4179, 0143-4179 KW - Glycerophospholipids KW - 0 KW - Phosphatidic Acids KW - Phospholipids KW - Receptors, Vasopressin KW - phosphatidylethanol KW - Arginine Vasopressin KW - 113-79-1 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Phospholipase D KW - EC 3.1.4.4 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Rats KW - Calcium -- metabolism KW - Animals KW - Phosphatidic Acids -- metabolism KW - Transfection KW - Enzyme Activation KW - Kinetics KW - Tetradecanoylphorbol Acetate -- pharmacology KW - CHO Cells KW - Hydrolysis KW - Cricetinae KW - Protein Kinase C -- metabolism KW - Arginine Vasopressin -- pharmacology KW - Phospholipase D -- metabolism KW - Protein Kinase C -- antagonists & inhibitors KW - Receptors, Vasopressin -- physiology KW - Phospholipids -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77369936?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Vasopressin+Vla+receptor-stimulated+phospholipase+D%3A+differential+regulation+of+transphosphatidylation+and+phospholipid+hydrolysis+by+protein+kinase+C+%5Bcorrected%5D.&rft.au=Garces%2C+Y%3BBriley%2C+E+M%3BFelder%2C+C+C&rft.aulast=Garces&rft.aufirst=Y&rft.date=1995-05-01&rft.volume=28&rft.issue=5&rft.spage=277&rft.isbn=&rft.btitle=&rft.title=Neuropeptides&rft.issn=01434179&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-10 N1 - Date created - 1995-08-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Neuropeptides 1995 Aug;29(2):101 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased susceptibility to N-nitrosomethylurea gastric carcinogenesis in transforming growth factor alpha transgenic mice with gastric hyperplasia. AN - 77342722; 7790317 AB - Glandular stomach carcinogenesis after N-nitrosomethylurea (NMU) treatment was examined in transgenic mice bearing a human transforming growth factor alpha (TGF-alpha) cDNA driven by the mouse metallothionein-I promoter (mouse line MT100) in the inbred mouse line FVB/N. Untreated MT100 mice exhibit a severe age-related gastric fundic hyperplasia. Both sexes of MT100 mice were given 10 weekly intragastric intubations of 0.5 mg NMU per mouse from 6 weeks of age and/or zinc chloride in drinking water to stimulate transgene expression from 5.5 weeks of age to the experiment termination. Animals were killed sequentially at 10, 19 and 29 experimental weeks. Several histochemical markers (AB-PAS, TGF-alpha, pepsinogen isozyme 1, proliferating cell nuclear antigen) were used. Abnormal histochemical patterns were found in untreated MT100 and NMU-treated MT100 mice for all 4 markers of differentiation and carcinogenesis. Precancerous lesions including atypical and/or adenomatous hyperplasia were found in the fundic region of 16/22 male and 8/22 female MT100 mice but not in 27 male and 24 female FVB/N mice treated with NMU. One of 22 MT100 males had fundic carcinoma. FVB/N mice treated with NMU had neither precancerous lesions nor carcinomas in the fundus. Well differentiated adenocarcinomas in the pyloric region were induced at incidences of 2/22 male and 1/22 female MT100 mice treated with NMU and 4/27 male and 4/24 female FVB/N mice treated with NMU. Both strains also had a high incidence (55 to 92%) of squamous cell carcinomas of the forestomach. In conclusion, TGF-alpha induced a hyperplastic lesion in the gastric fundus that appeared to predispose the MT100 mice to carcinogenesis by NMU. JF - Japanese journal of cancer research : Gann AU - Tamano, S AU - Jakubczak, J AU - Takagi, H AU - Merlino, G AU - Ward, J M AD - Veterinary and Tumor Pathology Section, National Cancer Institute, Frederick, MD 21702-1201, USA. Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 435 EP - 443 VL - 86 IS - 5 SN - 0910-5050, 0910-5050 KW - Pepsinogens KW - 0 KW - Transforming Growth Factor alpha KW - Methylnitrosourea KW - 684-93-5 KW - Index Medicus KW - Animals KW - Stomach -- pathology KW - Hyperplasia KW - Mice KW - Immunohistochemistry KW - Pepsinogens -- metabolism KW - Male KW - Female KW - Stomach Neoplasms -- pathology KW - Adenocarcinoma -- metabolism KW - Stomach Neoplasms -- metabolism KW - Transforming Growth Factor alpha -- genetics KW - Stomach Neoplasms -- chemically induced KW - Adenocarcinoma -- chemically induced KW - Precancerous Conditions -- chemically induced KW - Precancerous Conditions -- metabolism KW - Mice, Transgenic KW - Precancerous Conditions -- pathology KW - Adenocarcinoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77342722?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Japanese+journal+of+cancer+research+%3A+Gann&rft.atitle=Increased+susceptibility+to+N-nitrosomethylurea+gastric+carcinogenesis+in+transforming+growth+factor+alpha+transgenic+mice+with+gastric+hyperplasia.&rft.au=Tamano%2C+S%3BJakubczak%2C+J%3BTakagi%2C+H%3BMerlino%2C+G%3BWard%2C+J+M&rft.aulast=Tamano&rft.aufirst=S&rft.date=1995-05-01&rft.volume=86&rft.issue=5&rft.spage=435&rft.isbn=&rft.btitle=&rft.title=Japanese+journal+of+cancer+research+%3A+Gann&rft.issn=09105050&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-27 N1 - Date created - 1995-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Caffeine inhibits gene-specific repair of UV-induced DNA damage in hamster cells and in human xeroderma pigmentosum group C cells. AN - 77303312; 7767978 AB - We have studied the effect of caffeine on gene- and strand-specific DNA repair after exposure of Chinese hamster ovary cells and human xeroderma pigmentosum complementation group C (XPC) cells to ultraviolet irradiation (UV). In hamster cells, caffeine inhibited the repair of cyclobutane dimers (CPDs) in the dihydrofolate reductase (DHFR) gene by up to 66% after 8 h of repair incubation. This effect was dose-dependent, with more inhibition at 10 than at 1.5 mM caffeine. The inhibition was due to decreased repair in the transcribed strand of the hamster DHFR gene. This decrease in repair of CPDs in the DHFR gene correlated with an enhancement of UV-induced cell killing by caffeine. DNA repair was also measured in the overall genome by repair-replication analysis. In hamster cells, caffeine caused a modest enhancement of repair. Caffeine did not produce a significant effect on cell cycle progression up to 8 h after UV irradiation, but it caused a distinct block in early S phase during the 24 h post-irradiation period. In XPC cells, 10 mM caffeine inhibited the removal of CPDs from the transcribed strand of the DHFR gene by 92%. The removal of all photoproducts from the overall genome was inhibited by 26% in these cells. Since the residual repair in XPC cells is thought to occur in active genomic regions, we propose that caffeine preferentially inhibits gene-specific repair. JF - Carcinogenesis AU - Link, C J AU - Evans, M K AU - Cook, J A AU - Muldoon, R AU - Stevnsner, T AU - Bohr, V A AD - Radiation Oncology Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 1149 EP - 1155 VL - 16 IS - 5 SN - 0143-3334, 0143-3334 KW - Caffeine KW - 3G6A5W338E KW - Tetrahydrofolate Dehydrogenase KW - EC 1.5.1.3 KW - Index Medicus KW - Gene Expression -- drug effects KW - Xeroderma Pigmentosum KW - Animals KW - Humans KW - Transcription, Genetic KW - Tetrahydrofolate Dehydrogenase -- biosynthesis KW - DNA Replication -- drug effects KW - DNA Replication -- radiation effects KW - Cell Survival -- drug effects KW - Kinetics KW - CHO Cells KW - Cell Survival -- radiation effects KW - Cell Cycle -- radiation effects KW - Cell Cycle -- drug effects KW - Cell Line KW - Gene Expression -- radiation effects KW - Cricetinae KW - DNA Repair -- genetics KW - DNA Repair -- radiation effects KW - Ultraviolet Rays KW - DNA Damage KW - Caffeine -- pharmacology KW - DNA Repair -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77303312?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Caffeine+inhibits+gene-specific+repair+of+UV-induced+DNA+damage+in+hamster+cells+and+in+human+xeroderma+pigmentosum+group+C+cells.&rft.au=Link%2C+C+J%3BEvans%2C+M+K%3BCook%2C+J+A%3BMuldoon%2C+R%3BStevnsner%2C+T%3BBohr%2C+V+A&rft.aulast=Link&rft.aufirst=C&rft.date=1995-05-01&rft.volume=16&rft.issue=5&rft.spage=1149&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-05 N1 - Date created - 1995-07-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gender comparisons in human lung cancer: analysis of p53 mutations, anti-p53 serum antibodies and C-erbB-2 expression. AN - 77300329; 7767998 AB - Little is known about the molecular mechanisms of lung carcinogenesis in women. We initiated an investigation of the role of gender in pulmonary carcinogenesis by analysis of p53 mutations, immunohistochemistry, serum antibodies and c-erbB-2 expression in a series of 63 male and 44 female lung cancer patients whose tumors were resected at the Mayo Clinic between 1991 and 1992. There were 102 smokers and 5 never smoked. Adenocarcinoma was the more frequent histological type in women (62%) than in men (41%). Sequence analysis of exons 5-8 in 42 females and 49 males identified 44 p53 mutations in 42 tumors (46%). Base substitution mutations showed a preponderance of G:C-->T:A transversions, which were more frequent in women than men (40 versus 25%) and in individuals exposed to asbestos. c-erbB-2 immunohistochemical staining was identified more frequently in females (nine cases) than males (two cases). Marked immunohistochemical staining for p53 positively correlated with the presence of missense mutations in exons 5-8 (81%, P < 0.001). Seven missense mutations (four in exon 5, two in exon 6, one in exon 8) were identified in five of nine patients who had serum antibodies recognizing p53; tumors from these patients were also strongly positive for p53 by immunohistochemistry. These and other results indicate gender differences in the genetic and biochemical alterations in lung cancer and generate hypothesis regarding gender differences in lung cancer susceptibility. JF - Carcinogenesis AU - Guinee, D G AU - Travis, W D AU - Trivers, G E AU - De Benedetti, V M AU - Cawley, H AU - Welsh, J A AU - Bennett, W P AU - Jett, J AU - Colby, T V AU - Tazelaar, H AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 993 EP - 1002 VL - 16 IS - 5 SN - 0143-3334, 0143-3334 KW - c-erbB-2 KW - p53 KW - Autoantibodies KW - 0 KW - DNA, Neoplasm KW - Tumor Suppressor Protein p53 KW - Asbestos KW - 1332-21-4 KW - DNA KW - 9007-49-2 KW - Receptor, ErbB-2 KW - EC 2.7.10.1 KW - Index Medicus KW - Humans KW - Gene Expression KW - Adenocarcinoma -- genetics KW - Asbestos -- toxicity KW - DNA, Neoplasm -- isolation & purification KW - Carcinoma, Large Cell -- pathology KW - Smoking KW - Carcinoma, Squamous Cell -- pathology KW - Carcinoma, Squamous Cell -- genetics KW - Carcinoma, Large Cell -- genetics KW - Carcinoma, Small Cell -- genetics KW - Male KW - Carcinoma, Small Cell -- pathology KW - Immunoblotting KW - Protein Biosynthesis KW - Exons KW - Adenocarcinoma -- pathology KW - DNA -- isolation & purification KW - Polymerase Chain Reaction KW - DNA -- genetics KW - DNA, Neoplasm -- genetics KW - Middle Aged KW - Immunohistochemistry KW - Female KW - Immunoenzyme Techniques KW - Tumor Suppressor Protein p53 -- biosynthesis KW - Genes, p53 KW - Sex Characteristics KW - Genes, erbB-2 KW - Lung Neoplasms -- immunology KW - Point Mutation KW - Autoantibodies -- blood KW - Lung Neoplasms -- genetics KW - Tumor Suppressor Protein p53 -- immunology KW - Receptor, ErbB-2 -- biosynthesis KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77300329?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Gender+comparisons+in+human+lung+cancer%3A+analysis+of+p53+mutations%2C+anti-p53+serum+antibodies+and+C-erbB-2+expression.&rft.au=Guinee%2C+D+G%3BTravis%2C+W+D%3BTrivers%2C+G+E%3BDe+Benedetti%2C+V+M%3BCawley%2C+H%3BWelsh%2C+J+A%3BBennett%2C+W+P%3BJett%2C+J%3BColby%2C+T+V%3BTazelaar%2C+H&rft.aulast=Guinee&rft.aufirst=D&rft.date=1995-05-01&rft.volume=16&rft.issue=5&rft.spage=993&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-05 N1 - Date created - 1995-07-05 N1 - Date revised - 2017-01-13 N1 - Gene symbol - c-erbB-2; p53 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High frequency of K-ras mutations in spontaneous and vinyl carbamate-induced lung tumors of relatively resistant B6CF1 (C57BL/6J x BALB/cJ) mice. AN - 77296917; 7767966 AB - The murine K-ras proto-oncogene is hypothesized to be a pulmonary adenoma susceptibility gene. This postulate is supported by the previous demonstration of a preference for mutation of the K-ras allele from the susceptible parent in lung tumors of A/J x C3H F1 mice. We have examined K-ras activation in control and vinyl carbamate (VC) (single dose 0.03 mumol/g i.p.) treated B6CF1 mice, the progeny of resistant C57BL/6J and intermediately sensitive BALB/cJ parents. Thirty-four of 37 tumors from VC-treated mice and 17 of 23 from controls contained activating K-ras mutations. The spectra of mutations in codons 12 and 61 of K-ras were similar for the two groups, except that 7 tumors from VC-treated mice had A-->T transversions in the second base of codon 61; none were observed in tumors from saline-treated animals. PCR-based genotyping of first exon K-ras mutations revealed that the vast majority (15 of 18) of the mutations were in the BALB/cJ allele. Furthermore, the three tumors with mutated C57BL/6J K-ras were among the smallest tumors analyzed. These results are consistent with previous findings in other mouse hybrids showing parental bias for K-ras mutations and suggest that mutation of the allele of the susceptible parent may provide a growth advantage to the tumor. JF - Carcinogenesis AU - Massey, T E AU - Devereux, T R AU - Maronpot, R R AU - Foley, J F AU - Anderson, M W AD - Environmental Carcinogenesis Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 1065 EP - 1069 VL - 16 IS - 5 SN - 0143-3334, 0143-3334 KW - K-ras KW - Carcinogens KW - 0 KW - Codon KW - DNA Primers KW - Urethane KW - 3IN71E75Z5 KW - vinyl carbamate KW - 7Y2431GOM5 KW - Index Medicus KW - Animals KW - Immunity, Innate KW - Mice KW - Mice, Inbred BALB C KW - Polymerase Chain Reaction KW - Alleles KW - Base Sequence KW - Molecular Sequence Data KW - Mice, Inbred C57BL KW - Crosses, Genetic KW - Female KW - Male KW - Genes, ras KW - Urethane -- analogs & derivatives KW - Point Mutation KW - Lung Neoplasms -- genetics KW - Lung Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77296917?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=High+frequency+of+K-ras+mutations+in+spontaneous+and+vinyl+carbamate-induced+lung+tumors+of+relatively+resistant+B6CF1+%28C57BL%2F6J+x+BALB%2FcJ%29+mice.&rft.au=Massey%2C+T+E%3BDevereux%2C+T+R%3BMaronpot%2C+R+R%3BFoley%2C+J+F%3BAnderson%2C+M+W&rft.aulast=Massey&rft.aufirst=T&rft.date=1995-05-01&rft.volume=16&rft.issue=5&rft.spage=1065&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-05 N1 - Date created - 1995-07-05 N1 - Date revised - 2017-01-13 N1 - Gene symbol - K-ras N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - c-jun and multistage carcinogenesis: association of overexpression of introduced c-jun with progression toward a neoplastic endpoint in mouse JB6 cells sensitive to tumor promoter-induced transformation. AN - 77296529; 7766308 AB - Tumor promoters such as 12-O-tetradecanoylphorbol-13-acetate (TPA) and epidermal growth factor (EGF) induce neoplastic transformation, elevated c-jun protein expression, and activator protein-1 (AP-1)-dependent gene expression in JB6 mouse epidermal cells sensitive to tumor promoters (clone 415a P+ cells). In contrast, JB6 cells resistant to tumor promoter-induced transformation (clone 307b P- cells) exhibit a greatly reduced TPA or EGF inducible c-jun expression and AP-1 activity. We have recently shown that induced AP-1 is necessary for tumor promoter-induced transformation of P+ cells because introduction of a dominant negative c-jun mutant into P+ cells inhibits both AP-1 dependent transactivation and the transformation response to tumor promoter. The intent of the investigation presented here was to test the hypothesis that elevation of AP-1 activity is sufficient to cause progression to the P+ phenotype in P- cells or to the transformed phenotype in P+ cells. Clonally derived P+ and P- recipient cells transfected with a human c-jun expression construct and overexpressing c-jun protein were tested for progression by assaying for constitutive or inducible anchorage independent phenotype and nude-mouse tumorigenicity. Overexpression of c-jun did not produce progression in P- cells but did increase the probability of progression in P+ cells (two of five transfectant cell lines progressed to the tumor phenotype). In addition, c-jun overexpression did not increase AP-1 activity in any of the P-/c-jun transfectants or in the two of five P+/c-jun transfectants that acquired the transformed phenotype. The P+/c-jun transfectants that showed elevated AP-1 activity did not progress to the tumor phenotype, demonstrating that an increase in AP-1 activity is insufficient for this progression. Since P(+)-to-tumor phenotype progression occurred in cells overexpressing c-jun but not AP-1, we propose that P(+)-to-transformed phenotype progression is c-jun dependent and AP-1 independent. JF - Molecular carcinogenesis AU - Watts, R G AU - Ben-Ari, E T AU - Bernstein, L R AU - Birrer, M J AU - Winterstein, D AU - Wendel, E AU - Colburn, N H AD - Laboratory of Viral Carcinogenesis, NCI, FCRDC, Frederick, MD 21702, USA. Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 27 EP - 36 VL - 13 IS - 1 SN - 0899-1987, 0899-1987 KW - c-jun KW - fos KW - jun KW - neo KW - v-Ha-ras KW - Proto-Oncogene Proteins c-jun KW - 0 KW - RNA, Messenger KW - Transcription Factor AP-1 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Gene Expression -- drug effects KW - Sensitivity and Specificity KW - Animals KW - Skin Physiological Phenomena KW - Transcription Factor AP-1 -- metabolism KW - Skin -- metabolism KW - Humans KW - Cell Division -- physiology KW - Mice KW - Proto-Oncogene Proteins c-jun -- biosynthesis KW - RNA, Messenger -- genetics KW - Phenotype KW - Skin -- drug effects KW - RNA, Messenger -- metabolism KW - Transfection KW - Cells, Cultured KW - Transcription Factor AP-1 -- drug effects KW - Proto-Oncogene Proteins c-jun -- genetics KW - Skin Neoplasms -- genetics KW - Tetradecanoylphorbol Acetate -- toxicity KW - Skin Neoplasms -- chemically induced KW - Genes, jun -- drug effects KW - Cell Transformation, Neoplastic -- drug effects KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77296529?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=c-jun+and+multistage+carcinogenesis%3A+association+of+overexpression+of+introduced+c-jun+with+progression+toward+a+neoplastic+endpoint+in+mouse+JB6+cells+sensitive+to+tumor+promoter-induced+transformation.&rft.au=Watts%2C+R+G%3BBen-Ari%2C+E+T%3BBernstein%2C+L+R%3BBirrer%2C+M+J%3BWinterstein%2C+D%3BWendel%2C+E%3BColburn%2C+N+H&rft.aulast=Watts&rft.aufirst=R&rft.date=1995-05-01&rft.volume=13&rft.issue=1&rft.spage=27&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 - 1995-07-06 N1 - Date created - 1995-07-06 N1 - Date revised - 2017-01-13 N1 - Gene symbol - c-jun; fos; jun; neo; v-Ha-ras N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of the basal and carcinogen regulatory elements of the rat mdr1b promoter. AN - 77294643; 7766310 AB - In this report we characterized the transcriptional regulation of the rat mdr1b gene by xenobiotics. The expression of this gene was increased in primary rat hepatocytes and in the H4-II-E hepatoma cell line by exposure to carcinogens such as aflatoxin B1, N-acetoxy-2-acetylaminofluorene, and methyl methanesulfonate. Nuclear run-on experiments indicated that the higher steady-state levels of mdr1b mRNA were due to an increase in transcription. The 5'-flanking region of the mdr1b gene was isolated, sequenced, and functionally characterized in transient and stable transfection assays. A single transcription start site was identified for this gene; no alternate start sites were used after induction with aflatoxin B1. Deletion analysis of this promoter demonstrated that the sequence between nt -214 and -178 was critical for basal promoter activity. This region did not contain any consensus-binding sites for previously identified transcription factors. A negative regulatory region was also identified between nt -940 and -250. No specific carcinogen-responsive element was identified; the xenobiotic response required a large part of the promoter. These data suggest that the carcinogen induction of mdr1b expression is mediated through sequences that overlap or that are identical to the basal promoter element. JF - Molecular carcinogenesis AU - Silverman, J A AU - Hill, B A AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 50 EP - 59 VL - 13 IS - 1 SN - 0899-1987, 0899-1987 KW - MDR1 KW - mdr1a KW - mdr1b KW - Carcinogens KW - 0 KW - RNA, Messenger KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Transcription, Genetic -- drug effects KW - RNA, Messenger -- drug effects KW - Liver -- metabolism KW - Genomic Library KW - Liver -- physiology KW - DNA -- drug effects KW - Gene Deletion KW - Rats KW - Rats, Inbred F344 KW - Base Sequence KW - RNA, Messenger -- metabolism KW - Transfection KW - Cells, Cultured KW - Liver -- drug effects KW - DNA -- genetics KW - Molecular Sequence Data KW - Carcinogens -- pharmacology KW - Regulatory Sequences, Nucleic Acid -- drug effects KW - Promoter Regions, Genetic -- drug effects KW - Gene Expression Regulation -- drug effects KW - Drug Resistance, Multiple -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77294643?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Characterization+of+the+basal+and+carcinogen+regulatory+elements+of+the+rat+mdr1b+promoter.&rft.au=Silverman%2C+J+A%3BHill%2C+B+A&rft.aulast=Silverman&rft.aufirst=J&rft.date=1995-05-01&rft.volume=13&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 - 1995-07-06 N1 - Date created - 1995-07-06 N1 - Date revised - 2017-01-13 N1 - Gene symbol - MDR1; mdr1a; mdr1b N1 - Genetic sequence - L16546; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Five-year follow-up of a phase I study of didanosine in patients with advanced human immunodeficiency virus infection. AN - 77285283; 7751692 AB - Starting in 1988, 72 patients with advanced human immunodeficiency virus (HIV) infection were enrolled in a phase I study of didanosine at the National Cancer Institute. Beginning in 1992, patients with decreases in CD4 cell counts could switch to a combination of zidovudine and didanosine. The estimated median survival for all patients was 28 months (95% confidence interval, 23-46). However, for patients whose entry CD4 cell counts were 100-300/mm3, the estimated 4-year survival was 80%. Baseline CD4 and CD8 cell counts, hemoglobin, lymphocytes, sedimentation rates, diagnosis of AIDS, and fever were significant predictors of overall survival. Principal toxicities were pancreatitis and peripheral neuropathy; no new toxicities were seen with extended didanosine treatment that had not been observed in shorter-term studies. This 5-year follow-up shows that didanosine can be tolerated for > 4 years in some patients with advanced HIV infection and may have particular long-term utility in patients with moderately advanced immunosuppression. JF - The Journal of infectious diseases AU - Nguyen, B Y AU - Yarchoan, R AU - Wyvill, K M AU - Venzon, D J AU - Pluda, J M AU - Mitsuya, H AU - Broder, S AD - Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 1180 EP - 1189 VL - 171 IS - 5 SN - 0022-1899, 0022-1899 KW - Zidovudine KW - 4B9XT59T7S KW - Didanosine KW - K3GDH6OH08 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Zidovudine -- therapeutic use KW - Drug Therapy, Combination KW - Survival Rate KW - Humans KW - Adult KW - Disease Progression KW - Middle Aged KW - Follow-Up Studies KW - CD4 Lymphocyte Count KW - Male KW - Female KW - Didanosine -- therapeutic use KW - HIV Infections -- immunology KW - HIV Infections -- drug therapy KW - Didanosine -- administration & dosage KW - HIV Infections -- mortality KW - Didanosine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77285283?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+infectious+diseases&rft.atitle=Five-year+follow-up+of+a+phase+I+study+of+didanosine+in+patients+with+advanced+human+immunodeficiency+virus+infection.&rft.au=Nguyen%2C+B+Y%3BYarchoan%2C+R%3BWyvill%2C+K+M%3BVenzon%2C+D+J%3BPluda%2C+J+M%3BMitsuya%2C+H%3BBroder%2C+S&rft.aulast=Nguyen&rft.aufirst=B&rft.date=1995-05-01&rft.volume=171&rft.issue=5&rft.spage=1180&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+infectious+diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-22 N1 - Date created - 1995-06-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I and II trial of dose-intensified cyclophosphamide and GM-CSF in pediatric malignant brain tumors. AN - 77281239; 7749762 AB - Cyclophosphamide is commonly used in the treatment of children with malignant brain tumors. The purpose of this study was to develop a multicycle, high-dose intensity cyclophosphamide regimen with granulocyte-macrophage colony-stimulating factor (GM-CSF) and to assess its activity against malignant glioma and primitive neuroectodermal tumor (PNET). Twenty-three patients with brain tumors, including 15 with malignant glioma and six with PNET, were enrolled. Cyclophosphamide (1.8-2.25 g/m2/day for 2 days i.v.; total dose 3.6-4.5 g/m2) was administered and was followed by recombinant human GM-CSF (5 micrograms/kg/day s.c.) on days 3-11 or until the absolute granulocyte count reached 1.5 x 10(9)/L. With a total of 83 cycles administered, the mean dose intensity of cyclophosphamide ranged from 1.5 g/m2/week through cycle 2 (22 patients) to 0.8 g/m2/week through cycle 8 (two patients). No activity was seen against malignant glioma, and five of six patients with PNET had partial responses. The mean duration of a neutrophil count of < 0.5 x 10(9)/L was only 8 days; the platelet recovery was substantially longer. Fever during neutropenia occurred in 54 of 83 cycles. One patient died from transfusion-related graft-versus-host disease. A cyclophosphamide regimen equal to twice the dose intensity of that used in conventional therapy was administered. The regimen was active against PNET but inactive against malignant glioma. JF - Journal of pediatric hematology/oncology AU - Abrahamsen, T G AU - Lange, B J AU - Packer, R J AU - Venzon, D J AU - Allen, J C AU - Craig, C E AU - Patronas, N J AU - Katz, D A AU - Goldwein, J W AU - DeLaney, T F AD - Pediatric Branch, National Cancer Institute, Bethesda, MD, USA. Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 134 EP - 139 VL - 17 IS - 2 SN - 1077-4114, 1077-4114 KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Cyclophosphamide KW - 8N3DW7272P KW - Index Medicus KW - Granulocyte-Macrophage Colony-Stimulating Factor -- administration & dosage KW - Cyclophosphamide -- administration & dosage KW - Drug Administration Schedule KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Child KW - Adolescent KW - Male KW - Female KW - Child, Preschool KW - Neuroectodermal Tumors, Primitive -- drug therapy KW - Glioma -- drug therapy KW - Brain Neoplasms -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77281239?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+pediatric+hematology%2Foncology&rft.atitle=A+phase+I+and+II+trial+of+dose-intensified+cyclophosphamide+and+GM-CSF+in+pediatric+malignant+brain+tumors.&rft.au=Abrahamsen%2C+T+G%3BLange%2C+B+J%3BPacker%2C+R+J%3BVenzon%2C+D+J%3BAllen%2C+J+C%3BCraig%2C+C+E%3BPatronas%2C+N+J%3BKatz%2C+D+A%3BGoldwein%2C+J+W%3BDeLaney%2C+T+F&rft.aulast=Abrahamsen&rft.aufirst=T&rft.date=1995-05-01&rft.volume=17&rft.issue=2&rft.spage=134&rft.isbn=&rft.btitle=&rft.title=Journal+of+pediatric+hematology%2Foncology&rft.issn=10774114&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-20 N1 - Date created - 1995-06-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Minimal basal activity and lack of metal-induced activation of the metallothionein gene correlates with lobe-specific sensitivity to the carcinogenic effects of cadmium in the rat prostate. AN - 77276963; 7747280 AB - Metallothionein (MT), a high-affinity metal-binding protein, is known to detoxicate cadmium and may play an important role in cadmium carcinogenesis. In the rat, the ventral lobe of the prostate is sensitive to cadmium carcinogenesis, while the dorsolateral lobe is refractory. The possibility exists that the basis of this lobe-specific sensitivity may lie in the expression of the MT gene. Thus, the expression of the MT gene in lobes of the rat prostate was studied and, for comparative purposes, the expression of the MT gene in the liver, a tissue with well-defined high activity, was also assessed. MT gene expression was determined using a cDNA probe specific for MT-I, oligonucleotide probes specific for MT-I and MT-II, and an assay for cadmium-binding protein capacity. Basal levels of MT-I mRNA and cadmium-binding protein were much less in the ventral prostate than in the liver or dorsolateral prostate. Cadmium, given at a dose known to induce tumors of the ventral prostate (2.5 mumol/kg, sc), did not result in an increase in MT gene expression in the ventral prostate, as assessed by cadmium-binding protein levels or MT-I mRNA, over 72 hr. Small elevations of cadmium-binding protein capacity were detected at high doses of cadmium (25 and 40 mumol/kg) in the ventral prostate but no corresponding increases in MT mRNA were seen. In sharp contrast, hepatic MT gene expression was highly activated throughout the dosage range. Dose-response analysis 24 hr after cadmium administration (0.25 to 40 mumol/kg, sc) showed that MT-I and MT-II mRNA levels were increased in liver in a dose-dependent manner, while no evidence was found for MT gene activation in ventral prostate. In the dorsolateral prostate the high basal activity of the MT gene was shown, as assessed by MT-I and MT-II mRNA levels, which was not further elevated by cadmium treatments. Cadmium accumulation was much lower in the ventral prostate than in the liver. However, levels of cadmium that were sufficient to activate the hepatic MT gene had, in fact, reached the ventral prostate. Thus, the poor basal expression and lack of activation of the MT gene within the ventral lobe of the rat prostate may be the genetic basis to this tissue's sensitivity to the carcinogenic effects of cadmium. JF - Toxicology and applied pharmacology AU - Coogan, T P AU - Shiraishi, N AU - Waalkes, M P AD - Inorganic Carcinogenesis Section, National Cancer Institute, Frederick, Maryland 21702-1201, USA. Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 164 EP - 173 VL - 132 IS - 1 SN - 0041-008X, 0041-008X KW - Carcinogens KW - 0 KW - Chlorides KW - RNA, Messenger KW - Cadmium KW - 00BH33GNGH KW - Metallothionein KW - 9038-94-2 KW - Cadmium Chloride KW - J6K4F9V3BA KW - Index Medicus KW - Animals KW - Prostatic Neoplasms -- chemically induced KW - Liver -- metabolism KW - Organ Specificity KW - Transcriptional Activation KW - RNA, Messenger -- biosynthesis KW - Rats KW - Base Sequence KW - Rats, Wistar KW - Molecular Sequence Data KW - Blotting, Northern -- methods KW - Gene Expression Regulation -- drug effects KW - Male KW - Chlorides -- toxicity KW - Prostate -- drug effects KW - Metallothionein -- biosynthesis KW - Prostate -- anatomy & histology KW - Prostate -- metabolism KW - Carcinogens -- toxicity KW - Cadmium -- toxicity KW - Metallothionein -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77276963?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Minimal+basal+activity+and+lack+of+metal-induced+activation+of+the+metallothionein+gene+correlates+with+lobe-specific+sensitivity+to+the+carcinogenic+effects+of+cadmium+in+the+rat+prostate.&rft.au=Coogan%2C+T+P%3BShiraishi%2C+N%3BWaalkes%2C+M+P&rft.aulast=Coogan&rft.aufirst=T&rft.date=1995-05-01&rft.volume=132&rft.issue=1&rft.spage=164&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 - 1995-06-14 N1 - Date created - 1995-06-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An analysis of forty-two Wegener's granulomatosis patients treated with methotrexate and prednisone. AN - 77269780; 7748215 AB - To determine the efficacy of low-dose methotrexate (MTX) plus prednisone in the treatment of Wegener's granulomatosis (WG). An open-label study of weekly low-dose MTX plus prednisone for the treatment of WG was performed. Forty-two patients who did not have immediately life-threatening disease were enrolled into the study. Outcome was determined by clinical characteristics and pathologic, laboratory, and radiographic findings. Weekly administration of MTX and prednisone resulted in remission of disease in 30 of the 42 patients (71%). The median time to remission was 4.2 months. The estimated median time to relapse for all patients in whom remission was achieved was 29 months. Eight patients who had relapses were treated with a second course of MTX plus prednisone, and a second remission was induced in 6 of the 8 (75%). Weekly low-dose MTX was shown in this study to be an acceptable alternative form of therapy for selected patients with WG who do not have immediately life-threatening disease or who have developed serious cyclophosphamide-associated toxicity. JF - Arthritis and rheumatism AU - Sneller, M C AU - Hoffman, G S AU - Talar-Williams, C AU - Kerr, G S AU - Hallahan, C W AU - Fauci, A S AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 608 EP - 613 VL - 38 IS - 5 SN - 0004-3591, 0004-3591 KW - Prednisone KW - VB0R961HZT KW - Methotrexate KW - YL5FZ2Y5U1 KW - Abridged Index Medicus KW - Index Medicus KW - Administration, Oral KW - Opportunistic Infections -- epidemiology KW - Drug Administration Schedule KW - Humans KW - Aged KW - Recurrence KW - Drug Therapy, Combination KW - Prospective Studies KW - Adult KW - Follow-Up Studies KW - Middle Aged KW - Time Factors KW - Female KW - Male KW - Remission Induction KW - Prednisone -- adverse effects KW - Methotrexate -- adverse effects KW - Granulomatosis with Polyangiitis -- complications KW - Granulomatosis with Polyangiitis -- mortality KW - Methotrexate -- administration & dosage KW - Prednisone -- administration & dosage KW - Granulomatosis with Polyangiitis -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77269780?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=An+analysis+of+forty-two+Wegener%27s+granulomatosis+patients+treated+with+methotrexate+and+prednisone.&rft.au=Sneller%2C+M+C%3BHoffman%2C+G+S%3BTalar-Williams%2C+C%3BKerr%2C+G+S%3BHallahan%2C+C+W%3BFauci%2C+A+S&rft.aulast=Sneller&rft.aufirst=M&rft.date=1995-05-01&rft.volume=38&rft.issue=5&rft.spage=608&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 - 1995-06-12 N1 - Date created - 1995-06-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Including narcotic addiction treatment in an office-based practice. AN - 77267254; 7745777 JF - JAMA AU - Cooper, J R AD - Division of Clinical and Services Research, National Institute on Drug Abuse, Rockville, Md. 20857, USA. PY - 1995 SP - 1619 EP - 1620 VL - 273 IS - 20 SN - 0098-7484, 0098-7484 KW - Abridged Index Medicus KW - Index Medicus KW - United States KW - Humans KW - Drug and Narcotic Control KW - Private Practice -- legislation & jurisprudence KW - Opioid-Related Disorders -- therapy KW - Legislation, Medical UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77267254?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=JAMA&rft.atitle=Including+narcotic+addiction+treatment+in+an+office-based+practice.&rft.au=Cooper%2C+J+R&rft.aulast=Cooper&rft.aufirst=J&rft.date=1995-05-01&rft.volume=273&rft.issue=20&rft.spage=1619&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-14 N1 - Date created - 1995-06-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of the mutagenicity and mutagen specificity of ethylenimine with triethylenemelamine in the ad-3 region of heterokaryon 12 of Neurospora crassa. AN - 77256593; 7739603 AB - Studies have been performed to compare the mutagenicity and mutagenic specificity of the trifunctional alkylating agent, triethylenemelamine (TEM), and a closely related monofunctional agent, ethylenimine (EI), in the adenine-3 (ad-3) region of a 2-component heterokaryon (H-12) of Neurospora crassa. The primary objective of our studies was to characterize the genetic damage produced by each agent with regard to (1) mutagenic potency, and (2) the spectrum of specific-locus mutations induced in a lower eukaryotic organism. As in higher eukaryotes, specific-locus mutations in the ad-3 region of H-12 result from gene/point mutations, multilocus deletion mutations, and multiple-locus mutations. Specific-locus mutations resulting from gene/point mutation and multilocus deletion mutation can be detected in higher eukaryotes, but multiple-locus mutations can be detected only with difficulty or not at all. Our experiments with the ad-3 forward-mutation assay have demonstrated that TEM is a strong mutagen (maximum forward-mutation frequency between 100 and 1000 ad-3 mutations per 10(6) survivors) and EI is a moderate mutagen (maximum forward-mutation frequency between 10 and 100 ad-3 mutations per 10(6) survivors) for the induction of specific-locus mutations in the ad-3 region. Classical genetic tests were used to identify the different genotypic classes and subclasses among the EI- and TEM-induced ad-3 mutations from each experiment. The overall data base demonstrates that both EI- and TEM-induced ad-3 mutations result predominantly from gene/point mutations at the ad-3A and ad-3B loci (97.3% and 95.5%, respectively), and infrequently from multilocus deletion mutations (2.7% and 4.5%, respectively). Heterokaryon tests for allelic complementation on TEM- and EI-induced ad-3B mutations, however, have revealed a difference between the percentages showing allelic complementation (63.1% and 40.9%, respectively). Based on the specific revertibility of complementing and noncomplementing ad-3B mutations induced by other agents, this difference in the percentages of ad-3B mutations showing allelic complementation results from a difference between the spectrum of genetic alterations at the molecular level. In addition, comparison of the ratio of TEM-induced ad-3A and ad-3B mutations with those induced by EI has revealed a difference between the ad-3B/ad-3A ratios. Additional comparisons are made of the mutagenic effects of TEM and EI with those of other chemical mutagens and carcinogens in the ad-3 specific-locus assay in Neurospora. JF - Mutation research AU - de Serres, F J AU - Malling, H V AU - Ong, T M AD - Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709-2233, USA. Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 193 EP - 205 VL - 328 IS - 2 SN - 0027-5107, 0027-5107 KW - Aziridines KW - 0 KW - DNA, Fungal KW - Mutagens KW - aziridine KW - 54P5FEX9FH KW - Triethylenemelamine KW - F7IY6HZG9D KW - Adenine KW - JAC85A2161 KW - Index Medicus KW - Mutagenicity Tests KW - Genes, Fungal -- drug effects KW - Point Mutation KW - Genetic Complementation Test KW - DNA, Fungal -- drug effects KW - Genes, Lethal KW - Molecular Weight KW - Structure-Activity Relationship KW - Sequence Deletion KW - Triethylenemelamine -- toxicity KW - Neurospora crassa -- genetics KW - Mutagenesis, Site-Directed KW - Aziridines -- chemistry KW - Aziridines -- toxicity KW - Triethylenemelamine -- chemistry KW - Neurospora crassa -- drug effects KW - Mutagens -- toxicity KW - Mutagens -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77256593?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Comparison+of+the+mutagenicity+and+mutagen+specificity+of+ethylenimine+with+triethylenemelamine+in+the+ad-3+region+of+heterokaryon+12+of+Neurospora+crassa.&rft.au=de+Serres%2C+F+J%3BMalling%2C+H+V%3BOng%2C+T+M&rft.aulast=de+Serres&rft.aufirst=F&rft.date=1995-05-01&rft.volume=328&rft.issue=2&rft.spage=193&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 - 1995-06-07 N1 - Date created - 1995-06-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Decoying the cap- mRNA degradation system by a double-stranded RNA virus and poly(A)- mRNA surveillance by a yeast antiviral system. AN - 77256409; 7739557 AB - The major coat protein of the L-A double-stranded RNA virus of Saccharomyces cerevisiae covalently binds m7 GMP from 5' capped mRNAs in vitro. We show that this cap binding also occurs in vivo and that, while this activity is required for expression of viral information (killer toxin mRNA level and toxin production) in a wild-type strain, this requirement is suppressed by deletion of SKI1/XRN1/SEP1. We propose that the virus creates decapped cellular mRNAs to decoy the 5'-->3' exoribonuclease specific for cap- RNA encoded by XRN1. The SKI2 antiviral gene represses the copy numbers of the L-A and L-BC viruses and the 20S RNA replicon, apparently by specifically blocking translation of viral RNA. We show that SKI2, SKI3, and SKI8 inhibit translation of electroporated luciferase and beta-glucuronidase mRNAs in vivo, but only if they lack the 3' poly(A) structure. Thus, L-A decoys the SKI1/XRN1/SEP1 exonuclease directed at 5' uncapped ends, but translation of the L-A poly(A)- mRNA is repressed by Ski2,3,8p. The SKI2-SKI3-SKI8 system is more effective against cap+ poly(A)- mRNA, suggesting a (nonessential) role in blocking translation of fragmented cellular mRNAs. JF - Molecular and cellular biology AU - Masison, D C AU - Blanc, A AU - Ribas, J C AU - Carroll, K AU - Sonenberg, N AU - Wickner, R B AD - Section on Genetics of Simple Eukaryotes, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA. Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 2763 EP - 2771 VL - 15 IS - 5 SN - 0270-7306, 0270-7306 KW - Fungal Proteins KW - 0 KW - Killer Factors, Yeast KW - Mycotoxins KW - RNA Caps KW - RNA, Double-Stranded KW - RNA, Fungal KW - RNA, Messenger KW - Saccharomyces cerevisiae Proteins KW - Deoxyribonucleases KW - EC 3.1.- KW - Exoribonucleases KW - XRN1 protein, S cerevisiae KW - EC 3.1.11.- KW - Index Medicus KW - Protein Biosynthesis KW - Fungal Proteins -- metabolism KW - Mycotoxins -- genetics KW - Genes, Fungal KW - Deoxyribonucleases -- genetics KW - Suppression, Genetic KW - Capsid -- metabolism KW - Fungal Proteins -- genetics KW - Deoxyribonucleases -- metabolism KW - Models, Biological KW - RNA, Fungal -- genetics KW - RNA, Double-Stranded -- genetics KW - RNA, Fungal -- metabolism KW - Saccharomyces cerevisiae -- virology KW - RNA Caps -- metabolism KW - RNA, Messenger -- genetics KW - RNA, Double-Stranded -- metabolism KW - Saccharomyces cerevisiae -- genetics KW - RNA Viruses -- metabolism KW - Saccharomyces cerevisiae -- metabolism KW - RNA, Messenger -- metabolism KW - RNA Caps -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77256409?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Decoying+the+cap-+mRNA+degradation+system+by+a+double-stranded+RNA+virus+and+poly%28A%29-+mRNA+surveillance+by+a+yeast+antiviral+system.&rft.au=Masison%2C+D+C%3BBlanc%2C+A%3BRibas%2C+J+C%3BCarroll%2C+K%3BSonenberg%2C+N%3BWickner%2C+R+B&rft.aulast=Masison&rft.aufirst=D&rft.date=1995-05-01&rft.volume=15&rft.issue=5&rft.spage=2763&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 - 1995-06-02 N1 - Date created - 1995-06-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Bacteriol. 1968 Nov;96(5):1664-71 [5726307] Mol Cell Biol. 1995 May;15(5):2772-81 [7739558] J Biol Chem. 1976 Aug 25;251(16):5043-53 [821947] Nucleic Acids Res. 1976 Oct;3(10):2427-36 [792814] J Bacteriol. 1978 Dec;136(3):1002-7 [363683] Proc Natl Acad Sci U S A. 1978 Oct;75(10):4886-90 [283399] J Biol Chem. 1980 Apr 10;255(7):3080-5 [6244307] Proc Natl Acad Sci U S A. 1980 Jan;77(1):527-30 [6987655] Cell. 1980 Apr;19(4):923-33 [6991125] Cell. 1981 Mar;23(3):847-58 [6261960] Proc Natl Acad Sci U S A. 1982 Aug;79(15):4706-8 [6750608] Cell. 1982 Dec;31(2 Pt 1):429-41 [6819084] Nucleic Acids Res. 1983 Sep 24;11(18):6409-18 [6312422] Mol Cell Biol. 1984 Jan;4(1):92-100 [6366515] Mol Cell Biol. 1984 Apr;4(4):761-70 [6371496] J Virol. 1984 Oct;52(1):215-22 [6481853] Proc Natl Acad Sci U S A. 1986 Jun;83(12):4433-7 [3520572] J Virol. 1986 Oct;60(1):307-11 [3018296] Arch Biochem Biophys. 1987 Feb 1;252(2):339-47 [3545079] Virology. 1987 Mar;157(1):252-6 [3029964] Mol Cell Biol. 1987 Jan;7(1):420-6 [3550421] J Biol Chem. 1987 May 15;262(14):6785-7 [3553191] Genetics. 1987 Nov;117(3):399-408 [3319767] J Virol. 1988 Aug;62(8):2636-43 [2839690] Nature. 1988 Jul 28;334(6180):320-5 [2839775] Cell. 1988 Nov 18;55(4):663-71 [2460245] J Biol Chem. 1989 Apr 25;264(12):6716-23 [2651431] Mol Cell Biol. 1989 Mar;9(3):1100-8 [2657386] Yeast. 1989 May-Jun;5(3):149-58 [2660461] Cell. 1989 Sep 8;58(5):857-67 [2673535] Virology. 1989 Dec;173(2):408-14 [2596021] Cell. 1990 Jan 26;60(2):307-17 [2404612] Cell. 1990 Jul 13;62(1):15-24 [1973075] Gene. 1990 Jul 16;91(2):151-8 [1976572] Proc Natl Acad Sci U S A. 1990 Oct;87(19):7628-32 [1699230] J Virol. 1991 Jan;65(1):155-61 [1985195] Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):174-8 [1986362] Genetics. 1990 Dec;126(4):799-812 [2076815] Mol Cell Biol. 1991 May;11(5):2593-608 [1840632] Nucleic Acids Res. 1991 Apr 11;19(7):1385-91 [2027746] J Biol Chem. 1991 Jul 5;266(19):12779-83 [1648104] Mol Gen Genet. 1991 Aug;228(1-2):258-64 [1886610] Nucleic Acids Res. 1991 Sep 25;19(18):4949-53 [1656383] Genes Dev. 1991 Nov;5(11):2108-16 [1682219] Mol Microbiol. 1991 Oct;5(10):2339-43 [1724277] Mol Cell Biol. 1992 Aug;12(8):3390-8 [1630453] J Virol. 1992 Oct;66(10):6143-54 [1527853] Gene. 1992 Oct 12;120(1):51-7 [1398123] Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9612-6 [1384058] Annu Rev Microbiol. 1992;46:347-75 [1444259] Yeast. 1993 Jan;9(1):43-51 [8442386] Yeast. 1992 Dec;8(12):1007-14 [1284101] Yeast. 1993 Mar;9(3):251-66 [8488726] Mol Cell Biol. 1993 Jul;13(7):4331-41 [8321235] Mol Cell Biol. 1993 Aug;13(8):4826-35 [8336719] Mol Cell Biol. 1994 Apr;14(4):2664-74 [8139566] Nature. 1994 Aug 18;370(6490):578-81 [8052314] J Virol. 1974 Jun;13(6):1331-7 [4833611] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Factors mediating the interactions between epidermal and dermal cells in skin grafts that might be important for hair follicle development. AN - 77255911; 7738378 JF - The Journal of investigative dermatology AU - Kartasova, T AU - Scandurro, A B AU - Denning, M F AU - Wirth, P J AU - Yuspa, S H AU - Lichti, U AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 21S EP - 22S VL - 104 IS - 5 Suppl SN - 0022-202X, 0022-202X KW - Growth Substances KW - 0 KW - Index Medicus KW - Animals KW - 3T3 Cells KW - Melanocytes -- metabolism KW - Mice, Inbred C57BL KW - Keratinocytes -- cytology KW - Mice KW - Melanocytes -- cytology KW - Keratinocytes -- metabolism KW - Mice, Inbred BALB C KW - Growth Substances -- metabolism KW - Cell Line KW - Fibroblasts KW - Cell Division KW - Hair -- growth & development KW - Skin -- metabolism KW - Hair -- metabolism KW - Epidermis -- cytology KW - Epidermis -- metabolism KW - Skin -- cytology KW - Skin Transplantation -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77255911?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+investigative+dermatology&rft.atitle=Factors+mediating+the+interactions+between+epidermal+and+dermal+cells+in+skin+grafts+that+might+be+important+for+hair+follicle+development.&rft.au=Kartasova%2C+T%3BScandurro%2C+A+B%3BDenning%2C+M+F%3BWirth%2C+P+J%3BYuspa%2C+S+H%3BLichti%2C+U&rft.aulast=Kartasova&rft.aufirst=T&rft.date=1995-05-01&rft.volume=104&rft.issue=5+Suppl&rft.spage=21S&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+investigative+dermatology&rft.issn=0022202X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-08 N1 - Date created - 1995-06-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Generation of a drug resistance profile by quantitation of mdr-1/P-glycoprotein in the cell lines of the National Cancer Institute Anticancer Drug Screen. AN - 77254980; 7738186 AB - Identifying new chemotherapeutic agents and characterizing mechanisms of resistance may improve cancer treatment. The Anticancer Drug Screen of the National Cancer Institute uses 60 cell lines to identify new agents. Expression of mdr-1/P-glycoprotein was measured by quantitative PCR. Expression was detected in 39 cell lines; the highest levels were in renal and colon carcinomas. Expression was also detected in all melanomas and central nervous system tumors, but in only one ovarian carcinoma and one leukemia cell line. Using a modified version of the COMPARE program, a high correlation was found between expression of mdr-1 and cellular resistance to a large number of compounds. Evidence that these compounds are P-glycoprotein substrates includes: (a) enhancement of cytotoxicity by verapamil; (b) demonstration of cross-resistance in a multidrug-resistant cell line, (c) ability to antagonize P-glycoprotein, increasing vinblastine accumulation by decreasing efflux; and (d) inhibition of photoaffinity labeling by azidopine. Identification of many heretofore unrecognized compounds as substrates indicates that P-glycoprotein has a broader substrate specificity than previously recognized. This study confirms the validity of this novel approach and provides the basis for similar studies examining a diverse group of gene products, including other resistance mechanisms, putative drug targets, and genes involved in the cell cycle and apoptosis. JF - The Journal of clinical investigation AU - Alvarez, M AU - Paull, K AU - Monks, A AU - Hose, C AU - Lee, J S AU - Weinstein, J AU - Grever, M AU - Bates, S AU - Fojo, T AD - Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 2205 EP - 2214 VL - 95 IS - 5 SN - 0021-9738, 0021-9738 KW - mdr-1 KW - Antineoplastic Agents KW - 0 KW - P-Glycoprotein KW - Verapamil KW - CJ0O37KU29 KW - Abridged Index Medicus KW - Index Medicus KW - United States KW - Drug Screening Assays, Antitumor KW - Ovarian Neoplasms KW - Humans KW - Central Nervous System Neoplasms KW - Verapamil -- pharmacology KW - Melanoma KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Kidney Neoplasms KW - Lung Neoplasms KW - National Institutes of Health (U.S.) KW - Colonic Neoplasms KW - Cell Line KW - Female KW - P-Glycoprotein -- analysis KW - Gene Expression KW - Antineoplastic Agents -- toxicity KW - P-Glycoprotein -- biosynthesis KW - Drug Resistance, Multiple -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77254980?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+investigation&rft.atitle=Generation+of+a+drug+resistance+profile+by+quantitation+of+mdr-1%2FP-glycoprotein+in+the+cell+lines+of+the+National+Cancer+Institute+Anticancer+Drug+Screen.&rft.au=Alvarez%2C+M%3BPaull%2C+K%3BMonks%2C+A%3BHose%2C+C%3BLee%2C+J+S%3BWeinstein%2C+J%3BGrever%2C+M%3BBates%2C+S%3BFojo%2C+T&rft.aulast=Alvarez&rft.aufirst=M&rft.date=1995-05-01&rft.volume=95&rft.issue=5&rft.spage=2205&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+investigation&rft.issn=00219738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-05 N1 - Date created - 1995-06-05 N1 - Date revised - 2017-01-13 N1 - Gene symbol - mdr-1 N1 - SuppNotes - Cited By: Mol Pharmacol. 1988 Apr;33(4):454-62 [3162758] J Clin Oncol. 1987 Dec;5(12):1922-7 [3681376] Mol Pharmacol. 1989 Jan;35(1):105-15 [2563302] J Natl Cancer Inst. 1989 Jun 7;81(11):844-9 [2724349] Br J Haematol. 1989 May;72(1):40-4 [2736241] J Natl Cancer Inst. 1989 Jul 19;81(14):1088-92 [2738938] J Biol Chem. 1989 Aug 25;264(24):14376-81 [2569468] Cancer Res. 1989 Sep 15;49(18):5062-5 [2766278] Br J Cancer. 1989 Dec;60(6):815-8 [2574987] Int J Cancer. 1990 Feb 15;45(2):263-8 [1968051] J Natl Cancer Inst. 1990 Jul 4;82(13):1107-12 [2359136] Cancer. 1990 Sep 1;66(5):868-73 [1974821] Biochemistry. 1990 Nov 13;29(45):10351-6 [1979752] J Clin Oncol. 1991 Jan;9(1):17-24 [1670642] J Natl Cancer Inst. 1991 Jun 5;83(11):757-66 [2041050] Blood. 1991 Aug 1;78(3):586-92 [1859877] Int J Cancer. 1991 Nov 11;49(5):696-703 [1682280] N Engl J Med. 1991 Dec 5;325(23):1608-14 [1682809] Blood. 1992 Jan 15;79(2):473-6 [1370388] Cancer Res. 1992 Jun 1;52(11):3029-34 [1350507] Cancer Res. 1992 Jul 15;52(14):3892-900 [1617665] Leukemia. 1992 Sep;6(9):879-85 [1355575] J Cell Physiol. 1976 May;88(1):23-31 [57118] Biochim Biophys Acta. 1976 Nov 11;455(1):152-62 [990323] Cancer Res. 1981 May;41(5):1967-72 [7214365] Cancer Res. 1983 May;43(5):2267-72 [6831450] Cancer Res. 1985 Jul;45(7):3002-7 [4005839] Proc Natl Acad Sci U S A. 1987 Jan;84(1):265-9 [2432605] J Natl Cancer Inst. 1989 Jan 18;81(2):116-24 [2562856] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Combination therapy with interferon alfa-2a and interleukin-2 for the treatment of metastatic cancer. AN - 77253488; 7738617 AB - Here we report the long-term follow-up evaluation of a phase I/II study of toxicity and response of combination interferon alfa-2a (IFN alpha) and interleukin-2 (IL-2) in patients with metastatic cancer. From November 1987 through October 1990, 189 patients were treated with 379 courses. IFN alpha (3 x 10(6) U/m2) was administered three times per day as an intravenous (IV) bolus with IV IL-2 2.6 x 10(6) IU/m2 (six patients, group 1), 7.8 x 10(6) IU/m2 (32 patients, group 2), or 11.7 x 10(6) IU/m2 (26 patients, group 3). Subsequently, IFN alpha dose was escalated to 6 x 10(6) U/m2 plus IL-2 11.7 x 10(6) IU/m2 (22 patients, group 4). Two further dosage schedules of IL-2 were tested at 7.8 x 10(6) IU/m2 (29 patients, group 5) and 15.6 x 10(6) IU/m2 (74 patients, group 6); however, because of IFN alpha-related toxicity, these two groups received IFN alpha once per day (6 x 10(6) U/m2). A treatment course consisted of two cycles (maximum, 15 doses per cycle) separated by a 10-day interval. All patients were assessable for response: 82 patients had melanoma, 75 renal cell carcinoma (RCC), and 16 colorectal cancer. There were two treatment-related deaths. The objective response rate was 23% (43 patients). Response rates were 17%, 19%, 19%, 32%, 41%, and 16%, respectively, for groups 1 through 6. Ten responses are still ongoing (nine in RCC patients) at 57 to 74 months, and 21 patients are alive, for an overall 5-year survival rate of 11%. The median potential follow-up period was 65 months. Although a significantly higher response rate was noted for group 4 (highest dose of IFN alpha three times per day), no benefit for survival and increased toxicity were noted in this group. Based on these findings, we conclude that further studies of this combination treatment are not warranted. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Marincola, F M AU - White, D E AU - Wise, A P AU - Rosenberg, S A AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 1110 EP - 1122 VL - 13 IS - 5 SN - 0732-183X, 0732-183X KW - Interferon-alpha KW - 0 KW - Interleukin-2 KW - Recombinant Proteins KW - interferon alfa-2a KW - 47RRR83SK7 KW - Index Medicus KW - Kidney Neoplasms -- pathology KW - Drug Administration Schedule KW - Carcinoma, Renal Cell -- therapy KW - Melanoma -- mortality KW - Melanoma -- secondary KW - Lung Neoplasms -- secondary KW - Humans KW - Lung Neoplasms -- therapy KW - Aged KW - Child KW - Adult KW - Carcinoma, Renal Cell -- secondary KW - Treatment Outcome KW - Carcinoma, Renal Cell -- mortality KW - Middle Aged KW - Follow-Up Studies KW - Melanoma -- therapy KW - Adolescent KW - Male KW - Female KW - Survival Analysis KW - Interleukin-2 -- adverse effects KW - Interleukin-2 -- administration & dosage KW - Interferon-alpha -- adverse effects KW - Interferon-alpha -- administration & dosage KW - Immunotherapy -- adverse effects KW - Neoplasm Metastasis -- prevention & control KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77253488?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Combination+therapy+with+interferon+alfa-2a+and+interleukin-2+for+the+treatment+of+metastatic+cancer.&rft.au=Marincola%2C+F+M%3BWhite%2C+D+E%3BWise%2C+A+P%3BRosenberg%2C+S+A&rft.aulast=Marincola&rft.aufirst=F&rft.date=1995-05-01&rft.volume=13&rft.issue=5&rft.spage=1110&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 - 1995-06-05 N1 - Date created - 1995-06-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hair follicle development and hair growth from defined cell populations grafted onto nude mice. AN - 77252802; 7738395 JF - The Journal of investigative dermatology AU - Lichti, U AU - Scandurro, A B AU - Kartasova, T AU - Rubin, J S AU - LaRochelle, W AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 43S EP - 44S VL - 104 IS - 5 Suppl SN - 0022-202X, 0022-202X KW - Culture Media KW - 0 KW - Fgf7 protein, mouse KW - Fgf7 protein, rat KW - Fibroblast Growth Factor 10 KW - Growth Substances KW - Fibroblast Growth Factor 7 KW - 126469-10-1 KW - Fibroblast Growth Factors KW - 62031-54-3 KW - Hepatocyte Growth Factor KW - 67256-21-7 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Epidermis -- cytology KW - Hepatocyte Growth Factor -- metabolism KW - Mice, Nude KW - Fibroblasts -- cytology KW - Mice KW - Growth Substances -- metabolism KW - Rats KW - Cells, Cultured KW - Skin -- cytology KW - Cell Line KW - Hair -- transplantation KW - Hair -- growth & development KW - Hair -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77252802?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+investigative+dermatology&rft.atitle=Hair+follicle+development+and+hair+growth+from+defined+cell+populations+grafted+onto+nude+mice.&rft.au=Lichti%2C+U%3BScandurro%2C+A+B%3BKartasova%2C+T%3BRubin%2C+J+S%3BLaRochelle%2C+W%3BYuspa%2C+S+H&rft.aulast=Lichti&rft.aufirst=U&rft.date=1995-05-01&rft.volume=104&rft.issue=5+Suppl&rft.spage=43S&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+investigative+dermatology&rft.issn=0022202X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-08 N1 - Date created - 1995-06-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of chloride or glucose on the incidence of lactate-induced panic attacks. AN - 77240973; 7726308 AB - This study was designed to test the hypothesis that the addition of chloride to a lactate infusion would reduce the frequency of panic attacks. The subjects included 14 healthy volunteers and 20 patients meeting the DSM-IV criteria for panic disorder. All subjects received an infusion of lactate dissolved in 0.9% sodium chloride and an infusion of lactate dissolved in 5% dextrose in water on separate days in a random-order, double-blind procedure. Blood pressure, heart rate, and panic symptoms were measured at 3-minute intervals during the infusions. The occurrence of panic attacks was ascertained through the subjects' reports of losing control, panicking, or "going crazy" and the presence of at least four Research Diagnostic Criteria symptoms of a panic attack. Fifteen (75%) of the patients with panic disorder reported a panic attack during one of the infusions or both; no healthy volunteers had a panic attack. The patients with panic disorder were significantly more likely to have a panic attack during the lactate/sodium chloride infusion than during the infusion of lactate/5% dextrose in water. The number of panic attack symptoms reported at 3-minute intervals did not differ between the two types of infusion. The coadministration of glucose resulted in a reduced sensitivity to the panicogenic effects of lactate. The hypothesis that adding chloride to the infusion would reduce the frequency of lactate-induced panic attacks was not supported. JF - The American journal of psychiatry AU - George, D T AU - Lindquist, T AU - Nutt, D J AU - Ragan, P W AU - Alim, T AU - McFarlane, V AU - Leviss, J AU - Eckardt, M J AU - Linnoila, M AD - Laboratory of Clinical Studies, NIAAA, Bethesda, MD 20892, USA. Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 692 EP - 697 VL - 152 IS - 5 SN - 0002-953X, 0002-953X KW - Blood Glucose KW - 0 KW - Lactates KW - Lactic Acid KW - 33X04XA5AT KW - Sodium Chloride KW - 451W47IQ8X KW - Glucose KW - IY9XDZ35W2 KW - Abridged Index Medicus KW - Index Medicus KW - Heart Rate -- drug effects KW - Psychiatric Status Rating Scales KW - Infusions, Intravenous KW - Double-Blind Method KW - Humans KW - Incidence KW - Blood Pressure -- drug effects KW - Blood Glucose -- analysis KW - Male KW - Female KW - Panic Disorder -- chemically induced KW - Lactates -- pharmacology KW - Panic Disorder -- psychology KW - Panic Disorder -- epidemiology KW - Glucose -- pharmacology KW - Sodium Chloride -- administration & dosage KW - Sodium Chloride -- blood KW - Lactates -- administration & dosage KW - Glucose -- administration & dosage KW - Sodium Chloride -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77240973?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+psychiatry&rft.atitle=Effect+of+chloride+or+glucose+on+the+incidence+of+lactate-induced+panic+attacks.&rft.au=George%2C+D+T%3BLindquist%2C+T%3BNutt%2C+D+J%3BRagan%2C+P+W%3BAlim%2C+T%3BMcFarlane%2C+V%3BLeviss%2C+J%3BEckardt%2C+M+J%3BLinnoila%2C+M&rft.aulast=George&rft.aufirst=D&rft.date=1995-05-01&rft.volume=152&rft.issue=5&rft.spage=692&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+psychiatry&rft.issn=0002953X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-25 N1 - Date created - 1995-05-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo gene transfer into injured carotid arteries. Optimization and evaluation of acute toxicity. AN - 77238433; 7729028 AB - Adenoviral vectors are very attractive agents for use in in vivo arterial gene transfer. In a previous study, we demonstrated high-efficiency adenovirus-mediated gene transfer into medial smooth muscle cells of balloon-injured rat carotid arteries. We now further characterize this system by investigating the reproducibility of recombinant gene expression, the presence of acute adenovirus-associated toxicity in the vessel wall, and the optimal virus concentration for transduction. Balloon-injured rat carotid arteries were incubated with (1) an adenovirus expressing a beta-galactosidase gene (Av1LacZ4), (2) a related adenovirus without the recombinant gene (Addl312), or (3) control solutions. Recombinant gene expression was determined 3 days after gene transfer by measurement of beta-galactosidase activity in vessel extracts and by counting of smooth muscle cells in microscopic sections that were histochemically stained to detect recombinant beta-galactosidase activity. Adenovirus-associated toxicity was assessed in microscopic cross sections by counting of total smooth muscle cell nuclei in the media (to identify cell loss) and characterization of medial cellular infiltrates with histochemical stains for specific inflammatory cells (neutrophils, lymphocytes, macrophages, and monocytes). Maximum recombinant gene expression after incubation with Av1LacZ4 was produced by virus concentrations ranging from 2 x 10(10) to 5 x 10(10) plaque-forming units (pfu)/mL. Surprisingly, use of a higher concentration of Av1LacZ4 virus (1 x 10(11) pfu/mL) resulted in loss of recombinant gene expression. In addition, infusion of either Av1LacZ4 or Addl312 at 1 x 10(11) pfu/mL resulted in statistically significant decreases in medial smooth muscle cell number (53% decrease, P < 0.01 for Av1LacZ4; 39% decrease, P < .05 for Addl312) compared with vessels infused with control solution. This decrease in smooth muscle cell number was not present after the infusion of virus at lower concentrations. The number of neutrophils in vessel cross sections was significantly increased (fivefold; P < .05) after infusion of Av1LacZ4 at 1 x 10(11) pfu/mL compared with vessels infused with control solution. Lymphocytes, macrophages, and monocytes were present only in low numbers in all vessel cross sections and were not increased consequent to adenovirus infusion. This model of focal in vivo adenovirus-mediated gene transfer into the media of injured arteries is highly reproducible and allows high-level recombinant gene expression over a fairly narrow range of virus concentrations. Acute adenovirus-associated tissue toxicity, as demonstrated by medial smooth muscle cell loss and neutrophilic infiltrates, places an upper limit on virus concentration and associated recombinant gene expression and suggests the presence of a "window" of virus concentration in which either therapeutic or biological effects of recombinant genes can be studied in the absence of associated acute toxicity. JF - Circulation AU - Schulick, A H AU - Newman, K D AU - Virmani, R AU - Dichek, D A AD - Molecular Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md, USA. Y1 - 1995/05/01/ PY - 1995 DA - 1995 May 01 SP - 2407 EP - 2414 VL - 91 IS - 9 SN - 0009-7322, 0009-7322 KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - beta-Galactosidase -- genetics KW - beta-Galactosidase -- biosynthesis KW - Muscle, Smooth, Vascular -- enzymology KW - Muscle, Smooth, Vascular -- virology KW - Male KW - Gene Transfer Techniques KW - Genetic Vectors -- toxicity KW - Carotid Arteries -- virology KW - Carotid Arteries -- physiopathology KW - Adenoviridae -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77238433?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Circulation&rft.atitle=In+vivo+gene+transfer+into+injured+carotid+arteries.+Optimization+and+evaluation+of+acute+toxicity.&rft.au=Schulick%2C+A+H%3BNewman%2C+K+D%3BVirmani%2C+R%3BDichek%2C+D+A&rft.aulast=Schulick&rft.aufirst=A&rft.date=1995-05-01&rft.volume=91&rft.issue=9&rft.spage=2407&rft.isbn=&rft.btitle=&rft.title=Circulation&rft.issn=00097322&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-01 N1 - Date created - 1995-06-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Anti-IgM induces transforming growth factor-beta sensitivity in a human B-lymphoma cell line: inhibition of growth is associated with a downregulation of mutant p53. AN - 77234241; 7727777 AB - We wished to examine the role of transforming growth factor-beta (TGF-beta) in the regulation of human lymphoma cell growth. The RL cell line is an immunoglobulin M (IgM)+, IgD+ B lymphoma cell line, which does not constitutively express receptors for TGF-beta, and thus has lost the ability to respond to the inhibitory effects of TGF-beta. We demonstrate here that anti-Ig antibodies can efficiently upregulate the expression of TGF-beta receptors and promote sensitivity to growth inhibition by TGF-beta. Furthermore, because TGF-beta has been shown to function in late G1 of the cell cycle, we examined the ability of TGF-beta to modulate two tumor suppressor proteins known to be critical regulators of the G1/S transition, Rb and p53. Rb is a 105- to 110-kD phosphoprotein, which has been shown to maintain its growth suppressive function when it is found in the hypophosphorylated state. Wild-type p53 is a 53-kD phosphoprotein that appears to be important in preventing cell-cycle progression and promoting apoptosis in cells with DNA damage, whereas mutant p53 can overcome those functions. We show here that TGF-beta treatment of phorbol myristate acetate (PMA) or anti-Ig-activated RL cells results in growth inhibition through a dual effect on Rb and mutant p53. After TGF-beta treatment, we observe a predominance of Rb in the hypophosphorylated, growth suppressive form. In addition, we show a decrease in levels of mRNA and protein for mutant p53. We also show that, although these changes are sufficient to halt progression through the cell cycle, the cells do not appear to undergo extensive programmed cell death following 72 hours of TGF-beta treatment. Thus, although these lymphoma cells maintain the capacity to be negatively growth regulated by TGF-beta, the ability of TGF-beta to induce apoptosis must be independently controlled. JF - Blood AU - Beckwith, M AU - Ruscetti, F W AU - Sing, G K AU - Urba, W J AU - Longo, D L AD - Biological Carcinogenesis Development Program, Inc/DynCorp, National Cancer Institute, Frederick, MD 21702, USA. Y1 - 1995/05/01/ PY - 1995 DA - 1995 May 01 SP - 2461 EP - 2470 VL - 85 IS - 9 SN - 0006-4971, 0006-4971 KW - Antibodies, Anti-Idiotypic KW - 0 KW - Immunoglobulin M KW - Neoplasm Proteins KW - Receptors, Antigen, B-Cell KW - Receptors, Transforming Growth Factor beta KW - Retinoblastoma Protein KW - Transforming Growth Factor beta KW - Tumor Suppressor Protein p53 KW - anti-IgM KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured -- drug effects KW - Apoptosis -- physiology KW - Humans KW - Cell Division -- drug effects KW - Immunoglobulin M -- immunology KW - Drug Resistance KW - Rabbits KW - Receptors, Antigen, B-Cell -- immunology KW - Apoptosis -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - G1 Phase -- drug effects KW - G1 Phase -- physiology KW - Tumor Suppressor Protein p53 -- biosynthesis KW - Neoplasm Proteins -- biosynthesis KW - Receptors, Transforming Growth Factor beta -- genetics KW - Transforming Growth Factor beta -- pharmacology KW - Tumor Suppressor Protein p53 -- physiology KW - Lymphoma, Large B-Cell, Diffuse -- pathology KW - Retinoblastoma Protein -- physiology KW - Retinoblastoma Protein -- biosynthesis KW - Receptors, Transforming Growth Factor beta -- biosynthesis KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Neoplasm Proteins -- physiology KW - Up-Regulation -- drug effects KW - Neoplasm Proteins -- genetics KW - Tumor Suppressor Protein p53 -- genetics KW - Antibodies, Anti-Idiotypic -- pharmacology KW - Retinoblastoma Protein -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77234241?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Anti-IgM+induces+transforming+growth+factor-beta+sensitivity+in+a+human+B-lymphoma+cell+line%3A+inhibition+of+growth+is+associated+with+a+downregulation+of+mutant+p53.&rft.au=Beckwith%2C+M%3BRuscetti%2C+F+W%3BSing%2C+G+K%3BUrba%2C+W+J%3BLongo%2C+D+L&rft.aulast=Beckwith&rft.aufirst=M&rft.date=1995-05-01&rft.volume=85&rft.issue=9&rft.spage=2461&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-31 N1 - Date created - 1995-05-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Autocrine transforming growth factor alpha is dispensible for v-rasHa-induced epidermal neoplasia: potential involvement of alternate epidermal growth factor receptor ligands. AN - 77232271; 7728756 AB - Autocrine epidermal growth factor receptor activation by transforming growth factor alpha (TGF alpha) has been implicated in growth stimulation during epithelial neoplasia. Using keratinocytes isolated from mice with genetic defects in TGF alpha expression, we tested whether TGF alpha is required for transformation by the v-rasHa oncogene. Introduction of v-rasHa into primary epidermal cultures using a retroviral vector stimulated growth of both control (TGF alpha +/+, BALB/c) and TGF alpha-deficient (TGF alpha -/-, wa-1) keratinocytes. Moreover, v-rasHa elicited characteristic changes in marker expression (keratin 1 was suppressed; keratin 8 was induced), previously shown to be associated with epidermal growth factor (EGF) receptor activation, in both TGF alpha +/+ and TGF alpha -/- keratinocytes. v-rasHa markedly increased secreted (> 10-fold) and cell-associated (2-3-fold) TGF alpha levels in keratinocytes from TGF alpha +/+ and BALB/c mice, but not TGF alpha -/- or wa-1 mice. Based on Northern blot analysis, v-rasHa induced striking up-regulation of transcripts encoding the additional EGF family members amphiregulin, heparin-binding EGF-like growth factor, and betacellulin in cultured keratinocytes from all four mouse strains. Interestingly, in addition to the normal 4.5-kilobase TGF alpha transcript, wa-1 keratinocytes expressed two additional TGF alpha transcripts, 4.7 and 5.2 kilobases long. All three transcripts were up-regulated in response to v-rasHa, as well as exogenous TGF alpha or keratinocyte growth factor treatment, and were also detected in RNA isolated from wa-1 brain and skin. In vivo, v-rasHa keratinocytes from control as well as TGF alpha-deficient mice produced squamous tumors when grafted onto nude mice, and these lesions expressed high levels of amphiregulin, heparin-binding EGF-like growth factor, and betacellulin mRNA, regardless of their TGF alpha status. These findings indicate that TGF alpha is not essential for epidermal neoplasia induced by the v-rasHa oncogene and suggest that another EGF family member(s) may contribute to autocrine growth stimulation of ras-transformed keratinocytes. JF - Cancer research AU - Dlugosz, A A AU - Cheng, C AU - Williams, E K AU - Darwiche, N AU - Dempsey, P J AU - Mann, B AU - Dunn, A R AU - Coffey, R J AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1995/05/01/ PY - 1995 DA - 1995 May 01 SP - 1883 EP - 1893 VL - 55 IS - 9 SN - 0008-5472, 0008-5472 KW - v-rasHa KW - wa-1 KW - Ligands KW - 0 KW - Transforming Growth Factor alpha KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Phenotype KW - Keratinocytes -- physiology KW - Gene Expression Regulation, Neoplastic KW - Animals KW - Cell Division -- physiology KW - Keratinocytes -- cytology KW - Transcription, Genetic KW - Mice, Nude KW - Mice KW - Papilloma -- genetics KW - Mice, Inbred BALB C KW - Skin Neoplasms -- genetics KW - Genes, ras KW - Receptor, Epidermal Growth Factor -- metabolism KW - Transforming Growth Factor alpha -- genetics KW - Receptor, Epidermal Growth Factor -- genetics KW - Transforming Growth Factor alpha -- physiology KW - Receptor, Epidermal Growth Factor -- physiology KW - Transforming Growth Factor alpha -- metabolism KW - Skin Neoplasms -- metabolism KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77232271?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Autocrine+transforming+growth+factor+alpha+is+dispensible+for+v-rasHa-induced+epidermal+neoplasia%3A+potential+involvement+of+alternate+epidermal+growth+factor+receptor+ligands.&rft.au=Dlugosz%2C+A+A%3BCheng%2C+C%3BWilliams%2C+E+K%3BDarwiche%2C+N%3BDempsey%2C+P+J%3BMann%2C+B%3BDunn%2C+A+R%3BCoffey%2C+R+J%3BYuspa%2C+S+H&rft.aulast=Dlugosz&rft.aufirst=A&rft.date=1995-05-01&rft.volume=55&rft.issue=9&rft.spage=1883&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 - 1995-05-30 N1 - Date created - 1995-05-30 N1 - Date revised - 2017-01-13 N1 - Gene symbol - v-rasHa; wa-1 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retargeting of CTL by an efficiently refolded bispecific single-chain Fv dimer produced in bacteria. AN - 77229225; 7536774 AB - A single-chain bispecific Fv dimer (bs(sFv)2) having specificity for mouse CD3 epsilon chain and human transferrin receptor was produced in bacterial inclusion bodies. To overcome difficulties associated with in vitro protein folding, we used a novel renaturation approach to obtain active bs(sFv)2. The protein was dissolved in the weak ionic detergent sodium lauroylsarcosine, and disulfides were formed by oxidation in air. After oxidation, the bs(sFv)2 exhibited very little covalent aggregation and migrated as a single species in nonreducing SDS-PAGE, suggesting that disulfides were correctly paired. The detergent was removed using an ion exchange resin and the protein fractionated by size exclusion chromatography. The recovered 65-kDa protein was monomeric in non-denaturing solvent, homogeneous by SDS-PAGE, and comprised 15 to 20% of material applied to the gel filtration column. This protein bound specifically to both mouse CD3 epsilon chain and human transferrin receptor with affinities indistinguishable from those of the parental Fabs or single-chain Fvs. The bs(sFv)2 specifically redirected mouse cytotoxic T cells to lyse target cells expressing human transferrin receptor at picomolar concentrations. Bacterially produced and detergent oxidized bs(sFv)2 molecules may therefore provide the abundant amounts of homogeneous active material required to redirect cytotoxic cells against tumors and other unwanted cells in animal models and in patients. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Kurucz, I AU - Titus, J A AU - Jost, C R AU - Jacobus, C M AU - Segal, D M AD - Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/05/01/ PY - 1995 DA - 1995 May 01 SP - 4576 EP - 4582 VL - 154 IS - 9 SN - 0022-1767, 0022-1767 KW - Antibodies, Bispecific KW - 0 KW - Antigens, CD3 KW - Epitopes KW - Immunoglobulin Variable Region KW - Receptors, Antigen, T-Cell KW - Receptors, Transferrin KW - Recombinant Proteins KW - antigen T cell receptor, epsilon chain KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Electrophoresis, Polyacrylamide Gel KW - Humans KW - Amino Acid Sequence KW - Mice KW - Antigens, CD3 -- immunology KW - Recombinant Proteins -- immunology KW - Molecular Sequence Data KW - Cytotoxicity Tests, Immunologic KW - Flow Cytometry KW - Epitopes -- immunology KW - Cell Line KW - Protein Conformation KW - Antibodies, Bispecific -- biosynthesis KW - Antibodies, Bispecific -- immunology KW - Immunoglobulin Variable Region -- immunology KW - T-Lymphocytes, Cytotoxic -- immunology KW - Receptors, Transferrin -- immunology KW - Receptors, Antigen, T-Cell -- immunology KW - Antibodies, Bispecific -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77229225?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Retargeting+of+CTL+by+an+efficiently+refolded+bispecific+single-chain+Fv+dimer+produced+in+bacteria.&rft.au=Kurucz%2C+I%3BTitus%2C+J+A%3BJost%2C+C+R%3BJacobus%2C+C+M%3BSegal%2C+D+M&rft.aulast=Kurucz&rft.aufirst=I&rft.date=1995-05-01&rft.volume=154&rft.issue=9&rft.spage=4576&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 - 1995-05-24 N1 - Date created - 1995-05-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Active immunotherapy of cancer with a nonreplicating recombinant fowlpox virus encoding a model tumor-associated antigen. AN - 77227517; 7722321 AB - Some tumor cells express Ags that are potentially recognizable by T lymphocytes and yet do not elicit significant immune responses. To explore new immunotherapeutic strategies aimed at enhancing the recognition of these tumor-associated Ags (TAA), we developed an experimental mouse model consisting of a lethal clone of the BALB/c tumor line CT26 designated CT26.WT, which was transduced with the lacZ gene encoding beta-galactosidase, to create CT26.CL25. The growth rate and lethality of CT26.CL25 and CT26.WT were virtually identical despite the expression by CT26.CL25 of the model tumor Ag in vivo. A recombinant fowlpox virus (rFPV), which is replication incompetent in mammalian cells, was constructed that expressed the model TAA, beta-galactosidase, under the influence of the 40-kDa vaccinia virus early/late promoter. This recombinant, FPV.bg40k, functioned effectively in vivo as an immunogen, eliciting CD8+ T cells that could effectively lyse CT26.CL25 in vitro. FPV.bg40k protected mice from both subcutaneous and intravenous tumor challenge by CT26.CL25, and most surprisingly, mice bearing established 3-day pulmonary metastasis were found to have significant, Ag-specific decreases in tumor burden and prolonged survival after treatment with the rFPV. These observations constitute the first reported use of rFPV in the prevention and treatment of an experimental cancer and suggest that changing the context in which the immune system encounters a TAA can significantly and therapeutically alter the host immune response against cancer. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Wang, M AU - Bronte, V AU - Chen, P W AU - Gritz, L AU - Panicali, D AU - Rosenberg, S A AU - Restifo, N P AD - Howard Hughes Medical Institute-National Institutes of Health Research Scholars Program, Bethesda, MD 20814, USA. Y1 - 1995/05/01/ PY - 1995 DA - 1995 May 01 SP - 4685 EP - 4692 VL - 154 IS - 9 SN - 0022-1767, 0022-1767 KW - Antigens, Neoplasm KW - 0 KW - Vaccines, Synthetic KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Vaccinia virus -- immunology KW - Transfection -- immunology KW - Lung Neoplasms -- secondary KW - Lung Neoplasms -- therapy KW - Amino Acid Sequence KW - Mice KW - T-Lymphocytes, Cytotoxic -- immunology KW - Vaccines, Synthetic -- therapeutic use KW - Mice, Inbred BALB C KW - Molecular Sequence Data KW - beta-Galactosidase -- therapeutic use KW - Cytotoxicity Tests, Immunologic KW - Neoplasm Transplantation -- immunology KW - Female KW - Antigens, Neoplasm -- therapeutic use KW - Adenocarcinoma -- secondary KW - Adenocarcinoma -- therapy KW - Fowlpox virus -- immunology KW - Immunotherapy, Active -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77227517?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Active+immunotherapy+of+cancer+with+a+nonreplicating+recombinant+fowlpox+virus+encoding+a+model+tumor-associated+antigen.&rft.au=Wang%2C+M%3BBronte%2C+V%3BChen%2C+P+W%3BGritz%2C+L%3BPanicali%2C+D%3BRosenberg%2C+S+A%3BRestifo%2C+N+P&rft.aulast=Wang&rft.aufirst=M&rft.date=1995-05-01&rft.volume=154&rft.issue=9&rft.spage=4685&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 - 1995-05-24 N1 - Date created - 1995-05-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Vaccine. 1990 Oct;8(5):441-2 [2174596] Eur J Immunol. 1990 Jun;20(6):1311-6 [2114998] J Exp Med. 1991 Jun 1;173(6):1373-84 [1903428] Science. 1991 Jun 21;252(5013):1662-7 [2047875] Adv Immunol. 1991;49:281-355 [1853786] J Immunol. 1991 Aug 15;147(4):1453-9 [1907999] Vaccine. 1992;10(1):8-9 [1311489] AIDS Res Hum Retroviruses. 1991 Dec;7(12):991-8 [1667477] J Exp Med. 1992 Jun 1;175(6):1423-31 [1588273] J Immunol. 1992 Jul 1;149(1):53-9 [1607662] J Natl Cancer Inst. 1992 Jul 15;84(14):1084-91 [1619682] Eur J Immunol. 1992 Sep;22(9):2283-8 [1381312] Cell. 1992 Dec 11;71(6):963-72 [1333889] Cancer Res. 1993 Jan 1;53(1):176-82 [8416743] J Exp Med. 1993 Feb 1;177(2):265-72 [8426105] J Infect Dis. 1993 Mar;167(3):533-7 [8095059] Curr Opin Genet Dev. 1993 Feb;3(1):86-90 [8453278] J Exp Med. 1993 Apr 1;177(4):989-98 [8459226] J Immunol. 1993 May 15;150(10):4450-6 [8097755] J Exp Med. 1993 Aug 1;178(2):489-95 [8340755] J Immunol. 1993 Oct 15;151(8):3971-80 [7691936] Virology. 1993 Nov;197(1):439-44 [8212580] J Immunol. 1993 Nov 15;151(10):5408-15 [7693811] Immunol Cell Biol. 1993 Oct;71 ( Pt 5):391-7 [8270268] J Infect Dis. 1994 Jan;169(1):41-7 [8277196] J Immunol. 1994 Apr 15;152(8):3884-94 [8144958] J Virol. 1994 May;68(5):3145-53 [7908700] Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3515-9 [8170938] Science. 1994 Apr 29;264(5159):716-9 [7513441] Nature. 1994 Jun 2;369(6479):357 [8018207] J Exp Med. 1994 Jul 1;180(1):1-4 [8006576] Annu Rev Immunol. 1994;12:337-65 [8011285] Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6458-62 [8022805] Transgenic Res. 1994 May;3(3):182-94 [8025596] J Natl Cancer Inst. 1994 Aug 3;86(15):1159-66 [8028037] Cancer Res. 1980 Jul;40(7):2142-6 [6992981] J Biol Chem. 1978 Aug 10;253(15):5521-5 [97298] Vaccine. 1994 May;12(6):569-73 [8036832] EMBO J. 1983;2(4):593-7 [6313347] J Virol. 1986 Nov;60(2):436-49 [3021979] Mol Cell Biol. 1986 Aug;6(8):2895-902 [3785217] J Immunol. 1987 Jul 1;139(1):285-94 [3108401] Virology. 1987 Oct;160(2):336-45 [3310381] J Virol. 1988 Apr;62(4):1120-4 [2831375] Vaccine. 1988 Dec;6(6):497-503 [2854338] Immunogenetics. 1989;30(4):296-302 [2507447] Biotechniques. 1989 Oct;7(9):980-2, 984-6, 989-90 [2631796] Lancet. 1991 Mar 9;337(8741):567-72 [1671940] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synthetic oligonucleotide expressed by a recombinant vaccinia virus elicits therapeutic CTL. AN - 77225402; 7722317 AB - P815A is a naturally occurring tumor rejection Ag of the methylcholanthrene-induced murine mastocytoma P815. The gene encoding the Ag P815A, designated P1A, is identical to that encoded in the normal genome of the DBA/2 mouse. A recombinant vaccinia virus (rVV) was constructed that expressed a synthetic oligonucleotide encoding the minimal determinant peptide of the tumor-associated Ag. Although the rVV recombinant expressing this mini-gene was recognized efficiently in vitro, it was an ineffective immunogen in vivo. The addition of an endoplasmic reticulum insertion signal sequence to the NH2 terminus of the minimal determinant resulted in a rVV that elicited CD8+ T cells that could lyse P815 mastocytoma cells in vitro and that were therapeutic in vivo. Recombinant viruses expressing synthetic oligonucleotide sequences preceded by the insertion signal sequences allow the expression of Ag directly into the endoplasmic reticulum, where binding to MHC class I molecules is most efficient. Vaccines based on synthetic oligonucleotides could be constructed with ease and rapidity but, most importantly, such constructs avoid the dangers associated with the expression of full length genes encoding TAA that are potentially oncogenic. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Irvine, K R AU - McCabe, B J AU - Rosenberg, S A AU - Restifo, N P AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/05/01/ PY - 1995 DA - 1995 May 01 SP - 4651 EP - 4657 VL - 154 IS - 9 SN - 0022-1767, 0022-1767 KW - Oligonucleotides KW - 0 KW - Vaccines, Synthetic KW - Abridged Index Medicus KW - Index Medicus KW - Vaccinia virus -- genetics KW - Animals KW - Base Sequence KW - Molecular Sequence Data KW - Cytotoxicity Tests, Immunologic KW - Neoplasm Transplantation -- immunology KW - Mice KW - Amino Acid Sequence KW - Female KW - Mice, Inbred DBA KW - Oligonucleotides -- therapeutic use KW - Mast-Cell Sarcoma -- therapy KW - Vaccines, Synthetic -- immunology KW - Oligonucleotides -- immunology KW - T-Lymphocytes, Cytotoxic -- immunology KW - Vaccines, Synthetic -- therapeutic use KW - Mast-Cell Sarcoma -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77225402?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Synthetic+oligonucleotide+expressed+by+a+recombinant+vaccinia+virus+elicits+therapeutic+CTL.&rft.au=Irvine%2C+K+R%3BMcCabe%2C+B+J%3BRosenberg%2C+S+A%3BRestifo%2C+N+P&rft.aulast=Irvine&rft.aufirst=K&rft.date=1995-05-01&rft.volume=154&rft.issue=9&rft.spage=4651&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 - 1995-05-24 N1 - Date created - 1995-05-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1994 Jun 2;369(6479):357 [8018207] Cancer Res. 1994 Jun 15;54(12):3124-6 [8205528] J Exp Med. 1994 Jul 1;180(1):1-4 [8006576] J Natl Cancer Inst. 1994 Aug 3;86(15):1159-66 [8028037] Cancer Res. 1994 Aug 1;54(15):4155-61 [7518351] Crit Rev Oncol Hematol. 1985;2(4):355-99 [3886178] Cell. 1986 Mar 28;44(6):959-68 [2420472] J Exp Med. 1987 Jan 1;165(1):211-22 [2432149] J Immunol. 1987 Feb 1;138(3):989-95 [3100623] Proc Natl Acad Sci U S A. 1988 Feb;85(4):1052-6 [3422478] J Exp Med. 1988 Oct 1;168(4):1419-41 [3262710] Annu Rev Immunol. 1989;7:601-24 [2469442] J Immunol. 1989 May 15;142(10):3714-25 [2785562] J Exp Med. 1991 Jun 1;173(6):1373-84 [1903428] Science. 1991 Jun 21;252(5013):1662-7 [2047875] Adv Immunol. 1991;49:281-355 [1853786] J Exp Med. 1991 Aug 1;174(2):489-92 [1856631] J Biol Chem. 1991 Oct 25;266(30):19867-70 [1939050] Science. 1991 Dec 13;254(5038):1643-7 [1840703] Nature. 1992 Feb 13;355(6361):644-6 [1538752] J Natl Cancer Inst. 1992 Jul 15;84(14):1084-91 [1619682] J Immunol. 1992 Aug 1;149(3):972-80 [1634779] Eur J Immunol. 1992 Sep;22(9):2283-8 [1381312] Adv Immunol. 1992;52:1-123 [1442305] Cell. 1992 Dec 11;71(6):963-72 [1333889] J Exp Med. 1993 Feb 1;177(2):265-72 [8426105] Cancer Res. 1993 Jul 15;53(14):3257-61 [7686815] Eur J Immunol. 1993 Sep;23(9):2072-7 [8370389] Curr Opin Immunol. 1993 Oct;5(5):709-13 [8240732] J Immunol. 1994 Jan 15;152(2):381-7 [8283027] J Exp Med. 1994 Feb 1;179(2):473-9 [8294861] Cancer Res. 1994 Feb 15;54(4):1071-6 [7508819] Nature. 1994 Feb 17;367(6464):654-7 [8107851] J Exp Med. 1994 Mar 1;179(3):1005-9 [8113668] Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3515-9 [8170938] Science. 1994 Apr 29;264(5159):716-9 [7513441] J Immunol. 1981 Jun;126(6):2100-3 [6453154] J Exp Med. 1981 Oct 1;154(4):1033-42 [6457075] J Virol. 1994 Jun;68(6):3505-11 [7514677] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antigen processing in vivo and the elicitation of primary CTL responses. AN - 77224804; 7722298 AB - CD8+ T lymphocytes (TCD8+) play an important role in cellular immune responses. TCD8+ recognize MHC class I molecules complexed to peptides of 8 to 10 residues derived largely from cytosolic proteins. Proteins are generally thought to be fragmented in the cytoplasm and delivered to nascent class I molecules in the endoplasmic reticulum (ER) by a peptide transporter encoded by the MHC. To explore the extent to which TCD8+ induction in vivo is limited by proteolysis or peptide transport into the ER, mice were immunized with recombinant vaccinia viruses containing mini-genes encoding antigenic peptides (bypassing the need for proteolysis), or these peptides with a NH2-terminal ER insertion sequence (bypassing the requirements for both proteolysis and transport). Additionally, mice were immunized with recombinant vaccinia viruses encoding rapidly degraded fragments of proteins. We report that limitations in induction of TCD8+ responses vary among Ags: for some, full length proteins are as immunogenic as other forms tested; for others, maximal responses are induced by peptides or by peptides targeted to the ER. Most importantly, in every circumstance examined, targeting peptides to the ER never diminished, and in some cases greatly enhanced, the TCD8+ immune response and provide an important alternative strategy in the design of live viral or naked DNA vaccines for the treatment of cancer and infectious diseases. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Restifo, N P AU - Bacík, I AU - Irvine, K R AU - Yewdell, J W AU - McCabe, B J AU - Anderson, R W AU - Eisenlohr, L C AU - Rosenberg, S A AU - Bennink, J R AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/05/01/ PY - 1995 DA - 1995 May 01 SP - 4414 EP - 4422 VL - 154 IS - 9 SN - 0022-1767, 0022-1767 KW - Protein Sorting Signals KW - 0 KW - Vaccines, Synthetic KW - Abridged Index Medicus KW - Index Medicus KW - Protein Sorting Signals -- immunology KW - Orthomyxoviridae -- immunology KW - Animals KW - Molecular Sequence Data KW - Cytotoxicity Tests, Immunologic KW - Mice KW - Amino Acid Sequence KW - Mice, Inbred BALB C KW - Female KW - Vaccinia virus -- immunology KW - Vaccines, Synthetic -- immunology KW - T-Lymphocytes, Cytotoxic -- immunology KW - Antigen Presentation -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77224804?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Antigen+processing+in+vivo+and+the+elicitation+of+primary+CTL+responses.&rft.au=Restifo%2C+N+P%3BBac%C3%ADk%2C+I%3BIrvine%2C+K+R%3BYewdell%2C+J+W%3BMcCabe%2C+B+J%3BAnderson%2C+R+W%3BEisenlohr%2C+L+C%3BRosenberg%2C+S+A%3BBennink%2C+J+R&rft.aulast=Restifo&rft.aufirst=N&rft.date=1995-05-01&rft.volume=154&rft.issue=9&rft.spage=4414&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 - 1995-05-24 N1 - Date created - 1995-05-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Immunol. 1979 Mar;122(3):1162-5 [312820] Cancer Res. 1980 Jul;40(7):2142-6 [6992981] J Immunol. 1981 May;126(5):1814-9 [7217668] J Immunol. 1981 Jun;126(6):2100-3 [6453154] Virology. 1981 Oct 30;114(2):423-8 [7292985] Nature. 1984 Jun 28-Jul 4;309(5971):797-9 [6738696] Nature. 1984 Oct 11-17;311(5986):578-9 [6332992] Mol Cell Biol. 1985 Dec;5(12):3403-9 [3939316] Science. 1986 Sep 19;233(4770):1318-21 [3489291] Virology. 1987 Oct;160(2):336-45 [3310381] Cell. 1988 Jan 29;52(2):253-8 [2449284] Cell. 1988 Mar 25;52(6):843-52 [2450677] J Exp Med. 1988 Oct 1;168(4):1211-24 [2459295] Annu Rev Immunol. 1989;7:601-24 [2469442] Adv Immunol. 1989;47:187-376 [2683611] Nature. 1990 Nov 15;348(6298):213-6 [1700303] Curr Top Microbiol Immunol. 1990;163:153-84 [2242679] J Biol Chem. 1990 Nov 15;265(32):19638-43 [2174047] Curr Opin Immunol. 1993 Aug;5(4):484-91 [8216922] J Immunol. 1994 Jan 15;152(2):381-7 [8283027] J Immunol. 1994 Feb 1;152(3):1163-70 [8301122] Nature. 1994 Feb 17;367(6464):654-7 [8107851] J Exp Med. 1994 Mar 1;179(3):1005-9 [8113668] J Exp Med. 1994 Mar 1;179(3):901-9 [8113682] J Immunol. 1994 Apr 15;152(8):3884-94 [8144958] Nature. 1994 Apr 28;368(6474):864-7 [8159247] Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3515-9 [8170938] Science. 1994 Apr 29;264(5159):716-9 [7513441] Science. 1994 May 27;264(5163):1322-6 [8191286] Nature. 1994 Jun 2;369(6479):357 [8018207] J Exp Med. 1994 Jul 1;180(1):1-4 [8006576] Annu Rev Immunol. 1994;12:337-65 [8011285] Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6458-62 [8022805] EMBO J. 1994 Jul 15;13(14):3236-44 [8045254] Eur J Immunol. 1994 Aug;24(8):1863-8 [8056044] Science. 1994 Aug 26;265(5176):1231-4 [8066462] Science. 1994 Aug 26;265(5176):1234-7 [8066463] Nature. 1990 Dec 20-27;348(6303):738-41 [1979660] Nature. 1990 Dec 20-27;348(6303):741-4 [2259383] Nature. 1990 Dec 20-27;348(6303):744-7 [2259384] Science. 1990 Dec 21;250(4988):1723-6 [2270487] J Exp Med. 1991 Jun 1;173(6):1373-84 [1903428] Nature. 1991 May 23;351(6324):290-6 [1709722] Adv Immunol. 1991;49:281-355 [1853786] J Exp Med. 1991 Aug 1;174(2):425-34 [1713253] J Exp Med. 1991 Aug 1;174(2):489-92 [1856631] Experientia. 1994 Nov 30;50(11-12):1054-60 [7988665] J Immunol. 1991 Aug 15;147(4):1453-9 [1907999] J Virol. 1991 Oct;65(10):5401-9 [1716691] Nature. 1991 Oct 17;353(6345):662-4 [1922384] Eur J Immunol. 1991 Nov;21(11):2891-4 [1718764] J Biol Chem. 1991 Oct 25;266(30):19867-70 [1939050] J Exp Med. 1992 Jan 1;175(1):163-8 [1309852] J Exp Med. 1992 Feb 1;175(2):481-7 [1732413] Science. 1992 Mar 6;255(5049):1264-6 [1546329] J Immunol. 1992 May 15;148(10):3012-20 [1374447] J Exp Med. 1992 Jun 1;175(6):1423-31 [1588273] Science. 1992 Jul 10;257(5067):238-41 [1352912] J Exp Med. 1992 Aug 1;176(2):449-57 [1380062] Eur J Immunol. 1992 Sep;22(9):2283-8 [1381312] Eur J Immunol. 1992 Oct;22(10):2663-7 [1396971] J Exp Med. 1992 Nov 1;176(5):1453-7 [1402688] Curr Opin Immunol. 1992 Oct;4(5):603-7 [1418726] Adv Immunol. 1992;52:1-123 [1442305] Cell. 1992 Dec 11;71(6):963-72 [1333889] J Exp Med. 1993 Feb 1;177(2):265-72 [8426105] Cell. 1993 Jun 4;73(5):989-98 [8500184] Nature. 1993 Jun 10;363(6429):552-4 [8389422] Eur J Biochem. 1993 Jun 1;214(2):375-81 [7916687] Nature. 1993 Jul 8;364(6433):158-61 [8321286] Cancer Res. 1993 Jul 15;53(14):3257-61 [7686815] J Exp Med. 1993 Aug 1;178(2):489-95 [8340755] Nature. 1993 Sep 16;365(6443):262-4 [8371781] Nature. 1993 Sep 16;365(6443):264-7 [8396732] Nature. 1970 Aug 15;227(5259):680-5 [5432063] Nature. 1978 Jun 29;273(5665):723-8 [661981] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Coordinate regulation by diethylstilbestrol of the platelet-derived growth factor-A (PDGF-A) and -B chains and the PDGF receptor alpha- and beta-subunits in the mouse uterus and vagina: potential mediators of estrogen action. AN - 77222399; 7720681 AB - The effects of estrogen on the reproductive tract involve cell proliferation, migration, and differentiation, which need to be well coordinated. Polypeptide growth factors are believed to play a vital role in a number of these cellular processes. Among the growth factors now documented to be associated with estrogen action are epidermal growth factor, transforming growth factor-alpha (TGF alpha), transforming growth factor-beta 1 (TGF beta 1), TGF beta 2, TGF beta 3, and insulin-like growth factor-I (IGF-I). Platelet-derived growth factors (PDGFs) are also potent mitogens, which consist of two peptide chains, denoted A and B, that dimerize to isoforms (PDGF-AA, -AB, and -BB) which differ in their functional properties, secretory behavior, receptor binding, and physiological effects. To study the role of the PDGF-A and -B chains and the PDGF receptor subunits, alpha and beta, during estrogen action in the mouse reproductive tract, time-dependent changes in the expression of these genes were examined by Northern and in situ RNA analyses and by immunohistochemistry after a single treatment of immature CD-1 (17- to 19-day-old) mice with the synthetic estrogen, diethylstilbestrol (DES). Our results demonstrate estrogen modulation of the expression of messenger RNA (mRNA) and protein for the PDGF ligands and receptors in both the uterus and vagina of the mouse. Northern and in situ RNA analyses demonstrate time-dependent estrogen induction of the mRNA levels for these genes in both tissues within 3 h after treatment. However, distinctive mRNA expression profiles for the PDGF ligand and receptor genes are exhibited by the uterus and vagina in response to DES, especially in that the induction of transcripts for PDGF-A and both receptor subunits is more transient in the vagina than in the uterus. Steroid specificity studies demonstrate predominant estrogen-specific regulation of mRNA induction for these genes. Analysis of cell-specific RNA expression by in situ hybridization reveals prominent induction of transcripts for the PDGF chains and receptor subunits in the uterine and vaginal epithelium after estrogen treatment, although enhanced expression of mRNA is also noted in the stroma, particularly for the PDGF receptor subunit genes. Cellular localization of the PDGF ligand and receptor protein molecules by immunohistochemistry detected significant immunostaining for all of these proteins in both the uterus and vagina of control animals. After DES treatment, the uterus exhibits a significant decrease in the level of PDGF ligand and receptor proteins immunostained within 6 h, whereas less dramatic effects ar observed in the vagina.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Endocrinology AU - Gray, K AU - Eitzman, B AU - Raszmann, K AU - Steed, T AU - Geboff, A AU - McLachlan, J AU - Bidwell, M AD - Laboratory of Developmental and Reproductive Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 2325 EP - 2340 VL - 136 IS - 5 SN - 0013-7227, 0013-7227 KW - Antisense Elements (Genetics) KW - 0 KW - Estrogens KW - Macromolecular Substances KW - Platelet-Derived Growth Factor KW - RNA, Messenger KW - Receptors, Estrogen KW - platelet-derived growth factor A KW - Dihydrotestosterone KW - 08J2K08A3Y KW - Progesterone KW - 4G7DS2Q64Y KW - Estradiol KW - 4TI98Z838E KW - Diethylstilbestrol KW - 731DCA35BT KW - Dexamethasone KW - 7S5I7G3JQL KW - Receptors, Platelet-Derived Growth Factor KW - EC 2.7.10.1 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Blotting, Northern KW - Progesterone -- pharmacology KW - Dexamethasone -- pharmacology KW - Estradiol -- pharmacology KW - RNA, Messenger -- analysis KW - Mice KW - RNA, Messenger -- biosynthesis KW - Mice, Inbred Strains KW - In Situ Hybridization KW - Dihydrotestosterone -- pharmacology KW - Immunohistochemistry KW - Female KW - Vagina -- drug effects KW - Uterus -- metabolism KW - Diethylstilbestrol -- pharmacology KW - Gene Expression Regulation -- drug effects KW - Platelet-Derived Growth Factor -- biosynthesis KW - Estrogens -- physiology KW - Receptors, Estrogen -- physiology KW - Vagina -- metabolism KW - Uterus -- drug effects KW - Receptors, Platelet-Derived Growth Factor -- physiology KW - Receptors, Platelet-Derived Growth Factor -- biosynthesis KW - Platelet-Derived Growth Factor -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77222399?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Coordinate+regulation+by+diethylstilbestrol+of+the+platelet-derived+growth+factor-A+%28PDGF-A%29+and+-B+chains+and+the+PDGF+receptor+alpha-+and+beta-subunits+in+the+mouse+uterus+and+vagina%3A+potential+mediators+of+estrogen+action.&rft.au=Gray%2C+K%3BEitzman%2C+B%3BRaszmann%2C+K%3BSteed%2C+T%3BGeboff%2C+A%3BMcLachlan%2C+J%3BBidwell%2C+M&rft.aulast=Gray&rft.aufirst=K&rft.date=1995-05-01&rft.volume=136&rft.issue=5&rft.spage=2325&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-23 N1 - Date created - 1995-05-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Growth hormone-releasing hormone in testicular interstitial and germ cells: potential paracrine modulation of follicle-stimulating hormone action on Sertoli cell function. AN - 77219780; 7720679 AB - GH-releasing hormone (GHRH) is present in the interstitial and germ cells of the rat testis. In previous studies we found that GHRH is secreted from rat adult Leydig cells, in which it stimulates basal and LH-induced cAMP formation and steroidogenesis. In other studies cAMP production in Sertoli cells was found to be stimulated by GHRH. In the present report, we describe a potential paracrine action of GHRH in the Sertoli cell, with stimulation of cAMP formation in cultured adult and pubertal Sertoli cells. GHRH increased FSH-stimulated cAMP production in adult and pubertal cultures in a time-dependent manner. GHRH stimulation of basal and FSH-induced extracellular cAMP formation was more prominent in pubertal than in adult cultures. Immunocytochemical studies demonstrated the presence of GHRH-like immunoreactivity in rat interstitial cells from day 4 to adult life and in the acrosomal region of early and intermediate spermatids at stages III-VI of the seminiferous epithelium cycle. Immunoreactive GHRH was not observed in late spermatids and mature sperm or in Sertoli cells at any age. These results indicate that GHRH acts synergistically with FSH to promote cAMP production in Sertoli cells in culture. Testicular GHRH of Leydig and germ cell origin may be an important paracrine regulator of Sertoli cell function. Alternatively, GHRH present in germ cells may exert stage-specific intracrine functions. JF - Endocrinology AU - Fabbri, A AU - Ciocca, D R AU - Ciampani, T AU - Wang, J AU - Dufau, M L AD - Section on Molecular Endocrinology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 2303 EP - 2308 VL - 136 IS - 5 SN - 0013-7227, 0013-7227 KW - Antibodies KW - 0 KW - Follicle Stimulating Hormone KW - 9002-68-0 KW - Growth Hormone-Releasing Hormone KW - 9034-39-3 KW - Cyclic AMP KW - E0399OZS9N KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Aging -- physiology KW - Spermatids -- drug effects KW - Animals KW - Rats, Sprague-Dawley KW - Drug Interactions KW - Cells, Cultured KW - Spermatids -- physiology KW - Immunohistochemistry KW - Male KW - Testis -- growth & development KW - Sertoli Cells -- drug effects KW - Sertoli Cells -- cytology KW - Testis -- physiology KW - Growth Hormone-Releasing Hormone -- pharmacology KW - Cyclic AMP -- metabolism KW - Follicle Stimulating Hormone -- pharmacology KW - Growth Hormone-Releasing Hormone -- analysis KW - Sertoli Cells -- physiology KW - Growth Hormone-Releasing Hormone -- physiology KW - Testis -- cytology KW - Sexual Maturation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77219780?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Growth+hormone-releasing+hormone+in+testicular+interstitial+and+germ+cells%3A+potential+paracrine+modulation+of+follicle-stimulating+hormone+action+on+Sertoli+cell+function.&rft.au=Fabbri%2C+A%3BCiocca%2C+D+R%3BCiampani%2C+T%3BWang%2C+J%3BDufau%2C+M+L&rft.aulast=Fabbri&rft.aufirst=A&rft.date=1995-05-01&rft.volume=136&rft.issue=5&rft.spage=2303&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-23 N1 - Date created - 1995-05-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protection from radiation-induced chromosomal aberrations by the nitroxide Tempol. AN - 77210003; 7712443 AB - The nitroxide Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) is a stable, free radical that exhibits protection from ionizing radiation damage and from oxidative stress mediated through exposure of cells to superoxide or hydrogen peroxide. Radiation protection has been observed in both in vivo and in vitro models. To understand the mechanism of Tempol-mediated radioprotection better, the production of radiation-induced chromosome aberrations was evaluated. This study analyzed Tempol-mediated radioprotection of human peripheral blood lymphocytes (PBLs). Peripheral blood lymphocytes were exposed to control (0mM), 10 mM (Tp10), and 50 mM (Tp50) concentrations of Tempol for 20 minutes before irradiation with 0, 150, 300, and 450 cGy. One quarter ml whole blood was cultured in F12 medium and phytohemagglutinin at 37 degrees C for 49, 54, 59, and 64 hours. Colcemide was added to each sample for the last 5 hours before harvest. Cells were harvested, treated with hypotonic solution, and fixed before dropping on cold clean slides. Mitotic indices and frequency of dicentric, ring, and triradial chromosomal aberrations were determined at 1000x magnification for each treatment group at each collection point. Treatment of cells with Tempol alone did not induce the chromosomal aberration frequency above that for unirradiated controls. Radiation dose response curves for total chromosome aberration production revealed radioprotection for Tempol treatment for both 10 and 50 mM exposures. Tempol protection factors (assessed at 0.2 aberrations/cell level) for Tp 10 and Tp 50 were 2.2 and 2.8, respectively. Tempol protects against radiation-induced chromosome aberrations in human PBLs. This finding is consistent with and lends support to previous studies in which Tempol was reported to enhance cell survival and reduce radiation-induced DNA double strand breaks. JF - Cancer AU - Johnstone, P A AU - DeGraff, W G AU - Mitchell, J B AD - Radiation Biology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1995/05/01/ PY - 1995 DA - 1995 May 01 SP - 2323 EP - 2327 VL - 75 IS - 9 SN - 0008-543X, 0008-543X KW - Cyclic N-Oxides KW - 0 KW - Free Radicals KW - Radiation-Protective Agents KW - Spin Labels KW - DNA KW - 9007-49-2 KW - tempol KW - U78ZX2F65X KW - Abridged Index Medicus KW - Index Medicus KW - Regression Analysis KW - Radiation Dosage KW - Free Radicals -- administration & dosage KW - DNA Damage KW - Dose-Response Relationship, Drug KW - Humans KW - Dose-Response Relationship, Radiation KW - Metaphase KW - DNA -- drug effects KW - Cell Survival -- drug effects KW - Mitotic Index KW - Cell Survival -- radiation effects KW - Free Radicals -- pharmacology KW - DNA -- radiation effects KW - Male KW - Radiation-Protective Agents -- administration & dosage KW - Cyclic N-Oxides -- administration & dosage KW - Lymphocytes -- radiation effects KW - Cyclic N-Oxides -- pharmacology KW - Chromosome Aberrations KW - Chromosomes -- drug effects KW - Radiation-Protective Agents -- pharmacology KW - Lymphocytes -- drug effects KW - Chromosomes -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77210003?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer&rft.atitle=Protection+from+radiation-induced+chromosomal+aberrations+by+the+nitroxide+Tempol.&rft.au=Johnstone%2C+P+A%3BDeGraff%2C+W+G%3BMitchell%2C+J+B&rft.aulast=Johnstone&rft.aufirst=P&rft.date=1995-05-01&rft.volume=75&rft.issue=9&rft.spage=2323&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-18 N1 - Date created - 1995-05-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Multiple effects of mutations in human immunodeficiency virus type 1 integrase on viral replication. AN - 77205064; 7535863 AB - The integration of a DNA copy of the human immunodeficiency virus type 1 (HIV-1) genome into a chromosome of an infected cell is a pivotal step in virus replication. Integration requires the activity of the virus-encoded integrase, which enters the cell as a component of the virion. Results of numerous mutagenesis studies have identified amino acid residues and protein domains of HIV-1 integrase critical for in vitro activity, but only a few of these mutants have been studied for their effects on HIV replication. We have introduced site-directed changes into an infectious DNA clone of HIV-1 and show that integrase mutations can affect virus replication at a variety of steps. We identified mutations that altered virion morphology, levels of particle-associated integrase and reverse transcriptase, and viral DNA synthesis. One replication-defective mutant virus which had normal morphology and protein composition displayed increased levels of circular viral DNA following infection of a T-cell line. This virus also had a significant titer in a CD4-positive indicator cell assay, which requires the viral Tat protein. Although unintegrated viral DNA can serve as a template for Tat expression in infected indicator cells, this level of expression is insufficient to support a spreading viral infection in CD4-positive lymphocytes. JF - Journal of virology AU - Engelman, A AU - Englund, G AU - Orenstein, J M AU - Martin, M A AU - Craigie, R AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA. Y1 - 1995/05// PY - 1995 DA - May 1995 SP - 2729 EP - 2736 VL - 69 IS - 5 SN - 0022-538X, 0022-538X KW - pol KW - DNA Primers KW - 0 KW - DNA, Viral KW - DNA Nucleotidyltransferases KW - EC 2.7.7.- KW - Integrases KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - RNA-Directed DNA Polymerase KW - Index Medicus KW - AIDS/HIV KW - Defective Viruses -- genetics KW - DNA Primers -- genetics KW - HeLa Cells KW - Humans KW - Gene Expression KW - RNA-Directed DNA Polymerase -- metabolism KW - Defective Viruses -- physiology KW - Genes, pol KW - Cloning, Molecular KW - Mutagenesis, Site-Directed KW - DNA, Viral -- biosynthesis KW - Base Sequence KW - Point Mutation KW - Molecular Sequence Data KW - Virus Integration -- physiology KW - Virus Integration -- drug effects KW - Microscopy, Electron KW - Defective Viruses -- ultrastructure KW - DNA, Viral -- genetics KW - RNA-Directed DNA Polymerase -- genetics KW - Sequence Deletion KW - HIV-1 -- genetics KW - Virus Replication -- genetics KW - DNA Nucleotidyltransferases -- genetics KW - Virus Replication -- physiology KW - HIV-1 -- physiology KW - Mutation KW - DNA Nucleotidyltransferases -- physiology KW - HIV-1 -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77205064?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Multiple+effects+of+mutations+in+human+immunodeficiency+virus+type+1+integrase+on+viral+replication.&rft.au=Engelman%2C+A%3BEnglund%2C+G%3BOrenstein%2C+J+M%3BMartin%2C+M+A%3BCraigie%2C+R&rft.aulast=Engelman&rft.aufirst=A&rft.date=1995-05-01&rft.volume=69&rft.issue=5&rft.spage=2729&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 - 1995-05-10 N1 - Date created - 1995-05-10 N1 - Date revised - 2017-01-13 N1 - Gene symbol - pol N1 - SuppNotes - Cited By: EMBO J. 1993 Nov;12(11):4433-8 [7693456] J Virol. 1995 Jan;69(1):376-86 [7983732] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] Proc Natl Acad Sci U S A. 1985 Jul;82(13):4539-43 [2989831] J Virol. 1986 Aug;59(2):284-91 [3016298] Proc Natl Acad Sci U S A. 1986 Oct;83(20):7648-52 [2429313] J Virol. 1986 Nov;60(2):771-5 [2430111] J Virol. 1988 Jan;62(1):139-47 [3257102] Nucleic Acids Res. 1988 Aug 11;16(15):7351-67 [3045756] Proc Natl Acad Sci U S A. 1988 Sep;85(18):6944-8 [3413127] Proc Natl Acad Sci U S A. 1988 Dec;85(24):9580-4 [2849111] Cell. 1990 Apr 20;61(2):213-22 [2331748] Proc Natl Acad Sci U S A. 1990 Jul;87(13):5119-23 [2164223] J Virol. 1990 Oct;64(10):4709-17 [2204722] Mol Microbiol. 1990 Jun;4(6):961-75 [2170815] Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1339-43 [1847518] J Virol. 1991 Apr;65(4):2141-5 [2002557] Mol Microbiol. 1990 Oct;4(10):1771-7 [1963920] Nucleic Acids Res. 1991 Feb 25;19(4):851-60 [1850126] FEBS Lett. 1991 May 6;282(2):231-4 [1709876] J Virol. 1991 Aug;65(8):4350-8 [2072454] J Virol. 1991 Sep;65(9):4636-44 [1870194] Protein Eng. 1991 Apr;4(4):435-41 [1652750] EMBO J. 1991 Dec;10(12):3905-11 [1718745] Cell. 1991 Dec 20;67(6):1211-21 [1760846] Science. 1992 Feb 7;255(5045):723-6 [1738845] J Virol. 1992 Apr;66(4):2232-9 [1548759] Mol Cell Biol. 1992 May;12(5):2331-8 [1314954] AIDS Res Hum Retroviruses. 1991 Dec;7(12):971-3 [1812946] Virology. 1992 Jun;188(2):459-68 [1585629] Biochem Biophys Res Commun. 1992 Jun 30;185(3):874-80 [1627142] EMBO J. 1992 Aug;11(8):3053-8 [1322294] J Virol. 1992 Nov;66(11):6361-9 [1404595] Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9598-602 [1409671] J Virol. 1992 Dec;66(12):7414-9 [1433523] J Virol. 1993 Jan;67(1):425-37 [8416376] J Biol Chem. 1993 Jan 25;268(3):2113-9 [8420982] Nucleic Acids Res. 1993 Mar 25;21(6):1419-25 [8464733] Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3428-32 [8386373] EMBO J. 1993 Aug;12(8):3261-7 [8344263] EMBO J. 1993 Aug;12(8):3269-75 [8344264] Nucleic Acids Res. 1993 Jul 25;21(15):3507-11 [8346030] J Virol. 1994 Mar;68(3):1633-42 [8107224] Nucleic Acids Res. 1994 Mar 25;22(6):1037-43 [8152908] J Bacteriol. 1994 Jun;176(11):3257-68 [8195081] Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6654-8 [7912831] J Virol. 1994 Aug;68(8):4768-75 [8035478] J Virol. 1994 Aug;68(8):5311-20 [8035531] J Virol. 1994 Sep;68(9):5911-7 [8057470] J Virol. 1994 Dec;68(12):8401-5 [7966634] Annu Rev Biochem. 1994;63:133-73 [7526778] Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10593-7 [8248150] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Staining methods in gel electrophoresis, including the use of multiple detection methods. AN - 77313423; 7539685 AB - Polyacrylamide gel electrophoresis is a reliable and widely used technique for the separation, identification and characterization of proteins and protein mixtures. With the introduction of high resolution two-dimensional polyacrylamide gel electrophoresis in 1975 upward to 2000 individual polypeptides spots are easily separated on a single electrophoretic gel thereby necessitating the availability of highly sensitive protein detection methods. Although a plethora of protein-staining and -visualization protocols have been described utilizing both radioactive and non-radioactive reagents, many times the use of mono-dimensional detection procedures is insufficient to address the experimental questions asked. The present review highlights the utilization of combined protein-labeling and -staining methodologies in gel electrophoresis including selected applications in polyacrylamide gels and solid membrane matrixes. JF - Journal of chromatography. A AU - Wirth, P J AU - Romano, A AD - Biopolymer Chemistry Section, Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/04/28/ PY - 1995 DA - 1995 Apr 28 SP - 123 EP - 143 VL - 698 IS - 1-2 SN - 0021-9673, 0021-9673 KW - Proteins KW - 0 KW - Index Medicus KW - Staining and Labeling KW - Proteins -- chemistry KW - Electrophoresis, Polyacrylamide Gel -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77313423?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+chromatography.+A&rft.atitle=Staining+methods+in+gel+electrophoresis%2C+including+the+use+of+multiple+detection+methods.&rft.au=Wirth%2C+P+J%3BRomano%2C+A&rft.aulast=Wirth&rft.aufirst=P&rft.date=1995-04-28&rft.volume=698&rft.issue=1-2&rft.spage=123&rft.isbn=&rft.btitle=&rft.title=Journal+of+chromatography.+A&rft.issn=00219673&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-10 N1 - Date created - 1995-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structure and regulation of the gene encoding the neuron-specific protein kinase C substrate neurogranin (RC3 protein). AN - 77244353; 7730337 AB - A 13-kilobase pair genomic DNA encoding a 78-amino acid brain-specific calmodulin-binding protein kinase C (PKC) substrate, neurogranin (Ng/RC3; also known as RC3 or p17), has been sequenced. The Ng/RC3 gene is composed of four exons and three introns, with the protein-coding region located in the first and second exons. This gene was found to have multiple transcriptional start sites clustered within 20 base pairs (bp); it lacks the TATA, GC, and CCAAT boxes in the proximal upstream region of the start sites. The promoter activity was characterized by transfection of 293 cells with nested deletion mutants of the 5'-flanking region fused to the luciferase reporter gene. A minimal construct containing bp +11 to +256 was nearly as active as that covering bp -1508 to +256, whereas a shorter one covering bp +40 to +256 had a greatly reduced activity. Between bp +11 and +40 lies a 12-nucleotide sequence (CCCCGCCCACCC) containing overlapping binding sites for AP2 (CCGCCCACCC) and SP1 (CCCGCC); this region may be important for conferring the basal transcriptional activity of the Ng/RC3 gene. The expression of a Ng/RC3-luciferase fusion construct (-1508/+256) in transfected 293 cells was stimulated by phorbol 12-myristate 13-acetate (PMA), but not by cAMP, arachidonic acid, vitamin D, retinoic acid, or thyroxines T3 and T4. PMA caused a 2-4-fold stimulation of all the reporter gene constructs ranging from +11/+256 to -1508/+256. The stimulatory effects of PMA could be magnified by cotransfection with both Ca(2+)-dependent and -independent phorbol ester-binding PKC-alpha, -beta I, -beta II, -gamma, -delta, and -epsilon cDNAs, but not by non-phorbol ester-binding PKC-zeta cDNA. The Ng/RC3 and PKC-gamma genes have a similar expression pattern in the brain during development. These two genes share at least four conserved sequence segments 1.5 kilobase pair upstream from their transcriptional start sites and a gross similarity in that they possess several AT-rich segments within bp -550 to -950. A near homogeneous 20-kDa DNA-binding protein purified from rat brain was able to bind to these AT-rich regions of both Ng/RC3 and PKC-gamma genes with footprints containing ATTA, ATAA, and AATA sequences. JF - The Journal of biological chemistry AU - Sato, T AU - Xiao, D M AU - Li, H AU - Huang, F L AU - Huang, K P AD - Section on Metabolic Regulation, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/04/28/ PY - 1995 DA - 1995 Apr 28 SP - 10314 EP - 10322 VL - 270 IS - 17 SN - 0021-9258, 0021-9258 KW - Ng/RC3 KW - Calmodulin-Binding Proteins KW - 0 KW - DNA-Binding Proteins KW - NRGN protein, human KW - Nerve Tissue Proteins KW - Nrgn protein, rat KW - Neurogranin KW - 132654-77-4 KW - DNA KW - 9007-49-2 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Sequence Homology, Nucleic Acid KW - Humans KW - Transcription, Genetic KW - Amino Acid Sequence KW - Cloning, Molecular KW - Rats KW - Base Sequence KW - Promoter Regions, Genetic KW - Transfection KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Substrate Specificity KW - Cell Line, Transformed KW - DNA-Binding Proteins -- metabolism KW - Protein Kinase C -- metabolism KW - Protein Kinase C -- genetics KW - Neurons -- enzymology KW - Calmodulin-Binding Proteins -- genetics KW - Gene Expression Regulation KW - Nerve Tissue Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77244353?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Structure+and+regulation+of+the+gene+encoding+the+neuron-specific+protein+kinase+C+substrate+neurogranin+%28RC3+protein%29.&rft.au=Sato%2C+T%3BXiao%2C+D+M%3BLi%2C+H%3BHuang%2C+F+L%3BHuang%2C+K+P&rft.aulast=Sato&rft.aufirst=T&rft.date=1995-04-28&rft.volume=270&rft.issue=17&rft.spage=10314&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 - 1995-06-01 N1 - Date created - 1995-06-01 N1 - Date revised - 2017-01-13 N1 - Gene symbol - Ng/RC3 N1 - Genetic sequence - U22062; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunocytochemical localization of eight protein kinase C isozymes overexpressed in NIH 3T3 fibroblasts. Isoform-specific association with microfilaments, Golgi, endoplasmic reticulum, and nuclear and cell membranes. AN - 77236832; 7730383 AB - We have used immunocytochemical analyses to characterize the subcellular distribution of protein kinase C (PKC)-alpha, -beta I, -beta II, -gamma, -delta, -epsilon, -zeta, and -eta in NIH 3T3 fibroblasts that overexpress these different PKC isozymes. Immunofluorescence studies and Western blotting with antibodies specific for individual isoforms revealed that before activation the majority of the PKCs are not membrane-bound and are diffusely distributed throughout the cytoplasm. In addition, a fraction of PKC-delta and -eta appears membrane-bound and concentrated in the Golgi apparatus. Activation of each isozyme's kinase activity (with the exception of PKC-zeta) by treatment of these cells with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate results in isozyme-specific alterations of cell morphology, as well as in a rapid, selective redistribution of the different PKC isozymes to distinct subcellular structures. Within minutes after 12-O-tetradecanoylphorbol-13-acetate treatment, PKC-alpha and -epsilon concentrate at cell margins. In addition, PKC-alpha accumulates in the endoplasmic reticulum, PKC-beta II associates with actin-rich microfilaments of the cytoskeleton, PKC-gamma accumulates in Golgi organelles, and PKC-epsilon associates with nuclear membranes. Our results demonstrate that each activated PKC isozyme specifically associates with a particular cellular structure, presumably containing the substrate for that isozyme. These findings support the hypothesis that PKC substrate specificity in vivo is mediated, at least in part, by the restricted subcellular locale for each PKC isozyme and its target protein. JF - The Journal of biological chemistry AU - Goodnight, J A AU - Mischak, H AU - Kolch, W AU - Mushinski, J F AD - Molecular Genetics Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1995/04/28/ PY - 1995 DA - 1995 Apr 28 SP - 9991 EP - 10001 VL - 270 IS - 17 SN - 0021-9258, 0021-9258 KW - Actins KW - 0 KW - Isoenzymes KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Endoplasmic Reticulum -- enzymology KW - 3T3 Cells KW - Animals KW - Fibroblasts -- enzymology KW - Cell Membrane -- enzymology KW - Enzyme Activation KW - Biological Transport KW - Actins -- metabolism KW - Mice KW - Actin Cytoskeleton -- enzymology KW - Cloning, Molecular KW - Antibody Specificity KW - Cell Nucleus -- enzymology KW - Golgi Apparatus -- enzymology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Immunohistochemistry KW - Intracellular Membranes -- enzymology KW - Protein Kinase C -- metabolism KW - Protein Kinase C -- genetics KW - Isoenzymes -- immunology KW - Protein Kinase C -- immunology KW - Subcellular Fractions -- enzymology KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77236832?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Immunocytochemical+localization+of+eight+protein+kinase+C+isozymes+overexpressed+in+NIH+3T3+fibroblasts.+Isoform-specific+association+with+microfilaments%2C+Golgi%2C+endoplasmic+reticulum%2C+and+nuclear+and+cell+membranes.&rft.au=Goodnight%2C+J+A%3BMischak%2C+H%3BKolch%2C+W%3BMushinski%2C+J+F&rft.aulast=Goodnight&rft.aufirst=J&rft.date=1995-04-28&rft.volume=270&rft.issue=17&rft.spage=9991&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 - 1995-06-01 N1 - Date created - 1995-06-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Wegener's granulomatosis. AN - 77215569; 7715042 JF - JAMA AU - Sneller, M C AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/04/26/ PY - 1995 DA - 1995 Apr 26 SP - 1288 EP - 1291 VL - 273 IS - 16 SN - 0098-7484, 0098-7484 KW - Adrenal Cortex Hormones KW - 0 KW - Antibodies, Antineutrophil Cytoplasmic KW - Autoantibodies KW - Biomarkers KW - Cyclophosphamide KW - 8N3DW7272P KW - Prednisone KW - VB0R961HZT KW - Methotrexate KW - YL5FZ2Y5U1 KW - Abridged Index Medicus KW - Index Medicus KW - Autoantibodies -- metabolism KW - Prednisone -- therapeutic use KW - Humans KW - Prognosis KW - Cyclophosphamide -- adverse effects KW - Drug Therapy, Combination KW - Adrenal Cortex Hormones -- therapeutic use KW - Cyclophosphamide -- therapeutic use KW - Adult KW - Methotrexate -- therapeutic use KW - Middle Aged KW - Male KW - Granulomatosis with Polyangiitis -- pathology KW - Granulomatosis with Polyangiitis -- physiopathology KW - Granulomatosis with Polyangiitis -- diagnosis KW - Granulomatosis with Polyangiitis -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77215569?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=proceeding&rft.jtitle=JAMA&rft.atitle=Wegener%27s+granulomatosis.&rft.au=Sneller%2C+M+C&rft.aulast=Sneller&rft.aufirst=M&rft.date=1995-04-26&rft.volume=273&rft.issue=16&rft.spage=1288&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-16 N1 - Date created - 1995-05-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: JAMA. 1995 Oct 18;274(15):1199-200 [7563507] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Electrical and synaptic properties of embryonic luteinizing hormone-releasing hormone neurons in explant cultures. AN - 77249366; 7537379 AB - Voltage- and ligand-activated channels in embryonic neurons containing luteinizing hormone-releasing hormone (LHRH) were studied by patch-pipette, whole-cell current and voltage clamp techniques. LHRH neurons were maintained in explant cultures derived from olfactory pit regions of embryonic mice. Cells were marked intracellularly with Lucifer yellow following recording. Sixty-two cells were unequivocally identified as LHRH neurons by Lucifer yellow and LHRH immunocytochemistry. The cultured LHRH neurons had resting potentials around -50 mV, exhibited spontaneous discharges generated by intrinsic and/or synaptic activities and contained a time-dependent inward rectifier (Iir). Voltage clamp analysis of ionic currents in the LHRH neuron soma revealed a tetrodotoxin-sensitive Na+ current (INa) and two major types of K+ currents, a transient current (IA), a delayed rectifier current (IK) and low- and high-voltage-activated Ca2+ currents. Spontaneous depolarizing synaptic potentials and depolarizations induced by direct application of gamma-aminobutyrate were both inhibited by picrotoxin or bicuculline, demonstrating the presence of functional gamma-aminobutyrate type A synapses on these neurons. Responses to glutamate were found in LHRH neurons in older cultures. Thus, embryonic LHRH neurons not yet positioned in their postnatal environment in the forebrain contained a highly differentiated repertoire of voltage- and ligand-gated channels. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Kusano, K AU - Fueshko, S AU - Gainer, H AU - Wray, S AD - Laboratory of Neurochemistry, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/04/25/ PY - 1995 DA - 1995 Apr 25 SP - 3918 EP - 3922 VL - 92 IS - 9 SN - 0027-8424, 0027-8424 KW - Calcium Channels KW - 0 KW - Ion Channels KW - Tetraethylammonium Compounds KW - Picrotoxin KW - 124-87-8 KW - Gonadotropin-Releasing Hormone KW - 33515-09-2 KW - Tetrodotoxin KW - 4368-28-9 KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - Tetraethylammonium KW - 66-40-0 KW - Quinine KW - A7V27PHC7A KW - Index Medicus KW - Animals KW - Calcium Channels -- physiology KW - Cell Membrane -- drug effects KW - gamma-Aminobutyric Acid -- pharmacology KW - Synaptic Transmission -- drug effects KW - Ion Channels -- drug effects KW - Tetraethylammonium Compounds -- pharmacology KW - Action Potentials KW - Mice KW - Cell Membrane -- physiology KW - Ion Channels -- physiology KW - Patch-Clamp Techniques KW - Quinine -- pharmacology KW - Cells, Cultured KW - Picrotoxin -- pharmacology KW - Membrane Potentials -- drug effects KW - Tetrodotoxin -- pharmacology KW - Embryo, Mammalian KW - Organ Culture Techniques KW - Synapses -- physiology KW - Hypothalamus -- secretion KW - Hypothalamus -- physiology KW - Synapses -- drug effects KW - Neurons -- drug effects KW - Hypothalamus -- embryology KW - Neurons -- physiology KW - Gonadotropin-Releasing Hormone -- secretion KW - Neurons -- secretion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77249366?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Electrical+and+synaptic+properties+of+embryonic+luteinizing+hormone-releasing+hormone+neurons+in+explant+cultures.&rft.au=Kusano%2C+K%3BFueshko%2C+S%3BGainer%2C+H%3BWray%2C+S&rft.aulast=Kusano&rft.aufirst=K&rft.date=1995-04-25&rft.volume=92&rft.issue=9&rft.spage=3918&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 - 1995-06-01 N1 - Date created - 1995-06-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Dev Biol. 1994 Nov;166(1):331-48 [7958456] Neuroendocrinology. 1994 Apr;59(4):309-17 [7911229] Biol Reprod. 1981 Feb;24(1):44-9 [6781549] Neuroendocrinology. 1982;35(1):63-7 [7110525] Brain Res Bull. 1984 Apr;12(4):399-407 [6203621] Neuroendocrinology. 1984 Sep;39(3):256-60 [6504270] Neuroendocrinology. 1985 Jun;40(6):536-9 [3892354] Endocrinology. 1987 Dec;121(6):2251-5 [2824183] Neuroscience. 1988 Jun;25(3):729-49 [2457185] Science. 1988 Dec 23;242(4886):1654-64 [3059497] Nature. 1989 Mar 9;338(6211):161-4 [2645530] Peptides. 1988 Sep-Oct;9(5):1151-75 [3072535] Neuroendocrinology. 1989 Jul;50(1):51-8 [2547176] Proc Natl Acad Sci U S A. 1989 Oct;86(20):8132-6 [2682637] Neuron. 1990 Jul;5(1):1-10 [2196069] Neuroendocrinology. 1991 Mar;53(3):261-7 [2041587] Neuroscience. 1991;44(2):263-75 [1944887] Neuroendocrinology. 1991 Oct;54(4):327-39 [1758575] Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1852-5 [1542682] Proc Natl Acad Sci U S A. 1992 May 1;89(9):4149-53 [1570341] Endocrinology. 1992 Sep;131(3):1397-402 [1354602] Mol Pharmacol. 1992 Aug;42(2):197-202 [1325030] Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8462-6 [1326758] Endocrinology. 1992 Dec;131(6):2965-71 [1280208] Proc Natl Acad Sci U S A. 1993 May 1;90(9):3908-12 [8387201] Endocrinology. 1993 Nov;133(5):2379-90 [8404690] Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9630-4 [8415752] J Membr Biol. 1993 Oct;136(1):85-96 [7505828] Endocrinology. 1994 Mar;134(3):1023-30 [8119138] Neuroendocrinology. 1994 Mar;59(3):297-308 [8159279] J Neurophysiol. 1994 Feb;71(2):575-82 [8176426] J Physiol. 1977 Feb;265(2):465-88 [850203] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mapping of the serotonin 5-HT1D alpha autoreceptor gene (HTR1D) on chromosome 1 using a silent polymorphism in the coding region. AN - 77716505; 7485253 JF - American journal of medical genetics AU - Ozaki, N AU - Lappalainen, J AU - Dean, M AU - Virkkunen, M AU - Linnoila, M AU - Goldman, D AD - Clinical Psychobiology Branch, National Institute of Mental Health, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20892, USA. Y1 - 1995/04/24/ PY - 1995 DA - 1995 Apr 24 SP - 162 EP - 164 VL - 60 IS - 2 SN - 0148-7299, 0148-7299 KW - DNA Primers KW - 0 KW - Genetic Markers KW - Receptors, Serotonin KW - Index Medicus KW - Genetic Linkage KW - DNA Primers -- genetics KW - Humans KW - Alcoholism -- metabolism KW - Brain -- metabolism KW - Alcoholism -- genetics KW - Violence KW - Alcoholism -- psychology KW - Base Sequence KW - Molecular Sequence Data KW - Female KW - Male KW - Chromosomes, Human, Pair 1 -- genetics KW - Polymorphism, Genetic KW - Receptors, Serotonin -- genetics KW - Chromosome Mapping UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77716505?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mapping+of+the+serotonin+5-HT1D+alpha+autoreceptor+gene+%28HTR1D%29+on+chromosome+1+using+a+silent+polymorphism+in+the+coding+region.&rft.au=Ozaki%2C+N%3BLappalainen%2C+J%3BDean%2C+M%3BVirkkunen%2C+M%3BLinnoila%2C+M%3BGoldman%2C+D&rft.aulast=Ozaki&rft.aufirst=N&rft.date=1995-04-24&rft.volume=60&rft.issue=2&rft.spage=162&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 - 1995-12-15 N1 - Date created - 1995-12-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mapping of the serotonin 5-HT1D beta autoreceptor gene on chromosome 6 and direct analysis for sequence variants. AN - 77705967; 7485252 AB - Abnormal brain serotonin function may be characteristic of several neuropsychiatric disorders. Thus, it is important to identify polymorphic genes and screen for functional variants at loci coding for genes that control normal serotonin functions. 5-HT1D beta is a terminal serotonin autoreceptor which may play a role in regulating serotonin synthesis and release. Using an SSCP technique we screened for 5-HT1D beta coding sequence variants in psychiatrically interviewed populations, which included controls, alcoholics, and alcoholic arsonists and alcoholic violent offenders with low CSF concentrations of the main serotonin metabolite 5-HIAA. A common polymorphism was identified in the 5-HT1D beta gene with allele frequencies of 0.72 and 0.28. The SSCP variant was caused by a silent G to C substitution at nucleotide 861 of the coding region. This polymorphism could also be detected as a HincII RFLP of amplified DNA. DNAs from informative CEPH families were typed for the HincII RFLP and analyzed with respect to 20 linked markers on chromosome 6. Multipoint analysis placed the 5-HT1D beta receptor gene between markers D6S286 and D6S275. A maximum two-point lod score of 10.90 was obtained to D6S26, which had been previously localized on 6q14-15. Chromosomal aberrations involving this region have been previously shown to cause retinal anomalies, developmental delay, and abnormal brain development. This region also contains the gene for North Carolina-type macular dystrophy. JF - American journal of medical genetics AU - Lappalainen, J AU - Dean, M AU - Charbonneau, L AU - Virkkunen, M AU - Linnoila, M AU - Goldman, D AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20852, USA. Y1 - 1995/04/24/ PY - 1995 DA - 1995 Apr 24 SP - 157 EP - 161 VL - 60 IS - 2 SN - 0148-7299, 0148-7299 KW - DNA Primers KW - 0 KW - Genetic Markers KW - Receptor, Serotonin, 5-HT1B KW - Receptors, Serotonin KW - Hydroxyindoleacetic Acid KW - 54-16-0 KW - Index Medicus KW - Genetic Linkage KW - DNA Primers -- genetics KW - Humans KW - Hydroxyindoleacetic Acid -- cerebrospinal fluid KW - Brain -- metabolism KW - Alcoholism -- genetics KW - Polymorphism, Single-Stranded Conformational KW - Polymerase Chain Reaction KW - Base Sequence KW - Alcoholism -- cerebrospinal fluid KW - Molecular Sequence Data KW - Male KW - Chromosomes, Human, Pair 6 -- genetics KW - Genetic Variation KW - Receptors, Serotonin -- genetics KW - Chromosome Mapping UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77705967?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mapping+of+the+serotonin+5-HT1D+beta+autoreceptor+gene+on+chromosome+6+and+direct+analysis+for+sequence+variants.&rft.au=Lappalainen%2C+J%3BDean%2C+M%3BCharbonneau%2C+L%3BVirkkunen%2C+M%3BLinnoila%2C+M%3BGoldman%2C+D&rft.aulast=Lappalainen&rft.aufirst=J&rft.date=1995-04-24&rft.volume=60&rft.issue=2&rft.spage=157&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 - 1995-12-15 N1 - Date created - 1995-12-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Preservation of autoregulatory cerebral vasodilator responses to hypotension after inhibition of nitric oxide synthesis. AN - 77410851; 7620890 AB - Effects of inhibition of nitric oxide (NO) synthesis on the cerebrovascular autoregulatory vasodilator response to hypotension were studied in conscious rats. Cerebral blood flow (CBF) was determined with [14C]iodoantipyrine in a saline-treated control group and in three groups following inhibition of NO synthase activity by twice daily intraperitoneal injections of 50 mg/kg of NG-nitro-L-arginine methyl ester (L-NAME) for four days. In the saline-control group (n = 8) and in the L-NAME-treated Group (a) (n = 8) CBF was determined while systemic mean arterial blood pressure (MABP) remained at its resting level (means +/- S.D., 128 +/- 6 and 151 +/- 11 mmHg, respectively). In the other groups CBF was determined after MABP was reduced by blood withdrawal to 118 +/- 9 and 88 +/- 8 mmHg in Groups (b) (n = 8) and (c) (n = 8), respectively. Despite the elevated MABP, global CBF was significantly lower in L-NAME-treated Group (a) than in the saline-controls (P < 0.005), indicating cerebral vasoconstriction resulting from inhibition of NO synthesis. Global CBF was not significantly reduced further in the two groups with hypotension. Local CBF in the hypotensive rats showed no significant reductions below values in L-NAME-treated control rats (Group (a)) in 31 of 32 brain structures; the only exception was in the auditory cortex of the severely hypotensive rats (Group (c)). The autoregulatory mechanism for cerebral vasodilatation to compensate for reduced arterial blood pressure is maintained following inhibition of NO synthesis. JF - Brain research AU - Takahashi, S AU - Cook, M AU - Jehle, J AU - Kennedy, C AU - Sokoloff, L AD - Laboratory of Cerebral Metabolism, National Institute of Mental Health, Bethesda, MD 20892-4030, USA. Y1 - 1995/04/24/ PY - 1995 DA - 1995 Apr 24 SP - 21 EP - 28 VL - 678 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Nitric Oxide KW - 31C4KY9ESH KW - Arginine KW - 94ZLA3W45F KW - Antipyrine KW - T3CHA1B51H KW - iodoantipyrine KW - V30V6H1QX4 KW - NG-Nitroarginine Methyl Ester KW - V55S2QJN2X KW - Index Medicus KW - Animals KW - Vasodilation -- physiology KW - Blood Flow Velocity KW - Blood Pressure KW - Antipyrine -- analogs & derivatives KW - Homeostasis -- drug effects KW - Arginine -- pharmacology KW - Rats KW - Rats, Sprague-Dawley KW - Antipyrine -- pharmacology KW - Vasodilation -- drug effects KW - Arginine -- analogs & derivatives KW - Male KW - Hypotension -- chemically induced KW - Nitric Oxide -- antagonists & inhibitors KW - Cerebrovascular Circulation -- physiology KW - Cerebrovascular Circulation -- drug effects KW - Nitric Oxide -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77410851?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Preservation+of+autoregulatory+cerebral+vasodilator+responses+to+hypotension+after+inhibition+of+nitric+oxide+synthesis.&rft.au=Takahashi%2C+S%3BCook%2C+M%3BJehle%2C+J%3BKennedy%2C+C%3BSokoloff%2C+L&rft.aulast=Takahashi&rft.aufirst=S&rft.date=1995-04-24&rft.volume=678&rft.issue=1-2&rft.spage=21&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 - 1995-08-30 N1 - Date created - 1995-08-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Trends in pharmacologic management of hypertension in the United States. AN - 77218446; 7717791 AB - Two new classes of antihypertensive agents were introduced in the 1980s, but their effectiveness in preventing heart disease and stroke has not been demonstrated. Lack of evidence of their efficacy might reasonably be expected to discourage their widespread use in management of hypertension. Use of various classes of antihypertensive agents was estimated from published drug use information in an effort to estimate trends in antihypertensive drug use and evaluate the impact of these trends on costs of antihypertensive therapy in the United States. Proportionate use of the five major antihypertensive drug classes shifted markedly between 1982 and 1993. Diuretics accounted for 56% of all hypertensive drug mentions in 1982 but only 27% in 1993, a relative decline of 52%. Use of beta-blockers and central agents also declined during this period. Proportionate use of calcium antagonists showed the greatest gains, increasing from 0.3% to 27%, while the use of angiotensin-converting enzyme inhibitors increased from 0.8% to 24%. Given the higher costs of the newer agents, and assuming an estimated total cost of antihypertensive medications in 1992 of $7 billion, approximately $3.1 billion would have been saved had 1982 prescribing practices remained in effect in 1992. Use of calcium antagonists and angiotensin-converting enzyme inhibitors in hypertension has increased dramatically in the past 10 years. Without convincing evidence of the advantages of these agents, it is difficult to explain the continued decline in the use of less expensive agents, such as diuretics and beta-blockers, which are the only antihypertensive agents proved to reduce stroke and coronary disease in hypertensive patients. JF - Archives of internal medicine AU - Manolio, T A AU - Cutler, J A AU - Furberg, C D AU - Psaty, B M AU - Whelton, P K AU - Applegate, W B AD - Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, Bethesda, Md, USA. Y1 - 1995/04/24/ PY - 1995 DA - 1995 Apr 24 SP - 829 EP - 837 VL - 155 IS - 8 SN - 0003-9926, 0003-9926 KW - Antihypertensive Agents KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - United States KW - Drug Therapy -- economics KW - Cardiovascular Diseases -- mortality KW - Cardiovascular Diseases -- etiology KW - Humans KW - Confounding Factors (Epidemiology) KW - Adult KW - Treatment Outcome KW - Aged KW - Middle Aged KW - Male KW - Female KW - Cardiovascular Diseases -- prevention & control KW - Drug Therapy -- trends KW - Hypertension -- complications KW - Antihypertensive Agents -- economics KW - Antihypertensive Agents -- adverse effects KW - Antihypertensive Agents -- therapeutic use KW - Hypertension -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77218446?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+internal+medicine&rft.atitle=Trends+in+pharmacologic+management+of+hypertension+in+the+United+States.&rft.au=Manolio%2C+T+A%3BCutler%2C+J+A%3BFurberg%2C+C+D%3BPsaty%2C+B+M%3BWhelton%2C+P+K%3BApplegate%2C+W+B&rft.aulast=Manolio&rft.aufirst=T&rft.date=1995-04-24&rft.volume=155&rft.issue=8&rft.spage=829&rft.isbn=&rft.btitle=&rft.title=Archives+of+internal+medicine&rft.issn=00039926&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-16 N1 - Date created - 1995-05-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Arch Intern Med. 1996 Jan 8;156(1):110-1 [8526689] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation of JAK3, but not JAK1, is critical to interleukin-4 (IL4) stimulated proliferation and requires a membrane-proximal region of IL4 receptor alpha. AN - 77229709; 7721895 AB - The tyrosine kinases JAK1 and JAK3 have been shown to undergo tyrosine phosphorylation in response to interleukin-2 (IL), IL4, IL7, and IL9, cytokines which share the common IL2 receptor gamma-chain (IL2R gamma), and evidence has been found for a preferential coupling of JAK3 to IL2R gamma and JAK1 to IL2R beta. Here we show, using human premyeloid TF-1 cells, that IL4 stimulates JAK3 to a larger extent than JAK1, based upon three different evaluation criteria. These include a more vigorous tyrosine phosphorylation of JAK3 as measured by anti-phosphotyrosine immunoblotting, a more marked activation of JAK3 as determined by in vitro tyrosine kinase assays and a more manifest presence of JAK3 in activated IL4-receptor complexes. These observations suggest that IL4 receptor signal transduction does not depend on equimolar heterodimerization of JAK1 and JAK3 following IL4-induced heterodimerization of IL4R alpha and IL2R gamma. Indeed, when human IL4R alpha was stably expressed in mouse BA/F3 cells, robust IL4-induced proliferation and JAK3 activation occurred without detectable involvement of JAK1, JAK2, or TYK2. The present study suggests that JAK1 plays a subordinate role in IL4 receptor signaling, and that in certain cells exclusive JAK3 activation may mediate IL4-induced cell growth. Moreover, mutational analysis of human IL4R alpha showed that a membrane-proximal cytoplasmic region was critical for JAK3 activation, while the I4R motif was not, which is compatible with a role of JAK3 upstream of the recruitment of the insulin receptor substrate-1/4PS signaling proteins by IL4 receptors. JF - The Journal of biological chemistry AU - Malabarba, M G AU - Kirken, R A AU - Rui, H AU - Koettnitz, K AU - Kawamura, M AU - O'Shea, J J AU - Kalthoff, F S AU - Farrar, W L AD - Biological Carcinogenesis and Development Program, Program Resources Inc./DynCorp., National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1995/04/21/ PY - 1995 DA - 1995 Apr 21 SP - 9630 EP - 9637 VL - 270 IS - 16 SN - 0021-9258, 0021-9258 KW - Receptors, Interleukin KW - 0 KW - Receptors, Interleukin-4 KW - Interleukin-4 KW - 207137-56-2 KW - Tyrosine KW - 42HK56048U KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - JAK1 protein, human KW - EC 2.7.10.2 KW - JAK3 protein, human KW - Jak1 protein, mouse KW - Jak3 protein, mouse KW - Janus Kinase 1 KW - Janus Kinase 3 KW - Index Medicus KW - Animals KW - Phosphorylation KW - Cells, Cultured KW - Humans KW - Molecular Sequence Data KW - Rabbits KW - Mice KW - Amino Acid Sequence KW - Tyrosine -- metabolism KW - Signal Transduction KW - Interleukin-4 -- pharmacology KW - Receptors, Interleukin -- physiology KW - Protein-Tyrosine Kinases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77229709?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+of+JAK3%2C+but+not+JAK1%2C+is+critical+to+interleukin-4+%28IL4%29+stimulated+proliferation+and+requires+a+membrane-proximal+region+of+IL4+receptor+alpha.&rft.au=Malabarba%2C+M+G%3BKirken%2C+R+A%3BRui%2C+H%3BKoettnitz%2C+K%3BKawamura%2C+M%3BO%27Shea%2C+J+J%3BKalthoff%2C+F+S%3BFarrar%2C+W+L&rft.aulast=Malabarba&rft.aufirst=M&rft.date=1995-04-21&rft.volume=270&rft.issue=16&rft.spage=9630&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 - 1995-05-23 N1 - Date created - 1995-05-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacological properties of fetal rat hippocampal GABAA receptors. AN - 77372017; 7600675 AB - Cells were cultured from embryonic (E) day 17 and 19 rat hippocampal tissues for one or more days in serum-supplemented growth medium. Intracellular recordings in the whole-cell configuration were made at room temperature. GABAA receptor agonists were applied by pressure pulses from closely positioned pipettes. Most of the cells recorded under these conditions responded to one or another ligand. When the equilibrium potential for Cl- was set near 0 mV, current responses to GABA and other GABAA receptor agonists reversed polarity near 0 mV, suggesting a dominant role for Cl- ions in the response. Many cells also responded to the general anesthetics (-)pentobarbital and alfaxalone (3 alpha-hydroxy-5 alpha-pregnane-11,20-dione). Micromolar concentrations of these drugs, like the transmitter GABA, elicited membrane current responses that reversed near 0 mV. Sequential exposure of individual neurons to both anesthetics revealed sensitivity to one but not the other agent as well as some responding to both. These results indicate: (1) the GABAA receptor function emerges pre-natally in rat hippocampal neurons; (2) barbiturates can have several sites for binding to in GABAA receptor complexes. JF - Brain research. Developmental brain research AU - Valeyev, A Y AU - Dunlap, V S AU - Barker, J L AD - Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/04/18/ PY - 1995 DA - 1995 Apr 18 SP - 280 EP - 282 VL - 85 IS - 2 SN - 0165-3806, 0165-3806 KW - Anesthetics KW - 0 KW - Pregnanediones KW - Receptors, GABA-A KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - alphaxalone KW - BD07M97B2A KW - Pentobarbital KW - I4744080IR KW - Index Medicus KW - Rats KW - Fetus KW - Animals KW - Patch-Clamp Techniques KW - Anesthetics -- pharmacology KW - Cells, Cultured KW - Pregnanediones -- pharmacology KW - Drug Synergism KW - Embryo, Mammalian KW - Pentobarbital -- pharmacology KW - Hippocampus -- physiology KW - gamma-Aminobutyric Acid -- pharmacology KW - Hippocampus -- metabolism KW - Receptors, GABA-A -- drug effects KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77372017?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research.+Developmental+brain+research&rft.atitle=Pharmacological+properties+of+fetal+rat+hippocampal+GABAA+receptors.&rft.au=Valeyev%2C+A+Y%3BDunlap%2C+V+S%3BBarker%2C+J+L&rft.aulast=Valeyev&rft.aufirst=A&rft.date=1995-04-18&rft.volume=85&rft.issue=2&rft.spage=280&rft.isbn=&rft.btitle=&rft.title=Brain+research.+Developmental+brain+research&rft.issn=01653806&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-10 N1 - Date created - 1995-08-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The E12 inhibitory domain prevents homodimer formation and facilitates selective heterodimerization with the MyoD family of gene regulatory factors. AN - 77249560; 7737127 AB - Although the ubiquitous helix-loop-helix (HLH) protein E12 does not homodimerize efficiently, the myogenic factor MyoD forms an avid DNA-binding heterodimer with E12 through the conserved HLH dimerization domain. However, the mechanism which ensures this selective dimerization is not understood at present. In our functional studies of various amino acid changes in the E12 HLH domain, we found that a single substitution in E12 helix 1 can abolish the effect of the E12 inhibitory domain and results in the efficient DNA binding of the E12 homodimer. Competition experiments revealed that the inhibitory domain, in fact, blocks the dimerization of E12 rather than DNA binding. MyoD contains two glutamic residues in helix 2 that are required for efficient dimerization with E12. More importantly, these residues were not essential for dimerization with E12 mutants in which the dimerization inhibitory domain had been relaxed, or for dimerization with E47 which does not contain the inhibitory domain owing to the use of an alternative exon. The positions of these glutamic residues are conserved among the four myogenic factors. Thus, members of the MyoD family of gene regulatory proteins can overcome the E12 dimerization inhibitory domain through a mechanism involving, in part, the negatively charged amino acid residues in helix 2. This result describes a novel mechanism facilitating the selective formation of the MyoD(MRF)-E12 heterodimer that enhances dimerization specificity and may apply to other members of the E-protein family. JF - The EMBO journal AU - Shirakata, M AU - Paterson, B M AD - Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health 37/4A21, Bethesda, MD 20892, USA. Y1 - 1995/04/18/ PY - 1995 DA - 1995 Apr 18 SP - 1766 EP - 1772 VL - 14 IS - 8 SN - 0261-4189, 0261-4189 KW - E2A KW - DNA-Binding Proteins KW - 0 KW - MyoD Protein KW - TCF Transcription Factors KW - Tcf7l1 protein, mouse KW - Transcription Factor 7-Like 1 Protein KW - Transcription Factors KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - 3T3 Cells KW - DNA Mutational Analysis KW - Molecular Sequence Data KW - Mice KW - Amino Acid Sequence KW - Protein Binding KW - Structure-Activity Relationship KW - Protein Conformation KW - MyoD Protein -- metabolism KW - Helix-Loop-Helix Motifs KW - DNA-Binding Proteins -- genetics KW - MyoD Protein -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77249560?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+EMBO+journal&rft.atitle=The+E12+inhibitory+domain+prevents+homodimer+formation+and+facilitates+selective+heterodimerization+with+the+MyoD+family+of+gene+regulatory+factors.&rft.au=Shirakata%2C+M%3BPaterson%2C+B+M&rft.aulast=Shirakata&rft.aufirst=M&rft.date=1995-04-18&rft.volume=14&rft.issue=8&rft.spage=1766&rft.isbn=&rft.btitle=&rft.title=The+EMBO+journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-06 N1 - Date created - 1995-06-06 N1 - Date revised - 2017-01-13 N1 - Gene symbol - E2A N1 - SuppNotes - Cited By: Science. 1990 Aug 17;249(4970):771-4 [2202050] Genes Dev. 1994 Apr 15;8(8):970-80 [7926781] Science. 1990 Nov 23;250(4984):1104-10 [2174572] Genes Dev. 1990 Dec;4(12A):2086-97 [2176634] Cell. 1991 Jan 25;64(2):459-70 [1846322] Science. 1991 Feb 15;251(4995):761-6 [1846704] Proc Natl Acad Sci U S A. 1991 May 1;88(9):3782-6 [1902570] Cell. 1991 Jul 26;66(2):305-15 [1649701] Cell. 1991 Aug 9;66(3):423 [1868544] Mol Cell Biol. 1991 Nov;11(11):5603-11 [1922066] Genes Dev. 1992 Feb;6(2):166-76 [1737614] Cell. 1992 Feb 21;68(4):699-708 [1739975] Mol Cell Biol. 1992 Mar;12(3):1031-42 [1312219] Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3596-600 [1314394] EMBO J. 1992 May;11(5):1843-55 [1582413] Cell. 1988 Dec 23;55(6):1061-7 [3203380] Cell. 1989 Feb 24;56(4):607-17 [2537150] Cell. 1989 Mar 10;56(5):777-83 [2493990] EMBO J. 1989 Mar;8(3):701-9 [2721498] Genes Dev. 1989 May;3(5):628-40 [2473006] Genes Dev. 1989 Jul;3(7):986-96 [2777078] Science. 1990 Jan 26;247(4941):467-70 [2105528] Cell. 1990 Mar 9;60(5):733-46 [2155707] Genes Dev. 1989 Dec;3(12B):2050-61 [2560751] Cell. 1990 Apr 6;61(1):49-59 [2156629] Proc Natl Acad Sci U S A. 1990 Jun;87(12):4722-6 [2112746] Science. 1992 May 15;256(5059):1027-30 [1317057] Trends Genet. 1992 Apr;8(4):144-8 [1321521] Cell. 1992 Dec 24;71(7):1223-37 [1473154] Science. 1993 Jan 8;259(5092):230-4 [8421783] Genes Dev. 1993 Jan;7(1):55-71 [8422988] Cell. 1993 Jan 29;72(2):233-45 [8425220] Dev Biol. 1993 Mar;156(1):11-23 [8449363] Nature. 1993 May 6;363(6424):38-45 [8479534] Genes Dev. 1993 Jun;7(6):1047-58 [8504929] Development. 1993 Mar;117(3):1125-33 [8391976] Genes Dev. 1993 Dec;7(12A):2456-70 [8253390] Genes Dev. 1994 Jan;8(1):1-8 [8288123] EMBO J. 1994 Jan 1;13(1):180-9 [8306960] Cell. 1994 May 6;77(3):451-9 [8181063] Science. 1990 Aug 17;249(4970):774-8 [2389143] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Altering the regiospecificity of androstenedione hydroxylase activity in P450s 2a-4/5 by a mutation of the residue at position 481. AN - 77212024; 7711025 AB - Mouse P450 2a-5 (coumarin 7-hydroxylase) acquires androstenedione (AD) hydroxylase activity by substituting Phe at position 209 with Asn. However, this mutant P450 2a-5 (F209N) and the corresponding mutant P450 2a-4 (L209N) exhibit different regiospecificites of androstenedione (AD) hydroxylase activity. While the former mutant catalyzes both AD 15 alpha- and 7 alpha-hydroxylase activities at similar rates, the latter mutant maintains the original high specificity of AD 15 alpha-hydroxylase activity. The AD hydroxylase activities in chimeric enzymes of the mutants L209N and F209N show that the regiospecificites are determined by the carboxy-terminal halves of the P450 molecules. Mutations at each of the four different residues within the carboxy-terminal halves indicate that the differences in regiospecificity are determined by the Val/Ala mutation at position 481. As the size of the hydrophobic amino acid at position 481 becomes larger (Ala < Val < Ile), the regiospecificities toward the C15 position of the AD molecule are dramatically increased. The regiospecificity is also increased by placing positively-charged Arg at position 481, although the remaining 15 alpha-hydroxylase activity in this mutant is considerably lower than the other P450s. The results indicate that the size of the residue at position 481 is a key factor in regulating the regiospecificity of AD hydroxylase activity in the P450s. Modeling AD in the substrate-heme pocket of bacterial P450 101A provided further support that residue 481 may reside near the steroid molecule so as to possibly affect the AD hydroxylase activity. JF - Biochemistry AU - Iwasaki, M AU - Darden, T A AU - Pedersen, L G AU - Negishi, M AD - Pharmacogenetics Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/04/18/ PY - 1995 DA - 1995 Apr 18 SP - 5054 EP - 5059 VL - 34 IS - 15 SN - 0006-2960, 0006-2960 KW - Recombinant Fusion Proteins KW - 0 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - Steroid Hydroxylases KW - EC 1.14.- KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - Cytochrome P-450 CYP2A6 KW - steroid 15-alpha-hydroxylase KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Recombinant Fusion Proteins -- biosynthesis KW - Base Sequence KW - Models, Molecular KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Substrate Specificity KW - Sequence Homology, Amino Acid KW - Structure-Activity Relationship KW - Saccharomyces cerevisiae KW - Mixed Function Oxygenases -- chemistry KW - Mixed Function Oxygenases -- metabolism KW - Mixed Function Oxygenases -- biosynthesis KW - Cytochrome P-450 Enzyme System -- chemistry KW - Steroid Hydroxylases -- metabolism KW - Steroid Hydroxylases -- chemistry KW - Cytochrome P-450 Enzyme System -- metabolism KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Steroid Hydroxylases -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77212024?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Altering+the+regiospecificity+of+androstenedione+hydroxylase+activity+in+P450s+2a-4%2F5+by+a+mutation+of+the+residue+at+position+481.&rft.au=Iwasaki%2C+M%3BDarden%2C+T+A%3BPedersen%2C+L+G%3BNegishi%2C+M&rft.aulast=Iwasaki&rft.aufirst=M&rft.date=1995-04-18&rft.volume=34&rft.issue=15&rft.spage=5054&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-17 N1 - Date created - 1995-05-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Disruption of p53 function sensitizes breast cancer MCF-7 cells to cisplatin and pentoxifylline. AN - 77210070; 7712469 AB - The possibility that appropriately designed chemotherapy could act selectively against p53-defective tumor cells was explored in MCF-7 human breast cancer cells. These cells were chosen because they have normal p53 function but are representative of a tumor cell type that does not readily undergo p53-dependent apoptosis. Two sublines (MCF-7/E6 and MCF-7/mu-p53) were established in which p53 function was disrupted by transfection with either the human papillomavirus type-16 E6 gene or a dominant-negative mutant p53 gene. p53 function in MCF-7/E6 and MCF-7/mu-p53 cells was defective relative to control cells in that there were no increases in p53 or p21Waf1/Cip1 protein levels and no G1 arrest following exposure to ionizing radiation. Survival assays showed that p53 disruption sensitized MCF-7 cells to cisplatin (CDDP) but not to several other DNA-damaging agents. CDDP sensitization was not limited to MCF-7 cells since p53 disruption in human colon carcinoma RKO cells also enhanced sensitivity to CDDP. Contrary to the other DNA-damaging agents tested, CDDP-induced DNA lesions are repaired extensively by nucleotide excision, and in agreement with a defect in this process, MCF-7/E6 and MCF-7/mu-p53 cells exhibited a reduced ability to repair a CDDP-damaged chloramphenicol acetyltransferase-reporter plasmid transfected into the cells. Therefore, we attributed the increased CDDP sensitivity of MCF-7 cells with disrupted p53 to defects in G1 checkpoint control, nucleotide excision repair, or both. The G2 checkpoint inhibitor pentoxifylline exhibited synergism with CDDP in killing MCF-7/E6 cells but did not affect sensitivity of the control cells. Moreover, pentoxifylline inhibited G2 checkpoint function to a greater extent in MCF-7/E6 than in the parental cells. These results suggested that, in the absence of p53 function, cancer cells are more vulnerable to G2 checkpoint abrogators. Our results show that a combination of CDDP and pentoxifylline is capable of synergistic and preferential killing of p53-defective tumor cells that do not readily undergo apoptosis. JF - Cancer research AU - Fan, S AU - Smith, M L AU - Rivet, D J AU - Duba, D AU - Zhan, Q AU - Kohn, K W AU - Fornace, A J AU - O'Connor, P M AD - Laboratory of Molecular Pharmacology, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1995/04/15/ PY - 1995 DA - 1995 Apr 15 SP - 1649 EP - 1654 VL - 55 IS - 8 SN - 0008-5472, 0008-5472 KW - p53 KW - Etoposide KW - 6PLQ3CP4P3 KW - Doxorubicin KW - 80168379AG KW - Methyl Methanesulfonate KW - AT5C31J09G KW - Cisplatin KW - Q20Q21Q62J KW - Pentoxifylline KW - SD6QCT3TSU KW - Index Medicus KW - Clone Cells KW - Etoposide -- pharmacology KW - Gamma Rays KW - Humans KW - Breast Neoplasms KW - Papillomaviridae -- genetics KW - G1 Phase -- radiation effects KW - Methyl Methanesulfonate -- pharmacology KW - Oncogenes KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Doxorubicin -- pharmacology KW - Transfection KW - Apoptosis -- drug effects KW - G1 Phase -- drug effects KW - Genes, Viral KW - Cell Survival -- radiation effects KW - Cell Line KW - Pentoxifylline -- pharmacology KW - Genes, p53 KW - Cisplatin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77210070?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+p53+function+sensitizes+breast+cancer+MCF-7+cells+to+cisplatin+and+pentoxifylline.&rft.au=Fan%2C+S%3BSmith%2C+M+L%3BRivet%2C+D+J%3BDuba%2C+D%3BZhan%2C+Q%3BKohn%2C+K+W%3BFornace%2C+A+J%3BO%27Connor%2C+P+M&rft.aulast=Fan&rft.aufirst=S&rft.date=1995-04-15&rft.volume=55&rft.issue=8&rft.spage=1649&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 - 1995-05-15 N1 - Date created - 1995-05-15 N1 - Date revised - 2017-01-13 N1 - Gene symbol - p53 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevalence of androgen receptor gene mutations in latent prostatic carcinomas from Japanese men. AN - 77207662; 7712463 AB - The incidence rate of clinically apparent prostatic carcinoma is 8-fold higher in the United States than in Japan, while the prevalence of latent prostatic carcinoma, a presumed precursor to clinical carcinoma, is similar in the two countries. The purpose of this study was to investigate the hypothesis that this profound difference in incidence rates of clinical carcinoma reflects distinct profiles of molecular genetic alterations in the latent precursor lesions that occur in the two countries. A significant fraction of latent carcinomas from Japanese men were found to contain inactivating mutations of the androgen receptor gene, while no such mutations were found in latent carcinomas from American men. No mutations were found in clinical carcinomas from either country. These data offer a potential molecular genetic explanation that may partially account for the distinct prostatic carcinoma incidence rates in these two populations. JF - Cancer research AU - Takahashi, H AU - Furusato, M AU - Allsbrook, W C AU - Nishii, H AU - Wakui, S AU - Barrett, J C AU - Boyd, J AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/04/15/ PY - 1995 DA - 1995 Apr 15 SP - 1621 EP - 1624 VL - 55 IS - 8 SN - 0008-5472, 0008-5472 KW - Codon KW - 0 KW - DNA, Neoplasm KW - Receptors, Androgen KW - Index Medicus KW - Exons KW - Humans KW - Amino Acid Sequence KW - DNA, Neoplasm -- analysis KW - Frameshift Mutation KW - Japan -- epidemiology KW - Polymerase Chain Reaction KW - Base Sequence KW - Molecular Sequence Data KW - Point Mutation KW - Incidence KW - United States -- epidemiology KW - Male KW - Sequence Deletion KW - Prevalence KW - Prostatic Neoplasms -- pathology KW - Precancerous Conditions -- genetics KW - Prostatic Neoplasms -- epidemiology KW - Receptors, Androgen -- genetics KW - Prostatic Neoplasms -- genetics KW - Precancerous Conditions -- epidemiology KW - Mutation KW - Precancerous Conditions -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77207662?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Prevalence+of+androgen+receptor+gene+mutations+in+latent+prostatic+carcinomas+from+Japanese+men.&rft.au=Takahashi%2C+H%3BFurusato%2C+M%3BAllsbrook%2C+W+C%3BNishii%2C+H%3BWakui%2C+S%3BBarrett%2C+J+C%3BBoyd%2C+J&rft.aulast=Takahashi&rft.aufirst=H&rft.date=1995-04-15&rft.volume=55&rft.issue=8&rft.spage=1621&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 - 1995-05-15 N1 - Date created - 1995-05-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I study of the somatostatin analogue somatuline in patients with metastatic hormone-refractory prostate cancer. AN - 77192309; 7535186 AB - Somatuline, a somatostatin analogue, has proven to be effective in several animal models of prostate cancer. Preliminary clinical studies also have suggested antitumor activity in patients with prostate cancer. The authors conducted a dose-escalation trial of 25 patients with metastatic hormone-refractory prostate cancer. Dosages of 4, 7, 10, 13, 18, and 24 mg/day were administered by continuous intravenous infusion for at least 28 days. Plasma levels of insulin-like growth factor-I (IGF-I), but not those of IGF-II, declined modestly during therapy. Toxicities included grade I diarrhea, bloating, infection, nausea, and flatus. The gastrointestinal side effects were typically self-limiting and occurred during the initial portion of treatment cycles. In addition, three patients experienced grade II catheter-related infections. No clinical response was noted by either radiographic or tumor marker criteria. The maximally tolerated dose of somatuline was not determined. A continuous intravenous infusion of 24 mg/day of somatuline is well tolerated and could be evaluated in other types of cancer or possibly in less advanced prostate cancer, but no clinical activity was noted at this dose in patients with advanced metastatic hormone-refractory prostate cancer. JF - Cancer AU - Figg, W D AU - Thibault, A AU - Cooper, M R AU - Reid, R AU - Headlee, D AU - Dawson, N AU - Kohler, D R AU - Reed, E AU - Sartor, O AD - Clinical Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/04/15/ PY - 1995 DA - 1995 Apr 15 SP - 2159 EP - 2164 VL - 75 IS - 8 SN - 0008-543X, 0008-543X KW - Antineoplastic Agents KW - 0 KW - Peptides, Cyclic KW - lanreotide KW - 0G3DE8943Y KW - Somatostatin KW - 51110-01-1 KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Insulin-Like Growth Factor II KW - 67763-97-7 KW - Prostate-Specific Antigen KW - EC 3.4.21.77 KW - Octreotide KW - RWM8CCW8GP KW - Abridged Index Medicus KW - Index Medicus KW - Insulin-Like Growth Factor II -- analysis KW - Drug Administration Schedule KW - Aged, 80 and over KW - Humans KW - Prostate-Specific Antigen -- blood KW - Molecular Sequence Data KW - Insulin-Like Growth Factor I -- analysis KW - Aged KW - Middle Aged KW - Amino Acid Sequence KW - Male KW - Octreotide -- analogs & derivatives KW - Antineoplastic Agents -- administration & dosage KW - Neoplasms, Hormone-Dependent -- blood KW - Octreotide -- therapeutic use KW - Prostatic Neoplasms -- blood KW - Neoplasms, Hormone-Dependent -- drug therapy KW - Octreotide -- administration & dosage KW - Somatostatin -- analogs & derivatives KW - Prostatic Neoplasms -- drug therapy KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77192309?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer&rft.atitle=A+phase+I+study+of+the+somatostatin+analogue+somatuline+in+patients+with+metastatic+hormone-refractory+prostate+cancer.&rft.au=Figg%2C+W+D%3BThibault%2C+A%3BCooper%2C+M+R%3BReid%2C+R%3BHeadlee%2C+D%3BDawson%2C+N%3BKohler%2C+D+R%3BReed%2C+E%3BSartor%2C+O&rft.aulast=Figg&rft.aufirst=W&rft.date=1995-04-15&rft.volume=75&rft.issue=8&rft.spage=2159&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-04 N1 - Date created - 1995-05-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Probing the structure of a putative intermediate in homologous recombination: the third strand in the parallel DNA triplex is in contact with the major groove of the duplex. AN - 77229543; 7723038 AB - A three-stranded DNA that is a putative intermediate of homologous recombination is a novel DNA triplex, R-form DNA. In R-form DNA the third strand includes both purines and pyrimidines and is parallel to the identical strand of the duplex. To test and refine our previously proposed R-form base triplets we have used two approaches: (1) dimethyl sulfate protection of R-form DNA; and (2) thermal dissociation of R-form DNAs in which the duplex strands were substituted in a strand-specific manner with either 7-deaza-guanine or 7-deaza-adenine. Together, the footprinting and isosteric substitution results demonstrate that the third strand in R-form DNA is in contact with the purines in the N7 position in the major groove of the Watson-Crick duplex in three ((GC):G, (AT):A and (TA):T) out of the four possible triplets. Furthermore, these results suggest that the N7 positions of the duplex play a significant role in stabilizing the DNA-DNA contacts during the homology recognition process. JF - Journal of molecular biology AU - Kim, M G AU - Zhurkin, V B AU - Jernigan, R L AU - Camerini-Otero, R D AD - Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1810, USA. Y1 - 1995/04/14/ PY - 1995 DA - 1995 Apr 14 SP - 874 EP - 889 VL - 247 IS - 5 SN - 0022-2836, 0022-2836 KW - DNA, Viral KW - 0 KW - DNA-Binding Proteins KW - Purines KW - Sulfuric Acid Esters KW - triplex DNA KW - DNA KW - 9007-49-2 KW - Rec A Recombinases KW - EC 2.7.7.- KW - dimethyl sulfate KW - JW5CW40Z50 KW - Index Medicus KW - Hot Temperature KW - Nucleic Acid Denaturation KW - Base Sequence KW - Models, Molecular KW - Molecular Sequence Data KW - Purines -- chemistry KW - DNA, Viral -- chemistry KW - Recombination, Genetic -- genetics KW - DNA -- genetics KW - DNA -- chemistry KW - Bacteriophage M13 -- genetics KW - Nucleic Acid Conformation KW - DNA, Viral -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77229543?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+biology&rft.atitle=Probing+the+structure+of+a+putative+intermediate+in+homologous+recombination%3A+the+third+strand+in+the+parallel+DNA+triplex+is+in+contact+with+the+major+groove+of+the+duplex.&rft.au=Kim%2C+M+G%3BZhurkin%2C+V+B%3BJernigan%2C+R+L%3BCamerini-Otero%2C+R+D&rft.aulast=Kim&rft.aufirst=M&rft.date=1995-04-14&rft.volume=247&rft.issue=5&rft.spage=874&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-25 N1 - Date created - 1995-05-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of mitogen-activated protein kinase phosphatase during the cellular response to genotoxic stress. Inhibition of c-Jun N-terminal kinase activity and AP-1-dependent gene activation. AN - 77222983; 7721728 AB - Irradiation of mammalian cells with short wavelength ultraviolet light (UVC) evokes a cascade of phosphorylation events leading to altered gene expression. Both the classic mitogen-activated protein (MAP) kinases and the distantly related c-Jun N-terminal kinases (JNK) contribute to the response via phosphorylation of transcription factors including AP-1. These kinases are themselves regulated via reversible phosphorylation, and several recently identified specific MAP kinase phosphatases (MKP) have been implicated in down-regulating MAP kinase-dependent gene expression in response to mitogens. Here, we provide evidence that MKP-1 plays a role in regulating transcriptional activation in response to UVC as well as another genotoxic agent, methyl methanesulfonate (MMS). We further demonstrate that JNK is a likely target for MKP-1. JNK is shown to be activated by UVC and MMS treatment, while MAP kinase activation occurs only with UVC. Like JNK activation, MKP-1 mRNA is induced by both treatments, and elevated MKP-1 expression coincides with a decline in JNK activity. Constitutive expression of MKP-1 in vivo inhibits JNK activity and reduces UVC- and MMS-induced activation of AP-1-dependent reporter genes. JF - The Journal of biological chemistry AU - Liu, Y AU - Gorospe, M AU - Yang, C AU - Holbrook, N J AD - Section on Gene Expression and Aging, NIA, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1995/04/14/ PY - 1995 DA - 1995 Apr 14 SP - 8377 EP - 8380 VL - 270 IS - 15 SN - 0021-9258, 0021-9258 KW - JNK KW - MKP-1 KW - Cell Cycle Proteins KW - 0 KW - Immediate-Early Proteins KW - Mutagens KW - Transcription Factor AP-1 KW - Methyl Methanesulfonate KW - AT5C31J09G 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 - Phosphoprotein Phosphatases KW - EC 3.1.3.16 KW - Protein Phosphatase 1 KW - DUSP1 protein, human KW - EC 3.1.3.48 KW - Dual Specificity Phosphatase 1 KW - Dusp1 protein, rat KW - Protein Tyrosine Phosphatases KW - Index Medicus KW - Rats KW - Animals KW - Ultraviolet Rays KW - Methyl Methanesulfonate -- toxicity KW - HeLa Cells KW - Humans KW - Enzyme Induction KW - Substrate Specificity KW - Transcriptional Activation KW - Protein Tyrosine Phosphatases -- biosynthesis KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Protein Tyrosine Phosphatases -- metabolism KW - Protein Tyrosine Phosphatases -- genetics KW - Transcription Factor AP-1 -- metabolism KW - Immediate-Early Proteins -- metabolism KW - Mutagens -- toxicity KW - Immediate-Early Proteins -- biosynthesis KW - Immediate-Early Proteins -- genetics KW - Gene Expression Regulation, Enzymologic KW - Calcium-Calmodulin-Dependent Protein Kinases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77222983?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Role+of+mitogen-activated+protein+kinase+phosphatase+during+the+cellular+response+to+genotoxic+stress.+Inhibition+of+c-Jun+N-terminal+kinase+activity+and+AP-1-dependent+gene+activation.&rft.au=Liu%2C+Y%3BGorospe%2C+M%3BYang%2C+C%3BHolbrook%2C+N+J&rft.aulast=Liu&rft.aufirst=Y&rft.date=1995-04-14&rft.volume=270&rft.issue=15&rft.spage=8377&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 - 1995-05-19 N1 - Date created - 1995-05-19 N1 - Date revised - 2017-01-13 N1 - Gene symbol - JNK; MKP-1 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of the sorting signal motif within pro-opiomelanocortin for the regulated secretory pathway. AN - 77222433; 7721777 AB - The NH2-terminal region of pro-opiomelanocortin (POMC) is highly conserved across species, having two disulfide bridges that cause the formation of an amphipathic hairpin loop structure between the 2nd and 3rd cysteine residues (Cys8 to Cys20). The role that the NH2-terminal region of pro-opiomelanocortin plays in acting as a molecular sorting signal for the regulated secretory pathway was investigated by using site-directed mutagenesis either to disrupt one or more of the disulfide bridges or to delete the amphipathic loop entirely. When POMC was expressed in Neuro-2a cells, ACTH immunoreactive material was localized in punctate secretory granules in the cell body and along the neurites, with heavy labeling at the tips. ACTH was secreted from these POMC-transfected cells in a regulated manner. Disruption of both disulfide bridges or the second disulfide bridge or removal of the amphipathic hairpin loop resulted in constitutive secretion of the mutant POMC from the cells and a lack of punctate secretory granule immunostaining within the cells. We have modeled the NH2-terminal POMC Cys8 to Cys20 domain and have identified it as an amphipathic loop containing four highly conserved hydrophobic and acidic amino acid residues (Asp10-Leu11-Glu14-Leu1). Thus the sorting signal for POMC to the regulated secretory pathway appears to be encoded by a specific conformational motif comprised of a 13-amino acid amphipathic loop structure stabilized by a disulfide bridge, located at the NH2 terminus of the molecule. JF - The Journal of biological chemistry AU - Cool, D R AU - Fenger, M AU - Snell, C R AU - Loh, Y P AD - Section on Cellular Neurobiology, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/04/14/ PY - 1995 DA - 1995 Apr 14 SP - 8723 EP - 8729 VL - 270 IS - 15 SN - 0021-9258, 0021-9258 KW - Disulfides KW - 0 KW - Protein Sorting Signals KW - Pro-Opiomelanocortin KW - 66796-54-1 KW - Arginine KW - 94ZLA3W45F KW - Lysine KW - K3Z4F929H6 KW - Index Medicus KW - Animals KW - Arginine -- metabolism KW - Models, Molecular KW - Humans KW - Amino Acid Sequence KW - Mice KW - Disulfides -- metabolism KW - Lysine -- metabolism KW - Mutagenesis, Site-Directed KW - Cattle KW - Sequence Alignment KW - Molecular Sequence Data KW - Cell Line KW - Protein Conformation KW - Protein Sorting Signals -- metabolism KW - Protein Sorting Signals -- genetics KW - Pro-Opiomelanocortin -- genetics KW - Pro-Opiomelanocortin -- chemistry KW - Protein Sorting Signals -- chemistry KW - Pro-Opiomelanocortin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77222433?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Identification+of+the+sorting+signal+motif+within+pro-opiomelanocortin+for+the+regulated+secretory+pathway.&rft.au=Cool%2C+D+R%3BFenger%2C+M%3BSnell%2C+C+R%3BLoh%2C+Y+P&rft.aulast=Cool&rft.aufirst=D&rft.date=1995-04-14&rft.volume=270&rft.issue=15&rft.spage=8723&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 - 1995-05-19 N1 - Date created - 1995-05-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glycosylation of human truncated Fc epsilon RI alpha chain is necessary for efficient folding in the endoplasmic reticulum. AN - 77213959; 7713932 AB - The high affinity immunoglobulin E (IgE) receptor is an alpha beta gamma 2 tetrameric complex. The truncated extracellular segment (alpha t) of the heavily glycosylated alpha chain is sufficient for high affinity binding of IgE. Here we have expressed various alpha t mutants in eukaryotic and prokaryotic cells to analyze the role of glycosylation in the folding, stability, and secretion of alpha t. All seven N-linked glycosylation sites in alpha t are glycosylated and their mutations have an additive effect on the folding and secretion of alpha t. Mutation of the seven N-glycosylation sites (delta 1-7 alpha t) induces misfolding and retention of alpha t in the endoplasmic reticulum. Similarly, tunicamycin treatment reduces substantially the folding efficiency of wild-type alpha t. In contrast, no difference in folding efficiency is detected between wild-type alpha t and delta 1-7 alpha t expressed in Escherichia coli. In addition, maturation of N-linked oligosaccharides and addition of O-linked carbohydrates are not required for either the transport or the IgE-binding function of alpha t. Furthermore, complete enzymatic deglycosylation does not affect the stability and the IgE-binding capacity of alpha t. Therefore, glycosylation is not intrinsically necessary for proper folding of alpha t but is required for folding in the endoplasmic reticulum. Our data are compatible with the concept that specific interactions between N-linked oligosaccharides and the folding machinery of the endoplasmic reticulum are necessary for efficient folding of alpha t in eukaryotic cells. JF - The Journal of biological chemistry AU - Letourneur, O AU - Sechi, S AU - Willette-Brown, J AU - Robertson, M W AU - Kinet, J P AD - Molecular Allergy and Immunology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA. Y1 - 1995/04/07/ PY - 1995 DA - 1995 Apr 07 SP - 8249 EP - 8256 VL - 270 IS - 14 SN - 0021-9258, 0021-9258 KW - Antibodies KW - 0 KW - Peptides KW - Receptors, IgE KW - Tunicamycin KW - 11089-65-9 KW - Index Medicus KW - Animals KW - Antibodies -- immunology KW - Tunicamycin -- pharmacology KW - Humans KW - Biological Transport KW - Peptides -- immunology KW - Amino Acid Sequence KW - Glycosylation KW - Mutagenesis, Site-Directed KW - Molecular Sequence Data KW - CHO Cells KW - Cell Line KW - Cricetinae KW - Endoplasmic Reticulum -- metabolism KW - Receptors, IgE -- metabolism KW - Receptors, IgE -- genetics KW - Protein Folding UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77213959?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Glycosylation+of+human+truncated+Fc+epsilon+RI+alpha+chain+is+necessary+for+efficient+folding+in+the+endoplasmic+reticulum.&rft.au=Letourneur%2C+O%3BSechi%2C+S%3BWillette-Brown%2C+J%3BRobertson%2C+M+W%3BKinet%2C+J+P&rft.aulast=Letourneur&rft.aufirst=O&rft.date=1995-04-07&rft.volume=270&rft.issue=14&rft.spage=8249&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 - 1995-05-15 N1 - Date created - 1995-05-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The gastrin-releasing peptide receptor is rapidly phosphorylated by a kinase other than protein kinase C after exposure to agonist. AN - 77212152; 7713928 AB - Several guanine nucleotide-binding protein-coupled receptors are known to be rapidly phosphorylated after agonist exposure. In this study we show that the gastrin-releasing peptide receptor (GRP-R) is rapidly phosphorylated in response to agonist exposure. When [32P]orthophosphate-labeled cells were exposed to bombesin, the receptor was maximally phosphorylated on serine and threonine residues within 1 min. Although addition of 12-O-tetradecanoylphorbol 13-acetate also resulted in phosphorylation of the GRP-R, elimination of protein kinase C activity using the inhibitor 7-hydroxystaurosporine did not prevent bombesin-induced GRP-R phosphorylation. We conclude that a kinase other than protein kinase C is principally responsible for the rapid, agonist-induced phosphorylation of the GRP-R. JF - The Journal of biological chemistry AU - Kroog, G S AU - Sainz, E AU - Worland, P J AU - Akeson, M A AU - Benya, R V AU - Jensen, R T AU - Battey, J F AD - Laboratory of Biological Chemistry, NCI National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1995/04/07/ PY - 1995 DA - 1995 Apr 07 SP - 8217 EP - 8224 VL - 270 IS - 14 SN - 0021-9258, 0021-9258 KW - Immune Sera KW - 0 KW - Receptors, Bombesin KW - Protein Kinases KW - EC 2.7.- KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Bombesin KW - PX9AZU7QPK KW - Index Medicus KW - Animals KW - Phosphorylation KW - Transfection KW - Enzyme Activation KW - Cells, Cultured KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Mice KW - Bombesin -- pharmacology KW - Amino Acid Sequence KW - Mice, Inbred BALB C KW - Protein Kinase C -- metabolism KW - Protein Kinases -- metabolism KW - Receptors, Bombesin -- agonists KW - Receptors, Bombesin -- metabolism KW - Receptors, Bombesin -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77212152?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=The+gastrin-releasing+peptide+receptor+is+rapidly+phosphorylated+by+a+kinase+other+than+protein+kinase+C+after+exposure+to+agonist.&rft.au=Kroog%2C+G+S%3BSainz%2C+E%3BWorland%2C+P+J%3BAkeson%2C+M+A%3BBenya%2C+R+V%3BJensen%2C+R+T%3BBattey%2C+J+F&rft.aulast=Kroog&rft.aufirst=G&rft.date=1995-04-07&rft.volume=270&rft.issue=14&rft.spage=8217&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 - 1995-05-15 N1 - Date created - 1995-05-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant human eosinophil cationic protein. Ribonuclease activity is not essential for cytotoxicity. AN - 77210958; 7713881 AB - Eosinophil cationic protein (ECP) is a toxin secreted by activated human eosinophils that has anti-parasitic, antibacterial, and neurotoxic activities; ECP also has ribonuclease activity and structural homology to other mammalian ribonucleases. To determine the relationship between the ribonuclease activity and cytotoxicity of ECP, a method for producing recombinant ECP (rECP) in a prokaryotic expression system was devised. Periplasmic isolates from induced bacterial transfectants contained enzymatically active rECP; micromolar concentrations of rECP were shown to be toxic for Staphylococcus aureus (strain 502A). In contrast, recombinant eosinophil-derived neurotoxin, with 67% amino acid sequence identity to ECP, had little to no toxicity for S. aureus; these findings are analogous to those obtained with purified, granule-derived ECP and eosinophil-derived neurotoxin. Two single base pair mutations were introduced into the coding sequence of rECP (Lys38 to Arg and His128 to Asp) to convert ribonuclease active-site residues into non-functional counterparts. These mutations eliminated the ribonuclease activity of rECP but had no discernible effect on the antibacterial activity of this protein, demonstrating that ribonuclease activity and cytotoxicity are, in this case, independent functions of ECP. JF - The Journal of biological chemistry AU - Rosenberg, H F AD - Laboratory of Host Defenses, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/04/07/ PY - 1995 DA - 1995 Apr 07 SP - 7876 EP - 7881 VL - 270 IS - 14 SN - 0021-9258, 0021-9258 KW - Anti-Bacterial Agents KW - 0 KW - Blood Proteins KW - Cytotoxins KW - Eosinophil Granule Proteins KW - Inflammation Mediators KW - Recombinant Proteins KW - Ribonucleases KW - EC 3.1.- KW - Index Medicus KW - Recombinant Proteins -- pharmacology KW - Cytotoxins -- toxicity KW - Cell Survival -- drug effects KW - Humans KW - Molecular Sequence Data KW - Escherichia coli -- drug effects KW - Anti-Bacterial Agents -- pharmacology KW - Amino Acid Sequence KW - Cytotoxins -- pharmacology KW - Staphylococcus aureus -- drug effects KW - Inflammation Mediators -- toxicity KW - Blood Proteins -- toxicity KW - Inflammation Mediators -- pharmacology KW - Ribonucleases -- metabolism KW - Blood Proteins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77210958?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Recombinant+human+eosinophil+cationic+protein.+Ribonuclease+activity+is+not+essential+for+cytotoxicity.&rft.au=Rosenberg%2C+H+F&rft.aulast=Rosenberg&rft.aufirst=H&rft.date=1995-04-07&rft.volume=270&rft.issue=14&rft.spage=7876&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 - 1995-05-15 N1 - Date created - 1995-05-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bladder and kidney cancer following cyclophosphamide therapy for non-Hodgkin's lymphoma. AN - 77209287; 7707439 AB - Cyclophosphamide is an established bladder carcinogen, but few studies have examined the relationship between dose and effect. The largest analysis to date included only seven cases of bladder cancer. No investigation has estimated the risk of kidney cancer. The purpose of this study was to quantify the risk of bladder and kidney cancer following cyclophosphamide therapy. Within a cohort of 6171 two-year survivors of non-Hodgkin's lymphoma (NHL), 48 patients with secondary cancer of the urinary tract were identified and matched to 136 control subjects with NHL who did not develop a second malignancy. Detailed information on chemotherapeutic drugs and cumulative dose received was collected for all subjects. Radiation dose to the target organ was estimated from individual radiotherapy records. Evaluations of the risk of second cancer as a result of treatment with cyclophosphamide alone, radiation alone, or both therapies were made relative to those patients who were exposed to neither treatment modality. A significant 4.5-fold risk of bladder cancer (95% confidence interval [CI] = 1.5-13.6) followed therapy with cyclophosphamide, and risk was dependent upon cumulative dose. Among patients who received a total amount of cyclophosphamide of less than 20 g, a nonsignificant 2.4-fold risk of bladder cancer was apparent. Significantly elevated sixfold (95% CI = 1.3-29) and 14.5-fold (95% CI = 2.3-94) risks of bladder malignancy followed cumulative doses of 20-49 g and 50 g or more, respectively (P value for trend = .004). Radiotherapy given without cyclophosphamide was associated with a nonsignificant increased risk of bladder malignancy. Excess bladder cancer risk following treatment with both radiotherapy and cyclophosphamide was as expected if individual risks were summed. Neither radiotherapy nor cyclophosphamide was associated with excesses of kidney cancer. Cyclophosphamide-related bladder cancer is dose dependent. For patients given cumulative doses between 20 and 49 g, the absolute risk of bladder cancer is on the order of three excess cancers per 100 NHL patients after 15 years of follow-up. At cumulative doses of 50 g or more, the excess risk increases to approximately seven excess bladder cancers per 100 NHL patients. The strong dose-response relationship and high absolute risk of bladder cancer underscore the importance of limiting the cumulative dose of cyclophosphamide to what is required to achieve therapeutic end points. The risk of secondary bladder malignancy and other late sequelae of therapy must be carefully weighted against the curative gains provided by cyclophosphamide. Moreover, long-term side effects of therapy that might be acceptable in cancer treatment may need to be re-evaluated for patients with non-neoplastic disorders. JF - Journal of the National Cancer Institute AU - Travis, L B AU - Curtis, R E AU - Glimelius, B AU - Holowaty, E J AU - Van Leeuwen, F E AU - Lynch, C F AU - Hagenbeek, A AU - Stovall, M AU - Banks, P M AU - Adami, J AD - Epidemiology and Biostatistics Program, National Cancer Institute, Bethesda, Md, USA. Y1 - 1995/04/05/ PY - 1995 DA - 1995 Apr 05 SP - 524 EP - 530 VL - 87 IS - 7 SN - 0027-8874, 0027-8874 KW - Cyclophosphamide KW - 8N3DW7272P KW - Index Medicus KW - Radiotherapy, Adjuvant KW - Dose-Response Relationship, Drug KW - Humans KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Follow-Up Studies KW - Male KW - Female KW - Cyclophosphamide -- administration & dosage KW - Lymphoma, Non-Hodgkin -- drug therapy KW - Cyclophosphamide -- therapeutic use KW - Kidney Neoplasms -- chemically induced KW - Neoplasms, Second Primary -- chemically induced KW - Urinary Bladder Neoplasms -- chemically induced KW - Cyclophosphamide -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77209287?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Bladder+and+kidney+cancer+following+cyclophosphamide+therapy+for+non-Hodgkin%27s+lymphoma.&rft.au=Travis%2C+L+B%3BCurtis%2C+R+E%3BGlimelius%2C+B%3BHolowaty%2C+E+J%3BVan+Leeuwen%2C+F+E%3BLynch%2C+C+F%3BHagenbeek%2C+A%3BStovall%2C+M%3BBanks%2C+P+M%3BAdami%2C+J&rft.aulast=Travis&rft.aufirst=L&rft.date=1995-04-05&rft.volume=87&rft.issue=7&rft.spage=524&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 - 1995-05-11 N1 - Date created - 1995-05-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The complete nucleotide sequence of the mouse thyroid-specific enhancer-binding protein (T/EBP) gene: extensive identity of the deduced amino acid sequence with the human protein. AN - 77209920; 7711079 AB - A mouse thyroid-specific enhancer-binding protein (T/EBP) gene and its flanking regions have been cloned and completely sequenced. The gene consists of 2 exons and exhibits high similarity (83-97%) to the rat sequence throughout the coding region and including an intron and up to 1.3 kbp upstream to the ATG initiation codon. A cDNA clone encoding human T/EBP has been also isolated and sequenced. Comparison of the deduced amino acid sequence of T/EBP revealed an extensive identity of 98% between mouse and the human protein. JF - Biochimica et biophysica acta AU - Oguchi, H AU - Pan, Y T AU - Kimura, S AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/04/04/ PY - 1995 DA - 1995 Apr 04 SP - 304 EP - 306 VL - 1261 IS - 2 SN - 0006-3002, 0006-3002 KW - Codon KW - 0 KW - Nuclear Proteins KW - Transcription Factors KW - thyroid nuclear factor 1 KW - Index Medicus KW - Animals KW - Base Sequence KW - Sequence Alignment KW - Humans KW - Molecular Sequence Data KW - Introns KW - Mice KW - Amino Acid Sequence KW - Cloning, Molecular KW - Nuclear Proteins -- genetics KW - Transcription Factors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77209920?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochimica+et+biophysica+acta&rft.atitle=The+complete+nucleotide+sequence+of+the+mouse+thyroid-specific+enhancer-binding+protein+%28T%2FEBP%29+gene%3A+extensive+identity+of+the+deduced+amino+acid+sequence+with+the+human+protein.&rft.au=Oguchi%2C+H%3BPan%2C+Y+T%3BKimura%2C+S&rft.aulast=Oguchi&rft.aufirst=H&rft.date=1995-04-04&rft.volume=1261&rft.issue=2&rft.spage=304&rft.isbn=&rft.btitle=&rft.title=Biochimica+et+biophysica+acta&rft.issn=00063002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-15 N1 - Date created - 1995-05-15 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U19755; GENBANK; U19756 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Incorporation of chromosomal proteins HMG-14/HMG-17 into nascent nucleosomes induces an extended chromatin conformation and enhances the utilization of active transcription complexes. AN - 77231590; 7729423 AB - The role of chromosomal proteins HMG-14 and HMG-17 in the generation of transcriptionally active chromatin was studied in a Xenopus laevis egg extract which supports complementary DNA strand synthesis and chromatin assembly. Chromosomal proteins HMG-14/HMG-17 enhanced transcription from a chromatin template carrying a 5S rRNA gene, but not from a DNA template. The transcriptional potential of chromatin was enhanced only when these proteins were incorporated into the template during, but not after, chromatin assembly. HMG-14 and HMG-17 stimulate transcription by increasing the activity, and not the number, of transcribed templates. They unfold the chromatin template without affecting the nucleosomal repeat or decreasing the content of histone B4. We suggest that HMG-14/HMG-17 enhance transcription by inducing an extended conformation in the chromatin fiber, perhaps due to interactions with histone tails in nucleosomes. By disrupting the higher order chromatin structure HMG-14/HMG-17 increase the accessibility of target sequences to components of the transcriptional apparatus. JF - The EMBO journal AU - Trieschmann, L AU - Alfonso, P J AU - Crippa, M P AU - Wolffe, A P AU - Bustin, M AD - Laboratory of Molecular Carcinogenesis, NCI, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/04/03/ PY - 1995 DA - 1995 Apr 03 SP - 1478 EP - 1489 VL - 14 IS - 7 SN - 0261-4189, 0261-4189 KW - Chromatin KW - 0 KW - High Mobility Group Proteins KW - Nucleosomes KW - Peptides KW - RNA, Ribosomal, 5S KW - Recombinant Proteins KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - DNA -- metabolism KW - Amino Acid Sequence KW - Peptides -- pharmacology KW - Cell Fractionation KW - Xenopus laevis KW - RNA, Ribosomal, 5S -- biosynthesis KW - Oocytes -- metabolism KW - Recombinant Proteins -- metabolism KW - Blotting, Southern KW - Restriction Mapping KW - Molecular Sequence Data KW - Peptides -- chemistry KW - Chromosomes -- ultrastructure KW - Female KW - Chromatin -- metabolism KW - Nucleosomes -- metabolism KW - Transcription, Genetic KW - High Mobility Group Proteins -- metabolism KW - Chromatin -- ultrastructure KW - DNA Replication UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77231590?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+EMBO+journal&rft.atitle=Incorporation+of+chromosomal+proteins+HMG-14%2FHMG-17+into+nascent+nucleosomes+induces+an+extended+chromatin+conformation+and+enhances+the+utilization+of+active+transcription+complexes.&rft.au=Trieschmann%2C+L%3BAlfonso%2C+P+J%3BCrippa%2C+M+P%3BWolffe%2C+A+P%3BBustin%2C+M&rft.aulast=Trieschmann&rft.aufirst=L&rft.date=1995-04-03&rft.volume=14&rft.issue=7&rft.spage=1478&rft.isbn=&rft.btitle=&rft.title=The+EMBO+journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-30 N1 - Date created - 1995-05-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1984 Jan 25;259(2):699-702 [6229533] Nucleic Acids Res. 1990 Oct 11;18(19):5767-74 [2216769] Cell. 1984 Jun;37(2):645-52 [6722885] Exp Cell Res. 1985 Feb;156(2):295-310 [3881264] Cell. 1986 Feb 14;44(3):381-9 [3943130] Biochemistry. 1986 Jun 3;25(11):3447-54 [3730369] Exp Cell Res. 1986 Oct;166(2):486-96 [3743668] Biochim Biophys Acta. 1987 Aug 25;909(3):190-200 [3040101] EMBO J. 1988 Apr;7(4):1071-9 [3402432] Genes Dev. 1988 Oct;2(10):1284-95 [3060404] EMBO J. 1989 Feb;8(2):527-37 [2721490] Mol Cell Biol. 1991 Feb;11(2):655-65 [1990277] Mol Endocrinol. 1991 Jan;5(1):42-50 [1850110] Nucleic Acids Res. 1991 Feb 25;19(4):717-25 [2017359] Prog Nucleic Acid Res Mol Biol. 1991;40:143-84 [2031082] Nucleic Acids Res. 1991 Jun 11;19(11):3115-21 [2057367] Mol Cell Biol. 1991 Sep;11(9):4483-9 [1908554] Science. 1991 Oct 11;254(5029):238-45 [1718039] Methods Cell Biol. 1991;36:541-59 [1811151] Nature. 1970 Aug 15;227(5259):680-5 [5432063] Proc Natl Acad Sci U S A. 1977 Jan;74(1):79-83 [319461] Proc Natl Acad Sci U S A. 1979 Feb;76(2):630-4 [284387] J Biol Chem. 1979 Nov 25;254(22):11688-95 [500667] J Biol Chem. 1980 Apr 25;255(8):3673-84 [7364765] Cell. 1980 May;20(1):131-41 [6248230] Nucleic Acids Res. 1980 Sep 11;8(17):3757-78 [6449690] Biochemistry. 1981 Feb 17;20(4):910-5 [6452161] Cell. 1982 Feb;28(2):413-21 [7060135] Cell. 1982 Apr;28(4):781-91 [7201351] J Cell Biol. 1982 May;93(2):285-97 [7096439] Eur J Biochem. 1982 Oct;127(2):429-36 [6216108] J Biol Chem. 1983 Nov 10;258(21):13221-9 [6226664] Biochemistry. 1992 Sep 1;31(34):7977-88 [1510985] J Mol Biol. 1992 Aug 20;226(4):1009-25 [1518041] J Biol Chem. 1992 Sep 25;267(27):19587-95 [1527076] Cell. 1992 Nov 27;71(5):777-89 [1330326] EMBO J. 1992 Dec;11(12):4497-506 [1425584] J Mol Biol. 1992 Nov 20;228(2):442-9 [1453455] Exp Cell Res. 1993 Mar;205(1):1-15 [8453983] J Mol Biol. 1993 Apr 5;230(3):824-36 [8478937] Dev Biol. 1993 May;157(1):224-31 [8482412] J Biol Chem. 1993 May 25;268(15):11389-93 [8496189] J Biol Chem. 1993 Jun 25;268(18):13632-8 [8514795] Genes Dev. 1993 Aug;7(8):1521-34 [8339930] Genes Dev. 1993 Sep;7(9):1779-95 [8370526] Cell. 1993 Sep 10;74(5):887-98 [8374955] EMBO J. 1993 Oct;12(10):3855-64 [8404854] Genes Dev. 1993 Oct;7(10):2033-47 [8406006] Science. 1993 Dec 24;262(5142):2033-5 [8266099] J Mol Biol. 1994 Feb 11;236(1):189-98 [8107104] Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2339-43 [8134397] J Cell Biol. 1994 Aug;126(3):591-601 [8045925] Science. 1994 Aug 5;265(5173):796-9 [8047885] EMBO J. 1994 Oct 3;13(19):4524-35 [7925294] J Biol Chem. 1994 Nov 11;269(45):28436-42 [7961785] Cell. 1990 Jan 26;60(2):235-45 [2404611] EMBO J. 1990 Feb;9(2):573-82 [2303043] J Biol Chem. 1990 Mar 15;265(8):4592-9 [2307678] Nucleic Acids Res. 1990 Apr 25;18(8):2011-6 [1692412] Trends Genet. 1990 Feb;6(2):52-6 [2186529] Biochim Biophys Acta. 1990 Jul 30;1049(3):231-43 [2200521] J Mol Biol. 1990 Aug 20;214(4):897-910 [2388273] Proc Natl Acad Sci U S A. 1984 Jan;81(1):95-9 [6320177] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential use of the regulatory elements of the alpha B-crystallin enhancer in cultured murine lung (MLg), lens (alpha TN4-1) and muscle (C2C12) cells. AN - 77225553; 7536694 AB - The mouse alpha B-crystallin-encoding gene (alpha B-cry) is highly expressed in the lens and expressed to lesser extents in other tissues. Here, we investigated alpha B-cry expression in mouse-lung-derived MLg cells. Two sizes of MLg alpha B-cry transcripts comigrated with alpha B-cry transcripts contained in total and poly(A)+RNA from mouse lung, with preference for the larger species in the MLg cells. Expression of both alpha B-cry promoter/cat reporter gene constructs and alpha B-cry enhancer (nt -427/-259)/herpes simplex virus (HSV) thymidine kinase promoter (ptk)/human growth hormone reporter gene (hGH) constructs was studied in transfected MLg cells and the results compared with those obtained from alpha TN4-1 lens and C2C12 muscle cells. The alpha B-cry enhancer increased activity of the endogenous and tk promoters approx. 2-fold in the MLg cells, in contrast to its 3-7-fold effect in alpha TN4-1 cells and 17-20-fold effect in C2C12 myotubes. Site-specific mutagenesis of the previously identified enhancer control elements, alpha B-E-1 (nt -407 to -397), alpha BE-2 (-360 to -327) and MRF (-300 to -288), decreased enhancer strength in transfected MLg cells. DNase I footprinting showed that MLg nuclear proteins occupy only alpha BE-1 and alpha BE-2. Previous data have shown that lens cells use alpha BE-1, alpha BE-2 and alpha BE-3, while muscle cells use, in addition, the muscle regulatory factor-binding site (MRF). Thus, the present experiments correlate tissue-specific enhancer strength and the number of control elements utilized. JF - Gene AU - Haynes, J I AU - Gopal-Srivastava, R AU - Frederikse, P H AU - Piatigorsky, J AD - Laboratory of Molecular and Developmental Biology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/04/03/ PY - 1995 DA - 1995 Apr 03 SP - 151 EP - 158 VL - 155 IS - 2 SN - 0378-1119, 0378-1119 KW - ALPHAB-cry KW - Crystallins KW - 0 KW - DNA, Complementary KW - Poly A KW - 24937-83-5 KW - RNA KW - 63231-63-0 KW - Index Medicus KW - Animals KW - Gene Transfer Techniques KW - Humans KW - RNA -- analysis KW - Mice KW - Organ Specificity KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Cells, Cultured KW - Molecular Sequence Data KW - Gene Expression Regulation KW - Lens, Crystalline -- metabolism KW - Enhancer Elements, Genetic -- genetics KW - Lung -- metabolism KW - Crystallins -- genetics KW - Muscle, Skeletal -- metabolism KW - Crystallins -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77225553?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gene&rft.atitle=Differential+use+of+the+regulatory+elements+of+the+alpha+B-crystallin+enhancer+in+cultured+murine+lung+%28MLg%29%2C+lens+%28alpha+TN4-1%29+and+muscle+%28C2C12%29+cells.&rft.au=Haynes%2C+J+I%3BGopal-Srivastava%2C+R%3BFrederikse%2C+P+H%3BPiatigorsky%2C+J&rft.aulast=Haynes&rft.aufirst=J&rft.date=1995-04-03&rft.volume=155&rft.issue=2&rft.spage=151&rft.isbn=&rft.btitle=&rft.title=Gene&rft.issn=03781119&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-24 N1 - Date created - 1995-05-24 N1 - Date revised - 2017-01-13 N1 - Gene symbol - ALPHAB-cry N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Processing of complex sounds in the macaque nonprimary auditory cortex. AN - 85164634; pmid-7701330 AB - Neurons in the superior temporal gyrus of anesthetized rhesus monkeys were exposed to complex acoustic stimuli. Bandpassed noise bursts with defined center frequencies evoked responses that were greatly enhanced over those evoked by pure tones. This finding led to the discovery of at least one new cochleotopic area in the lateral belt of the nonprimary auditory cortex. The best center frequencies of neurons varied along a rostrocaudal axis, and the best bandwidths of the noise bursts varied along a mediolateral axis. When digitized monkey calls were used as stimuli, many neurons showed a preference for some calls over others. Manipulation of the calls' frequency structure and playback of separate components revealed different types of spectral integration. The lateral areas of the monkey auditory cortex appear to be part of a hierarchical sequence in which neurons prefer increasingly complex stimuli and may form an important stage in the preprocessing of communication sounds. JF - Science AU - Rauschecker, J P AU - Tian, B AU - Hauser, M AD - Laboratory of Neurophysiology, National Institute of Mental Health, Poolesville, MD 20837, USA. PY - 1995 SP - 111 EP - 114 VL - 268 IS - 5207 SN - 0036-8075, 0036-8075 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85164634?accountid=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=Processing+of+complex+sounds+in+the+macaque+nonprimary+auditory+cortex.&rft.au=Rauschecker%2C+J+P%3BTian%2C+B%3BHauser%2C+M&rft.aulast=Rauschecker&rft.aufirst=J&rft.date=1995-04-01&rft.volume=268&rft.issue=5207&rft.spage=111&rft.isbn=&rft.btitle=&rft.title=Science&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Normal metallothionein synthesis in fibroblasts obtained from children with Indian childhood cirrhosis or copper-associated childhood cirrhosis. AN - 77827321; 8581360 AB - We previously demonstrated decreased metallothionein (MT) synthesis in cultured fibroblasts obtained from an American boy with findings typical of Indian Childhood Cirrhosis (ICC). We now report normal basal, copper-induced, and zinc-induced MT synthesis in the fibroblasts of two Indian boys and one Irish boy with typical ICC and one Indian boy with copper-associated childhood cirrhosis. This suggests that etiologies other than impaired MT production should be sought as the primary defect in these disorders. JF - Biochemical and molecular medicine AU - Hahn, S H AU - Tanner, M S AU - Danks, D M AU - Gahl, W A AD - Section on Human Biochemical Genetics, National Institute of Child Health and Human Development, National Institutes of Health Bethesda, Maryland 20892, USA Y1 - 1995/04// PY - 1995 DA - April 1995 SP - 142 EP - 145 VL - 54 IS - 2 SN - 1077-3150, 1077-3150 KW - Sulfur Radioisotopes KW - 0 KW - Copper KW - 789U1901C5 KW - Metallothionein KW - 9038-94-2 KW - Zinc KW - J41CSQ7QDS KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Electrophoresis, Polyacrylamide Gel KW - Humans KW - Child KW - Autoradiography KW - Child, Preschool KW - India KW - Infant KW - Zinc -- pharmacology KW - Cysteine -- chemistry KW - Cells, Cultured KW - Female KW - Male KW - Fibroblasts -- drug effects KW - Liver Cirrhosis -- chemically induced KW - Metallothionein -- biosynthesis KW - Liver Cirrhosis -- drug therapy KW - Copper -- metabolism KW - Copper -- adverse effects KW - Metallothionein -- drug effects KW - Liver Cirrhosis -- metabolism KW - Fibroblasts -- cytology KW - Copper -- pharmacology KW - Fibroblasts -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77827321?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+molecular+medicine&rft.atitle=Normal+metallothionein+synthesis+in+fibroblasts+obtained+from+children+with+Indian+childhood+cirrhosis+or+copper-associated+childhood+cirrhosis.&rft.au=Hahn%2C+S+H%3BTanner%2C+M+S%3BDanks%2C+D+M%3BGahl%2C+W+A&rft.aulast=Hahn&rft.aufirst=S&rft.date=1995-04-01&rft.volume=54&rft.issue=2&rft.spage=142&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+molecular+medicine&rft.issn=10773150&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-15 N1 - Date created - 1996-03-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protein-DNA interactions during phenotypic differentiation. AN - 77648026; 7576307 AB - We have been studying the molecular mechanism of neuronal differentiation through which the multipotent precursor becomes limited to the final transmitter phenotype. Here we focused on the role of the 5' proximal regulatory cassette (-190; +53 bp) of the rat enkephalin (rENK) gene in the developmental regulation of the enkephalin phenotype. Several well characterized cis-elements, including AP2, CREB, NF1, and NFkB, reside on this region of the rENK gene. These motifs were sufficient to confer activity-dependent expression of the gene during neurodifferentiation when it was tested using transient transfection assays of primary developing spinal cord neurons treated with tetrodotoxin (TTX). This region was then used as a DNA probe in mobility shift assays, with nuclear proteins derived from phenotypically and ontogenetically distinct brain regions. Only a few low abundance protein-DNA complexes were detected and only with nuclear proteins derived from developing but not from adult brain. The spatiotemporal pattern of these complexes did not show correlation with enkephalin expression which was assessed by RT-PCR. We employed synthetic probes corresponding to consensus as well as ENK-specific sequences of the individual motifs to identify the nature of the observed bands. Although both consensus NF1 and enkCRE1(NF1) formed complexes with nuclear proteins derived from the striatum and cortex at various ages, the appearance of the bands was not correlated with ENK expression. Surprisingly, no complexes were detected if other ENK-specific motifs were used as probes. We also tested nuclear extracts derived from forskolin-induced and control C6 glioma cells, again using the whole proximal regulatory cassette as well as individual motifs. These experiments showed the formation of elaborate protein-DNA bands. There was no direct correlation between the appearance of bands and forskolin-induced ENK expression. Unexpectedly, all ENK-specific motifs formed specific and highly abundant protein-DNA complexes when nuclear extracts from the human tumor cell line (HeLa), which does not express ENK, were used. Based on these observations, we concluded that: 1. Interactions between the proximal regulatory cassette and additional probably far distant regions of the rENK gene and their binding proteins may be necessary to confer developmentally regulated, cell-specific expression of the ENK gene; and 2. Inducibility of the gene by common cis-elements can be governed by this region; however, the cell-specificity of the induction remains elusive. JF - Molecular neurobiology AU - Dobi, A L AU - Palkovits, M AU - Palkovits, C G AU - Santha, E AU - van Agoston, D AD - Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-4480, USA. PY - 1995 SP - 185 EP - 203 VL - 10 IS - 2-3 SN - 0893-7648, 0893-7648 KW - DNA Probes KW - 0 KW - DNA, Neoplasm KW - Enkephalins KW - Macromolecular Substances KW - Neoplasm Proteins KW - Nerve Tissue Proteins KW - Recombinant Fusion Proteins KW - Transcription Factors KW - Colforsin KW - 1F7A44V6OU KW - Tetrodotoxin KW - 4368-28-9 KW - DNA KW - 9007-49-2 KW - Cycloheximide KW - 98600C0908 KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - Animals KW - Cell Lineage KW - Astrocytes -- drug effects KW - Humans KW - Rats KW - Phenotype KW - Colforsin -- pharmacology KW - Promoter Regions, Genetic KW - Tumor Cells, Cultured KW - Cycloheximide -- pharmacology KW - Recombinant Fusion Proteins -- genetics KW - Molecular Sequence Data KW - Neoplasm Proteins -- metabolism KW - Spinal Cord -- cytology KW - Transcription Factors -- physiology KW - HeLa Cells KW - Cell Differentiation KW - Mice KW - Spinal Cord -- embryology KW - Ganglia, Spinal -- embryology KW - Ganglia, Spinal -- cytology KW - Tetrodotoxin -- toxicity KW - Rats, Sprague-Dawley KW - Base Sequence KW - Glioma -- pathology KW - Transfection KW - Cells, Cultured KW - DNA, Neoplasm -- genetics KW - Consensus Sequence KW - DNA, Neoplasm -- metabolism KW - Astrocytes -- metabolism KW - Enkephalins -- genetics KW - Neurons -- metabolism KW - Enkephalins -- biosynthesis KW - DNA -- metabolism KW - Neurons -- cytology KW - DNA -- genetics KW - Nerve Tissue Proteins -- metabolism KW - Gene Expression Regulation, Developmental -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77648026?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neurobiology&rft.atitle=Protein-DNA+interactions+during+phenotypic+differentiation.&rft.au=Dobi%2C+A+L%3BPalkovits%2C+M%3BPalkovits%2C+C+G%3BSantha%2C+E%3Bvan+Agoston%2C+D&rft.aulast=Dobi&rft.aufirst=A&rft.date=1995-04-01&rft.volume=10&rft.issue=2-3&rft.spage=185&rft.isbn=&rft.btitle=&rft.title=Molecular+neurobiology&rft.issn=08937648&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-29 N1 - Date created - 1995-11-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of 7-nitroindazole with other nitric oxide synthase inhibitors as attenuators of opioid withdrawal. AN - 77526988; 7568621 AB - Previously, we demonstrated that two nonselective inhibitors of nitric oxide synthase (NOS), L-NG-nitroarginine (L-NNA) and L-NG-nitroarginine methyl ester (L-NAME), reduced some signs of morphine withdrawal in rats. The present work extended these studies to include 7-nitroindazole (7-NI), an inhibitor specific for cerebral NOS, and N(5)-(1-iminoethyl)-L-ornithine (L-NIO), a potent inhibitor of endothelial NOS. Behavioral effects of these four NOS inhibitors and clonidine, an alpha 2-adrenoceptor, agonist, on morphine withdrawal in rats were assessed. Rats received one 75-mg morphine pellet subcutaneously (SC). Three days later, NOS inhibitors were administered IP 1 h before withdrawal was precipitated with naloxone (0.5 mg/kg, SC) and scored. 7-NI, L-NIO, L-NAME and L-NNA produced dose-related decreases in weight loss, diarrhea, wet dog shakes and grooming. 7-NI also reduced mastication, salivation and genital effects. Clonidine produced effects similar to 7-NI. In awake, morphine-naive and morphine-dependent rats not subjected to withdrawal, 7-NI was the only NOS inhibitor that did not increase blood pressure. Because 7-NI attenuated more signs of opioid withdrawal than L-NNA, L-NAME or L-NIO without causing hypertension, 7-NI appears to warrant further testing as a potential candidate for human use. JF - Psychopharmacology AU - Vaupel, D B AU - Kimes, A S AU - London, E D AD - Neuroimaging and Drug Action Section, National Institute on Drug Abuse, Baltimore, MD 21224, USA. Y1 - 1995/04// PY - 1995 DA - April 1995 SP - 361 EP - 368 VL - 118 IS - 4 SN - 0033-3158, 0033-3158 KW - Enzyme Inhibitors KW - 0 KW - Indazoles 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 - Heart Rate -- drug effects KW - Blood Pressure -- physiology KW - Analysis of Variance KW - Dose-Response Relationship, Drug KW - Heart Rate -- physiology KW - Blood Pressure -- drug effects KW - Time Factors KW - Male KW - Substance Withdrawal Syndrome -- physiopathology KW - Enzyme Inhibitors -- therapeutic use KW - Nitric Oxide Synthase -- antagonists & inhibitors KW - Indazoles -- pharmacology KW - Substance Withdrawal Syndrome -- drug therapy KW - Enzyme Inhibitors -- pharmacology KW - Indazoles -- therapeutic use KW - Opioid-Related Disorders -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77526988?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology&rft.atitle=Comparison+of+7-nitroindazole+with+other+nitric+oxide+synthase+inhibitors+as+attenuators+of+opioid+withdrawal.&rft.au=Vaupel%2C+D+B%3BKimes%2C+A+S%3BLondon%2C+E+D&rft.aulast=Vaupel&rft.aufirst=D&rft.date=1995-04-01&rft.volume=118&rft.issue=4&rft.spage=361&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-23 N1 - Date created - 1995-10-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer genes: single and susceptibility: exposing the difference. AN - 77505307; 7663529 AB - 'Single' genes, necessary and sufficient to cause cancer, are contrasted with 'susceptibility' genes that are neither, but may act in the presence of specific environmental exposures to alter the chances of cancer in the host. The former are rare, are of high absolute and relative risks, have minimal dependence on exposures and therefore have low population attributable risks. A small number of such genes are well established in the literature and typically exhibit familial aggregations of disease that serve as a starting point for genetic studies. 'Susceptibility' genes, as typified by the pharmacogenetic model, are common, have low relative and absolute risk, are strongly dependent upon exposure, and may have potentially high population attributable risks. Mechanistic and epidemiologic data are suggestive but currently fall short of confirmation for these associations. Familial aggregation is not a prominent feature and epidemiological study designs with careful exposure assessment is the investigative method of choice. Both approaches require interdisciplinary expertise and benefit from advances in molecular biology. JF - Pharmacogenetics AU - Caporaso, N AU - Goldstein, A AD - Genetic Epidemiology Branch, National Cancer Institute, NIH, Rockville, MD 20892, USA. Y1 - 1995/04// PY - 1995 DA - April 1995 SP - 59 EP - 63 VL - 5 IS - 2 SN - 0960-314X, 0960-314X KW - Index Medicus KW - Risk Factors KW - Humans KW - Environmental Exposure KW - Oncogenes KW - Neoplasms -- epidemiology KW - Genetic Predisposition to Disease KW - Neoplasms -- genetics KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77505307?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacogenetics&rft.atitle=Cancer+genes%3A+single+and+susceptibility%3A+exposing+the+difference.&rft.au=Caporaso%2C+N%3BGoldstein%2C+A&rft.aulast=Caporaso&rft.aufirst=N&rft.date=1995-04-01&rft.volume=5&rft.issue=2&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=Pharmacogenetics&rft.issn=0960314X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-10 N1 - Date created - 1995-10-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Review: pain associated with HIV infection. AN - 77452401; 11361383 JF - Pediatric AIDS and HIV infection AU - Hirschfeld, S AU - Morris, B K AD - Pediatric Branch, National Cancer Institute, Bethesda, MD, USA. Y1 - 1995/04// PY - 1995 DA - April 1995 SP - 63 EP - 74 VL - 6 IS - 2 SN - 1045-5418, 1045-5418 KW - Analgesics KW - 0 KW - Antiviral Agents KW - AIDS/HIV KW - Acute Disease KW - AIDS-Related Opportunistic Infections -- drug therapy KW - Pain Management KW - Anesthesia KW - Humans KW - Analgesics -- pharmacology KW - Pain Measurement KW - Chronic Disease KW - Antiviral Agents -- adverse effects KW - Analgesics -- adverse effects KW - Pain -- etiology KW - HIV Infections -- complications KW - Pain -- psychology KW - HIV Infections -- drug therapy KW - Pain -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77452401?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatric+AIDS+and+HIV+infection&rft.atitle=Review%3A+pain+associated+with+HIV+infection.&rft.au=Hirschfeld%2C+S%3BMorris%2C+B+K&rft.aulast=Hirschfeld&rft.aufirst=S&rft.date=1995-04-01&rft.volume=6&rft.issue=2&rft.spage=63&rft.isbn=&rft.btitle=&rft.title=Pediatric+AIDS+and+HIV+infection&rft.issn=10455418&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-21 N1 - Date created - 1995-09-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Endothelial changes in galactose-fed dogs. AN - 77385034; 7606918 AB - Specular microscopic studies indicate that the size (polymegathism) and shape (pleomorphism) of the hexagonal corneal endothelial cells change in diabetics. Similar morphometric changes of the corneal endothelium have also been experimentally observed in diabetic rats as well as in diabetic and galactose-fed dogs and concomitant administration of aldose reductase inhibitors reduced these morphological changes. The purpose of this study was to examine whether corneal endothelial changes in galactose-fed dogs are reversible by the marked reduction of galactitol production after stopping prolonged galactose feeding. Ten control dogs were fed a normal diet, while 48 dogs were fed a diet containing 30% galactose. The galactose diet was removed from 15 dogs after 24 months at which time pericyte ghosts in the retina had developed and another 15 dogs were removed from the galactose diet after 31 months when retinal microaneurysms had developed. Eighteen dogs remained on galactose diet throughout the study (38 months). Specular microscopy was conducted on members of all groups after 38 months of study and the photographs were analyzed in masked fashion on the Bambi image analysis system. The evaluation of the corneal endothelial cells revealed significant differences in the cell size and density between galactose-fed dogs in the three groups and normal, age-matched control dogs. Corneal endothelial changes were not significantly reduced in dogs fed galactose for either 24 months or 31 months and then fed a normal diet for 14 and 7 months, respectively, indicating that amelioration of endothelial cell changes requires therapy prior to the advent of endothelial morphologic changes. JF - Current eye research AU - Neuenschwander, H AU - Julia, C AU - Wyman, M AU - Kador, P F AD - Laboratory of Ocular Therapeutics, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/04// PY - 1995 DA - April 1995 SP - 319 EP - 322 VL - 14 IS - 4 SN - 0271-3683, 0271-3683 KW - Galactitol KW - 113ZQ1Y7DD KW - Galactose KW - X2RN3Q8DNE KW - Index Medicus KW - Animals KW - Cell Count -- drug effects KW - Dogs KW - Diet KW - Male KW - Galactitol -- metabolism KW - Cell Size -- drug effects KW - Endothelium, Corneal -- drug effects KW - Endothelium, Corneal -- metabolism KW - Galactosemias -- chemically induced KW - Galactose -- administration & dosage KW - Endothelium, Corneal -- pathology KW - Galactosemias -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77385034?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+eye+research&rft.atitle=Endothelial+changes+in+galactose-fed+dogs.&rft.au=Neuenschwander%2C+H%3BJulia%2C+C%3BWyman%2C+M%3BKador%2C+P+F&rft.aulast=Neuenschwander&rft.aufirst=H&rft.date=1995-04-01&rft.volume=14&rft.issue=4&rft.spage=319&rft.isbn=&rft.btitle=&rft.title=Current+eye+research&rft.issn=02713683&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-14 N1 - Date created - 1995-08-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - No point mutation but a codon 31ser-->arg polymorphism of the WAF-1/CIP-1/p21 tumor suppressor gene in nasopharyngeal carcinoma (NPC): the polymorphism distinguishes Caucasians from Chinese. AN - 77384547; 7606201 AB - Mutational inactivation of the p53 tumor suppressor gene is an infrequent event in human nasopharyngeal carcinoma (NPC), a malignancy showing a high incidence in southern China and southeast Asia. To examine the possible involvement of an activated p53 pathway in nasopharynx carcinogenesis, we have screened primary NPC biopsies for possible point mutations in WAF-1/CIP-1/p21, an effector gene transcriptionally regulated by and functioning as a mediator of the p53 tumor suppressor gene. Mutations in WAF-1/CIP-1/p21 might mimic p53 mutations in tumors having wild-type p53 such as most NPCs. The mutational analysis of WAF/CIP/p21 by PCR-single strand conformational polymorphism-direct sequencing revealed no point mutation in 41 primary NPC biopsies. A codon 31ser-->arg polymorphism was, however, detected. A striking difference in the distribution of the serine (WAF-ser) and arginine (WAF-arg) forms of WAF-1/CIP-1/p21 was observed when normal healthy Caucasians and Chinese were compared (P < 0.0001). The majority of Caucasians examined were found to be homozygous for WAF-ser (89%, n = 65), while Chinese living in areas of high NPC incidence show a greater than 86% homozygous or heterozygous WAF-arg (Taiwan, n = 66; Hunan, n = 32). The two forms of WAF-1/CIP-1/p21 were examined for potential functional differences in their ability to inhibit cyclin-dependent kinases and tumor cell growth. No significant differences were detected. Furthermore, no association between WAF-1/CIP-1/p21 genotype and NPC risk was observed in a case-control study of 76 NPC cases and 66 normal controls conducted in Taiwan.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Sun, Y AU - Hildesheim, A AU - Li, H AU - Li, Y AU - Chen, J Y AU - Cheng, Y J AU - Hayes, R B AU - Rothman, N AU - Bi, W F AU - Cao, Y AD - Cell Biology Section, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland, USA. PY - 1995 SP - 261 EP - 267 VL - 4 IS - 3 SN - 1055-9965, 1055-9965 KW - CDKN1A protein, human KW - 0 KW - Cdkn1a protein, mouse KW - Codon KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - Protein Kinase Inhibitors KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Animals KW - Taiwan KW - DNA Mutational Analysis KW - Humans KW - Mice KW - Mice, Nude KW - Genotype KW - Transfection -- genetics KW - Polymerase Chain Reaction -- methods KW - Cell Division -- genetics KW - Cell Line KW - Cell Transformation, Neoplastic -- genetics KW - Point Mutation -- genetics KW - Codon -- genetics KW - Polymorphism, Genetic -- genetics KW - Tumor Suppressor Protein p53 -- genetics KW - Nasopharyngeal Neoplasms -- genetics KW - Nasopharyngeal Neoplasms -- ethnology KW - European Continental Ancestry Group -- genetics KW - Asian Continental Ancestry Group -- genetics KW - Cyclins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77384547?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=No+point+mutation+but+a+codon+31ser--%26gt%3Barg+polymorphism+of+the+WAF-1%2FCIP-1%2Fp21+tumor+suppressor+gene+in+nasopharyngeal+carcinoma+%28NPC%29%3A+the+polymorphism+distinguishes+Caucasians+from+Chinese.&rft.au=Sun%2C+Y%3BHildesheim%2C+A%3BLi%2C+H%3BLi%2C+Y%3BChen%2C+J+Y%3BCheng%2C+Y+J%3BHayes%2C+R+B%3BRothman%2C+N%3BBi%2C+W+F%3BCao%2C+Y&rft.aulast=Sun&rft.aufirst=Y&rft.date=1995-04-01&rft.volume=4&rft.issue=3&rft.spage=261&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 - 1995-08-11 N1 - Date created - 1995-08-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Assessment of the reproductive toxicity of a complex mixture of 25 groundwater contaminants in mice and rats. AN - 77378949; 7601330 AB - The potential reproductive toxicity of a mixture of 25 chemicals (MIX) formulated to simulate contaminated groundwater supplies near hazardous waste dumps was evaluated in CD-1 Swiss mice and Sprague-Dawley rats using the reproductive assessment by continuous breeding protocol. Male and female mice and rats were exposed to MIX in the drinking water at concentrations of 1, 5, and 10% of a technically achievable stock solution. For mice, body weight and feed consumption were not affected by MIX but water consumption was decreased for both the 5 and 10% MIX groups in both F0 and F1 animals. For F0 mice, the number of live pups/litter was decreased at 10% MIX and the number of females/litter was decreased 10 and 17% at the mid and high MIX dose, respectively. Vaginal cytology was normal, as were testis weight and testicular spermatid head count. For F1 mice, fertility was unaffected, but there was a decreased number of female pups/litter (19%) and a decreased adjusted live pup weight at 10% MIX. At necropsy, cauda epididymal sperm concentration and spermatid head count were reduced (20%) in the presence of normal testis, epididymis, prostate, seminal vesicle, liver, and kidney/adrenal weight. Female estrous cyclicity was altered at 5 and 10% MIX with normal kidney/adrenal, uterus, and ovary/oviduct weight. For rats, F0 body weight and feed consumption were not affected by MIX but water consumption was decreased 10, 30, and 40% in the low-, medium-, and high-dose MIX groups, respectively, and 39% in the high-dose MIX F1 animals. Rat fertility was normal but there was a decreased number of male pups/litter (11%) and a decreased live pup weight (6%) at 10% MIX. Male and female (F1) pup weights were decreased on Postnatal Days 0, 4, 7, 14, and 21 (10% MIX) and remained lower through necropsy on Day 120 +/- 10. F1 fertility was normal but F2 pup weights were decreased (10% MIX). At necropsy, F1 (10% MIX) male body weight was decreased 16% and relative kidney, testis, epididymis, and prostate weights were increased in the presence of normal sperm concentration percentage motile sperm and percentage abnormal sperm. Estrous cyclicity was normal as were kidney/adrenal and ovary weight while female liver weight was reduced 14%. In summary, a "cocktail" of 25 chemicals commonly found in contaminated groundwater at or near hazardous waste sites was administered in drinking water at doses which resulted in severely decreased water consumption in both mice and rats.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Heindel, J J AU - Chapin, R E AU - George, J AU - Gulati, D K AU - Fail, P A AU - Barnes, L H AU - Yang, R S AD - National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/04// PY - 1995 DA - April 1995 SP - 9 EP - 19 VL - 25 IS - 1 SN - 0272-0590, 0272-0590 KW - Hazardous Waste KW - 0 KW - Water Pollutants, Chemical KW - Index Medicus KW - Animals KW - Litter Size -- drug effects KW - Sperm Count -- drug effects KW - Mice, Inbred ICR KW - Mice KW - Sperm Motility -- drug effects KW - Rats KW - Rats, Sprague-Dawley KW - Breeding KW - Drinking -- drug effects KW - Female KW - Male KW - Fertility -- drug effects KW - Organ Size -- drug effects KW - Reproduction -- drug effects KW - Water Pollutants, Chemical -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77378949?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Assessment+of+the+reproductive+toxicity+of+a+complex+mixture+of+25+groundwater+contaminants+in+mice+and+rats.&rft.au=Heindel%2C+J+J%3BChapin%2C+R+E%3BGeorge%2C+J%3BGulati%2C+D+K%3BFail%2C+P+A%3BBarnes%2C+L+H%3BYang%2C+R+S&rft.aulast=Heindel&rft.aufirst=J&rft.date=1995-04-01&rft.volume=25&rft.issue=1&rft.spage=9&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-10 N1 - Date created - 1995-08-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of atrial natriuretic peptide on diastolic filling in the stage 21 chick embryo. AN - 77363910; 7596686 AB - Atrial natriuretic peptide (ANP) exerts hemodynamic effects by direct venodilation in the chick embryo. We hypothesized that ANP-induced venodilation affects ventricular diastolic filling resulting in reduced ventricular preload. Chick ANP (0.1 microgram in 10 microL of normal saline) was suffused onto the vitelline vascular bed in stage 21 (3 1/2 d) chick embryos. Equivalent aliquots of normal saline were suffused as sham controls, and normal embryos received no suffusion. We measured simultaneously dorsal aortic blood velocity and atrioventricular blood velocity with a 20-MHz pulsed-Doppler velocity meter. Analog wave forms were digitally sampled at 500 Hz, and the dorsal aortic cross-sectional area was used to calculate dorsal aortic blood flow. Passive ventricular filling volume equaled dorsal aortic stroke volume multiplied by the fraction of passive area; active filling volume equaled dorsal aortic stroke volume multiplied by the fraction of active area. Data were summarized as mean +/- SEM (n > or = 7 per group) and analyzed by analysis of variance. Cycle lengths were similar in ANP-suffused, sham control, and normal embryos. Dorsal aortic blood flow decreased from 0.49 +/- 0.04 mm3/S at baseline to 0.27 +/- 0.05 mm3/S at 4 min post-ANP suffusion (p 0.05). Passive ventricular filling was reduced by ANP suffusion, whereas active filling was unaffected, resulting in a decreased passive/active filling ratio from 0.64 +/- 0.07 at baseline to 0.32 +/- 0.08 at 4 min in ANP-suffused embryos (p < 0.05). Passive/active ratio was unchanged in sham control and normal embryos. Thus, ANP-mediated vasodilation reduces cardiac output via decreased passive ventricular filling in the embryonic heart. JF - Pediatric research AU - Hu, N AU - Hansen, A L AU - Clark, E B AU - Keller, B B AD - National Institutes of Health SCOR in Pediatric Cardiovascular Diseases, University of Rochester School of Medicine and Dentistry, New York 14642, USA. Y1 - 1995/04// PY - 1995 DA - April 1995 SP - 465 EP - 468 VL - 37 IS - 4 Pt 1 SN - 0031-3998, 0031-3998 KW - Vasodilator Agents KW - 0 KW - Atrial Natriuretic Factor KW - 85637-73-6 KW - Index Medicus KW - Animals KW - Analysis of Variance KW - Blood Flow Velocity KW - Chick Embryo KW - Gestational Age KW - Cardiac Output, Low -- chemically induced KW - Atrial Natriuretic Factor -- pharmacology KW - Stroke Volume -- drug effects KW - Vasodilator Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77363910?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatric+research&rft.atitle=Effect+of+atrial+natriuretic+peptide+on+diastolic+filling+in+the+stage+21+chick+embryo.&rft.au=Hu%2C+N%3BHansen%2C+A+L%3BClark%2C+E+B%3BKeller%2C+B+B&rft.aulast=Hu&rft.aufirst=N&rft.date=1995-04-01&rft.volume=37&rft.issue=4+Pt+1&rft.spage=465&rft.isbn=&rft.btitle=&rft.title=Pediatric+research&rft.issn=00313998&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-03 N1 - Date created - 1995-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Flap opening in HIV-1 protease simulated by 'activated' molecular dynamics. AN - 77362501; 7796268 AB - We have used an 'activated' molecular dynamics approach to simulate flap opening in HIV-1 protease. An initial impulse for flap opening was provided by applying harmonic constraints to non-flap residues. After an initial 'melting' phase, the two beta-hairpin structures that constitute the flaps opened to a 25 A gap within 200 ps of simulation. Analysis of backbone torsion angles suggests that flap opening is related to conformational changes at Lys 45, Met 46, Gly 52 and Phe 53. In contrast, similar molecular dynamics simulations on the M46I mutant, which is associated with drug resistance, indicates that this mutation stabilizes the flaps in a closed conformation. JF - Nature structural biology AU - Collins, J R AU - Burt, S K AU - Erickson, J W AD - Structural Biochemistry Program, Frederick Biomedical Supercomputing Center, PRI/DynCorp, National Cancer Institute - Frederick Cancer Research and Development Center, Maryland 21702-1201, USA. Y1 - 1995/04// PY - 1995 DA - April 1995 SP - 334 EP - 338 VL - 2 IS - 4 SN - 1072-8368, 1072-8368 KW - HIV Protease Inhibitors KW - 0 KW - Recombinant Proteins KW - HIV Protease KW - EC 3.4.23.- KW - Index Medicus KW - AIDS/HIV KW - Mutagenesis, Site-Directed KW - Computer Simulation KW - Models, Molecular KW - Point Mutation KW - Drug Resistance, Microbial KW - HIV-1 -- enzymology KW - Amino Acid Sequence KW - Recombinant Proteins -- chemistry KW - Recombinant Proteins -- antagonists & inhibitors KW - Protein Structure, Secondary KW - HIV Protease Inhibitors -- chemistry KW - HIV Protease Inhibitors -- pharmacology KW - HIV Protease -- metabolism KW - HIV Protease -- chemistry KW - Protein Conformation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77362501?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+structural+biology&rft.atitle=Flap+opening+in+HIV-1+protease+simulated+by+%27activated%27+molecular+dynamics.&rft.au=Collins%2C+J+R%3BBurt%2C+S+K%3BErickson%2C+J+W&rft.aulast=Collins&rft.aufirst=J&rft.date=1995-04-01&rft.volume=2&rft.issue=4&rft.spage=334&rft.isbn=&rft.btitle=&rft.title=Nature+structural+biology&rft.issn=10728368&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-03 N1 - Date created - 1995-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Refined solution structure of the oligomerization domain of the tumour suppressor p53. AN - 77360114; 7796267 AB - The NMR solution structure of the oligomerization domain of the tumour suppressor p53 (residues 319-360) has been refined. The structure comprises a dimer of dimers, oriented in an approximately orthogonal manner. The present structure determination is based on 4,472 experimental NMR restraints which represents a three and half fold increase over our previous work in the number of NOE restraints at the tetramerization interface. A comparison with the recently solved 1.7 A resolution X-ray structure shows that the structures are very similar and that the average angular root-mean-square difference in the interhelical angles is about 1 degree. The results of recent extensive mutagenesis data and the possible effects of mutations which have been identified in human cancers are discussed in the light of the present structure. JF - Nature structural biology AU - Clore, G M AU - Ernst, J AU - Clubb, R AU - Omichinski, J G AU - Kennedy, W M AU - Sakaguchi, K AU - Appella, E AU - Gronenborn, A M AD - Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520, USA. Y1 - 1995/04// PY - 1995 DA - April 1995 SP - 321 EP - 333 VL - 2 IS - 4 SN - 1072-8368, 1072-8368 KW - Carbon Isotopes KW - 0 KW - Macromolecular Substances KW - Nitrogen Isotopes KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Animals KW - Models, Molecular KW - Biological Evolution KW - Humans KW - Vertebrates KW - Crystallography, X-Ray KW - Sequence Homology, Amino Acid KW - Magnetic Resonance Spectroscopy KW - Protein Structure, Secondary KW - Tumor Suppressor Protein p53 -- chemistry KW - Tumor Suppressor Protein p53 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77360114?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+structural+biology&rft.atitle=Refined+solution+structure+of+the+oligomerization+domain+of+the+tumour+suppressor+p53.&rft.au=Clore%2C+G+M%3BErnst%2C+J%3BClubb%2C+R%3BOmichinski%2C+J+G%3BKennedy%2C+W+M%3BSakaguchi%2C+K%3BAppella%2C+E%3BGronenborn%2C+A+M&rft.aulast=Clore&rft.aufirst=G&rft.date=1995-04-01&rft.volume=2&rft.issue=4&rft.spage=321&rft.isbn=&rft.btitle=&rft.title=Nature+structural+biology&rft.issn=10728368&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-03 N1 - Date created - 1995-08-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Nat Struct Biol. 1995 Apr;2(4):253-4 [7796256] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Malignant mesothelioma in thermoelectric power plant workers in Italy. AN - 77351856; 7793427 AB - Asbestos has been widely used in Italian thermoelectric power plants and instances of exposure to workers have been documented in a variety of jobs. Preventive measures were put into effect only in the late 1970s. We report here on four mesothelioma cases among workers of three Italian power plants where cohort studies were carried out, and on three additional cases recorded by a systematic survey carried out on this neoplasm in Tuscany. When the data of the cohorts sources are merged, a significant excess of lung cancer is also evident. Even without a quantitative assessment of exposure, this report shows the importance of asbestos risk in thermal power plants. The risk appears not to be restricted to any particular category of workers. JF - American journal of industrial medicine AU - Crosignani, P AU - Forastiere, F AU - Petrelli, G AU - Merler, E AU - Chellini, E AU - Pupp, N AU - Donelli, S AU - Magarotto, G AU - Rotondo, E AU - Perucci, C AD - Lombardy Cancer Registry, National Cancer Institute, Milan, Italy. Y1 - 1995/04// PY - 1995 DA - April 1995 SP - 573 EP - 576 VL - 27 IS - 4 SN - 0271-3586, 0271-3586 KW - Asbestos KW - 1332-21-4 KW - Index Medicus KW - Humans KW - Cohort Studies KW - Aged KW - Middle Aged KW - Italy -- epidemiology KW - Male KW - Mesothelioma -- epidemiology KW - Lung Neoplasms -- etiology KW - Lung Neoplasms -- epidemiology KW - Power Plants KW - Mesothelioma -- etiology KW - Occupational Diseases -- etiology KW - Asbestos -- adverse effects KW - Occupational Diseases -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77351856?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=Malignant+mesothelioma+in+thermoelectric+power+plant+workers+in+Italy.&rft.au=Crosignani%2C+P%3BForastiere%2C+F%3BPetrelli%2C+G%3BMerler%2C+E%3BChellini%2C+E%3BPupp%2C+N%3BDonelli%2C+S%3BMagarotto%2C+G%3BRotondo%2C+E%3BPerucci%2C+C&rft.aulast=Crosignani&rft.aufirst=P&rft.date=1995-04-01&rft.volume=27&rft.issue=4&rft.spage=573&rft.isbn=&rft.btitle=&rft.title=American+journal+of+industrial+medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-27 N1 - Date created - 1995-07-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Am J Ind Med. 2001 Apr;39(4):436-7; author reply 438 [11323795] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Anticytomegaloviral activity and safety of cidofovir in patients with human immunodeficiency virus infection and cytomegalovirus viruria. AN - 77343515; 7785989 AB - Cidofovir (HPMPC; (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine) is a nucleotide analog with activity against human cytomegalovirus (CMV). A phase I/II dose escalation trial was conducted with asymptomatic human immunodeficiency virus (HIV)-infected patients with CMV viruria to determine its pharmacokinetics, maximally tolerated dose, and preliminary antiviral activity against CMV. Qualitative CMV blood and urine cultures were monitored weekly to assess anti-CMV activity. Twenty-one HIV-infected persons with CD4 counts from 0 to 389 cells per microliters (median, 39) were enrolled in six dose-ranging groups. The first five groups enrolled four patients each to receive cidofovir infusions either weekly or biweekly for 4 weeks or every 3 weeks for 12 weeks. The sixth group enrolled one patient who received infusions of 5 mg/kg of body weight every other week. Patients receiving 0.5 or 1.5 mg/kg twice weekly experienced no serious toxicity. The first two patients who received 5 mg/kg twice weekly developed glycosuria and 2+ proteinuria. Subsequent patients received concomitant probenecid to attempt to ameliorate renal toxicity. Seventeen patients experienced proteinuria on one or more occasions; 6 of them experienced at least 2+ proteinuria. Four patients did not complete the study as planned because of renal toxicity. Positive CMV urine cultures reverted to negative in 2 of 8 patients receiving doses of < or = 1.5 mg/kg twice weekly and 11 of 13 patients receiving higher doses. Cidofovir has in vivo anti-CMV activity demonstrated by prolonged clearing of CMV viruria, although this observation is tempered by the fact that clearance of viremia could not be demonstrated. The dose-limiting toxicity is renal; however, concurrent administration of probenecid may be protective. The maximally tolerated weekly intravenous dose with probenecid is approximately 5 mg/kg. Efficacy trials with CMV disease will define the therapeutic utility and optimal dosing interval for cidofovir. JF - Antimicrobial agents and chemotherapy AU - Polis, M A AU - Spooner, K M AU - Baird, B F AU - Manischewitz, J F AU - Jaffe, H S AU - Fisher, P E AU - Falloon, J AU - Davey, R T AU - Kovacs, J A AU - Walker, R E AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/04// PY - 1995 DA - April 1995 SP - 882 EP - 886 VL - 39 IS - 4 SN - 0066-4804, 0066-4804 KW - Antiviral Agents KW - 0 KW - Organophosphonates KW - Organophosphorus Compounds KW - Cytosine KW - 8J337D1HZY KW - cidofovir KW - JIL713Q00N KW - Index Medicus KW - AIDS/HIV KW - Humans KW - Adult KW - Middle Aged KW - Urine -- microbiology KW - Male KW - Cytomegalovirus Infections -- drug therapy KW - Antiviral Agents -- therapeutic use KW - Organophosphorus Compounds -- therapeutic use KW - Cytosine -- therapeutic use KW - HIV Infections -- drug therapy KW - Cytosine -- pharmacokinetics KW - Cytosine -- analogs & derivatives KW - Organophosphorus Compounds -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77343515?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Anticytomegaloviral+activity+and+safety+of+cidofovir+in+patients+with+human+immunodeficiency+virus+infection+and+cytomegalovirus+viruria.&rft.au=Polis%2C+M+A%3BSpooner%2C+K+M%3BBaird%2C+B+F%3BManischewitz%2C+J+F%3BJaffe%2C+H+S%3BFisher%2C+P+E%3BFalloon%2C+J%3BDavey%2C+R+T%3BKovacs%2C+J+A%3BWalker%2C+R+E&rft.aulast=Polis&rft.aufirst=M&rft.date=1995-04-01&rft.volume=39&rft.issue=4&rft.spage=882&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 - 1995-07-20 N1 - Date created - 1995-07-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: JAMA. 1984 Jul 6;252(1):72-7 [6328055] Antimicrob Agents Chemother. 1994 Oct;38(10):2404-8 [7840578] J Med Chem. 1989 Jul;32(7):1457-63 [2544723] Ann Intern Med. 1990 Jan 1;112(1):35-49 [2403474] Lancet. 1990 Apr 28;335(8696):1044-5 [1970102] Virology. 1990 Nov;179(1):41-50 [2171213] J Med Virol. 1990 Nov;32(3):160-3 [1980687] J Infect Dis. 1991 Apr;163(4):716-9 [1849157] Ann Intern Med. 1991 Nov 1;115(9):665-73 [1656826] Ann Intern Med. 1992 Feb 15;116(4):311-3 [1733387] Antiviral Res. 1991 Jul;16(1):17-28 [1663727] Antiviral Res. 1991 Jul;16(1):41-52 [1663729] Antimicrob Agents Chemother. 1991 Nov;35(11):2262-6 [1666493] Ann Intern Med. 1993 Jan 1;118(1):12-7 [8093214] N Engl J Med. 1993 Dec 23;329(26):1922-6 [7902536] Antiviral Res. 1987 Dec;8(5-6):261-72 [3451698] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of myosin II isoforms containing insertions of amino acids in the flexible loop near the ATP-binding pocket. AN - 77341116; 7787079 JF - Biophysical journal AU - Kelley, C A AU - Adelstein, R S AD - Laboratory of Molecular Cardiology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/04// PY - 1995 DA - April 1995 VL - 68 IS - 4 Suppl SN - 0006-3495, 0006-3495 KW - MHC KW - RNA Precursors KW - 0 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - CDC2 Protein Kinase KW - EC 2.7.11.22 KW - Myosins KW - EC 3.6.4.1 KW - Index Medicus KW - RNA Precursors -- metabolism KW - Molecular Structure KW - Animals KW - CDC2 Protein Kinase -- metabolism KW - Biophysical Phenomena KW - Binding Sites KW - Biophysics KW - Oocytes -- metabolism KW - Alternative Splicing KW - Adenosine Triphosphate -- metabolism KW - In Vitro Techniques KW - Xenopus KW - RNA Precursors -- genetics KW - Female KW - Mutagenesis, Insertional KW - Myosins -- metabolism KW - Myosins -- chemistry KW - Myosins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77341116?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biophysical+journal&rft.atitle=Characterization+of+myosin+II+isoforms+containing+insertions+of+amino+acids+in+the+flexible+loop+near+the+ATP-binding+pocket.&rft.au=Kelley%2C+C+A%3BAdelstein%2C+R+S&rft.aulast=Kelley&rft.aufirst=C&rft.date=1995-04-01&rft.volume=68&rft.issue=4+Suppl&rft.spage=225S&rft.isbn=&rft.btitle=&rft.title=Biophysical+journal&rft.issn=00063495&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-27 N1 - Date created - 1995-07-27 N1 - Date revised - 2017-01-13 N1 - Gene symbol - MHC N1 - SuppNotes - Cited By: Eur J Biochem. 1989 Oct 1;184(3):611-6 [2806244] Biochem Biophys Res Commun. 1990 Jul 16;170(1):53-8 [2372298] J Cell Biol. 1991 Mar;112(5):915-24 [1999462] J Biol Chem. 1992 Sep 5;267(25):17864-71 [1355479] J Biol Chem. 1995 Jan 20;270(3):1395-401 [7836406] Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2856-9 [8464900] Am J Physiol. 1993 May;264(5 Pt 1):C1252-8 [7684561] J Biol Chem. 1993 Jun 15;268(17):12848-54 [8509418] Science. 1993 Jul 2;261(5117):50-8 [8316857] Nucleic Acids Res. 1993 Mar 25;21(6):1467-71 [8464739] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activity of hepatic drug metabolizing enzymes following oxazepam-dosed feed treatment in B6C3F1 mice. AN - 77293330; 7762012 AB - Oxazepam has been determined to be a potent hepatocarcinogen in mice. Evidence in the literature indicates that oxazepam is capable of inducing drug metabolizing enzymes in rodents and an association between enzyme induction and carcinogenesis has been proposed for other compounds such as phenobarbital. We examined the pattern of enzyme induction that occurs under bioassay conditions in male B6C3F1 mice. The results indicate that oxazepam is capable of inducing multiple drug metabolizing enzymes under bioassay conditions. Closer examination of the most induced samples suggests that oxazepam is a phenobarbital-type enzyme inducer. JF - Toxicology letters AU - Griffin, R J AU - Burka, L T AU - Cunningham, M L AD - Chemistry Branch, National Institute of Environmental Health Sciences MD C3-02, Research Triangle Park, NC 27709, USA. Y1 - 1995/04// PY - 1995 DA - April 1995 SP - 251 EP - 256 VL - 76 IS - 3 SN - 0378-4274, 0378-4274 KW - Oxazepam KW - 6GOW6DWN2A KW - Cytochromes b5 KW - 9035-39-6 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Oxidoreductases KW - EC 1.- KW - Aniline Hydroxylase KW - EC 1.14.14.- KW - Cytochrome P-450 CYP2B1 KW - EC 1.14.14.1 KW - Aminopyrine N-Demethylase KW - EC 1.5.3.- KW - Glucuronosyltransferase KW - EC 2.4.1.17 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Animals KW - Analysis of Variance KW - Random Allocation KW - Cytosol -- drug effects KW - Dose-Response Relationship, Drug KW - Glutathione Transferase -- metabolism KW - Glucuronosyltransferase -- metabolism KW - Mice KW - Eating KW - Oxidoreductases -- metabolism KW - Aminopyrine N-Demethylase -- metabolism KW - Enzyme Induction -- drug effects KW - Aniline Hydroxylase -- metabolism KW - Body Weight -- drug effects KW - Male KW - Organ Size -- drug effects KW - Liver -- enzymology KW - Oxazepam -- toxicity KW - Liver -- drug effects KW - Cytochromes b5 -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Oxazepam -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77293330?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+letters&rft.atitle=Activity+of+hepatic+drug+metabolizing+enzymes+following+oxazepam-dosed+feed+treatment+in+B6C3F1+mice.&rft.au=Griffin%2C+R+J%3BBurka%2C+L+T%3BCunningham%2C+M+L&rft.aulast=Griffin&rft.aufirst=R&rft.date=1995-04-01&rft.volume=76&rft.issue=3&rft.spage=251&rft.isbn=&rft.btitle=&rft.title=Toxicology+letters&rft.issn=03784274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-27 N1 - Date created - 1995-06-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxidative modification of fibrinogen inhibits thrombin-catalyzed clot formation. AN - 77270626; 7750804 AB - Plasma fibrinogen plays a central role in controlling hemostasis. In an earlier report, we found that fibrinogen is oxidized when whole plasma is treated with a metal-catalyzed oxidation system. These studies show that oxidative modification of purified human fibrinogen leads to an exposure-dependent loss of thrombin-induced clot formation. Inhibition of clotting occurred when either metal-catalyzed oxidation or gamma-irradiation was employed to generate oxidizing radicals. Both systems caused covalent modification of fibrinogen, assessed by measuring incorporation of protein carbonyls. Thrombin-catalyzed fibrinopeptide release was normal in irradiated fibrinogen and was only slightly diminished in protein exposed to metal-catalyzed oxidation, indicating that the inhibition of clotting activity was due to impaired fibrin monomer polymerization. Thus, oxidative modification of normal fibrinogen causes dysfibrinogenemia and constitutes a novel mechanism for inhibition of thrombosis. JF - Free radical biology & medicine AU - Shacter, E AU - Williams, J A AU - Levine, R L AD - Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 1995/04// PY - 1995 DA - April 1995 SP - 815 EP - 821 VL - 18 IS - 4 SN - 0891-5849, 0891-5849 KW - Free Radicals KW - 0 KW - Oxidants KW - Fibrinogen KW - 9001-32-5 KW - Iron KW - E1UOL152H7 KW - Thrombin KW - EC 3.4.21.5 KW - Ascorbic Acid KW - PQ6CK8PD0R KW - Index Medicus KW - Iron -- pharmacology KW - Humans KW - Dose-Response Relationship, Radiation KW - Ascorbic Acid -- pharmacology KW - Thrombin -- metabolism KW - Chromatography, High Pressure Liquid KW - Fibrinogen -- drug effects KW - Oxidants -- metabolism KW - Clot Retraction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77270626?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+radical+biology+%26+medicine&rft.atitle=Oxidative+modification+of+fibrinogen+inhibits+thrombin-catalyzed+clot+formation.&rft.au=Shacter%2C+E%3BWilliams%2C+J+A%3BLevine%2C+R+L&rft.aulast=Shacter&rft.aufirst=E&rft.date=1995-04-01&rft.volume=18&rft.issue=4&rft.spage=815&rft.isbn=&rft.btitle=&rft.title=Free+radical+biology+%26+medicine&rft.issn=08915849&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-21 N1 - Date created - 1995-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The hepatocarcinogen methapyrilene but not the analog pyrilamine induces sustained hepatocellular replication and protein alterations in F344 rats in a 13-week feed study. AN - 77221751; 7716764 AB - Methapyrilene (MPH) was a widely used antihistamine until it was found to produce hepatocellular carcinoma and cholangiocarcinoma in Fischer 344 rats. The structurally similar antihistamine pyrilamine (PYR) was marginally or noncarcinogenic in a similar study. The peroxisome proliferator Wy-14,643 was included in this study as a positive control. As part of a program to investigate the mechanisms whereby structurally similar chemicals produce different toxicities, we studied these three chemicals for the induction of cell proliferation in the liver of F344 rats. Male rats were treated for up to 13 weeks with feed dosed with MPH (HCl salt) at 0, 50, 100, 250, or 1000 ppm or PYR (maleate salt) at 1000 ppm to duplicate the route of administration and high-dose groups used in the carcinogenesis assay. In addition, the nongenotoxic hepatocarcinogen peroxisome proliferator Wy-14,643 was included as a positive cell-proliferating chemical. Cell proliferation was quantitated by measuring the incorporation of bromodeoxyuridine (BrDU) administered by osmotic minipump for 7 days and the appearance of proliferating cell nuclear antigen (PCNA) immunohistochemically. The BrDU-labeling index showed a large and sustained increase in rats treated with MPH at 250 and 1000 ppm, sustaining greater than 50% labeling in the higher dose group of 4-, 6-, and 13-week treatment groups. PYR at 1000 ppm demonstrated no significant increase in labeling above control levels at any time point. PCNA-labeling indexes showed similar but reduced increases for MPH and were comparable to control for the PYR dose groups. Two-dimensional gel electrophoresis was used for the detection of quantitative changes in gene expression and qualitative changes in the charges of specific mitochondrial and cytosolic proteins. Quantitative changes in 32 proteins induced by MPH and 39 changes induced by Wy-14,643 were detected throughout the 13-week study. Specific mitochondrial protein charge shifts were associated with high-dose MPH treatment that were not observed in animals treated with Wy-14,643. PYR induced no significant qualitative or quantitative protein alterations. Hepatocellular proliferation of the large magnitude observed following dietary administration of MPH, and not PYR may contribute to the mechanism of carcinogenesis of MPH. JF - Toxicology and applied pharmacology AU - Cunningham, M L AU - Pippin, L L AU - Anderson, N L AU - Wenk, M L AD - Chemistry Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/04// PY - 1995 DA - April 1995 SP - 216 EP - 223 VL - 131 IS - 2 SN - 0041-008X, 0041-008X KW - Carcinogens KW - 0 KW - Proliferating Cell Nuclear Antigen KW - Pyrimidines KW - pirinixic acid KW - 86C4MRT55A KW - Methapyrilene KW - A01LX40298 KW - Pyrilamine KW - HPE317O9TL KW - Index Medicus KW - Rats KW - Administration, Oral KW - Protein Biosynthesis KW - Animals KW - Rats, Inbred F344 KW - Dose-Response Relationship, Drug KW - Pyrimidines -- toxicity KW - Mitochondria, Liver -- metabolism KW - Body Weight -- drug effects KW - Cell Division -- drug effects KW - Carcinogens -- toxicity KW - Male KW - Proliferating Cell Nuclear Antigen -- biosynthesis KW - Pyrilamine -- toxicity KW - Liver -- drug effects KW - Methapyrilene -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77221751?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+hepatocarcinogen+methapyrilene+but+not+the+analog+pyrilamine+induces+sustained+hepatocellular+replication+and+protein+alterations+in+F344+rats+in+a+13-week+feed+study.&rft.au=Cunningham%2C+M+L%3BPippin%2C+L+L%3BAnderson%2C+N+L%3BWenk%2C+M+L&rft.aulast=Cunningham&rft.aufirst=M&rft.date=1995-04-01&rft.volume=131&rft.issue=2&rft.spage=216&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 - 1995-05-18 N1 - Date created - 1995-05-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Importance of the glutamate residue of KDEL in increasing the cytotoxicity of Pseudomonas exotoxin derivatives and for increased binding to the KDEL receptor. AN - 77221181; 7717988 AB - It was previously shown that amino acids 609-613 (REDLK) at the C-terminus of Pseudomonas exotoxin (PE) are necessary for cytotoxicity, presumably by directing the toxin to the endoplasmic reticulum (ER) [Chaudhary, Jinno, FitzGerald and Pastan (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 308-312]. Using the anti-[interleukin 2 receptor (IL2R)] immunotoxin anti-Tac(Fv)-PE38 (AT-PE38REDLK), it was found that removing the terminal lysine did not alter the activity, but replacing REDL with KDEL, the most common ER retention sequence, increased activity. To determine which amino acid in KDEL was responsible for the increase in activity, we tested eight C-terminal mutants of AT-PE38REDLK. Using IL2R-bearing MT-1 cells, we found that the glutamate residue of KDEL was required for high activity, as the cytotoxicity of AT-PE38 ending in KDEL, RDEL, KEEL or REEL was much greater than that of AT-PE38 ending in REDL, KEDL, RDDL or KDDL. Using freshly isolated lymphocytic leukaemia cells, AT-PE38 ending in KDEL, REEL or RDEL was more than 100-fold more cytotoxic than AT-PE38 ending in KEDL, REDL, RDDL or the native sequence REDLK. The RDEL sequence also improved the cytotoxic activity of an interleukin 4-PE38 toxin fusion protein. Improved cytotoxic activity correlated with improved binding of the C-termini to the KDEL receptor on rat Golgi membranes. These data indicate that the glutamate residue of KDEL improves the cytotoxicity of PE by increasing binding to a sorting receptor which transports the toxin from the transreticular Golgi apparatus to the ER, where it is translocated to the cytosol and inhibits protein synthesis. JF - The Biochemical journal AU - Kreitman, R J AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/04/01/ PY - 1995 DA - 1995 Apr 01 SP - 29 EP - 37 VL - 307 ( Pt 1) SN - 0264-6021, 0264-6021 KW - Bacterial Toxins KW - 0 KW - Exotoxins KW - Immunotoxins KW - KDEL receptor KW - Oligopeptides KW - Peptide Fragments KW - Protein Sorting Signals KW - Protein Synthesis Inhibitors KW - Receptors, Interleukin-2 KW - Receptors, Peptide KW - Recombinant Fusion Proteins KW - Virulence Factors KW - lysyl-aspartyl-glutamyl-leucine KW - 113516-56-6 KW - Glutamic Acid KW - 3KX376GY7L KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Endoplasmic Reticulum -- metabolism KW - Animals KW - Cytosol -- metabolism KW - Peptide Fragments -- toxicity KW - Immunotoxins -- toxicity KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Biological Transport KW - Amino Acid Sequence KW - Peptide Fragments -- chemical synthesis KW - Recombinant Fusion Proteins -- metabolism KW - Rats KW - Receptors, Interleukin-2 -- metabolism KW - Base Sequence KW - Carcinoma, Squamous Cell -- pathology KW - Molecular Sequence Data KW - Leukemia, Lymphocytic, Chronic, B-Cell -- pathology KW - Golgi Apparatus -- metabolism KW - Protein Synthesis Inhibitors -- toxicity KW - Receptors, Peptide -- metabolism KW - Glutamic Acid -- chemistry KW - Oligopeptides -- metabolism KW - Exotoxins -- toxicity KW - Exotoxins -- chemistry KW - Protein Synthesis Inhibitors -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77221181?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Biochemical+journal&rft.atitle=Importance+of+the+glutamate+residue+of+KDEL+in+increasing+the+cytotoxicity+of+Pseudomonas+exotoxin+derivatives+and+for+increased+binding+to+the+KDEL+receptor.&rft.au=Kreitman%2C+R+J%3BPastan%2C+I&rft.aulast=Kreitman&rft.aufirst=R&rft.date=1995-04-01&rft.volume=307+%28+Pt+1%29&rft.issue=&rft.spage=29&rft.isbn=&rft.btitle=&rft.title=The+Biochemical+journal&rft.issn=02646021&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-18 N1 - Date created - 1995-05-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1979 Nov 25;254(22):11655-63 [500665] Bioconjug Chem. 1993 Jan-Feb;4(1):63-8 [8431514] Cell. 1987 Jan 16;48(1):129-36 [3098436] Cell. 1987 Mar 13;48(5):899-907 [3545499] EMBO J. 1988 Apr;7(4):913-8 [3402439] J Biol Chem. 1989 Aug 25;264(24):14256-61 [2503515] Biochemistry. 1989 Jul 25;28(15):6440-6 [2551375] Annu Rev Cell Biol. 1989;5:1-23 [2688704] J Biol Chem. 1990 Jan 15;265(2):1094-101 [2295602] Proc Natl Acad Sci U S A. 1990 Jan;87(1):308-12 [2104981] J Biol Chem. 1990 Apr 15;265(11):5952-5 [2318841] Cell. 1990 Jun 29;61(7):1349-57 [2194670] Cell. 1990 Jun 29;61(7):1359-63 [2194671] J Cell Biol. 1990 Aug;111(2):369-77 [2199456] Biochem J. 1990 Jul 15;269(2):451-8 [2386485] Nature. 1990 Nov 8;348(6297):162-3 [2172835] J Biol Chem. 1990 Nov 25;265(33):20678-85 [2122978] J Biol Chem. 1993 Apr 5;268(10):7465-8 [8385108] Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7774-8 [8356083] Blood. 1994 Jan 15;83(2):426-34 [8286741] Int J Cancer. 1994 Sep 1;58(5):744-8 [8077061] Bioconjug Chem. 1993 Mar-Apr;4(2):112-20 [7873642] Proc Natl Acad Sci U S A. 1990 Dec;87(23):9491-4 [2251289] Trends Biochem Sci. 1990 Dec;15(12):483-6 [2077689] J Biol Chem. 1991 Apr 5;266(10):6015-8 [2007562] J Biol Chem. 1991 Sep 15;266(26):17376-81 [1910044] J Mol Biol. 1992 Mar 5;224(1):1-5 [1312604] EMBO J. 1992 Apr;11(4):1583-91 [1373379] J Biol Chem. 1992 May 25;267(15):10631-7 [1316906] Eur J Biochem. 1992 Jun 15;206(3):801-6 [1606962] Bioconjug Chem. 1992 Jan-Feb;3(1):58-62 [1616950] J Biol Chem. 1992 Jun 25;267(18):12420-3 [1618748] J Mol Biol. 1992 Aug 20;226(4):913-6 [1325562] Cancer Res. 1992 Oct 1;52(19):5379-85 [1394141] Blood. 1992 Nov 1;80(9):2344-52 [1421405] Anal Biochem. 1992 Sep;205(2):263-70 [1332541] J Biol Chem. 1992 Dec 15;267(35):25396-401 [1460035] Proc Natl Acad Sci U S A. 1986 Mar;83(5):1320-4 [3006045] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of tumor necrosis factor-alpha in cadmium-induced hepatotoxicity. AN - 77220346; 7536360 AB - Liver and kidney injury following acute or chronic exposure to cadmium is well characterized. While hepatocytes and endothelial cells of the sinusoids are thought to be the primary cellular targets in the liver, ultrastructural changes may vary depending upon the exposure regimen and the time following administration. Since acute and chronic liver disease is often associated with the presence of cytokines, we investigated the role of proinflammatory cytokines in cadmium-induced hepatotoxicity. Supernatants from cultured liver slices obtained from acute or subchronic cadmium-exposed rats and mice were collected and cytokine secretion was examined. In addition, mRNA transcripts for IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, MIP-2, IFN-gamma, and ICAM-1 from livers of treated mice were quantitated by reverse transcription-polymerase chain reaction. Modest increases in secretion of TNF-alpha, IL-1 alpha, and IL-6 were observed in response to cadmium which were enhanced in LPS-primed mice. Additionally, cadmium exposure increased IL-1 alpha, IL-1 beta, TNF-alpha, MIP-2, IL-6, and ICAM-1 mRNA transcripts in the liver. Immunohistochemical analysis revealed that TNF-alpha was associated with nonparenchymal cells in livers of cadmium-treated mice. Cadmium exposure produced a marked increase in plasma hepatocellular enzyme levels (i.e., AST, LDH, SDH), acute phase proteins (i.e., serum amyloid A), and foci formation in the liver, while focal inflammation and serum amyloid A (SAA) secretion, but not plasma enzymes, were further increased in cadmium-exposed mice primed with LPS. SAA secretion and focal inflammation were prevented by pretreatment with antibodies to TNF-alpha, indicating that these pathological manifestations are cytokine dependent. These data indicate that TNF-alpha, released from nonparenchymal cells as well as associated cytokines, are responsible for certain manifestations observed with cadmium-induced hepatotoxicity. JF - Toxicology and applied pharmacology AU - Kayama, F AU - Yoshida, T AU - Elwell, M R AU - Luster, M I AD - Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/04// PY - 1995 DA - April 1995 SP - 224 EP - 234 VL - 131 IS - 2 SN - 0041-008X, 0041-008X KW - Cytokines KW - 0 KW - Serum Amyloid A Protein KW - Tumor Necrosis Factor-alpha KW - Cadmium KW - 00BH33GNGH KW - RNA-Directed DNA Polymerase KW - EC 2.7.7.49 KW - Index Medicus KW - Animals KW - Serum Amyloid A Protein -- metabolism KW - Liver Neoplasms, Experimental -- metabolism KW - Cytokines -- secretion KW - Liver Neoplasms, Experimental -- chemically induced KW - Mice KW - RNA-Directed DNA Polymerase -- metabolism KW - Rats KW - Polymerase Chain Reaction KW - Rats, Inbred F344 KW - Base Sequence KW - Liver Neoplasms, Experimental -- pathology KW - Mice, Inbred C3H KW - Molecular Sequence Data KW - Enzyme-Linked Immunosorbent Assay KW - Cytokines -- isolation & purification KW - Female KW - Cadmium -- metabolism KW - Liver -- drug effects KW - Cadmium -- toxicity KW - Tumor Necrosis Factor-alpha -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77220346?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Role+of+tumor+necrosis+factor-alpha+in+cadmium-induced+hepatotoxicity.&rft.au=Kayama%2C+F%3BYoshida%2C+T%3BElwell%2C+M+R%3BLuster%2C+M+I&rft.aulast=Kayama&rft.aufirst=F&rft.date=1995-04-01&rft.volume=131&rft.issue=2&rft.spage=224&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 - 1995-05-18 N1 - Date created - 1995-05-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structural determinants of allosteric regulation in alternatively spliced AMPA receptors. AN - 77219588; 7718245 AB - The flip and flop splice variants of AMPA receptors show strikingly different sensitivity to allosteric regulation by cyclothiazide; heteromers assembled from GluR-A and GluR-B also exhibit splice variant-dependent differences in efficacy for activation by glutamate and kainate. The sensitivity for attenuation of desensitization by cyclothiazide for homomeric GluR-A was solely dependent upon exchange of Ser-750 (flip) and Asn-750 (flop), and was unaffected by mutagenesis of other divergent residues. In contrast, substantial alteration of the relative efficacy of glutamate versus kainate required mutation of multiple residues in the flip/flop region. Modulation by cyclothiazide was abolished by mutation of Ser-750 to Gin, the residue found at the homologous site in kainate-preferring subunits, whereas introduction of Ser at this site in GluR6 imparted sensitivity to cyclothiazide. JF - Neuron AU - Partin, K M AU - Bowie, D AU - Mayer, M L AD - Laboratory of Cellular and Molecular Neurophysiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-4495, USA. Y1 - 1995/04// PY - 1995 DA - April 1995 SP - 833 EP - 843 VL - 14 IS - 4 SN - 0896-6273, 0896-6273 KW - Benzothiadiazines KW - 0 KW - Macromolecular Substances KW - Receptors, AMPA KW - Receptors, Kainic Acid KW - Glutamine KW - 0RH81L854J KW - Glutamic Acid KW - 3KX376GY7L KW - Serine KW - 452VLY9402 KW - cyclothiazide KW - P71U09G5BW KW - Kainic Acid KW - SIV03811UC KW - Index Medicus KW - Animals KW - Kainic Acid -- pharmacology KW - Allosteric Regulation -- drug effects KW - Benzothiadiazines -- pharmacology KW - Humans KW - Amino Acid Sequence KW - Embryo, Nonmammalian KW - Glutamic Acid -- pharmacology KW - Receptors, Kainic Acid -- chemistry KW - Mutagenesis, Site-Directed KW - Xenopus laevis KW - Oocytes -- metabolism KW - Transfection KW - Point Mutation KW - Molecular Sequence Data KW - Kidney KW - Embryo, Mammalian KW - Receptors, AMPA -- drug effects KW - Alternative Splicing KW - Receptors, AMPA -- genetics KW - Receptors, AMPA -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77219588?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuron&rft.atitle=Structural+determinants+of+allosteric+regulation+in+alternatively+spliced+AMPA+receptors.&rft.au=Partin%2C+K+M%3BBowie%2C+D%3BMayer%2C+M+L&rft.aulast=Partin&rft.aufirst=K&rft.date=1995-04-01&rft.volume=14&rft.issue=4&rft.spage=833&rft.isbn=&rft.btitle=&rft.title=Neuron&rft.issn=08966273&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-23 N1 - Date created - 1995-05-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of the liver-enriched transcription factor HNF-1 alpha in expression of the CYP2E1 gene. AN - 77214374; 7710685 AB - The role of the trans-acting factor HNF-1 alpha in activating CYP2E1 gene expression was confirmed by transient co-transfection of an HNF-1 alpha expression plasmid and the CYP2E1 promoter fused to the chloramphenicol acetyl transferase (CAT) reporter gene. Only HNF-1 alpha, and not HNF-1 beta, HNF-4, C/EBP alpha, C/EBP beta, or DBP, was able to activate the CYP2E1 promoter. The extent of activation was proportional to the number of copies of the HNF-1 binding sequence upstream of the promoter. Removal or mutation of the HNF-1 binding sequence led to inactivation of the promoter in response to HNF-1 alpha. Gel-shift Western blot analysis using a synthetic HNF-1 binding sequence derived from CYP2E1 and rat liver nuclear extract revealed that the protein-DNA complex obtained with adult rat liver nuclear extract consisted of both HNF-1 alpha and HNF-1 beta proteins. The shifted bands produced by nuclear extracts from adult, where the endogenous CYP2E1 gene is active, and fetal rat liver, where the gene is inactive, were found to migrate differently, suggesting that the population of factors, possibly including different ratios of HNF-1 alpha and HNF-1 beta proteins, may change during development. However, the co-transfection study did not show cooperativity between the two factors. Elements upstream of the HNF-1 binding site were found to affect the activity of the promoter negatively in the transfection assay. DNase I hypersensitive site mapping revealed a hypersensitive site in this inhibiting element in the adult rat liver sample but not in liver from newborn animals. JF - DNA and cell biology AU - Liu, S Y AU - Gonzalez, F J AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/04// PY - 1995 DA - April 1995 SP - 285 EP - 293 VL - 14 IS - 4 SN - 1044-5498, 1044-5498 KW - CYP2E1 KW - DNA-Binding Proteins KW - 0 KW - HNF1A protein, human KW - HNF1B protein, human KW - Hepatocyte Nuclear Factor 1-alpha KW - Hnf1a protein, rat KW - Nuclear Proteins KW - Oligodeoxyribonucleotides KW - RNA, Messenger KW - Transcription Factors KW - Hepatocyte Nuclear Factor 1 KW - 126548-29-6 KW - Hepatocyte Nuclear Factor 1-beta KW - 138674-15-4 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Oxidoreductases, N-Demethylating KW - EC 1.5.- KW - Deoxyribonuclease I KW - EC 3.1.21.1 KW - Index Medicus KW - Aging -- metabolism KW - Animals KW - Humans KW - Protein Binding KW - Fetus -- metabolism KW - Rats KW - Promoter Regions, Genetic KW - Base Sequence KW - RNA, Messenger -- metabolism KW - Restriction Mapping KW - Molecular Sequence Data KW - Cell Line KW - Oxidoreductases, N-Demethylating -- genetics KW - Transcription Factors -- physiology KW - Liver -- cytology KW - Liver -- growth & development KW - Cytochrome P-450 Enzyme System -- genetics KW - Gene Expression Regulation, Enzymologic -- physiology KW - Liver -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77214374?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=DNA+and+cell+biology&rft.atitle=Role+of+the+liver-enriched+transcription+factor+HNF-1+alpha+in+expression+of+the+CYP2E1+gene.&rft.au=Liu%2C+S+Y%3BGonzalez%2C+F+J&rft.aulast=Liu&rft.aufirst=S&rft.date=1995-04-01&rft.volume=14&rft.issue=4&rft.spage=285&rft.isbn=&rft.btitle=&rft.title=DNA+and+cell+biology&rft.issn=10445498&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-16 N1 - Date created - 1995-05-16 N1 - Date revised - 2017-01-13 N1 - Gene symbol - CYP2E1 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Buthionine sulphoximine-mediated sensitisation of etoposide-resistant human breast cancer MCF7 cells overexpressing the multidrug resistance-associated protein involves increased drug accumulation. AN - 77211648; 7710938 AB - Preincubation of etoposide-resistant human MCF7 breast cancer cells (MCF7/VP) with buthionine sulphoximine (BSO) resulted in their sensitisation to etoposide and vincristine. Chemosensitisation was accompanied by elevated intracellular drug levels. In contrast, simultaneous exposure to BSO did not result in increased drug accumulation. Similar, but quantitatively smaller, effects were also observed when sensitive wild-type MCF7/WT cells were treated with BSO. In agreement with its effect on drug accumulation, BSO pretreatment also increased VP-16-stimulated cleavable complex formation between DNA topoisomerase II and cellular DNA. BSO treatment also led to a significant increase in acid-precipitable VP-16 levels in MCF7/VP, but not MCF7/WT cells. In contrast, no clear effects of BSO on drug efflux were observed and drug retention was only minimally increased after BSO treatment of both MCF7/WT and MCF7/VP cells and no difference between the two cell lines was detected. Thus, chemosensitisation by BSO appeared to be mediated through increased intracellular drug concentrations and/or protein binding. JF - British journal of cancer AU - Schneider, E AU - Yamazaki, H AU - Sinha, B K AU - Cowan, K H AD - Medicine Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/04// PY - 1995 DA - April 1995 SP - 738 EP - 743 VL - 71 IS - 4 SN - 0007-0920, 0007-0920 KW - Antimetabolites, Antineoplastic KW - 0 KW - P-Glycoprotein KW - Methionine Sulfoximine KW - 1982-67-8 KW - Buthionine Sulfoximine KW - 5072-26-4 KW - Vincristine KW - 5J49Q6B70F KW - Etoposide KW - 6PLQ3CP4P3 KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Kinetics KW - Humans KW - Breast Neoplasms KW - Vincristine -- toxicity KW - Female KW - Cell Line KW - Glutathione -- metabolism KW - Methionine Sulfoximine -- pharmacology KW - P-Glycoprotein -- biosynthesis KW - Methionine Sulfoximine -- analogs & derivatives KW - Etoposide -- toxicity KW - Etoposide -- metabolism KW - Drug Resistance, Multiple KW - Antimetabolites, Antineoplastic -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77211648?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Buthionine+sulphoximine-mediated+sensitisation+of+etoposide-resistant+human+breast+cancer+MCF7+cells+overexpressing+the+multidrug+resistance-associated+protein+involves+increased+drug+accumulation.&rft.au=Schneider%2C+E%3BYamazaki%2C+H%3BSinha%2C+B+K%3BCowan%2C+K+H&rft.aulast=Schneider&rft.aufirst=E&rft.date=1995-04-01&rft.volume=71&rft.issue=4&rft.spage=738&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 - 1995-05-12 N1 - Date created - 1995-05-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Anal Biochem. 1969 Mar;27(3):502-22 [4388022] Eur J Cancer. 1992;28A(8-9):1447-52 [1325177] Anal Biochem. 1976 May 7;72:248-54 [942051] Trends Biochem Sci. 1992 Nov;17(11):463-8 [1455517] Anticancer Res. 1992 Nov-Dec;12(6B):2127-32 [1363515] Cancer Res. 1993 Aug 15;53(16):3658-61 [8101765] Cancer Res. 1994 Jan 1;54(1):152-8 [7903202] Cytotechnology. 1993;12(1-3):155-70 [7765324] Cancer Res. 1994 Aug 15;54(16):4313-20 [8044778] Cancer Res. 1994 Sep 15;54(18):4833-6 [7915193] Cancer Res. 1984 Nov;44(11):5427-31 [6488194] Biochem Pharmacol. 1985 Jul 15;34(14):2583-6 [4040369] J Biol Chem. 1986 Nov 25;261(33):15544-9 [3782078] Biochem Pharmacol. 1987 Feb 15;36(4):527-36 [3030329] Cancer Res. 1987 Nov 15;47(22):5835-40 [3117357] Biochim Biophys Acta. 1988 Mar 31;949(3):264-72 [2831986] Cancer Res. 1989 Feb 1;49(3):511-5 [2535960] Mol Pharmacol. 1989 Mar;35(3):271-8 [2564628] Cancer Res. 1989 Aug 1;49(15):4120-5 [2568167] Cancer Res. 1990 Mar 1;50(5):1426-30 [1967979] Mol Pharmacol. 1990 Feb;37(2):192-7 [1968221] J Natl Cancer Inst. 1990 Jul 4;82(13):1107-12 [2359136] J Biol Chem. 1974 Nov 25;249(22):7130-9 [4436300] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterisation of high-level cisplatin-resistant cell lines established from a human hepatoma cell line and human KB adenocarcinoma cells: cross-resistance and protein changes. AN - 77210255; 7710928 AB - Human liver carcinoma cells (BEL-7404) and human KB adenocarcinoma cells were selected by stepwise increases in cisplatin. Drug sensitivity assays indicated that the IC50 value for 7404-CP7.5 cells was 49 micrograms ml-1 cisplatin, 111-fold higher than for the parental hepatoma cells. The IC50 value for KB-CP10 cells was 38 micrograms ml-1 cisplatin, which is 1152-fold higher than for the parental KB cells. The 7404-CP7.5 cells were cross-resistant to methotrexate (39 x), 5-fluorouracil (23 x) and 6-mercaptopurine (13 x), but were sensitive to drugs which are known substrates for the multidrug transporter (P-glycoprotein), including colchicine, vinblastine and actinomycin D. Similar cross-resistance patterns were observed for KB-CP10 cells. No evidence of DNA amplification or expression of the MDR1 gene was found. One-dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoresis showed increases in 52 kDa protein(s) in both the soluble cytosolic and crude membrane fractions in 7404-CP(r) cells and in KB-CP(r) cells. The amount of 52 kDa protein was proportional to the degree of resistance of the 7404-CP(r) cells to cisplatin. Two-dimensional gel analysis demonstrated that two polypeptides of molecular mass 52 and 50 kDa were overexpressed in the membrane fractions in both 7404-CP20 and KB-CP20 cells. Using amino acid microsequencing and Western blotting, major 52 kDa protein was identified as the mitochondrial heat shock protein hsp60. Two-dimensional gels of [35S]methionine-labelled polypeptides showed many other changes, including reduction in soluble proteins of approximately 57 kDa molecular weight in KB-CP20 cells, and of 35 kDa in both 7404-CP20 and KB-CP20 cells. These results suggest that alterations of certain proteins occur commonly in cisplatin-resistant cells, particularly proteins of molecular weight 52 and 50 kDa. JF - British journal of cancer AU - Shen, D W AU - Akiyama, S AU - Schoenlein, P AU - Pastan, I AU - Gottesman, M M AD - Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/04// PY - 1995 DA - April 1995 SP - 676 EP - 683 VL - 71 IS - 4 SN - 0007-0920, 0007-0920 KW - Antineoplastic Agents KW - 0 KW - Neoplasm Proteins KW - Methionine KW - AE28F7PNPL KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Clone Cells KW - Cytosol -- metabolism KW - KB Cells KW - Carcinoma, Hepatocellular KW - Electrophoresis, Polyacrylamide Gel KW - Humans KW - Methionine -- metabolism KW - Amino Acid Sequence KW - Molecular Weight KW - Liver Neoplasms KW - Blotting, Western KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Electrophoresis, Gel, Two-Dimensional KW - Neoplasm Proteins -- biosynthesis KW - Neoplasm Proteins -- isolation & purification KW - Cisplatin -- toxicity KW - Antineoplastic Agents -- toxicity KW - Drug Resistance KW - Neoplasm Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77210255?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Characterisation+of+high-level+cisplatin-resistant+cell+lines+established+from+a+human+hepatoma+cell+line+and+human+KB+adenocarcinoma+cells%3A+cross-resistance+and+protein+changes.&rft.au=Shen%2C+D+W%3BAkiyama%2C+S%3BSchoenlein%2C+P%3BPastan%2C+I%3BGottesman%2C+M+M&rft.aulast=Shen&rft.aufirst=D&rft.date=1995-04-01&rft.volume=71&rft.issue=4&rft.spage=676&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 - 1995-05-12 N1 - Date created - 1995-05-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1970 Aug 15;227(5259):680-5 [5432063] Cancer Res. 1994 May 15;54(10):2680-7 [8168097] Ann Intern Med. 1984 May;100(5):704-13 [6370067] Proc Natl Acad Sci U S A. 1985 Apr;82(7):2158-62 [3856890] Cancer Res. 1985 Sep;45(9):4178-84 [3928152] Science. 1986 May 2;232(4750):643-5 [3457471] Cancer Res. 1986 Sep;46(9):4379-83 [3731096] Cancer Res. 1987 Jan 15;47(2):414-8 [3539322] J Biol Chem. 1987 Jan 15;262(2):505-8 [3027054] Cancer Res. 1987 Apr 15;47(8):2056-61 [3828995] Biochem Pharmacol. 1988 Feb 1;37(3):443-7 [3337743] J Natl Cancer Inst. 1988 Mar 2;80(1):14-20 [2892943] Proc Natl Acad Sci U S A. 1988 Feb;85(3):650-3 [3422447] Cancer Res. 1988 Oct 15;48(20):5713-6 [3139281] Proc Natl Acad Sci U S A. 1990 Apr;87(7):2443-7 [2320566] Proc Natl Acad Sci U S A. 1990 May;87(9):3324-7 [2333286] J Biol Chem. 1990 Aug 5;265(22):13137-42 [2376590] Cancer Cells. 1990 Feb;2(2):35-43 [2204382] Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3070-4 [1348364] Science. 1992 Apr 10;256(5054):234-7 [1566071] Mol Biol Cell. 1992 May;3(5):507-20 [1611154] Br J Cancer. 1992 Aug;66(2):227-38 [1503895] Mol Cell Biol. 1992 Sep;12(9):3689-98 [1380646] Cancer Res. 1992 Nov 15;52(22):6375-9 [1423284] Int J Cancer. 1993 Jan 2;53(1):110-7 [8380054] Cancer Chemother Pharmacol. 1993;32(4):279-85 [8100743] Annu Rev Biochem. 1993;62:385-427 [8102521] J Biol Chem. 1993 Sep 25;268(27):20116-25 [8376370] Cancer Res. 1991 Jun 15;51(12):3237-42 [1645616] J Cell Sci. 1991 Mar;98 ( Pt 3):317-22 [1676033] Cancer Res. 1991 Sep 1;51(17):4557-64 [1873800] Cell. 1977 Dec;12(4):1133-41 [23215] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A controlled seroprevalence survey of primate handlers for evidence of asymptomatic herpes B virus infection. AN - 77202130; 7706783 AB - Herpes B virus (BV) is a common cause of recurring mucocutaneous infections in monkeys of the genus Macaca. Like its human counterpart, herpes simplex virus (HSV), BV establishes lifelong latency and can be reactivated from infected monkeys symptomatically or asymptomatically. Incidental infection of humans handling BV-shedding monkeys can result in fatal meningoencephalitis. To determine whether humans exposed to infected monkeys can acquire asymptomatic BV infections, 480 subjects were evaluated in a controlled seroprevalence study. Sera from 321 primate handlers, including many with repeated injuries inflicted by Macaca monkeys, and 159 people never exposed to monkeys were tested in blinded fashion by both competition ELISA and Western blot to determine the prevalence of BV and HSV seropositivity. Although 293 persons proved positive for HSV antibodies, no primate handlers or control subjects showed BV-specific antibody responses. There is no serologic evidence that BV causes asymptomatic infections in humans. JF - The Journal of infectious diseases AU - Freifeld, A G AU - Hilliard, J AU - Southers, J AU - Murray, M AU - Savarese, B AU - Schmitt, J M AU - Straus, S E AD - Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1995/04// PY - 1995 DA - April 1995 SP - 1031 EP - 1034 VL - 171 IS - 4 SN - 0022-1899, 0022-1899 KW - Antibodies, Viral KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Herpesvirus 2, Human -- immunology KW - Macaca KW - Humans KW - Adult KW - Animal Husbandry KW - Virus Shedding KW - Herpesvirus 1, Human -- immunology KW - Male KW - Female KW - Herpesviridae Infections -- transmission KW - Antibodies, Viral -- blood KW - Herpesvirus 1, Cercopithecine -- immunology KW - Occupational Diseases -- immunology KW - Herpesviridae Infections -- epidemiology KW - Occupational Diseases -- epidemiology KW - Herpesviridae Infections -- immunology KW - Primates KW - Herpesviridae Infections -- virology KW - Animal Technicians UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77202130?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+infectious+diseases&rft.atitle=A+controlled+seroprevalence+survey+of+primate+handlers+for+evidence+of+asymptomatic+herpes+B+virus+infection.&rft.au=Freifeld%2C+A+G%3BHilliard%2C+J%3BSouthers%2C+J%3BMurray%2C+M%3BSavarese%2C+B%3BSchmitt%2C+J+M%3BStraus%2C+S+E&rft.aulast=Freifeld&rft.aufirst=A&rft.date=1995-04-01&rft.volume=171&rft.issue=4&rft.spage=1031&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+infectious+diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-05 N1 - Date created - 1995-05-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Taxol inhibits neointimal smooth muscle cell accumulation after angioplasty in the rat. AN - 77201601; 7706494 AB - Despite significant improvements in the primary success rate of the medical and surgical treatments for atherosclerotic disease, including angioplasty, bypass grafting, and endarterectomy, secondary failure due to late restenosis continues to occur in 30-50% of individuals. Restenosis and the later stages in atherosclerotic lesions are due to a complex series of fibroproliferative responses to vascular injury involving potent growth-regulatory molecules (such as platelet-derived growth factor and basic fibroblast growth factor) and resulting in vascular smooth muscle cell (VSMC) proliferation, migration, and neointimal accumulation. We show here, based on experiments with both taxol and deuterium oxide, that microtubules are necessary for VSMCs to undergo the multiple transformations contributing to the development of the neointimal fibroproliferative lesion. Taxol was found to interfere both with platelet-derived growth factor-stimulated VSMC migration and with VSMC migration and with VSMC proliferation, at nanomolar levels in vitro. In vivo, taxol prevented medial VSMC proliferation and the neointimal VSMC accumulation in the rat carotid artery after balloon dilatation and endothelial denudation injury. This effect occurred at plasma levels approximately two orders of magnitude lower than that used clinically to treat human malignancy (peak levels achieved in this model were approximately 50-60 nM). Taxol may therefore be of therapeutic value in preventing human restenosis with minimal toxicity. JF - The Journal of clinical investigation AU - Sollott, S J AU - Cheng, L AU - Pauly, R R AU - Jenkins, G M AU - Monticone, R E AU - Kuzuya, M AU - Froehlich, J P AU - Crow, M T AU - Lakatta, E G AU - Rowinsky, E K AD - Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1995/04// PY - 1995 DA - April 1995 SP - 1869 EP - 1876 VL - 95 IS - 4 SN - 0021-9738, 0021-9738 KW - Platelet-Derived Growth Factor KW - 0 KW - Deuterium Oxide KW - J65BV539M3 KW - Paclitaxel KW - P88XT4IS4D KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Platelet-Derived Growth Factor -- pharmacology KW - Cell Division -- drug effects KW - Deuterium Oxide -- pharmacology KW - Microtubules -- drug effects KW - Rats KW - Muscle Development KW - Cell Communication -- drug effects KW - Cells, Cultured KW - Rats, Wistar KW - Cell Movement -- drug effects KW - Immunohistochemistry KW - Carotid Arteries -- drug effects KW - Tunica Intima -- growth & development KW - Tunica Intima -- drug effects KW - Muscle, Smooth, Vascular -- drug effects KW - Carotid Arteries -- surgery KW - Angioplasty, Balloon -- adverse effects KW - Paclitaxel -- pharmacology KW - Muscle, Smooth, Vascular -- pathology KW - Tunica Intima -- pathology KW - Carotid Arteries -- growth & development KW - Carotid Arteries -- pathology KW - Muscle, Smooth, Vascular -- growth & development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77201601?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+investigation&rft.atitle=Taxol+inhibits+neointimal+smooth+muscle+cell+accumulation+after+angioplasty+in+the+rat.&rft.au=Sollott%2C+S+J%3BCheng%2C+L%3BPauly%2C+R+R%3BJenkins%2C+G+M%3BMonticone%2C+R+E%3BKuzuya%2C+M%3BFroehlich%2C+J+P%3BCrow%2C+M+T%3BLakatta%2C+E+G%3BRowinsky%2C+E+K&rft.aulast=Sollott&rft.aufirst=S&rft.date=1995-04-01&rft.volume=95&rft.issue=4&rft.spage=1869&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+investigation&rft.issn=00219738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-09 N1 - Date created - 1995-05-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Cell Sci. 1969 Sep;5(2):433-51 [5362335] J Clin Invest. 1992 Nov;90(5):2044-9 [1430226] J Exp Med. 1972 Oct 1;136(4):769-89 [4626850] Biochemistry. 1973 Oct 9;12(21):4282-9 [4745672] Science. 1976 Apr 16;192(4236):218-26 [769162] J Clin Invest. 1976 Sep;58(3):731-41 [821969] Nature. 1977 Aug 25;268(5622):739-41 [895874] J Clin Invest. 1977 Nov;60(5):1191-201 [409735] Nature. 1977 Sep 15;269(5625):249-51 [593322] Nature. 1979 Feb 22;277(5698):665-7 [423966] Proc Natl Acad Sci U S A. 1979 Dec;76(12):6435-8 [293731] Proc Natl Acad Sci U S A. 1980 Mar;77(3):1561-5 [6103535] Sci Am. 1980 Aug;243(2):66-76 [7423178] Lab Invest. 1981 Apr;44(4):301-8 [7206628] Cell. 1981 Jan;23(1):61-71 [6111398] J Clin Oncol. 1995 Jan;13(1):180-90 [7799018] Pathol Microbiol (Basel). 1966;29(4):393-405 [5924733] Proc Natl Acad Sci U S A. 1981 May;78(5):3063-7 [7019919] J Cell Physiol. 1983 Apr;115(1):15-22 [6220020] Lab Invest. 1983 Sep;49(3):327-33 [6887785] Cell Struct Funct. 1984 Mar;9(1):45-52 [6722908] Biochim Biophys Acta. 1984 Jul 16;800(1):21-7 [6331518] Lab Invest. 1985 Nov;53(5):513-20 [3903345] Biochemistry. 1986 Jan 28;25(2):312-8 [2937447] Cell. 1986 Jul 18;46(2):155-69 [3013421] Ann N Y Acad Sci. 1986;466:919-32 [2873783] Cancer Treat Rep. 1987 Jan;71(1):53-9 [2878719] Cancer Res. 1987 Jun 15;47(12):3239-45 [2438036] Exp Cell Res. 1987 Sep;172(1):204-11 [2820767] J Cell Biol. 1988 Feb;106(2):403-13 [2828383] Am J Pathol. 1988 Feb;130(2):393-400 [3277442] Science. 1988 Jun 10;240(4858):1529-31 [2836952] Cancer Res. 1988 Jul 15;48(14):4093-100 [2898289] Cancer Res. 1988 Nov 15;48(22):6262-71 [2846150] Arteriosclerosis. 1989 May-Jun;9(3):269-78 [2655570] Cancer Res. 1989 Aug 15;49(16):4640-7 [2568175] Ann Intern Med. 1989 Aug 15;111(4):273-9 [2569287] Annu Rev Biochem. 1989;58:575-606 [2549857] J Histochem Cytochem. 1989 Nov;37(11):1659-65 [2572626] Atherosclerosis. 1989 Dec;80(2):149-57 [2692572] Cancer Res. 1990 Feb 1;50(3):710-6 [1967550] Nature. 1990 Jan 18;343(6255):233-8 [2405278] Proc Natl Acad Sci U S A. 1990 Jun;87(12):4600-4 [1972277] J Natl Cancer Inst. 1990 Aug 1;82(15):1247-59 [1973737] Science. 1991 Feb 8;251(4994):671-5 [1825142] Cell Regul. 1990 Jul;1(8):555-66 [1964089] Invest New Drugs. 1991 Feb;9(1):59-64 [1673965] Nature. 1993 Apr 29;362(6423):801-9 [8479518] Circ Res. 1993 Aug;73(2):223-31 [8101140] J Clin Oncol. 1993 Nov;11(11):2127-35 [7901342] Cancer Surv. 1993;17:283-304 [7907949] Circ Res. 1994 Jul;75(1):41-54 [8013081] Cell Growth Differ. 1991 Feb;2(2):115-27 [1648952] J Cell Sci. 1991 Apr;98 ( Pt 4):463-73 [1650376] Science. 1991 Sep 6;253(5024):1129-32 [1653454] Cancer Res. 1991 Nov 1;51(21):5866-75 [1657372] J Natl Cancer Inst. 1991 Dec 18;83(24):1797-805 [1683908] Circulation. 1992 Apr;85(4):1630-1 [1532546] Cancer Res. 1992 Jul 1;52(13):3776-81 [1352184] J Clin Oncol. 1992 Nov;10(11):1748-53 [1357110] J Am Chem Soc. 1971 May 5;93(9):2325-7 [5553076] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DDE and shortened duration of lactation in a northern Mexican town. AN - 77198281; 7702113 AB - Worldwide declines in the duration of lactation are cause for public health concern. Higher levels of dichlorodiphenyl dichloroethene (DDE) have been associated with shorter durations of lactation in the United States. This study examined whether this relationship would hold in an agricultural town in northern Mexico. Two hundred twenty-nine women were followed every 2 months from childbirth until weaning or until the child reached 18 months of age. DDE was measured in breast milk samples taken at birth, and women were followed to see how long they lactated. Median duration was 7.5 months in the lowest DDE group and 3 months in the highest. The effect was confined to those who had lactated previously, and it persisted after statistical adjustment for other factors. These results are not due to overtly sick children being weaned earlier. Previous lactation lowers DDE levels, which produces an artifactual association, but simulations using best estimates show that an effect as large as that found here would arise through this mechanism only 6% of the time. DDE may affect women's ability to lactate. This exposure may be contributing to lactation failure throughout the world. JF - American journal of public health AU - Gladen, B C AU - Rogan, W J AD - Statistics and Biomathematics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/04// PY - 1995 DA - April 1995 SP - 504 EP - 508 VL - 85 IS - 4 SN - 0090-0036, 0090-0036 KW - Agrochemicals KW - 0 KW - Dichlorodiphenyl Dichloroethylene KW - 4M7FS82U08 KW - Abridged Index Medicus KW - Index Medicus KW - Mexico KW - Humans KW - Adult KW - Adolescent KW - Time Factors KW - Male KW - Female KW - Proportional Hazards Models KW - Agrochemicals -- adverse effects KW - Lactation -- drug effects KW - Dichlorodiphenyl Dichloroethylene -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77198281?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+public+health&rft.atitle=DDE+and+shortened+duration+of+lactation+in+a+northern+Mexican+town.&rft.au=Gladen%2C+B+C%3BRogan%2C+W+J&rft.aulast=Gladen&rft.aufirst=B&rft.date=1995-04-01&rft.volume=85&rft.issue=4&rft.spage=504&rft.isbn=&rft.btitle=&rft.title=American+journal+of+public+health&rft.issn=00900036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-04 N1 - Date created - 1995-05-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Assoc Off Anal Chem. 1984 Jan-Feb;67(1):122-9 [6321428] Pestic Monit J. 1981 Dec;15(3):135-8 [7348797] Pediatrics. 1984 Oct;74(4 Pt 2):615-38 [6384916] Pediatrics. 1984 Oct;74(4 Pt 2):648-66 [6384917] Pediatrics. 1984 Oct;74(4 Pt 2):667-94 [6384918] Pediatrics. 1984 Oct;74(4 Pt 2):702-27 [6435089] Contraception. 1984 Dec;30(6):505-22 [6241559] J Toxicol Environ Health. 1986;17(1):23-36 [3950997] Toxicol Lett. 1987 Jan;35(1):73-81 [3810685] Am J Public Health. 1987 Oct;77(10):1294-7 [3115123] Home Healthc Nurse. 1989 Mar-Apr;7(2):27-33 [2745117] Int J Fertil. 1989;34 Suppl:34-9 [2576256] Bol Med Hosp Infant Mex. 1989 Nov;46(11):705-8 [2631739] Bol Med Hosp Infant Mex. 1990 May;47(5):318-23 [2390185] Arch Latinoam Nutr. 1991 Jun;41(2):182-96 [1811449] Arch Latinoam Nutr. 1991 Sep;41(3):307-26 [1824511] Acta Paediatr. 1992 Jun-Jul;81(6-7):550-7 [1392372] J Natl Cancer Inst. 1993 Apr 21;85(8):648-52 [8468722] J Natl Cancer Inst. 1994 Apr 20;86(8):589-99 [8145274] Pediatrics. 1984 Oct;74(4 Pt 2):603-14 [6384915] Acta Paediatr Scand Suppl. 1970;200:Suppl 200:1+ [5270855] Salud Publica Mex. 1978 Mar-Apr;20(2):215-30 [572585] Arch Environ Health. 1980 Sep-Oct;35(5):262-9 [7447495] Bull Pan Am Health Organ. 1980;14(3):286-92 [7459512] Bull Pan Am Health Organ. 1981;15(2):139-47 [7326501] Stud Fam Plann. 1981 Apr;12(4):134-55 [6755817] J Trop Pediatr. 1982 Oct;28(5):240-7 [7176008] Comment In: Am J Public Health. 1996 Jun;86(6):887-8 [8659672] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Josef Warkany. AN - 77194406; 7699554 JF - The Journal of pediatrics AU - Miller, R W AD - National Cancer Institute, Bethesda, MD 20892-7360, USA. Y1 - 1995/04// PY - 1995 DA - April 1995 SP - 669 EP - 672 VL - 126 IS - 4 SN - 0022-3476, 0022-3476 KW - Abridged Index Medicus KW - Index Medicus KW - History of medicine KW - Warkany KW - United States KW - History, 20th Century KW - Biobibliography as Topic KW - Austria KW - Pediatrics -- history KW - Teratology -- history UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77194406?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pediatrics&rft.atitle=Josef+Warkany.&rft.au=Miller%2C+R+W&rft.aulast=Miller&rft.aufirst=R&rft.date=1995-04-01&rft.volume=126&rft.issue=4&rft.spage=669&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pediatrics&rft.issn=00223476&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-01 N1 - Date created - 1995-05-01 N1 - Date revised - 2017-01-13 N1 - People - Warkany N1 - Last updated - 2017-01-18 N1 - SubjectsTermNotLitGenreText - Warkany ER - TY - JOUR T1 - Induction of p53-, MDM2-, and WAF1/CIP1-like molecules in insect cells by DNA-damaging agents. AN - 77193022; 7698255 AB - Cellular responses following DNA damage are ubiquitous in the biological world. In response to DNA damage, cell cycle checkpoints are activated, which delay cell cycle progression and most likely serve to allow time for repair. One important checkpoint in mammalian cells, activated in the G1 phase of the cell cycle, is dependent on the p53 tumor suppressor gene product. While p53 is responsible for inducing G1 arrest, the product of the MDM2 gene is believed to alleviate the arrest, allowing continuation of the cell cycle after a transient delay. Inasmuch as MDM2 and WAF1/CIP1 are transactivated by p53, while MDM2 binds to and modulates the activity of p53, a "feedback loop" is thus created. This pathway has been highly conserved in mammalian cells, but its presence outside of vertebrates is unknown. By using human MDM2 and WAF1/CIP1 cDNA probes, and monoclonal antibodies to p53 and Mdm2, we demonstrate in insect cell lines evidence for the existence of p53-, MDM2-, and WAF1/CIP1-like molecules and a p53-regulated pathway following treatment by DNA-damaging agents. JF - Experimental cell research AU - Bae, I AU - Smith, M L AU - Fornace, A J AD - Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/04// PY - 1995 DA - April 1995 SP - 541 EP - 545 VL - 217 IS - 2 SN - 0014-4827, 0014-4827 KW - CIP1 KW - MDM2 KW - WAF1 KW - p53 KW - CDKN1A protein, human KW - 0 KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - Nuclear Proteins KW - Proto-Oncogene Proteins KW - Tumor Suppressor Protein p53 KW - Methyl Methanesulfonate KW - AT5C31J09G KW - MDM2 protein, human KW - EC 2.3.2.27 KW - Proto-Oncogene Proteins c-mdm2 KW - Index Medicus KW - Animals KW - Ultraviolet Rays KW - DNA Damage KW - Humans KW - Cell Cycle -- genetics KW - Cell Line KW - Cell Cycle -- drug effects KW - Radiation, Ionizing KW - Gene Expression -- drug effects KW - Spodoptera -- genetics KW - Spodoptera -- drug effects KW - Tumor Suppressor Protein p53 -- genetics KW - Proto-Oncogene Proteins -- genetics KW - Drosophila -- genetics KW - Gene Expression -- radiation effects KW - Cyclins -- genetics KW - Methyl Methanesulfonate -- pharmacology KW - Drosophila -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77193022?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+cell+research&rft.atitle=Induction+of+p53-%2C+MDM2-%2C+and+WAF1%2FCIP1-like+molecules+in+insect+cells+by+DNA-damaging+agents.&rft.au=Bae%2C+I%3BSmith%2C+M+L%3BFornace%2C+A+J&rft.aulast=Bae&rft.aufirst=I&rft.date=1995-04-01&rft.volume=217&rft.issue=2&rft.spage=541&rft.isbn=&rft.btitle=&rft.title=Experimental+cell+research&rft.issn=00144827&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-28 N1 - Date created - 1995-04-28 N1 - Date revised - 2017-01-13 N1 - Gene symbol - CIP1; MDM2; WAF1; p53 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chelation of intracellular Ca2+ inhibits murine keratinocyte differentiation in vitro. AN - 77180279; 7896886 AB - The role of intracellular Ca2+ in the regulation of Ca(2+)-induced terminal differentiation of mouse keratinocytes was investigated using the intracellular Ca2+ chelator 1,2-bis(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA). A cell permeable acetoxymethyl (AM) ester derivative BAPTA (BAPTA/AM) was loaded into primary mouse keratinocytes in 0.05 mM Ca2+ medium, and then the cells were induced to differentiate by medium containing 0.12 or 0.5 mM Ca(2+) Intracellular BAPTA loaded by BAPTA/AM (15-30 microM) inhibited the expression of epidermal differentiation-specific proteins keratin 1 (K1), keratin 10 (K10), filaggrin and loricrin as detected by immunoblotting. The differentiation-associated redistribution of E-cadherin on the cell membrane was delayed but not inhibited as determined by immunofluorescence. BAPTA also inhibited the expression of K1, K10 and loricrin mRNA. Furthermore, BAPTA prevented the decrease in DNA synthesis induced by 0.12 and 0.5 mM Ca2+, indicating the drug was inhibiting differentiation but was not toxic to keratinocytes. To evaluate the influence of BAPTA on intracellular Ca2+, the concentration of intracellular free Ca2+ (Cai) in BAPTA-loaded keratinocytes was examined by digital image analysis using the Ca(2+)-sensitive fluorescent probe fura-2, and Ca2+ influx was measured by 45Ca2+ uptake studies. Increase in extracellular Ca2+ (Cao) in the culture medium of keratinocytes caused a sustained increase in both Cai and Ca2+ localized to ionomycin-sensitive intracellular stores in keratinocytes. BAPTA lowered basal Cai concentration and prevented the Cai increase. After 12 hours of BAPTA treatment, the basal level of Cai returned to the control value, but the Ca2+ localized in intracellular stores was substantially decreased. 45Ca2+ uptake was initially (within 30 min) increased in BAPTA-loaded cells. However, the total 45Ca2+ accumulation over 24 hours in BAPTA-loaded cells remained unchanged from control values. These results indicate that keratinocytes can maintain Cai and total cellular Ca2+ content in the presence of increased amount of intracellular Ca2+ buffer (e.g., BAPTA) by depleting intracellular Ca2+ stores over a long period. The inhibition by BAPTA of keratinocyte differentiation marker expression may result from depletion of the Ca(2+)-stores since this is the major change in intracellular Ca2+ detected at the time keratinocytes express the differentiation markers. In contrast, the redistribution of E-cadherin on the cell membrane may be more directly associated with Cai change. JF - Journal of cellular physiology AU - Li, L AU - Tucker, R W AU - Hennings, H AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1995/04// PY - 1995 DA - April 1995 SP - 105 EP - 114 VL - 163 IS - 1 SN - 0021-9541, 0021-9541 KW - Biomarkers KW - 0 KW - Cadherins KW - Chelating Agents KW - Egtazic Acid KW - 526U7A2651 KW - DNA KW - 9007-49-2 KW - 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid KW - K22DDW77C0 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Egtazic Acid -- analogs & derivatives KW - Cadherins -- metabolism KW - Cells, Cultured KW - Mice KW - Tissue Distribution KW - Cell Differentiation -- drug effects KW - Homeostasis -- drug effects KW - Egtazic Acid -- pharmacology KW - DNA -- biosynthesis KW - Calcium -- metabolism KW - Chelating Agents -- pharmacology KW - Keratinocytes -- cytology KW - Intracellular Membranes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77180279?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+physiology&rft.atitle=Chelation+of+intracellular+Ca2%2B+inhibits+murine+keratinocyte+differentiation+in+vitro.&rft.au=Li%2C+L%3BTucker%2C+R+W%3BHennings%2C+H%3BYuspa%2C+S+H&rft.aulast=Li&rft.aufirst=L&rft.date=1995-04-01&rft.volume=163&rft.issue=1&rft.spage=105&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+physiology&rft.issn=00219541&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-27 N1 - Date created - 1995-04-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ethylene oxide: induction of specific-locus mutations in the ad-3 region of heterokaryon 12 of Neurospora crassa and implications for genetic risk assessment of human exposure in the workplace. AN - 77179623; 7898502 AB - Ethylene oxide (ETO) is an important industrial intermediate used extensively in the production of ethylene glycol, as a fumigant, and as a sterilant of choice for various medical devices. The mutagenicity of ETO was studied for the induction of specific-locus mutations in the adenine-3 (ad-3) region of a two-component heterokaryon (H-12) of Neurospora crassa. The objectives of these studies with ETO were to rank its mutagenic potency and to compare its mutational spectrum for induced specific-locus mutations with other chemical mutagens in this lower eukaryotic organism. Specific-locus mutations in the ad-3 region of heterokaryon H12 result from gene/point mutations at the closely linked ad-3A and ad-3B loci, multilocus deletion mutations and multiple-locus mutations. These major genotypic classes are similar to the types of specific-locus mutations that can be detected in higher organisms. Conidial suspensions of H-12 were treated with five different concentrations of ETO (0.1-0.35%) for 3 h at 25 degrees C. Control and ETO-treated conidial suspensions were used to obtain dose-response curves for inactivation as well as the overall induction of ad-3 forward mutations using a non-selective method based on pigment accumulation rather than a requirement for adenine. The results from these experiments are: (1) the slope of the dose-response curve for ETO-induced specific-locus mutations in the ad-3 region is 1.49 +/- 0.07, and (2) the maximum forward-mutation frequency fell between 10 and 100 ad-3 mutations per 10(6) survivors; therefore, ETO is a moderate mutagen. Classical genetic tests were used to characterize the ETO-induced ad-3 mutations from each of two treatments (0.25 and 0.35%). The overall data base demonstrates that ETO-induced ad-3 mutations result from a high percentage (96.9%) of gene/point mutations at the ad-3A and ad-3B loci, as well as from a low percentage (3.1%) of multilocus deletion mutations. The mutagenic activity of ETO is compared with the mutagenic specificity of other chemical mutagens and carcinogens in the ad-3 forward-mutation assay in Neurospora. The utilization of the Neurospora specific-locus data on ETO and those from experiments in the mouse and Drosophila, by others, is discussed for genetic risk assessment of germ-cell effects resulting from human exposure to ETO in the workplace. JF - Mutation research AU - de Serres, F J AU - Brockman, H E AD - Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/04// PY - 1995 DA - April 1995 SP - 31 EP - 47 VL - 328 IS - 1 SN - 0027-5107, 0027-5107 KW - Air Pollutants, Occupational KW - 0 KW - DNA, Fungal KW - Mutagens KW - Adenine KW - JAC85A2161 KW - Ethylene Oxide KW - JJH7GNN18P KW - Index Medicus KW - Occupational Exposure KW - Dose-Response Relationship, Drug KW - Humans KW - Mutagens -- toxicity KW - Cell Nucleus -- drug effects KW - DNA, Fungal -- drug effects KW - Gene Deletion KW - Mutagenicity Tests KW - Mutagens -- classification KW - Point Mutation KW - Genetic Complementation Test KW - Genes, Lethal KW - Neurospora crassa -- genetics KW - Mutagenesis, Site-Directed KW - Genes, Fungal -- drug effects KW - Neurospora crassa -- drug effects KW - Air Pollutants, Occupational -- toxicity KW - Ethylene Oxide -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77179623?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Ethylene+oxide%3A+induction+of+specific-locus+mutations+in+the+ad-3+region+of+heterokaryon+12+of+Neurospora+crassa+and+implications+for+genetic+risk+assessment+of+human+exposure+in+the+workplace.&rft.au=de+Serres%2C+F+J%3BBrockman%2C+H+E&rft.aulast=de+Serres&rft.aufirst=F&rft.date=1995-04-01&rft.volume=328&rft.issue=1&rft.spage=31&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 - 1995-04-25 N1 - Date created - 1995-04-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nucleoprotein structure influences the response of the mouse mammary tumor virus promoter to activation of the cyclic AMP signalling pathway. AN - 77172715; 7891707 AB - Recent studies have provided evidence of crosstalk between steroid receptors and cyclic AMP (cAMP) signalling pathways in the regulation of gene expression. A synergism between intracellular phosphorylation inducers and either glucocorticoids or progestins has been shown to occur during activation of the mouse mammary tumor virus (MMTV) promoter. We have investigated the effect of 8-Br-cAMP and okadaic acid, modulators of cellular kinases and phosphatases, on the hormone-induced activation of the MMTV promoter in two forms: a transiently transfected template with a disorganized, accessible nucleoprotein structure and a stably replicating template with an ordered, inaccessible nucleoprotein structure. Both okadaic acid and 8-Br-cAMP synergize significantly with either glucocorticoids or progestins in activating the transiently transfected MMTV template. In contrast, 8-Br-cAMP, but not okadaic acid, is antagonistic to hormone-induced activation of the stably replicating MMTV template. Nuclear run-on experiments demonstrate that this inhibition is a transcriptional effect on both hormone-induced transcription and basal transcription. Surprisingly, 8-Br-cAMP does not inhibit glucocorticoid-induced changes in restriction enzyme access and nuclear factor 1 binding. However, association of a complex with the TATA box region is inhibited in the presence of 8-Br-cAMP. Thus, cAMP treatment interferes with the initiation process but does not inhibit interaction of the receptor with the template. Since the replicated, ordered MMTV templates and the transfected, disorganized templates show opposite responses to 8-Br-cAMP treatment, we conclude that chromatin structure can influence the response of a promoter to activation of the cAMP signalling pathway. JF - Molecular and cellular biology AU - Pennie, W D AU - Hager, G L AU - Smith, C L AD - Laboratory of Molecular Virology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1995/04// PY - 1995 DA - April 1995 SP - 2125 EP - 2134 VL - 15 IS - 4 SN - 0270-7306, 0270-7306 KW - Ethers, Cyclic KW - 0 KW - Nucleoproteins KW - Okadaic Acid KW - 1W21G5Q4N2 KW - 8-Bromo Cyclic Adenosine Monophosphate KW - 23583-48-4 KW - Dexamethasone KW - 7S5I7G3JQL KW - Phosphoprotein Phosphatases KW - EC 3.1.3.16 KW - Index Medicus KW - Phosphoprotein Phosphatases -- antagonists & inhibitors KW - Animals KW - Tumor Cells, Cultured KW - Models, Genetic KW - Dexamethasone -- pharmacology KW - Mice KW - Gene Expression Regulation -- drug effects KW - Ethers, Cyclic -- pharmacology KW - 8-Bromo Cyclic Adenosine Monophosphate -- pharmacology KW - Transcription, Genetic -- drug effects KW - Signal Transduction -- drug effects KW - Nucleoproteins -- metabolism KW - Signal Transduction -- genetics KW - Promoter Regions, Genetic -- genetics KW - Mammary Tumor Virus, Mouse -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77172715?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Nucleoprotein+structure+influences+the+response+of+the+mouse+mammary+tumor+virus+promoter+to+activation+of+the+cyclic+AMP+signalling+pathway.&rft.au=Pennie%2C+W+D%3BHager%2C+G+L%3BSmith%2C+C+L&rft.aulast=Pennie&rft.aufirst=W&rft.date=1995-04-01&rft.volume=15&rft.issue=4&rft.spage=2125&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 - 1995-04-20 N1 - Date created - 1995-04-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell Biol. 1991 Feb;11(2):688-98 [1846670] J Virol. 1992 Dec;66(12):7529-32 [1331537] Mol Cell Biol. 1991 May;11(5):2529-37 [1708094] Cell. 1991 May 31;65(5):775-83 [2040014] Cell. 1991 Jun 14;65(6):1023-31 [2044150] J Biol Chem. 1991 Oct 5;266(28):19095-102 [1655770] Cell Growth Differ. 1991 Oct;2(10):525-30 [1751408] Science. 1991 Dec 20;254(5039):1814-6 [1684878] Genes Dev. 1992 Feb;6(2):316-27 [1737621] Nucleic Acids Res. 1992 Jan 25;20(2):273-8 [1311071] Cell. 1975 Nov;6(3):299-305 [212202] Mol Cell Biol. 1983 Nov;3(11):2045-57 [6318079] Cell. 1984 Aug;38(1):29-38 [6088072] J Biol Chem. 1985 Feb 10;260(3):1676-81 [2981868] EMBO J. 1986 Sep;5(9):2237-40 [3023063] J Mol Biol. 1986 Aug 5;190(3):379-89 [3023641] Mol Cell Biol. 1986 Aug;6(8):2847-54 [3023950] Cell. 1987 Jan 30;48(2):261-70 [3026639] Science. 1987 Jul 17;237(4812):268-75 [3037703] Nucleic Acids Res. 1987 Sep 11;15(17):6973-89 [2821488] EMBO J. 1987 Aug;6(8):2321-8 [2822386] Science. 1988 Jul 15;241(4863):350-3 [2838908] Cell. 1988 Oct 7;55(1):27-39 [3048701] J Virol. 1988 Dec;62(12):4644-52 [2846876] Mol Cell Biol. 1988 Sep;8(9):3872-81 [2851730] Cell. 1990 Mar 9;60(5):719-31 [2155706] J Biol Chem. 1990 Apr 15;265(11):6494-500 [1690730] Nucleic Acids Res. 1990 Apr 25;18(8):2017-24 [2159634] Proc Natl Acad Sci U S A. 1990 Aug;87(16):6286-90 [2201024] Mol Cell Biol. 1990 Sep;10(9):4712-9 [2388623] Science. 1990 Sep 14;249(4974):1266-72 [2119054] Cell. 1990 Sep 21;62(6):1189-204 [2169351] Cell. 1990 Sep 21;62(6):1205-15 [2169352] Cell. 1990 Sep 21;62(6):1217-26 [2169353] J Virol. 1991 Jan;65(1):526-31 [1845907] J Mol Biol. 1990 Dec 20;216(4):859-72 [2176241] Science. 1990 Dec 21;250(4988):1740-3 [2176746] Bioessays. 1992 Jan;14(1):9-16 [1312335] Genes Dev. 1992 Mar;6(3):411-25 [1547940] Science. 1992 Mar 20;255(5051):1573-6 [1347958] J Biol Chem. 1992 Apr 15;267(11):7511-9 [1559989] Mol Endocrinol. 1992 Apr;6(4):607-20 [1316549] EMBO J. 1992 Sep;11(9):3297-306 [1505519] New Biol. 1992 May;4(5):527-40 [1387550] Mol Endocrinol. 1992 Sep;6(9):1451-7 [1435789] J Virol. 1993 Jan;67(1):415-24 [8380087] J Biol Chem. 1993 Jan 25;268(3):1580-5 [7678408] J Biol Chem. 1993 Mar 15;268(8):5353-6 [8449898] J Biol Chem. 1993 May 5;268(13):9262-6 [8387487] J Mol Biol. 1993 Jun 5;231(3):658-67 [8515443] Endocrinology. 1993 Aug;133(2):728-40 [8344212] Mol Endocrinol. 1993 Jun;7(6):731-42 [8395651] J Biol Chem. 1993 Oct 25;268(30):22933-40 [7693681] Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11202-6 [8248228] Mol Cell Biol. 1994 Jan;14(1):32-41 [8264599] Mol Cell Biol. 1994 Feb;14(2):1191-203 [8289800] J Virol. 1994 Mar;68(3):1993-7 [8107261] J Biol Chem. 1994 Apr 1;269(13):9568-73 [8144543] Nucleic Acids Res. 1994 May 11;22(9):1655-62 [8202368] Mol Endocrinol. 1994 May;8(5):568-76 [8058066] Mol Cell Biol. 1995 Jan;15(1):26-34 [7799933] Mol Cell Biol. 1992 Nov;12(11):4906-18 [1328867] Cell. 1991 Feb 8;64(3):565-72 [1846780] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutations in the p16INK4/MTS1/CDKN2, p15INK4B/MTS2, and p18 genes in primary and metastatic lung cancer. AN - 77171130; 7882351 AB - We examined the genomic status of cyclin-dependent kinase-4 and -6 inhibitors, p16INK4,p15INK4B, and p18, in 40 primary lung cancers and 31 metastatic lung cancers. Alterations of the p16INK4 gene were detected in 6 (2 insertions and 4 homozygous deletions) of 22 metastatic non-small cell lung cancers (NSCLCs; 27%), but none were detected in 25 primary NSCLCs, 15 primary small cell lung cancers (SCLCs), or 9 metastatic SCLCs, indicating that mutation in the p16INK4 gene is a late event in NSCLC carcinogenesis. Although three intragenic mutations of the p15INK4B gene were detected in 25 primary NSCLCs (12%) and five homozygous deletions of the p15INK4B gene were detected in 22 NSCLCs (23%), no genetic alterations of the p15INK4B gene were found in primary and metastatic SCLCs. The p18 gene was wild type in these 71 lung cancers, except 1 metastatic NSCLC which showed loss of heterozygosity. We also examined alterations of these three genes and expression of p16INK4 in 21 human lung cancer cell lines. Alterations of the p16INK4 and p15INK4B genes were detected in 71% of the NSCLC cell lines (n = 14) and 50% of the NSCLC cell lines (n = 14), respectively, but there were none in the 7 SCLC cell lines studied. No p18 mutations were detected in these 21 cell lines. These results indicate that both p16INK4 and p15INK4B gene mutations are associated with tumor progression of a subset of NSCLC, but not of SCLC, and that p15INK4B mutations might also be an early event in the molecular pathogenesis of a subset of NSCLC. JF - Cancer research AU - Okamoto, A AU - Hussain, S P AU - Hagiwara, K AU - Spillare, E A AU - Rusin, M R AU - Demetrick, D J AU - Serrano, M AU - Hannon, G J AU - Shiseki, M AU - Zariwala, M AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255. Y1 - 1995/04/01/ PY - 1995 DA - 1995 Apr 01 SP - 1448 EP - 1451 VL - 55 IS - 7 SN - 0008-5472, 0008-5472 KW - CDKN2 KW - MTS1 KW - MTS2 KW - p15INK4B KW - p16INK4 KW - p18 KW - DNA, Neoplasm KW - 0 KW - Index Medicus KW - Polymerase Chain Reaction KW - Base Sequence KW - Tumor Cells, Cultured KW - Polymorphism, Genetic KW - Humans KW - Molecular Sequence Data KW - DNA, Neoplasm -- genetics KW - DNA, Neoplasm -- analysis KW - Sequence Analysis, DNA KW - Carcinoma, Non-Small-Cell Lung -- genetics KW - Carcinoma, Small Cell -- secondary KW - Lung Neoplasms -- genetics KW - Carcinoma, Non-Small-Cell Lung -- secondary KW - Carcinoma, Small Cell -- genetics KW - Gene Deletion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77171130?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutations+in+the+p16INK4%2FMTS1%2FCDKN2%2C+p15INK4B%2FMTS2%2C+and+p18+genes+in+primary+and+metastatic+lung+cancer.&rft.au=Okamoto%2C+A%3BHussain%2C+S+P%3BHagiwara%2C+K%3BSpillare%2C+E+A%3BRusin%2C+M+R%3BDemetrick%2C+D+J%3BSerrano%2C+M%3BHannon%2C+G+J%3BShiseki%2C+M%3BZariwala%2C+M&rft.aulast=Okamoto&rft.aufirst=A&rft.date=1995-04-01&rft.volume=55&rft.issue=7&rft.spage=1448&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 - 1995-04-13 N1 - Date created - 1995-04-13 N1 - Date revised - 2017-01-13 N1 - Gene symbol - CDKN2; MTS1; MTS2; p15INK4B; p16INK4; p18 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Multiple regions of Harvey sarcoma virus RNA can dimerize in vitro. AN - 77165819; 7884897 AB - Retroviruses contain a dimeric RNA consisting of two identical molecules of plus-strand genomic RNA. The structure of the linkage between the two monomers is not known, but they are believed to be joined near their 5' ends. Darlix and coworkers have reported that transcripts of retroviral RNA sequences can dimerize spontaneously in vitro (see, for example, E. Bieth, C. Gabus, and J. L. Darlix, Nucleic Acids Res. 18:119-127, 1990). As one approach to identification of sequences which might participate in the linkage, we have mapped sequences derived from the 5' 378 bases of Harvey sarcoma virus (HaSV) RNA which can dimerize in vitro. We found that at least three distinct regions, consisting of nucleotides 37 to 229, 205 to 272, and 271 to 378, can form these dimers. Two of these regions contain nucleotides 205 to 226; computer analysis suggests that this region can form a stem-loop with an inverted repeat in the loop. We propose that this hypothetical structure is involved in dimer formation by these two transcripts. We also compared the thermal stabilities of each of these dimers with that of HaSV viral RNA. Dimers of nucleotides 37 to 229 and 205 to 272 both exhibited melting temperatures near that of viral RNA, while dimers of nucleotides 271 to 378 are quite unstable. We also found that dimers of nucleotides 37 to 378 formed at 37 degrees C are less thermostable than dimers of the same RNA formed at 55 degrees C. It seems possible that bases from all of these regions participate in the dimer linkage present in viral RNA. JF - Journal of virology AU - Feng, Y X AU - Fu, W AU - Winter, A J AU - Levin, J G AU - Rein, A AD - Laboratory of Molecular Virology and Carcinogenesis, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Maryland 21702-1201. Y1 - 1995/04// PY - 1995 DA - April 1995 SP - 2486 EP - 2490 VL - 69 IS - 4 SN - 0022-538X, 0022-538X KW - Biopolymers KW - 0 KW - RNA, Viral KW - Index Medicus KW - Base Sequence KW - Temperature KW - Molecular Sequence Data KW - Nucleic Acid Conformation KW - Cloning, Molecular KW - RNA, Viral -- chemistry KW - Harvey murine sarcoma virus -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77165819?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Multiple+regions+of+Harvey+sarcoma+virus+RNA+can+dimerize+in+vitro.&rft.au=Feng%2C+Y+X%3BFu%2C+W%3BWinter%2C+A+J%3BLevin%2C+J+G%3BRein%2C+A&rft.aulast=Feng&rft.aufirst=Y&rft.date=1995-04-01&rft.volume=69&rft.issue=4&rft.spage=2486&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 - 1995-04-10 N1 - Date created - 1995-04-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Virology. 1973 Apr;52(2):456-67 [4705382] Nucleic Acids Res. 1990 Dec 25;18(24):7287-92 [2259624] Nucleic Acids Res. 1991 May 11;19(9):2349-57 [1645868] Virology. 1991 Aug;183(2):611-9 [1853563] J Mol Biol. 1992 Jan 5;223(1):205-20 [1731069] J Virol. 1992 Feb;66(2):632-40 [1309906] Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3393-7 [8475087] J Virol. 1993 Sep;67(9):5443-9 [8350405] Biochemistry. 1993 Oct 26;32(42):11453-7 [8218211] J Virol. 1994 Feb;68(2):661-7 [8289369] Nucleic Acids Res. 1994 Jan 25;22(2):145-51 [8121797] Proc Natl Acad Sci U S A. 1994 May 24;91(11):4945-9 [8197162] Arch Virol Suppl. 1994;9:513-22 [8032280] J Virol. 1994 Aug;68(8):5013-8 [8035501] J Mol Biol. 1994 Jul 29;240(5):434-44 [8046749] J Virol. 1994 Sep;68(9):5863-70 [8057466] Biochemistry. 1994 Nov 15;33(45):13464-74 [7947755] J Mol Appl Genet. 1982;1(4):327-41 [6286831] Anal Biochem. 1986 Nov 15;159(1):227-32 [2433961] Cell. 1987 Apr 10;49(1):93-102 [3030568] J Virol. 1989 Mar;63(3):1384-92 [2536840] Proc Natl Acad Sci U S A. 1989 Oct;86(20):7706-10 [2479010] J Virol. 1990 Feb;64(2):774-83 [2153242] Nucleic Acids Res. 1990 Jan 11;18(1):119-27 [2155394] Curr Top Microbiol Immunol. 1990;157:125-52 [2394131] J Mol Biol. 1990 Dec 5;216(3):689-99 [2124274] J Virol. 1980 Nov;36(2):408-20 [6253666] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluating Birth Frequencies and Embryonic Lethality in Transgenesis Following Pronuclear Injection of HIV DNA. AN - 1859366187; 11725050 AB - The likelihood that expression of a foreign gene in a mammalian cell is deleterious to viability is confronted whenever novel transgenic animals are made. A pathological response to transgene expression is even desired in transgenic mouse models of human disease. The derivation of HIV-transgenic mice in our laboratory using multiple recombinant forms of an HIV provirus has resulted in mixed success best explained by the variable toxicity of the different transgenes. Employing a standardized approach to pronuclear injections, experimental variation amongst recombinant HIV transgenes was documented in terms of the percentage of pregnancies following embryo transfer into pseudopregnant mice and the percentage of transplanted embryos leading to term births in these pregnant females (giving rise to an index of birth success, SI). Results compiled over 5 years suggested that the SI reflected transgene toxicity, in this case of HIV gene products early in embryogenesis. These observations have guided the design of productive transgenes for mouse models of HIV-related diseases and may be generally applicable in transgenesis. Copyright 1995 S. Karger AG, Basel JF - Journal of biomedical science AU - Dickie, P. AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md., USA. Y1 - 1995/04// PY - 1995 DA - April 1995 SP - 146 EP - 153 VL - 2 IS - 2 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859366187?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+biomedical+science&rft.atitle=Evaluating+Birth+Frequencies+and+Embryonic+Lethality+in+Transgenesis+Following+Pronuclear+Injection+of+HIV+DNA.&rft.au=Dickie%2C+P.&rft.aulast=Dickie&rft.aufirst=P.&rft.date=1995-04-01&rft.volume=2&rft.issue=2&rft.spage=146&rft.isbn=&rft.btitle=&rft.title=Journal+of+biomedical+science&rft.issn=1423-0127&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2001-11-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of ifenprodil on stimulatory, discriminative stimulus, and convulsant effects of cocaine. AN - 1859345650; 11224333 AB - Ifenprodil, like cocaine, binds to the dopamine transporter and blocks uptake of dopamine. In this study, the ability of ifenprodil to mimic, enhance or block behavioral and toxic effects of cocaine was evaluated. Fixed-interval responding maintained by food presentation in rats was increased by cocaine but decreased by ifenprodil. Low rates of responding during timeout periods were also increased by cocaine but not ifenprodil. Ifenprodil neither increased locomotor activity nor augmented the stimulatory effect of cocaine; however, ifenprodil attenuated the stimulant effects of cocaine at doses 0.5 log unit lower than those required to reduce spontaneous activity when given alone. Ifenprodil neither substituted for nor augmented the discriminative stimulus effects of cocaine in rats discriminating 10mg/kg cocaine from saline. In contrast to cocaine, ifenprodil did not produce convulsions or signs of proconvulsant activity, and ifenprodil reduced the percentage of mice convulsing in the presence of cocaine. These results suggest that pharmacological actions in addition to blockade of dopamine uptake or novel interactions with the dopamine transporter may contribute to the non-stimulant behavioral profile and cocaine-blocking actions of ifenprodil. JF - Behavioural pharmacology AU - Witkin, J.M. AU - Acri, J.B. AD - Drug Development Group, Psychobiology Section, Addiction Research Center, National Institute on Drug Abuse, Baltimore, MD, USA. Y1 - 1995/04// PY - 1995 DA - April 1995 SP - 245 EP - 253 VL - 6 IS - 3 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859345650?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Behavioural+pharmacology&rft.atitle=Effects+of+ifenprodil+on+stimulatory%2C+discriminative+stimulus%2C+and+convulsant+effects+of+cocaine.&rft.au=Witkin%2C+J.M.%3BAcri%2C+J.B.&rft.aulast=Witkin&rft.aufirst=J.M.&rft.date=1995-04-01&rft.volume=6&rft.issue=3&rft.spage=245&rft.isbn=&rft.btitle=&rft.title=Behavioural+pharmacology&rft.issn=1473-5849&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2001-02-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Coexpression of a multidrug-resistance gene (MDR1) and herpes simplex virus thymidine kinase gene as part of a bicistronic messenger RNA in a retrovirus vector allows selective killing of MDR1-transduced cells AN - 1859164192; 9816003 AB - A new retroviral vector, pSXLC/pHa, was constructed to coexpress drug-selectable markers with a second gene of interest as a part of a bicistronic mRNA in a retroviral vector using an internal ribosome entry site (IRES) from encephalomyocarditis virus. This system was used to develop a new retroviral vector pHa-MDR-IRES-TK which expresses a single mRNA from which translation of the MDR1 gene is cap dependent and translation of the herpes simplex virus thymidine kinase gene is IRES dependent. The pHa-MDR-IRES-TK transfectants showed high levels of P-glycoprotein expression and multidrug resistance. More than 95% of the vincristine-resistant cells transfected or transduced with pHa-MDR-IRES-TK showed hypersensitivity to ganciclovir, which selects against cells expressing herpes simplex virus thymidine kinase. An amphotropic retrovirus titer of 7.8 x 10(4)/ml was obtained with this vector. This safety-modified vector should be useful for introducing the MDR1 gene into bone marrow cells to protect normal cells from the toxic effects of cancer chemotherapy because this vector allows the elimination of cancer cells that have been unintentionally transduced with the MDR1 vector. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Sugimoto AU - Hrycyna AU - Aksentijevich AU - Pastan AU - Gottesman AD - Laboratory of Cell Biology and Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/04// PY - 1995 DA - April 1995 SP - 447 EP - 457 VL - 1 IS - 4 SN - 1078-0432, 1078-0432 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859164192?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Coexpression+of+a+multidrug-resistance+gene+%28MDR1%29+and+herpes+simplex+virus+thymidine+kinase+gene+as+part+of+a+bicistronic+messenger+RNA+in+a+retrovirus+vector+allows+selective+killing+of+MDR1-transduced+cells&rft.au=Sugimoto%3BHrycyna%3BAksentijevich%3BPastan%3BGottesman&rft.aulast=Sugimoto&rft.aufirst=&rft.date=1995-04-01&rft.volume=1&rft.issue=4&rft.spage=447&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 created - 1999-01-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential requirement of a motif within the carboxyl-terminal domain of alpha-platelet-derived growth factor (alpha PDGF) receptor for PDGF focus forming activity chemotaxis, or growth. AN - 77202269; 7706238 AB - To determine the molecular basis for the transforming function of platelet-derived growth factor (PDGF)-A in NIH/3T3 cells, we have constructed chimerae consisting of the extracellular domain of the human CSF-1R (fms) linked to the cytoplasmic domain of the alpha PDGF receptor (alpha R) containing a series of deletion or point mutations. The ability of fms/alpha R chimerae to mediate CSF-1-dependent anchorage-independent growth, focus formation, and chemotaxis of NIH/3T3 cells was then examined. Our results provide evidence that a domain encompassing amino acid residues 977-1024 of the alpha PDGFR is required for ligand-dependent focus formation, but not chemotaxis or anchorage-independent growth, and that tyrosine residues within this domain constitute the major binding site for phospholipase C gamma. Therefore, our findings suggest that: (i) the focus forming function of alpha PDGFR correlates well with the ability of the receptor to bind phospholipase C gamma, and (ii) the mechanism of focus formation mediated by alpha PDGFR may be distinguished from that required for chemotaxis or anchorage-independent growth. JF - The Journal of biological chemistry AU - Yu, J C AU - Li, W AU - Wang, L M AU - Uren, A AU - Pierce, J H AU - Heidaran, M A AD - Laboratory of Cellular and Molecular Biology, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/03/31/ PY - 1995 DA - 1995 Mar 31 SP - 7033 EP - 7036 VL - 270 IS - 13 SN - 0021-9258, 0021-9258 KW - Platelet-Derived Growth Factor KW - 0 KW - Recombinant Fusion Proteins KW - Recombinant Proteins KW - Macrophage Colony-Stimulating Factor KW - 81627-83-0 KW - Receptor, Macrophage Colony-Stimulating Factor KW - EC 2.7.10.1 KW - Receptor, Platelet-Derived Growth Factor alpha KW - Receptors, Platelet-Derived Growth Factor KW - Type C Phospholipases KW - EC 3.1.4.- KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - 3T3 Cells KW - Animals KW - Recombinant Proteins -- pharmacology KW - Humans KW - Macrophage Colony-Stimulating Factor -- pharmacology KW - Platelet-Derived Growth Factor -- pharmacology KW - Cell Division -- drug effects KW - Cell Division -- physiology KW - Mice KW - Type C Phospholipases -- metabolism KW - Binding Sites KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Transfection KW - Recombinant Proteins -- metabolism KW - Point Mutation KW - Sequence Deletion KW - Chemotaxis -- physiology KW - Receptor, Macrophage Colony-Stimulating Factor -- physiology KW - Chemotaxis -- drug effects KW - Receptor, Macrophage Colony-Stimulating Factor -- biosynthesis KW - Receptors, Platelet-Derived Growth Factor -- physiology KW - Receptors, Platelet-Derived Growth Factor -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77202269?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Differential+requirement+of+a+motif+within+the+carboxyl-terminal+domain+of+alpha-platelet-derived+growth+factor+%28alpha+PDGF%29+receptor+for+PDGF+focus+forming+activity+chemotaxis%2C+or+growth.&rft.au=Yu%2C+J+C%3BLi%2C+W%3BWang%2C+L+M%3BUren%2C+A%3BPierce%2C+J+H%3BHeidaran%2C+M+A&rft.aulast=Yu&rft.aufirst=J&rft.date=1995-03-31&rft.volume=270&rft.issue=13&rft.spage=7033&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 - 1995-05-10 N1 - Date created - 1995-05-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of diverse functional elements in the upstream Sp1 domain of the rat luteinizing hormone receptor gene promoter. AN - 77201220; 7706295 AB - Transcription of the luteinizing hormone receptor gene is dependent on Sp1-induced promoter activation from two Sp1 binding domains (Sp1(2), and Sp1(4)) within the 173-base pair promoter. Of the two Sp1 binding domains, the canonical GC box (GGGCGG) was determined by mutation to be the binding element for only the Sp1(2) domain. The Sp1 binding element within the Sp1(4) domain was identified by mutation and immunological/competition studies as the 5'-GGG GTG GGG that conforms to a Zif-268 like three zinc finger binding domain, rather than the canonical 3' Sp1(4) GC box (GGGCGG). The guanines in the third trinucleotide (GGG GTG GGG) were not required for Sp1 binding, although they increased binding affinity. Non-Sp1 protein(s) bind the 3' Sp1(4) GC box, and by themselves exhibit transcriptional activity. Tissue specific differences were localized to this non-Sp1 binding domain, which functionally substituted for the downstream activating M1 regulatory domain in non-expressing but not in expressing cells. Mutations of both non-Sp1 and M1 domains were required for inhibition of promoter activity in constructs that retained the Sp1 binding elements in non-expressing cells, indicating that together these domains may play a role in regulation of luteinizing hormone receptor gene expression. JF - The Journal of biological chemistry AU - Tsai-Morris, C H AU - Geng, Y AU - Buczko, E AU - Dufau, M L AD - Section on Molecular Endocrinology, NICHHD, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/03/31/ PY - 1995 DA - 1995 Mar 31 SP - 7487 EP - 7494 VL - 270 IS - 13 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - Receptors, LH KW - Recombinant Fusion Proteins KW - Sp1 Transcription Factor KW - Luciferases KW - EC 1.13.12.- KW - Index Medicus KW - Animals KW - Recombinant Fusion Proteins -- biosynthesis KW - Transcription, Genetic KW - Binding Sites KW - Luciferases -- biosynthesis KW - Mutagenesis, Site-Directed KW - Rats KW - Regulatory Sequences, Nucleic Acid KW - Polymerase Chain Reaction KW - Base Sequence KW - Kinetics KW - Binding, Competitive KW - Molecular Sequence Data KW - Zinc Fingers KW - Promoter Regions, Genetic KW - Receptors, LH -- biosynthesis KW - Sp1 Transcription Factor -- metabolism KW - Receptors, LH -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77201220?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Characterization+of+diverse+functional+elements+in+the+upstream+Sp1+domain+of+the+rat+luteinizing+hormone+receptor+gene+promoter.&rft.au=Tsai-Morris%2C+C+H%3BGeng%2C+Y%3BBuczko%2C+E%3BDufau%2C+M+L&rft.aulast=Tsai-Morris&rft.aufirst=C&rft.date=1995-03-31&rft.volume=270&rft.issue=13&rft.spage=7487&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 - 1995-05-10 N1 - Date created - 1995-05-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - beta-Cystathionase from Bordetella avium. Role(s) of lysine 214 and cysteine residues in activity and cytotoxicity. AN - 77200268; 7706318 AB - beta-Cystathionase (EC 4.4.1.8) from Bordetella avium is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes the hydrolysis of L-cystine to yield pyruvic acid, NH3, and thiocysteine. The latter compound is highly toxic toward MC3T3-E1 osteogenic cells, rat osteosarcoma cells, and other cell lines maintained in tissue culture (Gentry-Weeks, C. R., Keith, J. M., and Thompson, J. (1993) J. Biol. Chem. 268, 7298-7314). Site-directed mutagenesis has established that lysine 214 of the sequence TKYVGGHSD, is primarily responsible for internal aldimine binding of PLP in the holoenzyme. Translation of the DNA sequence of the beta-cystathionase gene (metC) from B. avium, reveals 4 cysteine residues/enzyme subunit (M(r) = 42,600), and spectrophotometric analysis with 4,4'-dithiodipyridine showed that there were no disulfide linkages in the native protein. beta-Cystathionase is inhibited by sulfhydryl-reactive agents, including N-ethylmaleimide (NEM). To elucidate the mechanism of NEM inhibition, each of the 4 cysteine residues at positions 88, 117, 279, and 309 was individually replaced by alanine or glycine. The mutant proteins C88A, C117G, C279G, and C309A were purified to homogeneity, and each was assayed for enzyme activity, PLP-binding, NEM sensitivity, and susceptibility to chymotrypsin digestion. The activities of mutant proteins C88A and C279G were comparable with that of the native enzyme, and since both forms were inhibited by NEM, neither cysteine 88 nor 279 are prerequisite for enzyme activity. By elimination, cysteine residues 117 and 309 must be the targets for alkylation, and resultant inactivation of beta-cystathionase, by the -SH reactive agent. Substitution of cysteine 117 and 309 with glycine and alanine, respectively, yielded the inactive proteins C117G and C309A. PLP was not detectable in these proteins, and their absorption spectra lacked the peak (at 420 nm) that is characteristic of internal PLP-Schiff base formation. Edman degradation revealed that C117G (M(r) approximately 36,000) also lacked the first 63 amino acids comprising the N terminus of the native protein. The beta-cystathionase mutants C117G and C309A showed enhanced susceptibility to chymotrypsin digestion. Cysteine residues 117 and 309 may reside in conformationally sensitive environments, and in the native enzyme these amino acids most probably serve a structural function. Toxicity assays performed with the various mutant proteins obtained by site-directed mutagenesis established that only catalytically active forms of beta-cystathionase were were cytotoxic for tissue culture cells. JF - The Journal of biological chemistry AU - Gentry-Weeks, C R AU - Spokes, J AU - Thompson, J AD - Laboratory of Microbial Ecology, NIDR, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/03/31/ PY - 1995 DA - 1995 Mar 31 SP - 7695 EP - 7702 VL - 270 IS - 13 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - DNA, Bacterial KW - Recombinant Proteins KW - Chymotrypsin KW - EC 3.4.21.1 KW - Lyases KW - EC 4.- KW - cystathionine beta-lyase KW - EC 4.4.1.8 KW - Ethylmaleimide KW - O3C74ACM9V KW - Index Medicus KW - Animals KW - Peptide Mapping KW - Escherichia coli -- enzymology KW - Osteoblasts -- cytology KW - Salmonella typhimurium -- enzymology KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Point Mutation KW - Spectrophotometry KW - Recombinant Proteins -- chemistry KW - Ethylmaleimide -- pharmacology KW - Sequence Homology, Amino Acid KW - 3T3 Cells KW - Protein Biosynthesis KW - Mice KW - Amino Acid Sequence KW - Osteoblasts -- drug effects KW - Recombinant Proteins -- toxicity KW - Polymerase Chain Reaction KW - Base Sequence KW - Kinetics KW - DNA, Bacterial -- metabolism KW - Lyases -- toxicity KW - Cell Survival -- drug effects KW - Lyases -- chemistry KW - Bordetella -- enzymology KW - Lyases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77200268?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=beta-Cystathionase+from+Bordetella+avium.+Role%28s%29+of+lysine+214+and+cysteine+residues+in+activity+and+cytotoxicity.&rft.au=Gentry-Weeks%2C+C+R%3BSpokes%2C+J%3BThompson%2C+J&rft.aulast=Gentry-Weeks&rft.aufirst=C&rft.date=1995-03-31&rft.volume=270&rft.issue=13&rft.spage=7695&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 - 1995-05-10 N1 - Date created - 1995-05-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isolation of an amino-terminal deleted recombinant ADP-ribosylation factor 1 in an activated nucleotide-free state. AN - 77207840; 7708774 AB - ADP-ribosylation factors (ARFs) are approximately 20-kDa guanine nucleotide-binding proteins that activate cholera toxin ADP-ribosyltransferase in vitro and participate in intracellular vesicular membrane trafficking. ARFs are activated when bound GDP is replaced by GTP and inactivated by hydrolysis of bound GTP to yield ARF-GDP. Usually, ARFs are isolated in an inactive GDP-bound state and require addition of GTP along with detergent or phospholipid for activity. Purified mutant recombinant ARF1 lacking the first 13 amino acids (r delta 13ARF1-P) stimulated cholera toxin activity essentially equally with or without added GTP (and phospholipid or detergent), at least in part due to the presence of bound nucleotides, which later were identified as GTP and GDP. Nucleotide-free r delta 13ARF1 (r delta 13ARF1-F), prepared by dialysis against 7 M urea, was active without added GTP in the absence of SDS but inactive without added GTP in its presence. Renaturation of r delta 13ARF1-F in the presence of GTP, ITP, or GDP yielded, respectively, r delta 13ARF1-GTP and r delta 13ARF1-ITP, which were active, and r delta 13ARF1-GDP, which was inactive. Effects of phospholipids and detergents on nucleotide exchangeability evaluated as effects on activity of rARF1 and r delta 13ARF1-F differed. With r delta 13ARF1-F, 100 microM ITP and 100 microM GTP were essentially equally effective in the presence of cardiolipin or SDS. The finding that r delta 13ARF1 differs from rARF1 in the effects of phospholipids and detergents on nucleotide binding is consistent with the conclusion that the ARF amino terminus plays an important role in nucleotide binding and its specificity as well as the molecular conformation and associated activity. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Hong, J X AU - Zhang, X AU - Moss, J AU - Vaughan, M AD - Pulmonary-Critical Care Medicine Branch, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/03/28/ PY - 1995 DA - 1995 Mar 28 SP - 3056 EP - 3059 VL - 92 IS - 7 SN - 0027-8424, 0027-8424 KW - Carrier Proteins KW - 0 KW - Detergents KW - Phospholipids KW - Recombinant Proteins KW - Inosine Triphosphate KW - 132-06-9 KW - Guanosine Diphosphate KW - 146-91-8 KW - Guanosine Triphosphate KW - 86-01-1 KW - Cholera Toxin KW - 9012-63-9 KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - ADP-Ribosylation Factor 1 KW - EC 3.6.5.2 KW - ADP-Ribosylation Factors KW - Index Medicus KW - Recombinant Proteins -- biosynthesis KW - Phospholipids -- pharmacology KW - Guanosine Diphosphate -- metabolism KW - Guanosine Diphosphate -- analysis KW - Detergents -- pharmacology KW - Protein Binding KW - Mutagenesis KW - Cloning, Molecular KW - Guanosine Triphosphate -- metabolism KW - Recombinant Proteins -- isolation & purification KW - Guanosine Triphosphate -- analysis KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Escherichia coli KW - Cholera Toxin -- metabolism KW - Inosine Triphosphate -- metabolism KW - GTP-Binding Proteins -- biosynthesis KW - Carrier Proteins -- metabolism KW - GTP-Binding Proteins -- metabolism KW - GTP-Binding Proteins -- isolation & purification KW - Poly(ADP-ribose) Polymerases -- metabolism KW - Carrier Proteins -- biosynthesis KW - Sequence Deletion KW - Carrier Proteins -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77207840?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Isolation+of+an+amino-terminal+deleted+recombinant+ADP-ribosylation+factor+1+in+an+activated+nucleotide-free+state.&rft.au=Hong%2C+J+X%3BZhang%2C+X%3BMoss%2C+J%3BVaughan%2C+M&rft.aulast=Hong&rft.aufirst=J&rft.date=1995-03-28&rft.volume=92&rft.issue=7&rft.spage=3056&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 - 1995-05-11 N1 - Date created - 1995-05-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochim Biophys Acta. 1990 May 16;1034(2):195-9 [2112955] Biochemistry. 1990 Jan 30;29(4):855-61 [2111167] Biochem J. 1991 May 1;275 ( Pt 3):639-44 [1903923] J Biol Chem. 1991 Dec 5;266(34):23053-9 [1744102] J Biol Chem. 1992 Feb 15;267(5):3230-5 [1737779] J Biol Chem. 1992 May 5;267(13):9028-34 [1577740] J Biol Chem. 1992 Jun 25;267(18):13053-61 [1618803] Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6408-12 [1631136] Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6619-23 [1385876] J Biol Chem. 1992 Sep 5;267(25):17766-72 [1517219] Nature. 1992 Nov 26;360(6402):350-2 [1448151] Nature. 1992 Nov 26;360(6402):352-4 [1448152] J Biol Chem. 1993 Mar 5;268(7):4863-72 [8444865] J Biol Chem. 1993 May 5;268(13):9555-63 [8486645] J Biol Chem. 1994 Apr 1;269(13):9743-5 [8144566] Proc Natl Acad Sci U S A. 1990 Mar;87(6):2206-10 [2107548] Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3063-6 [8159707] J Biol Chem. 1994 Jun 3;269(22):15583-7 [8195204] J Biol Chem. 1994 Nov 25;269(47):29490-4 [7961931] Proc Natl Acad Sci U S A. 1981 Aug;78(8):4809-12 [6272274] J Biol Chem. 1984 May 25;259(10):6228-34 [6327671] Proc Natl Acad Sci U S A. 1987 Aug;84(15):5139-42 [3110784] J Biol Chem. 1988 Feb 5;263(4):1768-72 [3123477] Proc Natl Acad Sci U S A. 1988 Jul;85(13):4620-4 [3133654] Proc Natl Acad Sci U S A. 1988 Aug;85(15):5488-91 [3135549] J Biol Chem. 1989 Dec 15;264(35):21066-72 [2512288] J Biol Chem. 1991 Feb 15;266(5):2772-7 [1993656] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cutoff in potency implicates alcohol inhibition of N-methyl-D-aspartate receptors in alcohol intoxication. AN - 77207723; 7708732 AB - As the number of carbon atoms in an aliphatic n-alcohol is increased from one to five, intoxicating potency, lipid solubility, and membrane lipid disordering potency all increase in a similar exponential manner. However, the potency of aliphatic n-alcohols for producing intoxication reaches a maximum at six to eight carbon atoms and then decreases. The molecular basis of this "cutoff" effect is not understood, as it is not correlated with either the lipid solubility or the membrane disordering potency of the alcohols, which continue to increase exponentially. Since it has been suggested that inhibition of N-methyl-D-aspartate (NMDA) receptors by alcohols may play a role in alcohol intoxication, we investigated whether a series of aliphatic n-alcohols would exhibit a cutoff in potency for inhibition of NMDA receptors. We found that although potency for inhibition of NMDA receptors increased exponentially for alcohols with one to five carbon atoms, potency for inhibition of NMDA receptors reached a maximum at six to eight carbon atoms and then abruptly disappeared. This cutoff for alcohol inhibition of NMDA receptors is consistent with an interaction of the alcohols with a hydrophobic pocket on the receptor protein. In addition, the similarity of the cutoffs for alcohol inhibition of NMDA receptors and alcohol intoxication suggests that the cutoff for NMDA receptor inhibition may contribute to the cutoff for alcohol intoxication, which is consistent with an important role of NMDA receptors in alcohol intoxication. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Peoples, R W AU - Weight, F F AD - Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-8205, USA. Y1 - 1995/03/28/ PY - 1995 DA - 1995 Mar 28 SP - 2825 EP - 2829 VL - 92 IS - 7 SN - 0027-8424, 0027-8424 KW - Alcohols KW - 0 KW - Receptors, N-Methyl-D-Aspartate KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - N-Methylaspartate KW - 6384-92-5 KW - Index Medicus KW - Fetus KW - Animals KW - Dose-Response Relationship, Drug KW - Cells, Cultured KW - gamma-Aminobutyric Acid -- pharmacology KW - Mice KW - Membrane Potentials -- drug effects KW - Structure-Activity Relationship KW - Hippocampus -- physiology KW - Alcoholic Intoxication -- physiopathology KW - N-Methylaspartate -- pharmacology KW - Neurons -- drug effects KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Neurons -- physiology KW - Alcohols -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77207723?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cutoff+in+potency+implicates+alcohol+inhibition+of+N-methyl-D-aspartate+receptors+in+alcohol+intoxication.&rft.au=Peoples%2C+R+W%3BWeight%2C+F+F&rft.aulast=Peoples&rft.aufirst=R&rft.date=1995-03-28&rft.volume=92&rft.issue=7&rft.spage=2825&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 - 1995-05-11 N1 - Date created - 1995-05-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Int Rev Neurobiol. 1992;33:289-348 [1592568] Trends Pharmacol Sci. 1990 Oct;11(10):423-8 [2147794] Neuropharmacology. 1991 May;30(5):441-6 [1830936] Am J Physiol. 1978 Aug;235(2):E97-102 [686171] Neuropharmacology. 1978 Jul;17(7):451-61 [567755] J Pharmacol Exp Ther. 1981 Sep;218(3):669-75 [7264950] Annu Rev Pharmacol Toxicol. 1984;24:43-64 [6329077] Alcohol Clin Exp Res. 1993 Oct;17(5):1055-65 [7506499] Mol Pharmacol. 1994 Jun;45(6):1235-41 [7517499] Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):8200-4 [8058780] Nature. 1993 Jan 7;361(6407):31-9 [8421494] Pharmacol Rev. 1972 Dec;24(4):583-655 [4565956] J Pharmacol Exp Ther. 1991 Oct;259(1):235-40 [1656020] Nature. 1985 Jul 25-31;316(6026):349-51 [4022125] Nature. 1986 Feb 27-Mar 5;319(6056):774-6 [2869411] Proc Natl Acad Sci U S A. 1986 Jul;83(14):5116-20 [3460084] J Pharmacol Exp Ther. 1987 Sep;242(3):963-9 [2443645] Proc Natl Acad Sci U S A. 1989 Feb;86(3):1084-7 [2783782] Science. 1989 Mar 31;243(4899):1721-4 [2467382] Eur J Pharmacol. 1990 Nov 27;191(2):225-9 [2086240] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intrathecal administration of single-chain immunotoxin, LMB-7 [B3(Fv)-PE38], produces cures of carcinomatous meningitis in a rat model. AN - 77206840; 7708720 AB - LMB-7 [B3(Fv)-PE38] is a single-chain immunotoxin constructed from the murine monoclonal antibody B3 and a truncated from of Pseudomonas exotoxin PE38. Antibody B3 recognizes a carbohydrate epitope found on solid tumors that frequently invade the intrathecal space and cause neoplastic meningitis. We tested the therapeutic value of intrathecally administered LMB-7 by using a model of human neoplastic meningitis in athymic rats. This model is representative of a clinical situation in that antibody B3 cross-reacts with a number of normal tissues that can be used to monitor potential systemic toxicity. Treatment was begun 3 days after A431 tumor implantation. Without treatment, the animals median survival was 10 days. Intrathecal administration of 10 micrograms of LMB-7 in 40 microliters on days 3, 5, and 7 produced 4 of 10 and 8 of 10 long-term survivors (> 170 days) in two experiments. Of the long-term survivors, 2 of 4 and 7 of 8 survivors had no microscopic evidence of tumor and were considered histologic cures. Lack of significant toxicity in the effective dose range and specificity make LMB-7 an excellent candidate for intrathecal treatment of neoplastic meningitis in humans. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Pastan, I H AU - Archer, G E AU - McLendon, R E AU - Friedman, H S AU - Fuchs, H E AU - Wang, Q C AU - Pai, L H AU - Herndon, J AU - Bigner, D D AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1995/03/28/ PY - 1995 DA - 1995 Mar 28 SP - 2765 EP - 2769 VL - 92 IS - 7 SN - 0027-8424, 0027-8424 KW - Antibodies, Monoclonal KW - 0 KW - Exotoxins KW - Immunotoxins KW - immunotoxin LMB-7 KW - Index Medicus KW - Rats KW - Animals KW - Tumor Cells, Cultured KW - Rats, Nude KW - Injections, Spinal KW - Humans KW - Transplantation, Heterologous KW - Mice KW - Time Factors KW - Immunotoxins -- toxicity KW - Carcinoma, Squamous Cell -- physiopathology KW - Immunotoxins -- therapeutic use KW - Meningitis -- etiology KW - Immunotoxins -- administration & dosage KW - Meningitis -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77206840?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Intrathecal+administration+of+single-chain+immunotoxin%2C+LMB-7+%5BB3%28Fv%29-PE38%5D%2C+produces+cures+of+carcinomatous+meningitis+in+a+rat+model.&rft.au=Pastan%2C+I+H%3BArcher%2C+G+E%3BMcLendon%2C+R+E%3BFriedman%2C+H+S%3BFuchs%2C+H+E%3BWang%2C+Q+C%3BPai%2C+L+H%3BHerndon%2C+J%3BBigner%2C+D+D&rft.aulast=Pastan&rft.aufirst=I&rft.date=1995-03-28&rft.volume=92&rft.issue=7&rft.spage=2765&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 - 1995-05-11 N1 - Date created - 1995-05-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer Res. 1991 Dec 1;51(23 Pt 1):6363-71 [1933899] Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8616-20 [1924323] Neurol Clin. 1991 Nov;9(4):843-56 [1722000] Cancer Res. 1992 Jun 15;52(12):3402-8 [1596900] J Neurosurg. 1992 Nov;77(5):778-82 [1403122] Biotechnology (N Y). 1992 Jun;10(6):682-5 [1369490] JAMA. 1993 Jan 6;269(1):78-81 [8416411] Br J Cancer. 1993 Jan;67(1):144-51 [8427774] J Immunol. 1993 Apr 1;150(7):3054-61 [8454873] Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7538-42 [8356052] Blood. 1994 Jan 15;83(2):426-34 [8286741] Cancer Res. 1994 Mar 15;54(6):1517-28 [8137258] Cancer Res. 1994 Apr 15;54(8):2146-50 [8174121] Cancer Res. 1994 Sep 1;54(17):4710-4 [8062269] Cancer Res. 1994 Sep 1;54(17):4719-25 [8062270] Cancer. 1988 Mar 1;61(5):857-68 [3338052] Ann N Y Acad Sci. 1987;507:199-210 [3327413] Cancer Res. 1988 Sep 1;48(17):4725-9 [3409213] Proc Natl Acad Sci U S A. 1988 Aug;85(16):5879-83 [3045807] Cancer Res. 1987 Mar 15;47(6):1627-33 [3545451] Cancer Res. 1987 Jun 15;47(12):3039-51 [3555767] Science. 1988 Oct 21;242(4877):423-6 [3140379] Cancer Res. 1988 Dec 15;48(24 Pt 1):7022-32 [3191477] Cancer Res. 1990 Feb 1;50(3 Suppl):814s-819s [2404582] Cancer Res. 1990 Mar 15;50(6):1954-9 [2306744] Cancer Res. 1990 May 15;50(10):2936-42 [2334894] Proc Natl Acad Sci U S A. 1990 Jun;87(11):4207-11 [1693434] Cancer Res. 1991 Jul 15;51(14):3781-7 [1648444] J Neurosurg. 1992 Jan;76(1):1-12 [1727147] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hepatic expression of mature transforming growth factor beta 1 in transgenic mice results in multiple tissue lesions. AN - 77205771; 7708687 AB - Aberrant expression of transforming growth factor beta 1 (TGF-beta 1) has been implicated in a number of disease processes, particularly those involving fibrotic and inflammatory lesions. To determine the in vivo effects of overexpression of TGF-beta 1 on the function and structure of hepatic as well as extrahepatic tissues, transgenic mice were generated containing a fusion gene (Alb/TGF-beta 1) consisting of modified porcine TGF-beta 1 cDNA under the control of the regulatory elements of the mouse albumin gene. Five transgenic lines were developed, all of which expressed the Alb/TGF-beta 1 transgene selectively in hepatocytes. The transgenic line 25 expressing the highest level of the transgene in the liver also had high (> 10-fold over control) plasma levels of TGF-beta 1. Hepatic fibrosis and apoptotic death of hepatocytes developed in all the transgenic lines but was more pronounced in line 25. The fibrotic process was characterized by deposition of collagen around individual hepatocytes and within the space of Disse in a radiating linear pattern. Several extrahepatic lesions developed in line 25, including glomerulonephritis and renal failure, arteritis and myocarditis, as well as atrophic changes in pancreas and testis. The results from this transgenic model strongly support the proposed etiological role for TGF-beta 1 in a variety of fibrotic and inflammatory disorders. The transgenic model may also provide an appropriate paradigm for testing therapeutic interventions aimed at neutralizing the detrimental effects of this important cytokine. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Sanderson, N AU - Factor, V AU - Nagy, P AU - Kopp, J AU - Kondaiah, P AU - Wakefield, L AU - Roberts, A B AU - Sporn, M B AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/03/28/ PY - 1995 DA - 1995 Mar 28 SP - 2572 EP - 2576 VL - 92 IS - 7 SN - 0027-8424, 0027-8424 KW - Codon KW - 0 KW - DNA, Complementary KW - Transforming Growth Factor beta KW - Serine KW - 452VLY9402 KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Swine KW - Animals KW - Kidney -- pathology KW - Apoptosis KW - Myocardium -- pathology KW - Gene Expression KW - Mice KW - Mice, Transgenic KW - Inflammation KW - Mutagenesis, Site-Directed KW - Mice, Inbred CBA KW - Glomerulonephritis -- pathology KW - Cells, Cultured KW - Mitosis KW - Restriction Mapping KW - Mice, Inbred C57BL KW - Crosses, Genetic KW - Male KW - Female KW - Cell Division KW - Transforming Growth Factor beta -- biosynthesis KW - Liver -- pathology KW - Liver -- cytology KW - Liver -- metabolism KW - Liver Cirrhosis, Experimental -- metabolism KW - Transforming Growth Factor beta -- blood KW - Transforming Growth Factor beta -- genetics KW - Liver Cirrhosis, Experimental -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77205771?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hepatic+expression+of+mature+transforming+growth+factor+beta+1+in+transgenic+mice+results+in+multiple+tissue+lesions.&rft.au=Sanderson%2C+N%3BFactor%2C+V%3BNagy%2C+P%3BKopp%2C+J%3BKondaiah%2C+P%3BWakefield%2C+L%3BRoberts%2C+A+B%3BSporn%2C+M+B%3BThorgeirsson%2C+S+S&rft.aulast=Sanderson&rft.aufirst=N&rft.date=1995-03-28&rft.volume=92&rft.issue=7&rft.spage=2572&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 - 1995-05-11 N1 - Date created - 1995-05-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408-12 [4504350] N Engl J Med. 1994 Nov 10;331(19):1286-92 [7935686] J Biol Chem. 1983 Jun 10;258(11):7155-60 [6602130] Cell. 1985 May;41(1):211-9 [2859927] Acta Med Scand Suppl. 1985;703:111-26 [3911738] Genes Dev. 1987 May;1(3):268-76 [3678824] J Cell Biol. 1989 Feb;108(2):653-60 [2465297] J Cell Biol. 1989 Jun;108(6):2477-82 [2500447] J Biol Chem. 1989 Aug 15;264(23):13660-4 [2474534] Eur J Biochem. 1990 Feb 14;187(3):467-73 [2406131] Radiat Res. 1990 Apr;122(1):77-85 [2181527] J Cell Biol. 1990 Apr;110(4):1361-7 [2139036] J Clin Invest. 1990 Jun;85(6):1833-43 [1693377] J Clin Invest. 1990 Aug;86(2):453-62 [2200803] Cell. 1990 Oct 19;63(2):245-7 [2208284] Annu Rev Cell Biol. 1990;6:597-641 [2177343] N Engl J Med. 1991 Apr 4;324(14):933-40 [1900574] Cell. 1992 Feb 21;68(4):775-85 [1310899] Mol Carcinog. 1992;5(1):25-31 [1543539] EMBO J. 1992 Apr;11(4):1599-605 [1314170] Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5408-12 [1608949] Growth Factors. 1993;8(1):1-9 [8448037] Int Rev Exp Pathol. 1993;34 Pt B:43-67 [8458717] Cancer Res. 1993 Apr 15;53(8):1719-23 [8467484] Eur J Biochem. 1980 Nov;112(2):243-9 [6161811] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ligand-mediated changes in the tryptophan synthase indole tunnel probed by nile red fluorescence with wild type, mutant, and chemically modified enzymes. AN - 77180920; 7890774 AB - The bacterial tryptophan synthase alpha 2 beta 2 complex contains an unusual structural feature: an intramolecular tunnel that channels indole from the active site of the alpha subunit to the active site of the beta subunit 25 A away. Here we investigate the role of the tunnel in communication between the alpha and beta subunits using the polarity-sensitive fluorescent probe, Nile Red. Interaction of Nile Red in the nonpolar tunnel near beta subunit residues Cys-170 and Phe-280 is supported by studies with enzymes altered at these positions. Restricting the tunnel by enlarging Cys-170 by chemical modification or mutagenesis decreases the fluorescence of Nile Red by 30-70%. Removal of a partial restriction in the tunnel by replacing Phe-280 by Cys or Ser increases the fluorescence of Nile Red more than 2-fold. A binding site for Nile Red in this region near the pyridoxal phosphate coenzyme of the beta subunit is further supported by iodide quenching and fluorescence energy transfer experiments and by molecular modeling based on the three-dimensional structure of the alpha 2 beta 2 complex. Finally, studies using Nile Red as a sensitive probe of conformational changes in the tunnel reveal that allosteric ligands (alpha subunit) or active site ligands (beta subunit) decrease the fluorescence of Nile Red. We speculate that allosteric and active site ligands induce a tunnel restriction near Phe-280 that serves as a gate to control passage of indole through the tunnel. JF - The Journal of biological chemistry AU - Ruvinov, S B AU - Yang, X J AU - Parris, K D AU - Banik, U AU - Ahmed, S A AU - Miles, E W AU - Sackett, D L AD - Laboratory of Biochemical Pharmacology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1995/03/17/ PY - 1995 DA - 1995 Mar 17 SP - 6357 EP - 6369 VL - 270 IS - 11 SN - 0021-9258, 0021-9258 KW - Codon KW - 0 KW - Fluorescent Dyes KW - Indoles KW - Iodides KW - Ligands KW - Macromolecular Substances KW - Oligodeoxyribonucleotides KW - Oxazines KW - Recombinant Proteins KW - Serine KW - 452VLY9402 KW - Phenylalanine KW - 47E5O17Y3R KW - Pyridoxal Phosphate KW - 5V5IOJ8338 KW - Tryptophan KW - 8DUH1N11BX KW - Tryptophan Synthase KW - EC 4.2.1.20 KW - Cysteine KW - K848JZ4886 KW - nile red KW - P476F1L81G KW - Index Medicus KW - Spectrometry, Fluorescence KW - Computer Graphics KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- metabolism KW - Escherichia coli KW - Molecular Sequence Data KW - Point Mutation KW - Recombinant Proteins -- chemistry KW - Pyridoxal Phosphate -- metabolism KW - Computer Simulation KW - Models, Molecular KW - Amino Acid Sequence KW - Cloning, Molecular KW - Binding Sites KW - Base Sequence KW - Kinetics KW - Tryptophan Synthase -- metabolism KW - Tryptophan Synthase -- chemistry KW - Salmonella typhimurium -- enzymology KW - Protein Conformation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77180920?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Ligand-mediated+changes+in+the+tryptophan+synthase+indole+tunnel+probed+by+nile+red+fluorescence+with+wild+type%2C+mutant%2C+and+chemically+modified+enzymes.&rft.au=Ruvinov%2C+S+B%3BYang%2C+X+J%3BParris%2C+K+D%3BBanik%2C+U%3BAhmed%2C+S+A%3BMiles%2C+E+W%3BSackett%2C+D+L&rft.aulast=Ruvinov&rft.aufirst=S&rft.date=1995-03-17&rft.volume=270&rft.issue=11&rft.spage=6357&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 - 1995-04-18 N1 - Date created - 1995-04-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Involvement of the p53 tumor suppressor in repair of u.v.-type DNA damage. AN - 77198740; 7700629 AB - The tumor suppressor p53 plays a central role in the cellular responses to genotoxic stress. Besides its well known role in activation of the G1 checkpoint after exposure to agents like ionizing radiation and its role in apoptosis, the possibility exists that p53 may have additional roles, such as in DNA repair. For example, p53, is known to bind to single strand DNA such as would occur during repair events, and the proteins encoded by two p53-regulated genes have previously been found to bind to at least one protein involved in DNA damage processing including nucleotide excision repair (NER). NER is an important and versatile DNA repair mechanism, which is the major pathway for repair of u.v.-type lesions and damage by a variety of important carcinogens and mutagens. If components of the p53 pathway are involved in NER, then disruption of p53 function by mutations or expression of certain viral proteins could have important implications in carcinogenesis and cancer treatment. In the present study we show that disruption of normal p53 function in human colon carcinoma RKO cells with either the human papillomavirus E6 oncoprotein or a dominant-negative mutant p53 transgene results in reduced repair of u.v.-induced DNA damage. The E6 and mutant p53-containing cell lines demonstrated reduced repair of u.v.-induced DNA lesions in host cell reactivation experiments with reporter plasmids, and reduced repair in in vitro DNA repair assays. With this in vitro assay, extracts from the E6- and mutant p53-containing lines also showed loss of induced repair following cellular u.v.-irradiation. The reduced DNA repair activity of the transfected cell lines also correlated with reduced clonogenic survival following u.v.-irradiation. These results indicate that p53 and/or p53-regulated gene products function in the NER pathway and that this process is inducible by DNA damage. JF - Oncogene AU - Smith, M L AU - Chen, I T AU - Zhan, Q AU - O'Connor, P M AU - Fornace, A J AD - Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1995/03/16/ PY - 1995 DA - 1995 Mar 16 SP - 1053 EP - 1059 VL - 10 IS - 6 SN - 0950-9232, 0950-9232 KW - p53 KW - DNA Probes KW - 0 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Base Sequence KW - Tumor Cells, Cultured KW - DNA Damage KW - Humans KW - Molecular Sequence Data KW - Ultraviolet Rays KW - DNA Repair KW - Genes, p53 KW - DNA -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77198740?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Involvement+of+the+p53+tumor+suppressor+in+repair+of+u.v.-type+DNA+damage.&rft.au=Smith%2C+M+L%3BChen%2C+I+T%3BZhan%2C+Q%3BO%27Connor%2C+P+M%3BFornace%2C+A+J&rft.aulast=Smith&rft.aufirst=M&rft.date=1995-03-16&rft.volume=10&rft.issue=6&rft.spage=1053&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-03 N1 - Date created - 1995-05-03 N1 - Date revised - 2017-01-13 N1 - Gene symbol - p53 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - AFT1: a mediator of iron regulated transcriptional control in Saccharomyces cerevisiae. AN - 77223196; 7720713 AB - Using a scheme for selecting mutants of Saccharomyces cerevisiae with abnormalities of iron metabolism, we have identified a gene, AFT1, that mediates the control of iron uptake. AFT1 encodes a 78 kDa protein with a highly basic amino terminal domain and a glutamine-rich C-terminal domain, reminiscent of transcriptional activators. The protein also contains an amino terminal and a C-terminal region with 10% His residues. A dominant mutant allele of this gene, termed AFT1-1up, results in high levels of ferric reductase and ferrous iron uptake that are not repressed by exogenous iron. The increased iron uptake is associated with enhanced susceptibility to iron toxicity. These effects may be explained by the failure of iron to repress transcription of FRE1, FRE2 and FET3. FRE1 and FRE2 encode plasma membrane ferric reductases, obligatory for ferric iron assimilation, and FET3 encodes a copper-dependent membrane-associated oxidase required for ferrous iron uptake. Conversely, a strain with interruption of the AFT1 gene manifests low ferric reductase and ferrous iron uptake and is susceptible to iron deprivation, because of deficient expression of FRE1 and negligible expression of FRE2 and FET3. Thus, AFT1 functions to activate transcription of target genes in response to iron deprivation and thereby plays a central role in iron homeostasis. JF - The EMBO journal AU - Yamaguchi-Iwai, Y AU - Dancis, A AU - Klausner, R D AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. Y1 - 1995/03/15/ PY - 1995 DA - 1995 Mar 15 SP - 1231 EP - 1239 VL - 14 IS - 6 SN - 0261-4189, 0261-4189 KW - AFT1 KW - FET3 KW - FRE1 KW - FRE2 KW - AFT1 protein, S cerevisiae KW - 0 KW - Ferrous Compounds KW - Fungal Proteins KW - RNA, Fungal KW - RNA, Messenger KW - Saccharomyces cerevisiae Proteins KW - Transcription Factors KW - Oxidoreductases KW - EC 1.- KW - Ceruloplasmin KW - EC 1.16.3.1 KW - FET3 protein, S cerevisiae KW - FMN Reductase KW - EC 1.5.1.38 KW - NADH, NADPH Oxidoreductases KW - EC 1.6.- KW - ferric citrate iron reductase KW - EC 1.6.99.- KW - Index Medicus KW - NADH, NADPH Oxidoreductases -- genetics KW - RNA, Fungal -- analysis KW - RNA, Messenger -- analysis KW - Biological Transport KW - Amino Acid Sequence KW - Homeostasis KW - Sequence Analysis, DNA KW - Transcriptional Activation KW - Cloning, Molecular KW - Genes, Fungal -- genetics KW - Base Sequence KW - Oxidoreductases -- metabolism KW - Mutation -- physiology KW - Restriction Mapping KW - Molecular Sequence Data KW - NADH, NADPH Oxidoreductases -- metabolism KW - Gene Expression Regulation, Fungal KW - Ferrous Compounds -- metabolism KW - Transcription, Genetic -- drug effects KW - Transcription Factors -- metabolism KW - Fungal Proteins -- genetics KW - Transcription Factors -- genetics KW - Saccharomyces cerevisiae -- genetics KW - Fungal Proteins -- metabolism KW - Saccharomyces cerevisiae -- metabolism KW - Ferrous Compounds -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77223196?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+EMBO+journal&rft.atitle=AFT1%3A+a+mediator+of+iron+regulated+transcriptional+control+in+Saccharomyces+cerevisiae.&rft.au=Yamaguchi-Iwai%2C+Y%3BDancis%2C+A%3BKlausner%2C+R+D&rft.aulast=Yamaguchi-Iwai&rft.aufirst=Y&rft.date=1995-03-15&rft.volume=14&rft.issue=6&rft.spage=1231&rft.isbn=&rft.btitle=&rft.title=The+EMBO+journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-22 N1 - Date created - 1995-05-22 N1 - Date revised - 2017-01-13 N1 - Gene symbol - AFT1; FET3; FRE1; FRE2 N1 - Genetic sequence - Z48004; GENBANK N1 - SuppNotes - Cited By: Yeast. 1991 Jan;7(1):1-14 [2021081] Methods Enzymol. 1991;194:398-405 [1706459] Science. 1991 Jun 28;252(5014):1796-7 [1648261] Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6112-6 [2068090] J Biol Chem. 1991 Oct 5;266(28):19053-5 [1918023] Biol Trace Elem Res. 1991 Aug;30(2):125-44 [1723885] Proc Natl Acad Sci U S A. 1992 May 1;89(9):3869-73 [1570306] Biochim Biophys Acta. 1992 Jun 10;1135(2):141-6 [1616934] J Biol Chem. 1992 Oct 15;267(29):20774-81 [1400393] Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11730-4 [1334546] Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11735-9 [1281544] Genetics. 1992 Nov;132(3):665-73 [1468625] Cell. 1993 Jan 15;72(1):19-28 [8380757] Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):903-7 [8430103] Trends Biochem Sci. 1993 Feb;18(2):43-7 [8488557] Mol Cell Biol. 1993 Jul;13(7):4342-50 [8321236] Mol Cell Biol. 1993 Nov;13(11):7091-100 [8413298] EMBO J. 1993 Dec 15;12(13):5051-6 [8262047] Cell. 1994 Jan 28;76(2):393-402 [8293472] Cell. 1994 Jan 28;76(2):403-10 [8293473] Mol Cell Biol. 1994 May;14(5):3065-73 [8164662] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7321-5 [8041788] J Biol Chem. 1994 Oct 14;269(41):25660-7 [7929270] Methods Enzymol. 1983;101:181-91 [6310321] Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387-95 [6546423] Mol Gen Genet. 1985;200(1):110-3 [2993806] Biochemistry. 1987 Aug 25;26(17):5471-7 [2823881] Microbiol Rev. 1987 Dec;51(4):509-18 [2963952] Gene. 1987;60(2-3):237-43 [3327750] J Gen Microbiol. 1987 Nov;133(11):3229-36 [3328775] Cell. 1988 Sep 9;54(6):841-53 [3044612] Nature. 1989 Jun 8;339(6224):446-51 [2725678] Science. 1989 Jul 28;245(4916):371-8 [2667136] Mol Cell Biol. 1990 May;10(5):2294-301 [2183029] Cell. 1991 May 31;65(5):717-9 [2040012] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In situ cyclopentenyl cytosine infusion for the treatment of experimental brain tumors. AN - 77169423; 7882327 AB - Cyclopentenylcytosine (CPEC; NSC 375575) is a pyrimidine nucleoside analogue that has potent antitumor effects when tested in vitro and also when tested in experimental tumors outside the central nervous system. CPEC exerts its antiproliferative effect through inhibition of CTP synthetase and consequent depletion of CTP and dCTP pools required for cell replication. Due to its poor penetration of the bloodbrain barrier, CPEC has failed to demonstrate therapeutic efficacy in experimental brain tumors after systemic administration. We therefore examined the in vivo activation, distribution, and antitumor effect of CPEC after long-term regional infusion of the drug directly into experimental brain tumors in rats. HPLC analysis of CPEC incubated with homogenized human brain and brain tumor tissue showed minimal degradation of the drug over 24 h. Analysis of rat cerebral 9L gliosarcoma infused with tritium-labeled CPEC demonstrated intratumoral accumulation of the active metabolite CPEC-triphosphate and concomitant depletion of CTP to a much greater extent in tumor tissue than in the adjacent brain. Tumor tissue UTP also decreased, but no significant effects on other ribonucleoside triphosphates were detected. Only trace amounts (< 1%) of CPEC and its metabolites reached peripheral sites, including the liver and kidneys, after intratumoral infusion. Rats treated with continuous intratumoral infusion of CPEC for 4 weeks using s.c. implanted osmotic pumps survived significantly longer than control rats receiving intratumoral saline or i.p. CPEC (P < 0.0001). Long-term intratumoral infusion of CPEC was not associated with any detectable toxicity. Our results support the feasibility of using intratumoral administration of CPEC as a regional therapy for malignant brain tumors. JF - Cancer research AU - Viola, J J AU - Agbaria, R AU - Walbridge, S AU - Oshiro, E M AU - Johns, D G AU - Kelley, J A AU - Oldfield, E H AU - Ram, Z AD - Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland 20892-4255. Y1 - 1995/03/15/ PY - 1995 DA - 1995 Mar 15 SP - 1306 EP - 1309 VL - 55 IS - 6 SN - 0008-5472, 0008-5472 KW - Antineoplastic Agents KW - 0 KW - Cytidine KW - 5CSZ8459RP KW - Cytidine Triphosphate KW - 65-47-4 KW - cyclopentenyl cytosine KW - 69MO0NDN8K KW - Index Medicus KW - Rats KW - Drug Stability KW - Animals KW - Rats, Inbred F344 KW - Cytidine Triphosphate -- metabolism KW - Biotransformation KW - Tissue Distribution KW - Gliosarcoma -- drug therapy KW - Brain Neoplasms -- drug therapy KW - Brain Neoplasms -- metabolism KW - Cytidine -- administration & dosage KW - Gliosarcoma -- metabolism KW - Cytidine -- pharmacokinetics KW - Antineoplastic Agents -- therapeutic use KW - Cytidine -- analogs & derivatives KW - Cytidine -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77169423?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=In+situ+cyclopentenyl+cytosine+infusion+for+the+treatment+of+experimental+brain+tumors.&rft.au=Viola%2C+J+J%3BAgbaria%2C+R%3BWalbridge%2C+S%3BOshiro%2C+E+M%3BJohns%2C+D+G%3BKelley%2C+J+A%3BOldfield%2C+E+H%3BRam%2C+Z&rft.aulast=Viola&rft.aufirst=J&rft.date=1995-03-15&rft.volume=55&rft.issue=6&rft.spage=1306&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 - 1995-04-12 N1 - Date created - 1995-04-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of ETS1 in IL-2 gene expression. AN - 77167530; 7876544 AB - The ETS1 gene encodes a sequence-specific transcription factor binding to purine-rich DNA sequences (-GGAA-) present in the transcriptional regulatory regions of many cellular and viral promoters/enhancers, including many lymphokine genes. The ETS1 gene is expressed at high levels in resting T cells and at very low levels after T cell activation, suggesting it may suppress the expression of genes induced during T cell activation. To find out if ETS1 regulates expression of the IL-2 gene, we have ectopically expressed antisense (AS) ETS1 in Jurkat T cells to block the formation of ETS1 proteins. AS ETS1 transfectants produce higher levels of IL-2 compared with sense ETS1 transfectants. Expression of ETS1 DNA binding domain in Jurkat T cells also decreased the production of IL-2. In AS ETS1 transfectants, IL-2 formation was completely inhibited by cyclosporin A and FK590. The IL-2 promoter linked to a chloramphenicol acetyl transferase reporter gene has high activity in AS ETS1 transfectants, indicating that increased IL-2 production seems to be a result of transcriptional induction. Taken together, these results suggest the possibility that ETS1 may act as a negative regulator of IL-2 gene transcription and provide a rational approach toward engineering the endogenous expression of IL-2 in T cells. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Romano-Spica, V AU - Georgiou, P AU - Suzuki, H AU - Papas, T S AU - Bhat, N K AD - Laboratory of Molecular Oncology, National Cancer Institute, Frederick, MD 21702. Y1 - 1995/03/15/ PY - 1995 DA - 1995 Mar 15 SP - 2724 EP - 2732 VL - 154 IS - 6 SN - 0022-1767, 0022-1767 KW - ETS1 KW - ETS1 protein, human KW - 0 KW - Interleukin-2 KW - Proto-Oncogene Protein c-ets-1 KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-ets KW - Transcription Factors KW - Ionomycin KW - 56092-81-0 KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Abridged Index Medicus KW - Index Medicus KW - Chloramphenicol O-Acetyltransferase -- genetics KW - Humans KW - Transfection -- genetics KW - Transcription, Genetic -- genetics KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Promoter Regions, Genetic -- genetics KW - Ionomycin -- pharmacology KW - Cell Line KW - Proto-Oncogene Proteins -- biosynthesis KW - Interleukin-2 -- biosynthesis KW - Interleukin-2 -- genetics KW - Proto-Oncogene Proteins -- genetics KW - Proto-Oncogene Proteins -- physiology KW - Gene Expression Regulation -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77167530?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Role+of+ETS1+in+IL-2+gene+expression.&rft.au=Romano-Spica%2C+V%3BGeorgiou%2C+P%3BSuzuki%2C+H%3BPapas%2C+T+S%3BBhat%2C+N+K&rft.aulast=Romano-Spica&rft.aufirst=V&rft.date=1995-03-15&rft.volume=154&rft.issue=6&rft.spage=2724&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 - 1995-04-06 N1 - Date created - 1995-04-06 N1 - Date revised - 2017-01-13 N1 - Gene symbol - ETS1 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Linkage and expression of the argininosuccinate lyase/delta-crystallin genes of the duck: insertion of a CR1 element in the intergenic spacer. AN - 77180853; 7893758 AB - delta-Crystallin is the major component of the lenses of most birds and reptiles. In the chicken there are two closely linked, tandemly oriented genes. Almost all of the delta-crystallin of the embryonic chicken lens is produced by the 5' delta 1 gene. This high lens activity has been attributed to an enhancer in intron 3. The 3' delta 2 gene encodes the enzyme argininosuccinate lyase (ASL) which is expressed at a low level in the chicken lens. Both chicken delta-crystallin genes are also expressed slightly in heart and brain, with ASL/delta 2 predominating over delta 1. In the duck (Anas platyrhynchos), ASL/delta 2-crystallin serves as both enzyme and crystallin, resulting in very high levels of ASL activity in the lens. Here we show by genomic cloning that the ASL/delta- crystallin locus is highly conserved between duck and chicken, with the two duck delta-crystallin genes closely linked in tandem. The 4.6 kbp intergenic spacer in the duck locus is 79% identical to the 4 kbp chicken spacer, except for the existence of a 615 bp CR1 element, highly reiterated in the duck genome, 1.8 kbp upstream of the duck ASL/delta 2 gene. The CR1 sequence is a truncated LINE element containing the 3' half of an open reading frame for a retroviral pol-like reverse transcriptase. Sequence analysis revealed (i) that intron 3 of the duck ASL/delta 2 gene is very similar (80%) to intron 3 of the chicken delta 1 and ASL/delta 2 genes, especially in the region of the chicken delta 1 enhancer core (93% identical) and (ii) that the 3' boundary of exon 2 of the duck ASL/delta 2 gene has undergone a recent splice-site slippage event, resulting in a two amino acid insertion in the encoded polypeptide. Finally, reverse transcription/polymerase chain reaction experiments established that both delta-crystallin genes are equally expressed to a high level in the embryonic duck lens; by contrast, both delta-crystallin genes produce a low amount of mRNA in the heart and brain of the embryonic duck, with the enzymatically active ASL/delta 2 being preferentially expressed. JF - Biochimica et biophysica acta AU - Li, X AU - Wistow, G J AU - Piatigorsky, J AD - Section on Molecular Genetics, National Eye Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1995/03/14/ PY - 1995 DA - 1995 Mar 14 SP - 25 EP - 34 VL - 1261 IS - 1 SN - 0006-3002, 0006-3002 KW - pol KW - Crystallins KW - 0 KW - Eye Proteins KW - Argininosuccinate Lyase KW - EC 4.3.2.1 KW - Index Medicus KW - Genetic Linkage KW - Animals KW - Base Sequence KW - Sequence Alignment KW - Sequence Homology, Nucleic Acid KW - Open Reading Frames KW - Molecular Sequence Data KW - Gene Expression Regulation KW - Species Specificity KW - Mutagenesis, Insertional KW - Introns -- genetics KW - Genes, pol KW - Chickens -- genetics KW - Argininosuccinate Lyase -- genetics KW - Eye Proteins -- genetics KW - Ducks -- genetics KW - Argininosuccinate Lyase -- biosynthesis KW - Eye Proteins -- biosynthesis KW - Crystallins -- genetics KW - Repetitive Sequences, Nucleic Acid KW - Crystallins -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77180853?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochimica+et+biophysica+acta&rft.atitle=Linkage+and+expression+of+the+argininosuccinate+lyase%2Fdelta-crystallin+genes+of+the+duck%3A+insertion+of+a+CR1+element+in+the+intergenic+spacer.&rft.au=Li%2C+X%3BWistow%2C+G+J%3BPiatigorsky%2C+J&rft.aulast=Li&rft.aufirst=X&rft.date=1995-03-14&rft.volume=1261&rft.issue=1&rft.spage=25&rft.isbn=&rft.btitle=&rft.title=Biochimica+et+biophysica+acta&rft.issn=00063002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-25 N1 - Date created - 1995-04-25 N1 - Date revised - 2017-01-13 N1 - Gene symbol - pol N1 - Genetic sequence - U05895; GENBANK; U06050 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - CO binding kinetics of human cytochrome P450 3A4. Specific interaction of substrates with kinetically distinguishable conformers. AN - 77180775; 7890608 AB - The kinetics of CO binding to human cytochrome P450 3A4 was examined by the flash photolysis technique, employing the membrane-bound P450 expressed in baculovirus-infected SF9 insect cells. Triexponential kinetics was observed, indicating that P450 3A4 is composed of multiple, kinetically distinguishable conformers. To define the substrate specificity of individual P450 3A4 conformers we evaluated the effect of a series of substrates of varying sizes and structures on the CO binding kinetics. The rate of CO binding to the total mixture of P450 3A4 conformers was increased in the presence of nifedipine and erythromycin, decreased by quinidine, testosterone, and warfarin, and unaffected by cimetidine and 17 alpha-ethynylestradiol. A recently developed kinetic difference method (Koley, A. P., Robinson, R. C., Markowitz, A., and Friedman, F. K. (1994) Biochemistry 33, 2484-2489) was used to define the kinetic parameters of individual P450 3A4 conformers. The results showed that different conformers have distinct substrate specificities. The substrates had markedly variable effects on the CO binding kinetics of their target P450 3A4 conformers and thus differentially modulate their conformations. These results demonstrate that the interaction of a particular substrate with a specific P450 3A4 conformer can be assessed in the presence of multiple conformers. JF - The Journal of biological chemistry AU - Koley, A P AU - Buters, J T AU - Robinson, R C AU - Markowitz, A AU - Friedman, F K AD - Laboratory of Molecular Carcinogenesis, NCI National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1995/03/10/ PY - 1995 DA - 1995 Mar 10 SP - 5014 EP - 5018 VL - 270 IS - 10 SN - 0021-9258, 0021-9258 KW - Recombinant Proteins KW - 0 KW - Testosterone KW - 3XMK78S47O KW - Ethinyl Estradiol KW - 423D2T571U KW - Warfarin KW - 5Q7ZVV76EI KW - Erythromycin KW - 63937KV33D KW - Carbon Monoxide KW - 7U1EE4V452 KW - Cimetidine KW - 80061L1WGD KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - CYP3A protein, human KW - EC 1.14.14.1 KW - Cytochrome P-450 CYP3A KW - Nifedipine KW - I9ZF7L6G2L KW - Quinidine KW - ITX08688JL KW - Index Medicus KW - Animals KW - Spodoptera KW - Recombinant Proteins -- biosynthesis KW - Humans KW - Erythromycin -- pharmacology KW - Protein Binding KW - Warfarin -- pharmacology KW - Ethinyl Estradiol -- pharmacology KW - Nifedipine -- pharmacology KW - Testosterone -- pharmacology KW - Transfection KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Quinidine -- pharmacology KW - Cimetidine -- pharmacology KW - Substrate Specificity KW - Time Factors KW - Mixed Function Oxygenases -- metabolism KW - Mixed Function Oxygenases -- biosynthesis KW - Cytochrome P-450 Enzyme System -- metabolism KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Carbon Monoxide -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77180775?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=CO+binding+kinetics+of+human+cytochrome+P450+3A4.+Specific+interaction+of+substrates+with+kinetically+distinguishable+conformers.&rft.au=Koley%2C+A+P%3BButers%2C+J+T%3BRobinson%2C+R+C%3BMarkowitz%2C+A%3BFriedman%2C+F+K&rft.aulast=Koley&rft.aufirst=A&rft.date=1995-03-10&rft.volume=270&rft.issue=10&rft.spage=5014&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 - 1995-04-14 N1 - Date created - 1995-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carboxyl-terminal domain truncation alters apolipoprotein A-I in vivo catabolism. AN - 77180179; 7890663 AB - Apolipoprotein A-I (apoA-I), the major protein of high density lipoproteins, facilitates reverse cholesterol transport from peripheral tissue to liver. To determine the structural motifs important for modulating the in vivo catabolism of human apoA-I (h-apoA-I), we generated carboxyl-terminal truncation mutants at residues 201 (apoA-I201), 217 (apoA-I217), and 226 (apoA-I226) by site-directed mutagenesis. ApoA-I was expressed in Escherichia coli as a fusion protein with the maltose binding protein, which was removed by factor Xa cleavage. The in vivo kinetic analysis of the radioiodinated apoA-I in normolipemic rabbits revealed a markedly increased rate of catabolism for the truncated forms of apoA-I. The fractional catabolic rates (FCR) of 9.10 +/- 1.28/day (+/- S.D.) for apoA-I201, 6.34 +/- 0.81/day for apoA-I217, and 4.42 +/- 0.51/day for apoA-I226 were much faster than the FCR of recombinant intact apoA-I (r-apoA-I, 0.93 +/- 0.07/day) and h-apoA-I (0.91 +/- 0.34/day). All the truncated forms of apoA-I were associated with very high density lipoproteins, whereas the intact recombinant apoA-I (r-apoA-I) and h-apoA-I associated with HDL2 and HDL3. Gel filtration chromatography revealed that in contrast to r-apoA-I, the mutant apoA-I201 associated with a phospholipid-rich rabbit apoA-I containing particle. Analysis by agarose gel electrophoresis demonstrated that the same mutant migrated in the pre-beta position, but not within the alpha position as did r-apoA-I. These results indicate that the carboxyl-terminal region (residue 227-243) of apoA-I is critical in modulating the association of apoA-I with lipoproteins and in vivo metabolism of apoA-I. JF - The Journal of biological chemistry AU - Schmidt, H H AU - Remaley, A T AU - Stonik, J A AU - Ronan, R AU - Wellmann, A AU - Thomas, F AU - Zech, L A AU - Brewer, H B AU - Hoeg, J M AD - Molecular Disease Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1995/03/10/ PY - 1995 DA - 1995 Mar 10 SP - 5469 EP - 5475 VL - 270 IS - 10 SN - 0021-9258, 0021-9258 KW - Apolipoprotein A-I KW - 0 KW - DNA Primers KW - Recombinant Proteins KW - Index Medicus KW - Centrifugation, Density Gradient KW - Animals KW - Protein Structure, Secondary KW - Electrophoresis, Polyacrylamide Gel KW - Humans KW - Liver -- metabolism KW - Rabbits KW - Isoelectric Focusing KW - Cloning, Molecular KW - Recombinant Proteins -- isolation & purification KW - Base Sequence KW - Chromatography, Gel KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Restriction Mapping KW - Molecular Sequence Data KW - Electrophoresis, Agar Gel KW - Escherichia coli KW - Recombinant Proteins -- chemistry KW - Apolipoprotein A-I -- metabolism KW - Apolipoprotein A-I -- isolation & purification KW - Sequence Deletion KW - Apolipoprotein A-I -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77180179?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Carboxyl-terminal+domain+truncation+alters+apolipoprotein+A-I+in+vivo+catabolism.&rft.au=Schmidt%2C+H+H%3BRemaley%2C+A+T%3BStonik%2C+J+A%3BRonan%2C+R%3BWellmann%2C+A%3BThomas%2C+F%3BZech%2C+L+A%3BBrewer%2C+H+B%3BHoeg%2C+J+M&rft.aulast=Schmidt&rft.aufirst=H&rft.date=1995-03-10&rft.volume=270&rft.issue=10&rft.spage=5469&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 - 1995-04-14 N1 - Date created - 1995-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transforming G protein-coupled receptors potently activate JNK (SAPK). Evidence for a divergence from the tyrosine kinase signaling pathway. AN - 77179335; 7890682 AB - The expression of human muscarinic acetylcholine receptors (mAChRs) in NIH 3T3 cells has been used as a model for studying proliferative signaling through G protein-coupled receptors. In this biological system, the m1 class of mAChRs can effectively transduce mitogenic signals (Stephens, E.V., Kalinec, G., Brann, M.R., and Gutkind, J.S. (1993) Oncogene 8, 19-26) and induce malignant transformation if persistently activated (Gutkind, J.S., Novotny, E.A., Brann, M.R., and Robbins, K.C. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 4703-4708). Moreover, available evidence suggests that the m1-signaling pathway converges at the level of p21ras with that emerging from tyrosine kinase receptors (Crespo, P., Xu, N., Simonds, W.F., and Gutkind, J.S. (1994) Nature 369, 418-420). To explore nuclear events involved in growth regulation by G protein-coupled receptors in this setting, we compared the effect of platelet-derived growth factor (PDGF) and the cholinergic agonist, carbachol, on the expression of mRNA for members of the jun and fos family of nuclear proto-oncogenes. We found that activation of m1 receptors by carbachol induces the expression of a distinct set of nuclear transcription factors. In particular, carbachol caused a much greater induction of c-jun mRNA and AP-1 activity. These responses did not correlate with protein kinase C stimulation nor with the activation of mitogen-activated protein (MAP) kinases. Recently, it has been shown that a novel family of kinases structurally related to MAP kinases, stress-activated protein kinases, or Jun kinases (JNKs), phosphorylate in vivo the amino-terminal transactivating domain of the c-Jun protein, thereby increasing its transcriptional activity. In view of our results, this observation prompted us to ask whether m1 and PDGF can differentially activate JNKs. Here, we show that m1 mAChRs can induce a remarkable increase in JNK activity, which was temporally distinct from that of MAP kinase and was entirely protein kinase C independent. In contrast, PDGF failed to activate JNK in these cells, although it stimulated MAP kinase to an extent even greater than that for carbachol. These findings demonstrate that G protein-coupled receptors can signal through pathways leading to the activation of JNK, thus diverging at this level with those signaling routes utilized by tyrosine kinase receptors. JF - The Journal of biological chemistry AU - Coso, O A AU - Chiariello, M AU - Kalinec, G AU - Kyriakis, J M AU - Woodgett, J AU - Gutkind, J S AD - Molecular Signaling Unit, NIDR, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1995/03/10/ PY - 1995 DA - 1995 Mar 10 SP - 5620 EP - 5624 VL - 270 IS - 10 SN - 0021-9258, 0021-9258 KW - c-fos KW - c-jun KW - egr-1 KW - fos KW - fos b KW - fra-1 KW - jun KW - jun B KW - jun D KW - Platelet-Derived Growth Factor KW - 0 KW - Receptors, Muscarinic KW - Transcription Factor AP-1 KW - Carbachol KW - 8Y164V895Y KW - Receptor Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Protein Kinase C KW - EC 2.7.11.13 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 - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Gene Expression -- drug effects KW - 3T3 Cells KW - Animals KW - Transcription Factor AP-1 -- biosynthesis KW - Enzyme Activation KW - Humans KW - Platelet-Derived Growth Factor -- pharmacology KW - Mice KW - Protein Kinase C -- metabolism KW - Protein Kinase C -- antagonists & inhibitors KW - Transfection KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Genes, fos KW - Carbachol -- pharmacology KW - Cell Division KW - Genes, jun KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Genes, Immediate-Early -- drug effects KW - Receptors, Muscarinic -- biosynthesis KW - Receptor Protein-Tyrosine Kinases -- metabolism KW - Signal Transduction KW - Receptor Protein-Tyrosine Kinases -- biosynthesis KW - Receptors, Muscarinic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77179335?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Transforming+G+protein-coupled+receptors+potently+activate+JNK+%28SAPK%29.+Evidence+for+a+divergence+from+the+tyrosine+kinase+signaling+pathway.&rft.au=Coso%2C+O+A%3BChiariello%2C+M%3BKalinec%2C+G%3BKyriakis%2C+J+M%3BWoodgett%2C+J%3BGutkind%2C+J+S&rft.aulast=Coso&rft.aufirst=O&rft.date=1995-03-10&rft.volume=270&rft.issue=10&rft.spage=5620&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 - 1995-04-14 N1 - Date created - 1995-04-14 N1 - Date revised - 2017-01-13 N1 - Gene symbol - c-fos; c-jun; egr-1; fos; fos b; fra-1; jun; jun B; jun D N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Control of I kappa B-alpha proteolysis by site-specific, signal-induced phosphorylation. AN - 77161424; 7878466 AB - I kappa B-alpha inhibits transcription factor NF-kappa B by retaining it in the cytoplasm. Various stimuli, typically those associated with stress or pathogens, rapidly inactivate I kappa B-alpha. This liberates NF-kappa B to translocate to the nucleus and initiate transcription of genes important for the defense of the organism. Activation of NF-kappa B correlates with phosphorylation of I kappa B-alpha and requires the proteolysis of this inhibitor. When either serine-32 or serine-36 of I kappa B-alpha was mutated, the protein did not undergo signal-induced phosphorylation or degradation, and NF-kappa B could not be activated. These results suggest that phosphorylation at one or both of these residues is critical for activation of NF-kappa B. JF - Science (New York, N.Y.) AU - Brown, K AU - Gerstberger, S AU - Carlson, L AU - Franzoso, G AU - Siebenlist, U AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1876. Y1 - 1995/03/10/ PY - 1995 DA - 1995 Mar 10 SP - 1485 EP - 1488 VL - 267 IS - 5203 SN - 0036-8075, 0036-8075 KW - DNA-Binding Proteins KW - 0 KW - I-kappa B Proteins KW - NF-kappa B KW - NFKBIA protein, human KW - Nfkbia protein, mouse KW - Tumor Necrosis Factor-alpha KW - NF-KappaB Inhibitor alpha KW - 139874-52-5 KW - Ionomycin KW - 56092-81-0 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Humans KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Amino Acid Sequence KW - Ionomycin -- pharmacology KW - Mice KW - Transcriptional Activation KW - Phosphorylation KW - Transfection KW - Molecular Sequence Data KW - Point Mutation KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Mutation KW - Cell Line KW - Signal Transduction KW - T-Lymphocytes KW - DNA-Binding Proteins -- chemistry KW - DNA-Binding Proteins -- genetics KW - NF-kappa B -- metabolism KW - NF-kappa B -- antagonists & inhibitors KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77161424?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+%28New+York%2C+N.Y.%29&rft.atitle=Control+of+I+kappa+B-alpha+proteolysis+by+site-specific%2C+signal-induced+phosphorylation.&rft.au=Brown%2C+K%3BGerstberger%2C+S%3BCarlson%2C+L%3BFranzoso%2C+G%3BSiebenlist%2C+U&rft.aulast=Brown&rft.aufirst=K&rft.date=1995-03-10&rft.volume=267&rft.issue=5203&rft.spage=1485&rft.isbn=&rft.btitle=&rft.title=Science+%28New+York%2C+N.Y.%29&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-06 N1 - Date created - 1995-04-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prospects for pharmacotherapy of schizophrenia. AN - 77320685; 7539875 JF - Lancet (London, England) AU - Pickar, D AD - Experimental Therapeutics Branch, National Institute of Mental Health, Bethesda, MD 20892, USA. Y1 - 1995/03/04/ PY - 1995 DA - 1995 Mar 04 SP - 557 EP - 562 VL - 345 IS - 8949 SN - 0140-6736, 0140-6736 KW - Antipsychotic Agents KW - 0 KW - Isoxazoles KW - Piperidines KW - Receptors, Dopamine KW - Receptors, Dopamine D2 KW - Receptors, Serotonin KW - Clozapine KW - J60AR2IKIC KW - Risperidone KW - L6UH7ZF8HC KW - Abridged Index Medicus KW - Index Medicus KW - Receptors, Serotonin -- drug effects KW - Receptors, Dopamine -- drug effects KW - Piperidines -- pharmacology KW - Piperidines -- therapeutic use KW - Clozapine -- therapeutic use KW - Humans KW - Clozapine -- pharmacology KW - Receptors, Dopamine D2 -- drug effects KW - Isoxazoles -- therapeutic use KW - Isoxazoles -- pharmacology KW - Basal Ganglia Diseases -- chemically induced KW - Antipsychotic Agents -- therapeutic use KW - Antipsychotic Agents -- pharmacology KW - Schizophrenia -- drug therapy KW - Antipsychotic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77320685?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lancet+%28London%2C+England%29&rft.atitle=Prospects+for+pharmacotherapy+of+schizophrenia.&rft.au=Pickar%2C+D&rft.aulast=Pickar&rft.aufirst=D&rft.date=1995-03-04&rft.volume=345&rft.issue=8949&rft.spage=557&rft.isbn=&rft.btitle=&rft.title=Lancet+%28London%2C+England%29&rft.issn=01406736&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-07 N1 - Date created - 1995-07-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Lancet. 1995 Aug 12;346(8972):450 [7623602] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of HIV-1 gag protein subcellular targeting by protein kinase C. AN - 77167657; 7876252 AB - The human immunodeficiency virus type 1 internal structural protein precursor, p55, and its corresponding matrix proteolytic fragment, p17, are phosphorylated at Ser111 by protein kinase C. COS-7 cells transfected with plasmids encoding either the wild-type or Ser111-->Ala mutated human immunodeficiency virus type 1 gag gene matrix domain proteins were treated with phorbol 12-myristate 13-acetate (PMA), and the phosphorylation of the expressed p17 proteins was examined by radioimmunoprecipitation, SDS-polyacrylamide gel electrophoresis, and autoradiography. PMA treatment of transfected cells resulted in a 4-5-fold increase in wild-type p17 (but not mutated p17) phosphorylation; however, mutated p17 exhibited a low basal level of phosphorylation that was not affected by PMA, suggesting that additional sites were phosphorylated. PMA treatment of cells expressing wild-type p17 produced a dramatic shift in the localization of p17 from the cytosol to the membrane fraction within 8-15 min, followed by a slow quantitative dissociation of p17 back into the cytosol by 90 min. The cytosol-to-membrane translocation was dependent on N-myristoylated p17 since cells expressing p17 with a Gly2-->Ala mutation did not localize to the membrane. PMA also failed to induce the translocation of fully N-myristoylated Ser111-->Ala p17, suggesting that p17 phosphorylation at Ser111 was responsible for membrane association. This conclusion was confirmed by the finding of phosphorylated wild-type p17 in the membrane fraction only after PMA treatment. These results suggest that a "myristoyl-protein switch" regulates the reversible membrane targeting of p17 by protein kinase C-mediated phosphorylation. This signal may provide a mechanism for the cellular regulation of virus development through modulation of gag protein-related developmental steps such as capsid targeting, assembly, encapsidation, budding, and maturation. JF - The Journal of biological chemistry AU - Yu, G AU - Shen, F S AU - Sturch, S AU - Aquino, A AU - Glazer, R I AU - Felsted, R L AD - Laboratory of Biological Chemistry, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255. Y1 - 1995/03/03/ PY - 1995 DA - 1995 Mar 03 SP - 4792 EP - 4796 VL - 270 IS - 9 SN - 0021-9258, 0021-9258 KW - Gene Products, gag KW - 0 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - AIDS/HIV KW - Virus Replication KW - Animals KW - Base Sequence KW - Phosphorylation KW - Enzyme Activation KW - Molecular Sequence Data KW - Biological Transport KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Subcellular Fractions -- metabolism KW - Cell Line KW - Protein Kinase C -- metabolism KW - HIV-1 -- metabolism KW - HIV-1 -- physiology KW - Gene Products, gag -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77167657?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Regulation+of+HIV-1+gag+protein+subcellular+targeting+by+protein+kinase+C.&rft.au=Yu%2C+G%3BShen%2C+F+S%3BSturch%2C+S%3BAquino%2C+A%3BGlazer%2C+R+I%3BFelsted%2C+R+L&rft.aulast=Yu&rft.aufirst=G&rft.date=1995-03-03&rft.volume=270&rft.issue=9&rft.spage=4792&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 - 1995-04-05 N1 - Date created - 1995-04-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Peer Review in Toxicologic Pathology AN - 869568654; 13645618 AB - Peer review of histopathology findings in safety assessment studies involving rodents and other animals is a relatively recent procedure in Toxicologic Pathology. It serves to ensure the integrity of the pathology evaluation in safety studies, encourages consistency of diagnostic criteria and use of common terminology, and provides a method of continuing education for participants. The use of a standardized system of pathology nomenclature and diagnostic criteria, such as the Society of Toxicologic Pathologist's Guides for Toxicologic Pathology, is of great value in the procedure. Pathology reviews may involve government-sponsored bioassay programs, in-house industrial corporations, or individual peer reviews suggested or required by government regulatory agencies. Pathology Working Groups can be an integral part of the review process. The extent of the peer review is primarily dependent on the study results; however, other variables such as confidence of the data, study size and duration, complexity, and purpose are also important considerations. Essential components of any peer review, however, include selection of tissues/lesions for review, by a reviewing pathologist, discrepancy resolution, data modification, and documentation of all aspects of the review process. Specific procedures for pathology peer review are discussed. Disagreements among pathologists discovered in peer reviews can be resolved by several methods and examples will be presented. The entire pathology peer review process should be a learning experience for all involved and can help ensure the integrity of animal toxicology studies used for important regulatory decisions involving the use of chemicals in our society. JF - Toxicologic Pathology AU - Ward, Jerrold M AU - Hardisty, Jerry F AU - Hailey, James R AU - Streett, CSpencer AD - National Cancer Institute, Frederick, Maryland 21702-1201 Y1 - 1995/03// PY - 1995 DA - Mar 1995 SP - 226 EP - 234 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU UK VL - 23 IS - 2 SN - 0192-6233, 0192-6233 KW - Toxicology Abstracts KW - Nomenclature KW - Learning KW - Data processing KW - Reviews KW - X 24350:Industrial Chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/869568654?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+Pathology&rft.atitle=Peer+Review+in+Toxicologic+Pathology&rft.au=Ward%2C+Jerrold+M%3BHardisty%2C+Jerry+F%3BHailey%2C+James+R%3BStreett%2C+CSpencer&rft.aulast=Ward&rft.aufirst=Jerrold&rft.date=1995-03-01&rft.volume=23&rft.issue=2&rft.spage=226&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1177%2F019262339502300218 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-10-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Nomenclature; Learning; Data processing; Reviews DO - http://dx.doi.org/10.1177/019262339502300218 ER - TY - JOUR T1 - Verbal working memory dysfunction in schizophrenia: use of a Brown-Peterson paradigm. AN - 85273994; pmid-7667440 AB - Recent studies of schizophrenia have implicated deficits in processes related to working memory, but the cognitive features of these deficits have been incompletely characterized. We used a modified Brown-Peterson paradigm to compare working memory in patients with schizophrenia and in normal control subjects. Distractor conditions differed in processing demand, increasing in complexity from no distractor to counting backwards (serial threes). We found significant effects of group, of distractor condition, and of a group x distractor condition interaction. The significant interaction was the result of a more rapid decline in the performance of schizophrenic patients with concurrent articulation. In addition, the schizophrenic group also made significantly more intrusion errors. The study suggests that schizophrenic patients exhibit dysfunction of the verbal working memory system due to a diminution in its overall processing resources. JF - Psychiatry Research AU - Fleming, K AU - Goldberg, T E AU - Gold, J M AU - Weinberger, D R AD - NIMH Neurosciences Center at Saint Elizabeths, Washington, DC 20032, USA. PY - 1995 SP - 155 EP - 161 VL - 56 IS - 2 SN - 0165-1781, 0165-1781 KW - Schizophrenia KW - Memory, Short-Term KW - Human KW - Adult KW - Schizophrenic Language KW - Middle Age KW - Serial Learning KW - Retention (Psychology) KW - Male KW - Female KW - Verbal Learning KW - Schizophrenic Psychology KW - Mental Recall KW - Attention UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85273994?accountid=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=Psychiatry+Research&rft.atitle=Verbal+working+memory+dysfunction+in+schizophrenia%3A+use+of+a+Brown-Peterson+paradigm.&rft.au=Fleming%2C+K%3BGoldberg%2C+T+E%3BGold%2C+J+M%3BWeinberger%2C+D+R&rft.aulast=Fleming&rft.aufirst=K&rft.date=1995-03-01&rft.volume=56&rft.issue=2&rft.spage=155&rft.isbn=&rft.btitle=&rft.title=Psychiatry+Research&rft.issn=01651781&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Expression of AMPA, kainate, and NMDA receptor subunits in cochlear and vestibular ganglia. AN - 85241983; pmid-7891171 AB - Glutamate is believed to be the principal afferent neurotransmitter in the peripheral auditory and vestibular systems. In this report, we present a comprehensive molecular analysis of ionotropic glutamate receptor gene expression in the cochlear and vestibular ganglia of the rat. Fourteen glutamate receptor subunits were studied: GluR1-4 (including flip and flop variants), GluR5-7, KA1&2, NR1, and NR2A-D. Reverse transcription of RNA followed by DNA amplification with the polymerase chain reaction was used for the initial analysis. Immunocytochemistry and in situ hybridization with subunit-specific oligonucleotides were subsequently used for cellular localization of receptor expression. AMPA (GluR2-4), kainate (GluR5&6 and KA1&2), and NMDA receptor (NR1 and NR2A-D) subunit expression was detected. Based on the relative amounts of mRNA detected by in situ hybridization, the predominant receptors expressed by cochlear and vestibular ganglion cells appear to be GluR2, GluR3, GluR4, GluR5, and NR1. At a moderate level were GluR6, NR2B, and NR2D. KA1, KA2, NR2A, and NR2C mRNAs were also expressed in ganglion cells, but at lower levels. Only the AMPA receptor subunit GluR1 and the kainate receptor subunit GluR7 were not found to be expressed in vestibulocochlear neurons. These studies suggest that functional AMPA, kainate, and NMDA receptors are present at the hair cell/vestibulocochlear nerve synapse. JF - The Journal of Neuroscience AU - Niedzielski, A S AU - Wenthold, R J AD - Laboratory of Neurochemistry, NIDCD, NIH, Bethesda, Maryland 20892. PY - 1995 SP - 2338 EP - 2353 VL - 15 IS - 3 Pt 2 SN - 0270-6474, 0270-6474 KW - Vestibular Nerve KW - Animal KW - Receptors, Glutamate KW - Rats KW - Polymerase Chain Reaction KW - Base Sequence KW - In Situ Hybridization KW - Rats, Sprague-Dawley KW - Molecular Sequence Data KW - Cochlear Nerve KW - Ganglia, Sensory KW - Receptors, AMPA KW - Receptors, Kainic Acid KW - Receptors, N-Methyl-D-Aspartate KW - Male KW - Gene Expression Regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85241983?accountid=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=Expression+of+AMPA%2C+kainate%2C+and+NMDA+receptor+subunits+in+cochlear+and+vestibular+ganglia.&rft.au=Niedzielski%2C+A+S%3BWenthold%2C+R+J&rft.aulast=Niedzielski&rft.aufirst=A&rft.date=1995-03-01&rft.volume=15&rft.issue=3+Pt+2&rft.spage=2338&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 - News from the National Institute on Deafness and other Communication Disorders. AN - 85211627; pmid-8572129 JF - The American Journal of Otology AU - Snow, J B AD - National Institute on Deafness and other Communication Disorders, Bethesda, Maryland 20892, USA. PY - 1995 SP - 253 EP - 256 VL - 16 IS - 2 SN - 0192-9763, 0192-9763 KW - United States KW - Deafness KW - Hair Cells KW - Human KW - National Institutes of Health (U.S.) KW - Regeneration KW - Research KW - Cochlear Implants KW - Communication Disorders UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85211627?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+Journal+of+Otology&rft.atitle=News+from+the+National+Institute+on+Deafness+and+other+Communication+Disorders.&rft.au=Snow%2C+J+B&rft.aulast=Snow&rft.aufirst=J&rft.date=1995-03-01&rft.volume=16&rft.issue=2&rft.spage=253&rft.isbn=&rft.btitle=&rft.title=The+American+Journal+of+Otology&rft.issn=01929763&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Toxicity and carcinogenicity of t-butyl alcohol in rats and mice following chronic exposure in drinking water. AN - 77740131; 7491631 AB - t-Butyl alcohol (TBA) was administered in drinking water to F344/N rats and B6C3F1 mice for two years using 60 animals/dose/sex/species. Male rats received doses of 0, 1.25, 2.5, or 5 mg/ml and females received 0, 2.5, 5, or 10 mg/ml, resulting in average daily doses of approximately 85, 195, or 420 mg TBA/kg body weight for males and 175, 330, or 650 mg/kg for females. Ten rats per group were evaluated after 15 months. Male and female mice received doses of 0, 5, 10, or 20 mg/ml, resulting in average daily doses of approximately 535, 1,035, or 2,065 mg TBA/kg body weight for males and 510, 1,015, or 2,105 mg/kg for females. Survival was significantly reduced in male rats receiving 5 mg/ml, female rats receiving 10 mg/ml, and male mice receiving 20 mg/ml. Long-term exposure to TBA produced increased incidences of renal tubule adenoma and carcinoma in male rats; transitional epithelial hyperplasia of the kidney in male and female rats; follicular cell adenoma of the thyroid in female mice; and follicular cell hyperplasia of the thyroid and inflammation and hyperplasia of the urinary bladder in male and female mice. In addition, a slight increase in follicular cell adenoma or carcinoma of the thyroid (combined) in male mice may have been related to the administration of TBA. JF - Toxicology and industrial health AU - Cirvello, J D AU - Radovsky, A AU - Heath, J E AU - Farnell, D R AU - Lindamood, C AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. PY - 1995 SP - 151 EP - 165 VL - 11 IS - 2 SN - 0748-2337, 0748-2337 KW - Butanols KW - 0 KW - Carcinogens KW - tert-Butyl Alcohol KW - MD83SFE959 KW - Index Medicus KW - Drinking KW - Animals KW - Thyroid Neoplasms -- chemically induced KW - Kidney Neoplasms -- chemically induced KW - Mice KW - Kidney Neoplasms -- mortality KW - Rats KW - Rats, Inbred F344 KW - Body Weight -- drug effects KW - Urinary Bladder Diseases -- chemically induced KW - Thyroid Neoplasms -- mortality KW - Female KW - Male KW - Butanols -- toxicity KW - Carcinogens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77740131?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+industrial+health&rft.atitle=Toxicity+and+carcinogenicity+of+t-butyl+alcohol+in+rats+and+mice+following+chronic+exposure+in+drinking+water.&rft.au=Cirvello%2C+J+D%3BRadovsky%2C+A%3BHeath%2C+J+E%3BFarnell%2C+D+R%3BLindamood%2C+C&rft.aulast=Cirvello&rft.aufirst=J&rft.date=1995-03-01&rft.volume=11&rft.issue=2&rft.spage=151&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+industrial+health&rft.issn=07482337&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-02 N1 - Date created - 1996-01-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Toxicol Ind Health 1995 May-Jun;11(3):363 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Erythroleukaemia induction by the Friend spleen focus-forming virus. AN - 77496945; 7663048 AB - The Friend spleen focus-forming virus has been a valuable tool for understanding the molecular events involved in the multiple stages of leukaemia. As summarized in Figure 3, the primary effect of SFFV, which occurs within days, is to cause a polyclonal proliferation of erythroid precursor cells that can proliferate in the absence of their normal regulator erythropoietin. This is the direct result of the unique envelope glycoprotein encoded by SFFV, which is transported to the cell surface and apparently interacts with the EpoR or another component of the multimeric EpoR complex, resulting in the constitutive activation of the Epo signal transduction pathway. Within this proliferating population of erythroid cells is a rare cell that has undergone several genetic changes due to the integration of the viral genome in specific sites in the mouse DNA. This leads to the activation of a gene encoding the PU.1 transcription factor, whose high expression in erythroid cells may be the cause of the block in differentiation that is characteristic of SFFV-transformed erythroid cells. SFFV integration can also lead to the inactivation of the p53 tumour supressor gene, giving these cells a growth advantage in the mouse. The disease induced by SFFV in mice is very similar to polycythaemia vera in humans (Golde et al, 1981). The major clinical feature of polycythaemia vera is the continuous expansion of the number of mature red blood cells in the presence of low serum Epo levels. Also, BFU-E and CFU-E from these patients can form in the absence of Epo like the analogous cells from SFFV-infected mice (Casadevall et al, 1982). It is possible that haematopoietic cells from individuals suffering from this disease express a protein similar to the envelope glycoprotein of SFFV that can interact with the EpoR and lead to its constitutive activation. Alternatively, these patients may contain a mutant EpoR gene that is constitutively activated like the mutant EpoR described earlier. As we understand more fully how the SFFV envelope protein constitutively activates te EpoR complex, we can begin to design therapies to counteract its action that can then be applied to treating patients with polycythaemia vera or other human diseases associated with uncontrolled erythropoiesis. JF - Bailliere's clinical haematology AU - Ruscetti, S K AD - Laboratory of Molecular Oncology, National Cancer Institute, Frederick Cancer Research and Development Center MD 21702-1201, USA. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 225 EP - 247 VL - 8 IS - 1 SN - 0950-3536, 0950-3536 KW - EpoR KW - Fv-2 KW - Fv-2rr KW - PU.1 KW - Sfpi-1 KW - env KW - gag KW - p53 KW - pol KW - DNA-Binding Proteins KW - 0 KW - Receptors, Erythropoietin KW - Retroviridae Proteins, Oncogenic KW - Viral Envelope Proteins KW - glycoprotein gp55, Friend spleen focus-forming virus KW - v-Spi-1 protein, Friend spleen focus-forming virus KW - Erythropoietin KW - 11096-26-7 KW - Index Medicus KW - AIDS/HIV KW - Virus Replication KW - Animals KW - Erythropoiesis KW - Viral Envelope Proteins -- physiology KW - DNA-Binding Proteins -- genetics KW - Mice KW - Genome, Viral KW - Erythroid Precursor Cells -- virology KW - Erythropoietin -- physiology KW - Friend murine leukemia virus -- genetics KW - Receptors, Erythropoietin -- physiology KW - Hyperplasia KW - Friend murine leukemia virus -- physiology KW - Genes, env KW - DNA-Binding Proteins -- physiology KW - Erythroid Precursor Cells -- pathology KW - Signal Transduction KW - Mutagenesis, Insertional KW - Cell Transformation, Neoplastic KW - Cell Transformation, Viral KW - Viral Envelope Proteins -- genetics KW - Retroviridae Infections -- virology KW - Defective Viruses -- genetics KW - Tumor Virus Infections -- virology KW - Helper Viruses -- physiology KW - Leukemia, Erythroblastic, Acute -- virology KW - Spleen Focus-Forming Viruses -- physiology KW - Leukemia, Experimental -- virology KW - Defective Viruses -- pathogenicity KW - Helper Viruses -- genetics KW - Defective Viruses -- physiology KW - Spleen Focus-Forming Viruses -- pathogenicity KW - Spleen Focus-Forming Viruses -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77496945?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Erythroleukaemia+induction+by+the+Friend+spleen+focus-forming+virus.&rft.au=Ruscetti%2C+S+K&rft.aulast=Ruscetti&rft.aufirst=S&rft.date=1995-03-01&rft.volume=8&rft.issue=1&rft.spage=225&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 - 1995-10-10 N1 - Date created - 1995-10-10 N1 - Date revised - 2017-01-13 N1 - Gene symbol - EpoR; Fv-2; Fv-2rr; PU.1; Sfpi-1; env; gag; p53; pol N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Trapping of glutamate and glycine during open channel block of rat hippocampal neuron NMDA receptors by 9-aminoacridine. AN - 77467767; 7650609 AB - 1. N-methyl-D-aspartate (NMDA) receptor responses were recorded from rat hippocampal neurons grown in dissociated culture, using whole-cell, outside-out and nucleated patch recording techniques. Rapid perfusion was used to study voltage-dependent block of NMDA receptors by 9-aminoacridine (9-AA) and by Mg2+. 2. Large amplitude tail currents were evoked on depolarization to +60 mV after application at -100 mV of NMDA and 9-AA but not NMDA and Mg2+. These tail currents were resistant to block by competitive antagonists to the glutamate and glycine binding sites on NMDA receptors and were not evoked when either NMDA or 9-AA were applied alone. 3. The decay kinetics of the tail current were dependent on agonist affinity; the time required for 80% charge transfer was 10-fold briefer for NMDA than for glutamate and 7-fold briefer for L-alanine than for glycine. These results are in accord with a sequential model for block of NMDA receptors by 9-AA, in which neither glutamate nor glycine can dissociate from the open-blocked state of the receptor. 4. Tail current responses had amplitudes 2- to 4-fold larger than responses to maximally effective concentrations of glutamate and glycine, indicating that NMDA receptor channels accumulate in the open-blocked state during co-application of agonist and 9-AA. The rise time and decay kinetics of tail current responses were faster than the response to brief applications of a maximally effective concentration of glutamate. Together, these results suggest that at +60 mV recovery from block by 9-AA occurs faster than the rate of opening of NMDA receptors in response to glutamate. 5. Our experiments suggest that open channel block of NMDA receptors can provide a novel approach for measurement of both open probability and the first latency distribution for ion channel opening in response to the binding of agonists, and provide additional evidence suggesting that the delayed opening of NMDA receptor channels underlies slow activation and deactivation of responses to glutamate. JF - The Journal of physiology AU - Benveniste, M AU - Mayer, M L AD - Laboratory of Cellular and Molecular Neurophysiology, NICHD, Bethesda, MD 20892, USA. Y1 - 1995/03/01/ PY - 1995 DA - 1995 Mar 01 SP - 367 EP - 384 VL - 483 ( Pt 2) SN - 0022-3751, 0022-3751 KW - Receptors, N-Methyl-D-Aspartate KW - 0 KW - Glutamic Acid KW - 3KX376GY7L KW - Aminacrine KW - 78OY3Z0P7Z KW - Magnesium KW - I38ZP9992A KW - Glycine KW - TE7660XO1C KW - Index Medicus KW - Animals KW - Binding, Competitive -- physiology KW - Electrophysiology KW - Pregnancy KW - Ion Channel Gating -- physiology KW - Rats KW - Animals, Newborn KW - Rats, Sprague-Dawley KW - Kinetics KW - Hippocampus -- cytology KW - Magnesium -- pharmacology KW - Time Factors KW - Embryo, Mammalian KW - Female KW - Receptors, N-Methyl-D-Aspartate -- agonists KW - Glutamic Acid -- metabolism KW - Glycine -- metabolism KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Aminacrine -- pharmacology KW - Neurons -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77467767?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+physiology&rft.atitle=Trapping+of+glutamate+and+glycine+during+open+channel+block+of+rat+hippocampal+neuron+NMDA+receptors+by+9-aminoacridine.&rft.au=Benveniste%2C+M%3BMayer%2C+M+L&rft.aulast=Benveniste&rft.aufirst=M&rft.date=1995-03-01&rft.volume=483+%28+Pt+2%29&rft.issue=&rft.spage=367&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+physiology&rft.issn=00223751&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-28 N1 - Date created - 1995-09-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Neuron. 1991 Oct;7(4):605-13 [1681832] Neurosci Lett. 1991 Feb 25;123(2):187-91 [1709267] Neuron. 1992 Jan;8(1):181-7 [1370371] J Physiol. 1991 Apr;435:275-93 [1837562] J Neurosci. 1992 Feb;12(2):635-43 [1346806] Nature. 1992 Jun 25;357(6380):686-9 [1377360] Trends Biochem Sci. 1992 Sep;17(9):353-8 [1412713] J Physiol. 1992 May;450:643-72 [1359126] Proc Biol Sci. 1992 Dec 22;250(1329):279-86 [1283640] J Neurosci. 1993 Mar;13(3):1088-96 [8095067] J Physiol. 1992 Oct;456:143-79 [1293277] J Mol Biol. 1993 Feb 20;229(4):1101-24 [8445638] J Biol Chem. 1993 May 25;268(15):11348-55 [8496186] J Physiol. 1993 Feb;461:339-78 [8350269] Nature. 1993 Dec 9;366(6455):569-72 [7902955] J Pharmacol Exp Ther. 1994 Jan;268(1):503-14 [7507997] J Neurosci. 1994 Apr;14(4):2153-60 [7512634] Nature. 1994 May 19;369(6477):235-9 [7514273] Neuron. 1994 Jun;12(6):1291-300 [8011339] Eur J Pharmacol. 1994 Feb 21;253(1-2):1-8 [8013535] J Neurophysiol. 1994 Aug;72(2):754-61 [7983533] Proc R Soc Lond B Biol Sci. 1957 May 7;146(924):369-81 [13431862] Science. 1992 Jan 24;255(5043):470-2 [1346477] J Physiol. 1983 Jun;339:663-78 [6310093] Nature. 1984 Feb 2-8;307(5950):462-5 [6320006] Nature. 1984 May 17-23;309(5965):261-3 [6325946] J Physiol. 1985 Dec;369:501-57 [2419552] J Neurophysiol. 1987 Aug;58(2):251-66 [2443623] Proc Natl Acad Sci U S A. 1988 Feb;85(4):1307-11 [2448800] J Physiol. 1988 May;399:247-66 [2457089] Science. 1988 Aug 12;241(4867):835-7 [2841759] J Neurosci. 1990 Jun;10(6):1830-7 [1693952] J Neurophysiol. 1990 Jun;63(6):1373-84 [1972740] J Physiol. 1989 Aug;415:329-50 [2561788] Nature. 1990 Aug 9;346(6284):565-7 [1974037] J Physiol. 1990 Sep;428:313-31 [2172523] J Physiol. 1990 Sep;428:333-57 [2146385] Science. 1991 Nov 29;254(5036):1342-7 [1660187] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neurophysiological consequences of nitroxide antioxidants. AN - 77464972; 7648519 AB - Nitroxides are antioxidant compounds that have been shown to provide radioprotection in vivo and in vitro. Radioprotection in vivo is limited by toxicity, which appears to be neurologic in nature. To further evaluate the toxicity of these compounds, three representative nitroxides, Tempol, Tempamine, and Tempo, were examined in slices of guinea pig hippocampus. Each nitroxide increased the population spike and caused potentiation of excitatory postsynaptic potential--spike coupling. Repetitive activity and epileptiform activity were observed at the highest concentrations of Tempo and Tempamine. Tempol was the least toxic compound in this system, followed by Tempamine and Tempo. Additional studies are necessary to further define the effects of nitroxides on the central nervous system and to develop strategies to mitigate these effects. JF - Canadian journal of physiology and pharmacology AU - Hahn, S M AU - Lepinski, D L AU - DeLuca, A M AU - Mitchell, J B AU - Pellmar, T C AD - Radiation Biology Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 399 EP - 403 VL - 73 IS - 3 SN - 0008-4212, 0008-4212 KW - Antioxidants KW - 0 KW - Cyclic N-Oxides KW - Nitrogen Oxides KW - Spin Labels KW - tempol KW - U78ZX2F65X KW - TEMPO KW - VQN7359ICQ KW - Index Medicus KW - Evoked Potentials -- drug effects KW - Animals KW - Epilepsy -- physiopathology KW - Epilepsy -- chemically induced KW - Guinea Pigs KW - In Vitro Techniques KW - Cyclic N-Oxides -- pharmacology KW - Electrophysiology KW - Male KW - Microelectrodes KW - Nitrogen Oxides -- antagonists & inhibitors KW - Antioxidants -- pharmacology KW - Hippocampus -- cytology KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77464972?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Canadian+journal+of+physiology+and+pharmacology&rft.atitle=Neurophysiological+consequences+of+nitroxide+antioxidants.&rft.au=Hahn%2C+S+M%3BLepinski%2C+D+L%3BDeLuca%2C+A+M%3BMitchell%2C+J+B%3BPellmar%2C+T+C&rft.aulast=Hahn&rft.aufirst=S&rft.date=1995-03-01&rft.volume=73&rft.issue=3&rft.spage=399&rft.isbn=&rft.btitle=&rft.title=Canadian+journal+of+physiology+and+pharmacology&rft.issn=00084212&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-26 N1 - Date created - 1995-09-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Renal damage after total body irradiation in a mouse model for bone marrow transplantation: effect of radiation dose rate. AN - 77431230; 7631026 AB - Late renal damage after total body irradiation (TBI) and bone marrow transplantation (BMT) is a recently recognised morbidity. We have tested the effect of single fraction TBI given at two different dose rates on late kidney damage in a mouse model. TBI was given at either high dose rate (HDR; 0.71 Gy/min) or low dose rate (LDR; 0.08 Gy/min). Transplantation with syngeneic marrow cells was done 4-6 h after TBI. Kidney damage was tested using 51CrEDTA residual activity, blood urea nitrogen (BUN) and percentage haematocrit (Hct). TBI alone given at HDR or LDR caused progressive renal damage with no evidence of recovery or plateau. The time latency before the expression of damage was dependent on both dose and the end point used. It was shorter the higher the dose. 51CrEDTA detected renal damage at the same doses as BUN but earlier in time, while %Hct showed evidence of renal damage at doses lower than both BUN and 51CrEDTA. Using the 51CrEDTA the dose-response curves for renal damage were steep and continuously shifting towards lower doses as follow-up time after treatment increased. There was a sparing effect of reducing the dose rate that was more evident at follow-up times of less than a year than at 66 weeks after TBI. Thus, the dose modifying ratio (DMF), defined as the dose needed to cause renal damage in 50% of irradiated animals (ED50) using LDR divided by the ED50 using HDR, was dependent on the time of evaluation.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology AU - Safwat, A AU - Nielsen, O S AU - abd el-Bakky, H AU - Overgaard, J AD - Department of Radiotherapy, National Cancer Institute, Fom El-Khalig, Cairo, Egypt. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 203 EP - 209 VL - 34 IS - 3 SN - 0167-8140, 0167-8140 KW - Index Medicus KW - Radiation Dosage KW - Mice, Inbred Strains KW - Kidney Function Tests KW - Animals KW - Disease Models, Animal KW - Combined Modality Therapy -- adverse effects KW - Mice KW - Dose-Response Relationship, Radiation KW - Male KW - Whole-Body Irradiation -- adverse effects KW - Bone Marrow Transplantation -- adverse effects KW - Renal Insufficiency -- etiology KW - Renal Insufficiency -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77431230?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Radiotherapy+and+oncology+%3A+journal+of+the+European+Society+for+Therapeutic+Radiology+and+Oncology&rft.atitle=Renal+damage+after+total+body+irradiation+in+a+mouse+model+for+bone+marrow+transplantation%3A+effect+of+radiation+dose+rate.&rft.au=Safwat%2C+A%3BNielsen%2C+O+S%3Babd+el-Bakky%2C+H%3BOvergaard%2C+J&rft.aulast=Safwat&rft.aufirst=A&rft.date=1995-03-01&rft.volume=34&rft.issue=3&rft.spage=203&rft.isbn=&rft.btitle=&rft.title=Radiotherapy+and+oncology+%3A+journal+of+the+European+Society+for+Therapeutic+Radiology+and+Oncology&rft.issn=01678140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-06 N1 - Date created - 1995-09-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Persistent catalepsy associated with severe dyskinesias in rats treated with chronic injections of haloperidol decanoate. AN - 77407942; 7617800 AB - Patients who develop persistent parkinsonism while on chronic neuroleptic therapy may be predisposed towards the development of tardive dyskinesia (TD). We investigated this issue in an animal model of TD by examining the association between catalepsy and the syndrome of neuroleptic-induced vacuous chewing movements (VCMs). VCMs were measured every 3 weeks for 33 weeks while rats received injections of haloperidol decanoate. Catalepsy was measured after the second through the seventh injections of the depot neuroleptic. There were no correlations between the severity of catalepsy scores after the second or third injections of haloperidol and the severity of the overall VCM syndrome. However, the severity of the catalepsy score following the third through seventh injections of haloperidol strongly correlated with the concurrent number of VCMs. Persistent high catalepsy scores across the six catalepsy rating sessions were strongly associated with the development of persistent severe VCMs. These findings suggest that, to the extent that persistent parkinsonian signs in humans are associated with a propensity towards the development of TD, the VCM syndrome in rats is at least a partially faithful animal model of this relationship. JF - Psychopharmacology AU - Hyde, T M AU - Egan, M F AU - Wing, L L AU - Wyatt, R J AU - Weinberger, D R AU - Kleinman, J E AD - Clinical Brain Disorders Branch, National Institute of Mental Health, St. Elizabeths Hospital, Washington, DC 20032, USA. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 142 EP - 149 VL - 118 IS - 2 SN - 0033-3158, 0033-3158 KW - Antipsychotic Agents KW - 0 KW - haloperidol decanoate KW - AC20PJ4101 KW - Haloperidol KW - J6292F8L3D KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Dyskinesia, Drug-Induced -- etiology KW - Male KW - Haloperidol -- adverse effects KW - Parkinson Disease, Secondary -- chemically induced KW - Catalepsy -- chemically induced KW - Antipsychotic Agents -- pharmacology KW - Haloperidol -- pharmacology KW - Disease Models, Animal KW - Antipsychotic Agents -- adverse effects KW - Haloperidol -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77407942?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology&rft.atitle=Persistent+catalepsy+associated+with+severe+dyskinesias+in+rats+treated+with+chronic+injections+of+haloperidol+decanoate.&rft.au=Hyde%2C+T+M%3BEgan%2C+M+F%3BWing%2C+L+L%3BWyatt%2C+R+J%3BWeinberger%2C+D+R%3BKleinman%2C+J+E&rft.aulast=Hyde&rft.aufirst=T&rft.date=1995-03-01&rft.volume=118&rft.issue=2&rft.spage=142&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-18 N1 - Date created - 1995-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A preliminary risk-benefit assessment of paclitaxel. AN - 77403783; 7619331 AB - Paclitaxel is an antineoplastic agent, first isolated and described in 1971. Despite its novel structure and apparent activity in vitro, little interest was shown in developing the compound because of its scarcity, problems with its formulation and the mistaken assumption that its mechanism of action was similar to that of the vinca alkaloids. Approximately 10 years later, the unique mechanism of action of paclitaxel, its ability to stabilise microtubules, was discovered, and its activity against human tumour xenografts was demonstrated. Interest in the drug was reignited and clinical testing began. Severe hypersensitivity reactions were controlled in the phase II programme with a premedication regimen consisting of dexamethasone, histamine H1-antagonists and H2-antagonists. Neutropenia was dose limiting in all studies conducted in patients with solid tumours. This toxicity was schedule-dependent, and less severe when paclitaxel was administered as a 3-hour infusion regimen. Peripheral neuropathy was mild to moderate in the initial experience, and dose-dependent. However, when bone marrow support with haemopoietic growth factors was used to allow paclitaxel dose intensification, neurotoxicity became dose limiting. To date, substantial clinical efficacy has been demonstrated in ovarian, breast, non-small-cell lung, and head and neck cancers. Response rates were low in initial studies in melanoma, prostate, colon, cervix and renal cancer. In December 1992, US Food and Drug Administration approval was granted for the use of paclitaxel as second-line therapy in ovarian cancer patients. More recently, similar approval was granted for use in recurrent breast cancer. Nevertheless, important questions remain.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Drug safety AU - Bitton, R J AU - Figg, W D AU - Reed, E AD - Clinical Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 196 EP - 208 VL - 12 IS - 3 SN - 0114-5916, 0114-5916 KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Animals KW - Risk Factors KW - Humans KW - Clinical Trials as Topic KW - Paclitaxel -- adverse effects KW - Paclitaxel -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77403783?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+safety&rft.atitle=A+preliminary+risk-benefit+assessment+of+paclitaxel.&rft.au=Bitton%2C+R+J%3BFigg%2C+W+D%3BReed%2C+E&rft.aulast=Bitton&rft.aufirst=R&rft.date=1995-03-01&rft.volume=12&rft.issue=3&rft.spage=196&rft.isbn=&rft.btitle=&rft.title=Drug+safety&rft.issn=01145916&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-29 N1 - Date created - 1995-08-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicokinetics of the cholinomimetic compound benzyltrimethylammonium chloride in the male rat and mouse. AN - 77400823; 7618356 AB - 1. Benzyltrimethylammonium chloride (BTMAC)-derived radioactivity was rapidly eliminated from the F344 rat and the B6C3F1 mouse following p.o. administration of 0.63-63 mg/kg of [ring-U-14C] BTMAC. Greater than 90% of the radioactivity was excreted in urine and faeces within 24-h post-dosing. 2. BTMAC was poorly to moderately absorbed from the GI tract following p.o. administration. The percent of total dose absorbed did not exceed either 40% in the rat or 15% in the mouse. 3. Absorption was linear, but limited, over time following dermal administration of 63 mg/kg to the rat. Less than 10% of the total dose was absorbed from the skin within 24 h of BTMAC application. 4. Metabolism of BTMAC was minimal in both the rat and mouse. Toxicity (excessive cholinergic stimulation and mortality) appears to be attributable to the parent compound. 5. The limited absorption and rapid elimination of BTMAC should result in little or no bioaccumulation in tissues following repeated exposure to low levels of this compound. The results suggest that greater human health risks may be associated with acute high level exposure rather than chronic low level exposure. JF - Xenobiotica; the fate of foreign compounds in biological systems AU - Sanders, J M AU - Griffin, R J AU - Burka, L T AU - Matthews, H B AD - Chemistry Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 303 EP - 313 VL - 25 IS - 3 SN - 0049-8254, 0049-8254 KW - Cholinergic Agents KW - 0 KW - Quaternary Ammonium Compounds KW - benzyltrimethylammonium KW - 14800-24-9 KW - Neostigmine KW - 3982TWQ96G KW - Atropine KW - 7C0697DR9I KW - Index Medicus KW - Animals KW - Neostigmine -- pharmacology KW - Injections, Intravenous KW - Skin -- metabolism KW - Salivation -- drug effects KW - Intestinal Absorption KW - Mice KW - Chromatography, High Pressure Liquid KW - Rats KW - Rats, Inbred F344 KW - Absorption KW - Atropine -- pharmacology KW - Male KW - Quaternary Ammonium Compounds -- pharmacokinetics KW - Quaternary Ammonium Compounds -- administration & dosage KW - Quaternary Ammonium Compounds -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77400823?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Xenobiotica%3B+the+fate+of+foreign+compounds+in+biological+systems&rft.atitle=Toxicokinetics+of+the+cholinomimetic+compound+benzyltrimethylammonium+chloride+in+the+male+rat+and+mouse.&rft.au=Sanders%2C+J+M%3BGriffin%2C+R+J%3BBurka%2C+L+T%3BMatthews%2C+H+B&rft.aulast=Sanders&rft.aufirst=J&rft.date=1995-03-01&rft.volume=25&rft.issue=3&rft.spage=303&rft.isbn=&rft.btitle=&rft.title=Xenobiotica%3B+the+fate+of+foreign+compounds+in+biological+systems&rft.issn=00498254&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-18 N1 - Date created - 1995-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Critical issues in alcoholism research. AN - 77391926; 7607782 JF - The International journal of the addictions AU - Gordis, E AD - National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892-7003, USA. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 497 EP - 505 VL - 30 IS - 4 SN - 0020-773X, 0020-773X KW - Receptors, N-Methyl-D-Aspartate KW - 0 KW - Index Medicus KW - Receptors, N-Methyl-D-Aspartate -- drug effects KW - Risk Factors KW - Humans KW - Brain -- drug effects KW - Treatment Outcome KW - Forecasting KW - Social Environment KW - Alcoholism -- rehabilitation KW - Alcohol Drinking -- adverse effects KW - Alcohol Drinking -- prevention & control KW - Alcoholism -- genetics KW - Alcoholism -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77391926?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+the+addictions&rft.atitle=Critical+issues+in+alcoholism+research.&rft.au=Gordis%2C+E&rft.aulast=Gordis&rft.aufirst=E&rft.date=1995-03-01&rft.volume=30&rft.issue=4&rft.spage=497&rft.isbn=&rft.btitle=&rft.title=The+International+journal+of+the+addictions&rft.issn=0020773X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-16 N1 - Date created - 1995-08-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fluvoxamine treatment of alcoholic amnestic disorder. AN - 77389744; 7542052 AB - The serotonin uptake inhibitor fluvoxamine was assessed in treatment of alcohol-induced Korsakoff's syndrome (KS) using fixed (4 weeks, 200 mg/day) or individualized (6 weeks, plasma concentration > or = 400 ng/ml) dosing in randomized placebo-controlled double-blind crossover studies. Cognitive functions and concentrations of the major cerebrospinal fluid (CSF) metabolites of serotonin (5-HIAA), norepinephrine (MHPG), and dopamine (HVA) were determined in abstinent, nondepressed KS patients (aged 45-75), at baseline and placebo (3-4 weeks), and after 3-4 (n = 10) or 6 (n = 4) weeks of fluvoxamine administration. Fluvoxamine decreased CSF 5-HIAA compared to placebo (P < 0.003) without consistent changes in HVA or MHPG. Reductions in 5-HIAA correlated with improvements on the Wechsler Memory Scale Memory Quotient (P < 0.05), independent of effects on attention/vigilance or Beck Depression Inventory scores. Reductions in 5-HIAA correlated with plasma fluvoxamine (P < 0.03) only for fluvoxamine concentrations below 450 ng/ml. These findings suggest improvement of memory consolidation and/or retrieval in patients with Korsakoff's syndrome by fluvoxamine via serotonergic mechanisms. JF - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology AU - Martin, P R AU - Adinoff, B AU - Lane, E AU - Stapleton, J M AU - Bone, G A AU - Weingartner, H AU - Linnoila, M AU - Eckardt, M J AD - Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892, USA. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 27 EP - 33 VL - 5 IS - 1 SN - 0924-977X, 0924-977X KW - Hydroxyindoleacetic Acid KW - 54-16-0 KW - Fluvoxamine KW - O4L1XPO44W KW - Index Medicus KW - Hydroxyindoleacetic Acid -- metabolism KW - Humans KW - Treatment Outcome KW - Aged KW - Middle Aged KW - Time Factors KW - Male KW - Female KW - Cognition KW - Fluvoxamine -- therapeutic use KW - Alcohol Amnestic Disorder -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77389744?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neuropsychopharmacology+%3A+the+journal+of+the+European+College+of+Neuropsychopharmacology&rft.atitle=Fluvoxamine+treatment+of+alcoholic+amnestic+disorder.&rft.au=Martin%2C+P+R%3BAdinoff%2C+B%3BLane%2C+E%3BStapleton%2C+J+M%3BBone%2C+G+A%3BWeingartner%2C+H%3BLinnoila%2C+M%3BEckardt%2C+M+J&rft.aulast=Martin&rft.aufirst=P&rft.date=1995-03-01&rft.volume=5&rft.issue=1&rft.spage=27&rft.isbn=&rft.btitle=&rft.title=European+neuropsychopharmacology+%3A+the+journal+of+the+European+College+of+Neuropsychopharmacology&rft.issn=0924977X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-24 N1 - Date created - 1995-08-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of topical FK506 on endotoxin-induced uveitis (EIU) in the Lewis rat. AN - 77355179; 7540967 AB - FK506 is a macrolide antibiotic and a potent immunosuppressant. To investigate the effect of topical FK506 on acute ocular inflammation, we evaluated its action on the development of endotoxin-induced uveitis (EIU). At two different concentrations of 0.05% and 0.3%, topical FK506 was applied to Lewis rats with EIU. In aqueous, the mean number of inflammatory cells per microliter +/- SEM was 2,389 +/- 1,277, 1,571 +/- 1,562, 898 +/- 882, and 69 +/- 152 for rats treated with vehicle alone, 0.05%, 0.3% FK506, and 1% prednisolone acetate. The median of histological grades was 2, 1.5, 0.8, and 0.5 for animals treated with these 4 different regimens respectively. Analysis of aqueous protein showed a small reduction in FK506-treated animals. Mean blood levels of FK506 were low in rats treated with topical FK506 (0.05%, 0.84 ng/ml; 0.3%, 2.0 ng/ml) suggesting that its therapeutic effect was not secondary to the systemic absorption of the drug. Although FK506 is not as effective as prednisolone, 0.3% FK506 produced significant decreases in the mean aqueous inflammatory cell number and histological inflammatory score as compared to control vehicle alone. We conclude that topical FK506 can suppress EIU in a dose-dependent fashion and may be an alternative medication for patients with anterior uveitis and contra-indication to topical steroid. JF - Current eye research AU - Hikita, N AU - Chan, C C AU - Whitcup, S M AU - Nussenblatt, R B AU - Mochizuki, M AD - Laboratory of Immunology, National Eye Institute, NIH, Bethesda, MD 20892-1858, USA. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 209 EP - 214 VL - 14 IS - 3 SN - 0271-3683, 0271-3683 KW - Cell Adhesion Molecules KW - 0 KW - Endotoxins KW - Eye Proteins KW - Ophthalmic Solutions KW - Tacrolimus KW - WM0HAQ4WNM KW - Index Medicus KW - Animals KW - Rats, Inbred Lew KW - Dose-Response Relationship, Drug KW - Disease Models, Animal KW - Cell Adhesion Molecules -- analysis KW - Salmonella typhimurium KW - Anterior Eye Segment -- pathology KW - Rats KW - Aqueous Humor -- chemistry KW - Anterior Eye Segment -- drug effects KW - Administration, Topical KW - Female KW - Immunoenzyme Techniques KW - Eye Proteins -- analysis KW - Tacrolimus -- pharmacokinetics KW - Uveitis, Anterior -- prevention & control KW - Uveitis, Anterior -- chemically induced KW - Tacrolimus -- therapeutic use KW - Uveitis, Anterior -- pathology KW - Tacrolimus -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77355179?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+eye+research&rft.atitle=Effects+of+topical+FK506+on+endotoxin-induced+uveitis+%28EIU%29+in+the+Lewis+rat.&rft.au=Hikita%2C+N%3BChan%2C+C+C%3BWhitcup%2C+S+M%3BNussenblatt%2C+R+B%3BMochizuki%2C+M&rft.aulast=Hikita&rft.aufirst=N&rft.date=1995-03-01&rft.volume=14&rft.issue=3&rft.spage=209&rft.isbn=&rft.btitle=&rft.title=Current+eye+research&rft.issn=02713683&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-01 N1 - Date created - 1995-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombination rates across the HLA complex: use of microsatellites as a rapid screen for recombinant chromosomes. AN - 77353609; 7795597 AB - Meiotic recombination does not appear to occur randomly across chromosomes, but rather seems to be restricted to specific regions. A striking example of this phenomenon is illustrated by the HLA class II region. No recombination within the 100 kb encompassing the DRB1-DQA1-DQB1 loci has been reported, whereas the random association of TAP1 with TAP2 alleles suggests the presence of a hotspot for recombination within the 15 kb separating the closest variant sites of these two loci. Recombination rates between loci may provide clues to the functional properties of haplotypes. Absence of recombination may suggest the necessity to keep alleles of certain genes in phase and, alternatively, high recombination rates may suggest selective pressure to diversify haplotypes within the population. To address this issue, recombination rates across the HLA complex were determined using the 59 Centre d'Etude Polymorphisme Humain (CEPH) pedigrees. The allele frequencies of four microsatellite markers which map at sites ranging from the telomeric to centromeric ends of the complex were determined and the markers were used as a rapid means for identification of recombinant chromosomes. Typing these as well as other polymorphic loci within the HLA class I, II and III regions allowed assignment of the segments where recombination occurred. Recombination rates within the class II region (defined here as DRB1 to DPB1) and class III region (defined here as HLA-B to DRB1) regions were 0.74% and 0.94%, respectively, both of which are within an expected range given the standard of 1% recombination rate per megabase of DNA per meiosis.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Human molecular genetics AU - Martin, M AU - Mann, D AU - Carrington, M AD - Laboratory of Viral Carcinogenesis, PRI/DynCorp, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702, USA. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 423 EP - 428 VL - 4 IS - 3 SN - 0964-6906, 0964-6906 KW - DNA, Satellite KW - 0 KW - HLA-D Antigens KW - Index Medicus KW - Base Sequence KW - Alleles KW - Haplotypes KW - Gene Frequency KW - Humans KW - HLA-D Antigens -- genetics KW - Molecular Sequence Data KW - Chromosome Mapping KW - Male KW - Female KW - DNA, Satellite -- genetics KW - Major Histocompatibility Complex -- genetics KW - Recombination, Genetic KW - Chromosomes, Human -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77353609?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+molecular+genetics&rft.atitle=Recombination+rates+across+the+HLA+complex%3A+use+of+microsatellites+as+a+rapid+screen+for+recombinant+chromosomes.&rft.au=Martin%2C+M%3BMann%2C+D%3BCarrington%2C+M&rft.aulast=Martin&rft.aufirst=M&rft.date=1995-03-01&rft.volume=4&rft.issue=3&rft.spage=423&rft.isbn=&rft.btitle=&rft.title=Human+molecular+genetics&rft.issn=09646906&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-03 N1 - Date created - 1995-08-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Hum Mol Genet 1995 Dec;4(12):2423 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Serum creatinine levels in older adults: relationship with health status and medications. AN - 77351308; 7793337 AB - We aimed to examine the association of serum creatinine with health status and current medications in the population of older adults. We employed a cross-sectional study within an ongoing cohort of 3999 residents of three communities of the Established Populations for Epidemiologic Studies of the Elderly who had venepuncture at the 6-year follow-up when they were aged 71 years and older. Serum creatinine levels, history of diabetes and heart attack, current medications, and blood pressure were measured. Creatinine levels were higher in men than in women, and in blacks than in whites. Higher creatinine levels were observed in persons with a history of diabetes or heart attack, and in those reporting use of cimetidine and diuretic medications. Persons taking frusemide and the potassium-sparing diuretics had higher creatinine levels than those taking thiazides. This study confirms associations of higher creatinine with male sex, older age, black race, history of diabetes and cimetidine use reported from cross-sectional research in younger populations and in smaller, more selected groups of older adults. Longitudinal studies will be necessary to strengthen our understanding of the causes of changes in kidney function in the older population. JF - Age and ageing AU - Salive, M E AU - Jones, C A AU - Guralnik, J M AU - Agodoa, L Y AU - Pahor, M AU - Wallace, R B AD - Epidemiology, Demography and Biometry Program, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 142 EP - 150 VL - 24 IS - 2 SN - 0002-0729, 0002-0729 KW - Cardiovascular Agents KW - 0 KW - Cimetidine KW - 80061L1WGD KW - Creatinine KW - AYI8EX34EU KW - Index Medicus KW - Reference Values KW - Hypertension -- blood KW - Humans KW - Aged KW - Hypertension -- drug therapy KW - Myocardial Infarction -- blood KW - Aged, 80 and over KW - European Continental Ancestry Group KW - Diabetes Mellitus -- blood KW - Activities of Daily Living -- classification KW - Cimetidine -- therapeutic use KW - Cimetidine -- adverse effects KW - African Continental Ancestry Group KW - Male KW - Female KW - Myocardial Infarction -- drug therapy KW - Diabetes Mellitus -- drug therapy KW - Health Status Indicators KW - Cardiovascular Agents -- therapeutic use KW - Cardiovascular Agents -- adverse effects KW - Geriatric Assessment KW - Creatinine -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77351308?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Age+and+ageing&rft.atitle=Serum+creatinine+levels+in+older+adults%3A+relationship+with+health+status+and+medications.&rft.au=Salive%2C+M+E%3BJones%2C+C+A%3BGuralnik%2C+J+M%3BAgodoa%2C+L+Y%3BPahor%2C+M%3BWallace%2C+R+B&rft.aulast=Salive&rft.aufirst=M&rft.date=1995-03-01&rft.volume=24&rft.issue=2&rft.spage=142&rft.isbn=&rft.btitle=&rft.title=Age+and+ageing&rft.issn=00020729&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-27 N1 - Date created - 1995-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lack of effect of chronic morphine treatment and naloxone-precipitated withdrawal on tyrosine hydroxylase, galanin, and neuropeptide Y mRNA levels in the rat locus coeruleus. AN - 77342411; 7540319 AB - Morphine dependence was experimentally induced in rats by daily injection of increasing doses of morphine for seven days. Withdrawal was precipitated in half of the morphine-dependent rats by a single injection of naloxone on day 8. Behavioral signs of withdrawal were evident in the morphine/naloxone group. Gene expression in locus coeruleus (LC) neurons was investigated using quantitative in situ hybridization analysis. Messenger RNA (mRNA) levels for tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis, and for precursors to galanin (GAL) and neuropeptide Y (NPY), peptides that coexist with norepinephrine in LC neurons, were not altered by chronic morphine treatment or naloxone-precipitated withdrawal. In contrast, mRNA levels for c-fos were dramatically elevated in the LC following naloxone-precipitated withdrawal. Chronic morphine treatment caused a small decrease in levels of mRNA encoding the precursor to corticotropin-releasing factor (CRF) in Barrington's nucleus. Although long-term adaptations of LC neurons have previously been implicated in the development of morphine tolerance, dependence, and withdrawal, alterations in the levels of TH, GAL, or NPY mRNA in the LC apparently do not underlie this process. JF - Synapse (New York, N.Y.) AU - Holmes, P V AU - de Bartolomeis, A AU - Koprivica, V AU - Crawley, J N AD - Section on Behavioral Neuropharmacology, NIMH, Bethesda, Maryland 20892, USA. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 197 EP - 205 VL - 19 IS - 3 SN - 0887-4476, 0887-4476 KW - Neuropeptide Y KW - 0 KW - Neuropeptides KW - Peptides KW - Proto-Oncogene Proteins c-fos KW - RNA, Messenger KW - Naloxone KW - 36B82AMQ7N KW - Morphine KW - 76I7G6D29C KW - Galanin KW - 88813-36-9 KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Index Medicus KW - Rats KW - Gene Expression -- drug effects KW - Naloxone -- pharmacology KW - Animals KW - Rats, Sprague-Dawley KW - In Situ Hybridization KW - Proto-Oncogene Proteins c-fos -- genetics KW - Peptides -- genetics KW - Autoradiography KW - Time Factors KW - Male KW - Neuropeptide Y -- genetics KW - Substance Withdrawal Syndrome -- metabolism KW - RNA, Messenger -- metabolism KW - Morphine -- adverse effects KW - Tyrosine 3-Monooxygenase -- genetics KW - Locus Coeruleus -- metabolism KW - Neuropeptides -- genetics KW - Morphine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77342411?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Synapse+%28New+York%2C+N.Y.%29&rft.atitle=Lack+of+effect+of+chronic+morphine+treatment+and+naloxone-precipitated+withdrawal+on+tyrosine+hydroxylase%2C+galanin%2C+and+neuropeptide+Y+mRNA+levels+in+the+rat+locus+coeruleus.&rft.au=Holmes%2C+P+V%3Bde+Bartolomeis%2C+A%3BKoprivica%2C+V%3BCrawley%2C+J+N&rft.aulast=Holmes&rft.aufirst=P&rft.date=1995-03-01&rft.volume=19&rft.issue=3&rft.spage=197&rft.isbn=&rft.btitle=&rft.title=Synapse+%28New+York%2C+N.Y.%29&rft.issn=08874476&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-18 N1 - Date created - 1995-07-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biological mechanisms and perinatal exposure to abused drugs. AN - 77338010; 7784962 AB - Use of illicit and licit drugs during pregnancy is a major public health concern, as it can have adverse effects on the developing fetus. Infants born of women addicted to narcotics, cocaine, alcohol, or polydrugs often undergo a characteristic withdrawal syndrome and may have physical, behavioral, and/or neurological abnormalities. As it is not feasible to ascertain whether these functional changes in human infants are produced by abused substance(s) per se or by a combination of complex socioeconomic factors and polydrug use, researchers in recent years have developed and utilized various innovative animal models to assess drug-induced alterations and their biological mechanisms during the developmental period under a controlled environment. To promote interdisciplinary communications as well as to assess the progress and the future needs in this area, the National Institute on Drug Abuse (NIDA) held a technical review at which biomedical researchers discussed their current findings in various physiological systems. This report summarizes the major findings and the methodological and experimental issues discussed at the conference. The meeting was held in Washington, DC, on May 25 and 26, 1994. JF - Synapse (New York, N.Y.) AU - Thadani, P V AD - Division of Basic Research, National Institute on Drug Abuse, Rockville, Maryland 20857, USA. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 228 EP - 232 VL - 19 IS - 3 SN - 0887-4476, 0887-4476 KW - Benzodiazepines KW - 12794-10-4 KW - Methamphetamine KW - 44RAL3456C KW - Cocaine KW - I5Y540LHVR KW - Phencyclidine KW - J1DOI7UV76 KW - Index Medicus KW - United States KW - Animals KW - Benzodiazepines -- adverse effects KW - Methamphetamine -- adverse effects KW - Humans KW - National Institutes of Health (U.S.) KW - Congresses as Topic KW - Cocaine -- adverse effects KW - Phencyclidine -- adverse effects KW - Female KW - Pregnancy KW - Infant, Newborn -- growth & development KW - Infant, Newborn -- physiology KW - Neonatal Abstinence Syndrome -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77338010?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Synapse+%28New+York%2C+N.Y.%29&rft.atitle=Biological+mechanisms+and+perinatal+exposure+to+abused+drugs.&rft.au=Thadani%2C+P+V&rft.aulast=Thadani&rft.aufirst=P&rft.date=1995-03-01&rft.volume=19&rft.issue=3&rft.spage=228&rft.isbn=&rft.btitle=&rft.title=Synapse+%28New+York%2C+N.Y.%29&rft.issn=08874476&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-18 N1 - Date created - 1995-07-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Radiation safety training program at the National Institutes of Health. AN - 77337931; 7783932 AB - At the U.S. Public Health Service's National Institutes of Health (NIH), one of the world's largest biomedical and clinical research institutions, 70 to 80% of all research is performed using radiation or radioactive materials. To maintain a safe environment and minimize risks to the health and safety of the employees, patients, visitors, and the surrounding community, a radiation protection program is required. Under U.S. Nuclear Regulatory Commission licenses and NIH policies, the Radiation Safety Branch (RSB), Division of Safety, administers a comprehensive radiation safety program covering over 3,500 NIH laboratories and some 7,000 laboratory and ancillary staff workers. The NIH radiation protection program provides for the effective supervision, control, and monitoring of all radioactive materials and radiation sources at NIH. This includes activities such as radiation exposure monitoring, laboratory inspections, waste management, consulting, environmental monitoring, and training. Training is considered an integral part of the radiation safety program. RSB offers an extensive training program with over 20 different training courses each year. For example, in 1993 some 6,700 employees attended 243 classes. JF - Military medicine AU - Holcomb, W F AD - National Institutes of Health, Division of Safety, Radiation Safety Branch, Bethesda, MD 20892, USA. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 115 EP - 120 VL - 160 IS - 3 SN - 0026-4075, 0026-4075 KW - Index Medicus KW - United States KW - Humans KW - Occupational Health KW - Radiation Protection KW - Inservice Training KW - National Institutes of Health (U.S.) KW - Radioactive Hazard Release -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77337931?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Radiation+safety+training+program+at+the+National+Institutes+of+Health.&rft.au=Holcomb%2C+W+F&rft.aulast=Holcomb&rft.aufirst=W&rft.date=1995-03-01&rft.volume=160&rft.issue=3&rft.spage=115&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 - 1995-07-14 N1 - Date created - 1995-07-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Humoral and cellular immune responses in rhesus macaques infected with human immunodeficiency virus type 2. AN - 77336715; 7786583 AB - Eighteen rhesus macaques were inoculated with either an infectious molecularly cloned human immunodeficiency virus type 2 (HIV-2)SBL/ISY, or with one of eight mutants defective in one or more accessory genes. The immune responses generated by the macaques were monitored for up to 2 years postinfection. All the macaques except those that received mutants lacking the vpr or vif genes demonstrated low to moderate antibody titers. Macaques inoculated with vpx- mutants exhibited a persistent serological response, suggesting continuous virus expression even in the absence of detectable virus in the peripheral blood mononuclear cells (PBMCs). Neutralizing antibodies developed in only four macaques. In general, low-level cytotoxic T lymphocyte (CTL) activity, not clearly HIV-2 specific, was detected in PBMCs. However, one virus-negative macaque exhibited significant HIV-2-specific CTL activity in an enriched CD8+ cell population from PBMCs, suggesting clearance of the viral infection. In addition, CTL activity against the Env and Gag/Pol epitopes of HIV-2 by CD8+ lymphocytes from the spleens and lymph nodes of two infected macaques, in one case requiring CD8+ T cell enrichment and in the other clearly evident in unfractionated tissue lymphocytes, was demonstrated for the first time. This sequestration of tissue CTLs occurred in the absence of significant levels of circulating CTLs in the blood. Our results suggest that routine monitoring of PBMCs may sometimes be inadequate for detecting cell-mediated immune responses. Elucidation of immune correlates of vaccine protection may therefore require sampling of lymphoid tissues and assessment of enriched CD8+ populations. JF - AIDS research and human retroviruses AU - Abimiku, A G AU - Franchini, G AU - Aldrich, K AU - Myagkikh, M AU - Markham, P AU - Gard, E AU - Gallo, R C AU - Robert-Guroff, M AD - Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 383 EP - 393 VL - 11 IS - 3 SN - 0889-2229, 0889-2229 KW - nef KW - vif KW - vpr KW - vpx KW - HIV Antibodies KW - 0 KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Genes, vpr KW - Antibody Formation KW - Genes, vif KW - Genes, nef KW - Mutagenesis KW - Lymphocyte Activation KW - Cytotoxicity, Immunologic KW - Lymphocytes -- immunology KW - Immunity, Cellular KW - HIV Antibodies -- blood KW - Neutralization Tests KW - Enzyme-Linked Immunosorbent Assay KW - Macaca mulatta KW - Time Factors KW - Lymphocytes -- virology KW - Acquired Immunodeficiency Syndrome -- blood KW - Defective Viruses -- immunology KW - Acquired Immunodeficiency Syndrome -- immunology KW - HIV-2 -- genetics KW - Genes, Viral KW - HIV-2 -- immunology KW - Gene Deletion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77336715?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Humoral+and+cellular+immune+responses+in+rhesus+macaques+infected+with+human+immunodeficiency+virus+type+2.&rft.au=Abimiku%2C+A+G%3BFranchini%2C+G%3BAldrich%2C+K%3BMyagkikh%2C+M%3BMarkham%2C+P%3BGard%2C+E%3BGallo%2C+R+C%3BRobert-Guroff%2C+M&rft.aulast=Abimiku&rft.aufirst=A&rft.date=1995-03-01&rft.volume=11&rft.issue=3&rft.spage=383&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 - 1995-07-27 N1 - Date created - 1995-07-27 N1 - Date revised - 2017-01-13 N1 - Gene symbol - nef; vif; vpr; vpx N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Heat-shock proteins Hsp104 and Hsp70 reactivate mRNA splicing after heat inactivation. AN - 77333207; 7780741 AB - The heat-shock protein Hsp104 plays a crucial role in the survival of cells exposed to high temperatures and other severe stresses, but its specific functions and the biological pathways on which it operates have been unclear. Indeed, very little is known about the specific cellular processes in which any of the heat-shock proteins acts to affect thermotolerance. One essential process that is particularly sensitive to heat in many organisms is the splicing of intervening sequences from mRNA precursors. We have examined the role of Hsp104 in the repair of splicing after disruption by heat shock. When splicing in the budding yeast Saccharomyces cerevisiae was disrupted by a brief heat shock, it recovered much more rapidly in wild-type strains than in strains containing hsp104 mutations. Constitutive expression of Hsp104 promoted the recovery of heat-damaged splicing in the absence of other protein synthesis, but did not protect splicing from the initial disruption, suggesting that Hsp104 functions to repair splicing after heat damage rather than to prevent the initial damage. A modest reduction in the recovery of splicing after heat shock in an hsp70 mutant suggested that Hsp70 may also function in the repair of splicing. The roles of Hsp104 and Hsp70 were confirmed by the ability of the purified proteins to restore splicing in extracts that had been heat-inactivated in vitro. Together, these two proteins were able to restore splicing to a greater degree than could be accomplished by an optimal concentration of either protein alone. Our findings provide the first demonstration of the roles of heat-shock proteins in a biological process that is known to be particularly sensitive to heat in vivo. The results support previous genetic arguments that the Hsp104 and Hsp70 proteins have different, but related, functions in protecting cells from the toxic effects of high temperatures. Because Hsp104 and Hsp70 are able to function in vitro, after the heat-damaged substrate or substrates have been generated, neither protein is required to bind to its target(s) during heating in order to effect repair. JF - Current biology : CB AU - Vogel, J L AU - Parsell, D A AU - Lindquist, S AD - Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/03/01/ PY - 1995 DA - 1995 Mar 01 SP - 306 EP - 317 VL - 5 IS - 3 SN - 0960-9822, 0960-9822 KW - HSP104 KW - HSP70 KW - hps70 KW - hsp104 KW - Fungal Proteins KW - 0 KW - HSP70 Heat-Shock Proteins KW - Heat-Shock Proteins KW - RNA, Messenger KW - Saccharomyces cerevisiae Proteins KW - HsP104 protein, S cerevisiae KW - 143012-44-6 KW - Index Medicus KW - Genotype KW - Hot Temperature KW - Fungal Proteins -- metabolism KW - Kinetics KW - Gene Expression KW - Species Specificity KW - Mutation KW - Saccharomyces cerevisiae -- genetics KW - Heat-Shock Proteins -- metabolism KW - HSP70 Heat-Shock Proteins -- metabolism KW - Saccharomyces cerevisiae -- metabolism KW - HSP70 Heat-Shock Proteins -- biosynthesis KW - RNA, Messenger -- metabolism KW - RNA Splicing KW - Heat-Shock Proteins -- biosynthesis KW - Heat-Shock Proteins -- isolation & purification KW - HSP70 Heat-Shock Proteins -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77333207?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+biology+%3A+CB&rft.atitle=Heat-shock+proteins+Hsp104+and+Hsp70+reactivate+mRNA+splicing+after+heat+inactivation.&rft.au=Vogel%2C+J+L%3BParsell%2C+D+A%3BLindquist%2C+S&rft.aulast=Vogel&rft.aufirst=J&rft.date=1995-03-01&rft.volume=5&rft.issue=3&rft.spage=306&rft.isbn=&rft.btitle=&rft.title=Current+biology+%3A+CB&rft.issn=09609822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-20 N1 - Date created - 1995-07-20 N1 - Date revised - 2017-01-13 N1 - Gene symbol - HSP104; HSP70; hps70; hsp104 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alcohol-related cancer risk: a toxicokinetic hypothesis. AN - 77320516; 7772272 AB - Consumption of alcoholic beverages is an accepted social custom world-wide. This makes its involvement in events contributing to human cancer risk very important. Although it is neither tumorigenic nor genotoxic in animals, ethanol can potentiate the carcinogenic risk associated with certain environmentally present agents. The reasons for such a synergistic action are speculative, but among theories postulated may be ethanol's ability to modify the toxicokinetics/dynamics of carcinogen metabolism. Experiments conducted with rodents and primates support this hypothesis, demonstrating increased exposure of posthepatic organs to nitrosamines when given in combination with ethanol, followed by enhancement of DNA adduct formation and, at least in rodents, of tumor development. In addition, ethanol may induce enzymes responsible for carcinogen activation, including hepatic cytochrome P450 2E1 in rodents and humans, and in lung, kidney, and brain in rodents. Studies have also shown that these effects can extend to the next generation via maternal and in utero fetal exposure. What impact such ethanol-induced modulations have on tumorigenesis during childhood and later stages of life needs to be investigated further. JF - Alcohol (Fayetteville, N.Y.) AU - Anderson, L M AU - Chhabra, S K AU - Nerurkar, P V AU - Souliotis, V L AU - Kyrtopoulos, S A AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702, USA. PY - 1995 SP - 97 EP - 104 VL - 12 IS - 2 SN - 0741-8329, 0741-8329 KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Animals KW - Risk Factors KW - Humans KW - Models, Biological KW - Ethanol -- adverse effects KW - Neoplasms -- chemically induced KW - Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77320516?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.atitle=Alcohol-related+cancer+risk%3A+a+toxicokinetic+hypothesis.&rft.au=Anderson%2C+L+M%3BChhabra%2C+S+K%3BNerurkar%2C+P+V%3BSouliotis%2C+V+L%3BKyrtopoulos%2C+S+A&rft.aulast=Anderson&rft.aufirst=L&rft.date=1995-03-01&rft.volume=12&rft.issue=2&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.issn=07418329&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-12 N1 - Date created - 1995-07-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nitric oxide synthase-containing neurons in sensory ganglia of the rat are susceptible to capsaicin-induced cytotoxicity. AN - 77317016; 7539899 AB - Nitric oxide synthase in lumbar dorsal root ganglia of neonatal rat was studied by reduced nicotinamide adenine dinucleotide phosphate diaphorase and in situ hybridization histochemistry. Induction of nitric oxide synthase in neonatal capsaicin-treated rats after sciatic axotomy was compared with the axotomy-induced nitric oxide synthase increase observed in vehicle-treated littermates. In neonatal capsaicin-treated animals, the number of neurons constitutively labeled by reduced nicotinamide adenine dinucleotide phosphate diaphorase was greatly reduced as compared to vehicle-treated littermates. Nitric oxide synthase messenger RNA was not readily identified constitutively in dorsal root ganglion neurons. Seven days after sciatic transection the induction of reduced nicotinamide adenine dinucleotide phosphate diaphorase and nitric oxide synthase messenger RNA found in the vehicle-treated group was not observed in the capsaicin group. The presence of nitric oxide synthase in dorsal root ganglion neurons thus does not appear to protect against Ca(2+)-mediated capsaicin-induced cytotoxicity. However, since some nitric oxide synthase dorsal root ganglion neurons persist after the capsaicin neurotoxicity, nitric oxide synthase expression must occur in a neurochemically diverse subpopulation of small (< 1000 microns2) neurons. The capsaicin sensitivity of most nitric oxide synthase dorsal root ganglion neurons indicates that they have unmyelinated axons and are likely to be involved in nociception. JF - Neuroscience AU - Ren, K AU - Ruda, M A AD - Neurobiology and Anesthesiology Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 505 EP - 511 VL - 65 IS - 2 SN - 0306-4522, 0306-4522 KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Amino Acid Oxidoreductases KW - EC 1.4.- KW - NADPH Dehydrogenase KW - EC 1.6.99.1 KW - Capsaicin KW - S07O44R1ZM KW - Index Medicus KW - Rats KW - NADPH Dehydrogenase -- metabolism KW - Animals, Newborn KW - Animals KW - Rats, Sprague-Dawley KW - Sciatic Nerve -- cytology KW - Sciatic Nerve -- drug effects KW - Female KW - Pregnancy KW - Ganglia, Spinal -- cytology KW - Capsaicin -- toxicity KW - Amino Acid Oxidoreductases -- metabolism KW - Neurons, Afferent -- drug effects KW - Ganglia, Spinal -- drug effects KW - Neurons, Afferent -- enzymology KW - Ganglia, Spinal -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77317016?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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&rft.atitle=Nitric+oxide+synthase-containing+neurons+in+sensory+ganglia+of+the+rat+are+susceptible+to+capsaicin-induced+cytotoxicity.&rft.au=Ren%2C+K%3BRuda%2C+M+A&rft.aulast=Ren&rft.aufirst=K&rft.date=1995-03-01&rft.volume=65&rft.issue=2&rft.spage=505&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-10 N1 - Date created - 1995-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An approximate generalized linear model with random effects for informative missing data. AN - 77297879; 7766771 AB - This paper develops a class of models to deal with missing data from longitudinal studies. We assume that separate models for the primary response and missingness (e.g., number of missed visits) are linked by a common random parameter. Such models have been developed in the econometrics (Heckman, 1979, Econometrica 47, 153-161) and biostatistics (Wu and Carroll, 1988, Biometrics 44, 175-188) literature for a Gaussian primary response. We allow the primary response, conditional on the random parameter, to follow a generalized linear model and approximate the generalized linear model by conditioning on the data that describes missingness. The resultant approximation is a mixed generalized linear model with possibly heterogeneous random effects. An example is given to illustrate the approximate approach, and simulations are performed to critique the adequacy of the approximation for repeated binary data. JF - Biometrics AU - Follmann, D AU - Wu, M AD - Office of Biostatistics Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892, USA. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 151 EP - 168 VL - 51 IS - 1 SN - 0006-341X, 0006-341X KW - Buprenorphine KW - 40D3SCR4GZ KW - Methadone KW - UC6VBE7V1Z KW - Index Medicus KW - Methadone -- therapeutic use KW - Buprenorphine -- therapeutic use KW - Biometry -- methods KW - Random Allocation KW - Dose-Response Relationship, Drug KW - Humans KW - Bayes Theorem KW - Substance-Related Disorders -- rehabilitation KW - Longitudinal Studies KW - Time Factors KW - Mathematics KW - Models, Statistical KW - Randomized Controlled Trials as Topic -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77297879?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=An+approximate+generalized+linear+model+with+random+effects+for+informative+missing+data.&rft.au=Follmann%2C+D%3BWu%2C+M&rft.aulast=Follmann&rft.aufirst=D&rft.date=1995-03-01&rft.volume=51&rft.issue=1&rft.spage=151&rft.isbn=&rft.btitle=&rft.title=Biometrics&rft.issn=0006341X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-30 N1 - Date created - 1995-06-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modified immunoassays for polyether toxins: implications of biological matrixes, metabolic states, and epitope recognition. AN - 77294952; 7538840 AB - Polyether marine toxins are responsible for the seafood intoxication phenomena known as neurotoxic shellfish poisoning (due to brevetoxins), ciguatera (due to ciguatoxin), and diarrheic shellfish poisoning (due to okadaic acid). Using traditional techniques of hapten (pure toxin) conjugation to protein to create complete antigen, animal immunization and antibody isolation, and specific antibody subpopulation purification, discriminating antibodies have been isolated that detect brevetoxins and ciguatoxin, but not okadaic acid, in a dose-dependent fashion. Using microorganic chemistry and purified toxins, a unique set of tools has been created for the study of polyether ladder toxin accumulation; depuration; and specific site localization in tissues, food sources, and clinical samples. Developed test protocols can detect toxin in dinoflagellate cells, in extracts from food sources, in seawater and culture media, and in human serum samples. Enzyme-linked immunosorbent assay protocols developed for eventual collaborative testing have been successful in limited applications within the laboratory (correlation coefficient of 0.92 excluding 2 outliers), and alternative formats are being developed to optimize the basic test for use in research laboratories, regulatory laboratories, and field inspections. JF - Journal of AOAC International AU - Baden, D G AU - Melinek, R AU - Sechet, V AU - Trainer, V L AU - Schultz, D R AU - Rein, K S AU - Tomas, C R AU - Delgado, J AU - Hale, L AD - NIEHS Marine and Freshwater Biomedical Sciences Center, University of Miami, FL 33149, USA. PY - 1995 SP - 499 EP - 508 VL - 78 IS - 2 SN - 1060-3271, 1060-3271 KW - Antibodies KW - 0 KW - Epitopes KW - Marine Toxins KW - Oxocins KW - brevetoxin KW - 98225-48-0 KW - Index Medicus KW - Sensitivity and Specificity KW - Epitopes -- analysis KW - Cross Reactions KW - Enzyme-Linked Immunosorbent Assay -- methods KW - Marine Toxins -- isolation & purification KW - Antibodies -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77294952?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+AOAC+International&rft.atitle=Modified+immunoassays+for+polyether+toxins%3A+implications+of+biological+matrixes%2C+metabolic+states%2C+and+epitope+recognition.&rft.au=Baden%2C+D+G%3BMelinek%2C+R%3BSechet%2C+V%3BTrainer%2C+V+L%3BSchultz%2C+D+R%3BRein%2C+K+S%3BTomas%2C+C+R%3BDelgado%2C+J%3BHale%2C+L&rft.aulast=Baden&rft.aufirst=D&rft.date=1995-03-01&rft.volume=78&rft.issue=2&rft.spage=499&rft.isbn=&rft.btitle=&rft.title=Journal+of+AOAC+International&rft.issn=10603271&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-26 N1 - Date created - 1995-06-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer mortality among workers in abattoirs and meatpacking plants: an update. AN - 77269736; 7747745 AB - Workers in abattoirs and meatpacking plants have potential for exposure to bovine leukemia virus (BLV) and bovine papilloma viruses (BPV), which are oncogenic in cattle. These workers also have increased exposure to human papilloma viruses (HPV) and certain chemical carcinogens. We investigated whether such a group showed increased risk of cancers. We report mortality results after an additional 9-year follow-up of a previously studied group of 5,522 workers in abattoirs and 4,589 workers in meatpacking plants. Excess risk of all cancers combined, cancers of the lung, buccal cavity and pharynx, esophagus, colon, bladder, kidney, and bone was observed. Since factors such as tobacco smoking, alcohol, and diet, which have known associations with some of these cancers, were not taken into account, the significance of these findings is not known, except for lung cancer, for which occupational factors are probably involved. Because some of these findings have been consistently reported before, studies that will control for confounding factors as well are now urgently needed. JF - American journal of industrial medicine AU - Johnson, E S AU - Dalmas, D AU - Noss, J AU - Matanoski, G M AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 389 EP - 403 VL - 27 IS - 3 SN - 0271-3586, 0271-3586 KW - Carcinogens KW - 0 KW - Index Medicus KW - Occupational Exposure KW - Sex Factors KW - Bovine papillomavirus 1 KW - Humans KW - Papillomaviridae KW - Esophageal Neoplasms -- mortality KW - New Jersey -- epidemiology KW - Leukemia Virus, Bovine KW - Risk Factors KW - Colonic Neoplasms -- mortality KW - Cohort Studies KW - Confounding Factors (Epidemiology) KW - Middle Aged KW - Follow-Up Studies KW - Lung Neoplasms -- mortality KW - Female KW - Male KW - Abattoirs KW - Neoplasms -- mortality KW - Meat-Packing Industry KW - Occupational Diseases -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77269736?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=Cancer+mortality+among+workers+in+abattoirs+and+meatpacking+plants%3A+an+update.&rft.au=Johnson%2C+E+S%3BDalmas%2C+D%3BNoss%2C+J%3BMatanoski%2C+G+M&rft.aulast=Johnson&rft.aufirst=E&rft.date=1995-03-01&rft.volume=27&rft.issue=3&rft.spage=389&rft.isbn=&rft.btitle=&rft.title=American+journal+of+industrial+medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-15 N1 - Date created - 1995-06-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Long-term exposure to the anti-inflammatory agent phenylbutazone induces kidney tumors in rats and liver tumors in mice. AN - 77267767; 7744695 AB - Long-term toxicity and carcinogenicity of phenylbutazone, a nonsteroidal anti-inflammatory drug, were evaluated in F344/N rats and B6C3F1 mice. In 2-year studies, phenylbutazone was given in corn oil by gavage 5 days per week to groups of 50 rats of each sex at doses of 0, 50, or 100 mg/kg body weight, and to groups of 50 mice at doses of 0, 150, or 300 mg/kg body weight. Body weights and survival were similar among groups. Major target organs are kidneys in rats and liver in mice. Kidney: inflammation, papillary necrosis, and mineralization in both sexes of rats, and hyperplasia and dilatation of the pelvis epithelium, and cysts in female rats. Uncommon tubular cell tumors of the kidney were found in 13 exposed rats: 5 in the 50 mg group and 4 in the 100 mg group of males; 4 in dosed female rats; none in controls. In female rats, dose-related increases in hyperplasia of the pelvis transitional epithelium, and 2 carcinomas were discovered. Urinary bladder: papillomas of the transitional epithelium were seen in 2 low-dose male and in 1 low-dose female rats. Forestomach: ulcers in rats, with acanthosis, hyperkeratosis, and basal cell hyperplasia in female rats; however, no neoplasms were associated with these lesions. Liver: primarily in male mice exposed to phenylbutazone, hemorrhage, centrilobular cytomegaly and karyomegaly, fatty metamorphosis, cellular degeneration, and coagulative necrosis were seen; clear cell foci were observed in male mice. In summary, under the conditions of these 2-year oral intubation studies, phenylbutazone is associated with renal carcinogenicity in rats, as evidenced by increases in tubular cell neoplasms in both sexes. Evidence of carcinogenicity for male mice was shown by increased incidences and multiplicity of liver tumors. No carcinogenic activity was found for female mice. JF - Japanese journal of cancer research : Gann AU - Kari, F AU - Bucher, J AU - Haseman, J AU - Eustis, S AU - Huff, J AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 252 EP - 263 VL - 86 IS - 3 SN - 0910-5050, 0910-5050 KW - Corn Oil KW - 8001-30-7 KW - Phenylbutazone KW - GN5P7K3T8S KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Liver -- pathology KW - Hyperplasia KW - Kidney -- pathology KW - Adenoma -- chemically induced KW - Mice KW - Adenoma -- pathology KW - Species Specificity KW - Male KW - Female KW - Kidney Neoplasms -- pathology KW - Liver Neoplasms -- pathology KW - Kidney Neoplasms -- chemically induced KW - Phenylbutazone -- toxicity KW - Liver Neoplasms -- chemically induced KW - Phenylbutazone -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77267767?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Japanese+journal+of+cancer+research+%3A+Gann&rft.atitle=Long-term+exposure+to+the+anti-inflammatory+agent+phenylbutazone+induces+kidney+tumors+in+rats+and+liver+tumors+in+mice.&rft.au=Kari%2C+F%3BBucher%2C+J%3BHaseman%2C+J%3BEustis%2C+S%3BHuff%2C+J&rft.aulast=Kari&rft.aufirst=F&rft.date=1995-03-01&rft.volume=86&rft.issue=3&rft.spage=252&rft.isbn=&rft.btitle=&rft.title=Japanese+journal+of+cancer+research+%3A+Gann&rft.issn=09105050&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-12 N1 - Date created - 1995-06-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - When measurement errors correlate with truth: surprising effects of nondifferential misclassification. AN - 77263484; 7742402 AB - Most of the literature on the effect of nondifferential misclassification and errors in variables either addresses binary exposure variables or discusses continuous variables in the classical error model, where the error is assumed to be uncorrelated with the true value. In both of these situations, an imperfectly measured exposure always attenuates the relation, at least in the univariate setting. Furthermore, measuring a confounder with error independent of the exposure, even while measuring the exposure of interest perfectly, leads to partial control of the confounding. For many variables measured in epidemiology, particularly those based on self-report, however, errors are often correlated with the true value, and these rules may not apply. Epidemiologists need to be wary of deviations from the classical error model, since poor measurement might occasionally explain a positive finding even when the error does not differ by disease status. JF - Epidemiology (Cambridge, Mass.) AU - Wacholder, S AD - Biostatistics Branch, National Cancer Institute, Rockville, MD 20852, USA. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 157 EP - 161 VL - 6 IS - 2 SN - 1044-3983, 1044-3983 KW - Index Medicus KW - Biometry KW - Humans KW - Confounding Factors (Epidemiology) KW - Epidemiologic Methods KW - Environmental Exposure KW - Models, Statistical KW - Bias (Epidemiology) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77263484?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=When+measurement+errors+correlate+with+truth%3A+surprising+effects+of+nondifferential+misclassification.&rft.au=Wacholder%2C+S&rft.aulast=Wacholder&rft.aufirst=S&rft.date=1995-03-01&rft.volume=6&rft.issue=2&rft.spage=157&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 - 1995-06-13 N1 - Date created - 1995-06-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Age, gender, and other predictors of the wasting syndrome among HIV-1-infected injecting drug users. AN - 77263388; 7742405 AB - We conducted a study to identify predictors of the wasting syndrome among human immunodeficiency virus 1 (HIV-1)-seropositive injecting drug users. We enrolled 113 cases (defined as an unexplained loss of > 10% baseline weight) and 226 controls (defined as < 5% weight loss or any weight gain) from a HIV-1-seropositive cohort of injecting drug users (N = 630) into a nested case-control study. Crude predictors of wasting included: older age [odds ratio (OR) for a 1-year difference = 1.06], female gender (OR = 1.66), more years spent injecting drugs (OR for 1-year difference = 1.05), presence of diarrhea (OR = 3.78), lower percentage of CD4 T-lymphocytes (OR for 10-unit difference = 0.73), and higher log beta 2-microglobulin concentration (OR for 1 log difference = 11.3). After adjusting for CD4 cell level, beta 2-microglobulin concentration, diarrhea, gender, length and frequency of drug use, age, the presence of thrush, and education, independent predictors of weight loss in HIV-seropositive injecting drug users were female gender (OR = 2.23) and increasing age (OR for 1-year difference = 1.06). Frequency and duration of drug use were not strongly associated with the odds of developing wasting syndrome in this HIV-1-seropositive cohort. These data indicate that HIV wasting syndrome in injecting drug users is distinct from complications of drug use. JF - Epidemiology (Cambridge, Mass.) AU - Sorkin, J D AU - Bolton, P A AU - Greenblatt, J AU - Sithisarankul, P AU - Vlahov, D AU - Graham, N M AD - Epidemiology, Demography, and Biometry Program, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 172 EP - 177 VL - 6 IS - 2 SN - 1044-3983, 1044-3983 KW - Index Medicus KW - AIDS/HIV KW - Odds Ratio KW - Risk Factors KW - Humans KW - Adult KW - Case-Control Studies KW - CD4 Lymphocyte Count KW - Male KW - Female KW - Multivariate Analysis KW - HIV Infections -- physiopathology KW - Weight Loss KW - HIV-1 KW - HIV Infections -- epidemiology KW - Substance Abuse, Intravenous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77263388?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Age%2C+gender%2C+and+other+predictors+of+the+wasting+syndrome+among+HIV-1-infected+injecting+drug+users.&rft.au=Sorkin%2C+J+D%3BBolton%2C+P+A%3BGreenblatt%2C+J%3BSithisarankul%2C+P%3BVlahov%2C+D%3BGraham%2C+N+M&rft.aulast=Sorkin&rft.aufirst=J&rft.date=1995-03-01&rft.volume=6&rft.issue=2&rft.spage=172&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 - 1995-06-13 N1 - Date created - 1995-06-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Adenocarcinoma of the lung. AN - 77257666; 7742726 JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Patel, A R AU - Obrams, G I Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 175 EP - 180 VL - 4 IS - 2 KW - Genetic Markers KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Environmental Exposure KW - Disease Models, Animal KW - Genetic Predisposition to Disease KW - Lung Neoplasms -- prevention & control KW - Lung Neoplasms -- etiology KW - Adenocarcinoma -- etiology KW - Adenocarcinoma -- classification KW - Lung Neoplasms -- genetics KW - Adenocarcinoma -- genetics KW - Adenocarcinoma -- prevention & control KW - Lung Neoplasms -- classification KW - Lung Neoplasms -- pathology KW - Adenocarcinoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77257666?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=Adenocarcinoma+of+the+lung.&rft.au=Patel%2C+A+R%3BObrams%2C+G+I&rft.aulast=Patel&rft.aufirst=A&rft.date=1995-03-01&rft.volume=4&rft.issue=2&rft.spage=175&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 - 1995-06-15 N1 - Date created - 1995-06-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bispecific antibodies retarget murine T cell cytotoxicity against syngeneic breast cancer in vitro and in vivo. AN - 77238948; 7728777 AB - Bispecific antibodies with specificity for CD3 and a tumor antigen can redirect cytolytic T cells to kill tumor targets, regardless of their natural specificity. To assess the clinical potential of bispecific antibodies for treatment of human cancers we have, in the present study, adapted a totally synergeic mouse model to the targeting of mouse T cells against mouse tumors in immunocompetent mice. We show that gp52 of the mouse mammary tumor virus (MTV) can serve as a tumor-specific antigen for redirected cellular cytotoxicity. Chemically crosslinked and genetically engineered bispecific antibodies with specificities for gp52 and murine CD3 epsilon-chain induced activated mouse T cells to specifically lyse mouse mammary tumor cells from cultured lines and primary tumors from C3H-MTV+ mice. Retargeted T cells also blocked the growth of mammary tumors in vitro as well as their growth in syngeneic mice. These findings identify murine MTV-induced mammary adenocarcinomas as a solid-tumor, animal model for retargeting T cells with bispecific antibodies against syngeneic breast cancer. JF - Cancer immunology, immunotherapy : CII AU - Moreno, M B AU - Titus, J A AU - Cole, M S AU - Tso, J Y AU - Le, N AU - Paik, C H AU - Bakács, T AU - Zacharchuk, C M AU - Segal, D M AU - Wunderlich, J R AD - Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 182 EP - 190 VL - 40 IS - 3 SN - 0340-7004, 0340-7004 KW - Antibodies, Bispecific KW - 0 KW - Antigens, Viral, Tumor KW - Receptor-CD3 Complex, Antigen, T-Cell KW - Index Medicus KW - Animals KW - Antigens, Viral, Tumor -- immunology KW - Mice, Inbred C57BL KW - Mice, Inbred C3H KW - Cytotoxicity Tests, Immunologic KW - Antigens, Viral, Tumor -- analysis KW - Mice KW - Mammary Tumor Virus, Mouse -- immunology KW - Mice, Inbred BALB C KW - Receptor-CD3 Complex, Antigen, T-Cell -- immunology KW - Antibodies, Bispecific -- immunology KW - T-Lymphocytes, Cytotoxic -- immunology KW - Adenocarcinoma -- immunology KW - Cytotoxicity, Immunologic -- immunology KW - Mammary Neoplasms, Experimental -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77238948?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+immunology%2C+immunotherapy+%3A+CII&rft.atitle=Bispecific+antibodies+retarget+murine+T+cell+cytotoxicity+against+syngeneic+breast+cancer+in+vitro+and+in+vivo.&rft.au=Moreno%2C+M+B%3BTitus%2C+J+A%3BCole%2C+M+S%3BTso%2C+J+Y%3BLe%2C+N%3BPaik%2C+C+H%3BBak%C3%A1cs%2C+T%3BZacharchuk%2C+C+M%3BSegal%2C+D+M%3BWunderlich%2C+J+R&rft.aulast=Moreno&rft.aufirst=M&rft.date=1995-03-01&rft.volume=40&rft.issue=3&rft.spage=182&rft.isbn=&rft.btitle=&rft.title=Cancer+immunology%2C+immunotherapy+%3A+CII&rft.issn=03407004&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-30 N1 - Date created - 1995-05-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of lymphokine secretion and mRNA expression in the CD45RA+ and CD45RO+ subsets of human peripheral blood CD4+ and CD8+ lymphocytes. AN - 77202795; 7705392 AB - Flow cytometric analysis of human peripheral blood T lymphocytes demonstrated that the majority of the CD4+ cells were CD29+ or CD45RO+ "mature" cells while the CD8+ cells were primarily CD45RA+ "native" cells. After an initial separation into CD4+ and CD8+ cells and a secondary separation into CD45 subsets, lymphokine secretion was assessed after phorbol 12-myristate 13-acetate and ionomycin or fixed anti-CD3 stimulation. Within the respective CD45 subsets, CD4+ cells produced more interleukin (IL)-2, IL-4, and IL-6; but the CD8+ cells secreted more interferon-gamma and granulocyte/macrophage-colony-stimulating factor. Tumor necrosis factor-alpha secretion was similar in the matched CD45 subsets. Northern analysis revealed a parallel pattern of lymphokine mRNA expression in the four lymphocyte subsets. These results suggest that human CD8+ peripheral blood lymphocytes have a significant capacity to secrete lymphokines, and that the low lymphokine production observed in unseparated CD8+ cells reflects the higher percentage of less functional CD45RA+ cells. JF - European journal of immunology AU - Conlon, K AU - Osborne, J AU - Morimoto, C AU - Ortaldo, J R AU - Young, H A AD - Laboratory of Experimental Immunology, National Cancer Institute, Frederick, MD 21702-1201, USA. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 644 EP - 648 VL - 25 IS - 3 SN - 0014-2980, 0014-2980 KW - Antigens, CD3 KW - 0 KW - Lymphokines KW - RNA, Messenger KW - Ionomycin KW - 56092-81-0 KW - Antigens, CD45 KW - EC 3.1.3.48 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - AIDS/HIV KW - Antigens, CD3 -- immunology KW - T-Lymphocyte Subsets -- drug effects KW - Lymphocyte Activation -- immunology KW - Humans KW - T-Lymphocyte Subsets -- immunology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Ionomycin -- pharmacology KW - RNA, Messenger -- biosynthesis KW - CD8-Positive T-Lymphocytes -- drug effects KW - CD8-Positive T-Lymphocytes -- immunology KW - CD4-Positive T-Lymphocytes -- immunology KW - Antigens, CD45 -- immunology KW - CD4-Positive T-Lymphocytes -- drug effects KW - Lymphokines -- secretion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77202795?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+immunology&rft.atitle=Comparison+of+lymphokine+secretion+and+mRNA+expression+in+the+CD45RA%2B+and+CD45RO%2B+subsets+of+human+peripheral+blood+CD4%2B+and+CD8%2B+lymphocytes.&rft.au=Conlon%2C+K%3BOsborne%2C+J%3BMorimoto%2C+C%3BOrtaldo%2C+J+R%3BYoung%2C+H+A&rft.aulast=Conlon&rft.aufirst=K&rft.date=1995-03-01&rft.volume=25&rft.issue=3&rft.spage=644&rft.isbn=&rft.btitle=&rft.title=European+journal+of+immunology&rft.issn=00142980&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-09 N1 - Date created - 1995-05-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vitro evidence for a dual role of tumor necrosis factor-alpha in human immunodeficiency virus type 1 encephalopathy. AN - 77190414; 7695238 AB - Microglial cell activation, myelin alteration, and abundant tumor necrosis factor (TNF)-alpha message have been observed in the brains of some human immunodeficiency virus type 1 (HIV-1)-infected and demented patients. We therefore used cultures of purified human microglia and oligodendrocytes derived from adult human brain to examine the role of TNF-alpha in HIV-1 encephalopathy. Human microglia synthesize TNF-alpha message and protein in vitro. When these cells were infected with HIV-1 JrFL and maintained in the presence of TNF-alpha antibodies, soluble TNF-alpha receptors, or the TNF-alpha inhibitor pentoxifylline, viral replication was delayed or strongly inhibited. Both human microglia and oligodendrocytes express the two TNF receptors, TNF-R1, which has been implicated in cytotoxicity, and TNF-R2. While TNF-alpha may enhance HIV-1 replication in an autocrine manner, it is not toxic for microglia. In contrast, recombinant human TNF-alpha causes oligodendrocyte death in a dose-dependent manner. In situ detection of DNA fragmentation in some cells indicated that oligodendrocyte death may occur by apoptosis. Addition of live microglia or medium conditioned by these cells also resulted in 30 to 40% oligodendrocyte death, which was largely prevented by TNF-alpha inhibitors. We propose that TNF-alpha plays a dual role in HIV-1 encephalopathy, enhancing viral replication by activated microglia and damaging oligodendrocytes. Thus, TNF-alpha inhibitors may alleviate some of the neurological manifestations of acquired immunodeficiency syndrome. JF - Annals of neurology AU - Wilt, S G AU - Milward, E AU - Zhou, J M AU - Nagasato, K AU - Patton, H AU - Rusten, R AU - Griffin, D E AU - O'Connor, M AU - Dubois-Dalcq, M AD - Laboratory of Viral and Molecular Pathogenesis, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-4160. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 381 EP - 394 VL - 37 IS - 3 SN - 0364-5134, 0364-5134 KW - Antibodies KW - 0 KW - Antigens, CD KW - HIV Core Protein p24 KW - RNA, Messenger KW - Receptors, Tumor Necrosis Factor KW - Receptors, Tumor Necrosis Factor, Type I KW - Recombinant Proteins KW - Tumor Necrosis Factor-alpha KW - Pentoxifylline KW - SD6QCT3TSU KW - Index Medicus KW - AIDS/HIV KW - Pentoxifylline -- pharmacology KW - Humans KW - RNA, Messenger -- analysis KW - Receptors, Tumor Necrosis Factor -- analysis KW - Virus Replication -- physiology KW - HIV Core Protein p24 -- drug effects KW - Polymerase Chain Reaction KW - Base Sequence KW - Virus Replication -- drug effects KW - Cells, Cultured KW - Apoptosis -- drug effects KW - Molecular Sequence Data KW - HIV Core Protein p24 -- metabolism KW - Antibodies -- analysis KW - Oligodendroglia -- drug effects KW - AIDS Dementia Complex -- physiopathology KW - Tumor Necrosis Factor-alpha -- physiology KW - HIV-1 -- physiology KW - Tumor Necrosis Factor-alpha -- genetics KW - Oligodendroglia -- physiology KW - Microglia -- chemistry KW - Microglia -- virology KW - Oligodendroglia -- virology KW - Microglia -- physiology KW - Oligodendroglia -- chemistry KW - Tumor Necrosis Factor-alpha -- antagonists & inhibitors KW - HIV-1 -- drug effects KW - Microglia -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77190414?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+neurology&rft.atitle=In+vitro+evidence+for+a+dual+role+of+tumor+necrosis+factor-alpha+in+human+immunodeficiency+virus+type+1+encephalopathy.&rft.au=Wilt%2C+S+G%3BMilward%2C+E%3BZhou%2C+J+M%3BNagasato%2C+K%3BPatton%2C+H%3BRusten%2C+R%3BGriffin%2C+D+E%3BO%27Connor%2C+M%3BDubois-Dalcq%2C+M&rft.aulast=Wilt&rft.aufirst=S&rft.date=1995-03-01&rft.volume=37&rft.issue=3&rft.spage=381&rft.isbn=&rft.btitle=&rft.title=Annals+of+neurology&rft.issn=03645134&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-26 N1 - Date created - 1995-04-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Ann Neurol. 1995 Sep;38(3):483 [7668840] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA adducts of chemical carcinogens. AN - 77189120; 7697795 JF - Carcinogenesis AU - Dipple, A AD - Chemistry of Carcinogenesis Laboratory, NCI-Frederick Cancer Research and Development Center, MD 21702. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 437 EP - 441 VL - 16 IS - 3 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - DNA Adducts KW - Index Medicus KW - Biotransformation KW - Amination KW - Alkylation KW - Carcinogens -- pharmacokinetics KW - Carcinogens -- chemistry KW - Carcinogens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77189120?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=DNA+adducts+of+chemical+carcinogens.&rft.au=Dipple%2C+A&rft.aulast=Dipple&rft.aufirst=A&rft.date=1995-03-01&rft.volume=16&rft.issue=3&rft.spage=437&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-03 N1 - Date created - 1995-05-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The rat 17 alpha-hydroxylase-17,20-desmolase (CYP17) active site: computerized homology modeling and site directed mutagenesis. AN - 77187924; 7696141 AB - A homology model of the rat 17 alpha-hydroxylase-17,20 desmolase (CYP17) steroid binding domain was derived from the alpha/beta F supersecondary structural element of the 3 alpha/20 beta hydroxysteroid dehydrogenase (HSD) of Streptomyces hydrogenans that constitutes a major segment of the C19 steroid binding cavity. A CYP17 arginine-rich domain, including Arg346, Arg361 and Arg363, that has previously been shown to be important to CYP17 catalytic activity, is conserved in this HSD structural element between two HSD domains known to be important to C19 steroid binding. These two HSD motifs, in addition to a C-terminal domain at the apex of the steroid binding cavity, are also present in similar though not identical forms in the rat CYP17 sequence. The model was evaluated in terms of both hydroxylase/lyase activity and stability of CYP17 mutant proteins (Tyr334Phe, Phe343Ile, Arg357Ala, Arg361Ala, Asp345Ala), and further tested with mutagenesis of Glu353, Glu358, and Tyr431. Those amino acids located at folding junctions in the model steroid binding domain (Glu358, Arg361, and Tyr431) are each individually required to prevent degradation of the nascent protein, as well as for basic hydroxylase/lyase activity. Genomic analysis of the rat CYP17 gene reveals that this domain is contained in exon 6, and a correlation exists between the length of exon 6 and the boundaries of the HSD supersecondary element. These studies demonstrate that exon 6 of the rat CYP17 is essential for CYP17 activity, and may be structurally related to the NAD-linked prokaryote alpha/beta F supersecondary element. JF - The Journal of steroid biochemistry and molecular biology AU - Buczko, E AU - Koh, Y C AU - Miyagawa, Y AU - Dufau, M L AD - Section on Molecular Endocrinology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 209 EP - 218 VL - 52 IS - 3 SN - 0960-0760, 0960-0760 KW - CYP17 KW - Pregnenes KW - 0 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Cortisone Reductase KW - EC 1.1.1.53 KW - Steroid 17-alpha-Hydroxylase KW - EC 1.14.14.19 KW - Aldehyde-Lyases KW - EC 4.1.2.- KW - Index Medicus KW - Streptomyces -- enzymology KW - Cortisone Reductase -- chemistry KW - Animals KW - Protein Structure, Secondary KW - Gene Expression KW - Amino Acid Sequence KW - Microsomes -- enzymology KW - Structure-Activity Relationship KW - Binding Sites KW - Rats KW - Mutagenesis, Site-Directed KW - Exons -- genetics KW - Base Sequence KW - Conserved Sequence -- genetics KW - Molecular Sequence Data KW - Pregnenes -- metabolism KW - Cortisone Reductase -- genetics KW - Cell Line KW - Computer Simulation KW - Cytochrome P-450 Enzyme System -- genetics KW - Aldehyde-Lyases -- metabolism KW - Cytochrome P-450 Enzyme System -- chemistry KW - Cytochrome P-450 Enzyme System -- metabolism KW - Models, Chemical KW - Sequence Homology, Amino Acid KW - Aldehyde-Lyases -- chemistry KW - Aldehyde-Lyases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77187924?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+steroid+biochemistry+and+molecular+biology&rft.atitle=The+rat+17+alpha-hydroxylase-17%2C20-desmolase+%28CYP17%29+active+site%3A+computerized+homology+modeling+and+site+directed+mutagenesis.&rft.au=Buczko%2C+E%3BKoh%2C+Y+C%3BMiyagawa%2C+Y%3BDufau%2C+M+L&rft.aulast=Buczko&rft.aufirst=E&rft.date=1995-03-01&rft.volume=52&rft.issue=3&rft.spage=209&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+steroid+biochemistry+and+molecular+biology&rft.issn=09600760&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-28 N1 - Date created - 1995-04-28 N1 - Date revised - 2017-01-13 N1 - Gene symbol - CYP17 N1 - Genetic sequence - U14953; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Diabeteslike proliferative retinal changes in galactose-fed dogs. AN - 77174552; 7887849 AB - To determine whether diabeteslike lesions associated with the proliferative stage of diabetic retinopathy develop in galactose-fed dogs, since studies designed to define the complex biochemical effects of prolonged hyperglycemia on retinal vessels have been hampered by the lack of an animal model that mirrors both the early and advanced stages of diabetic retinopathy. Eyes from 9-month-old male beagles fed a daily diet containing either 30% nonnutrient filler (control diet) or 30% galactose (galactose diet) for up to 84 months were enucleated and histologically examined. Retinal vessel changes associated with the proliferative stage were observed in two of nine galactose-fed dogs while the remainder demonstrated retinal changes that included the appearance of microaneurysms, acellular capillary beds associated with areas of nonperfusion, and intraretinal microvascular abnormalities. Proliferative changes were evidenced by the formation of preretinal fibrous membranes and the appearance of fibrovascular membranes on the retinal surface and on the posterior hyaloid membrane. No retinal lesions were observed in similar dogs fed a control diet for up to 84 months. The galactose-fed dog appears to be the first animal model that can develop diabeteslike retinal vessel changes associated with both the early and advanced stages of retinopathy, including the proliferative stage. JF - Archives of ophthalmology (Chicago, Ill. : 1960) AU - Kador, P F AU - Takahashi, Y AU - Wyman, M AU - Ferris, F AD - National Eye Institute, National Institutes of Health, Bethesda, Md. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 352 EP - 354 VL - 113 IS - 3 SN - 0003-9950, 0003-9950 KW - Galactose KW - X2RN3Q8DNE KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Vitreous Hemorrhage -- chemically induced KW - Retinal Neovascularization -- pathology KW - Cataract -- chemically induced KW - Disease Models, Animal KW - Cataract -- etiology KW - Vitreous Hemorrhage -- etiology KW - Hyperglycemia -- chemically induced KW - Diabetes Mellitus, Experimental -- pathology KW - Retinal Neovascularization -- chemically induced KW - Dogs KW - Retina -- pathology KW - Hyperglycemia -- pathology KW - Male KW - Retinal Vessels -- pathology KW - Diabetic Retinopathy -- pathology KW - Diabetic Retinopathy -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77174552?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+ophthalmology+%28Chicago%2C+Ill.+%3A+1960%29&rft.atitle=Diabeteslike+proliferative+retinal+changes+in+galactose-fed+dogs.&rft.au=Kador%2C+P+F%3BTakahashi%2C+Y%3BWyman%2C+M%3BFerris%2C+F&rft.aulast=Kador&rft.aufirst=P&rft.date=1995-03-01&rft.volume=113&rft.issue=3&rft.spage=352&rft.isbn=&rft.btitle=&rft.title=Archives+of+ophthalmology+%28Chicago%2C+Ill.+%3A+1960%29&rft.issn=00039950&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-10 N1 - Date created - 1995-04-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Arch Ophthalmol. 1995 Mar;113(3):275-6 [7887838] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hymenoptera, hypersensitivity, and history: a prologue to current day concepts and practices in the diagnosis, treatment, and prevention of insect sting allergy. AN - 77174286; 7889376 JF - Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology AU - Cohen, S G AU - Bianchine, P J AD - Intramural Research Division, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 198 EP - 217; quiz 217-21 VL - 74 IS - 3 SN - 1081-1206, 1081-1206 KW - Index Medicus KW - History of medicine KW - Loveless Mary KW - Benson KW - Barnard KW - Animals KW - History, 20th Century KW - Humans KW - History, 19th Century KW - Philately -- history KW - Hypersensitivity -- diagnosis KW - Insect Bites and Stings -- immunology KW - Hypersensitivity -- history KW - Hypersensitivity -- prevention & control KW - Hymenoptera -- immunology KW - Insect Bites and Stings -- history UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77174286?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+allergy%2C+asthma+%26+immunology+%3A+official+publication+of+the+American+College+of+Allergy%2C+Asthma%2C+%26+Immunology&rft.atitle=Hymenoptera%2C+hypersensitivity%2C+and+history%3A+a+prologue+to+current+day+concepts+and+practices+in+the+diagnosis%2C+treatment%2C+and+prevention+of+insect+sting+allergy.&rft.au=Cohen%2C+S+G%3BBianchine%2C+P+J&rft.aulast=Cohen&rft.aufirst=S&rft.date=1995-03-01&rft.volume=74&rft.issue=3&rft.spage=198&rft.isbn=&rft.btitle=&rft.title=Annals+of+allergy%2C+asthma+%26+immunology+%3A+official+publication+of+the+American+College+of+Allergy%2C+Asthma%2C+%26+Immunology&rft.issn=10811206&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-20 N1 - Date created - 1995-04-20 N1 - Date revised - 2017-01-13 N1 - People - Benson; Loveless Mary; Barnard N1 - Last updated - 2017-01-18 N1 - SubjectsTermNotLitGenreText - Benson; Loveless Mary; Barnard ER - TY - JOUR T1 - Gene specific DNA repair of damage induced in familial Alzheimer disease cells by ultraviolet irradiation or by nitrogen mustard. AN - 77173647; 7885382 AB - We have measured gene specific DNA repair in a normal human fibroblast cell line, and in fibroblast lines from two patients with familial Alzheimer disease (AD). Cells were treated with either ultraviolet radiation (UV) or the chemotherapeutic alkylating agent, nitrogen mustard (HN2). DNA damage formation and repair were studied in the active dihydrofolate reductase (DHFR) gene for the main lesions introduced by each of these two types of DNA damaging agents. The gene specific repair of UV induced cyclobutane pyrimidine dimers in the human DHFR gene was 86% complete in the AD cells after 24 h of repair incubation. This repair efficiency was similar to what we and others have found in normal human fibroblasts. After treatment of the AD cells with HN2, we found the frequency of HN2 induced lesions in the DHFR gene to be similar to the frequency in the transcriptionally inactive delta-globin gene. The gene specific repair of HN2 induced lesions in the DHFR gene was completed within 8-24 h in the normal fibroblast line and in the familial AD line, and the repair kinetics were similar for both cell lines. These results indicate that familial AD fibroblasts have normal gene specific repair of both UV induced and HN2 induced DNA damage in active genes. JF - Mutation research AU - Link, C J AU - Robbins, J H AU - Bohr, V A AD - Laboratory of Molecular Pharmacology, National Cancer Institute, NIH, Bethesda, MD 20892. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 115 EP - 121 VL - 336 IS - 2 SN - 0027-5107, 0027-5107 KW - Pyrimidine Dimers KW - 0 KW - Mechlorethamine KW - 50D9XSG0VR KW - Globins KW - 9004-22-2 KW - Tetrahydrofolate Dehydrogenase KW - EC 1.5.1.3 KW - Index Medicus KW - DNA Damage KW - Cells, Cultured KW - Humans KW - Globins -- genetics KW - Fibroblasts KW - DNA Repair -- physiology KW - Ultraviolet Rays -- adverse effects KW - Alzheimer Disease -- metabolism KW - Mechlorethamine -- adverse effects KW - Tetrahydrofolate Dehydrogenase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77173647?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Gene+specific+DNA+repair+of+damage+induced+in+familial+Alzheimer+disease+cells+by+ultraviolet+irradiation+or+by+nitrogen+mustard.&rft.au=Link%2C+C+J%3BRobbins%2C+J+H%3BBohr%2C+V+A&rft.aulast=Link&rft.aufirst=C&rft.date=1995-03-01&rft.volume=336&rft.issue=2&rft.spage=115&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 - 1995-04-12 N1 - Date created - 1995-04-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Esophagopleural fistula: a complication of photodynamic therapy. AN - 77170683; 7886521 AB - Mesothelioma of the pleura remains an incurable disease for which novel treatments are being investigated. One of these is intraoperative photodynamic therapy (PDT), using the principle of cell cytotoxicity produced by light-activated sensitization. We report a complication of this therapy that defined the maximal tolerated dose of PDT, ie, esophagopleural fistula, in two consecutive patients who had received the same dose of PDT at the time of extrapleural pneumonectomy. JF - Southern medical journal AU - Temeck, B K AU - Pass, H I AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Md 20892. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 271 EP - 274 VL - 88 IS - 3 SN - 0038-4348, 0038-4348 KW - Abridged Index Medicus KW - Index Medicus KW - Pneumonectomy KW - Dose-Response Relationship, Drug KW - Combined Modality Therapy KW - Humans KW - Adult KW - Middle Aged KW - Male KW - Female KW - Mesothelioma -- drug therapy KW - Pleural Diseases -- chemically induced KW - Esophageal Fistula -- chemically induced KW - Photochemotherapy -- adverse effects KW - Mesothelioma -- surgery KW - Pleural Neoplasms -- drug therapy KW - Fistula -- chemically induced KW - Pleural Neoplasms -- surgery UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77170683?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Esophagopleural+fistula%3A+a+complication+of+photodynamic+therapy.&rft.au=Temeck%2C+B+K%3BPass%2C+H+I&rft.aulast=Temeck&rft.aufirst=B&rft.date=1995-03-01&rft.volume=88&rft.issue=3&rft.spage=271&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 - 1995-04-12 N1 - Date created - 1995-04-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nutrition and metal toxicity. AN - 77167098; 7879732 AB - Lead, cadmium, and mercury are toxic metals that are not essential for nutrition. However, the toxic effects of these metals may be mediated or enhanced by interactions or deficiencies of nutritionally essential metals. Lead competes with calcium, inhibiting the release of neurotransmitters, and interferes with the regulation of cell metabolism by binding to second-messenger calcium receptors, blocking calcium transport by calcium channels and calcium-sodium ATP pumps, and by competing for calcium-binding protein sites and uptake by mitochondria. Dietary deficiencies of calcium, iron, and zinc enhance the effects of lead on cognitive and behavioral development. Iron deficiency increases the gastrointestinal absorption of cadmium, and cadmium competes with zinc for binding sites on metallothionein, which is important in the storage and transport of zinc during development. Selenium protects from mercury and methyl mercury toxicity by preventing damage from free radicals or by forming inactive selenium mercury complexes. JF - The American journal of clinical nutrition AU - Goyer, R A AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27707. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 646S EP - 650S VL - 61 IS - 3 Suppl SN - 0002-9165, 0002-9165 KW - Metals KW - 0 KW - Iron KW - E1UOL152H7 KW - Calcium KW - SY7Q814VUP KW - Abridged Index Medicus KW - Index Medicus KW - Calcium -- metabolism KW - Animals KW - Drug Interactions KW - Humans KW - Iron -- deficiency KW - Diet KW - Metals -- poisoning KW - Nutritional Physiological Phenomena UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77167098?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+clinical+nutrition&rft.atitle=Nutrition+and+metal+toxicity.&rft.au=Goyer%2C+R+A&rft.aulast=Goyer&rft.aufirst=R&rft.date=1995-03-01&rft.volume=61&rft.issue=3+Suppl&rft.spage=646S&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+clinical+nutrition&rft.issn=00029165&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-31 N1 - Date created - 1995-03-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of the proximal promoter of the human histone H2A.Z gene. AN - 77166959; 7880446 AB - Histone H2A.Z is a distinct and evolutionarily conserved member of the histone H2A family whose synthesis, in contrast to that of most other histone species, is not dependent on DNA replication. The gene for H2A.Z lacks the signals involved in the 3' processing of replication-linked histone mRNA species and contains introns as well as polyadenylation signals. The H2A.Z gene proximal promoter, a 200-bp region upstream of the transcription start site that provides maximal activity in CAT reporter studies, contains three CCAAT and two GGGCGG elements as well as a consensus TATA element. In vitro DNase I footprint analysis of this region indicated that the central CCAAT and the distal GGGCGG elements were protected by factors present in HeLa nuclear extract. Site-directed mutations of selected promoter elements were generated in the H2A.Z gene promoter region of a CAT reporter construct by a novel one-step PCR procedure. Of the elements examined, the central CCAAT element was found to be the most important determinant of promoter activity; its disruption decreased CAT reporter activity by 65%. Disruption of the proximal CCAAT or the distal GGGCGG elements led to decreases in activity of 40%, while disruption of any of the other examined led to smaller decreases. Gel-mobility shift analysis showed that the three CCAAT elements had overlapping but not identical binding specificities for nuclear factors. The two GGGCGG elements both were found to bind transcription factor Sp1, but the distal element bound Sp1 with higher affinity. The findings show that the central and proximal CCAAT elements and the distal GGGCGG element appear to be the major determinants of the transcriptional activity of the H2A.Z gene. JF - DNA and cell biology AU - Hatch, C L AU - Bonner, W M AD - Laboratory of Molecular Pharmacology, DTP, DCT, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 257 EP - 266 VL - 14 IS - 3 SN - 1044-5498, 1044-5498 KW - Histones KW - 0 KW - Sp1 Transcription Factor KW - Transcription Factors KW - Deoxyribonuclease I KW - EC 3.1.21.1 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Transcription Factors -- metabolism KW - HeLa Cells KW - Deoxyribonuclease I -- metabolism KW - Humans KW - Sp1 Transcription Factor -- metabolism KW - Molecular Sequence Data KW - Genes, Reporter KW - Gene Expression Regulation KW - Promoter Regions, Genetic KW - Histones -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77166959?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=DNA+and+cell+biology&rft.atitle=Characterization+of+the+proximal+promoter+of+the+human+histone+H2A.Z+gene.&rft.au=Hatch%2C+C+L%3BBonner%2C+W+M&rft.aulast=Hatch&rft.aufirst=C&rft.date=1995-03-01&rft.volume=14&rft.issue=3&rft.spage=257&rft.isbn=&rft.btitle=&rft.title=DNA+and+cell+biology&rft.issn=10445498&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-12 N1 - Date created - 1995-04-12 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - L10137; GENBANK; L10138 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer chemoprevention agent development strategies for genistein. AN - 77166447; 7884556 AB - Cancer chemoprevention refers to the reduction of cancer incidence by administration of agents or drugs that inhibit, reverse or retard the cancer process. Genistein has demonstrated a wide variety of biological activities that make it a good candidate for a chemopreventive agent. Many agents, such as genistein, are currently being tested with the goal of developing safe and effective chemopreventive drugs for human use. Genistein was investigated as a potential chemopreventive agent in an azoxymethane-induced colon carcinogenesis model. Genistein was tested for its ability to inhibit aberrant colon crypts in the colon of F344 rats that had been treated with azoxymethane. Genistein was administered in the diet from 1 wk before the carcinogen to 4 wk after the first carcinogen dose for a total of 5 wk. At both doses, 75 and 150 mg/kg, the mean number of foci per colon was significantly reduced. Further development of this agent includes demonstration of the preventive efficacy in an in vivo tumorigenesis model, followed by preclinical pharmacology and toxicology testing. Phase 1, 2 and 3 clinical chemoprevention trials would be then performed to determine pharmacokinetics, safe doses, and effectiveness for New Drug Approval. JF - The Journal of nutrition AU - Steele, V E AU - Pereira, M A AU - Sigman, C C AU - Kelloff, G J AD - Chemoprevention Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 713S EP - 716S VL - 125 IS - 3 Suppl SN - 0022-3166, 0022-3166 KW - Antineoplastic Agents KW - 0 KW - Isoflavones KW - Genistein KW - DH2M523P0H KW - Index Medicus KW - Animals KW - Colon -- pathology KW - Dose-Response Relationship, Drug KW - Colon -- drug effects KW - Disease Models, Animal KW - Rats KW - Colonic Neoplasms -- epidemiology KW - Rats, Inbred F344 KW - Microvilli -- ultrastructure KW - Microvilli -- drug effects KW - Colon -- ultrastructure KW - Colonic Neoplasms -- drug therapy KW - Incidence KW - Colonic Neoplasms -- prevention & control KW - Time Factors KW - Male KW - Neoplasms, Experimental -- epidemiology KW - Antineoplastic Agents -- standards KW - Isoflavones -- pharmacology KW - Neoplasms, Experimental -- prevention & control KW - Neoplasms, Experimental -- drug therapy KW - Antineoplastic Agents -- therapeutic use KW - Isoflavones -- therapeutic use KW - Isoflavones -- standards KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77166447?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+nutrition&rft.atitle=Cancer+chemoprevention+agent+development+strategies+for+genistein.&rft.au=Steele%2C+V+E%3BPereira%2C+M+A%3BSigman%2C+C+C%3BKelloff%2C+G+J&rft.aulast=Steele&rft.aufirst=V&rft.date=1995-03-01&rft.volume=125&rft.issue=3+Suppl&rft.spage=713S&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+nutrition&rft.issn=00223166&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-12 N1 - Date created - 1995-04-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pneumocystis carinii pneumonia: a major complication of immunosuppressive therapy in patients with Wegener's granulomatosis. AN - 77164889; 7881673 AB - The risk factors and clinical and laboratory parameters in Pneumocystis carinii pneumonia in patients with Wegener's granulomatosis have not been well characterized. We undertook a retrospective chart review of all patients with a diagnosis of Wegener's granulomatosis and P. carinii pneumonia who were followed at the National Institute of Allergy and Infectious Diseases of the National Institutes of Health. The chart review focused on clinical, laboratory, and roentgenologic evidence of P. carinii pneumonia. Eleven cases of P. carinii pneumonia were diagnosed in some 180 patients with Wegener's granulomatosis, for an overall incidence of approximately 6%. All patients developed P. carinii pneumonia either during the initial course of treatment or during therapy for recurrent Wegener's granulomatosis. All patients were receiving daily glucocorticoids and a second immunosuppressive therapy. Lymphocytopenia was noted in all patients, with a mean +/- SEM total lymphocyte count of 303 +/- 69 cells/microL. All patients tested (10 of 11) were seronegative for human immunodeficiency virus (HIV) infection. Eight presented with worsening chest roentgenograms compared with baseline, whereas three presented with normal chest roentgenograms. We conclude that P. carinii is a common opportunistic pathogen in patients with Wegener's granulomatosis receiving immunosuppressive therapy. Therapeutic immunosuppression (daily glucocorticoids and immunosuppressive agents) and the resultant lymphocytopenia, as well as the lymphocyte and monocyte functional abnormalities caused by glucocorticoids, may be the most likely factors predisposing to P. carinii pneumonia in patients with Wegener's granulomatosis. Based on our data, all patients with Wegener's granulomatosis should be given chemoprophylaxis against P. carinii while they are receiving daily glucocorticoids.(ABSTRACT TRUNCATED AT 250 WORDS) JF - American journal of respiratory and critical care medicine AU - Ognibene, F P AU - Shelhamer, J H AU - Hoffman, G S AU - Kerr, G S AU - Reda, D AU - Fauci, A S AU - Leavitt, R Y AD - Department of Critical Care Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892-1662. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 795 EP - 799 VL - 151 IS - 3 Pt 1 SN - 1073-449X, 1073-449X KW - Immunosuppressive Agents KW - 0 KW - Prednisone KW - VB0R961HZT KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Prednisone -- adverse effects KW - Risk Factors KW - Prednisone -- therapeutic use KW - Humans KW - Retrospective Studies KW - Incidence KW - Middle Aged KW - Immunosuppressive Agents -- therapeutic use KW - Male KW - Female KW - Immunosuppressive Agents -- adverse effects KW - Opportunistic Infections -- epidemiology KW - Immunosuppression -- adverse effects KW - Granulomatosis with Polyangiitis -- complications KW - Pneumonia, Pneumocystis -- complications KW - Pneumonia, Pneumocystis -- epidemiology KW - Opportunistic Infections -- complications KW - Granulomatosis with Polyangiitis -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77164889?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+respiratory+and+critical+care+medicine&rft.atitle=Pneumocystis+carinii+pneumonia%3A+a+major+complication+of+immunosuppressive+therapy+in+patients+with+Wegener%27s+granulomatosis.&rft.au=Ognibene%2C+F+P%3BShelhamer%2C+J+H%3BHoffman%2C+G+S%3BKerr%2C+G+S%3BReda%2C+D%3BFauci%2C+A+S%3BLeavitt%2C+R+Y&rft.aulast=Ognibene&rft.aufirst=F&rft.date=1995-03-01&rft.volume=151&rft.issue=3+Pt+1&rft.spage=795&rft.isbn=&rft.btitle=&rft.title=American+journal+of+respiratory+and+critical+care+medicine&rft.issn=1073449X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-07 N1 - Date created - 1995-04-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Am J Respir Crit Care Med. 1995 Oct;152(4 Pt 1):1424 [7551403] Am J Respir Crit Care Med. 1995 Dec;152(6 Pt 1):2202 [8520798] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risks of withdrawing antipsychotic medications. AN - 77161468; 7872847 JF - Archives of general psychiatry AU - Wyatt, R J AD - Neuropsychiatry Branch, National Institute of Mental Health Neuroscience Center at St Elizabeth's, Washington, DC 20032. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 205 EP - 208 VL - 52 IS - 3 SN - 0003-990X, 0003-990X KW - Antipsychotic Agents KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Drug Administration Schedule KW - Risk-Taking KW - Risk Factors KW - Humans KW - Dyskinesia, Drug-Induced -- epidemiology KW - Schizophrenic Psychology KW - Follow-Up Studies KW - Dyskinesia, Drug-Induced -- etiology KW - Chronic Disease KW - Meta-Analysis as Topic KW - Recurrence KW - Substance Withdrawal Syndrome -- etiology KW - Substance Withdrawal Syndrome -- prevention & control KW - Antipsychotic Agents -- therapeutic use KW - Schizophrenia -- drug therapy KW - Antipsychotic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77161468?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+general+psychiatry&rft.atitle=Risks+of+withdrawing+antipsychotic+medications.&rft.au=Wyatt%2C+R+J&rft.aulast=Wyatt&rft.aufirst=R&rft.date=1995-03-01&rft.volume=52&rft.issue=3&rft.spage=205&rft.isbn=&rft.btitle=&rft.title=Archives+of+general+psychiatry&rft.issn=0003990X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-27 N1 - Date created - 1995-03-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thyroid cancer after exposure to external radiation: a pooled analysis of seven studies. AN - 77158920; 7871153 AB - The thyroid gland of children is especially vulnerable to the carcinogenic action of ionizing radiation. To provide insights into various modifying influences on risk, seven major studies with organ doses to individual subjects were evaluated. Five cohort studies (atomic bomb survivors, children treated for tinea capitis, two studies of children irradiated for enlarged tonsils, and infants irradiated for an enlarged thymus gland) and two case-control studies (patients with cervical cancer and childhood cancer) were studied. The combined studies include almost 120,000 people (approximately 58,000 exposed to a wide range of doses and 61,000 nonexposed subjects), nearly 700 thyroid cancers and 3,000,000 person years of follow-up. For persons exposed to radiation before age 15 years, linearity best described the dose response, even down to 0.10 Gy. At the highest doses (> 10 Gy), associated with cancer therapy, there appeared to be a decrease or leveling of risk. For childhood exposures, the pooled excess relative risk per Gy (ERR/Gy) was 7.7 (95% CI = 2.1, 28.7) and the excess absolute risk per 10(4) PY Gy (EAR/10(4) PY Gy) was 4.4 (95% CI = 1.9, 10.1). The attributable risk percent (AR%) at 1 Gy was 88%. However, these summary estimates were affected strongly by age at exposure even within this limited age range. The ERR was greater (P = 0.07) for females than males, but the findings from the individual studies were not consistent. The EAR was higher among women, reflecting their higher rate of naturally occurring thyroid cancer. The distribution of ERR over time followed neither a simple multiplicative nor an additive pattern in relation to background occurrence. Only two cases were seen within 5 years of exposure. The ERR began to decline about 30 years after exposure but was still elevated at 40 years. Risk also decreased significantly with increasing age at exposure, with little risk apparent after age 20 years. Based on limited data, there was a suggestion that spreading dose over time (from a few days to > 1 year) may lower risk, possibly due to the opportunity for cellular repair mechanisms to operate. The thyroid gland in children has one of the highest risk coefficients of any organ and is the only tissue with convincing evidence for risk about 1.10 Gy. JF - Radiation research AU - Ron, E AU - Lubin, J H AU - Shore, R E AU - Mabuchi, K AU - Modan, B AU - Pottern, L M AU - Schneider, A B AU - Tucker, M A AU - Boice, J D AD - Epidemiology and Biostatistics Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 259 EP - 277 VL - 141 IS - 3 SN - 0033-7587, 0033-7587 KW - Index Medicus KW - Space life sciences KW - Infant KW - Nuclear Warfare KW - Humans KW - Cohort Studies KW - Adult KW - Case-Control Studies KW - Child KW - Adolescent KW - Male KW - Female KW - Radiotherapy -- adverse effects KW - Child, Preschool KW - Thyroid Neoplasms -- epidemiology KW - Neoplasms, Radiation-Induced -- epidemiology KW - Thyroid Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77158920?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Radiation+research&rft.atitle=Thyroid+cancer+after+exposure+to+external+radiation%3A+a+pooled+analysis+of+seven+studies.&rft.au=Ron%2C+E%3BLubin%2C+J+H%3BShore%2C+R+E%3BMabuchi%2C+K%3BModan%2C+B%3BPottern%2C+L+M%3BSchneider%2C+A+B%3BTucker%2C+M+A%3BBoice%2C+J+D&rft.aulast=Ron&rft.aufirst=E&rft.date=1995-03-01&rft.volume=141&rft.issue=3&rft.spage=259&rft.isbn=&rft.btitle=&rft.title=Radiation+research&rft.issn=00337587&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-30 N1 - Date created - 1995-03-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Triethylenemelamine: induction of specific-locus mutations in the ad-3 region of heterokaryon 12 of Neurospora crassa. AN - 77153873; 7870102 AB - The mutagenicity of the trifunctional alkylating (or cross-linking) agent TEM (triethylenemelamine or 2,4,6-tris(1-aziridinyl)-1,3,5-triazine) in the adenine-3 (ad-3) region was studied with a two-component heterokaryon (H-12) of Neurospora crassa. The objective was to characterize the genetic damage produced by this chemical to determine the spectrum of specific-locus mutations induced in a lower eukaryotic organism and to compare this spectrum with that induced in the mouse. Specific-locus mutations in the ad-3 region of strain H-12 result from gene/point mutations, multiple-locus mutations, and multilocus deletion mutations at the closely linked ad-3A and ad-3B loci. These loci control two sequential biochemical reactions in the purine biosynthetic pathway. A 0.1 M solution of TEM was used to treat conidial suspensions of H-12 for 20, 40, 80, 120, or 170 min to obtain dose-response curves for (1) inactivation of conidia, and (2) the induction of specific-locus mutations in the ad-3 region. These experiments demonstrated that TEM is a strong mutagen (maximum forward-mutation frequency between 100 and 1000 ad-3 mutations per 10(6) survivors) for the induction of specific-locus mutations in the ad-3 region. Both biochemical and classical genetic tests were used to characterize the TEM-induced ad-3 mutations from each of the five treatment groups to distinguish between the different genotypic classes and subclasses. The overall data base from these genetic studies demonstrates that TEM-induced ad-3 mutations result predominantly (95.5% [769/805]) from gene/point mutations at the ad-3A and ad-3B loci, and from a low percentage (4.5% [36/805) of multilocus deletion mutations. In addition, TEM induces an unusually high frequency of multiple-locus mutations with sites of recessive lethal damage closely linked with the ad-3 region. Comparison of the dose-response curves for the major classes and subclasses of TEM-induced ad-3 mutations demonstrates (1) that gene/point mutations and multilocus deletion mutations increase as the 1.4 power of TEM treatment time, and (2) that the two classes of TEM-induced multiple-locus ad-3 mutations consisting of gene/point mutations with separate sites of recessive lethal damage increase at about the 1.96 power of TEM treatment time. When the data from the present specific-locus studies are compared with those in the mouse, we find, insofar as such comparisons are possible, that a similar spectrum of specific-locus mutations has been induced by TEM in each assay system. JF - Mutation research AU - de Serres, F J AU - Malling, H V AD - Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709-2233. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 87 EP - 111 VL - 327 IS - 1-2 SN - 0027-5107, 0027-5107 KW - ad-3 KW - DNA, Fungal KW - 0 KW - Triethylenemelamine KW - F7IY6HZG9D KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - DNA Damage KW - Point Mutation KW - Genetic Complementation Test KW - Mice KW - DNA, Fungal -- drug effects KW - Genes, Lethal KW - Genes, Recessive KW - Neurospora crassa -- genetics KW - Genes, Fungal -- drug effects KW - Neurospora crassa -- drug effects KW - Triethylenemelamine -- pharmacology KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77153873?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Triethylenemelamine%3A+induction+of+specific-locus+mutations+in+the+ad-3+region+of+heterokaryon+12+of+Neurospora+crassa.&rft.au=de+Serres%2C+F+J%3BMalling%2C+H+V&rft.aulast=de+Serres&rft.aufirst=F&rft.date=1995-03-01&rft.volume=327&rft.issue=1-2&rft.spage=87&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 - 1995-03-30 N1 - Date created - 1995-03-30 N1 - Date revised - 2017-01-13 N1 - Gene symbol - ad-3 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Follicle-stimulating hormone concentrations in relation to active and passive smoking. AN - 77153412; 7862381 AB - To determine the association between various forms of tobacco exposure and ovarian status, as measured by FSH concentrations, in women 38-49 years old. Two hundred ninety women between 38-49 years old, who had not had hysterectomy or oophorectomy, completed a self-administered questionnaire that included information on tobacco exposure and had serum FSH levels measured on days 2-4 of the menstrual cycle. Linear regression was used to assess the relation between FSH and tobacco exposure. Controlling for age and other factors, FSH concentrations were 66% higher among current smokers (geometric mean FSH 14.0 mIU/mL) and 39% higher among nonsmokers with passive smoke exposure (11.7 mIU/mL), compared to nonsmoking women without passive smoke exposure (8.4 mIU/mL). The estimated increase in FSH for each year of age was greater for current smokers than for nonsmokers (16 versus 6%, respectively). Ex-smokers did not have higher FSH concentrations, and there was no association between prenatal exposure to tobacco smoke and FSH. Both active and passive smoking are associated with elevated FSH concentrations in women 38-49 years old. The effect, limited to women with current exposure, is consistent with a shorter duration of the menopausal transition period. JF - Obstetrics and gynecology AU - Cooper, G S AU - Baird, D D AU - Hulka, B S AU - Weinberg, C R AU - Savitz, D A AU - Hughes, C L AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 407 EP - 411 VL - 85 IS - 3 SN - 0029-7844, 0029-7844 KW - Tobacco Smoke Pollution KW - 0 KW - Follicle Stimulating Hormone KW - 9002-68-0 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Linear Models KW - Adult KW - Surveys and Questionnaires KW - Case-Control Studies KW - Middle Aged KW - Female KW - Smoking -- blood KW - Follicle Stimulating Hormone -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77153412?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Obstetrics+and+gynecology&rft.atitle=Follicle-stimulating+hormone+concentrations+in+relation+to+active+and+passive+smoking.&rft.au=Cooper%2C+G+S%3BBaird%2C+D+D%3BHulka%2C+B+S%3BWeinberg%2C+C+R%3BSavitz%2C+D+A%3BHughes%2C+C+L&rft.aulast=Cooper&rft.aufirst=G&rft.date=1995-03-01&rft.volume=85&rft.issue=3&rft.spage=407&rft.isbn=&rft.btitle=&rft.title=Obstetrics+and+gynecology&rft.issn=00297844&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-23 N1 - Date created - 1995-03-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutational analysis of the redox-sensitive transcriptional regulator OxyR: regions important for oxidation and transcriptional activation. AN - 77152900; 7868602 AB - OxyR is a redox-sensitive transcriptional regulator of the LysR family which activates the expression of genes important for the defense against hydrogen peroxide in Escherichia coli and Samonella typhimurium. OxyR is sensitive to oxidation and reduction, and only oxidized OxyR is able to activate transcription of its target genes. Using site-directed mutagenesis, we found that one cysteine residue (C-199) is critical for the redox sensitivity of OxyR, and a C-199-->S mutation appears to lock the OxyR protein in the reduced form. We also used a random mutagenesis approach to isolate eight constitutively active mutants. All of the mutations are located in the C-terminal half of the protein, and four of the mutations map near the critical C-199 residue. In vivo as well as in vitro transcription experiments showed that the constitutive mutant proteins were able to activate transcription under both oxidizing and reducing conditions, and DNase I footprints showed that this activation is due to the ability of the mutant proteins to induce cooperative binding of RNA polymerase. Unexpectedly, RNA polymerase was also found to reciprocally affect OxyR binding. JF - Journal of bacteriology AU - Kullik, I AU - Toledano, M B AU - Tartaglia, L A AU - Storz, G AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 1275 EP - 1284 VL - 177 IS - 5 SN - 0021-9193, 0021-9193 KW - oxyR KW - Bacterial Proteins KW - 0 KW - DNA-Binding Proteins KW - Escherichia coli Proteins KW - Repressor Proteins KW - Transcription Factors KW - oxyR protein, E coli KW - LysR protein, Bacteria KW - 87609-37-8 KW - Hydrogen Peroxide KW - BBX060AN9V KW - DNA-Directed RNA Polymerases KW - EC 2.7.7.6 KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Cysteine -- genetics KW - DNA Mutational Analysis KW - Drug Resistance, Microbial -- genetics KW - Hydrogen Peroxide -- pharmacology KW - Amino Acid Sequence KW - Transcription Factors -- genetics KW - Selection, Genetic KW - Protein Binding KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Oxidation-Reduction KW - Base Sequence KW - DNA-Directed RNA Polymerases -- metabolism KW - Molecular Sequence Data KW - Binding Sites -- genetics KW - Sequence Homology, Amino Acid KW - Bacterial Proteins -- genetics KW - Signal Transduction -- genetics KW - Escherichia coli -- genetics KW - Transcription, Genetic KW - Oxidative Stress -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77152900?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+bacteriology&rft.atitle=Mutational+analysis+of+the+redox-sensitive+transcriptional+regulator+OxyR%3A+regions+important+for+oxidation+and+transcriptional+activation.&rft.au=Kullik%2C+I%3BToledano%2C+M+B%3BTartaglia%2C+L+A%3BStorz%2C+G&rft.aulast=Kullik&rft.aufirst=I&rft.date=1995-03-01&rft.volume=177&rft.issue=5&rft.spage=1275&rft.isbn=&rft.btitle=&rft.title=Journal+of+bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-27 N1 - Date created - 1995-03-27 N1 - Date revised - 2017-01-13 N1 - Gene symbol - oxyR N1 - SuppNotes - Cited By: Nucleic Acids Res. 1990 Feb 25;18(4):979-88 [2107533] J Bacteriol. 1995 Mar;177(5):1285-91 [7868603] J Biol Chem. 1990 Jul 5;265(19):10797-800 [2193024] J Gen Microbiol. 1990 Mar;136(3):455-62 [2167922] J Biol Chem. 1991 Jun 15;266(17):10830-8 [2040603] J Biochem. 1991 Feb;109(2):262-6 [1864839] J Mol Biol. 1991 Oct 20;221(4):1325-44 [1942054] Mol Microbiol. 1991 Nov;5(11):2719-25 [1779761] Cell. 1992 May 15;69(4):659-67 [1586946] Mol Plant Microbe Interact. 1989 May-Jun;2(3):97-106 [2520822] Nature. 1992 Jun 25;357(6380):655-60 [1614514] Genes Dev. 1993 Jan;7(1):149-60 [8422984] Mol Microbiol. 1993 Mar;7(6):859-64 [8483417] Annu Rev Microbiol. 1993;47:597-626 [8257110] Nature. 1970 Aug 15;227(5259):680-5 [5432063] Can J Biochem. 1975 Mar;53(3):298-307 [1125817] J Bacteriol. 1978 Jun;134(3):1141-56 [149110] Nature. 1978 Aug 24;274(5673):762-5 [355890] Methods Enzymol. 1979;68:245-67 [232214] J Mol Biol. 1984 Oct 25;179(2):233-56 [6502713] Proc Natl Acad Sci U S A. 1984 Nov;81(22):6929-33 [6390428] Cell. 1985 Jul;41(3):753-62 [2988786] Proc Natl Acad Sci U S A. 1987 Dec;84(24):8917-21 [3321061] J Bacteriol. 1989 Jan;171(1):130-40 [2701932] Proc Natl Acad Sci U S A. 1989 May;86(10):3484-8 [2471187] J Biol Chem. 1989 Jul 25;264(21):12330-8 [2501303] EMBO J. 1989 Aug;8(8):2403-10 [2551682] Mol Gen Genet. 1989 Sep;218(3):371-6 [2511419] J Mol Biol. 1989 Dec 20;210(4):709-19 [2693740] Mol Microbiol. 1989 Nov;3(11):1567-77 [2615655] J Biol Chem. 1990 Mar 5;265(7):3844-50 [2406264] EMBO J. 1994 Jan 1;13(1):138-46 [8306957] Cell. 1994 Sep 9;78(5):897-909 [8087856] Mol Microbiol. 1994 Jul;13(2):265-72 [7984106] Methods Enzymol. 1994;234:217-23 [7528872] Science. 1990 Apr 13;248(4952):189-94 [2183352] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential effects of P-glycoprotein inhibitors on NIH3T3 cells transfected with wild-type (G185) or mutant (V185) multidrug transporters. AN - 77151748; 7866993 AB - Multidrug resistance (MDR) may be associated with the expression of the MDR1 gene which encodes the 170-kDa cell surface P-glycoprotein (PGP) acting as an energy-dependent multidrug efflux pump. This pump can be inhibited by a variety of drugs including cyclosporin A, quinidine, and verapamil. Substrate specificity of the MDR1 gene product can be altered by a point mutation at amino acid residue 185 in which valine is substituted for glycine, but the effect of this mutation on inhibition of PGP is unknown. Multidrug-resistant NIH3T3 cells transfected with the MDR1 retroviral vector pHaMDR-1/A (G185) or pHaMDR1/A (V185) expressing comparable levels of PGP were compared for patterns of drug resistance and inhibition of drug resistance by MDR reversing agents. The NIH-MDR-G185 transfectants were somewhat preferentially resistant to daunorubicin, taxol, and vinblastine. The mutant (V185) conferred increased resistance to colchicine. This MDR phenotype in both NIH-MDR-G185- and NIH-MDR-V185-transfected NIH3T3 cells was overcome by the addition of cyclosporin A, quinidine, or verapamil. Verapamil was the most potent of the three agents affecting wild-type PGP. However, specific inhibitors showed different potency with wild-type or mutant transporters, depending on the cytotoxic drug whose resistance was being reversed. For example, cyclosporin A at a concentration of 1 microgram/ml, was a powerful reverser of taxol and colchicine resistance for the mutant drug transporter, but was much less effective for the wild-type transporter. In contrast, verapamil reversed resistance to vinblastine more efficiently for the wild-type transporter than for the mutant transporter. These results suggest that the sensitivity of a multidrug transporter to a reversing agent will depend on the reversing agent, the cytotoxic drug, and the presence or absence of mutations which alter substrate specificity. JF - Cancer research AU - Cardarelli, C O AU - Aksentijevich, I AU - Pastan, I AU - Gottesman, M M AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255. Y1 - 1995/03/01/ PY - 1995 DA - 1995 Mar 01 SP - 1086 EP - 1091 VL - 55 IS - 5 SN - 0008-5472, 0008-5472 KW - MDR1 KW - Antineoplastic Agents KW - 0 KW - Carrier Proteins KW - Membrane Glycoproteins KW - P-Glycoprotein KW - Cyclosporine KW - 83HN0GTJ6D KW - Verapamil KW - CJ0O37KU29 KW - Quinidine KW - ITX08688JL KW - Colchicine KW - SML2Y3J35T KW - Index Medicus KW - Phenotype KW - Colchicine -- toxicity KW - Drug Screening Assays, Antitumor KW - Animals KW - Cell Survival -- drug effects KW - Cyclosporine -- pharmacology KW - Quinidine -- pharmacology KW - Membrane Glycoproteins -- analysis KW - Mice KW - Verapamil -- pharmacology KW - Cell Death -- drug effects KW - Biological Transport, Active KW - Carrier Proteins -- pharmacokinetics KW - P-Glycoprotein -- genetics KW - P-Glycoprotein -- analysis KW - 3T3 Cells -- drug effects KW - Transfection KW - 3T3 Cells -- physiology KW - Carrier Proteins -- genetics KW - Antineoplastic Agents -- pharmacokinetics KW - Point Mutation KW - Antineoplastic Agents -- pharmacology KW - P-Glycoprotein -- antagonists & inhibitors KW - Drug Resistance, Multiple -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77151748?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+effects+of+P-glycoprotein+inhibitors+on+NIH3T3+cells+transfected+with+wild-type+%28G185%29+or+mutant+%28V185%29+multidrug+transporters.&rft.au=Cardarelli%2C+C+O%3BAksentijevich%2C+I%3BPastan%2C+I%3BGottesman%2C+M+M&rft.aulast=Cardarelli&rft.aufirst=C&rft.date=1995-03-01&rft.volume=55&rft.issue=5&rft.spage=1086&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 - 1995-03-30 N1 - Date created - 1995-03-30 N1 - Date revised - 2017-01-13 N1 - Gene symbol - MDR1 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of cell-type-specific interleukin-2 receptor alpha-chain gene expression: potential role of physical interactions between Elf-1, HMG-I(Y), and NF-kappa B family proteins. AN - 77149944; 7862168 AB - The interleukin 2 receptor alpha-chain (IL-2R alpha) gene is rapidly and potently induced in T cells in response to mitogenic stimuli. Previously, an inducible enhancer between nucleotides -299 and -228 that contains NF-kappa B and CArG motifs was identified. We now report the characterization of a second essential positive regulatory element located between nucleotides -137 and -64 that binds Elf-1 and HMG-I(Y). This element had maximal activity in lymphoid cells, paralleling the cell type specificity of Elf-1 expression. Transcription from the IL-2R alpha promoter was inhibited when either the Elf-1 or the HMG-I(Y) binding site was mutated. Coexpression of both proteins activated transcription of the -137 to -64 element in COS-7 cells. Elf-1 physically associated with HMG-I and with NF-kappa B p50 and c-Rel in vitro, suggesting that protein-protein interactions might functionally coordinate the actions of the upstream and downstream positive regulatory elements. This is the first report of a physical interaction between an Ets family member and NF-kappa B family proteins. These findings provide significant new insights into the protein-protein and protein-DNA interactions that regulate cell-type-specific and inducible IL-2R alpha gene expression and also have implications for other genes regulated by Elf-1 and NF-kappa B family proteins. JF - Molecular and cellular biology AU - John, S AU - Reeves, R B AU - Lin, J X AU - Child, R AU - Leiden, J M AU - Thompson, C B AU - Leonard, W J AD - Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 1786 EP - 1796 VL - 15 IS - 3 SN - 0270-7306, 0270-7306 KW - DNA Primers KW - 0 KW - DNA-Binding Proteins KW - ELF1 protein, human KW - Elf1 protein, mouse KW - High Mobility Group Proteins KW - Macromolecular Substances KW - NF-kappa B KW - Nuclear Proteins KW - Oligonucleotide Probes KW - Receptors, Interleukin-2 KW - Recombinant Proteins KW - Transcription Factors KW - HMGA1a Protein KW - 124544-67-8 KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Nuclear Proteins -- isolation & purification KW - Chloramphenicol O-Acetyltransferase -- biosynthesis KW - Recombinant Proteins -- biosynthesis KW - Sequence Homology, Nucleic Acid KW - Humans KW - Transcription, Genetic KW - Mutagenesis, Site-Directed KW - Tumor Cells, Cultured KW - Molecular Sequence Data KW - Nuclear Proteins -- metabolism KW - T-Lymphocytes -- immunology KW - Mice KW - Cell Nucleus KW - Binding Sites KW - Polymerase Chain Reaction KW - Base Sequence KW - T-Lymphocytes -- metabolism KW - Transfection KW - Enhancer Elements, Genetic KW - Cercopithecus aethiops KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Line KW - NF-kappa B -- isolation & purification KW - Regulatory Sequences, Nucleic Acid KW - Gene Expression Regulation -- physiology KW - High Mobility Group Proteins -- isolation & purification KW - Transcription Factors -- metabolism KW - Transcription Factors -- isolation & purification KW - Receptors, Interleukin-2 -- biosynthesis KW - Gene Expression Regulation -- drug effects KW - DNA-Binding Proteins -- isolation & purification KW - Receptors, Interleukin-2 -- genetics KW - High Mobility Group Proteins -- metabolism KW - NF-kappa B -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77149944?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Regulation+of+cell-type-specific+interleukin-2+receptor+alpha-chain+gene+expression%3A+potential+role+of+physical+interactions+between+Elf-1%2C+HMG-I%28Y%29%2C+and+NF-kappa+B+family+proteins.&rft.au=John%2C+S%3BReeves%2C+R+B%3BLin%2C+J+X%3BChild%2C+R%3BLeiden%2C+J+M%3BThompson%2C+C+B%3BLeonard%2C+W+J&rft.aulast=John&rft.aufirst=S&rft.date=1995-03-01&rft.volume=15&rft.issue=3&rft.spage=1786&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 - 1995-03-23 N1 - Date created - 1995-03-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nucleic Acids Res. 1992 Jan 25;20(2):376 [1311073] Science. 1994 Mar 11;263(5152):1453-4 [8128231] Cell. 1994 Apr 8;77(1):5-8 [8156597] Trends Genet. 1994 Mar;10(3):94-100 [8178371] Nature. 1994 May 26;369(6478):330-3 [8183373] Nature. 1994 May 26;369(6478):333-6 [7514277] EMBO J. 1994 Jun 15;13(12):2822-30 [8026467] Cell. 1987 Jun 19;49(6):741-52 [3034433] Nucleic Acids Res. 1987 Jul 10;15(13):5490 [3037497] Genes Dev. 1987 Dec;1(10):1147-60 [2828167] Cell. 1988 Jun 3;53(5):827-36 [2836068] Nature. 1988 Jun 23;333(6175):776-8 [2838755] Biochem Int. 1988 May;16(5):963-71 [3262346] Immunol Rev. 1994 Apr;138:61-86 [8070818] Mol Cell Biol. 1994 Oct;14(10):6452-63 [7935370] Proc Natl Acad Sci U S A. 1981 Dec;78(12):7575-8 [6278479] FEBS Lett. 1983 Feb 21;152(2):163-7 [6297996] Nucleic Acids Res. 1983 Mar 11;11(5):1475-89 [6828386] Nature. 1984 Oct 18-24;311(5987):626-31 [6090948] Nature. 1984 Oct 18-24;311(5987):631-5 [6090949] Proc Natl Acad Sci U S A. 1985 Sep;82(18):6281-5 [3929255] Science. 1985 Nov 8;230(4726):633-9 [2996141] Nucleic Acids Res. 1985 Nov 11;13(21):7579-89 [2999698] Mol Cell Biol. 1985 Dec;5(12):3610-6 [3915782] Anal Biochem. 1986 Aug 15;157(1):53-62 [3464222] Science. 1986 Nov 14;234(4778):859-63 [3095922] Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1291-5 [1741383] Mol Cell Biol. 1992 Mar;12(3):1043-53 [1545787] Cell. 1992 Apr 3;69(1):185-95 [1555239] J Exp Med. 1992 May 1;175(5):1391-9 [1569404] Science. 1992 Jul 17;257(5068):379-82 [1631559] Cell Growth Differ. 1992 May;3(5):327-34 [1633115] Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6958-62 [1495986] Trends Biochem Sci. 1992 Jul;17(7):251-6 [1502727] Mol Cell Biol. 1992 Sep;12(9):4067-75 [1508203] J Virol. 1992 Oct;66(10):5890-7 [1527846] Cell. 1992 Nov 27;71(5):777-89 [1330326] Chromosoma. 1992 Oct;101(10):602-8 [1385053] Cell. 1993 Apr 9;73(1):147-57 [8462096] Cell. 1993 Apr 9;73(1):5-8 [8462103] Cell. 1993 Sep 10;74(5):887-98 [8374955] J Biol Chem. 1993 Oct 5;268(28):21137-46 [8407950] Mol Cell Biol. 1993 Oct;13(10):6201-10 [8413220] Nucleic Acids Res. 1993 Sep 11;21(18):4259-67 [8414980] EMBO J. 1993 Dec;12(12):4667-76 [8223476] J Exp Med. 1993 Nov 1;178(5):1681-92 [8228815] Genes Dev. 1993 Dec;7(12A):2418-30 [8253387] Science. 1993 Dec 17;262(5141):1874-7 [8266076] Science. 1993 Dec 17;262(5141):1877-80 [8266077] Science. 1993 Dec 17;262(5141):1880-3 [8266078] Mol Cell Biol. 1994 Feb;14(2):1153-9 [8289796] Proc Natl Acad Sci U S A. 1986 Dec;83(24):9694-8 [3099289] Cell. 1987 Apr 10;49(1):47-56 [3030566] J Biol Chem. 1987 Apr 15;262(11):5079-86 [3031040] Cell. 1988 Dec 23;55(6):989-1003 [3203386] Proc Natl Acad Sci U S A. 1989 Apr;86(7):2331-5 [2494663] Science. 1989 Apr 28;244(4903):466-9 [2497520] Science. 1989 May 5;244(4904):551-6 [2785715] Mol Cell Biol. 1989 May;9(5):2114-23 [2701943] Oncogene. 1989 Jul;4(7):935-42 [2666912] EMBO J. 1989 Jul;8(7):2023-8 [2529117] J Cell Biol. 1989 Nov;109(5):1975-82 [2808516] Mol Cell Biol. 1990 Feb;10(2):850-3 [2153927] Mol Cell Biol. 1990 Mar;10(3):1249-53 [2137553] Proc Natl Acad Sci U S A. 1990 Mar;87(5):1830-4 [2308942] Genes Dev. 1990 Apr;4(4):667-79 [2163347] Nature. 1990 Jul 12;346(6280):191-3 [2114554] Cell. 1990 Sep 7;62(5):1007-18 [2203531] Cell. 1990 Oct 5;63(1):47-61 [2208281] Science. 1990 Nov 9;250(4982):814-8 [2237431] Science. 1991 Mar 22;251(5000):1490-3 [2006423] New Biol. 1989 Oct;1(1):83-92 [2518691] New Biol. 1990 Jul;2(7):642-7 [2083254] Science. 1991 Aug 16;253(5021):762-8 [1876833] Nature. 1991 Dec 19-26;354(6354):531-4 [1722028] Mol Cell Biol. 1992 Feb;12(2):894-903 [1732752] Cell. 1992 Feb 7;68(3):597-612 [1339307] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The transcriptional activator GCN4 contains multiple activation domains that are critically dependent on hydrophobic amino acids. AN - 77149894; 7862116 AB - GCN4 is a transcriptional activator in the bZIP family that regulates amino acid biosynthetic genes in the yeast Saccharomyces cerevisiae. Previous work suggested that the principal activation domain of GCN4 is a highly acidic segment of approximately 40 amino acids located in the center of the protein. We conducted a mutational analysis of GCN4 with a single-copy allele expressed under the control of the native promoter and translational control elements. Our results indicate that GCN4 contains two activation domains of similar potency that can function independently to promote high-level transcription of the target genes HIS3 and HIS4. One of these domains is coincident with the acidic activation domain defined previously; the other extends over the N-terminal one-third of the protein. Both domains are partially dependent on the coactivator protein ADA2. Each domain appears to be composed of two or more small subdomains that have additive effects on transcription and that can cooperate in different combinations to promote high-level expression of HIS3 and HIS4. At least three of these subdomains are critically dependent on bulky hydrophobic amino acids for their function. Five of the important hydrophobic residues, Phe-97, Phe-98, Met-107, Tyr-110, and Leu-113, fall within a region of proposed sequence homology between GCN4 and the herpesvirus acidic activator VP16. The remaining three residues, Trp-120, Leu-123, and Phe-124, are highly conserved between GCN4 and its Neurospora counterpart, cpc-1. Because of the functional redundancy in the activation domain, mutations at positions 97 and 98 must be combined with mutations at positions 120 to 124 to observe a substantial reduction in activation by full-length GCN4, and substitution of all eight hydrophobic residues was required to inactivate full-length GCN4. These hydrophobic residues may mediate important interactions between GCN4 and one or more of its target proteins in the transcription initiation complex. JF - Molecular and cellular biology AU - Drysdale, C M AU - Dueñas, E AU - Jackson, B M AU - Reusser, U AU - Braus, G H AU - Hinnebusch, A G AD - Section on Molecular Genetics of Lower Eukaryotes, National Institute of Child Health and Human Development, Bethesda, Maryland 20892. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 1220 EP - 1233 VL - 15 IS - 3 SN - 0270-7306, 0270-7306 KW - GCN4 KW - HIS3 KW - HIS4 KW - DNA-Binding Proteins KW - 0 KW - Fungal Proteins KW - Recombinant Proteins KW - Saccharomyces cerevisiae Proteins KW - Transcription Factors KW - Alcohol Oxidoreductases KW - EC 1.1.- KW - HIS4 protein, S cerevisiae KW - EC 1.1.1.23 KW - Protein Kinases KW - EC 2.7.- KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Aminohydrolases KW - EC 3.5.4.- KW - Pyrophosphatases KW - EC 3.6.1.- KW - Hydro-Lyases KW - EC 4.2.1.- KW - imidazoleglycerolphosphate dehydratase KW - EC 4.2.1.19 KW - Index Medicus KW - Recombinant Proteins -- biosynthesis KW - Hydro-Lyases -- biosynthesis KW - Transcription Factors -- metabolism KW - Gene Expression KW - Transcription, Genetic KW - Mutagenesis KW - Recombinant Proteins -- metabolism KW - Hydro-Lyases -- genetics KW - Molecular Sequence Data KW - Transcription Factors -- chemistry KW - Recombinant Proteins -- chemistry KW - beta-Galactosidase -- biosynthesis KW - Sequence Deletion KW - Immunoblotting KW - DNA Mutational Analysis KW - Amino Acid Sequence KW - Transcription Factors -- biosynthesis KW - Transcription Factors -- genetics KW - Transcriptional Activation KW - Binding Sites KW - Polymerase Chain Reaction KW - Mutagenesis, Insertional KW - Fungal Proteins -- chemistry KW - Protein Kinases -- metabolism KW - Fungal Proteins -- metabolism KW - Saccharomyces cerevisiae -- metabolism KW - Genes, Fungal KW - Protein Kinases -- biosynthesis KW - Fungal Proteins -- biosynthesis KW - Fungal Proteins -- genetics KW - Protein Kinases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77149894?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=The+transcriptional+activator+GCN4+contains+multiple+activation+domains+that+are+critically+dependent+on+hydrophobic+amino+acids.&rft.au=Drysdale%2C+C+M%3BDue%C3%B1as%2C+E%3BJackson%2C+B+M%3BReusser%2C+U%3BBraus%2C+G+H%3BHinnebusch%2C+A+G&rft.aulast=Drysdale&rft.aufirst=C&rft.date=1995-03-01&rft.volume=15&rft.issue=3&rft.spage=1220&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 - 1995-03-23 N1 - Date created - 1995-03-23 N1 - Date revised - 2017-01-13 N1 - Gene symbol - GCN4; HIS3; HIS4 N1 - SuppNotes - Cited By: Nature. 1988 Jun 16;333(6174):635-40 [3287180] Cell. 1993 Jan 29;72(2):247-60 [7678780] Science. 1988 Jun 24;240(4860):1759-64 [3289117] Mol Cell Biol. 1988 Sep;8(9):3827-36 [3065626] Nature. 1989 Mar 2;338(6210):39-44 [2521923] Genetics. 1989 May;122(1):19-27 [2659436] Cell. 1989 Jun 16;57(6):947-54 [2661015] Mol Cell Biol. 1989 Nov;9(11):4882-8 [2689869] Nature. 1990 Jun 28;345(6278):783-6 [2193231] Nature. 1990 Jul 26;346(6282):329-31 [2142753] Nature. 1990 Nov 1;348(6296):82-5 [2234066] Science. 1991 Jan 4;251(4989):87-90 [1846049] Cell. 1991 Mar 8;64(5):971-81 [2001592] Mol Cell Biol. 1991 May;11(5):2723-35 [2017175] Nature. 1991 Jun 13;351(6327):588-90 [1646402] Nature. 1991 Oct 10;353(6344):569-71 [1922364] Science. 1991 Oct 25;254(5031):539-44 [1948029] Science. 1992 May 29;256(5061):1333-5 [1598579] Cell. 1992 Jul 24;70(2):251-65 [1638630] Nature. 1970 Aug 15;227(5259):680-5 [5432063] Anal Biochem. 1976 May 7;72:248-54 [942051] Cell. 1980 Mar;19(3):753-64 [6244896] Proc Natl Acad Sci U S A. 1983 Sep;80(17):5374-8 [6351059] Gene. 1983 Nov;25(1):71-82 [6319233] Cell. 1986 Apr 25;45(2):201-7 [3516411] Cell. 1986 Sep 12;46(6):885-94 [3530496] Cell. 1987 Mar 13;48(5):847-53 [3028647] Science. 1987 Aug 21;237(4817):874-80 [3303332] EMBO J. 1987 Sep;6(9):2781-4 [3678204] Methods Enzymol. 1987;154:164-75 [3323810] Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):883-7 [8381535] Cell. 1993 Feb 26;72(4):481-3 [8440015] Cell. 1993 Feb 26;72(4):575-85 [8440021] Cell. 1993 Feb 26;72(4):587-94 [8440022] Nature. 1993 Jun 24;363(6431):741-4 [8515819] Cell. 1993 Nov 5;75(3):519-30 [8221891] Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):192-6 [8278363] Nature. 1994 Mar 31;368(6470):466-9 [8133894] Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2488-92 [8146144] Cell. 1994 Apr 8;77(1):1-3 [8156586] Cell. 1994 Apr 8;77(1):5-8 [8156597] Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3520-4 [8170939] Nature. 1994 May 19;369(6477):252-5 [8183347] Cell. 1994 May 20;77(4):599-608 [8187178] Mol Cell Biol. 1994 Sep;14(9):6021-9 [8065335] Genes Dev. 1994 May 15;8(10):1235-46 [7926727] Mol Cell Biol. 1994 Dec;14(12):7920-32 [7969132] J Virol. 1992 Sep;66(9):5500-8 [1323708] EMBO J. 1992 Nov;11(11):4145-52 [1396595] Mol Cell Biol. 1992 Dec;12(12):5700-10 [1333044] Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12028-32 [1465435] Cell. 1992 Dec 24;71(7):1223-37 [1473154] Proc Natl Acad Sci U S A. 1988 Jun;85(11):3728-32 [2967496] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dopamine transporter cysteine mutants: second extracellular loop cysteines are required for transporter expression. AN - 77148830; 7861176 AB - Studies with thiol-modifying reagents have suggested that cysteines might play important roles in the function of the dopamine transporter (DAT). To identify DAT cysteines with important thiol groups, we have studied six mutant dopamine transporters in which cysteines were replaced by alanines. Substitutions of cysteines assigned to the DAT's second putative extracellular loop--positions 180 and 189--dramatically decreased the expression of the mutant transporters. Substitutions at positions 90, 242, 305, and 345 had no significant effect in decreasing dopamine uptake, MPP+ uptake, or cocaine analogue binding. Immunostaining COS cells transfected with Cys180 and Cys189 to Ala mutants revealed reduced membrane staining and prominent staining in perinuclear regions consistent with Golgi apparatus. These results suggest that cysteines i the DAT second extracellular loop may provide sulfide residues crucial to full transporter expression, at least in part, through interference with membrane insertion. Conceivably, they might also provide the targets for the influences of thiol-modifying reagents in modifying the function of the wild-type DAT expressed in striatal membranes. JF - Journal of neurochemistry AU - Wang, J B AU - Moriwaki, A AU - Uhl, G R AD - Division of Intramural Research, National Institute on Drug Abuse, Baltimore, MD 21224. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 1416 EP - 1419 VL - 64 IS - 3 SN - 0022-3042, 0022-3042 KW - Carrier Proteins KW - 0 KW - Dopamine Plasma Membrane Transport Proteins KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Recombinant Proteins KW - (1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester KW - 50370-56-4 KW - Cocaine KW - I5Y540LHVR KW - Cysteine KW - K848JZ4886 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Cysteine -- chemistry KW - Cocaine -- analogs & derivatives KW - In Vitro Techniques KW - Cercopithecus aethiops KW - Dopamine -- metabolism KW - Cell Membrane -- metabolism KW - Cocaine -- metabolism KW - Structure-Activity Relationship KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77148830?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Dopamine+transporter+cysteine+mutants%3A+second+extracellular+loop+cysteines+are+required+for+transporter+expression.&rft.au=Wang%2C+J+B%3BMoriwaki%2C+A%3BUhl%2C+G+R&rft.aulast=Wang&rft.aufirst=J&rft.date=1995-03-01&rft.volume=64&rft.issue=3&rft.spage=1416&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 - 1995-03-17 N1 - Date created - 1995-03-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protection and potentiation of 1-methyl-4-phenylpyridinium-induced toxicity by cytochrome P450 inhibitors and inducer may be due to the altered uptake of the toxin. AN - 77148097; 7861152 AB - Earlier studies from our laboratory have demonstrated that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity could be modulated by inhibitors and inducer of cytochrome P450 (P450) in an in vitro model consisting of sagittal slices of mouse brain. To understand the molecular mechanisms underlying the role of P450 on MPTP toxicity, it was undertaken to study the effect of the modulators of P450 on the toxicity of the metabolite of MPTP, namely, 1-methyl-4-phenylpyridinium ion (MPP+). Incubation of mouse brain slices with various concentrations of MPP+ (1-100 microM) resulted in dose-dependent inhibition of mitochondrial enzyme NADH-dehydrogenase (NADH-DH) and leakage of the cytosolic enzyme lactate dehydrogenase from the slice into the medium. MPP(+)-induced toxicity was abolished by pretreatment of the slices with inhibitors of monoamine oxidase (MAO; pargyline and deprenyl) or inhibitors of P450 (piperonyl butoxide or SKF-525A) or dopamine uptake blocker (GBR-12909), as measured by the activity of NADH-DH in slices and leakage of lactate dehydrogenase from the slice into the medium. Slices prepared from mice pretreated with phenobarbital (an inducer of P450) potentiated the toxic effects of MPP+. Pretreatment of slices with MAO-inhibitor, P450 inhibitors, or dopamine uptake blocker attenuated the uptake of MPP+ into the slices. In contrast, MPP+ uptake was significantly increased in slices prepared from phenobarbital-pretreated mice. Thus, both MAO and P450 inhibitors abolish the toxicity of MPP+ in the sagittal slices of mouse brain by altering the uptake of the toxin into the slices. JF - Journal of neurochemistry AU - Sriram, K AU - Pai, K S AU - Ravindranath, V AD - Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bangalore, India. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 1203 EP - 1208 VL - 64 IS - 3 SN - 0022-3042, 0022-3042 KW - Monoamine Oxidase Inhibitors KW - 0 KW - Piperazines KW - vanoxerine KW - 90X28IKH43 KW - Proadifen KW - A510CA4CBT KW - Piperonyl Butoxide KW - LWK91TU9AH KW - 1-Methyl-4-phenylpyridinium KW - R865A5OY8J KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Animals KW - Proadifen -- pharmacology KW - Phenobarbital -- pharmacology KW - In Vitro Techniques KW - Mice KW - Piperazines -- pharmacology KW - Monoamine Oxidase Inhibitors -- pharmacology KW - Male KW - Piperonyl Butoxide -- pharmacology KW - Biological Transport -- drug effects KW - 1-Methyl-4-phenylpyridinium -- toxicity KW - Brain -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77148097?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Protection+and+potentiation+of+1-methyl-4-phenylpyridinium-induced+toxicity+by+cytochrome+P450+inhibitors+and+inducer+may+be+due+to+the+altered+uptake+of+the+toxin.&rft.au=Sriram%2C+K%3BPai%2C+K+S%3BRavindranath%2C+V&rft.aulast=Sriram&rft.aufirst=K&rft.date=1995-03-01&rft.volume=64&rft.issue=3&rft.spage=1203&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 - 1995-03-17 N1 - Date created - 1995-03-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Virion incorporation of envelope glycoproteins with long but not short cytoplasmic tails is blocked by specific, single amino acid substitutions in the human immunodeficiency virus type 1 matrix. AN - 77140179; 7853546 AB - Incorporation of envelope glycoproteins into a budding retrovirus is an essential step in the formation of an infectious virus particle. By using site-directed mutagenesis, we identified specific amino acid residues in the matrix domain of the human immunodeficiency virus type 1 (HIV-1) Gag protein that are critical to the incorporation of HIV-1 envelope glycoproteins into virus particles. Pseudotyping analyses were used to demonstrate that two heterologous envelope glycoproteins with short cytoplasmic tails (the envelope of the amphotropic murine leukemia virus and a naturally truncated HIV-2 envelope) are efficiently incorporated into HIV-1 particles bearing the matrix mutations. Furthermore, deletion of the cytoplasmic tail of HIV-1 transmembrane envelope glycoprotein gp41 from 150 to 7 or 47 residues reversed the incorporation block imposed by the matrix mutations. These results suggest the existence of a specific functional interaction between the HIV-1 matrix and the gp41 cytoplasmic tail. JF - Journal of virology AU - Freed, E O AU - Martin, M A AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-0460. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 1984 EP - 1989 VL - 69 IS - 3 SN - 0022-538X, 0022-538X KW - Gene Products, gag KW - 0 KW - HIV Envelope Protein gp41 KW - Viral Envelope Proteins KW - Index Medicus KW - AIDS/HIV KW - Virus Replication KW - Mutagenesis, Site-Directed KW - HeLa Cells KW - Humans KW - Cytoplasm KW - Morphogenesis KW - HIV Envelope Protein gp41 -- metabolism KW - Virion -- metabolism KW - Leukemia Virus, Murine -- ultrastructure KW - HIV-2 -- ultrastructure KW - Structure-Activity Relationship KW - Sequence Deletion KW - Viral Envelope Proteins -- metabolism KW - Gene Products, gag -- metabolism KW - HIV-1 -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77140179?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Virion+incorporation+of+envelope+glycoproteins+with+long+but+not+short+cytoplasmic+tails+is+blocked+by+specific%2C+single+amino+acid+substitutions+in+the+human+immunodeficiency+virus+type+1+matrix.&rft.au=Freed%2C+E+O%3BMartin%2C+M+A&rft.aulast=Freed&rft.aufirst=E&rft.date=1995-03-01&rft.volume=69&rft.issue=3&rft.spage=1984&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 - 1995-03-13 N1 - Date created - 1995-03-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1989 Nov;63(11):4670-5 [2677400] J Virol. 1989 Oct;63(10):4395-403 [2778881] Nature. 1989 Oct 19;341(6243):573-4 [2677749] Proc Natl Acad Sci U S A. 1990 Jan;87(2):523-7 [2405382] Science. 1990 Feb 16;247(4944):848-52 [2305256] J Virol. 1990 May;64(5):2298-308 [1691314] J Virol. 1990 Aug;64(8):3770-8 [2164597] AIDS. 1990 Jun;4(6):575-6 [2386620] Cell. 1990 Oct 5;63(1):77-86 [2170021] J Virol. 1991 Jan;65(1):162-9 [1845882] J Virol. 1991 Aug;65(8):4350-8 [2072454] AIDS. 1991 Jun;5(6):617-37 [1652977] AIDS. 1991 Jun;5(6):639-54 [1883539] Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):70-4 [1729720] J Virol. 1992 Apr;66(4):2232-9 [1548759] J Virol. 1992 Jun;66(6):3306-15 [1583717] Virology. 1992 Jul;189(1):167-77 [1604808] J Virol. 1992 Aug;66(8):4966-71 [1629961] J Virol. 1992 Sep;66(9):5472-8 [1501283] J Virol. 1992 Sep;66(9):5667-70 [1501299] J Virol. 1992 Nov;66(11):6616-25 [1357190] J Virol. 1993 Jan;67(1):213-21 [8416370] J Virol. 1993 May;67(5):2824-31 [8474176] J Virol. 1993 Jun;67(6):3077-86 [8497044] J Virol. 1993 Nov;67(11):6387-94 [8411340] Nature. 1993 Oct 14;365(6447):666-9 [8105392] J Virol. 1993 Dec;67(12):7067-76 [7693966] J Virol. 1994 Mar;68(3):1689-96 [8107229] J Virol. 1994 Apr;68(4):2503-12 [8139032] J Virol. 1994 May;68(5):3232-42 [8151785] J Virol. 1994 Jul;68(7):4620-7 [8207836] Virology. 1994 Aug 15;203(1):8-19 [8030287] J Virol. 1994 Aug;68(8):5311-20 [8035531] Nature. 1994 Aug 25;370(6491):666-8 [8065455] J Virol. 1983 Jun;46(3):1056-60 [6190011] J Virol. 1983 Jun;46(3):920-36 [6304351] J Mol Biol. 1984 Apr 5;174(2):297-317 [6325711] Cell. 1986 May 9;45(3):375-85 [2421920] Science. 1986 Jul 18;233(4761):343-6 [2425430] Nature. 1987 Apr 16-22;326(6114):662-9 [3031510] J Virol. 1987 Oct;61(10):2981-8 [3041017] Nature. 1987 Nov 12-18;330(6144):184-6 [2823148] J Virol. 1988 Jan;62(1):139-47 [3257102] Science. 1988 Jun 10;240(4858):1522-5 [2836951] Proc Natl Acad Sci U S A. 1988 Aug;85(16):5941-5 [3261862] Proc Natl Acad Sci U S A. 1988 Dec;85(24):9580-4 [2849111] J Virol. 1989 Nov;63(11):4709-14 [2795718] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Int-6, a highly conserved, widely expressed gene, is mutated by mouse mammary tumor virus in mammary preneoplasia. AN - 77138817; 7853537 AB - With a unique mouse mammary tumor model system in which mouse mammary tumor virus (MMTV) insertional mutations can be detected during progression from preneoplasia to frank malignancy, including metastasis, we have discovered a new common integration site (designated Int-6) for MMTV in mouse mammary tumors. MMTV was integrated into Int-6 in a mammary hyperplastic outgrowth line, its tumors and metastases, and two independent mammary tumors arising in unrelated mice. The Int-6 gene is ubiquitously expressed as a 1.4-kb RNA species in adult tissues and is detected beginning at day 8 of embryonic development. The nucleotide sequence of Int-6 is unrelated to any of the known genes in the GenBank database. MMTV integrates within introns of the gene in the opposite transcriptional orientation. In each tumor tested, this results in the expression of a truncated Int-6/long terminal repeat (LTR) chimeric RNA species which is terminated at a cryptic termination signal in the MMTV LTR. Since the nonrearranged Int-6 alleles in these tumors contain no mutations, we favor the conclusion that truncation of the Int-6 gene product either biologically activates its function or represents a dominant-negative mutation. JF - Journal of virology AU - Marchetti, A AU - Buttitta, F AU - Miyazaki, S AU - Gallahan, D AU - Smith, G H AU - Callahan, R AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 1932 EP - 1938 VL - 69 IS - 3 SN - 0022-538X, 0022-538X KW - Int-6 KW - Eukaryotic Initiation Factor-3 KW - 0 KW - Proto-Oncogene Proteins KW - RNA, Messenger KW - RNA, Neoplasm KW - Index Medicus KW - Animals KW - Gene Expression Regulation, Viral KW - Sequence Homology, Nucleic Acid KW - Mammary Neoplasms, Experimental -- genetics KW - Amino Acid Sequence KW - Mice KW - RNA, Neoplasm -- genetics KW - RNA, Messenger -- genetics KW - Cloning, Molecular KW - Base Sequence KW - Genes KW - Restriction Mapping KW - Proviruses -- genetics KW - Molecular Sequence Data KW - Mutation KW - Cell Transformation, Viral KW - Mutagenesis, Insertional KW - Precancerous Conditions -- microbiology KW - Precancerous Conditions -- genetics KW - Virus Integration KW - Proto-Oncogene Proteins -- genetics KW - Mammary Tumor Virus, Mouse -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77138817?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Int-6%2C+a+highly+conserved%2C+widely+expressed+gene%2C+is+mutated+by+mouse+mammary+tumor+virus+in+mammary+preneoplasia.&rft.au=Marchetti%2C+A%3BButtitta%2C+F%3BMiyazaki%2C+S%3BGallahan%2C+D%3BSmith%2C+G+H%3BCallahan%2C+R&rft.aulast=Marchetti&rft.aufirst=A&rft.date=1995-03-01&rft.volume=69&rft.issue=3&rft.spage=1932&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 - 1995-03-13 N1 - Date created - 1995-03-13 N1 - Date revised - 2017-01-13 N1 - Gene symbol - Int-6 N1 - Genetic sequence - S75224; GENBANK; S75223; S75221 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1968 Sep;61(1):53-60 [4301594] Virology. 1993 May;194(1):157-65 [8386870] Cell. 1982 Nov;31(1):99-109 [6297757] Cell. 1984 Jun;37(2):529-36 [6327073] Cancer Res. 1984 Aug;44(8):3426-37 [6430550] Annu Rev Biochem. 1985;54:897-930 [2992362] J Biol Chem. 1985 Oct 15;260(23):12492-9 [2413024] J Biol Chem. 1986 Feb 25;261(6):2987-93 [3005275] J Virol. 1987 Jan;61(1):66-74 [3023708] Nature. 1987 Apr 30-May 6;326(6116):833 [3574458] Cell. 1987 Aug 14;50(4):649-57 [3111720] Cell. 1988 Nov 18;55(4):619-25 [3180222] Proc Natl Acad Sci U S A. 1989 Aug;86(15):5678-82 [2548184] EMBO J. 1990 Mar;9(3):907-13 [1690126] Protein Eng. 1990 Apr;3(5):433-42 [2349213] Biochim Biophys Acta. 1990 Sep 24;1054(3):267-84 [2207178] Cell Growth Differ. 1990 Oct;1(10):503-10 [2278881] J Virol. 1992 Apr;66(4):2594-9 [1312643] Proc Natl Acad Sci U S A. 1982 Jul;79(13):4113-7 [6287466] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human T-cell lymphotropic virus type I-associated adult T-cell leukemia. The Joseph Goldberger Clinical Investigator Lecture. AN - 77136738; 7853633 JF - JAMA AU - Waldmann, T A AD - Metabolism Branch, National Cancer Institutes, National Institutes of Health, Bethesda, Md 20892. Y1 - 1995/03/01/ PY - 1995 DA - 1995 Mar 01 SP - 735 EP - 737 VL - 273 IS - 9 SN - 0098-7484, 0098-7484 KW - Antibodies, Monoclonal KW - 0 KW - Immunotoxins KW - Receptors, Interleukin-2 KW - Recombinant Fusion Proteins KW - Yttrium Radioisotopes KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Humans KW - Adult KW - Human T-lymphotropic virus 1 -- immunology KW - Leukemia, T-Cell -- immunology KW - Human T-lymphotropic virus 1 -- pathogenicity KW - Female KW - Structure-Activity Relationship KW - Remission Induction KW - Yttrium Radioisotopes -- therapeutic use KW - Radioimmunotherapy KW - Receptors, Interleukin-2 -- physiology KW - Leukemia-Lymphoma, Adult T-Cell -- radiotherapy KW - Leukemia-Lymphoma, Adult T-Cell -- immunology KW - Leukemia-Lymphoma, Adult T-Cell -- diagnosis KW - Receptors, Interleukin-2 -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77136738?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=proceeding&rft.jtitle=JAMA&rft.atitle=Human+T-cell+lymphotropic+virus+type+I-associated+adult+T-cell+leukemia.+The+Joseph+Goldberger+Clinical+Investigator+Lecture.&rft.au=Waldmann%2C+T+A&rft.aulast=Waldmann&rft.aufirst=T&rft.date=1995-03-01&rft.volume=273&rft.issue=9&rft.spage=735&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-14 N1 - Date created - 1995-03-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Writer's cramp. AN - 77074007; 11256908 JF - The Journal of the Association of Physicians of India AU - Harsha, S AU - Taly, A B AD - Department of Neurology, National Institute of Mental Health & Neuro Sciences, Bangalore. Y1 - 1995/03// PY - 1995 DA - March 1995 SP - 193 EP - 196 VL - 43 IS - 3 SN - 0004-5772, 0004-5772 KW - Botulinum Toxins KW - EC 3.4.24.69 KW - Index Medicus KW - Botulinum Toxins -- therapeutic use KW - Humans KW - Electrophysiology KW - Muscle Cramp -- physiopathology KW - Muscle Cramp -- therapy KW - Muscle Cramp -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77074007?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+the+Association+of+Physicians+of+India&rft.atitle=Writer%27s+cramp.&rft.au=Harsha%2C+S%3BTaly%2C+A+B&rft.aulast=Harsha&rft.aufirst=S&rft.date=1995-03-01&rft.volume=43&rft.issue=3&rft.spage=193&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+the+Association+of+Physicians+of+India&rft.issn=00045772&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-10 N1 - Date created - 2001-03-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protein kinase C epsilon is localized to the Golgi via its zinc-finger domain and modulates Golgi function. AN - 77161028; 7877991 AB - Protein kinase C (PKC) is a multigene family of serine/threonine kinases that are central to many signal transduction pathways. Among the PKC isozymes, only PKC epsilon has been reported to exhibit full oncogenic potential. PKC epsilon also displays unique substrate specificity and intracellular localization. To examine the interrelationship between the biological effects and domain structure of PKC epsilon, NIH 3T3 cells were stably transfected to overexpress different epitope-tagged fragments of PKC epsilon. The overexpressed proteins each contain the epsilon-tag peptide at the C terminus to allow ready detection with an antibody specific for the tag. The holo-PKC epsilon was found to localize with the Golgi network and other compartments, whereas the zinc-finger domain localized exclusively at the Golgi. Golgi-specific glycosaminoglycan sulfation was strongly inhibited in cells overexpressing either holo-PKC epsilon or its zinc-finger domain, while the secretion of sulfated glycosaminoglycans into the medium was impaired in cells expressing the PKC epsilon zinc-finger domain. Thus, these results suggest that PKC epsilon may be involved in specifically regulating Golgi-related processes. Further, the results indicate that PKC epsilon domains other than the kinase domain may also have biological activity and that the zinc-finger domain may function as a subcellular localization signal. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Lehel, C AU - Olah, Z AU - Jakab, G AU - Anderson, W B AD - Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1995/02/28/ PY - 1995 DA - 1995 Feb 28 SP - 1406 EP - 1410 VL - 92 IS - 5 SN - 0027-8424, 0027-8424 KW - DNA Primers KW - 0 KW - Glycosaminoglycans KW - Isoenzymes KW - Recombinant Proteins KW - Sulfates KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - Prkce protein, mouse KW - EC 2.7.1.- KW - PRKCE protein, human KW - EC 2.7.11.13 KW - Protein Kinase C KW - Protein Kinase C-epsilon KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Phorbol 12,13-Dibutyrate -- metabolism KW - Mice KW - Glycosaminoglycans -- metabolism KW - Sulfates -- metabolism KW - Base Sequence KW - Transfection KW - Cell Compartmentation KW - Molecular Sequence Data KW - Zinc Fingers KW - DNA Primers -- chemistry KW - Protein Kinase C -- metabolism KW - Golgi Apparatus -- enzymology KW - Golgi Apparatus -- metabolism KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77161028?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Protein+kinase+C+epsilon+is+localized+to+the+Golgi+via+its+zinc-finger+domain+and+modulates+Golgi+function.&rft.au=Lehel%2C+C%3BOlah%2C+Z%3BJakab%2C+G%3BAnderson%2C+W+B&rft.aulast=Lehel&rft.aufirst=C&rft.date=1995-02-28&rft.volume=92&rft.issue=5&rft.spage=1406&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 - 1995-04-04 N1 - Date created - 1995-04-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Cell Biol. 1991 Jan;112(1):39-54 [1986006] Anal Biochem. 1994 Aug 15;221(1):94-102 [7527191] Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):7988-92 [1832772] J Cell Biol. 1992 Feb;116(4):863-74 [1734020] J Cell Biol. 1992 Mar;116(5):1071-80 [1740466] Eur J Cell Biol. 1992 Jun;58(1):35-43 [1644064] Cell Motil Cytoskeleton. 1992;22(4):250-6 [1516148] J Biol Chem. 1992 Oct 15;267(29):20878-86 [1400402] J Cell Biol. 1973 Apr;57(1):175-89 [4691393] Nature. 1983 Feb 17-23;301(5901):621-3 [6828143] Science. 1992 Oct 23;258(5082):607-14 [1411571] J Biol Chem. 1993 Jan 25;268(3):1749-56 [8420951] J Biol Chem. 1993 Mar 25;268(9):6090-6 [8454583] Proc Natl Acad Sci U S A. 1983 Jul;80(14):4208-12 [6308606] Cell. 1984 Dec;39(2 Pt 1):405-16 [6498939] Cell. 1988 Feb 12;52(3):447-58 [3162207] Cancer Res. 1988 Apr 1;48(7):1910-9 [3127041] FEBS Lett. 1989 Jan 30;243(2):351-7 [2917656] Proc Natl Acad Sci U S A. 1989 Mar;86(6):1786-90 [2928302] J Cell Biol. 1989 Aug;109(2):697-704 [2668303] J Biol Chem. 1990 Apr 15;265(11):6296-300 [2318854] Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2915-9 [8464907] Biochem J. 1993 Apr 15;291 ( Pt 2):329-43 [8484714] J Biol Chem. 1993 May 25;268(15):11105-12 [8496173] Trends Biochem Sci. 1993 May;18(5):172-7 [8392229] Oncogene. 1993 Aug;8(8):2095-104 [8336936] Cell. 1993 Aug 13;74(3):405-7 [8394217] Nature. 1993 Aug 26;364(6440):818-21 [7689177] J Biol Chem. 1994 Jan 21;269(3):2118-24 [8294465] J Biol Chem. 1994 Feb 11;269(6):4653-60 [8308036] J Biol Chem. 1994 Feb 18;269(7):4761-6 [8106444] J Electron Microsc Tech. 1991 Feb;17(2):132-49 [2013818] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HIV-1 expression induced by anti-cancer agents in latently HIV-1-infected ACH2 cells. AN - 77158876; 7532407 AB - The expression of human immunodeficiency virus type 1 (HIV-1) in infected cells is induced (or enhanced) by a number of agents including phorbol myristate acetate (PMA), phytohemagglutinin (PHA), certain infectious agents, certain cytokines, and ultraviolet light. ACH2 cells represent latently HIV-1-infected T-cells, which produce only a low level of HIV-1 in vitro. We found that various anti-cancer agents including 5-azacytidine (5-AZC), 5-fluorouracil (5-FU), methotrexate, cytosine arabinoside, and vinblastine potentiated the expression of HIV-1 in ACH2 cells. There was no evidence of altered DNA methylation patterns in ACH2 cells cultured with 5-FU unlike with 5-AZC. The NF-kappa B binding activity was found to be enhanced in ACH2 cells exposed to 5-FU (but not in those exposed to 5-AZC) as assessed by the mobility shift assay using an oligonucleotide containing two NF-kappa B binding sites. These data suggest that the use of certain anti-cancer agents may induce (or enhance) the expression of HIV-1. JF - Biochemical and biophysical research communications AU - O'Brien, M C AU - Ueno, T AU - Jahan, N AU - Zajac-Kaye, M AU - Mitsuya, H AD - Experimental Retrovirology Section, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1995/02/27/ PY - 1995 DA - 1995 Feb 27 SP - 903 EP - 909 VL - 207 IS - 3 SN - 0006-291X, 0006-291X KW - Antineoplastic Agents KW - 0 KW - NF-kappa B KW - Phytohemagglutinins KW - Cytarabine KW - 04079A1RDZ KW - Vinblastine KW - 5V9KLZ54CY KW - DNA KW - 9007-49-2 KW - Azacitidine KW - M801H13NRU KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Fluorouracil KW - U3P01618RT KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - AIDS/HIV KW - Vinblastine -- pharmacology KW - Azacitidine -- pharmacology KW - Methotrexate -- pharmacology KW - DNA -- metabolism KW - Phytohemagglutinins -- pharmacology KW - Cell Survival KW - Cytarabine -- pharmacology KW - Base Sequence KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Fluorouracil -- pharmacology KW - Methylation KW - Cell Line KW - NF-kappa B -- metabolism KW - CD4-Positive T-Lymphocytes -- virology KW - HIV-1 -- growth & development KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77158876?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=HIV-1+expression+induced+by+anti-cancer+agents+in+latently+HIV-1-infected+ACH2+cells.&rft.au=O%27Brien%2C+M+C%3BUeno%2C+T%3BJahan%2C+N%3BZajac-Kaye%2C+M%3BMitsuya%2C+H&rft.aulast=O%27Brien&rft.aufirst=M&rft.date=1995-02-27&rft.volume=207&rft.issue=3&rft.spage=903&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-23 N1 - Date created - 1995-03-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effects of adenosine A3 receptor stimulation on seizures in mice. AN - 77306363; 7774659 AB - We have previously shown that acute preischemic adenosine A3 receptor stimulation results in an increased postischemic damage, while chronic stimulation of this receptor diminishes it. Since several pathophysiological phenomena are common for both ischemia and seizures, we have explored the effect of acute and chronic administration of the adenosine A3 receptor selective agonist IB-MECA (N6-(3-iodobenzyl) adenosine-5'-N-methylcarboxamide) prior to seizures induced by N-methyl-D-aspartate (NMDA), pentamethylenetetrazole, or electric shock. At 100 micrograms/kg, acutely injected IB-MECA was protective in chemically but not electrically induced seizures. In chronic administration of IB-MECA, significant protection against chemically induced seizures was obtained in all studied measures, i.e., seizure latency, neurological impairment, and survival. Although threshold voltage was unchanged in electrically induced seizures, a chronic regimen of IB-MECA significantly reduced postepileptic mortality. Since the combination of an arteriole-constricting compound 48/80 and hypotension-inducing clonidine injected prior to NMDA results in a significant protection against seizures, and since acute stimulation of adenosine A3 receptor causes both arteriolar constriction and severe hypotension, there is a possibility that the protection obtained by the acutely administered drug may result from inadequate delivery of chemoconvulsants to the brain. It is, however, unknown whether the protective effect of chronically administered IB-MECA is related to the effect of the drug on blood flow, neuronal mechanisms, or both. JF - European journal of pharmacology AU - Von Lubitz, D K AU - Carter, M F AU - Deutsch, S I AU - Lin, R C AU - Mastropaolo, J AU - Meshulam, Y AU - Jacobson, K A AD - NIH/NIDDK, Molecular Recognition Section, Bethesda, MD 20892, USA. Y1 - 1995/02/24/ PY - 1995 DA - 1995 Feb 24 SP - 23 EP - 29 VL - 275 IS - 1 SN - 0014-2999, 0014-2999 KW - Purinergic P1 Receptor Agonists KW - 0 KW - N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine KW - 152918-18-8 KW - p-Methoxy-N-methylphenethylamine KW - 4091-50-3 KW - N-Methylaspartate KW - 6384-92-5 KW - Adenosine KW - K72T3FS567 KW - Clonidine KW - MN3L5RMN02 KW - Pentylenetetrazole KW - WM5Z385K7T KW - Index Medicus KW - Injections, Intraperitoneal KW - Animals KW - p-Methoxy-N-methylphenethylamine -- toxicity KW - Drug Interactions KW - Pentylenetetrazole -- toxicity KW - N-Methylaspartate -- toxicity KW - Clonidine -- toxicity KW - Mice KW - Electroshock KW - Male KW - Adenosine -- pharmacology KW - Adenosine -- administration & dosage KW - Adenosine -- analogs & derivatives KW - Seizures -- etiology KW - Seizures -- drug therapy KW - Seizures -- prevention & control KW - Adenosine -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77306363?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+effects+of+adenosine+A3+receptor+stimulation+on+seizures+in+mice.&rft.au=Von+Lubitz%2C+D+K%3BCarter%2C+M+F%3BDeutsch%2C+S+I%3BLin%2C+R+C%3BMastropaolo%2C+J%3BMeshulam%2C+Y%3BJacobson%2C+K+A&rft.aulast=Von+Lubitz&rft.aufirst=D&rft.date=1995-02-24&rft.volume=275&rft.issue=1&rft.spage=23&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 - 1995-07-10 N1 - Date created - 1995-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Active site mapping of the catalytic mouse primase subunit by alanine scanning mutagenesis. AN - 77156617; 7876136 AB - In the eukaryotic cell, DNA synthesis is initiated by DNA primase associated with DNA polymerase alpha. The eukaryotic primase is composed of two subunits, p49 and p58, where the p49 subunit contains the catalytic active site. Mutagenesis of the cDNA for the p49 subunit was initiated to demonstrate a functional correlation of conserved residues among the eukaryotic primases and DNA polymerases. Fourteen invariant charged residues in the smaller catalytic mouse primase subunit, p49, were changed to alanine. These mutant proteins were expressed, purified, and enzymatically characterized for primer synthesis. Analyses of the mutant proteins indicate that residues 104-111 are most critical for primer synthesis and form part of the active site. Alanine substitution in residues Glu105, Asp109, and Asp111 produced protein with no detectable activity in direct primase assays, indicating that these residues may form part of a conserved carboxylic triad also observed in the active sites of DNA polymerases and reverse transcriptases. All other mutant proteins showed a dramatic decrease in catalysis, while mutation of two residues, Arg162 and Arg163, caused an increase in Km(NTP). Analysis of these mutant proteins in specific assays designed to separately investigate dinucleotide formation (initiation) and elongation of primer indicates that these two activities utilize the same active site within the p49 subunit. Finally, mutations in three active site codons produced protein with reduced affinity with the p58 subunit, suggesting that p58 may interact directly with active site residues. JF - The Journal of biological chemistry AU - Copeland, W C AU - Tan, X AD - Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709. Y1 - 1995/02/24/ PY - 1995 DA - 1995 Feb 24 SP - 3905 EP - 3913 VL - 270 IS - 8 SN - 0021-9258, 0021-9258 KW - DNA, Complementary KW - 0 KW - DNA KW - 9007-49-2 KW - DNA Primase KW - EC 2.7.7.- KW - RNA Nucleotidyltransferases KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - Animals KW - DNA -- metabolism KW - Humans KW - Temperature KW - Amino Acid Sequence KW - Mice KW - Protein Binding KW - Binding Sites KW - Enzyme Stability KW - Kinetics KW - Molecular Sequence Data KW - Catalysis KW - RNA Nucleotidyltransferases -- metabolism KW - Alanine -- genetics KW - RNA Nucleotidyltransferases -- genetics KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77156617?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Active+site+mapping+of+the+catalytic+mouse+primase+subunit+by+alanine+scanning+mutagenesis.&rft.au=Copeland%2C+W+C%3BTan%2C+X&rft.aulast=Copeland&rft.aufirst=W&rft.date=1995-02-24&rft.volume=270&rft.issue=8&rft.spage=3905&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 - 1995-03-31 N1 - Date created - 1995-03-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synthesis and antimalarial activities of 12 beta-allyldeoxoartemisinin and its derivatives. AN - 77153962; 7861409 AB - Synthesis of 12 beta-allyldeoxoartemisinin from dihydroartemisinin and subsequent transformations to other 12 beta-alkyldeoxoartemisinins are described. All compounds were tested in vitro versus two drug-resistant strains (Plasmodium falciparum) of malaria. The in vivo activity and toxicity of the most active compound, 12 beta-propyldeoxoartemisinin, were comparable to that of arteether. JF - Journal of medicinal chemistry AU - Pu, Y M AU - Ziffer, H AD - Laboratory of Chemical Physics, NIDDK, Bethesda, Maryland 20892-0510. Y1 - 1995/02/17/ PY - 1995 DA - 1995 Feb 17 SP - 613 EP - 616 VL - 38 IS - 4 SN - 0022-2623, 0022-2623 KW - 12-allyldeoxoartemisinin KW - 0 KW - Antimalarials KW - Artemisinins KW - Sesquiterpenes KW - Index Medicus KW - Animals KW - Dogs KW - Mice KW - Plasmodium falciparum -- drug effects KW - Antimalarials -- pharmacology KW - Sesquiterpenes -- chemical synthesis KW - Sesquiterpenes -- pharmacology KW - Antimalarials -- chemical synthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77153962?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+medicinal+chemistry&rft.atitle=Synthesis+and+antimalarial+activities+of+12+beta-allyldeoxoartemisinin+and+its+derivatives.&rft.au=Pu%2C+Y+M%3BZiffer%2C+H&rft.aulast=Pu&rft.aufirst=Y&rft.date=1995-02-17&rft.volume=38&rft.issue=4&rft.spage=613&rft.isbn=&rft.btitle=&rft.title=Journal+of+medicinal+chemistry&rft.issn=00222623&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-21 N1 - Date created - 1995-03-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A specific sequence of the laminin alpha 2 chain critical for the initiation of heterotrimer assembly. AN - 77141504; 7852414 AB - Triple-stranded laminin molecules assemble via an alpha-helical coiled-coil structure spanning approximately 600 amino acid residues of each chain. We reported that the C termini of the beta 1 and gamma 1 chains direct the specific dimer and trimer assembly (Utani, A., Nomizu, M., Timpl, R., Roller, P.P., and Yamada, Y. (1994) J. Biol. Chem. 269, 19167-19175). In this study, we focused on the mechanism of trimer formation of the alpha 2 chain utilizing three different approaches. First, competition assays using mutated recombinant alpha 2 chain defined a 25-amino acid sequence at the C terminus of the long arm as an essential site for assembly with beta 1 and gamma 1 chain. Site-specific mutations and synthetic peptides of this site revealed that both positively charged amino acid residues and the alpha-helical structure within this site were critical. Second, overexpression studies of recombinant alpha 2 chain long arm confirmed that the C-terminal end was critical for the trimer assembly within NIH 3T3 cells. Third, circular dichroism spectroscopic examination of the complexes reconstituted in vitro revealed dynamic conformational changes of the alpha 2 and gamma 1 chains in the process of assembly. These studies also revealed that the proper folding of the extreme C terminus of alpha 2 chain was critical for the stability of trimer. From these data, it is concluded that the C terminus of alpha 2 chain long arm is required for the effective initiation of laminin heterotrimer assembly. JF - The Journal of biological chemistry AU - Utani, A AU - Nomizu, M AU - Sugiyama, S AU - Miyamoto, S AU - Roller, P P AU - Yamada, Y AD - Laboratory of Developmental Biology, NIDR, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1995/02/17/ PY - 1995 DA - 1995 Feb 17 SP - 3292 EP - 3298 VL - 270 IS - 7 SN - 0021-9258, 0021-9258 KW - Laminin KW - 0 KW - Macromolecular Substances KW - Peptides KW - Recombinant Fusion Proteins KW - Recombinant Proteins KW - Index Medicus KW - Peptides -- chemical synthesis KW - Recombinant Fusion Proteins -- biosynthesis KW - 3T3 Cells KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Protein Processing, Post-Translational KW - Circular Dichroism KW - Amino Acid Sequence KW - Mice KW - Myocardium -- metabolism KW - Recombinant Fusion Proteins -- chemistry KW - Cloning, Molecular KW - Chromatography, Affinity KW - Mutagenesis, Site-Directed KW - Animals, Newborn KW - Transfection KW - Point Mutation KW - Molecular Sequence Data KW - Peptides -- chemistry KW - Recombinant Proteins -- chemistry KW - Sequence Homology, Amino Acid KW - Protein Conformation KW - Laminin -- chemistry KW - Protein Structure, Secondary KW - Laminin -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77141504?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+specific+sequence+of+the+laminin+alpha+2+chain+critical+for+the+initiation+of+heterotrimer+assembly.&rft.au=Utani%2C+A%3BNomizu%2C+M%3BSugiyama%2C+S%3BMiyamoto%2C+S%3BRoller%2C+P+P%3BYamada%2C+Y&rft.aulast=Utani&rft.aufirst=A&rft.date=1995-02-17&rft.volume=270&rft.issue=7&rft.spage=3292&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 - 1995-03-15 N1 - Date created - 1995-03-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronic desensitization and down-regulation of the gastrin-releasing peptide receptor are mediated by a protein kinase C-dependent mechanism. AN - 77140480; 7852420 AB - The cellular basis of down-regulation and desensitization in phospholipase C-linked receptors is unclear. Recent studies with some receptors suggest that elements in the carboxyl terminus of the receptor are important in mediating these processes. Three mutant gastrin-releasing peptide receptors (GRP-R) were studied: one whose last 37 carboxyl-terminal amino acids were eliminated (construct MGT346); one that replaced all of the carboxyl-terminal Ser and Thr eliminated in MGT346 with Ala, Asn, or Gly (construct JF1); and one that selectively replaced the Ser and Thr of the protein kinase C consensus sequence (PKC-CS) located within the same region with alanine (construct TS360AA). Desensitization was assessed by measuring the ability to activate phospholipase C and increase cellular [3H]inositol phosphates, or increase [Ca2+]i, after pre-exposure to 3 nM bombesin for 24 h. Wild-type GRP-R was maximally desensitized and down-regulated after a 24-h exposure to 3 nM bombesin, and removal of the PKC-CS alone markedly attenuated each process. Elimination of additional serines and threonines by truncation (MGT346) or replacement (JF1) did not decrease down-regulation or desensitization further. To confirm the necessity of second messenger activation in mediating down-regulation, we further investigated two additional mutant GRP-R that bound agonist with high affinity but fail to activate phospholipase C (constructs R139G and A263E). Neither construct underwent significant down-regulation. Removal of all GRP-R carboxyl-terminal Ser or Thr, either by MGT346 or JF1, reduced internalization by > 80%, whereas elimination of the PKC-CS in TS360AA only attenuated internalization by 21 +/- 2%. These data suggest that activation of the distal carboxyl-terminal PKC-CS is essential for chronic desensitization and down-regulation of the GRP-R, and provide no evidence for involvement of second messenger-independent processes. In contrast, internalization is equally regulated by both second messenger-dependent and independent processes. JF - The Journal of biological chemistry AU - Benya, R V AU - Kusui, T AU - Battey, J F AU - Jensen, R T AD - Digestive Diseases Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-1804. Y1 - 1995/02/17/ PY - 1995 DA - 1995 Feb 17 SP - 3346 EP - 3352 VL - 270 IS - 7 SN - 0021-9258, 0021-9258 KW - Inositol Phosphates KW - 0 KW - Receptors, Bombesin KW - Protein Kinase C KW - EC 2.7.11.13 KW - Bombesin KW - PX9AZU7QPK KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - 3T3 Cells KW - Down-Regulation KW - Transfection KW - Kinetics KW - Mice KW - Amino Acid Sequence KW - Consensus Sequence KW - Cell Membrane -- metabolism KW - Sequence Deletion KW - Protein Kinase C -- metabolism KW - Inositol Phosphates -- metabolism KW - Bombesin -- metabolism KW - Bombesin -- pharmacology KW - Receptors, Bombesin -- metabolism KW - Receptors, Bombesin -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77140480?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Chronic+desensitization+and+down-regulation+of+the+gastrin-releasing+peptide+receptor+are+mediated+by+a+protein+kinase+C-dependent+mechanism.&rft.au=Benya%2C+R+V%3BKusui%2C+T%3BBattey%2C+J+F%3BJensen%2C+R+T&rft.aulast=Benya&rft.aufirst=R&rft.date=1995-02-17&rft.volume=270&rft.issue=7&rft.spage=3346&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 - 1995-03-15 N1 - Date created - 1995-03-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - No point mutation but decreased expression of the p16/MTS1 tumor suppressor gene in nasopharyngeal carcinomas. AN - 77153181; 7862458 AB - Nasopharyngeal carcinoma (NPC) is a malignancy which occurs at high incidence in southern China and southeast Asia. The molecular mechanism of this disease, however, is not well understood. Recently, a homozygous deletion and/or loss of heterozygosity on chromosome 9p21-22 was found in several primary NPCs (Huang et al., Cancer Res. 54: 4003-4006, 1994), suggesting that a potential tumor suppressor gene(s) residing in this region may play a role in nasopharyngeal carcinogenesis. Since p16/MTS1, a potential tumor suppressor gene, whose mutations/deletions are frequently found in variety of tumor cells, was mapped to chromosome 9p21, we investigated the possible involvement of this gene in the development of NPC by mutational and Northern blot analysis. SSCP-direct sequencing revealed no point mutations of the p16/MTS-1 gene in any of 42 primary NPC biopsies from three geographical regions nor in two NPC cell lines. We did, however, observe a codon 140ala-->thr polymorphism in the gene, which has been previously reported as a point mutation. Furthermore, Northern analysis revealed a decreased expression of the p16/MTS1 gene in two out of two NPC cell lines as compared with immortalized/nontransformed cell lines. These results suggest that down regulation rather than a point mutation of the p16/MTS1 gene may play a role in the genesis of NPC. JF - Oncogene AU - Sun, Y AU - Hildesheim, A AU - Lanier, A E AU - Cao, Y AU - Yao, K T AU - Raab-Traub, N AU - Yang, C S AD - Cell Biology Section, National Cancer Institute, Frederick Cancer Research & Development Center, Maryland. Y1 - 1995/02/16/ PY - 1995 DA - 1995 Feb 16 SP - 785 EP - 788 VL - 10 IS - 4 SN - 0950-9232, 0950-9232 KW - MTS1 KW - p16 KW - Carrier Proteins KW - 0 KW - Cyclin-Dependent Kinase Inhibitor p16 KW - DNA Primers KW - RNA, Messenger KW - RNA, Neoplasm KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - Base Sequence KW - Humans KW - Point Mutation KW - Molecular Sequence Data KW - RNA, Neoplasm -- genetics KW - Chromosomes, Human, Pair 9 KW - RNA, Messenger -- genetics KW - DNA Primers -- chemistry KW - Carrier Proteins -- genetics KW - Nasopharyngeal Neoplasms -- genetics KW - Carcinoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77153181?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=No+point+mutation+but+decreased+expression+of+the+p16%2FMTS1+tumor+suppressor+gene+in+nasopharyngeal+carcinomas.&rft.au=Sun%2C+Y%3BHildesheim%2C+A%3BLanier%2C+A+E%3BCao%2C+Y%3BYao%2C+K+T%3BRaab-Traub%2C+N%3BYang%2C+C+S&rft.aulast=Sun&rft.aufirst=Y&rft.date=1995-02-16&rft.volume=10&rft.issue=4&rft.spage=785&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-22 N1 - Date created - 1995-03-22 N1 - Date revised - 2017-01-13 N1 - Gene symbol - MTS1; p16 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional alpha 3-glycine receptors in rat adrenal. AN - 77307520; 7774687 AB - The adrenal medulla contains high-affinity strychnine binding sites, presumed to be receptors for glycine. In this study, glycine injection (400 pmol) via a cannula attached to a microdialysis probe increased in vivo concentrations of catecholamines in the adrenal microdialysate in anesthetized rats. Strychnine perfusion (20 pmol/20 min) blocked these responses. To identify receptors potentially mediating this effect, we tested for RNA transcripts of the three known alpha subunits of strychnine binding site, using the reverse transcription-polymerase chain reaction. Only mRNA encoding the alpha 3 isoform was found in the rat adrenal. The findings suggest that in the rat adrenal, glycine stimulates catecholamine release by binding to strychnine binding sites and that those sites probably contain the alpha 3 isoform. JF - European journal of pharmacology AU - Yadid, G AU - Goldstein, D S AU - Pacak, K AU - Kopin, I J AU - Golomb, E AD - Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA. Y1 - 1995/02/15/ PY - 1995 DA - 1995 Feb 15 SP - 399 EP - 401 VL - 288 IS - 3 SN - 0014-2999, 0014-2999 KW - RNA, Messenger KW - 0 KW - Receptors, Glycine KW - Strychnine KW - H9Y79VD43J KW - Glycine KW - TE7660XO1C KW - Index Medicus KW - Rats KW - Polymerase Chain Reaction KW - Animals KW - Rats, Sprague-Dawley KW - Base Sequence KW - Glycine -- pharmacology KW - Molecular Sequence Data KW - Gene Expression KW - Strychnine -- pharmacology KW - RNA, Messenger -- genetics KW - Male KW - Receptors, Glycine -- metabolism KW - Adrenal Medulla -- drug effects KW - Adrenal Medulla -- metabolism KW - Receptors, Glycine -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77307520?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Functional+alpha+3-glycine+receptors+in+rat+adrenal.&rft.au=Yadid%2C+G%3BGoldstein%2C+D+S%3BPacak%2C+K%3BKopin%2C+I+J%3BGolomb%2C+E&rft.aulast=Yadid&rft.aufirst=G&rft.date=1995-02-15&rft.volume=288&rft.issue=3&rft.spage=399&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 - 1995-07-11 N1 - Date created - 1995-07-11 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - J00691; GENBANK; X57281; Y00276; M55250 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structural domains of interleukin-2 receptor beta critical for signal transduction: kinase association and nuclear complex-formation. AN - 77157315; 7532397 AB - The structural domains of interleukin-2 receptor beta (IL-2R beta) were examined, characterizing the protein domains, associated phosphoproteins and nuclear complexes of IL-2-induced signal transduction. A series of IL-2R beta cytoplasmic deletion mutants were constructed and transfected into a murine pre-B-cell line, Ba/F3. The proliferative response of characterized clones was determined. A minimal linear cytoplasmic sequence required for proliferation and a sequence motif (PQPLXP) needed along with Box1-Box2 for IL-2-induced proliferation were identified. Anti-phosphotyrosine Western-blot analysis of a stimulated biologically active clone showed several IL-2-induced tyrosylphosphorylated proteins with molecular masses ranging from 45 to 116 kDa. In vitro kinase studies of biologically active clone-receptor complexes showed a 116 kDa protein (p116) to be the major tyrosine-phosphorylated component. The presence of the p116 kinase in the receptor complex correlates with IL-2-induced proliferation. An IL-2-inducible p116 kinase has recently been characterized as a Jak kinase family member and named Jak3. Nuclear complexes were formed with the GRR oligomer only when the IL-2R beta mutant supported proliferation. This led us to conclude that Box1-Box2 and PQPLXP motifs associate with Jak3 and that this association is an essential element in the IL-2 signal-transduction pathway culminating in the formation of a nuclear complex. JF - The Biochemical journal AU - Howard, O M AU - Kirken, R A AU - Garcia, G G AU - Hackett, R H AU - Farrar, W L AD - Biological Carcinogenesis and Development Program, NCI-Frederick Cancer Research and Development Center, MD 21702. Y1 - 1995/02/15/ PY - 1995 DA - 1995 Feb 15 SP - 217 EP - 224 VL - 306 ( Pt 1) SN - 0264-6021, 0264-6021 KW - Receptors, Interleukin-2 KW - 0 KW - Phosphotyrosine KW - 21820-51-9 KW - Tyrosine KW - 42HK56048U KW - Protein Kinases KW - EC 2.7.- KW - Index Medicus KW - Animals KW - Humans KW - Amino Acid Sequence KW - Mice KW - Lymphocytes KW - Plasmids KW - Tyrosine -- analysis KW - Structure-Activity Relationship KW - Gene Deletion KW - Mutagenesis KW - Base Sequence KW - Transfection KW - Molecular Sequence Data KW - Tyrosine -- metabolism KW - Tyrosine -- analogs & derivatives KW - Cell Line KW - Cell Division KW - Protein Kinases -- metabolism KW - Receptors, Interleukin-2 -- metabolism KW - Cell Nucleus -- metabolism KW - Receptors, Interleukin-2 -- genetics KW - Receptors, Interleukin-2 -- chemistry KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77157315?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Biochemical+journal&rft.atitle=Structural+domains+of+interleukin-2+receptor+beta+critical+for+signal+transduction%3A+kinase+association+and+nuclear+complex-formation.&rft.au=Howard%2C+O+M%3BKirken%2C+R+A%3BGarcia%2C+G+G%3BHackett%2C+R+H%3BFarrar%2C+W+L&rft.aulast=Howard&rft.aufirst=O&rft.date=1995-02-15&rft.volume=306+%28+Pt+1%29&rft.issue=&rft.spage=217&rft.isbn=&rft.btitle=&rft.title=The+Biochemical+journal&rft.issn=02646021&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-21 N1 - Date created - 1995-03-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1993 Dec 9;366(6455):580-3 [7504784] Nature. 1993 Nov 11;366(6451):129-35 [8232552] Lymphokine Cytokine Res. 1993 Oct;12(5):309-12 [8260540] Science. 1993 Dec 17;262(5141):1874-7 [8266076] Science. 1993 Dec 17;262(5141):1877-80 [8266077] Science. 1994 Jan 7;263(5143):89-92 [8272872] Science. 1994 Jan 7;263(5143):92-5 [8272873] J Biol Chem. 1994 Feb 18;269(7):5364-8 [7508935] Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1819-23 [8127887] Nature. 1994 Jul 14;370(6485):151-3 [8022485] Nature. 1994 Jul 14;370(6485):153-7 [8022486] Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6374-8 [8022790] J Biol Chem. 1994 Jul 15;269(28):18267-70 [8034567] J Biol Chem. 1994 Jul 22;269(29):19136-41 [7518451] Nature. 1970 Aug 15;227(5259):680-5 [5432063] Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350-4 [388439] J Biol Chem. 1989 Jul 25;264(21):12562-7 [2787319] Cell. 1989 Dec 1;59(5):837-45 [2590941] Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3314-8 [1826565] Science. 1991 Jun 14;252(5012):1523-8 [2047859] J Immunol. 1991 Aug 15;147(4):1253-60 [1869821] Biochem Soc Trans. 1991 Apr;19(2):277-87 [1889610] Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11349-53 [1662392] Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2674-8 [1557373] Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2789-93 [1557384] Science. 1992 Jul 17;257(5068):379-82 [1631559] J Biol Chem. 1992 Aug 5;267(22):15281-4 [1639773] Biochem J. 1992 Aug 1;285 ( Pt 3):851-6 [1497623] J Biol Chem. 1992 Nov 15;267(32):22752-8 [1429625] Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11194-8 [1280821] Baillieres Clin Haematol. 1992 Jul;5(3):551-73 [1457964] Int Immunol. 1992 Nov;4(11):1233-43 [1472476] Eur J Immunol. 1993 Jan;23(1):131-5 [8419163] EMBO J. 1993 Feb;12(2):759-68 [8440263] Mol Cell Biol. 1993 Mar;13(3):1788-95 [8382775] Eur J Immunol. 1993 Apr;23(4):988-91 [8458387] Proc Natl Acad Sci U S A. 1993 May 1;90(9):4201-5 [8483935] J Biol Chem. 1993 Jun 15;268(17):12617-23 [8389761] Int J Cancer. 1993 Jun 19;54(4):571-7 [8099900] Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5544-8 [7685905] Cell. 1993 Jul 30;74(2):227-36 [8343951] Cell. 1993 Jul 30;74(2):237-44 [8343952] Biochem J. 1993 Sep 1;294 ( Pt 2):339-42 [7690544] Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8429-33 [8378315] Science. 1993 Sep 24;261(5129):1730-3 [8378773] Cell. 1993 Sep 24;74(6):1079-87 [7691413] EMBO J. 1993 Nov;12(11):4181-9 [8223433] J Biol Chem. 1993 Oct 25;268(30):22765-70 [7693677] Nature. 1993 Dec 9;366(6455):583-5 [7504785] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Multiple steroid-binding orientations: alteration of regiospecificity of dehydroepiandrosterone 2- and 7-hydroxylase activities of cytochrome P-450 2a-5 by mutation of residue 209. AN - 77155888; 7864823 AB - The mutation of Ala-117 to Val conferred dehydroepiandrosterone (DHEA) hydroxylase activity on cytochrome P-450 2a-4, with the production of both 2 alpha- and 7 alpha-hydroxyDHEA at similar rates. P-450 2a-5 which has Val at position 117, acquired high DHEA hydroxylase activity by mutation of Phe-209. Mutant F209L of P-450 2a-5 exhibited strong regiospecificity at the 2-position of the DHEA molecule with the production of 2 alpha-hydroxy DHEA as the major metabolite. On the other hand, mutant F209V of P-450 2a-5 showed the 7-position to be the major hydroxylation site, 7 beta-hydroxyDHEA and 7 alpha-OHDHEA being produced. Therefore the regiospecificity of DHEA hydroxylase activity of P-450 2a-5 is altered between the 2- and 7-position depending on the amino acid at position 209. Modelling of the DHEA molecule in the pocket of bacterial P-450cam showed that the steroid can be accommodated in at least two orientations for which the 2- or 7- position is near the sixth axial position of the haem. Moreover, these two orientations, which are of similar energy, can be interconverted by a 180 degrees rotation of the steroid molecule around its long axis. These results support the hypothesis that the steroid molecule in the pocket is in dynamic equilibrium with multiple binding orientations and that the equilibrium is apparently determined by a few critical residues including those at positions 117 and 209. JF - The Biochemical journal AU - Iwasaki, M AU - Davis, D G AU - Darden, T A AU - Pedersen, L G AU - Negishi, M AD - National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709. Y1 - 1995/02/15/ PY - 1995 DA - 1995 Feb 15 SP - 29 EP - 33 VL - 306 ( Pt 1) SN - 0264-6021, 0264-6021 KW - Recombinant Proteins KW - 0 KW - Heme KW - 42VZT0U6YR KW - Dehydroepiandrosterone KW - 459AG36T1B KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - Steroid Hydroxylases KW - EC 1.14.- KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - Cytochrome P-450 CYP2A6 KW - Index Medicus KW - Saccharomyces cerevisiae -- genetics KW - Molecular Structure KW - Models, Molecular KW - Heme -- chemistry KW - Molecular Conformation KW - Chromatography, High Pressure Liquid KW - Structure-Activity Relationship KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Mixed Function Oxygenases -- chemistry KW - Mixed Function Oxygenases -- metabolism KW - Cytochrome P-450 Enzyme System -- genetics KW - Cytochrome P-450 Enzyme System -- chemistry KW - Steroid Hydroxylases -- metabolism KW - Dehydroepiandrosterone -- chemistry KW - Cytochrome P-450 Enzyme System -- metabolism KW - Mixed Function Oxygenases -- genetics KW - Dehydroepiandrosterone -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77155888?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Biochemical+journal&rft.atitle=Multiple+steroid-binding+orientations%3A+alteration+of+regiospecificity+of+dehydroepiandrosterone+2-+and+7-hydroxylase+activities+of+cytochrome+P-450+2a-5+by+mutation+of+residue+209.&rft.au=Iwasaki%2C+M%3BDavis%2C+D+G%3BDarden%2C+T+A%3BPedersen%2C+L+G%3BNegishi%2C+M&rft.aulast=Iwasaki&rft.aufirst=M&rft.date=1995-02-15&rft.volume=306+%28+Pt+1%29&rft.issue=&rft.spage=29&rft.isbn=&rft.btitle=&rft.title=The+Biochemical+journal&rft.issn=02646021&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-21 N1 - Date created - 1995-03-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochem Biophys Res Commun. 1983 Dec 16;117(2):479-85 [6661238] J Mol Biol. 1987 Jun 5;195(3):687-700 [3656428] Biochem Pharmacol. 1988 Dec 15;37(24):4778-80 [3202910] J Biol Chem. 1989 Apr 15;264(11):6465-71 [2703500] Nature. 1989 Jun 22;339(6226):632-4 [2733794] J Biol Chem. 1991 Feb 25;266(6):3380-2 [1995602] Arch Biochem Biophys. 1994 Feb 15;309(1):52-7 [8117113] J Biol Chem. 1992 Jan 5;267(1):83-90 [1730627] Methods Enzymol. 1991;206:11-30 [1784202] Trends Pharmacol Sci. 1992 Mar;13(3):122-6 [1574808] J Biol Chem. 1993 Jan 15;268(2):759-62 [8419350] Biochem J. 1993 Apr 15;291 ( Pt 2):569-73 [8484736] J Biol Chem. 1991 Nov 25;266(33):22515-21 [1718996] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Efficacy of the quinocarmycins KW2152 and DX-52-1 against human melanoma lines growing in culture kand in mice. AN - 77141997; 7850800 AB - Quinocarmycin monicitrate (KW2152) and its analogue, DX-52-1, demonstrated specificity for melanomas in the National Cancer Institute in vitro human tumor cell line drug screen. In contrast to most cell lines, a 50% reduction in tumor cell burden (as measured protein) at the end of a 48-h drug incubation was produced in five of eight melanoma lines by KW2152 concentrations (LC50s) ranging from 0.49 to 10.93 microM and by DX-52-1 concentrations ranging from 0.71 to 7.33 microM. Using the COMPARE algorithm, the patterns of differential cytotoxicity for both agents at the LC50 level of effect most closely resembled those for actinomycin D, mithramycin, and Adriamycin. In in vivo studies, both KW2152 (40 mg/kg/day) and DX-52-1 (90 mg/kg/day) caused partial and complete regressions of staged s.c.-implanted LOX IMVI melanoma xenografts following i.p. administration on days 5, 9, and 13 and produced tumor growth delays of 231 and 181%, respectively (P < 0.001). Activity was augmented by more prolonged therapy. Statistically significant growth inhibition of SK-MEL-2, UACC-62, UACC-257, and M14, but not SK-MEL-5 and MALME-3M, melanoma xenografts also was observed following every fourth or seventh day i.p. treatments. Based on these findings, DX-52-1 has been selected by the National Cancer Institute for development to clinical trial especially against melanomas. This agent represents one of the first to be selected for preclinical development based on disease-panel specificity discovered in the National Cancer Institute cancer drug screen. JF - Cancer research AU - Plowman, J AU - Dykes, D J AU - Narayanan, V L AU - Abbott, B J AU - Saito, H AU - Hirata, T AU - Grever, M R AD - Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1995/02/15/ PY - 1995 DA - 1995 Feb 15 SP - 862 EP - 867 VL - 55 IS - 4 SN - 0008-5472, 0008-5472 KW - Antibiotics, Antineoplastic KW - 0 KW - Isoquinolines KW - quinocarcin KW - 84573-33-1 KW - DX 52-1 KW - 96251-59-1 KW - Index Medicus KW - Sensitivity and Specificity KW - Neoplasm Transplantation KW - Isoquinolines -- pharmacology KW - Drug Screening Assays, Antitumor KW - Animals KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Transplantation, Heterologous KW - Mice, Nude KW - Mice KW - Follow-Up Studies KW - Models, Biological KW - Antibiotics, Antineoplastic -- pharmacology KW - Melanoma -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77141997?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Efficacy+of+the+quinocarmycins+KW2152+and+DX-52-1+against+human+melanoma+lines+growing+in+culture+kand+in+mice.&rft.au=Plowman%2C+J%3BDykes%2C+D+J%3BNarayanan%2C+V+L%3BAbbott%2C+B+J%3BSaito%2C+H%3BHirata%2C+T%3BGrever%2C+M+R&rft.aulast=Plowman&rft.aufirst=J&rft.date=1995-02-15&rft.volume=55&rft.issue=4&rft.spage=862&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 - 1995-03-14 N1 - Date created - 1995-03-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Long-term repopulation of irradiated mice with limiting numbers of purified hematopoietic stem cells: in vivo expansion of stem cell phenotype but not function. AN - 77137197; 7849289 AB - Hematopoietic stem cells were isolated from normal adult mouse bone marrow based on surface antigen expression (Thy-1.1(low)Lin(neg)Ly-6A/E+) and further selected for low retention of rhodamine 123. This population of cells (Rh-123low) could mediate radioprotection and long-term (greater than 12 months) repopulation after transplantation of as few as 25 cells. Transfer of five genetically marked Rh-123low cells in the presence of 10(5) normal bone marrow cells resulted in reconstitution of peripheral blood by greater than 10% donor cells in 64% (30 of 47) of recipient mice. Of 46 animals surviving after 24 weeks, 10 had over 50% donor-derived cells in peripheral blood. Two general patterns of long-term reconstitution were observed: one in which many donor-derived cells were observed 5 to 6 weeks after reconstitution and another in which donor-derived cells were rare initially but expanded with time. This result suggests that two classes of long-term repopulating hematopoietic stem cells exist, differing in their ability to function early in the course of transplantation. Alternatively, distinct anatomic sites of engraftment may dictate these two outcomes from a single type of cell. As an approach to measure the extent of self-renewal by the injected cells, recipients of five or 200 stem cells were killed 8 to 13 months after the transplants, and Thy-1.1(low)Lin(neg)Ly-6A/E+ progeny of the original injected cells were isolated for a second transplant. While a numerical expansion of cells expressing the cell surface phenotype of stem cells was observed, along with activity in the colony-forming unit-spleen assay, the expanded cells were vastly inferior in radioprotection and long-term reconstitution assays when compared with cells freshly isolated from normal animals. This result demonstrates that in stem cell expansion experiments, cell surface antigen expression is not an appropriate indicator of stem cell function. JF - Blood AU - Spangrude, G J AU - Brooks, D M AU - Tumas, D B AD - Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT. Y1 - 1995/02/15/ PY - 1995 DA - 1995 Feb 15 SP - 1006 EP - 1016 VL - 85 IS - 4 SN - 0006-4971, 0006-4971 KW - Antigens, Surface KW - 0 KW - Cesium Radioisotopes KW - Fluorescent Dyes KW - Rhodamines KW - Rhodamine 123 KW - 1N3CZ14C5O KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Radiation Protection KW - Monocytes -- radiation effects KW - B-Lymphocytes -- radiation effects KW - Cell Separation KW - Phenotype KW - Chimera KW - Monocytes -- cytology KW - Flow Cytometry KW - Bone Marrow -- radiation effects KW - T-Lymphocytes -- immunology KW - Antigens, Surface -- analysis KW - T-Lymphocytes -- cytology KW - Granulocytes -- radiation effects KW - B-Lymphocytes -- cytology KW - B-Lymphocytes -- immunology KW - Mice KW - Mice, Inbred Strains KW - Cells, Cultured KW - Mice, Inbred C57BL KW - T-Lymphocytes -- radiation effects KW - Granulocytes -- cytology KW - Hematopoietic Stem Cells -- cytology KW - Hematopoietic Stem Cell Transplantation KW - Hematopoietic Stem Cells -- physiology KW - Hematopoietic Stem Cells -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77137197?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Long-term+repopulation+of+irradiated+mice+with+limiting+numbers+of+purified+hematopoietic+stem+cells%3A+in+vivo+expansion+of+stem+cell+phenotype+but+not+function.&rft.au=Spangrude%2C+G+J%3BBrooks%2C+D+M%3BTumas%2C+D+B&rft.aulast=Spangrude&rft.aufirst=G&rft.date=1995-02-15&rft.volume=85&rft.issue=4&rft.spage=1006&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-16 N1 - Date created - 1995-03-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The hematologic toxicity of interleukin-2 in patients with metastatic melanoma and renal cell carcinoma. AN - 77136771; 7842405 AB - High dose interleukin-2 (IL-2) has been found to produce durable antitumor responses in some patients, benefiting most greatly those patients with melanoma and renal cell carcinoma. In this paper, the hematologic toxicity and changes resulting from high dose IL-2 alone administered by intravenous bolus are discussed. One hundred ninety-nine consecutive patients treated with high dose IL-2 alone from January 1, 1988 to December 31, 1992 were included in this study. All patients had a diagnosis of metastatic melanoma or metastatic renal cell carcinoma and were treated at the National Cancer Institute (Bethesda, MD). Anemia, requiring erythrocyte transfusions, occurred in 14% of all treatment courses, with a median of two units of erythrocytes transfused. Severe leukopenia ( < 1,000 leukocytes/mm3) was rare (1.5% of all patients) and was not associated with any infectious complications. Severe thrombocytopenia ( < 30,000 platelets/mm3) occurred in 2.2% of all treatment cycles, with two patients experiencing a grade 3 hemorrhage, defined as gross blood loss, and one patient experiencing a grade 4 hemorrhage, defined as a debilitating blood loss. Defects in the coagulation pathway were common: abnormal partial thromboplastin time and prothrombin time values occurred in 64% and 25% of the treatment cycles, respectively. In addition, a mean clearance of 93% of lymphocytes from the peripheral blood was observed within 24 hours after initiating IL-2 therapy. This was followed by rebound lymphocytosis to a mean of 198% of baseline on posttreatment Day 4. There were no treatment-related deaths. During IL-2 therapy, adverse sequelae of anemia, thrombocytopenia, coagulopathy, and leukopenia were usually mild, transient and rarely limited therapy. A profound decrease in lymphocytes in the peripheral circulation occurred within 24 hours after initiating therapy, with a rebound occurring after stopping IL-2. No specific hematologic parameter was associated significantly with a patient's increased probability of responding to therapy. JF - Cancer AU - MacFarlane, M P AU - Yang, J C AU - Guleria, A S AU - White, R L AU - Seipp, C A AU - Einhorn, J H AU - White, D E AU - Rosenberg, S A AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1995/02/15/ PY - 1995 DA - 1995 Feb 15 SP - 1030 EP - 1037 VL - 75 IS - 4 SN - 0008-543X, 0008-543X KW - Interleukin-2 KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Thrombocytopenia -- therapy KW - Humans KW - Anemia -- chemically induced KW - Retrospective Studies KW - Aged KW - Child KW - Leukocyte Count KW - Blood Coagulation Disorders -- chemically induced KW - Leukopenia -- chemically induced KW - Adult KW - Blood Transfusion KW - Thrombocytopenia -- chemically induced KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Anemia -- therapy KW - Kidney Neoplasms -- pathology KW - Kidney Neoplasms -- therapy KW - Interleukin-2 -- adverse effects KW - Carcinoma, Renal Cell -- therapy KW - Melanoma -- secondary KW - Melanoma -- blood KW - Skin Neoplasms -- therapy KW - Skin Neoplasms -- pathology KW - Skin Neoplasms -- blood KW - Hematologic Diseases -- chemically induced KW - Interleukin-2 -- blood KW - Interleukin-2 -- therapeutic use KW - Carcinoma, Renal Cell -- secondary KW - Melanoma -- therapy KW - Hematologic Diseases -- therapy KW - Carcinoma, Renal Cell -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77136771?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer&rft.atitle=The+hematologic+toxicity+of+interleukin-2+in+patients+with+metastatic+melanoma+and+renal+cell+carcinoma.&rft.au=MacFarlane%2C+M+P%3BYang%2C+J+C%3BGuleria%2C+A+S%3BWhite%2C+R+L%3BSeipp%2C+C+A%3BEinhorn%2C+J+H%3BWhite%2C+D+E%3BRosenberg%2C+S+A&rft.aulast=MacFarlane&rft.aufirst=M&rft.date=1995-02-15&rft.volume=75&rft.issue=4&rft.spage=1030&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-06 N1 - Date created - 1995-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular analysis of the same HIV peptide functionally binding to both a class I and a class II MHC molecule. AN - 77133398; 7530749 AB - Although several peptides have been found to bind to both class I and class II molecules, the basis for this binding of the same peptide to two classes of MHC molecules has not been compared previously. We have analyzed one such peptide, P18 from the V3 loop of HIV-1 gp160, which we have previously shown to be recognized by CD8+ CTL with the class I molecule H-2Dd, and by CD4+ Th cells with the class II molecule I-Ad. With the use of truncated and substituted peptides, we found that the minimal core peptides are very similar, that the residues required for class I binding precisely fit the recently identified consensus motif for peptides binding to Dd (XGPX[R/K/H]XXX(X) [L/I/F]), and that at least three of the same residues are involved in binding to class II I-Ad. In addition, several of the same residues are involved in TCR interaction when the peptide is presented by class I and class II molecules. Modeling shows results to be consistent with the crystal structure of a peptide-class II MHC complex. Thus, the recognition of this versatile peptide by CD4+ Th cells with class II MHC molecules and by CD8+ cytotoxic T cells with class I MHC molecules is remarkably similar in both the core peptide used and the role of different residues in the ternary complex. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Takeshita, T AU - Takahashi, H AU - Kozlowski, S AU - Ahlers, J D AU - Pendleton, C D AU - Moore, R L AU - Nakagawa, Y AU - Yokomuro, K AU - Fox, B S AU - Margulies, D H AD - Molecular Immunogenetics and Vaccine Research Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1995/02/15/ PY - 1995 DA - 1995 Feb 15 SP - 1973 EP - 1986 VL - 154 IS - 4 SN - 0022-1767, 0022-1767 KW - Epitopes KW - 0 KW - H-2 Antigens KW - HIV Envelope Protein gp120 KW - HIV envelope protein gp120 (305-321) KW - Histocompatibility Antigen H-2D KW - Histocompatibility Antigens Class II KW - Peptide Fragments KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Models, Molecular KW - Amino Acid Sequence KW - Mice KW - Mice, Inbred BALB C KW - Protein Binding KW - Structure-Activity Relationship KW - Lymphocyte Activation KW - Mutagenesis, Site-Directed KW - Sequence Alignment KW - Binding, Competitive KW - Molecular Sequence Data KW - Epitopes -- immunology KW - Cell Line KW - Protein Conformation KW - Peptide Fragments -- metabolism KW - HIV-1 -- immunology KW - HIV Envelope Protein gp120 -- immunology KW - Histocompatibility Antigens Class II -- metabolism KW - CD8-Positive T-Lymphocytes -- immunology KW - H-2 Antigens -- immunology KW - CD4-Positive T-Lymphocytes -- immunology KW - HIV Envelope Protein gp120 -- metabolism KW - Histocompatibility Antigens Class II -- immunology KW - Peptide Fragments -- immunology KW - H-2 Antigens -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77133398?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Molecular+analysis+of+the+same+HIV+peptide+functionally+binding+to+both+a+class+I+and+a+class+II+MHC+molecule.&rft.au=Takeshita%2C+T%3BTakahashi%2C+H%3BKozlowski%2C+S%3BAhlers%2C+J+D%3BPendleton%2C+C+D%3BMoore%2C+R+L%3BNakagawa%2C+Y%3BYokomuro%2C+K%3BFox%2C+B+S%3BMargulies%2C+D+H&rft.aulast=Takeshita&rft.aufirst=T&rft.date=1995-02-15&rft.volume=154&rft.issue=4&rft.spage=1973&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 - 1995-02-27 N1 - Date created - 1995-02-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of two endogenous Na+,K(+)-ATPase inhibitors, marinobufagenin and ouabain, on isolated rat aorta. AN - 77302842; 7768267 AB - Previously, we reported that the venom of Bufo marinus toad contains a Na+,K(+)-ATPase inhibitor with potent vasoconstrictor activity. In the present study, using thin-layer chromatography in Silicagel 60 F254 + 366, we separated a vasoactive substance from a mixture of steroids from Bufo marinus venom. Based on chromatographic mobility of this substance and typical color reaction after its vizualization with SbCl3, we identified it as a previously described steroid, marinobufagenin. Vasoconstrictor and Na+,K+ pump inhibitory properties of marinobufagenin were studied in isolated rat aortic rings and compared with those of ouabain. Ouabain (10-100 mumol.1-1) produced weak vasoconstriction, which was blocked by 2 mumol.1-1 phentolamine. 10 mumol.1-1 ouabain stimulated, and at higher concentrations inhibited, the Na+,K+ pump. 2 mumol.1-1 phentolamine abolished the activating effect of 10 mumol.1-1 ouabain on the Na+,K+ pump, but did not alter the inhibitory action of higher concentrations of ouabain. By contrast, marunibufagenin elicited rapid and strong vasoconstriction and inhibited ouabain-sensitive 86Rb uptake. Antidigoxin antibody antagonized the vasoconstrictor responses to marinobufagenin, but not to ouabain. 2 mumol.1-1 phentolamine did not alter the constrictor effect of marinobufagenin. In solid-phase digoxin immunoassay, marinobufagenin demonstrated higher digoxin-like immunoreactivity than ouabain. JF - European journal of pharmacology AU - Bagrov, A Y AU - Roukoyatkina, N I AU - Pinaev, A G AU - Dmitrieva, R I AU - Fedorova, O V AD - Laboratory of Behavioral Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 1995/02/14/ PY - 1995 DA - 1995 Feb 14 SP - 151 EP - 158 VL - 274 IS - 1-3 SN - 0014-2999, 0014-2999 KW - Amphibian Venoms KW - 0 KW - Antibodies, Monoclonal KW - Bufanolides KW - Digitalis Glycosides KW - Vasoconstrictor Agents KW - marinobufagenin KW - 470-42-8 KW - Ouabain KW - 5ACL011P69 KW - Sodium-Potassium-Exchanging ATPase KW - EC 3.6.3.9 KW - Phentolamine KW - Z468598HBV KW - Index Medicus KW - Aorta -- metabolism KW - Amphibian Venoms -- chemistry KW - Animals KW - Drug Interactions KW - Phentolamine -- pharmacology KW - Amphibian Venoms -- pharmacology KW - Rats KW - Bufo marinus KW - Aorta -- drug effects KW - Muscle Contraction -- drug effects KW - In Vitro Techniques KW - Digitalis Glycosides -- pharmacology KW - Chromatography, Thin Layer KW - Male KW - Female KW - Immunoassay KW - Sodium-Potassium-Exchanging ATPase -- antagonists & inhibitors KW - Vasoconstrictor Agents -- pharmacology KW - Bufanolides -- isolation & purification KW - Muscle, Smooth, Vascular -- drug effects KW - Bufanolides -- pharmacology KW - Ouabain -- pharmacology KW - Sodium-Potassium-Exchanging ATPase -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77302842?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effects+of+two+endogenous+Na%2B%2CK%28%2B%29-ATPase+inhibitors%2C+marinobufagenin+and+ouabain%2C+on+isolated+rat+aorta.&rft.au=Bagrov%2C+A+Y%3BRoukoyatkina%2C+N+I%3BPinaev%2C+A+G%3BDmitrieva%2C+R+I%3BFedorova%2C+O+V&rft.aulast=Bagrov&rft.aufirst=A&rft.date=1995-02-14&rft.volume=274&rft.issue=1-3&rft.spage=151&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 - 1995-07-05 N1 - Date created - 1995-07-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interaction of polycyclic aromatic hydrocarbons and flavones with cytochromes P450 in the endoplasmic reticulum: effect on CO binding kinetics. AN - 77138103; 7849053 AB - The flash photolysis technique was used to examine the kinetics of CO binding to cytochromes P450 in rat liver microsomes. The effect of polycyclic aromatic hydrocarbons (PAHs) and flavones was used to distinguish the kinetic behavior of the PAH-metabolizing P450 1A1 from that of the remaining multiple microsomal P450s. Applying this approach to microsomes from 3-methylcholanthrene-treated rats showed that although all tested PAHs accelerated CO binding to P450 1A1, the extent varied markedly for different PAHs. The tricyclic PAHs phenanthrene and anthracene enhanced CO binding by 37- and 49-fold, respectively, while several tetracyclic and pentacyclic PAHs increased the rate by 3-16-fold. The results indicate that PAHs exert a dual effect on the rate of CO binding to P450 1A1: a general enhancement via widening of the CO access channel and a reduction that is dependent on PAH size. Although 5,6-benzoflavone increased the rate of CO binding to P450 1A1 by 3.5-fold, it additionally decelerated binding to a constitutive P450 by 15-fold. This flavone thus exerts markedly different effects on two P450s within the same microsomal sample. In contrast, the sole effect of 7,8-benzoflavone was acceleration of CO binding to P450 1A1 by 18-fold. The divergent effects of these isomeric flavones, which only differ in positioning of an aromatic ring, illustrate the sensitivity of CO binding to substrate structure. The varying effects of these PAHs and flavones on CO binding kinetics show that they differentially modulate P450 conformation and access of ligands to the P450 heme and demonstrate that binding of carcinogens to a specific target P450 can be evaluated in its native microsomal milieu. JF - Biochemistry AU - Koley, A P AU - Robinson, R C AU - Markowitz, A AU - Friedman, F K AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1995/02/14/ PY - 1995 DA - 1995 Feb 14 SP - 1942 EP - 1947 VL - 34 IS - 6 SN - 0006-2960, 0006-2960 KW - Benz(a)Anthracenes KW - 0 KW - Flavonoids KW - Phenanthrenes KW - Polycyclic Compounds KW - benzotriphenylene KW - 215-58-7 KW - phenanthrene KW - 448J8E5BST KW - Methylcholanthrene KW - 56-49-5 KW - Carbon Monoxide KW - 7U1EE4V452 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Rats KW - Photolysis KW - Animals KW - Rats, Sprague-Dawley KW - Methylcholanthrene -- pharmacology KW - Microsomes, Liver -- metabolism KW - Kinetics KW - Phenanthrenes -- pharmacology KW - Benz(a)Anthracenes -- pharmacology KW - Male KW - Structure-Activity Relationship KW - Endoplasmic Reticulum -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Polycyclic Compounds -- pharmacology KW - Flavonoids -- pharmacology KW - Carbon Monoxide -- metabolism KW - Polycyclic Compounds -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77138103?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Interaction+of+polycyclic+aromatic+hydrocarbons+and+flavones+with+cytochromes+P450+in+the+endoplasmic+reticulum%3A+effect+on+CO+binding+kinetics.&rft.au=Koley%2C+A+P%3BRobinson%2C+R+C%3BMarkowitz%2C+A%3BFriedman%2C+F+K&rft.aulast=Koley&rft.aufirst=A&rft.date=1995-02-14&rft.volume=34&rft.issue=6&rft.spage=1942&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-13 N1 - Date created - 1995-03-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interactions of erythro-ifenprodil, threo-ifenprodil, erythro-iodoifenprodil, and eliprodil with subtypes of sigma receptors. AN - 77251059; 7737340 AB - Observations of sigma (sigma) receptor heterogeneity have prompted interest in identifying ligands for sigma receptor subtypes. Selective ligands for the sigma-2 are unavailable, but [3H]ifenprodil labels sigma-2 sites. Therefore, isomers and analogues of ifenprodil were compared as potential sigma-2 ligands. Threo-ifenprodil and erythro-ifenprodil had high affinity (Ki congruent to 2 nM) for sigma-2 sites; erythro-iodoifenprodil had moderate affinity (Ki congruent to 46 nM); eliprodil had lowest affinity (Ki congruent to 630 nM). Threo-ifenprodil, which has less affinity for alpha 1-adrenoceptors than erythro-ifenprodil, was slightly more selective than erythro-ifenprodil for sigma-2 sites. These results identify threo-ifenprodil as potentially useful for studies of sigma-2 receptors. JF - European journal of pharmacology AU - Hashimoto, K AU - London, E D AD - Neuroimaging and Drug Action Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 1995/02/06/ PY - 1995 DA - 1995 Feb 06 SP - 307 EP - 310 VL - 273 IS - 3 SN - 0014-2999, 0014-2999 KW - Ligands KW - 0 KW - Piperidines KW - Receptors, N-Methyl-D-Aspartate KW - Receptors, sigma KW - iodoifenprodil KW - ifenprodil KW - R8OE3P6O5S KW - Pentazocine KW - RP4A60D26L KW - eliprodil KW - YW62A6TW29 KW - Index Medicus KW - Rats KW - Animals KW - Stereoisomerism KW - Rats, Inbred F344 KW - Drug Interactions KW - Pentazocine -- metabolism KW - Kinetics KW - In Vitro Techniques KW - Binding, Competitive -- drug effects KW - Male KW - Piperidines -- pharmacology KW - Receptors, sigma -- drug effects KW - Receptors, sigma -- metabolism KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Piperidines -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77251059?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Interactions+of+erythro-ifenprodil%2C+threo-ifenprodil%2C+erythro-iodoifenprodil%2C+and+eliprodil+with+subtypes+of+sigma+receptors.&rft.au=Hashimoto%2C+K%3BLondon%2C+E+D&rft.aulast=Hashimoto&rft.aufirst=K&rft.date=1995-02-06&rft.volume=273&rft.issue=3&rft.spage=307&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 - 1995-06-08 N1 - Date created - 1995-06-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of rat liver AdoHcy hydrolase in a Rhodobacter capsulatus ahcY mutant restores pigment formation and photosynthetic growth. AN - 77143550; 7857275 AB - An amino acid alignment of fourteen S-adenosylhomocysteine hydrolases shows that sequences from six photosynthetic species and one species possibly derived from algae have an internal 36 to 41 amino acid sequence that is not present in hydrolase sequences from seven non-photosynthetic species. In the photosynthetic eubacterium Rhodobacter capsulatus, the StLB1 strain has a disrupted hydrolase gene, and hydrolase activity is not detectable. Photopigment synthesis and photosynthetic growth are significantly reduced in the StLB1 strain. Introduction of rat hydrolase cDNA into the StLB1 strain restored hydrolase activity, photopigment synthesis and photosynthetic growth. The results show that the 36 amino acid sequence of Rhodobacter capsulatus S-adenosylhomocysteine hydrolase does not have a photosynthesis specific function. JF - Biochemical and biophysical research communications AU - Aksamit, R R AU - Buggy, J J AU - Bauer, C E AD - Laboratory of General and Comparative Biochemistry, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892. Y1 - 1995/02/06/ PY - 1995 DA - 1995 Feb 06 SP - 265 EP - 272 VL - 207 IS - 1 SN - 0006-291X, 0006-291X KW - ahcY KW - Oligodeoxyribonucleotides KW - 0 KW - Pigments, Biological KW - Recombinant Proteins KW - Hydrolases KW - EC 3.- KW - Adenosylhomocysteinase KW - EC 3.3.1.1 KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Humans KW - Amino Acid Sequence KW - Cloning, Molecular KW - Mutagenesis, Site-Directed KW - Rats KW - Base Sequence KW - Conserved Sequence KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Plants -- enzymology KW - Pigments, Biological -- biosynthesis KW - Rhodobacter capsulatus -- metabolism KW - Photosynthesis KW - Hydrolases -- metabolism KW - Rhodobacter capsulatus -- growth & development KW - Hydrolases -- genetics KW - Gene Expression KW - Rhodobacter capsulatus -- genetics KW - Mutation KW - Hydrolases -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77143550?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=Expression+of+rat+liver+AdoHcy+hydrolase+in+a+Rhodobacter+capsulatus+ahcY+mutant+restores+pigment+formation+and+photosynthetic+growth.&rft.au=Aksamit%2C+R+R%3BBuggy%2C+J+J%3BBauer%2C+C+E&rft.aulast=Aksamit&rft.aufirst=R&rft.date=1995-02-06&rft.volume=207&rft.issue=1&rft.spage=265&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-14 N1 - Date created - 1995-03-14 N1 - Date revised - 2017-01-13 N1 - Gene symbol - ahcY N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gender differences in a longitudinal study of age-associated hearing loss. AN - 85160880; pmid-7876442 AB - Current studies are inconclusive regarding specific patterns of gender differences in age-associated hearing loss. This paper presents results from the largest and longest longitudinal study reported to date of changes in pure-tone hearing thresholds in men and women screened for otological disorders and noise-induced hearing loss. Since 1965, the Baltimore Longitudinal Study of Aging has collected hearing thresholds from 500 to 8000 Hz using a pulsed-tone tracking procedure. Mixed-effects regression models were used to estimate longitudinal patterns of change in hearing thresholds in 681 men and 416 women with no evidence of otological disease, unilateral hearing loss, or noise-induced hearing loss. The results show (1) hearing sensitivity declines more than twice as fast in men as in women at most ages and frequencies, (2) longitudinal declines in hearing sensitivity are detectable at all frequencies among men by age 30, but the age of onset of decline is later in women at most frequencies and varies by frequency in women, (3) women have more sensitive hearing than men at frequencies above 1000 Hz but men have more sensitive hearing than women at lower frequencies, (4) learning effects bias cross-sectional and short-term longitudinal studies, and (5) hearing levels and longitudinal patterns of change are highly variable, even in this highly selected group. These longitudinal findings document gender differences in hearing levels and show that age-associated hearing loss occurs even in a group with relatively low-noise occupations and with no evidence of noise-induced hearing loss. JF - The Journal of the Acoustical Society of America AU - Pearson, J D AU - Morrell, C H AU - Gordon-Salant, Sandra M AU - Brant, L J AU - Metter, E J AU - Klein, L L AU - Fozard, J L AD - Longitudinal Studies Branch, National Institute on Aging, Baltimore, Maryland 21224.; Department of Speech and Hearing Sciences, College of Behavioral and Social Sciences, University of Maryland PY - 1995 SP - 1196 EP - 1205 VL - 97 IS - 2 SN - 0001-4966, 0001-4966 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85160880?accountid=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=Gender+differences+in+a+longitudinal+study+of+age-associated+hearing+loss.&rft.au=Pearson%2C+J+D%3BMorrell%2C+C+H%3BGordon-Salant%2C+Sandra+M%3BBrant%2C+L+J%3BMetter%2C+E+J%3BKlein%2C+L+L%3BFozard%2C+J+L&rft.aulast=Pearson&rft.aufirst=J&rft.date=1995-02-01&rft.volume=97&rft.issue=2&rft.spage=1196&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 - Last updated - 2010-05-07 ER - TY - JOUR T1 - The NIEHS Superfund Basic Research Program: overview and areas of future research directions. AN - 77413973; 7621795 AB - The National Institute of Environmental Health Sciences' Superfund Basic Research Program is currently funding 142 separate research projects within 18 programs encompassing 29 universities and institutions around the United States. The research under this program covers a wide range of interdisciplinary science from both the biomedical and nonbiomedical perspectives. This is a unique program of technology-driven research. Nonetheless, there are some areas of research that should be investigated or investigated further, should funds become available. Environmental health risk posed by the location of Superfund sites may be distributed inequitably across socioeconomic status and racial groups. Since one in five children now lives below the poverty line, an important aspect of environmental equity must be the investigation of the health effects of environmental factors on children. The multidisciplinary investigation of the effects of hazardous substance exposure on children is an area that needs much research due to the fact that most of the toxicologic data available are based on adults and animals. This program is funding 27 projects on ecologic damage posed by hazardous wastes. Much more research is needed in the investigation of toxic effects on natural succession of ecosystems as well as on their effects on biodiversity to further our understanding of the food web in the role of bioavailability in human health, and to examine the bioaccumulation of these chemicals as it relates to their fate and transport. This program is researching and developing many innovative technologies for detecting, assessing, and reducing toxic materials in the environment.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Environmental health perspectives AU - Suk, W A AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 3 EP - 5 VL - 103 Suppl 1 SN - 0091-6765, 0091-6765 KW - Index Medicus KW - United States KW - Financing, Government KW - Academies and Institutes KW - Environmental Health -- trends KW - Forecasting UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77413973?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+NIEHS+Superfund+Basic+Research+Program%3A+overview+and+areas+of+future+research+directions.&rft.au=Suk%2C+W+A&rft.aulast=Suk&rft.aufirst=W&rft.date=1995-02-01&rft.volume=103+Suppl+1&rft.issue=&rft.spage=3&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 - 1995-08-31 N1 - Date created - 1995-08-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thapsigargin induces IL-2 receptor alpha-chain in human peripheral and Jurkat T cells via a protein kinase C-independent mechanism. AN - 77412264; 7622191 AB - Thapsigargin (TG), an inhibitor of Ca(2+)-ATPase, depletes intracellular Ca2+ stores and induces a sustained Ca2+ influx without altering phosphatidyl inositol levels. TG plus phorbol myristate acetate (PMA) but not TG alone induced IL-2 in Jurkat T cells, suggesting that TG had no effect on protein kinase C (PKC). However, TG induced increases in IL-2R alpha protein as well as IL-2R alpha mRNA in Jurkat T cells in a dose-dependent manner. A similar increase in IL-2R alpha by TG was also observed in human peripheral T cells. Further, like PMA, TG markedly induced NF kappa B in Jurkat T cells. However, TG and PMA exhibited a synergistic action on IL-2R alpha expression, suggesting that TG and PMA induce IL-2R alpha through distinct pathways. PMA- but not TG-induced IL-2R alpha is inhibited by the PKC inhibitor H7, whereas TG- but not PMA-induced IL-2R alpha was inhibited by cholera toxin, forskolin and 1,9-dideoxy forskolin. In toto, these results suggest that TG induces IL-2R alpha in human T cells through a PKC-independent pathway. JF - Immunology letters AU - Sei, Y AU - Reich, H AD - Laboratory of Neuroscience, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 75 EP - 80 VL - 45 IS - 1-2 SN - 0165-2478, 0165-2478 KW - Alkaloids KW - 0 KW - Hydroquinones KW - Isoquinolines KW - NF-kappa B KW - Neoplasm Proteins KW - Piperazines KW - RNA, Messenger KW - RNA, Neoplasm KW - Receptors, Interleukin-2 KW - Terpenes KW - Colforsin KW - 1F7A44V6OU KW - 2,5-di-tert-butylhydroquinone KW - 26XK13B61B KW - Calcimycin KW - 37H9VM9WZL KW - Thapsigargin KW - 67526-95-8 KW - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine KW - 84477-87-2 KW - Cholera Toxin KW - 9012-63-9 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Calcium-Transporting ATPases KW - EC 3.6.3.8 KW - Staurosporine KW - H88EPA0A3N KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - 1,9-dideoxyforskolin KW - OAW710HWIX KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - RNA, Neoplasm -- biosynthesis KW - Neoplasm Proteins -- biosynthesis KW - Humans KW - Cholera Toxin -- pharmacology KW - Colforsin -- analogs & derivatives KW - Calcium-Transporting ATPases -- antagonists & inhibitors KW - Calcimycin -- pharmacology KW - Piperazines -- pharmacology KW - RNA, Messenger -- biosynthesis KW - NF-kappa B -- genetics KW - Gene Expression Regulation, Leukemic -- drug effects KW - Hydroquinones -- pharmacology KW - Calcium -- metabolism KW - Isoquinolines -- pharmacology KW - NF-kappa B -- biosynthesis KW - Base Sequence KW - Colforsin -- pharmacology KW - Neoplasm Proteins -- genetics KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Alkaloids -- pharmacology KW - Drug Synergism KW - T-Lymphocytes -- metabolism KW - Leukemia-Lymphoma, Adult T-Cell -- pathology KW - Signal Transduction -- drug effects KW - Receptors, Interleukin-2 -- biosynthesis KW - Leukemia-Lymphoma, Adult T-Cell -- genetics KW - Gene Expression Regulation -- drug effects KW - Terpenes -- pharmacology KW - T-Lymphocytes -- drug effects KW - Protein Kinase C -- physiology KW - Receptors, Interleukin-2 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77412264?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Immunology+letters&rft.atitle=Thapsigargin+induces+IL-2+receptor+alpha-chain+in+human+peripheral+and+Jurkat+T+cells+via+a+protein+kinase+C-independent+mechanism.&rft.au=Sei%2C+Y%3BReich%2C+H&rft.aulast=Sei&rft.aufirst=Y&rft.date=1995-02-01&rft.volume=45&rft.issue=1-2&rft.spage=75&rft.isbn=&rft.btitle=&rft.title=Immunology+letters&rft.issn=01652478&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-29 N1 - Date created - 1995-08-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - General considerations in assessing neurotoxicity using neuroanatomical methods. AN - 77371125; 7599531 AB - Neurotoxicology is a major focus of scientists and policy makers. Neurotoxicological investigations provide vital information needed by regulatory scientists to protect public health and can also elucidate fundamental mechanisms governing nervous system function and enhance our understanding of neurodegenerative diseases as well. A definition of neurotoxicity, developed by the Interagency Committee on Neurotoxicology, includes both permanent and reversible adverse effects on the nervous system. There are a number of factors that can greatly affect the outcome of any study designed to assess neurotoxicity, such as the choice of animal species, dose and dosage regimen, and route of administration. In considering neuroanatomical methodologies for assessing neurotoxicity, it is important to evaluate each technique for such factors as: limits of detection (sensitivity and signal to noise ratio), ability to be quantified, sampling problems, what is being measured and what can interfere with this measurement. Other questions relating to the strengths and weaknesses of neuroanatomical techniques that should be addressed include: is the technique difficult to perform? Is it reproducible? Which elements of the nervous system are best evaluated? Does the technique reveal the neuronal circuitry involved in the neurotoxic effect? Is successful application of the technique dependent on timing factors? Clearly, there are many factors that can influence the assessment of neurotoxicity so that it is best to base this assessment on converging data based on complementary techniques. JF - Neurochemistry international AU - Erinoff, L AD - Neuroscience Research Branch, National Institute on Drug Abuse, Rockville, MD 20857, USA. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 111 EP - 114 VL - 26 IS - 2 SN - 0197-0186, 0197-0186 KW - Index Medicus KW - Sensitivity and Specificity KW - Animals KW - Reproducibility of Results KW - Dose-Response Relationship, Drug KW - Humans KW - Species Specificity KW - Neuroanatomy -- methods KW - Nervous System -- drug effects KW - Nervous System -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77371125?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurochemistry+international&rft.atitle=General+considerations+in+assessing+neurotoxicity+using+neuroanatomical+methods.&rft.au=Erinoff%2C+L&rft.aulast=Erinoff&rft.aufirst=L&rft.date=1995-02-01&rft.volume=26&rft.issue=2&rft.spage=111&rft.isbn=&rft.btitle=&rft.title=Neurochemistry+international&rft.issn=01970186&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-07 N1 - Date created - 1995-08-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemical induction of interleukin-8, a proinflammatory chemokine, in human epidermal keratinocyte cultures and its relation to cytogenetic toxicity. AN - 77365617; 7600258 AB - Tumor promoters, proinflammatory cytokines, endotoxins, and protein synthesis inhibitors can modulate cell cycle kinetics of various cell types, stimulate production of reactive oxygen species, and induce keratinocytes to produce interleukin-8 (IL-8), a potent chemotactant for polymorphonuclear neutrophils and T lymphocytes. The aim of this study was to determine whether perturbations of cytogenetic responses correlated with the induction of IL-8 expression. Cultures of primary human keratinocytes were grown in serum-free medium with 5 mumol/L bromodeoxyuridine to label DNA and exposed either to phorbol-13-myristate-12-acetate (PMA) (0.0001-100 ng/ml), cycloheximide (CHX) (0.01-50 micrograms), lipopolysaccharide (0.1-100 micrograms/ml), tumor necrosis factor-alpha (TNF alpha) (3.13-50 ng/ml), or interleukin-1 alpha (IL-1 alpha) (1-182 pg/ml). Metaphase chromosome preparations were stained by a fluorescence-plus-Giemsa technique to differentiate sister chromatids. For IL-8 production, keratinocytes were grown to 70% confluency and then exposed to chemicals for 24 h. Immunoreactive IL-8 was quantitated from the supernatants by ELISA. With the exception of benzo(a)pyrene used as a positive control, none of the agents induced sister chromatid exchanges. However, PMA and TNF alpha induced IL-8 production that coincided with significant cell cycle inhibition. IL-1 alpha had no effect on cytogenetic endpoints, yet stimulated a 6.3-fold increase in IL-8. CHX inhibited cell cycle progression and mitotic activity at concentrations that were 200 times lower than required for IL-8 induction; however, puromycin (0.31-10 micrograms/ml), another protein synthesis inhibitor, did not induce IL-8. At all concentrations tested, TNF alpha reduced the mitotic index by approximately 45%, slowed cell cycle progression by approximately 3.5 h, and induced a flat, albeit large, IL-8 response at concentrations > or = 12.5 ng/ml. These agent-specific response patterns suggest that induction of IL-8 production is not always the inevitable result of cell cycle perturbations or genetic damage. JF - Cell biology and toxicology AU - Wilmer, J L AU - Luster, M I AD - National Institute of Environmental Health Sciences, Environmental Immunology and Neurobiology Section, Research Triangle Park, North Carolina, USA. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 37 EP - 50 VL - 11 IS - 1 SN - 0742-2091, 0742-2091 KW - Culture Media, Serum-Free KW - 0 KW - Interleukin-1 KW - Interleukin-8 KW - Lipopolysaccharides KW - Phorbol Esters KW - Tumor Necrosis Factor-alpha KW - Cycloheximide KW - 98600C0908 KW - Bromodeoxyuridine KW - G34N38R2N1 KW - Index Medicus KW - Phorbol Esters -- pharmacology KW - Cells, Cultured KW - Humans KW - Cycloheximide -- pharmacology KW - Epidermis -- metabolism KW - Metaphase KW - Cell Cycle -- drug effects KW - DNA Damage -- drug effects KW - Interleukin-1 -- pharmacology KW - Interleukin-8 -- biosynthesis KW - Lipopolysaccharides -- pharmacology KW - Keratinocytes -- drug effects KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Keratinocytes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77365617?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+biology+and+toxicology&rft.atitle=Chemical+induction+of+interleukin-8%2C+a+proinflammatory+chemokine%2C+in+human+epidermal+keratinocyte+cultures+and+its+relation+to+cytogenetic+toxicity.&rft.au=Wilmer%2C+J+L%3BLuster%2C+M+I&rft.aulast=Wilmer&rft.aufirst=J&rft.date=1995-02-01&rft.volume=11&rft.issue=1&rft.spage=37&rft.isbn=&rft.btitle=&rft.title=Cell+biology+and+toxicology&rft.issn=07422091&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-07 N1 - Date created - 1995-08-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Data analysis: statistical analysis and use of historical control data. AN - 77341280; 7784636 AB - Survival-adjusted methods for the statistical analysis of tumor data from long-term rodent carcinogenicity studies are described. Although most of these methods require knowledge of whether individual tumors are "fatal" or "incidental," such determinations may be difficult. Several methods for dealing with this and with other data analysis issues are discussed. Historical control tumor data may be useful in the interpretation of rodent carcinogenicity studies, particularly for rare tumors and for borderline effects. Although statistical methods are available for using historical control data in a formal testing framework, the primary difficulty is establishing a database that is truly comparable to the study under evaluation with respect to those factors known to influence tumor occurrence. Major sources of variability in tumor incidence include the animal room environment, dietary factors/body weight, gross necropsy and slide preparation procedures, and histopathology diagnosis. The National Toxicology Program's use of historical control data is briefly described and illustrated. JF - Regulatory toxicology and pharmacology : RTP AU - Haseman, J K AD - Statistics and Biomathematics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 52 EP - 9; discussion 81-6 VL - 21 IS - 1 SN - 0273-2300, 0273-2300 KW - Index Medicus KW - Rats KW - Body Weight KW - Mice, Inbred Strains KW - Animals KW - Adrenal Cortex Neoplasms -- pathology KW - Rats, Inbred F344 KW - Liver Neoplasms, Experimental -- pathology KW - Liver Neoplasms, Experimental -- chemically induced KW - Mice KW - Pheochromocytoma -- pathology KW - Adrenal Cortex Neoplasms -- chemically induced KW - Male KW - Female KW - Survival Analysis KW - Carcinogenicity Tests -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77341280?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Data+analysis%3A+statistical+analysis+and+use+of+historical+control+data.&rft.au=Haseman%2C+J+K&rft.aulast=Haseman&rft.aufirst=J&rft.date=1995-02-01&rft.volume=21&rft.issue=1&rft.spage=52&rft.isbn=&rft.btitle=&rft.title=Regulatory+toxicology+and+pharmacology+%3A+RTP&rft.issn=02732300&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-19 N1 - Date created - 1995-07-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synergistic effects of IL-6 and IFN-gamma on carcinoembryonic antigen (CEA) and HLA expression by human colorectal carcinoma cells: role for endogenous IFN-beta. AN - 77329936; 7780031 AB - When administered as single agents, both interferon gamma (IFN-gamma) and interleukin 6 (IL-6) significantly increase carcinoembryonic antigen (CEA) and HLA class I antigen expression on the surface of human colorectal tumour cells. Studies were carried out to determine whether by combining those cytokines a synergistic enhancement of CEA and HLA expression could result. The findings revealed that the administration of 20 units IFN-gamma along with 1.7 ng IL-6, concentrations of each cytokine that individually induced minimal antigenic changes, together synergistically increased CEA and HLA class I as well as induced qualitative changes in HLA expression on WiDr human colon carcinoma cells. The magnitude of the synergistic increases in CEA and HLA class I expression were reminiscent of the level of antigen augmentation observed when administering 20- to 100-fold higher amounts of each cytokine as a single agent. Also, the addition of IL-6 potentiated the IFN-gamma induction of HLA class II expression. The combined administration of IL-6 potentiated the IFN-gamma did not have any additive or synergistic effects on the growth suppression of those tumour cells. Interestingly, utilization of specific neutralizing antibodies for type I interferons abrogated the increases of CEA and HLA expression seen with IL-6 treatment alone or in combination with IFN-gamma. Moreover, reverse transcriptase/polymerase chain reaction analyses revealed a constitutive expression as well as a temporal increase of IFN-beta mRNA transcripts in colon tumour cells treated with IL-6. Therefore, the findings provide indirect evidence that IFN-beta production seems to play a critical role in the ability of IL-6 to upregulate antigen expression alone or in combination with IFN-gamma. These findings provide insight into cytokine combinations that synergistically upregulate tumour-associated and normal HLA antigen expression on the surface of human tumour cells. Those results provide the rationale for the combined use of such cytokines to heighten tumour cell recognition in monoclonal antibody- or cell-mediated-based immunotherapeutic approaches. JF - Cytokine AU - Dansky-Ullmann, C AU - Salgaller, M AU - Adams, S AU - Schlom, J AU - Greiner, J W AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 118 EP - 129 VL - 7 IS - 2 SN - 1043-4666, 1043-4666 KW - Antibodies, Monoclonal KW - 0 KW - Carcinoembryonic Antigen KW - HLA-D Antigens KW - Histocompatibility Antigens Class I KW - Interleukin-6 KW - RNA, Messenger KW - Recombinant Proteins KW - Interferon-gamma KW - 82115-62-6 KW - Index Medicus KW - Tumor Cells, Cultured KW - Humans KW - Polymerase Chain Reaction -- methods KW - RNA, Messenger -- analysis KW - Flow Cytometry KW - Antibodies, Monoclonal -- pharmacology KW - Drug Synergism KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Colonic Neoplasms KW - RNA, Messenger -- biosynthesis KW - Colorectal Neoplasms KW - Cell Line KW - Gene Expression -- drug effects KW - Carcinoembryonic Antigen -- biosynthesis KW - Histocompatibility Antigens Class I -- biosynthesis KW - Interferon-gamma -- pharmacology KW - Interleukin-6 -- pharmacology KW - HLA-D Antigens -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77329936?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytokine&rft.atitle=Synergistic+effects+of+IL-6+and+IFN-gamma+on+carcinoembryonic+antigen+%28CEA%29+and+HLA+expression+by+human+colorectal+carcinoma+cells%3A+role+for+endogenous+IFN-beta.&rft.au=Dansky-Ullmann%2C+C%3BSalgaller%2C+M%3BAdams%2C+S%3BSchlom%2C+J%3BGreiner%2C+J+W&rft.aulast=Dansky-Ullmann&rft.aufirst=C&rft.date=1995-02-01&rft.volume=7&rft.issue=2&rft.spage=118&rft.isbn=&rft.btitle=&rft.title=Cytokine&rft.issn=10434666&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-18 N1 - Date created - 1995-07-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Variation in the association of alcohol consumption with five DSM-IV alcohol problem domains. AN - 77313492; 7771666 AB - Data from a nationally representative sample of the U.S. adult population were used to investigate the association between alcohol consumption and five discrete problem domains included in the DSM-IV formulations for alcohol abuse and dependence. Two dimensions of consumption were considered in the analysis: average daily ethanol intake and the relative frequency of drinking five or more drinks. The sample consisted of 22,102 adults defined as current drinkers. After controlling for various sociodemographic characteristics, family history of alcoholism, and age at onset of drinking, both consumption measures retained significant levels of association within all five problem domains. The magnitudes of the odds ratios at selected levels of consumption were approximately 50% greater for the domains of impaired control, continued drinking despite problems and hazardous drinking than for the domains of tolerance and withdrawal. Moreover, the factors that modified the effect of the consumption measures varied markedly across domains, with age, college education, and race the most consistent modifiers of the effect of alcohol consumption. JF - Alcoholism, clinical and experimental research AU - Dawson, D A AU - Grant, B F AU - Harford, T C AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20892, USA. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 66 EP - 74 VL - 19 IS - 1 SN - 0145-6008, 0145-6008 KW - Index Medicus KW - Odds Ratio KW - Humans KW - Alcohol Drinking -- adverse effects KW - Alcohol Withdrawal Delirium -- diagnosis KW - Alcohol Drinking -- epidemiology KW - Psychometrics KW - Alcohol Withdrawal Delirium -- epidemiology KW - Cross-Sectional Studies KW - Risk Factors KW - Adult KW - Health Surveys KW - Sampling Studies KW - Alcohol Drinking -- psychology KW - Alcohol Withdrawal Delirium -- psychology KW - Incidence KW - Adolescent KW - Male KW - Female KW - Alcoholism -- epidemiology KW - Alcoholism -- diagnosis KW - Psychiatric Status Rating Scales -- statistics & numerical data KW - Alcoholism -- genetics KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77313492?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Variation+in+the+association+of+alcohol+consumption+with+five+DSM-IV+alcohol+problem+domains.&rft.au=Dawson%2C+D+A%3BGrant%2C+B+F%3BHarford%2C+T+C&rft.aulast=Dawson&rft.aufirst=D&rft.date=1995-02-01&rft.volume=19&rft.issue=1&rft.spage=66&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 - 1995-07-06 N1 - Date created - 1995-07-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of human LAK-cell activity by the anti-depressant trifluoperazine. AN - 77305347; 7768666 AB - The anti-depressive drug trifluoperazine (TFP) was studied on in vitro immune responses. TFP proved to be an inhibitor of lymphokine-activated killer (LAK) cells in its generative step, as well as in its effector phase. Natural killer (NK) activity and interleukin-2 (IL-2) or mitogen-induced lymphocyte proliferation were just as sensitive to the drug effects, whereas the division of tumor cells was more resistant. The mechanism through which TFP suppresses these lymphocytic systems remains unclear. It does not, however, affect an early stage of cellular activation as the addition of the drug as late as 24 h after the start of the culture was still inhibitory for lymphocyte mitogenesis. Neither the expression of CD25, nor that of CD56 was affected by TFP, and exogenous IL-2 was unable to overcome the suppression of proliferation. In relation to cell-mediated cytotoxicity, TFP partially interfered with the effector/target binding. However, addition of lectin to the assay did not overcome the inhibition of lysis produced by the drug. Although further work remains to be done, the effect of TFP on immune responses must be taken into consideration when treating immunosuppressed patients. JF - Immunopharmacology AU - de La Rocque, L AU - Campos, M M AU - Olej, B AU - Castilho, F AU - Mediano, I F AU - Rumjanek, V M AD - Basic Research Center, National Cancer Institute, Rio de Janeiro, Brazil. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 1 EP - 10 VL - 29 IS - 1 SN - 0162-3109, 0162-3109 KW - Antigens, Differentiation, T-Lymphocyte KW - 0 KW - Interleukin-2 KW - Mitogens KW - Receptors, Interleukin-2 KW - Trifluoperazine KW - 214IZI85K3 KW - Dipeptidyl Peptidase 4 KW - EC 3.4.14.5 KW - Index Medicus KW - Mitogens -- pharmacology KW - Interleukin-2 -- pharmacology KW - Humans KW - Receptors, Interleukin-2 -- biosynthesis KW - Cell Division -- drug effects KW - Leukemia, Erythroblastic, Acute -- pathology KW - Killer Cells, Natural -- drug effects KW - Lymphocyte Activation -- drug effects KW - T-Lymphocytes -- metabolism KW - Lymphocyte Activation -- genetics KW - Antigens, Differentiation, T-Lymphocyte -- genetics KW - Antigens, Differentiation, T-Lymphocyte -- drug effects KW - Dipeptidyl Peptidase 4 -- biosynthesis KW - Tumor Cells, Cultured KW - Binding, Competitive KW - Flow Cytometry KW - T-Lymphocytes -- drug effects KW - Immunosuppression KW - Leukemia, T-Cell -- pathology KW - Killer Cells, Lymphokine-Activated -- drug effects KW - Trifluoperazine -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77305347?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Immunopharmacology&rft.atitle=Inhibition+of+human+LAK-cell+activity+by+the+anti-depressant+trifluoperazine.&rft.au=de+La+Rocque%2C+L%3BCampos%2C+M+M%3BOlej%2C+B%3BCastilho%2C+F%3BMediano%2C+I+F%3BRumjanek%2C+V+M&rft.aulast=de+La+Rocque&rft.aufirst=L&rft.date=1995-02-01&rft.volume=29&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Immunopharmacology&rft.issn=01623109&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-30 N1 - Date created - 1995-06-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization and mapping of three new mammalian ATP-binding transporter genes from an EST database. AN - 77301613; 7766993 AB - Analysis of the human expressed sequence tag (EST) database identified four clones that contain sequences of previously uncharacterized genes, members of the ATP-binding cassette (ABC) superfamily. Two new ABC genes (EST20237, 31252) are located at Chromosome (Chr) 1q42 and 1q25 respectively in humans, as determined by FISH; at locations distinct from previously mapped genes of this superfamily. Two additional clones, EST 600 and EST 1596, were found to represent different ATP-binding domains of the same gene, ABC2. This gene was localized to 9q34 in humans by FISH and to the proximal region of Chr 2 in mice by linkage analysis. All genes display extensive diversity in sequence and expression pattern. We present several approaches to characterizing EST clones and demonstrate that the analysis of EST clones from different tissues is a powerful approach to identify new members of important gene families. Some drawbacks of using EST databases, including chimerism of cDNA clones, are discussed. JF - Mammalian genome : official journal of the International Mammalian Genome Society AU - Allikmets, R AU - Gerrard, B AU - Glavac, D AU - Ravnik-Glavac, M AU - Jenkins, N A AU - Gilbert, D J AU - Copeland, N G AU - Modi, W AU - Dean, M AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702-1201, USA. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 114 EP - 117 VL - 6 IS - 2 SN - 0938-8990, 0938-8990 KW - ABC2 KW - PGY1 KW - DNA, Complementary KW - 0 KW - Index Medicus KW - Animals KW - DNA, Complementary -- genetics KW - Sequence Alignment KW - Humans KW - Molecular Sequence Data KW - Mice, Inbred C57BL KW - Gene Expression KW - Databases, Factual KW - Mice KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Muridae -- genetics KW - Cloning, Molecular KW - Genes KW - Multigene Family KW - ATP-Binding Cassette Transporters -- genetics KW - Mammals -- genetics KW - Chromosome Mapping UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77301613?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mammalian+genome+%3A+official+journal+of+the+International+Mammalian+Genome+Society&rft.atitle=Characterization+and+mapping+of+three+new+mammalian+ATP-binding+transporter+genes+from+an+EST+database.&rft.au=Allikmets%2C+R%3BGerrard%2C+B%3BGlavac%2C+D%3BRavnik-Glavac%2C+M%3BJenkins%2C+N+A%3BGilbert%2C+D+J%3BCopeland%2C+N+G%3BModi%2C+W%3BDean%2C+M&rft.aulast=Allikmets&rft.aufirst=R&rft.date=1995-02-01&rft.volume=6&rft.issue=2&rft.spage=114&rft.isbn=&rft.btitle=&rft.title=Mammalian+genome+%3A+official+journal+of+the+International+Mammalian+Genome+Society&rft.issn=09388990&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-05 N1 - Date created - 1995-07-05 N1 - Date revised - 2017-01-13 N1 - Gene symbol - ABC2; PGY1 N1 - Genetic sequence - U18237; GENBANK; U18235; U18236 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Correlations among Hill parameters reflect models of activating ligand-gated ion channels. AN - 77298740; 7762081 AB - Molecular biology has contributed a concept, novel in pharmacology, in which the receptor is an independent variable. Site-directed mutagenesis of ligand-gated ion channels is now commonplace. The mutant receptor is usually characterized by the Hill parameters that describe concentration-response curves from transfected, voltage-clamped cells. In this article, Charles Spivak describes how to convert parameters for realistic models of channel activation into Hill parameters. Correlations among the Hill parameters that the models enforce can be useful in tentatively assigning a physiological function to the mutation site. JF - Trends in pharmacological sciences AU - Spivak, C E AD - Division of Intramural Research, National Institute on Drug Abuse, Baltimore, MD 21224, USA. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 39 EP - 42 VL - 16 IS - 2 SN - 0165-6147, 0165-6147 KW - Ligands KW - 0 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Molecular Conformation KW - Models, Biological KW - Ion Channel Gating -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77298740?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Correlations+among+Hill+parameters+reflect+models+of+activating+ligand-gated+ion+channels.&rft.au=Spivak%2C+C+E&rft.aulast=Spivak&rft.aufirst=C&rft.date=1995-02-01&rft.volume=16&rft.issue=2&rft.spage=39&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 - 1995-06-23 N1 - Date created - 1995-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Serotonin, schizophrenia and antipsychotic drug action. AN - 77295444; 7539288 AB - A rapidly growing body of data suggests that dysfunction in serotonergic (5-HT) function may be involved in the pathophysiology of schizophrenia, and that pharmacologic agents for this illness have their therapeutic effects mediated through serotonergic mechanisms. The purpose of this paper is to critically review data relevant to 5-HT's role in the pathophysiology and drug treatment of schizophrenia. Pathophysiologic evidence includes the psychotomimetic effects of lysergic acid (LSD), postmortem studies, single-dose 'challenge' studies and investigations of CSF and peripheral levels of 5-HT and its metabolites. The current nomenclature, potential therapeutic effects and importance of 5-HT receptor subtype antagonism will be examined. In addition, relatively novel strategies of 5-HT uptake blockade and direct acting 5-HT agonists will be assessed. A hypothesis of cortical-subcortical imbalance with an increase in subcortical 5-HT function responsible for positive symptoms and a decrease in prefrontal 5-HT function responsible for negative symptoms is proposed. Future implications of these data are discussed. JF - Schizophrenia research AU - Breier, A AD - National Institute of Mental Health, Experimental Therapeutics Branch, Bethesda, Maryland 20892, USA. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 187 EP - 202 VL - 14 IS - 3 SN - 0920-9964, 0920-9964 KW - Antipsychotic Agents KW - 0 KW - Isoxazoles KW - Piperazines KW - Piperidines KW - amperozide KW - 0M2W3TAG39 KW - Serotonin KW - 333DO1RDJY KW - Tryptophan KW - 8DUH1N11BX KW - Clozapine KW - J60AR2IKIC KW - Risperidone KW - L6UH7ZF8HC KW - 1-(3-chlorophenyl)piperazine KW - REY0CNO998 KW - Index Medicus KW - Tryptophan -- pharmacology KW - Tryptophan -- adverse effects KW - Humans KW - Piperazines -- therapeutic use KW - Basal Ganglia Diseases -- etiology KW - Piperazines -- adverse effects KW - Clozapine -- adverse effects KW - Piperazines -- pharmacology KW - Piperidines -- adverse effects KW - Piperidines -- pharmacology KW - Isoxazoles -- adverse effects KW - Clozapine -- pharmacology KW - Isoxazoles -- pharmacology KW - Schizophrenia -- blood KW - Serotonin -- cerebrospinal fluid KW - Serotonin -- blood KW - Schizophrenia -- drug therapy KW - Serotonin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77295444?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Schizophrenia+research&rft.atitle=Serotonin%2C+schizophrenia+and+antipsychotic+drug+action.&rft.au=Breier%2C+A&rft.aulast=Breier&rft.aufirst=A&rft.date=1995-02-01&rft.volume=14&rft.issue=3&rft.spage=187&rft.isbn=&rft.btitle=&rft.title=Schizophrenia+research&rft.issn=09209964&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-06 N1 - Date created - 1995-07-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Combination intraventricular therapy with thiotepa and cytarabine in meningeal carcinomatosis due to breast cancer: in vitro evidence for supra-additive cytotoxicity. AN - 77290628; 7756682 AB - Metastatic spread of tumors to the meninges is a frequent complication of many malignancies and is difficult to treat. We describe the case of a patient who developed carcinomatous involvement of the meninges from a breast adenocarcinoma. Despite intrathecal treatment with conventional and experimental agents, the patient's cerebrospinal fluid (CSF) was not cleared of malignant cells until thiotepa and cytarabine were given in combination. This clinical observation led us to assess the in vitro activity of the combination of thiotepa and cytarabine in clonogenic cell survival assays. The human breast adenocarcinoma cell line MCF-7WT and its doxorubicin-resistant variant MCF-7ADR were exposed to thiotepa and cytarabine either singly or in combination. We have found that the combination of the two drugs resulted in more than additive cytotoxicity than would have been predicted from the cytotoxicity of either drug given alone. We discuss the implications of these findings on the clinical management of patients with carcinomatous spread to the meninges. JF - Anti-cancer drugs AU - Liebmann, J AU - Gurtler, J AD - Radiation Biology Branch, National Cancer Institute, Bethesda, MD 20895, USA. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 40 EP - 44 VL - 6 IS - 1 SN - 0959-4973, 0959-4973 KW - Cytarabine KW - 04079A1RDZ KW - Cyclophosphamide KW - 8N3DW7272P KW - Thiotepa KW - 905Z5W3GKH KW - perfosfamide KW - U880A4FUDA KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Salvage Therapy KW - Drug Resistance KW - Cytarabine -- administration & dosage KW - Injections, Intraventricular KW - Cytarabine -- pharmacology KW - Cyclophosphamide -- analogs & derivatives KW - Thiotepa -- pharmacology KW - Breast Neoplasms -- pathology KW - Thiotepa -- administration & dosage KW - Middle Aged KW - Drug Synergism KW - Female KW - Meningeal Neoplasms -- secondary KW - Meningeal Neoplasms -- drug therapy KW - Adenocarcinoma -- secondary KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Adenocarcinoma -- drug therapy KW - Adenocarcinoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77290628?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anti-cancer+drugs&rft.atitle=Combination+intraventricular+therapy+with+thiotepa+and+cytarabine+in+meningeal+carcinomatosis+due+to+breast+cancer%3A+in+vitro+evidence+for+supra-additive+cytotoxicity.&rft.au=Liebmann%2C+J%3BGurtler%2C+J&rft.aulast=Liebmann&rft.aufirst=J&rft.date=1995-02-01&rft.volume=6&rft.issue=1&rft.spage=40&rft.isbn=&rft.btitle=&rft.title=Anti-cancer+drugs&rft.issn=09594973&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-26 N1 - Date created - 1995-06-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Specific protein kinase C isozymes mediate the induction of keratinocyte differentiation markers by calcium. AN - 77289592; 7756173 AB - The maturation of epidermal keratinocytes is a tightly regulated, stepwise process which requires protein kinase C (PKC) activation. We investigated the effect of elevated extracellular Ca2+, a potent differentiation signal which increases cellular sn-1,2-diacylglycerol levels, on the PKC isozyme profile of cultured murine keratinocytes. Five PKC isozymes (alpha, delta, epsilon, zeta, and eta) were detected by immunoblotting. During Ca(2+)-induced differentiation, total cellular PKC alpha decreased, PKC epsilon and eta increased 3-5-fold, and the level of other PKC isozymes was relatively unchanged. PKC alpha underwent a progressive translocation from the soluble to the particulate fraction following elevation of extracellular Ca2+. The kinetics of PKC alpha translocation corresponded with the induction of keratinocyte differentiation markers. Both PKC delta and epsilon were selectively lost from the soluble fraction of keratinocytes exposed to elevated extracellular Ca2+, resulting in an increase in the proportion of these isoforms in the particulate fraction. PKC eta increased in both the soluble and particulate fractions, while PKC zeta did not change in amount or distribution during keratinocyte differentiation. Selective down-regulation of PKC isoforms by either 12-deoxyphorbol-13-phenylacetate or bryostatin 1 inhibited Ca(2+)-induced expression of differentiation markers at doses most specific for the down-regulation of PKC alpha. Taken together, these observations suggest that the induction of keratinocyte differentiation by Ca2+ results in the activation of specific PKC isozymes. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Denning, M F AU - Dlugosz, A A AU - Williams, E K AU - Szallasi, Z AU - Blumberg, P M AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 149 EP - 157 VL - 6 IS - 2 SN - 1044-9523, 1044-9523 KW - Biomarkers KW - 0 KW - Bryostatins KW - Isoenzymes KW - Lactones KW - Macrolides KW - Phorbol Esters KW - bryostatin 1 KW - 37O2X55Y9E KW - 12-deoxyphorbolphenylacetate KW - 58821-98-0 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Immunoblotting KW - Enzyme Activation KW - Mice KW - Mice, Inbred BALB C KW - Lactones -- pharmacology KW - Evaluation Studies as Topic KW - Phorbol Esters -- pharmacology KW - Biomarkers -- chemistry KW - Subcellular Fractions -- physiology KW - Cell Differentiation -- drug effects KW - Down-Regulation -- drug effects KW - Isoenzymes -- antagonists & inhibitors KW - Protein Kinase C -- antagonists & inhibitors KW - Isoenzymes -- physiology KW - Keratinocytes -- drug effects KW - Keratinocytes -- cytology KW - Calcium -- pharmacology KW - Protein Kinase C -- physiology KW - Calcium -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77289592?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Specific+protein+kinase+C+isozymes+mediate+the+induction+of+keratinocyte+differentiation+markers+by+calcium.&rft.au=Denning%2C+M+F%3BDlugosz%2C+A+A%3BWilliams%2C+E+K%3BSzallasi%2C+Z%3BBlumberg%2C+P+M%3BYuspa%2C+S+H&rft.aulast=Denning&rft.aufirst=M&rft.date=1995-02-01&rft.volume=6&rft.issue=2&rft.spage=149&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 - 1995-06-23 N1 - Date created - 1995-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effects of anticonvulsant compounds on 4-aminopyridine-induced de novo synthesis of neurotransmitter amino acids in rat hippocampus in vitro. AN - 77289561; 7750507 AB - 4-Aminopyridine, a voltage-dependent potassium channel blocker, causes tonic-clonic and electrographic seizures in vivo and evokes epileptiform activity and release of glutamate, aspartate and GABA in vitro. This study examined the effects of 4-aminopyridine (4AP) on de novo synthesis of neuroactive amino acids and a subsequent response to various anticonvulsant compounds (phenytoin, carbamazepine, phenobarbital, valproate, ethosuximide, diazepam, lamotrigine, felbamate, losigamone, U54494A, CPP, MK801 and CNQX) using a hippocampal slice preparation. 4-Aminopyridine had a minimal effect on total tissue concentrations of glutamate, aspartate, and GABA, but caused a significant increase in their de novo synthesis. Phenytoin, carbamazepine, lamotrigine, losigamone and U54494A were the only compounds which were effective in blocking the 4AP-induced increase in all newly synthesized amino acids. It appears that these compounds inhibit 4AP effects in this paradigm by blocking depolarization, probably at use-dependent voltage-sensitive sodium channels. Therefore, this paradigm may be useful in selectively identifying anticonvulsants which act by blocking depolarization. JF - Epilepsy research AU - Kapetanovic, I M AU - Yonekawa, W D AU - Kupferberg, H J AD - Preclinical Pharmacology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 113 EP - 120 VL - 20 IS - 2 SN - 0920-1211, 0920-1211 KW - Anticonvulsants KW - 0 KW - Nerve Tissue Proteins KW - Neurotransmitter Agents KW - Tetrodotoxin KW - 4368-28-9 KW - 4-Aminopyridine KW - BH3B64OKL9 KW - Glucose KW - IY9XDZ35W2 KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Animals KW - Glucose -- metabolism KW - In Vitro Techniques KW - Nerve Tissue Proteins -- metabolism KW - Tetrodotoxin -- pharmacology KW - Male KW - Anticonvulsants -- pharmacology KW - 4-Aminopyridine -- pharmacology KW - Hippocampus -- metabolism KW - Neurotransmitter Agents -- biosynthesis KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77289561?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epilepsy+research&rft.atitle=The+effects+of+anticonvulsant+compounds+on+4-aminopyridine-induced+de+novo+synthesis+of+neurotransmitter+amino+acids+in+rat+hippocampus+in+vitro.&rft.au=Kapetanovic%2C+I+M%3BYonekawa%2C+W+D%3BKupferberg%2C+H+J&rft.aulast=Kapetanovic&rft.aufirst=I&rft.date=1995-02-01&rft.volume=20&rft.issue=2&rft.spage=113&rft.isbn=&rft.btitle=&rft.title=Epilepsy+research&rft.issn=09201211&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-16 N1 - Date created - 1995-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanisms, chemical carcinogenesis, and risk assessment: cell proliferation and cancer. AN - 77287861; 7755018 AB - Mechanisms of carcinogenesis--and in particular chemically associated carcinogenicity--have attracted considerable scientific and public attention in the last decade. Much insight has been gained that will lead to more reasoned and better prevention, intervention, and treatment for the reduction of environmentally caused cancers. However, there seems to be an exaggerated tendency to embrace "mechanisms" not yet fully characterized, completely tested, unequivocally proven, and consensus accepted. More than 100 agents and exposure circumstances have been identified as causally or strongly associated with human cancers; for many the evidence was discovered first in experimental animals. More chemicals have been uncovered as carcinogenic in experimental animals, with as yet no or little available information in exposed human populations. Additional and expanded mechanistic and epidemiological studies should further elucidate the relevance of these agents to adverse human health effects, including cancers. Claims are being posed that certain chemical-specific "mechanisms" in experimental systems are irrelevant to humans, and thus chemicals thought to be aberrantly carcinogenic in animals would present no cancer hazard to exposed humans. Nonetheless before undeniable proof becomes available, we must continue to proceed with sensitive and responsible caution. This commentary offers a central and personal view of one such mechanism: cell proliferation and cancer. JF - American journal of industrial medicine AU - Huff, J AD - Environmental Carcinogenesis Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 293 EP - 300 VL - 27 IS - 2 SN - 0271-3586, 0271-3586 KW - Carcinogens KW - 0 KW - Index Medicus KW - Rats KW - Animals KW - Humans KW - Risk Assessment KW - Neoplasms -- pathology KW - Carcinogens -- pharmacokinetics KW - Neoplasms -- chemically induced KW - Cell Division -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77287861?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=Mechanisms%2C+chemical+carcinogenesis%2C+and+risk+assessment%3A+cell+proliferation+and+cancer.&rft.au=Huff%2C+J&rft.aulast=Huff&rft.aufirst=J&rft.date=1995-02-01&rft.volume=27&rft.issue=2&rft.spage=293&rft.isbn=&rft.btitle=&rft.title=American+journal+of+industrial+medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-21 N1 - Date created - 1995-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bone marrow aplasia and severe skin rash after a single low dose of methotrexate. AN - 77282539; 7538828 AB - A 64 year old man with recurrent metastatic squamous cell carcinoma of the head and neck developed severe skin rash and bone marrow aplasia 4 and 7 days, respectively, following a single dose of 40 mg/m2 methotrexate (MTX). Skin rash involved regions of the face, lower abdomen, back, buttocks and both upper thighs. Biopsy of the skin rash demonstrated superficial perivascular lymphocytic infiltrate and was consistent with a drug reaction. Peripheral blood count revealed pancytopenia and a bone marrow biopsy was consistent with aplasia. Blood counts returned to normal 6 days after institution of granulocyte colony stimulating factor therapy. In the absence of mucositis or diarrhea, severe dermatologic toxicity following a single low dose of the drug suggests an 'allergic' or acute hypersensitivity reaction to MTX in this patient. Development of an extensive skin rash following a single dose of MTX may be an early warning sign for life-threatening bone marrow aplasia. JF - Anti-cancer drugs AU - Copur, S AU - Dahut, W AU - Chu, E AU - Allegra, C J AD - NCI-Navy Medical Oncology Branch, National Cancer Institute, Bethesda, MD 20889-5105, USA. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 154 EP - 157 VL - 6 IS - 1 SN - 0959-4973, 0959-4973 KW - Immunologic Factors KW - 0 KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Granulocyte Colony-Stimulating Factor -- therapeutic use KW - Combined Modality Therapy KW - Immunologic Factors -- therapeutic use KW - Humans KW - Middle Aged KW - Male KW - Laryngeal Neoplasms -- therapy KW - Drug Eruptions -- etiology KW - Carcinoma, Squamous Cell -- secondary KW - Methotrexate -- adverse effects KW - Pancytopenia -- therapy KW - Methotrexate -- therapeutic use KW - Carcinoma, Squamous Cell -- drug therapy KW - Pancytopenia -- chemically induced KW - Laryngeal Neoplasms -- drug therapy KW - Carcinoma, Squamous Cell -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77282539?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anti-cancer+drugs&rft.atitle=Bone+marrow+aplasia+and+severe+skin+rash+after+a+single+low+dose+of+methotrexate.&rft.au=Copur%2C+S%3BDahut%2C+W%3BChu%2C+E%3BAllegra%2C+C+J&rft.aulast=Copur&rft.aufirst=S&rft.date=1995-02-01&rft.volume=6&rft.issue=1&rft.spage=154&rft.isbn=&rft.btitle=&rft.title=Anti-cancer+drugs&rft.issn=09594973&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-26 N1 - Date created - 1995-06-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effects of anticonvulsant agents on 4-aminopyridine induced epileptiform activity in rat hippocampus in vitro. AN - 77279571; 7750510 AB - Six anticonvulsant drugs, phenytoin (PHT), carbamazepine (CBZ), valproate (VPA), U-54494A, losigamone (LOS), and D-20443, were studied using rat hippocampal slices and standard electrophysiological techniques. The K+ channel blocker, 4-aminopyridine (4-AP), was used as neuronal stimulant. The extracellular parameters evaluated in areas CA3 and CA1 were: (1) interictal-type bursting, (2) evoked population spike (PS) amplitude, (3) latency to PS onset, and (4) duration of the excitatory postsynaptic potential (EPSP). VPA was ineffective in altering any of the parameters. PHT and CBZ partially reversed the increase in EPSP duration produced by 4-AP in area CA3, while the spontaneous bursting was not affected. The experimental drugs, U-54494A, LOS, and D-20443 (dihydrochloride salt of D-23129 from Asta Medica), tended to reverse to varying degrees the 4-AP effects, especially the increase in the EPSP duration. U-54494A tended to depress responses even under control conditions. LOS partially reversed the 4-AP excitation, but abolished bursting in only one of five slices. D-20443 abolished bursting in all slices. It also partially reversed the 4-AP induced increase in the EPSP duration without depressing the normal evoked potential. The results show that 4-AP induced changes in vitro can help differentiate drugs with similar in vivo spectrums of anticonvulsant activity. While the drug induced changes may not truly define the mechanisms of action of these promising new agents, these experimental anticonvulsants can be differentiated from standard agents using the experimental paradigm in this study. JF - Epilepsy research AU - Yonekawa, W D AU - Kapetanovic, I M AU - Kupferberg, H J AD - Preclinical Pharmacology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 137 EP - 150 VL - 20 IS - 2 SN - 0920-1211, 0920-1211 KW - Anticonvulsants KW - 0 KW - 4-Aminopyridine KW - BH3B64OKL9 KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Injections, Intraperitoneal KW - Evoked Potentials -- drug effects KW - Animals KW - In Vitro Techniques KW - Electrophysiology KW - Male KW - Anticonvulsants -- pharmacology KW - Epilepsy -- physiopathology KW - Epilepsy -- chemically induced KW - 4-Aminopyridine -- pharmacology KW - Hippocampus -- physiopathology KW - Anticonvulsants -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77279571?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epilepsy+research&rft.atitle=The+effects+of+anticonvulsant+agents+on+4-aminopyridine+induced+epileptiform+activity+in+rat+hippocampus+in+vitro.&rft.au=Yonekawa%2C+W+D%3BKapetanovic%2C+I+M%3BKupferberg%2C+H+J&rft.aulast=Yonekawa&rft.aufirst=W&rft.date=1995-02-01&rft.volume=20&rft.issue=2&rft.spage=137&rft.isbn=&rft.btitle=&rft.title=Epilepsy+research&rft.issn=09201211&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-16 N1 - Date created - 1995-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biosynthesis of bone sialoprotein by a human osteoclast-like cell line (FLG 29.1). AN - 77277103; 7754798 AB - Biosynthesis of bone sialoprotein (BSP) by a human osteoclastic cell line (FLG 29.1) during its differentiation induced by phorbol 12-myristate 13-acetate (TPA) was studied using metabolic radiolabeling experiments. The FLG 29.1 cells were metabolically radiolabeled with [3H]glucosamine and [35S]sulfate, and the labeled glycoproteins were analyzed by anion exchange chromatography, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoprecipitation experiments. One of the major glycoproteins synthesized by the TPA-treated FLG 29.1 cells was sulfated, had an identical electrophoretic mobility to purified BSP, and could be immunoprecipitated with a specific antibody against human BSP (LF 6). Thus, this glycoprotein was tentatively identified as the BSP. Furthermore, mRNA for BSP was also detected in TPA-treated FLG 29.1 cells by RNA-polymerase chain reaction. Most BSP synthesized by FLG 29.1 cells remained cell-associated, and this is in contrast with those synthesized by osteoblasts, where the protein is rapidly released into the extracellular matrix. Immunocytochemistry using an anti-BSP antibody showed a prominent paranuclear (suggestive of Golgi apparatus) localization of BSP in the TPA-treated FLG 29.1 cells after permeabilization, while untreated cells were not significantly immunostained. Localization of BSP at the plasma membrane was also demonstrated in the TPA-treated FLG 29.1 cells by the fluorescence-activated cell sorting analysis. Since TPA has been demonstrated to induce expression of various osteoclastic characteristics in FLG 29.1 cells, induction of BSP expression by TPA suggests that the protein may play a role during the differentiation process of osteoclasts or in functions of differentiated osteoclasts. JF - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research AU - Masi, L AU - Brandi, M L AU - Robey, P G AU - Crescioli, C AU - Calvo, J C AU - Bernabei, P AU - Kerr, J M AU - Yanagishita, M AD - Bone Research Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 187 EP - 196 VL - 10 IS - 2 SN - 0884-0431, 0884-0431 KW - Glycoproteins KW - 0 KW - IBSP protein, human KW - Integrin-Binding Sialoprotein KW - RNA, Messenger KW - Sialoglycoproteins KW - Sulfates KW - Thrombin KW - EC 3.4.21.5 KW - Glucosamine KW - N08U5BOQ1K KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Extracellular Matrix -- metabolism KW - Electrophoresis, Polyacrylamide Gel KW - Humans KW - Chemical Fractionation KW - Amino Acid Sequence KW - Chromatography, Ion Exchange KW - Sulfates -- chemistry KW - RNA, Messenger -- genetics KW - Precipitin Tests KW - Autoradiography KW - Isotope Labeling KW - Polymerase Chain Reaction KW - Antibody Specificity KW - Base Sequence KW - RNA, Messenger -- metabolism KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Flow Cytometry KW - Glucosamine -- chemistry KW - Cell Differentiation -- drug effects KW - Thrombin -- metabolism KW - Immunohistochemistry KW - Cell Line KW - Osteoclasts -- cytology KW - Glycoproteins -- analysis KW - Sialoglycoproteins -- genetics KW - Glycoproteins -- metabolism KW - Sialoglycoproteins -- biosynthesis KW - Osteoclasts -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77277103?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+bone+and+mineral+research+%3A+the+official+journal+of+the+American+Society+for+Bone+and+Mineral+Research&rft.atitle=Biosynthesis+of+bone+sialoprotein+by+a+human+osteoclast-like+cell+line+%28FLG+29.1%29.&rft.au=Masi%2C+L%3BBrandi%2C+M+L%3BRobey%2C+P+G%3BCrescioli%2C+C%3BCalvo%2C+J+C%3BBernabei%2C+P%3BKerr%2C+J+M%3BYanagishita%2C+M&rft.aulast=Masi&rft.aufirst=L&rft.date=1995-02-01&rft.volume=10&rft.issue=2&rft.spage=187&rft.isbn=&rft.btitle=&rft.title=Journal+of+bone+and+mineral+research+%3A+the+official+journal+of+the+American+Society+for+Bone+and+Mineral+Research&rft.issn=08840431&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-19 N1 - Date created - 1995-06-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The macrophage, TNF, and other cytokines. AN - 77260004; 7538021 AB - A complex interplay of peptides known as the cytokines may have a tremendous influence over a number of inflammatory related conditions. Tumor necrosis factor occupies an early and central role in the initiation of cascades that ultimately influences a number of cell types involved in tissue inflammation, tissue rejection, cancer, and injuries from ischemia reperfusion. Only now are the cascades being defined and therapies being designed to interrupt the toxic effects of these cytokines and to treat malignancy. JF - Chest surgery clinics of North America AU - Pass, H I AU - Mew, D AU - Pass, H A AU - Temeck, B K AD - Section of Thoracic Oncology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 73 EP - 90 VL - 5 IS - 1 SN - 1052-3359, 1052-3359 KW - Colony-Stimulating Factors KW - 0 KW - Cytokines KW - Interleukins KW - Tumor Necrosis Factor-alpha KW - Interferons KW - 9008-11-1 KW - Index Medicus KW - Animals KW - Leukemia -- therapy KW - Anorexia -- etiology KW - Graft Rejection -- etiology KW - Humans KW - Immunotherapy KW - Shock, Septic -- etiology KW - Neoplasms -- physiopathology KW - Clinical Trials as Topic KW - Mice KW - Interleukins -- physiology KW - Neoplasms -- therapy KW - Respiratory Distress Syndrome, Adult -- etiology KW - Interferons -- physiology KW - Colony-Stimulating Factors -- physiology KW - In Vitro Techniques KW - Heart Diseases -- etiology KW - Cricetinae KW - Cytokines -- therapeutic use KW - Macrophages -- physiology KW - Cytokines -- physiology KW - Tumor Necrosis Factor-alpha -- physiology KW - Cytokines -- antagonists & inhibitors KW - Tumor Necrosis Factor-alpha -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77260004?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chest+surgery+clinics+of+North+America&rft.atitle=The+macrophage%2C+TNF%2C+and+other+cytokines.&rft.au=Pass%2C+H+I%3BMew%2C+D%3BPass%2C+H+A%3BTemeck%2C+B+K&rft.aulast=Pass&rft.aufirst=H&rft.date=1995-02-01&rft.volume=5&rft.issue=1&rft.spage=73&rft.isbn=&rft.btitle=&rft.title=Chest+surgery+clinics+of+North+America&rft.issn=10523359&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-09 N1 - Date created - 1995-06-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metabolism and elimination of oxazepam in F344 rats. AN - 77245878; 7736917 AB - The antianxiety agent, oxazepam, is a mouse liver carcinogen as determined by a National Toxicology Program bioassay. An equivalent study in the F344 rat is currently in progress. In an effort to gain insight into whether the mouse or rat will be a better model for human risk assessment, extensive comparative metabolism studies have been conducted in both rodent species and compared with the human literature. In this study, male rats were treated with 25, 250, or 500 mg/kg of radiolabeled oxazepam. In addition, sex comparisons were made at 500 mg/kg after 0 and 14 days of 2500 ppm oxazepam in the feed to mimic bioassay conditions. Similar studies have already been conducted in mice. Recovery of administered activity was dose-dependent, with recovery approaching 100% at the low dose. In all groups, the order of importance of route of elimination was fecal > urinary > expired. No significant sex-dependent differences were detected. Oxidative metabolism and sulfate conjugation were the major routes of metabolism. Pretreatment of animals with oxazepam-dosed feed resulted in evidence of hepatic enzyme induction. The rate of elimination for all three routes of elimination was elevated by dosed feed treatment. With regard to metabolite profile and routes of elimination, the rat is less like a human than the mouse. JF - Drug metabolism and disposition: the biological fate of chemicals AU - Griffin, R J AU - Burka, L T AD - National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 232 EP - 239 VL - 23 IS - 2 SN - 0090-9556, 0090-9556 KW - Oxazepam KW - 6GOW6DWN2A KW - Index Medicus KW - Rats KW - Eating -- drug effects KW - Animals KW - Rats, Inbred F344 KW - Drug Administration Schedule KW - Sex Factors KW - Dose-Response Relationship, Drug KW - Male KW - Female KW - Oxazepam -- pharmacology KW - Oxazepam -- pharmacokinetics KW - Oxazepam -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77245878?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.atitle=Metabolism+and+elimination+of+oxazepam+in+F344+rats.&rft.au=Griffin%2C+R+J%3BBurka%2C+L+T&rft.aulast=Griffin&rft.aufirst=R&rft.date=1995-02-01&rft.volume=23&rft.issue=2&rft.spage=232&rft.isbn=&rft.btitle=&rft.title=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.issn=00909556&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-05 N1 - Date created - 1995-06-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The diagnosis and management of uveitis. AN - 77236995; 7729329 AB - The diagnosis and management of uveitis is complicated and challenging. The protean signs and symptoms seen in patients with uveitis may lead to a diagnostic dilemma. A carefully taken history with particular attention to demographic factors and meticulous physical examination are crucial to guiding diagnostic testing. Tailoring the diagnostic approach in patients with uveitis frequently yields useful data in contrast to blanketing every possible uveitic entity. It is also important to distinguish among various aetiologies, including infectious and neoplastic causes which may respond to specific therapy. Medical treatment of noninfectious uveitis must have clear objectives including reduction of inflammation, relief of symptoms and restoration of visual functioning. Familiarity with possible symptoms and signs of adverse drug reactions is essential early in the course of treatment so that their effects may be minimised. Appropriate therapy of presumed autoimmune uveitis is based on disease severity, presence or absence of bilateral disease and the health status of the patient. JF - Drugs AU - Anglade, E AU - Whitcup, S M AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 213 EP - 223 VL - 49 IS - 2 SN - 0012-6667, 0012-6667 KW - Adrenal Cortex Hormones KW - 0 KW - Cyclosporins KW - Immunosuppressive Agents KW - Cyclophosphamide KW - 8N3DW7272P KW - 6-Mercaptopurine KW - E7WED276I5 KW - Azathioprine KW - MRK240IY2L KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Methotrexate -- pharmacology KW - Humans KW - 6-Mercaptopurine -- therapeutic use KW - Azathioprine -- therapeutic use KW - Cyclosporins -- therapeutic use KW - Azathioprine -- pharmacology KW - Clinical Trials as Topic KW - Cyclosporins -- pharmacology KW - Cyclosporins -- administration & dosage KW - Cyclophosphamide -- therapeutic use KW - Azathioprine -- administration & dosage KW - Methotrexate -- therapeutic use KW - 6-Mercaptopurine -- administration & dosage KW - 6-Mercaptopurine -- pharmacology KW - Methotrexate -- administration & dosage KW - Administration, Topical KW - Cyclophosphamide -- pharmacology KW - Adrenal Cortex Hormones -- therapeutic use KW - Adrenal Cortex Hormones -- pharmacology KW - Adrenal Cortex Hormones -- administration & dosage KW - Uveitis -- diagnosis KW - Uveitis -- epidemiology KW - Immunosuppressive Agents -- therapeutic use KW - Uveitis -- drug therapy KW - Immunosuppressive Agents -- pharmacology KW - Immunosuppressive Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77236995?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drugs&rft.atitle=The+diagnosis+and+management+of+uveitis.&rft.au=Anglade%2C+E%3BWhitcup%2C+S+M&rft.aulast=Anglade&rft.aufirst=E&rft.date=1995-02-01&rft.volume=49&rft.issue=2&rft.spage=213&rft.isbn=&rft.btitle=&rft.title=Drugs&rft.issn=00126667&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-01 N1 - Date created - 1995-06-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Involvement of H1 and other chromatin proteins in the formation of DNA-protein cross-links induced by visible light in the presence of methylene blue. AN - 77211905; 7714672 AB - The formation of DNA-protein cross-links (DPCs), induced by irradiation with visible light, was studied in methylene blue-treated (MB-treated) chromatin and H1-depleted chromatin. The effects of the MB concentration and radiation dose were studied using sodium dodecylsulphate-chloroform-isoamyl alcohol assay and sodium dodecylsulphate-polyacrylamide gel electrophoresis. Under identical experimental conditions, DPC formation was less in H1-depleted chromatin (70%) than in chromatin (92%). The non-histone proteins and core proteins of chromatin contributed towards DPC formation. Of the core proteins, H2A was more cross-linked than H4, whereas the bands for H2B and H3 melted into one in chromatin and H1-depleted chromatin. In both cases, the gel pattern showed the appearance of two new protein bands with approximate molecular weights of 27 kDa and 29 kDa as a result of histone-histone cross-linking. Viscometric studies showed that the dissociation of the compact structure of chromatin in 2 M NaCl was more extensive in irradiated, MB-treated, H1-depleted chromatin than in irradiated, MB-treated chromatin, indicating a reduction in the amount of DPC formation in H1-depleted chromatin. JF - Journal of photochemistry and photobiology. B, Biology AU - Lalwani, R AU - Maiti, S AU - Mukherji, S AD - Department of Biophysics, Chittaranjan National Cancer Institute, Calcutta, India. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 117 EP - 122 VL - 27 IS - 2 SN - 1011-1344, 1011-1344 KW - Chromatin KW - 0 KW - Cross-Linking Reagents KW - DNA, Neoplasm KW - Histones KW - Methylene Blue KW - T42P99266K KW - Index Medicus KW - Photochemistry KW - Animals KW - Sarcoma 180 -- metabolism KW - Electrophoresis, Polyacrylamide Gel KW - Kinetics KW - Light KW - Dose-Response Relationship, Radiation KW - Protein Binding KW - Molecular Weight KW - Male KW - DNA, Neoplasm -- radiation effects KW - DNA, Neoplasm -- drug effects KW - Methylene Blue -- pharmacology KW - Chromatin -- radiation effects KW - Histones -- radiation effects KW - Chromatin -- drug effects KW - Histones -- drug effects KW - Histones -- isolation & purification KW - DNA, Neoplasm -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77211905?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+photochemistry+and+photobiology.+B%2C+Biology&rft.atitle=Involvement+of+H1+and+other+chromatin+proteins+in+the+formation+of+DNA-protein+cross-links+induced+by+visible+light+in+the+presence+of+methylene+blue.&rft.au=Lalwani%2C+R%3BMaiti%2C+S%3BMukherji%2C+S&rft.aulast=Lalwani&rft.aufirst=R&rft.date=1995-02-01&rft.volume=27&rft.issue=2&rft.spage=117&rft.isbn=&rft.btitle=&rft.title=Journal+of+photochemistry+and+photobiology.+B%2C+Biology&rft.issn=10111344&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-18 N1 - Date created - 1995-05-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recent cancer trends in the United States. AN - 77210408; 7707404 AB - Cancer incidence rates have been reported to be increasing in the United States, although trends vary according to form of cancer. We identify the cancers accounting for the rising incidence, quantify the changes that have occurred from the mid-1970s to the early 1990s, and contrast incidence and mortality trends to provide clues to the determinants of the temporal patterns. Sex-, race-, and age-specific and age-adjusted incidence rates for the 5-year periods 1987-1991 versus 1975-1979 were calculated for 28 cancers among men and 30 cancers among women using data from the Surveillance, Epidemiology, and End Results (SEER) Program of cancer registration covering about 10% of the U.S. population. Similar rates were computed using national mortality data. Cancers were ranked according to the change in incidence rates over the two periods. Age-adjusted incidence rates for all cancers combined increased by 18.6% among males and 12.4% among females from 1975-1979 to 1987-1991, due largely to rising rates for prostate cancer among men and for breast and lung cancers among women. National mortality rates for all cancers combined rose less steeply, 3% and 6% among men and women, respectively, driven mostly by continuing increases in lung cancer mortality, while death rates for the majority of the cancers were steady or declining. Total cancer incidence rose at all ages, but with different tumors responsible for the increases at different ages: leukemia and brain/nervous system cancer among children; testicular cancer, nonmelanoma skin cancer (largely Kaposi's sarcoma), non-Hodgkin's lymphoma, and melanoma among young and middle-aged adults; and prostate, breast, and lung cancers among older individuals. In contrast, mortality rates for all cancers combined declined among both males and females under age 55 years, increasing only among older persons. Trends in cancer incidence and mortality differ. For most cancers, incidence rates are rising, while mortality rates are generally stable or declining. Much of the recent increase in cancer incidence can be explained by known factors. Improved detection appears to account for most of the increases in breast cancer among women and prostate cancer among men. On the other hand, cigarette smoking is the major determinant of the rise in lung cancer among women, acquired immunodeficiency syndrome has led to increases in non-Hodgkin's lymphoma and Kaposi's sarcoma among young and middle-aged men, and sunlight exposure patterns have affected the trends in melanoma. Some trends remain unexplained, however, and may reflect changing exposures to carcinogens yet to be identified and clarified. JF - Journal of the National Cancer Institute AU - Devesa, S S AU - Blot, W J AU - Stone, B J AU - Miller, B A AU - Tarone, R E AU - Fraumeni, J F AD - Division of Cancer Etiology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-7368, USA. Y1 - 1995/02/01/ PY - 1995 DA - 1995 Feb 01 SP - 175 EP - 182 VL - 87 IS - 3 SN - 0027-8874, 0027-8874 KW - Index Medicus KW - Humans KW - SEER Program KW - Continental Population Groups KW - Incidence KW - Models, Statistical KW - United States -- epidemiology KW - Sex Distribution KW - Male KW - Female KW - Age Distribution KW - Neoplasms -- mortality KW - Neoplasms -- epidemiology KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77210408?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Recent+cancer+trends+in+the+United+States.&rft.au=Devesa%2C+S+S%3BBlot%2C+W+J%3BStone%2C+B+J%3BMiller%2C+B+A%3BTarone%2C+R+E%3BFraumeni%2C+J+F&rft.aulast=Devesa&rft.aufirst=S&rft.date=1995-02-01&rft.volume=87&rft.issue=3&rft.spage=175&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 - 1995-05-09 N1 - Date created - 1995-05-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Natl Cancer Inst. 1995 Feb 1;87(3):159-60 [7707397] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis and quantitation of splicing variants of the TPA-inducible PGHS-1 mRNA in rat tracheal epithelial cells. AN - 77157768; 7864644 AB - Previously we reported that 12-myristate 13-acetate diester (TPA) and dexamethasone regulate the expression of a putative prostaglandin G/H synthase-1 (PGHS-1) gene in a transformed, immortalized rat tracheal epithelial cell line (EGV-6). Here we report the cloning and sequencing of the cDNA for this gene. Two transcripts of similar size but differing in their 5' ends were detected. One transcript contains the complete 5' coding and noncoding regions, while the other form has an apparently intronic sequence in place of these regions. This aberrantly spliced form lacks codons 1-36. Northern analysis and quantitative PCR indicated that more than 90% of the PGHS-1 mRNA in EGV-6 cells has the aberrantly spliced 5' end. TPA treatment increases the expression of only the complete PGHS-1 mRNA, elevating it to 50% of the total PGHS-1 transcript pool. Levels of the aberrant mRNA are not affected by TPA treatment. A comparison among EGV-6 cells, primary rat tracheal epithelial (RTE) cultures, and rat fibroblasts showed that all three cell lines have similar levels of the aberrantly spliced PGHS-1 mRNA. RTE cells and fibroblasts, unlike EGV-6 cells, also contain properly spliced PGHS-1 mRNA, at levels 100-fold higher than the level of aberrant PGHS-1 mRNA. TPA does not regulate either of the PGHS-1 transcripts in RTE or rat fibroblast cells. These results confirm the induction of functional PGHS-1 mRNA by TPA only in EGV-6 cells. JF - Archives of biochemistry and biophysics AU - Kitzler, J AU - Hill, E AU - Hardman, R AU - Reddy, N AU - Philpot, R AU - Eling, T E AD - Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709. Y1 - 1995/02/01/ PY - 1995 DA - 1995 Feb 01 SP - 856 EP - 863 VL - 316 IS - 2 SN - 0003-9861, 0003-9861 KW - Prostaglandin-Endoperoxide Synthases KW - EC 1.14.99.1 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Sequence Homology, Nucleic Acid KW - Amino Acid Sequence KW - Sequence Analysis, DNA KW - Genome KW - Cloning, Molecular KW - Gene Amplification KW - Rats KW - Base Sequence KW - Epithelial Cells KW - Cells, Cultured KW - Gene Expression Regulation, Enzymologic -- drug effects KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - RNA Splicing -- genetics KW - Genetic Variation KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Trachea -- metabolism KW - Trachea -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77157768?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Analysis+and+quantitation+of+splicing+variants+of+the+TPA-inducible+PGHS-1+mRNA+in+rat+tracheal+epithelial+cells.&rft.au=Kitzler%2C+J%3BHill%2C+E%3BHardman%2C+R%3BReddy%2C+N%3BPhilpot%2C+R%3BEling%2C+T+E&rft.aulast=Kitzler&rft.aufirst=J&rft.date=1995-02-01&rft.volume=316&rft.issue=2&rft.spage=856&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 - 1995-03-17 N1 - Date created - 1995-03-17 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U18060; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sensitivity to cadmium-induced genotoxicity in rat testicular cells is associated with minimal expression of the metallothionein gene. AN - 77156766; 7871536 AB - Cadmium is a carcinogenic metal. Although the mechanism of tumor induction is unknown, DNA/metal interactions may be involved. Metallothionein can protect against cadmium toxicity in our previous work it was shown to reduce cadmium genotoxicity in cultured cells. To extend these results, the genotoxicity of cadmium was studied in R2C cells, a rat testicular Leydig cell line. The R2C cells were very sensitive to cadmium-induced single-strand DNA damage (SSD), as measured by alkaline elution. SSD occurred in R2C cells after treatment with 25 and 50 microM CdCl2 for 2 hr. Prior work showed other cells required much higher levels of cadmium (approximately 500 microM) to induce genotoxicity. The genotoxic levels of cadmium (25-50 microM) were not cytotoxic in R2C cells as assessed by a metabolic activity (MTT) assay. Pretreatment of R2C cells with a low cadmium dose (2 microM, 24 hr) had no effect on cadmium-induced SSD, in contrast to prior work in other cells where such pretreatments reduced SSD through metallothionein gene activation. In fact, cadmium or zinc treatments resulted in little or no increase in metallothionein gene expression in R2C cells as determined by Northern blot analysis for metallothionein mRNA using cDNA or oligonucleotide probes and radioimmunoassay for metallothionein protein production. Basal metallothionein mRNA was essentially nondetectable. Induction of a cadmium-binding protein in R2C cells did occur, as determined by Cd-heme assay, but did not induce tolerance to SSD. In vivo, the Leydig cell is a target for cadmium carcinogenicity and its cadmium-binding protein is thought not to be a true metallothionein. These results indicate that R2C cells are sensitive to cadmium-induced genotoxicity and that this sensitivity is associated with minimal expression of the metallothionein gene. JF - Toxicology and applied pharmacology AU - Shiraishi, N AU - Hochadel, J F AU - Coogan, T P AU - Koropatnick, J AU - Waalkes, M P AD - Inorganic Carcinogenesis Section, PRI DynCorp, Frederick Cancer Research, National Cancer Institute, Frederick, Maryland 21702-1201. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 229 EP - 236 VL - 130 IS - 2 SN - 0041-008X, 0041-008X KW - Chlorides KW - 0 KW - DNA, Single-Stranded KW - Mutagens KW - RNA, Messenger KW - Cadmium KW - 00BH33GNGH KW - Metallothionein KW - 9038-94-2 KW - Cadmium Chloride KW - J6K4F9V3BA KW - Index Medicus KW - Rats KW - Animals KW - DNA, Single-Stranded -- drug effects KW - Base Sequence KW - Tumor Cells, Cultured KW - DNA Damage KW - Cells, Cultured KW - RNA, Messenger -- drug effects KW - Molecular Sequence Data KW - Gene Expression KW - Male KW - Chlorides -- toxicity KW - Cadmium -- toxicity KW - Mutagens -- toxicity KW - Metallothionein -- genetics KW - Leydig Cells -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77156766?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Sensitivity+to+cadmium-induced+genotoxicity+in+rat+testicular+cells+is+associated+with+minimal+expression+of+the+metallothionein+gene.&rft.au=Shiraishi%2C+N%3BHochadel%2C+J+F%3BCoogan%2C+T+P%3BKoropatnick%2C+J%3BWaalkes%2C+M+P&rft.aulast=Shiraishi&rft.aufirst=N&rft.date=1995-02-01&rft.volume=130&rft.issue=2&rft.spage=229&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 - 1995-03-29 N1 - Date created - 1995-03-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential regulation by anti-tumor-promoting 12-deoxyphorbol-13-phenylacetate reveals distinct roles of the classical and novel protein kinase C isozymes in biological responses of primary mouse keratinocytes. AN - 77155601; 7870033 AB - 12-Deoxyphorbol-13-phenylacetate (dPP) is the prototype for a new class of phorbol derivatives that function as protein kinase C (PKC) activators with potent anti-tumor-promoting activity. To explore the mechanism of action of dPP, we have conducted detailed analyses of the translocation and down-regulation patterns of individual PKC isozymes in mouse primary keratinocytes upon dPP treatment. PKC-alpha, -delta, and -epsilon were very quickly (within 2-5 min) translocated from the soluble fraction to the Triton X-100-soluble particulate fraction. PKC-delta and -epsilon were translocated with 2 orders of magnitude higher potency than was PKC-alpha. After translocation, PKC-alpha, -delta, -eta, and -epsilon were down-regulated; the down-regulation of PKC-epsilon contrasts with its retention after phorbol-12-myristate-13-acetate or bryostatin treatment. As was the case with translocation, dPP down-regulated the novel PKC isozymes (delta, epsilon, and eta) with 2 orders of magnitude higher potency (ED50, about 1-2 nM), compared with PKC-alpha (ED50, about 100 nM). dPP induced transglutaminase activity, ornithine decarboxylase activity, and cornification with potencies similar to that for PKC-alpha translocation. On the other hand, dPP caused inhibition of EGF binding with a potency similar to that for the translocation of the novel PKC isozymes. Although the generality of its selectivity in different cell types remains to be determined, at least in keratinocytes dPP is a powerful tool for dissecting the involvement of the classical and novel PKC isozymes in biological responses. The unique regulatory pattern of PKC-epsilon could contribute to the anti-tumor-promoting activity of dPP. JF - Molecular pharmacology AU - Szallasi, Z AU - Kosa, K AU - Smith, C B AU - Dlugosz, A A AU - Williams, E K AU - Yuspa, S H AU - Blumberg, P M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 258 EP - 265 VL - 47 IS - 2 SN - 0026-895X, 0026-895X KW - Isoenzymes KW - 0 KW - Phorbol Esters KW - 12-deoxyphorbolphenylacetate KW - 58821-98-0 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Animals KW - Down-Regulation KW - Cells, Cultured KW - Biological Transport KW - Mice KW - Mice, Inbred BALB C KW - Protein Kinase C -- metabolism KW - Phorbol Esters -- pharmacology KW - Keratinocytes -- enzymology KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77155601?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Differential+regulation+by+anti-tumor-promoting+12-deoxyphorbol-13-phenylacetate+reveals+distinct+roles+of+the+classical+and+novel+protein+kinase+C+isozymes+in+biological+responses+of+primary+mouse+keratinocytes.&rft.au=Szallasi%2C+Z%3BKosa%2C+K%3BSmith%2C+C+B%3BDlugosz%2C+A+A%3BWilliams%2C+E+K%3BYuspa%2C+S+H%3BBlumberg%2C+P+M&rft.aulast=Szallasi&rft.aufirst=Z&rft.date=1995-02-01&rft.volume=47&rft.issue=2&rft.spage=258&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 - 1995-03-29 N1 - Date created - 1995-03-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of gavage versus dosed feed administration on the toxicokinetics of benzyl acetate in rats and mice. AN - 77152887; 7868001 AB - Effects of gavage versus dosed feed administration on the toxicokinetics of benzyl acetate were studied in male F344 rats and B6C3F1 mice. Benzyl acetate was rapidly hydrolysed to benzyl alcohol and then oxidized to benzoic acid. After gavage administration of benzyl acetate in corn oil at 500 mg/kg (rats) and 1000 mg/kg (mice), high benzoic acid plasma concentrations were observed. In contrast, much lower benzoic acid plasma concentrations were found after dosed feed administration at about 615 mg/kg/day for rats and about 850 mg/kg/day for mice. Results show that although the daily doses of benzyl acetate are comparable, bolus gavage administration effectively saturated the benzoic acid elimination pathway whereas dosed feed administration did not. In contrast, hippuric acid plasma concentrations were similar after both gavage and dosed feed administration due to the depletion of the glycine supply pool. Study results could explain the different toxicity and carcinogenicity responses of benzyl acetate observed in 2-yr chronic gavage and dosed feed studies. JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association AU - Yuan, J H AU - Goehl, T J AU - Abdo, K AU - Clark, J AU - Espinosa, O AU - Bugge, C AU - Garcia, D AD - National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 151 EP - 158 VL - 33 IS - 2 SN - 0278-6915, 0278-6915 KW - Air Pollutants, Occupational KW - 0 KW - Benzoates KW - Benzyl Alcohols KW - Benzyl Compounds KW - Carcinogens KW - Hippurates KW - benzyl acetate KW - 0ECG3V79ZJ KW - Corn Oil KW - 8001-30-7 KW - Benzoic Acid KW - 8SKN0B0MIM KW - Benzyl Alcohol KW - LKG8494WBH KW - hippuric acid KW - TE0865N2ET KW - Glycine KW - TE7660XO1C KW - Index Medicus KW - Administration, Oral KW - Animals KW - Computer Simulation KW - Benzoates -- blood KW - Benzyl Alcohols -- metabolism KW - Glycine -- metabolism KW - Carcinogens -- toxicity KW - Mice KW - Hippurates -- blood KW - Benzyl Alcohols -- blood KW - Hydrolysis KW - Chromatography, High Pressure Liquid KW - Rats KW - Oxidation-Reduction KW - Rats, Inbred F344 KW - Carcinogens -- metabolism KW - In Vitro Techniques KW - Male KW - Air Pollutants, Occupational -- metabolism KW - Benzyl Compounds -- pharmacokinetics KW - Benzyl Compounds -- administration & dosage KW - Benzyl Compounds -- toxicity KW - Air Pollutants, Occupational -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77152887?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effects+of+gavage+versus+dosed+feed+administration+on+the+toxicokinetics+of+benzyl+acetate+in+rats+and+mice.&rft.au=Yuan%2C+J+H%3BGoehl%2C+T+J%3BAbdo%2C+K%3BClark%2C+J%3BEspinosa%2C+O%3BBugge%2C+C%3BGarcia%2C+D&rft.aulast=Yuan&rft.aufirst=J&rft.date=1995-02-01&rft.volume=33&rft.issue=2&rft.spage=151&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 - 1995-03-27 N1 - Date created - 1995-03-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HPLC investigation on Ni(II)-mediated DNA damage in the presence of t-butyl hydroperoxide and glutathione. AN - 77150443; 7861128 AB - By use of HPLC with UV and electrochemical detection, the present study demonstrates that reaction of Ni2+ with t-butyl hydroperoxide in the presence of glutathioine (GSH) generates 8-hydroxy-2'-deoxyguanosine (8-OH-dG) from 2'-deoxyguanosine (dG) and from dG residues in calf thymus DNA at physiological pH. No significant amount of 8-OH-dG was generated in the absence of GSH, indicating an important role of GSH in enhancing the reactivity of Ni2+ toward lipid hydroperoxide to oxidize dG or dG residues in DNA. The rate of dG conversion to 8-OH-dG depends on the concentration of the reagents. During a two hour incubation of 0.75 mM dG, 10 mM t-butyl hydroperoxide, 1 mM Ni2+, and 2 mM GSH at room temperature under ambient air, dG was converted to 8-OH-dG with a yield of about 0.2%. For dG residues in DNA, 24 hour incubation at 37 degrees C yielded 0.1% 8-OH-dG. The 8-OH-dG generation from both dG and dG residues in DNA was inhibited by superoxide dismutase, catalase, and ethanol (hydroxyl radical scavenger), implying the involvement of oxygen free radicals in the 8-OH-dG generation process. The metal ion chelators, deferoxamine and EDTA, efficiently inhibited the 8-OH-dG formation. Similar results were obtained for the conversion of dG residues in calf thymus DNA to 8-OH-dG. Electrophoretic assays of DNA strand breaks showed that Ni2+ caused DNA double-strand breaks in the presence of t-butyl hydroperoxide and GSH. Because GSH is ubiquitously present in cellular systems at relatively high concentration, and the exposure of cells to Ni2+ results in the generation of lipid hydroperoxides, the 8-OH-dG generation and DNA double-strand breaks caused by the reaction of Ni2+ with lipid hydroperoxides in the presence of GSH may be an important mechanism in Ni(2+)-induced carcinogenesis. The inhibitory effect of chelators suggests a possible prevention strategy against Ni(2+)-induced toxicity and carcinogenesis. JF - Journal of inorganic biochemistry AU - Shi, X AU - Mao, Y AU - Ahmed, N AU - Jiang, H AD - Laboratory of Experimental Pathology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 91 EP - 102 VL - 57 IS - 2 SN - 0162-0134, 0162-0134 KW - Peroxides KW - 0 KW - Reactive Oxygen Species KW - Ethanol KW - 3K9958V90M KW - Nickel KW - 7OV03QG267 KW - 8-oxo-7-hydrodeoxyguanosine KW - 88847-89-6 KW - DNA KW - 9007-49-2 KW - tert-Butylhydroperoxide KW - 955VYL842B KW - Edetic Acid KW - 9G34HU7RV0 KW - Catalase KW - EC 1.11.1.6 KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Deoxyguanosine KW - G9481N71RO KW - Glutathione KW - GAN16C9B8O KW - Deferoxamine KW - J06Y7MXW4D KW - Index Medicus KW - Animals KW - Reactive Oxygen Species -- metabolism KW - Ethanol -- pharmacology KW - DNA -- metabolism KW - Hydrogen-Ion Concentration KW - Catalase -- pharmacology KW - Cattle KW - Deoxyguanosine -- metabolism KW - Superoxide Dismutase -- pharmacology KW - Deferoxamine -- pharmacology KW - Kinetics KW - Edetic Acid -- pharmacology KW - Deoxyguanosine -- analogs & derivatives KW - Peroxides -- pharmacology KW - Nickel -- pharmacology KW - Glutathione -- pharmacology KW - Chromatography, High Pressure Liquid KW - DNA Damage -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77150443?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+inorganic+biochemistry&rft.atitle=HPLC+investigation+on+Ni%28II%29-mediated+DNA+damage+in+the+presence+of+t-butyl+hydroperoxide+and+glutathione.&rft.au=Shi%2C+X%3BMao%2C+Y%3BAhmed%2C+N%3BJiang%2C+H&rft.aulast=Shi&rft.aufirst=X&rft.date=1995-02-01&rft.volume=57&rft.issue=2&rft.spage=91&rft.isbn=&rft.btitle=&rft.title=Journal+of+inorganic+biochemistry&rft.issn=01620134&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-23 N1 - Date created - 1995-03-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanistic data indicate that 1,3-butadiene is a human carcinogen. AN - 77148236; 7859343 AB - A review of the epidemiological and mechanistic data on 1,3-butadiene indicates that this chemical is a human carcinogen for which the mouse is an appropriate model for assessing human cancer risk. Butadiene is carcinogenic at multiple organ sites in laboratory animals, including the induction of lymphomas in mice, while epidemiological studies have consistently found associations between occupational exposure to butadiene and increased mortality from lymphatic and hematopoietic cancers. Activated oncogenes and inactivated tumor suppressor genes in butadiene-induced tumors in mice are analogous to genetic alterations frequently observed in human cancers. Butadiene is metabolized to mutagenic and carcinogenic epoxides in all mammalian species studied, including humans. These metabolites form N7-alkylguanine adducts which have been detected in liver DNA of mice exposed to butadiene and in urine of exposed workers. Increases in hprt mutations were observed in lymphocytes from mice exposed to butadiene and in occupationally exposed humans. The mutational spectra for butadiene and its epoxide metabolites at the hprt locus in mouse lymphocytes are similar to the mutational spectrum of ethylene oxide; all of these chemicals exhibit a high percentage of frameshift mutations. Ethylene oxide, an alkylating agent that also forms an N7-alkylguanine adduct, was recently classified by the International Agency for Research on Cancer as a human carcinogen. Based on these data, we suggest that cancer induction by ethylene oxide and butadiene involve similar molecular mechanisms. JF - Carcinogenesis AU - Melnick, R L AU - Kohn, M C AD - Environmental Carcinogenesis Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 157 EP - 163 VL - 16 IS - 2 SN - 0143-3334, 0143-3334 KW - Butadienes KW - 0 KW - Carcinogens KW - Mutagens KW - 1,3-butadiene KW - JSD5FGP5VD KW - Index Medicus KW - Neoplasms, Experimental -- epidemiology KW - Animals KW - Neoplasms, Experimental -- chemically induced KW - Humans KW - Butadienes -- toxicity KW - Neoplasms -- chemically induced KW - Neoplasms -- epidemiology KW - Carcinogens -- toxicity KW - Mutagens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77148236?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mechanistic+data+indicate+that+1%2C3-butadiene+is+a+human+carcinogen.&rft.au=Melnick%2C+R+L%3BKohn%2C+M+C&rft.aulast=Melnick&rft.aufirst=R&rft.date=1995-02-01&rft.volume=16&rft.issue=2&rft.spage=157&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-23 N1 - Date created - 1995-03-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxotremorine-m potentiation of glucose-induced insulin release from rat islets involves M3 muscarinic receptors. AN - 77147499; 7864111 AB - cDNAs encoding for M1 and M3 muscarinic acetylcholine (ACh) receptors were detected in rat pancreatic islet cells by polymerase chain reaction (PCR) amplification techniques. A new cholinergic agonist, oxotremorine-m (oxo-m), in the presence of glucose (5.6 mM), produced a dose-dependent potentiation of insulin secretion saturating at approximately 5 microM. This effect was suppressed by the L-type Ca2+ channel blocker nifedipine. Higher doses of oxo-m (50 microM) induced a biphasic insulin response both at low (5.6 mM) or high (16.7 mM) glucose concentrations. In a Ca(2+)-deficient medium containing glucose (5.6 mM), oxo-m evoked only a reduced first phase of insulin secretion. The potentiating effects of oxo-m were inhibited by the muscarinic receptor antagonists 4-diphenylacetoxy-N-methylpiperidine methiodide (M3), hexahydro-sila-difenidol hydrochloride, p-fluoro analogue (M3 > M1 > M2), and pirenzepine (M1) in a dose-dependent manner; half-maximal inhibitory concentration values were approximately 5, 20, and 340 nM, respectively. The PCR results demonstrate the presence of M1 and M3 muscarinic ACh receptors in the islet tissue, and the secretion data strongly suggest that the potentiation of glucose-induced insulin release evoked by oxo-m depends on the activation of a muscarinic M3-subtype receptor present in the beta-cell membrane. JF - The American journal of physiology AU - Boschero, A C AU - Szpak-Glasman, M AU - Carneiro, E M AU - Bordin, S AU - Paul, I AU - Rojas, E AU - Atwater, I AD - Laboratory of Cell Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - E336 EP - E342 VL - 268 IS - 2 Pt 1 SN - 0002-9513, 0002-9513 KW - Insulin KW - 0 KW - Molecular Probes KW - RNA, Messenger KW - Receptors, Muscarinic KW - Oxotremorine KW - 5RY0UWH1JL KW - oxotremorine M KW - 63939-65-1 KW - Glucose KW - IY9XDZ35W2 KW - Potassium KW - RWP5GA015D KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Rats KW - Osmolar Concentration KW - Calcium -- metabolism KW - Molecular Probes -- genetics KW - Animals KW - Base Sequence KW - RNA, Messenger -- metabolism KW - Extracellular Space -- metabolism KW - Molecular Sequence Data KW - Drug Synergism KW - Potassium -- metabolism KW - Female KW - Receptors, Muscarinic -- genetics KW - Oxotremorine -- pharmacology KW - Glucose -- pharmacology KW - Receptors, Muscarinic -- classification KW - Insulin -- metabolism KW - Oxotremorine -- analogs & derivatives KW - Islets of Langerhans -- metabolism KW - Receptors, Muscarinic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77147499?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Oxotremorine-m+potentiation+of+glucose-induced+insulin+release+from+rat+islets+involves+M3+muscarinic+receptors.&rft.au=Boschero%2C+A+C%3BSzpak-Glasman%2C+M%3BCarneiro%2C+E+M%3BBordin%2C+S%3BPaul%2C+I%3BRojas%2C+E%3BAtwater%2C+I&rft.aulast=Boschero&rft.aufirst=A&rft.date=1995-02-01&rft.volume=268&rft.issue=2+Pt+1&rft.spage=E336&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 - 1995-03-21 N1 - Date created - 1995-03-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemically induced mammary gland cancer in the National Toxicology Program's carcinogenesis bioassay. AN - 77147422; 7859345 AB - Incidences of breast cancer change in populations as people migrate from one area of the world to another, suggesting that environmental factors contribute to this disease. There is a continuing effort to identify these environmental factors and the role that exposures to specific chemicals play in this disease. Results from experimental studies show that chemicals identified to cause mammary gland cancer in rodents are frequently mutagenic chemicals, suggesting that genetic damage is an important mechanism for the induction of this cancer. Prevalent classes of chemicals that were identified to cause mammary gland cancer in rodents in studies by the National Toxicology Program include halogenated hydrocarbons, aromatic amino/nitro compounds and epoxide-forming chemicals. Results from these experimental studies will help to elucidate mechanisms and possible causes of breast cancer in humans. JF - Carcinogenesis AU - Dunnick, J K AU - Elwell, M R AU - Huff, J AU - Barrett, J C AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27514. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 173 EP - 179 VL - 16 IS - 2 SN - 0143-3334, 0143-3334 KW - p53 KW - Index Medicus KW - Animals KW - Humans KW - Environmental Exposure KW - Carcinogenicity Tests KW - Incidence KW - Female KW - Mammary Neoplasms, Experimental -- chemically induced KW - Mammary Neoplasms, Experimental -- epidemiology KW - Breast Neoplasms -- epidemiology KW - Breast Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77147422?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chemically+induced+mammary+gland+cancer+in+the+National+Toxicology+Program%27s+carcinogenesis+bioassay.&rft.au=Dunnick%2C+J+K%3BElwell%2C+M+R%3BHuff%2C+J%3BBarrett%2C+J+C&rft.aulast=Dunnick&rft.aufirst=J&rft.date=1995-02-01&rft.volume=16&rft.issue=2&rft.spage=173&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-23 N1 - Date created - 1995-03-23 N1 - Date revised - 2017-01-13 N1 - Gene symbol - p53 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chrysotile asbestos stimulates platelet-derived growth factor-AA production by rat lung fibroblasts in vitro: evidence for an autocrine loop. AN - 77147086; 7865215 AB - We have investigated the mitogenic and chemotactic role of platelet-derived growth factor (PDGF) in pulmonary fibrogenesis induced by chrysotile asbestos. Since fibroblasts phagocytize asbestos in the lung interstitium, we have sought to learn whether the fibers alter the production of PDGF-like molecules by rat lung fibroblasts or induce mitogenesis of these fibroblasts in vitro. Conditioned medium as well as cell lysates from fibroblasts exposed to asbestos contained approximately 4-fold more PDGF than unexposed cells as detected by Western blot. Two distinct molecular weight forms of PDGF (36 and 18 kD) were detected by Western blotting. We postulate that these PDGF-like molecules are homologues of human PDGF-AA since we could not detect any PDGF in a sensitive enzyme immunoassay that recognized only PDGF-BB and PDGF-AB. Furthermore, PDGF-A chain mRNA was readily detected by Northern analysis, whereas PDGF-B chain mRNA was not detected by conventional Northern analysis. However, message amplification using a reverse transcriptase polymerase chain reaction allowed detection of the B-chain message. A significant dose-dependent mitogenic effect of asbestos was found by using both a cell proliferation assay and nuclear labeling with bromodeoxyuridine when fibroblasts were exposed under serum-free conditions. This mitogenesis induced directly by asbestos was blocked almost entirely with an anti-PDGF antibody that neutralized all three PDGF isoforms. Thus, these data support our hypothesis that an autocrine loop for PDGF-AA is operative in vitro following exposure to asbestos in lung fibroblasts, and we suggest that this signaling pathway could be significant in the pathogenesis of pulmonary fibrosis. JF - American journal of respiratory cell and molecular biology AU - Lasky, J A AU - Coin, P G AU - Lindroos, P M AU - Ostrowski, L E AU - Brody, A R AU - Bonner, J C AD - Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 162 EP - 170 VL - 12 IS - 2 SN - 1044-1549, 1044-1549 KW - Asbestos, Serpentine KW - 0 KW - Platelet-Derived Growth Factor KW - RNA, Messenger KW - platelet-derived growth factor A KW - Index Medicus KW - Rats KW - Fibroblasts -- drug effects KW - Animals KW - Cattle KW - RNA, Messenger -- metabolism KW - Humans KW - In Vitro Techniques KW - Cell Division -- drug effects KW - Fibroblasts -- cytology KW - RNA, Messenger -- genetics KW - Phagocytosis KW - Fibroblasts -- metabolism KW - Microscopy, Electron, Scanning KW - Platelet-Derived Growth Factor -- antagonists & inhibitors KW - Asbestos, Serpentine -- toxicity KW - Lung -- cytology KW - Lung -- drug effects KW - Platelet-Derived Growth Factor -- genetics KW - Lung -- metabolism KW - Platelet-Derived Growth Factor -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77147086?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chrysotile+asbestos+stimulates+platelet-derived+growth+factor-AA+production+by+rat+lung+fibroblasts+in+vitro%3A+evidence+for+an+autocrine+loop.&rft.au=Lasky%2C+J+A%3BCoin%2C+P+G%3BLindroos%2C+P+M%3BOstrowski%2C+L+E%3BBrody%2C+A+R%3BBonner%2C+J+C&rft.aulast=Lasky&rft.aufirst=J&rft.date=1995-02-01&rft.volume=12&rft.issue=2&rft.spage=162&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 - 1995-03-30 N1 - Date created - 1995-03-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase II study of paclitaxel in relapsed non-Hodgkin's lymphomas. AN - 77145733; 7531220 AB - To assess the efficacy and toxicity of paclitaxel administered as a 96-hour infusion to patients with relapsed non-Hodgkin's lymphomas (NHLs). Eligible patients had relapsed NHL and measurable disease and were considered incurable. Paclitaxel was infused at a dose of 140 mg/m2 every 3 weeks. Premedications to prevent paclitaxel hypersensitivity reactions were not administered and no patients received corticosteroids. Expression of the multidrug resistance (mdr-1) gene was determined in tumor from 17 patients by mRNA quantitative polymerase chain reaction (PCR). Thirty-one patients received a total of 99 cycles of paclitaxel. Two patients were not assessable for response. The median age was 50 years, 71% had stage IV disease, and intermediate/high-grade histology was present in 65% of patients. Patients had received a median of three prior chemotherapy regimens, and 68% of patients had responded to the previous chemotherapy (chemotherapy-sensitive). Of 29 assessable patients, five (17%) achieved a partial response (PR). With a median potential follow-up time of 17 months, the median event-free and overall survival durations were 1.6 and 7.5 months, respectively. No correlation was found between response to paclitaxel and extent of prior treatment or response. The mdr-1 gene was easily detectable in 14 of 17 tumor biopsies, but was low in all but one sample. The most serious toxicity was grade 4 neutropenia, which occurred during 14% of cycles. Paclitaxel was well tolerated, but had a low response rate in patients with relapsed NHLs. There was no clear association between response to paclitaxel and extent of our response to prior treatment. Most patients had chemotherapy-sensitive disease, which suggests that the low response rate to paclitaxel was probably not due to general chemotherapy resistance. Paclitaxel provided good palliation in a minority of patients and is a reasonable agent to consider for use in patients who have failed to respond to standard chemotherapy. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Wilson, W H AU - Chabner, B A AU - Bryant, G AU - Bates, S AU - Fojo, A AU - Regis, J AU - Jaffe, E S AU - Steinberg, S M AU - Goldspiel, B R AU - Cheson, B D AD - Medicine Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 381 EP - 386 VL - 13 IS - 2 SN - 0732-183X, 0732-183X KW - mdr-1 KW - RNA, Messenger KW - 0 KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Disease-Free Survival KW - Humans KW - Aged KW - Palliative Care KW - RNA, Messenger -- genetics KW - Infusions, Parenteral KW - Recurrence KW - Drug Resistance, Multiple KW - Polymerase Chain Reaction KW - Adult KW - Middle Aged KW - Female KW - Male KW - Paclitaxel -- administration & dosage KW - Lymphoma, Non-Hodgkin -- genetics KW - Lymphoma, Non-Hodgkin -- drug therapy KW - Paclitaxel -- toxicity KW - Lymphoma, Non-Hodgkin -- mortality KW - Paclitaxel -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77145733?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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+study+of+paclitaxel+in+relapsed+non-Hodgkin%27s+lymphomas.&rft.au=Wilson%2C+W+H%3BChabner%2C+B+A%3BBryant%2C+G%3BBates%2C+S%3BFojo%2C+A%3BRegis%2C+J%3BJaffe%2C+E+S%3BSteinberg%2C+S+M%3BGoldspiel%2C+B+R%3BCheson%2C+B+D&rft.aulast=Wilson&rft.aufirst=W&rft.date=1995-02-01&rft.volume=13&rft.issue=2&rft.spage=381&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 - 1995-03-06 N1 - Date created - 1995-03-06 N1 - Date revised - 2017-01-13 N1 - Gene symbol - mdr-1 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risks for exposures to and infection with HIV among health care providers in the emergency department. AN - 77144777; 7851317 AB - This article reviews the information available that is relevant to the risk of occupational infection with HIV, attempts to frame this evidence in perspective for emergency health care providers, and underscores the strategies that have been shown to be effective in reducing these risks. JF - Emergency medicine clinics of North America AU - Henderson, D K AD - Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 199 EP - 211 VL - 13 IS - 1 SN - 0733-8627, 0733-8627 KW - Antiviral Agents KW - 0 KW - Index Medicus KW - AIDS/HIV KW - Antiviral Agents -- therapeutic use KW - Risk Factors KW - Needlestick Injuries -- prevention & control KW - Humans KW - Emergency Service, Hospital KW - Universal Precautions KW - Cross Infection -- prevention & control KW - Occupational Exposure KW - HIV Infections -- transmission KW - Infectious Disease Transmission, Patient-to-Professional -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77144777?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Emergency+medicine+clinics+of+North+America&rft.atitle=Risks+for+exposures+to+and+infection+with+HIV+among+health+care+providers+in+the+emergency+department.&rft.au=Henderson%2C+D+K&rft.aulast=Henderson&rft.aufirst=D&rft.date=1995-02-01&rft.volume=13&rft.issue=1&rft.spage=199&rft.isbn=&rft.btitle=&rft.title=Emergency+medicine+clinics+of+North+America&rft.issn=07338627&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-16 N1 - Date created - 1995-03-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Varicella-zoster virus open reading frame 1 encodes a membrane protein that is dispensable for growth of VZV in vitro. AN - 77140512; 7856096 AB - Varicella-zoster virus (VZV) encodes 69 unique open reading frames, 5 of which do not have herpes simplex virus type 1 (HSV-1) homologs. One of the 5, ORF1, is predicted to encode a protein of 108 amino acids. We identified a 470-base RNA corresponding to ORF1. To determine whether ORF1 encodes a protein, an 11-amino-acid epitope was inserted in frame after the ninth codon of the ORF1 open reading frame. A recombinant virus carrying this epitope expressed a protein that was immunoprecipitated with monoclonal antibody to the epitope. The ORF1 protein was detected in the membrane of infected cells. The size of ORF1 protein expressed in VZV-infected cells was slightly larger than the size expressed by translation in vitro, suggesting that the protein may undergo post-translational modification in infected cells. Insertion of stop codons immediately before the epitope in the ORF1 gene resulted in a recombinant virus that did not express ORF1 protein and that was not growth impaired in cell culture. Thus, ORF1 encodes a protein that localizes to the membrane of VZV-infected cells and that is dispensable for virus growth in vitro. JF - Virology AU - Cohen, J I AU - Seidel, K E AD - Medical Virology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1995/02/01/ PY - 1995 DA - 1995 Feb 01 SP - 835 EP - 842 VL - 206 IS - 2 SN - 0042-6822, 0042-6822 KW - Antibodies, Monoclonal KW - 0 KW - Oligodeoxyribonucleotides KW - Viral Envelope Proteins KW - Index Medicus KW - Protein Biosynthesis KW - Sequence Homology, Nucleic Acid KW - Humans KW - Protein Processing, Post-Translational KW - Cosmids KW - Melanoma KW - Base Sequence KW - Tumor Cells, Cultured KW - Transfection KW - Kinetics KW - Restriction Mapping KW - Molecular Sequence Data KW - Cell Line KW - Mutagenesis, Insertional KW - Sequence Deletion KW - Herpesvirus 1, Human -- genetics KW - Herpesvirus 3, Human -- growth & development KW - Herpesvirus 3, Human -- genetics KW - Open Reading Frames KW - Viral Envelope Proteins -- biosynthesis KW - Herpesvirus 3, Human -- metabolism KW - Viral Envelope Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77140512?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Virology&rft.atitle=Varicella-zoster+virus+open+reading+frame+1+encodes+a+membrane+protein+that+is+dispensable+for+growth+of+VZV+in+vitro.&rft.au=Cohen%2C+J+I%3BSeidel%2C+K+E&rft.aulast=Cohen&rft.aufirst=J&rft.date=1995-02-01&rft.volume=206&rft.issue=2&rft.spage=835&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-16 N1 - Date created - 1995-03-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulation of IL-8 receptor expression on purified human T lymphocytes is associated with changed chemotactic responses to IL-8. AN - 77139081; 7852848 AB - Interleukin-8 is a member of the chemokine superfamily and is a major mediator of acute inflammation. Although IL-8 has been reported by some laboratories also to be a chemoattractant for T lymphocytes, this has been difficult to confirm and remains a controversial issue. By using freshly purified human T cells (90-95% CD3+), we could demonstrate consistent directional migration of T cells to recombinant human IL-8. IL-8 was as potent as RANTES, MIP1 alpha, and MIP1 beta in inducing T cell chemotaxis. Highly purified T cells, however, incubated at 37 degrees C for more than 12 h or cultured overnight with anti-CD3 antibody cross-linked to plastic dishes, showed a markedly reduced capacity to migrate in response to IL-8. This was associated with a decrease in binding of radioiodinated IL-8 to T cells. Northern blot and polymerase chain reaction analyses showed that freshly purified T cells expressed mRNA for both IL-8 receptor type A and type B. Steady-state levels of mRNA for the IL-8RA and IL-8RB genes were also reduced by incubation of the cells with or without anti-CD3 for 12 h at 37 degrees C. These results indicate that T cells are indeed one of the target cell populations for IL-8. The regulation of IL-8 receptor expression on T lymphocytes may contribute to the pathophysiological role of IL-8 in inducing the homing and infiltration of T cells. JF - Journal of leukocyte biology AU - Xu, L AU - Kelvin, D J AU - Ye, G Q AU - Taub, D D AU - Ben-Baruch, A AU - Oppenheim, J J AU - Wang, J M AD - Biological Carcinogenesis and Development Program, Program Resources Inc./DynCorp, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 335 EP - 342 VL - 57 IS - 2 SN - 0741-5400, 0741-5400 KW - IL-8RA KW - IL-8RB KW - Antibodies, Monoclonal KW - 0 KW - Chemotactic Factors KW - Interleukin-8 KW - RNA, Messenger KW - Receptors, Interleukin KW - Receptors, Interleukin-8A KW - Index Medicus KW - Chromatography, Affinity KW - Base Sequence KW - Blotting, Northern KW - RNA, Messenger -- metabolism KW - Humans KW - RNA, Messenger -- analysis KW - Molecular Sequence Data KW - Antibodies, Monoclonal -- pharmacology KW - T-Lymphocytes -- ultrastructure KW - Chemotaxis, Leukocyte -- drug effects KW - T-Lymphocytes -- physiology KW - Receptors, Interleukin -- physiology KW - T-Lymphocytes -- drug effects KW - Interleukin-8 -- pharmacology KW - Chemotactic Factors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77139081?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Modulation+of+IL-8+receptor+expression+on+purified+human+T+lymphocytes+is+associated+with+changed+chemotactic+responses+to+IL-8.&rft.au=Xu%2C+L%3BKelvin%2C+D+J%3BYe%2C+G+Q%3BTaub%2C+D+D%3BBen-Baruch%2C+A%3BOppenheim%2C+J+J%3BWang%2C+J+M&rft.aulast=Xu&rft.aufirst=L&rft.date=1995-02-01&rft.volume=57&rft.issue=2&rft.spage=335&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 - 1995-03-14 N1 - Date created - 1995-03-14 N1 - Date revised - 2017-01-13 N1 - Gene symbol - IL-8RA; IL-8RB N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Stimulation of cyclic GMP accumulation by sodium nitroprusside is potentiated via a Gs mechanism in intact pinealocytes. AN - 77133381; 7830064 AB - Cyclic GMP accumulation in pinealocytes is elevated > 100-fold by norepinephrine (NE) through a mechanism involving conjoint activation of alpha 1- and beta 1-adrenergic receptors. Little or no stimulation occurs if either alpha 1- or beta 1-adrenergic receptors alone are activated. It appears that alpha 1-adrenergic effects are mediated by Ca2+ acting in part through nitric oxide (NO), and beta 1-adrenergic effects are mediated by Gs. In the study presented here we investigated effects of adrenergic agonists or related postreceptor-active agents on stimulation of pineal cyclic GMP accumulation by the NO generator sodium nitroprusside (NP). The cyclic GMP response to NP (1 mM) was potentiated by NE and isoproterenol (ISO) but not by phenylephrine, indicating that activation of beta 1-adrenergic receptors potentiates the effects of NP. Similarly, vasoactive intestinal peptide (VIP), cholera toxin (CTX), and forskolin, all of which are known to mimic the effects of ISO in this system, also potentiated the effects of NP. In contrast, neither dibutyryl cyclic AMP nor agents that elevate intracellular Ca2+ levels caused marked potentiation of the effects of NP on pineal cyclic GMP. Depletion (90%) of Gs alpha by 21-h treatment with CTX reduced beta-adrenergic potentiation of NP. These findings indicate that beta-adrenergic agonists and VIP potentiate the effects of NP through a mechanism involving Gs. The molecular basis of this action may be an increase in guanylyl cyclase responsiveness to NO. JF - Journal of neurochemistry AU - White, B H AU - Klein, D C AD - Section on Neuroendocrinology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 711 EP - 717 VL - 64 IS - 2 SN - 0022-3042, 0022-3042 KW - Adrenergic alpha-Agonists KW - 0 KW - Adrenergic beta-Agonists KW - Receptors, Adrenergic KW - Nitroprusside KW - 169D1260KM KW - Colforsin KW - 1F7A44V6OU KW - Cholera Toxin KW - 9012-63-9 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Cyclic GMP KW - H2D2X058MU KW - Index Medicus KW - Rats KW - Animals KW - Colforsin -- pharmacology KW - Adrenergic beta-Agonists -- pharmacology KW - Adrenergic alpha-Agonists -- pharmacology KW - Cells, Cultured KW - Cholera Toxin -- pharmacology KW - Receptors, Adrenergic -- physiology KW - Pineal Gland -- metabolism KW - Cyclic GMP -- metabolism KW - Pineal Gland -- cytology KW - Pineal Gland -- drug effects KW - GTP-Binding Proteins -- physiology KW - Nitroprusside -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77133381?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Stimulation+of+cyclic+GMP+accumulation+by+sodium+nitroprusside+is+potentiated+via+a+Gs+mechanism+in+intact+pinealocytes.&rft.au=White%2C+B+H%3BKlein%2C+D+C&rft.aulast=White&rft.aufirst=B&rft.date=1995-02-01&rft.volume=64&rft.issue=2&rft.spage=711&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 - 1995-02-21 N1 - Date created - 1995-02-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Translocation and activation of protein kinase C by the plasma cell tumor-promoting alkane pristane. AN - 77130695; 7834620 AB - Pristane (2,6,10,14-tetramethylpentadecane) is a C19-isoalkane that promotes the development of plasmacytomas in genetically susceptible BALB/c mice. Similarities between the effects of pristane and protein kinase C (PKC)-activating phorbol esters suggested that the tumor promoting activity of pristane might involve the activation of PKC. Here we show that up to 5 mol% of pristane can be homogeneously incorporated into phosphatidylcholine/phosphatidylserine bilayers. Membrane-incorporated pristane partially activated PKC and increased phorbol ester binding to the bilayer by more than 50%. Pristane (50 microM) delivered as an inclusion complex with beta-cyclodextrin to promyelocytic HL-60 leukemia cells induced a partial long-term translocation of PKC to the cell membrane. This was accompanied by differentiation of HL-60 cells into macrophage-like cells. It is concluded that activation of PKC may comprise an important aspect of the tumor promoting potential of pristane. JF - Cancer research AU - Janz, S AU - Gawrisch, K AU - Lester, D S AD - Laboratory of Genetics, National Cancer Institute, NIH, Bethesda, Maryland 20892. Y1 - 1995/02/01/ PY - 1995 DA - 1995 Feb 01 SP - 518 EP - 524 VL - 55 IS - 3 SN - 0008-5472, 0008-5472 KW - Carcinogens KW - 0 KW - Lipid Bilayers KW - Terpenes KW - pristane KW - 26HZV48DT1 KW - Arachidonic Acid KW - 27YG812J1I KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Macrophages -- cytology KW - Animals KW - Phorbol 12,13-Dibutyrate -- metabolism KW - Dose-Response Relationship, Drug KW - Enzyme Activation KW - Arachidonic Acid -- pharmacology KW - Humans KW - Cell Division -- drug effects KW - Mice KW - Mice, Inbred BALB C KW - Macrophages -- drug effects KW - Protein Binding KW - Rats KW - Brain -- enzymology KW - Tumor Cells, Cultured KW - Phosphorylation KW - Monocytes -- cytology KW - Kinetics KW - Leukemia, Promyelocytic, Acute KW - Monocytes -- drug effects KW - Cell Differentiation -- drug effects KW - Subcellular Fractions -- enzymology KW - Cell Line KW - Protein Kinase C -- metabolism KW - Carcinogens -- pharmacology KW - Terpenes -- metabolism KW - Plasmacytoma -- chemically induced KW - Terpenes -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77130695?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Translocation+and+activation+of+protein+kinase+C+by+the+plasma+cell+tumor-promoting+alkane+pristane.&rft.au=Janz%2C+S%3BGawrisch%2C+K%3BLester%2C+D+S&rft.aulast=Janz&rft.aufirst=S&rft.date=1995-02-01&rft.volume=55&rft.issue=3&rft.spage=518&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 - 1995-02-28 N1 - Date created - 1995-02-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Genetic polymorphism and cancer susceptibility: fourteenth Sapporo Cancer Seminar. AN - 77129011; 7834645 JF - Cancer research AU - Gonzalez, F J Y1 - 1995/02/01/ PY - 1995 DA - 1995 Feb 01 SP - 710 EP - 715 VL - 55 IS - 3 KW - Carcinogens KW - 0 KW - DNA Adducts KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Sulfotransferases KW - EC 2.8.2.- KW - Index Medicus KW - Sulfotransferases -- genetics KW - Rats KW - Animals KW - Carcinogens -- metabolism KW - Disease Susceptibility KW - Neoplasms, Experimental -- chemically induced KW - Cytochrome P-450 Enzyme System -- genetics KW - Neoplasms, Experimental -- genetics KW - Humans KW - Carcinogens -- toxicity KW - Mice KW - Polymorphism, Genetic KW - Neoplasms -- epidemiology KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77129011?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=Cancer+research&rft.atitle=Genetic+polymorphism+and+cancer+susceptibility%3A+fourteenth+Sapporo+Cancer+Seminar.&rft.au=Gonzalez%2C+F+J&rft.aulast=Gonzalez&rft.aufirst=F&rft.date=1995-02-01&rft.volume=55&rft.issue=3&rft.spage=710&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 - 1995-02-28 N1 - Date created - 1995-02-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The PEST-like sequence of I kappa B alpha is responsible for inhibition of DNA binding but not for cytoplasmic retention of c-Rel or RelA homodimers. AN - 77128007; 7823953 AB - In most cells, proteins belonging to the Rel/NF-kappa B family of transcription factors are held in inactive form in the cytoplasm by an inhibitor protein, I kappa B alpha. Stimulation of the cells leads to degradation of the inhibitor and transit of active DNA-binding Rel/NF-kappa B dimers to the nucleus. I kappa B alpha is also able to inhibit DNA binding by Rel/NF-kappa B dimers in vitro, suggesting that it may perform the same function in cells when the activating signal is no longer present. Structurally, the human I kappa B alpha molecule can be divided into three sections: a 70-amino-acid N terminus with no known function, a 205-residue midsection composed of six ankyrin-like repeats, and a very acidic 42-amino-acid C terminus that resembles a PEST sequence. In this study we examined how the structural elements of the I kappa B alpha protein correlate with its functional capabilities both in vitro and in vivo. Using a battery of I kappa B alpha mutants, we show that (i) a dimer binds a single I kappa B alpha molecule, (ii) the acidic C-terminal region of I kappa B alpha is not required for protein-protein binding and does not mask the nuclear localization signal of the dimer, (iii) the same C-terminal region is required for inhibition of DNA binding, and (iv) this inhibition may be accomplished by direct interaction between the PEST-like region and the DNA-binding region of one of the subunits of the dimer. JF - Molecular and cellular biology AU - Ernst, M K AU - Dunn, L L AU - Rice, N R AD - Laboratory of Molecular Virology and Carcinogenesis, National Cancer Institute Frederick Cancer Research and Development Center, Maryland 21702-1201. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 872 EP - 882 VL - 15 IS - 2 SN - 0270-7306, 0270-7306 KW - DNA-Binding Proteins KW - 0 KW - I-kappa B Proteins KW - Macromolecular Substances KW - NF-kappa B KW - NFKBIA protein, human KW - Nfkbia protein, mouse KW - Oligodeoxyribonucleotides KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-rel KW - Transcription Factor RelA KW - Transcription Factors KW - NF-KappaB Inhibitor alpha KW - 139874-52-5 KW - Index Medicus KW - Animals KW - Transcription Factors -- metabolism KW - Humans KW - Amino Acid Sequence KW - Mice KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Transfection KW - Molecular Sequence Data KW - Consensus Sequence KW - Cell Line KW - Proto-Oncogene Proteins -- metabolism KW - DNA-Binding Proteins -- biosynthesis KW - DNA-Binding Proteins -- isolation & purification KW - NF-kappa B -- metabolism KW - NF-kappa B -- antagonists & inhibitors KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77128007?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=The+PEST-like+sequence+of+I+kappa+B+alpha+is+responsible+for+inhibition+of+DNA+binding+but+not+for+cytoplasmic+retention+of+c-Rel+or+RelA+homodimers.&rft.au=Ernst%2C+M+K%3BDunn%2C+L+L%3BRice%2C+N+R&rft.aulast=Ernst&rft.aufirst=M&rft.date=1995-02-01&rft.volume=15&rft.issue=2&rft.spage=872&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 - 1995-02-16 N1 - Date created - 1995-02-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1992 Mar 20;68(6):1109-20 [1339305] Gene Expr. 1993;3(2):135-50 [8268718] Genes Dev. 1992 May;6(5):775-87 [1577272] Proc Natl Acad Sci U S A. 1992 May 15;89(10):4333-7 [1533932] Mol Cell Biol. 1992 Jul;12(7):3094-106 [1620118] Nature. 1992 Aug 13;358(6387):597-9 [1501714] Mol Cell Biol. 1992 Sep;12(9):4067-75 [1508203] Genes Dev. 1992 Oct;6(10):1899-913 [1340770] Cell. 1992 Oct 16;71(2):243-53 [1423592] J Virol. 1993 Jan;67(1):288-93 [8416374] J Virol. 1993 Feb;67(2):832-42 [8419648] Mol Cell Biol. 1993 Feb;13(2):852-60 [8423807] Mol Biol Cell. 1992 Dec;3(12):1339-52 [1493333] EMBO J. 1993 Jan;12(1):201-11 [7679069] EMBO J. 1993 Jan;12(1):213-22 [8428580] Int Rev Cytol. 1993;143:1-62 [8449662] Science. 1993 Mar 26;259(5103):1912-5 [8096091] Genes Dev. 1993 Apr;7(4):705-18 [8458581] Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2532-6 [8460169] Nucleic Acids Res. 1993 Apr 25;21(8):1727-34 [8493089] Mol Cell Biol. 1993 Jun;13(6):3301-10 [8497253] Mol Cell Biol. 1993 Jun;13(6):3557-66 [8497270] J Biol Chem. 1993 Jun 5;268(16):11803-10 [8505309] Genes Dev. 1993 Jul;7(7A):1266-76 [8319912] EMBO J. 1993 Jul;12(7):2781-8 [8334994] Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):908-12 [8302865] Mol Cell Biol. 1993 Oct;13(10):6089-101 [8413211] Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1346-50 [8108414] EMBO J. 1994 Feb 15;13(4):861-70 [8112299] Mol Cell Biol. 1994 Jun;14(6):3915-26 [8196632] Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5350-4 [8202491] Biochemistry. 1979 Feb 20;18(4):690-3 [84683] Science. 1986 Oct 17;234(4774):364-8 [2876518] Cell. 1988 Apr 22;53(2):211-7 [3129195] J Virol. 1988 Dec;62(12):4730-6 [2846883] Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):8962-6 [8415639] Cell. 1991 Jun 28;65(7):1281-9 [1829648] EMBO J. 1993 Dec;12(12):4685-95 [8223478] J Biol Chem. 1993 Oct 25;268(30):22703-9 [8226780] Nucleic Acids Res. 1993 Sep 25;21(19):4516-23 [7694229] Oncogene. 1989 Jul;4(7):935-42 [2666912] Genes Dev. 1989 Nov;3(11):1689-98 [2691328] Nature. 1990 Mar 1;344(6261):36-42 [2137557] Mol Cell Biol. 1990 May;10(5):2327-34 [2183031] Cell. 1990 Apr 20;61(2):255-65 [2184941] Cell. 1990 Sep 7;62(5):1007-18 [2203531] Cell. 1991 Mar 8;64(5):961-9 [2001591] EMBO J. 1991 Jul;10(7):1817-25 [2050119] Genes Dev. 1991 Aug;5(8):1464-76 [1907941] Nature. 1991 Dec 5;354(6352):395-8 [1956402] EMBO J. 1991 Dec;10(13):4159-67 [1756723] Mol Cell Biol. 1992 Feb;12(2):444-54 [1732726] Mol Cell Biol. 1992 Feb;12(2):685-95 [1531086] Cell. 1992 Mar 20;68(6):1121-33 [1547506] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transcriptional regulation of the mouse alpha A-crystallin gene: activation dependent on a cyclic AMP-responsive element (DE1/CRE) and a Pax-6-binding site. AN - 77127768; 7823934 AB - Two cis-acting promoter elements (-108 to -100 and -49 to -33) of the mouse alpha A-crystallin gene, which is highly expressed in the ocular lens, were studied. Here we show that DE1 (-108 to -100; 5'TGACGGTG3'), which resembles the consensus cyclic AMP (cAMP)-responsive element sequence (CRE; 5'TGACGT[A/C][A/G]3'), behaves like a functional CRE site. Transfection experiments and electrophoretic mobility shift assays (EMSAs) using site-specific mutations correlated a loss of function with deviations from the CRE consensus sequence. Results of EMSAs in the presence of antisera against CREB, delta CREB, and CREM were consistent with the binding of CREB-like proteins to the DE1 sequence. Stimulation of alpha A-crystallin promoter activity via 8-bromo-cAMP, forskolin, or human T-cell leukemia virus type I Tax1 in transfections and reduction of activity of this site in cell-free transcription tests by competition with the somatostatin CRE supported the idea that DE1 is a functional CRE. Finally, Pax-6, a member of the paired-box family of transcription factors, activated the mouse alpha A-crystallin promoter in cotransfected COP-8 fibroblasts and bound to the -59 to -29 promoter sequence in EMSAs. These data provide evidence for a synergistic role of Pax-6 and CREB-like proteins for high expression of the mouse alpha A-crystallin gene in the lens. JF - Molecular and cellular biology AU - Cvekl, A AU - Kashanchi, F AU - Sax, C M AU - Brady, J N AU - Piatigorsky, J AD - Laboratory of Molecular and Developmental Biology, National Eye Institute, Bethesda, Maryland 20892-2730. Y1 - 1995/02// PY - 1995 DA - February 1995 SP - 653 EP - 660 VL - 15 IS - 2 SN - 0270-7306, 0270-7306 KW - Crystallins KW - 0 KW - Cyclic AMP Response Element-Binding Protein KW - DNA Primers KW - DNA-Binding Proteins KW - Eye Proteins KW - Gene Products, tax KW - Homeodomain Proteins KW - PAX6 Transcription Factor KW - PAX6 protein, human KW - Paired Box Transcription Factors KW - Pax6 protein, mouse KW - Repressor Proteins KW - Transcription Factors KW - Cyclic AMP Response Element Modulator KW - 135844-64-3 KW - Colforsin KW - 1F7A44V6OU KW - 8-Bromo Cyclic Adenosine Monophosphate KW - 23583-48-4 KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Transcription Factors -- metabolism KW - Sequence Homology, Nucleic Acid KW - Humans KW - Repressor Proteins -- metabolism KW - Transcription, Genetic KW - Human T-lymphotropic virus 1 -- metabolism KW - Mutagenesis, Site-Directed KW - Colforsin -- pharmacology KW - Molecular Sequence Data KW - Gene Products, tax -- metabolism KW - Rabbits KW - Cell Nucleus KW - 8-Bromo Cyclic Adenosine Monophosphate -- pharmacology KW - Transcriptional Activation KW - Cloning, Molecular KW - Binding Sites KW - Polymerase Chain Reaction KW - Regulatory Sequences, Nucleic Acid KW - Base Sequence KW - Transfection KW - Consensus Sequence KW - Cell Line KW - Promoter Regions, Genetic KW - Cyclic AMP Response Element-Binding Protein -- metabolism KW - Lens, Crystalline -- metabolism KW - Mice -- genetics KW - Gene Expression Regulation KW - Crystallins -- genetics KW - Crystallins -- biosynthesis KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77127768?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Transcriptional+regulation+of+the+mouse+alpha+A-crystallin+gene%3A+activation+dependent+on+a+cyclic+AMP-responsive+element+%28DE1%2FCRE%29+and+a+Pax-6-binding+site.&rft.au=Cvekl%2C+A%3BKashanchi%2C+F%3BSax%2C+C+M%3BBrady%2C+J+N%3BPiatigorsky%2C+J&rft.aulast=Cvekl&rft.aufirst=A&rft.date=1995-02-01&rft.volume=15&rft.issue=2&rft.spage=653&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 - 1995-02-16 N1 - Date created - 1995-02-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: DNA. 1988 Jan-Feb;7(1):47-55 [3349904] Proc Natl Acad Sci U S A. 1988 May;85(10):3396-400 [2835770] Mol Cell Biol. 1988 May;8(5):1947-56 [2898727] Cell. 1988 Sep 23;54(7):1043-51 [3416355] Annu Rev Biochem. 1988;57:479-504 [3052280] J Biol Chem. 1988 Dec 5;263(34):18466-72 [2848037] Science. 1988 Dec 9;242(4884):1430-3 [2974179] Biochem Biophys Res Commun. 1989 Jan 16;158(1):319-25 [2912453] Mol Cell Biol. 1989 Mar;9(3):1083-91 [2725488] Mol Cell Biol. 1989 Apr;9(4):1498-506 [2542772] Cell. 1989 Nov 17;59(4):675-80 [2573431] J Biol Chem. 1989 Nov 25;264(33):19837-44 [2584197] Mol Cell Biol. 1989 Oct;9(10):4272-81 [2555687] Dev Biol. 1990 Jan;137(1):68-76 [2295367] Cell. 1990 Jan 26;60(2):247-57 [2153462] Curr Eye Res. 1990 Jan;9(1):31-7 [2178867] Trends Neurosci. 1990 May;13(5):184-8 [1693237] Mol Cell Biol. 1990 Jul;10(7):3700-8 [1694016] Proc Natl Acad Sci U S A. 1990 Jul;87(14):5258-62 [2142528] Mol Cell Biol. 1990 Dec;10(12):6192-203 [2147221] Mol Cell Biol. 1990 Dec;10(12):6813-6 [2247086] Cell. 1991 Feb 22;64(4):739-49 [1847666] Mol Endocrinol. 1990 Aug;4(8):1087-94 [2149870] Genes Dev. 1991 Apr;5(4):594-604 [1672661] Proc Natl Acad Sci U S A. 1991 May 1;88(9):3652-6 [2023914] Cell. 1991 Sep 6;66(5):873-84 [1889089] Nucleic Acids Res. 1991 Sep 11;19(17):4601-9 [1653949] Nature. 1991 Dec 19-26;354(6354):522-5 [1684639] Cell. 1991 Dec 20;67(6):1059-74 [1684738] Nature. 1992 Jan 2;355(6355):80-4 [1370576] Nature. 1992 Feb 20;355(6362):750 [1346927] Development. 1991 Dec;113(4):1435-49 [1687460] J Biol Chem. 1992 Jun 25;267(18):12868-75 [1352291] Mol Cell Biol. 1992 Sep;12(9):4230-41 [1508216] Exp Eye Res. 1992 Mar;54(3):461-70 [1381680] Curr Opin Genet Dev. 1992 Aug;2(4):582-8 [1525511] J Mol Evol. 1992 Oct;35(4):337-45 [1404419] Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10449-53 [1438232] Mol Cell Biol. 1993 Jan;13(1):18-27 [8380220] Mol Biol Evol. 1993 Jan;10(1):103-26 [8450753] J Mol Biol. 1993 Mar 20;230(2):425-35 [8464058] Mol Endocrinol. 1993 Feb;7(2):145-53 [8385737] DNA Cell Biol. 1993 Mar;12(2):183-90 [8471166] Development. 1990 Sep;110(1):131-9 [2081455] Endocr Rev. 1993 Jun;14(3):269-90 [8319595] Nucleic Acids Res. 1993 Jun 11;21(11):2633-40 [8332460] Genes Dev. 1993 Oct;7(10):2048-61 [8406007] Gene. 1993 Sep 15;131(2):159-65 [8406008] Science. 1993 Oct 15;262(5132):395-9 [8211160] Genes Dev. 1993 Nov;7(11):2120-34 [7901121] Mol Cell Biol. 1993 Dec;13(12):7257-66 [8246948] Mol Cell Biol. 1994 Jan;14(1):456-62 [8264613] Cell Growth Differ. 1993 Dec;4(12):1041-50 [8117618] J Biol Chem. 1994 Mar 18;269(11):8355-61 [8132558] Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3112-6 [8159713] Am J Hum Genet. 1994 May;54(5):801-11 [7909985] Nat Genet. 1992 Nov;2(3):232-9 [1345175] Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5642-6 [8202541] Science. 1994 Aug 5;265(5173):785-9 [7914031] DNA Cell Biol. 1994 Sep;13(9):891-900 [7917011] Mol Cell Biol. 1994 Nov;14(11):7363-76 [7935450] Nat Genet. 1994 Aug;7(4):463-71 [7951315] Genes Dev. 1994 Sep 1;8(17):2022-34 [7958875] Adv Enzymol Relat Areas Mol Biol. 1994;69:155-201 [7817868] Exp Eye Res. 1968 Apr;7(2):301-11 [4869207] Proc Natl Acad Sci U S A. 1980 Jul;77(7):3855-9 [6933441] Differentiation. 1981;19(3):134-53 [7030840] Nucleic Acids Res. 1981 Dec 11;9(23):6231-50 [6275353] Proc Natl Acad Sci U S A. 1982 Apr;79(7):2360-4 [6285380] Methods Enzymol. 1983;101:582-98 [6888276] Proc Natl Acad Sci U S A. 1985 Apr;82(8):2334-8 [3857584] Proc Natl Acad Sci U S A. 1985 Dec;82(23):7815-9 [3865198] J Virol. 1987 Jul;61(7):2175-81 [3035218] Science. 1987 Sep 11;237(4820):1324-9 [2888190] Proc Natl Acad Sci U S A. 1986 Sep;83(18):6682-6 [2875459] Differentiation. 1986;33(2):168-74 [3569698] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Diurnal variation in tardive dyskinesia. AN - 77354981; 7792342 AB - Tardive dyskinesia (TD) is a common movement disorder that is associated with chronic neuroleptic exposure. To better characterize the clinical aspects of TD, we investigated the diurnal pattern of involuntary movements by blindly rating videotaped examinations of patients from the morning shortly after awakening and later in the same afternoon. In 10 patients, average TD ratings were worse in the afternoon than in the morning, especially in the case of limb-trunk dyskinesias. These findings suggest that it is important to rate patients at the same time of day in TD studies. Moreover, patients should be evaluated at least several hours after awakening. JF - Psychiatry research AU - Hyde, T M AU - Egan, M F AU - Brown, R J AU - Weinberger, D R AU - Kleinman, J E AD - Clinical Brain Disorders Branch, NIMH Neuroscience Research Center, Saint Elizabeths Hospital, Washington, DC 20032, USA. Y1 - 1995/01/31/ PY - 1995 DA - 1995 Jan 31 SP - 53 EP - 57 VL - 56 IS - 1 SN - 0165-1781, 0165-1781 KW - Haloperidol KW - J6292F8L3D KW - Index Medicus KW - Haloperidol -- adverse effects KW - Haloperidol -- therapeutic use KW - Videotape Recording KW - Humans KW - Adult KW - Neurologic Examination -- drug effects KW - Schizophrenic Psychology KW - Schizophrenia -- drug therapy KW - Middle Aged KW - Chronic Disease KW - Male KW - Female KW - Circadian Rhythm KW - Dyskinesia, Drug-Induced -- diagnosis KW - Dyskinesia, Drug-Induced -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77354981?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychiatry+research&rft.atitle=Diurnal+variation+in+tardive+dyskinesia.&rft.au=Hyde%2C+T+M%3BEgan%2C+M+F%3BBrown%2C+R+J%3BWeinberger%2C+D+R%3BKleinman%2C+J+E&rft.aulast=Hyde&rft.aufirst=T&rft.date=1995-01-31&rft.volume=56&rft.issue=1&rft.spage=53&rft.isbn=&rft.btitle=&rft.title=Psychiatry+research&rft.issn=01651781&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-27 N1 - Date created - 1995-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structure of an antibody-lysozyme complex unexpected effect of conservative mutation. AN - 77139952; 7531245 AB - The structure of the complex between the Fab HyHEL-5 and chicken lysozyme revealed a large interface region containing 23 lysozyme and 28 Fab residues. Arg68 of the lysozyme is centrally placed in this interface and theoretical studies together with binding assays of this Fab to different avian lysozymes have previously shown that this arginine residue is an important contributor to the binding. The Arg68-->Lys mutant binds 10(3) times less well to the HyHEL-5 Fab. We have examined the refined crystal structure of the complex of this mutant lysozyme with the Fab. No global changes occur, but there is an introduction of a new water molecule into the interface that mediates the hydrogen bonding interactions between the lysine and residues on the Fab. These data are compared with the effects of similar changes on the inhibition of serine proteases such as trypsin where the energetic effects of this substitution are small. JF - Journal of molecular biology AU - Chacko, S AU - Silverton, E AU - Kam-Morgan, L AU - Smith-Gill, S AU - Cohen, G AU - Davies, D AD - NIDDK, National Institutes of Health, Bethesda, MD. Y1 - 1995/01/20/ PY - 1995 DA - 1995 Jan 20 SP - 261 EP - 274 VL - 245 IS - 3 SN - 0022-2836, 0022-2836 KW - Immunoglobulin Fab Fragments KW - 0 KW - Macromolecular Substances KW - Recombinant Proteins KW - Water KW - 059QF0KO0R KW - Aprotinin KW - 9087-70-1 KW - Arginine KW - 94ZLA3W45F KW - Muramidase KW - EC 3.2.1.17 KW - Trypsin KW - EC 3.4.21.4 KW - Index Medicus KW - Trypsin -- chemistry KW - Animals KW - Models, Molecular KW - Water -- chemistry KW - Protein Binding KW - Mutagenesis, Site-Directed KW - Chickens KW - Arginine -- genetics KW - Recombinant Proteins -- immunology KW - Crystallography KW - Binding Sites -- genetics KW - Recombinant Proteins -- chemistry KW - Aprotinin -- chemistry KW - Hydrogen Bonding KW - Immunoglobulin Fab Fragments -- chemistry KW - Muramidase -- genetics KW - Immunoglobulin Fab Fragments -- genetics KW - Muramidase -- immunology KW - Immunoglobulin Fab Fragments -- immunology KW - Mutation KW - Muramidase -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77139952?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+biology&rft.atitle=Structure+of+an+antibody-lysozyme+complex+unexpected+effect+of+conservative+mutation.&rft.au=Chacko%2C+S%3BSilverton%2C+E%3BKam-Morgan%2C+L%3BSmith-Gill%2C+S%3BCohen%2C+G%3BDavies%2C+D&rft.aulast=Chacko&rft.aufirst=S&rft.date=1995-01-20&rft.volume=245&rft.issue=3&rft.spage=261&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-09 N1 - Date created - 1995-03-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Age, thymopoiesis, and CD4+ T-lymphocyte regeneration after intensive chemotherapy. AN - 77089754; 7800006 AB - Inadequate reconstitution of CD4+ T lymphocytes is an important clinical problem complicating chemotherapy, human immunodeficiency virus infection, and bone marrow transplantation, but relatively little is known about how CD4+ T lymphocytes regenerate. There are two main possibilities: bone marrow-derived progenitors could reconstitute the lymphocyte population using a thymus-dependent pathway, or thymus-independent pathways could predominate. Previous studies have suggested that the CD45RA glycoprotein on CD4+ T lymphocytes is a marker for progeny generated by a thymus-dependent pathway. We studied 15 patients 1 to 24 years of age who had undergone intensive chemotherapy for cancer. The absolute numbers of CD4+ T lymphocytes in peripheral blood and the expression of CD45 isoforms (CD45RA and CD45RO) on these lymphocytes were studied serially during lymphocyte regeneration after the completion of therapy. Radiographic imaging of the thymus was performed concomitantly. There was an inverse relation between the patients' ages and the CD4+ T-lymphocyte counts six months after therapy was completed (r = -0.92). The CD4+ recovery correlated quantitatively with the appearance of CD45RA+CD4+ T lymphocytes in the blood (r = 0.64). There was a higher proportion of CD45RA+CD4+ T lymphocytes in patients with thymic enlargement after chemotherapy than in patients without such enlargement (two-sided P = 0.015). Thymus-dependent regeneration of CD4+ T lymphocytes occurs primarily in children, whereas even young adults have deficiencies in this pathway. Our results suggest that rapid T-cell regeneration requires residual thymic function in patients receiving high-dose chemotherapy. JF - The New England journal of medicine AU - Mackall, C L AU - Fleisher, T A AU - Brown, M R AU - Andrich, M P AU - Chen, C C AU - Feuerstein, I M AU - Horowitz, M E AU - Magrath, I T AU - Shad, A T AU - Steinberg, S M AD - Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1995/01/19/ PY - 1995 DA - 1995 Jan 19 SP - 143 EP - 149 VL - 332 IS - 3 SN - 0028-4793, 0028-4793 KW - Antineoplastic Agents KW - 0 KW - Cyclophosphamide KW - 8N3DW7272P KW - Antigens, CD45 KW - EC 3.1.3.48 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Cyclophosphamide -- administration & dosage KW - CD4 Lymphocyte Count -- drug effects KW - Humans KW - Child KW - Sarcoma -- drug therapy KW - Antigens, CD45 -- biosynthesis KW - Child, Preschool KW - Infant KW - Lymphoma, Non-Hodgkin -- drug therapy KW - Brain Neoplasms -- drug therapy KW - Cyclophosphamide -- therapeutic use KW - Adult KW - Antigens, CD45 -- analysis KW - Adolescent KW - Aging -- physiology KW - Thymus Gland -- cytology KW - CD4-Positive T-Lymphocytes -- physiology KW - CD4-Positive T-Lymphocytes -- immunology KW - Thymus Gland -- physiology KW - Antineoplastic Agents -- therapeutic use KW - Thymus Gland -- drug effects KW - Hematopoiesis, Extramedullary -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77089754?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Age%2C+thymopoiesis%2C+and+CD4%2B+T-lymphocyte+regeneration+after+intensive+chemotherapy.&rft.au=Mackall%2C+C+L%3BFleisher%2C+T+A%3BBrown%2C+M+R%3BAndrich%2C+M+P%3BChen%2C+C+C%3BFeuerstein%2C+I+M%3BHorowitz%2C+M+E%3BMagrath%2C+I+T%3BShad%2C+A+T%3BSteinberg%2C+S+M&rft.aulast=Mackall&rft.aufirst=C&rft.date=1995-01-19&rft.volume=332&rft.issue=3&rft.spage=143&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 - 1995-01-24 N1 - Date created - 1995-01-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: N Engl J Med. 1995 Jun 15;332(24):1650-1; author reply 1652 [7753154] N Engl J Med. 1995 Jun 15;332(24):1651-2 [7753155] N Engl J Med. 1995 Jun 15;332(24):1651; author reply 1652 [7646663] N Engl J Med. 1995 Jan 19;332(3):182-3 [7800012] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhancement by recombinant human interferon alfa of the reversal of multidrug resistance by MRK-16 monoclonal antibody. AN - 77209160; 7707396 AB - The anti-P-glycoprotein monoclonal antibody MRK-16 mediates the reversal of multidrug resistance. Recombinant human interferon alfa (rHuIFN alpha) enhances the cytotoxic activity of diverse chemotherapeutics and may modulate multidrug resistance. Our purpose was to determine the outcome of combination treatment with MRK-16, rHuIFN alpha-2a, and cytotoxic agents on tumor cells that express P-glycoprotein (Pgp). Three Pgp-expressing, multidrug-resistant human tumor cell lines were used: the MDR1 retrovirus-infected HT-29 colon adenocarcinoma (HT-29mdr1), the doxorubicin (Adriamycin)-resistant MCF-7 (AdrR MCF-7) breast carcinoma, and the de novo Pgp-acquired, HCT-15 colon carcinoma. The parental cell lines HT-29par and MCF-7 were used as controls. The in vitro effects of MRK-16 and rHuIFN alpha-2a were studied on: (a) chemosensitivity of parental and multidrug-resistant cell lines to vincristine, doxorubicin, or paclitaxel (Taxol); (b) intracellular drug concentrations; and (c) Pgp expression. The efficacy of vincristine alone or in combination with MRK-16 and/or rHuIFN alpha-2a was assessed against HT-29mdr1 cells in female, athymic NCr-nu/nu mice. For vincristine, the IC50 (i.e., the concentration that causes 50% inhibition of cell growth) was 7.0 ng/mL in HT-29mdr1 cells. Pretreatment of HT-29mdr1 cells with MRK-16 partially restored vincristine sensitivity (IC50 = 4.8 ng/mL), which was enhanced by noncytotoxic concentrations of rHuIFN alpha-2a (IC50 = 2.9 ng/mL) via a mechanism independent of Pgp modulation or [3H]vincristine efflux. rHuIFN alpha-2a potentiated MRK-16 reversal of multidrug resistance with both doxorubicin and paclitaxel on HT-29mdr1 cells and with vincristine on AdrR MCF-7 and HCT-15 tumor cells. Treatment of mice with 1 mg/kg vincristine weekly for 3 weeks, beginning 10 days after tumor injection, significantly increased the median survival times of the HT-29par tumor-bearing mice (60 days versus 35 days; P < .0001) but was only marginally therapeutic for HT-29mdr1 tumor-bearing mice (52 days versus 46 days). Pretreatment with MRK-16 (500 micrograms) and rHuIFN alpha-2a (5 x 10(4) U), alone or in combination, 24 hours before vincristine therapy did not affect the survival of HT-29par tumor-bearing mice. In contrast, the survival of mice bearing HT-29mdr1 tumors was significantly increased following treatment with MRK-16 before vincristine (80 days; P < .0001). Administration of a nontherapeutic dose of rHuIFN alpha-2a (5 x 10(4) U) with MRK-16 before vincristine treatment further increased the median survival times of HT-29mdr1 tumor-bearing mice (116 days; P < .0001). MRK-16 used in combination with rHuIFN alpha-2a was significantly more effective than MRK-16 in overcoming multidrug resistance. JF - Journal of the National Cancer Institute AU - Fogler, W E AU - Pearson, J W AU - Volker, K AU - Ariyoshi, K AU - Watabe, H AU - Riggs, C W AU - Wiltrout, R H AU - Longo, D L AD - Biological Response Modifiers Program, National Cancer Institute (NCI), NCI-Frederick Cancer Research and Development Center (FCRDC), Md 21702-1201, USA. Y1 - 1995/01/18/ PY - 1995 DA - 1995 Jan 18 SP - 94 EP - 104 VL - 87 IS - 2 SN - 0027-8874, 0027-8874 KW - Antibodies, Monoclonal KW - 0 KW - Antineoplastic Agents KW - Interferon-alpha KW - P-Glycoprotein KW - Recombinant Proteins KW - interferon alfa-2a KW - 47RRR83SK7 KW - Vincristine KW - 5J49Q6B70F KW - Doxorubicin KW - 80168379AG KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Paclitaxel -- administration & dosage KW - Animals KW - Humans KW - Vincristine -- administration & dosage KW - Doxorubicin -- administration & dosage KW - Mice KW - Mice, Nude KW - Neoplasm Transplantation KW - Tumor Cells, Cultured KW - Colonic Neoplasms -- therapy KW - Flow Cytometry KW - Drug Synergism KW - Time Factors KW - Female KW - Interferon-alpha -- therapeutic use KW - Drug Resistance, Multiple -- immunology KW - Antineoplastic Agents -- therapeutic use KW - P-Glycoprotein -- immunology KW - Antibodies, Monoclonal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77209160?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Enhancement+by+recombinant+human+interferon+alfa+of+the+reversal+of+multidrug+resistance+by+MRK-16+monoclonal+antibody.&rft.au=Fogler%2C+W+E%3BPearson%2C+J+W%3BVolker%2C+K%3BAriyoshi%2C+K%3BWatabe%2C+H%3BRiggs%2C+C+W%3BWiltrout%2C+R+H%3BLongo%2C+D+L&rft.aulast=Fogler&rft.aufirst=W&rft.date=1995-01-18&rft.volume=87&rft.issue=2&rft.spage=94&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 - 1995-05-09 N1 - Date created - 1995-05-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Natl Cancer Inst. 1995 Jan 18;87(2):73-5 [7707392] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I clinical trial of flavone-8-acetic acid in combination with interleukin 2. AN - 77207369; 7707385 JF - Journal of the National Cancer Institute AU - Holmund, J T AU - Kopp, W C AU - Wiltrout, R H AU - Longo, D L AU - Urba, W J AU - Janik, J E AU - Sznol, M AU - Conlon, K C AU - Fenton, R G AU - Hornung, R AD - Clinical Research Branch, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702, USA. Y1 - 1995/01/18/ PY - 1995 DA - 1995 Jan 18 SP - 134 EP - 136 VL - 87 IS - 2 SN - 0027-8874, 0027-8874 KW - Antineoplastic Agents KW - 0 KW - Flavonoids KW - Interleukin-2 KW - flavone acetic acid KW - 87626-55-9 KW - Index Medicus KW - Drug Administration Schedule KW - Carcinoma -- secondary KW - Melanoma -- secondary KW - Humans KW - Carcinoma -- drug therapy KW - Melanoma -- drug therapy KW - Treatment Outcome KW - Male KW - Female KW - Neoplasms -- drug therapy KW - Neoplasms -- pathology KW - Interleukin-2 -- therapeutic use KW - Flavonoids -- adverse effects KW - Antineoplastic Agents -- therapeutic use KW - Flavonoids -- therapeutic use KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77207369?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=A+phase+I+clinical+trial+of+flavone-8-acetic+acid+in+combination+with+interleukin+2.&rft.au=Holmund%2C+J+T%3BKopp%2C+W+C%3BWiltrout%2C+R+H%3BLongo%2C+D+L%3BUrba%2C+W+J%3BJanik%2C+J+E%3BSznol%2C+M%3BConlon%2C+K+C%3BFenton%2C+R+G%3BHornung%2C+R&rft.aulast=Holmund&rft.aufirst=J&rft.date=1995-01-18&rft.volume=87&rft.issue=2&rft.spage=134&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 - 1995-05-09 N1 - Date created - 1995-05-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cyclopentenyl uracil: an effective inhibitor of uridine salvage in vivo. AN - 77138164; 7840797 AB - Cyclopentenyl uracil, a non-cytotoxic inhibitor of uridine kinase, was found to effectively block the salvage of circulating uridine by host and tumor tissues in the intact mouse. Dose-response characteristics of the inhibition were determined. Large doses (1 g/kg) of cyclopentenyl uracil were required, and the effect of a single dose fell rapidly over a 24-hr period. A sustained inhibition of uridine salvage of > 64-79% could be maintained by multiple doses of 1 g/kg given on an every 8-hr schedule. Mice given cyclopentenyl uracil (1 g/kg) every 8 hr for 5 days continued to gain weight and showed no signs of toxicity; however, the combination of cyclopentenyl uracil with a non-toxic dose of N-(phosphonacetyl)-L-aspartic acid (PALA; 200 mg/kg daily for 5 days) was lethal to mice, indicating that circulating uridine modifies the toxicity of agents that act on enzymes of the de novo pyrimidine pathway. Although the duration of action and potency of cyclopentenyl uracil are not ideal, this is the first demonstration of an effective inhibition of uridine salvage in the intact mouse with a non-cytotoxic agent. This makes possible the evaluation of concurrent inhibition of de novo and salvage routes to pyrimidine nucleotides as an approach to chemotherapy. JF - Biochemical pharmacology AU - Cysyk, R L AU - Malinowski, N AU - Marquez, V AU - Zaharevitz, D AU - August, E M AU - Moyer, J D AD - Laboratory of Medicinal Chemistry, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1995/01/18/ PY - 1995 DA - 1995 Jan 18 SP - 203 EP - 207 VL - 49 IS - 2 SN - 0006-2952, 0006-2952 KW - Pyrimidine Nucleotides KW - 0 KW - Uracil Nucleotides KW - Uracil KW - 56HH86ZVCT KW - cyclopentenyluracil KW - 90597-20-9 KW - Uridine Kinase KW - EC 2.7.1.48 KW - Uridine KW - WHI7HQ7H85 KW - Index Medicus KW - Animals KW - Pyrimidine Nucleotides -- biosynthesis KW - Leukemia L1210 -- metabolism KW - Mice KW - Mice, Inbred BALB C KW - Uracil Nucleotides -- metabolism KW - Mice, Inbred DBA KW - Uracil -- analogs & derivatives KW - Uridine -- metabolism KW - Uridine Kinase -- antagonists & inhibitors KW - Uracil -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77138164?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=Cyclopentenyl+uracil%3A+an+effective+inhibitor+of+uridine+salvage+in+vivo.&rft.au=Cysyk%2C+R+L%3BMalinowski%2C+N%3BMarquez%2C+V%3BZaharevitz%2C+D%3BAugust%2C+E+M%3BMoyer%2C+J+D&rft.aulast=Cysyk&rft.aufirst=R&rft.date=1995-01-18&rft.volume=49&rft.issue=2&rft.spage=203&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-28 N1 - Date created - 1995-02-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Behavioral and endocrine responses to clomipramine in panic disorder patients with or without alcoholism. AN - 77216732; 7718674 AB - Central nervous system serotonin functions may differ between certain subgroups of alcoholics, patients with panic disorder, and healthy volunteers. To investigate these possibilities we administered the serotonin uptake inhibitor, clomipramine (12.5 mg, i.v.), to patients with alcohol dependence, patients with panic disorder with or without alcohol dependence, and healthy volunteers. Alcoholics did not differ from healthy volunteers in their neuroendocrine or behavioral responses. In contrast, patients with panic disorder exhibited marked dysphoric reactions and/or panic attacks following low-dose i.v. clomipramine, whereas their neuroendocrine responses were similar to the other two groups. Patients with panic disorder may have super-sensitive postsynaptic serotonin receptors in areas of their central nervous system, which are important for mood regulation. JF - Biological psychiatry AU - George, D T AU - Nutt, D J AU - Rawlings, R R AU - Phillips, M J AU - Eckardt, M J AU - Potter, W Z AU - Linnoila, M AD - Laboratory of Clinical Studies, DICBR, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA. Y1 - 1995/01/15/ PY - 1995 DA - 1995 Jan 15 SP - 112 EP - 119 VL - 37 IS - 2 SN - 0006-3223, 0006-3223 KW - Receptors, Serotonin KW - 0 KW - Serotonin KW - 333DO1RDJY KW - Adrenocorticotropic Hormone KW - 9002-60-2 KW - Prolactin KW - 9002-62-4 KW - Clomipramine KW - NUV44L116D KW - Hydrocortisone KW - WI4X0X7BPJ KW - Index Medicus KW - Brain -- physiopathology KW - Single-Blind Method KW - Infusions, Intravenous KW - Humans KW - Adult KW - Arousal -- physiology KW - Middle Aged KW - Personality Assessment KW - Male KW - Female KW - Receptors, Serotonin -- physiology KW - Receptors, Serotonin -- drug effects KW - Panic Disorder -- physiopathology KW - Prolactin -- blood KW - Panic Disorder -- psychology KW - Serotonin -- physiology KW - Alcoholism -- physiopathology KW - Alcoholism -- psychology KW - Hydrocortisone -- blood KW - Adrenocorticotropic Hormone -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77216732?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Behavioral+and+endocrine+responses+to+clomipramine+in+panic+disorder+patients+with+or+without+alcoholism.&rft.au=George%2C+D+T%3BNutt%2C+D+J%3BRawlings%2C+R+R%3BPhillips%2C+M+J%3BEckardt%2C+M+J%3BPotter%2C+W+Z%3BLinnoila%2C+M&rft.aulast=George&rft.aufirst=D&rft.date=1995-01-15&rft.volume=37&rft.issue=2&rft.spage=112&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 - 1995-05-19 N1 - Date created - 1995-05-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A neural network model for survival data. AN - 77196685; 7701159 AB - Neural networks have received considerable attention recently, mostly by non-statisticians. They are considered by many to be very promising tools for classification and prediction. In this paper we present an approach to modelling censored survival data using the input-output relationship associated with a simple feed-forward neural network as the basis for a non-linear proportional hazards model. This approach can be extended to other models used with censored survival data. The proportional hazards neural network parameters are estimated using the method of maximum likelihood. These maximum likelihood based models can be compared, using readily available techniques such as the likelihood ratio test and the Akaike criterion. The neural network models are illustrated using data on the survival of men with prostatic carcinoma. A method of interpreting the neural network predictions based on the factorial contrasts is presented. JF - Statistics in medicine AU - Faraggi, D AU - Simon, R AD - Biometric Research Branch, National Cancer Institute, Rockville, MD 20852. Y1 - 1995/01/15/ PY - 1995 DA - 1995 Jan 15 SP - 73 EP - 82 VL - 14 IS - 1 SN - 0277-6715, 0277-6715 KW - Placebos KW - 0 KW - Diethylstilbestrol KW - 731DCA35BT KW - Index Medicus KW - Prostatic Neoplasms -- mortality KW - Diethylstilbestrol -- therapeutic use KW - Humans KW - Prostatic Neoplasms -- drug therapy KW - Likelihood Functions KW - Male KW - Neural Networks (Computer) KW - Survival Analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77196685?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Statistics+in+medicine&rft.atitle=A+neural+network+model+for+survival+data.&rft.au=Faraggi%2C+D%3BSimon%2C+R&rft.aulast=Faraggi&rft.aufirst=D&rft.date=1995-01-15&rft.volume=14&rft.issue=1&rft.spage=73&rft.isbn=&rft.btitle=&rft.title=Statistics+in+medicine&rft.issn=02776715&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-28 N1 - Date created - 1995-04-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Generation of tumor-specific CTLs from melanoma patients by using peripheral blood stimulated with allogeneic melanoma tumor cell lines. Fine specificity and MART-1 melanoma antigen recognition. AN - 77119545; 7814882 AB - PBLs were isolated from 13 patients with metastatic melanoma. Mixed lymphocyte tumor cell cultures (ML TCs) were established (15 times) by using irradiated HLA-matched (one class I locus) allogeneic melanoma tumor cell lines (13 times) or autologous melanoma tumor cell lines (two times) in medium containing 120 IU/ml IL-2 and 100 IU/ml IL-4. PBLs grew to levels that could be assessed for functional reactivity 9 of 15 times. In seven of nine cases, CD3+CD8+ CTLs grew from MLTCs that were tumor specific; five were restricted by HLA-A2 and two were restricted by HLA-A24. Four of the tumor-specific CTL lines lysed autologous fresh tumor cells. Tumor-specific CTLs from two of three patients had cytolytic activity identical with tumor-infiltrating lymphocytes (TIL) derived from tumor biopsies removed earlier and grown in high concentrations (6000 IU/ml) of IL-2. Three of the HLA-A2-restricted tumor-specific CTLs were shown to recognize 293 cells transfected with HLA-A2.1 cDNA and the gene encoding the melanoma Ag, MART-1. In addition, these CTLs recognized the T2 cell line pulsed exogenously with the peptide MART-1(27-35), which is the nine-amino acid immunodominant epitope of the MART-1 Ag recognized on melanoma tumor cells by nearly all HLA-A2-restricted TIL. Thus, we have demonstrated the ability to generate tumor-specific CTLs from PBLs that are similar in their reactivity to TIL. This technique obviates the need for autologous tumor tissue and suggests that PBLs contain sufficient CTL precursors for use in generating antitumor CTLs for cellular immunotherapy trials. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Stevens, E J AU - Jacknin, L AU - Robbins, P F AU - Kawakami, Y AU - el Gamil, M AU - Rosenberg, S A AU - Yannelli, J R AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1995/01/15/ PY - 1995 DA - 1995 Jan 15 SP - 762 EP - 771 VL - 154 IS - 2 SN - 0022-1767, 0022-1767 KW - Antigens, Neoplasm KW - 0 KW - HLA-A Antigens KW - Melanoma-Specific Antigens KW - Neoplasm Proteins KW - Abridged Index Medicus KW - Index Medicus KW - Lymphocyte Activation KW - Lymphocyte Culture Test, Mixed -- methods KW - Lymphocytes, Tumor-Infiltrating -- immunology KW - Humans KW - Molecular Sequence Data KW - Cytotoxicity Tests, Immunologic KW - Amino Acid Sequence KW - Immunophenotyping KW - Tumor Cells, Cultured -- immunology KW - Neoplasm Proteins -- immunology KW - T-Lymphocytes, Cytotoxic -- immunology KW - Melanoma -- immunology KW - HLA-A Antigens -- immunology KW - Antigens, Neoplasm -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77119545?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Generation+of+tumor-specific+CTLs+from+melanoma+patients+by+using+peripheral+blood+stimulated+with+allogeneic+melanoma+tumor+cell+lines.+Fine+specificity+and+MART-1+melanoma+antigen+recognition.&rft.au=Stevens%2C+E+J%3BJacknin%2C+L%3BRobbins%2C+P+F%3BKawakami%2C+Y%3Bel+Gamil%2C+M%3BRosenberg%2C+S+A%3BYannelli%2C+J+R&rft.aulast=Stevens&rft.aufirst=E&rft.date=1995-01-15&rft.volume=154&rft.issue=2&rft.spage=762&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 - 1995-02-09 N1 - Date created - 1995-02-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of aluminium on the hepatic inositol polyphosphate phosphatase. AN - 77119070; 7832774 AB - There is speculation that some of the toxic effects of Al3+ may originate from it perturbing inositol phosphate/Ca2+ signalling. For example, in permeabilized L1210 mouse lymphoma cells, 10-50 microM Al3+ activated Ins(1,3,4,5)P4-dependent Ca2+ mobilization and Ins(1,3,4,5)P4 3-phosphatase activity [Loomis-Husselbee, Cullen, Irvine and Dawson (1991) Biochem. J. 277, 883-885]. Ins(1,3,4,5)P4 3-phosphatase activity is performed by a multiple inositol polyphosphate phosphatase (MIPP) that also attacks Ins(1,3,4,5,6)P5 and InsP6 [Craxton, Ali and Shears (1995) Biochem. J. 305, 491-498]: 5-50 microM Al3+ increased MIPP activity towards both Ins(1,3,4,5)P4 (by 30%) and Ins(1,3,4,5,6)P5 (by up to 500%), without affecting metabolism of InsP6. Higher concentrations of Al3+ inhibited metabolism of all three substrates, and in the case of InsP6, Al3+ altered the pattern of accumulating products. When 1-50 microM Al3+ was present, InsP6 became a less effective inhibitor of Ins(1,3,4,5)P4 3-phosphatase activity; this effect did not depend on the presence of cellular membranes, contrary to a previous proposal. The latter phenomenon largely explains how, in a cell-free system where Ins(1,3,4,5)P4 3-phosphatase is inhibited by endogenous InsP6, the addition of Al3+ can apparently increase the enzyme activity. However, there was no effect of either 10 or 25 microM Al3+ (in either the presence or absence of apotransferrin) on inositol phosphate profiles in either Jurkat E6-1 lymphoma cells or AR4-2J pancreatoma cells. JF - The Biochemical journal AU - Ali, N AU - Craxton, A AU - Sumner, M AU - Shears, S B AD - Inositol Lipid Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709. Y1 - 1995/01/15/ PY - 1995 DA - 1995 Jan 15 SP - 557 EP - 561 VL - 305 ( Pt 2) SN - 0264-6021, 0264-6021 KW - Inositol Phosphates KW - 0 KW - Phytic Acid KW - 7IGF0S7R8I KW - Aluminum KW - CPD4NFA903 KW - Phosphoric Monoester Hydrolases KW - EC 3.1.3.2 KW - multiple inositol-polyphosphate phosphatase KW - EC 3.1.3.62 KW - phosphatidylinositol-3-phosphatase KW - EC 3.1.3.64 KW - Index Medicus KW - Tumor Cells, Cultured KW - Dose-Response Relationship, Drug KW - Humans KW - Phosphoric Monoester Hydrolases -- drug effects KW - Inositol Phosphates -- metabolism KW - Aluminum -- pharmacology KW - Phytic Acid -- metabolism KW - Microsomes, Liver -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77119070?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Biochemical+journal&rft.atitle=Effects+of+aluminium+on+the+hepatic+inositol+polyphosphate+phosphatase.&rft.au=Ali%2C+N%3BCraxton%2C+A%3BSumner%2C+M%3BShears%2C+S+B&rft.aulast=Ali&rft.aufirst=N&rft.date=1995-01-15&rft.volume=305+%28+Pt+2%29&rft.issue=&rft.spage=557&rft.isbn=&rft.btitle=&rft.title=The+Biochemical+journal&rft.issn=02646021&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-23 N1 - Date created - 1995-02-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Neurochem. 1990 Aug;55(2):551-8 [2115072] J Biol Chem. 1990 Jul 5;265(19):11167-76 [2358456] Biochem J. 1990 Jul 15;269(2):547-50 [2167073] Biochem J. 1990 Sep 15;270(3):837 [2173553] Biochem J. 1991 Aug 1;277 ( Pt 3):883-5 [1872818] J Biol Chem. 1991 Dec 25;266(36):24498-502 [1662211] Adv Second Messenger Phosphoprotein Res. 1992;26:211-23 [1419358] Mol Cell Biochem. 1993 Apr 21;121(2):109-18 [8391123] J Biol Chem. 1993 Mar 25;268(9):6161-7 [8384201] J Biol Chem. 1993 Jan 15;268(2):1032-8 [8419311] Biochem J. 1993 Jul 15;293 ( Pt 2):583-90 [8343137] Brain Res. 1993 Nov 26;629(1):133-40 [8287268] J Biol Chem. 1994 Feb 11;269(6):4337-42 [8308002] Biochem Pharmacol. 1994 Apr 20;47(8):1417-25 [8185649] J Neurochem. 1994 Jun;62(6):2219-23 [8189229] Biochem J. 1995 Jan 15;305 ( Pt 2):491-8 [7832765] Lancet. 1988 Oct 29;2(8618):1008-10 [2902440] J Biol Chem. 1990 Jun 15;265(17):9869-75 [2161845] FEBS Lett. 1990 Jul 16;267(2):301-4 [2379588] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Presentation of endogenous and exogenous antigens is not affected by inactivation of E1 ubiquitin-activating enzyme in temperature-sensitive cell lines. AN - 77119034; 7814864 AB - Little is known regarding the mechanism by which MHC class I-associated peptides are generated. Proteins can be targeted for degradation by the covalent attachment of ubiquitin. The first step in ubiquitin conjugation to proteins is its binding to E1 ubiquitin-activating enzyme. To study the role of ubiquitin-targeted protein degradation in Ag processing, we used two mutant cell lines with temperature-sensitive E1 proteins, and a recombinant vaccinia virus expressing wild-type human E1. One of the cell lines examined (hamster ts20 cells) was previously reported to have a minimal capacity after a 1-h incubation at 41 degrees C to present osmotically loaded OVA to a T cell hybridoma, as assessed by IL-2 release. Even after incubating the same cells for 1 h at 43 degrees C, we failed to detect an E1-related decrease in the presentation of biosynthesized or osmotically loaded OVA to splenic T cells, as measured by target cell lysis. We introduce the use of mouse tsA1S9 cells to Ag-processing studies and provide the initial biochemical characterization of their defect in protein ubiquitination. Relative to parental L929 cells, after thermal inactivation of E1, these cells actually demonstrate enhanced presentation of endogenous or exogenous viral Ags to T cells. Our findings do not support a role for protein ubiquitination in Ag processing, and indicate that either the temperature-sensitive cell lines examined do not exhibit a sufficient reduction in ubiquitin-conjugating activity to affect the generation of antigenic peptides, or that ubiquitin-targeted proteolysis is not essential for processing the two exogenous and six endogenous Ags examined. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Cox, J H AU - Galardy, P AU - Bennink, J R AU - Yewdell, J W AD - Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892. Y1 - 1995/01/15/ PY - 1995 DA - 1995 Jan 15 SP - 511 EP - 519 VL - 154 IS - 2 SN - 0022-1767, 0022-1767 KW - Antigens, Viral KW - 0 KW - Ovalbumin KW - 9006-59-1 KW - Ubiquitin-Protein Ligases KW - EC 2.3.2.27 KW - Ligases KW - EC 6.- KW - Ubiquitin-Activating Enzymes KW - EC 6.2.1.45 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Ovalbumin -- immunology KW - Mice KW - Hot Temperature KW - Blotting, Western KW - Mice, Inbred CBA KW - Antigens, Viral -- immunology KW - Transfection -- genetics KW - Mice, Inbred C57BL KW - Cytotoxicity Tests, Immunologic KW - Cell Line KW - Ligases -- genetics KW - Antigen Presentation -- physiology KW - Ligases -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77119034?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Presentation+of+endogenous+and+exogenous+antigens+is+not+affected+by+inactivation+of+E1+ubiquitin-activating+enzyme+in+temperature-sensitive+cell+lines.&rft.au=Cox%2C+J+H%3BGalardy%2C+P%3BBennink%2C+J+R%3BYewdell%2C+J+W&rft.aulast=Cox&rft.aufirst=J&rft.date=1995-01-15&rft.volume=154&rft.issue=2&rft.spage=511&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 - 1995-02-09 N1 - Date created - 1995-02-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synergistic effect of rapamycin and cyclosporin A in the treatment of experimental autoimmune uveoretinitis. AN - 77118932; 7814893 AB - Immunosuppressive drugs currently available for the treatment of autoimmune diseases display a narrow therapeutic window between efficacy and toxic side effects. The use of combinations of drugs that have a synergistic effect may expand this window and reduce the risk of toxicity. We evaluated the combination effect of rapamycin (Rapa) and cyclosporin A (CsA) in an autoimmune disease model of the eye. The dose-effect relationship of Rapa with CsA was measured in vitro on the inhibition of proliferation of retinal S-Ag-primed lymphocytes. A median effect analysis was performed and a combination index (CI) calculated for 50% inhibition of proliferation. Rapa and CsA were markedly synergistic over a wide dose range (lowest CI = 0.31). Calculated dose reduction factors indicated that Rapa could be reduced nine-fold and CsA reduced five-fold when these drugs were used in combination. These reduced doses were tested in vivo for the treatment of experimental autoimmune uveoretinitis (EAU). Twelve of 15 rats treated with CsA, 2 mg/kg/day, developed EAU with a median severity of 2.5. Fourteen of 15 rats treated with Rapa, 0.01 mg/kg/day, developed EAU with a median severity of 3.25. Complete inhibition of EAU was achieved in all 15 animals treated with the combination of Rapa and CsA (combined vs CsA alone, p < 0.0002; combined vs Rapa alone, p < 0.00001). The demonstrated synergistic relationship between Rapa and CsA will allow the use of reduced doses of each drug to achieve a therapeutic effect. The use of lower doses may reduce the toxicity of these drugs for the treatment of autoimmune uveitis. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Martin, D F AU - DeBarge, L R AU - Nussenblatt, R B AU - Chan, C C AU - Roberge, F G AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1995/01/15/ PY - 1995 DA - 1995 Jan 15 SP - 922 EP - 927 VL - 154 IS - 2 SN - 0022-1767, 0022-1767 KW - Antigens KW - 0 KW - Arrestin KW - Eye Proteins KW - Immunosuppressive Agents KW - Polyenes KW - Cyclosporine KW - 83HN0GTJ6D KW - Sirolimus KW - W36ZG6FT64 KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred Lew KW - Eye Proteins -- immunology KW - Drug Synergism KW - Lymph Nodes -- cytology KW - Antigens -- immunology KW - Male KW - Lymphocyte Activation -- drug effects KW - Retinitis -- drug therapy KW - Retinitis -- immunology KW - Cyclosporine -- therapeutic use KW - Autoimmune Diseases -- drug therapy KW - Uveitis -- immunology KW - Polyenes -- therapeutic use KW - Immunosuppressive Agents -- therapeutic use KW - Uveitis -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77118932?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Synergistic+effect+of+rapamycin+and+cyclosporin+A+in+the+treatment+of+experimental+autoimmune+uveoretinitis.&rft.au=Martin%2C+D+F%3BDeBarge%2C+L+R%3BNussenblatt%2C+R+B%3BChan%2C+C+C%3BRoberge%2C+F+G&rft.aulast=Martin&rft.aufirst=D&rft.date=1995-01-15&rft.volume=154&rft.issue=2&rft.spage=922&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 - 1995-02-09 N1 - Date created - 1995-02-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alpha 3 beta 1 and alpha 6 beta 1 integrins mediate laminin/merosin binding and function as costimulatory molecules for human thymocyte proliferation. AN - 77118767; 7814863 AB - Integrins comprise a superfamily of alpha beta heterodimers that serve as cell signaling as well as adhesion molecules. We demonstrate that the alpha 3 beta 1 and alpha 6 beta 1 integrins are laminin/merosin receptors expressed in human thymocytes. By reverse transcriptase-PCR analysis, we determined that the alpha 3A beta 1, but not the alpha 3B beta 1, cytoplasmic structural variant of alpha 3 beta 1 is expressed in thymocytes. In contrast, both alpha 6A beta 1 and alpha 6B beta 1 cytoplasmic structural variants of alpha 6 beta 1 are expressed. A small percentage (10 to 15%) of human thymocytes bind to immobilized laminin, and even fewer (3 to 5%) bind to merosin, the laminin isoform normally present in the thymus. This binding, however, can be increased to 39 to 41% after activation of thymocytes with Mn2+ (or PMA). Binding to either laminin or merosin is completely inhibited by anti-beta 1 mAb or by a mixture of anti-alpha 3 and anti-alpha 6 mAbs, indicating that both alpha 3 beta 1 and alpha 6 beta 1 participate in thymocyte adhesion to the laminin family of extracellular matrix proteins. The protein kinase C inhibitors, calphostin C and staurosporine, inhibit Mn(2+)-enhanced thymocyte binding, suggesting that protein kinase C activity is crucial for the binding. Furthermore, the data indicate that at least two divalent cation binding sites serve to regulate integrin binding activity. Finally, we show that both immobilized laminin and merosin have costimulatory function for anti-CD3-induced thymocyte proliferation, and both anti-alpha 3 and anti-alpha 6 mAbs can block this proliferative response. The cooperative function of alpha 3 beta 1 and alpha 6 beta 1 evidenced in the laminin/merosin binding and proliferation assays suggests that thymocyte-merosin interactions may play an important role in thymic T cell development. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Chang, A C AU - Salomon, D R AU - Wadsworth, S AU - Hong, M J AU - Mojcik, C F AU - Otto, S AU - Shevach, E M AU - Coligan, J E AD - Laboratory of Molecular Structure, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892. Y1 - 1995/01/15/ PY - 1995 DA - 1995 Jan 15 SP - 500 EP - 510 VL - 154 IS - 2 SN - 0022-1767, 0022-1767 KW - Integrin alpha3beta1 KW - 0 KW - Integrin alpha6beta1 KW - Integrins KW - Laminin KW - Receptors, Antigen, T-Cell KW - Manganese KW - 42Z2K6ZL8P KW - Protein Kinase C KW - EC 2.7.11.13 KW - Magnesium KW - I38ZP9992A KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Abridged Index Medicus KW - Index Medicus KW - Manganese -- pharmacology KW - Electrophoresis, Polyacrylamide Gel KW - Magnesium -- physiology KW - Humans KW - Receptors, Antigen, T-Cell -- immunology KW - Precipitin Tests KW - Protein Binding -- immunology KW - Child, Preschool KW - Infant KW - Polymerase Chain Reaction KW - Base Sequence KW - Cells, Cultured KW - Calcium -- physiology KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Protein Kinase C -- physiology KW - Signal Transduction KW - Thymus Gland -- cytology KW - Laminin -- metabolism KW - Lymphocyte Activation -- immunology KW - Integrins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77118767?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Alpha+3+beta+1+and+alpha+6+beta+1+integrins+mediate+laminin%2Fmerosin+binding+and+function+as+costimulatory+molecules+for+human+thymocyte+proliferation.&rft.au=Chang%2C+A+C%3BSalomon%2C+D+R%3BWadsworth%2C+S%3BHong%2C+M+J%3BMojcik%2C+C+F%3BOtto%2C+S%3BShevach%2C+E+M%3BColigan%2C+J+E&rft.aulast=Chang&rft.aufirst=A&rft.date=1995-01-15&rft.volume=154&rft.issue=2&rft.spage=500&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 - 1995-02-09 N1 - Date created - 1995-02-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Unscheduled activation of cyclin B1/Cdc2 kinase in human promyelocytic leukemia cell line HL60 cells undergoing apoptosis induced by DNA damage. AN - 77116634; 7812949 AB - We have studied changes in cyclin A- and B1-dependent kinases during apoptosis induced in human promyelocytic leukemia (HL60) cells treated with the topoisomerase I inhibitor camptothecin. We found that cyclin B1/Cdc2 kinase activity transiently increases within 30 min after camptothecin treatment. This increase is followed by a rapid inactivation of the cyclin B1/Cdc2 kinase that is associated with Cdc2 tyrosine phosphorylation without any change in Cdc2 or cyclin B1 protein levels. The DNA polymerase inhibitor aphidicolin abrogates camptothecin-induced changes in cyclin B1/Cdc2 kinase activity, indicating that DNA replication-induced DNA damage is essential for both Cdc2 alterations and apoptosis activation. Apoptosis and the initial cyclin B1/Cdc2 kinase activation were amplified using synchronized S-phase cells, and cyclin A/cdk2 kinase did not change under these conditions. The same transient activation and subsequent inactivation of cyclin B1/Cdc2 kinase were observed after DNA damage by etoposide or bis-(2-chloroethyl)methylamine hydrochloride. These observations suggest that DNA damage promotes the transient and unscheduled stimulation of cyclin B1/Cdc2 kinase activity in HL60 cells prior to apoptosis. JF - Cancer research AU - Shimizu, T AU - O'Connor, P M AU - Kohn, K W AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255. Y1 - 1995/01/15/ PY - 1995 DA - 1995 Jan 15 SP - 228 EP - 231 VL - 55 IS - 2 SN - 0008-5472, 0008-5472 KW - Cyclins KW - 0 KW - Aphidicolin KW - 38966-21-1 KW - Mechlorethamine KW - 50D9XSG0VR KW - Etoposide KW - 6PLQ3CP4P3 KW - CDC2 Protein Kinase KW - EC 2.7.11.22 KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Etoposide -- pharmacology KW - Aphidicolin -- pharmacology KW - Tumor Cells, Cultured KW - Phosphorylation KW - Camptothecin -- pharmacology KW - DNA Damage KW - Humans KW - Enzyme Activation -- drug effects KW - S Phase KW - Mechlorethamine -- pharmacology KW - Apoptosis -- genetics KW - CDC2 Protein Kinase -- metabolism KW - Apoptosis -- drug effects KW - Leukemia, Promyelocytic, Acute -- metabolism KW - Leukemia, Promyelocytic, Acute -- genetics KW - Cyclins -- metabolism KW - Leukemia, Promyelocytic, Acute -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77116634?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Unscheduled+activation+of+cyclin+B1%2FCdc2+kinase+in+human+promyelocytic+leukemia+cell+line+HL60+cells+undergoing+apoptosis+induced+by+DNA+damage.&rft.au=Shimizu%2C+T%3BO%27Connor%2C+P+M%3BKohn%2C+K+W%3BPommier%2C+Y&rft.aulast=Shimizu&rft.aufirst=T&rft.date=1995-01-15&rft.volume=55&rft.issue=2&rft.spage=228&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 - 1995-02-03 N1 - Date created - 1995-02-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Conservation of a common motif in enzymes catalyzing ADP-ribose transfer. Identification of domains in mammalian transferases. AN - 77134504; 7822277 AB - Bacterial toxin ADP-ribosyltransferases, e.g. diphtheria toxin (DT) and pertussis toxin, have in common consensus sequences involved in catalytic activity, which are localized to three regions. Region I is notable for a histidine or arginine; region II, approximately 50-75 amino acids downstream, is rich in aromatic/hydrophobic amino acids; and region III, further downstream, has a glutamate and other acidic amino acids. A similar motif was observed in the sequence of the glycosylphosphatidylinositol-linked muscle ADP-ribosyltransferase. Site-directed mutagenesis was performed to verify the role of this motif. Proteins were expressed in rat adenocarcinoma cells, released from the cell with phosphatidylinositol-specific phospholipase C, and quantified with polyclonal antibodies. Transferase His114 in region I aligned with His21 of DT; as with DT, the H114N mutant was active. Aromatic/hydrophobic amino acids (region II) were found approximately 30-50 amino acids downstream of this histidine. Although transferase has a Glu278-Tyr-Ile sequence characteristic of region III in DT, Glu278 was not critical for activity. In an alternative region III containing Glu238-Glu239-Glu240, Glu238 and Glu240 but not Glu239 were critical. Glu240 aligned with critical glutamates in DT, Pseudomonas exotoxin, and C3 transferase. Thus, the mammalian ADP-ribosyltransferases have motifs similar to toxin ADP-ribosyltransferases, suggesting that these sequences are important in ADP-ribose transfer reactions. JF - The Journal of biological chemistry AU - Takada, T AU - Iida, K AU - Moss, J AD - Pulmonary-Critical Care Medicine Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892-1434. Y1 - 1995/01/13/ PY - 1995 DA - 1995 Jan 13 SP - 541 EP - 544 VL - 270 IS - 2 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - Adenosine Diphosphate Ribose KW - 20762-30-5 KW - Glutamic Acid KW - 3KX376GY7L KW - Histidine KW - 4QD397987E KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - Index Medicus KW - Rats KW - Animals KW - Base Sequence KW - Glutamic Acid -- metabolism KW - Molecular Sequence Data KW - Rabbits KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Histidine -- metabolism KW - Catalysis KW - Poly(ADP-ribose) Polymerases -- chemistry KW - Adenosine Diphosphate Ribose -- metabolism KW - Poly(ADP-ribose) Polymerases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77134504?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Conservation+of+a+common+motif+in+enzymes+catalyzing+ADP-ribose+transfer.+Identification+of+domains+in+mammalian+transferases.&rft.au=Takada%2C+T%3BIida%2C+K%3BMoss%2C+J&rft.aulast=Takada&rft.aufirst=T&rft.date=1995-01-13&rft.volume=270&rft.issue=2&rft.spage=541&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 - 1995-02-13 N1 - Date created - 1995-02-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vitro processing of anthrax toxin protective antigen by recombinant PC1 (SPC3) and bovine intermediate lobe secretory vesicle membranes. AN - 77130624; 7840657 AB - Protective antigen (PA), an 83-kDa protein produced by Bacillus anthracis, requires proteolytic activation at a tetrabasic site (RKKR167) before it can combine with either edema factor or lethal factor on the cell surface. The complex is then endocytosed and the target cell intoxicated. Previous work has demonstrated that furin, a ubiquitously distributed, subtilisin-like protease, can perform this cleavage. In this study, another member of the furin family, PC1 (SPC3), was tested as a putative processing enzyme for PA. Recombinant PC1, partially purified from the medium of stably transfected L-cells, cleaved PA to a 63-kDa fragment (PA63) and a 20-kDa fragment (PA20). Amino-terminal sequence analysis of the 63 kDa product demonstrated that cleavage occurred between Arg167 and Ser168. The pH optimum for in vitro PA cleavage was 6.0 and the enzymatic activity was calcium-dependent. Medium from untransfected L-cells did not cleave PA. Site-directed mutagenesis of the tetrabasic cleavage site revealed that PC1 preferred to cleave sequences containing basic residues at positions -1 and -4 relative to the wild-type cleavage site, demonstrating that PC1 can cleave substrates at a monobasic residue site in vitro. Substrates having basic residues at the -1 and -2 positions were cleaved with approximately twofold less efficiency than wild-type PA. Mutants of PA containing basic residues in positions -1 and either -2 or -4 of the cleavage site were predicted to be substrates for PC1 and were more toxic to L-cells expressing PC1 than to untransfected L-cells. These results demonstrate that PA is cleaved by PC1 in vivo. Membranes from bovine intermediate lobe secretory vesicles which contain both prohormone convertases, PC1 and PC2, also cleaved PA to PA63 with a pH optimum of 5.5. Immunodepletion studies using antisera against PC1 and PC2 showed that these are the enzymes primarily responsible for the cleavage of PA in the membrane preparation. Thus, both recombinant PC1 and a membrane preparation containing endogenous PC1 can activate PA. JF - Archives of biochemistry and biophysics AU - Friedman, T C AU - Gordon, V M AU - Leppla, S H AU - Klimpel, K R AU - Birch, N P AU - Loh, Y P AD - Section on Cellular Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1995/01/10/ PY - 1995 DA - 1995 Jan 10 SP - 5 EP - 13 VL - 316 IS - 1 SN - 0003-9861, 0003-9861 KW - Antigens, Bacterial KW - 0 KW - Bacterial Toxins KW - Protease Inhibitors KW - Recombinant Proteins KW - anthrax toxin KW - Proprotein Convertases KW - EC 3.4.21.- KW - Subtilisins KW - Pcsk1 protein, mouse KW - EC 3.4.21.93 KW - Proprotein Convertase 1 KW - Proprotein Convertase 2 KW - EC 3.4.21.94 KW - Aspartic Acid Endopeptidases KW - EC 3.4.23.- KW - Index Medicus KW - Animals KW - L Cells (Cell Line) KW - Protease Inhibitors -- pharmacology KW - Membranes -- metabolism KW - Amino Acid Sequence KW - Mice KW - Subtilisins -- metabolism KW - Membranes -- enzymology KW - Cattle KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Substrate Specificity KW - Protein Processing, Post-Translational -- drug effects KW - Aspartic Acid Endopeptidases -- metabolism KW - Bacillus anthracis KW - Bacterial Toxins -- genetics KW - Aspartic Acid Endopeptidases -- genetics KW - Bacterial Toxins -- metabolism KW - Pituitary Gland -- enzymology KW - Bacterial Toxins -- toxicity KW - Pituitary Gland -- metabolism KW - Pituitary Gland -- secretion KW - Aspartic Acid Endopeptidases -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77130624?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=In+vitro+processing+of+anthrax+toxin+protective+antigen+by+recombinant+PC1+%28SPC3%29+and+bovine+intermediate+lobe+secretory+vesicle+membranes.&rft.au=Friedman%2C+T+C%3BGordon%2C+V+M%3BLeppla%2C+S+H%3BKlimpel%2C+K+R%3BBirch%2C+N+P%3BLoh%2C+Y+P&rft.aulast=Friedman&rft.aufirst=T&rft.date=1995-01-10&rft.volume=316&rft.issue=1&rft.spage=5&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 - 1995-03-02 N1 - Date created - 1995-03-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of cadmium on human ovarian cancer cells with acquired cisplatin resistance. AN - 77142547; 7850774 AB - Cadmium (Cd) dichloride is a compound that has teratogenic, mutagenic, and carcinogenic properties. Recent reports have suggested the possibility that this compound may also have tumor suppressive properties in some settings. For these reasons, we have studied the subcellular pharmacological profile of elemental cadmium in human ovarian cancer cells, when administered as cadmium dichloride. The cell lines A2780 and A2780/CP70 were used, which are well characterized with respect to their cellular response to platinum-based compounds. Cd was measured in all experiments with the use of atomic absorbance spectrometry with Zeeman background correction. In both cell lines, there were direct relationships between; drug dose and cellular accumulation of drug; cellular accumulation of drug and DNA damage levels; and DNA damage levels and cytotoxicity. These cell lines differed in that the cisplatin-resistant A2780/CP70 cell line, was also comparatively resistant to cadmium dichloride. This enhanced cellular resistance appeared to be mediated through decreased drug accumulation, and increased cellular tolerance to higher levels of DNA damage. Total genomic DNA repair and cytosolic inactivation of drug appeared not to differ substantively between these two cell lines. JF - Cancer letters AU - Lee, K B AU - Parker, R J AU - Reed, E AD - Clinical Pharmacology Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1995/01/06/ PY - 1995 DA - 1995 Jan 06 SP - 57 EP - 66 VL - 88 IS - 1 SN - 0304-3835, 0304-3835 KW - DNA, Neoplasm KW - 0 KW - Cadmium KW - 00BH33GNGH KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - DNA Repair KW - DNA Damage KW - Cells, Cultured KW - Humans KW - In Vitro Techniques KW - Drug Resistance KW - DNA, Neoplasm -- metabolism KW - Female KW - Ovarian Neoplasms -- metabolism KW - Cadmium -- metabolism KW - Cisplatin -- toxicity KW - Cadmium -- toxicity KW - Cisplatin -- metabolism KW - Ovarian Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77142547?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=Effect+of+cadmium+on+human+ovarian+cancer+cells+with+acquired+cisplatin+resistance.&rft.au=Lee%2C+K+B%3BParker%2C+R+J%3BReed%2C+E&rft.aulast=Lee&rft.aufirst=K&rft.date=1995-01-06&rft.volume=88&rft.issue=1&rft.spage=57&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-16 N1 - Date created - 1995-03-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Different ARF domains are required for the activation of cholera toxin and phospholipase D. AN - 77122365; 7814376 AB - ADP-ribosylation factors (ARFs), initially described as activators of cholera toxin ADP-ribosyltransferase activity, regulate intracellular vesicular membrane trafficking and stimulate a phospholipase D (PLD) isoform. ARF-like (ARL) proteins are structurally related to ARFs but do not activate cholera toxin and have relatively little effect on PLD. A new human ARL gene termed hARL1, which shares 57% amino acid identity with hARF1, was identified using a polymerase chain reaction-based cloning method. To determine whether different structural elements are responsible for the activation structural elements are responsible for the activation of the A subunit of cholera toxin and PLD, chimeric proteins were constructed by switching the amino-terminal 73 amino acids of ARF1 and ARL1. The recombinant rL73/F protein, in which the amino-terminal 73 amino acids of ARL1 replaced those of ARF1, activated the A subunit of cholera toxin, whereas the rF73/L protein, in which the NH2-terminal 73 amino acids of ARF1 replaced those of ARL1, was inactive. The two chimeric proteins had quite opposite effects on PLD activity. rF73/L activated PLD as effectively as rARF1, whereas rL73/F protein activated PLD only slightly. It appears that the amino-terminal region of ARF1 is not critical for its action as a GTP-dependent activator of cholera toxin, whereas it is necessary for activation of the putative effector enzyme, PLD. JF - The Journal of biological chemistry AU - Zhang, G F AU - Patton, W A AU - Lee, F J AU - Liyanage, M AU - Han, J S AU - Rhee, S G AU - Moss, J AU - Vaughan, M AD - Pulmonary-Critical Care Medicine Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1995/01/06/ PY - 1995 DA - 1995 Jan 06 SP - 21 EP - 24 VL - 270 IS - 1 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - Recombinant Fusion Proteins KW - Guanosine Triphosphate KW - 86-01-1 KW - Cholera Toxin KW - 9012-63-9 KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - Phospholipase D KW - EC 3.1.4.4 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - ADP-Ribosylation Factor 1 KW - EC 3.6.5.2 KW - ADP-Ribosylation Factors KW - Index Medicus KW - Recombinant Fusion Proteins -- metabolism KW - Base Sequence KW - Enzyme Activation KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Poly(ADP-ribose) Polymerases -- metabolism KW - Recombinant Fusion Proteins -- chemistry KW - Guanosine Triphosphate -- metabolism KW - Phospholipase D -- metabolism KW - GTP-Binding Proteins -- metabolism KW - GTP-Binding Proteins -- chemistry KW - Cholera Toxin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77122365?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Different+ARF+domains+are+required+for+the+activation+of+cholera+toxin+and+phospholipase+D.&rft.au=Zhang%2C+G+F%3BPatton%2C+W+A%3BLee%2C+F+J%3BLiyanage%2C+M%3BHan%2C+J+S%3BRhee%2C+S+G%3BMoss%2C+J%3BVaughan%2C+M&rft.aulast=Zhang&rft.aufirst=G&rft.date=1995-01-06&rft.volume=270&rft.issue=1&rft.spage=21&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 - 1995-02-03 N1 - Date created - 1995-02-03 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - L28997; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutational analysis of Saccharomyces cerevisiae ARF1. AN - 77120402; 7814365 AB - Wild type and eight point mutants of Saccharomyces cerevisiae ARF1 were expressed in yeast and bacteria to determine the roles of specific residues in in vivo and in vitro activities. Mutations at either Gly2 or Asp26 resulted in recessive loss of function. It was concluded that N-myristoylation is required for Arf action in cells but not for either nucleotide exchange or cofactor activities in vitro. Asp26 (homologous to Gly12 of p21ras) was essential for the binding of the activating nucleotide, guanosine 5'-3-O-(thio)triphosphate. This is in marked contrast to results obtained after mutagenesis of the homologous residue in p21ras or Gs alpha, and suggests a fundamental difference in the guanine nucleotide binding site of Arf with respect to these other GTP-binding proteins. Two dominant alleles were also identified, one activating dominant ([Q71L]Arf1) and the other ([N126I]) a negative dominant. A conditional allele, [W66R]Arf1, was characterized and shown to have approximately 300-fold lower specific activity in an in vitro Arf assay. Two high-copy suppressors of this conditional phenotype were cloned and sequenced. One of these suppressors, SFS4, was found to be identical to PBS2/HOG4, recently shown to encode a microtubule-associated protein kinase kinase in yeast. JF - The Journal of biological chemistry AU - Kahn, R A AU - Clark, J AU - Rulka, C AU - Stearns, T AU - Zhang, C J AU - Randazzo, P A AU - Terui, T AU - Cavenagh, M AD - Laboratory of Biological Chemistry, NCI, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1995/01/06/ PY - 1995 DA - 1995 Jan 06 SP - 143 EP - 150 VL - 270 IS - 1 SN - 0021-9258, 0021-9258 KW - Aspartic Acid KW - 30KYC7MIAI KW - Guanosine Triphosphate KW - 86-01-1 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - ADP-Ribosylation Factor 1 KW - EC 3.6.5.2 KW - ADP-Ribosylation Factors KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Aspartic Acid -- genetics KW - Cysteine -- genetics KW - DNA Mutational Analysis KW - Amino Acid Sequence KW - Protein Binding KW - Guanosine Triphosphate -- metabolism KW - Alleles KW - Genes, Dominant KW - Molecular Sequence Data KW - Point Mutation KW - Genes, Lethal KW - Saccharomyces cerevisiae -- metabolism KW - GTP-Binding Proteins -- metabolism KW - GTP-Binding Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77120402?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Mutational+analysis+of+Saccharomyces+cerevisiae+ARF1.&rft.au=Kahn%2C+R+A%3BClark%2C+J%3BRulka%2C+C%3BStearns%2C+T%3BZhang%2C+C+J%3BRandazzo%2C+P+A%3BTerui%2C+T%3BCavenagh%2C+M&rft.aulast=Kahn&rft.aufirst=R&rft.date=1995-01-06&rft.volume=270&rft.issue=1&rft.spage=143&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 - 1995-02-03 N1 - Date created - 1995-02-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Testing human hair for drugs of abuse. IV. Environmental cocaine contamination and washing effects. AN - 77146607; 7860035 AB - Active cocaine use results in sequestration of parent drug in hair. In addition, hair has unique physicochemical properties that permit absorption of cocaine from the environment. When hair is tested for evidence of cocaine, it is important to consider whether the positive test resulted from active drug use or environmental contamination. In a series of laboratory experiments, it was found that exposure of 'cut' hair to cocaine vapor ('crack' smoke) and to aqueous solutions of cocaine hydrochloride resulted in significant contamination of hair samples. Similar results were obtained with two subjects who were exposed to cocaine vapor in an unventilated room. The amount of contamination adsorbed by hair depended upon both time and extent of exposure. Washing the hair samples with methanol removed > 70% of the cocaine contaminant after cocaine vapor exposure, but was less effective (< 50%) following contamination with aqueous cocaine. Shampoo treatment cycles (overnight soaking) progressively removed increasing amounts of cocaine from the contaminated hair, but residual cocaine remained after 10 cycles. Studies were also performed to determine the usefulness of benzoylecgonine as a marker of active cocaine administration. Small amounts of benzoylecgonine (ca. 1 ng/mg) were formed in hair as a result of environmental contamination with cocaine. Also, it was found that benzoylecgonine could be adsorbed from illicit cocaine contaminated with benzoylecgonine. It was concluded that positive hair test results should be interpreted cautiously due to the possibility of environmental contamination from cocaine and related constituents. JF - Forensic science international AU - Wang, W L AU - Cone, E J AD - Addiction Research Center, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224. Y1 - 1995/01/05/ PY - 1995 DA - 1995 Jan 05 SP - 39 EP - 51 VL - 70 IS - 1-3 SN - 0379-0738, 0379-0738 KW - benzoylecgonine KW - 5353I8I6YS KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Air Pollution KW - Humans KW - Environmental Exposure KW - Decontamination KW - Cocaine -- analysis KW - Cocaine -- analogs & derivatives KW - Hair -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77146607?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Forensic+science+international&rft.atitle=Testing+human+hair+for+drugs+of+abuse.+IV.+Environmental+cocaine+contamination+and+washing+effects.&rft.au=Wang%2C+W+L%3BCone%2C+E+J&rft.aulast=Wang&rft.aufirst=W&rft.date=1995-01-05&rft.volume=70&rft.issue=1-3&rft.spage=39&rft.isbn=&rft.btitle=&rft.title=Forensic+science+international&rft.issn=03790738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-17 N1 - Date created - 1995-03-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Residues affecting the catalysis and inhibition of rat lens aldose reductase. AN - 77113349; 7811733 AB - Aldose reductase (AR), the first enzyme of the polyol pathway, has been implicated in diabetic complications. Results of recent clinical studies have shown that compounds that inhibit aldose reductase (ARIs) and block the flux of glucose through the polyol pathway have provided benefit to diabetic neuropathic patients. Since many ARIs show broad substrate specificity, emphasis on the structure-function properties of the AR enzyme will help in the refinement and design of future inhibitors. To this end, catalysis and inhibition of rat lens aldose reductase was examined following site-directed mutagenesis. Replacement of tyrosine 48 with phenylalanine (Y48F) resulted in an enzyme form with less than 0.25% activity with DL-glyceraldehyde and no detectable activity with p-nitrobenzaldehyde or xylose, although circular dichroism spectra and NADPH binding affinity were similar to wild-type AR. Mutation of histidine 110 to glutamine (H110Q) also resulted in a less active protein with an approximate 3-fold decrease in kcat for the reduction of DL-glyceraldehyde; slight or no activity was measured with other substrates and an increase of 195-fold over wild type was observed in the Km for glyceraldehyde. H110Q was less sensitive to inhibition by aldose reductase inhibitors. The most dramatic change was seen with imeristat, which showed an 1800-fold increase in IC50. Mutation of cysteine 298 to serine (C298S) affected enzyme function by increasing kcat 2- to 4-fold and increasing Km 15- to 48-fold, with DL-glyceraldehyde, p-nitrobenzaldehyde or xylose as substrates. As a result kcat/Km, catalytic efficiency, dropped to approx. 10% of control. Inhibition of C298S was not noticeably different from wild type. Substitution of histidine 187 or 200 with glutamine (H187Q, H200Q) had little effect on AR catalysis or inhibition. Based on structural and mutagenesis studies of human AR and the conservation of amino acids between human and rat, these data would indicate that Y48, H110, and C298 are important residues in the active site of rat AR and that Y48 is most likely the proton donor during substrate reduction by rat lens aldose reductase. In addition, these studies indicate that mutagenesis of H110 also affects aldose reductase inhibition. JF - Biochimica et biophysica acta AU - Carper, D A AU - Hohman, T C AU - Old, S E AD - National Eye Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1995/01/05/ PY - 1995 DA - 1995 Jan 05 SP - 67 EP - 73 VL - 1246 IS - 1 SN - 0006-3002, 0006-3002 KW - Recombinant Proteins KW - 0 KW - Glutamine KW - 0RH81L854J KW - Histidine KW - 4QD397987E KW - NADP KW - 53-59-8 KW - Aldehyde Reductase KW - EC 1.1.1.21 KW - Index Medicus KW - Animals KW - Electrophoresis, Polyacrylamide Gel KW - Humans KW - Hydrogen-Ion Concentration KW - NADP -- metabolism KW - Structure-Activity Relationship KW - Binding Sites KW - Rats KW - Mutagenesis, Site-Directed KW - Blotting, Western KW - Kinetics KW - Escherichia coli KW - Substrate Specificity KW - Catalysis KW - Aldehyde Reductase -- chemistry KW - Aldehyde Reductase -- metabolism KW - Aldehyde Reductase -- antagonists & inhibitors KW - Lens, Crystalline -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77113349?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochimica+et+biophysica+acta&rft.atitle=Residues+affecting+the+catalysis+and+inhibition+of+rat+lens+aldose+reductase.&rft.au=Carper%2C+D+A%3BHohman%2C+T+C%3BOld%2C+S+E&rft.aulast=Carper&rft.aufirst=D&rft.date=1995-01-05&rft.volume=1246&rft.issue=1&rft.spage=67&rft.isbn=&rft.btitle=&rft.title=Biochimica+et+biophysica+acta&rft.issn=00063002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-07 N1 - Date created - 1995-02-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regioselectivity of alkylation of cyclomaltoheptaose (beta-cyclodextrin) and synthesis of its mono-2-O-methyl, -ethyl, -allyl, and -propyl derivatives. AN - 77192542; 7697652 AB - Mono-2-O-methyl-, -2-O-ethyl-, and -2-O-allyl-cyclomaltoheptaose were prepared by alkylations of cyclomaltoheptaose in dilute aqueous alkali, and mono-2-O-propylcyclomaltoheptaose was obtained by hydrogenation of the allyl derivative. All the 2-O-alkyl derivatives were less soluble in water than was cyclomaltoheptaose. All formed inclusion complexes with toluene in aqueous solution, but only the methyl ether was less soluble in the water-toluene system than in water. The solubilities of the other ethers in water were enhanced by the addition of toluene. Partial methylation of cyclomaltoheptase with 13C-enriched dimethyl sulfate in dilute aqueous alkali yielded mixtures of products. The substitution patterns were analyzed by GLC-MS of the alditol acetates, prepared by hydrolysis, reduction, and acetylation, and by 13C NMR after complete permethylation with nonenriched reagent. The results showed that methylation at O-2 is a predominant but not an exclusive reaction; as expected, the regioselectivity decreases with increasing degree of methylation. JF - Carbohydrate research AU - Jindrich, J AU - Pitha, J AU - Lindberg, B AU - Seffers, P AU - Harata, K AD - National Institutes of Health, NIA/GRC, Baltimore, MD 21224. Y1 - 1995/01/03/ PY - 1995 DA - 1995 Jan 03 SP - 75 EP - 80 VL - 266 IS - 1 SN - 0008-6215, 0008-6215 KW - Cyclodextrins KW - 0 KW - beta-Cyclodextrins KW - betadex KW - JV039JZZ3A KW - Index Medicus KW - Magnetic Resonance Spectroscopy KW - Alkylation KW - Cyclodextrins -- chemistry KW - Cyclodextrins -- chemical synthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77192542?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carbohydrate+research&rft.atitle=Regioselectivity+of+alkylation+of+cyclomaltoheptaose+%28beta-cyclodextrin%29+and+synthesis+of+its+mono-2-O-methyl%2C+-ethyl%2C+-allyl%2C+and+-propyl+derivatives.&rft.au=Jindrich%2C+J%3BPitha%2C+J%3BLindberg%2C+B%3BSeffers%2C+P%3BHarata%2C+K&rft.aulast=Jindrich&rft.aufirst=J&rft.date=1995-01-03&rft.volume=266&rft.issue=1&rft.spage=75&rft.isbn=&rft.btitle=&rft.title=Carbohydrate+research&rft.issn=00086215&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-04 N1 - Date created - 1995-05-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The chemistry of poisons in amphibian skin. AN - 77125608; 7816854 AB - Poisons are common in nature, where they often serve the organism in chemical defense. Such poisons either are produced de novo or are sequestered from dietary sources or symbiotic organisms. Among vertebrates, amphibians are notable for the wide range of noxious agents that are contained in granular skin glands. These compounds include amines, peptides, proteins, steroids, and both water-soluble and lipid-soluble alkaloids. With the exception of the alkaloids, most seem to be produced de novo by the amphibian. The skin of amphibians contains many structural classes of alkaloids previously unknown in nature. These include the batrachotoxins, which have recently been discovered to also occur in skin and feathers of a bird, the histrionicotoxins, the gephyrotoxins, the decahydroquinolines, the pumiliotoxins and homopumiliotoxins, epibatidine, and the samandarines. Some amphibian skin alkaloids are clearly sequestered from the diet, which consists mainly of small arthropods. These include pyrrolizidine and indolizidine alkaloids from ants, tricyclic coccinellines from beetles, and pyrrolizidine oximes, presumably from millipedes. The sources of other alkaloids in amphibian skin, including the batrachotoxins, the decahydroquinolines, the histrionicotoxins, the pumiliotoxins, and epibatidine, are unknown. While it is possible that these are produced de novo or by symbiotic microorganisms, it appears more likely that they are sequestered by the amphibians from as yet unknown dietary sources. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Daly, J W AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health, Bethesda, MD 20892. Y1 - 1995/01/03/ PY - 1995 DA - 1995 Jan 03 SP - 9 EP - 13 VL - 92 IS - 1 SN - 0027-8424, 0027-8424 KW - Amphibian Venoms KW - 0 KW - Bridged Bicyclo Compounds KW - Bridged Bicyclo Compounds, Heterocyclic KW - Pyridines KW - epibatidine KW - M6K314F1XX KW - histrionicotoxin KW - TC29F9M9XW KW - Index Medicus KW - Molecular Structure KW - Animals KW - Pyridines -- chemistry KW - Bridged Bicyclo Compounds -- toxicity KW - Bridged Bicyclo Compounds -- chemistry KW - Pyridines -- toxicity KW - Invertebrates KW - Birds KW - Amphibians -- physiology KW - Amphibian Venoms -- chemistry KW - Skin Physiological Phenomena KW - Amphibian Venoms -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77125608?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=The+chemistry+of+poisons+in+amphibian+skin.&rft.au=Daly%2C+J+W&rft.aulast=Daly&rft.aufirst=J&rft.date=1995-01-03&rft.volume=92&rft.issue=1&rft.spage=9&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 - 1995-02-09 N1 - Date created - 1995-02-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1967 Apr;57(4):893-8 [5231352] Science. 1971 Feb 26;171(3973):757-70 [5541160] Experientia. 1971 May 15;27(5):506 [5132572] Science. 1980 May 2;208(4443):503-5 [6245447] Science. 1980 Jun 20;208(4450):1383-5 [6246586] Toxicon. 1984;22(6):905-19 [6523513] Science. 1985 Jun 7;228(4704):1154-60 [3890182] Peptides. 1985;6 Suppl 3:7-12 [3868775] Toxicon. 1987;25(10):1023-95 [3321567] Science. 1990 Apr 13;248(4952):173-7 [2183350] Proc Natl Acad Sci U S A. 1990 Jun;87(12):4836-9 [2352951] Annu Rev Biochem. 1990;59:395-414 [2197979] J Nat Prod. 1990 Mar-Apr;53(2):407-21 [2380714] J Nat Prod. 1992 Jun;55(6):707-22 [1522417] Toxicon. 1992 Aug;30(8):887-98 [1523680] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10960-3 [1438301] Science. 1992 Oct 30;258(5083):799-801 [1439786] J Nat Prod. 1993 Jul;56(7):1016-38 [8377013] Toxicon. 1994 Mar;32(3):279-85 [8016850] Toxicon. 1994 Jun;32(6):657-63 [7940573] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structure and function of the tympanic membrane: a review. AN - 85319026; pmid-7610903 AB - Advances made in the last three decades of research on morphological, cell biological, and immunobiological aspects of the tympanic membrane of laboratory animals and humans are reviewed. The tympanic membrane is composed of the pars flaccida and pars tensa with considerable variations in their size and thickness. Both pars flaccida and pars tensa consist of an epidermal layer, a lamina propria, and a mucosal epithelial layer. The fibrils of the fibrous layer contain a large amount of type II and type III collagen, and a small amount of type I collagen. It has been suggested that such an unusual collagen composition is the underlying reason for the unique physical feature of the pars tensa of the tympanic membrane. A large number of mast cells are found in the Shrapnell's membrane and these cells are suggested to be responsible for the production of middle ear effusion. The cellular basis for the epidermal migration and the role of epidermal and fibroblast growth factors in epidermal cell proliferation and in wound healing are also reviewed. Future research directions on tympanic membrane biology and pathobiology are discussed. JF - Acta oto-rhino-laryngologica Belgica AU - Lim, D J AD - Laboratory of Cellular Biology, National Institute on Deafness and other Communication Disorders (NIDCD), National Institutes of Health (NIH), Rockville, MD 20850, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 101 EP - 115 VL - 49 IS - 2 SN - 0001-6497, 0001-6497 KW - Index Medicus KW - National Library of Medicine KW - Humans KW - Microscopy, Electron KW - Mast Cells -- ultrastructure KW - Microscopy, Electron, Scanning KW - Tympanic Membrane -- innervation KW - Tympanic Membrane -- ultrastructure KW - Tympanic Membrane -- blood supply KW - Tympanic Membrane -- anatomy & histology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85319026?accountid=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=Acta+oto-rhino-laryngologica+Belgica&rft.atitle=Structure+and+function+of+the+tympanic+membrane%3A+a+review.&rft.au=Lim%2C+D+J&rft.aulast=Lim&rft.aufirst=D&rft.date=1995-01-01&rft.volume=49&rft.issue=2&rft.spage=101&rft.isbn=&rft.btitle=&rft.title=Acta+oto-rhino-laryngologica+Belgica&rft.issn=00016497&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2009-01-27 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Developmental plasticity and memory. AN - 85269321; pmid-7755902 AB - The cerebral cortex of young kittens is known to be highly malleable during early postnatal development. However, most studies of developmental plasticity have been conducted in primary visual cortex. It has long been unclear to what extent similar plasticity exists in higher cortical areas. We have now studied developmental plasticity in the anterior ectosylvian (AE) region of the cat's parietal association cortex, which receives input from different sensory modalities. One area in this cortical region, which is predominantly visual in normal cats, area AEV, is taken over almost completely by auditory and somatosensory inputs, when cats are binocularly deprived of vision from birth. Furthermore, when single auditory neurons are tested with sound sources in free-field at different locations, they show sharper spatial tuning in visually deprived cats. This compensatory, crossmodal plasticity was explored at the behavioral level by testing visually deprived cats in an auditory localization task, and these cats could indeed localize sound sources more precisely than normal cats. These findings are interpreted as a form of adaptation of the young brain to an altered environment. Similar adaptation is still possible in adult brains by virtue of associative learning and long-term memory. It is argued that the synaptic mechanisms by which associative memories are stored in the cerebral cortex are similar to those in developmental plasticity, only the increment of learning is smaller in adult animals. JF - Behavioural Brain Research AU - Rauschecker, J P AD - Laboratory of Neurophysiology, NIMH, Poolesville, MD 20837, USA. PY - 1995 SP - 7 EP - 12 VL - 66 IS - 1-2 SN - 0166-4328, 0166-4328 KW - Visual Cortex KW - Learning KW - Synapses KW - Association Learning KW - Sensory Deprivation KW - Aging KW - Animal KW - Parietal Lobe KW - Cerebral Cortex KW - Memory KW - Perception KW - Cats KW - Retention (Psychology) KW - Neuronal Plasticity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85269321?accountid=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=Behavioural+Brain+Research&rft.atitle=Developmental+plasticity+and+memory.&rft.au=Rauschecker%2C+J+P&rft.aulast=Rauschecker&rft.aufirst=J&rft.date=1995-01-01&rft.volume=66&rft.issue=1-2&rft.spage=7&rft.isbn=&rft.btitle=&rft.title=Behavioural+Brain+Research&rft.issn=01664328&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Esophageal function and occurrence of Barrett's esophagus in Zollinger-Ellison syndrome. AN - 85254599; pmid-8549876 AB - Manifestations of esophageal disease are present in up to 60% of patients with Zollinger-Ellison syndrome (ZES), although esophageal function has been studied in only a few patients and the prevalence of Barrett's mucosa is unknown in these patients. It is unclear whether the high prevalence of esophageal disease is related to gastric acid hypersecretion alone or to abnormalities of esophageal motility or lower esophageal sphincter (LES) function in addition. To address these issues in the present study esophageal function was evaluated prospectively in 92 consecutive patients with ZES (66 with active disease, 26 disease-free after curative resection) seen during a 1-year period after controlling acid hypersecretion. In the patients with active disease the mean basal acid output (BAO) was 33 +/- 3.0 mEq/h, the maximal acid output (MAO) was 56 +/- 4.0 mEg/h, fasting serum gastrin was 8,736 +/- 4,813 pg/ml and duration of disease prior to study was 12.5 +/- 2.0 years. At the time of manometry, gastric acid secretion was controlled in all patients and no patient had evidence of gastroesophageal reflux disease at upper gastrointestinal endoscopy. Esophageal manometry revealed normal motility in 85% of patients. Eleven percent had low LES pressures, and only 1% of patients had an elevated LES pressure. The frequency of Barrett's mucosa (3%) was similar to that found in the general population but much less than that reported in patients with idiopathic GERD. No correlation was noted between LES pressures or manometric abnormalities and the fasting serum gastrin, BAO, MAO or the presence or absence of multiple endocrine neoplasia type I or previous vagotomy. Esophageal manometric results and LES pressure were similar in disease-free patients and those with active ZES. In conclusion, these results suggest that hypergastrinemia or other disease-specific abnormalities are not contributing to the high incidence of esophageal disease in patients with ZES because esophageal function in patients with ZES is similar to normals. Specifically, motility disorders in patients with ZES occur in similar frequency to normals, and LES pressure is normal in most patients. Despite the high levels of acid secretion and prominence of symptoms, the occurrence of Barrett's mucosa was uncommon (3%) raising the possibility of additional protective mechanisms in patients with ZES. JF - Digestion AU - Strader, D B AU - Benjamin, S B AU - Orbuch, M AU - Lubensky, T A AU - Gibril, F AU - Weber, C AU - Fishbeyn, V A AU - Jensen, R T AU - Metz, D C AD - Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1995 SP - 347 EP - 356 VL - 56 IS - 5 SN - 0012-2823, 0012-2823 KW - Human KW - Aged KW - Biopsy KW - Gastrins KW - Prospective Studies KW - Zollinger-Ellison Syndrome KW - Gastric Acid KW - Adult KW - Middle Age KW - Barrett Esophagus KW - Follow-Up Studies KW - Manometry KW - Endoscopy, Digestive System KW - Male KW - Female UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85254599?accountid=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=Digestion&rft.atitle=Esophageal+function+and+occurrence+of+Barrett%27s+esophagus+in+Zollinger-Ellison+syndrome.&rft.au=Strader%2C+D+B%3BBenjamin%2C+S+B%3BOrbuch%2C+M%3BLubensky%2C+T+A%3BGibril%2C+F%3BWeber%2C+C%3BFishbeyn%2C+V+A%3BJensen%2C+R+T%3BMetz%2C+D+C&rft.aulast=Strader&rft.aufirst=D&rft.date=1995-01-01&rft.volume=56&rft.issue=5&rft.spage=347&rft.isbn=&rft.btitle=&rft.title=Digestion&rft.issn=00122823&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - A process-based view of memory. AN - 85215973; pmid-9375216 JF - Journal of the International Neuropsychological Society AU - Blaxton, T A AD - National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1995 SP - 112 EP - 114 VL - 1 IS - 1 SN - 1355-6177, 1355-6177 KW - Verbal Learning KW - Human KW - Brain Damage, Chronic KW - Neuropsychological Tests KW - Amnesia KW - Mental Recall KW - Retention (Psychology) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85215973?accountid=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&rft.atitle=A+process-based+view+of+memory.&rft.au=Blaxton%2C+T+A&rft.aulast=Blaxton&rft.aufirst=T&rft.date=1995-01-01&rft.volume=1&rft.issue=1&rft.spage=112&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+International+Neuropsychological+Society&rft.issn=13556177&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Pediatric audiologic profile in type 1 and type 2 neurofibromatosis. AN - 85170902; pmid-7696678 AB - The neurofibromatoses with two subclasses known as NF1 and NF2 are two genetically distinct, autosomal dominantly inherited conditions with significant ramifications in the human auditory system. NF1 is a multisystem progressive disorder that can frequently involve portions of the auditory system in diverse and subtle ways and in which no characteristic audiologic findings can be discerned. NF2 is characterized by the presence of bilateral vestibular schwannomas, sometimes associated with multiple intracranial and spinal tumors. In 43 children with NF1, significant auditory system involvement was found by pure-tone, immittance, and auditory brainstem response (ABR) evaluation. Indications are that audiologists need to contribute to the diagnosis and management in this condition. In 13 children with NF2, handicapping hearing loss was not the primary or usual presenting symptom. However, current findings suggest that ABR and acoustic reflex studies are always indicated in the pediatric NF2 population and are as valid and significant as in adults with NF2. JF - Journal of the American Academy of Audiology AU - Pikus, A T AD - Neuro-Otology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland. PY - 1995 SP - 54 EP - 62 VL - 6 IS - 1 SN - 1050-0545, 1050-0545 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85170902?accountid=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+American+Academy+of+Audiology&rft.atitle=Pediatric+audiologic+profile+in+type+1+and+type+2+neurofibromatosis.&rft.au=Pikus%2C+A+T&rft.aulast=Pikus&rft.aufirst=A&rft.date=1995-01-01&rft.volume=6&rft.issue=1&rft.spage=54&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Academy+of+Audiology&rft.issn=10500545&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Molecular probes for muscarinic receptors: functionalized congeners of selective muscarinic antagonists. AN - 77964953; 10188781 AB - The muscarinic agonist oxotremorine and the tricyclic muscarinic antagonists pirenzepine and telenzepine have been derivatized using a functionalized congener approach for the purpose of synthesizing high affinity ligand probes that are suitable for conjugation with prosthetic groups, for receptor cross-linking, fluorescent and radioactive detection, etc. A novel fluorescent conjugate of TAC (telenzepine amine congener), an n-decylamino derivative of the m1-selective antagonist, with the fluorescent trisulfonated pyrene dye Cascade Blue may be useful for assaying the receptor as an alternative to radiotracers. In a rat m3 receptor mutant containing a single amino acid substitution in the sixth transmembrane domain (Asn507 to Ala) the parent telenzepine lost 636-fold in affinity, while TAC lost only 27-fold. Thus, the decylamino group of TAC stabilizes the bound state and thus enhances potency by acting as a distal anchor in the receptor binding site. We have built a computer-assisted molecular model of the transmembrane regions of muscarinic receptors based on homology with the G-protein coupled receptor rhodopsin, for which a low resolution structure is known. We have coordinated the antagonist pharmacophore (tricyclic and piperazine moieties) with residues of the third and seventh helices of the rat m3 receptor. Although the decylamino chain of TAC is likely to be highly flexible and may adopt many conformations, we located one possible site for a salt bridge formation with the positively charged -NH3+ group, i.e. Asp113 in helix II. JF - Life sciences AU - Jacobson, K A AU - Fischer, B AU - van Rhee, A M AD - Molecular Recognition Section, Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 823 EP - 830 VL - 56 IS - 11-12 SN - 0024-3205, 0024-3205 KW - Ligands KW - 0 KW - Muscarinic Antagonists KW - Parasympathomimetics KW - Receptors, Cell Surface KW - Receptors, Muscarinic KW - telenzepine KW - 0990EG3K10 KW - Pirenzepine KW - 3G0285N20N KW - Oxotremorine KW - 5RY0UWH1JL KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Molecular Structure KW - Animals KW - Fluorescence KW - Oxotremorine -- pharmacology KW - Oxotremorine -- chemistry KW - Models, Molecular KW - Pirenzepine -- analogs & derivatives KW - Receptors, Cell Surface -- metabolism KW - Rats KW - Pirenzepine -- chemistry KW - Mutagenesis, Site-Directed KW - Pirenzepine -- pharmacology KW - Parasympathomimetics -- pharmacology KW - GTP-Binding Proteins -- metabolism KW - Parasympathomimetics -- chemistry KW - Muscarinic Antagonists -- chemistry KW - Muscarinic Antagonists -- pharmacology KW - Receptors, Muscarinic -- chemistry KW - Molecular Probe Techniques KW - Receptors, Muscarinic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77964953?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Molecular+probes+for+muscarinic+receptors%3A+functionalized+congeners+of+selective+muscarinic+antagonists.&rft.au=Jacobson%2C+K+A%3BFischer%2C+B%3Bvan+Rhee%2C+A+M&rft.aulast=Jacobson&rft.aufirst=K&rft.date=1995-01-01&rft.volume=56&rft.issue=11-12&rft.spage=823&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 - 1999-04-19 N1 - Date created - 1999-04-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Life Sci. 1986 May 5;38(18):1653-62 [3754610] Proc Natl Acad Sci U S A. 1989 Sep;86(17):6572-6 [2771944] J Med Chem. 1990 Feb;33(2):741-8 [2153827] Annu Rev Pharmacol Toxicol. 1990;30:633-73 [2188581] J Mol Biol. 1990 Jun 20;213(4):899-929 [2359127] FASEB J. 1990 Aug;4(11):2934-40 [2165950] Brain Res Bull. 1990 Aug;25(2):311-7 [2224542] J Biol Chem. 1990 Dec 15;265(35):21590-5 [2174879] J Biol Chem. 1990 Dec 25;265(36):22181-6 [2176206] J Med Chem. 1991 Jul;34(7):2133-45 [2066986] Mol Pharmacol. 1991 Jul;40(1):8-15 [1649965] Bioconjug Chem. 1991 Mar-Apr;2(2):77-88 [1868116] Mol Pharmacol. 1992 Apr;41(4):695-8 [1349154] Life Sci. 1992;51(5):345-51 [1625525] Mol Pharmacol. 1992 Jul;42(1):123-33 [1635550] Bioconjug Chem. 1992 May-Jun;3(3):234-40 [1520727] Nature. 1993 Apr 22;362(6422):770-2 [8469290] J Med Chem. 1993 Apr 16;36(8):967-76 [8478909] Trends Pharmacol Sci. 1993 Aug;14(8):308-13 [8249149] J Med Chem. 1993 Nov 26;36(24):3937-46 [8254622] J Neurosci. 1994 Jul;14(7):4147-58 [8027768] J Biol Chem. 1994 Jul 22;269(29):18870-6 [8034642] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation and function of the multidrug resistance genes in liver. AN - 77960949; 9224499 AB - The P-glycoproteins are integral membrane proteins that function as ATP-dependent transporters. The multidrug resistance genes which encode P-gp comprise a small gene family, with 2 members in humans and 3 in rodents. The P-gp encoded by the mdr1 gene functions as a drug efflux pump to remove drugs from cells and may serve as a barrier to protect cells from cytotoxic agents. In normal tissues, P-gp is localized on the luminal surface of transporting epithelia in the liver, kidney, small intestine, testes, and blood-brain barrier. Transient exposure to drugs transcriptionally increases the level of expression of the mdr1 genes, however, the cellular pathways critical to this regulation are yet unknown. This observation may have some implications on the level of expression in tumors and response to chemotherapy. Examination of the basal level of MDR expression in tumors may not be a reliable predictor of the effect of P-gp on chemotherapy. Induction of MDR transcription by drugs may further impede the effectiveness of anti-cancer agents. This is most obvious for drugs which are substrates for P-gp transport, however, it also applies significantly to compounds which are not themselves substrates but affect the response to other drugs simultaneously or subsequently administered. A clear understanding of the mechanisms that regulate basal and drug-induced mdr transcription will facilitate development of novel agents which circumvent this obstacle or permit targeted modification of mdr expression. Expressed on the bile canalicular surface of the liver, P-gps represent the first ATP-dependent biliary transporters to be characterized. The P-gp encoded by mdr2 is the major form of P-gp expressed in normal liver and transports phospholipids into bile. A defect in this protein leads to severe liver disease caused by chronic inflammation of the biliary system that results from high concentrations of free bile salts. The cellular origin and molecular basis of the ensuing liver tumors in these mice are unclear. It is possible that the chronic damage to the biliary ductules causes an increased growth rate of the surrounding cells, including putative stem cells in the liver. Thus, these mice may serve as a model for carcinogenesis in which the liver is under constant promotion placing the proliferating cells at increased risk to further genetic alterations or expansion of preexisting, but normally quiescent, mutations. Mdr2-deficient animals may also provide a model for human chronic inflammatory liver disease. Clearly, these exciting results indicate that further characterization of the P-gps as normal physiologic canalicular membrane transporters is necessary. JF - Progress in liver diseases AU - Silverman, J A AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 101 EP - 123 VL - 13 SN - 1060-913X, 1060-913X KW - P-Glycoprotein KW - 0 KW - Phospholipids KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Index Medicus KW - Molecular Structure KW - Animals KW - Humans KW - Phospholipids -- metabolism KW - Gene Expression KW - Mice KW - Genome KW - Cloning, Molecular KW - Phenotype KW - P-Glycoprotein -- genetics KW - P-Glycoprotein -- metabolism KW - Adenosine Triphosphate -- metabolism KW - ATP-Binding Cassette Transporters -- genetics KW - P-Glycoprotein -- chemistry KW - Liver -- metabolism KW - Drug Resistance, Multiple -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77960949?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+liver+diseases&rft.atitle=Regulation+and+function+of+the+multidrug+resistance+genes+in+liver.&rft.au=Silverman%2C+J+A%3BThorgeirsson%2C+S+S&rft.aulast=Silverman&rft.aufirst=J&rft.date=1995-01-01&rft.volume=13&rft.issue=&rft.spage=101&rft.isbn=&rft.btitle=&rft.title=Progress+in+liver+diseases&rft.issn=1060913X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-08-26 N1 - Date created - 1997-08-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transforming growth factor beta1, ras and p53 in silica-induced fibrogenesis and carcinogenesis. AN - 77954084; 8929685 AB - The pathogenesis of mesenchymal and epithelial lung reactions was studied after a single intratracheal instillation of quartz into rats. Relationships between transforming growth factor beta1 (TGF-beta1) and the ras and p53 genes were investigated in silicosis and associated lung cancer. Immunohistochemical reactivity to mature TGF-beta1 was localized intracellularly in fibroblasts and macrophages at the periphery of silicotic granulomas and in stroma adjacent to hyperplastic alveolar type II cells and extracellularly in connective tissue matrix adjacent to hyperplastic alveolar type II cells. TGF-beta1 precursor was localized intracellularly in hyperplastic alveolar type II cells adjacent to granulomas and in the cells of adenomas, but not in carcinomas. Hematite-treated controls showed no reactivity to TGF-beta1. Immunohistochemical localization of pan-reactive p21 ras protein in quartz-treated rat lungs was increased in hyperplastic alveolar type II cells adjacent to granulomas, but not in adenomas and carcinomas. Foci of nuclear immunoreactivity to p53 protein were observed in 25% of the carcinomas. JF - Scandinavian journal of work, environment & health AU - Williams, A O AU - Saffiotti, U AD - Laboratory of Experimental Pathology, National Cancer Institute, Bethesda, Maryland 20892-0041, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 30 EP - 34 VL - 21 Suppl 2 SN - 0355-3140, 0355-3140 KW - Carcinogens KW - 0 KW - Transforming Growth Factor beta KW - Silicon Dioxide KW - 7631-86-9 KW - Proto-Oncogene Proteins p21(ras) KW - EC 3.6.5.2 KW - Index Medicus KW - Animals KW - Silicosis -- pathology KW - Genes, p53 -- drug effects KW - Lung Neoplasms -- immunology KW - Rats KW - Culture Techniques KW - Rats, Inbred F344 KW - Carcinogens -- metabolism KW - Injections, Spinal KW - Silicosis -- immunology KW - Immunohistochemistry KW - Female KW - Male KW - Lung Neoplasms -- pathology KW - Silicon Dioxide -- pharmacology KW - Proto-Oncogene Proteins p21(ras) -- metabolism KW - Silicon Dioxide -- administration & dosage KW - Transforming Growth Factor beta -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77954084?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Transforming+growth+factor+beta1%2C+ras+and+p53+in+silica-induced+fibrogenesis+and+carcinogenesis.&rft.au=Williams%2C+A+O%3BSaffiotti%2C+U&rft.aulast=Williams&rft.aufirst=A&rft.date=1995-01-01&rft.volume=21+Suppl+2&rft.issue=&rft.spage=30&rft.isbn=&rft.btitle=&rft.title=Scandinavian+journal+of+work%2C+environment+%26+health&rft.issn=03553140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-02 N1 - Date created - 1997-04-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Direct interaction between crystalline silica and DNA - a proposed model for silica carcinogenesis. AN - 77954041; 8929683 AB - Crystalline silica in aqueous buffer produced oxygen radicals that mediated in vitro DNA (deoxyribonucleic acid) strand breakage. The oxidized DNA base, thymine glycol, was also produced. The hydroxyl radical, responsible for most DNA damage, has a reaction distance of about 15 Angstroms, requiring close contact of silica with DNA. Fourier transform infrared spectroscopy of incubations of quartz particles with DNA showed distinct alterations in both DNA and quartz spectra and therefore indicated extensive hydrogen bonding between surface silanol groups and the phosphate-sugar backbone of DNA. Electron microscopy and energy dispersive X-ray spectroscopy of alveolar epithelial cells in fetal rat lung, exposed to quartz in culture, showed localization of quartz particles in the nuclei and mitotic spindles. Direct interaction of crystalline silica with DNA may be important in silica carcinogenesis by anchoring DNA close to sites of free radical production on the silica surface, or by interfering with DNA replication, repair, or the mitotic process. JF - Scandinavian journal of work, environment & health AU - Daniel, L N AU - Mao, Y AU - Williams, A O AU - Saffiotti, U AD - Laboratory of Experimental Pathology, National Cancer Institute, Bethesda, Maryland 20892-0041, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 22 EP - 26 VL - 21 Suppl 2 SN - 0355-3140, 0355-3140 KW - Carcinogens KW - 0 KW - Silicon Dioxide KW - 7631-86-9 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Rats KW - Crystallization KW - Spectroscopy, Fourier Transform Infrared KW - Animals KW - Cell Transformation, Neoplastic -- metabolism KW - Microscopy, Electron KW - Cell Line KW - Carcinogens -- metabolism KW - Silicon Dioxide -- metabolism KW - DNA -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77954041?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Direct+interaction+between+crystalline+silica+and+DNA+-+a+proposed+model+for+silica+carcinogenesis.&rft.au=Daniel%2C+L+N%3BMao%2C+Y%3BWilliams%2C+A+O%3BSaffiotti%2C+U&rft.aulast=Daniel&rft.aufirst=L&rft.date=1995-01-01&rft.volume=21+Suppl+2&rft.issue=&rft.spage=22&rft.isbn=&rft.btitle=&rft.title=Scandinavian+journal+of+work%2C+environment+%26+health&rft.issn=03553140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-02 N1 - Date created - 1997-04-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Muscarinic acetylcholine receptors: structural basis of ligand binding and G protein coupling. AN - 77948407; 10188793 AB - Muscarinic acetylcholine receptors (m1-m5) were studied by a combined molecular genetic/pharmacologic approach to elucidate the molecular characteristics of the ligand binding site and of the receptor domains involved in G protein coupling. Site-directed mutagenesis studies of the rat m3 muscarinic receptor suggest that the acetylcholine binding domain is formed by a series of hydrophilic amino acids located in the "upper" half of transmembrane domains (TM) III, V, VI, and VII. Moreover, we showed that mutational modification of a TM VI Asn residue (Asn507 in the rat m3 receptor sequence) which is characteristic for the muscarinic receptor family has little effect on high-affinity acetylcholine binding and receptor activation, but results in dramatic reductions in binding affinities for certain subclasses of muscarinic antagonists. The N-terminal portion of the third intracellular loop (i3) of muscarinic and other G protein-coupled receptors has been shown to play a central role in determining the G protein coupling profile of a given receptor subtype. Insertion mutagenesis studies with the rat m3 muscarinic receptor suggest that this region forms an amphiphilic alpha-helix and that the hydrophobic side of this helix represents an important G protein recognition surface. Further mutational analysis of this receptor segment showed that Tyr254 located at the N-terminus of the i3 loop of the m3 muscarinic receptor plays a key role in muscarinic receptor-induced Gq activation. The studies described here, complemented by biochemical and biophysical approaches, should eventually lead to a detailed structural model of the ligand-receptor-G protein complex. JF - Life sciences AU - Wess, J AU - Blin, N AU - Mutschler, E AU - Blüml, K AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 915 EP - 922 VL - 56 IS - 11-12 SN - 0024-3205, 0024-3205 KW - Ligands KW - 0 KW - Receptor, Muscarinic M3 KW - Receptors, Muscarinic KW - Tyrosine KW - 42HK56048U KW - Carbachol KW - 8Y164V895Y KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Rats KW - Mutagenesis, Site-Directed KW - Animals KW - Models, Molecular KW - Dose-Response Relationship, Drug KW - Molecular Sequence Data KW - Cell Membrane KW - Tyrosine -- genetics KW - Amino Acid Sequence KW - Carbachol -- pharmacology KW - Receptors, Muscarinic -- genetics KW - GTP-Binding Proteins -- metabolism KW - Receptors, Muscarinic -- drug effects KW - Receptors, Muscarinic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77948407?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Muscarinic+acetylcholine+receptors%3A+structural+basis+of+ligand+binding+and+G+protein+coupling.&rft.au=Wess%2C+J%3BBlin%2C+N%3BMutschler%2C+E%3BBl%C3%BCml%2C+K&rft.aulast=Wess&rft.aufirst=J&rft.date=1995-01-01&rft.volume=56&rft.issue=11-12&rft.spage=915&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 - 1999-04-19 N1 - Date created - 1999-04-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Acetaminophen-induced hepatotoxicity is associated with early changes in NF-kB and NF-IL6 DNA binding activity. AN - 77947199; 9117441 AB - Nuclear transcription factors, such as NF-kB and NF-IL6, are believed to play an important role in regulating the expression of genes that encode for products involved in tissue damage and inflammation and, thus, may represent early biomarkers for chemical toxicities. In the present study changes in DNA binding activity of these factors were examined in livers of mice administered hepatotoxic doses of acetaminophen (APAP). NF-kB and NF-IL6 DNA binding occurred constitutively in control mouse liver. However, within 4 hr following administration of hepatotoxic doses of APAP, their binding activities were transiently lost and is in contrast to AP-1 transcription factor where activation occurs under similar conditions. These changes corresponded with increased release of inflammatory mediators (IL-6, serum amyloid A) and increased levels of enzymatic markers of hepatocyte damage. Similarly, treatment of mice with gadolinium chloride, an inhibitor of Kupffer cell activation and known to protect against APAP-induced hepatotoxicity, reduced the observed pathophysiological response in the liver while altering the APAP-associated changes in NF-kB DNA binding activity. NF-kB was found predominantly in parenchymal and endothelial cells and was composed primarily of relatively inactive p50 homodimer subunits in control liver. Taken together, these studies suggest that hepatotoxicity is associated with early and complex changes in DNA binding activities of specific transcription factors. In particular, NF-kB and NF-IL6 may serve as negative regulators of hepatocyte-derived inflammatory mediators and is analogous to that previously observed in certain other cell systems such as B lymphocytes. JF - Journal of inflammation AU - Blazka, M E AU - Germolec, D R AU - Simeonova, P AU - Bruccoleri, A AU - Pennypacker, K R AU - Luster, M I AD - Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. PY - 1995 SP - 138 EP - 150 VL - 47 IS - 3 SN - 1078-7852, 1078-7852 KW - Analgesics, Non-Narcotic KW - 0 KW - Biomarkers KW - CCAAT-Enhancer-Binding Proteins KW - DNA receptor KW - DNA-Binding Proteins KW - NF-kappa B KW - Nuclear Proteins KW - Oligonucleotide Probes KW - Receptors, Cell Surface KW - Acetaminophen KW - 362O9ITL9D KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Gene Expression -- drug effects KW - Animals KW - Mice KW - Receptors, Cell Surface -- metabolism KW - Mice, Inbred C3H KW - Mice, Inbred C57BL KW - Oligonucleotide Probes -- chemistry KW - Receptors, Cell Surface -- genetics KW - Immunohistochemistry KW - Female KW - Receptors, Cell Surface -- drug effects KW - NF-kappa B -- drug effects KW - Liver -- cytology KW - Nuclear Proteins -- genetics KW - Liver -- drug effects KW - DNA -- metabolism KW - Analgesics, Non-Narcotic -- toxicity KW - DNA-Binding Proteins -- genetics KW - DNA-Binding Proteins -- drug effects KW - Liver -- metabolism KW - Nuclear Proteins -- drug effects KW - Nuclear Proteins -- metabolism KW - NF-kappa B -- genetics KW - Acetaminophen -- toxicity KW - NF-kappa B -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77947199?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+inflammation&rft.atitle=Acetaminophen-induced+hepatotoxicity+is+associated+with+early+changes+in+NF-kB+and+NF-IL6+DNA+binding+activity.&rft.au=Blazka%2C+M+E%3BGermolec%2C+D+R%3BSimeonova%2C+P%3BBruccoleri%2C+A%3BPennypacker%2C+K+R%3BLuster%2C+M+I&rft.aulast=Blazka&rft.aufirst=M&rft.date=1995-01-01&rft.volume=47&rft.issue=3&rft.spage=138&rft.isbn=&rft.btitle=&rft.title=Journal+of+inflammation&rft.issn=10787852&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-21 N1 - Date created - 1997-04-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metabolic processing and disposition of 2-amino-3-methylimidazo[4,5-f] quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in nonhuman primates. AN - 77943121; 8844797 AB - The metabolic processing and disposition of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), three heterocyclic amine mutagens and carcinogens derived from cooked food, was examined in cynomolgus monkeys. IQ is an established hepatocarcinogen in cynomolgus monkeys; however, the carcinogenicity of MeIQx and PhIP is not yet known. IQ was extensively metabolized with little parent compound excreted in urine. Urinary metabolites of IQ arise from a combination of cytochrome P-450 mediated N-demethylation, N-hydroxylation, or ring oxidation at the C-5 position and conjugation with sulfate or glucuronide. IQ was also conjugated at the exocyclic amino group forming IQ-sulfamate and IQ-N-glucuronide. Enteric bacteria biotransformed IQ and its N-demethylated metabolite to 7-oxo-IQ and N-demethyl-7-oxo-IQ, respectively. N-Hydroxy-IQ-N-glucuronide was found in urine of monkeys indicating that metabolic activation via cytochrome P-450-mediated N-hydroxylation occurs in vivo and supporting the theory N-hydroxy-IQ plays a role in the initiation of IQ-induced hepatocarcinogenesis. At least eight urinary metabolites of MeIQx were seen in monkeys fed MeIQx. As was found with IQ, metabolites of MeIQx arise from conjugation with sulfate and glucuronide at the exocyclic amino group, and by cytochrome P-450 mediated oxidation at the C-5 position followed by conjugation with sulfate or glucuronide In contrast to IQ, a significant amount of the dose of MeIQx was excreted unchanged in the urine of monkeys. PhIP was extensively metabolized with a predominant route of metabolism being cytochrome P-450-mediated 4'hydroxylation followed by sulfate conjugation to form PhIP-4'-sulfate. No sulfate conjugation at the exocyclic amino group of PhIP was observed. An N-hydroxy-PhIP-N-glucuronide was also found in urine and bile indicating that metabolic activation of PhIP via N-hydroxylation occurs in vivo in monkeys and suggesting that PhIP may ultimately be carcinogenic to monkeys. JF - Princess Takamatsu symposia AU - Snyderwine, E G AU - Turesky, R J AU - Buonarati, M H AU - Turteltaub, K W AU - Adamson, R H AD - National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 69 EP - 77 VL - 23 KW - Carcinogens KW - 0 KW - Imidazoles KW - Mutagens KW - Quinolines KW - Quinoxalines KW - 2-amino-3-methylimidazo(4,5-f)quinoline KW - 30GL3D3T0G KW - 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline KW - 77500-04-0 KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - Index Medicus KW - Hot Temperature KW - Animals KW - Quinolines -- metabolism KW - Macaca fascicularis KW - Biotransformation KW - Food KW - Cooking KW - Quinolines -- pharmacokinetics KW - Imidazoles -- pharmacokinetics KW - Carcinogens -- metabolism KW - Mutagens -- metabolism KW - Imidazoles -- metabolism KW - Carcinogens -- pharmacokinetics KW - Quinoxalines -- metabolism KW - Quinoxalines -- pharmacokinetics KW - Mutagens -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77943121?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Princess+Takamatsu+symposia&rft.atitle=Metabolic+processing+and+disposition+of+2-amino-3-methylimidazo%5B4%2C5-f%5D+quinoline+%28IQ%29%2C+2-amino-3%2C8-dimethylimidazo%5B4%2C5-f%5Dquinoxaline+%28MeIQx%29%2C+and+2-amino-1-methyl-6-phenylimidazo%5B4%2C5-b%5Dpyridine+%28PhIP%29+in+nonhuman+primates.&rft.au=Snyderwine%2C+E+G%3BTuresky%2C+R+J%3BBuonarati%2C+M+H%3BTurteltaub%2C+K+W%3BAdamson%2C+R+H&rft.aulast=Snyderwine&rft.aufirst=E&rft.date=1995-01-01&rft.volume=23&rft.issue=&rft.spage=69&rft.isbn=&rft.btitle=&rft.title=Princess+Takamatsu+symposia&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-06 N1 - Date created - 1997-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - NIDA-NIAAA workshop: efficacy of therapies in drug and alcohol addiction. Strategies for treatment of alcohol problems. AN - 77939012; 8851638 AB - Well-controlled clinical trials have been performed to determine efficacy of alternative alcoholism treatment strategies. Six effective treatment approaches are discussed, and a research project example demonstrates the benefits of each. The treatments considered are: brief intervention, behavioral contracting, naltrexone, social skills training, the community reinforcement approach, and patient-treatment matching. JF - Psychopharmacology bulletin AU - Allen, J P AU - Litten, R Z AU - Fertig, J B Y1 - 1995 PY - 1995 DA - 1995 SP - 665 EP - 669 VL - 31 IS - 4 KW - Index Medicus KW - Humans KW - Substance-Related Disorders -- therapy KW - Alcoholism -- therapy KW - Substance-Related Disorders -- drug therapy KW - Substance-Related Disorders -- psychology KW - Alcoholism -- psychology KW - Alcoholism -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77939012?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Psychopharmacology+bulletin&rft.atitle=NIDA-NIAAA+workshop%3A+efficacy+of+therapies+in+drug+and+alcohol+addiction.+Strategies+for+treatment+of+alcohol+problems.&rft.au=Allen%2C+J+P%3BLitten%2C+R+Z%3BFertig%2C+J+B&rft.aulast=Allen&rft.aufirst=J&rft.date=1995-01-01&rft.volume=31&rft.issue=4&rft.spage=665&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 - 1996-12-05 N1 - Date created - 1996-12-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Quantitative versus qualitative urinalysis for benzoylecgonine in clinical trials for the assessment of cocaine use. AN - 77936667; 8851639 AB - Urinalysis of benzoylecgonine (BE) concentrations is a primary outcome measure for evaluating medications for treating cocaine addiction. Using simulated BE data from a set of simple clinical models, the advantages of quantitative versus qualitative urinalysis were evaluated, as well as the advantages of once-weekly versus thrice-weekly sampling schedules. A 60 percent reduction in cocaine use, either in daily amount or in weekly frequency, was considered clinically significant. Quantitative urinalysis can detect reductions in both amount and frequency, whereas qualitative urinalysis can detect only a decrease in frequency. For quantitative urinalysis, changes are more easily detected when urine is collected three times a week than when it is collected once a week. For qualitative urinalysis, the majority rule analysis for a thrice-weekly sampling schedule yields an artificially high estimate of the percentage of positive samples, whereas a once-weekly schedule gives a highly variable estimate. JF - Psychopharmacology bulletin AU - Li, S H AU - Chiang, C N AU - Tai, B C AU - Marschke, C K AU - Hawks, R L AD - National Institute on Drug Abuse, NIH, Rockville, MD 20857, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 671 EP - 679 VL - 31 IS - 4 SN - 0048-5764, 0048-5764 KW - Narcotics KW - 0 KW - benzoylecgonine KW - 5353I8I6YS KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Substance Abuse Detection KW - Humans KW - Treatment Outcome KW - Substance-Related Disorders -- therapy KW - Substance-Related Disorders -- diagnosis KW - Cocaine -- analogs & derivatives KW - Cocaine -- urine KW - Narcotics -- pharmacokinetics KW - Substance-Related Disorders -- urine KW - Cocaine -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77936667?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Quantitative+versus+qualitative+urinalysis+for+benzoylecgonine+in+clinical+trials+for+the+assessment+of+cocaine+use.&rft.au=Li%2C+S+H%3BChiang%2C+C+N%3BTai%2C+B+C%3BMarschke%2C+C+K%3BHawks%2C+R+L&rft.aulast=Li&rft.aufirst=S&rft.date=1995-01-01&rft.volume=31&rft.issue=4&rft.spage=671&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 - 1996-12-05 N1 - Date created - 1996-12-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comorbidity between DSM-IV drug use disorders and major depression: results of a national survey of adults. AN - 77936272; 8838629 AB - This study describes detailed patterns of comorbidity between Diagnostic and Statistical Manual of Mental Disorders (4th ed. [DSM-IV]; American Psychiatric Association, 1994) drug use disorders and major depression in the United States for 1992. Data were derived from the National Longitudinal Alcohol Epidemiologic Survey (NLAES), a national probability survey consisting of 42,862 respondents, 18 years old and older, residing in the contiguous United States. The sampling design included oversampling of Blacks and young adults (18-29 years old). Comorbidity rates and associations between DSM-IV drug use disorders (i.e., prescription drugs, sedatives, tranquilizers, amphetamines, cannabis, cocaine, and hallucinogens) and major depression were expressed as odds ratios with confidence intervals adjusted for the complex design characteristics of the NLAES. Comorbidity analyses were presented by gender, ethnicity, and age for past-year, prior-to-past-year, and lifetime diagnoses. The results showed that virtually all odds ratios were significantly greater than 1, demonstrating that comorbidity of a variety of drug use disorders and major depression is pervasive in the general population. Diagnostic and subgroup variations in comorbidity were noted. As expected, the association between drug dependence and major depression was greater than the association between abuse and major depression. The association between abuse and major depression was greater for women than men for prescription drugs, sedatives, tranquilizers, and amphetamines, but not for cocaine or hallucinogens. Men generally demonstrated stronger relations between drug dependence and major depression. Implications of the results are discussed in terms of professional help seeking, the self-medication hypothesis, and differential social-control theory. JF - Journal of substance abuse AU - Grant, B F AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse, and Alcoholism, Bethesda, MD 20892-7003, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 481 EP - 497 VL - 7 IS - 4 SN - 0899-3289, 0899-3289 KW - Psychotropic Drugs KW - 0 KW - Street Drugs KW - Index Medicus KW - Odds Ratio KW - Humans KW - Aged KW - Longitudinal Studies KW - Comorbidity KW - Self Medication -- psychology KW - Psychiatric Status Rating Scales KW - Adult KW - Sampling Studies KW - Confidence Intervals KW - Middle Aged KW - Adolescent KW - Personality Assessment KW - United States -- epidemiology KW - Female KW - Male KW - Depressive Disorder -- epidemiology KW - Substance-Related Disorders -- diagnosis KW - Alcoholism -- epidemiology KW - Alcoholism -- diagnosis KW - Substance-Related Disorders -- classification KW - Alcoholism -- classification KW - Depressive Disorder -- diagnosis KW - Depressive Disorder -- classification KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77936272?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Comorbidity+between+DSM-IV+drug+use+disorders+and+major+depression%3A+results+of+a+national+survey+of+adults.&rft.au=Grant%2C+B+F&rft.aulast=Grant&rft.aufirst=B&rft.date=1995-01-01&rft.volume=7&rft.issue=4&rft.spage=481&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 - 1996-12-05 N1 - Date created - 1996-12-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Historical total and respirable silica dust exposure levels in mines and pottery factories in China. AN - 77935154; 8929687 AB - Historical exposure estimates of total dust and respirable silica were made in a recent nested case-referent study of lung cancer among mine and pottery workers in China. Exposure to total dust and respirable silica was assessed in 20 mines and 9 pottery factories. The average total dust concentration was 7.26 mg center dot m-3, with a range from 17.68 mg center dot m-3 in the 1950s to 3.85 mg center dot m-3 in the 1980s, while the average respirable silica dust was 1.22 mg center dot m-3, with a range from 3.89 mg center dot m-3 in the 1950s to 0.43 mg center dot m-3 in the 1980s. The highest respirable silica dust occurred in the underground mining operations (1.43 mg center dot m-3), particularly for manual drillers (9.03 mg center dot m-3). Among all facility types, tungsten mines had the highest respirable silica dust exposure (1.75 mg center dot m-3), while the lowest exposure occurred in copper-iron mines (0.32 mg center dot m-3). JF - Scandinavian journal of work, environment & health AU - Dosemeci, M AU - McLaughlin, J K AU - Chen, J Q AU - Hearl, F AU - Chen, R G AU - McCawley, M AU - Wu, Z AU - Peng, K L AU - Chen, A L AU - Rexing, S H AD - Epidemiology and Biostatistics Program, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 39 EP - 43 VL - 21 Suppl 2 SN - 0355-3140, 0355-3140 KW - Dust KW - 0 KW - Silicon Dioxide KW - 7631-86-9 KW - Index Medicus KW - Dust -- analysis KW - Humans KW - China -- epidemiology KW - Retrospective Studies KW - Time Factors KW - Ceramics KW - Occupational Exposure -- statistics & numerical data KW - Mining -- statistics & numerical data KW - Silicon Dioxide -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77935154?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Historical+total+and+respirable+silica+dust+exposure+levels+in+mines+and+pottery+factories+in+China.&rft.au=Dosemeci%2C+M%3BMcLaughlin%2C+J+K%3BChen%2C+J+Q%3BHearl%2C+F%3BChen%2C+R+G%3BMcCawley%2C+M%3BWu%2C+Z%3BPeng%2C+K+L%3BChen%2C+A+L%3BRexing%2C+S+H&rft.aulast=Dosemeci&rft.aufirst=M&rft.date=1995-01-01&rft.volume=21+Suppl+2&rft.issue=&rft.spage=39&rft.isbn=&rft.btitle=&rft.title=Scandinavian+journal+of+work%2C+environment+%26+health&rft.issn=03553140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-04-02 N1 - Date created - 1997-04-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Histopathology of IQ-induced hepatocarcinogenesis in nonhuman primates. AN - 77928658; 8844819 AB - This study describes histopathological findings in 26 nonhuman primates (cynomolgus and rhesus monkeys) with liver tumors after dosing with IQ for time periods of 27 to 72 months. In most of the cases 2-5 well-defined tumor nodules were present in the liver at the time of autopsy. In 5 cases there were numerous nodules occupying most of the liver. Intrahepatic vascular invasion was observed in 14 cases, and lung metastases in 6 cases. The histology of 72 nodules from 21 cases with well-defined tumors and the 5 cases with massive involvement was studied. The majority of the tumors represented well to moderately well-differentiated hepatocellular carcinoma (HCC). Trabecular pattern was most common, followed by solid and pseudoglandular patterns. Five nodules displayed poorly differentiated pleomorphic variant of HCC with large, often multinucleated, tumor cells. Spindle cell and clear cell variants of HCC were seen in one nodule each. Two nodules were classified as cholangiocarcinomas. Immunostaining for cytokeratins 7 and 19 did not prove to be reliable markers for tumors of bile duct origin, since they were also expressed in some of the poorly differentiated HCC. The most common microscopic finding of the noncancerous portions of the liver were clear cell foci, composed of large, glycogen rich hepatocytes with small eccentric nuclei. Other lesions commonly found were dysplastic hepatocyte foci around the central veins and proliferating bile ductular-like (oval) cells along the portal areas and portal tracts. JF - Princess Takamatsu symposia AU - Thorgeirsson, U P AU - Gomez, D E AU - Nagy, P AU - Sinha, C C AU - Adamson, R H AD - Division of Cancer Etiology, National Cancer Institute Bethesda, Maryland 20892, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 274 EP - 280 VL - 23 KW - Carcinogens KW - 0 KW - Quinolines KW - 2-amino-3-methylimidazo(4,5-f)quinoline KW - 30GL3D3T0G KW - Index Medicus KW - Neoplasm Invasiveness KW - Animals KW - Macaca fascicularis KW - Dose-Response Relationship, Drug KW - Neoplasm Metastasis KW - Incidence KW - Macaca mulatta KW - Time Factors KW - Quinolines -- toxicity KW - Liver -- pathology KW - Liver Neoplasms, Experimental -- pathology KW - Liver -- drug effects KW - Carcinogens -- toxicity KW - Liver Neoplasms, Experimental -- chemically induced KW - Liver -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77928658?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Princess+Takamatsu+symposia&rft.atitle=Histopathology+of+IQ-induced+hepatocarcinogenesis+in+nonhuman+primates.&rft.au=Thorgeirsson%2C+U+P%3BGomez%2C+D+E%3BNagy%2C+P%3BSinha%2C+C+C%3BAdamson%2C+R+H&rft.aulast=Thorgeirsson&rft.aufirst=U&rft.date=1995-01-01&rft.volume=23&rft.issue=&rft.spage=274&rft.isbn=&rft.btitle=&rft.title=Princess+Takamatsu+symposia&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-06 N1 - Date created - 1997-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Studies on the carcinogenic and myocardial effects of 2-amino-3-methylimidazo [4,5-f] quinoline (IQ) in nonhuman primates. AN - 77926617; 8844817 AB - The heterocyclic aromatic amine 2-amino-3-methylimidazo [4,5-f] quinoline (IQ) is one of three heterocyclic amine mutagens currently being evaluated for carcinogenic activity in nonhuman primates, primarily cynomolgus monkeys. IQ was administered by gavage five times a week at doses of 10 or 20 mg/kg. Thus far IQ induced tumors in 50 percent of the monkeys at the 10 mg/kg dose and in 85 percent of the monkeys at the 20 mg/kg dose. Because H and E sections of the myocardium from IQ-treated animals demonstrated inflammatory infiltrate and studies of IQ-DNA adducts in monkeys, by the 32P-postlabeling method, showed high levels of adducts in the heart a systematic study of cardiac pathologic changes associated with chronic administration of IQ was undertaken. Both light and electron microscopic abnormalities were seen. The possibility exists that heterocyclic aromatic amines may be etiologic factors for human cancer and myocardial disease. JF - Princess Takamatsu symposia AU - Adamson, R H AU - Farb, A AU - Virmani, R AU - Snyderwine, E G AU - Thorgeirsson, S S AU - Takayama, S AU - Sugimura, T AU - Dalgard, D W AU - Thorgeirsson, U P AD - Division of Cancer Etiology, National Cancer Institute Bethesda, Maryland 20892-4255, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 260 EP - 267 VL - 23 KW - Carcinogens KW - 0 KW - DNA Adducts KW - Imidazoles KW - Quinolines KW - Quinoxalines KW - 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline KW - 77500-04-0 KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - 2-amino-3,4-dimethylimidazo(4,5-f)quinoline KW - G2Q7M1P33X KW - Index Medicus KW - Meat KW - Administration, Oral KW - Hot Temperature KW - Animals KW - Necrosis KW - Macaca fascicularis KW - DNA Adducts -- analysis KW - Fibrosis KW - Lung Neoplasms -- secondary KW - Humans KW - Cooking KW - Lung Neoplasms -- chemically induced KW - Inflammation KW - Quinolines -- toxicity KW - Liver Neoplasms, Experimental -- secondary KW - Imidazoles -- toxicity KW - Carcinogens -- administration & dosage KW - Myocardium -- pathology KW - Imidazoles -- administration & dosage KW - Carcinogens -- toxicity KW - Liver Neoplasms -- chemically induced KW - Heart -- drug effects KW - Liver Neoplasms, Experimental -- chemically induced KW - Myocardium -- ultrastructure KW - Quinolines -- administration & dosage KW - Myocardium -- metabolism KW - Liver Neoplasms -- pathology KW - Liver Neoplasms, Experimental -- pathology KW - Quinoxalines -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77926617?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Princess+Takamatsu+symposia&rft.atitle=Studies+on+the+carcinogenic+and+myocardial+effects+of+2-amino-3-methylimidazo+%5B4%2C5-f%5D+quinoline+%28IQ%29+in+nonhuman+primates.&rft.au=Adamson%2C+R+H%3BFarb%2C+A%3BVirmani%2C+R%3BSnyderwine%2C+E+G%3BThorgeirsson%2C+S+S%3BTakayama%2C+S%3BSugimura%2C+T%3BDalgard%2C+D+W%3BThorgeirsson%2C+U+P&rft.aulast=Adamson&rft.aufirst=R&rft.date=1995-01-01&rft.volume=23&rft.issue=&rft.spage=260&rft.isbn=&rft.btitle=&rft.title=Princess+Takamatsu+symposia&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-06 N1 - Date created - 1997-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Possible relationship between tissue distribution of DNA adducts and genotoxicity of food-derived heterocyclic amines. AN - 77923160; 8844799 AB - During the past decade and a half, a number of potent mutagens belonging to the class of heterocyclic aromatic amines (HCA) have been isolated and identified from cooked fish, beef, fowl and other meat, and from beef extracts. Several of these HCA mutagens have also been found to be carcinogenic in rodent bioassays, and one of these compounds, 2-amino-3-methylimidazo-[4,5-f]-quinoline (IQ), has recently been found to cause hepatocellular carcinoma in cynomolgus monkeys. The potential etiological role of these mutagens and carcinogens in human cancer prompted us to evaluate the genotoxicity of these compounds in both nonhuman primates and rodents, with particular emphasis on the formation and tissue distribution of DNA adducts. We selected three compounds for this study based on several factors including chemical structure, mutagenic activity in vitro, concentration in cooked food, and carcinogenic activity in the rodent test system. These were IQ, 2-amino-3,8-dimethylimidazo[4,5-f]-quinoxaline (8-MeIQx), and 2-amino-1-methyl-6-phenylimidazo-[4,5-b]-pyridine (PhIP). To maximize the sensitivity of the DNA adduct measurements, we have employed the 32P-postlabeling method to analyze levels and tissue distribution of DNA adducts derived from IQ 8-MeIQx, and PhIP. We have measured DNA adduct formation for all three compounds in various tissues and white blood cells of monkeys following both acute and chronic administration. Both IQ and PhIP form high levels of adducts in a number of organs, particularly liver, kidney, and heart. In contrast, administration of 8-MeIQx to the cynomolgus monkeys results in the formation of only low adduct levels with many tissues showing no detectable levels of adducts. Studies in rodents have also shown that IQ and PhIP from DNA adducts in a number of organs in addition to those that are targets for carcinogenic effects of these agents. Although high DNA adduct levels of HCA are generally found in target organs for HCA induced carcinogenesis the widespread distribution of the adducts in organs not associated with the carcinogenic effects suggest that HCA exposure may be a possible etiological factor in cardiovascular diseases and other degenerative ailments. JF - Princess Takamatsu symposia AU - Thorgeirsson, S S AU - Davis, C D AU - Schut, H A AU - Adamson, R H AU - Snyderwine, E G AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 85 EP - 92 VL - 23 KW - Amines KW - 0 KW - DNA Adducts KW - Heterocyclic Compounds KW - Mutagens KW - Quinolines KW - Quinoxalines KW - 2-amino-3-methylimidazo(4,5-f)quinoline KW - 30GL3D3T0G KW - 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline KW - 77500-04-0 KW - Index Medicus KW - Quinolines -- toxicity KW - Animals KW - Poultry KW - Quinolines -- metabolism KW - Macaca fascicularis KW - Humans KW - Quinoxalines -- metabolism KW - Liver Neoplasms -- chemically induced KW - Tissue Distribution KW - Primates KW - Hot Temperature KW - Cattle KW - Fishes KW - Quinoxalines -- toxicity KW - Cooking KW - Quinoxalines -- pharmacokinetics KW - Quinolines -- pharmacokinetics KW - Carcinoma, Hepatocellular -- chemically induced KW - Meat KW - Heterocyclic Compounds -- metabolism KW - Heterocyclic Compounds -- pharmacokinetics KW - Mutagens -- metabolism KW - Amines -- metabolism KW - Mutagens -- pharmacokinetics KW - DNA Adducts -- metabolism KW - Amines -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77923160?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Princess+Takamatsu+symposia&rft.atitle=Possible+relationship+between+tissue+distribution+of+DNA+adducts+and+genotoxicity+of+food-derived+heterocyclic+amines.&rft.au=Thorgeirsson%2C+S+S%3BDavis%2C+C+D%3BSchut%2C+H+A%3BAdamson%2C+R+H%3BSnyderwine%2C+E+G&rft.aulast=Thorgeirsson&rft.aufirst=S&rft.date=1995-01-01&rft.volume=23&rft.issue=&rft.spage=85&rft.isbn=&rft.btitle=&rft.title=Princess+Takamatsu+symposia&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-06 N1 - Date created - 1997-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Overview: medications development for the treatment of drug abuse. AN - 77911836; 8775832 AB - Drug abuse is of great public concern, and effective treatment strategies for opiate and cocaine dependence are urgently needed for the general addict population as well as for pregnant women and their infants. NIDA's effort to develop new pharmacotherapies as an adjunct to the treatment of opiate addiction has already led to the approval of LAAM and an NDA development program for buprenorphine. The momentum achieved by the new Medications Development Program's success with opiate addiction treatment must now be applied to the development of new treatments for cocaine addiction. With recent advances in neuroscience, imaging techniques, and pharmaceutical technology, the development of medications for significantly improving drug abuse treatment in a variety of directions holds real promise. JF - NIDA research monograph AU - Vocci, F AU - Chiang, C N AU - Cummings, L AU - Hawks, R AD - Medications Development Division, National Institute on Drug Abuse, Rockville, MD 20857, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 4 EP - 15 VL - 149 SN - 1046-9516, 1046-9516 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Humans KW - Infant, Newborn KW - Female KW - Pregnancy KW - Pregnancy Complications -- drug therapy KW - Opioid-Related Disorders -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77911836?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Overview%3A+medications+development+for+the+treatment+of+drug+abuse.&rft.au=Vocci%2C+F%3BChiang%2C+C+N%3BCummings%2C+L%3BHawks%2C+R&rft.aulast=Vocci&rft.aufirst=F&rft.date=1995-01-01&rft.volume=149&rft.issue=&rft.spage=4&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-16 N1 - Date created - 1996-10-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - P300 amplitudes vary inversely with continuum of risk in first degree male relatives of alcoholics. AN - 77911776; 8750356 AB - First degree relatives of alcoholics show significantly reduced P300 amplitudes. This phenomenon is though to be a vulnerability marker of alcoholism. Relatives of alcoholics with higher family loading and early onset alcoholism are at greater risk for developing alcoholism. The high risk population may comprise subtypes differentiated by family history and/or age at onset of alcoholism, with differing risks, measurable in terms of the expression of the vulnerability marker. Four groups of alcohol-naive sons/male siblings of alcoholics (n = 64) were studied. The groups were constructed on the permutation of two defining characteristics: high family loading (two or more first degree alcoholic relatives) and early onset alcohol dependence (before 25 years) in the relatives. Comparison of P300 amplitude in an auditory paradigm showed significant inter-group differences as well as progressive increase/normalization of amplitudes from the high loading-early onset group (HR1) to the low loading-late onset group (HR4), with the latter being indistinguishable from a separate group of (control) normals. There were no significant differences of P300 latency among the groups. We conclude that P300 amplitudes vary inversely with the presumed continuum of risk in those at high risk for developing alcoholism. JF - Psychiatric genetics AU - Benegal, V AU - Jain, S AU - Subbukrishna, D K AU - Channabasavanna, S M AD - Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India. Y1 - 1995 PY - 1995 DA - 1995 SP - 149 EP - 156 VL - 5 IS - 4 SN - 0955-8829, 0955-8829 KW - Index Medicus KW - Reference Values KW - Age Factors KW - Age of Onset KW - Sex Characteristics KW - Risk Factors KW - Humans KW - Adult KW - Male KW - Female KW - Risk Assessment KW - Alcoholism -- epidemiology KW - Evoked Potentials, Auditory -- genetics KW - Nuclear Family KW - Alcoholism -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77911776?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychiatric+genetics&rft.atitle=P300+amplitudes+vary+inversely+with+continuum+of+risk+in+first+degree+male+relatives+of+alcoholics.&rft.au=Benegal%2C+V%3BJain%2C+S%3BSubbukrishna%2C+D+K%3BChannabasavanna%2C+S+M&rft.aulast=Benegal&rft.aufirst=V&rft.date=1995-01-01&rft.volume=5&rft.issue=4&rft.spage=149&rft.isbn=&rft.btitle=&rft.title=Psychiatric+genetics&rft.issn=09558829&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-11 N1 - Date created - 1996-10-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cutaneous manifestations of Taxol therapy. AN - 77910206; 8729957 AB - Taxol is a novel chemotherapeutic agent that has produced substantial responses in early clinical studies [1]. Taxol has excellent activity in a number of malignancies based on recently completed clinical trials, including a 30% response rate in platinum-refractory ovarian cancer patients [2-5]. We are currently conducting trials of dose-intense taxol with granulocyte colony stimulating factor (G-CSF) support in relapsed or refractory ovarian cancer patients. Such dose intensification produces a major response rate in 50% of patients with this disease [6]. Taxol was supplied in 5 ml ampules (6 mg/ml) in polyethoxylated castor oil (Cremophor EL) 50% and dehydrated alcohol and the dose was diluted in either 0.9% sodium chloride or 5% dextrose at concentrations of 0.6 to 1.2 mg/ml. We have noted 3 patients with previously unreported cutaneous manifestations which we believe are taxol related and also report our overall complication rate with the administration of taxol by peripheral intravenous lines. JF - Investigational new drugs AU - Link, C J AU - Sarosy, G A AU - Kohn, E C AU - Christian, M C AU - Davis, P AU - Adamo, D O AU - Reed, E AD - Medicine Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 261 EP - 263 VL - 13 IS - 3 SN - 0167-6997, 0167-6997 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Drug Therapy, Combination KW - Neoplasm Staging KW - Humans KW - Middle Aged KW - Granulocyte Colony-Stimulating Factor -- drug effects KW - Extravasation of Diagnostic and Therapeutic Materials -- complications KW - Female KW - Nail Diseases -- chemically induced KW - Paclitaxel -- adverse effects KW - Antineoplastic Agents, Phytogenic -- adverse effects KW - Ovarian Neoplasms -- pathology KW - Antineoplastic Agents, Phytogenic -- therapeutic use KW - Paclitaxel -- therapeutic use KW - Dermatitis, Contact -- etiology KW - Ovarian Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77910206?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Investigational+new+drugs&rft.atitle=Cutaneous+manifestations+of+Taxol+therapy.&rft.au=Link%2C+C+J%3BSarosy%2C+G+A%3BKohn%2C+E+C%3BChristian%2C+M+C%3BDavis%2C+P%3BAdamo%2C+D+O%3BReed%2C+E&rft.aulast=Link&rft.aufirst=C&rft.date=1995-01-01&rft.volume=13&rft.issue=3&rft.spage=261&rft.isbn=&rft.btitle=&rft.title=Investigational+new+drugs&rft.issn=01676997&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-21 N1 - Date created - 1996-10-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Medications and behavioral therapies: the whole may be greater than the sum of the parts. AN - 77904497; 8742768 JF - NIDA research monograph AU - Onken, L S AU - Blaine, J D AU - Boren, J J AD - Clinical and Experimental Therapeutics Branch, National Institute on Drug Abuse, Rockville, MD 20857, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 1 EP - 4 VL - 150 SN - 1046-9516, 1046-9516 KW - Index Medicus KW - Humans KW - Substance-Related Disorders -- therapy KW - Substance-Related Disorders -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77904497?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Medications+and+behavioral+therapies%3A+the+whole+may+be+greater+than+the+sum+of+the+parts.&rft.au=Onken%2C+L+S%3BBlaine%2C+J+D%3BBoren%2C+J+J&rft.aulast=Onken&rft.aufirst=L&rft.date=1995-01-01&rft.volume=150&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-16 N1 - Date created - 1996-10-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Strategies for phase II cancer chemoprevention trials: cervix, endometrium, and ovary. AN - 77904369; 8747372 AB - Well-designed and conducted Phase II clinical trials are very important to cancer chemoprevention drug development. Three critical aspects govern the design and conduct of these trials--well-characterized agents, suitable cohorts, and reliable biomarkers for measuring efficacy that can serve as surrogate endpoints for cancer incidence. Requirements for the agent are experimental or epidemiological data showing chemopreventive efficacy, safety on chronic administration, and a mechanistic rationale for the chemopreventive activity observed. Agents that meet these criteria for chemoprevention of cervical cancer include antiproliferative drugs (e.g., 2-difluoromethylornithine), retinoids, folic acid, antioxidant vitamins and other agents that prevent cellular oxidative damage. Because of the significant cervical cancer risk associated with human papilloma virus (HPV) infection, agents that interfere with the activity of HPV products may also prove to be effective chemopreventives. In endometrium, unopposed estrogen exposure has been associated with cancer incidence. Thus, pure antiestrogens and progestins may be chemopreventive in this tissue. Ovarian cancer risk is correlated to ovulation frequency; therefore, oral contraceptives are potentially chemopreventive in the ovary. Recent clinical observations also suggest that retinoids, particularly all-trans-N-4-hydroxyphenylretinamide, may be chemopreventive in this tissue. The cohort should be suitable for measuring the chemopreventive activity of the agent and the intermediate biomarkers chosen. In the cervix, patients with cervical intraepithelial neoplasia (CIN) and in endometrium, patients with atypical hyperplasia, fit these criteria. Defining a cohort for a Phase II trial in the ovary is more difficult. This tissue is less accessible for biopsy; consequently, the presence of precancerous lesions is more difficult to confirm. The criteria for biomarkers are that they fit expected biological mechanisms (i.e., differential expression in normal and high-risk tissue, on or closely linked to the causal pathway for the cancer, modulated by chemopreventive agents, and short latency compared with cancer), may be assayed reliably and quantitatively, measured easily, and correlate to decrease cancer incidence. They must occur in sufficient incidence to allow their biological and statistical evaluation relevant to cancer. Since carcinogenesis is a multipath process, single biomarkers are difficult to validate as surrogate endpoints, perhaps appearing on only one or a few of the many possible causal pathways. Panels of biomarkers, particularly those representing the range of carcinogenesis pathways, may prove more useful as surrogate endpoints. It is important to avoid solely on biomarkers that do not describe cancer but represent isolated events that may or may not be on the causal pathway or otherwise associated with carcinogenesis. These include markers of normal cellular processes that may be increased or expressed during carcinogenesis. Chemoprevention trials should be designed to evaluate fully the two or three biomarkers that appear to be the best models of the cancer. Additional biomarkers should be considered only if they can be analyzed efficiently and the sample size allows more important biomarkers to be evaluated completely. Two types of biomarkers that stand out regarding their high correlation to cancer and their ability to be quantified are measures of intraepithelial neoplasia and indicators of cellular proliferation. Measurements made by computer-assisted image analysis that are potentially useful as surrogate endpoint biomarkers include nuclear polymorphism comprising nuclear size, shape (roundness), and texture (DNA distribution patterns); nucleolar size and number of nucleoli/nuclei; DNA ploidy, and proliferation biomarkers such as S-phase fraction and PCNA... JF - Journal of cellular biochemistry. Supplement AU - Kelloff, G J AU - Boone, C W AU - Crowell, J A AU - Nayfield, S G AU - Hawk, E AU - Steele, V E AU - Lubet, R A AU - Sigman, C C AD - Chemoprevention Branch (CB), Division of Cancer Prevention and Control (DCPC), National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 1 EP - 9 VL - 23 SN - 0733-1959, 0733-1959 KW - Anticarcinogenic Agents KW - 0 KW - Biomarkers, Tumor KW - Index Medicus KW - Clinical Trials, Phase II as Topic KW - Humans KW - Patient Selection KW - Female KW - Uterine Cervical Neoplasms -- prevention & control KW - Endometrial Neoplasms -- prevention & control KW - Endometrial Neoplasms -- chemistry KW - Anticarcinogenic Agents -- therapeutic use KW - Uterine Cervical Neoplasms -- chemistry KW - Biomarkers, Tumor -- analysis KW - Ovarian Neoplasms -- chemistry KW - Ovarian Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77904369?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+biochemistry.+Supplement&rft.atitle=Strategies+for+phase+II+cancer+chemoprevention+trials%3A+cervix%2C+endometrium%2C+and+ovary.&rft.au=Kelloff%2C+G+J%3BBoone%2C+C+W%3BCrowell%2C+J+A%3BNayfield%2C+S+G%3BHawk%2C+E%3BSteele%2C+V+E%3BLubet%2C+R+A%3BSigman%2C+C+C&rft.aulast=Kelloff&rft.aufirst=G&rft.date=1995-01-01&rft.volume=23&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+biochemistry.+Supplement&rft.issn=07331959&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-26 N1 - Date created - 1996-09-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibitors of nitric oxide synthase and the opioid withdrawal syndrome. AN - 77902374; 8742786 AB - The NOS inhibitors L-NARG and L-NAME attenuate weight loss and wet dog shakes, two specific signs of opioid withdrawal in rats. NMMA is more potent than L-NAME, consistent with the in vivo actions of these compounds as inhibitors of NOS. In addition, NMMA antagonizes naloxone-induced jumping in morphine-dependent rats. The NOS inhibitors generally increase teeth chattering in precipitated withdrawal. The profile of the diminished withdrawal signs produced by these drugs differs from that produced by clonidine, which stimulates locomotor activity and does not increase teeth chattering in precipitated opioid withdrawal (Kimes et al. 1990). These findings suggest that administration of inhibitors of NOS may be an effective treatment of the opioid withdrawal syndrome alone or in combination with clonidine (U.S. patent #5,225,40). JF - NIDA research monograph AU - London, E D AU - Kimes, A S AU - Vaupel, D B AD - Addiction Research Center, National Institute on Drug Abuse, Baltimore, MD 21224, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 170 EP - 181 VL - 147 SN - 1046-9516, 1046-9516 KW - Nitroarginine KW - 2149-70-4 KW - omega-N-Methylarginine KW - 27JT06E6GR KW - Arginine KW - 94ZLA3W45F KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - NG-Nitroarginine Methyl Ester KW - V55S2QJN2X KW - Index Medicus KW - Rats KW - Animals KW - Morphine Dependence -- drug therapy KW - Nitric Oxide Synthase -- antagonists & inhibitors KW - Substance Withdrawal Syndrome -- drug therapy KW - Substance Withdrawal Syndrome -- psychology KW - Morphine Dependence -- psychology KW - Arginine -- analogs & derivatives KW - Arginine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77902374?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inhibitors+of+nitric+oxide+synthase+and+the+opioid+withdrawal+syndrome.&rft.au=London%2C+E+D%3BKimes%2C+A+S%3BVaupel%2C+D+B&rft.aulast=London&rft.aufirst=E&rft.date=1995-01-01&rft.volume=147&rft.issue=&rft.spage=170&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 - 1996-10-24 N1 - Date created - 1996-10-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - C-JUN/AP-1 as possible mediators of tumor necrosis factor-alpha-induced apoptotic response in mouse JB6 tumor cells. AN - 77889383; 8747598 AB - Sensitivity to cell killing by tumor necrosis factor (TNF)-alpha was seen in the JB6-derived transformed mouse RT101 cell variants previously described as resistant to 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced killing, while the TPA-sensitive variants were resistant to killing by TNF-alpha. Morphological and biochemical changes characteristic of apoptosis were found to precede TNF-alpha-induced cell death in TNF-alpha-sensitive (TNFs) but not TNF-alpha-resistant (TNFr) cells. In TNFr cells, TNF-alpha increased the cell cycle rate. The onset of cellular damage in TNFs cells, as indicated by propidium iodide uptake, was seen as early as 6 h after TNF-alpha treatment. 4,6-diamidino-2-phenylindole staining revealed chromosomal condensation approximately 4-6 h after TNF-alpha treatment. The DNA oligonucleosomal ladder of 180 bp and its multiples, a characteristic feature of apoptosis, was seen at 48 h. Little or no significant differences were found in the basal or induced levels of mRNA expression of several potential apoptosis mediator genes or apoptosis inhibitor genes. A dephosphorylated species of anti-c-Jun immunoprecipitated protein appeared in TNFs cells at 3 h posttreatment, accompanied by a parallel increase in AP-1 activity. Higher constitutive levels of the antioxidant enzymes superoxide dismutase and catalase were found in TNFr cells, but TNF-alpha did not significantly affect the activities of these enzymes or differentially induce their expression. The findings suggest that the preferential and transient increase in c-Jun dephosphorylation and AP-1 transcriptional activity may contribute to the preferential apoptotic response in TNFs cells; and that the greater constitutive oxidant defense in TNFr cells may contribute to their resistance. JF - Oncology research AU - Singh, N AU - Sun, Y AU - Nakamura, K AU - Smith, M R AU - Colburn, N H AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick, MD 21702-1201, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 353 EP - 362 VL - 7 IS - 7-8 SN - 0965-0407, 0965-0407 KW - Antioxidants KW - 0 KW - Chromatin KW - Growth Inhibitors KW - Proto-Oncogene Proteins c-jun KW - Transcription Factor AP-1 KW - Tumor Necrosis Factor-alpha KW - Index Medicus KW - Genetic Variation KW - Animals KW - Antioxidants -- metabolism KW - Chromatin -- drug effects KW - Cell Division -- drug effects KW - Mice KW - Cell Line, Transformed KW - Time Factors KW - Growth Inhibitors -- metabolism KW - Transcription Factor AP-1 -- metabolism KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Apoptosis -- drug effects KW - Proto-Oncogene Proteins c-jun -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77889383?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=C-JUN%2FAP-1+as+possible+mediators+of+tumor+necrosis+factor-alpha-induced+apoptotic+response+in+mouse+JB6+tumor+cells.&rft.au=Singh%2C+N%3BSun%2C+Y%3BNakamura%2C+K%3BSmith%2C+M+R%3BColburn%2C+N+H&rft.aulast=Singh&rft.aufirst=N&rft.date=1995-01-01&rft.volume=7&rft.issue=7-8&rft.spage=353&rft.isbn=&rft.btitle=&rft.title=Oncology+research&rft.issn=09650407&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-02-11 N1 - Date created - 1997-02-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Subgroup variation in U.S. drinking patterns: results of the 1992 national longitudinal alcohol epidemiologic study. AN - 77888862; 8749792 AB - Data from the 1992 National Longitudinal Alcohol Epidemiologic Study (NLAES) revealed that 44% of U.S. adults 18 years of age and older were current drinkers who had consumed at least 12 drinks in the year preceding the interview. Twenty-two percent were former drinkers, and 34% were lifetime abstainers. These figures represent an 8% decrease in the prevalence of current drinking relative to 1988. The proportion of current drinkers decreased with age, was higher for men than women, increased with education and income, was lower than average among Black and Hispanic adults, was highest among never-married adults and lowest among those who were widowed, was lower in the South than in other regions, and was lower in rural than urban areas. The probabilities of ever having consumed five or more (5+) drinks or having been intoxicated in the past year revealed similar patterns to those already noted, but the probabilities of heavy drinking or intoxication on a weekly or more frequent basis showed no variation by race or ethnicity. Average daily consumption of more than 1 ounce of ethanol differed from the preceding measure of heavy drinking in its variation across population subgroups, declining less sharply with age and exhibiting a U-shaped pattern with respect to income. Examination of the prevalence of heavy drinking among current drinkers rather than within the total population revealed several differences, the most striking reversal being that the probability of heavy drinking decreased with education and income. Multiple logistic regression models predicting the various drinking outcomes indicated that most of the differentials held true after adjusting for intercorrelation among the sociodemographic variables. JF - Journal of substance abuse AU - Dawson, D A AU - Grant, B F AU - Chou, S P AU - Pickering, R P AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892-7003, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 331 EP - 344 VL - 7 IS - 3 SN - 0899-3289, 0899-3289 KW - Index Medicus KW - Regression Analysis KW - Probability KW - Educational Status KW - Alcoholic Intoxication -- epidemiology KW - Humans KW - Aged KW - Longitudinal Studies KW - Socioeconomic Factors KW - Cross-Sectional Studies KW - Adult KW - Incidence KW - Middle Aged KW - Adolescent KW - United States -- epidemiology KW - Female KW - Male KW - Alcoholism -- rehabilitation KW - Alcoholism -- epidemiology KW - Alcohol Drinking -- epidemiology KW - Temperance -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77888862?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Subgroup+variation+in+U.S.+drinking+patterns%3A+results+of+the+1992+national+longitudinal+alcohol+epidemiologic+study.&rft.au=Dawson%2C+D+A%3BGrant%2C+B+F%3BChou%2C+S+P%3BPickering%2C+R+P&rft.aulast=Dawson&rft.aufirst=D&rft.date=1995-01-01&rft.volume=7&rft.issue=3&rft.spage=331&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 - 1996-09-27 N1 - Date created - 1996-09-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neoplastic transformation by quartz in the BALB/3T3/A31-1-1 cell line and the effects of associated minerals. AN - 77884511; 8732883 AB - Quartz, the most common form of crystalline silica, was tested quantitatively for neoplastic transformation in the mouse embryo cell line, BALB/3T3/A31-1-1. Five quartz dust samples of respirable size [Min-U-Sil 5 (MQZ); hydrofluoric-acid-etched MQZ (HFMQZ); Chinese standard quartz (CSQZ); DQ12; and F600] all induced significant levels of neoplastic transformation, showing dose-dependent increases in the frequency of morphologically transformed foci at lower tested doses and a plateau level of response at higher doses. The plateau levels reached by the five tested samples did not differ substantially (maximum transformation frequencies per 10(5) cells ranging from 53.2 for MQZ to 28.3 for HFMQZ). F600 had minimal cytotoxicity but transforming activity comparable to the other samples. Cells from all tested transformed foci, when injected s.c. in nude mice, grew as sarcomas. Cytogenetic analysis showed that all tested silica-transformed cell lines had acquired one to five additional marker chromosomes, of types not seen in untreated control lines, indicative of induced chromosomal translocations and amplification. Increased expression of one or more of five genes (p53, myc, H-ras, K-ras, and abl) was observed in several quartz-transformed cell lines. No transforming activity was found for hematite and anatase (both nontoxic), and for rutile (more toxic than MQZ). Combined exposure (1:1 w/w per unit culture area) of each of these dusts with MQZ showed that hematite and anatase inhibited MQZ toxicity as well as transformation, whereas rutile markedly enhanced MQZ toxicity but not MQZ-induced transformation. JF - Teratogenesis, carcinogenesis, and mutagenesis AU - Saffiotti, U AU - Ahmed, N AD - Laboratory of Experimental Pathology, DBS, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-0041, USA. PY - 1995 SP - 339 EP - 356 VL - 15 IS - 6 SN - 0270-3211, 0270-3211 KW - Carcinogens KW - 0 KW - Minerals KW - Quartz KW - 14808-60-7 KW - Index Medicus KW - Neoplasm Transplantation KW - Karyotyping KW - Animals KW - 3T3 Cells KW - Cell Survival -- drug effects KW - Dose-Response Relationship, Drug KW - Mice, Nude KW - Mice KW - Mice, Inbred BALB C KW - Chromosome Mapping KW - Neoplasms, Experimental -- chemically induced KW - Neoplasms, Experimental -- genetics KW - Carcinogens -- toxicity KW - Minerals -- pharmacology KW - Neoplasms, Experimental -- pathology KW - Cell Transformation, Neoplastic KW - Quartz -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77884511?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Teratogenesis%2C+carcinogenesis%2C+and+mutagenesis&rft.atitle=Neoplastic+transformation+by+quartz+in+the+BALB%2F3T3%2FA31-1-1+cell+line+and+the+effects+of+associated+minerals.&rft.au=Saffiotti%2C+U%3BAhmed%2C+N&rft.aulast=Saffiotti&rft.aufirst=U&rft.date=1995-01-01&rft.volume=15&rft.issue=6&rft.spage=339&rft.isbn=&rft.btitle=&rft.title=Teratogenesis%2C+carcinogenesis%2C+and+mutagenesis&rft.issn=02703211&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-04 N1 - Date created - 1996-10-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular genetics of lung cancer. AN - 77877263; 8718524 AB - The identification of genetic abnormalities in lung cancer and their consequences for cell growth, differentiation and function offer insights into normal cellular function and carcinogenesis. The integration of this knowledge with data from other fields, including epidemiology, toxicology, carcinogen metabolism, clinical genetics and clinical cancer therapy, promises advancements in lung cancer risk assessment, screening, prevention, prognostic assessment and therapy. JF - Cancer surveys AU - Greenblatt, M S AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 293 EP - 313 VL - 25 SN - 0261-2429, 0261-2429 KW - Carcinogens KW - 0 KW - Index Medicus KW - Mass Screening KW - Genetic Variation KW - Animals KW - DNA Repair KW - Risk Factors KW - Humans KW - Prognosis KW - Point Mutation KW - Cell Cycle KW - Cell Transformation, Neoplastic KW - Risk Assessment KW - Lung Neoplasms -- prevention & control KW - Lung Neoplasms -- diagnosis KW - Lung Neoplasms -- epidemiology KW - Lung Neoplasms -- genetics KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77877263?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+surveys&rft.atitle=Molecular+genetics+of+lung+cancer.&rft.au=Greenblatt%2C+M+S%3BHarris%2C+C+C&rft.aulast=Greenblatt&rft.aufirst=M&rft.date=1995-01-01&rft.volume=25&rft.issue=&rft.spage=293&rft.isbn=&rft.btitle=&rft.title=Cancer+surveys&rft.issn=02612429&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-11 N1 - Date created - 1996-10-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comments on the physics and chemistry of trehalose as a storage medium for hemoglobin-based blood substitutes: "from Kramers Theory to the Battlefield". AN - 77871263; 8646336 AB - A glass of the naturally-occurring sugar trehalose may be a suitable medium for the storage of hemoglobin-based blood substitutes. Trehalose has many or possibly all of the properties required for this purpose, including solubilization of hemoglobin to a very high concentration, lack of toxicity, slowing of oxidation to the non-oxygen binding methemoglobin, stability at room temperature and above, and ease of transport. It should also be possible to prepare hemoglobin extremely rapidly for injection into the circulation in situations where blood replacement is required immediately, as in a domestic emergency room or on the battlefield. These practical considerations are briefly discussed, as well as the theoretical reasons for slowing of chemical reactions in the glassy state. JF - Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine AU - Hagen, S J AU - Hofrichter, H J AU - Bunn, H F AU - Eaton, W A AD - Laboratory of Chemical Physics, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda 20892-0520, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 423 EP - 426 VL - 2 IS - 6 SN - 1246-7820, 1246-7820 KW - Blood Substitutes KW - 0 KW - Trehalose KW - B8WCK70T7I KW - Index Medicus KW - Physical Phenomena KW - Physics KW - Molecular Sequence Data KW - Carbohydrate Sequence KW - Trehalose -- chemistry KW - Drug Storage -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77871263?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Transfusion+clinique+et+biologique+%3A+journal+de+la+Societe+francaise+de+transfusion+sanguine&rft.atitle=Comments+on+the+physics+and+chemistry+of+trehalose+as+a+storage+medium+for+hemoglobin-based+blood+substitutes%3A+%22from+Kramers+Theory+to+the+Battlefield%22.&rft.au=Hagen%2C+S+J%3BHofrichter%2C+H+J%3BBunn%2C+H+F%3BEaton%2C+W+A&rft.aulast=Hagen&rft.aufirst=S&rft.date=1995-01-01&rft.volume=2&rft.issue=6&rft.spage=423&rft.isbn=&rft.btitle=&rft.title=Transfusion+clinique+et+biologique+%3A+journal+de+la+Societe+francaise+de+transfusion+sanguine&rft.issn=12467820&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-07-25 N1 - Date created - 1996-07-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Candidate genes in alcoholism. AN - 77867207; 8612062 AB - Individual alleles identified by candidate gene analysis have been shown to profoundly influence certain complex behavioral syndromes including vulnerability to alcoholism. The alcohol and aldehyde dehydrogenase polymorphisms, ADH2(2) and ALDH2(2), respectively, are associated with lower vulnerability to alcoholism both in the Orient and also in North America among populations of Taiwanese and Koreans who have immigrated there. Protein structural variants have recently been identified for a series of genes involved in dopamine and serotonin function. Three dopamine receptors exhibit such structural variants, and these include the DRD2 dopamine receptor, which has three relatively rare amino acid substitutions. Structural polymorphisms were detected in five serotonin receptors (5HT1A, 5HT1Db, 5HT2A, 5HT2C, and 5HT7). Association studies between neurotransmitter gene variants and alcoholism are at an earlier stage than with ADH2(2)/ALDH2(2), but results are thus far negative (dopamine DRD4 receptor), equivocal (dopamine DRD2 receptor), or preliminary (tryptophan hydroxylase, 5HT2C and 5HT1Db). JF - Clinical neuroscience (New York, N.Y.) AU - Goldman, D AD - Laboratory of Neurogenetics, NIAAA, NIH, Rockville, MD 20852, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 174 EP - 181 VL - 3 IS - 3 SN - 1065-6766, 1065-6766 KW - Index Medicus KW - Alleles KW - Humans KW - Alcoholism -- genetics KW - Genes -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77867207?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neuroscience+%28New+York%2C+N.Y.%29&rft.atitle=Candidate+genes+in+alcoholism.&rft.au=Goldman%2C+D&rft.aulast=Goldman&rft.aufirst=D&rft.date=1995-01-01&rft.volume=3&rft.issue=3&rft.spage=174&rft.isbn=&rft.btitle=&rft.title=Clinical+neuroscience+%28New+York%2C+N.Y.%29&rft.issn=10656766&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-06-04 N1 - Date created - 1996-06-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 alterations in progenitor lesions of the bronchus, esophagus, oral cavity, and colon. AN - 77859661; 8925519 AB - Human cancers are believed to develop in multiple stages. There is morphologic evidence for this in many tissues, including cancers of the lung, esophagus, head and neck, skin, colon, cervix, and bladder; and corresponding genetic models are developing. This article summarizes reports describing the timing and frequency of p53 alterations (i.e., mutation and/or protein accumulation) in progenitor lesions of human lung, esophagus (both squamous and Barrett's), head and neck, and colon. In squamous lesions of the lung, esophagus, and head and neck, there is evidence for p53 alteration in a minority of the earliest dysplasias and in a majority of the late or severe dysplasias. It is not known whether all of the alterations are caused by mutations or by epigenetic factors. In sporadic colonic adenomas, there is also evidence for p53 protein accumulation in early adenomas, but it is clear that p53 mutations occur mostly in the stage of late adenoma or carcinoma. The causes of the protein accumulation in the earlier stages are not clear. Strategies for early diagnosis based on detecting p53 mutations in body fluids including sputum, urine, and stool have been published (Sidransky D. J. Natl Cancer Inst 1994; 86:995-956). Although substantial technical hurdles remain, the high frequency and early occurrence of these mutations make the p53 tumor suppressor gene an attractive target for early detection and early therapeutic intervention in many common human cancers. JF - Cancer detection and prevention AU - Bennett, W P AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 503 EP - 511 VL - 19 IS - 6 SN - 0361-090X, 0361-090X KW - DNA, Neoplasm KW - 0 KW - RNA, Neoplasm KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Tumor Suppressor Protein p53 -- biosynthesis KW - Humans KW - DNA, Neoplasm -- analysis KW - Neoplasms, Squamous Cell KW - RNA, Neoplasm -- analysis KW - Immunohistochemistry KW - Precancerous Conditions -- genetics KW - Colonic Neoplasms -- genetics KW - Genes, p53 KW - Bronchial Neoplasms -- genetics KW - Oropharyngeal Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77859661?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=p53+alterations+in+progenitor+lesions+of+the+bronchus%2C+esophagus%2C+oral+cavity%2C+and+colon.&rft.au=Bennett%2C+W+P&rft.aulast=Bennett&rft.aufirst=W&rft.date=1995-01-01&rft.volume=19&rft.issue=6&rft.spage=503&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 - 1996-11-27 N1 - Date created - 1996-11-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - AIDS, drugs, and the adolescent. AN - 77849148; 8594469 JF - NIDA research monograph AU - Steel, E AD - National Institute on Drug Abuse, Rockville, MD 20852, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 130 EP - 145 VL - 156 SN - 1046-9516, 1046-9516 KW - Index Medicus KW - AIDS/HIV KW - Humans KW - Adolescent KW - United States -- epidemiology KW - Acquired Immunodeficiency Syndrome -- complications KW - Adolescent Behavior KW - Acquired Immunodeficiency Syndrome -- epidemiology KW - Acquired Immunodeficiency Syndrome -- psychology KW - Substance-Related Disorders -- complications KW - Substance-Related Disorders -- psychology KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77849148?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=AIDS%2C+drugs%2C+and+the+adolescent.&rft.au=Steel%2C+E&rft.aulast=Steel&rft.aufirst=E&rft.date=1995-01-01&rft.volume=156&rft.issue=&rft.spage=130&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-04-09 N1 - Date created - 1996-04-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Advances in adolescent drug abuse treatment. AN - 77815901; 8594467 JF - NIDA research monograph AU - Rahdert, E AU - Czechowicz, D AD - Division of Clinical and Services Research, National Institute on Drug Abuse, Rockville, MD 20857, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 1 EP - 6 VL - 156 SN - 1046-9516, 1046-9516 KW - Index Medicus KW - Humans KW - Adolescent KW - Substance-Related Disorders -- therapy KW - Substance-Related Disorders -- diagnosis KW - Adolescent Behavior KW - Substance-Related Disorders -- rehabilitation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77815901?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Advances+in+adolescent+drug+abuse+treatment.&rft.au=Rahdert%2C+E%3BCzechowicz%2C+D&rft.aulast=Rahdert&rft.aufirst=E&rft.date=1995-01-01&rft.volume=156&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-04-09 N1 - Date created - 1996-04-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neuroendocrine responses to intravenous infusion of arecoline in patients with Alzheimer's disease. AN - 77812234; 8584603 AB - We have reported that arecoline, a muscarinic receptor agonist replicably enhanced verbal memory in five of nine subjects with Alzheimer's disease (AD). To investigate the mechanism of cognitive improvement, circulating hormone measurements were made during high-dose acute and low-dose chronic intravenous (i.v.) arecoline administration to AD patients. Acute hormone responses were measured during, and for 6 h after, infusion of arecoline 5 mg i.v. over 30 min. Chronic responses were measured in cognitive responders during continuous i.v. infusion of arecoline escalating over 2 weeks (0.5-40 mg/day) and then during a 1 week infusion of the dose optimizing cognition (4-16 mg/day). Acute arecoline administered to 14 subjects produced unpleasant side-effects (e.g. nausea, vomiting), mean adrenocorticotrophic hormone (p = .0006), cortisol (p = .0001) and beta-endorphin (p = .0001) levels were elevated. During chronic arecoline treatment, no side-effects occurred and plasma cortisol, adrenocorticotrophic hormone and beta-endorphin levels were unchanged in nine subjects overall and in five cognitive responders. Thus, high-dose arecoline activates the hypothalamic-pituitary-adrenal (HPA) axis and may increase other anterior pituitary hormone levels, likely representing a 'stress response', but cognition-enhancing, low doses of arecoline do not produce a glucocorticoid response. Hence, arecoline-induced memory improvement is not due to the induction of 'stress' nor to the elevation of peripheral corticosteroid levels. JF - Psychoneuroendocrinology AU - Asthana, S AU - Raffaele, K C AU - Greig, N H AU - Berardi, A AU - Morris, P P AU - Schapiro, M B AU - Rapoport, S I AU - Blackman, M R AU - Soncrant, T T AD - Unit on Pharmacology and Pharmacokinetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 623 EP - 636 VL - 20 IS - 6 SN - 0306-4530, 0306-4530 KW - Hormones KW - 0 KW - Muscarinic Agonists KW - Arecoline KW - 4ALN5933BH KW - beta-Endorphin KW - 60617-12-1 KW - Adrenocorticotropic Hormone KW - 9002-60-2 KW - Hydrocortisone KW - WI4X0X7BPJ KW - Index Medicus KW - Hypothalamo-Hypophyseal System -- drug effects KW - Drug Administration Schedule KW - Infusions, Intravenous KW - Dose-Response Relationship, Drug KW - Humans KW - Hypothalamo-Hypophyseal System -- physiopathology KW - Arousal -- physiology KW - Aged KW - beta-Endorphin -- blood KW - Hydrocortisone -- blood KW - Mental Recall -- physiology KW - Aged, 80 and over KW - Arousal -- drug effects KW - Pituitary-Adrenal System -- physiopathology KW - Middle Aged KW - Neuropsychological Tests KW - Mental Recall -- drug effects KW - Pituitary-Adrenal System -- drug effects KW - Male KW - Female KW - Adrenocorticotropic Hormone -- blood KW - Alzheimer Disease -- physiopathology KW - Alzheimer Disease -- drug therapy KW - Alzheimer Disease -- psychology KW - Hormones -- blood KW - Arecoline -- adverse effects KW - Muscarinic Agonists -- administration & dosage KW - Arecoline -- administration & dosage KW - Muscarinic Agonists -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77812234?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Neuroendocrine+responses+to+intravenous+infusion+of+arecoline+in+patients+with+Alzheimer%27s+disease.&rft.au=Asthana%2C+S%3BRaffaele%2C+K+C%3BGreig%2C+N+H%3BBerardi%2C+A%3BMorris%2C+P+P%3BSchapiro%2C+M+B%3BRapoport%2C+S+I%3BBlackman%2C+M+R%3BSoncrant%2C+T+T&rft.aulast=Asthana&rft.aufirst=S&rft.date=1995-01-01&rft.volume=20&rft.issue=6&rft.spage=623&rft.isbn=&rft.btitle=&rft.title=Psychoneuroendocrinology&rft.issn=03064530&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-21 N1 - Date created - 1996-03-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Purification of bacteriophage T4 DNA replication proteins. AN - 77770644; 8594379 JF - Methods in enzymology AU - Nossal, N G AU - Hinton, D M AU - Hobbs, L J AU - Spacciapoli, P AD - Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20893-0830, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 560 EP - 584 VL - 262 SN - 0076-6879, 0076-6879 KW - DNA, Single-Stranded KW - 0 KW - DNA-Binding Proteins KW - Recombinant Proteins KW - Viral Proteins KW - gene 43 protein, Enterobacteria phage T4 KW - DNA KW - 9007-49-2 KW - Durapatite KW - 91D9GV0Z28 KW - DNA Primase KW - EC 2.7.7.- KW - RNA Nucleotidyltransferases KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Ribonuclease H KW - EC 3.1.26.4 KW - DNA Helicases KW - EC 3.6.4.- KW - DNA Ligases KW - EC 6.5.1.- KW - Index Medicus KW - Animals KW - Chromatography, Ion Exchange -- methods KW - DNA Helicases -- isolation & purification KW - Ribonuclease H -- metabolism KW - Mutagenesis KW - Recombinant Proteins -- isolation & purification KW - Chromatography, DEAE-Cellulose -- methods KW - Recombinant Proteins -- metabolism KW - DNA Ligases -- metabolism KW - DNA Ligases -- isolation & purification KW - Male KW - DNA, Single-Stranded -- metabolism KW - Salmon KW - RNA Nucleotidyltransferases -- isolation & purification KW - RNA Nucleotidyltransferases -- metabolism KW - DNA Helicases -- metabolism KW - DNA -- metabolism KW - Spermatozoa KW - Electrophoresis, Polyacrylamide Gel -- methods KW - Plasmids KW - Chromatography -- methods KW - Ribonuclease H -- isolation & purification KW - Chromatography, Affinity -- methods KW - Viral Proteins -- isolation & purification KW - Bacteriophage T4 -- metabolism KW - Viral Proteins -- metabolism KW - Bacteriophage T4 -- genetics KW - DNA-Binding Proteins -- isolation & purification KW - DNA Replication KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77770644?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+of+bacteriophage+T4+DNA+replication+proteins.&rft.au=Nossal%2C+N+G%3BHinton%2C+D+M%3BHobbs%2C+L+J%3BSpacciapoli%2C+P&rft.aulast=Nossal&rft.aufirst=N&rft.date=1995-01-01&rft.volume=262&rft.issue=&rft.spage=560&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 - 1996-04-08 N1 - Date created - 1996-04-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Discovery and in vitro development of AIDS antiviral drugs as biopharmaceuticals. AN - 77742442; 7495676 AB - The goal of developing an effective drug against HIV-1 and AIDS has been approached by several routes, with enough encouraging results to stimulate further efforts. Compounds active against HIV-1 have been discovered for many of the functions in the reproductive cycle recognized as virus-specific targets. Discoveries have been made in cell-based assays as well as mechanistic assays, and the value of both types of assays in the drug discovery process has been discussed. Although the final test of a drug's efficacy comes in the clinical experience, submission of an antiviral compound to an in vitro developmental gauntlet can save much time, effort, expense, and human resource in the in vivo developmental regimen required prior to human use. Emergence of viral resistance to drugs in several structural classes has compromised their clinical efficacy, suggesting that development of other potential drugs in those classes may not be good investments. Strains of HIV-1 resistant to specific compound classes are used to categorize new active discoveries for possible developmental exclusion, and defining the mechanism of action of such a new compound may confirm the discouraging judgement. On the other hand, novel compounds which exhibit a broad range of activity in drug-resistant and other HIV-1 strains deserve greater scrutiny. Clinicians most likely will be hesitant to treat patients with compounds shown to act on virus-cell surface interactions, given the failure in the past of several such compounds in clinical studies. But a compound shown to have a unique and novel mechanism of action will be looked upon more favorably, and surviving other tests of potency, solubility, and stability will be unhesitatingly presented for in vivo development. The partial successes of drugs currently in clinical use against AIDS offers great encouragement that other more-effective, less-toxic drugs will be found. Exquisite techniques for identifying new targets on virus gene products, the selection of compounds on activity paradigms, and the enormous variety of compounds becoming available through synthesis libraries, all offer opportunities for anti-HIV drug discovery, which, in our view, cannot fail to present potent antiviral compounds which will survive the rigorous preclinical and clinical tests leading to a drug effective against AIDS. JF - Advances in pharmacology (San Diego, Calif.) AU - Rice, W G AU - Bader, J P AD - Laboratory of Antiviral Drug Mechanisms, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21701-1201, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 389 EP - 438 VL - 33 SN - 1054-3589, 1054-3589 KW - Antiviral Agents KW - 0 KW - Index Medicus KW - AIDS/HIV KW - Humans KW - In Vitro Techniques KW - HIV-1 KW - Drug Design KW - Pharmaceutical Services KW - Antiviral Agents -- pharmacology KW - Acquired Immunodeficiency Syndrome -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77742442?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+pharmacology+%28San+Diego%2C+Calif.%29&rft.atitle=Discovery+and+in+vitro+development+of+AIDS+antiviral+drugs+as+biopharmaceuticals.&rft.au=Rice%2C+W+G%3BBader%2C+J+P&rft.aulast=Rice&rft.aufirst=W&rft.date=1995-01-01&rft.volume=33&rft.issue=&rft.spage=389&rft.isbn=&rft.btitle=&rft.title=Advances+in+pharmacology+%28San+Diego%2C+Calif.%29&rft.issn=10543589&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-18 N1 - Date created - 1996-01-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of chronic naloxone administration on vacuous chewing movements and catalepsy in rats treated with long-term haloperidol decanoate. AN - 77732404; 8535858 AB - Most antipsychotic medications produce motoric side effects, including parkinsonism and tardive dyskinesia (TD). Correlates of these behaviors in rats (catalepsy and vacuous chewing movements, respectively) were used as a model to assess the usefulness of chronic naloxone administration in symptom reduction. Previous studies have suggested that increased neurotransmission in the endogenous opioid system modulates neuroleptic-induced motoric side effects. Rats were treated with haloperidol decanoate or vehicle for 27 weeks, and withdrawn for 30 weeks. Subsequently, naloxone (0.5 to 2.0 mg/kg SC twice daily) was given for 5 weeks. Long-term haloperidol treatment produced a syndrome of vacuous chewing movements (VCMs) that persisted during the drug withdrawal period. Catalepsy developed rapidly and also persisted. Naloxone treatment had little effect on VCMs but increased catalepsy scores in both haloperidol and vehicle treated groups. Naloxone reduced rearing and grooming in haloperidol rats while increasing these measures in vehicle treated rats. The results indicate that neuroleptic-induced motoric side effects are not reversed by naloxone in rats. Furthermore, they suggest that increased opioid neurotransmission may not underlie the expression of VCMs. This does not rule out the possibility that endogenous opioid system may be involved in the development of VCMs. To the extent that this animal model is valid, naloxone may not be effective in treating TD and neuroleptic-induced parkinsonism in humans. JF - Brain research bulletin AU - Egan, M F AU - Ferguson, J N AU - Hyde, T M AD - Neuropsychiatry Branches, National Institute of Mental Health, NIMH, Washington, DC, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 355 EP - 363 VL - 38 IS - 4 SN - 0361-9230, 0361-9230 KW - Anti-Dyskinesia Agents KW - 0 KW - Narcotic Antagonists KW - Naloxone KW - 36B82AMQ7N KW - Haloperidol KW - J6292F8L3D KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Grooming -- drug effects KW - Substance Withdrawal Syndrome -- psychology KW - Male KW - Haloperidol -- antagonists & inhibitors KW - Haloperidol -- adverse effects KW - Anti-Dyskinesia Agents -- adverse effects KW - Naloxone -- pharmacology KW - Anti-Dyskinesia Agents -- pharmacology KW - Catalepsy -- chemically induced KW - Catalepsy -- psychology KW - Haloperidol -- pharmacology KW - Dyskinesia, Drug-Induced -- psychology KW - Anti-Dyskinesia Agents -- antagonists & inhibitors KW - Stereotyped Behavior -- drug effects KW - Narcotic Antagonists -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77732404?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+bulletin&rft.atitle=Effects+of+chronic+naloxone+administration+on+vacuous+chewing+movements+and+catalepsy+in+rats+treated+with+long-term+haloperidol+decanoate.&rft.au=Egan%2C+M+F%3BFerguson%2C+J+N%3BHyde%2C+T+M&rft.aulast=Egan&rft.aufirst=M&rft.date=1995-01-01&rft.volume=38&rft.issue=4&rft.spage=355&rft.isbn=&rft.btitle=&rft.title=Brain+research+bulletin&rft.issn=03619230&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-08 N1 - Date created - 1996-02-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The CYP2A gene subfamily: species differences, regulation, catalytic activities and role in chemical carcinogenesis. AN - 77693043; 7581481 AB - The CYP2A subfamily has been characterized in several mammalian species including mouse, rat, rabbit, hamster, cattle and human. Marked species differences have been demonstrated in the catalytic activities and regulation of this subfamily. In humans, the CYP2A genes are found as a cluster on the long arm of chromosome 19 with the CYP2B and CYP2F genes. Marked interindividual differences in expression of the CYP2A6 gene was found in livers analyzed in vitro and in humans phenotyped in vivo by using coumarin, a specific substrate for the enzyme. Efforts are underway to determine the existence of mutant and variant CYP2A6 alleles in the human population. Since CYP2A6 is able to metabolically-activate chemical carcinogens and is expressed in extrahepatic tissue, it will be of interest to determine whether genetic differences in expression of the gene is associated with cancer risk. JF - Pharmacogenetics AU - Fernandez-Salguero, P AU - Gonzalez, F J AD - National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - S123 EP - S128 VL - 5 Spec No SN - 0960-314X, 0960-314X KW - CYP2A KW - Carcinogens KW - 0 KW - Coumarins KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - coumarin KW - A4VZ22K1WT KW - Steroid Hydroxylases KW - EC 1.14.- KW - steroid hormone 6-beta-hydroxylase KW - EC 1.14.14.1 KW - Index Medicus KW - Animals KW - Liver -- enzymology KW - Humans KW - Mice KW - Rabbits KW - Chromosome Mapping KW - Phenotype KW - Rats KW - Cattle KW - Gene Expression Regulation, Enzymologic KW - Coumarins -- metabolism KW - Substrate Specificity KW - Species Specificity KW - Cricetinae KW - Carcinogens -- metabolism KW - Cytochrome P-450 Enzyme System -- genetics KW - Multigene Family KW - Chromosomes, Human, Pair 19 KW - Neoplasms -- epidemiology KW - Carcinogens -- toxicity KW - Steroid Hydroxylases -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Steroid Hydroxylases -- genetics KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77693043?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacogenetics&rft.atitle=The+CYP2A+gene+subfamily%3A+species+differences%2C+regulation%2C+catalytic+activities+and+role+in+chemical+carcinogenesis.&rft.au=Fernandez-Salguero%2C+P%3BGonzalez%2C+F+J&rft.aulast=Fernandez-Salguero&rft.aufirst=P&rft.date=1995-01-01&rft.volume=5+Spec+No&rft.issue=&rft.spage=S123&rft.isbn=&rft.btitle=&rft.title=Pharmacogenetics&rft.issn=0960314X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-30 N1 - Date created - 1995-11-30 N1 - Date revised - 2017-01-13 N1 - Gene symbol - CYP2A N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Altered protein synthesis in p53 null and hemizygous transgenic mouse embryonic fibroblasts. AN - 77690319; 8534750 AB - Embryonic fibroblasts derived from p53-deficient transgenic mice showed distinct phenotypic and biological changes in vitro. In this study, we investigated the possible impact of p53 on the synthesis of other cellular proteins by comparing the protein profiles of p53 null (-/-), hemizygous (+/-) and p53 positive homozygous (+/+) cells using high resolution two dimensional gel electrophoresis. A total of more than 850 proteins were detected in each cell line labeled with 35S-methionine by using computerized image analysis, and a number of proteins were detected with qualitative or quantitative changes in p53-/- cells and to a lesser extent in p53+/- cells. Specifically, seven proteins became undetectable, and no new proteins were detected in p53-/- cells. Neither newly expressed nor absent proteins were detected in p53+/- cell line. Quantitatively, a total of 97 and 59 proteins were detected with significant quantitative changes (3 fold or greater) in p53-/- and p53+/- cells, respectively. Generally, most protein changes fell into one of the following four patterns: 1) progressively decreased synthesis in cells from p53+/+ to p53+/- to p53-/- cells; 2) progressively increased synthesis in cells from p53+/+ to p53+/- to p53-/- cells; 3) decreased synthesis only in p53-/- cells; and 4) increased synthesis only in p53-/- cells. A 70 kD heat shock protein (Hsp 70) was identified and showed a greater than 1,000-fold increase in p53-/- cells compared to that in p53+/+ cells. Transferrin, tropomyosin, and proliferating cell nuclear antigen (PCNA) have also been identified and measured in this study. Synthesis of transferrin and tropomyosin was significantly increased or decreased, respectively in p53-/- cells, whereas expression of PCNA showed no significant change in p53-/- cells despite their much higher (3-4 times) proliferation rate than the other two cell lines (p53+/+ and p53+/- cells). We conclude that disruption of a single important gene, p53, results in a cascade of protein changes which are related to the loss of p53 mediated negative growth effects on cell cycle control. JF - Applied and theoretical electrophoresis : the official journal of the International Electrophoresis Society AU - He, C AU - Merrick, B A AU - Patterson, R M AU - Selkirk, J K AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 15 EP - 24 VL - 5 IS - 1 SN - 0954-6642, 0954-6642 KW - Fetal Proteins KW - 0 KW - Index Medicus KW - Phenotype KW - Animals KW - Reference Values KW - Cells, Cultured KW - Electrophoresis, Gel, Two-Dimensional KW - Mice KW - Mice, Transgenic KW - Embryo, Mammalian -- metabolism KW - Image Processing, Computer-Assisted KW - Fibroblasts -- metabolism KW - Alleles KW - Genes, p53 KW - Fetal Proteins -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77690319?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Applied+and+theoretical+electrophoresis+%3A+the+official+journal+of+the+International+Electrophoresis+Society&rft.atitle=Altered+protein+synthesis+in+p53+null+and+hemizygous+transgenic+mouse+embryonic+fibroblasts.&rft.au=He%2C+C%3BMerrick%2C+B+A%3BPatterson%2C+R+M%3BSelkirk%2C+J+K&rft.aulast=He&rft.aufirst=C&rft.date=1995-01-01&rft.volume=5&rft.issue=1&rft.spage=15&rft.isbn=&rft.btitle=&rft.title=Applied+and+theoretical+electrophoresis+%3A+the+official+journal+of+the+International+Electrophoresis+Society&rft.issn=09546642&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-08 N1 - Date created - 1996-02-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tumor necrosis factor-alpha and nitric oxide production in endotoxin-primed rats administered carbon tetrachloride. AN - 77687293; 7475981 AB - Tumor necrosis factor-alpha (TNF alpha) is elevated in the sera of rats administered non-lethal doses of carbon tetrachloride (CCl4) followed by endotoxin. Elevated TNF alpha levels are correlated with the increased release of hepatic enzymes indicating hepatic damage. Under these conditions, nitric oxide (NO) was also produced in the liver as evidenced by the formation of nitrosyl complexes which were measured by electron paramagnetic resonance (EPR) spectroscopy. Decreased nitrosyl complex formation occurred in livers following treatment with either an inhibitor or macrophage activation (gadolinium trichloride; GdCl3), an inhibitor of cytokine responses (dexamethasone) or a NO synthase inhibitor (NG-monomethyl-L-arginine; 1-NMA), GdCl3 or dexamethasone treatment decreased, while 1-NMA treatment increased, TNF alpha serum level. Taken together, these data suggest that TNF alpha and NO are induced following CCl4 and LPS exposure and may be important regulators in the hepatotoxicity of this liver injury model. JF - Life sciences AU - Chamulitrat, W AU - Blazka, M E AU - Jordan, S J AU - Luster, M I AU - Mason, R P AD - Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 2273 EP - 2280 VL - 57 IS - 24 SN - 0024-3205, 0024-3205 KW - Endotoxins KW - 0 KW - Enzyme Inhibitors KW - Tumor Necrosis Factor-alpha KW - omega-N-Methylarginine KW - 27JT06E6GR KW - Nitric Oxide KW - 31C4KY9ESH KW - Dexamethasone KW - 7S5I7G3JQL KW - Arginine KW - 94ZLA3W45F KW - Gadolinium KW - AU0V1LM3JT KW - Carbon Tetrachloride KW - CL2T97X0V0 KW - L-Iditol 2-Dehydrogenase KW - EC 1.1.1.14 KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Aspartate Aminotransferases KW - EC 2.6.1.1 KW - Alanine Transaminase KW - EC 2.6.1.2 KW - gadolinium chloride KW - P7082WY76D KW - Index Medicus KW - Gadolinium -- pharmacology KW - Animals KW - Chemical and Drug Induced Liver Injury KW - Dexamethasone -- pharmacology KW - Macrophage Activation -- drug effects KW - Arginine -- pharmacology KW - Rats KW - Aspartate Aminotransferases -- blood KW - Rats, Sprague-Dawley KW - Alanine Transaminase -- blood KW - L-Iditol 2-Dehydrogenase -- blood KW - Nitric Oxide Synthase -- antagonists & inhibitors KW - Electron Spin Resonance Spectroscopy KW - Kinetics KW - L-Lactate Dehydrogenase -- blood KW - Escherichia coli KW - Enzyme Inhibitors -- pharmacology KW - Arginine -- analogs & derivatives KW - Male KW - Carbon Tetrachloride -- pharmacology KW - Liver -- drug effects KW - Liver -- metabolism KW - Tumor Necrosis Factor-alpha -- biosynthesis KW - Nitric Oxide -- biosynthesis KW - Endotoxins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77687293?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Tumor+necrosis+factor-alpha+and+nitric+oxide+production+in+endotoxin-primed+rats+administered+carbon+tetrachloride.&rft.au=Chamulitrat%2C+W%3BBlazka%2C+M+E%3BJordan%2C+S+J%3BLuster%2C+M+I%3BMason%2C+R+P&rft.aulast=Chamulitrat&rft.aufirst=W&rft.date=1995-01-01&rft.volume=57&rft.issue=24&rft.spage=2273&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 - 1995-12-21 N1 - Date created - 1995-12-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronomodulated 5-day infusion of floxuridine and L-folinic acid in patients with advanced malignancies: a feasibility and tolerability study. AN - 77681264; 8528973 AB - The best schedule for administering floxuridine (FUDR) has not yet been established. Duration of infusion, need (and dosage) of leucovorin (folinic acid, FA), and circadian timing need to be further specified. Nevertheless, FUDR delivery according to circadian rhythms has allowed increase of dose intensity without enhancing the side effects. A 5-day infusional schedule combining FUDR and L-FA was devised as an attempt to increase dose intensity and to provide therapy every 3 weeks to patients with advanced cancer. An ambulatory programmable-in-time pump was used for this purpose. Fourteen patients entered this trial. Two dose levels (mg/kg x 5 days) were evaluated: 0.5 mg/kg/day in six patients and 0.525 mg/kg/day in eight patients. Both patient groups received a concurrent infusion of L-FA 10 mg/m2/day i.v. The delivery patterns of both FUDR and L-FA varied sinusoidally during the 24 hours with a maximum at 18.00 hours. Courses were repeated every 3 weeks. Of 35 courses, treatment produced mucosites greater than grade 2 in only two of them. No severe diarrhea, the dose-limiting toxicity of FUDR when infused over 14 days, was encountered at the dose levels tested. This 5-day chronotherapy schedule allowed delivery of a larger amount of FUDR than the flat delivery described in a previous report. A daily dose of 0.525 mg/kg FUDR, combined with 10 mg/mg2 L-FA, with intraindividual dose escalation according to tolerance, is recommended for future investigations of the activity of this chronotherapy schedule. JF - The Journal of infusional chemotherapy AU - Garufi, C AU - Lévi, F AU - Giunta, S AU - Aschelter, A AU - Pace, R AU - Nisticò, C AU - Terzoli, E AD - Service of Complementary Medical Oncology, Regina Elena National Cancer Institute, Rome, Italy. Y1 - 1995 PY - 1995 DA - 1995 SP - 134 EP - 137 VL - 5 IS - 3 Suppl 1 SN - 1060-0051, 1060-0051 KW - Antidotes KW - 0 KW - Antimetabolites, Antineoplastic KW - Floxuridine KW - 039LU44I5M KW - Leucovorin KW - Q573I9DVLP KW - Index Medicus KW - Kidney Neoplasms -- drug therapy KW - Drug Administration Schedule KW - Humans KW - Colorectal Neoplasms -- physiopathology KW - Aged KW - Carcinoma, Renal Cell -- drug therapy KW - Carcinoma, Renal Cell -- physiopathology KW - Colorectal Neoplasms -- drug therapy KW - Stomach Neoplasms -- drug therapy KW - Feasibility Studies KW - Adult KW - Chronobiology Phenomena KW - Stomach Neoplasms -- physiopathology KW - Middle Aged KW - Kidney Neoplasms -- physiopathology KW - Infusions, Intravenous -- instrumentation KW - Male KW - Female KW - Infusions, Intravenous -- methods KW - Floxuridine -- administration & dosage KW - Neoplasms -- drug therapy KW - Antimetabolites, Antineoplastic -- administration & dosage KW - Floxuridine -- therapeutic use KW - Antidotes -- administration & dosage KW - Leucovorin -- administration & dosage KW - Neoplasms -- physiopathology KW - Antidotes -- therapeutic use KW - Antimetabolites, Antineoplastic -- therapeutic use KW - Leucovorin -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77681264?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+infusional+chemotherapy&rft.atitle=Chronomodulated+5-day+infusion+of+floxuridine+and+L-folinic+acid+in+patients+with+advanced+malignancies%3A+a+feasibility+and+tolerability+study.&rft.au=Garufi%2C+C%3BL%C3%A9vi%2C+F%3BGiunta%2C+S%3BAschelter%2C+A%3BPace%2C+R%3BNistic%C3%B2%2C+C%3BTerzoli%2C+E&rft.aulast=Garufi&rft.aufirst=C&rft.date=1995-01-01&rft.volume=5&rft.issue=3+Suppl+1&rft.spage=134&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+infusional+chemotherapy&rft.issn=10600051&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-01 N1 - Date created - 1996-02-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A quantum mechanical model of the hydration and acidity of the active site in aspartic proteases. AN - 77678989; 8540370 JF - Advances in experimental medicine and biology AU - Topol, I A AU - Cachau, R E AU - Burt, S K AU - Erickson, J W AD - Structural Biochemistry Program, Frederick Biomedical Supercomputing Center, PRI/DynCorp, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 549 EP - 554 VL - 362 SN - 0065-2598, 0065-2598 KW - Recombinant Proteins KW - 0 KW - Aspartic Acid Endopeptidases KW - EC 3.4.23.- KW - Index Medicus KW - Quantum Theory KW - Mutagenesis, Site-Directed KW - Thermodynamics KW - Recombinant Proteins -- metabolism KW - Hydrogen-Ion Concentration KW - Point Mutation KW - Molecular Sequence Data KW - Crystallography, X-Ray KW - Amino Acid Sequence KW - Recombinant Proteins -- chemistry KW - Electrochemistry KW - Protein Conformation KW - Catalysis KW - Binding Sites KW - Aspartic Acid Endopeptidases -- metabolism KW - Aspartic Acid Endopeptidases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77678989?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+experimental+medicine+and+biology&rft.atitle=A+quantum+mechanical+model+of+the+hydration+and+acidity+of+the+active+site+in+aspartic+proteases.&rft.au=Topol%2C+I+A%3BCachau%2C+R+E%3BBurt%2C+S+K%3BErickson%2C+J+W&rft.aulast=Topol&rft.aufirst=I&rft.date=1995-01-01&rft.volume=362&rft.issue=&rft.spage=549&rft.isbn=&rft.btitle=&rft.title=Advances+in+experimental+medicine+and+biology&rft.issn=00652598&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-02-06 N1 - Date created - 1996-02-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic heterogeneity in mammalian specific-locus mutation systems. AN - 77664380; 7588643 JF - Environmental and molecular mutagenesis AU - Malling, H V AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 187 EP - 188 VL - 26 IS - 3 SN - 0893-6692, 0893-6692 KW - Mutagens KW - 0 KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Mammals KW - Spermatogonia -- drug effects KW - Risk Factors KW - Humans KW - Oocytes -- drug effects KW - Mice, Inbred C3H KW - Mutagens -- toxicity KW - Mice KW - Male KW - Female KW - Mutagenesis, Site-Directed KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77664380?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+and+molecular+mutagenesis&rft.atitle=Genetic+heterogeneity+in+mammalian+specific-locus+mutation+systems.&rft.au=Malling%2C+H+V&rft.aulast=Malling&rft.aufirst=H&rft.date=1995-01-01&rft.volume=26&rft.issue=3&rft.spage=187&rft.isbn=&rft.btitle=&rft.title=Environmental+and+molecular+mutagenesis&rft.issn=08936692&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-18 N1 - Date created - 1995-12-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I clinical trial of continuous infusion cyclopentenyl cytosine. AN - 77658144; 7554044 AB - Cyclopentenyl cytosine (CPE-C) is an investigational drug that is active against human solid tumor xenografts. The 5'-triphosphate of CPE-C inhibits CTP synthase, and depletes CTP and dCTP pools. We conducted a phase I clinical trial of CPE-C given as a 24-h continuous i.v. infusion every 3 weeks in 26 adults with solid tumors. The starting dose rate, 1 mg/m2 per h, was selected on the basis of both preclinical studies and pharmacokinetic data from two patients obtained after a test dose of 24 mg/m2 CPE-C as an i.v. bolus. Dose escalation was guided by clinical toxicity. A total of 87 cycles were given, and ten patients received four or more cycles. The mean CPE-C steady-state plasma levels (Cpss) increased linearly from 0.4 microM to 3.1 microM at dose levels ranging from 1 to 5.9 mg/m2 per h (actual body weight); the mean total body clearance was 146 +/- 38 ml/min per m2. CPE-C was eliminated by both renal excretion of intact drug and deamination to cyclopentenyl uracil in an apparent 2:1 ratio. CTP synthase activity in intact bone marrow mononuclear cells was inhibited by 58% to 100% at 22 h compared to matched pretreatment samples at all CPE-C dose levels. When all data were combined, flux through CTP synthase was decreased by 89.6% +/- 3.1% at 22 h (mean +/- SE, n = 16), and remained inhibited by 67.6% +/- 7.7% (n = 10) for at least 24 h post-CPE-C infusion. Granulocyte and platelet toxicities were dose-dependent, and dose-limiting myelosuppression occurred during the initial cycle in two of three patients treated with 5.9 mg/m2 per h. Four of 11 patients (4 of 20 cycles) who received 4.7 mg/m2 per h CPE-C experienced hypotension 24-48 h after completion of the CPE-C infusion during their first (n = 2), third (n = 1) and sixth cycles (n = 1), respectively. Two of these patients died with refractory hypotension despite aggressive hydration and cardiopulmonary resuscitation. One of 12 patients (28 total cycles) treated with 3.5 mg/m2 per h CPE-C experienced orthostatic hypotension during cycle 1, and this patient had a second episode of orthostatic hypotension at a lower dose (3.0 mg/m2 per h). Hypotension was not seen in patients receiving < or = 2.5 mg/m2 per h CPE-C.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Cancer chemotherapy and pharmacology AU - Politi, P M AU - Xie, F AU - Dahut, W AU - Ford, H AU - Kelley, J A AU - Bastian, A AU - Setser, A AU - Allegra, C J AU - Chen, A P AU - Hamilton, J M AD - NCI-Navy Medical Oncology Branch, National Cancer Institute, Bethesda, MD 20889, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 513 EP - 523 VL - 36 IS - 6 SN - 0344-5704, 0344-5704 KW - Antineoplastic Agents KW - 0 KW - Cytidine KW - 5CSZ8459RP KW - cyclopentenyl cytosine KW - 69MO0NDN8K KW - Ligases KW - EC 6.- KW - Carbon-Nitrogen Ligases KW - EC 6.3.- KW - CTP synthetase KW - EC 6.3.4.2 KW - Index Medicus KW - Hypotension -- chemically induced KW - Ligases -- antagonists & inhibitors KW - Infusions, Intravenous KW - Humans KW - Adult KW - Ligases -- metabolism KW - Metabolic Clearance Rate KW - Bone Marrow -- enzymology KW - Aged KW - Middle Aged KW - Male KW - Female KW - Chromatography, High Pressure Liquid KW - Neoplasms -- drug therapy KW - Antineoplastic Agents -- administration & dosage KW - Cytidine -- adverse effects KW - Antineoplastic Agents -- pharmacokinetics KW - Cytidine -- administration & dosage KW - Cytidine -- pharmacokinetics KW - Cytidine -- analogs & derivatives KW - Neoplasms -- metabolism KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77658144?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phase+I+clinical+trial+of+continuous+infusion+cyclopentenyl+cytosine.&rft.au=Politi%2C+P+M%3BXie%2C+F%3BDahut%2C+W%3BFord%2C+H%3BKelley%2C+J+A%3BBastian%2C+A%3BSetser%2C+A%3BAllegra%2C+C+J%3BChen%2C+A+P%3BHamilton%2C+J+M&rft.aulast=Politi&rft.aufirst=P&rft.date=1995-01-01&rft.volume=36&rft.issue=6&rft.spage=513&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 - 1995-11-21 N1 - Date created - 1995-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Heterozygosity for an exon 12 splicing mutation and a W234G missense mutation in an American child with chronic tyrosinemia type 1. AN - 77655428; 7550234 AB - Hereditary tyrosinemia type 1, an autosomal recessive disorder caused by deficiency of fumarylace-toacetate hydrolase (FAH), manifests in either an acute or a chronic form. We used reverse transcription and the polymerase chain reaction to amplify the FAH cDNA of a 12-year-old American boy with chronic tyrosinemia type 1. The patient is a compound heterozygote for mutations in the FAH gene. One allele contains a missense mutation in codon 234 changing a tryptophan to a glycine; this allele was of maternal origin. Mutagenesis and transfection into COS cells demonstrated that the W234G mutation abolishes FAH activity. The patient's paternally derived allele is a splicing mutation in the +5 position of intron 12, causing either insertion of a 105 bp fragment due to a cryptic splice site, or skipping of exon 12, or skipping of both exons 12 and 13. The chronic phenotype of tyrosinemia type 1 in this patient may be due to some residual, correct splicing by the allele with the splicing mutation. JF - Human mutation AU - Hahn, S H AU - Krasnewich, D AU - Brantly, M AU - Kvittingen, E A AU - Gahl, W A AD - Section of Human Biochemical Genetics, Human Genetics Branch, NICHD, NIH, Bethesda, Maryland 20892, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 66 EP - 73 VL - 6 IS - 1 SN - 1059-7794, 1059-7794 KW - Tyrosine KW - 42HK56048U KW - Index Medicus KW - Base Sequence KW - Exons KW - Humans KW - Heterozygote KW - DNA Mutational Analysis KW - Molecular Sequence Data KW - Chronic Disease KW - Child KW - Male KW - RNA Splicing -- genetics KW - Amino Acid Metabolism, Inborn Errors -- genetics KW - Tyrosine -- genetics KW - Tyrosine -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77655428?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+mutation&rft.atitle=Heterozygosity+for+an+exon+12+splicing+mutation+and+a+W234G+missense+mutation+in+an+American+child+with+chronic+tyrosinemia+type+1.&rft.au=Hahn%2C+S+H%3BKrasnewich%2C+D%3BBrantly%2C+M%3BKvittingen%2C+E+A%3BGahl%2C+W+A&rft.aulast=Hahn&rft.aufirst=S&rft.date=1995-01-01&rft.volume=6&rft.issue=1&rft.spage=66&rft.isbn=&rft.btitle=&rft.title=Human+mutation&rft.issn=10597794&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-21 N1 - Date created - 1995-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Early features of zidovudine-associated myopathy: histopathological findings and clinical correlations. AN - 77644900; 7572071 AB - Zidovudine-induced myopathy is characterized by reversible muscle weakness, wasting, myalgia, fatigue, and elevated creatine kinase (CK). Some zidovudine-treated patients with normal muscle strength experience excessive fatigue, myalgia, or transient mild CK elevations that improve when zidovudine is stopped. To determine the cause of these symptoms, we studied 13 physically fit, HIV-infected men who developed fatigue, myalgia, and reduced endurance, while taking zidovudine for a mean period of 20 months (2-39 months), with neurological evaluation and muscle biopsy processed for enzyme histochemistry and electron microscopy (EM). All subjects had normal muscle strength. In 6 of the 13 patients, muscle biopsies were normal by enzyme histochemistry. EM, however, demonstrated proliferation of normal or abnormal mitochondria, and increased amounts of lipid, glycogen, and lipofuscin. Electromyographic (EMG) studies (5/5) and serum CK (6/6) were normal. The other 7 individuals had signs of moderate to severe mitochondrial abnormalities shown by both light microscopy and EM, characterized by severe destruction, vacuolization, and rare paracrystalline inclusions. Most had elevated CK (4 out of 7) and normal EMG (5 out of 7). The severity of morphological abnormalities did not correlate with duration of HIV infection, zidovudine therapy, or zidovudine dosage. We conclude that in zidovudine-treated patients, symptoms of fatigue, myalgia, reduced endurance, and exercise intolerance represent early signs of zidovudine-induced mitochondriotoxicity, which causes an energy shortage within the muscle fibers even when muscle strength is still normal. Zidovudine, a DNA chain terminator, results in overt myopathy when a critical threshold of molecular, histological, and biochemical dysfunction of mitochondria is crossed, which seems to vary between individuals. JF - Acta neuropathologica AU - Cupler, E J AU - Danon, M J AU - Jay, C AU - Hench, K AU - Ropka, M AU - Dalakas, M C AD - Neuromuscular Diseases Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1382, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 1 EP - 6 VL - 90 IS - 1 SN - 0001-6322, 0001-6322 KW - Zidovudine KW - 4B9XT59T7S KW - Index Medicus KW - AIDS/HIV KW - Muscle Fatigue KW - Humans KW - Adult KW - Electromyography KW - Middle Aged KW - Biopsy KW - Electrophysiology KW - HIV KW - Muscular Diseases -- pathology KW - Zidovudine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77644900?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neuropathologica&rft.atitle=Early+features+of+zidovudine-associated+myopathy%3A+histopathological+findings+and+clinical+correlations.&rft.au=Cupler%2C+E+J%3BDanon%2C+M+J%3BJay%2C+C%3BHench%2C+K%3BRopka%2C+M%3BDalakas%2C+M+C&rft.aulast=Cupler&rft.aufirst=E&rft.date=1995-01-01&rft.volume=90&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Acta+neuropathologica&rft.issn=00016322&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-11-22 N1 - Date created - 1995-11-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I trial of pentosan polysulfate. AN - 77643227; 7499109 AB - Pentosan polysulfate is a semisynthetic pentasaccharide heparinoid derived from beechwood shavings. A total of nineteen patients with various adult solid tumors were treated with three dose levels (15, 22.5, and 30 mg/m2/dose) of subcutaneous pentosan polysulfate every 6 hours. The dose limiting toxicities were thrombocytopenia and elevated transaminases at the dose of 30 mg/m2 every 6 hours. The recommended starting dose for phase II trials is 22.5 mg/m2 given every 6 hours. There was an increase in anticoagulant activity as measured by activated partial thromboplastin time (aPTT) at the dose of 22.5 mg/m2 every 6 hours in most patients. There were no objective responses and three patients had stable disease lasting 16, 19 and 76 weeks. JF - Investigational new drugs AU - Swain, S M AU - Parker, B AU - Wellstein, A AU - Lippman, M E AU - Steakley, C AU - DeLap, R AD - National Cancer Institute, Medical Oncology Branch, Bethesda, Maryland, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 55 EP - 62 VL - 13 IS - 1 SN - 0167-6997, 0167-6997 KW - Anticoagulants KW - 0 KW - Antineoplastic Agents KW - Pentosan Sulfuric Polyester KW - 37300-21-3 KW - Index Medicus KW - Clinical Trials, Phase II as Topic KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Injections, Subcutaneous KW - Male KW - Female KW - Neoplasms -- drug therapy KW - Anticoagulants -- adverse effects KW - Pentosan Sulfuric Polyester -- adverse effects KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77643227?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Investigational+new+drugs&rft.atitle=Phase+I+trial+of+pentosan+polysulfate.&rft.au=Swain%2C+S+M%3BParker%2C+B%3BWellstein%2C+A%3BLippman%2C+M+E%3BSteakley%2C+C%3BDeLap%2C+R&rft.aulast=Swain&rft.aufirst=S&rft.date=1995-01-01&rft.volume=13&rft.issue=1&rft.spage=55&rft.isbn=&rft.btitle=&rft.title=Investigational+new+drugs&rft.issn=01676997&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-18 N1 - Date created - 1996-01-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isolation and utilization of epidermal keratinocytes for oncogene research. AN - 77637374; 8531694 JF - Methods in enzymology AU - Dlugosz, A A AU - Glick, A B AU - Tennenbaum, T AU - Weinberg, W C AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 3 EP - 20 VL - 254 SN - 0076-6879, 0076-6879 KW - Biomarkers, Tumor KW - 0 KW - Indicators and Reagents KW - Index Medicus KW - Animals KW - Fetus KW - Neoplasms, Experimental -- genetics KW - Humans KW - Gene Expression KW - Infant, Newborn KW - Cell Differentiation KW - Plasmids KW - Neoplasms -- genetics KW - Animals, Newborn KW - Cells, Cultured KW - Biomarkers, Tumor -- analysis KW - Male KW - Transfection -- methods KW - Oncogenes KW - Culture Techniques -- methods KW - Epidermis -- cytology KW - Epidermis -- metabolism KW - Keratinocytes -- cytology KW - Culture Techniques -- instrumentation KW - Keratinocytes -- metabolism KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77637374?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Isolation+and+utilization+of+epidermal+keratinocytes+for+oncogene+research.&rft.au=Dlugosz%2C+A+A%3BGlick%2C+A+B%3BTennenbaum%2C+T%3BWeinberg%2C+W+C%3BYuspa%2C+S+H&rft.aulast=Dlugosz&rft.aufirst=A&rft.date=1995-01-01&rft.volume=254&rft.issue=&rft.spage=3&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 - 1996-02-01 N1 - Date created - 1996-02-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mental health/substance abuse treatment in managed care: the Massachusetts Medicaid experience. AN - 77635196; 7498890 AB - Massachusetts was the first state to introduce a statewide specialty mental health managed care plan for its Medicaid program. This study assesses the impact of this program on expenditures, access, and relative quality. Over a one-year period, expenditures were reduced by 22 percent below predicted levels without managed care, without any overall reduction in access or relative quality. Reduced lengths-of-stay, lower prices, and fewer inpatient admissions were the major factors. However, for one population segment--children and adolescents--readmission rates increased slightly, and providers for this group were less satisfied than they were before managed care was adopted. Less costly types of twenty-four-hour care were substituted for inpatient hospital care. This experience supports the usefulness of a managed care program for mental health and substance abuse services, and the applicability of such a program to high-risk populations. JF - Health affairs (Project Hope) AU - Callahan, J J AU - Shepard, D S AU - Beinecke, R H AU - Larson, M J AU - Cavanaugh, D AD - National Institute of Mental Health (NIMH) Training Program, Mental Health Services Research, Heller School, Brandeis University, Waltham, MA, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 173 EP - 184 VL - 14 IS - 3 SN - 0278-2715, 0278-2715 KW - Index Medicus KW - United States KW - Massachusetts KW - Humans KW - Disability Evaluation KW - Cost Control -- trends KW - Patient Admission -- economics KW - State Health Plans -- economics KW - Mental Disorders -- rehabilitation KW - Medicaid -- organization & administration KW - Managed Care Programs -- economics KW - Substance-Related Disorders -- economics KW - Substance-Related Disorders -- rehabilitation KW - Mental Disorders -- economics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77635196?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+affairs+%28Project+Hope%29&rft.atitle=Mental+health%2Fsubstance+abuse+treatment+in+managed+care%3A+the+Massachusetts+Medicaid+experience.&rft.au=Callahan%2C+J+J%3BShepard%2C+D+S%3BBeinecke%2C+R+H%3BLarson%2C+M+J%3BCavanaugh%2C+D&rft.aulast=Callahan&rft.aufirst=J&rft.date=1995-01-01&rft.volume=14&rft.issue=3&rft.spage=173&rft.isbn=&rft.btitle=&rft.title=Health+affairs+%28Project+Hope%29&rft.issn=02782715&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-18 N1 - Date created - 1996-01-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cell transformation by dbl oncogene. AN - 77577387; 7476452 JF - Methods in enzymology AU - Zangrilli, D AU - Eva, A AD - Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 347 EP - 358 VL - 256 SN - 0076-6879, 0076-6879 KW - Guanine Nucleotide Exchange Factors KW - 0 KW - Mcf2 protein, mouse KW - Proto-Oncogene Proteins KW - Retroviridae Proteins, Oncogenic KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Mice KW - Neoplasms, Experimental -- pathology KW - Cloning, Molecular KW - Mutagenesis KW - Mice, Inbred Strains KW - Proto-Oncogene Proteins -- biosynthesis KW - Genetic Vectors KW - Restriction Mapping KW - Protein-Tyrosine Kinases -- biosynthesis KW - Proto-Oncogene Proteins -- genetics KW - Sequence Deletion KW - Retroviridae Proteins, Oncogenic -- genetics KW - Oncogenes KW - Proto-Oncogenes KW - Retroviridae Proteins, Oncogenic -- biosynthesis KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77577387?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cell+transformation+by+dbl+oncogene.&rft.au=Zangrilli%2C+D%3BEva%2C+A&rft.aulast=Zangrilli&rft.aufirst=D&rft.date=1995-01-01&rft.volume=256&rft.issue=&rft.spage=347&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 - 1995-12-15 N1 - Date created - 1995-12-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Considerations concerning the murine hepatocarcinogenicity of selected chlorinated hydrocarbons. AN - 77576960; 8532724 AB - Of the chlorinated hydrocarbons discussed above, all six are associated with induction of hepatocellular neoplasia in mice. None of the six is considered to be potent mutagen and most are without any significant genotoxic activity as assessed by conventional in vitro testing schemes. Although some of the agents have biological effects in common (see Figure 4), there is no single biological response (mode of action) that they all share to provide a mechanistic basis for the observed murine hepatocarcinogenicity. Based upon the information currently available for each of the chlorinated hydrocarbons discussed above, it is probable that some modes of action may be more contributory to the rodent carcinogenic response than others; however, no mode of action, pathway, or mechanism should be considered to be mutually exclusive. The murine hepatocarcinogenic effect of TriCE is most probably contingent upon its species-specific metabolism to trichloroacetic acid and DCA. There is fairly consistent evidence that cytotoxicity and reparative hyperplasia are associated with doses of TriCE that cause induction of liver neoplasms. The possibility that peroxisome proliferation is playing a role in the induction of mouse hepatocellular neoplasia remains a tempting explanation, since higher intracellular steady states of H2O2 production would be consistent with observed enhanced cellular proliferation as well as the possibility of in vivo DNA damage. The mouse hepatocarcinogenicity associated with TetCE most probably is associated with species-specific metabolic production of trichloroacetic acid. As with TriCE, cytotoxicity and reparative hyperplasia may represent a potential mode of action for the observed hepatocarcinogenicity. Once again, the potential for enhanced peroxisome proliferation is consistent with enhanced cell proliferation and oxygen radical damage would help explain the random point mutations in ras proto-oncogenes documented in DNA from TetCE-induced mouse liver tumors. DCA-induced mouse hepatocellular neoplasia is probably influenced by cytotoxicity and reparative hyperplasia, but there is also recent evidence that DCA may directly damage DNA, implying an in vivo genotoxic mechanism may be operational. Likewise, altered expression of several genes suggests that subversion of signal transduction may play a role in the induction or progression of liver tumor development. As with TetCE and TriCE, a role for peroxisome proliferation is still a consideration, although the liver tumor response is obvious at doses too low to cause peroxisome proliferation.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Progress in clinical and biological research AU - Maronpot, R R AU - Anna, C H AU - Devereux, T R AU - Lucier, G W AU - Butterworth, B E AU - Anderson, M W AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 305 EP - 323 VL - 391 SN - 0361-7742, 0361-7742 KW - Hydrocarbons, Chlorinated KW - 0 KW - Polychlorinated Dibenzodioxins KW - Trichloroethylene KW - 290YE8AR51 KW - Methylene Chloride KW - 588X2YUY0A KW - Chloroform KW - 7V31YC746X KW - Dichloroacetic Acid KW - 9LSH52S3LQ KW - Tetrachloroethylene KW - TJ904HH8SN KW - Index Medicus KW - Animals KW - Dichloroacetic Acid -- toxicity KW - Methylene Chloride -- toxicity KW - Polychlorinated Dibenzodioxins -- toxicity KW - Chloroform -- toxicity KW - Mice KW - Tetrachloroethylene -- toxicity KW - Trichloroethylene -- toxicity KW - Male KW - Liver Neoplasms, Experimental -- genetics KW - Hydrocarbons, Chlorinated -- toxicity KW - Liver Neoplasms, Experimental -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77576960?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Progress+in+clinical+and+biological+research&rft.atitle=Considerations+concerning+the+murine+hepatocarcinogenicity+of+selected+chlorinated+hydrocarbons.&rft.au=Maronpot%2C+R+R%3BAnna%2C+C+H%3BDevereux%2C+T+R%3BLucier%2C+G+W%3BButterworth%2C+B+E%3BAnderson%2C+M+W&rft.aulast=Maronpot&rft.aufirst=R&rft.date=1995-01-01&rft.volume=391&rft.issue=&rft.spage=305&rft.isbn=&rft.btitle=&rft.title=Progress+in+clinical+and+biological+research&rft.issn=03617742&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-30 N1 - Date created - 1996-01-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transforming growth factor-beta s in mammary tumorigenesis: promoters or antipromoters? AN - 77575135; 8532712 JF - Progress in clinical and biological research AU - Wakefield, L M AU - Letterio, J J AU - Geiser, A G AU - Flanders, K C AU - O'Shaughnessy, J AU - Roberts, A B AU - Sporn, M B AD - Laboratory of Chemoprevention and Medicine Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 133 EP - 148 VL - 391 SN - 0361-7742, 0361-7742 KW - Anticarcinogenic Agents KW - 0 KW - Carcinogens KW - Transforming Growth Factor beta KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured KW - Humans KW - Up-Regulation -- drug effects KW - Disease Progression KW - Cell Division -- drug effects KW - Female KW - Transforming Growth Factor beta -- pharmacology KW - Mammary Neoplasms, Experimental -- chemically induced KW - Anticarcinogenic Agents -- pharmacology KW - Carcinogens -- toxicity KW - Mammary Neoplasms, Experimental -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77575135?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Progress+in+clinical+and+biological+research&rft.atitle=Transforming+growth+factor-beta+s+in+mammary+tumorigenesis%3A+promoters+or+antipromoters%3F&rft.au=Wakefield%2C+L+M%3BLetterio%2C+J+J%3BGeiser%2C+A+G%3BFlanders%2C+K+C%3BO%27Shaughnessy%2C+J%3BRoberts%2C+A+B%3BSporn%2C+M+B&rft.aulast=Wakefield&rft.aufirst=L&rft.date=1995-01-01&rft.volume=391&rft.issue=&rft.spage=133&rft.isbn=&rft.btitle=&rft.title=Progress+in+clinical+and+biological+research&rft.issn=03617742&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-30 N1 - Date created - 1996-01-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Side effects of rapamycin in the rat. AN - 77573852; 8564638 AB - The side effects of Rapamycin was evaluated by histopathological examination of the heart, kidneys, and eyes of treated Lewis rats. Rapamycin was administered during 14 days by continuous intravenous infusions at doses of 0.5, 1.0, and 1.5 mg/kg/day. Focal myocardial infarction was observed in three of five rats with Rapamycin given at 1.5 mg/kg/day and two of 22 rats with 1.0 mg/kg/day. There were no sign of myocardial toxicity at a Rapamycin dose of 0.5 mg/kg/day. The retina of one eye of a rat treated at a dose of 1.5 mg/kg/day had a small area of focal ischemic necrosis. The kidneys were normal at all doses. JF - Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics AU - Chan, C C AU - Martin, D F AU - Xu, D AU - Roberge, F G AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 177 EP - 181 VL - 11 IS - 2 SN - 1080-7683, 1080-7683 KW - Immunosuppressive Agents KW - 0 KW - Polyenes KW - Sirolimus KW - W36ZG6FT64 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred Lew KW - Infusions, Intravenous KW - Myocardium -- pathology KW - Dose-Response Relationship, Drug KW - Infusion Pumps, Implantable KW - Male KW - Myocardial Infarction -- pathology KW - Kidney -- pathology KW - Myocardial Infarction -- chemically induced KW - Polyenes -- administration & dosage KW - Kidney -- drug effects KW - Heart -- drug effects KW - Eye -- pathology KW - Retinal Necrosis Syndrome, Acute -- pathology KW - Eye -- drug effects KW - Retinal Necrosis Syndrome, Acute -- chemically induced KW - Immunosuppressive Agents -- toxicity KW - Polyenes -- toxicity KW - Immunosuppressive Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77573852?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+ocular+pharmacology+and+therapeutics+%3A+the+official+journal+of+the+Association+for+Ocular+Pharmacology+and+Therapeutics&rft.atitle=Side+effects+of+rapamycin+in+the+rat.&rft.au=Chan%2C+C+C%3BMartin%2C+D+F%3BXu%2C+D%3BRoberge%2C+F+G&rft.aulast=Chan&rft.aufirst=C&rft.date=1995-01-01&rft.volume=11&rft.issue=2&rft.spage=177&rft.isbn=&rft.btitle=&rft.title=Journal+of+ocular+pharmacology+and+therapeutics+%3A+the+official+journal+of+the+Association+for+Ocular+Pharmacology+and+Therapeutics&rft.issn=10807683&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-03-07 N1 - Date created - 1996-03-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of growth factors in mouse skin tumor promotion and premalignant progression. AN - 77571009; 8532731 JF - Progress in clinical and biological research AU - Yuspa, S H AU - Hennings, H AU - Dlugosz, A AU - Tennenbaum, T AU - Glick, A AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 39 EP - 48 VL - 391 SN - 0361-7742, 0361-7742 KW - Carcinogens KW - 0 KW - Fgf7 protein, mouse KW - Fibroblast Growth Factor 10 KW - Growth Substances KW - Transforming Growth Factor alpha KW - Transforming Growth Factor beta KW - Fibroblast Growth Factor 7 KW - 126469-10-1 KW - Fibroblast Growth Factors KW - 62031-54-3 KW - Index Medicus KW - Animals KW - Cells, Cultured KW - Disease Progression KW - Mice KW - Skin Neoplasms -- physiopathology KW - Transforming Growth Factor beta -- physiology KW - Precancerous Conditions -- physiopathology KW - Transforming Growth Factor alpha -- physiology KW - Skin Neoplasms -- chemically induced KW - Carcinogens -- toxicity KW - Growth Substances -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77571009?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Progress+in+clinical+and+biological+research&rft.atitle=The+role+of+growth+factors+in+mouse+skin+tumor+promotion+and+premalignant+progression.&rft.au=Yuspa%2C+S+H%3BHennings%2C+H%3BDlugosz%2C+A%3BTennenbaum%2C+T%3BGlick%2C+A&rft.aulast=Yuspa&rft.aufirst=S&rft.date=1995-01-01&rft.volume=391&rft.issue=&rft.spage=39&rft.isbn=&rft.btitle=&rft.title=Progress+in+clinical+and+biological+research&rft.issn=03617742&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-01-30 N1 - Date created - 1996-01-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structural models of Na+, Ca2+, and K+ channels. AN - 77528019; 7676315 AB - The structure determination of voltage-gated channels by the combination of molecular modeling and mutagenesis experiments is a long term, iterative process. As such, the models should be considered as a work in progress, with changes expected as more data becomes available. The primary role of the models is that they assimilate the known data and provide ideas for further experiments to elucidate the real structures. Although the models presented here have already gone through two or three cycles of development and testing, many aspects remain tentative. Perhaps the most significant result so far is that the P segment was experimentally confirmed to form the ion-selective part of the channel. In a subsequent cycle of testing and modeling, the specific residues responsibility for Na+ and Ca2+ selectivity have been identified and the selectivity filter of K+ channels is now predicted to be formed by the side chains, but rather by the carbonyl oxygens of the conserved Gly-Tyr-Gly sequence backbone. As another example, the 9p residue of the P segment of K+ channels was originally modeled as either being buried in the protein or accessible channels was originally modeled as either being buried in the protein or accessible from inside the cell only. However, once mutation of this residue to histidine was found to affect blockade by extracellular TEA, protons, Zn2+ and histidine reagents (DeBiasi et al., 1993), the models were updated to have this and the hydrophilic residues in the first part of P form a helix that comprises part of the extracellular, outer vestibular of the pore. While this motif was used also for Na+ and Ca2+ pore models (see Fig. 2) where the putative helices are amphipathic, it remains to be verified. Modeling of the size and shape of the outer vestibule of K+ channels was also aided by the data for the binding of CTX in the extracellular entrance to the pore. Similarly, experiments with peptide toxins such as mu and omega conotoxins may prove useful in modeling the outer vestibules of the Na+ and/or Ca2+ channels. While important advances have been made, it is important to realize that these approaches are still very new. In the future we are likely to see improvements on both the theoretical and experimental sides which will greatly advance the process.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Society of General Physiologists series AU - Guy, H R AU - Durell, S R AD - Laboratory of Mathematical Biology, DCBDC, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 1 EP - 16 VL - 50 SN - 0094-7733, 0094-7733 KW - Calcium Channels KW - 0 KW - Potassium Channels KW - Sodium Channels KW - Index Medicus KW - Animals KW - Ion Transport KW - Binding Sites KW - Calcium Channels -- physiology KW - Models, Molecular KW - Sodium Channels -- physiology KW - Potassium Channels -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77528019?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Society+of+General+Physiologists+series&rft.atitle=Structural+models+of+Na%2B%2C+Ca2%2B%2C+and+K%2B+channels.&rft.au=Guy%2C+H+R%3BDurell%2C+S+R&rft.aulast=Guy&rft.aufirst=H&rft.date=1995-01-01&rft.volume=50&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Society+of+General+Physiologists+series&rft.issn=00947733&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-19 N1 - Date created - 1995-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of 1,3-butadiene, benzene, and other volatile organics from wok oil emissions. AN - 77494866; 7663151 AB - As part of a program to determine the underlying factors responsible for genotoxicity and perhaps lung cancer risk in Chinese women, we qualitatively identified the volatile components emitted during the heating of cooking oils to 265 degrees C. 1,3-Butadiene, benzene, and a series of aldehydes, olefins, and saturated hydrocarbons were elucidated in vapors from Chinese rapeseed oil. On a relative basis, the intensity of 1,3-butadiene vapors from this were 15.7-, 6.3-, and 1.4-fold greater than in the vapors from peanut, soybean, and Canola oils, respectively. Thus, the Chinese rapeseed oil yielded a higher emission rate of 1,3-butadiene than the other three oils investigated. The benzene formation rate followed a similar trend, i.e., its intensity in Chinese rapeseed oil was 14-, 6.6-, and 1.7-fold greater than in vapors from peanut, soybean, and Canola oils, respectively. JF - Journal of exposure analysis and environmental epidemiology AU - Pellizzari, E D AU - Michael, L C AU - Thomas, K W AU - Shields, P G AU - Harris, C AD - National Cancer Institute, National Institutes of Health, Laboratory of Human Carcinogenesis, Bethesda, Maryland, USA. PY - 1995 SP - 77 EP - 87 VL - 5 IS - 1 SN - 1053-4245, 1053-4245 KW - Butadienes KW - 0 KW - Hydrocarbons KW - Plant Oils KW - Soybean Oil KW - 8001-22-7 KW - Benzene KW - J64922108F KW - 1,3-butadiene KW - JSD5FGP5VD KW - Index Medicus KW - Lung Neoplasms -- epidemiology KW - Butadienes -- isolation & purification KW - Humans KW - China -- epidemiology KW - Gas Chromatography-Mass Spectrometry KW - Volatilization KW - Benzene -- isolation & purification KW - Lung Neoplasms -- chemically induced KW - Female KW - Hot Temperature KW - Arachis KW - Hydrocarbons -- isolation & purification KW - Brassica UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77494866?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Identification+of+1%2C3-butadiene%2C+benzene%2C+and+other+volatile+organics+from+wok+oil+emissions.&rft.au=Pellizzari%2C+E+D%3BMichael%2C+L+C%3BThomas%2C+K+W%3BShields%2C+P+G%3BHarris%2C+C&rft.aulast=Pellizzari&rft.aufirst=E&rft.date=1995-01-01&rft.volume=5&rft.issue=1&rft.spage=77&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 - 1995-10-12 N1 - Date created - 1995-10-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mentally disordered criminal offenders: five years' data from the Tokyo district public prosecutor's office. AN - 77491454; 7657429 JF - International journal of law and psychiatry AU - Inada, T AU - Minagawa, F AU - Iwashita, S AU - Tokui, T AD - National Institute of Mental Health, National Center of Neurology and Psychiatry, Chiba, Japan. Y1 - 1995 PY - 1995 DA - 1995 SP - 221 EP - 230 VL - 18 IS - 2 SN - 0160-2527, 0160-2527 KW - Index Medicus KW - Educational Status KW - Humans KW - Affective Disorders, Psychotic -- psychology KW - Substance-Related Disorders -- psychology KW - Intellectual Disability -- psychology KW - Demography KW - Japan -- epidemiology KW - Marital Status KW - Homicide -- psychology KW - Intellectual Disability -- complications KW - Risk Factors KW - Affective Disorders, Psychotic -- complications KW - Adult KW - Schizophrenic Psychology KW - Substance-Related Disorders -- complications KW - Female KW - Male KW - Mental Disorders -- epidemiology KW - Crime -- statistics & numerical data KW - Mental Disorders -- psychology KW - Criminal Psychology KW - Mental Disorders -- complications KW - Crime -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77491454?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+law+and+psychiatry&rft.atitle=Mentally+disordered+criminal+offenders%3A+five+years%27+data+from+the+Tokyo+district+public+prosecutor%27s+office.&rft.au=Inada%2C+T%3BMinagawa%2C+F%3BIwashita%2C+S%3BTokui%2C+T&rft.aulast=Inada&rft.aufirst=T&rft.date=1995-01-01&rft.volume=18&rft.issue=2&rft.spage=221&rft.isbn=&rft.btitle=&rft.title=International+journal+of+law+and+psychiatry&rft.issn=01602527&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-10-03 N1 - Date created - 1995-10-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Int J Law Psychiatry. 2002 Jul-Aug;25(4):303-29 [12613047] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glucocorticoid receptor thiols and steroid-binding activity. AN - 77470460; 7651222 JF - Methods in enzymology AU - Simons, S S AU - Pratt, W B AD - Steroid Hormones Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 406 EP - 422 VL - 251 SN - 0076-6879, 0076-6879 KW - Affinity Labels KW - 0 KW - DNA-Binding Proteins KW - HSP90 Heat-Shock Proteins KW - Peptide Fragments KW - Receptors, Glucocorticoid KW - Recombinant Proteins KW - Steroids KW - Sulfhydryl Compounds KW - Sulfhydryl Reagents KW - methyl methanethiosulfonate KW - 2949-92-0 KW - Thioredoxins KW - 52500-60-4 KW - Methyl Methanesulfonate KW - AT5C31J09G KW - Chymotrypsin KW - EC 3.4.21.1 KW - Trypsin KW - EC 3.4.21.4 KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Animals KW - Models, Structural KW - Peptide Fragments -- isolation & purification KW - Thioredoxins -- metabolism KW - Liver -- metabolism KW - Amino Acid Sequence KW - Methyl Methanesulfonate -- analogs & derivatives KW - Binding Sites KW - Methyl Methanesulfonate -- pharmacology KW - Rats KW - Mutagenesis, Site-Directed KW - Peptide Fragments -- chemistry KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Sulfhydryl Reagents -- pharmacology KW - HSP90 Heat-Shock Proteins -- metabolism KW - Recombinant Proteins -- chemistry KW - Protein Conformation KW - Receptors, Glucocorticoid -- chemistry KW - DNA-Binding Proteins -- chemistry KW - Sulfhydryl Compounds -- analysis KW - Receptors, Glucocorticoid -- metabolism KW - Steroids -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77470460?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Glucocorticoid+receptor+thiols+and+steroid-binding+activity.&rft.au=Simons%2C+S+S%3BPratt%2C+W+B&rft.aulast=Simons&rft.aufirst=S&rft.date=1995-01-01&rft.volume=251&rft.issue=&rft.spage=406&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 - 1995-09-28 N1 - Date created - 1995-09-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Stereoselective metabolism of halothane enantiomers to trifluoroacetylated liver proteins. AN - 77456548; 7641575 JF - Drug metabolism reviews AU - Martin, J L AU - Meinwald, J AU - Radford, P AU - Liu, Z AU - Graf, M L AU - Pohl, L R AD - Laboratory of Chemical Pharmacology, NHLBI, NIH, Bethesda, Maryland 20892, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 179 EP - 189 VL - 27 IS - 1-2 SN - 0360-2532, 0360-2532 KW - Enflurane KW - 91I69L5AY5 KW - Isoflurane KW - CYS9AKD70P KW - Halothane KW - UQT9G45D1P KW - Index Medicus KW - Enflurane -- metabolism KW - Mice, Inbred Strains KW - Immunoblotting KW - Animals KW - Stereoisomerism KW - Isoflurane -- metabolism KW - Mice KW - Immunohistochemistry KW - Female KW - Halothane -- metabolism KW - Liver -- drug effects KW - Halothane -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77456548?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+metabolism+reviews&rft.atitle=Stereoselective+metabolism+of+halothane+enantiomers+to+trifluoroacetylated+liver+proteins.&rft.au=Martin%2C+J+L%3BMeinwald%2C+J%3BRadford%2C+P%3BLiu%2C+Z%3BGraf%2C+M+L%3BPohl%2C+L+R&rft.aulast=Martin&rft.aufirst=J&rft.date=1995-01-01&rft.volume=27&rft.issue=1-2&rft.spage=179&rft.isbn=&rft.btitle=&rft.title=Drug+metabolism+reviews&rft.issn=03602532&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-21 N1 - Date created - 1995-09-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isotope effect studies on the cytochrome P450 enzymes. AN - 77453729; 7641584 AB - Isotope effect experiments provide a powerful tool for study of the fundamental aspects of the enzymology of the cytochrome P450 enzymes. Competition between alternate pathways not only allows P450 isotope effects to be observed, but also provides mechanistic information on both oxygen activation and substrate oxidation. Indeed, the kind of knowledge that isotope effect studies can provide is not readily obtainable by other methodologies. JF - Drug metabolism reviews AU - Korzekwa, K R AU - Gillette, J R AU - Trager, W F AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 45 EP - 59 VL - 27 IS - 1-2 SN - 0360-2532, 0360-2532 KW - Isotopes KW - 0 KW - Testosterone KW - 3XMK78S47O KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Deuterium KW - AR09D82C7G KW - Steroid Hydroxylases KW - EC 1.14.- KW - steroid hormone 6-beta-hydroxylase KW - EC 1.14.14.1 KW - Index Medicus KW - Deuterium -- metabolism KW - Animals KW - Steroid Hydroxylases -- metabolism KW - Mutation KW - Testosterone -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77453729?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+metabolism+reviews&rft.atitle=Isotope+effect+studies+on+the+cytochrome+P450+enzymes.&rft.au=Korzekwa%2C+K+R%3BGillette%2C+J+R%3BTrager%2C+W+F&rft.aulast=Korzekwa&rft.aufirst=K&rft.date=1995-01-01&rft.volume=27&rft.issue=1-2&rft.spage=45&rft.isbn=&rft.btitle=&rft.title=Drug+metabolism+reviews&rft.issn=03602532&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-21 N1 - Date created - 1995-09-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical implications of clozapine discontinuation: report of an NIMH workshop. AN - 77432666; 7543218 AB - In September 1994, the National Institute of Mental Health convened a group of scientists to discuss the clinical effects of rapid clozapine discontinuation, especially in light of the introduction of risperidone for the treatment of schizophrenia. Despite concern over recent reports of clinical deterioration (psychotic exacerbations, somatic withdrawal symptoms, and extrapyramidal side effects) in a few patients abruptly discontinued from clozapine, there is currently insufficient information to determine the magnitude of the problems associated with clozapine withdrawal. However, clinicians are reminded that the withdrawal schedule for clozapine indicates a gradual tapering schedule (unless the patient is experiencing severe side effects); that switching patients from clozapine to risperidone does not mean that such tapering is unnecessary; and that the use of risperidone may not produce all of the same effects as clozapine in some treatment-refractory patients. JF - Schizophrenia bulletin AU - Shore, D AU - Matthews, S AU - Cott, J AU - Lieberman, J A AD - Division of Clinical and Treatment Research, NIMH, Rockville, MD 20857, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 333 EP - 338 VL - 21 IS - 2 SN - 0586-7614, 0586-7614 KW - Antipsychotic Agents KW - 0 KW - Isoxazoles KW - Piperidines KW - Clozapine KW - J60AR2IKIC KW - Risperidone KW - L6UH7ZF8HC KW - Index Medicus KW - United States KW - Drug Administration Schedule KW - United States Food and Drug Administration KW - Piperidines -- therapeutic use KW - Humans KW - Antipsychotic Agents -- therapeutic use KW - Isoxazoles -- therapeutic use KW - Clozapine -- therapeutic use KW - Substance Withdrawal Syndrome -- diagnosis KW - Schizophrenic Psychology KW - Substance Withdrawal Syndrome -- psychology KW - Schizophrenia -- drug therapy KW - Clozapine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77432666?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Schizophrenia+bulletin&rft.atitle=Clinical+implications+of+clozapine+discontinuation%3A+report+of+an+NIMH+workshop.&rft.au=Shore%2C+D%3BMatthews%2C+S%3BCott%2C+J%3BLieberman%2C+J+A&rft.aulast=Shore&rft.aufirst=D&rft.date=1995-01-01&rft.volume=21&rft.issue=2&rft.spage=333&rft.isbn=&rft.btitle=&rft.title=Schizophrenia+bulletin&rft.issn=05867614&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-07 N1 - Date created - 1995-09-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of the attention deficit in schizophrenia: a study of patients and their relatives in Ireland. AN - 77427250; 7629753 AB - County Roscommon, a rural area in the western part of Ireland, was the site of a family study of schizophrenia. As part of this study, we have assessed several elements of attention, identified by principal components analysis in previous investigations, in a group of subjects with schizophrenia, first-degree relatives of subjects with schizophrenia and age- and education-matched controls. The schizophrenic subjects performed significantly more poorly than the controls; the performance of the relatives fell somewhere between the other two groups. Those relatives with a DSM-III-R diagnosis (most frequently, alcohol abuse or an affective disorder) tended to perform more poorly on some of the attention elements than relatives without a diagnosis; in contrast, control subjects with diagnoses were not distinguishable from other controls. The attention elements appeared to differ in their capacity to differentiate the groups and each seemed to have a distinctive profile. The effects of alcohol abuse were also considered. The results obtained with this cohort may provide clues concerning the pathophysiological basis of schizophrenia and the heterogeneity of its expression. JF - Journal of psychiatric research AU - Mirsky, A F AU - Yardley, S L AU - Jones, B P AU - Walsh, D AU - Kendler, K S AD - Laboratory of Psychology and Psychopathology, NIMH, Bethesda, MD 20892, USA. PY - 1995 SP - 23 EP - 42 VL - 29 IS - 1 SN - 0022-3956, 0022-3956 KW - Index Medicus KW - Humans KW - Ireland KW - Aged KW - Substance-Related Disorders -- diagnosis KW - Psychiatric Status Rating Scales KW - Adult KW - Cohort Studies KW - Task Performance and Analysis KW - Middle Aged KW - Substance-Related Disorders -- complications KW - Female KW - Male KW - Reaction Time KW - Cognition Disorders -- etiology KW - Cognition Disorders -- diagnosis KW - Schizophrenia -- diagnosis KW - Schizophrenia -- genetics KW - Schizophrenia -- complications KW - Attention UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77427250?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+psychiatric+research&rft.atitle=Analysis+of+the+attention+deficit+in+schizophrenia%3A+a+study+of+patients+and+their+relatives+in+Ireland.&rft.au=Mirsky%2C+A+F%3BYardley%2C+S+L%3BJones%2C+B+P%3BWalsh%2C+D%3BKendler%2C+K+S&rft.aulast=Mirsky&rft.aufirst=A&rft.date=1995-01-01&rft.volume=29&rft.issue=1&rft.spage=23&rft.isbn=&rft.btitle=&rft.title=Journal+of+psychiatric+research&rft.issn=00223956&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-09-07 N1 - Date created - 1995-09-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Preclinical pharmacologic evaluation of geldanamycin as an antitumor agent. AN - 77422923; 7628050 AB - The plasma pharmacokinetics of the anti-tumor antibiotic geldanamycin (GM: NSC 122750), a naturally occurring benzoquinoid ansamycin, was characterized in mice and a beagle dog. Concentrations of GM well above 0.1 microgram/ml, which was typically effective against neoplastic cell lines responsive to the drug in vitro, were achieved in the plasma of the mice and the dog treated by i.v. injection. However, the systemic duration of the drug was relatively short. Plasma levels decayed below 0.1 microgram/ml within 3-4 h after administration of the apparent maximum tolerated doses, which were approximately 20 mg/kg for the mice and 4 mg/kg for the dog. The drug exhibited linear pharmacokinetic behavior within the dose ranges studied. However, there were significant interspecies differences in its disposition. Whereas the mean biological half-life of GM was slightly longer in the mice (77.7 min) than in the dog (57.9 min), its mean residence time in the dog (46.6 min) was more than twofold greater than that observed in the mice (20.7 min). Nevertheless, the drug was cleared from plasma much faster by the dog (49.4 ml/min per kg) than by the mice (30.5 ml/min per kg). These apparent anomalies were principally associated with differences in the relative significance of the terminal phase upon overall drug disposition. The liver appeared to be the principal target organ of acute drug toxicity in the dog. Doses of 2.0 and 4.2 mg/kg both produced elevations in serum levels of the transaminases and other indicators of liver function characteristic of acute hepatic necrosis. Additional effects included symptoms of minor gastrointestinal toxicity and alterations in serum chemistry parameters consistent with less severe nephrotoxicity. Drug-related toxicity appeared to be reversible. In consideration of the potential for acute hepatotoxic reactions to GM, as well as to the other benzoquinoid ansamycins based upon structural analogy, additional pharmacological and therapeutic information is required to ascertain whether these compounds are viable candidates for clinical development. JF - Cancer chemotherapy and pharmacology AU - Supko, J G AU - Hickman, R L AU - Grever, M R AU - Malspeis, L AD - Laboratory of Pharmaceutical Chemistry, National Cancer Institute, Frederick, MD 21701, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 305 EP - 315 VL - 36 IS - 4 SN - 0344-5704, 0344-5704 KW - Antibiotics, Antineoplastic KW - 0 KW - Benzoquinones KW - Lactams, Macrocyclic KW - Quinones KW - geldanamycin KW - Z3K3VJ16KU KW - Index Medicus KW - Animals KW - Drug Screening Assays, Antitumor KW - Liver -- pathology KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Metabolic Clearance Rate KW - Mice KW - Chromatography, High Pressure Liquid KW - Mice, Inbred Strains KW - Necrosis KW - Half-Life KW - Liver -- drug effects KW - Dogs KW - Female KW - Male KW - Quinones -- pharmacokinetics KW - Antibiotics, Antineoplastic -- pharmacology KW - Quinones -- adverse effects KW - Quinones -- pharmacology KW - Antibiotics, Antineoplastic -- pharmacokinetics KW - Antibiotics, Antineoplastic -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77422923?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Preclinical+pharmacologic+evaluation+of+geldanamycin+as+an+antitumor+agent.&rft.au=Supko%2C+J+G%3BHickman%2C+R+L%3BGrever%2C+M+R%3BMalspeis%2C+L&rft.aulast=Supko&rft.aufirst=J&rft.date=1995-01-01&rft.volume=36&rft.issue=4&rft.spage=305&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 - 1995-09-05 N1 - Date created - 1995-09-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Possible role of oxidative damage in metal-induced carcinogenesis. AN - 77418373; 7627727 AB - This review presents and evaluates evidence relevant to the mechanisms of metal carcinogenicity with special emphasis on the emerging hypothesis of the oxidative nature of metals' effect on DNA. The carcinogenic transition metals are capable of in vivo binding with the cell nucleus and causing promutagenic damage that includes DNA base modifications, inter- and intramolecular crosslinking of DNA and proteins, DNA strand breaks, rearrangements, and depurination. The chemistry of that damage and the resulting mutations observed in vitro and in metal-induced tumors are both characteristic for oxidative attack on DNA. The underlying mechanism involves various kinds of active oxygen and other radical species arising from metal-catalyzed redox reactions of O2, H2O2, lipid peroxides, and others, with certain amino acids, peptides, and proteins. Other metal-mediated pathogenic effects, such as enhancement of lipid peroxidation, stimulation of inflammation, inhibition of cellular antioxidant defenses, and inhibition of DNA repair, may also contribute to that mechanism. Thus far, published data revealing the oxidative character of metal-induced promutagenic DNA alterations are particularly strong for two of the most powerful human metal carcinogens, chromium and nickel. However, without excluding contribution of other effects, the promotion of oxidative damage tends to take the leading role in explaining mechanisms of carcinogenicity and acute toxicity of certain other metals as well. JF - Cancer investigation AU - Kasprzak, K S AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 411 EP - 430 VL - 13 IS - 4 SN - 0735-7907, 0735-7907 KW - Carcinogens KW - 0 KW - Environmental Pollutants KW - Metals KW - Reactive Oxygen Species KW - DNA KW - 9007-49-2 KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Mutagenesis -- drug effects KW - Animals KW - Humans KW - DNA -- metabolism KW - DNA -- drug effects KW - Reactive Oxygen Species -- metabolism KW - Environmental Pollutants -- metabolism KW - Environmental Pollutants -- toxicity KW - Carcinogens -- metabolism KW - Oxygen -- toxicity KW - DNA Damage KW - Oxygen -- metabolism KW - Carcinogens -- toxicity KW - Reactive Oxygen Species -- toxicity KW - Metals -- metabolism KW - Metals -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77418373?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Possible+role+of+oxidative+damage+in+metal-induced+carcinogenesis.&rft.au=Kasprzak%2C+K+S&rft.aulast=Kasprzak&rft.aufirst=K&rft.date=1995-01-01&rft.volume=13&rft.issue=4&rft.spage=411&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 - 1995-09-07 N1 - Date created - 1995-09-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Epidemiology. Introduction. AN - 77417131; 7624550 JF - Recent developments in alcoholism : an official publication of the American Medical Society on Alcoholism, the Research Society on Alcoholism, and the National Council on Alcoholism AU - Dufour, M C AU - Fuller, R K AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland 20892, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 3 EP - 7 VL - 12 SN - 0738-422X, 0738-422X KW - Index Medicus KW - Cross-Sectional Studies KW - Risk Factors KW - Humans KW - Adult KW - Incidence KW - Aged KW - Middle Aged KW - United States -- epidemiology KW - Female KW - Alcoholism -- rehabilitation KW - Alcoholism -- epidemiology KW - Alcohol Drinking -- adverse effects KW - Alcohol Drinking -- prevention & control KW - Alcohol Drinking -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77417131?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Recent+developments+in+alcoholism+%3A+an+official+publication+of+the+American+Medical+Society+on+Alcoholism%2C+the+Research+Society+on+Alcoholism%2C+and+the+National+Council+on+Alcoholism&rft.atitle=Epidemiology.+Introduction.&rft.au=Dufour%2C+M+C%3BFuller%2C+R+K&rft.aulast=Dufour&rft.aufirst=M&rft.date=1995-01-01&rft.volume=12&rft.issue=&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Recent+developments+in+alcoholism+%3A+an+official+publication+of+the+American+Medical+Society+on+Alcoholism%2C+the+Research+Society+on+Alcoholism%2C+and+the+National+Council+on+Alcoholism&rft.issn=0738422X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-30 N1 - Date created - 1995-08-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of growth hormone and prolactin immune development and function. AN - 77365522; 7596216 AB - Growth hormone and prolactin are neuroendocrine hormones that exert numerous effects on immune system function and development. Several fundamental questions are addressed in this review. Do neuroendocrine hormones affect specific immune cell types? What is the physiological significance of these effects? Can these effects be exploited clinically? While it is clear that there are indeed significant interactions between the neuroendocrine and immune systems, there are relatively few examples with demonstrated physiological significance. Present studies indicate that growth hormone and prolactin may exert markedly different effects on immune cell types depending on their stage in differentiation. Recent emphasis has also been focussed on the use of these hormones or their antagonists clinically in the treatment of AIDS, cancer, and autoimmune disease states due to their pleiotropic effects and low toxicity after systemic administration. However, we do not yet have a clear picture of how the influence of neuroendocrine hormones may be used to favorably alter pathophysiologic processes affecting immune function and development. JF - Life sciences AU - Murphy, W J AU - Rui, H AU - Longo, D L AD - Biological Carcinogenesis and Development Program, Program Resources, Inc./Dyn Corp, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 1 EP - 14 VL - 57 IS - 1 SN - 0024-3205, 0024-3205 KW - Prolactin KW - 9002-62-4 KW - Growth Hormone KW - 9002-72-6 KW - Index Medicus KW - Animals KW - Humans KW - Immunity, Cellular -- physiology KW - Immune System -- growth & development KW - Prolactin -- physiology KW - Growth Hormone -- physiology KW - Immune System -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77365522?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effects+of+growth+hormone+and+prolactin+immune+development+and+function.&rft.au=Murphy%2C+W+J%3BRui%2C+H%3BLongo%2C+D+L&rft.aulast=Murphy&rft.aufirst=W&rft.date=1995-01-01&rft.volume=57&rft.issue=1&rft.spage=1&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 - 1995-08-03 N1 - Date created - 1995-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytochromes P450 expression systems. AN - 77363582; 7598499 AB - Catalytically active cytochrome P450 enzymes have been successfully expressed in bacterial, yeast, and mammalian cells. A variety of expression vectors have been used, resulting in both transient and stable expression. The system of choice depends on the goals of a particular project. Factors such as expense, ease of use, and yields required should govern the decision whether to use bacterial, yeast, insect, or mammalian cDNA expression. High-level expression of mammalian P450s in bacteria usually requires modifications of the amino-terminal region of the enzyme. The Escherichia coli P450-OR fusion proteins may also come of age for use in fermentation-production processes for the chemical industry. Many cytochromes P450 have been expressed in yeast, with variable levels of expression. Baculovirus, albeit somewhat tedious in having to individualize expression conditions, can produce high levels of enzyme. The standard mammalian cell expression systems, both transient and stable, have been of tremendous value to drug metabolism and carcinogenesis research and will continue to play a role in these areas. JF - Annual review of pharmacology and toxicology AU - Gonzalez, F J AU - Korzekwa, K R AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 369 EP - 390 VL - 35 SN - 0362-1642, 0362-1642 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Bacteria -- genetics KW - Animals KW - Insects -- genetics KW - Humans KW - Genetic Vectors KW - Yeasts -- genetics KW - Viruses -- genetics KW - Cytochrome P-450 Enzyme System -- genetics KW - Cloning, Molecular -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77363582?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annual+review+of+pharmacology+and+toxicology&rft.atitle=Cytochromes+P450+expression+systems.&rft.au=Gonzalez%2C+F+J%3BKorzekwa%2C+K+R&rft.aulast=Gonzalez&rft.aufirst=F&rft.date=1995-01-01&rft.volume=35&rft.issue=&rft.spage=369&rft.isbn=&rft.btitle=&rft.title=Annual+review+of+pharmacology+and+toxicology&rft.issn=03621642&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-01 N1 - Date created - 1995-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carcinogens in foods: heterocyclic amines and cancer and heart disease. AN - 77363280; 7598010 AB - Carcinogens occur naturally in the foods we eat, including a number of HCAs that have been identified in foods (beef, pork, poultry and fish) as a result of cooking. These compounds are formed during the normal cooking process by the reaction of creatine with various amino acids. The HCAs have been identified as a result of their high mutagenic activity in the Ames test. The HCAs can be separated into two types, the nonimidazole and the imidazole type, the latter of which is the predominant type present in Western foods. Both types of HCAs have been found to be carcinogenic in rodent bioassays. Of the three imidazole compounds presently under evaluation in nonhuman primates, IQ has been found to be a potent carcinogen, inducing hepatocellular carcinoma in a majority of the animals in approximately one-seventh of their life span. In addition, a high proportion of the nonhuman primates also had focal IQ-induced myocardial lesions as observed by both light and electron microscopic findings. This information, along with other toxicology data on the HCAs, much of which is cited in this paper, allows the inference to be made that HCAs may be a risk factor for both cancer and cardiovascular disease in humans. JF - Advances in experimental medicine and biology AU - Adamson, R H AU - Thorgeirsson, U P AD - Division of Cancer Etiology, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 211 EP - 220 VL - 369 SN - 0065-2598, 0065-2598 KW - Amines KW - 0 KW - Carcinogens KW - Index Medicus KW - Animals KW - Risk Factors KW - Humans KW - Food Analysis KW - Neoplasms -- etiology KW - Neoplasms, Experimental -- etiology KW - Food -- adverse effects KW - Amines -- toxicity KW - Carcinogens -- toxicity KW - Neoplasms, Experimental -- pathology KW - Heart Diseases -- etiology KW - Heart Diseases -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77363280?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+experimental+medicine+and+biology&rft.atitle=Carcinogens+in+foods%3A+heterocyclic+amines+and+cancer+and+heart+disease.&rft.au=Adamson%2C+R+H%3BThorgeirsson%2C+U+P&rft.aulast=Adamson&rft.aufirst=R&rft.date=1995-01-01&rft.volume=369&rft.issue=&rft.spage=211&rft.isbn=&rft.btitle=&rft.title=Advances+in+experimental+medicine+and+biology&rft.issn=00652598&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-03 N1 - Date created - 1995-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alcohol in the elderly. AN - 77361448; 7598449 AB - Although older individuals drink less and report fewer alcohol-related problems than do younger individuals, alcohol use and abuse are significant health issues for older patients. The signs and symptoms of alcohol problems and dependence in the elderly may not only differ from those of young problem drinkers, but may also be present at lower levels of alcohol consumption. Older alcoholics do well in alcohol treatment. Therefore, discussion of alcohol consumption is a critical part of every history and physical examination for all patients, including older individuals. JF - Annual review of medicine AU - Dufour, M AU - Fuller, R K AD - National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland 20892-7003, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 123 EP - 132 VL - 46 SN - 0066-4219, 0066-4219 KW - Index Medicus KW - Cross-Sectional Studies KW - Diagnosis, Differential KW - Patient Care Team KW - Humans KW - Adult KW - Incidence KW - Aged KW - Middle Aged KW - United States -- epidemiology KW - Physical Examination KW - Male KW - Female KW - Alcoholism -- rehabilitation KW - Alcoholism -- epidemiology KW - Alcoholism -- diagnosis KW - Alcohol Drinking -- adverse effects KW - Alcoholism -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77361448?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annual+review+of+medicine&rft.atitle=Alcohol+in+the+elderly.&rft.au=Dufour%2C+M%3BFuller%2C+R+K&rft.aulast=Dufour&rft.aufirst=M&rft.date=1995-01-01&rft.volume=46&rft.issue=&rft.spage=123&rft.isbn=&rft.btitle=&rft.title=Annual+review+of+medicine&rft.issn=00664219&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-28 N1 - Date created - 1995-07-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rolipram, a selective c-AMP phosphodiesterase inhibitor suppresses oro-facial dyskinetic movements in rats. AN - 77346518; 7791505 AB - Since striatal dopamine D2 receptor supersensitivity in the etiology of tardive dyskinesia has been suggested and dopamine D2 receptors are known to inhibit adenylate cyclase activity resulting in a decrease of cyclic adenosine 3',5'-monophosphate (cAMP) levels, we hypothesized that an increase in cAMP levels ameliorates the condition. In the present study, 21-day haloperidol treatment (1.5 mg/kg I.P.) in rats resulted in an increase in striatal [3H]-spiperone (D2) binding whereas [3H] SCH23390 (D1) binding was unaltered. This haloperidol treatment also induced a significantly increase in the frequency of involuntary chewing movements and tongue protrusions, which are considered as a model of tardive dyskinesia. These dyskinetic movements were suppressed by administration of rolipram (0.5 and 1.0 mg/kg I.P.), an inhibitor of the cAMP phosphodiesterase type IV. The present results suggest that selective cAMP phosphodiesterase type IV inhibitors could be putative therapeutic drugs for tardive dyskinesia. JF - Life sciences AU - Sasaki, H AU - Hashimoto, K AU - Maeda, Y AU - Inada, T AU - Kitao, Y AU - Fukui, S AU - Iyo, M AD - Division of Drug Dependence and Psychotropic Drug Clinical Research, National Institute of Mental Health, Ichikawa, Japan. Y1 - 1995 PY - 1995 DA - 1995 SP - PL443 EP - PL447 VL - 56 IS - 25 SN - 0024-3205, 0024-3205 KW - Benzazepines KW - 0 KW - Pyrrolidinones KW - 3',5'-Cyclic-AMP Phosphodiesterases KW - EC 3.1.4.17 KW - Haloperidol KW - J6292F8L3D KW - Rolipram KW - K676NL63N7 KW - Index Medicus KW - Rats KW - Haloperidol -- adverse effects KW - Animals KW - Rats, Sprague-Dawley KW - Benzazepines -- metabolism KW - Male KW - Dyskinesia, Drug-Induced -- drug therapy KW - Pyrrolidinones -- therapeutic use KW - 3',5'-Cyclic-AMP Phosphodiesterases -- antagonists & inhibitors KW - Pyrrolidinones -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77346518?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Rolipram%2C+a+selective+c-AMP+phosphodiesterase+inhibitor+suppresses+oro-facial+dyskinetic+movements+in+rats.&rft.au=Sasaki%2C+H%3BHashimoto%2C+K%3BMaeda%2C+Y%3BInada%2C+T%3BKitao%2C+Y%3BFukui%2C+S%3BIyo%2C+M&rft.aulast=Sasaki&rft.aufirst=H&rft.date=1995-01-01&rft.volume=56&rft.issue=25&rft.spage=PL443&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 - 1995-07-24 N1 - Date created - 1995-07-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vagal tone regulation during sustained attention in boys exposed to opiates in utero. AN - 77343227; 7785481 AB - Attention and learning problems among children exposed to opiates in utero have been previously reported but are difficult to interpret due to imprecise measurement and inadequate control of postnatal factors. In this study, we used a behavior-based measure of attention (continuous-performance tasks) and a physiological index of sustained attention (cardiac vagal tone) to measure more precisely the process of sustained attention. Boys, aged 7 to 12, exposed to opiates in utero, were compared to boys whose mothers began using illicit substances after the child's birth (environmental controls), and boys whose mothers were non-drug users. This three-group design was intended to isolate in utero effects from postnatal environmental influences. Vagal tone, a measure of heart-rate variability sensitive to vagal influences on the heart, was measured pre- and postbaseline and during the three tasks of the Gordon Diagnostic System (Delay, Vigilance, and Distractibility). Vagal tone has been found to be sensitive to changes in environmental demand for sustained attention in infants, school-age children, and adults. Results indicated that when distractors were added to the vigilance task (Distractibility task), opiate-exposed boys failed to suppress vagal tone compared to both control groups. However, both the opiate-exposed boys and the environmental controls made fewer correct responses than non-drug-exposed controls on this task. These results indicate that normal physiological responses to increased attentional demand may be impaired in boys exposed in utero to opiates in this age range. However, the poor Distractibility scores of both the opiate-exposed and environmental controls suggests an important role of environmental influences on attentional performance. JF - Addictive behaviors AU - Hickey, J E AU - Suess, P E AU - Newlin, D B AU - Spurgeon, L AU - Porges, S W AD - Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224, USA. PY - 1995 SP - 43 EP - 59 VL - 20 IS - 1 SN - 0306-4603, 0306-4603 KW - Heroin KW - 70D95007SX KW - Methadone KW - UC6VBE7V1Z KW - Index Medicus KW - Reaction Time -- drug effects KW - Brain -- drug effects KW - Humans KW - Child KW - Pattern Recognition, Visual -- physiology KW - Reaction Time -- physiology KW - Psychomotor Performance -- physiology KW - Pregnancy KW - Brain -- physiopathology KW - Pattern Recognition, Visual -- drug effects KW - Psychomotor Performance -- drug effects KW - Neuropsychological Tests KW - Personality Assessment KW - Female KW - Male KW - Methadone -- adverse effects KW - Heroin -- adverse effects KW - Methadone -- therapeutic use KW - Vagus Nerve -- physiopathology KW - Heroin Dependence -- physiopathology KW - Arousal -- physiology KW - Vagus Nerve -- drug effects KW - Arousal -- drug effects KW - Attention -- physiology KW - Heroin Dependence -- rehabilitation KW - Attention -- drug effects KW - Heroin Dependence -- psychology KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77343227?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Addictive+behaviors&rft.atitle=Vagal+tone+regulation+during+sustained+attention+in+boys+exposed+to+opiates+in+utero.&rft.au=Hickey%2C+J+E%3BSuess%2C+P+E%3BNewlin%2C+D+B%3BSpurgeon%2C+L%3BPorges%2C+S+W&rft.aulast=Hickey&rft.aufirst=J&rft.date=1995-01-01&rft.volume=20&rft.issue=1&rft.spage=43&rft.isbn=&rft.btitle=&rft.title=Addictive+behaviors&rft.issn=03064603&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-19 N1 - Date created - 1995-07-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protein kinase C in cell signaling: strategies for the development of selective inhibitors. AN - 77338708; 7785505 AB - Protein kinase C plays a central role in the cellular signaling pathway for the lipophilic second messenger sn-1,2-diacylglycerol, which is involved in many biological responses, including tumor promotion and inflammation. A major effort has been directed at understanding diversity within this system in order to develop strategies for selective inhibition. Two classes of ligands for the regulatory domain of protein kinase C have been identified which, although they function in vitro as activators of the enzyme, paradoxically behave in vivo as partial antagonists. Identification of targets for the phorbol esters distinct from protein kinase C argues that antagonists acting on the regulatory and catalytic domains of protein kinase C will have different spectra of action. JF - Agents and actions. Supplements AU - Blumberg, P M AU - Acs, G AU - Acs, P AU - Areces, L B AU - Kazanietz, M G AU - Lewin, N E AU - Szallasi, Z AD - Molecular Mechanisms of Tumor Promotion Section, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 87 EP - 100 VL - 47 SN - 0379-0363, 0379-0363 KW - 1,2-diacylglycerol KW - 0 KW - Bryostatins KW - Diglycerides KW - Lactones KW - Macrolides KW - Phorbol Esters KW - bryostatin 1 KW - 37O2X55Y9E KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Regulatory Sequences, Nucleic Acid KW - Phorbol Esters -- pharmacology KW - Animals KW - Second Messenger Systems KW - Phorbol Esters -- metabolism KW - Humans KW - Lactones -- metabolism KW - Lactones -- pharmacology KW - Diglycerides -- metabolism KW - Binding Sites KW - Protein Kinase C -- metabolism KW - Protein Kinase C -- antagonists & inhibitors KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77338708?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Agents+and+actions.+Supplements&rft.atitle=Protein+kinase+C+in+cell+signaling%3A+strategies+for+the+development+of+selective+inhibitors.&rft.au=Blumberg%2C+P+M%3BAcs%2C+G%3BAcs%2C+P%3BAreces%2C+L+B%3BKazanietz%2C+M+G%3BLewin%2C+N+E%3BSzallasi%2C+Z&rft.aulast=Blumberg&rft.aufirst=P&rft.date=1995-01-01&rft.volume=47&rft.issue=&rft.spage=87&rft.isbn=&rft.btitle=&rft.title=Agents+and+actions.+Supplements&rft.issn=03790363&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-20 N1 - Date created - 1995-07-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of intraperitoneal ATP on tumor growth and bone marrow radiation tolerance. AN - 77326426; 7779434 AB - Transplants of a spontaneous murine fibrosarcoma (FSaII) treated with intraperitoneal ATP were studied in vitro, and in both C3H and nu/nu mice. Daily ATP treatment prolonged tumor volume doubling time in vivo and in vitro. Daily ATP treatments at the maximally tolerated dose (2 mmol/kg i.p.) did not significantly affect the pH or the PCr/Pi, or beta ATP/Pi ratios (measured by MRS). In contrast to the reduced tumor growth rate, there was no change in bone marrow recovery after whole body irradiation. ATP is minimally toxic to animals at active dose levels. It slows tumor growth rate without adversely affecting bone marrow radiation tolerance. ATP might therefore be useful as a biological modifier of chemotherapy or radiation therapy. JF - Acta oncologica (Stockholm, Sweden) AU - Froio, J AU - Abraham, E H AU - Soni, R AU - Epstein, A AU - Okunieff, P AD - Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 419 EP - 422 VL - 34 IS - 3 SN - 0284-186X, 0284-186X KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Index Medicus KW - Injections, Intraperitoneal KW - Animals KW - Tumor Cells, Cultured KW - Dose-Response Relationship, Drug KW - Mice, Inbred C3H KW - Radiation Tolerance KW - Mice, Nude KW - Mice KW - Dose-Response Relationship, Radiation KW - Cell Cycle -- radiation effects KW - Male KW - Female KW - Cell Cycle -- drug effects KW - Magnetic Resonance Spectroscopy KW - Fibrosarcoma -- metabolism KW - Bone Marrow -- pathology KW - Adenosine Triphosphate -- administration & dosage KW - Cell Survival -- drug effects KW - Energy Metabolism -- radiation effects KW - Energy Metabolism -- drug effects KW - Cell Division -- drug effects KW - Fibrosarcoma -- pathology KW - Cell Survival -- radiation effects KW - Bone Marrow -- radiation effects KW - Bone Marrow -- drug effects KW - Adenosine Triphosphate -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77326426?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Acta+oncologica+%28Stockholm%2C+Sweden%29&rft.atitle=Effect+of+intraperitoneal+ATP+on+tumor+growth+and+bone+marrow+radiation+tolerance.&rft.au=Froio%2C+J%3BAbraham%2C+E+H%3BSoni%2C+R%3BEpstein%2C+A%3BOkunieff%2C+P&rft.aulast=Froio&rft.aufirst=J&rft.date=1995-01-01&rft.volume=34&rft.issue=3&rft.spage=419&rft.isbn=&rft.btitle=&rft.title=Acta+oncologica+%28Stockholm%2C+Sweden%29&rft.issn=0284186X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-18 N1 - Date created - 1995-07-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Basic fibroblast growth factor radioprotects bone marrow and not RIF1 tumor. AN - 77324965; 7779437 AB - We examined the potential of bFGF to function as a radioprotector of bone marrow (BM). Total intravenous doses of bFGF ranged from 1 to 24 micrograms/mouse, in 2 divided doses. Whole body radiation (WBI) was given in a single fraction to C3H mice. Histologic observations were performed on femur BM at various times after bFGF (or placebo) treatment. Thigh radiation in thigh-tumor bearing mice was delivered in a single fraction. bFGF increased the LD50/30 of mice in a dose dependent fashion, with an apparent maximum protection obtained with > or = 6 micrograms given half 24 h and half 4 h before irradiation. BM histology shows prominent recovery of megakaryocytes and all cell lineages along with less loss in cellularity compared to control irradiated animals. No radioprotection of RIF1 tumors after bFGF was detected. These results indicate that bFGF may be a selective radioprotector of normal tissue. JF - Acta oncologica (Stockholm, Sweden) AU - Okunieff, P AU - Abraham, E H AU - Moini, M AU - Snyder, M L AU - Gloe, T R AU - Capogrossi, M C AU - Ding, I AD - Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 435 EP - 438 VL - 34 IS - 3 SN - 0284-186X, 0284-186X KW - Radiation-Protective Agents KW - 0 KW - Fibroblast Growth Factor 2 KW - 103107-01-3 KW - Index Medicus KW - Animals KW - Whole-Body Irradiation KW - Dose-Response Relationship, Drug KW - Mice, Inbred C3H KW - Lethal Dose 50 KW - Cell Division -- drug effects KW - Mice KW - Dose-Response Relationship, Radiation KW - Female KW - Cell Line KW - Cell Division -- radiation effects KW - Fibroblast Growth Factor 2 -- pharmacology KW - Bone Marrow -- pathology KW - Neoplasms, Radiation-Induced -- pathology KW - Fibrosarcoma -- pathology KW - Radiation-Protective Agents -- pharmacology KW - Bone Marrow -- radiation effects KW - Bone Marrow -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77324965?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Acta+oncologica+%28Stockholm%2C+Sweden%29&rft.atitle=Basic+fibroblast+growth+factor+radioprotects+bone+marrow+and+not+RIF1+tumor.&rft.au=Okunieff%2C+P%3BAbraham%2C+E+H%3BMoini%2C+M%3BSnyder%2C+M+L%3BGloe%2C+T+R%3BCapogrossi%2C+M+C%3BDing%2C+I&rft.aulast=Okunieff&rft.aufirst=P&rft.date=1995-01-01&rft.volume=34&rft.issue=3&rft.spage=435&rft.isbn=&rft.btitle=&rft.title=Acta+oncologica+%28Stockholm%2C+Sweden%29&rft.issn=0284186X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-18 N1 - Date created - 1995-07-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Proliferating cell nuclear antigen staining of Fischer-344/N rat spleens affected by large granular lymphocyte leukemia. AN - 77316571; 7770695 AB - Large granular lymphocyte (LGL) leukemia commonly occurs in the Fischer-344/N rat. The high spontaneous incidence complicates the interpretation of results from chronic carcinogenicity studies that use this rat strain. As a result, a comprehensive characterization of LGL leukemia is necessary to help understand the leukemogenic process and the applicability of staging for assessing the progression of this disease. In the current study, the proliferation rate of LGL leukemia cells from untreated control Fischer-344 (F-344) rats in 3 stages of leukemia compared to nonleukemic age-matched rats was determined by immunohistochemical staining for proliferating cell nuclear antigen (PCNA). In histologic sections of spleen from aged F-344/N rats affected by LGL leukemia, there was a significant increase of both PCNA labeling and mitotic indices that was most advanced in the spleen of rats with more severe LGL leukemia. These results support biological significance for the morphologic staging system currently in use. JF - Toxicologic pathology AU - Stefanski, S A AU - Greenwell, A AU - Merrick, B A AU - Brown, T T AU - Reynolds, S H AD - Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. PY - 1995 SP - 1 EP - 6 VL - 23 IS - 1 SN - 0192-6233, 0192-6233 KW - Proliferating Cell Nuclear Antigen KW - 0 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Neoplasm Staging KW - Mitotic Index KW - Immunohistochemistry KW - Male KW - Female KW - Leukemia, Lymphoid -- pathology KW - Spleen -- pathology KW - Spleen -- immunology KW - Proliferating Cell Nuclear Antigen -- analysis KW - Leukemia, Lymphoid -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77316571?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Proliferating+cell+nuclear+antigen+staining+of+Fischer-344%2FN+rat+spleens+affected+by+large+granular+lymphocyte+leukemia.&rft.au=Stefanski%2C+S+A%3BGreenwell%2C+A%3BMerrick%2C+B+A%3BBrown%2C+T+T%3BReynolds%2C+S+H&rft.aulast=Stefanski&rft.aufirst=S&rft.date=1995-01-01&rft.volume=23&rft.issue=1&rft.spage=1&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 - 1995-07-05 N1 - Date created - 1995-07-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Degranulating cytotoxic lymphocytes inflict multiple damage pathways on target cells. AN - 77308598; 7774284 JF - Current topics in microbiology and immunology AU - Henkart, P A AU - Williams, M S AU - Nakajima, H AD - Experimental Immunology Branch, NCI-National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 75 EP - 93 VL - 198 SN - 0070-217X, 0070-217X KW - Cytotoxins KW - 0 KW - DNA KW - 9007-49-2 KW - Serine Endopeptidases KW - EC 3.4.21.- KW - Index Medicus KW - Animals KW - Leukemia, Basophilic, Acute -- immunology KW - DNA -- metabolism KW - Exocytosis KW - Cytotoxins -- genetics KW - Models, Biological KW - Rats KW - Cytotoxicity, Immunologic KW - Transfection KW - Serine Endopeptidases -- genetics KW - Cytotoxins -- immunology KW - Cytoplasmic Granules -- immunology KW - Serine Endopeptidases -- immunology KW - T-Lymphocytes, Cytotoxic -- physiology KW - T-Lymphocytes, Cytotoxic -- immunology KW - Cell Degranulation -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77308598?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Degranulating+cytotoxic+lymphocytes+inflict+multiple+damage+pathways+on+target+cells.&rft.au=Henkart%2C+P+A%3BWilliams%2C+M+S%3BNakajima%2C+H&rft.aulast=Henkart&rft.aufirst=P&rft.date=1995-01-01&rft.volume=198&rft.issue=&rft.spage=75&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 - 1995-07-12 N1 - Date created - 1995-07-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A new subclass of alkaloids from a dendrobatid poison frog: a structure for deoxypumiliotoxin 251H. AN - 77297073; 7760066 AB - Deoxypumiliotoxin 251H [4], representing a new subclass of the pumiliotoxin-A class of alkaloids, has been isolated from a dendrobatid frog, Epipedobates tricolor. The structure, elucidated by nmr, gc-Ftir, and mass spectral analyses, is proposed to be an 8-methyl-6-(5-hydroxy-2-methylhexylidene)-1-azabicyclo[4.3.0]nonan e. The absolute stereochemistry and the relative configuration of the hydroxyl group are unknown. JF - Journal of natural products AU - Jain, P AU - Garraffo, H M AU - Spande, T F AU - Yeh, H J AU - Daly, J W AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes, and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0820. Y1 - 1995/01// PY - 1995 DA - January 1995 SP - 100 EP - 104 VL - 58 IS - 1 SN - 0163-3864, 0163-3864 KW - Alkaloids KW - 0 KW - deoxypumiliotoxin 251H KW - Index Medicus KW - Spectroscopy, Fourier Transform Infrared KW - Mass Spectrometry KW - Animals KW - Chromatography, Gas KW - Anura KW - Magnetic Resonance Spectroscopy KW - Alkaloids -- chemistry KW - Alkaloids -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77297073?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+natural+products&rft.atitle=A+new+subclass+of+alkaloids+from+a+dendrobatid+poison+frog%3A+a+structure+for+deoxypumiliotoxin+251H.&rft.au=Jain%2C+P%3BGarraffo%2C+H+M%3BSpande%2C+T+F%3BYeh%2C+H+J%3BDaly%2C+J+W&rft.aulast=Jain&rft.aufirst=P&rft.date=1995-01-01&rft.volume=58&rft.issue=1&rft.spage=100&rft.isbn=&rft.btitle=&rft.title=Journal+of+natural+products&rft.issn=01633864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-29 N1 - Date created - 1995-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunofluorescence techniques for the identification of immune effector cells in rat heart: applications to the study of the myocarditis induced by interleukin-2. AN - 77296391; 7539083 AB - A detailed description is presented of immunohistochemical methods for identification of various types of immune effector cells in rat heart, involving the use of antibodies conjugated with different fluorochromes for the simultaneous demonstration of 2 or 3 different antigens by means of fluorescence microscopy. The initial results of the application of these techniques to the study of the myocarditis induced by interleukin-2 (IL-2) are also presented. Antibodies used included: OX6 antibody (for MHC class II molecules, mainly expressed by dendritic cells): W3/25 and OX8 antibody, for the demonstration of the rat equivalents of CD5 and CD8, respectively: asialo-GM1 ganglioside antibody for the identification of natural killer (NK) cells and lymphokine activated killer (LAK) cells, and ED2 antibody for labeling of macrophages. Fluorochromes used were: fluorescein isothiocyanate (green), tetramethylrhodamine isothiocyanate (red), Texas red sulfonyl chloride (red), and 7-amino-4-methylcoumarin-3-acetic acid (blue). IL-2-induced myocarditis was characterized histologically by infiltration of the myocardium by mononuclear inflammatory cells, microvascular alteration, interstitial edema, and myocyte damage and necrosis. In the initial stages, NK/LAK cells were the predominant type of infiltrating lymphocytes; however, the numbers of these cells decreased sharply in subsequent stages. Macrophages also were initially abundant, and continued to be prevalent throughout the late stages. CD8+ lymphocytes were more numerous than CD4+ lymphocytes. Dendritic-cells showed a diffuse increase in number and also accumulated around foci of myocyte necrosis. Three phenotypes of dendritic cells were recognized, and the possible implications of these findings are discussed. It is hoped that these techniques will prove useful for the immunohistochemical evaluation of various inflammatory diseases of the heart. JF - Journal of molecular and cellular cardiology AU - Yamamoto, A AU - Wenthold, R J AU - Zhang, J AU - Herman, E H AU - Ferrans, V J AD - Pathology Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995/01// PY - 1995 DA - January 1995 SP - 307 EP - 319 VL - 27 IS - 1 SN - 0022-2828, 0022-2828 KW - Antibodies KW - 0 KW - Antigens, CD KW - Antigens, CD5 KW - Antigens, CD8 KW - Biomarkers KW - Histocompatibility Antigens Class II KW - Interleukin-2 KW - Index Medicus KW - Animals KW - Antigens, CD -- analysis KW - Cell Count KW - Antigens, CD8 -- analysis KW - Killer Cells, Lymphokine-Activated -- immunology KW - Histocompatibility Antigens Class II -- analysis KW - Rats KW - Microscopy, Fluorescence KW - Killer Cells, Lymphokine-Activated -- pathology KW - Rats, Sprague-Dawley KW - Biomarkers -- analysis KW - Time Factors KW - Fluorescent Antibody Technique KW - Immunohistochemistry KW - Male KW - Dendritic Cells -- pathology KW - Dendritic Cells -- immunology KW - Macrophages -- pathology KW - Macrophages -- immunology KW - Myocardium -- immunology KW - Myocardium -- pathology KW - Myocarditis -- pathology KW - Myocarditis -- immunology KW - Myocarditis -- chemically induced KW - T-Lymphocytes -- pathology KW - T-Lymphocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77296391?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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+and+cellular+cardiology&rft.atitle=Immunofluorescence+techniques+for+the+identification+of+immune+effector+cells+in+rat+heart%3A+applications+to+the+study+of+the+myocarditis+induced+by+interleukin-2.&rft.au=Yamamoto%2C+A%3BWenthold%2C+R+J%3BZhang%2C+J%3BHerman%2C+E+H%3BFerrans%2C+V+J&rft.aulast=Yamamoto&rft.aufirst=A&rft.date=1995-01-01&rft.volume=27&rft.issue=1&rft.spage=307&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+and+cellular+cardiology&rft.issn=00222828&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-26 N1 - Date created - 1995-06-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Current status of paclitaxel in the treatment of breast cancer. AN - 77266718; 7749130 AB - Paclitaxel is a highly active single agent as therapy for previously untreated as well as doxorubicin-refractory metastatic breast cancer, with associated response rates of 62% and 20-48%, respectively. Complete responses with paclitaxel occur chiefly in breast cancer patients whose metastatic disease has not been previously treated with chemotherapy. Early data suggest a possible dose-response relationship for paclitaxel in metastatic breast cancer, but the optimal dose has not yet been defined. The optimal duration of infusional paclitaxel treatment is also not yet known. A study of 96-hour infusional paclitaxel in the treatment of doxorubicin- or mitoxantrone-refractory metastatic breast cancer patients has demonstrated a 48% response rate suggesting that prolonged exposures to paclitaxel may offer a therapeutic advantage. Randomized trials of 3- vs 96-hour paclitaxel are ongoing or planned. The relative efficacy of paclitaxel versus standard chemotherapy as front-line or salvage therapy for metastatic breast cancer is currently under study. In addition, two randomized trials are under way in node positive breast cancer patients to study whether treatment with paclitaxel following standard or high dose doxorubicin and cyclophosphamide adjuvant therapy results in improved patient benefit. Combining paclitaxel with other active agents in the treatment of metastatic breast cancer is an area of active investigation. Combined paclitaxel and doxorubicin, administered concurrently or sequentially, is associated with modest complete response rates in metastatic breast cancer patients. Sequential paclitaxel-->doxorubicin administration is associated with more mucositis than is doxorubicin-->paclitaxel when paclitaxel is administered over 24 hours. High doses of cyclophosphamide can be combined with 24- or 72-hour infusional paclitaxel, and phase II studies of this combination are warranted. Early data suggest that administering biweekly paclitaxel and cisplatin to previously untreated metastatic breast cancer patients is associated with high response rates, and confirmatory studies of this combination and schedule are planned. Preclinical data suggest that cell cycle considerations may be important in combining doxorubicin and possibly other agents with paclitaxel. Paclitaxel is an excellent substrate for P-glycoprotein, the protein product of the multidrug resistance-1 (mdr-1) gene, and phase I trials are under way combining paclitaxel with several known blockers of Pgp function. Finally, pilot studies are under way to determine whether the radiation sensitizing effects of paclitaxel can be exploited as part of radiation therapy for patients with locally advanced breast cancer. JF - Breast cancer research and treatment AU - O'Shaughnessy, J A AU - Cowan, K H AD - Medical Breast Cancer Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 27 EP - 37 VL - 33 IS - 1 SN - 0167-6806, 0167-6806 KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Paclitaxel KW - P88XT4IS4D KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Drug Administration Schedule KW - Humans KW - Doxorubicin -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Cisplatin -- administration & dosage KW - Paclitaxel -- administration & dosage KW - Breast Neoplasms -- drug therapy KW - Paclitaxel -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77266718?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Current+status+of+paclitaxel+in+the+treatment+of+breast+cancer.&rft.au=O%27Shaughnessy%2C+J+A%3BCowan%2C+K+H&rft.aulast=O%27Shaughnessy&rft.aufirst=J&rft.date=1995-01-01&rft.volume=33&rft.issue=1&rft.spage=27&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 - 1995-06-22 N1 - Date created - 1995-06-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genomic organization of a mouse glyceraldehyde 3-phosphate dehydrogenase gene (Gapd-s) expressed in post-meiotic spermatogenic cells. AN - 77249101; 7736666 AB - The Gapd-s gene encodes an isoform of the glyceraldehyde 3-phosphate dehydrogenase enzyme expressed only in post-meiotic spermatogenic cells. Two clones containing the Gapd-s gene were isolated from a mouse genomic library. Sequencing and restriction enzyme analysis demonstrated that this single-copy gene contains 11 exons and spans 9596 base pairs. The locations of Gapd-s exons and introns are conserved when compared to the corresponding portions of the chicken and human somatic Gapd genes. The promoter region contains no TATA box, although there is a potential SP1 recognition site within exon 1. Like other TATA-less genes, primer extension analysis reveals some heterogeneity in the site of transcription initiation with Gapd-s transcripts initiating from three discrete sites. Northern analysis demonstrated that a 1.5-kb Gapd-s mRNA is expressed in the testis in at least three mammalian orders, indicating that the Gapd-s gene appeared early in mammalian evolution. Using GAPD-deficient bacteria, mouse GAPD-S was shown to be capable of functioning as a glycolytic enzyme. Since GAPD has been proposed to be a key enzyme regulating glycolysis in spermatogenic cells, GAPD-S may represent a potential target for toxicological or contraceptive agents affecting fertility by interfering with glycolysis. JF - Developmental genetics AU - Welch, J E AU - Brown, P R AU - O'Brien, D A AU - Eddy, E M AD - Gamete Biology Section, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 179 EP - 189 VL - 16 IS - 2 SN - 0192-253X, 0192-253X KW - Gapd-s KW - DNA KW - 9007-49-2 KW - Glyceraldehyde-3-Phosphate Dehydrogenases KW - EC 1.2.1.- KW - Index Medicus KW - Animals KW - Mice, Inbred ICR KW - Exons KW - Transcription, Genetic KW - Mice KW - Rats KW - Rats, Sprague-Dawley KW - Base Sequence KW - Blotting, Southern KW - Introns KW - Molecular Sequence Data KW - TATA Box KW - Species Specificity KW - Glycolysis KW - Male KW - Spermatozoa -- enzymology KW - Glyceraldehyde-3-Phosphate Dehydrogenases -- metabolism KW - Spermatozoa -- cytology KW - Meiosis KW - Glyceraldehyde-3-Phosphate Dehydrogenases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77249101?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Developmental+genetics&rft.atitle=Genomic+organization+of+a+mouse+glyceraldehyde+3-phosphate+dehydrogenase+gene+%28Gapd-s%29+expressed+in+post-meiotic+spermatogenic+cells.&rft.au=Welch%2C+J+E%3BBrown%2C+P+R%3BO%27Brien%2C+D+A%3BEddy%2C+E+M&rft.aulast=Welch&rft.aufirst=J&rft.date=1995-01-01&rft.volume=16&rft.issue=2&rft.spage=179&rft.isbn=&rft.btitle=&rft.title=Developmental+genetics&rft.issn=0192253X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-06 N1 - Date created - 1995-06-06 N1 - Date revised - 2017-01-13 N1 - Gene symbol - Gapd-s N1 - Genetic sequence - U09964; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oligomerization of the HIV type 2 Nef protein: mutational analysis of the heptad leucine repeat motif and cysteine residues. AN - 77247041; 7734198 AB - The human immunodeficiency virus type 2 (HIV-2) Nef protein expressed in Escherichia coli forms highly stable homooligomeric complexes in vitro. Similarly, the native protein synthesized in the persistently infected H9 T cell line also forms stable homooligomers in vivo. To determine whether homooligomer formation is mediated by the leucine zipper-type sequence located in the middle region of the protein, site-directed mutagenesis was used to introduce double and triple point mutations at heptad leucine positions L1, L2, and L4 within the HIV-2NIHZ Nef protein sequence. Here, we show that substitution of a serine residue for the L1 (residue 108) and L2 (residue 115) heptad leucines, and a glutamine residue for the L4 (residue 129) heptad leucine, did not prevent Nef homooligomer formation in vitro. However, a more drastic substitution of alpha-helix-breaking proline residue for the L2 and L4 heptad leucines significantly abrogated ability of the protein to form stable homooligomers. In addition, because significantly higher levels of the Nef oligomers were consistently observed under the nonreducing SDS-PAGE condition, site-specific mutagenesis was also used to examine the role of cysteine residues in generating disulfide-linked Nef dimers in vitro. Here, we also show that single cysteine-to-glycine substitutions at positions 28, 32, or 55 drastically reduced covalent Nef dimer formation and thermal stability of the Nef protein in vitro. Therefore, these results demonstrate that the leucine zipper-type motif in the HIV-2 Nef protein mediates stable homooligomer formation in vitro, and also establish a role for covalent disulfide bonds in the formation of linked Nef dimers and thermal stability of the monomer Nef in vitro. JF - AIDS research and human retroviruses AU - Hodge, D R AU - Chen, Y M AU - Samuel, K P AD - Laboratory of Molecular Oncology, National Cancer Institute, Frederick Research and Development Center, Maryland 21702, USA. Y1 - 1995/01// PY - 1995 DA - January 1995 SP - 65 EP - 79 VL - 11 IS - 1 SN - 0889-2229, 0889-2229 KW - Gene Products, nef KW - 0 KW - Oligonucleotides KW - Recombinant Fusion Proteins KW - nef Gene Products, Human Immunodeficiency Virus KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - AIDS/HIV KW - Mutagenesis, Site-Directed KW - Recombinant Fusion Proteins -- biosynthesis KW - Escherichia coli -- metabolism KW - Cysteine -- chemistry KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Escherichia coli -- genetics KW - Amino Acid Sequence KW - Leucine Zippers -- genetics KW - Gene Products, nef -- genetics KW - Gene Products, nef -- biosynthesis KW - Gene Products, nef -- chemistry KW - HIV-2 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77247041?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Oligomerization+of+the+HIV+type+2+Nef+protein%3A+mutational+analysis+of+the+heptad+leucine+repeat+motif+and+cysteine+residues.&rft.au=Hodge%2C+D+R%3BChen%2C+Y+M%3BSamuel%2C+K+P&rft.aulast=Hodge&rft.aufirst=D&rft.date=1995-01-01&rft.volume=11&rft.issue=1&rft.spage=65&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 - 1995-06-06 N1 - Date created - 1995-06-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interference by nonsteroidal anti-inflammatory drugs in EMIT and TDx assays for drugs of abuse. AN - 77231185; 7723297 AB - Fourteen nonsteroidal anti-inflammatory drugs were evaluated for interference in EMIT and TDx assays for drugs of abuse. Only tolmetin demonstrated significant interferences in the EMIT assay. Urine samples that contained high concentrations of tolmetin (1800 mg/L) had characteristic high molar absorptivity at the wavelength used in EMIT assays (340 nm). Consequently, EMIT analysis of samples resulted in instrument error alarms on a Hitachi 704 instrument and depressed milliabsorbance values (delta A) relative to calibrators. Similar results were obtained with urine samples collected from an arthritic patient after the administration of 200 and 400 mg of tolmetin. When tolmetin samples were mixed with drugs of abuse, depressed delta A values were noted in all assays. Samples containing opiates and cannabinoids tested negative, and instrument error alarms were produced with samples that contained amphetamines. A gas chromatographic-mass spectrometric (GC-MS) assay for benzoylecgonine in the presence of tolmetin was successful, and no interferences were noted. Similar interferences by tolmetin were not observed in TDx assays, probably because of the different wavelength (525 nm) used in this assay. However, a potential for false-positive results in the TDx benzodiazepine assay was noted for urine samples containing high concentrations of fenoprofen, flurbiprofen, indomethacin, ketoprofen, and tolmetin. Generally, it was concluded that the presence of tolmetin in urine samples could lead to the production of unacceptable results by the EMIT assay for drugs of abuse. However, TDx and GC-MS assays were useful alternatives for the analysis of urine samples suspected of containing tolmetin. JF - Journal of analytical toxicology AU - Joseph, R AU - Dickerson, S AU - Willis, R AU - Frankenfield, D AU - Cone, E J AU - Smith, D R AD - Addiction Research Center, National Institute on Drug Abuse, Baltimore, MD 21224. PY - 1995 SP - 13 EP - 17 VL - 19 IS - 1 SN - 0146-4760, 0146-4760 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Cannabinoids KW - Narcotics KW - Street Drugs KW - benzoylecgonine KW - 5353I8I6YS KW - Tolmetin KW - D8K2JPN18B KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Drug Interactions KW - Enzyme Multiplied Immunoassay Technique KW - Cocaine -- urine KW - Humans KW - Tolmetin -- therapeutic use KW - Spectrophotometry, Ultraviolet KW - Narcotics -- urine KW - Calibration KW - Tolmetin -- chemistry KW - Tolmetin -- urine KW - Cocaine -- analogs & derivatives KW - Arthritis -- urine KW - Cannabinoids -- urine KW - Gas Chromatography-Mass Spectrometry KW - Health Personnel KW - Arthritis -- drug therapy KW - Anti-Inflammatory Agents, Non-Steroidal -- urine KW - Anti-Inflammatory Agents, Non-Steroidal -- chemistry KW - Anti-Inflammatory Agents, Non-Steroidal -- metabolism KW - Street Drugs -- metabolism KW - Street Drugs -- urine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77231185?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+analytical+toxicology&rft.atitle=Interference+by+nonsteroidal+anti-inflammatory+drugs+in+EMIT+and+TDx+assays+for+drugs+of+abuse.&rft.au=Joseph%2C+R%3BDickerson%2C+S%3BWillis%2C+R%3BFrankenfield%2C+D%3BCone%2C+E+J%3BSmith%2C+D+R&rft.aulast=Joseph&rft.aufirst=R&rft.date=1995-01-01&rft.volume=19&rft.issue=1&rft.spage=13&rft.isbn=&rft.btitle=&rft.title=Journal+of+analytical+toxicology&rft.issn=01464760&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-25 N1 - Date created - 1995-05-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neuroleptic-induced vacuous chewing movements in rodents: incidence and effects of long-term increases in haloperidol dose. AN - 77230738; 7724705 AB - Rats treated chronically with neuroleptics develop vacuous chewing movements (VCMs), similar in some respects to tardive dyskinesia (TD) in man. The VCM syndrome was used as a model of TD to examine the ability of increased neuroleptic doses to produce long-term suppression of dyskinetic movements. The incidence and persistence of the VCM syndrome in individual rats were also assessed to look for affected and unaffected subgroups. Rats were initially treated for 15 weeks and haloperidol decanoate. For the next 21 weeks, half the group received a 50-150% increase in dose while the other half continued to receive the same dose. Animals were also followed during a 28-week withdrawal period. Total VCM ratings showed a skewed distribution, with some rats exhibiting few movements while others developed marked and persistent movements. Increasing doses did not suppress VCMs, nor did they exacerbate movements during the withdrawal period. To the extent that the VCM syndrome models TD, the absence of long-term suppression of the VCM syndrome suggests that, at this dosage range, increasing depot neuroleptic doses may not be a useful long-term strategy for TD suppression. JF - Psychopharmacology AU - Egan, M F AU - Hyde, T M AU - Kleinman, J E AU - Wyatt, R J AD - Neuropsychiatry Branch, National Institute of Mental Health, NIMH Neuroscience Research Center at St. Elizabeths, Washington, DC 20032, USA. Y1 - 1995/01// PY - 1995 DA - January 1995 SP - 74 EP - 81 VL - 117 IS - 1 SN - 0033-3158, 0033-3158 KW - Delayed-Action Preparations KW - 0 KW - Haloperidol KW - J6292F8L3D KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Dose-Response Relationship, Drug KW - Substance Withdrawal Syndrome -- psychology KW - Male KW - Haloperidol -- pharmacology KW - Haloperidol -- administration & dosage KW - Dyskinesia, Drug-Induced -- psychology KW - Dyskinesia, Drug-Induced -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77230738?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology&rft.atitle=Neuroleptic-induced+vacuous+chewing+movements+in+rodents%3A+incidence+and+effects+of+long-term+increases+in+haloperidol+dose.&rft.au=Egan%2C+M+F%3BHyde%2C+T+M%3BKleinman%2C+J+E%3BWyatt%2C+R+J&rft.aulast=Egan&rft.aufirst=M&rft.date=1995-01-01&rft.volume=117&rft.issue=1&rft.spage=74&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-25 N1 - Date created - 1995-05-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chromosomal mapping of loci influencing sensitivity to cocaine-induced seizures in BXD recombinant inbred strains of mice. AN - 77226791; 7724703 AB - Among inbred mice, genetic factors mediate differences in sensitivity to the convulsant properties of cocaine; however, the gene(s) underlying cocaine's effects have not been identified. To help elucidate the gene(s) responsible for cocaine seizure susceptibility, we used recombinant inbred-quantitative trait loci (RI-QTL) analyses to identify chromosomal loci associated with cocaine-induced seizures. RI-QTL analyses seek to identify associations between a quantitative measure of a particular phenotype and one or more previously mapped marker genes across a panel of RI strains. This report describes an RI-QTL analysis of cocaine seizure susceptibility among 26 BXD RI strains. These strains showed a skewed, bimodal range of seizure susceptibility which could be the result of one or more modifying genes acting in concert with a major gene to influence cocaine sensitivity. Correlating the percent seizures displayed by each strain following 60 mg/kg cocaine with chromosomal marker data for these strains revealed a number of significant correlations clustered in two regions on chromosomes 12 and 6. This is the first identification of putative chromosomal loci associated with a cocaine-related phenotype and should facilitate identification of the gene(s) underlying cocaine toxicity and other cocaine-related phenotypes. JF - Psychopharmacology AU - Miner, L L AU - Marley, R J AD - Genetics Section, National Institute on Drug Abuse, Baltimore, MD 21224, USA. Y1 - 1995/01// PY - 1995 DA - January 1995 SP - 62 EP - 66 VL - 117 IS - 1 SN - 0033-3158, 0033-3158 KW - Genetic Markers KW - 0 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Phenotype KW - Mice, Inbred Strains KW - Animals KW - Dose-Response Relationship, Drug KW - Recombination, Genetic KW - Mice, Inbred C57BL KW - Mice KW - Male KW - Mice, Inbred DBA KW - Seizures -- chemically induced KW - Seizures -- genetics KW - Cocaine -- pharmacology KW - Chromosome Mapping UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77226791?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology&rft.atitle=Chromosomal+mapping+of+loci+influencing+sensitivity+to+cocaine-induced+seizures+in+BXD+recombinant+inbred+strains+of+mice.&rft.au=Miner%2C+L+L%3BMarley%2C+R+J&rft.aulast=Miner&rft.aufirst=L&rft.date=1995-01-01&rft.volume=117&rft.issue=1&rft.spage=62&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-25 N1 - Date created - 1995-05-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The addictive role of nicotine in tobacco use. AN - 77226609; 7724694 JF - Psychopharmacology AU - Henningfield, J E AU - Heishman, S J AD - Clinical Pharmacology Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 1995/01// PY - 1995 DA - January 1995 SP - 11 EP - 13 VL - 117 IS - 1 SN - 0033-3158, 0033-3158 KW - Nicotine KW - 6M3C89ZY6R KW - Index Medicus KW - Animals KW - Humans KW - Tobacco Use Disorder -- psychology KW - Smoking -- psychology KW - Substance-Related Disorders -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77226609?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology&rft.atitle=The+addictive+role+of+nicotine+in+tobacco+use.&rft.au=Henningfield%2C+J+E%3BHeishman%2C+S+J&rft.aulast=Henningfield&rft.aufirst=J&rft.date=1995-01-01&rft.volume=117&rft.issue=1&rft.spage=11&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-25 N1 - Date created - 1995-05-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transformation-resistant mos revertant is unable to activate MAP kinase kinase in response to v-mos or v-raf. AN - 77218570; 7718484 AB - To study the mechanism by which v-mos induces cell transformation, we generated a transformed rat cell line (DTM) containing two functional copies of mos, one encoding the p37v-mos of the m1 wild-type strain of Moloney murine sarcoma virus (Mo-MuSV) and the other the p85gag-mos fusion protein of the ts110 mutant of Moloney murine sarcoma virus. Subsequently, we isolated a revertant cell line (F-1) following transfection of DTM with a mutant retroviral construct (pIC4Neo) carrying a selectable marker. Like DTM, the F-1 revertant contained two integrated copies of v-mos, expressed mos containing viral RNA, and contained rescuable transforming viruses. The revertant did not grow in soft agar, showed a greatly reduced ability to form tumors in nude mice, and exhibited organized tubulin and actin structures similar to those found in normal cells. Revertant cells were resistant to retransformation by v-mos and v-raf but could be retransformed by v-ras. MAP kinase (ERK-2) and MAP kinase kinase (MKK-1) activity, which are constitutively elevated in v-mos- and v-raf-transformed cells, exhibits levels in the F-1 revertant similar to those seen in nontransformed cells. F-1 and normal REF-1 cells express elevated levels of protein phosphatases in comparison to DTM cells. In vivo treatment with okadaic acid, a potent protein phosphatase inhibitor, leads to an increase in MKK-1 and MAP kinase activity in F-1 cells but not in REF-1. The results support the hypothesis that mos acts through the MAP kinase cascade (MKK-1 and ERK-2) to induce cell transformation and that blocking v-mos activation of that cascade (possibly because of increased levels of phosphatase) prevents transformation. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Topol, L Z AU - Marx, M AU - Calothy, G AU - Blair, D G AD - Laboratory of Molecular Oncology, National Cancer Institute, Frederick, Maryland 21702. Y1 - 1995/01// PY - 1995 DA - January 1995 SP - 27 EP - 38 VL - 6 IS - 1 SN - 1044-9523, 1044-9523 KW - v-mos KW - v-raf KW - v-ras KW - Cytoskeletal Proteins KW - 0 KW - DNA Probes KW - Ethers, Cyclic KW - Oncogene Proteins v-mos KW - Retroviridae Proteins, Oncogenic KW - Okadaic Acid KW - 1W21G5Q4N2 KW - Protein Kinases KW - EC 2.7.- KW - Oncogene Proteins v-raf KW - EC 2.7.11.1 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Mitogen-Activated Protein Kinase Kinases KW - EC 2.7.12.2 KW - Phosphoprotein Phosphatases KW - EC 3.1.3.16 KW - ras Proteins KW - EC 3.6.5.2 KW - Index Medicus KW - Calcium-Calmodulin-Dependent Protein Kinases -- genetics KW - Cell Line, Transformed -- cytology KW - Animals KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Enzyme Activation KW - Cytoskeletal Proteins -- chemistry KW - Transcription, Genetic KW - Ethers, Cyclic -- pharmacology KW - ras Proteins -- physiology KW - Rats KW - DNA Probes -- genetics KW - Transfection -- genetics KW - Phosphoprotein Phosphatases -- metabolism KW - Cell Line, Transformed -- enzymology KW - Genes, ras KW - Protein Kinases -- metabolism KW - Retroviridae Proteins, Oncogenic -- genetics KW - Cell Transformation, Viral -- genetics KW - Oncogene Proteins v-mos -- genetics KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77218570?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Transformation-resistant+mos+revertant+is+unable+to+activate+MAP+kinase+kinase+in+response+to+v-mos+or+v-raf.&rft.au=Topol%2C+L+Z%3BMarx%2C+M%3BCalothy%2C+G%3BBlair%2C+D+G&rft.aulast=Topol&rft.aufirst=L&rft.date=1995-01-01&rft.volume=6&rft.issue=1&rft.spage=27&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 - 1995-05-19 N1 - Date created - 1995-05-19 N1 - Date revised - 2017-01-13 N1 - Gene symbol - v-mos; v-raf; v-ras N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Only late, nonmitotic stages of granulocyte differentiation in 32Dcl3 cells are blocked by ectopic expression of murine c-myb and its truncated forms. AN - 77216059; 7536440 AB - In murine leukemia virus-induced myeloid leukemias, insertional mutagenesis of the c-myb locus has been shown to occur frequently. Proto-oncogene activation is achieved in most leukemias by integration of murine leukemia virus upstream of exons 3 or 4 or by integration into exon 9 with consequent truncation of the protein. The present study investigates the effect of ectopic expression of full-length c-myb or c-myb containing amino- or carboxyl-terminal truncations (minus 47 and 248 amino acids, respectively) on granulocyte differentiation in vitro. Recombinant myb retroviruses were used to infect an interleukin 3-dependent progenitor cell line, 32Dcl3, which undergoes terminal differentiation to mature neutrophilic granulocytes in the presence of granulocyte colony-stimulating factor. Overexpression of c-myb did not abrogate the interleukin 3 dependency of the parental cell line. However, cells expressing all forms of c-myb were blocked at an intermediate stage of granulocyte differentiation and continued to proliferate in the presence of granulocyte colony-stimulating factor. After 14 days in medium with granulocyte colony-stimulating factor, myb-expressing cultures predominantly consisted of promyelocytes with some myelocytes and almost undetectable numbers of neutrophilic granulocytes. This suggested that early stages of granulocyte differentiation were not inhibited, a finding that was further supported by the induction of myeloperoxidase, a biochemical marker of promyelocytes. Interestingly, the expression of lactoferrin, known to be a marker of late stages of granulocyte differentiation, was completely inhibited in the cells infected with myb viruses. It was concluded that c-myb expression blocked granulocyte differentiation to the terminal mitotic stages and that deletion of the NH2-terminal 47 amino acids and/or the COOH-terminal 248 amino acids of c-myb neither enhanced nor diminished this effect. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Bies, J AU - Mukhopadhyaya, R AU - Pierce, J AU - Wolff, L AD - Laboratory of Genetics, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1995/01// PY - 1995 DA - January 1995 SP - 59 EP - 68 VL - 6 IS - 1 SN - 1044-9523, 1044-9523 KW - c-myb KW - Interleukin-3 KW - 0 KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-myb KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Peroxidase KW - EC 1.11.1.7 KW - Glyceraldehyde-3-Phosphate Dehydrogenases KW - EC 1.2.1.- KW - Lactoferrin KW - EC 3.4.21.- KW - Index Medicus KW - Animals KW - Apoptosis KW - Peroxidase -- genetics KW - Interleukin-3 -- pharmacology KW - Cell Differentiation -- genetics KW - Mice KW - Granulocyte Colony-Stimulating Factor -- pharmacology KW - Mutagenesis KW - Base Sequence KW - Lactoferrin -- genetics KW - Gene Expression -- genetics KW - Transfection KW - Genetic Vectors KW - Molecular Sequence Data KW - Retroviridae -- genetics KW - Cell Line KW - Cell Division KW - Glyceraldehyde-3-Phosphate Dehydrogenases -- genetics KW - Proto-Oncogene Proteins -- biosynthesis KW - Oncogenes KW - Granulocytes -- metabolism KW - Proto-Oncogene Proteins -- genetics KW - Granulocytes -- virology KW - Granulocytes -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77216059?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Only+late%2C+nonmitotic+stages+of+granulocyte+differentiation+in+32Dcl3+cells+are+blocked+by+ectopic+expression+of+murine+c-myb+and+its+truncated+forms.&rft.au=Bies%2C+J%3BMukhopadhyaya%2C+R%3BPierce%2C+J%3BWolff%2C+L&rft.aulast=Bies&rft.aufirst=J&rft.date=1995-01-01&rft.volume=6&rft.issue=1&rft.spage=59&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 - 1995-05-19 N1 - Date created - 1995-05-19 N1 - Date revised - 2017-01-13 N1 - Gene symbol - c-myb N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Topoisomerase inhibitors. A review of their therapeutic potential in cancer. AN - 77202027; 7705211 AB - The nuclear enzymes topoisomerase I and II are critical for DNA function and cell survival, and recent studies have identified these enzymes as cellular targets for several clinically active anticancer drugs. Topoisomerase II inhibitors (anthracyclines, epipodophyllotoxins, etc.) are active against several types of tumours. However, treatment with these drugs often results in the development of the multi-drug resistance. Because topoisomerase II-active drugs have several different modes of action, different mechanisms of resistance, including decreased activation and increased detoxification by glutathione-dependent enzymes, have also been implicated. Unlike topoisomerase II, topoisomerase I is not a cell cycle-dependent enzyme and, therefore, it is a more desirable cellular target for anticancer drug development. Topoisomerase I inhibitors, such as camptothecin and its derivatives, have shown significant activity against a broad range of tumours and, in general, are not substrates for either the multi-drug-resistance P-170 glycoprotein or the multi-drug-resistance-associated protein. Because of manageable toxicity and encouraging activity against solid tumours, topoisomerase I-active drugs offer promise in the clinical management of human tumours. JF - Drugs AU - Sinha, B K AD - Biochemical and Molecular Pharmacology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1995/01// PY - 1995 DA - January 1995 SP - 11 EP - 19 VL - 49 IS - 1 SN - 0012-6667, 0012-6667 KW - Antibiotics, Antineoplastic KW - 0 KW - Antineoplastic Agents KW - Topoisomerase I Inhibitors KW - Topoisomerase II Inhibitors KW - irinotecan KW - 0H43101T0J KW - 9-aminocamptothecin KW - 5MB77ICE2Q KW - Topotecan KW - 7M7YKX2N15 KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - DNA Topoisomerases, Type II KW - EC 5.99.1.3 KW - Podophyllotoxin KW - L36H50F353 KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - DNA Topoisomerases, Type I -- chemistry KW - Neoplasms -- drug therapy KW - Animals KW - Humans KW - DNA Topoisomerases, Type II -- chemistry KW - Antibiotics, Antineoplastic -- therapeutic use KW - Camptothecin -- analogs & derivatives KW - Camptothecin -- therapeutic use KW - Antineoplastic Agents -- therapeutic use KW - Podophyllotoxin -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77202027?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drugs&rft.atitle=Topoisomerase+inhibitors.+A+review+of+their+therapeutic+potential+in+cancer.&rft.au=Sinha%2C+B+K&rft.aulast=Sinha&rft.aufirst=B&rft.date=1995-01-01&rft.volume=49&rft.issue=1&rft.spage=11&rft.isbn=&rft.btitle=&rft.title=Drugs&rft.issn=00126667&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-09 N1 - Date created - 1995-05-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Smoking without nicotine delivery decreases withdrawal in 12-hour abstinent smokers. AN - 77194433; 7700960 AB - The contribution of sensory factors to smoking satisfaction and nicotine withdrawal symptoms was assessed by evaluating responses to three types of cigarettes: a regular cigarette, a de-nicotinized cigarette (de-nic), and a lettuce leaf cigarette. Doses were varied by requiring subjects to smoke cigarettes using a five-port cigarette manifold. The ratio of the regular or de-nic cigarettes to the lettuce cigarettes was varied across the following values: zero, one, two, and four of five. Seven male smokers were tobacco-deprived for 12 h before testing. On one test day they smoked the de-nic cigarettes, and on another day they smoked the regular cigarettes. Ratings of satisfaction and cigarette linking were directly related to the number of regular or de-nic cigarettes, but were generally higher after the regular cigarette. The regular and de-nic cigarettes were equivalent in reducing acute withdrawal symptoms. Expired CO was similar on both experimental days. The regular cigarette dose-dependently increased plasma nicotine, but the de-nic cigarette did not increase plasma nicotine. These results indicate that sensory characteristics of cigarettes contribute to the abuse liability of smoke-delivered nicotine. The results suggest that smoking cigarettes that do not provide nicotine may temporarily suppress cigarette withdrawal symptoms. JF - Pharmacology, biochemistry, and behavior AU - Butschky, M F AU - Bailey, D AU - Henningfield, J E AU - Pickworth, W B AD - Addiction Research Center, National Institute on Drug Abuse, Baltimore, MD 21224. Y1 - 1995/01// PY - 1995 DA - January 1995 SP - 91 EP - 96 VL - 50 IS - 1 SN - 0091-3057, 0091-3057 KW - Nicotine KW - 6M3C89ZY6R KW - Index Medicus KW - Pupil -- drug effects KW - Humans KW - Adult KW - Skin Temperature -- drug effects KW - Blood Pressure -- drug effects KW - Pulse -- drug effects KW - Male KW - Nicotine -- pharmacology KW - Smoking Cessation KW - Substance Withdrawal Syndrome -- psychology KW - Nicotine -- blood KW - Smoking -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77194433?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacology%2C+biochemistry%2C+and+behavior&rft.atitle=Smoking+without+nicotine+delivery+decreases+withdrawal+in+12-hour+abstinent+smokers.&rft.au=Butschky%2C+M+F%3BBailey%2C+D%3BHenningfield%2C+J+E%3BPickworth%2C+W+B&rft.aulast=Butschky&rft.aufirst=M&rft.date=1995-01-01&rft.volume=50&rft.issue=1&rft.spage=91&rft.isbn=&rft.btitle=&rft.title=Pharmacology%2C+biochemistry%2C+and+behavior&rft.issn=00913057&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-04 N1 - Date created - 1995-05-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Approaches to the development and marketing approval of drugs that prevent cancer. AN - 77191502; 7894318 AB - The broad concept of chemoprevention applies to the prevention of clinical cancer by the administration of chemical agents. Current approaches to the development and marketing approval of drugs to prevent cancer are described by a Working Group from the National Cancer Institute and the Food and Drug Administration. A strategy is presented that identifies candidate drugs, with examples that illustrate how drugs are characterized for efficacy through in vitro transformation modulation and mechanistic assays, and in vivo tumor modulation models of carcinogenesis. Requirements and recommendations for safety evaluation in toxicology testing are given, and the evaluation of pharmacokinetic and pharmacodynamic drug effects and potential surrogate end point biomarkers in Phase I trials are discussed. Appropriate subject populations are identified. Phase II trials should emphasize the evaluation of surrogate end point biomarkers that are highly correlated with cancer incidence and may serve as an estimate of cancer incidence reduction. In Phase III trials the interim analysis of a validated surrogate end point of cancer incidence may facilitate timely and cost-effective marketing of efficacious drugs. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Kelloff, G J AU - Johnson, J R AU - Crowell, J A AU - Boone, C W AU - DeGeorge, J J AU - Steele, V E AU - Mehta, M U AU - Temeck, J W AU - Schmidt, W J AU - Burke, G AD - National Cancer Institute, Division of Cancer Prevention and Control, Bethesda, Maryland 20892. PY - 1995 SP - 1 EP - 10 VL - 4 IS - 1 SN - 1055-9965, 1055-9965 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - United States KW - Drug Screening Assays, Antitumor KW - Animals KW - United States Food and Drug Administration KW - Clinical Trials, Phase II as Topic KW - Clinical Trials, Phase III as Topic KW - Humans KW - Clinical Trials, Phase I as Topic KW - National Institutes of Health (U.S.) KW - Drug Approval KW - Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77191502?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Approaches+to+the+development+and+marketing+approval+of+drugs+that+prevent+cancer.&rft.au=Kelloff%2C+G+J%3BJohnson%2C+J+R%3BCrowell%2C+J+A%3BBoone%2C+C+W%3BDeGeorge%2C+J+J%3BSteele%2C+V+E%3BMehta%2C+M+U%3BTemeck%2C+J+W%3BSchmidt%2C+W+J%3BBurke%2C+G&rft.aulast=Kelloff&rft.aufirst=G&rft.date=1995-01-01&rft.volume=4&rft.issue=1&rft.spage=1&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 - 1995-04-24 N1 - Date created - 1995-04-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recent studies in leukemia epidemiology. AN - 77191023; 7696358 AB - Epidemiologic studies of leukemia have focused on risks related to low-dose but potentially wide-spread exposures of modern living, such as electromagnetic fields, residence near nuclear power plants, and smoking. With the exception of smoking, none of these exposures has been conclusively shown to be related to leukemia risk. Other exposures such as diet, viruses, and hair dyes have also been considered. Investigators are beginning to take advantage of technical advances to refine epidemiologic studies. The inclusion of data on histopathology, cytogenetics, immunophenotype, and molecular genetics may enhance risk factor identification and lead to a better understanding of the pathogenesis of leukemia. JF - Current opinion in oncology AU - Sandler, D P AD - Environmental and Molecular Epidemiology Section, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1995/01// PY - 1995 DA - January 1995 SP - 12 EP - 18 VL - 7 IS - 1 SN - 1040-8746, 1040-8746 KW - ALL-1 KW - BCR-ABL KW - MLL KW - Index Medicus KW - Risk Factors KW - Humans KW - Environmental Exposure KW - Middle Aged KW - Male KW - Female KW - Child, Preschool KW - Leukemia -- epidemiology KW - Leukemia -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77191023?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+opinion+in+oncology&rft.atitle=Recent+studies+in+leukemia+epidemiology.&rft.au=Sandler%2C+D+P&rft.aulast=Sandler&rft.aufirst=D&rft.date=1995-01-01&rft.volume=7&rft.issue=1&rft.spage=12&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+oncology&rft.issn=10408746&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-02 N1 - Date created - 1995-05-02 N1 - Date revised - 2017-01-13 N1 - Gene symbol - ALL-1; BCR-ABL; MLL N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Confirmed assignment of a novel human tyrosine kinase gene (JAK1A) to 1p32.3-->p31.3 by nonisotopic in situ hybridization. AN - 77190342; 7698020 AB - JAK1A is a recently isolated class 3 (nonreceptor) tyrosine kinase that has catalytic domain sequence homology with other kinases and is known to be ubiquitously expressed in all human tissues thus far examined. The gene for this enzyme had previously been localized to chromosome 1 using somatic cell hybrids and linkage analyses. In the present study, fluorescence in situ hybridization was utilized to confirm its localization and regionally assign the gene to chromosome region 1p32.3-->p31.3. JF - Cytogenetics and cell genetics AU - Modi, W S AU - Farrar, W L AU - Howard, O M AD - Biological Carcinogenesis and Development Program, Program Resources Inc./DynCorp., NCI-Frederick Cancer Research and Development Center, MD 21702-1201, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 232 EP - 234 VL - 69 IS - 3-4 SN - 0301-0171, 0301-0171 KW - JAK1A KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - JAK1 protein, human KW - EC 2.7.10.2 KW - Janus Kinase 1 KW - Index Medicus KW - In Situ Hybridization KW - Humans KW - Chromosome Mapping KW - Chromosomes, Human, Pair 1 KW - Protein-Tyrosine Kinases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77190342?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Confirmed+assignment+of+a+novel+human+tyrosine+kinase+gene+%28JAK1A%29+to+1p32.3--%26gt%3Bp31.3+by+nonisotopic+in+situ+hybridization.&rft.au=Modi%2C+W+S%3BFarrar%2C+W+L%3BHoward%2C+O+M&rft.aulast=Modi&rft.aufirst=W&rft.date=1995-01-01&rft.volume=69&rft.issue=3-4&rft.spage=232&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 - 1995-05-04 N1 - Date created - 1995-05-04 N1 - Date revised - 2017-01-13 N1 - Gene symbol - JAK1A N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Illegitimate recombinations between c-myc and immunoglobulin loci are remodeled by deletions in mouse plasmacytomas but not in Burkitt's lymphomas. AN - 77186403; 7895518 AB - Recombinations between c-myc and immunoglobulin loci are a hallmark of Burkitt's lymphomas and mouse plasmacytomas. Analyzing the fine structure of these illegitimate rearrangements has revealed differences between the recombinations in these two tumors. Recombinations are nearly reciprocal in Burkitt's lymphomas, whereas in most BALB/c plasmacytomas large stretches of c-myc sequences have been deleted. The recombinations detected during preneoplastic development of plasmacytomas, in contrast, have most of the c-myc sequences retained on either one of the translocated chromosomes. We conclude that initial recombination structures are subjected to secondary changes in mouse plasmacytomas. In Burkitt's lymphomas the primary recombination sequence is preserved in tumor cells. JF - Current topics in microbiology and immunology AU - Müller, J R AU - Janz, S AU - Potter, M AD - Laboratory of Genetics, NCI, NIH. Y1 - 1995 PY - 1995 DA - 1995 SP - 425 EP - 429 VL - 194 SN - 0070-217X, 0070-217X KW - c-myc KW - Immunoglobulin Heavy Chains KW - 0 KW - Terpenes KW - pristane KW - 26HZV48DT1 KW - Index Medicus KW - Terpenes -- toxicity KW - Animals KW - Granuloma -- chemically induced KW - Humans KW - Chromosomes, Human, Pair 8 -- ultrastructure KW - Mice KW - Translocation, Genetic KW - Polymerase Chain Reaction KW - Mice, Inbred Strains KW - Precancerous Conditions -- genetics KW - Base Sequence KW - Sequence Alignment KW - Molecular Sequence Data KW - Chromosomes, Human, Pair 14 -- ultrastructure KW - Granuloma -- genetics KW - Peritonitis -- chemically induced KW - Peritonitis -- pathology KW - Plasmacytoma -- genetics KW - Plasmacytoma -- chemically induced KW - Genes, myc KW - Recombination, Genetic KW - Burkitt Lymphoma -- genetics KW - Genes, Immunoglobulin KW - Immunoglobulin Heavy Chains -- genetics KW - Sequence Deletion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77186403?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Illegitimate+recombinations+between+c-myc+and+immunoglobulin+loci+are+remodeled+by+deletions+in+mouse+plasmacytomas+but+not+in+Burkitt%27s+lymphomas.&rft.au=M%C3%BCller%2C+J+R%3BJanz%2C+S%3BPotter%2C+M&rft.aulast=M%C3%BCller&rft.aufirst=J&rft.date=1995-01-01&rft.volume=194&rft.issue=&rft.spage=425&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 - 1995-04-24 N1 - Date created - 1995-04-24 N1 - Date revised - 2017-01-13 N1 - Gene symbol - c-myc N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacokinetics of michellamine B, a naphthylisoquinoline alkaloid with in vitro activity against human immunodeficiency virus types 1 and 2, in the mouse and dog. AN - 77185335; 7695336 AB - Michellamine B (MB) is a naturally occurring naphthylisoquinoline alkaloid of novel chemical structure with activity against human immunodeficiency virus (HIV) types 1 and 2 in vitro. In conjunction with its preclinical evaluation, the plasma pharmacokinetics of MB was characterized in mice and dogs treated by intravenous infusions of 1- and 15-min durations, respectively. At doses ranging from 1 to 9 mg/kg of body weight, the drug exhibited apparent first-order kinetics in both species, affording triexponential plasma concentration-time profiles. Treatment with doses of 5 to 9 mg/kg provided peak plasma levels within the range that completely inhibits the cytopathic effects of HIV upon cultured human lymphoblastoid cells (50 to 100 micrograms/ml) without evidence of toxicity. MB had a biological half-life of 2.8 +/- 0.8 h in mice, with a mean residence time of 2.1 +/- 0.3 h, and a total plasma clearance of 2.4 +/- 0.5 ml/min/kg (mean +/- standard deviation; n = 3); however, the terminal-phase contribution to the area under the plasma profile from time zero to infinity was 44.6% +/- 12.9%. In contrast, the terminal phase was the primary determinant of drug disposition in dogs, accounting for 74.1% +/- 2.8% (n = 3) of the area under the curve. Furthermore, the systemic duration of MB was significantly longer in the dogs than in mice, as indicated by mean values of the apparent half-life (11.6 +/- 1.2 h), mean residence time (12.3 +/- 1.8 h), and clearance (0.50 +/- 0.08 ml/min/kg). However, there were no statistical difference between its apparent volume of distribution in the mice (0.60 +/- 0.08 liters/kg) and dogs (0.50 +/- 0.07 liters/kg). A single dog was also treated with a total dose of 97 mg/kg given as a 72-h constant-rate intravenous infusion, since prolonged systemic exposure to potentially therapeutic drug concentrations will very likely be required for clinical anti-HIV effects. Within 4 h after starting the infusion, the plasma MB concentration exceeded 18 micrograms/ml, it reported 50% effective concentration against HIV in vitro, and subsequently increased to 41 micrograms/ml at the end of the infusion. There were no clinical or pathological indications of toxicity. Whereas the total plasma clearance (0.48 ml/min/kg) was within the range observed for dogs treated by 15-min infusion, extension of the postinfusion sampling period from 24 h to 4 days facilitated better definition of the terminal exponential phase, yielding a value of 25.6 h for the biological half-life of MB. The amount of drug excreted by dogs unchanged in the urine ranged from 3.7 to 11.1% of the administered dose. Thus, the major pathways by which the drug is eliminated from the body remain to be identified. On the basis of these findings, continued development of MB as a novel lead compound for the treatment of HIV infection is warranted. JF - Antimicrobial agents and chemotherapy AU - Supko, J G AU - Malspeis, L AD - Laboratory of Pharmaceutical Chemistry, National Cancer Institute, Frederick, Maryland 21701, USA. Y1 - 1995/01// PY - 1995 DA - January 1995 SP - 9 EP - 14 VL - 39 IS - 1 SN - 0066-4804, 0066-4804 KW - Antiviral Agents KW - 0 KW - Isoquinolines KW - Naphthalenes KW - michellamine A KW - 137793-81-8 KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Infusions, Intravenous KW - Dose-Response Relationship, Drug KW - Dogs KW - Metabolic Clearance Rate KW - Mice KW - Male KW - Female KW - Antiviral Agents -- administration & dosage KW - Naphthalenes -- administration & dosage KW - Antiviral Agents -- pharmacokinetics KW - Isoquinolines -- pharmacokinetics KW - HIV-2 -- drug effects KW - Naphthalenes -- pharmacokinetics KW - Naphthalenes -- toxicity KW - Isoquinolines -- toxicity KW - Isoquinolines -- administration & dosage KW - HIV-1 -- drug effects KW - Antiviral Agents -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77185335?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pharmacokinetics+of+michellamine+B%2C+a+naphthylisoquinoline+alkaloid+with+in+vitro+activity+against+human+immunodeficiency+virus+types+1+and+2%2C+in+the+mouse+and+dog.&rft.au=Supko%2C+J+G%3BMalspeis%2C+L&rft.aulast=Supko&rft.aufirst=J&rft.date=1995-01-01&rft.volume=39&rft.issue=1&rft.spage=9&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 - 1995-04-26 N1 - Date created - 1995-04-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer Chemother Rep. 1966 May;50(4):219-44 [4957125] J Pharm Sci. 1972 Apr;61(4):536-41 [5014309] Cancer Res. 1975 May;35(5):1354-64 [804350] J Pharmacokinet Biopharm. 1980 Oct;8(5):497-507 [7252793] Cancer Res. 1958 Aug;18(7):853-6 [13573353] Cancer Treat Rep. 1986 Jan;70(1):73-80 [3753662] J Med Chem. 1991 Dec;34(12):3402-5 [1766007] Science. 1993 May 28;260(5112):1286-93 [7684163] Anal Biochem. 1994 Jan;216(1):52-60 [8135366] J Pharm Sci. 1985 Feb;74(2):229-31 [3989700] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 is not mutated in hepatocellular carcinomas from Alaska Natives. AN - 77184398; 7894327 AB - Hepatocellular carcinoma is common among Alaska Natives. The known risk factor in this population is hepatitis B viral infection; fungal toxins, including aflatoxin B1, have not been detected in foodstuffs. In this series of 14 patients (including 4 siblings and 2 second cousins), 3 patients were less than 12 years old at diagnosis of hepatocellular carcinoma, 8 patients were 13-24 years old, and 3 patients were more than 60 years old. Since p53 mutations occur in 29% of hepatocellular carcinomas worldwide, we tested the tumors for p53 mutations and serum samples for anti-p53 antibodies. Serum samples from these 14 patients did not contain detectable levels of anti-p53 antibodies. Loss of heterozygosity within the p53 locus was not detected in any of 9 informative cases. Immunohistochemical analysis for p53 protein accumulation was negative in all of 11 tumors. DNA sequence analysis of 12 tumor samples showed no evidence of p53 mutation in the highly conserved regions included in exons 5-8. These data, combined with one case from a previous report, indicate a mutation frequency of 0 of 13, which differs significantly from the worldwide frequency of 29% (chi 2 3.9; P = 0.048). These results indicate that liver carcinogenesis among Alaska Natives occurs independently of a traditional p53 pathway. The familial clustering and early onset in this population strongly suggest an inherited genetic predisposition to develop liver cancer. Germline mutations in a tumor suppressor or a cancer susceptibility gene are likely. Future studies of these samples should include investigations of candidate suppressor or susceptibility genes which map to chromosomal regions commonly deleted in liver cancers. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - De Benedetti, V M AU - Welsh, J A AU - Trivers, G E AU - Harpster, A AU - Parkinson, A J AU - Lanier, A P AU - McMahon, B J AU - Bennett, W P AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892. PY - 1995 SP - 79 EP - 82 VL - 4 IS - 1 SN - 1055-9965, 1055-9965 KW - Antibodies KW - 0 KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Chromosome Deletion KW - Polymorphism, Genetic -- genetics KW - Humans KW - Aged KW - Child KW - Sequence Analysis, DNA KW - Chromosome Mapping KW - Exons -- genetics KW - Genes, Tumor Suppressor -- genetics KW - Heterozygote KW - Adult KW - Middle Aged KW - Alaska KW - Genetic Predisposition to Disease KW - Adolescent KW - Antibodies -- analysis KW - Male KW - Female KW - Liver Neoplasms -- metabolism KW - Carcinoma, Hepatocellular -- metabolism KW - Carcinoma, Hepatocellular -- ethnology KW - Carcinoma, Hepatocellular -- genetics KW - Inuits -- genetics KW - Mutation -- genetics KW - Tumor Suppressor Protein p53 -- immunology KW - Tumor Suppressor Protein p53 -- genetics KW - Indians, North American -- genetics KW - Liver Neoplasms -- genetics KW - Liver Neoplasms -- ethnology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77184398?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=p53+is+not+mutated+in+hepatocellular+carcinomas+from+Alaska+Natives.&rft.au=De+Benedetti%2C+V+M%3BWelsh%2C+J+A%3BTrivers%2C+G+E%3BHarpster%2C+A%3BParkinson%2C+A+J%3BLanier%2C+A+P%3BMcMahon%2C+B+J%3BBennett%2C+W+P&rft.aulast=De+Benedetti&rft.aufirst=V&rft.date=1995-01-01&rft.volume=4&rft.issue=1&rft.spage=79&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 - 1995-04-24 N1 - Date created - 1995-04-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of plasmacytomas in genetically susceptible mice with silicone gels. AN - 77184320; 7895524 AB - Silicone gels injected intraperitoneally into strains of mice related to BALB/c develop plasmacytomas in approximately the same numbers and with similar phenotypes as previously obtained with pristane. Silicone gels produce few side effects and are well tolerated for long periods. Silicone gels contain several components that are potentially biologically active: residual vinyl groups and platinum. Microscopic and histological evidence suggests the silicone gel is degraded over a long period of time. Preliminary studies with long chain liquid dimethylpolysiloxanes with viscosities of 1000 cSt and 12,500 cSt have not produced plasmacytomas as yet. The plasmacytomagenic action of the gel appears to be due to the release of liquids from the gel matrix. JF - Current topics in microbiology and immunology AU - Potter, M AU - Morrison, S AU - Miller, F AD - Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD. Y1 - 1995 PY - 1995 DA - 1995 SP - 83 EP - 91 VL - 194 SN - 0070-217X, 0070-217X KW - Gels KW - 0 KW - Oils KW - Silicones KW - Terpenes KW - pristane KW - 26HZV48DT1 KW - Paraffin KW - 8002-74-2 KW - paraffin oils KW - 8012-95-1 KW - Index Medicus KW - Terpenes -- toxicity KW - Injections, Intraperitoneal KW - Peritonitis -- immunology KW - Animals KW - Granuloma -- chemically induced KW - Granuloma -- immunology KW - Mice KW - Chronic Disease KW - Oils -- toxicity KW - Peritonitis -- chemically induced KW - Genetic Predisposition to Disease KW - Cell Transformation, Neoplastic KW - Schistosomiasis mansoni -- immunology KW - Plasmacytoma -- genetics KW - Plasmacytoma -- chemically induced KW - Silicones -- toxicity KW - Mice, Inbred BALB C -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77184320?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Induction+of+plasmacytomas+in+genetically+susceptible+mice+with+silicone+gels.&rft.au=Potter%2C+M%3BMorrison%2C+S%3BMiller%2C+F&rft.aulast=Potter&rft.aufirst=M&rft.date=1995-01-01&rft.volume=194&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 - 1995-04-24 N1 - Date created - 1995-04-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tryptophan synthase. Structure, function, and protein engineering. AN - 77183272; 7900177 JF - Sub-cellular biochemistry AU - Miles, E W AD - Enzyme Structure and Function Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1995 PY - 1995 DA - 1995 SP - 207 EP - 254 VL - 24 SN - 0306-0225, 0306-0225 KW - Macromolecular Substances KW - 0 KW - Multienzyme Complexes KW - Recombinant Proteins KW - Tryptophan Synthase KW - EC 4.2.1.20 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Protein Structure, Secondary KW - Recombinant Proteins -- biosynthesis KW - Recombinant Proteins -- metabolism KW - Models, Molecular KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Recombinant Proteins -- chemistry KW - Salmonella typhimurium -- enzymology KW - Binding Sites KW - Multienzyme Complexes -- chemistry KW - Multienzyme Complexes -- metabolism KW - Tryptophan Synthase -- biosynthesis KW - Multienzyme Complexes -- biosynthesis KW - Tryptophan Synthase -- metabolism KW - Tryptophan Synthase -- chemistry KW - Protein Folding KW - Protein Engineering -- methods KW - Protein Conformation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77183272?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Sub-cellular+biochemistry&rft.atitle=Tryptophan+synthase.+Structure%2C+function%2C+and+protein+engineering.&rft.au=Miles%2C+E+W&rft.aulast=Miles&rft.aufirst=E&rft.date=1995-01-01&rft.volume=24&rft.issue=&rft.spage=207&rft.isbn=&rft.btitle=&rft.title=Sub-cellular+biochemistry&rft.issn=03060225&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-27 N1 - Date created - 1995-04-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interacisternal A-particle (IAP) genes show similar patterns of hypomethylation in established and primary mouse plasmacytomas. AN - 77181872; 7895516 AB - Alterations in cell programming associated with neoplastic transformation may involve widespread changes in patterns of DNA methylation. Increased expression of IAP elements in plasmacytomas compared with LPS-stimulated normal B-cells is accompanied by extensive hypomethylation of IAP sequences (Mietz and Kuff 1990), subsets of which are revealed with the LS2, LS3 and T1 probes. Multiple common LS- and PC-specific IAP loci are hypomethylated in established plasmacytomas, showing that hypomethylation does not occur entirely randomly. Many of the same IAP loci are hypomethylated in primary plasmacytomas induced by two different methods, as soon as recognizable tumor tissue can be isolated. In primary tumors hypomethylation frequently appears to occur in DNA flanking the IAP elements. In the established tumors the hypomethylated sites occur primarily in the IAP LTR, suggesting that for these loci hypomethylation begins in the flanking DNA and is extended into the IAP LTRs during progression of the tumors. The newly hypomethylated IAP LTRs in primary plasmacytomas (as compared to normal B cells) may provide a set of reporter genes for chromosomal regions that are characteristically hypomethylated in these transformed cells and that may contain cellular genes whose activation is related to the transformation process. JF - Current topics in microbiology and immunology AU - Lueders, K K AU - Kuff, E L AD - Laboratory of Biochemistry, National Cancer Institute, Bethesda, MD 20892. Y1 - 1995 PY - 1995 DA - 1995 SP - 405 EP - 414 VL - 194 SN - 0070-217X, 0070-217X KW - c-myc KW - v-Ha-ras KW - DNA, Neoplasm KW - 0 KW - Terpenes KW - pristane KW - 26HZV48DT1 KW - 5-Methylcytosine KW - 6R795CQT4H KW - Mineral Oil KW - 8020-83-5 KW - Cytosine KW - 8J337D1HZY KW - Index Medicus KW - Terpenes -- toxicity KW - Animals KW - Tumor Cells, Cultured KW - Mineral Oil -- toxicity KW - Proviruses -- genetics KW - Mice KW - Mice, Inbred BALB C KW - Methylation KW - Cell Transformation, Viral KW - DNA, Neoplasm -- chemistry KW - Cytosine -- analysis KW - Plasmacytoma -- genetics KW - Plasmacytoma -- chemically induced KW - Plasmacytoma -- pathology KW - Genes, Intracisternal A-Particle KW - DNA, Neoplasm -- genetics KW - Cytosine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77181872?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Interacisternal+A-particle+%28IAP%29+genes+show+similar+patterns+of+hypomethylation+in+established+and+primary+mouse+plasmacytomas.&rft.au=Lueders%2C+K+K%3BKuff%2C+E+L&rft.aulast=Lueders&rft.aufirst=K&rft.date=1995-01-01&rft.volume=194&rft.issue=&rft.spage=405&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 - 1995-04-24 N1 - Date created - 1995-04-24 N1 - Date revised - 2017-01-13 N1 - Gene symbol - c-myc; v-Ha-ras N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Classification of mouse lymphomas. AN - 77181721; 7895485 JF - Current topics in microbiology and immunology AU - Fredrickson, T N AU - Hartley, J W AU - Morse, H C AU - Chattopadhyay, S K AU - Lennert, K AD - Registry of Experimental Cancers, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1995 PY - 1995 DA - 1995 SP - 109 EP - 116 VL - 194 SN - 0070-217X, 0070-217X KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Plasmacytoma -- chemically induced KW - Plasmacytoma -- pathology KW - Plasmacytoma -- classification KW - Mice KW - Lymphoma -- classification KW - Lymphoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77181721?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Classification+of+mouse+lymphomas.&rft.au=Fredrickson%2C+T+N%3BHartley%2C+J+W%3BMorse%2C+H+C%3BChattopadhyay%2C+S+K%3BLennert%2C+K&rft.aulast=Fredrickson&rft.aufirst=T&rft.date=1995-01-01&rft.volume=194&rft.issue=&rft.spage=109&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 - 1995-04-24 N1 - Date created - 1995-04-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genomic instability in B-cells and diversity of recombinations that activate c-myc. AN - 77177762; 7895512 AB - Genetic rearrangements activating the proto-oncogene c-myc comprise a mandatory oncogenic step in plasma cell tumor development in BALB/cAnPt mice. In the majority of plasmacytomas, c-myc activating rearrangements take the form of reciprocal chromosomal translocations t(12;15) that juxtapose c-myc to the immunoglobulin heavy chain alpha locus (IgH alpha) in particular the switch alpha region (S alpha). The genetic basis for the prevalence of S alpha/c-myc recombinations in BALB/cAnPt plasmacytomas is not known but may be related to a hypothetical regional genomic instability of the c-myc and IgH alpha loci in BALB/cAnPt mice. We wished to test whether the genomic instability of both loci might be revealed by the diversity of genetic recombinations that can be observed in IgH alpha and c-myc. We employed PCR methods to detect new recombinations of c-myc and IgH alpha in the preneoplastic stage of plasma cell tumor development and found that c-myc can be joined to more genes or genomic regions than known before. This is indicative but does not formally prove a particular genomic instability of c-myc and IgH alpha in BALB/cAnPt B cells. Since defective DNA repair provides a mechanistic explanation for genomic instability, we measured the efficiency of repair in IgH alpha and c-myc using an assay that quantitates the removal of UV-induced pyrimidine dimers within specific genomic regions. We used plasmacytoma XRPC 24 as a model system and found that both IgH alpha and c-myc were poorly repaired, whereas c-abl, a proto-oncogene not related to conventional pristane-induced plasmacytoma-genesis, was efficiently repaired. JF - Current topics in microbiology and immunology AU - Janz, S AU - Jones, G M AU - Müller, J R AU - Potter, M AD - Laboratory of Genetics, NCI, NIH. Y1 - 1995 PY - 1995 DA - 1995 SP - 373 EP - 380 VL - 194 SN - 0070-217X, 0070-217X KW - ODC KW - c-abl KW - c-myc KW - DNA, Neoplasm KW - 0 KW - Immunoglobulin Heavy Chains KW - Terpenes KW - pristane KW - 26HZV48DT1 KW - Index Medicus KW - Terpenes -- toxicity KW - Polymerase Chain Reaction KW - Animals KW - Granuloma -- chemically induced KW - Genes, Switch KW - DNA, Neoplasm -- genetics KW - Peritonitis -- chemically induced KW - Mice KW - Granuloma -- genetics KW - Genetic Predisposition to Disease KW - Peritonitis -- genetics KW - Mice, Inbred BALB C KW - Immunoglobulin Heavy Chains -- genetics KW - Translocation, Genetic KW - Precancerous Conditions -- genetics KW - Plasmacytoma -- genetics KW - DNA Repair KW - Plasmacytoma -- chemically induced KW - Genes, myc KW - Precancerous Conditions -- chemically induced KW - Recombination, Genetic KW - Gene Expression Regulation KW - B-Lymphocytes -- metabolism KW - Gene Rearrangement, B-Lymphocyte UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77177762?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genomic+instability+in+B-cells+and+diversity+of+recombinations+that+activate+c-myc.&rft.au=Janz%2C+S%3BJones%2C+G+M%3BM%C3%BCller%2C+J+R%3BPotter%2C+M&rft.aulast=Janz&rft.aufirst=S&rft.date=1995-01-01&rft.volume=194&rft.issue=&rft.spage=373&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 - 1995-04-24 N1 - Date created - 1995-04-24 N1 - Date revised - 2017-01-13 N1 - Gene symbol - ODC; c-abl; c-myc N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A pilot study of amiodarone with infusional doxorubicin or vinblastine in refractory breast cancer. AN - 77166614; 7882454 AB - Increasing evidence suggests that P-glycoprotein (Pgp) expression can mediate drug resistance in refractory breast cancer. We studied 33 patients with refractory breast cancer enrolled in a pilot study of oral amiodarone as a Pgp antagonist given in combination with infusional doxorubicin or vinblastine. Whenever possible, tumors were biopsied and Pgp expression was assayed. Patients received either 60 mg/m2 doxorubicin over 96 h or 8.5 mg/m2 vinblastine over 120 h by continuous intravenous infusion. Beginning with the second cycle of chemotherapy, 600-800 mg amiodarone was given orally each day. Patients who experienced toxicity due to amiodarone but were responding to chemotherapy were placed on quinidine. Partial responses were observed in 9 of 33 patients on study and were sometimes observed after the first cycle of chemotherapy, before amiodarone was given, suggesting that some patients may have responded to treatment because of the infusional schedule. Toxicities were primarily the known side effects of the antineoplastic agents and of amiodarone. The major amiodarone toxicity was gastrointestinal, with nausea, vomiting, anorexia, or diarrhea being noted in 21 patients. Biopsy samples were obtained from 29 patients and in 21 cases, viable tumor tissue was present and the results were interpretable. Of the 21 samples, 9 had Pgp expression as determined by immunohistochemical staining; 12 were considered negative. The presence of Pgp expression was associated with an acceleration of the time to treatment failure. Whereas normal-tissue toxicities related to the combination of a Pgp antagonist with chemotherapy were not observed, amiodarone was associated with too many untoward effects to be utilized as a drug resistance-reversing agent. JF - Cancer chemotherapy and pharmacology AU - Bates, S E AU - Meadows, B AU - Goldspiel, B R AU - Denicoff, A AU - Le, T B AU - Tucker, E AU - Steinberg, S M AU - Elwood, L J AD - National Institutes of Health, Bethesda, MD 20892. Y1 - 1995 PY - 1995 DA - 1995 SP - 457 EP - 463 VL - 35 IS - 6 SN - 0344-5704, 0344-5704 KW - P-Glycoprotein KW - 0 KW - Vinblastine KW - 5V9KLZ54CY KW - Doxorubicin KW - 80168379AG KW - Amiodarone KW - N3RQ532IUT KW - Index Medicus KW - Administration, Oral KW - Infusions, Intravenous KW - Humans KW - Adult KW - Drug Resistance KW - Aged KW - Pilot Projects KW - Middle Aged KW - Biopsy KW - P-Glycoprotein -- biosynthesis KW - Immunohistochemistry KW - Female KW - Breast Neoplasms -- drug therapy KW - Doxorubicin -- adverse effects KW - Amiodarone -- therapeutic use KW - Doxorubicin -- blood KW - Vinblastine -- blood KW - Doxorubicin -- administration & dosage KW - Amiodarone -- adverse effects KW - Breast Neoplasms -- ultrastructure KW - Vinblastine -- therapeutic use KW - Amiodarone -- blood KW - Vinblastine -- administration & dosage KW - Doxorubicin -- therapeutic use KW - Vinblastine -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Amiodarone -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77166614?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+pilot+study+of+amiodarone+with+infusional+doxorubicin+or+vinblastine+in+refractory+breast+cancer.&rft.au=Bates%2C+S+E%3BMeadows%2C+B%3BGoldspiel%2C+B+R%3BDenicoff%2C+A%3BLe%2C+T+B%3BTucker%2C+E%3BSteinberg%2C+S+M%3BElwood%2C+L+J&rft.aulast=Bates&rft.aufirst=S&rft.date=1995-01-01&rft.volume=35&rft.issue=6&rft.spage=457&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 - 1995-04-13 N1 - Date created - 1995-04-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Injection drug users, crack-cocaine users, and human services utilization: an exploratory study. AN - 77152259; 7863375 AB - Estimates of the number of people addicted to heroin and cocaine run into the millions. How these drug abusers interact with the social services system is not well understood. To gain insight into the nature and extent of such interactions, an exploratory study was conducted to gather information on the perceptions and utilization of human services by 44 drug abusers not in treatment. Twenty-nine injection drug users and 15 crack-cocaine users participated in focus group sessions and structured interviews. Participants were recruited by indigenous outreach workers in Dayton and Columbus, Ohio. Findings revealed a very high rate of service use by the drug users. The results raise questions about the role and efficacy of the social services system in identifying drug users and addressing their needs. In addition, the findings raise perplexing questions regarding the effectiveness of acquired immune deficiency syndrome risk-reduction efforts among injection drug users and crack-cocaine users. JF - Social work AU - Ashery, R S AU - Carlson, R G AU - Falck, R S AU - Siegal, H A AD - National Institute on Drug Abuse, Community Research Branch, Rockville. Y1 - 1995/01// PY - 1995 DA - January 1995 SP - 75 EP - 82 VL - 40 IS - 1 SN - 0037-8046, 0037-8046 KW - Crack Cocaine KW - 0 KW - Index Medicus KW - Focus Groups KW - Humans KW - Adult KW - Pilot Projects KW - Utilization Review KW - Male KW - Female KW - Ohio KW - Social Work, Psychiatric KW - Substance Abuse, Intravenous -- rehabilitation KW - Patient Acceptance of Health Care -- statistics & numerical data KW - Substance Abuse, Intravenous -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77152259?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Social+work&rft.atitle=Injection+drug+users%2C+crack-cocaine+users%2C+and+human+services+utilization%3A+an+exploratory+study.&rft.au=Ashery%2C+R+S%3BCarlson%2C+R+G%3BFalck%2C+R+S%3BSiegal%2C+H+A&rft.aulast=Ashery&rft.aufirst=R&rft.date=1995-01-01&rft.volume=40&rft.issue=1&rft.spage=75&rft.isbn=&rft.btitle=&rft.title=Social+work&rft.issn=00378046&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-17 N1 - Date created - 1995-03-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Onset of menopause in women exposed to diethylstilbestrol in utero. AN - 77140366; 7847565 AB - As part of a larger health survey, we sought to determine whether prenatal exposure to diethylstilbestrol is associated with onset of early menopause or menopausal symptoms. Diagnosis of premature ovarian failure and symptoms of menopause were determined in a telephone interview with 542 women whose mothers participated in a randomized clinical trial of the use of diethylstilbestrol in pregnancy in the early 1950s. These women were aged 37 to 39 at the time of the interview. Medical records were obtained to confirm diagnosis of premature ovarian failure. The prevalence of menopausal symptoms (specifically hot flashes and night sweats) did not differ for exposed and unexposed women. One exposed woman and no unexposed women had a medically confirmed diagnosis of premature ovarian failure. Prenatal diethylstilbestrol exposure was not related to diagnosis or symptoms of menopause in this study. Further follow-up will be necessary to determine if a difference in age at menopause emerges as these women become older. JF - American journal of obstetrics and gynecology AU - Hornsby, P P AU - Wilcox, A J AU - Herbst, A L AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina. Y1 - 1995/01// PY - 1995 DA - January 1995 SP - 92 EP - 95 VL - 172 IS - 1 Pt 1 SN - 0002-9378, 0002-9378 KW - Diethylstilbestrol KW - 731DCA35BT KW - Abridged Index Medicus KW - Index Medicus KW - Climacteric KW - Randomized Controlled Trials as Topic KW - Age of Onset KW - Sweating KW - Humans KW - Cohort Studies KW - Adult KW - Primary Ovarian Insufficiency -- epidemiology KW - Incidence KW - Female KW - Pregnancy KW - Menopause -- drug effects KW - Diethylstilbestrol -- pharmacology KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77140366?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+obstetrics+and+gynecology&rft.atitle=Onset+of+menopause+in+women+exposed+to+diethylstilbestrol+in+utero.&rft.au=Hornsby%2C+P+P%3BWilcox%2C+A+J%3BHerbst%2C+A+L&rft.aulast=Hornsby&rft.aufirst=P&rft.date=1995-01-01&rft.volume=172&rft.issue=1+Pt+1&rft.spage=92&rft.isbn=&rft.btitle=&rft.title=American+journal+of+obstetrics+and+gynecology&rft.issn=00029378&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-09 N1 - Date created - 1995-03-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Early changes in sex hormones are not evident in mice exposed to the uterine carcinogens chloroethane or bromoethane. AN - 77133866; 7839365 AB - Chloroethane and bromoethane have been shown to cause a marked uterine tumor response in B6C3F1 mice exposed for 2 years. These chemicals are nearly unique in this regard among the nearly 400 chemicals studied by the National Toxicology Program, and the reasons for this carcinogenic activity are unclear. The possible relationship of changes in blood concentrations of sex hormones to this response was evaluated by examining the estrous cycle of mice prior to and during a 21-day exposure to concentrations of the haloethanes which resulted in the tumorigenic response in the 2-year studies. Serum concentrations of estradiol and progesterone were determined at the termination of the exposures and compared to exposure group and stage of the estrous cycle. No consistent patterns of change were found in estrous cyclicity or in blood concentrations of sex hormones. Thus, the findings suggest that early changes in circulating sex hormones are not important contributing factors in the uterine neoplasia caused by these chemicals. JF - Toxicology and applied pharmacology AU - Bucher, J R AU - Morgan, D L AU - Adkins, B AU - Travlos, G S AU - Davis, B J AU - Morris, R AU - Elwell, M R AD - National Institute of Environmental Health Sciences, Mantech Inc., Research Triangle Park, North Carolina. Y1 - 1995/01// PY - 1995 DA - January 1995 SP - 169 EP - 173 VL - 130 IS - 1 SN - 0041-008X, 0041-008X KW - Hydrocarbons, Brominated KW - 0 KW - Mutagens KW - Ethyl Chloride KW - 46U771ERWK KW - Progesterone KW - 4G7DS2Q64Y KW - Estradiol KW - 4TI98Z838E KW - bromoethane KW - LI8384T9PH KW - Index Medicus KW - Animals KW - Ovary -- pathology KW - Uterine Neoplasms -- chemically induced KW - Ovary -- drug effects KW - Disease Models, Animal KW - Mice KW - Radioimmunoassay KW - Estrus -- drug effects KW - Female KW - Uterus -- metabolism KW - Estradiol -- blood KW - Ethyl Chloride -- administration & dosage KW - Hydrocarbons, Brominated -- administration & dosage KW - Mutagens -- toxicity KW - Ethyl Chloride -- toxicity KW - Mutagens -- administration & dosage KW - Progesterone -- blood KW - Uterus -- drug effects KW - Hydrocarbons, Brominated -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77133866?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Early+changes+in+sex+hormones+are+not+evident+in+mice+exposed+to+the+uterine+carcinogens+chloroethane+or+bromoethane.&rft.au=Bucher%2C+J+R%3BMorgan%2C+D+L%3BAdkins%2C+B%3BTravlos%2C+G+S%3BDavis%2C+B+J%3BMorris%2C+R%3BElwell%2C+M+R&rft.aulast=Bucher&rft.aufirst=J&rft.date=1995-01-01&rft.volume=130&rft.issue=1&rft.spage=169&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 - 1995-02-24 N1 - Date created - 1995-02-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of nitric oxide-stimulated ADP-ribosylation of various proteins from the mouse macrophage cell line ANA-1 using sodium nitroprusside and the novel nitric oxide-donating compound diethylamine dinitric oxide. AN - 77131865; 7530278 AB - We examined the ability of nitric oxide (NO) to stimulate the ADP-ribosylation of proteins from the mouse macrophage cell line ANA-1. To demonstrate a specific effect of NO, we used a novel compound named diethylamine dinitric oxide (DEA/NO; 1,1-diethyl-2-hydroxy-2-nitrosohydrazine, sodium salt; [Et2NN(O)NO]Na), which releases NO in aqueous solution at neutral pH. DEA/NO stimulated the ADP-ribosylation of at least three cytosolic proteins (M(r) = 28,000, 33,000 and 39,000) from ANA-1 macrophages. The effect of DEA/NO on the ADP-ribosylation of the predominant target p39 was dose dependent (EC50 = 80 microM). Moreover, the effect of DEA/NO was attributed specifically to released NO rather than diethylamine or nitrite. Sodium nitroprusside (SNP) also stimulated the ADP-ribosylation of cytosolic proteins from ANA-1 mouse macrophages. However, SNP exhibited different time- and dose-dependent effects on the modification of p39. NO synthesized via the activity of interferon-gamma plus lipopolysaccharide-induced NO synthase also enhanced the ADP-ribosylation of p39, confirming that the effects of DEA/NO and SNP could be attributed to NO or reactive nitrogen oxide species. Neither pertussis toxin nor cholera toxin stimulated the ADP-ribosylation of p39; however, cholera toxin stimulated the ADP-ribosylation of proteins with approximate molecular weight of 28,000 and 33,000. These data suggest that the induced expression of NO synthase in tumoricidal macrophages may be associated with autocrine and paracrine effects of NO that include the ADP-ribosylation of various proteins. Moreover, these results indicate that DEA/NO and related compounds may be useful as pharmacologic tools for investigating the effects of NO and reactive nitrogen oxide species on macrophages. JF - Journal of leukocyte biology AU - Sheffler, L A AU - Wink, D A AU - Melillo, G AU - Cox, G W AD - Macrophage Cell Biology Section, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201. Y1 - 1995/01// PY - 1995 DA - January 1995 SP - 152 EP - 159 VL - 57 IS - 1 SN - 0741-5400, 0741-5400 KW - Hydrazines KW - 0 KW - Nitrogen Oxides KW - Virulence Factors, Bordetella KW - Nitroprusside KW - 169D1260KM KW - Adenosine Diphosphate Ribose KW - 20762-30-5 KW - Nitric Oxide KW - 31C4KY9ESH KW - 1,1-diethyl-2-hydroxy-2-nitrosohydrazine KW - 86831-65-4 KW - Cholera Toxin KW - 9012-63-9 KW - Arginine KW - 94ZLA3W45F KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Amino Acid Oxidoreductases KW - EC 1.4.- KW - Pertussis Toxin KW - EC 2.4.2.31 KW - Index Medicus KW - Animals KW - Cytosol -- metabolism KW - Amino Acid Oxidoreductases -- metabolism KW - Blotting, Northern KW - Arginine -- metabolism KW - Dose-Response Relationship, Drug KW - Electrophoresis, Polyacrylamide Gel KW - Cholera Toxin -- pharmacology KW - Mice KW - Cell Fractionation KW - Virulence Factors, Bordetella -- pharmacology KW - Cell Line KW - Macrophages -- cytology KW - Hydrazines -- pharmacology KW - Nitric Oxide -- pharmacology KW - Nitric Oxide -- metabolism KW - Nitroprusside -- pharmacology KW - Macrophages -- drug effects KW - Hydrazines -- metabolism KW - Adenosine Diphosphate Ribose -- metabolism KW - Macrophages -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77131865?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Characterization+of+nitric+oxide-stimulated+ADP-ribosylation+of+various+proteins+from+the+mouse+macrophage+cell+line+ANA-1+using+sodium+nitroprusside+and+the+novel+nitric+oxide-donating+compound+diethylamine+dinitric+oxide.&rft.au=Sheffler%2C+L+A%3BWink%2C+D+A%3BMelillo%2C+G%3BCox%2C+G+W&rft.aulast=Sheffler&rft.aufirst=L&rft.date=1995-01-01&rft.volume=57&rft.issue=1&rft.spage=152&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 - 1995-02-23 N1 - Date created - 1995-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Endogenous formation of N-nitrosomorpholine in mice from 15NO2 by inhalation and morpholine by gavage. AN - 77130627; 7834809 AB - Male CD-1 mice were exposed to an nominal concentration of 20 p.p.m. of 15N-nitrogen dioxide (15NO2) for 6 h/day for 4 days and for 2 h on the day 5, and to 1 g morpholine/kg body wt by gavage daily for five consecutive days. N-Nitrosomorpholine (NMOR) was found in whole mice, stomachs, skins with hair, and remains. The sum of individual tissue concentrations measured separately was 3421 ng/tissue, where the average skin weighed 4.3 g, the average stomach weighed 1.0 g and the average remains weighed 22.2 g. The average whole mouse weighed 27.7 g and contained a total of 3903 ng of NMOR. The concentration of NMOR was highest in the skin, next highest in the stomach, and lowest in the remains. However, the total quantity of NMOR per tissue, while highest in the skin (83%), was next highest in the remains (14.8%) and lowest in the stomach (2.2%). GC-MS analysis served to distinguish between the NMOR of 15NO2 origin and that of other origin. All of the NMOR in the whole mouse homogenates was identified as 15NMOR. In the stomach 73% was identified as 14NMOR, representing 1.6% of the total NMOR in the mouse, and 27% as 15NMOR, representing 0.6% of the total NMOR in the mouse. N-Nitrosamine formation in vivo is discussed as a possibly ongoing mammalian process. JF - Carcinogenesis AU - Van Stee, E W AU - Sloane, R A AU - Simmons, J E AU - Moorman, M P AU - Brunnemann, K D AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1995/01// PY - 1995 DA - January 1995 SP - 89 EP - 92 VL - 16 IS - 1 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - Morpholines KW - Nitrogen Isotopes KW - Nitrosamines KW - N-nitrosomorpholine KW - 3L25FO7FN7 KW - morpholine KW - 8B2ZCK305O KW - Nitrogen Dioxide KW - S7G510RUBH KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Gas Chromatography-Mass Spectrometry KW - Mice KW - Administration, Inhalation KW - Male KW - Nitrogen Dioxide -- metabolism KW - Carcinogens -- metabolism KW - Nitrosamines -- metabolism KW - Morpholines -- administration & dosage KW - Nitrogen Dioxide -- administration & dosage KW - Morpholines -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77130627?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Endogenous+formation+of+N-nitrosomorpholine+in+mice+from+15NO2+by+inhalation+and+morpholine+by+gavage.&rft.au=Van+Stee%2C+E+W%3BSloane%2C+R+A%3BSimmons%2C+J+E%3BMoorman%2C+M+P%3BBrunnemann%2C+K+D&rft.aulast=Van+Stee&rft.aufirst=E&rft.date=1995-01-01&rft.volume=16&rft.issue=1&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-27 N1 - Date created - 1995-02-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of psychological symptoms between drug abusers seeking and not seeking treatment. AN - 77124089; 7807072 JF - The Journal of nervous and mental disease AU - Montoya, I D AU - Haertzen, C AU - Hess, J M AU - Covi, L AU - Fudala, P J AU - Johnson, R E AU - Gorelick, D A AD - National Institute on Drug Abuse, Intramural Research Program, NIH/NIDA/IRP, Baltimore, Maryland 21224. Y1 - 1995/01// PY - 1995 DA - January 1995 SP - 50 EP - 53 VL - 183 IS - 1 SN - 0022-3018, 0022-3018 KW - Cocaine KW - I5Y540LHVR KW - Abridged Index Medicus KW - Index Medicus KW - Opioid-Related Disorders -- psychology KW - Humans KW - Opioid-Related Disorders -- therapy KW - Comorbidity KW - Volunteers -- psychology KW - Opioid-Related Disorders -- epidemiology KW - Psychiatric Status Rating Scales KW - Adult KW - Middle Aged KW - Clinical Protocols KW - Female KW - Male KW - Substance-Related Disorders -- therapy KW - Mental Disorders -- diagnosis KW - Patient Acceptance of Health Care KW - Mental Disorders -- epidemiology KW - Substance-Related Disorders -- psychology KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77124089?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+nervous+and+mental+disease&rft.atitle=Comparison+of+psychological+symptoms+between+drug+abusers+seeking+and+not+seeking+treatment.&rft.au=Montoya%2C+I+D%3BHaertzen%2C+C%3BHess%2C+J+M%3BCovi%2C+L%3BFudala%2C+P+J%3BJohnson%2C+R+E%3BGorelick%2C+D+A&rft.aulast=Montoya&rft.aufirst=I&rft.date=1995-01-01&rft.volume=183&rft.issue=1&rft.spage=50&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+nervous+and+mental+disease&rft.issn=00223018&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-01 N1 - Date created - 1995-02-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Nerv Ment Dis. 1993 Aug;181(8):467-74 [8360638] Br J Soc Clin Psychol. 1977 Nov;16(4):347-56 [588890] J Stud Alcohol. 1982 Mar;43(3):240-51 [7120995] Am J Psychiatry. 1983 Sep;140(9):1205-7 [6614231] Int J Addict. 1985 Mar;20(3):449-59 [4018938] Arch Gen Psychiatry. 1985 Nov;42(11):1072-7 [4051685] Arch Gen Psychiatry. 1986 Feb;43(2):107-13 [3947206] Am J Drug Alcohol Abuse. 1986;12(1-2):17-29 [3788897] J Nerv Ment Dis. 1988 Dec;176(12):719-25 [3199107] Arch Gen Psychiatry. 1991 Jan;48(1):43-51 [1984761] Arch Gen Psychiatry. 1992 Jun;49(6):464-71 [1599371] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytotoxic effects of sigma ligands: sigma receptor-mediated alterations in cellular morphology and viability. AN - 77122480; 7823122 AB - The morphological effects of several neuroleptics as well as other novel and prototypic sigma ligands were examined by addition to cultures of C6 glioma cells. Sigma ligands caused loss of processes, assumption of spherical shape, and cessation of cell division. The time course and magnitude of this effect were dependent on the concentration of sigma ligand. Continued exposure to sigma compounds ultimately resulted in cell death. However, the morphological effect was reversible when sigma ligand was removed shortly after rounding. The potency of compounds to produce these effects generally correlated with binding affinity at sigma receptors of C6 glioma cell membranes labeled with [3H](+)-pentazocine. At a concentration of 100 microM, haloperidol, reduced haloperidol, fluphenazine, perphenazine, trifluoperazine, BD737, LR172, BD1008, and SH344 produced significant effects in 3-6 hr of exposure. Other compounds, such as trifluperidol, thioridazine, and (-)-butaclamol, produced significant effects by 24 hr of exposure. Despite the requirement of micromolar concentrations of ligand (some compounds were effective at 30 microM), the effect showed a remarkable specificity for compounds exhibiting sigma receptor binding affinity. Neuroleptics lacking potent sigma affinity [e.g., (-)-sulpiride, (+)-butaclamol, and clozapine] and other compounds that lack significant sigma affinity but that are agonists or antagonists at dopamine, serotonin, adrenergic, glutamate, phencyclidine, GABA, opiate, or muscarinic cholinergic receptors were without effect on cellular morphology at concentrations up to 300 microM over a period of 72 hr. Likewise, blockers and activators of Na+, K+, and Ca2+ channels and a monoamine oxidase inhibitor devoid of sigma affinity were without effect. Interestingly, 1,3-di-o-tolylguanidine (DTG), (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine [(+)-3-PPP], (+)-pentazocine, (+)-cyclazocine, and other sigma-active benzomorphans and morphinans appeared inactive in up to 72 hr of culture. However, these compounds interacted synergistically with a subeffective dose of BD737 (30 microM) to produce effects usually in 6 hr or less. Also, the pH of the culture medium had a profound effect on the activity of sigma compounds. Increasing the pH from the normal range of 7.2-7.4 to pH 8.3-8.5 shifted the dose curves (30, 100, 300 microM) for all sigma compounds to the left. Under these conditions, DTG, (+)-3-PPP, and benzomorphans produced effects in 24 hr or less.(ABSTRACT TRUNCATED AT 400 WORDS) JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Vilner, B J AU - de Costa, B R AU - Bowen, W D AD - Unit on Receptor Biochemistry and Pharmacology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892. Y1 - 1995/01// PY - 1995 DA - January 1995 SP - 117 EP - 134 VL - 15 IS - 1 Pt 1 SN - 0270-6474, 0270-6474 KW - Antipsychotic Agents KW - 0 KW - Ethylenediamines KW - Ligands KW - Piperazines KW - Receptors, sigma KW - ethylenediamine KW - 60V9STC53F KW - Index Medicus KW - Rats KW - Animals KW - Tumor Cells, Cultured KW - Hydrogen-Ion Concentration KW - Antipsychotic Agents -- pharmacology KW - Ethylenediamines -- pharmacology KW - Piperazines -- pharmacology KW - Drug Synergism KW - Cell Survival KW - Glioma -- physiopathology KW - Glioma -- pathology KW - Receptors, sigma -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77122480?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Cytotoxic+effects+of+sigma+ligands%3A+sigma+receptor-mediated+alterations+in+cellular+morphology+and+viability.&rft.au=Vilner%2C+B+J%3Bde+Costa%2C+B+R%3BBowen%2C+W+D&rft.aulast=Vilner&rft.aufirst=B&rft.date=1995-01-01&rft.volume=15&rft.issue=1+Pt+1&rft.spage=117&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 - 1995-02-14 N1 - Date created - 1995-02-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of recA mutants with altered SOS functions. AN - 77122456; 7528894 AB - The Escherichia coli RecA protein has at least three roles in SOS mutagenesis: (1) derepression of the SOS regulon by mediating LexA cleavage; (2) activation of the UmuD mutagenesis protein by mediating its cleavage; and (3) targeting the Umu-like mutagenesis proteins to DNA. Using a combined approach of molecular and physiological assays, it is now possible to determine which of the three defined steps has been altered in any recA mutant. In this study, we have focused on the ability of six particular recA mutants (recA85, recA430, recA432, recA433, recA435 and recA730) to perform these functions. Phenotypically, recA85 and recA730 were similar in that in lexA+ and lexA(Def) backgrounds, they exhibited constitutive coprotease activity towards the UmuD mutagenesis protein. Somewhat surprisingly, in a lexA(Ind-) background, UmuD cleavage was damage inducible, suggesting that the repressed level of the RecA* protein cannot spontaneously achieve a fully activated state. Although isolated in separate laboratories, the nucleotide sequence of the recA85 and recA730 mutants revealed that they were identical, with both alleles possessing a Glu38-->Lys change in the mutant protein. The recA430, recA433 and recA435 mutants were found to be defective for both lambda mutagenesis and UmuD cleavage. lambda mutagenesis was fully restored, however, to the recA433 and recA435 strains by a low copy plasmid expressing the mutagenically active UmuD' protein. In contrast, lambda mutagenesis was only partially restored to a recA430 strain by a high copy UmuD' plasmid, suggesting that RecA430 may also be additionally defective in targeting the Umu proteins to DNA. Sequence analysis of the recA433 and recA435 alleles revealed identical substitutions resulting in Arg243-->His. The recA432 mutation had a complex phenotype in that its coprotease activity towards UmuD depended upon the lexA background: inducible in lexA+ strains, inefficient in lexA(Ind-) cells and constitutive in a lexA(Def) background. The recA432 mutant was found to carry a Pro119-->Ser substitution, a residue believed to be at the RecA subunit interface; thus this complex phenotype may result from alterations in the assembly of RecA multimers. JF - Mutation research AU - Ennis, D G AU - Levine, A S AU - Koch, W H 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 - 1995/01// PY - 1995 DA - January 1995 SP - 39 EP - 48 VL - 336 IS - 1 SN - 0027-5107, 0027-5107 KW - Bacterial Proteins KW - 0 KW - Escherichia coli Proteins KW - Rec A Recombinases KW - EC 2.7.7.- KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - UmuD protein, E coli KW - Index Medicus KW - Base Sequence KW - Bacterial Proteins -- genetics KW - Molecular Sequence Data KW - Rec A Recombinases -- genetics KW - SOS Response (Genetics) KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77122456?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Analysis+of+recA+mutants+with+altered+SOS+functions.&rft.au=Ennis%2C+D+G%3BLevine%2C+A+S%3BKoch%2C+W+H%3BWoodgate%2C+R&rft.aulast=Ennis&rft.aufirst=D&rft.date=1995-01-01&rft.volume=336&rft.issue=1&rft.spage=39&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 - 1995-02-01 N1 - Date created - 1995-02-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - What if Americans drank less? The potential effect on the prevalence of alcohol abuse and dependence. AN - 77121315; 7832263 AB - Several advisory committees have recently recommended that alcohol consumption be limited to moderate levels. Moderate drinking has been defined generally as not more than two drinks per day for healthy men and not more than one drink per day for healthy, nonpregnant women. The impact of reducing alcohol consumption to within the recommended guidelines on the prevalence of two serious alcohol-related problems was examined by modeling the relationship between average daily ethanol intake and alcohol abuse and dependence. The recommended drinking guidelines, both in their existing form and modified by a measure of impairment, were applied to the observed distribution of consumption derived from a large representative survey of the US general population. The results demonstrated that restricting drinking to the maximum allowable levels under the existing and the modified guidelines would reduce the prevalence of alcohol abuse and dependence by 14.2% and 47.1%, respectively, in the adult US general population. Implications of these findings are discussed in terms of the validity of the assumptions underlying the models and the nature and direction of future research that would form the basis of newly developed guidelines for safe drinking limits. JF - American journal of public health AU - Archer, L AU - Grant, B F AU - Dawson, D A AD - National Institute on Alcohol Abuse and Alcoholism, Rockville, Md. 20892. Y1 - 1995/01// PY - 1995 DA - January 1995 SP - 61 EP - 66 VL - 85 IS - 1 SN - 0090-0036, 0090-0036 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Guidelines as Topic KW - United States -- epidemiology KW - Male KW - Female KW - Prevalence KW - Alcoholism -- epidemiology KW - Alcohol Drinking KW - Alcoholism -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77121315?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+public+health&rft.atitle=What+if+Americans+drank+less%3F+The+potential+effect+on+the+prevalence+of+alcohol+abuse+and+dependence.&rft.au=Archer%2C+L%3BGrant%2C+B+F%3BDawson%2C+D+A&rft.aulast=Archer&rft.aufirst=L&rft.date=1995-01-01&rft.volume=85&rft.issue=1&rft.spage=61&rft.isbn=&rft.btitle=&rft.title=American+journal+of+public+health&rft.issn=00900036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-23 N1 - Date created - 1995-02-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Med. 1980 Feb;68(2):164-9 [7355889] Circulation. 1977 Dec;56(6):1067-74 [923047] Am J Public Health. 1982 Aug;72(8):823-8 [7091478] Br J Addict. 1984 Jun;79(2):185-96 [6611166] Alcohol Clin Exp Res. 1986 Dec;10(6):564-9 [3544906] Alcohol Clin Exp Res. 1987 Apr;11(2):167-75 [3296836] JAMA. 1988 Aug 5;260(5):652-6 [3392790] N Engl J Med. 1988 Aug 4;319(5):267-73 [3393181] JAMA. 1988 Nov 4;260(17):2529-32 [3172427] Lancet. 1991 Aug 24;338(8765):464-8 [1678444] Drug Alcohol Depend. 1991 Oct;28(3):225-39 [1661228] N Engl J Med. 1992 May 21;326(21):1406-16 [1533273] Int J Epidemiol. 1978 Jun;7(2):113-20 [681057] Am J Public Health. 1993 Sep;83(9):1277-83 [8363004] Lancet. 1981 Mar 14;1(8220 Pt 1):580-3 [6110820] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutations in the glucose-6-phosphatase gene are associated with glycogen storage disease types 1a and 1aSP but not 1b and 1c. AN - 77118961; 7814621 AB - Glycogen storage disease (GSD) type 1, which is caused by the deficiency of glucose-6-phosphatase (G6Pase), is an autosomal recessive disease with heterogenous symptoms. Two models of G6Pase catalysis have been proposed to explain the observed heterogeneities. The translocase-catalytic unit model proposes that five GSD type 1 subgroups exist which correspond to defects in the G6Pase catalytic unit (1a), a stabilizing protein (1aSP), the glucose-6-P (1b), phosphate/pyrophosphate (1c), and glucose (1d) translocases. Conversely, the conformation-substrate-transport model suggests that G6Pase is a single multifunctional membrane channel protein possessing both catalytic and substrate (or product) transport activities. We have recently demonstrated that mutations in the G6Pase catalytic unit cause GSD type 1a. To elucidate whether mutations in the G6Pase gene are responsible for other GSD type 1 subgroups, we characterized the G6Pase gene of GSD type 1b, 1c, and 1aSP patients. Our results show that the G6Pase gene of GSD type 1b and 1c patients is normal, consistent with the translocase-catalytic unit model of G6Pase catalysis. However, a mutation in exon 2 that converts an Arg at codon 83 to a Cys (R83C) was identified in both G6Pase alleles of the type 1aSP patient. The R83C mutation was also demonstrated in one homozygous and five heterogenous GSD type 1a patients, indicating that type 1aSP is a misclassification of GSD type 1a. We have also analyzed the G6Pase gene of seven additional type 1a patients and uncovered two new mutations that cause GSD type 1a. JF - The Journal of clinical investigation AU - Lei, K J AU - Shelly, L L AU - Lin, B AU - Sidbury, J B AU - Chen, Y T AU - Nordlie, R C AU - Chou, J Y AD - Human Genetics Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1995/01// PY - 1995 DA - January 1995 SP - 234 EP - 240 VL - 95 IS - 1 SN - 0021-9738, 0021-9738 KW - Glucose-6-Phosphatase KW - EC 3.1.3.9 KW - Abridged Index Medicus KW - Index Medicus KW - Genome, Human KW - Homozygote KW - Models, Molecular KW - Humans KW - Amino Acid Sequence KW - Sequence Analysis, DNA KW - Cloning, Molecular KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Alleles KW - Base Sequence KW - Transfection KW - Cells, Cultured KW - Heterozygote KW - Molecular Sequence Data KW - Mutation -- genetics KW - Glycogen Storage Disease Type I -- genetics KW - Glycogen Storage Disease Type I -- classification KW - Glycogen Storage Disease Type I -- enzymology KW - Glucose-6-Phosphatase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77118961?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+investigation&rft.atitle=Mutations+in+the+glucose-6-phosphatase+gene+are+associated+with+glycogen+storage+disease+types+1a+and+1aSP+but+not+1b+and+1c.&rft.au=Lei%2C+K+J%3BShelly%2C+L+L%3BLin%2C+B%3BSidbury%2C+J+B%3BChen%2C+Y+T%3BNordlie%2C+R+C%3BChou%2C+J+Y&rft.aulast=Lei&rft.aufirst=K&rft.date=1995-01-01&rft.volume=95&rft.issue=1&rft.spage=234&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+investigation&rft.issn=00219738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-09 N1 - Date created - 1995-02-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1986 Dec 15;261(35):16571-8 [3023356] J Biol Chem. 1980 Sep 25;255(18):8381-4 [6251055] Adv Enzymol Relat Areas Mol Biol. 1989;62:93-117 [2543189] FASEB J. 1990 Sep;4(12):2978-88 [2168325] J Inherit Metab Dis. 1990;13(3):247-9 [2172641] Biochemistry. 1979 Nov 27;18(24):5294-9 [518835] J Clin Invest. 1994 May;93(5):1994-9 [8182131] J Biol Chem. 1980 Nov 10;255(21):10396-406 [6253473] J Pediatr. 1980 Dec;97(6):906-10 [6255119] J Biol Chem. 1983 Aug 25;258(16):9739-44 [6309784] Biochim Biophys Acta. 1985 May 28;815(3):468-76 [3838905] Biochem J. 1985 Sep 1;230(2):489-95 [2996501] Eur J Biochem. 1992 Sep 15;208(3):643-50 [1327763] Eur J Pediatr. 1993;152 Suppl 1:S33-8 [8391445] Somat Cell Mol Genet. 1993 May;19(3):275-83 [8332935] Science. 1993 Oct 22;262(5133):580-3 [8211187] Clin Chim Acta. 1988 Apr 15;173(2):183-91 [2837351] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human polymorphism in drug metabolism: mutation in the dihydropyrimidine dehydrogenase gene results in exon skipping and thymine uracilurea. AN - 77116855; 7832988 AB - A condition called thymine uracilurea has been described that is due to a lack of dihydropyrimidine dehydrogenase (DPD) activity. Cancer patients experiencing acute 5-fluorouracil toxicity also have lower-than-normal DPD activities. However, to date, the molecular basis of this disorder has not been addressed. In this study, the phenotype and genotype of a family that presents a patient showing no DPD activity was determined. Fibroblast mRNAs from the patient and four family members were subjected to reverse transcriptase polymerase chain reaction (RT-PCR) using primers generated from the human DPD cDNA sequence. DPD mRNA from the patient was found to lack a segment of 165 nucleotides that results from exon skipping. DPD mRNA from the parents and a sibling were found to be heterozygous for the deleted and the normal mRNA, while a brother had two normal transcripts. DPD activities and levels of DPD protein correlated with genotype; the deficient patient had no detectable DPD protein. PCR analysis of the genomic DNA from this family revealed that the defective mRNA is not due to a deletion of a portion of the gene that contains the exon, thus implying that the mutation is the result of an as yet nonidentified point mutation that causes faulty splicing. JF - DNA and cell biology AU - Meinsma, R AU - Fernandez-Salguero, P AU - Van Kuilenburg, A B AU - Van Gennip, A H AU - Gonzalez, F J AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, MD 20892. Y1 - 1995/01// PY - 1995 DA - January 1995 SP - 1 EP - 6 VL - 14 IS - 1 SN - 1044-5498, 1044-5498 KW - DPYD KW - RNA, Messenger KW - 0 KW - Uracil KW - 56HH86ZVCT KW - Oxidoreductases KW - EC 1.- KW - Dihydrouracil Dehydrogenase (NADP) KW - EC 1.3.1.2 KW - Thymine KW - QR26YLT7LT KW - Index Medicus KW - Pedigree KW - Fibroblasts -- enzymology KW - Thymine -- metabolism KW - Uracil -- metabolism KW - Humans KW - RNA, Messenger -- analysis KW - Child, Preschool KW - Genotype KW - Base Sequence KW - Cells, Cultured KW - Polymerase Chain Reaction -- methods KW - Fibroblasts -- chemistry KW - Molecular Sequence Data KW - Netherlands KW - Female KW - Male KW - Sequence Deletion KW - Exons -- genetics KW - Oxidoreductases -- genetics KW - Polymorphism, Genetic KW - Purine-Pyrimidine Metabolism, Inborn Errors -- enzymology KW - Purine-Pyrimidine Metabolism, Inborn Errors -- ethnology KW - Point Mutation KW - Oxidoreductases -- deficiency KW - Purine-Pyrimidine Metabolism, Inborn Errors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77116855?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=DNA+and+cell+biology&rft.atitle=Human+polymorphism+in+drug+metabolism%3A+mutation+in+the+dihydropyrimidine+dehydrogenase+gene+results+in+exon+skipping+and+thymine+uracilurea.&rft.au=Meinsma%2C+R%3BFernandez-Salguero%2C+P%3BVan+Kuilenburg%2C+A+B%3BVan+Gennip%2C+A+H%3BGonzalez%2C+F+J&rft.aulast=Meinsma&rft.aufirst=R&rft.date=1995-01-01&rft.volume=14&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=DNA+and+cell+biology&rft.issn=10445498&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-27 N1 - Date created - 1995-02-27 N1 - Date revised - 2017-01-13 N1 - Gene symbol - DPYD N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Distinct mechanisms for Ca2+ entry induced by OKT3 and Ca2+ depletion in Jurkat T cells. AN - 77116842; 7813624 AB - Ca2+ influx triggered by antigen binding to T cell receptors (TCR) is an early event in T cell activation. An additional Ca2+ influx induced by depletion of intracellular Ca2+ (CDCI) has been characterized in human Jurkat T cells that is both temporally and mechanistically distinct from TCR-mediated Ca2+ influx (TCRCI). Both TCRCI and CDCI were insensitive to voltage-gated Ca2+ channel antagonists (e.g., nifedipine, verapamil, and omega-conotoxin G) and pertussis toxin, yet were voltage-sensitive and inhibited by SKF 96365 (a receptor-gated Ca2+ channel blocker) and cholera toxin. However, TCRCI but not CDCI was associated with a significant increase in inositol phosphate (IP chi) levels and inhibited by phorbol ester, while CDCI but not TCRCI was inhibited by Sr2+, forskolin (FSK), and 1,9-dideoxy FSK in a cAMP-independent fashion. Moreover, TCR stimulation did not deplete thapsigargin-sensitive Ca2+ stores, suggesting that TCRCI is not merely a consequence of Ca2+ depletion. These results indicate that Ca2+ entry following the depletion of intracellular Ca2+ stores or TCR stimulation occur through distinct cellular mechanisms coexisting in Jurkat T cells. JF - Experimental cell research AU - Sei, Y AU - Takemura, M AU - Gusovsky, F AU - Skolnick, P AU - Basile, A AD - Laboratory of Neuroscience, NIDDK, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1995/01// PY - 1995 DA - January 1995 SP - 222 EP - 231 VL - 216 IS - 1 SN - 0014-4827, 0014-4827 KW - Calcium Channel Blockers KW - 0 KW - Cations, Divalent KW - Inositol Phosphates KW - Muromonab-CD3 KW - Receptors, Antigen, T-Cell KW - Virulence Factors, Bordetella KW - Colforsin KW - 1F7A44V6OU KW - 8-Bromo Cyclic Adenosine Monophosphate KW - 23583-48-4 KW - Bucladesine KW - 63X7MBT2LQ KW - Cholera Toxin KW - 9012-63-9 KW - Pertussis Toxin KW - EC 2.4.2.31 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - 1,9-dideoxyforskolin KW - OAW710HWIX KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Cations, Divalent -- metabolism KW - Inositol Phosphates -- biosynthesis KW - Humans KW - Receptors, Antigen, T-Cell -- metabolism KW - Cholera Toxin -- pharmacology KW - Colforsin -- analogs & derivatives KW - Bucladesine -- pharmacology KW - 8-Bromo Cyclic Adenosine Monophosphate -- pharmacology KW - Ion Transport KW - Virulence Factors, Bordetella -- pharmacology KW - Colforsin -- pharmacology KW - Tumor Cells, Cultured KW - Calcium Channel Blockers -- pharmacology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Lymphocyte Activation -- physiology KW - Ion Channel Gating -- physiology KW - Calcium -- metabolism KW - T-Lymphocytes -- metabolism KW - Ion Channel Gating -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77116842?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+cell+research&rft.atitle=Distinct+mechanisms+for+Ca2%2B+entry+induced+by+OKT3+and+Ca2%2B+depletion+in+Jurkat+T+cells.&rft.au=Sei%2C+Y%3BTakemura%2C+M%3BGusovsky%2C+F%3BSkolnick%2C+P%3BBasile%2C+A&rft.aulast=Sei&rft.aufirst=Y&rft.date=1995-01-01&rft.volume=216&rft.issue=1&rft.spage=222&rft.isbn=&rft.btitle=&rft.title=Experimental+cell+research&rft.issn=00144827&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-09 N1 - Date created - 1995-02-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adenovirally mediated gene transfer into experimental solid brain tumors and leptomeningeal cancer cells. AN - 77116174; 7815137 AB - Among the appealing features of adenoviruses as vectors for transfer of genes into the central nervous system (CNS) are that they are not neurotoxic, they can accommodate the insertion of several large genes, they are not associated with the hazards of insertional mutagenesis, and they can be concentrated to a high-titer preparation. The authors evaluated the feasibility of using adenovirally mediated gene transfer into cultured human glioma cells and in rat models of solid brain tumors and meningeal cancer. Replication-deficient adenoviral vector particles carrying a nuclear-localizing lacZ gene were injected into established 9L cerebral gliomas in Fischer rats. In addition, the adenoviral vector was injected into the subarachnoid space, either simultaneously with intrathecal tumor inoculation or after establishing leptomeningeal cancer. The brains and spinal cords were removed at various intervals for histochemical evaluation for beta-galactosidase activity using X-Gal staining. Additional rats received a stereotactic intracerebral injection of the vector into normal brain. No clinical abnormalities were observed in the injected rats. Injection of the adenoviral vector into normal brain resulted in diffuse transduction of astrocytes, microglia, neurons, and endothelial cells at the injection site. Injection of a high-concentration vector preparation into cerebral gliomas resulted in effective tumor transduction. Intrathecal injection of the vector in rats with meningeal cancer resulted in transduction of the infiltrating tumor in the subarachnoid space when injections were given simultaneously with, or 7 days after, tumor inoculation. Transduction rates of both solid and leptomeningeal tumors correlated with the number of injected particles. These results suggest that adenoviral vectors can efficiently transduce solid brain tumors and that the vectors survive in the cerebrospinal fluid for a sufficient period of time to allow leptomeningeal tumor transduction. Adenoviral vector should be evaluated for its potential use in therapeutic gene transfer approaches in malignancies of the CNS. JF - Journal of neurosurgery AU - Viola, J J AU - Ram, Z AU - Walbridge, S AU - Oshiro, E M AU - Trapnell, B AU - Tao-Cheng, J H AU - Oldfield, E H AD - Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland. Y1 - 1995/01// PY - 1995 DA - January 1995 SP - 70 EP - 76 VL - 82 IS - 1 SN - 0022-3085, 0022-3085 KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Tumor Cells, Cultured KW - Gene Expression KW - Lac Operon KW - Brain Neoplasms -- pathology KW - Meningeal Neoplasms -- therapy KW - Glioma -- pathology KW - Brain Neoplasms -- therapy KW - Gene Transfer Techniques KW - Brain Neoplasms -- genetics KW - Meningeal Neoplasms -- pathology KW - Glioma -- therapy KW - Glioma -- genetics KW - Meningeal Neoplasms -- genetics KW - Adenoviridae -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77116174?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Adenovirally+mediated+gene+transfer+into+experimental+solid+brain+tumors+and+leptomeningeal+cancer+cells.&rft.au=Viola%2C+J+J%3BRam%2C+Z%3BWalbridge%2C+S%3BOshiro%2C+E+M%3BTrapnell%2C+B%3BTao-Cheng%2C+J+H%3BOldfield%2C+E+H&rft.aulast=Viola&rft.aufirst=J&rft.date=1995-01-01&rft.volume=82&rft.issue=1&rft.spage=70&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 - 1995-02-09 N1 - Date created - 1995-02-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytokine levels and systemic toxicity in patients undergoing isolated limb perfusion with high-dose tumor necrosis factor, interferon gamma, and melphalan. AN - 77091901; 7799030 AB - Isolated limb perfusion (ILP) with tumor necrosis factor (TNF), interferon gamma, and melphalan (M) has been reported to result in high response rates for extremity melanoma and sarcoma. We have evaluated the relationship of systemic TNF exposure to induction of several secondary mediators and incidence of systemic toxicity. Nineteen patients with extremity melanoma (n = 16) or sarcoma (n = 3), underwent 90-minute ILP with TNF-alpha, interferon gamma (0.2 mg), and M (10 to 13 mg/L of limb volume) (TNF/IFN/M) (n = 12), or M alone (n = 7). Continuous intraoperative monitoring (CIM) for systemic leak from the perfusion circuit was performed using radioactive iodine-131 albumin. Cytokine levels in the perfusate and systemic circulation during and after ILP were measured by enzyme-linked immunosorbent assay. Systemic leaks > or = 1% from the perfusion circuit occurred in six patients who received TNF/IFN/M and in four who received M alone. Hypotension that required vasopressor support occurred in six of six patients with evidence of a leak (> or = 1%) and zero of six patients without a leak (< 1%). These six patients had significantly higher peak systemic TNF levels during and after perfusion than patients without a leak (2.8 and 8.2 ng/mL v 0.7 and 2.0 ng/mL, respectively; P < .05). All patients who received TNF/IFN/M had significantly greater increases in systemic interleukin-6 (IL-6) levels than in patients with M alone (12,395 +/- 10,374 pg/mL v 79.4 +/- 7.2 pg/mL, respectively; P < .001). Intracellular adhesion molecule (ICAM), IL-8, and TNF-R levels were also increased after ILP with TNF/IFN/M. ILP with TNF/IFN/M can be safely performed, as I131 albumin provides a sensitive measure of systemic leakage from the perfusion circuit. Patients with a measured leak of > or = 1% develop mild and transient postoperative hypotension with significantly higher systemic TNF levels and lower perfusate TNF levels than in patients without leaks. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Thom, A K AU - Alexander, H R AU - Andrich, M P AU - Barker, W C AU - Rosenberg, S A AU - Fraker, D L AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1995/01// PY - 1995 DA - January 1995 SP - 264 EP - 273 VL - 13 IS - 1 SN - 0732-183X, 0732-183X KW - Cytokines KW - 0 KW - Interleukin-6 KW - Interleukin-8 KW - Receptors, Tumor Necrosis Factor KW - Tumor Necrosis Factor-alpha KW - Interferon-gamma KW - 82115-62-6 KW - Melphalan KW - Q41OR9510P KW - Index Medicus KW - Chemotherapy, Cancer, Regional Perfusion KW - Humans KW - Aged KW - Arm KW - Interleukin-8 -- blood KW - Leg KW - Interleukin-6 -- blood KW - Aged, 80 and over KW - Adult KW - Middle Aged KW - Receptors, Tumor Necrosis Factor -- metabolism KW - Female KW - Male KW - Cytokines -- blood KW - Tumor Necrosis Factor-alpha -- administration & dosage KW - Melanoma -- blood KW - Skin Neoplasms -- therapy KW - Histiocytoma, Benign Fibrous -- therapy KW - Leiomyosarcoma -- therapy KW - Sarcoma, Ewing -- therapy KW - Skin Neoplasms -- blood KW - Histiocytoma, Benign Fibrous -- blood KW - Melphalan -- administration & dosage KW - Interferon-gamma -- administration & dosage KW - Sarcoma, Ewing -- blood KW - Melanoma -- therapy KW - Tumor Necrosis Factor-alpha -- metabolism KW - Leiomyosarcoma -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77091901?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Cytokine+levels+and+systemic+toxicity+in+patients+undergoing+isolated+limb+perfusion+with+high-dose+tumor+necrosis+factor%2C+interferon+gamma%2C+and+melphalan.&rft.au=Thom%2C+A+K%3BAlexander%2C+H+R%3BAndrich%2C+M+P%3BBarker%2C+W+C%3BRosenberg%2C+S+A%3BFraker%2C+D+L&rft.aulast=Thom&rft.aufirst=A&rft.date=1995-01-01&rft.volume=13&rft.issue=1&rft.spage=264&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 - 1995-01-23 N1 - Date created - 1995-01-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemoprevention. AN - 77091627; 7804897 AB - Chemoprevention has been shown to be an extremely promising approach to the prevention of invasive cancer. Through the identification of chemopreventive agents that inhibit or reverse the process of carcinogenesis, new strategies of early intervention can be developed for patients at high risk that potentially prevent the onset of invasive and metastatic phases of cancer. This articles reviews the present efforts in chemoprevention research, including the identification of promising agents, screening, and preclinical and clinical evaluations. JF - CA: a cancer journal for clinicians AU - Greenwald, P AU - Kelloff, G AU - Burch-Whitman, C AU - Kramer, B S AD - Division of Cancer Prevention and Control, National Cancer Institute, Bethesda, Maryland. PY - 1995 SP - 31 EP - 49 VL - 45 IS - 1 SN - 0007-9235, 0007-9235 KW - Anticarcinogenic Agents KW - 0 KW - Biomarkers, Tumor KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Genes, Tumor Suppressor -- drug effects KW - Oncogenes -- drug effects KW - Humans KW - Clinical Trials as Topic KW - Disease Models, Animal KW - Neoplasms, Experimental -- prevention & control KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Anticarcinogenic Agents -- therapeutic use KW - Neoplasms -- prevention & control KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77091627?accountid=14244 L2 - http://onlinelibrary.wiley.com/doi/10.3322/canjclin.45.1.31/pdf LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-02 N1 - Date created - 1995-02-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interleukin-2-transduced lymphocytes grow in an autocrine fashion and remain responsive to antigen. AN - 77091596; 7803791 AB - The maintenance of T lymphocytes in vivo after adoptive transfer for immunotherapy requires the systemic administration of interleukin-2 (IL-2), but prolonged administration of IL-2 is associated with substantial toxicity. The constitutive production of IL-2 by T cells may be an alternative method to prolong T-cell survival and potentially augment antitumor responses. To study the effects of constitutive production of IL-2 on the growth and antigen reactivity of a murine T cell, the sperm-whale myoglobin (SWM) specific T-cell line 14.1 was retrovirally transduced with the cDNA for IL-2. Cells that were transduced with vectors without an internal promoter were able to proliferate in the absence of exogenously added IL-2, and to grow in an autocrine fashion. These vectors used an internal ribosomal entry site (IRES) to allow translation of the neomycin phosphotransferase (neor) gene. In contrast, the cells transduced with an IL-2 vector in which the neor gene was under the transcriptional control of an internal SV-40 promoter failed to proliferate or grow in the absence of exogenously added IL-2. The proliferation of the cells growing without IL-2 could be inhibited with antibodies to the IL-2 receptor or to human IL-2, indicating that they were still IL-2 dependent. Despite their autocrine growth, no tumor formation was observed in syngeneic mice injected subcutaneously with the transduced cells, and the cells retained their antigen reactivity and specificity. These results suggest that autocrine growth of T cells for therapy will not interfere with effector function. JF - Blood AU - Treisman, J AU - Hwu, P AU - Minamoto, S AU - Shafer, G E AU - Cowherd, R AU - Morgan, R A AU - Rosenberg, S A AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1995/01/01/ PY - 1995 DA - 1995 Jan 01 SP - 139 EP - 145 VL - 85 IS - 1 SN - 0006-4971, 0006-4971 KW - Antibodies KW - 0 KW - DNA, Complementary KW - Interleukin-2 KW - Receptors, Interleukin-2 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - DNA, Complementary -- genetics KW - Cell Division -- drug effects KW - Mice KW - Mice, Inbred BALB C KW - Receptors, Interleukin-2 -- immunology KW - Base Sequence KW - Receptors, Interleukin-2 -- physiology KW - Antibodies -- pharmacology KW - Genetic Vectors KW - Molecular Sequence Data KW - Retroviridae -- genetics KW - Repetitive Sequences, Nucleic Acid KW - Female KW - Gene Transfer Techniques KW - Interleukin-2 -- immunology KW - Interleukin-2 -- genetics KW - T-Lymphocytes -- immunology KW - Interleukin-2 -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77091596?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Interleukin-2-transduced+lymphocytes+grow+in+an+autocrine+fashion+and+remain+responsive+to+antigen.&rft.au=Treisman%2C+J%3BHwu%2C+P%3BMinamoto%2C+S%3BShafer%2C+G+E%3BCowherd%2C+R%3BMorgan%2C+R+A%3BRosenberg%2C+S+A&rft.aulast=Treisman&rft.aufirst=J&rft.date=1995-01-01&rft.volume=85&rft.issue=1&rft.spage=139&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-02 N1 - Date created - 1995-02-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structural requirements for double-stranded RNA binding, dimerization, and activation of the human eIF-2 alpha kinase DAI in Saccharomyces cerevisiae. AN - 77090975; 7799945 AB - The protein kinase DAI is activated upon viral infection of mammalian cells and inhibits protein synthesis by phosphorylation of the alpha subunit of translation initiation factor 2 (eIF-2 alpha). DAI is activated in vitro by double-stranded RNAs (dsRNAs), and binding of dsRNA is dependent on two copies of a conserved sequence motif located N terminal to the kinase domain in DAI. High-level expression of DAI in Saccharomyces cerevisiae cells is lethal because of hyperphosphorylation of eIF-2 alpha; at lower levels, DAI can functionally replace the protein kinase GCN2 and stimulate translation of GCN4 mRNA. These two phenotypes were used to characterize structural requirements for DAI function in vivo, by examining the effects of amino acid substitutions at matching positions in the two dsRNA-binding motifs and of replacing one copy of the motif with the other. We found that both copies of the dsRNA-binding motif are required for high-level kinase function and that the N-terminal copy is more important than the C-terminal copy for activation of DAI in S. cerevisiae. On the basis of these findings, we conclude that the requirements for dsRNA binding in vitro and for activation of DAI kinase function in vivo closely coincide. Two mutant alleles containing deletions of the first or second binding motif functionally complemented when coexpressed in yeast cells, strongly suggesting that the active form of DAI is a dimer. In accord with this conclusion, overexpression of four catalytically inactive alleles containing different deletions in the protein kinase domain interfered with wild-type DAI produced in the same cells. Interestingly, three inactivating point mutations in the kinase domain were all recessive, suggesting that dominant interference involves the formation of defective heterodimers rather than sequestration of dsRNA activators by mutant enzymes. We suggest that large structural alterations in the kinase domain impair an interaction between the two protomers in a DAI dimer that is necessary for activation by dsRNA or for catalysis of eIF-2 alpha phosphorylation. JF - Molecular and cellular biology AU - Romano, P R AU - Green, S R AU - Barber, G N AU - Mathews, M B AU - Hinnebusch, A G AD - Section on Molecular Genetics of Lower Eukaryotes, National Institute of Child Health and Human Development, Bethesda, Maryland 20892. Y1 - 1995/01// PY - 1995 DA - January 1995 SP - 365 EP - 378 VL - 15 IS - 1 SN - 0270-7306, 0270-7306 KW - Eukaryotic Initiation Factor-2 KW - 0 KW - Macromolecular Substances KW - RNA, Double-Stranded KW - Recombinant Proteins KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - eIF-2 Kinase KW - Index Medicus KW - Protein Biosynthesis KW - Enzyme Activation KW - Humans KW - Amino Acid Sequence KW - Protein Binding KW - Structure-Activity Relationship KW - Saccharomyces cerevisiae KW - RNA, Double-Stranded -- metabolism KW - Mutagenesis, Site-Directed KW - Gene Expression Regulation, Enzymologic KW - Genes, Dominant KW - Phosphorylation KW - Eukaryotic Initiation Factor-2 -- metabolism KW - Genetic Complementation Test KW - Molecular Sequence Data KW - Protein-Serine-Threonine Kinases -- chemistry KW - Protein-Serine-Threonine Kinases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77090975?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Structural+requirements+for+double-stranded+RNA+binding%2C+dimerization%2C+and+activation+of+the+human+eIF-2+alpha+kinase+DAI+in+Saccharomyces+cerevisiae.&rft.au=Romano%2C+P+R%3BGreen%2C+S+R%3BBarber%2C+G+N%3BMathews%2C+M+B%3BHinnebusch%2C+A+G&rft.aulast=Romano&rft.aufirst=P&rft.date=1995-01-01&rft.volume=15&rft.issue=1&rft.spage=365&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 - 1995-01-24 N1 - Date created - 1995-01-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Annu Rev Biochem. 1991;60:717-55 [1883206] Science. 1991 Jul 26;253(5018):407-14 [1862342] Biochemistry. 1991 Oct 22;30(42):10356-61 [1718419] Methods Enzymol. 1991;200:38-62 [1956325] Cell. 1992 Feb 7;68(3):585-96 [1739968] J Biol Chem. 1992 Apr 15;267(11):7671-6 [1373135] EMBO J. 1992 Apr;11(4):1553-62 [1348691] Virology. 1992 May;188(1):47-56 [1373554] J Biol Chem. 1992 May 25;267(15):10729-36 [1375230] Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5447-51 [1351683] Microbiol Rev. 1992 Jun;56(2):291-315 [1620067] J Virol. 1992 Oct;66(10):5805-14 [1382142] Science. 1992 Sep 18;257(5077):1685-9 [1382315] Mol Cell Biol. 1992 Nov;12(11):5238-48 [1357546] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10837-41 [1279695] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10979-83 [1438302] Mol Cell Biol. 1992 Dec;12(12):5801-15 [1448107] Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):232-6 [7678339] Proc Natl Acad Sci U S A. 1993 May 15;90(10):4616-20 [8099443] Proc Natl Acad Sci U S A. 1993 May 15;90(10):4621-5 [8099444] Eur J Biochem. 1993 Jun 15;214(3):945-8 [8100524] Genes Dev. 1992 Dec;6(12B):2478-90 [1364113] Virology. 1994 Jan;198(1):92-9 [7505074] Mol Cell Biol. 1995 Jan;15(1):358-64 [7799944] Proc Natl Acad Sci U S A. 1978 Mar;75(3):1121-5 [274704] J Biol Chem. 1979 Oct 25;254(20):10180-3 [489592] Mol Cell Biol. 1984 Jul;4(7):1326-33 [6095062] Proc Natl Acad Sci U S A. 1985 Jul;82(13):4341-5 [3859866] J Biol Chem. 1987 Nov 15;262(32):15538-44 [3479429] Mol Cell Biol. 1988 Jul;8(7):2964-75 [3043201] Genetics. 1989 May;122(1):19-27 [2659436] Mol Cell Biol. 1989 Apr;9(4):1576-86 [2725516] Eur J Biochem. 1989 Jan 2;178(3):581-9 [2912723] Proc Natl Acad Sci U S A. 1989 Jun;86(12):4579-83 [2660141] Nucleic Acids Res. 1989 Jun 26;17(12):4895 [2748349] Immunol Today. 1988 Jun;9(6):161-2 [3256321] Cell. 1990 Jul 27;62(2):379-90 [1695551] Mol Cell Biol. 1991 Nov;11(11):5497-505 [1717830] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Unique insertion sequence and pattern of CD4 expression in variants selected with immunotoxins from human immunodeficiency virus type 1-infected T cells. AN - 77089416; 7983770 AB - To study the variability of human immunodeficiency virus type 1 (HIV-1), we used immunotoxins to select for variants within a population of H9 cells persistently infected with a molecular clone of HIV-1 designated NL4-3. Chimeric immunotoxin CD4-PE40 (a chimeric fusion protein consisting of the amino-terminal two domains of CD4 and the carboxy-terminal domains of Pseudomonas exotoxin A) was used to select for cells lacking cell surface expression of HIV Env (envelope proteins gp160, gp120, and gp41). The cells described here (A1, A7, C9, and E9) fail to express HIV proteins because they have markedly diminished transcription of the integrated provirus (A1, A7, and E9) or no HIV provirus (C9). Analysis demonstrated that two different cloned variants, A1 and E9, contain the complementary sequence of tRNA(3Lys) (45 bp) inserted 3' to the primer-binding site, following by a 169-bp deletion through the start of the gag gene. No HIV mRNA was detected by Northern (RNA) blotting, but PCR demonstrated the presence of the viral message. These variants were found very infrequently in the unselected H9/NL4-3 cell population, and they contained proviruses distinct from that found in the dominant population. In addition, all of these variants had similar patterns of CD4 surface expression that allowed them to escape reinfection within the tissue culture. The data are discussed with regard to mechanisms and errors of HIV reverse transcription, as well as the evolution of mutants within a population of persistently infected cells. JF - Journal of virology AU - Fang, H AU - Pincus, S H AD - Laboratory of Microbial Structure and Function, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840. Y1 - 1995/01// PY - 1995 DA - January 1995 SP - 75 EP - 81 VL - 69 IS - 1 SN - 0022-538X, 0022-538X KW - Antigens, CD4 KW - 0 KW - CD4-Pseudomonas toxin KW - DNA, Viral KW - Exotoxins KW - Immunotoxins KW - RNA, Messenger KW - RNA, Viral KW - Recombinant Proteins KW - Index Medicus KW - AIDS/HIV KW - Recombinant Proteins -- pharmacology KW - Humans KW - Transcription, Genetic KW - RNA, Messenger -- genetics KW - Cloning, Molecular KW - Base Sequence KW - RNA, Messenger -- metabolism KW - Molecular Sequence Data KW - Proviruses -- genetics KW - Genes, Viral KW - RNA, Viral -- genetics KW - RNA, Viral -- metabolism KW - Cell Line KW - HIV-1 -- genetics KW - Exotoxins -- pharmacology KW - Antigens, CD4 -- genetics KW - Antigens, CD4 -- biosynthesis KW - Immunotoxins -- pharmacology KW - T-Lymphocytes -- virology KW - HIV-1 -- drug effects KW - T-Lymphocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77089416?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Unique+insertion+sequence+and+pattern+of+CD4+expression+in+variants+selected+with+immunotoxins+from+human+immunodeficiency+virus+type+1-infected+T+cells.&rft.au=Fang%2C+H%3BPincus%2C+S+H&rft.aulast=Fang&rft.aufirst=H&rft.date=1995-01-01&rft.volume=69&rft.issue=1&rft.spage=75&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 - 1995-01-05 N1 - Date created - 1995-01-05 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - L32865; GENBANK N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1989 Mar;86(6):1987-91 [2538826] Nature. 1988 Sep 22;335(6188):369-72 [2843774] J Exp Med. 1990 Sep 1;172(3):745-57 [1696955] J Immunol. 1990 Feb 15;144(4):1257-62 [2303707] Proc Natl Acad Sci U S A. 1989 Dec;86(23):9539-43 [2480605] J Infect Dis. 1990 Dec;162(6):1233-8 [2230256] J Infect Dis. 1991 Jan;163(1):64-70 [1984477] J Immunol. 1991 Jun 15;146(12):4315-24 [1710247] J Virol. 1991 Sep;65(9):4786-97 [1714517] Viral Immunol. 1992 Summer;5(2):163-72 [1319711] Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):332-6 [8419938] Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):6900-3 [7688465] J Virol. 1993 Nov;67(11):6365-78 [8411338] J Virol. 1994 Apr;68(4):2726-30 [7511177] FASEB J. 1994 Jun;8(9):593-600 [8005387] Eur J Biochem. 1979 Jun;97(1):305-18 [225173] J Virol. 1981 Apr;38(1):239-48 [6165830] J Virol. 1986 Feb;57(2):674-7 [2418216] J Virol. 1986 Aug;59(2):284-91 [3016298] Proc Natl Acad Sci U S A. 1988 Sep;85(18):6944-8 [3413127] J Virol. 1988 Oct;62(10):3779-88 [3047430] J Immunol. 1989 May 1;142(9):3070-5 [2540236] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Monotherapy for fever and neutropenia in cancer patients: a randomized comparison of ceftazidime versus imipenem. AN - 77089034; 7799016 AB - To compare the efficacy of ceftazidime and imipenem monotherapy for fever and neutropenia, and to determine whether fewer antimicrobial modifications (additions or changes) are required by the broader-spectrum agent, imipenem. Adult and pediatric patients undergoing chemotherapy for solid tumors, leukemias, or lymphomas were randomized to receive open-label ceftazidime or imipenem on presentation with fever and neutropenia. Success with or without modifications of the initial antibiotic was defined as survival through neutropenia; failure was death due to infection. Comparisons were based on numbers of modifications made to each monotherapy during the course of neutropenia, in patients stratified as having unexplained fever or a documented infection. Among 204 ceftazidime and 195 imipenem recipients, the overall success rate with or without modification was more than 98%, regardless of initial antibiotic regimen. Modifications occurred in half of all episodes, primarily in patients with documented infections on either monotherapy. Antianaerobic agents were more frequently added to ceftazidime (P < .001), but addition of other antibiotics, including vancomycin and aminoglycosides, was similar between the two monotherapy groups. Imipenem therapy was associated with significantly greater toxicity, manifested by Clostridium difficile-associated diarrhea and by nausea and vomiting, which required discontinuation of imipenem in 10% of recipients. Ceftazidime and imipenem are both effective in the management of fever and chemotherapy-related neutropenia, provided that modifications are made in response to clinical and microbiologic data that emerge during the course of neutropenia. Imipenem, despite its broader antimicrobial spectrum, does not significantly decrease the overall need for antibiotic modifications and is more often complicated by gastrointestinal toxicity. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Freifeld, A G AU - Walsh, T AU - Marshall, D AU - Gress, J AU - Steinberg, S M AU - Hathorn, J AU - Rubin, M AU - Jarosinski, P AU - Gill, V AU - Young, R C AD - Pediatric Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1995/01// PY - 1995 DA - January 1995 SP - 165 EP - 176 VL - 13 IS - 1 SN - 0732-183X, 0732-183X KW - Vancomycin KW - 6Q205EH1VU KW - Imipenem KW - 71OTZ9ZE0A KW - Ceftazidime KW - 9M416Z9QNR KW - Acyclovir KW - X4HES1O11F KW - Index Medicus KW - Acyclovir -- therapeutic use KW - Humans KW - Fever of Unknown Origin -- drug therapy KW - Aged KW - Child KW - Cause of Death KW - Child, Preschool KW - Prospective Studies KW - Adult KW - Middle Aged KW - Adolescent KW - Vancomycin -- therapeutic use KW - Female KW - Male KW - Ceftazidime -- adverse effects KW - Neutropenia -- mortality KW - Bacterial Infections -- microbiology KW - Imipenem -- adverse effects KW - Neutropenia -- etiology KW - Fever -- mortality KW - Fever -- drug therapy KW - Fever -- etiology KW - Neoplasms -- complications KW - Ceftazidime -- therapeutic use KW - Imipenem -- therapeutic use KW - Neutropenia -- drug therapy KW - Bacterial Infections -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77089034?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Monotherapy+for+fever+and+neutropenia+in+cancer+patients%3A+a+randomized+comparison+of+ceftazidime+versus+imipenem.&rft.au=Freifeld%2C+A+G%3BWalsh%2C+T%3BMarshall%2C+D%3BGress%2C+J%3BSteinberg%2C+S+M%3BHathorn%2C+J%3BRubin%2C+M%3BJarosinski%2C+P%3BGill%2C+V%3BYoung%2C+R+C&rft.aulast=Freifeld&rft.aufirst=A&rft.date=1995-01-01&rft.volume=13&rft.issue=1&rft.spage=165&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 - 1995-01-23 N1 - Date created - 1995-01-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Parent monitoring and the incidence of drug sampling in urban elementary school children. AN - 77087785; 7801962 AB - An epidemiologic study of urban-dwelling children aged 8-10 years in Baltimore, Maryland, was undertaken to test the hypothesis that close monitoring and supervision by parents might signal a reduced risk of drug use in the elementary school years. Drug use, monitoring by parents, peer drug use, and other suspected risk factors for early drug use were first assessed in 1989, identifying 947 children with no prior history of drug use. One year later, 4.2 percent of these children were found to have started using alcohol, tobacco, or other drugs on their own for the first time during the follow-up observation interval. Risk of starting drug use was higher for children with lower levels of parent monitoring (relative risk = 4.39, 95% confidence interval 1.48-13.0). In addition, for children with declining levels of parent monitoring, there was an increased risk of starting to use drugs on their own. JF - American journal of epidemiology AU - Chilcoat, H D AU - Dishion, T J AU - Anthony, J C AD - Etiology Branch, National Institute on Drug Abuse, Baltimore, MD. Y1 - 1995/01/01/ PY - 1995 DA - 1995 Jan 01 SP - 25 EP - 31 VL - 141 IS - 1 SN - 0002-9262, 0002-9262 KW - Street Drugs KW - 0 KW - Index Medicus KW - Prospective Studies KW - Logistic Models KW - Humans KW - Incidence KW - Child KW - Baltimore -- epidemiology KW - Urban Population KW - Male KW - Female KW - Parenting KW - Substance-Related Disorders -- prevention & control KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77087785?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+epidemiology&rft.atitle=Parent+monitoring+and+the+incidence+of+drug+sampling+in+urban+elementary+school+children.&rft.au=Chilcoat%2C+H+D%3BDishion%2C+T+J%3BAnthony%2C+J+C&rft.aulast=Chilcoat&rft.aufirst=H&rft.date=1995-01-01&rft.volume=141&rft.issue=1&rft.spage=25&rft.isbn=&rft.btitle=&rft.title=American+journal+of+epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-20 N1 - Date created - 1995-01-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Summary of the 29th United States-Japan joint Conference on Cholera and Related Diarrheal Diseases. AN - 77086683; 7798685 JF - The Journal of infectious diseases AU - Lang, D R AU - Guerrant, R L Y1 - 1995/01// PY - 1995 DA - January 1995 SP - 8 EP - 12 VL - 171 IS - 1 KW - Bacterial Toxins KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Virulence KW - Animals KW - Vibrio cholerae -- pathogenicity KW - Humans KW - Escherichia coli -- pathogenicity KW - Bacteroides Infections -- microbiology KW - Bacterial Toxins -- toxicity KW - Bacteroides fragilis -- pathogenicity KW - Bacteroides Infections -- epidemiology KW - Shigella -- pathogenicity KW - Dysentery, Bacillary -- microbiology KW - Escherichia coli Infections -- microbiology KW - Cholera -- microbiology KW - Escherichia coli Infections -- epidemiology KW - Cholera -- epidemiology KW - Diarrhea -- epidemiology KW - Dysentery, Bacillary -- epidemiology KW - Diarrhea -- microbiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77086683?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=The+Journal+of+infectious+diseases&rft.atitle=Summary+of+the+29th+United+States-Japan+joint+Conference+on+Cholera+and+Related+Diarrheal+Diseases.&rft.au=Lang%2C+D+R%3BGuerrant%2C+R+L&rft.aulast=Lang&rft.aufirst=D&rft.date=1995-01-01&rft.volume=171&rft.issue=1&rft.spage=8&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+infectious+diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-24 N1 - Date created - 1995-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cigarette use and the estimation of lung cancer attributable to radon in the United States. AN - 77086414; 7997518 AB - Residential exposure to radioactive radon and its decay products has been estimated to account for 10-12% of all lung cancer deaths in the U.S. It has been difficult to evaluate fully the impact of cigarette smoking, the most important cause of lung cancer, on this estimate, because factors for patterns of tobacco use have not been included in the risk models, since risk models are derived from studies of underground miners exposed to radon and detailed data on smoking are limited. Lung cancer risk estimates for exposure to radon progeny in smoker and non-smoker populations are obtained by applying the same risk model to each population group, thereby assuming the joint effects of smoking and exposure to radon progeny are multiplicative. However, in miners, joint relative risks (RR) for the two exposures are most consistent with an intermediate relationship between multiplicative and additive, so that the present approach likely results in an overestimate of risk in smokers and an underestimate of risk in nonsmokers. Lubin et al. (National Institutes of Health Publication No. 94-3644, 1994) present an ad hoc approach for adjusting risk models to incorporate smoking status. The approach is based on the relative magnitude of the effects of radon progeny in smokers and nonsmokers and therefore may not be applicable to non-miner populations if the proportion of smokers and the RR for smoking differ. We show that the modification can be derived explicitly by assuming an arithmetic mixture model for the joint RR for smoking and exposure to radon progeny. In this way, smoking parameters in the population of interest (the proportion of smokers and the RR of smoking) can be used directly to adjust radon progeny risk models and obtain risk estimates that are specific for smokers and nonsmokers. With an intermediate RR relationship for smoking and radon progeny, the attributable percentage of lung cancer deaths from residential radon may be twofold greater in non-smokers than in smokers. JF - Radiation research AU - Lubin, J H AU - Steindorf, K AD - Epidemiologic Methods Section, National Cancer Institute, Bethesda, Maryland 20892-7368. Y1 - 1995/01// PY - 1995 DA - January 1995 SP - 79 EP - 85 VL - 141 IS - 1 SN - 0033-7587, 0033-7587 KW - Radon KW - Q74S4N8N1G KW - Index Medicus KW - Space life sciences KW - Occupational Exposure KW - Sex Factors KW - Air Pollution, Indoor KW - Risk Factors KW - Humans KW - Mining KW - United States -- epidemiology KW - Male KW - Female KW - Lung Neoplasms -- etiology KW - Lung Neoplasms -- epidemiology KW - Housing KW - Neoplasms, Radiation-Induced -- epidemiology KW - Models, Statistical KW - Smoking -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77086414?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Radiation+research&rft.atitle=Cigarette+use+and+the+estimation+of+lung+cancer+attributable+to+radon+in+the+United+States.&rft.au=Lubin%2C+J+H%3BSteindorf%2C+K&rft.aulast=Lubin&rft.aufirst=J&rft.date=1995-01-01&rft.volume=141&rft.issue=1&rft.spage=79&rft.isbn=&rft.btitle=&rft.title=Radiation+research&rft.issn=00337587&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-19 N1 - Date created - 1995-01-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retinoid treatment of experimental allergic encephalomyelitis. IL-4 production correlates with improved disease course. AN - 77085536; 7527821 AB - Experimental allergic encephalomyelitis (EAE) is an autoimmune disease characterized by central nervous system inflammation and demyelination. Retinoids regulate cell differentiation and growth by binding to and activating retinoic acid receptors, which seem to be nuclear transcription factors. The effect of retinoids on chronic relapsing EAE produced by the transfer of myelin basic protein (MBP)-specific lymph node cells (LNC) was studied. All-trans-retinoic acid (tRA) inhibited the proliferation of MBP-specific LNC in vitro. However, the capacity of these cells to transfer EAE was markedly reduced by concentrations of tRA that only mildly inhibited T cell proliferation. The presence of tRA during in vitro MBP-specific LNC activation resulted in a considerable increase in IL-4 mRNA, whereas mRNA for IL-2, TNF-alpha, and IFN-gamma was decreased. Increased IL-4 also was detected in culture supernatants. However, the presence of a neutralizing Ab to IL-4 (11B11) during MBP-specific LNC activation in vitro did not reverse the inhibition of encephalitogenicity caused by tRA. The administration of retinoids in vivo resulted in an improved clinical course, even when given after disease onset. These findings suggest that T cell activation in the presence of tRA results in the development of T cells of the Th2 phenotype, which, in turn, might be responsible for the decrease in the encephalitogenicity of MBP-specific T cells. The modulation by retinoids of an immune response dominated by Th1-like T cells to one in which the protective cytokines of Th2-like cells predominate may have potential relevance for human demyelinating diseases such as multiple sclerosis. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Racke, M K AU - Burnett, D AU - Pak, S H AU - Albert, P S AU - Cannella, B AU - Raine, C S AU - McFarlin, D E AU - Scott, D E AD - Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. Y1 - 1995/01/01/ PY - 1995 DA - 1995 Jan 01 SP - 450 EP - 458 VL - 154 IS - 1 SN - 0022-1767, 0022-1767 KW - Biomarkers KW - 0 KW - Myelin Basic Protein KW - Fenretinide KW - 187EJ7QEXL KW - Interleukin-4 KW - 207137-56-2 KW - Tretinoin KW - 5688UTC01R KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Guinea Pigs KW - T-Lymphocytes -- transplantation KW - Mice KW - Myelin Basic Protein -- toxicity KW - Lymphocyte Activation -- drug effects KW - Mice, Inbred Strains KW - Polymerase Chain Reaction KW - Cells, Cultured KW - Spinal Cord -- pathology KW - Gene Expression Regulation -- drug effects KW - T-Lymphocytes -- immunology KW - Female KW - Myelin Basic Protein -- immunology KW - Interleukin-4 -- genetics KW - Encephalomyelitis, Autoimmune, Experimental -- drug therapy KW - Tretinoin -- pharmacology KW - Fenretinide -- therapeutic use KW - Fenretinide -- pharmacology KW - Encephalomyelitis, Autoimmune, Experimental -- pathology KW - Encephalomyelitis, Autoimmune, Experimental -- immunology KW - Interleukin-4 -- biosynthesis KW - Tretinoin -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77085536?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Retinoid+treatment+of+experimental+allergic+encephalomyelitis.+IL-4+production+correlates+with+improved+disease+course.&rft.au=Racke%2C+M+K%3BBurnett%2C+D%3BPak%2C+S+H%3BAlbert%2C+P+S%3BCannella%2C+B%3BRaine%2C+C+S%3BMcFarlin%2C+D+E%3BScott%2C+D+E&rft.aulast=Racke&rft.aufirst=M&rft.date=1995-01-01&rft.volume=154&rft.issue=1&rft.spage=450&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 - 1995-01-19 N1 - Date created - 1995-01-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of antigen receptor signaling in B cells from mice with a retrovirus-induced acquired immunodeficiency syndrome. AN - 77085529; 7995937 AB - MAIDS is a retrovirus-induced immunodeficiency syndrome in mice that has similarities to human AIDS. Because the functional defects in B cells from retroviral immunodeficiency syndromes have not been characterized in detail, we examined early and late parameters of B cell responses to IgM cross-linking in B cells from MAIDS and normal mice. Splenic B cells from mice with MAIDS have defective in vitro proliferative responses to LPS and anti-IgM-mediated stimuli, as well as to PMA plus calcium ionophore, indicating a generalized defect in proliferative response potential independent of specific receptor-mediated signaling. When early signaling parameters were analyzed in response to IgM cross-linking, it was found that calcium flux in B cells from MAIDS mice was significantly reduced; this reduction was not accounted for by quantitative differences in cell-surface IgM expression and therefore indicates a defect in early signal transduction through the IgM receptor. The tyrosine phosphorylation response to IgM cross-linking was also markedly deficient; tyrosine phosphorylation of Ig-alpha, Ig-beta, and an undefined protein of 80 kDa was detected in MAIDS B cells after anti-IgM stimulation, at levels substantially less than those observed in normal B cells. Multiple other tyrosine phosphorylation events observed in normal B cells, including phosphorylation of GTPase-activating protein, P13-kinase, and syk kinase, were not detected in MAIDS B cells in response to IgM cross-linking. The defect in tyrosine phosphorylation seemed to correlate with reduced surface IgM levels on a subpopulation of MAIDS B cells. B cells from mice expressing the MAIDS retrovirus-induced immunodeficiency thus reflect defects in early signaling through the Ag-specific IgM receptor as well as a generalized defect in proliferative responsiveness. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Selvey, L A AU - Morse, H C AU - June, C H AU - Hodes, R J AD - Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1995/01/01/ PY - 1995 DA - 1995 Jan 01 SP - 171 EP - 179 VL - 154 IS - 1 SN - 0022-1767, 0022-1767 KW - B29 KW - mb1 KW - src KW - syk KW - Enzyme Precursors KW - 0 KW - Immunoglobulin D KW - Immunoglobulin M KW - Intracellular Signaling Peptides and Proteins KW - Ionophores KW - Lipopolysaccharides KW - Receptors, Antigen, B-Cell KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - SYK protein, human KW - EC 2.7.10.2 KW - Syk Kinase KW - Syk protein, mouse KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Enzyme Precursors -- metabolism KW - Lipopolysaccharides -- pharmacology KW - Protein Processing, Post-Translational KW - Immunoglobulin M -- immunology KW - Spleen -- pathology KW - Mice KW - Protein-Tyrosine Kinases -- metabolism KW - Lymphocyte Activation KW - Immunoglobulin D -- immunology KW - Phosphorylation KW - Ionophores -- pharmacology KW - Mice, Inbred C57BL KW - Calcium -- physiology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Immunologic Capping KW - Immunoglobulin M -- biosynthesis KW - Immunoglobulin D -- biosynthesis KW - Receptors, Antigen, B-Cell -- biosynthesis KW - B-Lymphocytes -- pathology KW - Receptors, Antigen, B-Cell -- immunology KW - Murine Acquired Immunodeficiency Syndrome -- immunology KW - B-Lymphocytes -- immunology KW - Murine Acquired Immunodeficiency Syndrome -- pathology KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77085529?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Analysis+of+antigen+receptor+signaling+in+B+cells+from+mice+with+a+retrovirus-induced+acquired+immunodeficiency+syndrome.&rft.au=Selvey%2C+L+A%3BMorse%2C+H+C%3BJune%2C+C+H%3BHodes%2C+R+J&rft.aulast=Selvey&rft.aufirst=L&rft.date=1995-01-01&rft.volume=154&rft.issue=1&rft.spage=171&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 - 1995-01-19 N1 - Date created - 1995-01-19 N1 - Date revised - 2017-01-13 N1 - Gene symbol - B29; mb1; src; syk N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neuropsychological functioning in detoxified alcoholics between 18 and 35 years of age. AN - 77083855; 7802120 AB - The authors determined 1) cognitive functioning in detoxified alcoholics who had alcohol-related problems for a relatively brief time and 2) relationships between neuropsychological test scores and recent and chronic alcohol consumption patterns, childhood symptoms of hyperactivity/minimal brain dysfunction, and extent of familial alcoholism. The subjects were 101 detoxified, drug-free alcoholics between 18 and 35 years of age who had consumed excessive amounts of alcohol (average of 114 g four to five times per week) for an average of 6 years. An average of 39 days after the last drink each alcoholic was given an extensive battery of neuropsychological tests assessing language skills, attention, motor skills, intelligence, memory, and cognitive functioning related to the frontal regions of the brain. Only four individuals evidenced mild cognitive dysfunction. Current psychiatric condition, anxiety and depressive states, and liver dysfunction were not related to cognition. Relationships of cognition of lifetime estimates of alcohol consumption (average of 189 kg) and number of days from last drink to testing were determined to be nonlinear and suggested that greater lifetime consumption predicted worse performance and that longer abstinence predicted better performance. Neither extent of familial alcoholism nor number of childhood signs and symptoms of hyperactivity/minimal brain dysfunction was predictive of cognition except that more antisocial behavior predicted poorer cognitive functioning. Cognition in young alcoholics, averaging 6 years of excessive alcohol consumption, was within normal limits, even though greater lifetime consumption predicted lower test scores and longer abstinence predicted higher scores. JF - The American journal of psychiatry AU - Eckardt, M J AU - Stapleton, J M AU - Rawlings, R R AU - Davis, E Z AU - Grodin, D M AD - Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Md 20892-1250. Y1 - 1995/01// PY - 1995 DA - January 1995 SP - 53 EP - 59 VL - 152 IS - 1 SN - 0002-953X, 0002-953X KW - Abridged Index Medicus KW - Index Medicus KW - Probability KW - Age Factors KW - Humans KW - Alcohol Drinking KW - Comorbidity KW - Antisocial Personality Disorder -- epidemiology KW - Attention Deficit Disorder with Hyperactivity -- epidemiology KW - Risk Factors KW - Adult KW - Antisocial Personality Disorder -- diagnosis KW - Temperance KW - Adolescent KW - Female KW - Male KW - Alcoholism -- rehabilitation KW - Cognition Disorders -- diagnosis KW - Alcoholism -- epidemiology KW - Cognition Disorders -- epidemiology KW - Alcoholism -- diagnosis KW - Neuropsychological Tests UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77083855?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+psychiatry&rft.atitle=Neuropsychological+functioning+in+detoxified+alcoholics+between+18+and+35+years+of+age.&rft.au=Eckardt%2C+M+J%3BStapleton%2C+J+M%3BRawlings%2C+R+R%3BDavis%2C+E+Z%3BGrodin%2C+D+M&rft.aulast=Eckardt&rft.aufirst=M&rft.date=1995-01-01&rft.volume=152&rft.issue=1&rft.spage=53&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+psychiatry&rft.issn=0002953X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-25 N1 - Date created - 1995-01-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Target cell populations in virus-associated hepatocarcinogenesis. AN - 76180400; 8875621 AB - Studies on the natural course of virus-associated hepatocellular carcinoma (HCC) in high risk areas, particularly hepatitis B virus (HBV), have shown a stage of persistent liver cell hyperplasia characterized by a low level elevation of serum alpha-fetoprotein (AFP). We have recently identified a population of epithelial cells with distinct structure and expression of cytokeratin and AFP in non-neoplastic liver tissues from humans with HBV-associated HCC. These cells were characterized by oval nuclei, scant pale cytoplasm, small cell size, and cross-reactivity to a monoclonal antibody against rat oval cells. These human epithelial cells, putative human oval-type cells, stained strongly positive for cytokeratin 19 and displayed considerable heterogeneity in AFP and albumin expression. These findings suggest that a cell population structurally and phenotypically similar to oval cells seen in the early stages of chemical hepatocarcinogenesis in the rat is also present in humans in regenerating liver lesions observed in HBV-associated HCC. Hepatitis B surface antigen (HBsAg) was detected in 69, 81, and 85% of oval-type cells, transitional cells, and hepatocytes, respectively, but not in bile ducts or ductular cells. Also, high levels of expression of transforming growth factor alpha (TGF-alpha) were frequently seen in oval-type and transitional cells expressing HBsAg. These data suggest the possibility that oval-type cells are a target cell population for HBV infection; in the presence of elevated TGF-alpha expression, these cells may constitute a progenitor population for human HCC. JF - Princess Takamatsu symposia AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 163 EP - 170 VL - 25 KW - Hepatitis B Core Antigens KW - 0 KW - Hepatitis B Surface Antigens KW - Transforming Growth Factor alpha KW - Index Medicus KW - Rats KW - Animals KW - Liver -- pathology KW - Hepatitis B Core Antigens -- analysis KW - Hepatitis B Surface Antigens -- analysis KW - Humans KW - Transforming Growth Factor alpha -- analysis KW - Liver Neoplasms -- pathology KW - Hepatitis B -- complications KW - Hepatitis B -- pathology KW - Carcinoma, Hepatocellular -- etiology KW - Carcinoma, Hepatocellular -- pathology KW - Liver Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76180400?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Princess+Takamatsu+symposia&rft.atitle=Target+cell+populations+in+virus-associated+hepatocarcinogenesis.&rft.au=Thorgeirsson%2C+S+S&rft.aulast=Thorgeirsson&rft.aufirst=S&rft.date=1995-01-01&rft.volume=25&rft.issue=&rft.spage=163&rft.isbn=&rft.btitle=&rft.title=Princess+Takamatsu+symposia&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-16 N1 - Date created - 1997-01-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation of resident tissue-specific macrophages by swainsonine. AN - 75503442; 8835286 AB - The induction of macrophage tumoricidal activity by swainsonine (8a beta-indolizidine-1 alpha, 2 alpha, 8 beta-triol), an indolizidine alkaloid, has been implicated as possibly an important immune effector mechanism involved in the suppression of tumor growth and metastasis in vital organs such as the lung, liver and spleen (Olden, K. et al. The potential importance of swainsonine in therapy for cancers and immunology. Pharmacol. Ther. 50:285-290; 1991). The present study further explores this possibility by determining whether resident tissue-specific macrophages of several mouse strains can be rendered tumoricidal by systemic administration of swainsonine. We found that systemically administered swainsonine could increase the tumoricidal activity of both alveolar (lung) and splenic macrophages. The activity was enhanced as much as 3- to 4-fold over that obtained with macrophages from organs of control animals and was both dose- and time-dependent. The level and extent of activation by swainsonine was comparable to that achieved with traditional macrophage-activating agents, such as lipopolysaccharide and interferon-gamma. The fact that swainsonine activated highly purified (> 95%) cultures of macrophages from the various sources suggests a direct mechanism of activation. Furthermore, the in vivo activation of macrophages in immune-compromised animals (SCID and nude) lends credence to this suggestion. These findings provide a plausible explanation for the observations that systemically administered swainsonine inhibits organ colonization of metastatic cells and growth of SC tumor xenografts, whereas the growth of tumor cells is not inhibited by swainsonine in culture. JF - Oncology research AU - Das, P C AU - Roberts, J D AU - White, S L AU - Olden, K AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 425 EP - 433 VL - 7 IS - 9 SN - 0965-0407, 0965-0407 KW - Adjuvants, Immunologic KW - 0 KW - Lipopolysaccharides KW - Interferon-gamma KW - 82115-62-6 KW - Swainsonine KW - RSY4RK37KQ KW - Index Medicus KW - Injections, Intraperitoneal KW - Macrophages -- cytology KW - Neoplasms -- drug therapy KW - Animals KW - Spleen -- cytology KW - Dose-Response Relationship, Drug KW - Lipopolysaccharides -- pharmacology KW - Interferon-gamma -- pharmacology KW - Macrophages, Peritoneal -- drug effects KW - Mice KW - Cell Death -- drug effects KW - Macrophages -- drug effects KW - Macrophages, Alveolar -- drug effects KW - Mice, Inbred C3H KW - Spleen -- drug effects KW - Time Factors KW - Swainsonine -- administration & dosage KW - Adjuvants, Immunologic -- administration & dosage KW - Swainsonine -- pharmacology KW - Adjuvants, Immunologic -- pharmacology KW - Macrophage Activation -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75503442?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Activation+of+resident+tissue-specific+macrophages+by+swainsonine.&rft.au=Das%2C+P+C%3BRoberts%2C+J+D%3BWhite%2C+S+L%3BOlden%2C+K&rft.aulast=Das&rft.aufirst=P&rft.date=1995-01-01&rft.volume=7&rft.issue=9&rft.spage=425&rft.isbn=&rft.btitle=&rft.title=Oncology+research&rft.issn=09650407&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-01-30 N1 - Date created - 1997-01-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hypothese evolutive du versant instable de Trafoi en Val Venosta (Alto Adige, Italie) TT - Evolution hypothesis for slope stability of Trafoi, Venosta Valley (upper Adige River, Italy) AN - 742922986; 2010-064492 JF - Incontro Internazionale dei Giovani Ricercatori in Geologia Applicata = International Meeting of Young Researchers in Applied Geology AU - Corbi, Ileana AU - Mortara, Giovanni AU - Silvano, Sandro AU - Tetamo, Giuseppina AU - Colla, Maurizio AU - Cravero, Masantonio AU - Crivellari, Riccardo AU - Mancini, Susanna AU - Mandrone, Giuseppe AU - Marini, Paola AU - Masciocco, Luciano AU - Sassone, Paolo Y1 - 1995 PY - 1995 DA - 1995 SP - 50 EP - 55 PB - [varies], [varies] VL - 2 KW - geologic hazards KW - erosion KW - Trafoi Italy KW - Europe KW - Italy KW - Southern Europe KW - Mount Zandila KW - Trafoi Creek KW - mass movements KW - drainage basins KW - Venosta Valley KW - storms KW - Trentino-Alto Adige Italy KW - Mount Tarres KW - hydrology KW - rainfall KW - Alto Adige KW - sedimentation KW - Adige River KW - Valtellina KW - glacial features KW - models KW - risk assessment KW - geomorphology KW - slope stability KW - 23:Geomorphology KW - 22:Environmental geology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/742922986?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ageorefmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Incontro+Internazionale+dei+Giovani+Ricercatori+in+Geologia+Applicata+%3D+International+Meeting+of+Young+Researchers+in+Applied+Geology&rft.atitle=Hypothese+evolutive+du+versant+instable+de+Trafoi+en+Val+Venosta+%28Alto+Adige%2C+Italie%29&rft.au=Corbi%2C+Ileana%3BMortara%2C+Giovanni%3BSilvano%2C+Sandro%3BTetamo%2C+Giuseppina%3BColla%2C+Maurizio%3BCravero%2C+Masantonio%3BCrivellari%2C+Riccardo%3BMancini%2C+Susanna%3BMandrone%2C+Giuseppe%3BMarini%2C+Paola%3BMasciocco%2C+Luciano%3BSassone%2C+Paolo&rft.aulast=Corbi&rft.aufirst=Ileana&rft.date=1995-01-01&rft.volume=2&rft.issue=&rft.spage=50&rft.isbn=&rft.btitle=&rft.title=Incontro+Internazionale+dei+Giovani+Ricercatori+in+Geologia+Applicata+%3D+International+Meeting+of+Young+Researchers+in+Applied+Geology&rft.issn=&rft_id=info:doi/ LA - French DB - GeoRef N1 - Conference title - II incontro internazionale dei giovani ricercatori in geologia applicata N1 - Copyright - GeoRef, Copyright 2012, American Geosciences Institute. N1 - Date revised - 2010-01-01 N1 - Number of references - 7 N1 - Document feature - illus. incl. sketch map N1 - Last updated - 2012-06-07 N1 - CODEN - #06494 N1 - SubjectsTermNotLitGenreText - Adige River; Alto Adige; drainage basins; erosion; Europe; geologic hazards; geomorphology; glacial features; hydrology; Italy; mass movements; models; Mount Tarres; Mount Zandila; rainfall; risk assessment; sedimentation; slope stability; Southern Europe; storms; Trafoi Creek; Trafoi Italy; Trentino-Alto Adige Italy; Valtellina; Venosta Valley ER - TY - JOUR T1 - Women's Health Research: Public Policy and Sociology AN - 61414462; 9601907 AB - In just a few years, the amount & nature of scientific research on women's health has emerged as a major policy issue being addressed at the highest levels of the federal government, in the mainstream media, & within medical, scientific, health, & women's organizations. Sociologists have made significant contributions to both the process by which the women's health research issue has ascended to public awareness & the content of its agenda. Many of these contributions go unrecognized & other potential contributions by medical sociologists remain unrealized. To advance both science & practice in women's health, sociologists are urged to participate more directly in the policy debates. 113 References. Adapted from the source document. JF - Journal of Health and Social Behavior AU - Auerbach, Judith D AU - Figert, Anne E AD - Office AIDS Research National Instits Health, Bldg 31 Rm 4C06 Bethesda MD 20892 judith-auerbach@nih.gov Y1 - 1995///0, PY - 1995 DA - 0, 1995 SP - 115 EP - 131 SN - 0022-1465, 0022-1465 KW - women's health, research/policy concerns, sociology's role KW - Policy Making KW - Medical Sociology KW - Womens Health Care KW - Health Policy KW - article KW - 2462: policy, planning, forecasting; policy sciences KW - 2045: sociology of health and medicine; sociology of medicine & health care UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61414462?accountid=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+Health+and+Social+Behavior&rft.atitle=Women%27s+Health+Research%3A+Public+Policy+and+Sociology&rft.au=Auerbach%2C+Judith+D%3BFigert%2C+Anne+E&rft.aulast=Auerbach&rft.aufirst=Judith&rft.date=1995-01-01&rft.volume=&rft.issue=&rft.spage=115&rft.isbn=&rft.btitle=&rft.title=Journal+of+Health+and+Social+Behavior&rft.issn=00221465&rft_id=info:doi/ LA - English DB - Sociological Abstracts N1 - Date revised - 2007-04-01 N1 - Last updated - 2016-09-28 N1 - CODEN - JHSBA5 N1 - SubjectsTermNotLitGenreText - Womens Health Care; Medical Sociology; Health Policy; Policy Making ER - TY - JOUR T1 - Heart failure: management of patients with left-ventricular systolic dysfunction AN - 57520174; 51524 AB - Heart failure is a major public health problem. This quick reference guide for clinicians provides recommendations concerning the outpatient evaluation and care of the most common cause of heart failure. It is intended for use by a broad range of health care practitioners. The recommendations are placed in a logical framework organized around a clinical algorithm. The recommendations are presented in a very abbreviated form. JF - Journal of Geriatric Drug Therapy AU - Agency for Health Care Policy and Research AU - National Heart, Lung, and Blood Institute AD - Agency for Health Care Policy and Research ; National Heart, Lung, and Blood Institute Y1 - 1995///0, PY - 1995 DA - 0, 1995 SP - 5 EP - 27 VL - 9 IS - 4 SN - 8756-4629, 8756-4629 KW - USA KW - Guidelines KW - Patients KW - Clinical management KW - Heart diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/57520174?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Geriatric+Drug+Therapy&rft.atitle=Heart+failure%3A+management+of+patients+with+left-ventricular+systolic+dysfunction&rft.au=Agency+for+Health+Care+Policy+and+Research%3BNational+Heart%2C+Lung%2C+and+Blood+Institute&rft.aulast=Agency+for+Health+Care+Policy+and+Research&rft.aufirst=&rft.date=1995-01-01&rft.volume=9&rft.issue=4&rft.spage=5&rft.isbn=&rft.btitle=&rft.title=Journal+of+Geriatric+Drug+Therapy&rft.issn=87564629&rft_id=info:doi/ LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Date revised - 2001-08-07 N1 - Document feature - il. tables. refs N1 - Last updated - 2016-09-27 N1 - CODEN - JGDTEF N1 - SubjectsTermNotLitGenreText - Heart diseases; Patients; Clinical management; Guidelines; USA ER - TY - JOUR T1 - Characterization of mammalian ADP-ribosylation cycles AN - 21345036; 7574602 AB - NAD: arginine ADP-ribosyltransferases catalyze the transfer of the ADP-ribose moiety from NAD to an arginine in an acceptor protein, whereas ADP-ribosylarginine hydrolases remove ADP-ribose, regenerating free arginine and completing an ADP-ribosylation cycle. A family of four mono-ADP-ribosyltransferases was isolated and characterized from turkey erythrocytes. Transferases from rabbit and human skeletal muscle were cloned. The muscle transferases are glycosylphosphatidylinositol-anchored proteins and highly conserved across mammalian species. The rat T cell alloantigen RT6.2 has significant amino acid sequence identity to the muscle ADP-ribosyltransferase. Mammalian cells transformed with the RT6.2 coding region cDNA expressed NAD glycohydrolase activity. Sequences of RT6.2, rabbit muscle transferase and several of the bacterial toxin ADP-ribosyltransferases contain regions of amino acid similarity which, in the bacterial toxin ADP-ribosyltransferases, from the NAD-binding and active-site domains. ADP-ribosylarginine hydrolase, initially purified from turkey erythrocytes, was cloned from rat, mouse, and human brain. Deduced amino acid sequences of the rat and mouse hydrolases were 94% identical with five conserved cysteines whereas the human hydrolase sequence was 83% identical to that of the rat, with four conserved cysteines. It is unclear how an intracellular hydrolase acts in concert with a surface ADP-ribosyltransferase. Author JF - Biochimie AU - Okazaki, I J AU - Zolkiewska, A AU - Takada, T AU - Moss, J AD - Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, Bldg 10, room 5N307, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 319 EP - 325 PB - Elsevier Science Ltd., The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:usinfo-f@elsevier.com], [URL:http://www.elsevier.nl] VL - 77 IS - 5 SN - 0300-9084, 0300-9084 KW - Microbiology Abstracts B: Bacteriology KW - ADP-ribosylation KW - mono-ADP-ribosyltransferase KW - RT6.2 protein KW - glycosylphosphatidylinositol anchor KW - ADP-ribosylarginine hydrolase KW - Coding KW - Arginine KW - NAD(P) super(+)-arginine ADP-ribosyltransferase KW - Erythrocytes KW - Brain KW - Toxins KW - hydrolase KW - Mammalian cells KW - NAD KW - Cysteine KW - Alloantigens KW - Lymphocytes T KW - Conserved sequence KW - Skeletal muscle KW - Amino acid sequence KW - J 02410:Animal Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21345036?accountid=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=Biochimie&rft.atitle=Characterization+of+mammalian+ADP-ribosylation+cycles&rft.au=Okazaki%2C+I+J%3BZolkiewska%2C+A%3BTakada%2C+T%3BMoss%2C+J&rft.aulast=Okazaki&rft.aufirst=I&rft.date=1995-01-01&rft.volume=77&rft.issue=5&rft.spage=319&rft.isbn=&rft.btitle=&rft.title=Biochimie&rft.issn=03009084&rft_id=info:doi/10.1016%2F0300-9084%2896%2988141-7 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-02-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Coding; NAD(P) super(+)-arginine ADP-ribosyltransferase; Arginine; Erythrocytes; Brain; Toxins; hydrolase; NAD; Mammalian cells; Cysteine; Alloantigens; Lymphocytes T; Conserved sequence; Skeletal muscle; ADP-ribosylation; Amino acid sequence DO - http://dx.doi.org/10.1016/0300-9084(96)88141-7 ER - TY - JOUR T1 - Helicobacter hepaticus, a recently recognized bacterial pathogen, associated with chronic hepatitis and hepatocellular neoplasia in laboratory mice. AN - 20668064; 9420666 JF - Emerging Infectious Diseases AU - Rice, J M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, Maryland, USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 129 EP - 131 PB - U.S. National Center for Infectious Diseases, 1600 Clifton Rd VL - 1 IS - 4 SN - 1080-6040, 1080-6040 KW - Microbiology Abstracts B: Bacteriology; Virology & AIDS Abstracts KW - Hepatitis KW - Bacteria KW - Helicobacter hepaticus KW - Pathogens KW - Neoplasia KW - V 22400:Human Diseases KW - J 02300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20668064?accountid=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=Emerging+Infectious+Diseases&rft.atitle=Helicobacter+hepaticus%2C+a+recently+recognized+bacterial+pathogen%2C+associated+with+chronic+hepatitis+and+hepatocellular+neoplasia+in+laboratory+mice.&rft.au=Rice%2C+J+M&rft.aulast=Rice&rft.aufirst=J&rft.date=1995-01-01&rft.volume=1&rft.issue=4&rft.spage=129&rft.isbn=&rft.btitle=&rft.title=Emerging+Infectious+Diseases&rft.issn=10806040&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-06-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Hepatitis; Pathogens; Neoplasia; Bacteria; Helicobacter hepaticus ER - TY - JOUR T1 - Rational cancer therapy AN - 19875519; 3783009 AB - As our knowledge of the basis of different cancers grows, so does the arsenal of specific weapons with which to fight the disease. JF - Nature Medicine AU - Lowy AU - Willumsen, B M AD - Lab. Cell. Oncol., NCI/NIH, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 747 EP - 748 VL - 1 IS - 8 SN - 1078-8956, 1078-8956 KW - H-ras gene KW - K-ras gene KW - N-ras gene KW - farnesyl protein transferase KW - mice KW - cancer KW - gene therapy KW - Human Genome 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/19875519?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Medicine&rft.atitle=Rational+cancer+therapy&rft.au=Lowy%3BWillumsen%2C+B+M&rft.aulast=Lowy&rft.aufirst=&rft.date=1995-01-01&rft.volume=1&rft.issue=8&rft.spage=747&rft.isbn=&rft.btitle=&rft.title=Nature+Medicine&rft.issn=10788956&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2010-08-21 ER - TY - CONF T1 - The lack of an ovarian effect of lifetime talc exposure in F344/N rats and B6C3F1 mice AN - 17090795; 3902174 AB - There has been some concern reported about the perineal exposure to talc and the occurrence of ovarian cancer in women, although other studies have failed to find such an association. Talc particles have also been reported to be present in the ovaries of women regardless of history of talc exposure. An NTP study of lifetime whole body exposure talc exposure offered the opportunity to determine whether rodents would have ovarian talc particles after inhalation, oral, and dermal exposure for more than 2 years. JF - Regulatory Toxicology and Pharmacology AU - Boorman, G A AU - Seely, J C Y1 - 1995 PY - 1995 DA - 1995 SP - 242 EP - 243 VL - 21 IS - 2 KW - talc KW - rats KW - mice KW - Toxicology Abstracts KW - inhalation KW - lesions KW - ovaries KW - skin KW - toiletries KW - X 24140:Cosmetics, toiletries & household products UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17090795?accountid=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=Regulatory+Toxicology+and+Pharmacology&rft.atitle=The+lack+of+an+ovarian+effect+of+lifetime+talc+exposure+in+F344%2FN+rats+and+B6C3F1+mice&rft.au=Boorman%2C+G+A%3BSeely%2C+J+C&rft.aulast=Boorman&rft.aufirst=G&rft.date=1995-01-01&rft.volume=21&rft.issue=2&rft.spage=242&rft.isbn=&rft.btitle=&rft.title=Regulatory+Toxicology+and+Pharmacology&rft.issn=02732300&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Receptors, alkaloids from frog skins: Selective probes for ion channels, nicotinic AN - 17068597; 3894029 AB - Amphibian skin has provided a wide range of biologically active alkaloids, many of which have unique profiles of pharmacological activity and therapeutic potential. Over three hundred alkaloids have been identified and structures of over a dozen different classes of alkaloids have been elucidated. These include the batrachotoxins, which were shown to be potent and selective activators and ligands for sodium channels, the histrionicotoxins, which were shown to be potent non-competitive blockers and ligands for nicotinic receptor channel complexes, the pumiliotoxins and related allo- and homo-pumiliotoxins, which were shown to have myotonic and cardiotonic activity due to effects on sodium channels, and epibatidine, which was shown to have potent antinociceptive activity due to selective agonist activity at nicotinic receptors. These alkaloids are known in nature only in amphibian skin, except for homobatrachotoxin, which was recently identified in feathers and skin of a bird. Further classes of alkaloids from amphibian skin include monocyclic pyrrolidines and piperidines, bicyclic decahydroquinolines, pyrrolizidines, indolizidines, and quinolizidines and tricyclic gephyrotoxins, pyrrolizidine oximes, pseudophrynamines, and coccinellines. These alkaloids also have activity at ion channels. It appears likely that all of the frog skin alkaloids are taken up and sequestered into the skin from the diet, which for such amphibians consists mainly of small arthropods. The pyrrolidines, piperidines, 3,5-disubstituted pyrrolizidines and 3,5-disubstituted indolizidines appear likely to be derived from ants, the coccinellines and related tricyclics from beetles and the pyrrolizidine oximes from millipedes. The origins of the batrachotoxins, histrionicotoxins, pumiliotoxins and epibatidine are of particular interest in view of their remarkable biological activities. JF - Brazilian Journal of Medical and Biological Research AU - Daly, J W AD - NIH, NIDDK, Bldg. 8, Rm. 1A17, Bethesda, MD 20892-0820, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 1033 EP - 1042 VL - 28 IS - 10 SN - 0100-879X, 0100-879X KW - alkaloids KW - acetylcholine receptors (nicotinic) KW - ion channels KW - Toxicology Abstracts KW - Phyllobates KW - skin KW - X 24173:Animals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17068597?accountid=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=Brazilian+Journal+of+Medical+and+Biological+Research&rft.atitle=Receptors%2C+alkaloids+from+frog+skins%3A+Selective+probes+for+ion+channels%2C+nicotinic&rft.au=Daly%2C+J+W&rft.aulast=Daly&rft.aufirst=J&rft.date=1995-01-01&rft.volume=28&rft.issue=10&rft.spage=1033&rft.isbn=&rft.btitle=&rft.title=Brazilian+Journal+of+Medical+and+Biological+Research&rft.issn=0100879X&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 - Phyllobates; skin ER - TY - JOUR T1 - Inhibitors of HIV nucleocapsid protein zinc fingers as candidates for the treatment of AIDS AN - 17066584; 3891826 AB - Strategies for the treatment of human immunodeficiency virus-type 1 (HIV-1) infection must contend with the obstacle of drug resistance. HIV-1 nucleocapsid protein zinc fingers are prime antiviral targets because they are mutationally intolerant and are required both for acute infection and virion assembly. Nontoxic disulfide-substituted benzamides were identified that attack the zinc fingers, inactivate cell-free virions, inhibit acute and chronic infections, and exhibit broad antiretroviral activity. The compounds were highly synergistic with other antiviral agents, and resistant mutants have not been detected. Zinc finger-reactive compounds may offer an anti-HIV strategy that restricts drug-resistance development. JF - Science (Washington) AU - Rice, W G AU - Supko, J G AU - Malspeis, L AU - Buckheit, RW Jr AU - Clanton, D AU - Bu, Ming AU - Graham, L AU - Schaeffer, CA AU - Turpin, JA AU - Domagala, J AU - Gogliotti, R AU - Bader, J P AU - Halliday, S M AU - Coren, L AU - Henderson, LE AD - Dep. Antiviral Drug Mechanisms, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Building 431T-B, P.O. Box B Frederick, MD 21702, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 1194 EP - 1197 VL - 270 IS - 5239 SN - 0036-8075, 0036-8075 KW - benzamides KW - nucleocapsid protein KW - zinc finger KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - antiviral agents KW - human immunodeficiency virus 1 KW - acquired immune deficiency syndrome KW - V 22002:AIDS: Molecular and in vitro aspects KW - W3 33190:Therapy: Other KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17066584?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+%28Washington%29&rft.atitle=Inhibitors+of+HIV+nucleocapsid+protein+zinc+fingers+as+candidates+for+the+treatment+of+AIDS&rft.au=Rice%2C+W+G%3BSupko%2C+J+G%3BMalspeis%2C+L%3BBuckheit%2C+RW+Jr%3BClanton%2C+D%3BBu%2C+Ming%3BGraham%2C+L%3BSchaeffer%2C+CA%3BTurpin%2C+JA%3BDomagala%2C+J%3BGogliotti%2C+R%3BBader%2C+J+P%3BHalliday%2C+S+M%3BCoren%2C+L%3BHenderson%2C+LE&rft.aulast=Rice&rft.aufirst=W&rft.date=1995-01-01&rft.volume=270&rft.issue=5239&rft.spage=1194&rft.isbn=&rft.btitle=&rft.title=Science+%28Washington%29&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - antiviral agents; acquired immune deficiency syndrome; human immunodeficiency virus 1 ER - TY - JOUR T1 - Are there alternative avian influenza viruses for generation of stable attenuated avian-human influenza A reassortant viruses? AN - 17053399; 3885880 AB - The present study evaluated gull influenza A viruses as donors of attenuating genes for the production of live, attenuated influenza A H1N1 and H3N2 avian-human (ah) reassortant viruses for use as vaccines to prevent disease due to influenza A viruses in humans. The previously evaluated duck influenza A viruses were abandoned as donors of attenuating avian influenza virus genes because clinical evaluation of H1N1 and H3N2 ah reassortant virus vaccines derived from duck viruses documented residual virulence of H1N1 reassortants for seronegative infants and young children. Gull influenza A viruses occupy an independent ecologic niche and are rarely isolated from species other than gulls. The possibility of using gull influenza A viruses as donors of internal gene segments in ah reassortant viruses was evaluated in the present study using three different gull viruses and three human influenza A viruses. Gull-human H3N2 reassortant influenza A viruses with the desired 6-2 genotype (six internal avian influenza virus genes and the two human influenza virus surface glycoprotein genes) were readily generated and were found to be attenuated for squirrel monkeys and chimpanzees. However, ah reassortant viruses with gull and human influenza A H1N1 genes were difficult to generate, and reassortants that had the desired genotype of six gull virus genes with human influenza A H1 and N1 genes were not isolated despite repeated attempts. The gull PB2, NP and NS genes were not present in any of the gull-human H1N1 reassortants generated. The under-representation of these three gene segments suggests that reassortants bearing one or more of these three gene segments might have reduced viability indicative of a functional incompatibility in their gene products. The difficulties encountered in the generation of a 6-2 gull-human H1N1 reassortant virus are sufficient to conclude that the gull influenza A viruses tested would not be useful as donors of sets of six internal genes to attenuate human influenza A viruses. This study also identifies influenza virus gene segments that appear to be incompatible for generation of reassortants. Elucidation of the molecular basis of this restriction may provide information on intergenic interactions involved in virion assembly or packaging. JF - Virus Research AU - Subbarao, K AU - Webster, R G AU - Kawaoka, Y AU - Murphy, B R AD - Respir. Viruses Sect., Lab. Infect. Dis., NIAID/NIH, Bldg. 7, Rm. 106, 7 Cent. Dr. MSC 0720, Bethesda, MD, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 105 EP - 118 VL - 39 IS - 2-3 SN - 0168-1702, 0168-1702 KW - NS gene KW - influenza virus (avian) KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - vaccines KW - histocompatibility KW - influenza A virus KW - W3 33365:Vaccines (other) KW - V 22097:Immunization: Vaccines & vaccination: Human KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17053399?accountid=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=Virus+Research&rft.atitle=Are+there+alternative+avian+influenza+viruses+for+generation+of+stable+attenuated+avian-human+influenza+A+reassortant+viruses%3F&rft.au=Subbarao%2C+K%3BWebster%2C+R+G%3BKawaoka%2C+Y%3BMurphy%2C+B+R&rft.aulast=Subbarao&rft.aufirst=K&rft.date=1995-01-01&rft.volume=39&rft.issue=2-3&rft.spage=105&rft.isbn=&rft.btitle=&rft.title=Virus+Research&rft.issn=01681702&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - vaccines; histocompatibility; influenza A virus ER - TY - JOUR T1 - High-efficiency transfer of the T cell co-stimulatory molecule B7-2 to lymphoid cells using high-titer recombinant adeno-associated virus vectors AN - 17039292; 3876169 AB - Adeno-associated virus (AAV) is a single-stranded DNA virus that can either integrate or replicate in host cells. Production of recombinant viral particles (rAAV) requires expression of the viral structural genes and the viral inverted terminal repeats in cis. By using an SV40 replicon to amplify the structural genes, the yield of recombinant viral particles was increased 60-fold over a nonreplicating helper plasmid. The rAAV particles produced by this system have similar physical properties to wild-type particles, including buoyant density, size, and morphology. This novel rAAV packaging system was used to produce rAAV particles that contain the gene for the T cell co-stimulatory protein B7-2. Transduction of the human nonadherent lymphoid cell line LP-1 with these particles significantly increased the percentage of cells expressing B7-2 from 6.8% to 78.0%. Expression of B7-2 in the human lymphoid cell line RPMI-8226 was also substantially increased. Targeting of tumor cells grown in suspension was hampered by low-efficiency transduction using other viral or nonviral vector systems. Our new packaging system for recombinant AAV should allow generation of sufficient quantities of B7-2 containing particles to develop tumor vaccines for non-Hodgkin's lymphoma. JF - Human Gene Therapy AU - Chiorini, JA AU - Wendtner, C M AU - Urcelay, E AU - Safer, B AU - Hallek, M AU - Kotin, R M AD - NIH/NHLBI/MHB, Bldg 10/7D18, 10 Cent. Dr. MSC 1654, Bethesda, MD 20892-1654, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 1531 EP - 1541 VL - 6 IS - 12 SN - 1043-0342, 1043-0342 KW - B7-2 antigen KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Genetics Abstracts KW - gene therapy KW - adenovirus KW - lymphocytes T KW - cloning vectors KW - DNA KW - tumor cells KW - lymphoma KW - lymphoid cells KW - F 06818:Cancer immunotherapy KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17039292?accountid=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=High-efficiency+transfer+of+the+T+cell+co-stimulatory+molecule+B7-2+to+lymphoid+cells+using+high-titer+recombinant+adeno-associated+virus+vectors&rft.au=Chiorini%2C+JA%3BWendtner%2C+C+M%3BUrcelay%2C+E%3BSafer%2C+B%3BHallek%2C+M%3BKotin%2C+R+M&rft.aulast=Chiorini&rft.aufirst=JA&rft.date=1995-01-01&rft.volume=6&rft.issue=12&rft.spage=1531&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - gene therapy; lymphocytes T; cloning vectors; DNA; tumor cells; lymphoma; lymphoid cells; adenovirus ER - TY - JOUR T1 - The identification of the single-stranded DNA-binding domain of the Escherichia coli RecA protein AN - 17034747; 3867645 AB - To identify the ssDNA-binding domain of Escherichia coli RecA protein, we examined the ssDNA-binding capabilities of synthetic peptides, the sequences of which were derived from the C- and N-termini and from sequences within loops L1 and L2 of the RecA molecule identified from the crystal structure. Synthetic peptides derived from amino acid residues 185 - 219 of several bacterial RecA proteins, which include loop L2 of RecA, bound to ssDNA in filter-binding assays, whereas three separate synthetic peptides corresponding to single point mutants of E. coli RecA in this region did not. The binding of RecA to ssDNA examined using a gel-shift assay was inhibited by a synthetic peptide derived from this ssDNA-binding region, but not by synthetic peptides derived from amino acid residues 301 - 329 of the C-terminus or from N-terminal residues 6-39 A peptide corresponding to amino acid positions 152 - 169 of the RecA molecule and spanning loop L1 and its flanking regions did not bind ssDNA at peptide concentrations up to 250 mu M. We have also defined a synthetic 20-amino-acid peptide that comprises amino acid residues 193 - 212 and includes loop L2 of RecA as the minimum unit that can bind to ssDNA from this region of RecA. Finally, two maltose-binding protein-RecA fusion proteins were made, one containing amino acid residues 185 - 224 of RecA and the other the last 51 C-terminal residues of RecA (amino acid residues 303-353). In contrast to the C-terminus-derived fusion protein, the fusion protein containing the putative DNA-binding site demonstrated significant binding to single-stranded oligonucleotides in both filter-binding and gel-shift assays. These findings suggest that a portion of the region extending from amino acid residues 193-212 is either part of or the whole ssDNA-binding domain of the RecA protein. JF - European Journal of Biochemistry AU - Gardner, R V AU - Voloshin, ON AU - Camerini-Otero, R D AD - Genet. and Biochem. Branch, Natl. Inst. Health (NIDDK), Bldg. 10, Rm. 9D20, 10 Cent. Drive MSC 1810, Bethesda, MD 20892-1810, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 419 EP - 425 VL - 233 IS - 2 SN - 0014-2956, 0014-2956 KW - RecA protein KW - single-stranded DNA-binding protein KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Escherichia coli KW - crystal structure 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/17034747?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+Journal+of+Biochemistry&rft.atitle=The+identification+of+the+single-stranded+DNA-binding+domain+of+the+Escherichia+coli+RecA+protein&rft.au=Gardner%2C+R+V%3BVoloshin%2C+ON%3BCamerini-Otero%2C+R+D&rft.aulast=Gardner&rft.aufirst=R&rft.date=1995-01-01&rft.volume=233&rft.issue=2&rft.spage=419&rft.isbn=&rft.btitle=&rft.title=European+Journal+of+Biochemistry&rft.issn=00142956&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; crystal structure ER - TY - JOUR T1 - Incidence of benign gastrointestinal tumors among atomic bomb survivors AN - 17033183; 3868628 AB - Using the Hiroshima and Nagasaki tumor and tissue registries, benign tumors of the stomach, colon, and rectum were identified among members of the Life Span Study cohort of atomic bomb survivors. During the period 1958-1989, a total of 470 cases with histologically confirmed benign gastrointestinal tumors (163 stomach, 215 colon, and 92 rectum) were identified among approximately 80,000 Life Span Study members with known radiation doses, who were alive in 1958. Restricting the analysis to adenomatous tumors not detected at autopsy, a dose-response relation was observed for stomach tumors (excess relative risk at 1 sievert (ERR sub(1Sv)): 0.53; 95% confidence interval (Cl) -0.01 to 1.43). However, there was little evidence of a dose response for colon tumors (ERR sub(1Sv) = 0.14; 95% Cl -0.20 to 0.76), and no evidence was present for rectal tumors (ERR sub(1Sv) = -0.25; 95% Cl undetermined to 0.80). The excess relative risk (ERR) for benign tumors of the stomach is consistent with the excess found for stomach cancer. For cancer of the rectum, the dose response was not significant, but the point estimate of the excess relative risk was positive. The excess relative risk for benign colon tumors is less than that reported for colon cancer (ERR sub(1Sv) = 0.72). The authors observed a dramatic increase in colon tumors detected after 1985, suggesting that the relatively recent introduction of colonoscopy may be influencing these results. JF - American Journal of Epidemiology AU - Ron, E AU - Wong, F L AU - Mabuchi, K AD - Radiation Epidemiol. Branch (EPN-408), NCI/NIH, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 68 EP - 75 VL - 142 IS - 1 SN - 0002-9262, 0002-9262 KW - environmental health KW - tumors KW - gastrointestinal tract KW - man KW - Toxicology Abstracts; Pollution Abstracts; Health & Safety Science Abstracts KW - ionizing radiation KW - atomic bombs KW - gastrointestinal tract diseases KW - cancer KW - X 24210:Radiation & radioactive materials KW - P 8000:RADIATION KW - H SE3.9.1:RADIATION HAZARDS UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17033183?accountid=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+of+benign+gastrointestinal+tumors+among+atomic+bomb+survivors&rft.au=Ron%2C+E%3BWong%2C+F+L%3BMabuchi%2C+K&rft.aulast=Ron&rft.aufirst=E&rft.date=1995-01-01&rft.volume=142&rft.issue=1&rft.spage=68&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - atomic bombs; environmental health; cancer; ionizing radiation; gastrointestinal tract diseases; tumors; gastrointestinal tract; man ER - TY - JOUR T1 - Control of P1 plasmid replication by iterons AN - 17031474; 3871252 AB - The incA locus of plasmid P1 controls plasmid copy number by inhibiting the replication origin, oriR. Both loci contain repeat sequences (iterons) that bind the P1 RepA protein. Regulation appears to occur by contact of incA and oriR loci of daughter plasmids mediated by RepA-bound iterons. Synthetic incA iteron arrays were constructed with altered numbers, sequences or spacing of iterons. Using these in in vitro and in vivo assays, we examined two models: (i) that the origin and incA loci form a stable 1:1 complex in which multiple iterons of each locus are paired with those of the other, and (ii) that individual incA iterons act as freely diffusing nucleoprotein units that contact origin iterons in a random and dynamic fashion. The data presented here strongly favour the latter case. The origin, with its five iterons, acts as a target but not as an effector of regulation. We present a model for replication control based on random, dynamic contacts between incA iterons and the origin. This system would display randomness with respect to choice of templates and timing of initiation if multiple replicon copies were present, but would tend to act in a machine-like fashion in concert with the cell cycle if just two copies were present in a dividing cell. JF - Molecular Microbiology AU - Abeles, AL AU - Reaves, L D AU - Youngren-Grimes, B AU - Austin, S J AD - Lab. Chromosome Biol., ABL-Basic Res. Program, NCI-Frederick Cancer Res. and Dev. Cent., Frederick, Maryland 21702-1201, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 903 EP - 912 VL - 18 IS - 5 SN - 0950-382X, 0950-382X KW - plasmid P1 KW - incA gene KW - iterons KW - repeated sequence KW - RepA protein KW - replication origins KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - J 02760:Plasmids KW - G 07200:P PLASMIDS UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17031474?accountid=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=Control+of+P1+plasmid+replication+by+iterons&rft.au=Abeles%2C+AL%3BReaves%2C+L+D%3BYoungren-Grimes%2C+B%3BAustin%2C+S+J&rft.aulast=Abeles&rft.aufirst=AL&rft.date=1995-01-01&rft.volume=18&rft.issue=5&rft.spage=903&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 - Typhoid fever in the park: Epidemiology of an outbreak at a cultural interface AN - 17028612; 3869142 AB - The number of reported outbreaks of typhoid fever in the United States has recently increased. Only six were reported from 1980-1989, but seven outbreaks were reported in 1990. In August 1990, health officials in Montgomery County, Maryland, were notified of two cases of typhoid fever among persons who had attended both a family picnic attended by 60 persons and a Latin Food Festival attended by 100,000 people. We obtained interviews, blood and stool cultures, and Vi serologies from attendees at and food handlers for the picnic. We defined cases as culture-confirmed or probable. Of the 60 picnic attendees, 24 (40%) had cases, of which 16 were culture confirmed. Those who ate potato salad were at increased risk of disease. Picnic attendees who also attended the Latin Food Festival were not at significantly greater risk of disease than those who did not, and we found no evidence of disease among other festival attendees. The potato salad was prepared with intensive handling and without adequate temperature control by a recent immigrant from El Salvador who was asymptomatic, did not attend the picnic, had Salmonella typhi (S. typhi) in her stool, and had elevated Vi antibodies, strongly suggestive of the carrier state. Outbreaks of typhoid fever are a threat for cosmopolitan communities. While currently available control measures are unlikely to prevent all outbreaks, thorough investigation can identify previously unrecognized carriers. JF - Journal of Community Health AU - Cote, T R AU - Convery, H AU - Robinson, D AU - Ries, A AU - Barrett, T AU - Frank, L AU - Furlong, W AU - Horan, J AU - Dwyer, D AD - NCI Viral Epidemiol. Branch, EPN-434, 6130 Executive Blvd., Rockville, MD 20852, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 451 EP - 458 VL - 20 IS - 6 SN - 0094-5145, 0094-5145 KW - USA, Maryland, Montgomery Cty. KW - typhoid fever KW - infection KW - mayonnaise KW - salad dressings KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Health & Safety Science Abstracts KW - Salmonella typhi KW - epidemiology KW - diseases KW - food contamination KW - H SM10.33:TYPHOID FEVER KW - A 01017:Human foods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17028612?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Community+Health&rft.atitle=Typhoid+fever+in+the+park%3A+Epidemiology+of+an+outbreak+at+a+cultural+interface&rft.au=Cote%2C+T+R%3BConvery%2C+H%3BRobinson%2C+D%3BRies%2C+A%3BBarrett%2C+T%3BFrank%2C+L%3BFurlong%2C+W%3BHoran%2C+J%3BDwyer%2C+D&rft.aulast=Cote&rft.aufirst=T&rft.date=1995-01-01&rft.volume=20&rft.issue=6&rft.spage=451&rft.isbn=&rft.btitle=&rft.title=Journal+of+Community+Health&rft.issn=00945145&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Salmonella typhi; epidemiology; food contamination; diseases; typhoid fever; infection; mayonnaise; salad dressings ER - TY - JOUR T1 - Analysis of the DnaK molecular chaperone system of Francisella tularensis AN - 17017792; 3849424 AB - We have cloned the Francisella tularensis (Ft) grpE-dnaK-dnaJ heat-shock genes which are organized in that order. These genes allow heterologous genetic complementation of each respective mutant strain of Escherichia coli (Ec) for bacteriophage lambda growth. The nucleotide sequences of the Ft grpE-dnaK-dnaJ genes and the deduced amino-acid sequences share significant homologies with their respective Ec counterparts. The Ft DnaK and DnaJ proteins cross:react with polyclonal antibodies raised against the respective Ec proteins. The grpE-dnaK-dnaJ genes of Ft are organized in a fashion that is more characteristic of Gram super(+) bacteria. JF - Gene AU - Zuber, M AU - Hoover, T A AU - Dertzbaugh, M T AU - Court, D L AD - Mol. Control and Genet. Sect., ABL-Basic Res. Program, NCI-Frederick Cancer Res. and Dev. Cent., P.O. Box B, Frederick, MD 21702-1201, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 149 EP - 152 VL - 164 IS - 1 SN - 0378-1119, 0378-1119 KW - DnaK protein KW - chaperones KW - amino acid sequence prediction KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - nucleotide sequence KW - Escherichia coli KW - Francisella tularensis KW - N 14640:Structure & sequence KW - G 07321:GENERAL KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17017792?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gene&rft.atitle=Analysis+of+the+DnaK+molecular+chaperone+system+of+Francisella+tularensis&rft.au=Zuber%2C+M%3BHoover%2C+T+A%3BDertzbaugh%2C+M+T%3BCourt%2C+D+L&rft.aulast=Zuber&rft.aufirst=M&rft.date=1995-01-01&rft.volume=164&rft.issue=1&rft.spage=149&rft.isbn=&rft.btitle=&rft.title=Gene&rft.issn=03781119&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Francisella tularensis; Escherichia coli; nucleotide sequence ER - TY - JOUR T1 - Tyrphostin AG17, [(3,5-di-tert-butyl-4- hydroxybenzylidene)-malononitrile], inhibits cell growth by disrupting mitochondria AN - 17017350; 3854060 AB - [(3,5-Di-tert-butyl-4- hydroxybenzylidene)-malononitrile] (AG17), a "tyrphostin" tyrosine kinase antagonist, was found to inhibit tumor cell growth with 50% growth inhibition ranging from 0.7 to 4.0 mu M in a panel of 13 human tumor cell lines, as evaluated by tetrazolium dye reduction and inhibition of precursor incorporation into macromolecules. The promyelocytic leukemia cell line HL-60(TB), was the most sensitive with irreversible total growth inhibition after 12 h of exposure to 1.5 mu M drug. Antiproliferative effects of AG17 in HL-60(TB) cells were temporally related to disruption of mitochondrial function, which occurred within 1 h after drug exposure as demonstrated by a significantly decreased mass of ATP in drug-treated cells, loss of the fluorescent mitochondrial membrane potential probe rhodamine 123, and ultrastructural examination of mitochondria using fluorescence and electron microscopy. Specific decreases of total or tyrosine-phosphorylated substrate at concentrations of the drug not affecting ATP levels were not detected. These data raise the possibility that AG17 may act in part by altering mitochondrial function and/or structure, and that impairment of mitochondrial function may be exploitable as a potentially useful mechanism to modulate tumor cell proliferation. This study also emphasizes the importance of evaluating carefully the effects of potential protein kinase antagonists, since these structures have effects in intact cells in addition to what might be expected from in vitro enzyme assays. JF - Cancer Research AU - Burger, A M AU - Kaur, G AU - Alley, M C AU - Supko, J G AU - Malspeis, L AU - Grever, M R AU - Sausville, E A AD - NCI/NIH, EPN 843, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 2794 EP - 2799 VL - 55 IS - 13 SN - 0008-5472, 0008-5472 KW - (3,5-di-tert-butyl-4- hydroxybenzylidine)-malononitrile KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - mitochondria KW - cell proliferation KW - inhibitors KW - tumors KW - cell disruption KW - W3 33370:Antibiotics KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17017350?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Research&rft.atitle=Tyrphostin+AG17%2C+%5B%283%2C5-di-tert-butyl-4-+hydroxybenzylidene%29-malononitrile%5D%2C+inhibits+cell+growth+by+disrupting+mitochondria&rft.au=Burger%2C+A+M%3BKaur%2C+G%3BAlley%2C+M+C%3BSupko%2C+J+G%3BMalspeis%2C+L%3BGrever%2C+M+R%3BSausville%2C+E+A&rft.aulast=Burger&rft.aufirst=A&rft.date=1995-01-01&rft.volume=55&rft.issue=13&rft.spage=2794&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 - 2011-12-14 N1 - SubjectsTermNotLitGenreText - cell proliferation; mitochondria; inhibitors; tumors; cell disruption ER - TY - JOUR T1 - A WHO collaborative study on assays of the antigenic content of inactivated poliovirus vaccines AN - 17015682; 3857720 AB - In the first phase of a two part WHO Collaborative study, fourteen laboratories from ten countries estimated the antigenic content of six trivalent inactivated poliovirus vaccine preparations using in vitro methods. All laboratories used a candidate standard method for D antigen assay (method A) and eight contributed results from established 'in-house' methods (method B). All methods assayed D antigen in an antigen capture ELISA format. Monoclonal antibodies were used as detector reagents in method A and in some laboratories for method B. The average difference in potency estimates for duplicate preparations A and C was used to assess within assay variation. Overall this was found to be 22% and 19% for methods A and B respectively. Within laboratory variation was measured as the geometric coefficient of variation for between assay repeatability. Results for methods A and B, 28% and 26% respectively were again very similar. Variation in potency estimates between laboratories was in the range 2- to 5-fold for most samples and most laboratories irrespective of the method used. However, a maximum 24-fold difference occurred when all results were taken into account. Method A gave significantly enhanced potency estimates for the type 3 component of preparation B, a vaccine shown to be immunogenic in humans in clinical trials, compared to method B. Method A also failed to assay the type 3 component of preparation F which was prepared by inactivation of the Sabin 3 strain of poliovirus. Further work is required to identify monoclonal antibodies, or combinations of monoclonal antibodies, suitable for universal application in D antigen assays of inactivated poliovirus vaccines. Further work is also required to improve control of the antigen-capture ELISA in some laboratories. The second phase of this WHO Collaborative Study evaluated the proficiency of in vivo potency assays. These results together with an evaluation of the correlation of immunogenicity and antigenic assay plus assessment of candidate reference materials will be reported separately. JF - Biologicals AU - Wood, D J AU - Heath, AB AU - Sawyer, LA AD - Div. AIDS, NIAID/NIH, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 83 EP - 94 VL - 23 IS - 1 SN - 1045-1056, 1045-1056 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - antigenic characteristics KW - vaccines KW - poliovirus KW - poliomyelitis KW - immunogenicity KW - V 22097:Immunization: Vaccines & vaccination: Human KW - A 01097:Viruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17015682?accountid=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=Biologicals&rft.atitle=A+WHO+collaborative+study+on+assays+of+the+antigenic+content+of+inactivated+poliovirus+vaccines&rft.au=Wood%2C+D+J%3BHeath%2C+AB%3BSawyer%2C+LA&rft.aulast=Wood&rft.aufirst=D&rft.date=1995-01-01&rft.volume=23&rft.issue=1&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=Biologicals&rft.issn=10451056&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - poliovirus; poliomyelitis; vaccines; antigenic characteristics; immunogenicity ER - TY - JOUR T1 - GrpE alters the affinity of DnaK for ATP and Mg super(2+). Implications for the mechanism of nucleotide exchange AN - 17008983; 3844011 AB - DnaK, DnaJ, and GrpE heat shock proteins of Escherichia coli activate site-specific DNA binding by the RepA replication initiator protein of plasmid P1 in a reaction dependent on ATP and Mg super(2+). We previously showed that GrpE is essential for in vitro RepA activation specifically at about 1 mu M free Mg super(2+). In this paper, we demonstrate that GrpE lowers the requirement of DnaK ATPase for Mg super(2+), resulting in a large stimulation of ATP hydrolysis at about 1 mu M Mg super(2+) with and without DnaJ and RepA. In contrast to its effect on the Mg super(2+) requirement, GrpE increases the ATP requirement for DnaK ATPase and dramatically lowers the affinity of DnaK for ATP in the absence of Mg super(2+). We propose that GrpE not only lowers the affinity of DnaK for nucleotide but, by increasing affinity of DnaK for Mg super(2+), also weakens the interactions of Mg super(2+) with nucleotide prior to its release. JF - Journal of Biological Chemistry AU - Skowyra, D AU - Wickner, S AD - Lab. Mol. Biol., NCI/NIH, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 26282 EP - 26285 VL - 270 IS - 44 SN - 0021-9258, 0021-9258 KW - GrpE protein KW - DnaK protein KW - ATP KW - magnesium KW - Microbiology Abstracts B: Bacteriology KW - heat shock proteins KW - Escherichia coli KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17008983?accountid=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=GrpE+alters+the+affinity+of+DnaK+for+ATP+and+Mg+super%282%2B%29.+Implications+for+the+mechanism+of+nucleotide+exchange&rft.au=Skowyra%2C+D%3BWickner%2C+S&rft.aulast=Skowyra&rft.aufirst=D&rft.date=1995-01-01&rft.volume=270&rft.issue=44&rft.spage=26282&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; heat shock proteins ER - TY - CONF T1 - The impact of glutathione S-transferase M1 and cytochrome P450 1A1 genotypes on white-blood-cell polycyclic aromatic hydrocarbon-DNA adduct levels in humans AN - 17008600; 3842576 AB - Carcinogenic polycyclic aromatic hydrocarbons (PAHs) form DNA adducts via a complex metabolic activation pathway that includes cytochrome P450 (CYP) 1A1, whereas intermediate metabolites can be detoxified by conjugation through pathways including glutathione S-transferase M1 (GSTM1). PAH-DNA adducts can be measured in peripheral white blood cells (WBCs) and should reflect the net effect of competing activation and detoxification pathways and DNA repair as well as exposure. We have previously shown that WBC PAH-DNA adducts measured by an enzyme-linked immunosorbent assay (ELISA) were associated with recent, frequent consumption of charbroiled food among 47 nonsmoking wildland fire-fighters who provided two blood samples 8 wk apart. In the investigation reported here, which was performed in the same population, we measured the association between the GSTM1 null genotype, which results in loss of enzyme activity, and PAH-DNA adduct levels, hypothesizing that subjects with this genotype would have higher levels of DNA adducts because of their decreased ability to detoxify PAH metabolites. However, PAH-DNA adduct levels were nonsignificantly lower in subjects with the GSTM1 null genotype (n = 28) compared with other subjects (n = 19) (median 0.04 fmol/ mu g DNA vs 0.07 fmol/ mu g DNA, respectively, P = 0.45, Wilcoxon rank-sum test). Adduct levels were also lower in the nine subjects heterozygous or homozygous for the CYP1A1 exon 7 polymorphism (which codes for a valine rather than isoleucine and is thought to be associated with greater CYP1A1 activity) compared with the 38 wild-type subjects (P= 0.12). In the entire group, there was a positive association between consuming charbroiled food and PAH-DNA adduct formation (r = 0.24, P = 0.02, Spearman rank-order correlation). This association was weaker in the subgroup of subjects with the GSTM1 null genotype (r = 0.03, P = 0.84) and stronger among the remaining subjects (r = 0.57, P = 0.0002). These results suggest that the GSTM1 null genotype and CYP1A1 exon 7 polymorphism are not associated with increased susceptibility for PAH-DNA adduct formation in peripheral WBCs measured by ELISA in nonsmoking populations. JF - Molecular Carcinogenesis AU - Rothman, N AU - Shields, P G AU - Poirier, M C AU - Harrington, A M AU - Ford, D P AU - Strickland, P T Y1 - 1995 PY - 1995 DA - 1995 SP - 63 EP - 68 PB - JOHN WILEY & SONS, INC. VL - 14 IS - 1 KW - glutathione transferase KW - cytochrome P4501A1 KW - gentotype-environment interactions KW - Biochemistry Abstracts 2: Nucleic Acids; Toxicology Abstracts KW - DNA adducts KW - leukocytes KW - polycyclic aromatic hydrocarbons KW - man KW - N 14630:Chemical reactions & interactions, including effects of radiation KW - X 24190:Polycyclic hydrocarbons UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17008600?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Carcinogenesis&rft.atitle=The+impact+of+glutathione+S-transferase+M1+and+cytochrome+P450+1A1+genotypes+on+white-blood-cell+polycyclic+aromatic+hydrocarbon-DNA+adduct+levels+in+humans&rft.au=Rothman%2C+N%3BShields%2C+P+G%3BPoirier%2C+M+C%3BHarrington%2C+A+M%3BFord%2C+D+P%3BStrickland%2C+P+T&rft.aulast=Rothman&rft.aufirst=N&rft.date=1995-01-01&rft.volume=14&rft.issue=1&rft.spage=63&rft.isbn=&rft.btitle=&rft.title=Molecular+Carcinogenesis&rft.issn=08991987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - The search for DNA homology does not limit stable homologous pairing promoted by RecA protein AN - 17007972; 3844305 AB - Background: The basic molecular mechanisms that govern the search for DNA homology and subsequent homologous pairing during genetic recombination are not understood. RecA is the central homologous recombination protein of Escherichia coli; because several RecA homologues have been identified in eukaryotic cells, it is likely that the mechanisms employed by RecA are conserved throughout evolution. Analysis of the kinetics of the homologous search and pairing reactions catalyzed by RecA should therefore provide insights of general relevance into the mechanisms by which macromolecules locate, and interact with, specific DNA targets. Results: RecA forms three-stranded synaptic complexes with a single-stranded oligonucleotide and a homologous region in duplex DNA. The kinetics of this initial pairing reaction were characterized using duplex DNA molecules of various concentrations and complexities containing a single target site, as well as various concentrations of homologous single-stranded oligonucleotides. The formation of the synaptic complex follows apparent second-order reaction kinetics with a rate proportional to the concentrations of both the homologous single-stranded oligonucleotide and the target sites within the duplex DNA. The reaction rate is independent of the complexity of duplex DNA in the reaction. We propose a kinetic scheme in which the RecA-single-stranded DNA filament interacts with duplex DNA and locates its target in a relatively fast reaction. We also suggest that complex conformational changes occur during the subsequent rate-limiting step. Conclusions: We conclude that, during the formation of synaptic complexes by RecA, the search for homology is not rate-limiting, and that the iteration frequency of the search is around 10 super(2)-10 super(3) s super(-1). This value agrees well with what has been calculated as the minimum number for such a frequency in genome-wide searches, and limits the possible structures involved in the search for homology to those involving very soft (low energy) interactions. Furthermore, from the order of the reaction at the DNA concentrations found in eukaryotic nuclei, and the rate constant of the overall reaction, we predict that the search for homology is also not the rate-limiting step in the genome-wide searches implicated in meiosis and in gene targeting. JF - Current Biology AU - Yancey-Wrona, JE AU - Camerini-Otero, R D AD - NIH/NIDDK, Genet. and Biochem. Branch, Bethesda, MD 20892-1810, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 1149 EP - 1158 VL - 5 IS - 10 SN - 0334-1763, 0334-1763 KW - homologous recombination KW - RecA protein KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Escherichia coli KW - J 02727:Amino acids, peptides and proteins KW - N 14940:Nucleic acid-binding proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17007972?accountid=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=The+search+for+DNA+homology+does+not+limit+stable+homologous+pairing+promoted+by+RecA+protein&rft.au=Yancey-Wrona%2C+JE%3BCamerini-Otero%2C+R+D&rft.aulast=Yancey-Wrona&rft.aufirst=JE&rft.date=1995-01-01&rft.volume=5&rft.issue=10&rft.spage=1149&rft.isbn=&rft.btitle=&rft.title=Current+Biology&rft.issn=03341763&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 ER - TY - JOUR T1 - The non-inducible nature of super-repressors of the gal operon in Escherichia coli AN - 17007914; 3844274 AB - We isolated and characterized mutant repressors (GalR) of the gal operon in Escherichia coli. These repressors (super-repressors), called GalR super(s), have a non-inducible phenotype. Repression of the gal operon by super-repressors cannot be lifted by inducer. The mutant galR genes, galR super(s), have been cloned and the mutational changes determined. Two of them, galR super(s) sub(uv7) and galR super(s) sub(78), were located in the proposed sugar binding domains of the repressor. The repressor from wild-type (galR super(+)), as well as from mutant galR super(s) sub(uv7), was purified and characterized biochemically. The results showed that, like wild-type GalR super(+), GalR super(s) sub(uv7) binds to DNA normally and represses transcription from the P1 promoter and stimulates that from the P2 promoter of the gal operon. Nevertheless, compared to GalR super(+), GalR super(s) sub(uv7) is much less sensitive to the presence of the inducer, D-galactose. The affinity of D-galactose to GalR super(s) sub(uv7) is 10 to 30-fold lower, as measured by the effect of the inducer on GalR tryptophan fluorescence; GalR complexes with DNA and on GalR repression of transcription. Our results suggest that the super-repressor phenotype of GalR super(s) sub(uv7) is because of a defect in D-galactose binding rather than a defect in the ligand-induced allosteric change or increased affinity for the operator. JF - Journal of Molecular Biology AU - Zhou, Yan-Ning AU - Chatterjee, S AU - Roy, S AU - Adhya, S AD - Lab. Mol. Biol., NCI/NIH, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 414 EP - 425 VL - 253 IS - 3 SN - 0022-2836, 0022-2836 KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - gal operon KW - gene regulation KW - Escherichia coli KW - repressors KW - J 02740:Genetics and evolution KW - N 14662:Gene regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17007914?accountid=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=The+non-inducible+nature+of+super-repressors+of+the+gal+operon+in+Escherichia+coli&rft.au=Zhou%2C+Yan-Ning%3BChatterjee%2C+S%3BRoy%2C+S%3BAdhya%2C+S&rft.aulast=Zhou&rft.aufirst=Yan-Ning&rft.date=1995-01-01&rft.volume=253&rft.issue=3&rft.spage=414&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; gal operon; repressors; gene regulation ER - TY - JOUR T1 - Photocross-links between single-stranded DNA and Escherichia coli RecA protein map to loops L1 (amino acid residues 157-164) and L2 (amino acid residues 195-209) AN - 17003731; 3850408 AB - To function as a repair and recombination protein, RecA has to be assembled as an active filament on single-stranded DNA in the presence of ATP or its analogs. We have identified amino acids in the primary DNA binding site of RecA that interact with single-stranded DNA by photocross-linking. A nucleoprotein complex consisting of RecA protein bound to a monosubstituted oligonucleotide bearing a 5-iododeoxyuracil cross-linking moiety was irradiated with long wavelength ultraviolet radiation to effect cross-linking with RecA protein. Subsequent trypsin digestion, followed by purification and peptide sequencing, revealed the cross-linking of two independent peptides, amino acid residues 153-169 and 199-216. Met super(164) from loop L1 and Phe super(203) from loop L2 were determined to be the exact points of cross-linking. Thus, our data confirm and extend predictions about the DNA binding domain of RecA protein based on the molecular structure of RecA. JF - Journal of Biological Chemistry AU - Malkov, V A AU - Camerini-Otero, R D AD - Genet. and Biochem. Branch, NIDDK, Natl. Inst. Health, Bldg. 10, Rm. 9D15, 10 Cent. Dr., Bethesda, MD 20892-1810, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 30230 EP - 30233 VL - 270 IS - 50 SN - 0021-9258, 0021-9258 KW - RecA protein KW - ATP KW - S-iododeoxyuracil KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - nucleoproteins KW - U.V. radiation KW - DNA KW - Escherichia coli KW - J 02727:Amino acids, peptides and proteins KW - N 14940:Nucleic acid-binding proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17003731?accountid=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=Photocross-links+between+single-stranded+DNA+and+Escherichia+coli+RecA+protein+map+to+loops+L1+%28amino+acid+residues+157-164%29+and+L2+%28amino+acid+residues+195-209%29&rft.au=Malkov%2C+V+A%3BCamerini-Otero%2C+R+D&rft.aulast=Malkov&rft.aufirst=V&rft.date=1995-01-01&rft.volume=270&rft.issue=50&rft.spage=30230&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; DNA; nucleoproteins; U.V. radiation ER - TY - JOUR T1 - Comparison of protein binding to DNA in vivo and in vitro: Defining an effective intracellular target AN - 17002343; 3850043 AB - We have quantitatively evaluated the affinity of a set of target sites for the integration host factor (IHF) protein of Escherichia coli by their performance as competitors in an electrophoretic mobility shift assay. We also determined how well each of these sites is filled by IHF in vivo. The data show that several natural sites have an affinity not much greater than that required for intracellular occupancy. The data also indicate that very little of the IHF in a cell is present as free protein available for binding, suggesting that binding to non-specific targets dominates the operation of this system. The correlation between in vitro affinity and in vivo occupancy provides a ready means to assess the likely physiological significance of putative IHF sites. It also provides a general method to assess the importance of non-specific interactions by DNA binding proteins inside a cell. JF - EMBO Journal AU - Yang, Shu-wei AU - Nash, HA AD - Lab. Mol. Biol., NIMH, Bethesda, MD 20892-4034, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 6292 EP - 6300 VL - 14 IS - 24 SN - 0261-4189, 0261-4189 KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - DNA KW - Escherichia coli KW - integrated host factor 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/17002343?accountid=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=EMBO+Journal&rft.atitle=Comparison+of+protein+binding+to+DNA+in+vivo+and+in+vitro%3A+Defining+an+effective+intracellular+target&rft.au=Yang%2C+Shu-wei%3BNash%2C+HA&rft.aulast=Yang&rft.aufirst=Shu-wei&rft.date=1995-01-01&rft.volume=14&rft.issue=24&rft.spage=6292&rft.isbn=&rft.btitle=&rft.title=EMBO+Journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; DNA; integrated host factor ER - TY - JOUR T1 - DNA adducts 2-amino-3-methylimidazol[4,5-f]quinoline (IQ) in colon, bladder, and kidney of congenic mice differing in Ah responsiveness and N-acetyltransferase genotype AN - 17001107; 3841604 AB - Heterocyclic amines, suspected as cancer initiators, require metabolic activation to exert genotoxicity. The food carcinogen 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ) undergoes activation via N-hydroxylation by cytochrome P450 1A2, followed by O-esterification by N-acetyltransferase. We examined the effects of the Ah locus and acetylator polymorphisms (implicated in human colon and bladder cancer risk) on levels of super(32)P-postlabeled IQ-DNA adducts in C57BL/6 mice congenic for slow acetylation and/or Ah nonresponsiveness. Some were pretreated with beta -naphthoflavone ( beta NF), an inducer of cytochromes P450 1A. Guanine adducts were detected in all organs, the predominant one corresponding to N super(2)-(deoxyguanosin-8-yl)-IQ. In the kidney, beta NF pretreatment reduced total adducts by 50% in Ah-responsive animals (P = 0.021); the Ah or acetylator phenotype did not otherwise affect total adducts. In the colon of Ah-nonresponsive animals, rapid acetylators had 3-fold more adducts than slow acetylators (P = 0.0001, vehicle-pretreated; P = 0.0031, beta NF-pretreated). In Ah-responsive mice of either acetylator phenotype, beta NF pretreatment reduced total adducts in the colon by 70% (P = 0.0003). A significant interaction of phenotypes occurred in the bladder; beta NF-pretreatment caused a 2.5-fold increase in adducts but only in the Ah-responsive, rapid acetylator mice. In sum, these polymorphisms influenced the level of IQ-DNA adducts in the kidney, urinary bladder, and colon in complex ways. JF - Cancer Research AU - Nerurkar, P V AU - Schut, HAJ AU - Anderson, L M AU - Riggs, C W AU - Snyderwine, E G AU - Thorgeirsson, S S AU - Weber, W W AU - Rice, J M AU - Levy, G N AD - Lab. Comparative Carcinogenesis, NCI-FCRDC, Bldg. 538, Rm. 205E, Frederick, MD 21702-1201, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 3043 EP - 3049 VL - 55 IS - 14 SN - 0008-5472, 0008-5472 KW - 2-amino-3-methylimidazo[4,5-f]quinoline KW - N-acetyltransferase KW - mice KW - Ah locus KW - Toxicology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - urinary bladder KW - DNA adducts KW - food KW - colon KW - kidney KW - X 24120:Food, additives & contaminants KW - N 14630:Chemical reactions & interactions, including effects of radiation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17001107?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Research&rft.atitle=DNA+adducts+2-amino-3-methylimidazol%5B4%2C5-f%5Dquinoline+%28IQ%29+in+colon%2C+bladder%2C+and+kidney+of+congenic+mice+differing+in+Ah+responsiveness+and+N-acetyltransferase+genotype&rft.au=Nerurkar%2C+P+V%3BSchut%2C+HAJ%3BAnderson%2C+L+M%3BRiggs%2C+C+W%3BSnyderwine%2C+E+G%3BThorgeirsson%2C+S+S%3BWeber%2C+W+W%3BRice%2C+J+M%3BLevy%2C+G+N&rft.aulast=Nerurkar&rft.aufirst=P&rft.date=1995-01-01&rft.volume=55&rft.issue=14&rft.spage=3043&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 - DNA adducts; colon; urinary bladder; kidney; food ER - TY - JOUR T1 - Mutagenesis in Escherichia coli by three O super(6)-substituted guanines in double-stranded or gapped plasmids AN - 17000166; 3842841 AB - Plasmids were constructed with guanine (G) or O super(6)-methyl-(m super(6)G), O super(6)-ethyl-(e super(6)G), or O super(6)-benzyl-(b super(6)G) guanine in the initiation codon (ATG) of the lacZ' gene. Four deoxyuridine residues were incorporated near the modified guanine in the complementary strand. The deoxyuridine-containing plasmids exhibited similarly high transformation efficiencies in ung super(-) Escherichia coli, although the frequency of mutations induced by m super(6)G, e super(6)G, and b super(6)G residues was relatively low. Treatment of the plasmids with uracil-DNA glycosylase (UDG), to remove the uracil residues, or UDG and exonuclease III, to create a gap in the deoxyuridine-containing strand, reduced transformation efficiency for adduct-containing plasmids but did not affect transformation efficiency for control plasmids. However, the same treatments dramatically enhanced mutagenesis by m super(6)G, e super(6)G, and b super(6)G. These results were consistent with blockage of replication by the modified guanines in double-stranded plasmids resulting in preferential replication of the complementary strand. Replication past the modified guanines was forced in the gapped plasmids. The frequency of modified guanine-induced mutations in gapped vectors was similar in strains of E. coli that were proficient in DNA polymerase III but deficient in either DNA polymerase I or II or both polymerase I and II suggesting either that polymerase III was primarily responsible for adduct bypass in all strains or that the probability of base misinsertion during bypass by either polymerase I or II was similar to that for polymerase III. Repair studies with gapped plasmids indicated that m super(6)G was subject to repair by Ada methyltransferase and to postreplication processing by methylation-directed mismatch repair. Neither e super(6)G nor b super(6)G were similarly repaired. Both m super(6)G and e super(6)G efficiently coded for thymine incorporation although b super(6)G appeared to be less miscoding. JF - Biochemistry (Washington) AU - Pauly, G T AU - Hughes, SH AU - Moschel, R C AD - Chem. Carcinogenesis Lab., ABL-Basic Res. Program, NCI-FCRDC, P.O. Box B, Frederick, MD 21702, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 8924 EP - 8930 VL - 34 IS - 27 SN - 0006-2960, 0006-2960 KW - guanine KW - DNA-directed DNA polymerase KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - mutagenesis KW - Escherichia coli KW - plasmids KW - J 02725:DNA KW - N 14681:Mutagenesis techniques UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17000166?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry+%28Washington%29&rft.atitle=Mutagenesis+in+Escherichia+coli+by+three+O+super%286%29-substituted+guanines+in+double-stranded+or+gapped+plasmids&rft.au=Pauly%2C+G+T%3BHughes%2C+SH%3BMoschel%2C+R+C&rft.aulast=Pauly&rft.aufirst=G&rft.date=1995-01-01&rft.volume=34&rft.issue=27&rft.spage=8924&rft.isbn=&rft.btitle=&rft.title=Biochemistry+%28Washington%29&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; plasmids; mutagenesis ER - TY - JOUR T1 - Characterization of DNA adducts formed by anti-benzo[g]chrysene 11,12-dihydrodiol 13,14-epoxide AN - 16997849; 3835652 AB - The anti-11,12-dihydrodiol 13,14-epoxide of benzo[g]chrysene, a fjord-region-containing hydrocarbon, was found to react with DNA in vitro to yield, as the major product, an adduct in which the epoxide of the 11R,12S,13S,14R enantiomer was opened trans by the amino group of deoxyadenosine. The structures of this adduct and other deoxyadenosine and deoxyguanosine adducts were established by spectroscopic methods. In reactions with deoxyguanylic acid, a product tentatively identified as a 7-substituted guanine was also detected. The mutagenic properties of this dihydrodiol epoxide in shuttle vector pSP189 showed that mutation at AT pairs accounted for 39% of base change mutations whereas chemical findings indicated that about 60% of adducts formed in calf thymus DNA involved adenines. Since calf thymus DNA is 56% AT and the target supF gene is 41% AT, the findings represent a fairly close relationship between adduct formation and mutagenic response. Overall, the chemical and mutagenic selectivities for the two purine bases in DNA were similar, though not identical, to those for the only other fjord-region-containing hydrocarbon studied in depth, i.e., benzo[c]phenanthrene. A major difference for these two hydrocarbon derivatives, however, is that benzo[c]phenanthrene dihydrodiol epoxides react to much higher extents ( approximately 4-fold) with DNA than did the benzo[g]-chrysene derivative. JF - Chemical Research in Toxicology AU - Szeliga, J AU - Page, JE AU - Hilton, B D AU - Kiselyov, A S AU - Harvey, R G AU - Dunayevskiy, Y M AU - Vouros, P AU - Dipple, A AD - Chem. Carcinog. Lab., ABL-Basic Res. Program, and Chem. Synthesis and Anal. Lab., SAIC Frederick, NCI-FCRDC, Frederick, MD 21702, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 1014 EP - 1019 VL - 8 IS - 8 SN - 0893-228X, 0893-228X KW - anti-benzo(g)chrysene 11,12-dihydrodiol 13,14-epoxide KW - benzo(g)chrysene 11,12-dihydrodiol 13,14-epoxide KW - Toxicology Abstracts KW - DNA adducts KW - polycyclic aromatic hydrocarbons KW - X 24190:Polycyclic hydrocarbons UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16997849?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+Research+in+Toxicology&rft.atitle=Characterization+of+DNA+adducts+formed+by+anti-benzo%5Bg%5Dchrysene+11%2C12-dihydrodiol+13%2C14-epoxide&rft.au=Szeliga%2C+J%3BPage%2C+JE%3BHilton%2C+B+D%3BKiselyov%2C+A+S%3BHarvey%2C+R+G%3BDunayevskiy%2C+Y+M%3BVouros%2C+P%3BDipple%2C+A&rft.aulast=Szeliga&rft.aufirst=J&rft.date=1995-01-01&rft.volume=8&rft.issue=8&rft.spage=1014&rft.isbn=&rft.btitle=&rft.title=Chemical+Research+in+Toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - DNA adducts; polycyclic aromatic hydrocarbons ER - TY - JOUR T1 - Production of infectious human respiratory syncytial virus from cloned cDNA confirms an essential role for the transcription elongation factor from the 5' proximal open reading frame of the M2 mRNA in gene expression and provides a capability for vaccine development AN - 16994811; 3839803 AB - Infectious human respiratory syncytial virus (RSV) was produced by the intracellular coexpression of five plasmid-borne cDNAs. One cDNA encoded a complete positive-sense version of the RSV genome (corresponding to the replicative intermediate RNA or antigenome), and each of the other four encoded a separate RSV protein, namely, the major nucleocapsid N protein, the nucleocapsid P phosphoprotein, the major polymerase L protein, or the protein from the 5' proximal open reading frame of the M2 mRNA [M2(ORF1)]. RSV was not produced if any of the five plasmids was omitted. The requirement for the M2(ORF1) protein is consistent with its recent identification as a transcription elongation factor and confirms its importance for RSV gene expression. It should thus be possible to introduce defined changes into infectious RSV. This should be useful for basic studies of RSV molecular biology and pathogenesis; in addition, there are immediate applications to the development of live attenuated vaccine strains bearing predetermined defined attenuating mutations. JF - Proceedings of the National Academy of Sciences, USA AU - Collins, P L AU - Hill, M G AU - Camargo, E AU - Grosfeld, H AU - Chanock, R M AU - Murphy, B R AD - Lab. Infect. Dis., 7 Cent. Dr., MSC 0720, NIAID/NIH, Bethesda, MD 20892-0720, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 11563 EP - 11567 VL - 92 IS - 25 SN - 0027-8424, 0027-8424 KW - L protein KW - M2(ORF1) protein KW - N protein KW - P protein KW - transcription elongation factors KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Virology & AIDS Abstracts KW - respiratory syncytial virus KW - vaccines KW - RNA viruses KW - W3 33365:Vaccines (other) KW - V 22097:Immunization: Vaccines & vaccination: Human KW - W 30965:Miscellaneous, Reviews KW - N 14553:Transcription initiation, elongation & termination UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16994811?accountid=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=Production+of+infectious+human+respiratory+syncytial+virus+from+cloned+cDNA+confirms+an+essential+role+for+the+transcription+elongation+factor+from+the+5%27+proximal+open+reading+frame+of+the+M2+mRNA+in+gene+expression+and+provides+a+capability+for+vaccine+development&rft.au=Collins%2C+P+L%3BHill%2C+M+G%3BCamargo%2C+E%3BGrosfeld%2C+H%3BChanock%2C+R+M%3BMurphy%2C+B+R&rft.aulast=Collins&rft.aufirst=P&rft.date=1995-01-01&rft.volume=92&rft.issue=25&rft.spage=11563&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 - 2011-12-14 N1 - SubjectsTermNotLitGenreText - vaccines; RNA viruses; respiratory syncytial virus ER - TY - JOUR T1 - High bladder cancer mortality in rural New England (United States): An etiologic study AN - 16992809; 3835740 AB - An interview study of next-of-kin of 325 persons who died of bladder cancer and 673 individuals who died of other causes in Vermont and New Hampshire (United States) was conducted to assess reasons for the persistent pattern of elevated bladder cancer mortality for both genders in rural New England. There was some evidence of elevated risks for both leather and textile workers that rose to over twofold for workers who also lived near these industries and for persons with French-Canadian ancestry. Occupational exposures in the textile and leather industry may explain at least a portion of the excess bladder cancer risk in rural New England. JF - Cancer Causes & Control AU - Morris Brown, L AU - Hoar Zahm, S AU - Hoover, R N AU - Fraumeni, JF Jr AD - Epidemiol. and Biostat. Program, NCI/NIH, Executive Plaza N., Rm. 415, 6130 Executive Blvd., MSC 7368, Bethesda, MD 20892-7368, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 361 EP - 368 VL - 6 IS - 4 SN - 0957-5243, 0957-5243 KW - Toxicology Abstracts KW - urinary bladder KW - carcinogenesis KW - pollution sources KW - textile industry KW - leather KW - occupational exposure KW - man KW - X 24152:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16992809?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Causes+%26+Control&rft.atitle=High+bladder+cancer+mortality+in+rural+New+England+%28United+States%29%3A+An+etiologic+study&rft.au=Morris+Brown%2C+L%3BHoar+Zahm%2C+S%3BHoover%2C+R+N%3BFraumeni%2C+JF+Jr&rft.aulast=Morris+Brown&rft.aufirst=L&rft.date=1995-01-01&rft.volume=6&rft.issue=4&rft.spage=361&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - urinary bladder; carcinogenesis; textile industry; pollution sources; occupational exposure; man; leather ER - TY - JOUR T1 - Interleukin 2 induces CD8 super(+) T cell-mediated suppression of human immunodeficiency virus replication in CD4 super(+) T cells and this effect overrides its ability to stimulate virus expression AN - 16992447; 3830994 AB - The nonlytic suppression of human immunodeficiency virus (HIV) production from infected CD4 super(+) T cells by CD8 super(+) lymphocytes from HIV-infected individuals is one of the most potent host-mediated antiviral activities observed in vitro. We demonstrate that the pleiotropic cytokine interleukin 2 (IL-2), but not IL-12, is a potent inducer of the CD8 super(+) HIV suppressor phenomenon. IL-2 induces HIV expression in peripheral blood or lymph node mononuclear cells from HIV-infected individuals in the absence of CD8 super(+) T cells. However, IL-2 induces CD8 super(+) T cells to suppress HIV expression when added back to these cultures, and this effect dramatically supersedes the ability of IL-2 to induce HIV expression. Five to 25 times fewer CD8 super(+) cells were required to obtain comparable levels of inhibition of viral protein if they were activated in the presence of IL-2 as compared with IL-12 or no exogenous cytokine. Furthermore, IL-2 appeared either to induce a qualitative increase in HIV suppressor cell activity or to increase the relative frequency of suppressor cells in the activated (CD25 super(+)) CD8 super(+) populations. Analyses of proviral levels in peripheral blood mononuclear cells suggest that CD8 super(+) T cell-mediated lysis of in vivo infected cells is not induced by IL-2. These results have implications for our understanding of the effects of impaired IL-2 production during HIV disease as well as the overall effects of IL-2-based immunotherapy on HIV replication in vivo. JF - Proceedings of the National Academy of Sciences, USA AU - Kinter, AL AU - Bende, S M AU - Hardy, E C AU - Jackson, R AU - Fauci, A S AD - Lab. Immunoregul., NIAID/NIH, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 10985 EP - 10989 VL - 92 IS - 24 SN - 0027-8424, 0027-8424 KW - CD25 antigen KW - CD4 antigen KW - CD8 antigen KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - interleukin 2 KW - interleukin 12 KW - lymphocytes T KW - human immunodeficiency virus 1 KW - man KW - F 06773:Interferons KW - W3 33150:Cytokine based KW - F 06756:Function KW - V 22003:AIDS: Immunological aspects KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16992447?accountid=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=Interleukin+2+induces+CD8+super%28%2B%29+T+cell-mediated+suppression+of+human+immunodeficiency+virus+replication+in+CD4+super%28%2B%29+T+cells+and+this+effect+overrides+its+ability+to+stimulate+virus+expression&rft.au=Kinter%2C+AL%3BBende%2C+S+M%3BHardy%2C+E+C%3BJackson%2C+R%3BFauci%2C+A+S&rft.aulast=Kinter&rft.aufirst=AL&rft.date=1995-01-01&rft.volume=92&rft.issue=24&rft.spage=10985&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 - 2011-12-14 N1 - SubjectsTermNotLitGenreText - interleukin 2; interleukin 12; lymphocytes T; man; human immunodeficiency virus 1 ER - TY - JOUR T1 - Alterations in the heme biosynthetic pathway from the III-V semiconductor metal, indium arsenide (InAs) AN - 16986744; 3819210 AB - The effects of indium and arsenic on the heme biosynthetic pathway have been well documented but the effects of indium arsenide (InAs), the next possible generation of the III-V semiconductors, are unknown. Male Syrian golden hamsters were given s.c. injections of sodium arsenite (As super(3+)), indium chloride (In super(3+)) or indium arsenide (InAs). Erythrocyte delta -aminolevulinic acid dehydratase (ALAD) activity was inhibited in all exposure groups, while hepatic ALAD activity was not significantly changed. In contrast, the activity of renal ALAD was found to be statistically decreased by As super(3+) at 10 days, but increased at 30 days, while In super(3+) and InAs inhibited this enzyme activity at all time points. In vitro studies showed that hepatic ALAD activity was more sensitive to In super(3+) than As super(3+), suggesting that the effects of InAs in vivo on this enzyme are due primarily to the In rather than the As moiety. Studies of urinary porphyrin excretion patterns in animals treated with InAs showed marked, early 2-4-fold increases in the excretion of the penta-, hexa- and heptacarboxyl porphyrin at 1-5 days which continued through day 30 of the study. In contrast, there was a slow and steady rise in the excretion of coproporphyrin I and Ill which reached a maximum at day 30. The results of these studies indicate that both the In and As moieties of InAs are biologically active following InAs exposure and that the enzymes in the heme pathway, such as ALAD, may have great utility as markers of exposure/toxicity for these agents. JF - Chemico-Biological Interactions AU - Conner, E A AU - Yamauchi, H AU - Fowler, BA AD - NIH/NCI/DCE/LEC, Build. 37, Rm 3C12, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 273 EP - 285 VL - 96 IS - 3 SN - 0009-2797, 0009-2797 KW - porphyrins KW - hamsters KW - indium arsenide KW - arsenic KW - Toxicology Abstracts KW - heme KW - semiconduction KW - enzymes KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16986744?accountid=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=Chemico-Biological+Interactions&rft.atitle=Alterations+in+the+heme+biosynthetic+pathway+from+the+III-V+semiconductor+metal%2C+indium+arsenide+%28InAs%29&rft.au=Conner%2C+E+A%3BYamauchi%2C+H%3BFowler%2C+BA&rft.aulast=Conner&rft.aufirst=E&rft.date=1995-01-01&rft.volume=96&rft.issue=3&rft.spage=273&rft.isbn=&rft.btitle=&rft.title=Chemico-Biological+Interactions&rft.issn=00092797&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 - heme; semiconduction; enzymes ER - TY - JOUR T1 - Effects of Escherichia coli dnaE antitumor alleles in a proofreading-deficient mutD5 strain AN - 16986452; 3819002 AB - We have previously isolated seven mutants of Escherichia coli which replicate their DNA with increased fidelity. These mutants were isolated as suppressors of the elevated mutability of a mismatch-repair-defective mutL strain. Each mutant was shown to contain a single amino acid substitution in the dnaE gene product, the alpha (i.e., polymerase) subunit of DNA polymerase III holoenzyme responsible for replicating the E. coli chromosome. The mechanism(s) by which these antimutators exert their effect is of interest. Here, we have examined the effects of the antimutator alleles in a mutD5 mutator strain. This strain carries a mutation in the dnaQ gene, which results in defective exonucleolytic proofreading. Our results show that dnaE mutations also confer a strong antimutator phenotype in this background, the effects being generally much greater than those observed previously in the mutL background. The results suggest that the dnaE antimutator alleles can exert their effect independently of exonucleolytic proofreading activity. The large magnitude of the antimutator effects in the mutD5 background can be ascribed, at least in part, to the (additional) restoration of DNA mismatch repair, which is generally impaired in mutD5 strains because of error saturation. The high mutability of mutD5 strains was exploited to isolate a strong new dnaE antimutator allele on the basis of its ability to suppress the high reversion rate of an A- T arrow right T - A transversion in this background. A model suggesting how the dnaE antimutator alleles might exert their effects in proofreading-proficient and -deficient backgrounds is presented. JF - Journal of Bacteriology AU - Fijalkowska, I J AU - Schaaper, R M AD - NIEHS, E3-01, P.O. Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 5979 EP - 5986 VL - 177 IS - 20 SN - 0021-9193, 0021-9193 KW - dnaE gene KW - mutD5 gene KW - Microbiology Abstracts B: Bacteriology KW - Escherichia coli KW - proofreading KW - antimutator KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16986452?accountid=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=Effects+of+Escherichia+coli+dnaE+antitumor+alleles+in+a+proofreading-deficient+mutD5+strain&rft.au=Fijalkowska%2C+I+J%3BSchaaper%2C+R+M&rft.aulast=Fijalkowska&rft.aufirst=I&rft.date=1995-01-01&rft.volume=177&rft.issue=20&rft.spage=5979&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; antimutator; proofreading ER - TY - JOUR T1 - Ethanol induces CYP2E1 by protein stabilization. Role of ubiquitin conjugation in the rapid degradation of CYP2E1 AN - 16984798; 3833380 AB - In the present study, we demonstrate that ethanol induces CYP2E1 by protein stabilization in vivo. The control half-life of CYP2E1 was determined to be 6-7 h followed by a slower secondary phase. The half-life of ethanol-stabilized CYP2E1 was calculated to be 38 h. The mechanism underlying the rapid degradation of CYP2E1 was also investigated and appears to involve the ubiquitin-proteasome proteolytic pathway. An in vitro assay using the cytosolic fraction was developed to further characterize CYP2E1 degradation. Using this assay, 40-50% loss of CYP2E1 was observed in 1 h, coincident with the formation of high M sub(r) ubiquitin-CYP2E1 conjugates. At concentrations approximating those found in vivo, ethanol protects CYP2E1 from cytosolic degradation. No loss of CYP2B1/2 was observed under identical conditions, suggesting that this reaction is specific for certain P-450s which are rapidly turned over. JF - Journal of Biological Chemistry AU - Roberts, B J AU - Song, B-J AU - Soh, Y AU - Park, S S AU - Shoaf, SE AD - Lab. Clin. Stud., NIAAA, 10 Cent. Dr., MSC-1256, Bethesda, MD 20892-1256, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 29632 EP - 29635 VL - 270 IS - 50 SN - 0021-9258, 0021-9258 KW - ethanol KW - CYP2E1 KW - ubiquitin KW - cytochrome P4502E1 KW - Toxicology Abstracts KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16984798?accountid=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+Biological+Chemistry&rft.atitle=Ethanol+induces+CYP2E1+by+protein+stabilization.+Role+of+ubiquitin+conjugation+in+the+rapid+degradation+of+CYP2E1&rft.au=Roberts%2C+B+J%3BSong%2C+B-J%3BSoh%2C+Y%3BPark%2C+S+S%3BShoaf%2C+SE&rft.aulast=Roberts&rft.aufirst=B&rft.date=1995-01-01&rft.volume=270&rft.issue=50&rft.spage=29632&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 - Induction of protective immunity to schistosomiasis with immunologically cross-reactive Lumbricus molecules AN - 16982258; 3818982 AB - Immunologically cross-reactive molecules of Schistosoma japonicum and Lumbricus terrestris were identified by antibodies derived from human and rodent sera. Pooled IgG from schistosomiasis patients but not uninfected individuals bound multiple antigens of identical molecular weight in both soluble S. japonicum worm antigen preparations (SWAP) and soluble earthworm preparations (SEWP). These antigens had molecular weights corresponding to 18, 40, 62, 64, 74, 97, and >110 kDa. Three of these antigens of 74, 97 and >110 kDa were immuno-affinity purified using antibodies derived from schistosomiasis patients' sera. Vaccination of mice with SEWP produced murine antibodies which bound parasite molecules of 40, 74, 97, and >110 kDa and induced 36% protection from S. japonicum infection. Antibody production to S. japonicum paramyosin, a molecule previously shown to induce protection from schistosome infection, was prominently expressed m the protected murine immune sera. The study shows that Lumbricus sp. represent a potential source for paramyosin and other candidate vaccine molecules for schistosomiasis. JF - International Journal for Parasitology AU - Wisnewski, A V AU - Kresina, T F AD - NIDDK, DDN, NIH, Build. 45, 6AN-12A, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 503 EP - 510 VL - 25 IS - 4 SN - 0020-7519, 0020-7519 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Lumbricus terrestris KW - cross-reactivity KW - antibodies KW - schistosomiasis KW - immunoreactivity KW - Schistosoma japonicum KW - W3 33120:Receptor based (antibodies, etc.) KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16982258?accountid=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+for+Parasitology&rft.atitle=Induction+of+protective+immunity+to+schistosomiasis+with+immunologically+cross-reactive+Lumbricus+molecules&rft.au=Wisnewski%2C+A+V%3BKresina%2C+T+F&rft.aulast=Wisnewski&rft.aufirst=A&rft.date=1995-01-01&rft.volume=25&rft.issue=4&rft.spage=503&rft.isbn=&rft.btitle=&rft.title=International+Journal+for+Parasitology&rft.issn=00207519&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - antibodies; cross-reactivity; schistosomiasis; immunoreactivity; Lumbricus terrestris; Schistosoma japonicum ER - TY - JOUR T1 - Clearance of circulating filarial antigen as a measure of the macrofilaricidal activity of diethylcarbamazine in Wuchereria bancrofti infection AN - 16980648; 3826900 AB - Small doses of diethylcarbamazine (DEC) clear microfilariae (MF) from the blood of Wuchereria bancrofti-infected persons, but the dose and regimen required to kill adult worms is not clearly defined. A prospective study was undertaken to examine the macrofilaricidal effect of DEC and the ability of an assay for circulating filarial antigen (CFA) to define the effect. Twenty-five MF-positive subjects and 7 MF-negative but CFA-positive subjects were treated with DEC and followed for 18 months. Of the 25 MF-positive patients, 24 cleared MF, and 22 of 26 CFA-positive subjects cleared CFA. A significantly greater decrease in antifilarial IgG4 was seen in patients who cleared CFA than in those who did not. The complete clearance of CFA observed after therapy with DEC indicates that assessment of CFA clearance is a useful means for detecting macrofilaricidal effects of antifilarial chemotherapy. JF - Journal of Infectious Diseases AU - McCarthy, J S AU - Guinea, A AU - Weil, G J AU - Ottesen, E A AD - Lab. Parasit. Dis., NIAID/NIH, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 521 EP - 526 VL - 172 IS - 2 SN - 0022-1899, 0022-1899 KW - Wucheria bancrofti KW - circulating filarial antigen KW - diethylcarbamazine KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - filariasis KW - antigens KW - W3 33190:Therapy: Other KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16980648?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Infectious+Diseases&rft.atitle=Clearance+of+circulating+filarial+antigen+as+a+measure+of+the+macrofilaricidal+activity+of+diethylcarbamazine+in+Wuchereria+bancrofti+infection&rft.au=McCarthy%2C+J+S%3BGuinea%2C+A%3BWeil%2C+G+J%3BOttesen%2C+E+A&rft.aulast=McCarthy&rft.aufirst=J&rft.date=1995-01-01&rft.volume=172&rft.issue=2&rft.spage=521&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - filariasis; antigens ER - TY - JOUR T1 - A murine antibody to Shigella dysenteriae type 1 employs V-genes that contain a rearranged codon for the lambda light chain AN - 16980195; 3811544 AB - The cDNA coding for a hybridoma anti Shigella dysenteriae type 1 antibody (3707 E9) has been cloned, and sequenced. Binding patterns with fragments of the bacterial polysaccharide antigen had already been studied in detail. The VH sequence utilizes the VH441 gene, first identified amongst beta -(1,6)galactan-binding antibodies, while the VL is closely related to the V lambda 1 gene. We found that the VL sub(3707 E9) gene employed a VL-J combinatorial joining leading to a rare Trp- arrow right Leu substitution at position L96. JF - Molecular Immunology AU - Miller, CE AU - Huppi, K AU - Siwarski, D AU - Karpas, A AU - Newman, A AU - Mainhart, C AU - Glaudemans, CPJ AD - Lab. Med. Chem., NIDDK, Natl. Inst. Health, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 679 EP - 682 VL - 32 IS - 9 SN - 0161-5890, 0161-5890 KW - polysaccharides KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - hybridoma KW - genes KW - Shigella dysenteriae KW - nucleotide sequence KW - immunoglobulins KW - cDNA KW - variable region KW - J 02831:Techniques and reagents KW - F 06065:Genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16980195?accountid=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+Immunology&rft.atitle=A+murine+antibody+to+Shigella+dysenteriae+type+1+employs+V-genes+that+contain+a+rearranged+codon+for+the+lambda+light+chain&rft.au=Miller%2C+CE%3BHuppi%2C+K%3BSiwarski%2C+D%3BKarpas%2C+A%3BNewman%2C+A%3BMainhart%2C+C%3BGlaudemans%2C+CPJ&rft.aulast=Miller&rft.aufirst=CE&rft.date=1995-01-01&rft.volume=32&rft.issue=9&rft.spage=679&rft.isbn=&rft.btitle=&rft.title=Molecular+Immunology&rft.issn=01615890&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Shigella dysenteriae; hybridoma; immunoglobulins; variable region; genes; cDNA; nucleotide sequence ER - TY - JOUR T1 - Passive immunotherapy for retroviral disease: Influence of major histocompatibility complex type and T-cell responsiveness AN - 16978421; 3822995 AB - Administration of virus-specific antibodies is known to be an effective early treatment for some viral infections. Such immunotherapy probably acts by antibody-mediated neutralization of viral infectivity and is often thought to function independently of T-cell-mediated immune responses. In the present experiments, we studied passive antibody therapy using Friend murine leukemia virus complex as a model for an immunosuppressive retroviral disease in adult mice. The results showed that antibody therapy could induce recovery from a well-established retroviral infection. However, the success of therapy was dependent on the presence of both CD4 super(+) and CD8 super(+) T lymphocytes. Thus, cell-mediated responses were required for recovery from infection even in the presence of therapeutic levels of antibody. The major histocompatibility type of the mice was also an important factor determining the relative success of antibody therapy in this system, but it was less critical for low-dose than for high-dose infections. Our results imply that limited T-cell responsiveness as dictated by major histocompatibility genes and/or stage of disease may have contributed to previous immunotherapy failures in AIDS patients. Possible strategies to improve the efficacy of future therapies are discussed. JF - Proceedings of the National Academy of Sciences, USA AU - Hasenkrug, K J AU - Brooks, D M AU - Chesebro, B AD - Lab. Persistent Viral Dis., Rocky Mountain Lab., NIAID/NIH, 903 S. 4th St., Hamilton, MT 59840, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 10492 EP - 10495 VL - 92 IS - 23 SN - 0027-8424, 0027-8424 KW - CD4 antigen KW - CD8 antigen KW - Friend leukemia virus KW - mice KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - immunity (cell-mediated) KW - retrovirus KW - lymphocytes T KW - antibodies KW - immunotherapy KW - major histocompatibility complex KW - W3 33160:Antibody based KW - V 22096:Immunization: Passive KW - F 06824:Animal KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16978421?accountid=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=Passive+immunotherapy+for+retroviral+disease%3A+Influence+of+major+histocompatibility+complex+type+and+T-cell+responsiveness&rft.au=Hasenkrug%2C+K+J%3BBrooks%2C+D+M%3BChesebro%2C+B&rft.aulast=Hasenkrug&rft.aufirst=K&rft.date=1995-01-01&rft.volume=92&rft.issue=23&rft.spage=10492&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 - 2011-12-14 N1 - SubjectsTermNotLitGenreText - immunity (cell-mediated); retrovirus; lymphocytes T; antibodies; immunotherapy; major histocompatibility complex ER - TY - JOUR T1 - The Ig-related killer cell inhibitory receptor binds zinc and requires zinc for recognition of HLA-C on target cells AN - 16976730; 3821289 AB - Members of the Ig superfamily are predominantly receptors that mediate interactions between cells or provide signals to cells when binding specific ligands. Here we describe an Ig-related receptor that requires zinc for its function. Killer cell inhibitory receptors (KIR) belonging to the Ig superfamily mediate inhibition of NK cells upon recognition of HLA-C molecules on target cells. An abundance of histidine residues in the first extracellular domain of KIR, including the signature zinc binding motif HEXXH, suggested that this receptor may bind zinc. Two distinct KIR molecules that mediate recognition of HLA-Cw4 and -Cw8, respectively, bound specifically to zinc affinity columns. Furthermore, addition of the zinc chelator 1,10-phenanthroline during chromium release assays reversed the inhibition of killing by NK clones specific for HLA-Cw4 or HLA-Cw8, demonstrating that zinc is necessary for the inhibitory function of KIR. Such functionally relevant zinc binding has not been described for other members of the Ig superfamily and may represent a novel regulatory mechanism for Ag receptor-ligand interactions. JF - Journal of Immunology AU - Rajagopalan, S AU - Winter, C C AU - Wagtmann, N AU - Long, E O AD - LIG-NIAID-Natl. Inst. Health Twinbrook II, 12441 Parklawn Dr., Rockville, MD 20852-1727, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 4143 EP - 4146 VL - 155 IS - 9 SN - 0022-1767, 0022-1767 KW - C determinants KW - killer cell inhibitory receptors KW - zinc KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - immunoglobulins KW - histocompatibility antigen HLA KW - natural killer cells KW - man KW - W 30965:Miscellaneous, Reviews KW - W3 33000:General topics and reviews KW - F 06757:NK cells UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16976730?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunology&rft.atitle=The+Ig-related+killer+cell+inhibitory+receptor+binds+zinc+and+requires+zinc+for+recognition+of+HLA-C+on+target+cells&rft.au=Rajagopalan%2C+S%3BWinter%2C+C+C%3BWagtmann%2C+N%3BLong%2C+E+O&rft.aulast=Rajagopalan&rft.aufirst=S&rft.date=1995-01-01&rft.volume=155&rft.issue=9&rft.spage=4143&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - immunoglobulins; histocompatibility antigen HLA; natural killer cells; man ER - TY - JOUR T1 - Quantitation and biological properties of released and cell-bound lipooligosaccharides from nontypeable Haemophilus influenzae AN - 16976429; 3814015 AB - Nontypeable Haemophilus influenzae (NTHi) is a major pathogen causing otitis media in children. NTHi releases lipooligosaccharide (LOS) as outer membrane fragments during its growth. The release of LOS may play an important role in the pathogenicity of otitis media caused by this organism. The amounts of LOS in bacterial cells and growth media for five NTHi strains were determined by quantitative silver staining after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These strains were estimated to have 1.6 x 10 super(6) to 4.8 x 10 super(6) LOS molecules per bacterium. During a 3-day growth period, these NTHi strains released variable but significant amounts of LOS into the growth medium. Cells started to release detectable amounts of LOS into the medium at 2 to 5 h and continued to do so for up to 48 or 72 h. The concentrations of LOS in the culture supernatants released by these five strains were 10 to 55 mu g/ml at 24 h and 40 to 100 mu g/ml at 72 h, which was 34 to 189% of the cell-bound LOS concentration. The biological properties of released and cell-bound LOSs from two representative strains were compared. Released LOS showed an approximately 10-fold increase in inducing human monocytes to produce tumor necrosis factor alpha, interleukin 1 beta , and interleukin 6, a 13- to 28-fold increase in mouse lethal toxicity, and a 16- to 37-fold increase in the clotting of Limulus amebocyte lysate. These results suggested that released LOS or its inflammatory mediators play a more important role than the LOS in bacteria in the pathogenicity of otitis media caused by this organism. JF - Infection and Immunity AU - Gu, Xin-Xing AU - Tsai, Chao-Ming AU - Apicella, MA AU - Lim, D J AD - Lab. Cell. Biol., NIDCD/NIH, Bldg. 29, Rm. 402, 8800 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 4115 EP - 4120 VL - 63 IS - 10 SN - 0019-9567, 0019-9567 KW - lipooligosaccharides KW - Microbiology Abstracts B: Bacteriology KW - Haemophilus influenzae KW - outer membranes KW - J 02730:Carbohydrates UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16976429?accountid=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=Quantitation+and+biological+properties+of+released+and+cell-bound+lipooligosaccharides+from+nontypeable+Haemophilus+influenzae&rft.au=Gu%2C+Xin-Xing%3BTsai%2C+Chao-Ming%3BApicella%2C+MA%3BLim%2C+D+J&rft.aulast=Gu&rft.aufirst=Xin-Xing&rft.date=1995-01-01&rft.volume=63&rft.issue=10&rft.spage=4115&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Haemophilus influenzae; outer membranes ER - TY - JOUR T1 - The role of human immunodeficiency virus type 1 envelope glycoproteins in virus infection AN - 16976368; 3822994 AB - Enveloped viruses enter cells by a two-step process. The first step involves the binding of a viral surface protein to receptors on the plasma membrane of the host cell. After receptor binding, a membrane fusion reaction takes place between the lipid bilayer of the viral envelope and host cell membranes. This fusion reaction can occur either at the plasma membrane or in acidic endosomes following receptor-mediated endocytosis. In either case, the membrane fusion reaction delivers the viral nucleocapsid into the host cytoplasm, allowing the infection to proceed. Viral proteins embedded in the lipid bilayer of the viral envelope (known variously as surface, spike, or envelope proteins) catalyze receptor binding and membrane fusion reactions. The critical involvement of these viral proteins in receptor binding and membrane fusion has stimulated intensive investigation aimed at understanding the mechanisms by which these proteins function. In this article, we provide a brief overview of the roles envelope (Env) super(1) glycoproteins play in the human immunodeficiency virus type 1 (HIV-1) life cycle. JF - Journal of Biological Chemistry AU - Freed, E O AU - Martin, MA AD - Lab. Mol. Microbiol., NIAID/NIH, Bethesda, MD 20892-0460, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 23883 EP - 23886 VL - 270 IS - 41 SN - 0021-9258, 0021-9258 KW - glycoprotein gp120 KW - glycoprotein gp160 KW - glycoprotein gp41 KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - reviews KW - envelopes KW - human immunodeficiency virus 1 KW - W3 33340:Other proteins, peptides, amino acids KW - V 22002:AIDS: Molecular and in vitro aspects KW - W 30965:Miscellaneous, Reviews KW - F 06860:CMI UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16976368?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=The+role+of+human+immunodeficiency+virus+type+1+envelope+glycoproteins+in+virus+infection&rft.au=Freed%2C+E+O%3BMartin%2C+MA&rft.aulast=Freed&rft.aufirst=E&rft.date=1995-01-01&rft.volume=270&rft.issue=41&rft.spage=23883&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - reviews; envelopes; human immunodeficiency virus 1 ER - TY - JOUR T1 - Protective effect of N-acetylcysteine against heterocyclic amine-induced cardiotoxicity in cultured myocytes and in rats AN - 16975928; 3813247 AB - Cooked meat contains many mutagenic/carcinogenic heterocyclic amines (HAs), including 2-amino-3-methylimidazo[4,5-f] quinoline (IQ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP). The reactive N-hydroxylamine metabolites N-hydroxy-IQ and N-hydroxy-PhIP are toxic to isolated rat cardiomyocytes. This study examined whether antioxidant agents protect against N-hydroxylamine-induced cardiotoxicity. In isolated rat cardiomyocytes, N-acetylcysteine, alpha -tocopherol and glutathione were protective against N-hydroxylamine-mediated lactate dehydrogenase release into the medium, suggesting that a free radical mechanism may be partly involved in HA-induced cardiotoxicity. Since N-acetylcysteine was by far the most protective of the agents investigated, the effects of N-acetylcysteine on HA-induced ultrastructural damage were further examined both in vitro and in vivo. Isolated cardiomyocytes treated with 1.2 mM N-acetylcysteine before and during exposure to N-hydroxy-IQ or N-hydroxy-PhIP showed a smaller percentage of ultrastructural abnormalities, such as myofilament loss, sarcoplasmic reticulum swelling and abnormal mitochondria. N-Acetylcysteine pretreatment also significantly reduced the percentage of cardiac cells with T-tubule dilation and myelin figures in adult rats dosed with IQ. The protective effect of N-acetylcysteine was not associated with a reduction in HA-DNA adducts, as assessed by super(32)P-postlabelling analysis of DNA from isolated cardiomyocytes treated with N-hydroxylamines. DNA adduct formation per se, therefore, may not be associated with the observed cardiotoxic effects of the HAs. Further studies are required to confirm the involvement of a free radical mechanism in HA cardiotoxicity. JF - Food and Chemical Toxicology AU - Davis, C D AU - Snyderwine, E G AD - Lab. Exp. Carcinog., Div. Cancer Etiol., NCI, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 641 EP - 651 VL - 33 IS - 8 SN - 0278-6915, 0278-6915 KW - acetylcysteine KW - rats KW - Toxicology Abstracts KW - antioxidants KW - heart KW - meat KW - cardiotoxins KW - free radicals KW - myocytes KW - X 24120:Food, additives & contaminants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16975928?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Food+and+Chemical+Toxicology&rft.atitle=Protective+effect+of+N-acetylcysteine+against+heterocyclic+amine-induced+cardiotoxicity+in+cultured+myocytes+and+in+rats&rft.au=Davis%2C+C+D%3BSnyderwine%2C+E+G&rft.aulast=Davis&rft.aufirst=C&rft.date=1995-01-01&rft.volume=33&rft.issue=8&rft.spage=641&rft.isbn=&rft.btitle=&rft.title=Food+and+Chemical+Toxicology&rft.issn=02786915&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - myocytes; cardiotoxins; free radicals; heart; antioxidants; meat ER - TY - JOUR T1 - Structure and function of ARF proteins: Activators of cholera toxin and critical components of intracellular vesicular transport processes AN - 16973047; 3814813 AB - During the 1980s, several cellular factors that enhanced cholera toxin-catalyzed ADP-ribosylation of G sub(s alpha ) or activation of adenylyl cyclase were described. Kahn and Gilman reported the first purification of an similar to 20-kDa membrane-associated protein that enhanced ADP-ribosylation of G sub(s alpha ) and named it ADP-ribosylation factor or ARF. Two soluble ARFs purified later stimulated toxin-catalyzed ADP-ribosylation of G sub(s alpha ) and simple guanidino compounds (e.g. arginine) as well as toxin auto-ADP-ribosylation in a GTP-dependent manner. It was shown in kinetic studies that ARF interacted with the toxin catalytic subunit to lower the apparent K sub(m) for both ADP-ribose donor (NAD) and acceptor (agmatine). Thus, ARF seemed to be an allosteric activator of the toxin, active with GTP bound, and inactive with bound GDP. Whether ARF has an effect on cholera toxin activity in intoxicated cells remains unknown, but its more recently recognized physiological actions are clearly quite different. Because of limitations of space, this Minireview deals only with the functions of ARF in eukaryotic cells, where these proteins have a critical role in vesicular membrane trafficking in both exocytic and endocytic pathways, and the relationship of ARF structure to its biochemical actions. Recent, more complete reviews consider also ARF cDNA and genomic sequences, as well as data on distribution and expression of ARF proteins and mRNAs. JF - Journal of Biological Chemistry AU - Moss, J AU - Vaughan, M AD - Pulm.-Crit. Care Med. Branch, NHLBI/NIH, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 12327 EP - 12330 VL - 270 IS - 21 SN - 0021-9258, 0021-9258 KW - ARF protein KW - cholera toxin KW - Microbiology Abstracts B: Bacteriology; Toxicology Abstracts KW - Vibrio cholerae KW - eukaryotes KW - activation KW - X 24171:Microbial KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16973047?accountid=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=Structure+and+function+of+ARF+proteins%3A+Activators+of+cholera+toxin+and+critical+components+of+intracellular+vesicular+transport+processes&rft.au=Moss%2C+J%3BVaughan%2C+M&rft.aulast=Moss&rft.aufirst=J&rft.date=1995-01-01&rft.volume=270&rft.issue=21&rft.spage=12327&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Vibrio cholerae; eukaryotes; activation ER - TY - JOUR T1 - Cytokines in the management of infectious complications in children with cancer AN - 16971913; 3819094 AB - Children receiving cancer therapy are susceptible to infectious complications that compromise the ability to deliver therapy in a timely manner and may adversely affect outcome. The most significant risk factor is severe neutropenia. The recently discovered myeloid growth factors have the potential to abrogate neutropenia post-intensive therapy and to possibly reduce infectious complications. In addition, these agents can augment effector cell response to established infection. Recently, in various clinical trials, the use of cytokines has been shown to decrease the incidence and severity of infectious complications in pediatric patients, especially those receiving intensive chemotherapy or autologous bone marrow transplant. However, to date, cytokine therapy has not impacted on survival rates. This is an important consideration since these agents are very costly. In an effort to direct the rational use of these agents and to limit the cost, it will be necessary to conduct randomized pediatric studies to examine not only clinical endpoints but also the impact of cytokines on the cost of therapy. JF - International Journal of Pediatric Hematology/Oncology AU - Chanock, S J AU - Freifeld, A G AD - NCI, 10/13N240, NIH, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 173 EP - 183 VL - 2 IS - 2 SN - 1070-2903, 1070-2903 KW - colony-stimulating factors KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - complications KW - treatment KW - neutropenia KW - children KW - tumors KW - F 06774:Other cytokines (TNF, GM-CSF) KW - W3 33150:Cytokine based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16971913?accountid=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+Pediatric+Hematology%2FOncology&rft.atitle=Cytokines+in+the+management+of+infectious+complications+in+children+with+cancer&rft.au=Chanock%2C+S+J%3BFreifeld%2C+A+G&rft.aulast=Chanock&rft.aufirst=S&rft.date=1995-01-01&rft.volume=2&rft.issue=2&rft.spage=173&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Pediatric+Hematology%2FOncology&rft.issn=10702903&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - complications; treatment; children; neutropenia; tumors ER - TY - JOUR T1 - Temperature-related differential expression of antigens in the Lyme disease spirochete, Borrelia burgdorferi AN - 16971088; 3818749 AB - Previous studies have demonstrated that Borrelia burgdorferi in the midguts of infected ticks shows increased expression of the antigenic outer surface protein OspC after the ticks have ingested a blood meal. This differential expression is at least partly due to a change in temperature, as an increase in OspC levels is also observed when cultures are shifted from 23 to 35 degree C. Immunoblotting of bacterial lysates with sera from infected mice indicated that the levels of several additional antigens were also increased in bacterial cultures shifted to 35 degree C; we have identified one antigen as OspE. We have also observed differential expression of OspF, which has been proposed to be coexpressed in an operon with the gene encoding OspE. JF - Infection and Immunity AU - Stevenson, B AU - Schwan, T G AU - Rosa, P A AD - Lab. Microbiol. Struct. and Funct., Rocky Mountain Lab., NIAID/NIH, 903 S. Fourth St., Hamilton, MT 59840, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 4535 EP - 4539 VL - 63 IS - 11 SN - 0019-9567, 0019-9567 KW - temperature KW - OspC protein KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Borrelia burgdorferi KW - immunoblotting KW - antigens KW - Lyme disease KW - J 02832:Antigenic properties and virulence KW - F 06008:Bacteria UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16971088?accountid=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=Temperature-related+differential+expression+of+antigens+in+the+Lyme+disease+spirochete%2C+Borrelia+burgdorferi&rft.au=Stevenson%2C+B%3BSchwan%2C+T+G%3BRosa%2C+P+A&rft.aulast=Stevenson&rft.aufirst=B&rft.date=1995-01-01&rft.volume=63&rft.issue=11&rft.spage=4535&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Borrelia burgdorferi; Lyme disease; immunoblotting; antigens ER - TY - JOUR T1 - Role of cytokines in children with HIV infection AN - 16969700; 3819087 AB - As of June, 1994 over 5700 children in the United States have been diagnosed with the Acquired Immunodeficiency Syndrome (AIDS) caused by infection with the human immunodeficiency virus type-1 (HIV-1). HIV infection in children differs from adults mainly in the early onset of encephalopathy and the often very short period of asymptomatic infection. Hematopoietic growth factors (cytokines) have been used to promote the proliferation and differentiation of stem cells to overcome bone marrow suppression in HIV-infected children and adults. These agents have also been explored for their potential to enhance and support the host immune system, and preliminary results also indicate an important role in the pathogenesis of HIV disease (Table 1). The endogenous levels of cytokines and hematopoietic growth factors are often altered by HIV-infection. It is possible that some disease manifestations are directly related to these changes (e.g., increased levels of tumor necrosis factor and the development of wasting syndrome, or increased interleukin-1 levels and encephalopathy). The rate of viral replication is not only influenced by the level of certain cytokines but in turn also induces a cytokine response. Because of these multiple interactions it is often complicated to define the therapeutic indications of cytokines and growth factors in HIV-infected patients and benefits have to be balanced carefully against potential disadvantages. JF - International Journal of Pediatric Hematology/Oncology AU - Mueller, BU AD - Pediatric., NCI, Bldg. 10, Rm. 13N240, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 151 EP - 161 VL - 2 IS - 2 SN - 1070-2903, 1070-2903 KW - colony-stimulating factors KW - cytokines KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - pediatrics KW - replication KW - human immunodeficiency virus KW - infection KW - growth factors KW - F 06774:Other cytokines (TNF, GM-CSF) KW - W3 33150:Cytokine based KW - V 22003:AIDS: Immunological aspects KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16969700?accountid=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+Pediatric+Hematology%2FOncology&rft.atitle=Role+of+cytokines+in+children+with+HIV+infection&rft.au=Mueller%2C+BU&rft.aulast=Mueller&rft.aufirst=BU&rft.date=1995-01-01&rft.volume=2&rft.issue=2&rft.spage=151&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Pediatric+Hematology%2FOncology&rft.issn=10702903&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - pediatrics; replication; infection; growth factors; human immunodeficiency virus ER - TY - JOUR T1 - Oxidative biotransformation of oxazepam to reactive and nonreactive products in rat, mouse and human microsomes AN - 16968959; 3821264 AB - The oxidative metabolism of oxazepam by human, B6C3F1 mouse and F344 rat microsomes was examined. The major metabolite in all three species was 6-chloro-4-phenyl-2(1H)-quinazolinecarboxylic acid (CPQ-carboxylic acid). In addition, rat microsomes produced 4'-hydroxyoxazepam and oxazepam-dihydrodiol in NADPH-containing incubations. Covalent protein adducts were increased by the addition of NADPH to rat and mouse microsomes but not human microsomes. The magnitude of adduct formation was rats > mice > humans. Formation of oxazepam-dihydrodiol was reduced by the addition of cyclohexene oxide and GSH to the incubations. Two additional metabolites were produced under these conditions. One of these was tentatively identified as a GSH conjugate. Covalent adduct formation was unaffected by GSH or cyclohexene oxide. These results suggest that adduct formation occurred via an unknown reactive product rather than via oxazepam-epoxide, and that the relative rates of oxidative metabolism in vitro parallel that in vivo for the three species examined. JF - Human & Experimental Toxicology AU - Griffin, R J AU - Burka, L T AU - Demby, K B AD - NIEHS, PO Box 12233, MD C3-02, Research Triangle Park, NC 27709, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 779 EP - 786 VL - 14 IS - 10 SN - 0144-5952, 0144-5952 KW - oxazepam KW - rats KW - mice KW - benzodiazepines KW - Toxicology Abstracts KW - metabolism KW - hypnotics KW - man KW - X 24114:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16968959?accountid=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=Human+%26+Experimental+Toxicology&rft.atitle=Oxidative+biotransformation+of+oxazepam+to+reactive+and+nonreactive+products+in+rat%2C+mouse+and+human+microsomes&rft.au=Griffin%2C+R+J%3BBurka%2C+L+T%3BDemby%2C+K+B&rft.aulast=Griffin&rft.aufirst=R&rft.date=1995-01-01&rft.volume=14&rft.issue=10&rft.spage=779&rft.isbn=&rft.btitle=&rft.title=Human+%26+Experimental+Toxicology&rft.issn=01445952&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 - man; metabolism; hypnotics ER - TY - JOUR T1 - Systemic gene therapy: Biodistribution and long-term expression of a transgene in mice AN - 16968420; 3816836 AB - We have investigated the in vivo efficacy of a systemic gene transfer method, which combines a liposomal delivery system (DLS liposomes) with episomally replicative DNA plasmids to effect long-term expression of a transgene in cells. A single i.v. injection of a plasmid DNA vector containing the luciferase gene as a marker was administered with the DLS liposomes in BALB/c mice. The luciferase gene and its product were found in all mouse tissues tested as determined by PCR analysis and immunohistochemistry. Luciferase activity was also detected in all tissues tested and was present in lung, liver, spleen, and heart up to 3 months postinjection. In contrast to the nonepisomal vectors tested (pRSV-luc and pCMVintlux), human papovavirus (BKV)-derived episomal vectors showed long-term transgene expression. We found that these episomal vectors replicated extrachromosomally in lung 2 weeks postinjection. Results indicated that transgene expression in specific tissues depended on the promoter element used, DNA/liposome formulation, dose of DNA per injection, and route of administration. JF - Proceedings of the National Academy of Sciences, USA AU - Thierry, A R AU - Lunardi-Iskandar, Y AU - Bryant, J L AU - Rabinovich, P AU - Gallo, R C AU - Mahan, L C AD - Lab. Tumor Cell Biol., Bldg. 37, Rm. 6A09, NCI, 37 Convent Dr., Bethesda, MD 20892-4255, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 9742 EP - 9746 VL - 92 IS - 21 SN - 0027-8424, 0027-8424 KW - DNA KW - episomal DNA vectors KW - gene therapy KW - gene transfer KW - liposomal delivery system KW - liposomes KW - luc gene KW - Biotechnology and Bioengineering Abstracts; Human Genome 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/16968420?accountid=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=Systemic+gene+therapy%3A+Biodistribution+and+long-term+expression+of+a+transgene+in+mice&rft.au=Thierry%2C+A+R%3BLunardi-Iskandar%2C+Y%3BBryant%2C+J+L%3BRabinovich%2C+P%3BGallo%2C+R+C%3BMahan%2C+L+C&rft.aulast=Thierry&rft.aufirst=A&rft.date=1995-01-01&rft.volume=92&rft.issue=21&rft.spage=9742&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 - 2011-12-14 N1 - SubjectsTermNotLitGenreText - gene transfer; gene therapy; liposomes; DNA ER - TY - JOUR T1 - Neuronal protective and rescue effects of deprenyl against MPP super(+) dopaminergic toxicity AN - 16965538; 3819377 AB - Intranigral infusion of 1-Methyl-4-phenylpyridinium ion (MPP super(+), 2.1-16.8 nmol) dose-dependently injured nigral neurons as reflected by reduced dopamine levels in the ipsilateral striatum four days after the infusion of this toxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Coadministration of deprenyl (4.2 nmol) with MPP super(+) into the substantia nigra protected against MPP super(+)-induced moderate (20-50%) but not severe (over 70%) nigral injury as reflected in striatal dopamine reductions. However, supplementary treatment with deprenyl (0.25 mg/kg, s.c., twice daily for 4 days) after intranigral infusion of MPP super(+) significantly rescued nigral neurons from more severe damage caused by a higher MPP super(+) does (8.4 nmol) manifested by a lesser striatal dopamine decrease (-31%) compared to the non-deprenyl treated group (-70%). Thus, in addition to the blockade of bioactivation of MPTP, deprenyl can protect and/or rescue nigral neurons from MPP super(+)-induced dopaminergic neurotoxicity. These in vivo data add further evidence to suggest that deprenyl, a putative and clinically unproven neuroprotective agent, may be of value in slowing the progressive nigral degeneration in "early" Parkinson's disease, but may prove to be less so in its terminal stages. JF - Journal of Neural Transmission AU - Wu, R-M AU - Murphy, D L AU - Chiueh, C C AD - Unit Neurotoxicol. and Neuroprotect., Neuropharmacol., Lab. Clin. Sci., NIMH/NIH Clin. Cent. 10/3D-41, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 53 EP - 61 VL - 100 IS - 1 SN - 0300-9564, 0300-9564 KW - deprenyl KW - MPP super(+) KW - dopamine KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - laboratory animals KW - neurotoxicity KW - substantia nigra KW - neostriatum KW - N3 11104:Mammals (except primates) KW - X 24115:Pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16965538?accountid=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+Neural+Transmission&rft.atitle=Neuronal+protective+and+rescue+effects+of+deprenyl+against+MPP+super%28%2B%29+dopaminergic+toxicity&rft.au=Wu%2C+R-M%3BMurphy%2C+D+L%3BChiueh%2C+C+C&rft.aulast=Wu&rft.aufirst=R-M&rft.date=1995-01-01&rft.volume=100&rft.issue=1&rft.spage=53&rft.isbn=&rft.btitle=&rft.title=Journal+of+Neural+Transmission&rft.issn=03009564&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 - neurotoxicity; substantia nigra; neostriatum; laboratory animals ER - TY - JOUR T1 - Immunization with recombinant varicella-zoster virus expressing herpes simplex virus type 2 glycoprotein D reduces the severity of genital herpes in guinea pigs AN - 16965489; 3822158 AB - Varicella-zoster virus (VZV) is an attractive candidate for a live-virus vector for the delivery of foreign antigens. The Oka vaccine strain of VZV is safe and effective in humans, and recombinant Oka VZV (ROka) can be generated by transfecting cells with a set of overlapping cosmid DNAs. By this method, the herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) gene was inserted into an intergenic site in the unique short region of the Oka VZV genome. Expression of gD2 in cells infected with the recombinant Oka strain VZV (ROka-gD2) was confirmed by antibody staining of fixed cells and by immunoblot analysis. Immune electron microscopy demonstrated the presence of gD2 in the envelope of ROka-gD2 virions. The ability of ROka-gD2 to protect guinea pigs against HSV-2 challenge was assessed by inoculating animals with three doses of uninfected human fibroblasts, fibroblasts infected with ROka VZV, or fibroblasts infected with ROka-gD2. Neutralizing antibodies specific for HSV-2 developed in animals immunized with ROka-gD2. Forty days after the third inoculation, animals were challenged intravaginally with HSV-2. Inoculation of guinea pigs with ROka-gD2 significantly reduced the severity of primary HSV-2 infection (P < 0.001). These experiments demonstrate that the Oka strain of VZV can be used as a live virus vector to protect animals from disease with a heterologous virus. JF - Journal of Virology AU - Heineman, T C AU - Connelly, B L AU - Bourne, N AU - Stanberry, L R AU - Cohen, J AD - Lab. Clin. Invest., NIAID/NIH, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 8109 EP - 8113 VL - 69 IS - 12 SN - 0022-538X, 0022-538X KW - glycoprotein D KW - guinea-pigs KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts; Virology & AIDS Abstracts KW - immunization KW - herpes simplex virus 2 KW - neutralization KW - vaccines KW - antibodies KW - immunity (humoral) KW - varicella-zoster virus KW - W3 33365:Vaccines (other) KW - F 06807:Active immunization KW - V 22097:Immunization: Vaccines & vaccination: Human KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16965489?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Virology&rft.atitle=Immunization+with+recombinant+varicella-zoster+virus+expressing+herpes+simplex+virus+type+2+glycoprotein+D+reduces+the+severity+of+genital+herpes+in+guinea+pigs&rft.au=Heineman%2C+T+C%3BConnelly%2C+B+L%3BBourne%2C+N%3BStanberry%2C+L+R%3BCohen%2C+J&rft.aulast=Heineman&rft.aufirst=T&rft.date=1995-01-01&rft.volume=69&rft.issue=12&rft.spage=8109&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - immunization; vaccines; neutralization; antibodies; immunity (humoral); herpes simplex virus 2; varicella-zoster virus ER - TY - JOUR T1 - The reproductive and developmental toxicity of indium in the Swiss mouse AN - 16902883; 3806830 AB - Indium is increasingly used in a variety of industries, and while there are few studies of its developmental toxicity, there are no reports of its potential reproductive toxicity. These studies were undertaken to investigate the possible reproductive toxicity of indium and to determine the relative vulnerability of males and females. We used, initially, a 21-day combined developmental/reproductive toxicity protocol. Oral exposures to InCl sub(3) ( less than or equal to 250 mg/kg) were without effect on the male reproductive system or liver. A kidney effect was demonstrated in males by a decrease in urinary N-acetyl glucosaminidase. The ability of females to become pregnant was unaffected. However, fetal development was adversely affected, manifested as increased intrauterine deaths in the presence of reduced maternal weight gain. A developmental toxicity study identified no increase in fetal malformations, but verified the increased fetal deaths, in the absence of effects on adjusted maternal body weight. In vitro toxicity studies showed that the embryolethality was at least in part a result of direct toxicity to the conceptus, with effective doses in the low micromolar range. A limited disposition study showed that fetuses contained low micromolar concentrations of indium, more indium than maternal liver, and comparable to levels that were toxic in vitro. Although studies of greater exposure duration are required for risk assessment, these data indicate that fetal development is likely to be more affected by indium than female or male reproduction, with adverse effects occurring at low micromolar levels in vivo and at exposures that may or may not affect body weight. JF - Fundamental and Applied Toxicology AU - Chapin, R E AU - Harris, M W AU - Hunter, ES III AU - Davis, B J AU - Collins, B J AU - Lockhart, A C AD - Reprod. Toxicol. Group, Natl. Toxicol. Program/NIEHS, Research Triangle Park, NC 27709, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 140 EP - 148 VL - 27 IS - 1 SN - 0272-0590, 0272-0590 KW - mice KW - indium KW - Toxicology Abstracts KW - fetuses KW - reproduction KW - body weight KW - teratogenicity KW - X 24152:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16902883?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+Applied+Toxicology&rft.atitle=The+reproductive+and+developmental+toxicity+of+indium+in+the+Swiss+mouse&rft.au=Chapin%2C+R+E%3BHarris%2C+M+W%3BHunter%2C+ES+III%3BDavis%2C+B+J%3BCollins%2C+B+J%3BLockhart%2C+A+C&rft.aulast=Chapin&rft.aufirst=R&rft.date=1995-01-01&rft.volume=27&rft.issue=1&rft.spage=140&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+Applied+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - reproduction; fetuses; teratogenicity; body weight ER - TY - JOUR T1 - Detection of human herpesvirus 6 in plasma of children with primary infection and immunosuppressed patients by polymerase chain reaction AN - 16900547; 3804678 AB - A sensitive and specific polymerase chain reaction method for the detection of human herpes-virus 6 (HHV-6) DNA in serum or plasma has been developed. In total, 157 human serum or plasma samples were studied. HHV-6 DNA was detected in 6 (85.7%) of 7 children with exanthem subitum, 3 (23.1%) of 13 bone marrow transplant (BMT) recipients, 4 (22.2%) of 18 human immunodeficiency virus (HIV)-infected patients, 1 (2.6%) of 39 patients with chronic fatigue syndrome, and none of 37 healthy adults. In the HHV-6-positive BMT recipients, HHV-6 plasma DNA was transiently detected during episodes of fever and respiratory infection. In children with exanthem subitum and in 1 HIV-infected patient, the HHV-6 strains were characterized as variant B, whereas variant A was detected in all other patients. Detection of viral DNA in serum or plasma is a marker of active infection that can be used to investigate the role of HHV-6 in human disease. JF - Journal of Infectious Diseases AU - Secchiero, P AU - Carrigan AU - Asano, Y AU - Benedetti, L AU - Crowley, R W AU - Komaroff, AL AU - Gallo, R C AU - Lusso, P AD - Lab. Tumor Cell Biol., NCI, Bldg. 37, Rm. 6A11, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 273 EP - 280 VL - 171 IS - 2 SN - 0022-1899, 0022-1899 KW - herpesvirus (human) 6 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - plasma KW - DNA KW - children KW - immunocompromised hosts KW - polymerase chain reaction KW - man KW - W 30965:Miscellaneous, Reviews KW - V 22121:Diagnosis KW - W3 33130:Genetic based (PCR, etc.) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16900547?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Infectious+Diseases&rft.atitle=Detection+of+human+herpesvirus+6+in+plasma+of+children+with+primary+infection+and+immunosuppressed+patients+by+polymerase+chain+reaction&rft.au=Secchiero%2C+P%3BCarrigan%3BAsano%2C+Y%3BBenedetti%2C+L%3BCrowley%2C+R+W%3BKomaroff%2C+AL%3BGallo%2C+R+C%3BLusso%2C+P&rft.aulast=Secchiero&rft.aufirst=P&rft.date=1995-01-01&rft.volume=171&rft.issue=2&rft.spage=273&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - plasma; DNA; children; immunocompromised hosts; man; polymerase chain reaction ER - TY - JOUR T1 - Both a precursor and a mature population of dendritic cells can bind HIV. However, only the mature population that expresses CD80 can pass infection to unstimulated CD4 super(+) T cells AN - 16894736; 3805828 AB - Dendritic cells (DC) are the principle APC involved in primary immune responses; their major function is to obtain Ag in tissues, migrate to lymphoid organs, and activate T cells. DC are also the first immune cells to arrive at sites of inflammation on mucous membranes, the major site of sexual transmission of HIV. We have demonstrated previously that three populations of cells that can develop a dendritic morphology are present in peripheral blood. Two of these populations can express CD83, a marker of DC, and appear to be at different stages of maturation: 1) a precursor population and 2) a mature immunostimulatory DC. Precursor-derived DC express high levels of CD86 (B7-2) and HLA-DR but no CD80 (B7-1), whereas mature DC have high levels of expression of all three markers. Mature DC in peripheral blood bind HIV to their surface and induce infection when added to autologous CD4 super(+) T cells in the absence of added stimuli, such as mitogens. These mature DC, when isolated directly from peripheral blood, appear to be conjugated to T cells, and these conjugates are infected easily and productively with HIV. These findings suggest a role for DC in early HIV infection in which they bind virus and interact with T cells locally or after migrating to a lymphoid organ, thus establishing a productive infection. Furthermore, they likely play a role in the propagation of HIV infection by activating T cells in the presence of HIV, which leads to viral replication and immune cell destruction. JF - Journal of Immunology AU - Weissman, D AU - Li, Yuexia AU - Orenstein, J M AU - Fauci, A S AD - LIR/NIAID/NIH, 10 Cent. Dr. MSC 1576, Bethesda, MD 20892-1576, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 4111 EP - 4117 VL - 155 IS - 8 SN - 0022-1767, 0022-1767 KW - CD4 antigen KW - CD80 antigen KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts; Immunology Abstracts KW - lymphocytes T KW - human immunodeficiency virus KW - dendritic cells KW - man KW - W3 33365:Vaccines (other) KW - V 22003:AIDS: Immunological aspects KW - W 30965:Miscellaneous, Reviews KW - F 06742:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16894736?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunology&rft.atitle=Both+a+precursor+and+a+mature+population+of+dendritic+cells+can+bind+HIV.+However%2C+only+the+mature+population+that+expresses+CD80+can+pass+infection+to+unstimulated+CD4+super%28%2B%29+T+cells&rft.au=Weissman%2C+D%3BLi%2C+Yuexia%3BOrenstein%2C+J+M%3BFauci%2C+A+S&rft.aulast=Weissman&rft.aufirst=D&rft.date=1995-01-01&rft.volume=155&rft.issue=8&rft.spage=4111&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - lymphocytes T; dendritic cells; man; human immunodeficiency virus ER - TY - JOUR T1 - Repression and activation of transcription by Gal and Lac repressors: Involvement of alpha subunit of RNA polymerase AN - 16892750; 3807108 AB - Gal or Lac repressor binding to an upstream DNA segment, in the absence of DNA looping, represses the P1 promoter located on the same face and activates the P2 promoter situated on the opposite face of the DNA helix in the gal operon. Both inhibition and stimulation of transcription requires the physical presence of the C-terminal domain of the alpha subunit of RNA polymerase although the latter is not required for transcription itself. We propose that Gal and Lac repressors inhibit or stimulate transcription initiation by disabling or stimulating RNA polymerase activity at a post-binding step by directly or indirectly altering the C-terminal alpha domain to an unfavorable state at P1 or a more favorable state at P2, respectively. JF - EMBO Journal AU - Choy, HE AU - Park, Seong Weon AU - Aki, T AU - Parrack, P AU - Fujita, N AU - Ishihama, A AU - Adhya, S AD - Lab. Mol. Biol., NCI/NIH, Bethesda, MD 20892-4255, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 4523 EP - 4529 VL - 14 IS - 18 SN - 0261-4189, 0261-4189 KW - Gal repressor KW - Lac repressor KW - DNA-directed RNA polymerase KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - gal operon KW - gene regulation KW - DNA KW - J 02725:DNA KW - N 14662:Gene regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16892750?accountid=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=EMBO+Journal&rft.atitle=Repression+and+activation+of+transcription+by+Gal+and+Lac+repressors%3A+Involvement+of+alpha+subunit+of+RNA+polymerase&rft.au=Choy%2C+HE%3BPark%2C+Seong+Weon%3BAki%2C+T%3BParrack%2C+P%3BFujita%2C+N%3BIshihama%2C+A%3BAdhya%2C+S&rft.aulast=Choy&rft.aufirst=HE&rft.date=1995-01-01&rft.volume=14&rft.issue=18&rft.spage=4523&rft.isbn=&rft.btitle=&rft.title=EMBO+Journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - DNA; gal operon; gene regulation ER - TY - JOUR T1 - Evaluation of retroviral vectors based on the gibbon ape leukemia virus AN - 16891130; 3797263 AB - The gibbon ape leukemia viruses (GaLVs) are primate-derived C-type retroviruses with a broad host range. Using an infectious, full-length clone of the GaLV SEATO strain, we have determined that this virus replicates efficiently in 13 of 17 human cell lines tested. In fact, the SB lymphoblast cell line, while resistant to infection by wild-type amphotropic mouse leukemia virus (A-MLV), was infected by GaLV-SEATO. We constructed vectors containing GaLV components and compared the performance of genomes containing an enhancer and promoter derived either from the SEATO or SF strains of GaLV. The GaLV vector genomes were packaged in a Moloney (Mo)MLV core with either an A-MLV or GaLV SEATO envelope. We found that, in some cases, the vector genome appeared to be critical in obtaining optimal infection. For example, vectors with a GaLV SF-based genome infected the human HL60 cell line, whereas vectors with a GaLV SEATO-based genome did not. We also found that most, but not all, of the human cell lines tested were more susceptible to vectors packaged with the GaLV SEATO than A-MLV envelope. The source of the viral core was also important, in that some human cells appeared susceptible to infection only with GaLV genomes packaged in particles composed of a GaLV core and envelope. Our results show that GaLV-based packageable genomes can be expressed in target cells not efficiently infected by vectors containing MoMLV-based genomes. These results suggest that judicious combinations of retroviral genomes and structural components can significantly improve gene transfer into human cells. JF - Gene Therapy AU - Eglitis, MA AU - Schneiderman, R D AU - Rice, P M AU - Eiden, M V AD - Unit Mol. Virol., Lab. Cell Biol., NIMH, Bldg. 36, Rm. 2D10, 36 Convent Dr. MSC 4068, Bethesda, MD 20892-4068, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 486 EP - 492 VL - 2 IS - 7 SN - 0969-7128, 0969-7128 KW - Moloney leukemia virus KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - gene transfer KW - retrovirus KW - cloning vectors KW - gibbon ape leukemia virus KW - man KW - N 14682:Cloning vectors 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/16891130?accountid=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=Evaluation+of+retroviral+vectors+based+on+the+gibbon+ape+leukemia+virus&rft.au=Eglitis%2C+MA%3BSchneiderman%2C+R+D%3BRice%2C+P+M%3BEiden%2C+M+V&rft.aulast=Eglitis&rft.aufirst=MA&rft.date=1995-01-01&rft.volume=2&rft.issue=7&rft.spage=486&rft.isbn=&rft.btitle=&rft.title=Gene+Therapy&rft.issn=09697128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - gene transfer; retrovirus; cloning vectors; man; gibbon ape leukemia virus ER - TY - JOUR T1 - Stress and antidepressants differentially regulate neurotrophin 3 mRNA expression in the locus coeruleus AN - 16890834; 3806440 AB - The mechanisms by which stress and antidepressants exert opposite effects on the course of clinical depression are not known. However, potential candidates might include neurotrophic factors that regulate the development, plasticity, and survival of neurons. To explore this hypothesis, we examined the effects of stress and antidepressants on neurotrophin expression in the locus coeruleus (LC), which modulates many of the behavioral and physiological responses to stress and has been implicated in mood disorders. Using in situ hybridization, we demonstrate that neurotrophin 3 (NT-3) is expressed in noradrenergic neurons of the LC. Recurrent, but not acute, immobilization stress increased NT-3 mRNA levels in the LC. In contrast, chronic treatment with antidepressants decreased NT-3 mRNA levels. The effect occurred in response to antidepressants that blocked norepinephrine uptake, whereas serotonin-specific reuptake inhibitors did not alter NT-3 levels. Electroconvulsive seizures also decreased NT-3 expression in the LC as well as the hippocampus. Ntrk3 (neurotrophic tyrosine kinase receptor type 3; formerly TrkC), the receptor for NT-3, is expressed in the LC, but its mRNA levels did not change with stress or antidepressant treatments. Because NT-3 is known to be trophic for LC neurons, our results raise the possibility that some of the effects of stress and antidepressants on LC function and plasticity could be mediated through NT-3. Moreover, the coexpression of NT-3 and its receptor in the LC suggests the potential for autocrine mechanisms of action. JF - Proceedings of the National Academy of Sciences, USA AU - Smith, MA AU - Makino, S AU - Altemus, M AU - Michelson, D AU - Hong, Sung-Kwan AU - Kvetnansky, R AU - Post, R M AD - Biol. Psychiatr. Branch, NIMH, Bldg. 10, Rm. 3N212, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 8788 EP - 8792 VL - 92 IS - 19 SN - 0027-8424, 0027-8424 KW - neurotrophin-3 KW - norepinephrine KW - serotonin KW - Ntrk3 protein KW - TrkC protein KW - rats KW - CSA Neurosciences Abstracts; Toxicology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - stress KW - mRNA KW - seizures KW - antidepressants KW - locus coeruleus KW - X 24117:Biochemistry KW - N3 11072:Neurotropic factors and their receptors KW - N 14662:Gene regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16890834?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Stress+and+antidepressants+differentially+regulate+neurotrophin+3+mRNA+expression+in+the+locus+coeruleus&rft.au=Smith%2C+MA%3BMakino%2C+S%3BAltemus%2C+M%3BMichelson%2C+D%3BHong%2C+Sung-Kwan%3BKvetnansky%2C+R%3BPost%2C+R+M&rft.aulast=Smith&rft.aufirst=MA&rft.date=1995-01-01&rft.volume=92&rft.issue=19&rft.spage=8788&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - mRNA; locus coeruleus; seizures; stress; antidepressants ER - TY - JOUR T1 - Identification of the von Hippel-Lindau (VHL) gene. Its role in renal cancer AN - 16890545; 3796661 AB - Renal carcinoma, the most common cancer of the kidney, occurs in over 27 000 individuals in the United States each year and is responsible for over 11 000 deaths annually. The incidence of renal carcinoma worldwide has been increasing at an annual rate of approximately 2%. Although renal carcinoma has been reported in children as young as 3 years, it most commonly occurs in adults between the ages of 50 and 70 years. Renal carcinoma affects males twice as frequently as females and accounts for approximately 3% of adult cancers. Although a number of hormonal, environmental, cellular, and genetic factors have been evaluated, little is known about the etiology of renal cancer. There is an increased incidence of renal cancer among workers exposed to asbestos and among leather workers, and a strong correlation has been found with cigarette smoking. In patients with end-stage renal disease, particularly in those patients who have acquired cystic disease, there is also an increase incidence of renal cancer. The risk of development of renal cancer in dialysis patients with acquired cystic disease has been estimated to be greater than 30 times higher than that in normal controls. Eighty percent to 85% of renal cancer is of the clear cell type or a variant of clear cell type. Five percent to 10% of renal carcinomas are papillary with the remainder made up of rare histologic types such as chromophobe renal cancer. Family history of renal carcinoma is associated with an increased risk of development of this malignancy in both men (odds ratio [OR]=4.1) and women (OR=4.8). This article will focus on new information on the genetic basis of human renal carcinoma. JF - Journal of the American Medical Association AU - Linehan, WM AU - Lerman, MI AU - Zbar, B AD - Urol. Oncol. Sect., Surg. Branch, Clin. Oncol. Program, NCI, Bldg. 10, Rm. 2B47, 10 Cent. DR MSC 1502, Bethesda, MD 20892-1502, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 564 EP - 570 VL - 273 IS - 7 SN - 0098-7484, 0098-7484 KW - kidney carcinoma KW - von Hippel-Lindau gene KW - Biotechnology and Bioengineering Abstracts; Oncogenes & Growth Factors Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Genetics Abstracts KW - reviews KW - tumor suppressor genes KW - Von Hippel-Lindau disease KW - kidney KW - man KW - carcinoma KW - G 07471:General KW - B 26400:HUMAN-RELATED ONCOGENES AND GROWTH FACTORS: CROSS REFERENCES KW - B 26416:Other tumor suppressor genes/antioncogenes KW - W 30965:Miscellaneous, Reviews KW - W3 33055:Genetic engineering (general) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16890545?accountid=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+the+American+Medical+Association&rft.atitle=Identification+of+the+von+Hippel-Lindau+%28VHL%29+gene.+Its+role+in+renal+cancer&rft.au=Linehan%2C+WM%3BLerman%2C+MI%3BZbar%2C+B&rft.aulast=Linehan&rft.aufirst=WM&rft.date=1995-01-01&rft.volume=273&rft.issue=7&rft.spage=564&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Medical+Association&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - reviews; tumor suppressor genes; Von Hippel-Lindau disease; kidney; man; carcinoma ER - TY - JOUR T1 - Molecular insights into cancer invasion: Strategies for prevention and intervention AN - 16890513; 3802149 AB - The diagnosis and treatment of solid tumors usually begins at a late stage when most patients already have occult or overt metastasis. Many years of cancer progression precede diagnosis of most solid tumors. Novel noncytotoxic therapeutics may be specially suited for administration during this interval. An important window of intervention can be defined as the period during which transition from a hyperproliferative state to acquisition of the capacity for invasion and metastasis occurs. Investigation of the molecular basis of invasion is uncovering strategies for delaying progression of preinvasive carcinoma and treatment of primary tumors and established metastasis. Although tumor cell invasion might not be rate limiting for the growth of metastasis, anti-invasive agents can block tumor angiogenesis and thereby indirectly block metastasis growth. Two classes of molecular anti-invasion target exist: (a) cell surface and extracellular proteins, which mediate sensing, adhesion, and proteolysis; and (b) signal transduction pathways, which regulate invasion, angiogenesis, and proliferation. Both categories of targets yield treatment approaches that are now being tested in the clinic. Metalloproteinase inhibitors, such as BB94, are based on the recognition that metalloproteinases play a necessary role in invasion and angiogenesis. The orally active signal transduction inhibitor carboxyamidotriazole modulates non-voltage-gated calcium influx-regulated signal pathways and reversibly inhibits tumor invasion, growth, and angiogenesis. Blockade of invasion, angiogenesis, or cellular signal pathways is likely to generate a cytostatic, rather than a cytotoxic effect. Cytostatic therapy constitutes an alternative paradigm for clinical translation that may complement conventional cytotoxic therapy. For patients with newly diagnosed solid tumors, long-term cytostatic therapy could potentially create a state of metastasis dormancy or delay the time to overt relapse following cytotoxic agent-induced remission. Clinical toxicity and pharmacology using oral cytostatic agents in phase I trials and in adjuvant settings will provide an important foundation for the translation of this approach to the preinvasive carcinoma period. JF - Cancer Research AU - Kohn, E C AU - Liotta, LA AD - Lab. Pathol., Div. Cancer Biol., Diagn. and Cent., NCI/NIH, Bethesda, MD 28092, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 1856 EP - 1862 VL - 55 IS - 9 SN - 0008-5472, 0008-5472 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - reviews KW - signal transduction 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/16890513?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Research&rft.atitle=Molecular+insights+into+cancer+invasion%3A+Strategies+for+prevention+and+intervention&rft.au=Kohn%2C+E+C%3BLiotta%2C+LA&rft.aulast=Kohn&rft.aufirst=E&rft.date=1995-01-01&rft.volume=55&rft.issue=9&rft.spage=1856&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 - 2011-12-14 N1 - SubjectsTermNotLitGenreText - reviews; signal transduction; cancer ER - TY - JOUR T1 - Interactions of nickel(II) with histones. Stability and solution structure of complexes with CH sub(3)CO-Cys-Ala-Ile-His-NH sub(2), a putative metal binding sequence of histone H3 AN - 16890055; 3797685 AB - Nickle(II) compounds are established human carcinogens, but the molecular mechanisms underlying their activity are only partially known. One mechanism may include mediation by nickel of promutagenic oxidative DNA damage that depends on Ni(II) binding to chromatin. To characterize such binding at the histone moiety of chromatin, we synthesized the peptide CH sub(3)CO-Cys-Ala-Ile-His-NH sub(2) (L), a model of the evolutionary conserved motif in histone H3 with expected affinity for transition metals, and evaluated its reactivity toward Ni(II). Combined spectroscopic (UV/vis, CD, NMR) and potentiometric measurements showed that, at physiological pH, mixtures of Ni(II) and L yielded unusual macrochelate complexes, NiL and NiL sub(2), in which the metal cation was bound through Cys and His side chains in a square-planar arrangement. Above pH 9, a NiH- sub(3)L complex was formed, structurally analogous to typical square-planar nickel complexes. These complexes are expected to catalyze oxidation reactions, and therefore, coordination of Ni(II) by the L motif in core histone H3 may be a key event in oxidative DNA base damage observed in the process of Ni(II)-induced carcinogenesis. JF - Chemical Research in Toxicology AU - Bal, W AU - Lukszo, J AU - Jezowska-Bojczuk, M AU - Kasprzak, K S AD - NCI-FCRDC, Bldg. 538, Rm. 205, Frederick, MD 21702-1201, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 682 EP - 693 VL - 8 IS - 5 SN - 0893-228X, 0893-228X KW - nickel KW - histones KW - histone H3 KW - heavy metals KW - Toxicology Abstracts KW - X 24163:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16890055?accountid=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=Interactions+of+nickel%28II%29+with+histones.+Stability+and+solution+structure+of+complexes+with+CH+sub%283%29CO-Cys-Ala-Ile-His-NH+sub%282%29%2C+a+putative+metal+binding+sequence+of+histone+H3&rft.au=Bal%2C+W%3BLukszo%2C+J%3BJezowska-Bojczuk%2C+M%3BKasprzak%2C+K+S&rft.aulast=Bal&rft.aufirst=W&rft.date=1995-01-01&rft.volume=8&rft.issue=5&rft.spage=682&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 - Induction of an outer surface protein on Borrelia burgdorferi during tick feeding AN - 16888217; 3798089 AB - Lyme disease spirochetes, Borrelia burgdorferi sensu lato, are maintained in zoonotic cycles involving ticks and small mammals. In unfed ticks, the spirochetes produce one outer surface protein, OspA, but not OspC. During infection in mammals, immunological data suggest that the spirochetes have changed their surface, now expressing OspC but little or no OspA. We find by in vitro growth experiments that this change is regulated in part by temperature; OspC is produced by spirochetes at 32-37 degree C but not at 24 degree C. Furthermore, spirochetes in the midgut of ticks that have fully engorged on mice now have OspC on their surface. Thus two environmental cues, an increase in temperature and tick feeding, trigger a major alteration of the spirochetal outer membrane. This rapid synthesis of OspC by spirochetes during tick feeding may play an essential role in the capacity of these bacteria to successfully infect mammalian hosts, including humans, when transmitted by ticks. JF - Proceedings of the National Academy of Sciences, USA AU - Schwan, T G AU - Piesman, J AU - Golde, W T AU - Dolan, M C AU - Rosa, P A AD - Lab. Microb. Struct. and Funct., Rocky Mountain Lab., NIAID, Hamilton, MT 59840, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 2909 EP - 2913 VL - 92 IS - 7 SN - 0027-8424, 0027-8424 KW - protein C KW - temperature KW - Entomology Abstracts; Microbiology Abstracts B: Bacteriology KW - membrane proteins KW - Borrelia burgdorferi KW - Ixodidae KW - feeding KW - Ixodes scapularis KW - blood meals KW - Acari KW - Lyme disease KW - J 02870:Invertebrate bacteriology KW - Z 05206:Medical & veterinary entomology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16888217?accountid=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=Induction+of+an+outer+surface+protein+on+Borrelia+burgdorferi+during+tick+feeding&rft.au=Schwan%2C+T+G%3BPiesman%2C+J%3BGolde%2C+W+T%3BDolan%2C+M+C%3BRosa%2C+P+A&rft.aulast=Schwan&rft.aufirst=T&rft.date=1995-01-01&rft.volume=92&rft.issue=7&rft.spage=2909&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Borrelia burgdorferi; Ixodes scapularis; Ixodidae; Acari; membrane proteins; feeding; Lyme disease; blood meals ER - TY - JOUR T1 - Pneumonia and bacteremia by pneumococcal serotype 16 in a human immunodeficiency virus-infected child with normal serum antibody response to 23-valent Pneumovax vaccine AN - 16884390; 3801219 AB - Growth hormone (GH) and insulin-like growth factor I (IGF-I) have been shown in animal studies to augment immune reconstitution. Accordingly, we are evaluating the impact of either recombinant human GH or recombinant human IGF-I to stimulate both axial skeletal growth and immune system reconstitution in HIV-infected children. As part of the immunologic evaluation, a 23-valent Pneumovax vaccine and a conjugated Haemophilus influenzae type b (Hib) vaccine are administered, and pre- and postimmunization titers are determined during therapy. The first subject on the study to receive IGF-I, a 17-year-old male patient with transfusion-acquired HIV and a bone age of 12 years, had an increase in antipneumococcal and anti-Hib titers that was consistent with that of a healthy person, even though this CD4 super(+) cell count was essentially 0. Serum titers for 12 types of pneumococcal serotypes are shown. The same patient, however, became bacteremic and had pneumonia from a serotype 16 pneumococcus, one not found in the multivalent vaccine. The patient never recovered from the illness and its complications. JF - Journal of Infectious Diseases AU - Hirschfeld, S AU - Schiffman, G AU - Tudor-Williams, G AU - Pizzo, P A AD - Pediatr. Branch, NCI, Bldg. 10, Room 13N240, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 761 EP - 762 VL - 171 IS - 3 SN - 0022-1899, 0022-1899 KW - Microbiology Abstracts B: Bacteriology KW - vaccines KW - Haemophilus influenzae KW - human immunodeficiency virus KW - children KW - immune response (humoral) KW - immunocompromised hosts KW - bacteremia KW - pneumonia KW - man KW - J 02845:Ear, nose and respiratory tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16884390?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Infectious+Diseases&rft.atitle=Pneumonia+and+bacteremia+by+pneumococcal+serotype+16+in+a+human+immunodeficiency+virus-infected+child+with+normal+serum+antibody+response+to+23-valent+Pneumovax+vaccine&rft.au=Hirschfeld%2C+S%3BSchiffman%2C+G%3BTudor-Williams%2C+G%3BPizzo%2C+P+A&rft.aulast=Hirschfeld&rft.aufirst=S&rft.date=1995-01-01&rft.volume=171&rft.issue=3&rft.spage=761&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Haemophilus influenzae; human immunodeficiency virus; pneumonia; bacteremia; immunocompromised hosts; immune response (humoral); children; man; vaccines ER - TY - JOUR T1 - An IL-12-based vaccination method for preventing fibrosis induced by schistosome infection AN - 16884253; 3794583 AB - The harmful fibrosis which often occurs in the context of infectious disease involves the excessive deposition of connective tissue matrix, particularly collagen, and is mostly resistant to pharmacological and immunological intervention. In schistosomiasis, fibrosis is associated with the granulomatous response to parasite eggs trapped in the liver. We have previously shown that interleukin (IL)-12 administered peritoneally with eggs prevents subsequent pulmonary granuloma formation on intravenous challenge with eggs. Here we show that sensitization with eggs plus IL-12 partly inhibits granuloma formation and dramatically reduces the tissue fibrosis induced by natural infection with Schistosoma mansoni worms. These results are an example of a vaccine against parasites which acts by preventing pathology rather than infection. IL-12 is known to favour the priming of Th1 rather than Th2 cells, and the effects on fibrosis are accompanied by replacement of the Th2-dominated pattern of cytokine expression characteristic of S. mansoni infection with one dominated by Th1 cytokines. Elevated Th2 cytokine expression and fibrosis are common manifestations of a wide variety of infectious diseases and atopic disorders which might be ameliorated by vaccination with antigen and IL-12. JF - Nature AU - Wynn, T A AU - Cheever, A W AU - Jankovic, D AU - Poindexter, R W AU - Caspar, P AU - Lewis, F A AU - Sher, A AD - Immunobiol. Sect. Lab. Parasit. Dis., NIAID/NIH, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 594 EP - 596 VL - 376 IS - 6541 SN - 0028-0836, 0028-0836 KW - cytokines KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Schistosoma mansoni KW - interleukin 12 KW - vaccines KW - eggs KW - granuloma KW - schistosomiasis KW - fibrosis KW - W3 33365:Vaccines (other) KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16884253?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=An+IL-12-based+vaccination+method+for+preventing+fibrosis+induced+by+schistosome+infection&rft.au=Wynn%2C+T+A%3BCheever%2C+A+W%3BJankovic%2C+D%3BPoindexter%2C+R+W%3BCaspar%2C+P%3BLewis%2C+F+A%3BSher%2C+A&rft.aulast=Wynn&rft.aufirst=T&rft.date=1995-01-01&rft.volume=376&rft.issue=6541&rft.spage=594&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - interleukin 12; vaccines; eggs; granuloma; schistosomiasis; fibrosis; Schistosoma mansoni ER - TY - JOUR T1 - Epidemiologic follow-up studies of breast augmentation patients AN - 16882498; 3803719 AB - Although hundreds of thousands of women in this country have had augmentation mammaplasty, little is known about long-term effects. Clinical studies have documented a decreased ability to detect breast lesions in women with implants, leading to concerns regarding breast cancer risk. There is also anecdotal evidence that implants might have effects on a variety of immune conditions. More recently, concern over carcinogenic effects has heightened given findings that the polyurethane foam, used in a minority of implants to envelope silicone gel, contains chemicals linked to cancer in laboratory animals. Only a few epidemiologic studies on long-term effects have been published, and all have had methodologic limitations, including the possibility of inappropriate comparison rates, limited and/or incomplete follow-up, absence of information on patients characteristics, and lack of specific information on types of implanted material. Several case-control and cohort studies are currently underway which are attempting to overcome methodologic limitations of previous studies. Past descriptive and analytic studies are reviewed. In addition, ongoing follow-up efforts are discussed, with attention given to the methodologic adjuncts necessary for allowing valid assessments of long-term disease effects. JF - Journal of Clinical Epidemiology AU - Brinton, LA AU - Toniolo, P AU - Pasternack, B S AD - Environ. Epidemiol. Branch, NCI, Executive Plaza North, Rm. 443, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 557 EP - 563 VL - 48 IS - 4 SN - 0895-4356, 0895-4356 KW - mammaplasty KW - silicone KW - silicones KW - prosthetics KW - breast KW - implants KW - man KW - Toxicology Abstracts; Health & Safety Science Abstracts KW - side effects KW - carcinogenicity KW - epidemiology KW - breast cancer KW - risk assessment KW - H SM10.21:CANCER KW - H SM3.3:HAZARD DETERMINATION KW - X 24113:Side effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16882498?accountid=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+Clinical+Epidemiology&rft.atitle=Epidemiologic+follow-up+studies+of+breast+augmentation+patients&rft.au=Brinton%2C+LA%3BToniolo%2C+P%3BPasternack%2C+B+S&rft.aulast=Brinton&rft.aufirst=LA&rft.date=1995-01-01&rft.volume=48&rft.issue=4&rft.spage=557&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Epidemiology&rft.issn=08954356&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - breast cancer; epidemiology; carcinogenicity; side effects; risk assessment; prosthetics; breast; implants; man ER - TY - JOUR T1 - Pyrimethamine and proguanil resistance-conferring mutations in Plasmodium falciparum dihydrofolate reductase: Polymerase chain reaction methods for surveillance in Africa AN - 16880924; 3794705 AB - As chloroquine resistance spreads across Africa, the dihydrofolate reductase (DHFR) inhibitors pyrimethamine and proguanil are being used as alternative first-line drugs for the treatment and prevention of Plasmodium falciparum malaria. Resistance to these drugs is conferred by point mutations in parasite DHFR. These point mutations can be detected by polymerase chain reaction (PCR) assays, but better methods for sample collection, DNA extraction, and a diagnostic PCR are needed to make these assays useful in malaria-endemic areas. Here we report methods for collecting fingerstick blood onto filter paper strips that are air-dried, then stored and transported at room temperature. Cell lysis and DNA extraction are accomplished by boiling in Chelex-100. We also report a nested PCR technique that has improved sensitivity and specificity. These procedures readily detect mixed infections of parasites with both sensitive and resistant genotypes (confirmed by direct sequencing) and are reliable at parasite densities less than 250/mm super(3) in field surveys. JF - American Journal of Tropical Medicine and Hygiene AU - Plowe, C V AU - Djimde, A AU - Bouare, M AU - Doumbo, O AU - Wellems, TE AD - Malaria Genet. Sect., Lab. Parasit. Dis., NIAID/NIH, Build. 4, Rm. 126, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 565 EP - 568 VL - 52 IS - 6 SN - 0002-9637, 0002-9637 KW - dihydrofolate reductase KW - proguanil KW - pyrimethamine KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - drug resistance KW - mutation KW - Plasmodium falciparum KW - polymerase chain reaction KW - K 03022:Protozoa KW - W 30965:Miscellaneous, Reviews KW - K 03063:Effects of physical & chemical factors KW - W3 33130:Genetic based (PCR, etc.) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16880924?accountid=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=American+Journal+of+Tropical+Medicine+and+Hygiene&rft.atitle=Pyrimethamine+and+proguanil+resistance-conferring+mutations+in+Plasmodium+falciparum+dihydrofolate+reductase%3A+Polymerase+chain+reaction+methods+for+surveillance+in+Africa&rft.au=Plowe%2C+C+V%3BDjimde%2C+A%3BBouare%2C+M%3BDoumbo%2C+O%3BWellems%2C+TE&rft.aulast=Plowe&rft.aufirst=C&rft.date=1995-01-01&rft.volume=52&rft.issue=6&rft.spage=565&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Tropical+Medicine+and+Hygiene&rft.issn=00029637&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - mutation; drug resistance; polymerase chain reaction; Plasmodium falciparum ER - TY - JOUR T1 - An automated computer vision and robotics-based technique for 3-D flexible biomolecular docking and matching AN - 16879862; 3800581 AB - The generation of binding modes between two molecules, also known as molecular docking, is a key problem in rational drug design and biomolecular recognition. Docking a ligand, e.g., a drug molecule or a protein molecule, to a protein receptor, involves recognition of molecular surfaces as molecules interact at their surface. Recent studies report that the activity of many molecules induces conformational transitions by 'hinge-bending', which involves movements of relatively rigid parts with respect to each other. In ligand-receptor binding, relative rotational movements of molecular substructures about their common hinges have been observed. For automatically predicting flexible molecular interactions, we adapt a new technique developed in Computer Vision and Robotics for the efficient recognition of partially occluded articulated objects. These type of objects consist of rigid parts which are connected by rotary joints (hinges). Our approach is based on an extension and generalization of the Geometric Hashing and Generalized Hough Transform paradigm for rigid object recognition. Unlike other techniques which match each part individually, our approach exploits forcefully and efficiently enough the fact that the different rigid parts do belong to the same flexible molecule. We show experimental results obtained by an implementation of the algorithm for rigid and flexible docking. While the 'correct', crystal-bound complex is obtained with a small RMSD, additional, predictive 'high scoring' binding modes are generated as well. The diverse applications and implications of this general, powerful tool are discussed. JF - Computer Applications in the Biosciences AU - Sandak, B AU - Nussinov, R AU - Wolfson, HJ AD - Lab. Math. Biol., PRI/Dynacorp, NCI-FCRF, Bldg 469, Rm 151, Frederick, MD 21712, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 87 EP - 99 VL - 11 IS - 1 SN - 0266-7061, 0266-7061 KW - Biotechnology and Bioengineering Abstracts; Agricultural and Environmental Biotechnology Abstracts KW - computer applications KW - binding KW - mathematical models KW - W2 32250:Others KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16879862?accountid=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=Computer+Applications+in+the+Biosciences&rft.atitle=An+automated+computer+vision+and+robotics-based+technique+for+3-D+flexible+biomolecular+docking+and+matching&rft.au=Sandak%2C+B%3BNussinov%2C+R%3BWolfson%2C+HJ&rft.aulast=Sandak&rft.aufirst=B&rft.date=1995-01-01&rft.volume=11&rft.issue=1&rft.spage=87&rft.isbn=&rft.btitle=&rft.title=Computer+Applications+in+the+Biosciences&rft.issn=02667061&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - computer applications; binding; mathematical models ER - TY - JOUR T1 - Interleukin-1 in the treatment of cancer AN - 16878898; 3800688 AB - Interleukin-1 (IL-1) is a cytokine with many activities central to immune function and hematopoiesis. Many IL-1 properties can be potentially exploited in the treatment of malignancy. This review describes the toxicities and antitumor effects observed in Phase I and II trials of IL-1 in cancer patients. The immunophysiology and the induction of cytokines by IL-1 has been examined in many of the Phase I trials and has aided in understanding IL-1 effects in humans. The influence of IL-1 on granulopoiesis and thrombopoiesis when given by different regimes is also reviewed in detail. JF - Pharmacology & Therapeutics AU - Curti, B D AU - Smith, JW II AD - Biol. Response Modifiers Program, Div. Cancer Treat., NCI-FCRDC, Frederick, MD 21701, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 291 EP - 302 VL - 65 IS - 3 SN - 0163-7258, 0163-7258 KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Toxicology Abstracts KW - side effects KW - interleukin 1 KW - antitumor activity KW - immunotherapy KW - granulopoiesis KW - cancer KW - man KW - F 06818:Cancer immunotherapy KW - W3 33150:Cytokine based KW - W 30965:Miscellaneous, Reviews KW - X 24113:Side effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16878898?accountid=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=Pharmacology+%26+Therapeutics&rft.atitle=Interleukin-1+in+the+treatment+of+cancer&rft.au=Curti%2C+B+D%3BSmith%2C+JW+II&rft.aulast=Curti&rft.aufirst=B&rft.date=1995-01-01&rft.volume=65&rft.issue=3&rft.spage=291&rft.isbn=&rft.btitle=&rft.title=Pharmacology+%26+Therapeutics&rft.issn=01637258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - side effects; interleukin 1; antitumor activity; immunotherapy; granulopoiesis; man; cancer ER - TY - JOUR T1 - Targeting cancer micrometastases with monoclonal antibodies: A binding-site barrier AN - 16878540; 3798451 AB - Monoclonal antibodies penetrate bulky tumors poorly after intravenous administration, in part because of specific binding to the target antigen. Experiments presented here demonstrate an analogous phenomenon in micrometastases; poor antibody penetration, attributable to a "binding-site barrier" phenomenon, can be seen in guinea pig micrometastases as small as 300 mu m in diameter. Increasing the dose of antibody can partially overcome this limitation, but at a cost in specificity. JF - Proceedings of the National Academy of Sciences, USA AU - Saga, T AU - Neumann, R D AU - Heya, T AU - Sato, J AU - Kinuya, S AU - Le, N AU - Paik, CH AU - Weinstein, J N AD - Lab. Mol. Pharmacol., Dev. Ther. Program, Div. Cancer Treat., NCI/NIH, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 8999 EP - 9003 VL - 92 IS - 19 SN - 0027-8424, 0027-8424 KW - pigs KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - lung KW - metastases KW - tumors KW - monoclonal antibodies KW - W3 33375:Antibodies KW - F 06063:Other KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16878540?accountid=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=Targeting+cancer+micrometastases+with+monoclonal+antibodies%3A+A+binding-site+barrier&rft.au=Saga%2C+T%3BNeumann%2C+R+D%3BHeya%2C+T%3BSato%2C+J%3BKinuya%2C+S%3BLe%2C+N%3BPaik%2C+CH%3BWeinstein%2C+J+N&rft.aulast=Saga&rft.aufirst=T&rft.date=1995-01-01&rft.volume=92&rft.issue=19&rft.spage=8999&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 - 2011-12-14 N1 - SubjectsTermNotLitGenreText - lung; metastases; tumors; monoclonal antibodies ER - TY - JOUR T1 - Highly attenuated HIV type 2 recombinant poxviruses, but not HIV-2 recombinant Salmonella vaccines, induce long-lasting protection in rhesus macaques AN - 16876263; 3792409 AB - Immunization schemes employing priming with vector-based vaccine candidates followed by subunit booster administrations have been explored and shown to have merit in the human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus systems. In this study, we have assessed the priming capacity of highly attenuated poxvirus vector (NYVAC and ALVAC)-based HIV-2 recombinants, as well as Salmonella typhimurium HIV-2 recombinants in rhesus macaques. ALVAC- and NYVAC-based vaccine candidates expressing the HIV-2 gag, pol, and env genes or NYVAC-based recombinants expressing either gp160 or gp120 were used to immunize rhesus macaques in combination protocols with alum-adjuvanted HIV-2 rgp160. Following intravenous challenge exposure with 100 infectious doses of the HIV-2 sub(SBL6669) parental virus genotype mixture, seven of eight animals were protected from infection. The seven protected animals were rechallenged 6 months postprimary challenge, without additional booster inoculations, with the same dose of the HIV-2 sub(SBL6669) parental virus. Five of the seven animals remained protected against HIV-2 infection at 6 months following the second challenge. In contrast, oral immunization with recombinant Salmonella expressing the HIV-2 gag and the gp120 portion of the envelope either alone or in combination with alum-adjuvanted rgp160 failed to confer protection. These results suggest that the NYVAC- and ALVAC-based recombinants may confer long-lasting protection and that these two highly attenuated poxvirus vaccine vectors may represent promising candidates for developing an acquired immunodeficiency syndrome vaccine. JF - AIDS Research and Human Retroviruses AU - Franchini, G AU - Robert-Guroff, M AU - Tartaglia, J AU - Aggarwal, A AU - Abimiku, A AU - Benson, J AU - Markham, P AU - Limbach, K AU - Hurteau, G AU - Fullen, J AU - Aldrich, K AU - Miller, N AU - Sadoff, J AU - Paoletti, E AU - Gallo, R C AD - Lab. Tumor Cell Biol., NCI/NIH, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 909 EP - 920 VL - 11 IS - 8 SN - 0889-2229, 0889-2229 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts; Virology & AIDS Abstracts KW - vaccines KW - macaca mulatta KW - human immunodeficiency virus KW - Salmonella typhimurium 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/16876263?accountid=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=AIDS+Research+and+Human+Retroviruses&rft.atitle=Highly+attenuated+HIV+type+2+recombinant+poxviruses%2C+but+not+HIV-2+recombinant+Salmonella+vaccines%2C+induce+long-lasting+protection+in+rhesus+macaques&rft.au=Franchini%2C+G%3BRobert-Guroff%2C+M%3BTartaglia%2C+J%3BAggarwal%2C+A%3BAbimiku%2C+A%3BBenson%2C+J%3BMarkham%2C+P%3BLimbach%2C+K%3BHurteau%2C+G%3BFullen%2C+J%3BAldrich%2C+K%3BMiller%2C+N%3BSadoff%2C+J%3BPaoletti%2C+E%3BGallo%2C+R+C&rft.aulast=Franchini&rft.aufirst=G&rft.date=1995-01-01&rft.volume=11&rft.issue=8&rft.spage=909&rft.isbn=&rft.btitle=&rft.title=AIDS+Research+and+Human+Retroviruses&rft.issn=08892229&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - vaccines; macaca mulatta; human immunodeficiency virus; Salmonella typhimurium ER - TY - JOUR T1 - Protective efficacy of a parenterally administered MOMP-derived synthetic oligopeptide vaccine in a murine model of Chlamydia trachomatis genital tract infection: Serum neutralizing IgG antibodies do not protect against chlamydial genital tract infection AN - 16875102; 3799262 AB - The protective efficacy of an alum-adsorbed, parenterally administered synthetic oligopeptide immunogen corresponding to antigenically common T-helper and neutralizing B-cell epitopes of the Chlamydia trachomatis major outer membrane protein was studied in a murine model of chlamydial genital tract infection. Mice produced high levels of anti-chlamydial serum IgG neutralizing antibodies following subcutaneous immunization with the alum-adsorbed oligopeptide. Lower but detectable levels of chlamydial specific IgG antibodies were found in vaginal washes. IgG1 was the predominant isotype present in sera and vaginal washes. Chlamydial-specific IgA was not present in either the sera or vaginal washes of immunized mice. Vaccinated and control mice were challenged intravaginally or intrauterinally with low, medium, or high doses of C. trachomatis serovar D challenge inocula. Protection was assessed by performing quantitative chlamydial cervico-vaginal cultures over the course of the infection period. There were no statistically significant differences between groups of immunized and control mice in either colonization, shedding, or duration of infection. These findings demonstrate that parenteral immunization with the oligopeptide (serum-neutralizing antibodies) is ineffective in preventing chlamydial genital tract infection. It is possible, since chlamydial infection is restricted to the genital tract mucosae, that a more accurate evaluation of the oligopeptide vaccine potential will require local rather than systemic immunization. JF - Vaccine AU - Su, Hua AU - Parnell, M AU - Caldwell, H D AD - Lab. Intracell. Parasites, Immunol. Sect., NIAID, Rocky Mountain Lab., Hamilton, MT 59840, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 1023 EP - 1032 VL - 13 IS - 11 SN - 0264-410X, 0264-410X KW - oligopeptides KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - genital tract KW - vaccines KW - antibodies KW - Chlamydia trachomatis KW - animal models KW - W3 33365:Vaccines (other) KW - J 02834:Vaccination and immunization KW - F 06807:Active immunization KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16875102?accountid=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=Vaccine&rft.atitle=Protective+efficacy+of+a+parenterally+administered+MOMP-derived+synthetic+oligopeptide+vaccine+in+a+murine+model+of+Chlamydia+trachomatis+genital+tract+infection%3A+Serum+neutralizing+IgG+antibodies+do+not+protect+against+chlamydial+genital+tract+infection&rft.au=Su%2C+Hua%3BParnell%2C+M%3BCaldwell%2C+H+D&rft.aulast=Su&rft.aufirst=Hua&rft.date=1995-01-01&rft.volume=13&rft.issue=11&rft.spage=1023&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - genital tract; vaccines; antibodies; animal models; Chlamydia trachomatis ER - TY - JOUR T1 - Frequency and fidelity of translesion synthesis of site-specific N-2-acetylaminofluorene adducts during DNA replication in a human cell extract AN - 16874040; 3794360 AB - We have previously analyzed the effects of site-specific N-2-acetylaminofluorene (AAF) adducts on the efficiency and frameshift fidelity of SV40-based DNA replication in a human cell extract. Here we use two sets of substrates to examine the probability of replication termination and error-free and error-prone bypass of AAF adducts. The substrates contained site-specific adducts at one of three guanines in a NarI sequence (5'-GGCGCC-3') placed within the lacZ alpha reporter gene and located on the template for either leading or lagging strand replication. The presence of the adduct at any position strongly reduces the efficiency of a single round of replication in a HeLa cell extract. Product analysis reveals preferential replication of the undamaged strand and termination of replication of the damaged strand occurring one nucleotide before incorporation opposite either a leading or lagging strand adduct. Products resistant to restriction endonuclease cleavage at the adducted site were generated in amounts consistent with 16-48% lesion bypass during replication. Most of this bypass was error-free. However, two-nucleotide deletion errors were detected in the replication products of DNA containing an AAF adduct in either the leading or lagging strand, but only when present at the third guanine position. Collectively, the data suggest that the replication apparatus in a HeLa cell extract generates a template-primer slippage error at an AAF adduct once for every 30-100 bypass events. JF - Journal of Biological Chemistry AU - Thomas, D C AU - Veaute, X AU - Fuchs, RPP AU - Kunkel, T A AD - Lab. Mol. Genet., NIEHS, Research Triangle Park, NC 27709, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 21226 EP - 21233 VL - 270 IS - 36 SN - 0021-9258, 0021-9258 KW - N-2-fluorenylacetamide KW - SV40 KW - replication fidelity KW - Toxicology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - DNA adducts KW - DNA biosynthesis KW - HeLa cells KW - replication KW - man KW - X 24190:Polycyclic hydrocarbons KW - N 14653:Effect of antibiotics, antimetabolites & mutagens UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16874040?accountid=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+Biological+Chemistry&rft.atitle=Frequency+and+fidelity+of+translesion+synthesis+of+site-specific+N-2-acetylaminofluorene+adducts+during+DNA+replication+in+a+human+cell+extract&rft.au=Thomas%2C+D+C%3BVeaute%2C+X%3BFuchs%2C+RPP%3BKunkel%2C+T+A&rft.aulast=Thomas&rft.aufirst=D&rft.date=1995-01-01&rft.volume=270&rft.issue=36&rft.spage=21226&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - DNA biosynthesis; replication; DNA adducts; HeLa cells; man ER - TY - JOUR T1 - Role of a potential endoplasmic reticulum retention sequence (RDEL) and the Golgi complex in the cytotonic activity of Escherichia coli heat-labile enterotoxin AN - 16872103; 3799528 AB - Recent experimental evidence indicates that Escherichia coli heat-labile enterotoxin and the closely related cholera toxin gain access to intracellular target substrates through a brefeldin A-sensitive pathway that may involve retrograde transport through the Golgi-endoplasmic reticulum network. The A subunits of both toxins possess a carboxy-terminal tetrapeptide sequence (KDEL in cholera toxin and RDEL in the heat-labile enterotoxins) that is known to mediate the retention of eukaryotic proteins in the endoplasmic reticulum. To investigate the potential role of the RDEL sequence in the toxic activity of the heat-labile enterotoxin we constructed mutant analogues of the toxin containing single substitutions (RDGL and RDEV) or a reversed sequence (LEDR). The single substitutions had little effect on Chinese hamster ovary cell elongation or the ability to stimulate cAMP accumulation in Caco-2 cells. Reversal of the sequence reduced the ability of the toxin to increase cAMP levels in Caco-2 cells by approximately 60% and decreased the ability to elicit elongation of Chinese hamster ovary cells. The effects of the heat-labile enterotoxin were not diminished in a mutant Chinese hamster ovary cell line (V.24.1) that belongs to the End4 complementation group and possesses a temperature-sensitive block in secretion that correlates directly with the disappearance of the Golgi stacks. Collectively, these findings suggest that the brefeldin A-sensitive process involved in intoxication by the heat-labile enterotoxin does not involve RDEL-dependent retrograde transport of the A subunit through the Golgi-endoplasmic reticulum complex. The results are more consistent with a model of internalization involving translocation of the A subunit from an endosomal or a trans-Golgi network compartment. JF - Molecular Microbiology AU - Cieplak, W Jr AU - Messer, R J AU - Konkel, ME AU - Grant, CCR AD - Lab. Intracell. Parasites, Rocky Mountain Lab., NIAID/NIH, Hamilton, MT 59840, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 789 EP - 800 VL - 16 IS - 4 SN - 0950-3827, 0950-3827 KW - Microbiology Abstracts B: Bacteriology KW - Golgi apparatus KW - sequence KW - endoplasmic reticulum KW - retention KW - Escherichia coli KW - enterotoxins KW - J 02823:In vitro and in vivo effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16872103?accountid=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=Role+of+a+potential+endoplasmic+reticulum+retention+sequence+%28RDEL%29+and+the+Golgi+complex+in+the+cytotonic+activity+of+Escherichia+coli+heat-labile+enterotoxin&rft.au=Cieplak%2C+W+Jr%3BMesser%2C+R+J%3BKonkel%2C+ME%3BGrant%2C+CCR&rft.aulast=Cieplak&rft.aufirst=W&rft.date=1995-01-01&rft.volume=16&rft.issue=4&rft.spage=789&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=09503827&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; enterotoxins; Golgi apparatus; endoplasmic reticulum; retention; sequence ER - TY - JOUR T1 - Occupational risks for cutaneous melanoma among men in Sweden AN - 16870997; 3801092 AB - A population-based linked-registry was used to evaluate incidence of malignant melanoma of the skin among Swedish men by industry and occupation. There were 3850 cutaneous melanoma cases identified in the 19-year follow-up of men employed in 1960. New associations were observed for men employed in the breweries and malt-processing industry and in shoe fabrication from leather and skins. Several findings supported associations previously reported in other countries, including an excess risk among workers in basic chemical production and the printing industry and among professional, technical, and white-collar workers. Risk overall was not increased among farmers, despite a significant excess of melanoma of the face, neck, and scalp. Although this linked registry analysis lacked information about specific agents, duration of employment, and occupational and recreational sun exposures, it did provide leads for new associations and confirmed previous ones. Nevertheless, because of these limitations, etiologic clues must be interpreted cautiously. JF - Journal of Occupational and Environmental Medicine AU - Linet AU - Malker, HSR AU - Chow, Wong-Ho AU - McLaughlin, J K AU - Weiner, JA AU - Stone, B J AU - Ericsson, JLE AU - Fraumeni, JF Jr AD - Epidemiol. and Biostat. Program, NCI, EPN 415, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 1127 EP - 1135 VL - 37 IS - 9 SN - 1076-2752, 1076-2752 KW - occupational health KW - melanoma KW - occupational hazards KW - man KW - Toxicology Abstracts; Risk Abstracts; Health & Safety Science Abstracts KW - males KW - skin KW - Sweden KW - R2 23080:Industrial and labor KW - H SM10.38:SKIN DISEASES KW - X 24152:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16870997?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Occupational+and+Environmental+Medicine&rft.atitle=Occupational+risks+for+cutaneous+melanoma+among+men+in+Sweden&rft.au=Linet%3BMalker%2C+HSR%3BChow%2C+Wong-Ho%3BMcLaughlin%2C+J+K%3BWeiner%2C+JA%3BStone%2C+B+J%3BEricsson%2C+JLE%3BFraumeni%2C+JF+Jr&rft.aulast=Linet&rft.aufirst=&rft.date=1995-01-01&rft.volume=37&rft.issue=9&rft.spage=1127&rft.isbn=&rft.btitle=&rft.title=Journal+of+Occupational+and+Environmental+Medicine&rft.issn=10762752&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Sweden; occupational health; skin; males; melanoma; occupational hazards; man ER - TY - JOUR T1 - Sequential addition of temperature-sensitive missense mutations into the PB2 gene of influenza A transfectant viruses can effect an increase in temperature sensitivity and attenuation and permits the rational design of a genetically engineered live influenza A virus vaccine AN - 16870609; 3794960 AB - We have previously described a strategy for the recovery of a synthetic influenza A virus wild-type (wt) PB2 gene (derived from influenza A/Ann Arbor/6/60 [AA] virus) into an infectious virus. It was possible to introduce an attenuating temperature-sensitive (ts) mutation at amino acid residue 265 of the AA wt PB2 gene and to rescue this mutant gene into infectious virus. Application of this new technology to influenza A virus vaccine development requires that multiple attenuating mutations be introduced to achieve a satisfactorily attenuated virus that retains the attenuation (att) phenotype following replication in vivo. In this report, we demonstrate that putative ts mutations at amino acids 112, 556, and 658 each indeed specify the ts and att phenotypes. Each of these mutations was introduced into a cDNA copy of the AA mutant mt265 PB2 gene to produce three double-mutant PB2 genes, each of which was rescued into an infectious virus. In general, the double-mutant PB2 transfectant viruses were more ts and attenuated in the lower respiratory tracts of hamsters than the single-mutant transfectant viruses, and the ts phenotype of two of three double-mutant PB2 tansfectant viruses was stable even after prolonged replication in the upper respiratory tracts of immunocompromised mice. Two triple-mutant PB2 transfectant viruses with three predicted amino acid substitutions resulting from five nucleotide substitutions in the cDNA were then generated. The triple-mutant PB2 transfectant viruses were more ts and more attenuated than the double-mutant PB2 transfectant viruses. These results indicate that sequential introduction of additional ts mutations into the PB2 gene can yield mutants that exhibit a stepwise increase in temperature sensitivity and attenuation compared with the preceding mutant(s) in the series. Furthermore, the level of temperature sensitivity of the transfectant viruses correlated significantly with the level of attenuation of these viruses in hamsters. Although the triple-mutant PB2 transfectant viruses were attenuated in hamsters, intranasal administration of these viruses elicited a vigorous serum hemagglutination-inhibiting antibody response, and this was associated with resistance of the lower respiratory tract to subsequent wt virus challenge. These observations suggest the feasibility of using PB2 reverse genetics to generate a live influenza A virus vaccine donor strain that contains three attenuating mutations in one gene. It is predicted that reassortant viruses derived from such a donor virus would have the properties of attenuation, genetic stability, immunogenicity, and protective efficacy against challenge with wt virus. JF - Journal of Virology AU - Subbarao, E K AU - Ju Park, E AU - Lawson, C M AU - Chen, A Y AU - Murphy, B R AD - RVS/LID/NIAID/NIH, Build. 7, Rm. 106, 7 Cent. Dr. MSC 0720, Bethesda, MD 20892-0720, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 5969 EP - 5977 VL - 69 IS - 10 SN - 0022-538X, 0022-538X KW - PB2 gene KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Virology & AIDS Abstracts KW - vaccines KW - transfection KW - cDNA KW - temperature-sensitive mutant KW - influenza A virus KW - missense mutant KW - F 06780:Genetics KW - V 22050:Viral genetics including virus reactivation KW - N 14681:Mutagenesis techniques KW - W 30965:Miscellaneous, Reviews KW - W3 33055:Genetic engineering (general) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16870609?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Virology&rft.atitle=Sequential+addition+of+temperature-sensitive+missense+mutations+into+the+PB2+gene+of+influenza+A+transfectant+viruses+can+effect+an+increase+in+temperature+sensitivity+and+attenuation+and+permits+the+rational+design+of+a+genetically+engineered+live+influenza+A+virus+vaccine&rft.au=Subbarao%2C+E+K%3BJu+Park%2C+E%3BLawson%2C+C+M%3BChen%2C+A+Y%3BMurphy%2C+B+R&rft.aulast=Subbarao&rft.aufirst=E&rft.date=1995-01-01&rft.volume=69&rft.issue=10&rft.spage=5969&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - vaccines; transfection; cDNA; temperature-sensitive mutant; missense mutant; influenza A virus ER - TY - JOUR T1 - Cold-passaged, temperature-sensitive mutants of human respiratory syncytial virus (RSV) are highly attenuated, immunogenic, and protective in seronegative chimpanzees, even when RSV antibodies are infused shortly before immunization AN - 16865662; 3784284 AB - A cold-passaged (cp) temperature-sensitive (ts) RSV mutant, designated RSV cpts-530, which possesses host-range mutations acquired during 52 passages at low temperature in bovine tissue culture and one or more ts mutations induced by chemical mutagenesis (shut-off temperature 39 degree C) was found previously to be tenfold restricted in its replication in mice as compared to wild-type virus and stable genetically in nude mice. In the current study, we introduced additional attenuating mutations, such as small-plaque (sp) or ts mutations, into cpts-530 by chemical mutagenesis with 5-fluorouracil, with the intent of obtaining derivatives of cpts-530 that were more attenuated in mice or chimpanzees and that were more stable genetically following replication in vivo. Fourteen mutants of RSV cpts-530 which had acquired an additional ts mutation were identified and found to be more restricted in replication in BALB/c mice than the cpts-530 parental strain. One mutant, designated cpts-530/1009 (shut-off temperature 36 degree C), was 30 times more restricted in replication in the nasal turbinates of mice and threefold more restricted in the nasopharynx of seronegative chimpanzees than its cpts-530 parent. Like its parent, this mutant was highly restricted (30 000-fold) in replication in the lower respiratory tract of chimpanzees even following direct intratracheal inoculation. The cpts-530 and cpts-530/1009 mutants exhibited a high level of stability of the ts phenotype during replication in chimpanzees. The immunogenicity and protective efficacy of the cpts-530/1009 mutant and that of two other previously described candidate live attenuated RSV vaccines were compared in seronegative chimpanzees, some of whom were pretreated with RSV immune globulin by the intravenous route to simulate the condition of the very young infant who possesses passively acquired maternal antibodies. The three candidate vaccine strains were immunogenic and induced significant resistance to RSV challenge in both groups of chimpanzees. Interestingly, the chimpanzees infused with RSV antibodies prior to immunization were primed more effectively for an unusually high serum neutralizing antibody response to infection with challenge virus than chimpanzees which did not receive such antibodies. This high level booster response occurred despite marked restriction of replication of the challenge virus. Thus, the cpts-530/1009 virus and related mutants exhibit many desirable characteristics which make them promising vaccine candidates. JF - Vaccine AU - Crowe, JE Jr AU - Bui, P T AU - Siber, G R AU - Elkins, W R AU - Chanock, R M AU - Murphy, B R AD - Resp. Viruses Sect., Lab. Infect. Dis., NIAID/NIH, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 847 EP - 855 VL - 13 IS - 9 SN - 0264-410X, 0264-410X KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts; Virology & AIDS Abstracts KW - attenuation KW - respiratory syncytial virus KW - temperature-sensitive mutant KW - immunogenicity KW - W3 33365:Vaccines (other) KW - F 06807:Active immunization KW - V 22097:Immunization: Vaccines & vaccination: Human KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16865662?accountid=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=Vaccine&rft.atitle=Cold-passaged%2C+temperature-sensitive+mutants+of+human+respiratory+syncytial+virus+%28RSV%29+are+highly+attenuated%2C+immunogenic%2C+and+protective+in+seronegative+chimpanzees%2C+even+when+RSV+antibodies+are+infused+shortly+before+immunization&rft.au=Crowe%2C+JE+Jr%3BBui%2C+P+T%3BSiber%2C+G+R%3BElkins%2C+W+R%3BChanock%2C+R+M%3BMurphy%2C+B+R&rft.aulast=Crowe&rft.aufirst=JE&rft.date=1995-01-01&rft.volume=13&rft.issue=9&rft.spage=847&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - attenuation; temperature-sensitive mutant; immunogenicity; respiratory syncytial virus ER - TY - JOUR T1 - Human immunodeficiency virus type 2 (HIV-2): Packaging signal and associated negative regulatory element AN - 16865106; 3784246 AB - Human immunodeficiency virus type 2 (HIV-2)-based retroviral vectors will have several desirable features as vehicles for gene therapy. These include target cell specificity, regulated expression, and attenuated cytopathicity. Such vectors require efficient packaging of RNA into retroviral particles which depends on a cis-acting sequence element called packaging signal or psi site. For most retroviruses, the principal part of this element is located between the major splice donor site and the gag initiator codon (AUG) in the leader sequence. The deletion of the corresponding region of HIV-2 did indeed cause a packaging defect; however, it did not abolish RNA encapsidation and viral infectivity. Additionally, deletions in this region resulted in an increase in intracellular viral RNA and extracellular p27 core antigen. However, only a fraction of the intracellular viral RNA was packaged into mature particles. These effects appeared to be sequence specific as deletion of the sequence elements upstream of the splice donor site did not result in increased viral RNA and proteins. A computer-assisted analysis of the leader sequence of viral RNA shows it to be rich in secondary structure, which was markedly altered in the deletion mutants. Thus, the leader sequence of HIV-2 between the splice donor site and the gag ATG has at least two regulatory functions: one positive, affecting encapsidation, and the other negative, regulating virus expression. Because there is only a limited sequence or structural homology between the corresponding region of HIV-1 and HIV-2, they are likely to differ in their pathways regulating packaging and gene expression. JF - Human Gene Therapy AU - Garzino-Demo, A AU - Gallo, R C AU - Arya, S K AD - Lab. Tumor Cell Biol., Nci, Build. 37, Rm. 6C24, 37 Convent Dr MSC 4255, Bethesda, MD 20892-4255, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 177 EP - 187 VL - 6 IS - 2 SN - 1043-0342, 1043-0342 KW - cloning vectors KW - genetic engineering KW - human immunodeficiency virus 2 KW - man KW - packaging efficiency KW - retrovirus KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts; Human Genome Abstracts KW - V 22002:AIDS: Molecular and in vitro aspects 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/16865106?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Human+immunodeficiency+virus+type+2+%28HIV-2%29%3A+Packaging+signal+and+associated+negative+regulatory+element&rft.au=Garzino-Demo%2C+A%3BGallo%2C+R+C%3BArya%2C+S+K&rft.aulast=Garzino-Demo&rft.aufirst=A&rft.date=1995-01-01&rft.volume=6&rft.issue=2&rft.spage=177&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - genetic engineering; retrovirus; cloning vectors; man; human immunodeficiency virus 2 ER - TY - JOUR T1 - A protein that binds to the P1 origin core and the oriC 13mer region in a methylation-specific fashion is the product of the host seqA gene AN - 16864515; 3788487 AB - The P1 plasmid replication origin P1oriR is controlled by methylation of four GATC adenine methylation sites within heptamer repeats. A comparable (13mer) region is present in the host origin, oriC. The two origins show comparable responses to methylation; negative control by recognition of hemimethylated DNA (sequestration) and a positive requirement for methylation for efficient function. We have isolated a host protein that recognizes the P1 origin region only when it is isolated from a strain proficient for adenine methylation. The substantially purified 22 kDa protein also binds to the 13mer region of oriC in a methylation-specific fashion. It proved to be the product of the seqA gene that acts in the negative control of oriC by sequestration. We conclude that the role of the SeqA protein in sequestration is to recognize the methylation state of P1oriR and oriC by direct DNA binding. Using synthetic substrates we show that SeqA binds exclusively to the hemimethylated forms of these origins, forms that are the immediate products of replication in a methylation-proficient strain. We also show that the protein can recognize sequences with multiple GATC sites, irrespective of the surrounding sequence. The basis for origin specificity is primarily the persistence of hemimethylated forms that are over-represented in the natural DNA preparations relative to controls. JF - EMBO Journal AU - Brendler, T AU - Abeles, A AU - Austin, S AD - Lab. Chromosome Biol., ABL-Basic Res. Program, NCI-Frederick Cancer Res. and Dev. Cent., Frederick, MD 21702-1201, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 4083 EP - 4089 VL - 14 IS - 16 SN - 0261-4189, 0261-4189 KW - SeqA gene KW - plasmid pP1 KW - replication origins KW - SeqA protein KW - Biochemistry Abstracts 2: Nucleic Acids; Virology & AIDS Abstracts; Microbiology Abstracts B: Bacteriology KW - DNA methylation KW - J 02725:DNA KW - V 22044:Viral nucleic acid synthesis & synthesis of virus-coded proteins KW - N 14940:Nucleic acid-binding proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16864515?accountid=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=EMBO+Journal&rft.atitle=A+protein+that+binds+to+the+P1+origin+core+and+the+oriC+13mer+region+in+a+methylation-specific+fashion+is+the+product+of+the+host+seqA+gene&rft.au=Brendler%2C+T%3BAbeles%2C+A%3BAustin%2C+S&rft.aulast=Brendler&rft.aufirst=T&rft.date=1995-01-01&rft.volume=14&rft.issue=16&rft.spage=4083&rft.isbn=&rft.btitle=&rft.title=EMBO+Journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - DNA methylation ER - TY - JOUR T1 - Transcription regulation by inflexibility of promoter DNA in a looped complex AN - 16862942; 3784029 AB - The gal operon of Escherichia coli is negatively regulated by repressor binding to bipartite operators separated by 11 helical turns of DNA. Synergistic binding of repressor to separate sites on DNA results in looping, with the intervening DNA as a topologically closed domain containing the two promoters. A closed DNA loop of 11 helical turns, which is in-flexible to torsional changes, disables the promoters either by resisting DNA unwinding needed for open complex formation or by impeding the processive DNA contacts by an RNA polymerase in flux during transcription initiation. Interaction between two proteins bound to different sites on DNA modulating the activity of the intervening segment toward other proteins by allostery may be a common mechanism of regulation in DNA-multiprotein complexes. JF - Proceedings of the National Academy of Sciences, USA AU - Choy, HE AU - Park, S-W AU - Parrack, P AU - Adhya, S AD - Lab. Mol. Biol., NCI/NIH, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 7327 EP - 7331 VL - 92 IS - 16 SN - 0027-8424, 0027-8424 KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - gal operon KW - gene regulation KW - Escherichia coli KW - promoters KW - J 02740:Genetics and evolution KW - N 14662:Gene regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16862942?accountid=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=Transcription+regulation+by+inflexibility+of+promoter+DNA+in+a+looped+complex&rft.au=Choy%2C+HE%3BPark%2C+S-W%3BParrack%2C+P%3BAdhya%2C+S&rft.aulast=Choy&rft.aufirst=HE&rft.date=1995-01-01&rft.volume=92&rft.issue=16&rft.spage=7327&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; gal operon; promoters; gene regulation ER - TY - JOUR T1 - Antidepressant-induced mania and cycle acceleration: A controversy revisited AN - 16860956; 3788029 AB - Objective: The longitudinal course of 51 patients with treatment-refractory bipolar disorder was examined to assess possible effects of heterocyclic antidepressants on occurrence of manic episodes and cycle acceleration. Method: Using criteria established from life charts, investigators rated the patients' episodes of mania or cycle acceleration as likely or unlikely to have been induced by antidepressant therapy. Discriminant function analyses were performed to assess predictors of vulnerability to antidepressant-induced mania or cycle acceleration. Further, the likelihood of future antidepressant-induced episodes in persons who had had one such episode was assessed. Conclusions: Mania is likely to be antidepressant-induced and not attributable to the expected course of illness in one-third of treatment-refractory bipolar patients, and rapid cycling is induced in one-fourth. Antidepressant-induced mania may be a marker for increased vulnerability to antidepressant-induced cycle acceleration. Antidepressant-induced cycle acceleration (but not antidepressant-induced mania) is associated with younger age at first treatment and may be more likely to occur in women and in bipolar II patients. JF - American Journal of Psychiatry AU - Altshuler, L L AU - Post, R M AU - Leverich, G S AU - Mikalauskas, K AU - Rosoff, A AU - Ackerman, L AD - Biol. Psychiatr. Branch, Build. 10, Rm. 3N212, NIMH, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 1130 EP - 1138 VL - 152 IS - 8 SN - 0002-953X, 0002-953X KW - antidepressants KW - Health & Safety Science Abstracts KW - side effects KW - H SE4.28:PHARMACEUTICALS UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16860956?accountid=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+Psychiatry&rft.atitle=Antidepressant-induced+mania+and+cycle+acceleration%3A+A+controversy+revisited&rft.au=Altshuler%2C+L+L%3BPost%2C+R+M%3BLeverich%2C+G+S%3BMikalauskas%2C+K%3BRosoff%2C+A%3BAckerman%2C+L&rft.aulast=Altshuler&rft.aufirst=L&rft.date=1995-01-01&rft.volume=152&rft.issue=8&rft.spage=1130&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Psychiatry&rft.issn=0002953X&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 - side effects ER - TY - JOUR T1 - Developmentally regulated expression of a Giardia lamblia cyst wall protein gene AN - 16859008; 3783940 AB - The protozoan Giardia lamblia is an obligate parasite of the mammalian small intestine. We studied the expression of a gene that encodes a protein component of the cyst wall, a complex structure assembled during the differentiation of trophozoites to cysts and which is critical to survival of the parasite outside its mammalian host. Transcripts from the cyst wall protein gene increase more than 100-fold during encystation, reaching a maximum between 5 and 24 hours after induction. Cyst wall protein expression also increases dramatically during encystation, and, prior to its incorporation into the nascent cyst wall, the protein is contained within the encystation-specific vesicles of encysting trophozoites. The sequence of the cloned gene predicts an acidic, leucine-rich polypeptide of M sub(r) 26 000 that contains 5.3 tandemly arranged copies of a degenerate 24-amino-acid repeat. A hydrophobic amino-terminal peptide probably serves as the initial signal that targets this protein to a secretory pathway involving vesicular localization during encystation and, ultimately, secretion to form the cyst wall. JF - Molecular Microbiology AU - Mowatt, M R AU - Lujan, H D AU - Cotten, D B AU - Bowers, B AU - Yee, J AU - Nash, TE AU - Stibbs, H H AD - Lab. Parasitic Dis., NIAID/NIH, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 955 EP - 963 VL - 15 IS - 5 SN - 0950-382X, 0950-382X KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - cysts KW - translation KW - Giardia lamblia KW - gene expression KW - encystment KW - monoclonal antibodies KW - enzyme-linked immunosorbent assay KW - W3 33120:Receptor based (antibodies, etc.) KW - K 03081:Protozoa KW - W 30965:Miscellaneous, Reviews KW - N 14662:Gene regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16859008?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Microbiology&rft.atitle=Developmentally+regulated+expression+of+a+Giardia+lamblia+cyst+wall+protein+gene&rft.au=Mowatt%2C+M+R%3BLujan%2C+H+D%3BCotten%2C+D+B%3BBowers%2C+B%3BYee%2C+J%3BNash%2C+TE%3BStibbs%2C+H+H&rft.aulast=Mowatt&rft.aufirst=M&rft.date=1995-01-01&rft.volume=15&rft.issue=5&rft.spage=955&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 - 2011-12-14 N1 - SubjectsTermNotLitGenreText - translation; cysts; encystment; gene expression; monoclonal antibodies; enzyme-linked immunosorbent assay; Giardia lamblia ER - TY - JOUR T1 - Reproductive factors and the risk of renal cell cancer among women AN - 16854567; 3783164 AB - In a population-based case-control study including 165 female cases and 227 controls, we assessed the risk of renal cell cancer associated with reproductive factors and use of oral contraceptives and menopausal hormones. Odds ratios were computed using logistic regression analyses. Risk was positively associated with number of births and inversely associated with age at first birth, with the largest increases in risk (more than 2-fold) among women with 5 or more births after age 25. After adjustment for age, smoking status, body mass index and age at first birth, women with 5 or more births had a 2-fold risk relative to those with 1 or 2 births. Age at first birth, however, was no longer a risk factor when the number of births was adjusted for. The association with parity was considerably stronger among women with a history of hypertension or above-median body mass index than among those without these conditions. In addition, risk was reduced among long-term oral contraceptive users but elevated among women who had had a hysterectomy or used menopausal hormones. Our findings suggest that reproductive factors, particularly the number of births, may play an etiologic role in renal cell cancer among women and deserve further study. JF - International Journal of Cancer AU - Chow, Wong-Ho AU - McLaughlin, J K AU - Mandel, J S AU - Blot, W J AU - Niwa, S AU - Fraumeni, JF Jr AD - NCI, 6130 Executive Blvd, EPN/415, Rockville, MD 20852, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 321 EP - 324 VL - 60 IS - 3 SN - 0020-7136, 0020-7136 KW - pregnancy-related hormones KW - Risk Abstracts KW - females KW - reproduction KW - kidney KW - cancer KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16854567?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Cancer&rft.atitle=Reproductive+factors+and+the+risk+of+renal+cell+cancer+among+women&rft.au=Chow%2C+Wong-Ho%3BMcLaughlin%2C+J+K%3BMandel%2C+J+S%3BBlot%2C+W+J%3BNiwa%2C+S%3BFraumeni%2C+JF+Jr&rft.aulast=Chow&rft.aufirst=Wong-Ho&rft.date=1995-01-01&rft.volume=60&rft.issue=3&rft.spage=321&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 N1 - SubjectsTermNotLitGenreText - kidney; cancer; reproduction; females ER - TY - JOUR T1 - A single-injection protein kinase A-directed antisense treatment to inhibit tumour growth AN - 16854375; 3782982 AB - Expression of the RI sub( alpha ) subunit of cAMP-dependent protein kinase type I is enhanced in human cancer cell lines, in primary tumours, in cells after transformation and in cells upon stimulation of growth. We have investigated the effect of sequence-specific inhibition of RI sub( alpha ) gene expression on in vivo tumour growth. We report that single injection RI sub( alpha ) antisense treatment results in a reduction in RI sub( alpha ) expression and inhibition of tumour growth. Tumour cells behaved like untransformed cells by making less protein kinase type I. The RI sub( alpha ) antisense, which produces a biochemical imprint for growth control, requires infrequent dosing to halt neoplastic growth in vivo. JF - Nature Medicine AU - Nesterova, M AU - Cho-Chung, Y S AD - Cell. Biochem. Sect., Lab. Tumor Immunol. and Biol., NCI/NIH, Build. 10, Rm. 5B-05, Bethesda, MD 20892-1750, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 528 EP - 533 VL - 1 IS - 6 SN - 1078-8956, 1078-8956 KW - RI sub( alpha ) subunit KW - antisense KW - cell growth KW - colon carcinoma KW - man KW - protein kinase A KW - tumors KW - Biotechnology and Bioengineering Abstracts; Human Genome Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Oncogenes & Growth Factors Abstracts KW - B 26320:Other oncogenes 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/16854375?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Medicine&rft.atitle=A+single-injection+protein+kinase+A-directed+antisense+treatment+to+inhibit+tumour+growth&rft.au=Nesterova%2C+M%3BCho-Chung%2C+Y+S&rft.aulast=Nesterova&rft.aufirst=M&rft.date=1995-01-01&rft.volume=1&rft.issue=6&rft.spage=528&rft.isbn=&rft.btitle=&rft.title=Nature+Medicine&rft.issn=10788956&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - antisense; tumors; man ER - TY - JOUR T1 - Human retroviruses in the second decade: A personal perspective AN - 16853794; 3783012 AB - Human retroviruses have developed novel strategies for their propagation and survival. A consequence of their success has been the induction of an extraordinarily diverse set of human diseases, including AIDS, cancers and neurological and inflammatory disorders. Early research focused on their characterization, linkage to these diseases, and the mechanisms involved. Research should now aim at the eradication of human retroviruses and on treatment of infected people. JF - Nature Medicine AU - Gallo, R C AD - Lab. Tumor Cell Biol., Build. 37, Rm. 6A09, NCI/NIH, 37 Convent Dr., Bethesda, MD 20892-4255, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 753 EP - 759 VL - 1 IS - 8 SN - 1078-8956, 1078-8956 KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - gene therapy KW - reviews KW - retrovirus KW - diseases KW - man KW - G 07313:Viruses 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/16853794?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Medicine&rft.atitle=Human+retroviruses+in+the+second+decade%3A+A+personal+perspective&rft.au=Gallo%2C+R+C&rft.aulast=Gallo&rft.aufirst=R&rft.date=1995-01-01&rft.volume=1&rft.issue=8&rft.spage=753&rft.isbn=&rft.btitle=&rft.title=Nature+Medicine&rft.issn=10788956&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - gene therapy; reviews; retrovirus; diseases; man ER - TY - JOUR T1 - High-yield production of diphtheria toxin mutants by high-density culture of C7( beta ) super(tox+) strains grown in a non-deferrated medium AN - 16853127; 3783944 AB - A high-density growth approach was utilized to produce mutated diphtheria toxin from two strains of Corynebacterium diphtheria: C7 ( beta ) super((tox-201, tox-9)) and C7( beta ) super((tox-107)). The cross-reacting mutants (CRM) of the diphtheria toxin are CRM9 and CRM107; both of them carry the mutation in their binding site and, as a result, have 1/300 of the systemic toxicity of the wild-type diptheria toxin. Since iron inhibits diphtheria toxin production, the traditional approach has been to grow the bacteria in a very low iron concentration. The procedure described here involved the use of a modified, non-deferrated, growth medium that provided fast and high-density growth of the bacteria, and which, when associated with simultaneous depletion of glucose and iron, enhanced the toxin production. Oxygen-enriched air was supplied to enable the bacteria to grow to a cell density giving an absorbance of 70 at 600 nm (15-20 g/l dry weight). The maximum toxin concentration in the culture supernatant was 150 mg/l. The CRM products, which remained stable following microfiltration and ultrafiltration, could be easily purified using a two-step chromatography procedure. JF - Applied Microbiology and Biotechnology AU - Fass, R AU - Bahar, S AU - Kaufman, J AU - Shiloach, J AD - Biotechnol. Unit, LCDB, NIDDK/NIH, Build. 6, Rm. B1-33, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 83 EP - 88 VL - 43 IS - 1 SN - 0175-7598, 0175-7598 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - toxins KW - media (culture) KW - Corynebacterium diphtheriae KW - mutants KW - W 30965:Miscellaneous, Reviews KW - W3 33055:Genetic engineering (general) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16853127?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Applied+Microbiology+and+Biotechnology&rft.atitle=High-yield+production+of+diphtheria+toxin+mutants+by+high-density+culture+of+C7%28+beta+%29+super%28tox%2B%29+strains+grown+in+a+non-deferrated+medium&rft.au=Fass%2C+R%3BBahar%2C+S%3BKaufman%2C+J%3BShiloach%2C+J&rft.aulast=Fass&rft.aufirst=R&rft.date=1995-01-01&rft.volume=43&rft.issue=1&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=Applied+Microbiology+and+Biotechnology&rft.issn=01757598&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - toxins; media (culture); mutants; Corynebacterium diphtheriae ER - TY - JOUR T1 - Prostate cancer risk in U.S. blacks and whites with a family history of cancer AN - 16853015; 3783163 AB - Prostate cancer occurs more frequently in U.S. blacks than whites. A population-based case-control study which investigated the association with family history of cancer was carried out among 981 men (479 black, 502 white) with pathologically confirmed prostate cancer, diagnosed between August 1, 1986, and April 30, 1989, and 1,315 controls (594 black, 721 white). Study subjects, aged 40-79, resided in Atlanta, Detroit, and 10 counties in New Jersey, geographic areas covered by population-based cancer registries. Prostate cancer risk was significantly elevated among those who reported a history of prostate cancer in first-degree relatives, with blacks and whites having similarly elevated risks. These risks were unchanged by statistical adjustment for job-related socio-economic status, education, income, and marital status. Overall, the ORs associated with history of prostate cancer in fathers and brothers were 2.5 and 5.3, respectively. Risks associated with a family history of prostate cancer were consistently elevated among younger and older subjects. Only small non-significant excesses of prostate cancer risk were associated with a family history of breast, colorectal, or other cancers. JF - International Journal of Cancer AU - Hayes, R B AU - Liff, J M AU - Pottern, L M AU - Greenberg, R S AU - Schoenberg, J B AU - Schwartz, A G AU - Swanson, G M AU - Silverman, D T AU - Brown, L M AU - Hoover, R N AU - Fraumeni, JF Jr AD - Epidemiol. and Biostat. Program, NCI/NIH, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 361 EP - 364 VL - 60 IS - 3 SN - 0020-7136, 0020-7136 KW - prostate KW - Risk Abstracts KW - genetics KW - ethnic groups KW - USA KW - cancer KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16853015?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Cancer&rft.atitle=Prostate+cancer+risk+in+U.S.+blacks+and+whites+with+a+family+history+of+cancer&rft.au=Hayes%2C+R+B%3BLiff%2C+J+M%3BPottern%2C+L+M%3BGreenberg%2C+R+S%3BSchoenberg%2C+J+B%3BSchwartz%2C+A+G%3BSwanson%2C+G+M%3BSilverman%2C+D+T%3BBrown%2C+L+M%3BHoover%2C+R+N%3BFraumeni%2C+JF+Jr&rft.aulast=Hayes&rft.aufirst=R&rft.date=1995-01-01&rft.volume=60&rft.issue=3&rft.spage=361&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 N1 - SubjectsTermNotLitGenreText - USA; ethnic groups; cancer; genetics ER - TY - JOUR T1 - Retroviral coexpression of a multidrug resistance gene (MDR1) and human alpha -galactosidase A for gene therapy of Fabry disease AN - 16852710; 3781119 AB - Human alpha -galactosidase A ( alpha -Gal A; EC. 3.2.1.22) is a lysosomal exoglycosidase encoded by a gene on Xq22. Deficiencies of this enzyme result in Fabry disease, an X-chromosome-linked recessive disorder that leads to premature death in affected males. For treatment of genetic diseases, we have developed a retroviral vector system, pSXLC/pHa, that enables coexpression of drug-selectable markers with a second nonselectable gene as part of a bicistronic message using the promoter from the Harvey murine sarcoma virus and an internal ribosomal entry site (IRES) from encephalomyocarditis virus. Retroviral vectors based on this system that carry the human alpha -Gal A cDNA either upstream (pHa- alpha Gal-IRES-MDR) or downstream (pHa-MDR-IRES- alpha Gal) from the IRES relative to the drug-selectable MDR1 (P-glycoprotein) cDNA were constructed. Each of eight independent vincristine-resistant, pHa- alpha Gal-IRES-MDR-transfected clones and all four vincristine-resistant, pHa- alpha Gal-IRES-MDR retrovirus-transduced clones showed significantly higher activity of alpha -Gal A than the parental cells. More than 50% of the vincristine-resistant, pHa-MDR-IRES- alpha Gal-transfected clones and all four vincristine-resistant, pHa-MDR-IRES- alpha Gal retrovirus-transduced clones showed significantly higher activity of alpha -Gal A than the parental cells. In these bicistronic vectors, the cDNA whose translation was cap-dependent (upstream) was expressed at higher levels than when the same cDNA was translated in an IRES-dependent manner (downstream). These vectors may prove useful in the gene therapy of Fabry disease. JF - Human Gene Therapy AU - Sugimoto, Y AU - Aksentijevich, I AU - Murray, G J AU - Brady, RO AU - Pastan, I AU - Gottesman, M M AD - Lab. Cell Biol., NCI/NINDS/NIH, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 905 EP - 915 VL - 6 IS - 7 SN - 1043-0342, 1043-0342 KW - Fabry's disease KW - MDR-1 gene KW - alpha -galactosidase KW - drug resistance KW - gene therapy KW - man KW - Biotechnology and Bioengineering Abstracts; Human Genome 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/16852710?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Retroviral+coexpression+of+a+multidrug+resistance+gene+%28MDR1%29+and+human+alpha+-galactosidase+A+for+gene+therapy+of+Fabry+disease&rft.au=Sugimoto%2C+Y%3BAksentijevich%2C+I%3BMurray%2C+G+J%3BBrady%2C+RO%3BPastan%2C+I%3BGottesman%2C+M+M&rft.aulast=Sugimoto&rft.aufirst=Y&rft.date=1995-01-01&rft.volume=6&rft.issue=7&rft.spage=905&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - gene therapy; drug resistance; Fabry's disease; man ER - TY - JOUR T1 - Revised minimum standards for description of new species of the class Mollicutes (division Tenericutes) AN - 16851702; 3785534 AB - In this paper the Subcommittee on the Taxonomy of Mollicutes proposes minimum standards for descriptions of new cultivable species of the class Mollicutes (trivial term, mollicutes) to replace the proposals published in 1972 and 1979. The major class characteristics of these organisms are the lack of a cell wall, the tendency to form fried-egg-type colonies on solid media, the passage of cells through 450- and 220-nm-pore-size membrane filters, the presence of small A-T-rich genomes, and the failure of the wall-less strains to revert to walled bacteria under appropriate conditions. Placement in orders, families, and genera is based on morphology, host origin, optimum growth temperature, and cultural and biochemical properties. Demonstration that an organism differs from previously described species requires a detailed serological analysis and further definition of some cultural and biochemical characteristics. The precautions that need to be taken in the application of these tests are defined. The subcommittee recommends the following basic requirements, most of which are derived from the International Code of Nomenclature of Bacteria, for naming a new species: (i) designation of a type strain; (ii) assignment to an order, a family, and a genus in the class, with selection of an appropriate specific epithet; (iii) demonstration that the type strain and related strains differ significantly from members of all previously named species; and (iv) deposition of the type strain in a recognized culture collection, such as the American Type Culture Collection or the National Collection of Type Cultures. The publication of the description should appear in a journal having wide circulation. If the journal is not the International Journal of Systematic Bacteriology, a reprint must be submitted to that journal so that the name may be considered for inclusion in a validation list as required by the International Code of Nomenclature of Bacteria. JF - International Journal of Systematic Bacteriology AU - Whitcomb, R F AU - Tully, J G AU - Bove, J M AU - Bradbury, J M AU - Christiansen, G AU - Kahane, I AU - Kirkpatrick, B C AU - Laigret, F AU - Leach, R H AU - Neimark, H C AU - Pollack, J D AU - Razin, S AU - Sears, B B AU - Taylor-Robinson, D Y1 - 1995 PY - 1995 DA - 1995 SP - 605 EP - 612 VL - 45 IS - 3 SN - 0020-7713, 0020-7713 KW - Tenericutes KW - Microbiology Abstracts B: Bacteriology KW - Mollicutes KW - reviews KW - systematics KW - taxonomy KW - J 02710:Identification, taxonomy and typing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16851702?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Systematic+Bacteriology&rft.atitle=Revised+minimum+standards+for+description+of+new+species+of+the+class+Mollicutes+%28division+Tenericutes%29&rft.au=Whitcomb%2C+R+F%3BTully%2C+J+G%3BBove%2C+J+M%3BBradbury%2C+J+M%3BChristiansen%2C+G%3BKahane%2C+I%3BKirkpatrick%2C+B+C%3BLaigret%2C+F%3BLeach%2C+R+H%3BNeimark%2C+H+C%3BPollack%2C+J+D%3BRazin%2C+S%3BSears%2C+B+B%3BTaylor-Robinson%2C+D&rft.aulast=Whitcomb&rft.aufirst=R&rft.date=1995-01-01&rft.volume=45&rft.issue=3&rft.spage=605&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Systematic+Bacteriology&rft.issn=00207713&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mollicutes; taxonomy; systematics; reviews ER - TY - JOUR T1 - Binding of syndecan-like cell surface proteoglycan receptors is required for Neisseria gonorrhoeae entry into human mucosal cells AN - 16851452; 3785455 AB - Bacterial invasion of human mucosal cells is considered to be a primary event in the pathogenesis of a gonococcal infection. Here we report that cell surface heparan sulfate proteoglycans may play a role in the establishment of an infection, by functioning as receptors for the invasion-promoting gonococcal opacity protein adhesin. Chemical modification and enzymatic removal of proteoglycan receptors from cultured epithelial cells abolished opacity protein-associated gonococcal invasion, and mutant cell lines defective in proteoglycan synthesis were poor substrates for gonococcal attachment. The addition of purified receptor and receptor analogues totally blocked gonococcal entry into the cells. Heparin-affinity chromatography and receptor binding assays using recombinant bacteria producing defined opacity proteins and reconstituted receptor or purified receptor fragments as probes, identified one particular member of the opacity protein family (MS11-Opa sub(30)) as the primary ligand for this novel class of receptors for bacteria. Heparan sulfate proteoglycans with gonococcal binding activity were purified from various cell types derived from target tissues of gonococcal infection, including ME-180 endocervical cells and primary cultures of human corneal epithelium. The physico-chemical properties of the receptor indicate that it may belong to the syndecan proteoglycan family. JF - EMBO Journal AU - Van Putten, JPM AU - Paul, S M AD - Lab. Microb. Struct. and Funct., Rocky Mt. Lab., NIAID/NIH, Hamilton, MT 59480, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 2144 EP - 2154 VL - 14 IS - 10 SN - 0261-4189, 0261-4189 KW - heparan sulfate KW - human cells KW - mucosal cells KW - proteoglycan receptors KW - syndecan KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Microbiology Abstracts B: Bacteriology KW - receptors KW - Neisseria gonorrhoeae KW - W3 33340:Other proteins, peptides, amino acids KW - W 30965:Miscellaneous, Reviews KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16851452?accountid=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=EMBO+Journal&rft.atitle=Binding+of+syndecan-like+cell+surface+proteoglycan+receptors+is+required+for+Neisseria+gonorrhoeae+entry+into+human+mucosal+cells&rft.au=Van+Putten%2C+JPM%3BPaul%2C+S+M&rft.aulast=Van+Putten&rft.aufirst=JPM&rft.date=1995-01-01&rft.volume=14&rft.issue=10&rft.spage=2144&rft.isbn=&rft.btitle=&rft.title=EMBO+Journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - receptors; Neisseria gonorrhoeae ER - TY - JOUR T1 - Selective killing of T cells by immunotoxins directed at distinct V sub( beta ) epitopes of the T cell receptor AN - 16850479; 3786771 AB - The potency and specificity of anti-T cell receptor (TcR)-directed immunotoxins were studied in two T cell leukemia lines, HPB-ALL and Jurkat, and in primary T cells. Immunoconjugates were synthesized using anti-CD3 sub( epsilon ) or distinct anti-V sub( beta ) antibodies cross-linked to CRM9, a binding site-mutant of diphtheria toxin. All TcR-expressing cells display the CD3 complex on the plasma membrane. HPB-ALL cells express the V sub( beta )5 gene product in the beta subunit of the TcR, while Jurkat cells express V sub( beta )8. V sub( beta ) expression in primary T cells isolated from buffy coats is heterogeneous. Primary T cell populations expressing specific V sub( beta ) epitopes in the TcR were generated by plating CD3 super(+) T cells on V sub( beta )-specific antibody-coated flasks or by positive immunomagnetic selection. Immunotoxins directed against the invariant CD3 epsilon epitope target and kill all T cells. Immunoconjugates targeted at distinct anti-V sub( beta ) epitopes are specific for cells that express the corresponding gene product in the TcR. The results demonstrate the ability of anti-TcR-based immunotoxins selectively to kill T cells with defined V sub( beta ) epitopes. These reagents may be clinically useful in disorders mediated by autoreactive T cell populations exhibiting V sub( beta ) restriction and in the treatment of clonal TcR-expressing lymphomas. JF - European Journal of Immunology AU - Rigaut, K D AU - Scharff, JE AU - Neville, DM Jr AD - NIMH, Lab. Mol. Biol. 36/1B08, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 2077 EP - 2082 VL - 25 IS - 7 SN - 0014-2980, 0014-2980 KW - beta chain KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - T-cell receptor KW - lymphocytes T KW - variable region KW - immunotoxins KW - immunoconjugates KW - F 06754:Surface KW - W3 33160:Antibody based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16850479?accountid=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=European+Journal+of+Immunology&rft.atitle=Selective+killing+of+T+cells+by+immunotoxins+directed+at+distinct+V+sub%28+beta+%29+epitopes+of+the+T+cell+receptor&rft.au=Rigaut%2C+K+D%3BScharff%2C+JE%3BNeville%2C+DM+Jr&rft.aulast=Rigaut&rft.aufirst=K&rft.date=1995-01-01&rft.volume=25&rft.issue=7&rft.spage=2077&rft.isbn=&rft.btitle=&rft.title=European+Journal+of+Immunology&rft.issn=00142980&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - T-cell receptor; lymphocytes T; variable region; immunoconjugates; immunotoxins ER - TY - JOUR T1 - Exposure assessment for a study of workers exposed to acrylonitrile. II. A computerized exposure assessment program AN - 16848756; 3781823 AB - The validity of exposure assessment in retrospective epidemiologic studies has often been questioned, in part because systematic methods have not been developed to estimate historical exposure levels when insufficient monitoring results are available. In addition, documentation as to how the exposure estimates are derived is often lacking. A previously published report described a data management system, called Job Exposure Profiles, that organized and maintained job-related information available on each job in a mortality study of workers exposed to acrylonitrile. This database, and a second one containing almost 19,000 acrylonitrile monitoring results with accompanying documentation (job, department, date, type of sample, etc.), were linked to a computerized, interactive exposure assessment program (EAP) to allow the user to develop historical exposure estimates. The EAP is the subject of this report. In this program, monitoring results were sorted into various subfiles based on their quantity and quality. JF - Applied Occupational & Environmental Hygiene AU - Stewart, P A AU - Triolo, H AU - Zey, J AU - White, D AU - Herrick, R F AU - Hornung, R AU - Dosemeci, M AU - Pottern, L M AD - NCI, Environ. Epidemiol. Branch, Rockville, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 698 EP - 706 VL - 10 IS - 8 SN - 1047-322X, 1047-322X KW - acrylonitrile KW - Health & Safety Science Abstracts KW - chemical industry KW - historical account KW - computer programs KW - mortality KW - occupational exposure KW - H SI6.3:HAZARD DETERMINATION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16848756?accountid=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=Applied+Occupational+%26+Environmental+Hygiene&rft.atitle=Exposure+assessment+for+a+study+of+workers+exposed+to+acrylonitrile.+II.+A+computerized+exposure+assessment+program&rft.au=Stewart%2C+P+A%3BTriolo%2C+H%3BZey%2C+J%3BWhite%2C+D%3BHerrick%2C+R+F%3BHornung%2C+R%3BDosemeci%2C+M%3BPottern%2C+L+M&rft.aulast=Stewart&rft.aufirst=P&rft.date=1995-01-01&rft.volume=10&rft.issue=8&rft.spage=698&rft.isbn=&rft.btitle=&rft.title=Applied+Occupational+%26+Environmental+Hygiene&rft.issn=1047322X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - occupational exposure; computer programs; mortality; historical account; chemical industry ER - TY - JOUR T1 - Generation, purification, and characterization of a recombinant source of human prostate-specific antigen AN - 16848356; 3781386 AB - Human prostate-specific antigen (PSA), a 33- to 34-kDa serine proteinase with extensive homology to glandular kallikrein, is a single-chain glycoprotein that contains 7% carbohydrate. The presence of PSA in the serum of patients with prostatic cancer is widely employed as a marker of disease status. PSA has also been thought of as a possible target for use in active specific immunotherapy protocols. To date, the source of PSA employed has been seminal fluid from different individuals; this has raised concerns about differences among PSA batches for standardization of assays. This report is the first description of the production and the purification of a recombinant source of PSA using a baculovirus expression system. A baculovirus recombinant of the cDNA encoding the full length PSA was expressed in insect cells yielding two major immunoreactive products of 31 and 29 kDa. The latter size conforms to the molecular weight of a core preprotein deduced from the sequence of the cDNA insert. The larger protein represents the N-linked glycosylated form of the preprotein. Western blot analysis showed that both the glycosylated and aglycosylated forms of PSA reacted with a polyclonal and two different monoclonal antibodies specific for PSA. bV-PSA, like commercially available PSA, showed also low-molecular-weight immunoreactive products when culture supernatants were concentrated or taken through steps of purification. bV-PSA was purified to a final product consisting of a major 29-kDa protein and a minor 31-kDa protein. This recombinant source of PSA will make it possible to further evaluate the biological, serological, and functional properties of the antigen and may serve as a more standardized source for serum assays to detect PSA. bV-PSA may also serve as a potential source for immunogen in active specific immunotherapy protocols. JF - Journal of Clinical Laboratory Analysis AU - Bei, R AU - Paranavitana, C AU - Milenic, D AU - Kashmiri, SVS AU - Schlom, J AD - Lab. Tumor Immunol. and Biol., NCI/NIH, Build. 10, Rm. 8B07, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 261 EP - 268 VL - 9 IS - 4 SN - 0887-8013, 0887-8013 KW - prostate-specific antigen KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - glycosylation KW - prostate KW - carcinoma KW - W3 33240:Immunology KW - W 30965:Miscellaneous, Reviews KW - F 06814:Tumor antigens UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16848356?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Clinical+Laboratory+Analysis&rft.atitle=Generation%2C+purification%2C+and+characterization+of+a+recombinant+source+of+human+prostate-specific+antigen&rft.au=Bei%2C+R%3BParanavitana%2C+C%3BMilenic%2C+D%3BKashmiri%2C+SVS%3BSchlom%2C+J&rft.aulast=Bei&rft.aufirst=R&rft.date=1995-01-01&rft.volume=9&rft.issue=4&rft.spage=261&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Laboratory+Analysis&rft.issn=08878013&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - glycosylation; prostate; carcinoma ER - TY - JOUR T1 - Pneumococcal conjugate vaccines: Review and update AN - 16847080; 3777923 AB - Approximately 15 million children under the age of 5 die each year worldwide; 96% of these deaths occur in developing countries. According to the World Health Organization (WHO), about 30%, or 4-5 million deaths, are due to acute respiratory infections. Among them, Streptococcus pneumoniae is the greatest killer. In developing countries, the highest incidence of pneumococcal disease occurs in children less than 2 years of age. It is the leading cause of death among this group, causing 9% of all deaths (i.e., approximately 1.2 million), even more than all diarrheal diseases combined. It is estimated that an improved vaccine against S. pneumoniae would protect 25-30% of those individuals who are now at risk. JF - Microbial Drug Resistance AU - Klein, D L AD - NIAID/NIH, 6003 Executive Blvd., Solar Bldg., Rm. 3B03 Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 49 EP - 58 VL - 1 IS - 1 SN - 1076-6294, 1076-6294 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - Streptococcus pneumoniae KW - vaccines KW - children KW - immunocompromised hosts KW - W3 33365:Vaccines (other) KW - J 02834:Vaccination and immunization KW - F 06807:Active immunization KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16847080?accountid=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=Microbial+Drug+Resistance&rft.atitle=Pneumococcal+conjugate+vaccines%3A+Review+and+update&rft.au=Klein%2C+D+L&rft.aulast=Klein&rft.aufirst=D&rft.date=1995-01-01&rft.volume=1&rft.issue=1&rft.spage=49&rft.isbn=&rft.btitle=&rft.title=Microbial+Drug+Resistance&rft.issn=10766294&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - vaccines; children; immunocompromised hosts; Streptococcus pneumoniae ER - TY - JOUR T1 - Interaction of M-SssI and M-HhaI with single-base mismatched oligodeoxynucleotide duplexes AN - 16844430; 3780454 AB - As part of an attempt to elucidate the mode of interaction of the CpG methyltransferase M-SssI with its substrate, we have prepared a series of double-stranded oligodeoxyribonucleotides containing one mismatch in the CpG recognition site. The mismatched duplexes were used to analyze the binding capabilities and enzymatic activity of M-SssI and M-HhaI (recognizes GCGC). We demonstrate here that M-SssI binds specifically to substrates containing either a C/A or G/T mismatch in the recognition sequence, i.e., 5'-GCGC/CACG-5' or 5'-GCGC/CGTG-5', respectively. The enzyme also shows significant enzymatic activity with these mismatched substrates. These results suggest that site recognition and methylation by M-SssI take place on the same strand. M-HhaI bound and methylated the C/A mismatch very efficiently, but recognition of the G/T mismatch was scarcely detectable. JF - Gene AU - Renbaum, P AU - Razin, A AD - Lab. Immunobiol., Build. 560, Room 1271, NCI, Frederick, MD 21702, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 177 EP - 179 VL - 157 IS - 1-2 SN - 0378-1119, 0378-1119 KW - DNA methyltransferase KW - DNA methyltransferase M-SssI KW - DNA methyltransferase M-HhaI KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - DNA KW - binding KW - base pairs KW - J 02728:Enzymes KW - N 14740:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16844430?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gene&rft.atitle=Interaction+of+M-SssI+and+M-HhaI+with+single-base+mismatched+oligodeoxynucleotide+duplexes&rft.au=Renbaum%2C+P%3BRazin%2C+A&rft.aulast=Renbaum&rft.aufirst=P&rft.date=1995-01-01&rft.volume=157&rft.issue=1-2&rft.spage=177&rft.isbn=&rft.btitle=&rft.title=Gene&rft.issn=03781119&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - binding; DNA; base pairs ER - TY - JOUR T1 - Pseudomonas exotoxin-mediated selection yields cells with altered expression of low-density lipoprotein receptor-related protein AN - 16842938; 3781257 AB - The alpha sub(2)-macroglobulin ( alpha sub(2)M) receptor/low-density lipoprotein receptor-related protein (LRP) is important for the clearance of proteases, protease-inhibitor complexes, and various ligands associated with lipid metabolism. While the regulation of receptor function is poorly understood, the addition of high concentrations of the 39-kD receptor-associated protein (RAP) to cells inhibits the binding and/or uptake of many of these ligands. Previously, we showed that Pseudomonas exotoxin (PE) could bind immobilized LRP. Also, the addition of RAP blocked toxin-mediated cell killing. These findings suggested that PE might use LRP to gain entry into toxin-sensitive cells. Here we report on a strategy to select PE-resistant lines of Chinese hamster ovary cells that express altered amounts of LRP. An important part of this strategy is to screen PE-resistant clones for those that retain sensitivity to both diphtheria toxin and to a fusion protein composed of lethal factor (from anthrax toxin) fused to the adenosine diphosphate-ribosylating domain of PE. Two lines, with obvious changes in their expression of LRP, were characterized in detail. The 14-2-1 line had significant amounts of LRP, but in contrast to wild-type cells, little or no receptor was displayed on the cell surface. Instead, receptor protein was found primarily within cells, much of it apparently in an unprocessed state. The 14-2-1 line showed no uptake of chymotrypsin- alpha sub(2)M and was 10-fold resistant to PE compared with wild-type cells. A second line, 13-5-1, had no detectable LRP mRNA or protein, did not internalize alpha sub(2)M-chymotrypsin, and exhibited a 100-fold resistance to PE. Resistance to PE appeared to be due to receptor-specific defects, since these mutant lines showed no resistance to a PE chimeric toxin that was internalized via the transferrin receptor. The results of this investigation confirm that LRP mediates the internalization of PE. JF - Journal of Cell Biology AU - FitzGerald, D J AU - Fryling, C M AU - Zdanovsky, A AU - Saelinger, C B AU - Kounnas, M AU - Winkles, JA AU - Strickland, D AU - Leppla, S AD - Lab. Mol. Biol., NCI/NIH, Div. Cancer Biol., Diagnosis and Cent., NIH, Build. 37 4B-03, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 1533 EP - 1541 VL - 129 IS - 6 SN - 0021-9525, 0021-9525 KW - lipoprotein (low density) receptors-related protein KW - alpha 2-macroglobulin receptors KW - Toxicology Abstracts KW - CHO cells KW - exotoxins KW - Pseudomonas KW - X 24171:Microbial UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16842938?accountid=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+Cell+Biology&rft.atitle=Pseudomonas+exotoxin-mediated+selection+yields+cells+with+altered+expression+of+low-density+lipoprotein+receptor-related+protein&rft.au=FitzGerald%2C+D+J%3BFryling%2C+C+M%3BZdanovsky%2C+A%3BSaelinger%2C+C+B%3BKounnas%2C+M%3BWinkles%2C+JA%3BStrickland%2C+D%3BLeppla%2C+S&rft.aulast=FitzGerald&rft.aufirst=D&rft.date=1995-01-01&rft.volume=129&rft.issue=6&rft.spage=1533&rft.isbn=&rft.btitle=&rft.title=Journal+of+Cell+Biology&rft.issn=00219525&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Pseudomonas; exotoxins; CHO cells ER - TY - JOUR T1 - Molecular mechanisms and implications for infection of lipopolysaccharide variation in Neisseria AN - 16839657; 3771498 AB - The lipopolysaccharides of the pathogenic Neisseria species are subject to structural variation owing to a combination of intrinsic changes in lipopolysaccharide (LPS) biosynthesis and external modification of the LPS molecule with sialic acid. This variation appears to control bacterial behaviour by altering their ability to interact with human cells and to evade host immune defences. This interconversion of LPS phenotypes, which is also observed during the natural infection, is probably due to environmental regulation of LPS biosynthesis superimposed on spontaneous changes in the DNA of distinct LPS loci. LPS variation may be a common strategy of mucosal pathogens to colonize and persist within the human host. JF - Molecular Microbiology AU - Van Putten, JPM AU - Robertson, B D AD - Rocky Mountain Lab., NIAID/NIH, Hamilton, MT 59840, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 847 EP - 853 VL - 16 IS - 5 SN - 0950-382X, 0950-382X KW - lipopolysaccharides KW - Microbiology Abstracts B: Bacteriology KW - Neisseria KW - protein structure KW - virulence KW - J 02730:Carbohydrates UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16839657?accountid=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=Molecular+mechanisms+and+implications+for+infection+of+lipopolysaccharide+variation+in+Neisseria&rft.au=Van+Putten%2C+JPM%3BRobertson%2C+B+D&rft.aulast=Van+Putten&rft.aufirst=JPM&rft.date=1995-01-01&rft.volume=16&rft.issue=5&rft.spage=847&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Neisseria; protein structure; virulence ER - TY - JOUR T1 - Identification of recombinant filarial proteins capable of inducing polyclonal and antigen-specific IgE and IgG4 antibodies AN - 16839544; 3775726 AB - Filarial infection is characterized by an immune response associated with the production of Ag-specific IgG4 and IgE and IL-4 and IL-5. To identify filarial Ags capable of inducing such responses and to analyze the role Ags themselves play in sustaining it, 24 recombinant filarial parasite proteins were screened for their ability to be recognized by sera from 67 individuals with tissue-invasive filarial infections. Among the recombinant proteins that were recognized by IgG4 or IgE Abs in 25% of the sera or more, two were selected on the basis of their ability to elicit polyclonal and Ag-specific IgE/IgG4 Abs in vitro. Ov27 (analogous to Ov7/cystatin, a cysteine protease inhibitor) and OvD5B (analogous to Ov33, an aspartyl protease inhibitor) induced both a polyclonal and Ag-specific IgE/IgG4 response that was blocked by neutralizing Abs to IL-4 and to IL-13 or by soluble IL-4 receptors. Recombinant human IFN- gamma and IL-12 also led to a decrease in the production of polyclonal and Ag-specific IgE/IgG4 Abs. In addition, these two recombinant proteins preferentially stimulated the secretion of IL-4, IL-5, and IL-10 (in contrast to IFN- gamma ). The data suggest that certain epitopes on filarial Ags preferentially elicit a Th2-type response and provide an in vitro model for dissecting the mechanisms underlying this preferential response. JF - Journal of Immunology AU - Garraud, O AU - Nkenfou, C AU - Bradley, JE AU - Perler, F B AU - Nutman, T B AD - Lab. Parasit. Dis., NIAID/NIH, Build. 4, Rm. 126, Bethesda, MD 20892-0425, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 1316 EP - 1325 VL - 155 IS - 3 SN - 0022-1767, 0022-1767 KW - Loa loa KW - immunoglobulin G4 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Onchocerca volvulus KW - immunoglobulin E KW - antibody response KW - proteins KW - antigens KW - man KW - F 06804:Helminths KW - W 30965:Miscellaneous, Reviews KW - W3 33055:Genetic engineering (general) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16839544?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunology&rft.atitle=Identification+of+recombinant+filarial+proteins+capable+of+inducing+polyclonal+and+antigen-specific+IgE+and+IgG4+antibodies&rft.au=Garraud%2C+O%3BNkenfou%2C+C%3BBradley%2C+JE%3BPerler%2C+F+B%3BNutman%2C+T+B&rft.aulast=Garraud&rft.aufirst=O&rft.date=1995-01-01&rft.volume=155&rft.issue=3&rft.spage=1316&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - immunoglobulin E; proteins; antibody response; man; antigens; Onchocerca volvulus ER - TY - JOUR T1 - Adherence of pilus super(-) Opa super(+) gonococci to epithelial cells in vitro involves heparan sulfate AN - 16839526; 3775835 AB - Neisseria gonorrhoeae attaches to host epithelial cells via pili and opacity-associated (Opa) outer membrane proteins. Pilus super(-) gonococci (Gc) of strain MS11 adhere to both human and nonhuman cells, but only when particular Opa proteins are expressed; OpaA super(+) variants adhere best, OpaC super(+) variants are next best, and the seven other Opa super(+) variants adhere poorly or not at all. The adherence of OpaA super(+) Gc to Chinese hamster ovary (CHO) cells is inhibited by heparin or heparan sulfate (HS), but not by chondroitin sulfate. OpaA super(+) Gc do not adhere to CHO cells devoid of HS proteoglycans; low concentrations of heparin restore OpaA super(+) Gc adherence to these HS-deficient CHO cells and high concentrations inhibit it. super(3)H-heparin binding to whole Gc parallels their adherence abilities (OpaA super(+) > OpaC super(+) > OpaH super(+) >> Opas B, D, E, F, G, I = Opa super(-) = 0). Opa proteins separated by SDS-PAGE also bind super(3)H-heparin. These data suggest that adherence of pilus super(-), Opa super(+) Gc involves HS-proteoglycan of eukaryotic cells. JF - Journal of Experimental Medicine AU - Chen, Tie AU - Belland, R J AU - Wilson, J AU - Swanson, J AD - Lab. Microb. Struct. and Funct., Rocky Mountain Lab., NIAID/NIH, Hamilton, MT 59840, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 511 EP - 517 VL - 182 IS - 2 SN - 0022-1007, 0022-1007 KW - Opa protein KW - heparan sulfate KW - Microbiology Abstracts B: Bacteriology KW - membrane proteins KW - cell adhesion KW - epithelium KW - Neisseria gonorrhoeae KW - J 02721:Cell cycle, morphology and motility UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16839526?accountid=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+Experimental+Medicine&rft.atitle=Adherence+of+pilus+super%28-%29+Opa+super%28%2B%29+gonococci+to+epithelial+cells+in+vitro+involves+heparan+sulfate&rft.au=Chen%2C+Tie%3BBelland%2C+R+J%3BWilson%2C+J%3BSwanson%2C+J&rft.aulast=Chen&rft.aufirst=Tie&rft.date=1995-01-01&rft.volume=182&rft.issue=2&rft.spage=511&rft.isbn=&rft.btitle=&rft.title=Journal+of+Experimental+Medicine&rft.issn=00221007&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Neisseria gonorrhoeae; membrane proteins; epithelium; cell adhesion ER - TY - JOUR T1 - Antisense phosphorothioate oligodeoxynucleotides alter HIV type 1 replication in cultured human macrophages and peripheral blood mononuclear cells AN - 16839487; 3781583 AB - The use of antisense oligodeoxynucleotides as antiviral drugs to combat HIV-1 infection may offer an alternative to traditional pharmacological therapies. We compared the effects of two 28-mer antisense phosphorothioate oligodeoxynucleotides [PS-oligo(dN)] with non-sequence-specific controls on HIV-1 replication in long-term human monocyte/macrophage and PBMC cultures. The anti-rev PS-oligo(dN) was complementary to the messenger RNA (mRNA) sequences derived from the overlapping region of the HIV-1 regulatory genes tat and rev, while anti-gag targeted the translational initiation site of the gag mRNA. In vitro cytotoxicity of the PS-oligo(dN) was evaluated at concentrations ranging from 0.1 to 10.0 mu M for a period of 20 days. Cell survival was 100% at 0.1 mu M, but decreased to 5% at 10.0 mu M in relation to the untreated control cultures. Our data demonstrate that replication of both the T cell-tropic and macrophage-tropic HIV-1 strains in primary cells can be inhibited by PS-oligo(dN) in a sequence-specific and dose-dependent manner at concentrations achievable in vivo. However, the sequence-dependent antiviral activity of the utilized PS-oligo(dN) was limited to a window of specificity at concentrations between 0.25 and 1.0 mu M. JF - AIDS Research and Human Retroviruses AU - Weichold, F F AU - Lisziewicz, J AU - Zeman, R A AU - Nerurkar, L S AU - Agrawal, S AU - Reitz, Jr AU - Gallo, R C AD - Build. 10, Rm. 7C103 NHLBI/NIH, 9000 Rockville Pike Bethesda, MD 20892-1652, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 863 EP - 868 VL - 11 IS - 7 SN - 0889-2229, 0889-2229 KW - oligodeoxyribonucleotides KW - phosphorothioate KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - antisense KW - replication KW - human immunodeficiency virus 1 KW - cytotoxicity KW - macrophages KW - V 22002:AIDS: Molecular and in vitro aspects KW - W 30965:Miscellaneous, Reviews KW - W3 33380:Antisense UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16839487?accountid=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=AIDS+Research+and+Human+Retroviruses&rft.atitle=Antisense+phosphorothioate+oligodeoxynucleotides+alter+HIV+type+1+replication+in+cultured+human+macrophages+and+peripheral+blood+mononuclear+cells&rft.au=Weichold%2C+F+F%3BLisziewicz%2C+J%3BZeman%2C+R+A%3BNerurkar%2C+L+S%3BAgrawal%2C+S%3BReitz%2C+Jr%3BGallo%2C+R+C&rft.aulast=Weichold&rft.aufirst=F&rft.date=1995-01-01&rft.volume=11&rft.issue=7&rft.spage=863&rft.isbn=&rft.btitle=&rft.title=AIDS+Research+and+Human+Retroviruses&rft.issn=08892229&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - antisense; replication; cytotoxicity; macrophages; human immunodeficiency virus 1 ER - TY - JOUR T1 - A novel phorbol ester from Excoecaria agallocha AN - 16838612; 3778308 AB - The novel phorbol ester 12-deoxyphorbol 13-(3E,5E-decadienoate) [1] was isolated as the anti-HIV principle of Excoecaria agallocha leaves and stems collected in northwest Australia. The structure was determined by spectral means. Compound 1 was also a potent displacer of [ super(3)H]-phorbol dibutyrate from rat brain membranes. JF - Journal of Natural Products AU - Erickson, K L AU - Beutler, JA AU - Cardellina, JH II AU - McMahon, J B AU - Newman, D J AU - Boyd, M R AD - Lab. Drug Dis. Res. Dev., Dev. Ther. Prog., Div. Cancer Treat., NCI-FCRDC, Frederick, MD 21702-1201, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 769 EP - 777 VL - 58 IS - 5 SN - 0163-3864, 0163-3864 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - esters KW - Excoecaria agallocha KW - human immunodeficiency virus KW - V 22002:AIDS: Molecular and in vitro aspects KW - W3 33370:Antibiotics KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16838612?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Natural+Products&rft.atitle=A+novel+phorbol+ester+from+Excoecaria+agallocha&rft.au=Erickson%2C+K+L%3BBeutler%2C+JA%3BCardellina%2C+JH+II%3BMcMahon%2C+J+B%3BNewman%2C+D+J%3BBoyd%2C+M+R&rft.aulast=Erickson&rft.aufirst=K&rft.date=1995-01-01&rft.volume=58&rft.issue=5&rft.spage=769&rft.isbn=&rft.btitle=&rft.title=Journal+of+Natural+Products&rft.issn=01633864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - esters; human immunodeficiency virus; Excoecaria agallocha ER - TY - JOUR T1 - IL-2 enhances the function of recombinant poxvirus-based vaccines in the treatment of established pulmonary metastases AN - 16835536; 3767599 AB - Neoplastic cells are generally poor immunogens. Transfection of the murine tumor CT-26 with beta -galactosidase ( beta -gal), a protein from Escherichia coli, did not alter its growth rate in vivo, or its lethality, and did not elicit a measurable anti- beta -gal immune response. Immunization with beta -gal-expressing recombinant vaccinia viruses (rVV) elicited specific anti- beta -gal cytolytic T lymphocytes, but rVV- beta -gal was only marginally therapeutic when given to tumor-bearing mice. With the aim of expanding the immune response against beta -gal, used here as a model tumor Ag, we gave mice exogenous IL-2 starting 12 h after the poxvirus. The therapeutic effectiveness of the combination of poxvirus and IL-2 was far greater than either of these treatments alone. When the cDNA for IL-2 was inserted into the viral genome of the rVV construct to make a double recombinant (drVV), antitumor activity was further augmented. One mechanism of action may be the enhanced activation or expansion of cytotoxic T cells, because a marked increase in primary cytotoxic responses against vaccinia determinants was observed. Interestingly, other cytokines (mGM-CSF, mTNF- alpha , and mIFN- gamma ) inserted into the rVV genome did not modify the efficacy of the rVV constructs. The increase in specific CTL responses against beta -gal by drVV expressing the tumor-associated Ags (TAA) and IL-2 was more pronounced in mice bearing the lacZ-transduced tumor than in those bearing the parental cell line, suggesting that the TAA presented by growing tumor cells can either pre-activate or otherwise amplify the immune response induced by the rVV. Unfortunately, in several long-term surviving mice, tumor recurred that no longer expressed beta -gal. These results indicate that treatment of disseminated tumors by using recombinant viruses expressing TAA can be enhanced by IL-2 provided exogenously, or encoded within the recombinant virus. JF - Journal of Immunology AU - Bronte, V AU - Tsung, K AU - Rao, J B AU - Chen, P W AU - Wang, M AU - Rosenberg, SA AU - Restifo, N P AD - Build. 10, Rm 2B42, NCI, 10 Cent. Dr., MSC 1502, Bethesda, MD 20892-1502, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 5282 EP - 5292 VL - 154 IS - 10 SN - 0022-1767, 0022-1767 KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - interleukin 2 KW - vaccines KW - lung KW - metastases KW - poxvirus KW - W3 33365:Vaccines (other) KW - F 06818:Cancer immunotherapy KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16835536?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunology&rft.atitle=IL-2+enhances+the+function+of+recombinant+poxvirus-based+vaccines+in+the+treatment+of+established+pulmonary+metastases&rft.au=Bronte%2C+V%3BTsung%2C+K%3BRao%2C+J+B%3BChen%2C+P+W%3BWang%2C+M%3BRosenberg%2C+SA%3BRestifo%2C+N+P&rft.aulast=Bronte&rft.aufirst=V&rft.date=1995-01-01&rft.volume=154&rft.issue=10&rft.spage=5282&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - interleukin 2; lung; vaccines; metastases; poxvirus ER - TY - JOUR T1 - Patellamide F, a new cytotoxic cyclic peptide from the colonial ascidian Lissoclinum patella AN - 16832552; 3774017 AB - Cytotoxicity-directed fractionation of an organic extract of the tunicate Lissoclinum patella afforded a new cyclic octapeptide, patellamide F [1]. The structure and absolute stereochemistry of 1 were established by a combination of spectroscopic and chemical methods. Three known cyclic peptides, patellamide B [2], ulithiacyclamide, and lissoclinamide 3, were also isolated and identified. JF - Journal of Natural Products AU - Rashid, MA AU - Gustafson, K R AU - Cardellina, JH II AU - Boyd, M R AD - Lab. Drug Dis. Res. Dev., Dev. Ther. Program, Div. Cancer Treat., NCI, Build. 1052, Rm. 121, Frederick, MD 21702-1201, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 594 EP - 597 VL - 58 IS - 4 SN - 0163-3864, 0163-3864 KW - aquatic drugs KW - biochemical composition KW - patellamide F KW - Biotechnology and Bioengineering Abstracts; Oceanic Abstracts; ASFA 1: Biological Sciences & Living Resources; Medical and Pharmaceutical Biotechnology Abstracts; ASFA Marine Biotechnology Abstracts KW - metabolites KW - Marine KW - Ascidiacea KW - cytotoxicity KW - Lissoclinum patella KW - pharmacology KW - biotechnology KW - peptides KW - Q4 27390:Toxins KW - W3 33340:Other proteins, peptides, amino acids KW - O 5040:Processing, Products and Marketing KW - Q1 08326:Physiology, biochemistry, biophysics KW - O 1085:Biotechnology KW - Q1 08625:Non-edible products KW - O 1050:Vertebrates, Urochordates and Cephalochordates KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16832552?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Natural+Products&rft.atitle=Patellamide+F%2C+a+new+cytotoxic+cyclic+peptide+from+the+colonial+ascidian+Lissoclinum+patella&rft.au=Rashid%2C+MA%3BGustafson%2C+K+R%3BCardellina%2C+JH+II%3BBoyd%2C+M+R&rft.aulast=Rashid&rft.aufirst=MA&rft.date=1995-01-01&rft.volume=58&rft.issue=4&rft.spage=594&rft.isbn=&rft.btitle=&rft.title=Journal+of+Natural+Products&rft.issn=01633864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2014-05-06 N1 - SubjectsTermNotLitGenreText - biotechnology; metabolites; biochemical composition; peptides; cytotoxicity; aquatic drugs; pharmacology; Ascidiacea; Lissoclinum patella; Marine ER - TY - JOUR T1 - Phage display of disulfide-stabilized Fv fragments AN - 16830148; 3772588 AB - Phage display of single-chain Fvs (scFvs) is a powerful tool to enrich and isolate specific antibody fragments from large pools (libraries) of Fv coding genes. However, many scFvs and scFv fusion proteins are unstable, not only as soluble proteins but also on the surface of phage. This limits and biases the recovery of specific Fv phage from display libraries to relatively stable scFvs. Also, the peptide linker in scFvs can diminish antigen binding of scFvs and scFv-fusion proteins. Disulfide-stabilized Fvs (dsFv) which have the V sub(H)-V sub(L) heterodimer stabilized by an interchain disulfide bond connecting framework regions in V sub(H) and V sub(L) rather than a peptide linker are more stable than scFvs and in some instances show better binding. To analyze whether these advantages can be utilized in a phage display system and to prove the feasibility of dsFv display, we constructed phage for dsFv display of the anti-Tac antibody and a dsFv-phage library. We find that dsFv phage can specifically bind antigen although the titer of dsFv phage in supernatants appears to be reduced compared to scFv phage. But this reduction in titer does not hamper the isolation of dsFv phages from large pools (libraries) as demonstrated by 'panning' of anti-Tac scFv and dsFv phages on living leukemia cells in suspension. In addition, dsFv phage are more stable than scFv phage. Therefore, display of dsFvs on phage is a useful alternative and addition to scFv-phage display. JF - Journal of Immunological Methods AU - Brinkmann, U AU - Chowdhury, P S AU - Roscoe, D M AU - Pastan, I AD - Lab. Mol. Biol., Div. Cancer Biol., NCI/NIH, Build. 37, Rm. 4E16, 37 Convent Dr, MSC 4255, Bethesda, MD 20892-4255, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 41 EP - 50 VL - 182 IS - 1 SN - 0022-1759, 0022-1759 KW - Fv KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - stabilization KW - immunoglobulins KW - disulfide bonds KW - genes KW - phages KW - W3 33375:Antibodies KW - F 06711:Monoclonal antibodies, hybridomas, antigens and antisera KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16830148?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunological+Methods&rft.atitle=Phage+display+of+disulfide-stabilized+Fv+fragments&rft.au=Brinkmann%2C+U%3BChowdhury%2C+P+S%3BRoscoe%2C+D+M%3BPastan%2C+I&rft.aulast=Brinkmann&rft.aufirst=U&rft.date=1995-01-01&rft.volume=182&rft.issue=1&rft.spage=41&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunological+Methods&rft.issn=00221759&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - stabilization; immunoglobulins; disulfide bonds; genes; phages ER - TY - JOUR T1 - Neutralization of primary HIV-1 isolates by anti-envelope monoclonal antibodies AN - 16829017; 3772644 AB - To evaluate human monoclonal antibodies (MAb) for neutralizing activity against primary HIV-1 isolates in peripheral blood mononuclear cells. Neutralization activity data were obtained from 11 laboratories on a coded panel consisting of six human MAb to HIV envelope V3, CD4-binding region or gp41. Hyperimmune globulin against HIV-1 and normal human immunoglobulin G were supplied as controls. Each laboratory received pre-titered virus for use in the studies. Each laboratory measured neutralization of the MAb against laboratory strain HIV sub(MN), genomic clone HIV sub(JR-CSF), two subtype B and one subtype D primary isolates. The titers of the centrally supplied virus stocks as determined by re-titration or back-titration varied among laboratories and were generally 10-100-fold less than provided. The neutralizing activity of each MAb varied by as much as a 1000-fold among laboratories. These differences may result from varying sensitivity in neutralization assay protocols and the differing susceptibility of primary cells to infection with HIV-1. To consolidate the data from multiple laboratories, the neutralization titers were compared by classifying antibodies as neutralizing if the antibody concentration for 50% virus inhibition was less than or equal to 10 mu g/ml. By this criterion, the CD4-binding region and gp41 MAb neutralized all four subtype B viruses and the subtype D isolate in a few of the laboratories. The V3 MAb neutralized only HIV sub(MN) and the closely related HIV sub(JR-CSF) viruses. JF - AIDS AU - D'Souza, M P AU - Milman, G AU - Bradac, JA AU - McPhee, D AU - Hanson, C V AU - Hendry, R M AD - Div. AIDS/NIAID, 6003 Executive Blvd., Solar Build., Room 2C35, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 867 EP - 872 VL - 9 IS - 8 SN - 0269-9370, 0269-9370 KW - CD4 antigen KW - glycoprotein gp41 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts; Virology & AIDS Abstracts KW - neutralization KW - human immunodeficiency virus 1 KW - monoclonal antibodies KW - W3 33375:Antibodies KW - V 22003:AIDS: Immunological aspects KW - W 30965:Miscellaneous, Reviews KW - F 06717:Agglutination, complement & neutralization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16829017?accountid=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=AIDS&rft.atitle=Neutralization+of+primary+HIV-1+isolates+by+anti-envelope+monoclonal+antibodies&rft.au=D%27Souza%2C+M+P%3BMilman%2C+G%3BBradac%2C+JA%3BMcPhee%2C+D%3BHanson%2C+C+V%3BHendry%2C+R+M&rft.aulast=D%27Souza&rft.aufirst=M&rft.date=1995-01-01&rft.volume=9&rft.issue=8&rft.spage=867&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 - 2011-12-14 N1 - SubjectsTermNotLitGenreText - neutralization; monoclonal antibodies; human immunodeficiency virus 1 ER - TY - JOUR T1 - Transfer of the MDR1 (multidrug resistance) gene: Protection of hematopoietic cells from cytotoxic chemotherapy, and selection of transduced cells in vivo AN - 16828968; 3772657 AB - Expression of the drug efflux pump P-glycoprotein, encoded by the multidrug resistance (MDR1) gene, has been identified as an impediment to successful chemotherapy of neoplastic diseases. More recently, its potential use for gene therapy has been analyzed. Expression of a full-length MDR1 cDNA in hematopoietic cells renders them resistant to various anticancer drugs, as first shown in a transgenic mouse model. Similarly, mouse hematopoietic progenitor cells in bone marrow or peripheral blood are protected from the toxicity of anticancer chemotherapy by retroviral transduction of the MDR1 gene. Furthermore, cells engineered to express P-glycoprotein survived after the administration of cytotoxic drugs, indicating that the gene could function as a selectable marker in vivo. Recently, MDR1 transduction into isolated pluripotent hematopoietic stem cells has been demonstrated. Clinical studies on MDR1 gene transfer into hematopoietic cells of cancer patients are being planned. Transfer of the MDR1 gene into hematopoietic precursor cells may allow the introduction and selection of otherwise non-selectable genes in bone marrow. The ability to select transduced cells can circumvent the low transduction efficiency that has hampered efficient gene therapy. Recently, fusion genes in which the MDR1 cDNA is fused to genes that correct genetic disorders have been constructed to facilitate gene therapy of inherited metabolic disorders. JF - Cytokines, Cellular & Molecular Therapy AU - Licht, T AU - Gottesman, M M AU - Pastan, I AD - Lab. Mol. Biol., NCI/DCDBC/NIH, 37 Convent Dr., MSC 4255, Build. 37, Room 4E16, Bethesda, MD 20892-4255, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 11 EP - 20 VL - 1 IS - 1 SN - 1355-6568, 1355-6568 KW - MDR1 gene KW - glycoprotein P KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - gene transfer KW - gene therapy KW - reviews KW - retrovirus KW - stem cells KW - drug resistance KW - bone marrow KW - W 30965:Miscellaneous, Reviews KW - W3 33055:Genetic engineering (general) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16828968?accountid=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=Cytokines%2C+Cellular+%26+Molecular+Therapy&rft.atitle=Transfer+of+the+MDR1+%28multidrug+resistance%29+gene%3A+Protection+of+hematopoietic+cells+from+cytotoxic+chemotherapy%2C+and+selection+of+transduced+cells+in+vivo&rft.au=Licht%2C+T%3BGottesman%2C+M+M%3BPastan%2C+I&rft.aulast=Licht&rft.aufirst=T&rft.date=1995-01-01&rft.volume=1&rft.issue=1&rft.spage=11&rft.isbn=&rft.btitle=&rft.title=Cytokines%2C+Cellular+%26+Molecular+Therapy&rft.issn=13556568&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - gene therapy; gene transfer; reviews; retrovirus; stem cells; drug resistance; bone marrow ER - TY - JOUR T1 - Heparin protects Opa super(+) Neisseria gonorrhoeae from the bactericidal action of normal human serum AN - 16828400; 3768272 AB - The pathobiological significance of lipooligosaccharide (LOS) and outer membrane opacity protein (Opa) changes in gonorrheal disease are poorly understood. We assessed variants of strain MS11mk with different LOS and Opa phenotypes for their liability to killing by normal human sera. LOS differences correlated with strikingly disparate susceptibilities to serum killing; LOSa variants were serum resistant, LOSb variants were serum sensitive, and sialylation of LOSb variants enhanced their survival (as reported previously). Opa phenotype had little influence on the killing of serum-sensitive LOSb cells that were incubated directly in normal human sera, but preincubation of Opa super(+) LOSb variants in heparin increased their serum resistance whereas Opa super(-) LOSb variants showed no change. Some Opa proteins conferred slightly higher resistance than others, but heparin preincubation increased serum resistance for variants expressing each of seven Opa proteins. These in vitro phenomena may relate to conditions within the male urethra where sulfate-containing proteoglycans are abundant and where antibody and complement may transude from blood plasma. The results suggest that the selective advantage for Opa super(+) Neisseria gonorrhoeae bacteria observed in vivo may reflect their ability to utilize host cell components to resist killing by host defenses. JF - Infection and Immunity AU - Chen, T AU - Swanson, J AU - Wilson, J AU - Belland, R J AD - Lab. Microb. Struct. and Funct., Rocky Mountain Lab., NIAID, Hamilton, MT 59840, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 1790 EP - 1795 VL - 63 IS - 5 SN - 0019-9567, 0019-9567 KW - Opa protein KW - heparin KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - serum KW - antibacterial activity KW - man KW - Neisseria gonorrhoeae 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/16828400?accountid=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=Heparin+protects+Opa+super%28%2B%29+Neisseria+gonorrhoeae+from+the+bactericidal+action+of+normal+human+serum&rft.au=Chen%2C+T%3BSwanson%2C+J%3BWilson%2C+J%3BBelland%2C+R+J&rft.aulast=Chen&rft.aufirst=T&rft.date=1995-01-01&rft.volume=63&rft.issue=5&rft.spage=1790&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Neisseria gonorrhoeae; serum; antibacterial activity; man ER - TY - JOUR T1 - Measuring interactions of MHC class I molecules using surface plasmon resonance AN - 16827796; 3772620 AB - To examine the molecular interactions between major histocompatibility complex (MHC)-encoded molecules and peptides, monoclonal antibodies (mAbs), or T cell receptors, we have developed model systems employing genetically engineered soluble MHC class I molecules (MHC-I), synthetic peptides, purified mAbs, and engineered solubilizable T cell receptors. Direct binding assays based on immobilization of one of the interacting components to the dextran modified gold biosensor surface of a surface plasmon resonance (SPR) detector have been developed for each of these systems. The peptide binding site of the MHC-I molecule can be sterically mapped by evaluation of a set of peptides immobilized through the thiol group of cysteine substitutions at each peptide position. Kinetic binding studies indicate that the MHC-I/peptide interaction is characterized by a low to moderate apparent k sub(ass) ( similar to 5000-60000 M super(-1) s super(-1)) and very small k sub(dis) ( similar to 10 super(-4)-10 super(-6) s super(-1)) consistent with the biological requirement for a long cell surface residence time to permit engagement with T cell receptors. Several mAb directed against different MHC-I epitopes were examined, and kinetic parameters of their interaction with MHC molecules were determined. These showed characteristic moderate association rate constants and moderate dissociation rate constants (k sub(ass) similar to 10 super(4)-10 super(6) M super(-1) s super(-1) and k sub(dis) similar to 10 super(-2)-10 super(-4) s super(-1)), characteristic of many antibody/protein antigen interactions. The interaction of an anti-idiotypic anti-TCR mAb with its purified cognate TCR was of moderate affinity and revealed kinetic binding similar to that of the anti-MHC mAbs. The previously determined interaction of a purified T cell receptor with its MHC-I/peptide ligand is characterized by kinetic constants more similar to those of the antibody/antigen interaction than of the MHC-I/peptide interaction, but is remarkable for rapid dissociation rates (apparent k sub(dis) similar to 10 super(-2) s super(-1)). Such binding studies of reactions involving the MHC-I molecules offer insight into the mechanisms responsible for the initial specific events required for the stimulation of T cells. JF - Journal of Immunological Methods AU - Khilko, S N AU - Jelonek, M T AU - Corr, M AU - Boyd, L F AU - Bothwell, ALM AU - Margulies, D H AD - Mol. Biol. Sect., Lab. Immunol., NIAID/NIH, Bethesda, MD 20892-1892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 77 EP - 94 VL - 183 IS - 1 SN - 0022-1759, 0022-1759 KW - class I molecules KW - surface plasmon resonance KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - biosensors KW - monoclonal antibodies KW - major histocompatibility complex KW - W3 33240:Immunology KW - F 06825:Human KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16827796?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunological+Methods&rft.atitle=Measuring+interactions+of+MHC+class+I+molecules+using+surface+plasmon+resonance&rft.au=Khilko%2C+S+N%3BJelonek%2C+M+T%3BCorr%2C+M%3BBoyd%2C+L+F%3BBothwell%2C+ALM%3BMargulies%2C+D+H&rft.aulast=Khilko&rft.aufirst=S&rft.date=1995-01-01&rft.volume=183&rft.issue=1&rft.spage=77&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunological+Methods&rft.issn=00221759&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - biosensors; monoclonal antibodies; major histocompatibility complex ER - TY - JOUR T1 - Occupational risk factors for brain tumors among women in Shanghai, China AN - 16827488; 3766149 AB - The etiology of brain cancer is not well understood and few studies have evaluated occupational risk factors among women. We evaluated occupation and industry at time of diagnosis for 276 incident primary brain tumor cases among women in Shanghai, China, for the period 1980-1984, identified through the Shanghai Cancer Registry. Standardized incidence ratios (SIRs) and their 95% confidence intervals (CIs) were calculated for all occupations and industries with at least three female cases. SIRs compared observed to expected numbers of cases, based on incidence rates for Shanghai and the number of women in each occupation and industry according to the 1982 census. Statistically significant excesses of brain tumors were seen among grain farmers (SIR = 6.5, 95% CI = 1.3-19.1), rubber workers (SIR = 5.0, 95% CI = 1.6-11.6), and workers in transportation equipment manufacture and repair (SIR = 2.3, 95% CI = 1.1-4.3). Risks among textile spinners and winders were of borderline significance (SIR = 1.7, 95% CI = 1.0-2.8). Elevated but nonsignificant risks of 2.0 or greater were seen among nurses, plastic products workers, sanitation workers, painters, and workers in manufacture of equipment for electrical generation, transmission, and distribution. Results for farmers, rubber workers, and painters are consistent with previously reported excesses among these occupations in men. The increase among nurses is a new finding, although elevated risks have been observed among male medical professionals. Risks were elevated with likely exposure to pesticides, particularly among those thought to have a high probability and a high level of exposure (SIR = 3.6, 95% CI = 1.2-8.5). JF - Journal of Occupational and Environmental Medicine AU - Heineman, E F AU - Gao, Yu-Tang AU - Dosemeci, M AU - McLaughlin, J K AD - Occup. Stud. Sect., NCI, 6130 Executive Blvd., Room 418, Rockville, MD 20852, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 288 EP - 293 VL - 37 IS - 3 SN - 1076-2752, 1076-2752 KW - occupational health KW - tumors KW - occupational hazards KW - man KW - Toxicology Abstracts; Risk Abstracts; Health & Safety Science Abstracts KW - females KW - brain KW - statistical analysis KW - China, People's Rep., Shanghai KW - cancer KW - H SI0.1:BASIC APPROACHES, CONCEPTS, AND THEORY KW - R2 23080:Industrial and labor KW - X 24240:Miscellaneous KW - R2 23060:Medical and environmental health KW - H SM10.21:CANCER UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16827488?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Occupational+and+Environmental+Medicine&rft.atitle=Occupational+risk+factors+for+brain+tumors+among+women+in+Shanghai%2C+China&rft.au=Heineman%2C+E+F%3BGao%2C+Yu-Tang%3BDosemeci%2C+M%3BMcLaughlin%2C+J+K&rft.aulast=Heineman&rft.aufirst=E&rft.date=1995-01-01&rft.volume=37&rft.issue=3&rft.spage=288&rft.isbn=&rft.btitle=&rft.title=Journal+of+Occupational+and+Environmental+Medicine&rft.issn=10762752&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - China, People's Rep., Shanghai; brain; cancer; occupational health; females; statistical analysis; tumors; occupational hazards; man ER - TY - JOUR T1 - Nucleic acid vaccines AN - 16826039; 3771110 AB - The use of nucleic acid-based vaccines is a novel approach to immunization that elicits immune responses similar to those induced by live, attenuated vaccines. Administration of nucleic acid vaccines results in the endogenous generation of viral proteins with native conformation, glycosylation profiles, and other posttranslational modifications that mimic antigen produced during natural viral infection. Nucleic acid vaccines have been shown to elicit both antibody and cytotoxic T-lymphocyte responses to diverse protein antigens. Advantages of nucleic acid-based vaccines include the simplicity of the vector, the ease of delivery, the duration of expression, and, to date, the lack of evidence of integration. Further studies are needed to assess the feasibility, safety, and efficacy of this new and promising technology. JF - Clinical Microbiology Reviews AU - Vogel AU - Sarver, N AD - Vaccine Prev. Res. Prog., Div. AIDS/NIAID/NIH, 6003 Executive Blvd., Rm. 2A28A, Bethesda, MD 20892-7620, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 406 EP - 410 VL - 8 IS - 3 SN - 0893-8512, 0893-8512 KW - nucleic acids KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - vectors KW - vaccines KW - safety KW - W3 33365:Vaccines (other) KW - F 06807:Active immunization KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16826039?accountid=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=Clinical+Microbiology+Reviews&rft.atitle=Nucleic+acid+vaccines&rft.au=Vogel%3BSarver%2C+N&rft.aulast=Vogel&rft.aufirst=&rft.date=1995-01-01&rft.volume=8&rft.issue=3&rft.spage=406&rft.isbn=&rft.btitle=&rft.title=Clinical+Microbiology+Reviews&rft.issn=08938512&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - vectors; vaccines; safety ER - TY - JOUR T1 - Specific and sensitive quantitation of transforming growth factor beta 3 by sandwich enzyme-linked immunosorbent assay AN - 16825542; 3774704 AB - Transforming growth factors beta (TGF- beta ) consist of a highly homologous family of 25 kDa dimers involved in a diverse array of biological functions. Progress in understanding the biology of the third isoform (TGF- beta 3) of this family has been limited by the absence of a quantitative assay for TGF- beta 3. Here we report the development of a sensitive and specific sandwich enzyme-linked immunosorbent assay (SELISA), which is based on an anti-TGF- beta mouse monoclonal IgG as the capture antibody and chicken anti-recombinant-hTGF- beta 3 IgY as the secondary antibody. This assay can quantitate TGF- beta 3 in complex biological fluids, with a detection limit of 2 pg and no cross-reactivity or interference with as high as 1000-fold molar excesses of either TGF- beta s 1, 2 or 1.2. This TGF- beta 3 SELISA is the first reported assay for the direct and sensitive quantitation of TGF- beta 3 in complex biological fluids. JF - Journal of Immunological Methods AU - Danielpour, D AU - Roberts, AB AD - Build. 41, Rm. C629, NCI/NIH, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 265 EP - 272 VL - 180 IS - 2 SN - 0022-1759, 0022-1759 KW - transforming growth factor- beta KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - enzyme-linked immunosorbent assay KW - W3 33240:Immunology KW - F 06723:Other labelling methods KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16825542?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunological+Methods&rft.atitle=Specific+and+sensitive+quantitation+of+transforming+growth+factor+beta+3+by+sandwich+enzyme-linked+immunosorbent+assay&rft.au=Danielpour%2C+D%3BRoberts%2C+AB&rft.aulast=Danielpour&rft.aufirst=D&rft.date=1995-01-01&rft.volume=180&rft.issue=2&rft.spage=265&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunological+Methods&rft.issn=00221759&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - enzyme-linked immunosorbent assay ER - TY - JOUR T1 - Cigarette smoking and alcohol consumption and the risk of pancreatic cancer: A case-control study in Shanghai, China AN - 16825419; 3773460 AB - Cancer of the pancreas has been rising in incidence in Shanghai, China since the early 1970s. In 1987-89, this malignancy ranked eighth in cancer incidence among men and ninth among women in Shanghai. To examine risk factors for this tumor in urban Shanghai, a population-based case-control study was conducted. Cases (n = 451) were permanent residents of Shanghai, 30 to 74 years of age, newly diagnosed with pancreatic cancer between 1 October 1990 and 30 June 1993. Deceased cases (19 percent) were excluded from the study. Controls (n = 1,552) were selected among Shanghai residents, frequency-matched to cases by gender and age. Cases and controls were interviewed about their demographic background and potential risk factors, including tobacco, alcohol and beverage consumption, diet, and medical history. Adjusted odds ratios (OR) and 95 percent confidence intervals (CI) were estimated using logistic regression models. Current cigarette smoking was associated with excess risk of pancreatic cancer in both men (OR = 1.6, CI = 1.1-2.2) and women (OR = 1.4, CI = 0.9-2.4). ORs increased significantly with number of cigarettes smoked per day, and with duration and pack-years of smoking. Risk increased three- to sixfold among those in the highest categories of cigarette consumption, while risk decreased with increasing years since smoking cessation. Former smokers who stopped smoking for 10 or more years had risks comparable to nonsmokers. No association was found between alcohol use and pancreatic cancer. JF - Cancer Causes & Control AU - Ji, Bu-Tian AU - Chow, Wong-Ho AU - Dai, Qi AU - McLaughlin, J K AU - Benichou, J AU - Hatch, M-C AU - Gao, Yu-Tang AU - Fraumeni, JF Jr AD - NCI, 6130 Executive Blvd, EPN 431, Rockville, MD 20852, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 369 EP - 376 VL - 6 IS - 4 SN - 0957-5243, 0957-5243 KW - alcohol KW - ethanol KW - pancreas KW - man KW - Toxicology Abstracts; Risk Abstracts; Health & Safety Science Abstracts KW - smoking KW - cigarettes KW - China, People's Rep., Shanghai KW - cancer KW - H SE4.26:DRUGS AND ALCOHOL KW - R2 23060:Medical and environmental health KW - X 24180:Social poisons & drug abuse KW - H SM10.21:CANCER UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16825419?accountid=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=Cigarette+smoking+and+alcohol+consumption+and+the+risk+of+pancreatic+cancer%3A+A+case-control+study+in+Shanghai%2C+China&rft.au=Ji%2C+Bu-Tian%3BChow%2C+Wong-Ho%3BDai%2C+Qi%3BMcLaughlin%2C+J+K%3BBenichou%2C+J%3BHatch%2C+M-C%3BGao%2C+Yu-Tang%3BFraumeni%2C+JF+Jr&rft.aulast=Ji&rft.aufirst=Bu-Tian&rft.date=1995-01-01&rft.volume=6&rft.issue=4&rft.spage=369&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - China, People's Rep., Shanghai; cigarettes; smoking; alcohol; cancer; ethanol; pancreas; man ER - TY - JOUR T1 - Identification of an immunologically cross-reactive 60-kilodalton Renibacterium salmoninarum protein distinct from p57: Implications for immunodiagnostics AN - 16822293; 3766335 AB - Renibacterium salmoninarum produces an abundant cell surface and secreted protein (p57) with a mass of 57 kilodaltons (kDa) that is targeted for use in antibody-based diagnostic assays. A recent report suggested that p57 has immunologically related comigrating homologs in other species of bacteria. Because of the implications of cross-reactivity for the utility of these assays, we evaluated the specificity of anti-p57 monoclonal antibodies (MAbs) and polyclonal anti-R. salmoninarum serum as probes for lysates of R. salmoninarum and nine other selected bacteria. Immunoblots were also probed with polyclonal antisera against the ubiquitous 60-kDa heat shock protein (hsp60) from Chlamydia psittaci. Consistent with the previous report, rabbit anti-R. salmoninarum serum produced in our laboratory recognized a 57-60-kDa protein in three other gram-positive bacteria; however, none of the seven anti-p57 MAbs recognized similarly sized proteins in any species other than R. salmoninarum. Immunoblotting with the anti-hsp60 sera demonstrated that the antigenically conserved 60-kDa heat shock proteins, which comigrate with p57, may be responsible for the described cross-reactivity. These results provide a possible explanation for the cross-reactivity of anti-R. salmoninarum polyclonal sera, and confirm the importance of examining the specificity of polyclonal and monoclonal antibody reagents prior to their use in diagnostic assays. JF - Journal of Aquatic Animal Health AU - Wood, P A AU - Wiens, G D AU - Rohovec, J S AU - Rockey, D D AD - Lab. Intracell. Parasites, Rocky Mountain Lab., NIAID/NIH, Hamilton, MT 59840, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 95 EP - 103 VL - 7 IS - 2 SN - 0899-7659, 0899-7659 KW - bacterial diseases KW - disease detection KW - fish diseases KW - ASFA 1: Biological Sciences & Living Resources; ASFA 3: Aquatic Pollution & Environmental Quality; ASFA Marine Biotechnology Abstracts; Microbiology Abstracts B: Bacteriology; ASFA Aquaculture Abstracts; Oceanic Abstracts KW - Freshwater KW - Renibacterium salmoninarum KW - immunology KW - immunoassays KW - Salmonidae KW - proteins KW - J 02832:Antigenic properties and virulence KW - O 1090:Instruments/Methods KW - Q1 08484:Species interactions: parasites and diseases KW - Q3 08582:Fish culture KW - Q4 27420:Other UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16822293?accountid=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+Aquatic+Animal+Health&rft.atitle=Identification+of+an+immunologically+cross-reactive+60-kilodalton+Renibacterium+salmoninarum+protein+distinct+from+p57%3A+Implications+for+immunodiagnostics&rft.au=Wood%2C+P+A%3BWiens%2C+G+D%3BRohovec%2C+J+S%3BRockey%2C+D+D&rft.aulast=Wood&rft.aufirst=P&rft.date=1995-01-01&rft.volume=7&rft.issue=2&rft.spage=95&rft.isbn=&rft.btitle=&rft.title=Journal+of+Aquatic+Animal+Health&rft.issn=08997659&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2014-05-06 N1 - SubjectsTermNotLitGenreText - immunology; fish diseases; immunoassays; disease detection; bacterial diseases; proteins; Renibacterium salmoninarum; Salmonidae; Freshwater ER - TY - JOUR T1 - Comparison of results from mouse bone marrow chromosome aberration and micronucleus tests AN - 16817693; 3761043 AB - Tests for the induction of chromosomal aberrations (ABS) and micronuclei (MN) in bone marrow cells of mice have been conducted on 65 chemicals. Although these tests were not conducted with the purpose of comparing the outcomes of these two in vivo genetic toxicity endpoints, the availability of these test results permits such a comparison. Based on studies to date, results from the 2 tests agree for more than 80% of the chemicals; 17 gave positive results in both tests, and 36 gave negative results in both. Seven chemicals were positive only for ABS and 5 were positive only for MN. Three chemicals that were originally concluded to be positive for ABS but not for MN were found to induce MN when the MN protocol was modified to more closely reflect the ABS protocol. Among the 12 chemicals for which there are discrepant results, there are only 2 for which the difference is convincing. One of these, selenium sulfide (MN negative, ABS positive) remains an enigma; further studies are being conducted. The second, isoprene (MN positive, ABS negative) will be difficult to pursue because the studies reported here were done by inhalation exposure. Based on the outcomes of these comparisons, protocol factors, rather than endpoint specificity, appear to be the major source of discrepant test results. Thus, these results do not support a recommendation that both tests be conducted in a primary testing scheme for genetic toxicity. JF - Environmental and Molecular Mutagenesis AU - Shelby, MD AU - Witt, K L AD - NIEHS, A2-03, P.O. Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 302 EP - 313 VL - 25 IS - 4 SN - 0893-6692, 0893-6692 KW - mice KW - Genetics Abstracts; Toxicology Abstracts KW - cytogenetics KW - chromosome aberrations KW - genotoxicity testing KW - micronuclei KW - bone marrow KW - G 07220:General theory/testing systems KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16817693?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+and+Molecular+Mutagenesis&rft.atitle=Comparison+of+results+from+mouse+bone+marrow+chromosome+aberration+and+micronucleus+tests&rft.au=Shelby%2C+MD%3BWitt%2C+K+L&rft.aulast=Shelby&rft.aufirst=MD&rft.date=1995-01-01&rft.volume=25&rft.issue=4&rft.spage=302&rft.isbn=&rft.btitle=&rft.title=Environmental+and+Molecular+Mutagenesis&rft.issn=08936692&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - bone marrow; chromosome aberrations; micronuclei; cytogenetics; genotoxicity testing ER - TY - JOUR T1 - Electro-transformation of Escherichia coli with plasmid DNA AN - 16813172; 3762735 AB - Methods and reagents is a unique monthly column that highlights current discussions in the newsgroup bionet.molbio.methds-reagnts, available on the Internet. This month's column discusses some reasons for switching to electroporation to transform bacteria with plasmid DNA. For details on how to partake in the newsgroup, see the accompanying box. JF - Trends in Biochemical Sciences AU - Hengen, P N AD - NCI-FCRDC, Frederick, MD 21702-1201, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 248 EP - 249 VL - 20 IS - 6 SN - 0968-0004, 0968-0004 KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Escherichia coli KW - plasmids KW - methodology KW - electroporation KW - J 02705:Others KW - N 14674:Transformation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16813172?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+Biochemical+Sciences&rft.atitle=Electro-transformation+of+Escherichia+coli+with+plasmid+DNA&rft.au=Hengen%2C+P+N&rft.aulast=Hengen&rft.aufirst=P&rft.date=1995-01-01&rft.volume=20&rft.issue=6&rft.spage=248&rft.isbn=&rft.btitle=&rft.title=Trends+in+Biochemical+Sciences&rft.issn=09680004&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; electroporation; plasmids; methodology ER - TY - JOUR T1 - Lipid metabolism in Chlamydia trachomatis-infected cells: Directed trafficking of Golgi-derived sphingolipids to the chlamydial inclusion AN - 16812269; 3763171 AB - Chlamydia trachomatis undergoes its entire life cycle within an uncharacterized intracellular vesicle that does not fuse with lysosomes. We used a fluorescent Golgi-specific probe, {N-[7-(4-nitrobenzo-2-oxa-1,3-diazole)] } aminocaproylsphingosine (C sub(6)-NBD-Cer), in conjunction with conventional fluorescence or confocal microscopy to identify interactions between the Golgi apparatus and the chlamydial inclusion. We observed not only a close physical association between the Golgi apparatus and the chlamydial inclusion but the eventual presence of a metabolite of this fluorescent probe associated with the chlamydiae themselves. Sphingomyelin, endogenously synthesized from C sub(6)-NBD-Cer, was specifically transported to the inclusion and incorporated into the cell wall of the intracellular chlamydiae. Incorporation of the fluorescent sphingolipid by chlamydiae was inhibited by brefeldin A. Chlamydiae therefore occupy a vesicle distal to the Golgi apparatus that receives anterograde vesicular traffic from the Golgi normally bound for the plasma membrane. Collectively, the data suggest that the chlamydial inclusion may represent a unique compartment within the trans-Golgi network. JF - Proceedings of the National Academy of Sciences, USA AU - Hackstadt, T AU - Scidmore, MA AU - Rockey, D D AD - Lab. Intracell. Parasites, NIAID/NIH, Rocky Mountain Lab., Hamilton, MT 59840, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 4877 EP - 4881 VL - 92 IS - 11 SN - 0027-8424, 0027-8424 KW - Microbiology Abstracts B: Bacteriology KW - inclusion bodies KW - Golgi apparatus KW - fluorescence KW - sphingolipids KW - Chlamydia trachomatis KW - translocation KW - J 02731:Lipids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16812269?accountid=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=Lipid+metabolism+in+Chlamydia+trachomatis-infected+cells%3A+Directed+trafficking+of+Golgi-derived+sphingolipids+to+the+chlamydial+inclusion&rft.au=Hackstadt%2C+T%3BScidmore%2C+MA%3BRockey%2C+D+D&rft.aulast=Hackstadt&rft.aufirst=T&rft.date=1995-01-01&rft.volume=92&rft.issue=11&rft.spage=4877&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Chlamydia trachomatis; sphingolipids; fluorescence; Golgi apparatus; inclusion bodies; translocation ER - TY - JOUR T1 - Lipid peroxidation in rats intoxicated with 3-nitropropionic acid AN - 16805902; 3754707 AB - Ingestion of mildewed sugarcane may cause acute toxicity in human. Studies have found that 3-nitropropionic acid (3-NPA), a mycotoxin produced by Arthrinium spp. contaminants of the sugarcanes, is the origin of the disease. Using an electron spin resonance technique, free radical signals were observed to be increased in liver of rats 15, 30 and 45 min after orally dosing with 80 mg/kg 3-nitropropionic acid (3-NPA). Concentrations of 3-NPA from 595 to 2380 mg/litre enhanced the formation of adrenochrome from adrenaline in mitochondria and microsome suspensions of liver and brain. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) as well as the content of malonidialdehyde (MDA) were significantly increased in liver of rats dosed with 80 mg/kg 3-NPA. There was also a cerebral increase of activity of SOD and content of MDA. These results suggest that 3-NPA is able to produce lipid peroxidation both in vivo and in vitro. JF - Toxicon AU - Fu, Yi-Tong AU - He, Feng-Sheng AU - Zhang, Shou-Lin AU - Zhang, Jin-Son AD - NINDS/NIH, Build. 49, Rm. 3B79, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 327 EP - 331 VL - 33 IS - 3 SN - 0041-0101, 0041-0101 KW - rats KW - 3-nitropropionic acid KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; Toxicology Abstracts KW - Arthrinium KW - lipid peroxidation KW - mycotoxins KW - K 03082:Mycotoxins KW - X 24171:Microbial UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16805902?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicon&rft.atitle=Lipid+peroxidation+in+rats+intoxicated+with+3-nitropropionic+acid&rft.au=Fu%2C+Yi-Tong%3BHe%2C+Feng-Sheng%3BZhang%2C+Shou-Lin%3BZhang%2C+Jin-Son&rft.aulast=Fu&rft.aufirst=Yi-Tong&rft.date=1995-01-01&rft.volume=33&rft.issue=3&rft.spage=327&rft.isbn=&rft.btitle=&rft.title=Toxicon&rft.issn=00410101&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Arthrinium; lipid peroxidation; mycotoxins ER - TY - JOUR T1 - Activities of amphotericin B and antifungal azoles alone and in combination against Pseudallescheria boydii AN - 16804903; 3755173 AB - In order to develop new approaches to treatment of infections due to Pseudallescheria boydii, the in vitro antifungal activity of amphotericin B alone and in combination with miconazole, itraconazole, and fluconazole was studied. Combinations of amphotericin B and antifungal azoles were synergistic, additive, or indifferent in their interaction against P. boydii. Antagonism was not observed. JF - Antimicrobial Agents & Chemotherapy AU - Walsh, T J AU - Peter, J AU - McGough, DA AU - Fothergill, A W AU - Rinaldi, M G AU - Pizzo, P A AD - Infect. Dis. Sect., NCI/NIH, Build. 10, Rm. 13N-240, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 1361 EP - 1364 VL - 39 IS - 6 SN - 0066-4804, 0066-4804 KW - amphotericin B KW - azoles KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - Pseudallescheria boydii KW - antifungal activity KW - A 01067:Antifungal & fungicidal KW - K 03063:Effects of physical & chemical factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16804903?accountid=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=Antimicrobial+Agents+%26+Chemotherapy&rft.atitle=Activities+of+amphotericin+B+and+antifungal+azoles+alone+and+in+combination+against+Pseudallescheria+boydii&rft.au=Walsh%2C+T+J%3BPeter%2C+J%3BMcGough%2C+DA%3BFothergill%2C+A+W%3BRinaldi%2C+M+G%3BPizzo%2C+P+A&rft.aulast=Walsh&rft.aufirst=T&rft.date=1995-01-01&rft.volume=39&rft.issue=6&rft.spage=1361&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 N1 - SubjectsTermNotLitGenreText - Pseudallescheria boydii; antifungal activity ER - TY - JOUR T1 - Identification of a gene involved in the biosynthesis of cyclopropanated mycolic acids in Mycobacterium tuberculosis AN - 16802544; 3755459 AB - Mycolic acids represent a major constituent of the mycobacterial cell wall complex, which provides the first line of defense against potentially lethal environmental conditions. Slow-growing pathogenic mycobacteria such as Mycobacterium tuberculosis modify their mycolic acids by cyclopropanation, whereas fast-growing saprophytic species such as Mycobacterium smegmatis do not, suggesting that this modification may be associated with an increase in oxidative stress experienced by the slow-growing species. We have demonstrated the transformation of the distal cis double bond in the major mycolic acid of M. smegmatis to a cis-cyclopropane ring upon introduction of cosmid DNA from M. tuberculosis. This activity was localized to a single gene (cma1) encoding a protein that was 34% identical to the cyclopropane fatty acid synthase from Escherichia coli. Adjacent regions of the DNA sequence encode open reading frames that display homology to other fatty acid biosynthetic enzymes, indicating that some of the genes required for mycolic acid biosynthesis may be clustered in this region. M. smegmatis overexpressing the cma1 gene product significantly resist killing by hydrogen peroxide, suggesting that this modification may be an important adaptation of slow-growing mycobacteria to oxidative stress. JF - Proceedings of the National Academy of Sciences, USA AU - Yuan, Ying AU - Lee, R E AU - Besra, G S AU - Belisle, J T AU - Barry, CE III AD - Lab. Intracell. Parasites, Tuberc. Res. Unit, NIAID, Rocky Mountain Lab., Hamilton, MT 59840, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 6630 EP - 6634 VL - 92 IS - 14 SN - 0027-8424, 0027-8424 KW - mycolic acids KW - cma1 gene KW - cyclopropane fatty acid synthase KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - cell walls KW - oxidative stress KW - Mycobacterium smegmatis KW - Mycobacterium tuberculosis KW - N 14640:Structure & sequence KW - G 07321:GENERAL KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16802544?accountid=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=Identification+of+a+gene+involved+in+the+biosynthesis+of+cyclopropanated+mycolic+acids+in+Mycobacterium+tuberculosis&rft.au=Yuan%2C+Ying%3BLee%2C+R+E%3BBesra%2C+G+S%3BBelisle%2C+J+T%3BBarry%2C+CE+III&rft.aulast=Yuan&rft.aufirst=Ying&rft.date=1995-01-01&rft.volume=92&rft.issue=14&rft.spage=6630&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mycobacterium tuberculosis; Mycobacterium smegmatis; cell walls; oxidative stress ER - TY - JOUR T1 - Cloning, sequencing and expression of the dnaJ gene of Coxiella burnetii AN - 16802429; 3755429 AB - A 6-kb EcoRI genomic DNA fragment of Coxiella burnetii, isolated from a recombinant bacteriophage lambda ZapII library, allowed heterologous genetic complementation of Escherichia coli deleted for its dnaJ gene. The C. burnetii dnaJ gene was expressed in E. coli and identified by Western blot analysis using polyclonal antibodies raised against purified E. coli DnaJ protein. Deletion mapping and genetic complementation demonstrated that C. burnetii dnaJ is present on a 2-kb EcoRI-HindIII genomic DNA fragment, from which the nt sequence of the C. burnetii dnaJ gene was determined. JF - Gene AU - Zuber, M AU - Hoover, T A AU - Court, D L AD - Lab. Chromosome Biol., ABL-Basic Res. Program, NCI-Frederick Cancer Res. and Dev. Cent., Frederick, MD 21702, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 99 EP - 102 VL - 152 IS - 1 SN - 0378-1119, 0378-1119 KW - dnaJ gene KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - heat shock proteins KW - cloning KW - nucleotide sequence KW - Coxiella burnetii KW - gene expression KW - N 14640:Structure & sequence KW - G 07321:GENERAL KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16802429?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gene&rft.atitle=Cloning%2C+sequencing+and+expression+of+the+dnaJ+gene+of+Coxiella+burnetii&rft.au=Zuber%2C+M%3BHoover%2C+T+A%3BCourt%2C+D+L&rft.aulast=Zuber&rft.aufirst=M&rft.date=1995-01-01&rft.volume=152&rft.issue=1&rft.spage=99&rft.isbn=&rft.btitle=&rft.title=Gene&rft.issn=03781119&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Coxiella burnetii; cloning; gene expression; nucleotide sequence; heat shock proteins ER - TY - JOUR T1 - Isolation and characterization of a syncytium-inducing, macrophage/T-cell line-tropic human immunodeficiency virus type 1 isolate that readily infects chimpanzee cells in vitro and in vivo AN - 16799586; 3754002 AB - Fresh human immunodeficiency virus type 1 (HIV-1) isolates from patients with AIDS were screened for infectivity in chimpanzee peripheral blood mononuclear cells (PBMC) to identify strains potentially able to generate high virus loads in an inoculated animal. Only 3 of 23 isolates obtained were infectious in chimpanzee cells. Of these three, only one (HIV-1 sub(DH12)) was able to initiate a productive infection in PBMC samples from all 25 chimpanzees tested. HIV-1 sub(DH12) tissue culture infections were characterized by extremely rapid replication kinetics, profound cytopathicity, and tropism for chimp and human PBMC, primary human macrophage, and several human T-cell lines. An infection was established within 1 week of inoculating a chimpanzee with 50 50% tissue culture infective doses of HIV-1 sub(DH12); cell-free virus was recovered from the plasma at weeks 1, 2, and 4 and was associated with the development of lymphadenopathy. Virus loads during the primary infection and at 6 months postinoculation were comparable to those reported in HIV-1-seropositive individuals. JF - Journal of Virology AU - Shibata, R AU - Hoggan, MD AU - Broscius, C AU - Englund, G AU - Theodore, T S AU - Buckler-White, A AU - Arthur, LO AU - Israel, Z AU - Martin, MA AD - Lab. Mol. Microbiol., NIAID/NIH, Bethesda, MD 20892-0460, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 4453 EP - 4462 VL - 69 IS - 7 SN - 0022-538X, 0022-538X KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - replication KW - human immunodeficiency virus 1 KW - isolation KW - cytopathology KW - infection KW - animal models KW - macrophages KW - man KW - Pan troglodytes KW - V 22002:AIDS: Molecular and in vitro aspects KW - W3 33240:Immunology KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16799586?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Virology&rft.atitle=Isolation+and+characterization+of+a+syncytium-inducing%2C+macrophage%2FT-cell+line-tropic+human+immunodeficiency+virus+type+1+isolate+that+readily+infects+chimpanzee+cells+in+vitro+and+in+vivo&rft.au=Shibata%2C+R%3BHoggan%2C+MD%3BBroscius%2C+C%3BEnglund%2C+G%3BTheodore%2C+T+S%3BBuckler-White%2C+A%3BArthur%2C+LO%3BIsrael%2C+Z%3BMartin%2C+MA&rft.aulast=Shibata&rft.aufirst=R&rft.date=1995-01-01&rft.volume=69&rft.issue=7&rft.spage=4453&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - replication; cytopathology; isolation; infection; animal models; macrophages; man; human immunodeficiency virus 1; Pan troglodytes ER - TY - JOUR T1 - Preferential binding of cisplatin to mitochondrial DNA of Chinese hamster ovary cells AN - 16799316; 3754117 AB - Some chemical carcinogens localize preferentially in mitochondrial DNA (mtDNA) when compared with genomic DNA (gDNA). Here we compare the ability of cisplatin (cis-diamminedichloroplatinum[II]) to induce DNA adducts in both genomic and mtDNA of Chinese hamster ovary (CHO) cells in culture. Cytotoxicity was examined by cell survival 4, 8 and 24 h after exposure to 50 mu M cisplatin. Cisplatin-DNA adducts were measured in DNA from nuclear and mitochondrial fractions by dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA), a sensitive competitive microtiter-based immunoassay utilizing antiserum elicited against cisplatin-modified DNA. An additional comparison of cisplatin-DNA binding in both compartments was performed by immunoelectron microscopy using the cisplatin-DNA antiserum and colloidal gold. DELFIA analysis of cisplatin-DNA adducts in gDNA and mtDNA showed a six-fold higher incorporation of drug into mtDNA as compared to gDNA. Morphometric studies of colloidal gold distribution in photomicrographs of CHO cells showed mtDNA to contain a four-fold higher concentration of cisplatin as compared to nuclear DNA. Therefore, both methods demonstrated a preferential binding of cisplatin to mtDNA versus gDNA. JF - Mutation Research-Mutation Research Letters AU - Olivero, O A AU - Semino, C AU - Kassim, A AU - Lopez-Larraza, D M AU - Poirier, M C AD - Lab. Cell. Carcinog. and Tumor Promot., NIH, Build. 37, Rm 3B12, 9000 Rockville Pike, NCI, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 221 EP - 230 VL - 346 IS - 4 SN - 0165-7992, 0165-7992 KW - cisplatin KW - hamsters KW - Biochemistry Abstracts 2: Nucleic Acids; Toxicology Abstracts KW - DNA adducts KW - metals KW - immunoassays KW - mitochondrial DNA KW - N 14630:Chemical reactions & interactions, including effects of radiation KW - X 24114:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16799316?accountid=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-Mutation+Research+Letters&rft.atitle=Preferential+binding+of+cisplatin+to+mitochondrial+DNA+of+Chinese+hamster+ovary+cells&rft.au=Olivero%2C+O+A%3BSemino%2C+C%3BKassim%2C+A%3BLopez-Larraza%2C+D+M%3BPoirier%2C+M+C&rft.aulast=Olivero&rft.aufirst=O&rft.date=1995-01-01&rft.volume=346&rft.issue=4&rft.spage=221&rft.isbn=&rft.btitle=&rft.title=Mutation+Research-Mutation+Research+Letters&rft.issn=01657992&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 - mitochondrial DNA; DNA adducts; immunoassays; metals ER - TY - JOUR T1 - Breastfeeding and breast cancer risk AN - 16799290; 3754943 AB - A population-based case-control study of breast cancer with a focus on premenopausal women under 45 years of age, conducted in three geographic regions of the United States, enabled the evaluation of risk in relation to varying breastfeeding practices. Among premenopausal parous women, a history of breastfeeding for two or more weeks was associated with a relative risk (RR) of 0.87. This relationship was not altered substantially by removing from the reference group women who had problems with breastfeeding in the first two weeks, including those with insufficient milk production. Risk was not related substantially to number of children breasfed or length of breastfeeding, although a relatively low risk was observed among those breastfeeding for the longest duration examined. Women who began to breastfeed at a young age (<22 years) experienced the greatest reduction in risk, but other timing parameters were not predictive of risk. Risks were not modified substantially by age or menopause status, although the number of menopausal subjects examined was limited. Use of medications to stop breast milk was unrelated to risk. The results of this study do not support the notion that breastfeeding substantially reduces breast cancer risk; however, this may reflect the fact that most of our study subjects breasfed only for limited periods of time (average breastfeeding per child of 30 weeks). JF - Cancer Causes & Control AU - Brinton, LA AU - Potischman, NA AU - Swanson, CA AU - Schoenberg, J B AU - Coates, R J AU - Gammon, MD AU - Malone, KE AU - Stanford, J L AU - Daling, J R AD - Environ. Epidemiol. Branch, NCI, Executive Plaza N., Room 443, Bethesda, MS 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 199 EP - 208 VL - 6 IS - 3 SN - 0957-5243, 0957-5243 KW - breast feeding KW - Risk Abstracts; Health & Safety Science Abstracts KW - breast cancer KW - USA KW - risk assessment KW - R2 23060:Medical and environmental health KW - H SM10.21:CANCER UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16799290?accountid=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=Breastfeeding+and+breast+cancer+risk&rft.au=Brinton%2C+LA%3BPotischman%2C+NA%3BSwanson%2C+CA%3BSchoenberg%2C+J+B%3BCoates%2C+R+J%3BGammon%2C+MD%3BMalone%2C+KE%3BStanford%2C+J+L%3BDaling%2C+J+R&rft.aulast=Brinton&rft.aufirst=LA&rft.date=1995-01-01&rft.volume=6&rft.issue=3&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 N1 - SubjectsTermNotLitGenreText - USA; breast cancer; risk assessment ER - TY - JOUR T1 - Flow cytometric analysis of the granulocyte respiratory burst: A comparison study of fluorescent probes AN - 16799028; 3750732 AB - Chronic granulomatous disease (CGD) is a rare recessive disorder caused by defects in the NADPH oxidase enzyme complex of phagocytes (neutrophils, eosinophils and monocytes). CGD phagocytes fail to produce superoxide and other reactive oxygen species following cell activation (Malech, 1993). The products of oxidase activation can be measured in individual cells by flow cytometry using specific fluorescent probes that increase fluorescence upon oxidation. This approach can be used to confirm a diagnosis of CGD, and to detect the normal/abnormal phagocyte mixture that characterizes the X-linked CGD carrier state. Three fluorescent probes have been described as useful for this purpose: 2'7'-dichlorofluorescin diacetate (DCF), 5,6-carboxy-2'7'-dichlorofluorescein diacetate, bis(acetoxymethyl) ester (C-DCF) and dihydrorhodamine 123 (DHR). A direct comparison between these three probes has not been reported. In this study we performed a direct comparison between these three probes, evaluating their ability in flow cytometric analysis to maximize fluorescent separation between activated CGD patient and normal granulocytes. Using a whole blood technique with phorbol myristate acetate (PMA) as an activator, it was found that DHR loaded normal granulocytes had a fluorescence intensity which, upon activation, was 48-fold higher than that of C-DCF loaded granulocytes and seven-fold higher than DCF loaded granulocytes. Use of sodium azide to decrease the catabolism of H sub(2)O sub(2) enhanced the fluorescence of DCF by 140%, C-DCF by 45% and DHR by 25%, suggesting that DCF is primarily sensitive to H sub(2)O sub(2). DCF and DHR were then evaluated for sensitivity in the detection of small percentages of normal cells in a CGD/normal granulocyte mixture. Normal sub-populations as small as 0.1% could clearly be distinguished using DHR, while DCF was insensitive at this level. Based on these findings, we used DHR in an effort to detect normal granulocytes in a CGD patient following therapeutic granulocyte transfusion. We were able to detect normal granulocytes in the circulation for up to 18 h after transfusion. With these data we show that DHR is the most sensitive flow cytometric indicator for the detection of oxygen reactive species in activated granulocytes and is the best probe for evaluating CGD patients and carriers. In addition, our data suggest that DHR is a useful tool for monitoring circulating normal granulocytes in CGD patients following transfusion, and potentially will be a sensitive probe for assessing the success of such future technologies as gene therapy for CGD. JF - Journal of Immunological Methods AU - Vowells, S J AU - Sekhsaria, S AU - Malech, H L AU - Shalit, M AU - Fleisher, T A AD - Lab. Host Def., NIAID/NIH, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 89 EP - 97 VL - 178 IS - 1 SN - 0022-1759, 0022-1759 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - respiratory burst KW - chronic granulomatous disease KW - fluorescence KW - immunodeficiency KW - leukocytes (granulocytic) KW - flow cytometry KW - man KW - W3 33240:Immunology KW - F 06727:Tests of leukocyte function KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16799028?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunological+Methods&rft.atitle=Flow+cytometric+analysis+of+the+granulocyte+respiratory+burst%3A+A+comparison+study+of+fluorescent+probes&rft.au=Vowells%2C+S+J%3BSekhsaria%2C+S%3BMalech%2C+H+L%3BShalit%2C+M%3BFleisher%2C+T+A&rft.aulast=Vowells&rft.aufirst=S&rft.date=1995-01-01&rft.volume=178&rft.issue=1&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunological+Methods&rft.issn=00221759&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - chronic granulomatous disease; respiratory burst; immunodeficiency; fluorescence; leukocytes (granulocytic); flow cytometry; man ER - TY - JOUR T1 - Synergistic inhibition of human immunodeficiency virus type 1 envelope glycoprotein-mediated cell fusion and infection by an antibody to CD4 domain 2 in combination with anti-gp120 antibodies AN - 16798989; 3754028 AB - Antibodies to several epitopes of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (gp120-gp41) can synergize in inhibiting HIV-1 infection. In the present study we tested the ability of a monoclonal antibody (MAb), 5A8, which interacts with CD4 domain 2, and other CD4-specific MAbs to synergize with antibodies against gp120. We have previously found that 5A8 inhibits HIV-1 entry without interfering with gp120 binding to CD4, presumably by affecting a postbinding membrane fusion event. Because antibodies to the gp120 V3 loop also affect post-CD4-gp120-binding events, 5A8 was first tested in combination with anti-V3 loop antibodies for possible synergy. The anti-V3 loop antibodies 0.5 beta , NEA-9205, and 110.5 acted synergistically with 5A8 in inhibiting syncytium formation between gp120-gp41- and CD4-expressing cells. A human MAb to an epitope of gp120 involved in CD4 binding, IAM 120-1B1, and another anti-CD4 binding site antibody, PC39.13, also exerted synergistic effects in combination with 5A8. Similarly, an antibody against the gp120 binding site on CD4, 6H10, acted synergistically with an anti-V3 loop antibody, NEA-9205. However, a control anti-CD4 antibody, OKT4, which does not significantly inhibit syncytium formation alone, produced only an additive effect when combined with NEA-9205. Serum from HIV-1-infected individuals, which presumably contains antibodies to the V3 loop and the CD4 binding site, exhibited a strong synergistic effect with 5A8 in inhibiting infection by a patient HIV-1 isolate (0104B) and in blocking syncytium formation. These results indicate that therapeutics based on antibodies affecting both non-gp120 binding and gp120 binding epitopes of the target receptor molecule, CD4, could be efficient in patients who already contain anti-gp120 antibodies and could also be used to enhance passive immunization against HIV-1 in combination with anti-gp120 antibodies. JF - Journal of Virology AU - Burkly, L AU - Mulrey, N AU - Blumenthal, R AU - Dimitrov, D S AD - NCI/NIH, Bldg. 10, Rm. 4A01, 10 Center Dr., MSC 1350, Bethesda, MD 20892-1350, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 4267 EP - 4273 VL - 69 IS - 7 SN - 0022-538X, 0022-538X KW - CD4 antigen KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts; Virology & AIDS Abstracts KW - cell fusion KW - human immunodeficiency virus 1 KW - inhibition KW - infection KW - synergism KW - monoclonal antibodies KW - immunization (passive) KW - syncytia KW - W3 33375:Antibodies KW - F 06806:Passive 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/16798989?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Virology&rft.atitle=Synergistic+inhibition+of+human+immunodeficiency+virus+type+1+envelope+glycoprotein-mediated+cell+fusion+and+infection+by+an+antibody+to+CD4+domain+2+in+combination+with+anti-gp120+antibodies&rft.au=Burkly%2C+L%3BMulrey%2C+N%3BBlumenthal%2C+R%3BDimitrov%2C+D+S&rft.aulast=Burkly&rft.aufirst=L&rft.date=1995-01-01&rft.volume=69&rft.issue=7&rft.spage=4267&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - cell fusion; inhibition; synergism; infection; immunization (passive); monoclonal antibodies; syncytia; human immunodeficiency virus 1 ER - TY - JOUR T1 - Autoinducer-mediated regulation of rhamnolipid biosurfactant synthesis in Pseudomonas aeruginosa AN - 16798842; 3753959 AB - The opportunistic human pathogen Pseudomonas aeruginosa produces a variety of virulence factors, including exotoxin A, elastase, alkaline protease, alginate, phospholipases, and extracellular rhamnolipids. The previously characterized rhlABR gene cluster encodes a regulatory protein (RhlR) and a rhamnosyltransferase (RhlAB), both of which are required for rhamnolipid synthesis. Another gene, rhlI, has now been identified downstream of the rhlABR gene cluster. The putative RhlI protein shares significant sequence similarity with bacterial autoinducer synthetases of the LuxI type. A P. aeruginosa rhlI mutant strain carrying a disrupted rhlI gene was unable to produce rhamnolipids and lacked rhamnosyltransferase activity. Rhamnolipid synthesis was restored by introducing a wild-type rhlI gene into such strains or, alternatively, by adding either the cell-free spent supernatant from a P. aeruginosa wild-type strain or synthetic N-acylhomoserine lactones. Half-maximal induction of rhamnolipid synthesis in the rhlI mutant strain required 0.5 mu M N-butyrylhomoserine lactone or 10 mu M N-(3-oxohexanoyl)homoserine lactone. The P. aeruginosa rhlA promoter was active in the heterologous host Pseudomonas putida when both the rhlR and rhlI genes were present or when the rhlR gene alone was supplied together with synthetic N-acylhomoserine lactones. The RhlR-RhlI regulatory system was found to be essential for the production of elastase as well, and cross-communication between the RhlR-RhlI rhamnolipid regulatory system and the LasR-LasI elastase regulatory system was demonstrated. JF - Proceedings of the National Academy of Sciences, USA AU - Ochsner, U A AU - Reiser, J AD - NINDS/NIH, Build. 10, Rm. 3D04, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 6424 EP - 6428 VL - 92 IS - 14 SN - 0027-8424, 0027-8424 KW - rhamnolipids KW - exotoxin A KW - elastase KW - alkaline phosphatase KW - alginate KW - phospholipase KW - rhlABR gene KW - RhlR protein KW - RhlAB protein KW - rhlI gene KW - LuxI protein KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - gene regulation KW - virulence KW - Pseudomonas aeruginosa KW - J 02731:Lipids KW - G 07321:GENERAL UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16798842?accountid=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=Autoinducer-mediated+regulation+of+rhamnolipid+biosurfactant+synthesis+in+Pseudomonas+aeruginosa&rft.au=Ochsner%2C+U+A%3BReiser%2C+J&rft.aulast=Ochsner&rft.aufirst=U&rft.date=1995-01-01&rft.volume=92&rft.issue=14&rft.spage=6424&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Pseudomonas aeruginosa; virulence; gene regulation ER - TY - JOUR T1 - Fertility in men exposed prenatally to diethylstilbestrol AN - 16798756; 3753320 AB - Prenatal exposure to diethylstilbestrol causes infertility in male mice and has been associated with malformations of the genital tract in men. However, little is known about the fertility of men who have been exposed prenatally to diethylstilbestrol. In 1950 through 1952, 1646 pregnant women were enrolled in a randomized, placebo-controlled clinical trial of diethylstilbestrol at Chicago Lying-in Hospital. We interviewed men who were born to the women during that study about their fertility. Four decades after their birth, we were able to trace 548 of the surviving sons (68 percent). Ninety percent consented to be interviewed (253 who had been exposed to diethylstilbestrol in utero and 241 who had not been exposed). Congenital malformations of the genitalia were reported three times as often by the diethylstilbestrol-exposed men as by the sons of the women in the placebo group. Within the exposed group, malformations were reported twice as often among those exposed to diethylstilbestrol before the 11th week of gestation as among those exposed later (P = 0.05). Men with genital malformations were nonetheless as fertile as other men. The diethylstilbestrol-exposed men (with or without genital malformations) had no impairment of fertility by any measure, including whether they had ever impregnated a woman, age at the birth of their first child, average number of children, medical diagnosis of a fertility problem, or length of time to conception in the most recent pregnancy of the female partner. Finally, diethylstilbestrol-exposed men had no impairment of sexual function, as indicated, for example, by the frequency of intercourse or reported episodes of decreased libido. High doses of diethylstilbestrol did not lead to impairment of fertility or sexual function in adult men who had been exposed to the drug in utero. JF - New England Journal of Medicine AU - Wilcox, A J AU - Baird, D D AU - Weinberg, C R AU - Hornsby, P P AU - Herbst, AL AD - Epidemiol. Branch, NIEHS, Research Triangle Park, NC 27709, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 1411 EP - 1416 VL - 332 IS - 21 SN - 0028-4793, 0028-4793 KW - diethylstilbestrol KW - man KW - Risk Abstracts; Health & Safety Science Abstracts; Toxicology Abstracts KW - side effects KW - fertility KW - prenatal experience KW - H SE4.28:PHARMACEUTICALS KW - R2 23060:Medical and environmental health KW - X 24113:Side effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16798756?accountid=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=New+England+Journal+of+Medicine&rft.atitle=Fertility+in+men+exposed+prenatally+to+diethylstilbestrol&rft.au=Wilcox%2C+A+J%3BBaird%2C+D+D%3BWeinberg%2C+C+R%3BHornsby%2C+P+P%3BHerbst%2C+AL&rft.aulast=Wilcox&rft.aufirst=A&rft.date=1995-01-01&rft.volume=332&rft.issue=21&rft.spage=1411&rft.isbn=&rft.btitle=&rft.title=New+England+Journal+of+Medicine&rft.issn=00284793&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 - fertility; side effects; prenatal experience; man ER - TY - JOUR T1 - The effect of nickel compounds on immuno-phenotype and natural killer cell function of normal human lymphocytes AN - 16798638; 3748350 AB - In order to elucidate effects of nickel on human lymphocytes in vitro, peripheral blood mononuclear cells from normal donors were initially tested for viability in the presence of increasing concentrations of two selected nickel salts, sparingly-soluble nickel subsulfide (Ni sub(3)S sub(2)), and promptly-soluble nickel sulfate (NiSO sub(4)). After establishing the toxicity profile, the cells were cultured for 24 h with each compound at three nontoxic concentrations, 0.01 mM, 0.02 mM, and 0.04 mM, to determine its effect on lymphocyte immunophenotype and function. Cells were also cultured in the presence of 0.01-0.04 mM magnesium acetate, Mg(CH sub(3)COO) sub(2), while still other cell samples were subjected to a mixture of Mg(CH sub(3)COO) sub(2) plus either Ni sub(3)S sub(2) or NiSO sub(4) at equimolar concentration. Following the culture, the immunophenotype of the cells was determined by indirect immunofluorescence, using monoclonal antibodies to major differentiation antigens of peripheral blood mononuclear cells, and their natural killer activity toward K562 target cells was measured. Both nickel salts were found to exert distinct effects on lymphocyte phenotype. Exposure of cells to Ni sub(3)S sub(2) resulted in the decline of CD4 and natural killer cell populations. NiSO sub(4) diminished the abundance of natural killer cells and, to a limited extent, also of CD4 cells. The nickel salts tested suppressed natural cytotoxicity of peripheral blood mononuclear cells, with Ni sub(3)S sub(2) acting more strongly than NiSO sub(4). The addition of Mg(CH sub(3)COO) sub(2) to a nickel salt during in vitro culture abolished the above inhibitory effects. Nickel and magnesium salts did not affect CD3, CD8, CD20, and CD11a cell populations. The results indicate that nickel salts have deleterious effects on human peripheral blood mononuclear cells in short-term in vitro culture, but the magnitude of these effects varies, depending on the cell subsets. JF - Toxicology AU - Zeromski, J AU - Jezewska, E AU - Sikora, J AU - Kasprzak, K S AD - Lab. Comp. Carcinog., NCI-FCRDC, Frederick, MD 21702-1201, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 39 EP - 48 VL - 97 IS - 1-3 SN - 0300-483X, 0300-483X KW - nickel subsulfide KW - nickel sulfate KW - heavy metals KW - Immunology Abstracts; Toxicology Abstracts KW - lymphocytes KW - natural killer cells KW - immunotoxicity KW - man KW - F 06791:Experimental KW - X 24161:Acute exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16798638?accountid=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=The+effect+of+nickel+compounds+on+immuno-phenotype+and+natural+killer+cell+function+of+normal+human+lymphocytes&rft.au=Zeromski%2C+J%3BJezewska%2C+E%3BSikora%2C+J%3BKasprzak%2C+K+S&rft.aulast=Zeromski&rft.aufirst=J&rft.date=1995-01-01&rft.volume=97&rft.issue=1-3&rft.spage=39&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - natural killer cells; lymphocytes; man; immunotoxicity ER - TY - JOUR T1 - Cytotoxicity, DNA adduct formation and DNA repair induced by 2-hydroxyamino 3-methylimidazo(4,5-f)quinoline and 2-hydroxyamino-1-methyl 6-phenylimidazo(4,5-b)pyridine in cultured human mammary epethelial cells AN - 16792891; 3752105 AB - 2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-hydroxyamino-1-methyl 6-phenylimidazo[4,5-b]pyridine (PhIP) are heterocyclic amines (HAs) found in cooked meats. Both compounds are mammary gland carcinogens in rats. The initiation of carcinogenesis by the HAs is believed to be associated with their DNA adduct formation that occurs after metabolic activation of the parent amines via cytochrome P-450-mediated N-hydroxylation and esterification. To assess the capacity of the human mammary epithelium to metabolically activate the HAs, we used the super(32)P-postlabeling method to measure the levels of DNA adducts in a culture of human mammary epithelial cells exposed to IQ, PhIP or their N-hydroxylamine metabolites. Whereas 50 mu M parent amines did not form detectable levels of DNA adducts in cultured human mammary epithelial cells after 24 h incubations, concentrations as low as 1 mu M N-hydroxylamines produced detectable levels of adducts after 2 h incubations. N-hydroxy-PhIP formed higher adduct levels than N-hydroxy-IQ at all concentrations tested. For example, following a 2 h incubation at 50 mu M, adduct levels (per 10 super(7) nucleotides) were 674 and 16 for N-hydroxy-PhIP and N-hydroxy-IQ, respectively. At similar initial adduct levels (10-11/10 super(7) nucleotides), 60-80% of IQ- and PhIP-DNA adducts were removed after 24 h, indicating that the mammary epithelial cell culture showed efficient repair of HA adducts. Whereas neither IQ nor PhIP was cytotoxic, both N-hydroxy-IQ and N-hydroxy-PhIP were cytotoxic as assessed by a dose-dependent inhibition of colony formation. After exposure to 0.1, 1, 10 or 50 mu M N-hydroxy-PhIP (or N-hydroxy-IQ), colony formation was 103 (94), 84 (74), 37 (29) and 3 (2)% of the control values, respectively. Only N-hydroxy-PhIP (at 10 and 50 mu M), however, was cytotoxic as assessed by the MTT cell survival assay (which measures the capacity of mitochondria to metabolize a tetrazolium salt). The ability of the N-hydroxylamines to form DNA adducts and to be cytotoxic in a culture of human mammary epithelial cells may implicate these metabolites as proximate carcinogenic forms of IQ and PhIP in the human mammary gland. However, whether there are inter-individual differences in N-hydroxylamine metabolism, adduct formation and repair in human mammary epithelial cells requires further study. The results from this study support the usefulness of cultured human mammary epithelial cells for studies on the genotoxicity and metabolism of the N-hydroxylamines of HA food mutagens. JF - Carcinogenesis AU - Fan, Liju AU - Schut, HAJ AU - Snyderwine, E G AD - Lab. Exp. Carcinog., NCI/NIH, Build. 37, Rm. 3C28, Bethesda, MD 20892-4255, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 775 EP - 779 VL - 16 IS - 4 SN - 0143-3334, 0143-3334 KW - 2-amino-3-methylimidazo(4,5-f)quinoline KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - heterocyclic amines KW - Biochemistry Abstracts 2: Nucleic Acids; Toxicology Abstracts KW - DNA adducts KW - hydroxylation KW - DNA repair KW - dose-response effects KW - mammary gland KW - man KW - N 14630:Chemical reactions & interactions, including effects of radiation KW - X 24120:Food, additives & contaminants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16792891?accountid=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=Cytotoxicity%2C+DNA+adduct+formation+and+DNA+repair+induced+by+2-hydroxyamino+3-methylimidazo%284%2C5-f%29quinoline+and+2-hydroxyamino-1-methyl+6-phenylimidazo%284%2C5-b%29pyridine+in+cultured+human+mammary+epethelial+cells&rft.au=Fan%2C+Liju%3BSchut%2C+HAJ%3BSnyderwine%2C+E+G&rft.aulast=Fan&rft.aufirst=Liju&rft.date=1995-01-01&rft.volume=16&rft.issue=4&rft.spage=775&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - DNA adducts; DNA repair; mammary gland; hydroxylation; dose-response effects; man ER - TY - JOUR T1 - Identification of group A rotavirus genes associated with virulence of a porcine rotavirus and host range restriction of a human rotavirus in the gnotobiotic piglet model AN - 16792422; 3747520 AB - Rotaviruses are the leading cause of severe diarrhea in infants and young children worldwide. Thus, the development of an effective rotavirus vaccine is a major public health goal. This study was performed to identify the gene or genes responsible for rotavirus virulence or host range restriction and attenuation in a natural host. Such knowledge could have an important bearing on the selection of candidate live vaccine strains. We addressed this issue by analyzing the response of gnotobiotic piglets to orally administered porcine x human rotavirus reassortants. It was possible to determine (i) which porcine rotavirus genes were required for the induction of diarrhea, and (ii) which human rotavirus genes are associated with the host range restriction because the parental porcine rotavirus (SB-1A strain) caused diarrhea in piglets, whereas the parental human rotavirus (DS-1 strain) was attenuated in piglets. Substitution of the 3rd (VP3) or 4th (VP4) or 9th (VP7) or 10th (NS28 (NSP4)) gene of the avirulent human strain for the corresponding gene of porcine rotavirus that was virulent for gnotobiotic piglets yielded viral reassortants that failed to induce diarrhea. Further analysis indicated that reassortants which possessed only one, two, or three of these porcine rotavirus genes on a background of human rotavirus genes also failed to induce diarrhea. However, diarrhea was induced when all four of these porcine rotavirus genes were included in a reassortant in which the remaining seven genes were derived from the human rotavirus. These observations suggest that it may be possible to attenuate wild-type human rotavirus strains that are virulent for humans by selective genetic reassortment with an animal rotavirus strain that is attenuated for humans. JF - Virology AU - Hoshino, Y AU - Saif, L J AU - Kang, S-Y AU - Sereno, M M AU - Chen, W K AU - Kapikian, A Z AD - Lab. Infect. Dis., NIAID/NIH, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 274 EP - 280 VL - 209 IS - 1 SN - 0042-6822, 0042-6822 KW - rotavirus (human) KW - rotavirus (porcine) KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Genetics Abstracts; Virology & AIDS Abstracts KW - vaccines KW - gnotobiotics KW - genes KW - host range KW - virulence KW - animal models KW - W3 33365:Vaccines (other) KW - V 22050:Viral genetics including virus reactivation KW - G 07313:Viruses KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16792422?accountid=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=Virology&rft.atitle=Identification+of+group+A+rotavirus+genes+associated+with+virulence+of+a+porcine+rotavirus+and+host+range+restriction+of+a+human+rotavirus+in+the+gnotobiotic+piglet+model&rft.au=Hoshino%2C+Y%3BSaif%2C+L+J%3BKang%2C+S-Y%3BSereno%2C+M+M%3BChen%2C+W+K%3BKapikian%2C+A+Z&rft.aulast=Hoshino&rft.aufirst=Y&rft.date=1995-01-01&rft.volume=209&rft.issue=1&rft.spage=274&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - vaccines; gnotobiotics; genes; host range; animal models; virulence ER - TY - JOUR T1 - Mycoplasma pneumoniae and Mycoplasma genitalium mixture in synovial fluid isolate AN - 16791860; 3749355 AB - A mycoplasma cultured from synovial fluid specimens from a patient with pneumonia and subsequent polyarthritis was identified initially as Mycoplasma pneumoniae. In retrospective studies, the culture was shown also to contain Mycoplasma genitalium. In this paper, the laboratory techniques employed in the identification and separation of the two species are presented, and evidence to implicate postinfectious autoimmunity is provided. An increasing number of reports of M. genitalium in human tissue sites and difficulties in isolation and identification of the organism in the clinical laboratory suggest the need for more extensive application of rapid and specific detection systems for both M. genitalium and M. pneumoniae in the clinical laboratory. JF - Journal of Clinical Microbiology AU - Tully, J G AU - Rose, D L AU - Baseman, J B AU - Dallo, S F AU - Lazzell, AL AU - Davis, C P AD - Mycoplasma Sect., NI-AID, Build. 550, NCI-FCRDC, Frederick, MD 21702, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 1851 EP - 1855 VL - 33 IS - 7 SN - 0095-1137, 0095-1137 KW - Microbiology Abstracts B: Bacteriology KW - Mycoplasma genitalium KW - Mycoplasma pneumoniae KW - mixed culture KW - J 02847:Genitourinary tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16791860?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Clinical+Microbiology&rft.atitle=Mycoplasma+pneumoniae+and+Mycoplasma+genitalium+mixture+in+synovial+fluid+isolate&rft.au=Tully%2C+J+G%3BRose%2C+D+L%3BBaseman%2C+J+B%3BDallo%2C+S+F%3BLazzell%2C+AL%3BDavis%2C+C+P&rft.aulast=Tully&rft.aufirst=J&rft.date=1995-01-01&rft.volume=33&rft.issue=7&rft.spage=1851&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Microbiology&rft.issn=00951137&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mycoplasma pneumoniae; Mycoplasma genitalium; mixed culture ER - TY - JOUR T1 - Benzene induces gene-duplicating but not gene-inactivating mutations at the glycophorin A locus in exposed humans AN - 16787640; 3747964 AB - Occupational exposure to benzene is known to cause leukemia, but the mechanism remains unclear. Unlike most other carcinogens, benzene and its metabolites are weakly or nonmutagenic in most simple gene mutation assays. Benzene and its metabolites do, however, produce chromosomal damage in a variety of systems. Here, we have used the glycophorin A (GPA) gene loss mutation assay to evaluate the nature of DNA damage produced by benzene in 24 workers heavily exposed to benzene and 23 matched control individuals in Shanghai, China. The GPA assay identifies stem cell or precursor erythroid cell mutations expressed in peripheral erythrocytes of MN-heterozygous subjects, distinguishing the NN and NO mutant variants. A significant increase in the NN GPA variant cell frequency (V sub(f)) was found in benzene-exposed workers as compared with unexposed control individuals (mean plus or minus SEM, 13.9 plus or minus 1.7 per million cells vs. 7.4 plus or minus 1.1 per million cells in control individuals; P = 0.0002). In contrast, no significant difference existed between the two groups for the NO V sub(f) (9.1 plus or minus 0.9 vs. 8.8 plus or minus 1.8 per million cells; P = 0.21). Further, lifetime cumulative occupational exposure to benzene was associated with the NN V sub(f) (P = 0.005) but not with the NO V sub(f) (P = 0.31), suggesting that NN mutations occur in longer-lived bone marrow stem cells. NN variants result from loss of the GPA M allele and duplication of the N allele, presumably through recombination mechanisms, whereas NO variants arise from gene inactivation, presumably due to point mutations and deletions. Thus, these results suggest that benzene produces gene-duplicating mutations but does not produce gene-inactivating mutations at the GPA locus in bone marrow cells of humans exposed to high benzene levels. This finding is consistent with data on the genetic toxicology of benzene and its metabolites and adds further weight to the hypothesis that chromosome damage and mitotic recombination are important in benzene-induced leukemia. JF - Proceedings of the National Academy of Sciences, USA AU - Rothman, N AU - Haas, R AU - Hayes, R B AU - Li, G-L AU - Wiemels, J AU - Campleman, S AU - Quintana, PJE AU - Xi, L-J AU - Dosemeci, M AU - Titenko-Holland, N AU - Meyer, K B AU - Lu, W AU - Zhang, L P AU - Brechtold, W AD - NIH/NCI, Executive Plaza North 418, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 4069 EP - 4073 VL - 92 IS - 9 SN - 0027-8424, 0027-8424 KW - benzene KW - glycophorin A KW - GPA gene KW - DNA damage KW - duplication KW - leukemia KW - man KW - Toxicology Abstracts; Human Genome Abstracts KW - China, People's Rep. KW - X 24155:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16787640?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Benzene+induces+gene-duplicating+but+not+gene-inactivating+mutations+at+the+glycophorin+A+locus+in+exposed+humans&rft.au=Rothman%2C+N%3BHaas%2C+R%3BHayes%2C+R+B%3BLi%2C+G-L%3BWiemels%2C+J%3BCampleman%2C+S%3BQuintana%2C+PJE%3BXi%2C+L-J%3BDosemeci%2C+M%3BTitenko-Holland%2C+N%3BMeyer%2C+K+B%3BLu%2C+W%3BZhang%2C+L+P%3BBrechtold%2C+W&rft.aulast=Rothman&rft.aufirst=N&rft.date=1995-01-01&rft.volume=92&rft.issue=9&rft.spage=4069&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - China, People's Rep.; duplication; DNA damage; leukemia; man ER - TY - JOUR T1 - Cellular characterization and retroviral transduction of short-term breast cancer cells AN - 16784742; 3747835 AB - The effort to develop cell lines from surgical specimens has been a difficult goal for years. We derived short-term primary human mammary carcinoma cell lines from breast tumors in 20 of 23 patients. Morphologically, cultured cells showed small cells with high nuclear cytoplasmic ratio and larger cells with abundant dense cytoplasm. The nuclei were round to oval with one to four nucleoli. Immunocytochemically, the cells stained positive for keratin. Tumor cells showed phenotypic overexpression of the breast tumor-associated antigen DF3 compared with normal mammary epithelial cells. The doubling time of tumor cells in vitro ranged from 2.6 to 3.6 days. The cultured cells were characterized as mammary carcinoma cells by their tumorigenicity in nude mice. Of 14 of the 23 short-term cell lines tested, 5 grew in nude mice and eventually regressed, 3 grew progressively in nude mice, and the remaining 6 did not grow within 3 months. To examine the feasibility of cytokine gene transfer into human mammary carcinoma cells, we introduced the cDNA for human tumor necrosis factor- alpha (TNF- alpha ) into short-term cell lines with a retroviral vector. In our short-term primary breast cancer cell lines derived from breast tumors, TNF- alpha secretion ranged between 89 ng/10 super(6) cells/48 h and 479 ng/10 super(6) cells/24 h. These findings indicate that short-term primary human mammary carcinoma cell lines can be grown consistently from breast tumors, and that retroviral mediated-cytokine gene transfer into short-term human mammary carcinoma cells is feasible and may be of potential use in immunotherapy trials. JF - Journal of Immunotherapy with Emphasis on Tumor Biology AU - Sgagias, M K AU - Gagneton, D C AU - Rosenberg, SA AU - Danforth, DN Jr AD - Surg. Branch, NCI/NIH, Build. 10, Rm. 2B38, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 88 EP - 97 VL - 17 IS - 2 SN - 1053-8550, 1053-8550 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - breast KW - gene transfer KW - retrovirus KW - transduction KW - man KW - carcinoma KW - F 06818:Cancer immunotherapy 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/16784742?accountid=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=Cellular+characterization+and+retroviral+transduction+of+short-term+breast+cancer+cells&rft.au=Sgagias%2C+M+K%3BGagneton%2C+D+C%3BRosenberg%2C+SA%3BDanforth%2C+DN+Jr&rft.aulast=Sgagias&rft.aufirst=M&rft.date=1995-01-01&rft.volume=17&rft.issue=2&rft.spage=88&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 - 2011-12-14 N1 - SubjectsTermNotLitGenreText - breast; gene transfer; retrovirus; transduction; man; carcinoma ER - TY - JOUR T1 - Mutational spectra for 5,6-dimethylchrysene 1,2-dihydrodiol 3,4-epoxides in the supF gene of pSP189 AN - 16783099; 3744284 AB - Dihydrodiol epoxides from 5,6-dimethylchrysene exhibit properties similar to those of fjord region-containing hydrocarbon derivatives in that they react extensively with deoxyadenosine residues in DNA and consequently generate substantial numbers of mutations at AT pairs as well as GC pairs. The syn-dihydrodiol epoxide favors reaction with deoxyadenosine (68% of adducts) to a greater extent than does the anti-dihydrodiol epoxide (52% of adducts), and point mutations at AT pairs (72% for syn- and 45% for anti-dihydrodiol epoxide) follow the same trend. A novel feature of the mutagenicity of the 5,6-dimethylchrysene derivatives is that they exhibit a higher fraction of AT arrow right GC transitions (28% and 26% for syn and anti, respectively) than has been seen for other hydrocarbon derivatives to date. JF - Chemical Research in Toxicology AU - Page, JE AU - Szeliga, J AU - Amin, S AU - Hecht, S S AU - Dipple, A AD - Chem. Carcinog. Lab., ABL-Basic Res. Program, NCI-FCRDC, P.O. Box B, Frederick, MD 21702, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 143 EP - 147 VL - 8 IS - 1 SN - 0893-228X, 0893-228X KW - 5,6-dimethylchrysene epoxides KW - plasmid pSP189 KW - supF gene KW - Genetics Abstracts; Toxicology Abstracts KW - mutation KW - X 24190:Polycyclic hydrocarbons KW - G 07221:Specific chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16783099?accountid=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=Mutational+spectra+for+5%2C6-dimethylchrysene+1%2C2-dihydrodiol+3%2C4-epoxides+in+the+supF+gene+of+pSP189&rft.au=Page%2C+JE%3BSzeliga%2C+J%3BAmin%2C+S%3BHecht%2C+S+S%3BDipple%2C+A&rft.aulast=Page&rft.aufirst=JE&rft.date=1995-01-01&rft.volume=8&rft.issue=1&rft.spage=143&rft.isbn=&rft.btitle=&rft.title=Chemical+Research+in+Toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - mutation ER - TY - JOUR T1 - Characterization of the umu-complementing operon from R391 AN - 16782901; 3745268 AB - In addition to conferring resistances to antibiotics and heavy metals, certain R factors carry genes involved in mutagenic DNA repair. These plasmid-encoded genes are structurally and functionally related to the chromosomally encoded umuDC genes of Escherichia coli and Salmonella typhimurium. Three such plasmid operons, mucAB, impCAB, and samAB, have been characterized at the molecular level. Recently, we have identified three additional umu-complementing operons from IncJ plasmid R391 and IncL/M plasmids R446b and R471a. We report here the molecular characterization of the R391 umu-complementing operon. The nucleotide sequence of the minimal R plasmid umu-complementing (rum) region revealed an operon of two genes, rumA sub((R391)) and rumB sub((R391)), with an upstream regulatory signal strongly resembling LexA-binding sites. Phylogenetic analysis revealed that the RumAB sub((R391)) proteins are approximately equally diverged in sequence from the chromosomal UmuDC proteins and the other plasmid-encoded Umu-like proteins and represent a new subfamily. Genetic characterization of the rumAB sub((R391)) operon revealed that in recA super(+) and recA1730 backgrounds, the rumAB sub((R391)) operon was phenotypically indistinguishable from mucAB. In contrast, however, the rumAB sub((R391)) operon gave levels of mutagenesis that were intermediate between those given by mucAB and umuDC in a recA430 strain. The latter phenotype was shown to correlate with the reduced posttranslational processing of the RumA sub((R391)) protein to its mutagenically active form, RumA' sub((R391)). Thus, the rumAB sub((R391)) operon appears to possess characteristics that are reminiscent of both chromosome and plasmid-encoded umu-like operons. JF - Journal of Bacteriology AU - Kulaeva, OI AU - Wootton, J C AU - Levine, A S AU - Woodgate, R AD - Build. 6, Rm. 1A13, NICHD/NIH, 9000 Rockville Pike, Bethesda, MD 20892-2725, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 2737 EP - 2743 VL - 177 IS - 10 SN - 0021-9193, 0021-9193 KW - rumAB(R391) gene KW - plasmid RW154 KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - nucleotide sequence KW - site-directed mutagenesis KW - Escherichia coli KW - Salmonella typhimurium KW - G 07321:GENERAL KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16782901?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=Characterization+of+the+umu-complementing+operon+from+R391&rft.au=Kulaeva%2C+OI%3BWootton%2C+J+C%3BLevine%2C+A+S%3BWoodgate%2C+R&rft.aulast=Kulaeva&rft.aufirst=OI&rft.date=1995-01-01&rft.volume=177&rft.issue=10&rft.spage=2737&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Salmonella typhimurium; nucleotide sequence; site-directed mutagenesis ER - TY - JOUR T1 - Structural and functional analyses of the transcription-translation proteins NusB and NusE AN - 16782788; 3745088 AB - The NusB and NusE (ribosomal protein S10) proteins function in transcription and translation. The two proteins form a complex that binds to the boxA sequence found in the leader RNA of rrn operons; boxA is required for transcription antitermination in rrn operons. Although binding of these two proteins to the boxA RNA of the bacteriophage lambda nut site has not been observed, both NusB and NusE as well as the RNA boxA sequence are required for lambda N-mediated antitermination. Studies identifying the amino acid changes caused by mutations in nusB and nusE and relating these changes to altered function are reported. It is concluded that boxA is essential for an effective NusB contribution to N-mediated antitermination and that by mutation NusB may be changed to allow more-effective binding to boxA variants. JF - Journal of Bacteriology AU - Court, D L AU - Patterson, T A AU - Baker, T AU - Costantino, N AU - Mao, X AU - Friedman, DI AD - Lab. Chrom. Biol., ABL-Basic Res. Prog., NCI-FCRDC, Frederick, MD 21702-1201, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 2589 EP - 2591 VL - 177 IS - 9 SN - 0021-9193, 0021-9193 KW - NusB protein KW - NusE protein KW - rrn operon KW - boxA gene KW - Microbiology Abstracts B: Bacteriology KW - RNA KW - J 02726:RNA and ribosomes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16782788?accountid=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=Structural+and+functional+analyses+of+the+transcription-translation+proteins+NusB+and+NusE&rft.au=Court%2C+D+L%3BPatterson%2C+T+A%3BBaker%2C+T%3BCostantino%2C+N%3BMao%2C+X%3BFriedman%2C+DI&rft.aulast=Court&rft.aufirst=D&rft.date=1995-01-01&rft.volume=177&rft.issue=9&rft.spage=2589&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - RNA ER - TY - JOUR T1 - Occupational exposures and female breast cancer mortality in the United States AN - 16782185; 3739833 AB - Mortality records from 24 states, gathered from 1984 to 1989 and coded for occupation and industry, were used to develop leads to workplace exposures as possible breast cancer risk factors. A case-control approach was used, with separate analyses for blacks and whites. After excluding homemakers, 33,509 cases and 117,794 controls remained. A job exposure matrix was used to estimate the probability and level of 31 workplace exposures. After adjusting for socioeconomic status, suggestive associations for probability and level of exposure were found for styrene, several organic solvents (methylene chloride, carbon tetrachloride, formaldehyde), and several metals/metal oxides and acid mists. Because of the methodologic limitations of this study, its primary value is in suggesting hypotheses for further evaluation. The findings for styrene, selected solvents, and metals and metal-related exposures deserve additional study. JF - Journal of Occupational and Environmental Medicine AU - Cantor, K P AU - Stewart, P A AU - Brinton, LA AU - Dosemeci, M AD - Environ. Epidemiol. Branch, NCI, 443 Executive Plaza N, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 336 EP - 348 VL - 37 IS - 3 SN - 1076-2752, 1076-2752 KW - man KW - Toxicology Abstracts; Risk Abstracts; Health & Safety Science Abstracts KW - females KW - occupational exposure KW - statistical analysis KW - breast cancer KW - USA KW - mortality KW - R2 23080:Industrial and labor KW - X 24240:Miscellaneous KW - H SI0.2:DATA ANALYSIS KW - R2 23060:Medical and environmental health KW - H SM10.21:CANCER UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16782185?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Occupational+and+Environmental+Medicine&rft.atitle=Occupational+exposures+and+female+breast+cancer+mortality+in+the+United+States&rft.au=Cantor%2C+K+P%3BStewart%2C+P+A%3BBrinton%2C+LA%3BDosemeci%2C+M&rft.aulast=Cantor&rft.aufirst=K&rft.date=1995-01-01&rft.volume=37&rft.issue=3&rft.spage=336&rft.isbn=&rft.btitle=&rft.title=Journal+of+Occupational+and+Environmental+Medicine&rft.issn=10762752&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - USA; occupational exposure; breast cancer; mortality; statistical analysis; females; man ER - TY - JOUR T1 - Employment practices and breast cancer among radiologic technologists AN - 16781664; 3739834 AB - A case-control study of breast cancer and employment practices among female radiologic technologists was conducted. The cohort from which cases and controls were derived included over 105,000 female medical radiation workers certified by the American Registry of Radiologic Technologists during 1926-1980. Breast cancer cases (n = 528) were individually matched to an average of five control subjects (n = 2628) based on year of birth, year of certification, and length of follow-up. Procedures most commonly performed by controls included fluoroscopy (93%), portable radiographs (92%), routine radiographs (92%), multifilm procedures (87%), dental x-rays (46%), radium therapy (31%), orthovoltage (23%), and cobalt-60 (21%). Breast cancer was not significantly increased with occupational experience with any of these procedures. Furthermore, risk was not related to number of years worked with a particular procedure. JF - Journal of Occupational and Environmental Medicine AU - Doody, M M AU - Mandel, J S AU - Boice, JD Jr AD - Radiat. Epidemiol. Branch, NCI, Executive Plaza N, Rm. 408, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 321 EP - 327 VL - 37 IS - 3 SN - 1076-2752, 1076-2752 KW - man KW - Toxicology Abstracts; Risk Abstracts; Health & Safety Science Abstracts KW - radiology KW - occupational exposure KW - statistical analysis KW - medical personnel KW - breast cancer KW - R2 23080:Industrial and labor KW - H SM7.3:HAZARD DETERMINATION KW - X 24210:Radiation & radioactive materials KW - H SM10.21:CANCER UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16781664?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Occupational+and+Environmental+Medicine&rft.atitle=Employment+practices+and+breast+cancer+among+radiologic+technologists&rft.au=Doody%2C+M+M%3BMandel%2C+J+S%3BBoice%2C+JD+Jr&rft.aulast=Doody&rft.aufirst=M&rft.date=1995-01-01&rft.volume=37&rft.issue=3&rft.spage=321&rft.isbn=&rft.btitle=&rft.title=Journal+of+Occupational+and+Environmental+Medicine&rft.issn=10762752&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - radiology; occupational exposure; breast cancer; medical personnel; statistical analysis; man ER - TY - JOUR T1 - Growth of Mycoplasma hyorhinis cultivar alpha on semisynthetic medium AN - 16778643; 3737058 AB - Serial passage of Mycoplasma hyorhinis cultivar alpha (formerly noncultivable strains) has been accomplished in modified CMRL-1066 medium with fetal bovine serum. In modified CMRL-1066 liquid medium, cultivar alpha strains grow at a similar rate and to equivalent titers when compared with BTS-7, the type strain of the species. Further experiments with BTS-7 demonstrate that the extent of growth obtained in the semidefined medium was comparable to growth in conventional mycoplasma medium. M. hyorhinis strains, including cultivar alpha strains, grow in serial passage when fetal bovine serum is replaced with bovine serum albumin, palmitic acid, and cholesterol. The results of these studies show that M. hyorhinis cultivar alpha strains are not nutritionally more fastidious than other mycoplasmas but that they are noncultivable on standard mycoplasma media because they are sensitive to high levels of inhibition activity by medium components. JF - Applied and Environmental Microbiology AU - Gardella, R S AU - Del Giudice, RA AD - PRI/DynCorp, NCI-FCRDC, P.O. Box B, Frederick, MD 21702, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 1976 EP - 1979 VL - 61 IS - 5 SN - 0099-2240, 0099-2240 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts B: Bacteriology KW - cultivars KW - media (culture) KW - Mycoplasma hyorhinis KW - A 01115:Mycoplasmas KW - J 02722:Biodegradation, growth, nutrition and leaching UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16778643?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Applied+and+Environmental+Microbiology&rft.atitle=Growth+of+Mycoplasma+hyorhinis+cultivar+alpha+on+semisynthetic+medium&rft.au=Gardella%2C+R+S%3BDel+Giudice%2C+RA&rft.aulast=Gardella&rft.aufirst=R&rft.date=1995-01-01&rft.volume=61&rft.issue=5&rft.spage=1976&rft.isbn=&rft.btitle=&rft.title=Applied+and+Environmental+Microbiology&rft.issn=00992240&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mycoplasma hyorhinis; media (culture); cultivars ER - TY - JOUR T1 - A novel phosphocholine antigen protects both normal and X-linked immune deficient mice against Streptococcus pneumoniae. Comparison of the 6-O-phosphocholine hydroxyhexanoate-conjugate with other phosphocholine-containing vaccines AN - 16776670; 3738369 AB - A novel form of phosphocholine (PC), p-nitrophenyl-6-(O-phosphocholine)hydroxyhexanoate (EPC) coupled to keyhole limpet hemocyanin (KLH) has been compared with unencapsulated, avirulent Streptococcus pneumoniae (R36a) and with the traditional thymus-dependent form of PC, diazophenylphosphocholine (DPPC)-conjugated KLH for its vaccine potential against virulent S. pneumoniae. Immunization with any of these three PC-containing Ags protects normal mice against a lethal challenge with 10 super(4) S. pneumoniae, whereas only EPC-KLH provides total protection to Xid mice. DPPC-KLH and unencapsulated S. pneumoniae confer less than 40% protection in Xid mice. Passive transfer of a PC-specific hybridoma Ab made from EPC-KLH-immunized Xid mice also provided protection against lethal challenge with S. pneumoniae. Protective anti-PC Ab were capable of binding to the surface of virulent bacteria, whereas anti-PC Ab incapable of binding to the bacterial surface failed to protect. Furthermore, serum Ab from EPC-KLH immunized and protected mice bound to S. pneumoniae, whereas secondary Abs from DPPC-KLH- or R36a-immunized mice failed to bind to the bacteria. EPC-KLH is potentially a vaccine candidate for pneumococcal prophylaxis in settings of immune compromise. JF - Journal of Immunology AU - Fischer, R T AU - Longo, D L AU - Kenny, J J AD - Biol. Carcinogenesis and Dev. Program, Program Resour., Inc./Dyn-Corp, NCI-FCRDC, Build. 567, Rm. 227, Frederick, MD 21702-1201, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 3373 EP - 3382 VL - 154 IS - 7 SN - 0022-1767, 0022-1767 KW - X-linked immune deficient mice KW - 6-O-phosphocholine hydroxyhexanoate KW - keyhole limpet hemocyanin KW - phosphocholine KW - Xid mice KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - vaccines KW - Streptococcus pneumoniae KW - immunodeficiency KW - conjugates KW - pneumonia KW - J 02834:Vaccination and immunization KW - F 06807:Active immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16776670?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunology&rft.atitle=A+novel+phosphocholine+antigen+protects+both+normal+and+X-linked+immune+deficient+mice+against+Streptococcus+pneumoniae.+Comparison+of+the+6-O-phosphocholine+hydroxyhexanoate-conjugate+with+other+phosphocholine-containing+vaccines&rft.au=Fischer%2C+R+T%3BLongo%2C+D+L%3BKenny%2C+J+J&rft.aulast=Fischer&rft.aufirst=R&rft.date=1995-01-01&rft.volume=154&rft.issue=7&rft.spage=3373&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Streptococcus pneumoniae; conjugates; vaccines; pneumonia; immunodeficiency ER - TY - JOUR T1 - CRP-DNA complexes: Inducing the A-like form in the binding sites with an extended central spacer AN - 16773245; 3737235 AB - The consensus DNA sequence for binding of the Escherichia coli cyclic AMP receptor protein (CRP) has two symmetrically related inverted recognition elements TGTGA:TCACA, separated by a variable spacer, normally 6 bp long. We have shown that the CRP-cAMP complex, when bound to synthetic binding sites with an extended 8 bp spacer segment, induces an increase in the DNA circular dichroism (CD). The CD change at lambda > 275 nm agrees with the shift of approximately one helical turn of DNA into A-like form. The B-conformation is preserved for CRP binding sites similar to that in the lac and uxaCA promoters with 6 bp spacers. Another effect accompanying DNA binding is a dramatic increase of the negative CD magnitude in the spectral region of the ligand cAMP, at lambda < 272 nm. This effect is observed when CRP binds to specific sites with 6 or 8 bp spacers as well as to non-specific DNA. We reason that the A-like form arises by compressing and unwinding the DNA in CRP-DNA complexes having 8 bp central spacers. This serves to maintain a fixed length and twisting angle and is controlled by the protein's relatively rigid frame. This model is consistent with the observation that some binding sites with 6 bp spacers may also show the CD increase inherent to the sites with the extended 8 bp spacers. These 6 bp spacers are characterized by an increased twisting angle that requires their unwinding to bind to CRP. We propose that a mutual adaptation between CRP and binding sites by local untwisting and a B arrow right A-like transition in the DNA is of general importance and may occur in other protein-DNA complexes, such as the complex of RNA polymerase with promoter DNA. JF - Journal of Molecular Biology AU - Ivanov, VI AU - Minchenkova, LE AU - Chernov, B K AU - McPhie, P AU - Ryu, S AU - Garges, S AU - Barber, A M AU - Zhurkin, V B AU - Adhya, S AD - NCI/NIH, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 228 EP - 240 VL - 245 IS - 3 SN - 0022-2836, 0022-2836 KW - CRP protein KW - cyclic AMP KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - DNA-binding protein KW - C.D. KW - transcription initiation KW - DNA KW - Escherichia coli KW - N 14930:Transcription factors KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16773245?accountid=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=CRP-DNA+complexes%3A+Inducing+the+A-like+form+in+the+binding+sites+with+an+extended+central+spacer&rft.au=Ivanov%2C+VI%3BMinchenkova%2C+LE%3BChernov%2C+B+K%3BMcPhie%2C+P%3BRyu%2C+S%3BGarges%2C+S%3BBarber%2C+A+M%3BZhurkin%2C+V+B%3BAdhya%2C+S&rft.aulast=Ivanov&rft.aufirst=VI&rft.date=1995-01-01&rft.volume=245&rft.issue=3&rft.spage=228&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; DNA; C.D.; DNA-binding protein; transcription initiation ER - TY - JOUR T1 - Cytokine gene expression in epidermis with biological effects following injection of naked DNA AN - 16771817; 3733600 AB - The epidermis is readily accessible for genetic manipulation and is easily monitored. Using pig skin because it is very similar to human skin morphologically, we have developed a method to transiently express biologically active factors in epidermis. Following direct injection of naked plasmid DNA into skin, DNA is taken up and transiently expressed at high levels of epidermal keratinocytes. Injection of interleukin-8 plasmid DNA into skin results in the appropriate biological response of neutrophil recruitment, demonstrating functional utility. In addition to this model's therapeutic uses, the biological effects of structural gene products on the epidermis could also be studied in vivo. JF - Nature Genetics AU - Hengge, U R AU - Chan, E F AU - Foster, R A AU - Walker, P S AU - Vogel, J C AD - Dermatol. Branch, NCI/NIH, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 161 EP - 166 VL - 10 IS - 2 SN - 1061-4036, 1061-4036 KW - DNA KW - gene expression KW - injection KW - interleukin 8 KW - pigs KW - skin KW - Biotechnology and Bioengineering Abstracts; Human Genome 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/16771817?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Genetics&rft.atitle=Cytokine+gene+expression+in+epidermis+with+biological+effects+following+injection+of+naked+DNA&rft.au=Hengge%2C+U+R%3BChan%2C+E+F%3BFoster%2C+R+A%3BWalker%2C+P+S%3BVogel%2C+J+C&rft.aulast=Hengge&rft.aufirst=U&rft.date=1995-01-01&rft.volume=10&rft.issue=2&rft.spage=161&rft.isbn=&rft.btitle=&rft.title=Nature+Genetics&rft.issn=10614036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - DNA; injection; gene expression; interleukin 8; skin ER - TY - JOUR T1 - Macaques immunized with HLA-DR are protected from challenge with simian immunodeficiency virus AN - 16771493; 3734177 AB - Macaques immunized with uninfected human cells have been shown to be protected from challenge with simian immunodeficiency virus (SIV) propagated in human cells. To identify the potential antigens involved in this protection, macaques were immunized with uninfected human cells, sucrose density gradient-purified culture fluid from uninfected human cells (mock virus), beta-2 microglobulin ( beta 2M), immunoaffinity-purified HLA class I and class II proteins from these human cells, and adjuvant. Although all macaques immunized with beta 2M and HLA class I developed high antibody titers to beta 2M, these animals were not protected from a subsequent challenge with infectious SIV grown in human cells. In contrast, the macaques immunized with class II protein (HLA-DR) and mock virus developed antibodies to class II protein and were protected from the intravenous infectious virus challenge. The class II protein- and mock virus-immunized animals which were protected from challenge were given boosters of the appropriate antigen and challenged with the same SIV propagated in macaque cells. All animals became infected, indicating that the protection seen with human class II protein did not extend to protection from infection with SIV containing macaque class II proteins. Since the virus released from SIV-infected macaque cells would contain macaque class II proteins, our results suggest that the initial SIV infected was completely prevented. In addition, the lack of protection from challenge with SIV propagated in macaque cells provided strong evidence that the protection was due to an immune response to the cellular proteins and not to epitopes cross-reactive between class II proteins and the viral proteins, since the identical virus proteins were present in both challenge stocks. These results are the first demonstration that immunization with a purified cellular protein can protect from virus infection. JF - Journal of Virology AU - Arthur, LO AU - Bess, JW Jr AU - Urban, R G AU - Strominger, J L AU - Morton, W R AU - Mann, D L AU - Henderson, LE AU - Benveniste, R E AD - AIDS Vaccine Prog., PRI/DynCorp, NCI-FCRDC, Frederick, MD 21702-1201, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 3117 EP - 3124 VL - 69 IS - 5 SN - 0022-538X, 0022-538X KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts; Virology & AIDS Abstracts KW - immunization KW - simian immunodeficiency virus KW - antigens KW - major histocompatibility complex 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/16771493?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Virology&rft.atitle=Macaques+immunized+with+HLA-DR+are+protected+from+challenge+with+simian+immunodeficiency+virus&rft.au=Arthur%2C+LO%3BBess%2C+JW+Jr%3BUrban%2C+R+G%3BStrominger%2C+J+L%3BMorton%2C+W+R%3BMann%2C+D+L%3BHenderson%2C+LE%3BBenveniste%2C+R+E&rft.aulast=Arthur&rft.aufirst=LO&rft.date=1995-01-01&rft.volume=69&rft.issue=5&rft.spage=3117&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - immunization; antigens; major histocompatibility complex; simian immunodeficiency virus ER - TY - JOUR T1 - Preparation and characterization of a disulfide-stabilized Fv fragment of the anti-Tac antibody: Comparison with its single-chain analog AN - 16767442; 3738537 AB - Recombinant DNA techniques now allow the production of "mini-antibodies" called Fv fragments. These have been produced either as the independent variable domains of the heavy and light chains non-covalently associated in one-to-one stoichiometry or as single-chain gene products with the two domains linked by an intervening peptide sequence. Although Fv fragments can have excellent binding properties, they are often difficult to produce in good yield and lack the characteristic stability of whole antibodies. To improve the stability of the Fv molecule, we have introduced a cysteine residue into conserved framework regions of both the heavy and light variable domains from the anti-Tac antibody at positions compatible with the formation of an interdomain disulfide linkage (i.e. V sub(H)-44 and V sub(L)-99). The mutant subunits form a disulfide-bonded Fv molecule, which binds to the alpha -subunit of the IL2 receptor (IL2R alpha ) with an affinity identical to that of humanized anti-Tac IgG. This disulfide-stabilized Fv (dsFv) proved to be substantially more resistant to denaturation by heat or urea treatment than the single-chain Fv (scFv). Furthermore, the yield of dsFv is similar to four-fold higher than that of the single-chain analog. JF - Molecular Immunology AU - Webber, KO AU - Reiter, Y AU - Brinkmann, U AU - Kreitman, R AU - Pastan, I AD - Lab. Mol. Biol., Div. Cancer Biol., Diagn. and Cent., NCI/NIH, 9000 Rockville Pike, Build. 37, Rm. 4E16, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 249 EP - 258 VL - 32 IS - 4 SN - 0161-5890, 0161-5890 KW - Fv KW - Tac antigen KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - stabilization KW - immunoglobulins KW - disulfide bonds KW - fragments KW - antibodies KW - immunotherapy KW - carcinoma KW - W3 33375:Antibodies KW - F 06818:Cancer immunotherapy KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16767442?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Immunology&rft.atitle=Preparation+and+characterization+of+a+disulfide-stabilized+Fv+fragment+of+the+anti-Tac+antibody%3A+Comparison+with+its+single-chain+analog&rft.au=Webber%2C+KO%3BReiter%2C+Y%3BBrinkmann%2C+U%3BKreitman%2C+R%3BPastan%2C+I&rft.aulast=Webber&rft.aufirst=KO&rft.date=1995-01-01&rft.volume=32&rft.issue=4&rft.spage=249&rft.isbn=&rft.btitle=&rft.title=Molecular+Immunology&rft.issn=01615890&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - stabilization; immunoglobulins; disulfide bonds; fragments; antibodies; immunotherapy; carcinoma ER - TY - JOUR T1 - Immunization with viruslike particles from cottontail rabbit papillomavirus (CRPV) can protect against experimental CRPV infection AN - 16766992; 3740690 AB - We tested the ability of vaccination with virus-like particles (VLPs) to protect domestic rabbits against papillomas induced by the cottontail rabbit papillomavirus (CRPV). A recombinant baculovirus system that expressed only the L1 major papillomavirus structural protein or L1 plus the minor L2 protein was used in insect cells as the source of VLPs. Groups of 10 rabbits were immunized with native or denatured VLPs from CRPV or type 1 bovine papillomavirus by using Freund's adjuvant. Alum was used as the adjuvant for an additional group immunized with CRPV L1-L2 VLPs. Animals were challenged with 5 x 10 super(10) and 2 x 10 super(11) particles on opposing flanks. No protection was seen in rabbits immunized with native or denatured bovine papillomavirus L1-L2 or with denatured CRPV L1-L2. In these groups, the lower and higher challenge doses resulted in 27 of 30 animals with extensive papillomas, with each of the remaining animals having a smaller number of persistent papillomas. Progression to carcinoma developed in 20 rabbits. Animals inoculated with native CRPV VLPs composed of L1 alone or L1-L2 developed many fewer lesions; the lower and higher challenge doses resulted in 17 of 29 and 5 of 29 rabbits, respectively, with no lesions, and the remainder developed only one to eight papillomas, which all regressed except for those on 1 rabbit. None developed cancer within 1 year of infection. Rabbits vaccinated with native CRPV VLPs developed high-titer antibodies in an enzyme-linked immunosorbent assay based on native VLPs, and passive transfer of serum or immunoglobulin G from rabbits immunized with CRPV VLPs protected against CRPV challenge. We conclude that native VLPs can induce antibody-mediated, type-specific protection against experimental papillomavirus infection. JF - Journal of Virology AU - Breitburd, F AU - Kirnbauer, R AU - Hubbert, N L AU - Nonnenmacher, B AU - Trin-Dinh-Desmarquet, C AU - Orth, G AU - Schiller, J T AU - Lowy AD - Lab. Cell. Oncol., NCI/NIH, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 3959 EP - 3963 VL - 69 IS - 6 SN - 0022-538X, 0022-538X KW - papilloma virus KW - rabbits KW - Biotechnology and Bioengineering Abstracts; Agricultural and Environmental Biotechnology Abstracts; Immunology Abstracts; Virology & AIDS Abstracts KW - virus-like particles KW - infection KW - immunity KW - vaccination KW - W2 32365:Vaccines KW - V 22098:Immunization: Vaccines & vaccination: Animal KW - W 30965:Miscellaneous, Reviews KW - F 06800:Viruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16766992?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Virology&rft.atitle=Immunization+with+viruslike+particles+from+cottontail+rabbit+papillomavirus+%28CRPV%29+can+protect+against+experimental+CRPV+infection&rft.au=Breitburd%2C+F%3BKirnbauer%2C+R%3BHubbert%2C+N+L%3BNonnenmacher%2C+B%3BTrin-Dinh-Desmarquet%2C+C%3BOrth%2C+G%3BSchiller%2C+J+T%3BLowy&rft.aulast=Breitburd&rft.aufirst=F&rft.date=1995-01-01&rft.volume=69&rft.issue=6&rft.spage=3959&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - virus-like particles; immunity; infection; vaccination ER - TY - JOUR T1 - Different mechanisms of aralkylation of adenosine at the 1- and N super(6)-positions AN - 16766876; 3735794 AB - The eight products resulting from opening of either enantiomer of styrene oxide at the alpha - or beta -carbon by the 1- or N super(6)-positions of adenosine were prepared and their configurations assigned. These markers allowed the mechanism of aralkylation of adenosine by styrene oxide to be investigated. It was found that formation of alpha -substituted products at the 1-position of adenosine involved total inversion of stereochemistry, whereas at the N super(6)-position inversion: retention was similar to 6:1. These differences in stereochemistry suggest that a more ionic form of styrene oxide is involved in N super(6)-aralkylation than in 1-aralkylation of adenosine. In the course of these studies, it was found that 1-substituted adenosines at the alpha - and beta -carbon of styrene oxide undergo Dimroth rearrangement at neutral pH and 37 degree C and that the former compound also deaminates fairly readily under these conditions. JF - Chemical Research in Toxicology AU - Qian, Chengyi AU - Dipple, A AD - Chem. Carcinog. Lab., ABL-Basic Res. Program, NCI-FCRDC, P.O. Box B, Frederick, MD 21702, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 389 EP - 395 VL - 8 IS - 3 SN - 0893-228X, 0893-228X KW - adenosine KW - styrene oxide KW - aralkylation KW - Toxicology Abstracts KW - carcinogenicity KW - mutagenicity KW - X 24117:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16766876?accountid=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=Different+mechanisms+of+aralkylation+of+adenosine+at+the+1-+and+N+super%286%29-positions&rft.au=Qian%2C+Chengyi%3BDipple%2C+A&rft.aulast=Qian&rft.aufirst=Chengyi&rft.date=1995-01-01&rft.volume=8&rft.issue=3&rft.spage=389&rft.isbn=&rft.btitle=&rft.title=Chemical+Research+in+Toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - mutagenicity; carcinogenicity ER - TY - JOUR T1 - Attributable risk of lung cancer in lifetime nonsmokers and long-term ex-smokers (Missouri, United States) AN - 16764823; 3736559 AB - A population-based, case-control study of incident lung cancer among women in Missouri (United States) who were lifetime nonsmokers and long-term ex-smokers was conducted between 1986 and 1992. The study included 618 lung cancer cases and 1,402 population-based, age matched controls. Information on lung-cancer risk factors was obtained by interviewing cases, next-of-kin of cases (36 percent and 64 percent of the cases, respectively) and controls. Year-long radon measurements also were sought in every dwelling occupied for the previous five to 30 years. Population attributable risks (PAR) for specific risk factors were computed for all subjects, for lifetime nonsmokers, for long-term ex-smokers, by histologic cell type (i.e., adenocarcinoma cf nonadenocarcinoma) and for direct interviews with case (for living cases) and for next-of-kin interviews (for dead cases or cases too ill to complete an interview). The mean age at lung cancer diagnosis was 71 years, and nearly 50 percent of the lung cancers were histologically confirmed adenocarcinomas. Almost 40 percent of all lung cancers among lifetime nonsmokers and almost 50 percent of lung cancers among all subjects could be explained by the risk factors under study. Dietary intake of saturated fat and nonmalignant lung disease were the two leading identified risk factors for lung cancer among the lifetime nonsmokers, followed by environmental tobacco smoke, and occupational exposures to known carcinogens. A small nonsignificant risk was found for study subjects exposed to median domestic radon concentration of 4 pCi/l (25-year time-weight average). Since only a small fraction of the population is exposed at this level, it is estimated that the PAR for domestic radon was less than two percent in Missouri. The risk for saturated fat intake was similar for lifetime nonsmokers, ex-smokers, adenocarcinoma cases, and nonadenocarcinoma cases; however, the increased risk was much more pronounced for next-of-kin interviews (PAR = 31 percent) than for interviews with the study subjects (PAR = nine percent). A similar pattern of PAR was identified among ex-smokers but, in this group, the lingering effect of a history of smoking was also very important. Along with saturated fat intake (PAR = 20 percent), the combined effect of previous active and passive smoking even after 15 years of cessation of active smoking was responsible for more lung cancer than any other risk factor under study (PAR = 59 percent). JF - Cancer Causes & Control AU - Alavanja, MCR AU - Brownson, R C AU - Benichou, J AU - Swanson, C AU - Boice, JD Jr AD - Epidemiol. and Biostat. Program, NCI, EPN/543, 6130 Executive Blvd., Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 209 EP - 216 VL - 6 IS - 3 SN - 0957-5243, 0957-5243 KW - lung cancer KW - radon KW - saturated fat KW - fats KW - tobacco smoking KW - Toxicology Abstracts; Risk Abstracts; Health & Safety Science Abstracts KW - diets KW - females KW - passive smoking KW - USA, Missouri KW - lung KW - cancer KW - R2 23060:Medical and environmental health KW - X 24180:Social poisons & drug abuse KW - H SM10.21:CANCER UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16764823?accountid=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=Attributable+risk+of+lung+cancer+in+lifetime+nonsmokers+and+long-term+ex-smokers+%28Missouri%2C+United+States%29&rft.au=Alavanja%2C+MCR%3BBrownson%2C+R+C%3BBenichou%2C+J%3BSwanson%2C+C%3BBoice%2C+JD+Jr&rft.aulast=Alavanja&rft.aufirst=MCR&rft.date=1995-01-01&rft.volume=6&rft.issue=3&rft.spage=209&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - USA, Missouri; lung cancer; radon; diets; passive smoking; females; lung; cancer; tobacco smoking ER - TY - JOUR T1 - Antitat gene therapy: A candidate for late-stage AIDS patients AN - 16759736; 3731808 AB - Antitat is an autoregulated gene expressing an inhibitory RNA with dual function: it sequesters the Tat protein by polymeric-TAR and blocks the translation of the Tat messenger RNA by antisense-Tat. Using human T cell lines and peripheral blood lymphocytes as the in vitro target, we have previously shown that antitat is an effective long-term suppressor of HIV-1, including 'field' isolates. To assess the efficacy of this inhibitory gene better in the setting of an infected individual with late-stage AIDS, we examined its antiviral activity in an in vivo established infection. Peripheral blood mononuclear cells isolated from AIDS patients were transduced with replication defective retroviral vectors carrying the antitat gene. In the absence of cell selection, the antitat gene blocked virus replication and allowed infected CD4 super(+) T cells to expand in culture. These results suggest that antitat gene therapy may be beneficial to block HIV-1 replication and reconstitute the immune system of late-phase AIDS patients. We introduced a new parameter, CRF, which defines the effectiveness of the ex vivo gene therapy treatment of AIDS patients. Antitat treatment was efficient in cells of all patients regardless of viral quasi-species, however, it was most potent in severely immunocompromised individuals. JF - Gene Therapy AU - Lisziewicz, J AU - Sun, D AU - Lisziewicz, A AU - Gallo, R C AD - Lab. Tumor Cell Biol., NCI, Build. 37, Rm. 6A09, 37 Convent Dr MSC 4255, Bethesda, MD 20892-4255, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 218 EP - 222 VL - 2 IS - 3 SN - 0969-7128, 0969-7128 KW - RNA KW - Tat protein KW - acquired immune deficiency syndrome KW - antisense KW - antitat gene KW - gene therapy KW - human immunodeficiency virus 1 KW - man KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Human Genome Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - V 22002:AIDS: Molecular and in vitro aspects 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/16759736?accountid=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=Antitat+gene+therapy%3A+A+candidate+for+late-stage+AIDS+patients&rft.au=Lisziewicz%2C+J%3BSun%2C+D%3BLisziewicz%2C+A%3BGallo%2C+R+C&rft.aulast=Lisziewicz&rft.aufirst=J&rft.date=1995-01-01&rft.volume=2&rft.issue=3&rft.spage=218&rft.isbn=&rft.btitle=&rft.title=Gene+Therapy&rft.issn=09697128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - antisense; gene therapy; RNA; man; acquired immune deficiency syndrome; human immunodeficiency virus 1 ER - TY - JOUR T1 - Further evidence for promoter-dependent development of hepatoblastoma in the mouse AN - 16759312; 3727887 AB - In previous studies, we found that male D2B6F1 mice fed phenobarbital (PB) for 53 weeks following N-nitrosodiethylamine (NDEA) initiation developed a high (70-80%) incidence of malignant hepatoblastomas. A very low (3.3%) incidence of such tumors occurred in the absence of promoter treatment in NDEA-initiated mice observed for 60 weeks, although nearly 50% of these animals developed hepatocellular lesions. To investigate whether hepatocellular lesions in NDEA-initiated mice or spontaneous hepatocellular lesions promoted by PB in mice given PB but no NDEA, progress to hepatoblastomas later in life, mice exposed to NDEA alone and PB alone were maintained for 110 weeks. Hepatocellular tumors (adenomas and carcinomas) occurred in almost all (97%) mice given NDEA alone. However, only 10% of NDEA-treated mice developed hepatoblastomas. Thus, despite its ability to induce hepatocellular neoplasms, NDEA treatment alone was rarely sufficient to induce hepatoblastomas in these mice. In contrast, PB treatment in the absence of NDEA initiation promoted the development of spontaneously occurring hepatocellular lesions, a significant number (37%) of which progressed to hepatoblastomas. Our observations clearly show that in this animal model the development of hepatoblastoma from its precursor cells (hepatocellular adenoma and carcinoma cells) occurs predominantly in the presence of promoting agents such as PB. JF - Cancer Letters AU - Diwan, BA AU - Henneman, J R AU - Rice, J M AD - Lab. Comparat. Carcinog., NCI/FCRDC, Frederick, MD 21702-1201, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 29 EP - 35 VL - 89 IS - 1 SN - 0304-3835, 0304-3835 KW - mice KW - phenobarbital KW - N-nitrosodiethylamine KW - Toxicology Abstracts KW - tumor-promoting agents KW - liver KW - hepatoma KW - X 24200:Nitrosamines & related compounds KW - X 24115:Pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16759312?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Letters&rft.atitle=Further+evidence+for+promoter-dependent+development+of+hepatoblastoma+in+the+mouse&rft.au=Diwan%2C+BA%3BHenneman%2C+J+R%3BRice%2C+J+M&rft.aulast=Diwan&rft.aufirst=BA&rft.date=1995-01-01&rft.volume=89&rft.issue=1&rft.spage=29&rft.isbn=&rft.btitle=&rft.title=Cancer+Letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - liver; hepatoma; tumor-promoting agents ER - TY - JOUR T1 - Water release associated with specific binding of gal repressor AN - 16753445; 3726017 AB - Water release coupled to the association of gal repressor with DNA is measured from the sensitivity of the biding constant to the solution osmotic pressure, using neutral solutes that are typically excluded from polar protein and DNA surfaces. Differences in water release for binding of repressor to different sequences are linked with differences in specificity and binding energies. With sucrose, the specific binding of repressor to operator sequences is accompanied by the release of 130 water molecules. No water release is seen for the weak, non-specific binding of repressor to poly(dI-dC)-(dI-dC). A difference in the release of six water molecules is seen even for the binding of gal repressor to two different operator sequences that differ in affinity by only a factor of two. JF - EMBO Journal AU - Garner, M M AU - Rau, D C AD - Lab. Theor. and Phys. Biol., NICHD, Build. 10, NIH, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 1257 EP - 1263 VL - 14 IS - 6 SN - 0261-4189, 0261-4189 KW - gal repressor KW - sucrose KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - hydration KW - DNA KW - Escherichia coli KW - osmotic stress KW - J 02725:DNA KW - N 14930:Transcription factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16753445?accountid=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=EMBO+Journal&rft.atitle=Water+release+associated+with+specific+binding+of+gal+repressor&rft.au=Garner%2C+M+M%3BRau%2C+D+C&rft.aulast=Garner&rft.aufirst=M&rft.date=1995-01-01&rft.volume=14&rft.issue=6&rft.spage=1257&rft.isbn=&rft.btitle=&rft.title=EMBO+Journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; DNA; hydration; osmotic stress ER - TY - JOUR T1 - Characterization of a specific interaction between Escherichia coli thymidylate synthase and Escherichia coli thymidylate synthase mRNA AN - 16753144; 3726023 AB - Previous studies have shown that human TS mRNA translation is controlled by a negative autoregulatory mechanism. In this study, an RNA electrophoretic gel mobility shift assay confirmed a direct interaction between Escherichia coli (E. coli) TS protein and its own E. coli TS mRNA. Two cis-acting sequences in the E. coli TS mRNA protein-coding region were identified, with one site corresponding to nucleotides 207-460 and the second site corresponding to nucleotides 461-807. Each of these mRNA sequences bind TS with a relative affinity similar to that of the full-length E. coli TS mRNA sequence (IC sub(50) = 1 nM). A third binding site was identified, corresponding to nucleotides 808-1015, although its relative affinity for TS (IC sub(50) = 5.1 nM) was lower than that of the other two cis-acting elements. E. coli TS proteins with mutations in amino acids located within the nucleotide-binding region retained the ability to bind RNA while proteins with mutations at either the nucleotide active site cysteine (C146S) or at amino acids located within the folate-binding region were unable to bind TS mRNA. These studies suggest that the regions on E. coli TS defined by the folate-binding site and/or critical cysteine sulfhydryl groups may represent important RNA binding domains. Further evidence is presented which demonstrates that the direct interaction with TS results in in vitro repression of E. coli TS mRNA translation. JF - Nucleic Acids Research AU - Voeller, D M AU - Changchien, Li-ming AU - Maley, G F AU - Maley, F AU - Takechi, T AU - Turner, R E AU - Montfort, W R AU - Allegra, C J AU - Chu, E AD - NCI-Navy Med. Oncol. Branch, NCI, Bethesda, MD 20889-5105, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 869 EP - 875 VL - 23 IS - 5 SN - 0305-1048, 0305-1048 KW - thymidylate synthase KW - folic acid KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - translation KW - RNA KW - Escherichia coli KW - J 02726:RNA and ribosomes KW - N 14940:Nucleic acid-binding proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16753144?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+Acids+Research&rft.atitle=Characterization+of+a+specific+interaction+between+Escherichia+coli+thymidylate+synthase+and+Escherichia+coli+thymidylate+synthase+mRNA&rft.au=Voeller%2C+D+M%3BChangchien%2C+Li-ming%3BMaley%2C+G+F%3BMaley%2C+F%3BTakechi%2C+T%3BTurner%2C+R+E%3BMontfort%2C+W+R%3BAllegra%2C+C+J%3BChu%2C+E&rft.aulast=Voeller&rft.aufirst=D&rft.date=1995-01-01&rft.volume=23&rft.issue=5&rft.spage=869&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; RNA; translation ER - TY - JOUR T1 - Addiction protein Phd of plasmid prophage P1 is a substrate of the ClpXp serine protease of Escherichia coli AN - 16746989; 3725985 AB - Plasmid-encoded addiction genes augment the apparent stability of various low copy number bacterial plasmids by selectively killing plasmid-free (cured) segregants or their progeny. The addiction module of plasmid prophage P1 consists of a pair of genes called phd and doc. Phd serves to prevent host death when the prophage is retained and, should retention mechanisms fail, Doc causes death on curing. Doc acts as a cell toxin to which Phd is an antidote. In this study we show that host mutants with defects in either subunit of the ClpXP protease survive the loss of a plasmid that contains a P1 addiction module. The small antidote protein Phd is fully stable in these two mutant hosts, whereas it is labile in a wild-type host. We conclude that the role of ClpXP in the addiction mechanism of P1 is to degrade the Phd protein. This conclusion situates P1 among plasmids that elicit severe withdrawal symptoms and are able to do so because they encode both a cell toxin and an actively degraded macromolecule that blocks the synthesis or function of the toxin. JF - Proceedings of the National Academy of Sciences, USA AU - Lehnherr, H AU - Yarmolinsky, M B AD - Lab. Biochem., NCI, Build. 37, Rm. 4D-15, 37 Convent Dr., MSC 4255, Bethesda, MD 20892-4255, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 3274 EP - 3277 VL - 92 IS - 8 SN - 0027-8424, 0027-8424 KW - Phd protein KW - ClpXP protein KW - serine proteinase KW - phd gene KW - doc gene KW - Microbiology Abstracts B: Bacteriology; Virology & AIDS Abstracts KW - cell death KW - phage P1 KW - toxins KW - Escherichia coli KW - plasmids KW - J 02728:Enzymes KW - V 22070:Phage-host interactions including lysogeny & transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16746989?accountid=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=Addiction+protein+Phd+of+plasmid+prophage+P1+is+a+substrate+of+the+ClpXp+serine+protease+of+Escherichia+coli&rft.au=Lehnherr%2C+H%3BYarmolinsky%2C+M+B&rft.aulast=Lehnherr&rft.aufirst=H&rft.date=1995-01-01&rft.volume=92&rft.issue=8&rft.spage=3274&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - phage P1; Escherichia coli; cell death; toxins; plasmids ER - TY - JOUR T1 - Tumorigenesis and metastasis of neoplastic Kaposi's sarcoma cell line in immunodeficient mice blocked by a human pregnancy hormone AN - 16743765; 3722033 AB - Kaposi's sarcoma (KS) occurs more often in men than in women and HIV-1-associated KS has a high occurrence in homosexual men (over 30%). Most cultures of KS tumours yield cells with properties of hyperplastic (not malignant) endothelial cells under the control of several cytokines. The role of HIV-1 may be in promoting high levels of some cytokines and providing stimulation to angiogenesis by the HIV-1 Tat protein, which synergizes with basic fibroblast growth factor in promoting these effects. Here we describe an immortalized AIDS-KS cell line (KS Y-1) and show that these cells produce malignant metastatic tumours in nude mice and are killed in vitro and in vivo (apparently by apoptosis) by a pregnancy hormone, the beta -chain of human chorionic gonadotropin. Similarly, chorionic gonadotropin kills KS SLK, cells from another neoplastic cell line (established from a non-HIV-associated KS), as well as the hyperplastic KS cells from clinical specimens grown in short-term culture, but does not kill normal endothelial cells. These results provide evidence that KS can evolve into a malignancy and have implications for the hormonal treatment of this tumour. JF - Nature AU - Lunardi-Iskandar, Y AU - Bryant, J L AU - Zeman, R A AU - Lam, V H AU - Samaniego, F AU - Besnier, J M AU - Hermans, P AU - Thierry, A R AU - Gill, P AU - Gallo, R C AD - Lab. Tumor Cell Biol., NCI, and Anim. Care Unit, Natl. Inst. Dent. Res., NIH, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 64 EP - 67 VL - 375 IS - 6526 SN - 0028-0836, 0028-0836 KW - chorionic gonadotropin KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - Kaposi's sarcoma KW - tumorigenesis KW - metastases KW - cell lines KW - acquired immune deficiency syndrome KW - V 22002:AIDS: Molecular and in vitro aspects KW - W3 33170:Cellular based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16743765?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=Tumorigenesis+and+metastasis+of+neoplastic+Kaposi%27s+sarcoma+cell+line+in+immunodeficient+mice+blocked+by+a+human+pregnancy+hormone&rft.au=Lunardi-Iskandar%2C+Y%3BBryant%2C+J+L%3BZeman%2C+R+A%3BLam%2C+V+H%3BSamaniego%2C+F%3BBesnier%2C+J+M%3BHermans%2C+P%3BThierry%2C+A+R%3BGill%2C+P%3BGallo%2C+R+C&rft.aulast=Lunardi-Iskandar&rft.aufirst=Y&rft.date=1995-01-01&rft.volume=375&rft.issue=6526&rft.spage=64&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Kaposi's sarcoma; tumorigenesis; metastases; cell lines; acquired immune deficiency syndrome ER - TY - JOUR T1 - Diagnostic assay for Helicobacter hepaticus based on nucleotide sequence of its 16S rRNA gene AN - 16741985; 3722322 AB - Conserved primers used to PCR amplify 95% of the Helicobacter hepaticus 16S rRNA gene. Its sequence was determined and aligned to those of related bacteria, enabling the selection of primers to highly diverged regions of the 16S rRNA gene and an oligonucleotide probe for the development of a PCR-liquid hybridization assay. This assay was shown to be both sensitive and specific for H. hepaticus 16S rRNA gene sequences. JF - Journal of Clinical Microbiology AU - Battles, J K AU - Williamson, J C AU - Pike, K M AU - Gorelick, P L AU - Ward, J M AU - Gonda, MA AD - Lab. Cell. Mol. Struct., Prog. Resour., Inc./DynCorp, NCI-FCRDC, P.O. Box B, Frederick, MD 21702-1201, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 1344 EP - 1347 VL - 33 IS - 5 SN - 0095-1137, 0095-1137 KW - rRNA 16S KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - nucleotide sequence KW - Helicobacter hepaticus KW - N 14414:Structure and sequence KW - W 30965:Miscellaneous, Reviews KW - W3 33130:Genetic based (PCR, etc.) KW - J 02846:Gastrointestinal tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16741985?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Clinical+Microbiology&rft.atitle=Diagnostic+assay+for+Helicobacter+hepaticus+based+on+nucleotide+sequence+of+its+16S+rRNA+gene&rft.au=Battles%2C+J+K%3BWilliamson%2C+J+C%3BPike%2C+K+M%3BGorelick%2C+P+L%3BWard%2C+J+M%3BGonda%2C+MA&rft.aulast=Battles&rft.aufirst=J&rft.date=1995-01-01&rft.volume=33&rft.issue=5&rft.spage=1344&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Microbiology&rft.issn=00951137&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - nucleotide sequence; Helicobacter hepaticus ER - TY - JOUR T1 - Nitrous oxide and spontaneous abortion in female dental assistants AN - 16738253; 3720268 AB - The relation between anesthetic gas exposure and spontaneous abortion remains unresolved. We examined the effect of nitrous oxide on spontaneous abortion among female dental assistants. Questionnaires were sent to 7,000 dental assistants aged 18-39 years who were registered in California in 1987; 4,856 (69%) responded. Analysis was based on 1,465 respondents whose most recent pregnancy was conceived while working full time. Women were asked how many hours a week they worked with nitrous oxide during this pregnancy and whether the excess gas was scavenged (vented). Relative risk of spontaneous abortion (through week 20) was calculated using a person-week model. This allowed women with current pregnancies (13%) or induced abortions (10%) to be included for appropriate time periods of risk. A total of 101 pregnancies (7%) ended as spontaneous abortions. An elevation in risk of spontaneous abortion was seen among women who worked with nitrous oxide for 3 or more hours per week in offices not using scavenging equipment (relative risk = 2.6, 95% confidence interval 1.3-5.0, adjusted for age, smoking, and number of amalgams prepared per week), but not among those using nitrous oxide in offices with scavenging equipment. This relation changed little when analyses were restricted to confirmed pregnancies or examined for several types of potential bias. Scavenging equipment appears to be important in protecting the reproductive health of women working with nitrous oxide. JF - American Journal of Epidemiology AU - Rowland, A S AU - Baird, D D AU - Shore, D L AU - Weinberg, C R AU - Savitz, DA AU - Wilcox, A J AD - Epidemiol. Branch A3-05, NIEHS, P.O. Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 531 EP - 538 VL - 141 IS - 6 SN - 0002-9262, 0002-9262 KW - nitrous oxide KW - dentistry KW - dental personnel KW - man KW - Toxicology Abstracts; Risk Abstracts; Health & Safety Science Abstracts KW - air pollution KW - occupational exposure KW - pregnancy KW - abortion KW - H SM3.8.2:CHEMICALS (CORROSION) KW - R2 23080:Industrial and labor KW - H SI0.8.2:CHEMICALS (CORROSION) KW - X 24113:Side effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16738253?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Epidemiology&rft.atitle=Nitrous+oxide+and+spontaneous+abortion+in+female+dental+assistants&rft.au=Rowland%2C+A+S%3BBaird%2C+D+D%3BShore%2C+D+L%3BWeinberg%2C+C+R%3BSavitz%2C+DA%3BWilcox%2C+A+J&rft.aulast=Rowland&rft.aufirst=A&rft.date=1995-01-01&rft.volume=141&rft.issue=6&rft.spage=531&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - occupational exposure; nitrous oxide; abortion; air pollution; pregnancy; dentistry; dental personnel; man ER - TY - JOUR T1 - Novel proteins of the phosphotransferase system encoded within the rpoN operon of Escherichia coli: Enzyme IIA super(Ntr) affects growth on organic nitrogen and the conditional lethality of an era super(ts) mutant AN - 16733659; 3717870 AB - Two rpoN-linked Delta Tn10-kan insertions suppress the conditionally lethal era super(ts) allele. One truncates rpoN while the second disrupts another gene (ptsN) in the rpoN operon and does not affect classical nitrogen regulation. Neither alter expression of era indicating that suppression is post-translational. Plasmid clones of ptsN prevent suppression by either disruption mutation indicating that this gene is important for lethality caused by era super(ts). rpoN and six neighboring genes were sequenced and compared with sequences in the database. Two of these genes encode proteins homologous to Enzyme IIA super(Fru) and HPr of the phosphoenolpyruvate:sugar phosphotransferase system. We designate these proteins IIA super(Ntr) (ptsN) and NPr (npr). Purified IIA super(Ntr) and NPr exchange phosphate appropriately with Enzyme I, HPr, and Enzyme IIA proteins of the phosphoenolpyruvate: sugar phosphotransferase system. Several sugars and tricarboxylic acid cycle intermediates inhibited growth of the ptsN disruption mutant on medium containing an amino acid or nucleoside base as a combined source of nitrogen, carbon, and energy. This growth inhibition was relieved by supplying the ptsN gene or ammonium salts but was not aleviated by altering levels of exogenously supplied cAMP. The results support our previous proposal of a novel mechanism linking carbon and nitrogen assimilation and relates IIA super(Ntr) to the unknown process regulated by the essential GTPase Era. JF - Journal of Biological Chemistry AU - Powell, B S AU - Court, D L AU - Inada, T AU - Nakamura, Y AU - Michotey, V AU - Cui, Xuewen AU - Reizer, A AU - Saier, MHJr AU - Reizer, J AD - Lab. Chromosome Biol., ABL-Basic Res. Program, NCI-Frederick Cancer Res. and Dev. Cent., Frederick, MD 21702-1201, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 4822 EP - 4839 VL - 270 IS - 9 SN - 0021-9258, 0021-9258 KW - rpoN operon KW - transposon Tn10 KW - era gene KW - ptsN gene KW - nitrogen KW - enzyme IIA KW - HPr protein KW - phosphoenolpyruvate-protein phosphotransferase KW - cyclic AMP KW - guanosinetriphosphatase KW - Era protein KW - amino acid sequence predictions KW - Genetics Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - nucleotide sequence KW - Escherichia coli KW - lethality KW - N 14640:Structure & sequence KW - G 07321:GENERAL KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16733659?accountid=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=Novel+proteins+of+the+phosphotransferase+system+encoded+within+the+rpoN+operon+of+Escherichia+coli%3A+Enzyme+IIA+super%28Ntr%29+affects+growth+on+organic+nitrogen+and+the+conditional+lethality+of+an+era+super%28ts%29+mutant&rft.au=Powell%2C+B+S%3BCourt%2C+D+L%3BInada%2C+T%3BNakamura%2C+Y%3BMichotey%2C+V%3BCui%2C+Xuewen%3BReizer%2C+A%3BSaier%2C+MHJr%3BReizer%2C+J&rft.aulast=Powell&rft.aufirst=B&rft.date=1995-01-01&rft.volume=270&rft.issue=9&rft.spage=4822&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; lethality; nucleotide sequence ER - TY - JOUR T1 - A small RNA acts as an antisilencer of the H-NS-silenced rcsA gene of Escherichia coli AN - 16730430; 3715215 AB - The regulation of capsular polysaccharide synthesis in Escherichia coli K-12 depends on the level of an unstable positive regulator, RcsA. The amount of RcsA protein is limited both by its rapid degradation by Lon, an ATP-dependent protease, and by its low level of synthesis. We have found that the low level of expression from the rcsA promoter is due to transcriptional silencing by the histone-like protein H-NS; this silencing is sensitive to both sequence and context in a region upstream of the -35 region of the promoter. A small (85-nt) RNA, DsrA, when overproduced, activates transcription of rcsA::lazZ fusions by counteracting H-NS silencing. DsrA RNA does not show any extended homology with the rcsA promoter or other sequenced regions of E. coli. Since the stimulation of rcsA transcription by this small RNA does not depend on any sequences from within rcsA transcript, DsrA acts, either directly or indirectly, on rcsA transcription initiation. JF - Proceedings of the National Academy of Sciences, USA AU - Sledjeski, D AU - Gottesman, S AD - Lab. Mol. Biol., NCI/NIH, Build. 37, Rm. 2E18, 37 Convent Dr., MSC 4255, Bethesda, MD 20892-4255, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 2003 EP - 2007 VL - 92 IS - 6 SN - 0027-8424, 0027-8424 KW - rcsA gene KW - polysaccharides KW - H-NS protein KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - transcription initiation KW - Escherichia coli KW - capsules KW - gene silencing KW - G 07321:GENERAL KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16730430?accountid=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=A+small+RNA+acts+as+an+antisilencer+of+the+H-NS-silenced+rcsA+gene+of+Escherichia+coli&rft.au=Sledjeski%2C+D%3BGottesman%2C+S&rft.aulast=Sledjeski&rft.aufirst=D&rft.date=1995-01-01&rft.volume=92&rft.issue=6&rft.spage=2003&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; capsules; gene silencing; transcription initiation ER - TY - JOUR T1 - Effects of acute and delayed effects of prior chronic cocaine administration on regional rates of cerebral protein synthesis in rats AN - 16729789; 3715829 AB - Single or repeated treatments with cocaine (15 mg/kg, i.p.) in rats modify rates of local cerebral protein synthesis (ICPS sub(leu)) measured with the [1- super(14)C]leucine method. A single dose of cocaine to naive rats reduced ICPS sub(leu) by about 10% throughout the brain; the most statistically significant reduction was in the nucleus accumbens, shell portion. A comparable dose of cocaine administered acutely after 1 wk of daily cocaine injections had no effects on ICPS sub(leu). Delayed effects of prior chronic cocaine treatment were studied in experiments in which one rat of each pair received injections with saline for 8 days and the other cocaine, and on the 15th day ICPS sub(leu) was measured. In these experiments delayed effects of the chronic cocaine treatment were observed; in the cocaine-treated rats ICPS sub(leu) was significantly increased in selective brain regions, i.e., prefrontal and primary olfactory cortex. The results suggest that acute effects of a single dose of cocaine and residual effects of chronic cocaine treatment on ICPS sub(leu) are distinctly different and occur in different regions of the brain. JF - Journal of Pharmacology and Experimental Therapeutics AU - Orzi, F AU - Sun, Yun AU - Pettigrew, K AU - Sokoloff, L AU - Smith, C B AD - Lab. Cereb. Metab., NIMH, Build. 36, Rm. 1A05, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 892 EP - 900 VL - 272 IS - 2 SN - 0022-3565, 0022-3565 KW - cocaine KW - rats KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - protein biosynthesis KW - cerebrum 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/16729789?accountid=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+Pharmacology+and+Experimental+Therapeutics&rft.atitle=Effects+of+acute+and+delayed+effects+of+prior+chronic+cocaine+administration+on+regional+rates+of+cerebral+protein+synthesis+in+rats&rft.au=Orzi%2C+F%3BSun%2C+Yun%3BPettigrew%2C+K%3BSokoloff%2C+L%3BSmith%2C+C+B&rft.aulast=Orzi&rft.aufirst=F&rft.date=1995-01-01&rft.volume=272&rft.issue=2&rft.spage=892&rft.isbn=&rft.btitle=&rft.title=Journal+of+Pharmacology+and+Experimental+Therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - protein biosynthesis; cerebrum ER - TY - JOUR T1 - Glycine reductase selenoprotein A is not a glycoprotein: The positive periodic acid-Schiff reagent test is the result of peptide bond cleavage and carbonyl group generation AN - 16728983; 3715331 AB - The complete amino acid sequence of Clostridium sticklandii selenoprotein A, a selenocysteine-containing protein component of the glycine reductase complex, has been established. Both the intact protein and peptide fragments produced by Staphylococcus aureus V8 protease or trypsin were purified by reversed-phase high-performance liquid chromatography and subjected to electrospray ionization mass spectrometric analysis and standard Edman degradation. Selenoprotein A consists of 157 amino acids with a chemical molecular weight of 17,011, in reasonable agreement with the observed molecular weight (17,022.7) determined from its ionization mass spectrum. The sequence of the amino-terminal region of the isolated native protein is Ser-Arg-Phe-Thr-Gly-Lys-Lys-Ile-Val-Ile-Ile-Gly-Asp-Arg-Asp-. An N-terminal methionine residue deduced from the gene sequence was not present. Although selenoprotein A reacted positively in a glycoprotein stain when using either the periodic acid-Schiff reagent procedure or a commercial glycan detection kit, no saccharide was detected by carbohydrate analyses after acid hydrolysis or methanolysis. Identity of the amino acid sequence determined by analysis with that deduced from the gene sequence is further evidence of the absence of bound carbohydrate. JF - Proceedings of the National Academy of Sciences, USA AU - Kimura, Y AU - Stadtman, T C AD - NHLBI/IR/LB, Bldg. 3, Rm. 108, 3 Cent. Dr., MSC 0320, Bethesda, MD 20892-0320, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 2189 EP - 2193 VL - 92 IS - 6 SN - 0027-8424, 0027-8424 KW - selenoprotein A KW - Microbiology Abstracts B: Bacteriology KW - amino acid sequence KW - Clostridium sticklandii KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16728983?accountid=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=Glycine+reductase+selenoprotein+A+is+not+a+glycoprotein%3A+The+positive+periodic+acid-Schiff+reagent+test+is+the+result+of+peptide+bond+cleavage+and+carbonyl+group+generation&rft.au=Kimura%2C+Y%3BStadtman%2C+T+C&rft.aulast=Kimura&rft.aufirst=Y&rft.date=1995-01-01&rft.volume=92&rft.issue=6&rft.spage=2189&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Clostridium sticklandii; amino acid sequence ER - TY - JOUR T1 - Reversal by cytidine of cyclopentenyl cytosine-induced toxicity in mice without compromise of antitumor activity AN - 16721713; 3712103 AB - Among nine compounds surveyed, cytidine was found to be the most effective in reversing the antiproliferative effects of cyclopentenyl cytosine (CPEC) on human T-lymphoblasts (MOLT-4) in culture. Cytidine, at concentrations of 1-25 mu M, enabled cells to maintain normal logarithmic growth when added up to 12 hr after exposure to a 200 nM concentration of the oncolytic nucleoside, CPEC. The most abundant CPEC metabolite, CPEC-5'-triphosphate, is a potent [K sub(1) approximately 6 mu M] inhibitor of CTP synthetase (EC 6.3.4.2). Accumulation of this inhibitor resulted in a depletion of CTP levels to 17% of their original cellular concentration. Exogenous cytidine reversed CPEC-induced cellular cytotoxicity by suppressing the formation of CPEC-5'-triphosphate by 70%, and by partially replenishing intracellular CTP to at least 60-70% of its original concentration. In vivo, cytidine (500 mg/kg) administered intraperitoneally 4 hr after each daily dose of CPEC (LD sub(10)-LD sub(100)) for 9 days reduced the toxicity and abolished the lethality of CPEC to non-tumored mice. Of greater practical importance is the finding that, under these experimental conditions, cytidine did not curtail the antineoplastic properties of CPEC in L1210 tumor-bearing mice. Moreover, the concentration range over which CPEC exhibited antineoplastic activity was extended with cytidine administration. JF - Biochemical Pharmacology AU - Ford, H Jr AU - Driscoll, J S AU - Hao, Zhang AU - Dobyns, KA AU - Rommel, ME AU - Stowe, E AU - Anderson, JO AU - Plowman, J AU - Waud, W R AU - Johns, D G AU - Cooney, DA AD - Lab. Med. Chem., Build. 37, Room 5C-24, NCI/NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 173 EP - 180 VL - 49 IS - 2 SN - 0006-2952, 0006-2952 KW - cytidine KW - cyclopentenyl cytosine KW - mice KW - Toxicology Abstracts KW - lymphoblasts KW - antineoplastic drugs KW - antitumor agents KW - X 24111:Acute exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16721713?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+Pharmacology&rft.atitle=Reversal+by+cytidine+of+cyclopentenyl+cytosine-induced+toxicity+in+mice+without+compromise+of+antitumor+activity&rft.au=Ford%2C+H+Jr%3BDriscoll%2C+J+S%3BHao%2C+Zhang%3BDobyns%2C+KA%3BRommel%2C+ME%3BStowe%2C+E%3BAnderson%2C+JO%3BPlowman%2C+J%3BWaud%2C+W+R%3BJohns%2C+D+G%3BCooney%2C+DA&rft.aulast=Ford&rft.aufirst=H&rft.date=1995-01-01&rft.volume=49&rft.issue=2&rft.spage=173&rft.isbn=&rft.btitle=&rft.title=Biochemical+Pharmacology&rft.issn=00062952&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 - antitumor agents; antineoplastic drugs; lymphoblasts ER - TY - JOUR T1 - Kinetics of chlamydial antigen processing and presentation to T cells by paraformaldehyde-fixed murine bone marrow-derived macrophages AN - 16716230; 3707081 AB - Macrophages are potential candidates for antigen presentation to chlamydial-specific CD4 super(+) T cells. We have studied the kinetics of chlamydial antigen processing and presentation by using paraformaldehyde-fixed bone marrow-derived macrophages (BMDM) and splenic T cells isolated from chlamydia-infected mice. BMDM were inoculated with different multiplicities of heat-killed chlamydial elementary bodies, and at different times postingestion, the macrophages were fixed with paraformaldehyde and used as antigen-presenting cells in T-cell proliferation assays. T-cell proliferative responses were shown to be dependent on the chlamydial inoculum size, with a multiplicity of 10 chlamydiae per macrophage producing optimum T-cell proliferation. Temporal experiments showed that peak T-cell proliferative responses occurred between 4 and 12 h postingestion of chlamydiae by BMDM. T cells proliferated strongly to antigen when presented by H-2-matched BMDM but not when presented by H-2-disparate BMDM, demonstrating that T-cell recognition of processed chlamydial antigen was major histocompatibility complex restricted. BMDM inoculated with 10 chlamydiae per cell and fixed at 8 h postinoculation were shown to be as stimulatory to T cells as conventional splenic antigen-presenting cells. Because large numbers of BMDM can be propagated in vitro, and experimental conditions that provide optimum presentation of processed chlamydial antigen to chlamydia-specific CD4 super(+) T cells can be defined, BMDM may be a potentially useful source for the isolation of naturally processed parasite antigen from major histocompatibility complex class II molecules. JF - Infection and Immunity AU - Su, H AU - Caldwell, H D AD - Lab. Intracell. Parasites, Rocky Mountain Lab., NIAID/NIH, Hamilton, MT 59840-2999, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 946 EP - 953 VL - 63 IS - 3 SN - 0019-9567, 0019-9567 KW - mice KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - lymphocytes T KW - antigen presentation KW - Chlamydia trachomatis KW - macrophages KW - antigens KW - F 06776:Cell cooperation (antigen presentation) KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16716230?accountid=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=Kinetics+of+chlamydial+antigen+processing+and+presentation+to+T+cells+by+paraformaldehyde-fixed+murine+bone+marrow-derived+macrophages&rft.au=Su%2C+H%3BCaldwell%2C+H+D&rft.aulast=Su&rft.aufirst=H&rft.date=1995-01-01&rft.volume=63&rft.issue=3&rft.spage=946&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Chlamydia trachomatis; lymphocytes T; antigens; macrophages; antigen presentation ER - TY - JOUR T1 - Michellamine B, a novel plant alkaloid, inhibits human immunodeficiency virus-induced cell killing by at least two distinct mechanisms AN - 16714837; 3710846 AB - Studies of the mechanism of action of michellamine B, a novel anti-human immunodeficiency virus (HIV) alkaloid from the tropical plant Ancistrocladus korupensis, have revealed that the compound acts at two distinct stages of the HIV life cycle. The compound had no direct effect on HIV virions and did not block the initial binding of HIV to target cells. Postinfection time course studies revealed that the agent partially inhibited HIV-induced cell killing and syncytium formation when added up to 48 h following acute infection; however, viral reproduction was fully inhibited only when the compound was added immediately after infection. Time-limited treatments of HIV-infected cells revealed that michellamine B had to be present continuously to provide maximum antiviral protection. HIV replication in cells in which infection was already fully established or in chronically infected cells was unaffected by michellamine B. Biochemical studies showed that michellamine B inhibited the enzymatic activities of reverse transcriptases (RTs) from both HIV type 1 and HIV type 2 as well as two different nonnucleoside drug-resistant RTs with specific amino acid substitutions. In addition, human DNA polymerases alpha and beta were inhibited by the alkaloid. Michellamine B exerted a potent dose-dependent inhibition of cell fusion in two independent cell-based fusion assays. Thus, michellamine B acts both at an early stage of the HIV life cycle by inhibiting RT as well as at later stages by inhibiting cellular fusion and syncytium formation. JF - Antimicrobial Agents & Chemotherapy AU - McMahon, J B AU - Currens, MJ AU - Gulakowski, R J AU - Buckheit, RW Jr AU - Lackman-Smith, C AU - Hallock, Y F AU - Boyd, M R AD - Drug Dis. Res. Dev., Dev. Ther. Prog., Div. Cancer Treat., NCI, Build. 1052, Rm. 121, Frederick, MD 21702-1201, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 484 EP - 488 VL - 39 IS - 2 SN - 0066-4804, 0066-4804 KW - michellamine B KW - Ancistrocladus korupensis KW - DNA-directed DNA polymerase KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - human immunodeficiency virus 1 KW - V 22002:AIDS: Molecular and in vitro aspects KW - A 01068:Antiviral & viricidal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16714837?accountid=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=Antimicrobial+Agents+%26+Chemotherapy&rft.atitle=Michellamine+B%2C+a+novel+plant+alkaloid%2C+inhibits+human+immunodeficiency+virus-induced+cell+killing+by+at+least+two+distinct+mechanisms&rft.au=McMahon%2C+J+B%3BCurrens%2C+MJ%3BGulakowski%2C+R+J%3BBuckheit%2C+RW+Jr%3BLackman-Smith%2C+C%3BHallock%2C+Y+F%3BBoyd%2C+M+R&rft.aulast=McMahon&rft.aufirst=J&rft.date=1995-01-01&rft.volume=39&rft.issue=2&rft.spage=484&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 N1 - SubjectsTermNotLitGenreText - human immunodeficiency virus 1 ER - TY - JOUR T1 - Effect of the FruR regulator on transcription of the pts operon in Escherichia coli AN - 16713094; 3710543 AB - The promoters of the pts operon of Escherichia coli are controlled by the cyclic AMP receptor protein (CRP) complexed with cAMP (CRP-cAMP). In addition, glucose stimulates pts operon expression in vivo. The pts promoter region has a fructose repressor (FruR)-binding site (the FruR box) that partially overlaps with one of the CRP-cAMP-binding sites. The effects of the pleiotropic transcriptional regulator FruR on pts operon expression were studied to determine whether the in vivo glucose effect on pts operon expression is mediated by FruR. In vitro, FruR can repress P1b transcription, which is activated by CRP-cAMP, and restore P1a transcription, which is repressed by CRP-cAMP. FruR can displace CRP-cAMP from its binding site in the presence of RNA polymerase even though FruR and CRP-cAMP can bind simultaneously to their partially overlapping binding sites in the absence of RNA polymerase. FruR had very little effect on the transcription of the P0 promoter, which is most important for regulation by glucose. Consistent with the in vitro results, pts P0 transcription did not increase as much in cells grown in the presence of fructose or in fruR super(-) mutant cells as in cells grown in the presence of glucose. The results suggest that FruR alone does not mediate the in vivo glucose effect on pts operon expression. JF - Journal of Biological Chemistry AU - Ryu, S AU - Ramseier, T M AU - Michotey, V AU - Saier, MH Jr AU - Garges, S AD - Lab. Mol. Biol., Build. 37, Rm. 2E06, NCI/NIH, Bethesda, MD 20892-4255, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 2489 EP - 2496 VL - 270 IS - 6 SN - 0021-9258, 0021-9258 KW - pts operon KW - cyclic AMP receptor protein KW - cyclic AMP KW - glucose KW - FruR protein KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Escherichia coli KW - transcription KW - J 02725:DNA KW - N 14662:Gene regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16713094?accountid=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=Effect+of+the+FruR+regulator+on+transcription+of+the+pts+operon+in+Escherichia+coli&rft.au=Ryu%2C+S%3BRamseier%2C+T+M%3BMichotey%2C+V%3BSaier%2C+MH+Jr%3BGarges%2C+S&rft.aulast=Ryu&rft.aufirst=S&rft.date=1995-01-01&rft.volume=270&rft.issue=6&rft.spage=2489&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; transcription ER - TY - JOUR T1 - Emergence of human immunodeficiency virus type 1 variants with resistance to multiple dideoxynucleosides in patients receiving therapy with dideoxynucleosides AN - 16710058; 3710256 AB - A set of mutations [Ala-62 arrow right Val(A62V), V75I, F77L, F116Y, and Q151M] in the polymerase domain of reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) confers on the virus a reduced sensitivity to multiple antiretroviral dideoxynucleosides and has been seen in HIV-1 variants isolated from patients receiving combination chemotherapy with 3'-azido-3'-deoxythymidine (AZT) plus 2',3'-dideoxycytidine (ddC) or 2',3'-dideoxyinosine (ddI). The IC sub(50) values of AZT, ddC, ddI, 2',3'-dideoxyguanosine, and 2',3'-didehydro-3'-deoxythymidine against an infectious clone constructed to include the five mutations were significantly higher than those of a wild-type infectious clone. The K sub(i) value for AZT 5'-triphosphate determined for the virus-associated RT from a posttherapy strain was 35-fold higher than that of RT from a pretherapy strain. Detailed analysis of HIV-1 strains isolated at various times during therapy showed that the Q151M mutation developed first in vivo, at the time when the viremia level suddenly increased, followed by the F116Y and F77L mutations. All five mutations ultimately developed, and the viremia level rose even further. Analyses based on the three-dimensional structure of HIV-1 RT suggest that the positions where at least several of the five mutations occur are located in close proximity to the proposed dNTP-binding site of RT and the first nucleotide position of the single-stranded template. JF - Proceedings of the National Academy of Sciences, USA AU - Shirasaka, T AU - Kavlick, M F AU - Ueno, T AU - Gao, Wen-Yi AU - Kojima, E AU - Alcaide, M L AU - Chokekijchai, S AU - Roy, B M AU - Arnold, E AU - Yarchoan, R AD - Exp. Retrovirol. Sect., Med. Branch, NCI/NIH, Build. 10, Rm. 5A11, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 2398 EP - 2402 VL - 92 IS - 6 SN - 0027-8424, 0027-8424 KW - RNA-directed DNA polymerase KW - dideoxynucleosides KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Virology & AIDS Abstracts KW - human immunodeficiency virus 1 KW - viremia KW - mutation KW - man KW - multidrug resistance KW - V 22002:AIDS: Molecular and in vitro aspects KW - N 14160:Biological properties 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/16710058?accountid=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=Emergence+of+human+immunodeficiency+virus+type+1+variants+with+resistance+to+multiple+dideoxynucleosides+in+patients+receiving+therapy+with+dideoxynucleosides&rft.au=Shirasaka%2C+T%3BKavlick%2C+M+F%3BUeno%2C+T%3BGao%2C+Wen-Yi%3BKojima%2C+E%3BAlcaide%2C+M+L%3BChokekijchai%2C+S%3BRoy%2C+B+M%3BArnold%2C+E%3BYarchoan%2C+R&rft.aulast=Shirasaka&rft.aufirst=T&rft.date=1995-01-01&rft.volume=92&rft.issue=6&rft.spage=2398&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 - 2011-12-14 N1 - SubjectsTermNotLitGenreText - viremia; mutation; man; multidrug resistance; human immunodeficiency virus 1 ER - TY - JOUR T1 - Swinholide A is a microfilament disrupting marine toxin that stabilizes actin dimers and severs actin filaments AN - 16709963; 3708331 AB - Swinholide A, isolated from the marine sponge Theonella swinhoei, is a 44-carbon ring dimeric dilactone macrolide with a 2-fold axis of symmetry. Recent studies have elucidated its unusual structure and shown that it has potent cytotoxic activity. We now report that swinholide A disrupts the actin cytoskeleton of cells grown in culture, sequesters actin dimers in vitro in both polymerizing and non-polymerizing buffers with a binding stoichiometry of one swinholide A molecule per actin dimer, and rapidly severs F-actin in vitro with high cooperativity. These unique properties are sufficient to explain the cytotoxicity of swinholide A. They also suggest that swinholide A might be a model for studies of the mechanism of action of F-actin severing proteins and be therapeutically useful in conditions where filamentous actin contributes to pathologically high viscosities. JF - Journal of Biological Chemistry AU - Bubb, M R AU - Spector, I AU - Bershadsky, AD AU - Korn, ED AD - Lab. Cell Biol., NHLBI/NIH, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 3463 EP - 3466 VL - 270 IS - 8 SN - 0021-9258, 0021-9258 KW - F-actin KW - actin KW - biological poisons KW - cytotoxins KW - microfilaments KW - swinholide A KW - toxins KW - Toxicology Abstracts; ASFA Marine Biotechnology Abstracts; ASFA 1: Biological Sciences & Living Resources KW - Marine KW - Porifera KW - muscles KW - Theonella swinhoei KW - proteins KW - marine organisms KW - Q4 27390:Toxins KW - Q1 08246:Physiology, biochemistry, biophysics KW - X 24173:Animals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16709963?accountid=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+Biological+Chemistry&rft.atitle=Swinholide+A+is+a+microfilament+disrupting+marine+toxin+that+stabilizes+actin+dimers+and+severs+actin+filaments&rft.au=Bubb%2C+M+R%3BSpector%2C+I%3BBershadsky%2C+AD%3BKorn%2C+ED&rft.aulast=Bubb&rft.aufirst=M&rft.date=1995-01-01&rft.volume=270&rft.issue=8&rft.spage=3463&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 - 2014-05-06 N1 - SubjectsTermNotLitGenreText - actin; biological poisons; muscles; proteins; marine organisms; toxins; microfilaments; cytotoxins; Porifera; Theonella swinhoei; Marine ER - TY - JOUR T1 - Transfection of Plasmodium falciparum within human red blood cells AN - 16709520; 3706516 AB - Plasmodium falciparum malaria parasites within human red blood cells (RBCs) have been successfully transfected to produce chloramphenicol acetyltransferase (CAT). Electroporation of parasitized RBCs was used to introduce plasmids that have CAT-encoding DNA flanked by 5' and 3' untranslated sequences of the P. falciparum hsp86, hrp3, and hrp2 genes. These flanking sequences were required for expression as their excision abolished CAT activity in transfected parasites. Transfection signals from native CAT-encoding DNA compared well with those from a synthetic DNA sequence adapted to the P. falciparum major codon bias, demonstrating effective expression of the bacterial sequence despite its use of rare P. falciparum codons. Transfected ring-stage parasites produced CAT signals at least as strong as transfected schizont-stage parasites even though ring stages are surrounded by more RBC cytoplasm than schizonts. The transfection of erythrocyte-stage P. falciparum parasites advances our ability to pursue genetic analysis of this major pathogen. JF - Proceedings of the National Academy of Sciences, USA AU - Wu, Yimin AU - Sifri, C D AU - Lei, Hsien-Hsien AU - Su, Xin-Zhuan AU - Wellems, TE AD - Lab. Parasitic Dis., NIAID/NIH, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 973 EP - 977 VL - 92 IS - 4 SN - 0027-8424, 0027-8424 KW - chloramphenicol O-acetyltransferase KW - hsp2 gene KW - hsp3 gene KW - hsp86 gene KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology; Biochemistry Abstracts 2: Nucleic Acids KW - erythrocytes KW - transfection KW - malaria KW - DNA KW - Plasmodium falciparum KW - man KW - K 03090:Protozoa: human KW - W3 33170:Cellular based KW - W 30965:Miscellaneous, Reviews KW - N 14672:Transfection UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16709520?accountid=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=Transfection+of+Plasmodium+falciparum+within+human+red+blood+cells&rft.au=Wu%2C+Yimin%3BSifri%2C+C+D%3BLei%2C+Hsien-Hsien%3BSu%2C+Xin-Zhuan%3BWellems%2C+TE&rft.aulast=Wu&rft.aufirst=Yimin&rft.date=1995-01-01&rft.volume=92&rft.issue=4&rft.spage=973&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 - 2011-12-14 N1 - SubjectsTermNotLitGenreText - erythrocytes; transfection; malaria; DNA; man; Plasmodium falciparum ER - TY - JOUR T1 - Mycoplasma adleri sp. nov., an isolate from a goat AN - 16678137; 3689090 AB - Mycoplasma sp. strain G145 super(T) (T = type strain) was isolated from a goat's abscessed ankle. Strain G145 super(T) required cholesterol or serum for growth and possessed characteristics similar to those of other members of the genus Mycoplasma. This strain was serologically distinct from previously described Mycoplasma species and from a group of currently unnamed strains thought to belong to the genus Mycoplasma. Strain G145 super(T) hydrolyzed arginine, but did not hydrolyze urea or ferment glucose. The guanine-plus-cytosine content of the DNA was 29.6 mol%. We propose that strain G145 (= ATCC 27948) is the type strain of a new species, for which we propose the name Mycoplasma adleri. JF - International Journal of Systematic Bacteriology AU - Del Giudice, RA AU - Rose, D L AU - Tully, J G AD - PRI/DynCorp, NCI-FCRDC, P.O. Box B, Frederick, MD 21702, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 29 EP - 31 VL - 45 IS - 1 SN - 0020-7713, 0020-7713 KW - sp. nov. KW - Microbiology Abstracts B: Bacteriology KW - Mycoplasma adleri KW - isolation KW - USA, Maryland KW - livestock KW - J 02710:Identification, taxonomy and typing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16678137?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Systematic+Bacteriology&rft.atitle=Mycoplasma+adleri+sp.+nov.%2C+an+isolate+from+a+goat&rft.au=Del+Giudice%2C+RA%3BRose%2C+D+L%3BTully%2C+J+G&rft.aulast=Del+Giudice&rft.aufirst=RA&rft.date=1995-01-01&rft.volume=45&rft.issue=1&rft.spage=29&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Systematic+Bacteriology&rft.issn=00207713&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mycoplasma adleri; USA, Maryland; isolation; livestock ER - TY - JOUR T1 - Spiroplasma ixodetis sp. nov., a new species from Ixodes pacificus ticks collected in Oregon AN - 16678021; 3689049 AB - Eight strains of mollicutes were isolated from pooled suspensions prepared from western black-legged ticks (Ixodes pacificus) collected in Oregon. Morphologic examination by electron and dark-field microscopic techniques showed that each strain consisted of a mixture of motile, tightly coiled helical cells, small coccoid cells with diameters ranging from 300 to 500 nm, and pleomorphic, straight or branched filamentous forms. All cellular forms were surrounded by a single cytoplasmic membrane, and there was no evidence of a cell wall. The organisms were filterable and fastidious in their growth requirements. The optimum temperature for growth was 30 degree C, but multiplication occurred at temperatures ranging from 23 to 32 degree C. The strains catabolized glucose but did not hydrolyze arginine or urea. The genome size of strain Y32 super(T) (T = type strain) was 2,220 kbp, and the DNA base composition (guanine-plus-cytosine content) of this organism was 25 plus or minus 1 mol%. The eight isolates were serologically related to each other but were not related to 37 other type or representative strains belonging to the genus Spiroplasma. Strain Y32 (= ATCC 33835) is the type strain of Spiroplasma ixodetis sp. nov. JF - International Journal of Systematic Bacteriology AU - Tully, J G AU - Rose, D L AU - Yunker, CE AU - Carle, P AU - Bove, J M AU - Williamson, D L AU - Whitcomb, R F AD - Mycoplasma Sect., Bldg. 550, NIAID, Frederick Cancer Res. Dev. Cent., Frederick, MD 21702, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 23 EP - 28 VL - 45 IS - 1 SN - 0020-7713, 0020-7713 KW - Spiroplasma ixodetis KW - sp. nov. KW - Oregon KW - Microbiology Abstracts B: Bacteriology KW - isolation KW - Ixodes pacificus KW - J 02710:Identification, taxonomy and typing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16678021?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Systematic+Bacteriology&rft.atitle=Spiroplasma+ixodetis+sp.+nov.%2C+a+new+species+from+Ixodes+pacificus+ticks+collected+in+Oregon&rft.au=Tully%2C+J+G%3BRose%2C+D+L%3BYunker%2C+CE%3BCarle%2C+P%3BBove%2C+J+M%3BWilliamson%2C+D+L%3BWhitcomb%2C+R+F&rft.aulast=Tully&rft.aufirst=J&rft.date=1995-01-01&rft.volume=45&rft.issue=1&rft.spage=23&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Systematic+Bacteriology&rft.issn=00207713&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Ixodes pacificus; isolation ER - TY - JOUR T1 - Programmed cell death in bacterial populations AN - 16669949; 3685158 AB - Multicellular organisms benefit not only from the death of competitors, but often, quite dramatically, from the programmed death of specific subpopulations of their own cells. Popular opinion to the contrary, programmed cell death is also alive and well in the microbial world. A striking report by Naito et al. in this issue of Science is a case in point. JF - Science (Washington) AU - Yarmolinsky, M B AD - Lab. Biochem., NCI, Build. 37, Rm. 4D-15, NIH, Bethesda, MD 20892-4255, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 836 EP - 837 VL - 267 IS - 5199 SN - 0036-8075, 0036-8075 KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - cell death KW - reviews KW - populations KW - apoptosis KW - G 07321:GENERAL KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16669949?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+%28Washington%29&rft.atitle=Programmed+cell+death+in+bacterial+populations&rft.au=Yarmolinsky%2C+M+B&rft.aulast=Yarmolinsky&rft.aufirst=M&rft.date=1995-01-01&rft.volume=267&rft.issue=5199&rft.spage=836&rft.isbn=&rft.btitle=&rft.title=Science+%28Washington%29&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - cell death; apoptosis; populations; reviews ER - TY - JOUR T1 - An autoregulated dual-function antitat gene for human immunodeficiency virus type 1 gene therapy AN - 16645335; 3681482 AB - One approach to gene therapy for AIDS is to block the replication of human immunodeficiency virus type 1 (HIV-1) by inhibiting the tat gene, whose product activates the expression of all HIV-1 genes. To accomplish this, we constructed an antitat gene expressing an RNA with dual (polymeric TAR and antisense-tat) function in an attempt to both sequester Tat protein and block its translation from mRNA. A minigene consisting of the antitat gene driven by the HIV-1 long terminal repeat was inserted into a double-copy retrovirus vector, such that antitat expression would be upregulated only in HIV-1-infected cells. After transduction of a T-lymphocytic cell line (Molt-3) the antitat gene inhibited HIV-1 replication. This inhibition was inversely correlated with the virus infectious dose. Virus replication was also inhibited for 5 months in two different T-cell lines after they had been infected at a high multiplicity of infection, suggesting that the antitat gene may be effective over long periods. Importantly, antitat blocked the replication and the cytopathic effect of HIV-1 in human peripheral blood mononuclear cells and led to as much as 4,000-fold inhibition of the replication of an HIV-1 field isolate as well as HIV-1 prototypes maintained in culture. These results suggest that antitat gene therapy has potential use for blocking HIV-1 replication in infected individuals. JF - Journal of Virology AU - Lisziewicz, J AU - Sun, D AU - Trapnell, B AU - Thomson, M AU - Chang, H-K AU - Ensoli, B AU - Peng, B AD - Lab. Tumor Cell Biol., Build. 37, Rm. 6A09, NCI, 37 Convent Dr. MSC 4255, Bethesda, MD 20892-4255, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 206 EP - 212 VL - 69 IS - 1 SN - 0022-538X, 0022-538X KW - Tat protein KW - antitat gene KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Genetics Abstracts; Virology & AIDS Abstracts KW - gene transfer KW - gene therapy KW - replication KW - human immunodeficiency virus 1 KW - inhibition KW - V 22002:AIDS: Molecular and in vitro aspects KW - G 07313:Viruses 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/16645335?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Virology&rft.atitle=An+autoregulated+dual-function+antitat+gene+for+human+immunodeficiency+virus+type+1+gene+therapy&rft.au=Lisziewicz%2C+J%3BSun%2C+D%3BTrapnell%2C+B%3BThomson%2C+M%3BChang%2C+H-K%3BEnsoli%2C+B%3BPeng%2C+B&rft.aulast=Lisziewicz&rft.aufirst=J&rft.date=1995-01-01&rft.volume=69&rft.issue=1&rft.spage=206&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - gene therapy; gene transfer; replication; inhibition; human immunodeficiency virus 1 ER - TY - JOUR T1 - Incorporation of bromodeoxyuridine (BrdU) in the bronchiolar-alveolar regions of the lungs following two inhalation exposures to chrysotile asbestos in strain A/J mice AN - 15906901; 4041863 AB - We have been studying early fibroproliferative events in the lungs of rodents exposed to aerosols of asbestos fibers. In the experiments presented here, incorporation of bromodeoxyuridine (BrdU) in the bronchiolar/alveolar (B/A) regions of the lungs in mice was assessed following two consecutive exposures to chrysotile asbestos. Six to 8-week-old male strain A/J mice, a strain with a high spontaneous incidence of B/A tumors, were exposed to inhaled asbestos fibers for two consecutive days (3 hours/day). A group of mice was also given an intraperitoneal injection of urethane, a known lung carcinogen in A/J mice, 48 h after initial inhalation exposure to asbestos. The groups of mice exposed to asbestos had significantly increased incorporation of BrdU in the nuclei of epithelial and interstitial cells in the B/A regions of the lung at 48 h, 72 h, and 2 weeks after initial exposure. By 1 month, the labeling indices in mice exposed to asbestos were not statistically significantly different from the controls; however, in the regions of the first alveolar duct bifurcations (ALDB), the primary site of initial asbestos deposition, there continued to be detectable labeling of the epithelial and interstitial cells. Because of considerable variability from duct to duct, there were no statistically significant differences between the asbestos-exposed mice and control groups at 3 months. We conclude that in A/J mice the initial proliferative response observed in the B/A regions of the lung after two 3-h inhalation exposures to asbestos is significantly prolonged through 2 weeks post-exposure. In addition, there was measurable labeling above control values in the epithelial and interstitial cells of the first alveolar duct bifurcations up to 3 months after exposure. Urethane had no apparent effect on the incorporation of BrdU into any cells of the B/A regions of the lung when administered after inhalation exposure to asbestos. Furthermore, although the A/J strain is highly susceptible to lung tumor formation, the unexposed control A/J mice showed no spontaneous increases in cell proliferation. JF - Journal of Environmental Pathology, Toxicology and Oncology AU - Dixon, D AU - Bowser, AD AU - Badgett, A AU - Haseman, J K AU - Brody, A R AD - NIEHS, P.O. Box 12233, MDC2-09, Research Triangle Park, NC 27709, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 205 EP - 213 VL - 14 IS - 3-4 SN - 0731-8898, 0731-8898 KW - asbestos KW - chrysotile KW - bromodeoxyuridine KW - Toxicology Abstracts KW - inhalation KW - lung KW - X 24154:Pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15906901?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Environmental+Pathology%2C+Toxicology+and+Oncology&rft.atitle=Incorporation+of+bromodeoxyuridine+%28BrdU%29+in+the+bronchiolar-alveolar+regions+of+the+lungs+following+two+inhalation+exposures+to+chrysotile+asbestos+in+strain+A%2FJ+mice&rft.au=Dixon%2C+D%3BBowser%2C+AD%3BBadgett%2C+A%3BHaseman%2C+J+K%3BBrody%2C+A+R&rft.aulast=Dixon&rft.aufirst=D&rft.date=1995-01-01&rft.volume=14&rft.issue=3-4&rft.spage=205&rft.isbn=&rft.btitle=&rft.title=Journal+of+Environmental+Pathology%2C+Toxicology+and+Oncology&rft.issn=07318898&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 - lung; inhalation ER - TY - JOUR T1 - Arterial thrombosis associated with granulocyte-macrophage colony-stimulating factor (GM-CSF) administration in breast cancer patients treated with dose-intensive chemotherapy: A report of two cases AN - 15852354; 4020347 AB - The occurrence of arterial thrombosis reported in other breast cancer series has largely been confined to the upper extremities, ipsilateral to a previous mastectomy site and clinically manifest as cerebral vascular accidents. This case report describes 2 patients who experienced iliac artery thrombosis temporally related to receiving granulocyte-macrophage colony-stimulating factor (GM-CSF) and dose-intensive chemotherapy for metastatic breast cancer. A review of the literature concerning arterial thrombosis as relevant to breast cancer treatment and GM-CSF is included. (DBO) JF - Cancer Investigation AU - Tolcher, A W AU - Giusti, R M AU - O'Shaughnessy, JA AU - Cowan, KH AD - Medicine Branch, Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 188 EP - 192 VL - 13 IS - 2 SN - 0735-7907, 0735-7907 KW - arterial thrombosis KW - Toxicology Abstracts KW - side effects KW - thrombosis KW - man KW - granulocyte-macrophage colony-stimulating factor KW - arteries KW - X 24116:Hematology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15852354?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Investigation&rft.atitle=Arterial+thrombosis+associated+with+granulocyte-macrophage+colony-stimulating+factor+%28GM-CSF%29+administration+in+breast+cancer+patients+treated+with+dose-intensive+chemotherapy%3A+A+report+of+two+cases&rft.au=Tolcher%2C+A+W%3BGiusti%2C+R+M%3BO%27Shaughnessy%2C+JA%3BCowan%2C+KH&rft.aulast=Tolcher&rft.aufirst=A&rft.date=1995-01-01&rft.volume=13&rft.issue=2&rft.spage=188&rft.isbn=&rft.btitle=&rft.title=Cancer+Investigation&rft.issn=07357907&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 - granulocyte-macrophage colony-stimulating factor; side effects; man; arteries; thrombosis ER - TY - CONF T1 - Using biomarkers of genetic susceptibility to enhance the study of cancer etiology AN - 15785327; 3982754 AB - There has been increasing interest in the interaction of genetic susceptibility and xenobiotic exposures in cancer etiology. Study of gene-environment interactions may increase our ability to characterize relatively low population risks if a substantial proportion of the population cancer burden is attributed to high risk among a smaller group of genetically susceptible members. Further, these studies may provide insight into the mechanism of carcinogenesis, which can help establish the biologic plausibility of an exposure-cancer relationship. Biologic processes important in tumorigenesis that exhibit substantial interindividual differences may function as susceptibility factors. Potential examples include polymorphic enzymes, which activate and detoxify procarcinogens and carcinogens (e.g., certain P450 enzymes, N-acetyltransferase [NAT2], glutathione S-transferase M1), and variation in the capacity to repair DNA. Biologic assays are now available to evaluate many of these functions at the DNA and phenotype level and can be readily incorporated into studies of cancer etiology. JF - Environmental Health Perspectives AU - Rothman, N AU - Hayes, R B Y1 - 1995 PY - 1995 DA - 1995 SP - 292 EP - 295 VL - 103 IS - 8 Supp. KW - biomarkers KW - genetic susceptibility KW - Toxicology Abstracts KW - NIH 95-218 KW - genotype-environment interactions KW - genes KW - DNA repair KW - xenobiotics KW - enzymes KW - cancer KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15785327?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=Using+biomarkers+of+genetic+susceptibility+to+enhance+the+study+of+cancer+etiology&rft.au=Rothman%2C+N%3BHayes%2C+R+B&rft.aulast=Rothman&rft.aufirst=N&rft.date=1995-01-01&rft.volume=103&rft.issue=8+Supp.&rft.spage=292&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 ER - TY - JOUR T1 - The erbstatin analogue methyl 2,5-dihydroxycinnamate cross-links proteins and is cytotoxic to normal and neoplastic epithelial cells by a mechanism independent of tyrosine kinase inhibition AN - 15783865; 3982579 AB - Differentiation therapy is an attractive option for the treatment of superficial, localized neoplastic lesions of the skin. Topical application of agents that induce differentiation could selectively inhibit tumor cell growth, inducing a program of cell death with the production of cross-linked protein envelopes as the terminal event of this process at the skin surface, effectively eliminating the neoplastic phenotype. The nonspecific kinase inhibitor staurosporine induces cornified envelope assembly in neoplastic keratinocytes and causes tumor regression (A. A. Dlugosz and S. H. Yuspa, Cancer Res., 51: 4677-4684, 1991). In pursuit of less toxic agents, specific tyrosine kinase inhibitors were tested for the ability to induce differentiation in keratinocyte-derived cells. Of a range of inhibitors tested, only MC was able to induce cross-linked protein and consequent cell death in mouse and human primary normal keratinocytes, 308 neoplastic mouse keratinocytes, HPV-18-infected immortalized human keratinocytes, and human lines SQCC-Y1 (squamous carcinoma) and A431 (epidermoid carcinoma). MC increased cross-linked protein in a dose-dependent manner (0.05-1 mM). To confirm differentiation, MC-treated mouse primary normal keratinocytes were tested for activation of the endogenous cross-linking enzyme transglutaminase, but no association was found between transglutaminase activity and MC-induced protein cross-linking. MC also induced protein cross-linking in the fibroblast cell line NIH3T3 and in B16 melanoma cells, in which cornified envelope assembly is not part of the differentiation process. This cross-linking occurred at 4 degree C, suggesting a nonphysiological process. Western blot analysis of an in vitro assay with purified EGF receptor showed that MC was able to cross-link the receptor. As in NIH3T3 cells, DTT inhibited cross-linking, suggesting that oxidation of MC or an acceptor group may be required for this effect. Thus, MC does not induce differentiation by a physiological mechanism in epithelial cells but causes chemical protein cross-linking into cornified envelope-like structures at high concentration. (DBO) JF - Cancer Research AU - Stanwell, C AU - Burke, TR Jr AU - Yuspa, SH AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Building 37, Room 3B25, Bethesda, MD 20893, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 4950 EP - 4956 VL - 55 IS - 21 SN - 0008-5472, 0008-5472 KW - methyl 2,5-dihydroxycinnamate KW - erbstatin KW - Toxicology Abstracts KW - cytotoxicity testing KW - antineoplastic drugs KW - epithelium KW - X 24117:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15783865?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Research&rft.atitle=The+erbstatin+analogue+methyl+2%2C5-dihydroxycinnamate+cross-links+proteins+and+is+cytotoxic+to+normal+and+neoplastic+epithelial+cells+by+a+mechanism+independent+of+tyrosine+kinase+inhibition&rft.au=Stanwell%2C+C%3BBurke%2C+TR+Jr%3BYuspa%2C+SH&rft.aulast=Stanwell&rft.aufirst=C&rft.date=1995-01-01&rft.volume=55&rft.issue=21&rft.spage=4950&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 - epithelium; cytotoxicity testing; antineoplastic drugs ER - TY - JOUR T1 - Promotion of N-nitrosodiethylamine-initiated hepatocellular tumors and hepatoblastomas by 2,3,7,8-tetrachlorodibenzo-p-dioxin or Aroclor 1254 in C57BL/6, DBA/2, and B6D2F1 mice AN - 15783806; 3982556 AB - To investigate the hypothesis that tumor promotion by chlorinated aromatic hydrocarbons involves Ah receptor occupation and subsequent induction of cytochromes P-450 1a-1, effects of Aroclor 1254 or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were examined in N-nitrosodiethylamine-initiated mice with different Ah receptor phenotype. Levels of cytochromes P-450 1a and 2b were measured by enzyme assay and Western immunoblots. Males of the C57BL/6, DBA/2, or (C57BL/6 x DBA/2)F sub(1) (hereafter referred to as "B6D2F1") strain were initiated with a single i.p. dose of N-nitrosodiethylamine (90 mg/kg body weight), followed by either multiple doses of TCDD (0.05 mu g/kg) weekly or Aroclor 1254 chronically in the diet (100 ppm) for 20 weeks, and then no treatment for 24 weeks. Lung tumor incidence or multiplicity was not altered by either of the promoters. Liver tumor incidence was similar among the three strains after N-nitrosodiethylamine alone (14, 21, and 21%, respectively). In DBA/2 mice, TCDD neither induced Cyp 1a nor promoted liver tumors. Aroclor caused an 8-fold induction of hepatic Cyp 2b, which was its maximum at the 12-week time point but did not promote tumors. Inductions of hepatic Cyp 1a by TCDD and 1a and 2b by Aroclor were similar in C57BL/6 and B6D2F1 mice, but tumor promotion responses were quite different. Dietary Aroclor significantly promoted liver tumors in C57BL/6 mice (59 versus 14%) but not in B6D2F1 mice (24 versus 21%). Repeated TCDD promoted only in B6D2F1 mice (52 versus 21%) and not in C57BL/6 mice (19 versus 14%). Thus, whereas these data confirm that a functional Ah receptor is required for liver tumor promotion, the degree of activation as measured by induction of Cyp 1a is not directly related to the degree of tumor-promoting capability. Other genetic factors must play a role in mediating the final tumor outcome. JF - Cancer Research AU - Beebe, LE AU - Fornwald, L W AU - Diwan, BA AU - Anver, M R AU - Anderson, L M AD - NCI-FCRDC, Building 538, Room 205-E, Frederick, MD 21702-1201, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 4875 EP - 4880 VL - 55 IS - 21 SN - 0008-5472, 0008-5472 KW - N-nitrosodiethylamine KW - TCDD KW - Aroclor 1254 KW - mice KW - Ah receptors KW - Toxicology Abstracts KW - chlorinated hydrocarbons KW - liver KW - tumors KW - X 24200:Nitrosamines & related compounds KW - X 24152:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15783806?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Research&rft.atitle=Promotion+of+N-nitrosodiethylamine-initiated+hepatocellular+tumors+and+hepatoblastomas+by+2%2C3%2C7%2C8-tetrachlorodibenzo-p-dioxin+or+Aroclor+1254+in+C57BL%2F6%2C+DBA%2F2%2C+and+B6D2F1+mice&rft.au=Beebe%2C+LE%3BFornwald%2C+L+W%3BDiwan%2C+BA%3BAnver%2C+M+R%3BAnderson%2C+L+M&rft.aulast=Beebe&rft.aufirst=LE&rft.date=1995-01-01&rft.volume=55&rft.issue=21&rft.spage=4875&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 - tumors; liver; chlorinated hydrocarbons ER - TY - CONF T1 - Diet and cancer: Future etiologic research AN - 15779986; 3982735 AB - In light of several credible diet and cancer hypotheses, we suggest strategies for advancing our understanding in this area. Two conceptual approaches can be taken in defining dietary exposure: the decompositional approach focuses on specific nutrients and other chemical constituents of food, whereas the integrative approach emphasizes the action of whole foods or food patterns (cuisines). Diet-cancer hypotheses can be organized according to this conceptual framework. We review four types of scientific investigation available to us for advancing the diet and cancer field: metabolic (clinical nutrition) studies; animal studies; observational epidemiologic investigations; and clinical trials. Each of these designs has its strengths and limitations. Observational epidemiologic studies and trials have the particular advantage of examining explicit cancer end points in humans. Results from metabolic and animal research, however, can complement the findings from epidemiologic studies and trials. Finally, we briefly review strategies for evaluating promising hypotheses linking diet to cancers of the large bowel, lung, breast, and prostate. JF - Environmental Health Perspectives AU - Schatzkin, A AU - Dorgan, J AU - Swanson, C AU - Potischman, N Y1 - 1995 PY - 1995 DA - 1995 SP - 171 EP - 175 VL - 103 IS - 8 Supp. KW - Toxicology Abstracts KW - NIH 95-218 KW - nutrition KW - reviews KW - diets KW - cancer KW - X 24120:Food, additives & contaminants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15779986?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=Diet+and+cancer%3A+Future+etiologic+research&rft.au=Schatzkin%2C+A%3BDorgan%2C+J%3BSwanson%2C+C%3BPotischman%2C+N&rft.aulast=Schatzkin&rft.aufirst=A&rft.date=1995-01-01&rft.volume=103&rft.issue=8+Supp.&rft.spage=171&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 ER - TY - CONF T1 - Hormones and breast and endometrial cancers: Preventive strategies and future research AN - 15779708; 3982737 AB - A number of hormonal approaches for prevention of endometrial and breast cancers have been proposed. Because of the hormonal responsiveness of both tumors, much attention has focused on effects of exogenous hormone use. Although estrogens in hormone replacement therapy increase the risk of endometrial cancer, the disease is substantially reduced by long-term use of oral contraceptives. The issues with breast cancer are more complex, mainly because of a variety of unresolved effects. Long-term estrogen use is associated with some increase in breast cancer risk, and certain patterns of oral contraceptives appear to predispose to early-onset disease. With respect to estrogens, preventive approaches for both tumors would include use for as limited periods of time as possible. Addition of a progestin appears to lower estrogen-associated endometrial disease, but its effect on breast cancer risk remains less clear. Additional studies on effects of detailed usage parameters should provide useful insights into etiologic mechanisms. Other preventive approaches for endometrial cancer that may work through hormonal mechanisms include staying thin, being physically active, and maintaining a vegetarian diet. Breast cancer risk may possibly be reduced by extended periods of breastfeeding, restriction of intake of alcoholic beverages, remaining thin later in life, and being physically active. Additional research is needed to clarify the biologic mechanisms of these associations. The bridging of epidemiology with the biologic sciences should clarify many unresolved issues and lead to better preventive approaches. JF - Environmental Health Perspectives AU - Hulka, B S AU - Brinton, LA Y1 - 1995 PY - 1995 DA - 1995 SP - 185 EP - 189 VL - 103 IS - 8 Supp. KW - breast KW - endometrium KW - estrogens KW - hormone replacement therapy KW - man KW - Risk Abstracts; Health & Safety Science Abstracts; Toxicology Abstracts KW - NIH 95-218 KW - side effects KW - reviews KW - hormones KW - breast cancer KW - cancer KW - R2 23060:Medical and environmental health KW - H SM10.21:CANCER KW - X 24113:Side effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15779708?accountid=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=Hormones+and+breast+and+endometrial+cancers%3A+Preventive+strategies+and+future+research&rft.au=Hulka%2C+B+S%3BBrinton%2C+LA&rft.aulast=Hulka&rft.aufirst=B&rft.date=1995-01-01&rft.volume=103&rft.issue=8+Supp.&rft.spage=185&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 ER - TY - CONF T1 - Ionizing radiation: Future etiologic research and preventive strategies AN - 15778956; 3982748 AB - Estimates of cancer risks following exposure to ionizing radiation traditionally have been based on the experience of populations exposed to substantial (and known) doses delivered over short periods of time. Examples include survivors of the atomic bombings at Hiroshima and Nagasaki, and persons treated with radiation for benign or malignant disease. Continued follow-up of these populations is important to determine the long-term effects of exposure in childhood, to characterize temporal patterns of excess risk for different types of cancer, and to understand better the interactions between radiation and other host and environmental factors. Most population exposure to radiation occurs at very low dose rates. For low linear energy transfer (LET) radiations, it often has been assumed that cancer risks per unit dose are lower following protracted exposure than following acute exposure. Studies of nuclear workers chronically exposed over a working lifetime provide data that can be used to test this hypothesis, and preliminary indications are that the risks per unit dose for most cancers other than leukemia are similar to those for acute exposure. However, these results are subject to considerable uncertainty, and further information on this question is needed. Residential radon is the major source of population exposure to high-LET radiation. Current estimates of the risk of lung cancer due to residential exposure to radon and radon daughters are based on the experience of miners exposed to much higher concentrations. Data indicate that lung cancer risk among miners is inversely associated with exposure rate, and also is influenced by the presence of other lung carcinogens such as arsenic in the mine environment. Further study of populations of radon-exposed miners would be informative, particularly those exposed at below-average levels. More direct evidence on the effects of residential exposure to radon also is desirable but might be difficult to come by, as risks associated with radon levels found in most homes might be too low to be quantified accurately in epidemiological studies. JF - Environmental Health Perspectives AU - Darby, S C AU - Inskip, P D Y1 - 1995 PY - 1995 DA - 1995 SP - 245 EP - 249 VL - 103 IS - 8 Supp. KW - Toxicology Abstracts KW - NIH 95-218 KW - ionizing radiation KW - radiation KW - cancer KW - X 24210:Radiation & radioactive materials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15778956?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=Ionizing+radiation%3A+Future+etiologic+research+and+preventive+strategies&rft.au=Darby%2C+S+C%3BInskip%2C+P+D&rft.aulast=Darby&rft.aufirst=S&rft.date=1995-01-01&rft.volume=103&rft.issue=8+Supp.&rft.spage=245&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 ER - TY - JOUR T1 - Modulation of cisplatin toxicity by glutathione AN - 15769304; 3982600 AB - Organ toxicity is the major limiting factor associated with chemotherapeutic treatment of malignancy. By raising the toxicity threshold of the organ to the detrimental effects of chemotherapeutic agents, larger and possibly curative doses may be administered without unacceptable side effects. Glutathione (GSH), a major nonprotein cellular thiol, participates in numerous cellular functions, including detoxification of chemotherapeutic agents. Previously, GSH was shown to protect against cisplatin-induced lethal toxicity. We find that in non-tumor bearing animals GSH injections (500 mg/kg body weight) prior to and after a single cisplatin injection (16 mg/kg) provided significant protection against the lethal effects of this drug (90% survival for GSH+cisplatin versus 35% for cisplatin alone). In addition, when GSH was given concurrently with the cisplatin, renal toxicity was markedly reduced as assessed by renal tubular dilation, tubular sloughing, and lumenal casts. When GSH was given with cisplatin no significant differences in the number of tumor cures was observed over cisplatin treatment alone; however, a small but statistically significant increase in tumor size was observed for cisplatin+GSH treated animals. Our results suggest that GSH may protect normal as well as malignant tissue and that further studies should be designed to determine a GSH dose and schedule regimen to be used with higher cisplatin dose schedules. JF - International Journal of Oncology AU - Bernstein, E F AU - Pass, HA AU - Glass, J AU - Deluca, A M AU - Cook, S AU - Fisher, J AU - Cook, JA AD - Radiation Biology Branch/NCI, Bldg. 10, Rm B3-B69, Bethesda, MD 20892-1002, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 353 EP - 358 VL - 7 IS - 2 SN - 1019-6439, 1019-6439 KW - cisplatin KW - glutathione KW - mice KW - Toxicology Abstracts KW - antineoplastic drugs KW - X 24112:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15769304?accountid=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=International+Journal+of+Oncology&rft.atitle=Modulation+of+cisplatin+toxicity+by+glutathione&rft.au=Bernstein%2C+E+F%3BPass%2C+HA%3BGlass%2C+J%3BDeluca%2C+A+M%3BCook%2C+S%3BFisher%2C+J%3BCook%2C+JA&rft.aulast=Bernstein&rft.aufirst=E&rft.date=1995-01-01&rft.volume=7&rft.issue=2&rft.spage=353&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - antineoplastic drugs ER - TY - CONF T1 - Agricultural exposures and cancer AN - 15769120; 3982740 AB - The purpose of this report is to review the literature on cancer among persons employed in agriculture, to characterize the value of this line of research, and to recommend future directions. Farmers, despite a generally favorable mortality, appear to experience elevated rates for several cancers, including leukemia, non-Hodgkin's lymphoma, multiple myeloma, soft-tissue sarcoma, and cancers of the skin, lip, stomach, brain, and prostate. The rates for several of these tumors (i.e., non-Hodgkin's lymphoma, multiple myeloma, skin, brain, and prostate) appear to be increasing in the general population. No set of established etiologic factors explains all the cancer excesses observed among farmers, although several are associated with naturally occurring or medically induced immunodeficiencies. This suggests that there may be factors in the agricultural environment that introduce immune system deficiencies. Farmers are exposed to a variety of substances that could operate through this mechanism, including pesticides, engine exhausts, solvents, dusts, and zoonotic microbes. Studies to further characterize the cancer risk among farmers, their dependents, and farm laborers, and to identify the exposures that may be involved would not only be useful in providing a safe work environment in agriculture but may furnish considerable insight into the causes for a number of tumors that are rising in incidence in the general population. JF - Environmental Health Perspectives AU - Blair, A AU - Zahm, SH Y1 - 1995 PY - 1995 DA - 1995 SP - 205 EP - 208 VL - 103 IS - 8 Supp. KW - man KW - Health & Safety Science Abstracts; Toxicology Abstracts KW - NIH 95-218 KW - reviews KW - agrochemicals KW - pesticides KW - occupational exposure KW - cancer KW - X 24132:Chronic exposure KW - H SM10.21:CANCER KW - H SE5.3:HAZARD DETERMINATION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15769120?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=Agricultural+exposures+and+cancer&rft.au=Blair%2C+A%3BZahm%2C+SH&rft.aulast=Blair&rft.aufirst=A&rft.date=1995-01-01&rft.volume=103&rft.issue=8+Supp.&rft.spage=205&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 ER - TY - CONF T1 - Nonhormonal drugs and cancer AN - 15764310; 3982738 AB - Nonhormonal drugs probably account for only a small proportion of human cancer but have contributed many valuable insights into carcinogenic mechanisms. The antineoplastics, radiopharmaceuticals, and a few other agents account for most of the known drug-induced cancer. A number of other agents are under suspicion, usually due to studies in laboratory animals or to preliminary clinical or epidemiologic observations. This group includes some drugs in widespread use such as clofibrate and cimetidine. For a few drugs that are carcinogenic in animals, such as dapsone and isoniazid, epidemiologic studies have shown little to no evidence of carcinogenicity. Recent experimental studies have shown tumor promotion by the commonly used antidepressants amitriptyline and fluoxetine and some antihistamines, which deserve epidemiologic investigation of cancer risk. Some drugs may also protect against cancer, as suggested by the lower risk of colorectal cancer among regular users of nonsteroidal antiinflammatory drugs. Pharmacoepidemiologic studies must take into account possible confounding by the original conditions for which drugs were taken and the typically long latency period of drug-induced cancer. Improved postmarketing surveillance, continued routine case-control surveillance, and ad hoc case-control and cohort studies are needed to evaluate drugs already in use as well as newly introduced agents. JF - Environmental Health Perspectives AU - Stolley, P D AU - Zahm, SH Y1 - 1995 PY - 1995 DA - 1995 SP - 191 EP - 196 VL - 103 IS - 8 Supp. KW - Toxicology Abstracts KW - NIH 95-218 KW - side effects KW - reviews KW - drugs KW - pharmaceuticals KW - cancer KW - X 24113:Side effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15764310?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=Nonhormonal+drugs+and+cancer&rft.au=Stolley%2C+P+D%3BZahm%2C+SH&rft.aulast=Stolley&rft.aufirst=P&rft.date=1995-01-01&rft.volume=103&rft.issue=8+Supp.&rft.spage=191&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 ER - TY - CONF T1 - Tobacco use and its contribution to early cancer mortality with a special emphasis on cigarette smoking AN - 15764213; 3982729 AB - This paper provides an overview of the relationship between tobacco use and early cancer mortality. It presents a retrospective examination of trends in smoking behavior and how these trends affected the national lung cancer mortality pattern during this century. Information on smoking prevalence is presented for black and white men and women for each 5-year birth cohort between 1885 and 1969. The author argues that the lung cancer mortality pattern observed in the United States since 1950 is entirely compatible with changes in smoking behavior among the various birth cohorts examined. The paper also reviews our current scientific knowledge about the etiological relationship between cigarette smoking and site-specific cancer mortality, with particular emphasis on lung cancer. Data on other forms of tobacco use and cancer mortality risks are included as are data on environmental tobacco smoke exposures and nonsmokers' lung cancer risk. Data are presented to demonstrate that cigarette use alone will be responsible for nearly one-third of the U.S. cancer deaths expected in the United States in 1995, or 168,000 premature cancer deaths. Among males, 38% of all cancer deaths are cigarette related, while among women 23% of all cancer deaths are due to cigarettes. These totals, however, include neither the cancer deaths that could reasonably be attributed to pipe, cigar, and smokeless tobacco use among males nor the estimated 3000 to 6000 environmental tobacco smoke-related lung cancer deaths that occur annually in nonsmokers. It is concluded that tobacco use, particularly the practice of cigarette smoking, is the single greatest cause of excess cancer mortality in U.S. populations. JF - Environmental Health Perspectives AU - Shopland Y1 - 1995 PY - 1995 DA - 1995 SP - 131 EP - 141 VL - 103 IS - 8 Supp. KW - man KW - Health & Safety Science Abstracts; Toxicology Abstracts KW - NIH 95-218 KW - cigarette smoking KW - cigarettes KW - smoking KW - tobacco KW - mortality KW - cancer KW - X 24180:Social poisons & drug abuse KW - H SM10.21:CANCER UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15764213?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=Tobacco+use+and+its+contribution+to+early+cancer+mortality+with+a+special+emphasis+on+cigarette+smoking&rft.au=Shopland&rft.aulast=Shopland&rft.aufirst=&rft.date=1995-01-01&rft.volume=103&rft.issue=8+Supp.&rft.spage=131&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 ER - TY - JOUR T1 - On the association between canine malignant lymphoma and opportunity for exposure to 2,4-dichlorophenoxyacetic acid AN - 15758000; 3980251 AB - In response to criticisms raised regarding a case-control study of canine malignant lymphoma, the results of several ancillary analyses are reported. The case-control study demonstrated a significant association between risk for canine malignant lymphoma and the opportunity for exposure to 2,4-dichlorophenoxyacetic acid herbicides. It is demonstrated that risk estimates do not vary by type of control group (i.e., tumor control or nontumor control group), by method of response (i.e., self-administered or telephone interview), or by geographic area. Questions related to the potential for referral bias, supposed inconsistencies in subject responses regarding frequency of herbicide use, and ambiguities regarding exposure classification are also examined. JF - Environmental Research AU - Hayes, H M AU - Tarone, R E AU - Cantor, K P AD - National Cancer Institute, EPN, Room 443, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 119 EP - 124 VL - 70 IS - 2 SN - 0013-9351, 0013-9351 KW - dogs KW - 2,4-dichlorophenoxyacetic acid KW - 2,4-D KW - Toxicology Abstracts KW - herbicides KW - lymphoma KW - X 24136:Environmental impact UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15758000?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Research&rft.atitle=On+the+association+between+canine+malignant+lymphoma+and+opportunity+for+exposure+to+2%2C4-dichlorophenoxyacetic+acid&rft.au=Hayes%2C+H+M%3BTarone%2C+R+E%3BCantor%2C+K+P&rft.aulast=Hayes&rft.aufirst=H&rft.date=1995-01-01&rft.volume=70&rft.issue=2&rft.spage=119&rft.isbn=&rft.btitle=&rft.title=Environmental+Research&rft.issn=00139351&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 - lymphoma; herbicides ER - TY - JOUR T1 - Identifying chemical carcinogens and assessing potential risk in short-term bioassays using transgenic mouse models AN - 15754869; 3979745 AB - Cancer is a worldwide public health concern. Identifying carcinogens and limiting their exposure is one approach to the problem of reducing risk. Currently, epidemiology and rodent bioassays are the means by which putative human carcinogens are identified. Both methods have intrinsic limitations: they are slow and expensive processes with many uncertainties. The development of methods to modify specific genes in the mammalian genome has provided promising new tools for identifying carcinogens and characterizing risk. Transgenic mice may provide advantages in shortening the time required for bioassays and improving the accuracy of carcinogen identification; transgenic mice might now be included in the testing armamentarium without abandoning the two-year bioassay, the current standard. We show that mutagenic carcinogens can be identified with increased sensitivity and specificity using hemizygous p53 mice in which one allele of the p53 gene has been inactivated. Furthermore, the TGAC transgenic model, carrying a v-Ha-ras construct, has developed papillomas and malignant tumors in response to a number of mutagenic and nonmutagenic carcinogens and tumor promoters, but not to noncarcinogens. We present a decision-tree approach that permits, at modest extra cost, the testing of more chemicals with improved ability to extrapolate from rodents to humans. JF - Environmental Health Perspectives AU - Tennant, R W AU - French, JE AU - Spalding, J W AD - NIEHS, PO Box 12233, Research Triangle Park, NC 27709 USA. Y1 - 1995 PY - 1995 DA - 1995 SP - 942 EP - 950 VL - 103 IS - 10 SN - 0091-6765, 0091-6765 KW - p53 gene KW - v-Ha-ras gene KW - Toxicology Abstracts KW - 95-218 KW - carcinogens KW - transgenic mice KW - bioassays KW - risk assessment KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15754869?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=Identifying+chemical+carcinogens+and+assessing+potential+risk+in+short-term+bioassays+using+transgenic+mouse+models&rft.au=Tennant%2C+R+W%3BFrench%2C+JE%3BSpalding%2C+J+W&rft.aulast=Tennant&rft.aufirst=R&rft.date=1995-01-01&rft.volume=103&rft.issue=10&rft.spage=942&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - risk assessment; bioassays; transgenic mice; carcinogens ER - TY - JOUR T1 - Plasmodium gallinaceum: Sporozoite invasion of Aedes aegypti salivary glands is inhibited by anti-gland antibodies and by lectins AN - 15746905; 3976349 AB - There is evidence which suggests that malaria sporozoites recognize mosquito salivary glands by specific receptor-ligand interactions. We are interested in identifying the putative salivary gland receptor(s) for sporozoite invasion. We used an in vivo bioassay for sporozoite invasion of salivary glands. In this assay, purified sporozoites from mature oocysts of Plasmodium gallinaceum were injected into Aedes aegypti mosquitoes and salivary glands were dissected at different time points after injection. One half of the maximum invasion of salivary glands by sporozoites occurred by 6 hr, and salivary gland sporozoite load did not increase further after 24 hr postinjection. This assay was used to determine the effect of experimental treatments with antibodies and lectins at 24 hr postinjection. We raised a rabbit polyclonal antiserum against female Ae. aegypti salivary glands which recognized tissue-specific determinants in the basal lamina of salivary glands. Purified IgG antibody fraction of the immune serum blocked sporozoite invasion in vivo. We tested a panel of 19 lectins and found 7 which bound to salivary glands. Of these 7, succinylated wheat germ agglutinin and wheat germ agglutinin completely blocked sporozoite invasion; Pisum sativum agglutinin and soybean agglutinin partially blocked; and concanavalin A, Dolichos biflorus agglutinin, and Phaseolus vulgaris erythroagglutinin did not block. Our results suggest that sporozoites interact with glycosylated salivary gland surface molecules which serve as receptors for invasion, and which may be in the salivary gland basal lamina. Because the putative sporozoite receptors contain immunogenic determinants, it is feasible to identify them by an immunological strategy. JF - Experimental Parasitology AU - Barreau, C AU - Touray, M AU - Pimenta, P F AU - Miller, L H AU - Vernick, K D AD - Lab. Parasitic Dis., NIAID, Natl. Institutes Health, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 332 EP - 343 VL - 81 IS - 3 SN - 0014-4894, 0014-4894 KW - biological vectors KW - lectins KW - salivary gland KW - sporozoites KW - ASFA 1: Biological Sciences & Living Resources; ASFA 3: Aquatic Pollution & Environmental Quality; Entomology Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - Aedes aegypti KW - antibodies KW - vectors KW - immunology KW - malaria KW - Plasmodium gallinaceum KW - Z 05206:Medical & veterinary entomology KW - Q1 08484:Species interactions: parasites and diseases KW - Q5 08524:Public health, medicines, dangerous organisms KW - K 03092:Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15746905?accountid=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=Experimental+Parasitology&rft.atitle=Plasmodium+gallinaceum%3A+Sporozoite+invasion+of+Aedes+aegypti+salivary+glands+is+inhibited+by+anti-gland+antibodies+and+by+lectins&rft.au=Barreau%2C+C%3BTouray%2C+M%3BPimenta%2C+P+F%3BMiller%2C+L+H%3BVernick%2C+K+D&rft.aulast=Barreau&rft.aufirst=C&rft.date=1995-01-01&rft.volume=81&rft.issue=3&rft.spage=332&rft.isbn=&rft.btitle=&rft.title=Experimental+Parasitology&rft.issn=00144894&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2014-05-06 N1 - SubjectsTermNotLitGenreText - vectors; biological vectors; immunology; malaria; antibodies; lectins; salivary gland; sporozoites; Aedes aegypti; Plasmodium gallinaceum ER - TY - JOUR T1 - The kinetics of RCC1 inclusion body formation in Escherichia coli AN - 15657733; 3941937 AB - The Regulator of Chromosome Condensation protein (RCC1) is located in both the soluble and inclusion body (lB) fractions of the whole cell lysate when expressed in Escherichia coli BL21 (pLysS) at temperatures below 30 degree C. When bacterial growth was carried out at 20 degree C, the majority of the RCC1 remained soluble up to 5.5 h postinduction. When the temperature was raised to 25 degree C, RCC1 IB was dominant by 1.5 h postinduction. The shift in RCC1 IB formation with temperature suggests that in addition to increased translation rates, folding and aggregation processes may contribute to RCC1 IB formation at higher temperatures. JF - Biotechnology and Bioengineering AU - Tsai, A M AU - Betenbaugh, MJ AU - Shiloach, J AD - Biotechnol. Unit, NIDDK, NIH, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 715 EP - 718 PB - JOHN WILEY & SONS VL - 48 IS - 6 SN - 0006-3592, 0006-3592 KW - RCC1 protein KW - Biotechnology and Bioengineering Abstracts; Agricultural and Environmental Biotechnology Abstracts; Microbiology Abstracts B: Bacteriology KW - inclusion bodies KW - Escherichia coli KW - W2 32340:Other peptides, proteins, amino acids KW - W 30965:Miscellaneous, Reviews KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15657733?accountid=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=Biotechnology+and+Bioengineering&rft.atitle=The+kinetics+of+RCC1+inclusion+body+formation+in+Escherichia+coli&rft.au=Tsai%2C+A+M%3BBetenbaugh%2C+MJ%3BShiloach%2C+J&rft.aulast=Tsai&rft.aufirst=A&rft.date=1995-01-01&rft.volume=48&rft.issue=6&rft.spage=715&rft.isbn=&rft.btitle=&rft.title=Biotechnology+and+Bioengineering&rft.issn=00063592&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - inclusion bodies; Escherichia coli ER - TY - JOUR T1 - Ozone exposure in humans: Inflammatory, small and peripheral airway responses AN - 15639184; 3935968 AB - We exposed eight normal adults to filtered air (FA) and 0.35 ppm ozone (O sub(3)) and compared responses in spirometry, including isovolume (isoV) flows at intermediate-to-low lung volumes, against levels of inflammatory markers in bronchoalveolar lavage fluid (BALF) and peripheral lung resistance (Rp) measured through a wedged bronchoscope. Spriometry was performed at the end, 25 min and 24 h after exposure, bronchoscopy at 24 h after exposure. The percentages of neutrophils, fibrinogen, albumin, PGE sub(2), PGF sub(2 alpha ), and kinins were elevated in BALF after O sub(3) compared with FA. The percentage reduction in (isoV) FEF sub(25-75) at 25 min and 24 h after administration of O sub(3) correlated closely with the rise in fibrinogen concentrations in BALF, a marker of altered vascular permeability. Rp, a measurement dominated by very small or peripheral airways, was unaffected in 7 of 8 subjects. The absence of change in Rp might have reflected insufficient penetration of O sub(3) into these airways to produce or sustain an effect for 24 h; alternatively, the bronchoscopic procedure which included atropine and lidocaine pretreatment may have reversed an O sub(3) effect. An unexpected finding was the significant association between baseline Rp (after FA) and the magnitude of the spirometric response to O sub(3). Our results suggest that small airway dysfunction in the immediate post-O sub(3) period is a marker of lung inflammation. JF - American Journal of Respiratory and Critical Care Medicine AU - Weinmann, G G AU - Liu, M C AU - Proud, D AU - Weidenbach-Gerbase, M AU - Hubbard, W AU - Frank, R AD - NIH/NHLBI/DLD/ABDP, Two Rockledge Cent., Suite 10018, 6701 Rockledge Dr. MSC 7952, Bethesda, MD 20892-7952, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 1175 EP - 1182 VL - 152 IS - 4 SN - 1073-449X, 1073-449X KW - ozone KW - Toxicology Abstracts KW - respiratory tract diseases KW - inflammation KW - lung KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15639184?accountid=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+Respiratory+and+Critical+Care+Medicine&rft.atitle=Ozone+exposure+in+humans%3A+Inflammatory%2C+small+and+peripheral+airway+responses&rft.au=Weinmann%2C+G+G%3BLiu%2C+M+C%3BProud%2C+D%3BWeidenbach-Gerbase%2C+M%3BHubbard%2C+W%3BFrank%2C+R&rft.aulast=Weinmann&rft.aufirst=G&rft.date=1995-01-01&rft.volume=152&rft.issue=4&rft.spage=1175&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Respiratory+and+Critical+Care+Medicine&rft.issn=1073449X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - lung; respiratory tract diseases; inflammation ER - TY - JOUR T1 - Sustained exposure to 1-aminocyclopropanecarboxylic acid, a glycine partial agonist, alters N-methyl-D-aspartate receptor function and subunit composition AN - 15603887; 3926813 AB - Partial agonists at the strychnine-insensitive glycine sites coupled to N-methyl-D-aspartate (NMDA) receptors reduce both glutamate-induced neurotoxicity in vitro and ischemia-induced neurodegeneration in vivo. Paradoxically, sustained exposure of cultured cerebellar granule cell neurons to glycinergic ligands, including glycine and the glycine partial agonists ( plus or minus )-3-amino-1-hydroxy-2-pyrrolidone, 1-aminocyclopropanecarboxylic acid (ACPC), and D-cycloserine, attenuates the neuroprotective effects of ( plus or minus )-3-amino-1-hydroxy-2-pyrrolidone and ACPC. In the present study, we investigated the mechanisms responsible for this attenuated neuroprotection. Three NMDA receptor-mediated responses were examined after sustained exposure to ACPC: glutamate-induced neurotoxicity, NMDA-stimulated increases in cGMP levels, and NMDA-stimulated increases in [Ca super(2+)] sub(i). Consistent with previous findings, coincubation with ACPC blocked glutamate-induced neurotoxicity, whereas sustained (24 hr) exposure to ACPC attenuated its protective effects. Moreover, sustained exposure to ACPC caused an apparent similar to 2-fold increase in the potency of both glutamate to act as a neurotoxin and NMDA to stimulate CGMP formation. Sustained exposure to ACPC also increased NMDA-stimulated [Ca super(2+)] sub(i) similar to 3-fold compared with control granule cell cultures but did not affect basal [Ca super(2+)] sub(i). This apparent increase in glutamate sensitivity may be attributable to a change in NMDA receptor subunit composition as sustained ACPC exposure resulted in a similar to 2.5-fold increase in NMDA receptor 2C RNA levels, without concomitant changes in the amounts of RNA encoding the NMDA receptor 2A, 2B, or 1 subunit. This is the first demonstration that sustained exposure to a glycinergic ligand can alter the expression of RNAs encoding NMDA receptor subunits. Because glycinergic ligands are potential clinical candidates, these results may have important implications for the treatment of neurodegenerative disorders. JF - Molecular Pharmacology AU - Fossom, L H AU - Basile, A S AU - Skolnick, P AD - Natl. Inst. Health, NIDDK, Lab. Neurosci., Bldg. 8, Rm. 111, Bethesda, MD 20892-0826, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 981 EP - 987 VL - 48 IS - 6 SN - 0026-895X, 0026-895X KW - 1-aminocyclopropanecarboxylic acid KW - N-methyl-D-aspartic acid receptors KW - NMDA receptors KW - Toxicology Abstracts KW - agonists KW - glycine KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15603887?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Pharmacology&rft.atitle=Sustained+exposure+to+1-aminocyclopropanecarboxylic+acid%2C+a+glycine+partial+agonist%2C+alters+N-methyl-D-aspartate+receptor+function+and+subunit+composition&rft.au=Fossom%2C+L+H%3BBasile%2C+A+S%3BSkolnick%2C+P&rft.aulast=Fossom&rft.aufirst=L&rft.date=1995-01-01&rft.volume=48&rft.issue=6&rft.spage=981&rft.isbn=&rft.btitle=&rft.title=Molecular+Pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - glycine; agonists ER - TY - JOUR T1 - Phencyclidine-induced increases in striatal neuron firing in behaving rats: Reversal by haloperidol and clozapine AN - 15602117; 3923527 AB - Amphetamine and related drugs of abuse facilitate dopamine transmission in the striatum. This action is believed to underlie the increase in firing of striatal motor-related neurons after amphetamine administration in behaving rats. The present study extended this electrophysiological investigation to phencyclidine (PCP), a nonamphetamine psychomotor stimulant that acts primarily as a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) glutamate receptors. Like amphetamine, PCP increased the activity of striatal motor-related neurons concomitant with behavioral activation. These effects were blocked by subsequent administration of either 1.0 mg/kg haloperidol or 20.0 mg/kg clozapine, typical and atypical neuroleptics, respectively. Dizocilpine (MK-801), another noncompetitive NMDA antagonist, mimicked the effect of PCP. Collectively, these results indicate that amphetamine and NMDA antagonists exert comparable effects on striatal motor-related neurons, suggesting that the response of these cells to psychomotor stimulants is regulated by a dopaminergic-glutamatergic influence. JF - Journal of Neural Transmission AU - White, I M AU - Flory, G S AU - Hooper, K C AU - Speciale, J AU - Banks, DA AU - Rebec, G V AD - Lab. Neurophysiology, NIMH, Poolseville, MD 20836, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 99 EP - 112 VL - 102 IS - 2 SN - 0300-9564, 0300-9564 KW - phencyclidine KW - haloperidol KW - clozapine KW - amphetamine KW - N-methyl-D-aspartic acid receptors KW - dizocilpine KW - rats KW - NMDA receptors KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - neuroleptics KW - neostriatum 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/15602117?accountid=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+Neural+Transmission&rft.atitle=Phencyclidine-induced+increases+in+striatal+neuron+firing+in+behaving+rats%3A+Reversal+by+haloperidol+and+clozapine&rft.au=White%2C+I+M%3BFlory%2C+G+S%3BHooper%2C+K+C%3BSpeciale%2C+J%3BBanks%2C+DA%3BRebec%2C+G+V&rft.aulast=White&rft.aufirst=I&rft.date=1995-01-01&rft.volume=102&rft.issue=2&rft.spage=99&rft.isbn=&rft.btitle=&rft.title=Journal+of+Neural+Transmission&rft.issn=03009564&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 - neostriatum; neuroleptics ER - TY - JOUR T1 - Studies on the expression and immunogenicity of the B50 melanoma antigen and its relationship with calreticulin AN - 15584499; 3916413 AB - B50 is a 50 kDa protein antigen originally identified and isolated from cultured B16 murine melanoma cells; it is found in close association with a melanoma-specific antigen termed B700. Using a specific rabbit antiserum, B50 (or B50 cross-reactive molecules) has been shown to be expressed by 35 out of 36 cell lines, including melanomas, sarcomas, fibrosarcomas, carcinomas, gliomas, immortalized and primary fibroblasts, melanocyte and keratinocyte cell lines obtained from murine, human, hamster, swine, and canine donors. B50 expression is localized on the cellular membrane and in the cytoplasm in varying amounts in seven of the nine cell lines tested. Mice immunized to B50 demonstrated a significant tumour rejection response when subsequently challenged with B16 F10 melanoma cells. Previous studies had indicated that B50 has significant N-terminal amino acid sequence homology with calreticulin. Calreticulin, a calcium-binding protein, is part of the Ro/SS-A complex. This complex is the primary autoantigenic determinant of the autoimmune diseases systemic lupus erythematosus and primary Sjogren's syndrome. We now show that sera from patients with those diseases contain antibodies which bind B50, although B50 itself does not bind calcium. Thus, B50 and calreticulin are closely related but distinct antigens. (DBO) JF - Melanoma Research AU - Bijwaard, K AU - Hearing, V J AU - Sontheimer, R AU - Lieu, Tsu-San AU - Vieira, W D AU - Gersten, D M AD - Lab. Cell Biol., Bldg. 37, Rm. 1B25, NCI/NIH, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 327 EP - 336 VL - 5 IS - 5 SN - 0960-8931, 0960-8931 KW - calreticulin KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - immunogenicity KW - melanoma KW - antigens KW - W3 33160:Antibody based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15584499?accountid=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=Melanoma+Research&rft.atitle=Studies+on+the+expression+and+immunogenicity+of+the+B50+melanoma+antigen+and+its+relationship+with+calreticulin&rft.au=Bijwaard%2C+K%3BHearing%2C+V+J%3BSontheimer%2C+R%3BLieu%2C+Tsu-San%3BVieira%2C+W+D%3BGersten%2C+D+M&rft.aulast=Bijwaard&rft.aufirst=K&rft.date=1995-01-01&rft.volume=5&rft.issue=5&rft.spage=327&rft.isbn=&rft.btitle=&rft.title=Melanoma+Research&rft.issn=09608931&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - immunogenicity; melanoma; antigens ER - TY - JOUR T1 - Designing amino acid sequences to fold with good hydrophobic cores AN - 15579717; 3910589 AB - We present two methods for designing amino acid sequences of proteins that will fold to have good hydrophobic cores. Given the coordinates of the desired target protein or polymer structure, the methods generate sequences of hydrophobic (H) and polar (P) monomers that are intended to fold to these structures. One method designs hydrophobic inside, polar outside; the other minimizes an energy function in a sequence evolution process. The sequences generated by these methods agree at the level of 60-80% of the sequence positions in 20 proteins in the Protein Data Bank. A major challenge in protein design is to create sequences that can fold uniquely, i.e. to a single conformation rather than to many. While an earlier lattice-based sequence evolution method was shown not to design unique folders, our method generates unique folders in lattice model tests. These methods may also be useful in designing other types of foldable polymer not based on amino acids. JF - Protein Engineering AU - Sun, S AU - Brem, R AU - Chan, H S AU - Dill, KA AD - NCI-FCRF, Frederick Biomed. Supercomputing Cent., PO Box B, Frederick, MD 21702, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 1205 EP - 1213 VL - 8 IS - 12 SN - 0269-2139, 0269-2139 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Agricultural and Environmental Biotechnology Abstracts KW - protein folding KW - amino acid sequence KW - hydrophobicity KW - proteins 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/15579717?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+Engineering&rft.atitle=Designing+amino+acid+sequences+to+fold+with+good+hydrophobic+cores&rft.au=Sun%2C+S%3BBrem%2C+R%3BChan%2C+H+S%3BDill%2C+KA&rft.aulast=Sun&rft.aufirst=S&rft.date=1995-01-01&rft.volume=8&rft.issue=12&rft.spage=1205&rft.isbn=&rft.btitle=&rft.title=Protein+Engineering&rft.issn=02692139&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - protein folding; amino acid sequence; hydrophobicity; proteins ER - TY - JOUR T1 - Recovery of insect cells using hollow fiber microfiltration AN - 15569339; 3906164 AB - An efficient method was developed for media separation and cell collection for eukaryotic cells growing in suspension. The method is based on tangential flow microfiltration using an open channel arrangement in a hollow fiber configuration. Best results (highest processing flux rate) for polysulfone hollow fibers were obtained using fibers with internal diameter of 0.75 mm, 0.45 mu m pore size, and a cell suspension flow at a shear rate of 14000 s super(-1) (0.032 L/min per fiber). A flux rate of 500 L/m super(2) h can be obtained by maintaining the surface area/cell ratio at 0.05 m super(2)/10 L of cells at a concentration of 2.5 x 10 super(6) cells/mL. Forty liters of infected insect cells can be concentrated 10 times in 20 min without affecting cell viability. JF - Biotechnology and Bioengineering AU - Trinh, L AU - Shiloach, J AD - Biotechnol. Unit, NIDDK, Natl. Inst. Health, Bethesda, MD 20892, USA Y1 - 1995 PY - 1995 DA - 1995 SP - 401 EP - 405 VL - 48 IS - 4 SN - 0006-3592, 0006-3592 KW - Inecta KW - Sf9 cells KW - Biotechnology and Bioengineering Abstracts; Entomology Abstracts; Agricultural and Environmental Biotechnology Abstracts KW - fibers KW - Spodoptera frugiperda KW - filtration KW - Noctuidae KW - Lepidoptera KW - W 30965:Miscellaneous, Reviews KW - W2 32220:Cell culture KW - Z 05156:Techniques UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15569339?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biotechnology+and+Bioengineering&rft.atitle=Recovery+of+insect+cells+using+hollow+fiber+microfiltration&rft.au=Trinh%2C+L%3BShiloach%2C+J&rft.aulast=Trinh&rft.aufirst=L&rft.date=1995-01-01&rft.volume=48&rft.issue=4&rft.spage=401&rft.isbn=&rft.btitle=&rft.title=Biotechnology+and+Bioengineering&rft.issn=00063592&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - fibers; filtration; Spodoptera frugiperda; Noctuidae; Lepidoptera ER - TY - JOUR T1 - Undivided Publication of Research Findings: A Uniform Editorial Policy of the Consortium of Editors of Journals Relating to Human Development AN - 1302527335 JF - Child Abuse and Neglect Y1 - 1995/01/01/ PY - 1995 DA - 1995 Jan 01 SP - 271 CY - Oxford PB - Pergamon Press. VL - 19 IS - 3 SN - 0145-2134 KW - Children And Youth - About UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1302527335?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Apio&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Child+Abuse+and+Neglect&rft.atitle=Undivided+Publication+of+Research+Findings%3A+A+Uniform+Editorial+Policy+of+the+Consortium+of+Editors+of+Journals+Relating+to+Human+Development&rft.au=&rft.aulast=&rft.aufirst=&rft.date=1995-01-01&rft.volume=19&rft.issue=3&rft.spage=271&rft.isbn=&rft.btitle=&rft.title=Child+Abuse+and+Neglect&rft.issn=01452134&rft_id=info:doi/ DB - Periodicals Index Online N1 - Last updated - 2013-02-24 ER -